REPOSITORIO

Oscar Flores‑Flores, Alejandro Zevallos‑Morales, Ivonne Carrión, Dalia Pawer, Lorena Rey, W. Checkley, J. R. Hurst, T. Siddharthan, Jose F. Parodi, Joseph J. Gallo and Suzanne L. Pollard.

Flores‑Flores et al. Int J Ment Health Syst (2020) 14:49

Background:
Despite the high levels of depression and anxiety symptoms in old age, the use of mental health services in this population is low. Help-seeking behaviors are shaped by how an individual perceives and experiences their illness. The objective of this study was to characterize the illness experiences of Peruvian older adults with depression and anxiety symptoms in order to lay the foundation for tailored community-based mental health interventions.

Methods:
In this qualitative study, we conducted in-depth interviews with a purposively selected sample of older adults (≥60 years) from peri-urban areas of Lima, Peru. We included individuals with only depressive symptoms (Patient Health Questionnaire-9≥10), only anxiety symptoms (Beck Anxiety Inventory≥16), with depressive and anxiety symptoms, and older adults who mentioned they had received mental health treatment/care. The interview guide included the following topics: perceptions and experiences about depression and anxiety; perceptions about the relationship between physical chronic diseases and mental health; experiences with mental health professionals and treatments, and coping mechanisms. Data collection was conducted between October 2018 and February 2019.

Results:
We interviewed 38 participants (23 women, 15 men) with a mean age of 67.9 years. Participants’ ideas and perceptions of depression and anxiety showed considerable overlap. Participants attributed depression and anxiety mainly to familial and fnancial problems, loneliness, loss of independence and past traumatic experiences. Coping strategies used by older adults included ‘self-refection and adaptation’ to circumstances, ‘do your part’, and seeking ‘emotional support’ mainly from non-professionals (relatives, friends, acquaintances, and religion).

Conclusions:
Illness experiences of depression and anxiety set the pathway for tailored community-based mental
health interventions for older adults. Overlapping narratives and perceptions of depression and anxiety suggest that these conditions should be addressed together. Mental health interventions hould incorporate addressing areas related to depression and anxiety such as prevention of loss of independence, trauma, and loneliness. Good acceptability of receiving emotional support for non-professionals might ofer an opportunity to incorporate them when delivering mental health care to older adults.

Francesca Schiaffino, Nora Pisanic, Josh M. Colston, Dixner Rengifo, Maribel Paredes Olortegui,
Valentino Shapiama, Pablo Peñataro Yori, Christopher D. Heaney, Meghan F. Davis, Margaret N. Kosek.

F. Schiaffino et al. / Science of the Total Environment 743 (2020) 140531

The performance of eight microbial source tracking (MST) markers was evaluated in a low-resource, tropical community located in Iquitos, Peru. Fecal samples from humans, dogs, cats, rats, goats, buffalos, guinea-pigs, chickens, ducks, pigeons, and parrots were collected (n = 117). All samples were tested with human (BacHum, HF183-Taqman), dog (BactCan), pig (Pig-2-Bac), and avian (LA35, Av4143, ND5, cytB) markers using quantitative PCR (qPCR). Internal validity metrics were calculated using all animal fecal samples, as well as animal fecal samples contextually relevant for the Peruvian Amazon. Overall, Pig-2-Bac performed best, with 100% sensitivity and 88.5% specificity to detect the correct fecal source. Human-associated markers showed a sensitivity of 80.0% and 76.7%, and specificity of 66.2% and 67.6%. When limiting the analysis to contextually relevant animal fecal samples for the Peruvian Amazon, Av143 surpassed cytB with 95.7% sensitivity and 81.8% specificity. BactCan demonstrated 100% sensitivity and 47.4% specificity. The gene copy number detected by BacHum and HF183-Taqman were positively correlated (Pearson’s correlation coefficient: 0.785), as well as avian markers cytB with Av4143 (Pearson’s correlation coefficient: 0.508) and nd5 (Pearson’s correlation coefficient: 0.949). These findings suggest that markers such as Av4143, Pig2Bac, cytb and BacHum have acceptable performance to be impactful in source attribution studies for zoonotic enteric disease transmission in this and similar low-resource communities.

Benjamin W. Barrett; Valerie A. Paz-Soldan; Diana Mendoza-Cervantes; Graciela Meza Sanchez; Jhonny J. Cordova López; Patti E. Gravitt; and Anne F. Rositch; on behalf of the Proyecto Precancer Study Group.

JCO Global Oncol 6:1237-1247.

PURPOSE
Cervical cancer (CC) is the most common and second-most deadly cancer among Peruvian women. Access to services is strongly associated with CC screening uptake. This study investigated geospatial features contributing to utilization of screening. We used geolocated data and screening information from a Knowledge, Attitudes, and Practice (KAP) survey implemented in Iquitos, Peru in 2017.
MATERIALS AND METHODS
The KAP collected cross-sectional CC screening history from 619 female interviewees age 18-65 years within 5 communities of varying urbanization levels. We used spatial statistics to determine if screened households tended to cluster together or cluster around facilities offering screening in greater numbers than expected, given the underlying population density.
RESULTS
On the basis of K-functions, screened households displayed greater clustering among each other as compared with clustering among unscreened households. Neighborhood-level factors, such as outreach, communication, or socioeconomic condition, may be functioning to generate pockets of screened households. Cross K-functions showed that screened households are generally located closer to health facilities than unscreened households. The significance of facility access is apparent and demonstrates that travel and time barriers to seeking health services must be addressed.
CONCLUSION This study highlights the importance of considering geospatial features when determining factors associated with CC screening uptake. Given the observed clustering of screened households, neighborhoodlevel dynamics should be further studied to understand how they may be influencing screening rates. In addition, results demonstrate that accessibility issues must be carefully considered when designing an effective cancer screening program that includes screening, follow-up, and treatment.

Sathvik Namburar, William Checkley, Oscar Flores-Flores, Karina M. Romero, Katherine Tomaino Fraser, Nadia N. Hansel, and Suzanne L. Pollard, GASP Study Investigators.

Journal of Physical Activity and Health, 2020, 17, 816-822

Background: The authors sought to examine physical activity patterns among children with and without asthma in 2 peri-urban communities in Lima, Peru, to identify socioeconomic and demographic risk factors for physical inactivity and examine the relationship between asthma and physical activity. Methods: The authors measured mean steps per day in 114 children (49 with
asthma and 65 without) using pedometers worn over a 1-week period. They also used the 3-day physical activity recall to determine the most common activities carried out by children. Results: The authors found that 84.2% of the children did not meet the daily international physical activity recommendations. Girls took significantly fewer mean steps per day as compared with boys (2258
fewer steps, 95% confidence interval, 1042–3474), but no other factors, including asthma status, showed significant differences in the mean daily steps. Mean daily steps were positively associated with higher socioeconomic status among girls, and current asthma had a larger inverse effect on daily steps in boys when compared with girls. Conclusion: Physical activity levels were below recommended guidelines in all children. There is a need for policy and neighborhood-level interventions to address low physical activity levels among Peruvian youth. Special focus should be given to increasing the physical activity levels in girls.

Sumona Datta, Robert H. Gilman, Rosario Montoya, Luz Quevedo Cruz, Teresa Valencia, Doug Huff, Matthew J. Saunders and Carlton A. Evans.

Eur Respir J 2020; 56: 1900495

Background: Global tuberculosis policy increasingly emphasises broad tuberculosis impacts and highlights he lack of evidence concerning tuberculosis-related quality of life (QOL).
Methods: Participants were recruited in 32 Peruvian communities between July 13, 2016 and February 24, 2018 and followed-up until November 8, 2019. Inclusion criteria were age ⩾15 years for “patients” (n=1545) starting treatment for tuberculosis disease in health centres; “contacts” (n=3180) who shared a patient’s household for ⩾6 h·week−1; and randomly selected “controls” (n=277). The EUROHIS-QOL questionnaire quantified satisfaction with QOL, health, energy, activities of daily living (ADL), self, relationships, money and living place.
Findings: Newly diagnosed tuberculosis was most strongly associated with lower QOL scores (p<0.001). Patients initially had lower QOL than controls for all EUROHIS-QOL questions (p⩽0.01), especially concerning health, ADL and self. Lower initial QOL in patients predicted adverse treatment outcomes and scores <13 points had 4.2-fold (95% CI 2.3–7.6) increased risk of death versus those with higher QOL scores (both p<0.001). Patient QOL was re-assessed 6 months later, and for patients with successful treatment QOL became similar to participants who had never had tuberculosis, whereas patients who did not complete treatment continued to have low QOL (p<0.001). Multidrug-resistant tuberculosis was associated with lower QOL before and during treatment (both p<0.001). Contacts had lower QOL if they lived with a patient who had low QOL score (p<0.0001) or were a caregiver for the patient (p<0.001).
Conclusions: Tuberculosis was associated with impaired psychosocioeconomic QOL which recovered with successful treatment. Low QOL scores predicted adverse treatment outcome. This brief EUROHIS-QOL eight-item questionnaire quantified the holistic needs of tuberculosis-affected people, potentially guiding patient-centred care.

Elizabeth T. Rogawski McQuade, Jie Liu, Gagandeep Kang, Margaret N. Kosek, Aldo A. M. Lima, Pascal O. Bessong, Amidou Samie, Rashidul Haque, Estomih R. Mduma, Sanjaya Shrestha, Jose Paulo Leite, Ladaporn Bodhidatta, Najeeha Iqbal, Nicola Page, Ireen Kiwelu, Zulfiqar Bhutta, Tahmeed Ahmed, Eric R. Houpt, and James A. Platts-Mills.

The Journal of Infectious Diseases 2020;222:1858–68

Background.
The degree of protection conferred by natural immunity is unknown for many enteropathogens, but it is important to support the development of enteric vaccines.
Methods.
We used the Andersen-Gill extension of the Cox model to estimate the effects of previous infections on the incidence of subsequent subclinical infections and diarrhea in children under 2 using quantitative molecular diagnostics in the MAL-ED cohort. We used cross-pathogen negative control associations to correct bias due to confounding by unmeasured heterogeneity of exposure and susceptibility.
Results.
Prior rotavirus infection was associated with a 50% lower hazard (calibrated hazard ratio [cHR], 0.50; 95% confidence interval [CI], 0.41–0.62) of subsequent rotavirus diarrhea. Strong protection was evident against Cryptosporidium diarrhea (cHR, 0.32; 95% CI, 0.20–0.51). There was also protection due to prior infections for norovirus GII (cHR against diarrhea, 0.67; 95% CI, 0.49–0.91), astrovirus (cHR, 0.62; 95% CI, 0.48–0.81), and Shigella (cHR, 0.79; 95% CI, 0.65–0.95). Minimal protection was observed for other bacteria, adenovirus 40/41, and sapovirus.
Conclusions.
Natural immunity was generally stronger for the enteric viruses than bacteria, potentially due to less antigenic diversity. Vaccines against major causes of diarrhea may be feasible but likely need to be more immunogenic than natural infection.

Josh M. Colston, Pablo Peñataro Yori, Lawrence H. Moulton, Maribel Paredes Olortegui, Peter S. Kosek, Dixner Rengifo Trigoso, Mery Siguas Salas, Francesca Schiaffino, Ruthly Francois, Fahmina Fardus-Reid, Jonathan R. Swann, Margaret N. Kosek.

PLoS Negl Trop Dis 13(11): e0007851.

Environmental enteric dysfunction (EED) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EED reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker’s association with linear growth in infancy and early childhood. 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects’ length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the bestfitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker’s adjusted effect on growth. Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score–a coefficient value of 0.50 (0.24, 0.75) for each log2 increase in plasma transferrin concentration. Other biomarkers with large effect size estimates included adiponectin, arginine, growth hormone, proline and serum amyloid P-component. The selected subset explained up to 23.0% of the variability in LAZ-score. Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EED. There is a need to systematically express the strength of association of biomarkers with linear growth or other outcomes to compare results across studies.

Gwenyth O Lee, Robert Schillinger, Nirupama Shivakumar, Sherine Whyte, Sayeeda Huq, Silvenus Ochieng Konyole, Justin Chileshe, Maribel Paredes-Olortegui, Victor Owino, Roger Yazbeck, Margaret N Kosek, Paul Kelly, Douglas Morrison.

Lee GO, et al. BMJ Open 2020;10:e035841.

Introduction
Environmental enteropathy (EE) is suspected to be a cause of growth faltering in children with sustained exposure to enteric pathogens, typically in resource-limited settings. A major hindrance to EE research is the lack of sensitive, non-invasive biomarkers. Current biomarkers measure intestinal permeability and inflammation, but not the functional capacity of the gut. Australian researchers have demonstrated proof of concept for an EE breath test based on using naturally 13Cenriched sucrose, derived from maize, to assay intestinal sucrase activity, a digestive enzyme that is impaired in villus blunting. Here, we describe a coordinated research project to optimise, validate and evaluate the usability of a breath test protocol based on highly enriched 13C-sucrose to quantify physiological dysfunction in EE in relevant target populations.

Methods and analysis
We use the 13C-sucrose breath test (13C-SBT) to evaluate intestinal sucrase activity in two phases. First, an optimisation and validation phase will (1) confirm that a 13C-SBT using highly enriched sucrose tracers reports similar information to the naturally enriched 13C-SBT; (2) examine the dose–response relationship of the test to an intestinal sucrase inhibitor; (3) validate the 13C-SBT in  aediatric coeliac disease (4) validate the highly enriched 13C-SBT against EE defined by biopsy in
adults and (5) validate the 13C-SBT against EE defined by the urinary lactulose:rhamnose ratio (LR) among children in Peru. Second, a cross-sectional study will be conducted in six resource-limited countries (Bangladesh, India, Jamaica, Kenya, Peru and Zambia) to test the usability of
the optimised 13C-SBT to assess EE among 600 children aged 12–15months old. Ethics and dissemination Ethical approval will be obtained from each participating study site. By working
as a consortium, the test, if shown to be informative of EE, will demonstrate strong evidence for utility across diverse, low-income and middle-income country paediatric populations.

Hannah Karen Mina Labayo, Monica J. Pajuelo, Kentaro Tohma, Lauren A. Ford-Siltz, Robert H. Gilman, Lilia Cabrera, Holger Mayta, Gerardo J. Sanchez, Anniuska Toledo Cornejo, Caryn Bern, Clyde Dapat, Tomonori Nochi, Gabriel I. Parra, Hitoshi Oshitani, Mayuko Saito.

H.K.M. Labayo et al. / EClinicalMedicine 27 (2020) 100561

Background: Norovirus (NV) causes acute gastroenteritis in infants. Humoral and fecal immunoglobulin A(IgA) responses have been correlated with protection against NV; however, the role of breast milk IgA against NV infection and associated diarrhea is still unknown. This study aimed to evaluate the protective role of NVspecific IgA (NV-IgA) in breast milk.

Methods: Ninety-five breast milk samples collected from mothers enrolled in a 2016
2017 Peruvian birth cohort study were tested for total IgA and NV-IgA by ELISA using GII¢4 variants and non-GII¢4 genotype virus-like particles (VLPs). Breast milk samples were grouped according to the NV infection and diarrheal status of infants: NV positive with diarrhea (NV+D+, n=18); NV positive without diarrhea (NV+D-, n=37); and NV negative without diarrhea (NV-D-, n=40). The percent positivity and titer of NV-IgA were compared among groups. The cross-reactivity was estimated based on the correlation of ratio between NV-IgA against GII¢4 variants and non-GII¢4 genotype VLPs.

Findings: NV-IgA had high positivity rates against different VLPs, especially against GII (89-100%). The NV+Dgroup had higher percent positivity (89% vs. 61%, p=0¢03) and median titer (1:100 vs 1:50, p=0¢03) of NV-IgA than the NV+D+ group against GI¢1 VLPs. A relatively high correlation between different GII¢4 variants (0¢87) and low correlation between genogroups (0¢23
0¢37) were observed.
Interpretation: Mothers with high positivity rates and titers of NV-IgA in breast milk had NV infected infants with reduced diarrheal symptoms. Antigenic relatedness to the genetic diversity of human norovirus was suggested.

Josiah L. Kephart, Magdalena Fandino-Del-Rio, Kendra N. Williams, Gary Malpartida, Alexander Lee, Kyle Steenland, Luke P. Naeher, Gustavo F. Gonzalesi, Marilu Chiang, William Checkley, Kirsten Koehler, CHAP trial Investigators.

Environment International 146 (2021) 106196

Background: Liquefied petroleum gas (LPG) stoves have been promoted in low- and middle-income countries (LMICs) as a clean energy alternative to biomass burning cookstoves.
Objective: We sought to characterize kitchen area concentrations and personal exposures to nitrogen dioxide (NO2) within a randomized controlled trial in the Peruvian Andes. The intervention included the provision of an LPG stove and continuous fuel distribution with behavioral messaging to maximize compliance.

Methods: We measured 48-hour kitchen area NO2 concentrations at high temporal resolution in homes of 50 intervention participants and 50 control participants longitudinally within a biomass-to-LPG intervention trial. We also collected 48-hour mean personal exposures to NO2 among a ubsample of 16 intervention and 9 control participants. We monitored LPG and biomass stove use continuously throughout the trial.

Results: In 367 post-intervention 24-hour kitchen area samples of 96 participants’ homes, geometric mean (GM) highest hourly NO2 concentration was 138 ppb (geometric standard deviation [GSD] 2.1) in the LPG intervention group and 450 ppb (GSD 3.1) in the biomass control group. Post-intervention 24-hour mean NO2 concentrations were a GM of 43 ppb (GSD 1.7) in the intervention group and 77 ppb (GSD 2.0) in the control group. Kitchen area NO2 concentrations exceeded the WHO indoor hourly guideline an average of 1.3 h per day among LPG intervention participants. GM 48-hour personal exposure to NO2 was 5 ppb (GSD 2.4) among 35 48-hour samples of 16 participants in the intervention group and 16 ppb (GSD 2.3) among 21 samples of 9 participants in the control group.

Discussion: In a biomass-to-LPG intervention trial in Peru, kitchen area NO2 concentrations were substantially lower within the LPG intervention group compared to the biomass-using control group. However, within the LPG intervention group, 69% of 24-hour kitchen area samples exceeded WHO indoor annual guidelines and 47% of samples exceeded WHO indoor hourly guidelines. Forty-eight-hour NO2 personal exposure was below WHO indoor annual guidelines for most participants in the LPG intervention group, and we did not measure personal exposure at high temporal resolution to assess exposure to cooking-related indoor concentration peaks. Further research is warranted to understand the potential health risks of LPG-related NO2 emissions and inform current campaigns which promote LPG as a clean-cooking option.

Jessica D. Brewer, Maria P. Santos, Karina Román, Amy R. Riley‐Powell, Richard A. Oberhelman, Valerie A. Paz‐Soldan.

Matern Child Nutr. 2020;16:e12915.

Abstract

In Peru, nearly half of children aged 6–36 months were diagnosed with anaemia in 2017. To address this disease, the Peruvian Ministry of Health implemented a national programme in 2014, distributing free micronutrient powders (MNPs) to all children of this age. However, rates of childhood anaemia remain high. The aim of this study was to explore factors at all levels of the Social‐Ecological Model that affect MNP use and adherence in Arequipa, an Andean city with childhood anaemia rates higher than the national average. We conducted in‐depth interviews with 20 health personnel and 24 caregivers and 12 focus group discussions with 105 caregivers.

We identified numerous barriers, including negative side effects (constipation, vomiting, and diarrhoea), poor taste of MNP, lack of familial and peer support for its use, insufficient informational resources provided by the health system, and limited human resources that constricted health personnel abilities to implement MNP programming successfully. Facilitators identified included concern about the long‐term effects of anaemia, support from organizations external to the health system, well‐coordinated care within the health system, and provision of resources by the Ministry of Health. We found that community or organizational and societal factors were key to limited MNP use and adherence, specifically the limited time health personnel have to address caregivers’ doubts during appointments and the lack of informational resources outside of these appointments. Potential policy implications could be to increase informational resources available outside of individualized counselling by strengthening existing collaborations with community organizations, increasing media coverage, and providing group counselling.

N. Giallourou, F. Fardus-Reid, G. Panic, K. Veselkov, B. J. J. McCormick, M. P. Olortegui, T. Ahmed, E. Mduma, P. P. Yori, M. Mahfuz, E. Svensen, M. M. M. Ahmed, J. M. Colston, M. N. Kosek, J. R. Swann.

Giallourou et al., Sci. Adv. 2020; 6 : eaay5969

Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growthconstrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.

Josh Colston, Maribel Paredes Olortegui, Benjamin Zaitchik, Pablo Peñataro Yori, Gagandeep Kang, Tahmeed Ahmed, Pascal Bessong, Esto Mduma, Zulfiqar Bhutta, Prakash Sunder Shrestha, Aldo Lima and Margaret Kosek.

Int. J. Environ. Res. Public Health 2020, 17, 487

Abstract:
Extreme floods pose multiple direct and indirect health risks. These risks include contamination of water, food, and the environment, often causing outbreaks of diarrheal disease. Evidence regarding the effects of flooding on individual diarrhea-causing pathogens is limited, but is urgently needed in order to plan and implement interventions and prioritize resources before climate-related disasters strike. This study applied a causal inference approach to data from a multisite study that deployed broadly inclusive diagnostics for numerous high-burden common enteropathogens. Relative risks (RRs) of infection with each pathogen during a flooding disaster that occurred at one of the sites—Loreto, Peru—were calculated from generalized linear models using a comparative interrupted time series framework with the other sites as a comparison group and adjusting for background seasonality. During the early period of the flood, increased risk of heat-stable enterotoxigenic E. coli (ST-ETEC) was identified (RR = 1.73 [1.10, 2.71]) along with a decreased risk of enteric adenovirus (RR = 0.36 [0.23, 0.58]). During the later period of the flood, sharp increases in the risk of rotavirus (RR = 5.30 [2.70, 10.40]) and sapovirus (RR = 2.47 [1.79, 3.41]) were observed, in addition to increases in transmission of Shigella spp. (RR = 2.86 [1.81, 4.52]) and Campylobacter spp. (RR = 1.41 (1.01, 1.07). Genotype-specific exploratory analysis reveals that the rise in rotavirus transmission during the flood was likely due to the introduction of a locally atypical, non-vaccine (G2P[4]) strain of the virus. Policy-makers should target interventions towards these pathogens—including vaccines as they become available—in settings where vulnerability to flooding is high as part of disaster preparedness strategies, while investments in radical, transformative, community-wide, and locally-tailored water and sanitation interventions are also needed.

Ramya Ambikapathi, Margaret N Kosek, Gwenyth O Lee, Maribel Paredes Olortegui, Benjamin Zaitchik, Pablo Penataro Yori, Aubrey Bauck and Laura E Caulfield.

Public Health Nutrition: 24(11), 3477–3487

Abstract

Objective:
In 2011–2012, severe El Nino Southern Oscillation (ENSO) conditions (La Nina) led to massive flooding and temporarily displacement in the Peruvian Amazon. Our aims were to examine the impact of this ENSO exposure on child diets, in particular: (1) frequency of food consumption patterns, (2) the amount of food consumed (g/d), (3) dietary diversity (DD), (4) consumption of donated foods, among children aged 9–36 months living in the outskirts of City of Iquitos in the Amazonian Peru.

Design:
This was a longitudinal study that used quantitative 24-h recall dietary data collection from children aged 9–36 months from 2010 to 2014 as part of the MAL-ED birth cohort study.

Setting:
Iquitos, Loreto, Peru.

Participants:
Two hundred and fifty-two mother–child dyads.

Results:
The frequency of grains, rice, dairy and sugar in meals reduced by 5–7 %, while the frequency of plantain in meals increased by 24 % after adjusting for covariates. ENSO exposure reduced girl’s intake of plantains and sugar. Despite seasonal fluctuations in the availability of fruits, vegetables and fish, DD remained constant across seasons and as children aged. However, DD was significantly reduced under moderate La Nina conditions by 0·32 ( ˜ P < 0·05) food groups. Adaptive social strategies such as consumption of donated foods were significantly higher among households with girls.

Conclusions:
This is the first empirical study to show differential effect of the ENSO on the dietary patterns of children, highlighting differences by gender. Public health nutrition programmes should be climate- and gender-sensitive in their efforts to safeguard the diets of vulnerable populations.

Elisa D. Romani, Trishul Siddharthan, Nair Lovatón, Carol C. Alvítez-Luna, Oscar Flores-Flores and Suzanne L. Pollard.

Romani et al. Trials (2020) 21:377

Introduction:
Asthma is the most common chronic disease among children worldwide, with 80% of asthmarelated deaths occurring in low- and middle-income countries (LMICs). While evidence-based guidelines exist for asthma treatment and management, adoption of guideline-based practices is low in high-income country and LMIC settings alike. While asthma prevalence among children and adolescents in Lima, Peru is in the range of 13%–19.6%, our data suggest that < 5% of children in low-resource communities are currently taking guideline-based therapies. There is an urgent need for effective, locally tailored solutions to address the asthma treatment gap in low-income communities in Peru.

Methods:
This study aims to develop and test a locally adapted intervention package to improve adoption of selfmanagement practices and utilization of preventive health services for asthma among children in Lima Norte. The intervention package was designed using a systematic, theory-based framework (Capability, Opportunity, Motivation – Behavior Framework) and is rooted in a multi-phased formative research approach. The main study design is an individually randomized implementation-effectiveness hybrid trial enrolling 110 children aged 5–17 years with asthma and their caregivers. Families allocated to the treatment group receive the supported self-management intervention package, while families allocated to the control group receive the standard of care plus asthma
education. We will follow participants monthly for six months and evaluate asthma control (Asthma Control Test), healthcare utilization, and medication adherence (Adherence to Refills and Medications Scale). Disease-specific quality of life for children (Pediatric Asthma Quality of Life Questionnaire) and caregivers (Pediatric Asthma Caregiver’s Quality of Life Questionnaire) will be evaluated at baseline, 3 months, and 6 months. We will also evaluate acceptability, feasibility, and fidelity of the intervention using mixed methods approaches.

Discussion:
The long-term goal of this study is to disseminate locally appropriate asthma management strategies in LMIC settings. This study will contribute to the body of knowledge surrounding approaches for developing and evaluating intervention strategies for asthma using systematic, theory-based approaches grounded in local context. Such strategies have the potential to inform the development and adaptation of appropriate and scalable solutions for asthma management in LMIC settings.

Saba Rouhani,1, Nicholas W. Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H. Moulton, Eric R. Houpt, Michael J. Barratt, Margaret N. Kosek, and Jeffrey I. Gordon.

Clinical Infectious Diseases 2020;71(4):1000–7

Background.
Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between ampylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.

Methods.
Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNAbased analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition were investigated using multiple linear regression adjusting for withinchild correlations, age, and breastfeeding. Indicator species analyses identified taxa specifically associated with Campylobacter burden.

Results.
Ninety-three percent (251) of children had Campylobacter present in asymptomatic fecal samples during the follow-up period. A 10% increase in the proportion of stools infected was associated with mean reductions of 0.02 length-for-age z scores (LAZ) at 3, 6, and 9 months thereafter (P < .01). We identified 13 bacterial taxa indicative of cumulative Campylobacter burden and 14 taxa significantly associated with high or low burden of enteroaggregative Escherichia coli, norovirus, or Giardia.

Conclusions.
Campylobacter infection is common in this cohort and associated with changes in microbial community composition. These results support the notion that disruptions to the fecal microbiota may help explain the observed effects of asymptomatic
infections on growth in early life

Ben Pascoe, Francesca Schiaffino, Susan Murray, Guillaume Méric, Sion C. Bayliss, Matthew D. Hitchings, Evangelos Mourkas, Jessica K. Calland, Rosa Burga, Pablo Peñataro Yori, Keith A. Jolley, Kerry K. Cooper, Craig T. Parker, Maribel Paredes Olortegui, Margaret N. Kosek, Samuel K. Sheppard.

PLoS Negl Trop Dis 14(8): e0008533.

Abstract
Campylobacter is the leading bacterial cause of gastroenteritis worldwide and its incidencethe is especially high in low- and middle-income countries (LMIC). Disease epidemiology in LMICs is different compared to high income countries like the USA or in Europe. Children in LMICs commonly have repeated and chronic infections even in the absence of symptoms, which can lead to deficits in early childhood development. In this study, we sequenced and characterized C. jejuni (n = 62) from a longitudinal cohort study of children under the age of 5 with and without diarrheal symptoms, and contextualized them within a global C. jejuni genome collection. Epidemiological differences in disease presentation were reflected in the genomes, specifically by the absence of some of the most common global diseasecausing lineages. As in many other countries, poultry-associated strains were likely a major source of human infection but almost half of local disease cases (15 of 31) were attributable to genotypes that are rare outside of Peru. Asymptomatic infection was not limited to a single (or few) human adapted lineages but resulted from phylogenetically divergent strains suggesting an important role for host factors in the cryptic epidemiology of campylobacteriosis in LMICs.

Caio M. B. França, Roxana Loayza, Yelin Roca, Ana Maria Montaño Arias, Freddy Tinajeros, Jose R. Loaiza, Anshule Takyar, Robert H. Gilman, Matthew J. Milleri.

Microbiol Resour Announc 9:e00230-20

ABSTRACT
We generated nine coding-complete chikungunya virus genome sequences
from blood samples collected during the early 2015 outbreak in Bolivia. Relative to
other publicly available chikungunya sequences, the Bolivian samples represent a
monophyletic group, suggesting that a single lineage was widely circulating in the
country between February and May 2015.

Elizabeth T. Rogawski McQuade, Fariha Shaheen, Furqan Kabir, Arjumand Rizvi, James A. Platts-Mills, Fatima Aziz, Adil Kalam, Shahida Qureshi, Sarah Elwood, Jie Liu, Aldo A. M. Lima, Gagandeep Kang, Pascal Bessong, Amidou Samie, Rashidul Haque, Estomih R. Mduma, Margaret N. Kosek, Sanjaya Shrestha, Jose Paulo Leite, Ladaporn Bodhidatta, Nicola Page, Ireen Kiwelu, Sadia Shakoor,
Ali Turab, Sajid Bashir Soofi, Tahmeed Ahmed, Eric R. Houpt, Zulfiqar Bhutta, Najeeha Talat Iqba.

PLoS Negl Trop Dis 14(8): e0008536.

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non- diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were
more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.

William Checkley, Kendra N. Williams, Josiah L. Kephart, Magdalena Fandino-Del-Rio, N. Kyle Steenland, Gustavo F. Gonzales, Luke P. Naeher, Steven A. Harvey, Lawrence H. Moulton, Victor G. Davila-Roman, Dina Goodman, Carla Tarazona-Meza, Catherine H. Miele, Suzanne Simkovich, Marilu Chiang, Ryan T. Chartier, Kirsten Koehler, and the CHAP Trial Investigators.

Rationale:
Approximately 40% of people worldwide are exposed to household air pollution (HAP) from the burning of biomass fuels. Previous efforts to document health benefits of HAP mitigation have been stymied by an inability to lower emissions to target levels.

Objectives:
We sought to determine if a household air pollution intervention with liquefied petroleum gas (LPG) improved cardiopulmonary health outcomes in adult women living in a resource-poor setting in Peru.

Methods: We conducted a randomized controlled field trial in 180 women aged 25–64 years living in rural Puno, Peru. Intervention women received an LPG stove, continuous fuel delivery for 1 year, education, and behavioral messaging, whereas control women were asked to continue their usual cooking practices. We assessed for stove use adherence using temperature loggers installed in both LPG and biomass stoves of intervention households.

Measurements and Main Results:
We measured blood pressure, peak expiratory flow (PEF), and respiratory symptoms using the St. George’s Respiratory Questionnaire at baseline and at 3–4 visits after randomization. Intervention women used their LPG stove exclusively for 98% of days. We did not find differences in average
postrandomization systolic blood pressure (intervention – control 0.7 mm Hg; 95% confidence interval, 22.1 to 3.4), diastolic blood pressure (0.3 mm Hg; 21.5 to 2.0), prebronchodilator peak
expiratory flow/height2 (0.14 L/s/m2; 20.02 to 0.29), postbronchodilator peak expiratory flow/height2 (0.11 L/s/m2; 20.05 to 0.27), or St. George’s Respiratory Questionnaire total score (21.4;
23.9 to 1.2) over 1 year in intention-to-treat analysis. There were no reported harms related to the intervention.

Conclusions:
We did not find evidence of a difference in blood pressure, lung function, or respiratory symptoms during the year-long intervention with LPG

Timothy L. McMurry, Elizabeth T. Rogawski McQuade, Jie Liu, Gagandeep Kang, Margaret N. Kosek, Aldo A. M. Lima, Pascal O. Bessong, Amidou Samie, Rashidul Haque, Estomih R. Mduma, Jose Paulo Leite, Ladaporn Bodhidatta, Najeeha T. Iqbal, Nicola Page, Ireen Kiwelu, Zulfiqar A. Bhutta, Tahmeed Ahmed, Eric R. Houpt, and James A. Platts-Mills.

Clinical Infectious Diseases 2021;72(11):e806–14

Background.
Prolonged enteropathogen shedding after diarrhea complicates the identification of etiology in subsequent episodes and is an important driver of pathogen transmission. A standardized approach has not been applied to estimate the duration of shedding for a wide range of pathogens.

Methods.
We used a multisite birth cohort of children 0–24 months of age from whom diarrheal and monthly nondiarrheal stools were previously tested by quantitative polymerase chain reaction for 29 enteropathogens. We modeled the probability of detection of the etiologic pathogen before and after diarrhea using a log-normal accelerated failure time survival model and estimated the median duration of pathogen carriage as well as differences in subclinical pathogen carriage 60 days after diarrhea onset in comparison to a prediarrhea baseline.

Results.
We analyzed 3247 etiologic episodes of diarrhea for the 9 pathogens with the highest attributable burdens of diarrhea. The median duration of postdiarrheal carriage varied widely by pathogen, from about 1 week for rotavirus (median, 8.1 days [95% confidence interval {CI}, 6.2–9.6]) to >1 month for Cryptosporidium (39.5 days [95% CI, 30.6–49.0]). The largest increases in subclinical pathogen carriage before and after diarrhea were seen for Cryptosporidium (prevalence difference between 30 days prior and 60 days after diarrhea onset, 0.30 [95% CI, .23–.39]) and Shigella (prevalence difference, 0.21 [95% CI, .16–.27]).

Conclusions.
Postdiarrheal shedding was widely variable between pathogens, with strikingly prolonged shedding seen for Cryptosporidium and Shigella. Targeted antimicrobial therapy and vaccination for these pathogens may have a relatively large impact on transmission.

Carla E. Tarazona-Meza, Corrine Hanson, Suzanne L. Pollard, Karina M. Romero Rivero, Rocio M. Galvez Davila, Sameera Talegawkar, Carlos Rojas, Jessica L. Rice, William Checkley and Nadia N. Hansel.

Tarazona-Meza et al. BMC Pulmonary Medicine (2020) 20:63

Background:
Asthma is one of the conditions that contributes to the global burden of respiratory diseases and has been previously associated with diet intake. The goal of this study was to determine the relationship between diet, assessed by a developed score, and asthma in Peruvian children.

Methods: This study was a cross sectional analysis nested within an unmatched case-control study of children in two peri-urban communities of Lima, Peru. We evaluated 767 children and adolescents (573 with asthma, 194 controls) between 9 and 19 years. Diet was assessed using a food frequency questionnaire (FFQ), with food groups classified as “healthy” or “unhealthy”. Asthma control, Lung function and atopy were assessed by Asthma Control Test, Spirometry and InmunoCAP 250 test, respectively.

Results:
Mean age of participants was 13.8 years (SD 2.6). Mean diet score was 5 (SD 1.23; range 2–8). Healthy Diet Score was associated with asthma status [OR 0.83, 95% CI (0.72, 0.95), p = 0.009] in adjusted analysis. Thus, participants with higher HDS, had lower odds of asthma. In sensitivity analyses, when adjusting for atopy, results did not change significantly. [OR 0.85, 95% CI (0.72, 0.99); p = 0.04]. No association between the HDS and asthma control, FEV1, nor FeNO were observed. Atopy did not modify the association between diet and asthma outcomes.

Conclusions: In our study cohort, better diet quality was associated with lower odds of asthma, but was not associated with asthma control. Diet modification may be a potential intervention to impact the increasing prevalence of this disease.

William H Elson, Emma Ortega, Michelle Kreutzberg-Martinez, Frederique Jacquerioz, Lilia N Cabrera, Richard A Oberhelman, Valerie A Paz-Soldan.

BMJ Open 2020;10:e037408.

Objectives
To describe and quantify the dengue-related knowledge, attitudes and practices of residents in an urban shantytown in Lima, Peru.

Design/setting
A cross-sectional survey of adults between 18 and 80 years living in approximately 120
blocks in Oasis, an urban shantytown situated in the lowto-middle income district of Villa El Salvador in Southern Lima. The survey was adapted from an existing survey previously used in Iquitos, Peru, and included questions relating to knowledge of dengue symptoms, transmission, prevention and current mosquito control practices.

Participants
A total of 240 surveys were completed with 80% of respondents being female and approximately 50%
of all respondents describing themselves as housewives. Results Although 97.9% of respondents had heard of dengue, only 6.2% of people knew someone who had experienced the disease. Approximately half (54.2%) of the respondents knew dengue was transmitted by mosquitoes and 51.7% were able to identify fever and one other correct symptom of dengue. Female sex was significantly associated with greater symptom knowledge (OR 2.22, 95% CI 1.08 to 4.72) and prevention knowledge (OR 2.12, 95% CI 1.06 to 4.21). Past or current higher education attendance was significantly associated with symptom knowledge (OR 2.56, 95% CI 1.25 to 5.44) and transmission knowledge (OR 3.46, 95% CI 1.69 to 7.57). Knowledge of dengue was not significantly associated with carrying out practices to control mosquitoes (OR 1.76, 95% CI 0.87 to 3.54).

Conclusions
This population demonstrated baseline dengue knowledge. However, this was incomplete and
substantially less when compared with endemic areas. Given the sporadic nature of dengue transmission in Lima, it is not surprising that knowledge of the disease was not associated with carrying out practices to reduce mosquitoes. However, as dengue transmission in Lima
is likely to increase, understanding how best to improve public knowledge of the disease and how to translate this into appropriate community action will be a key public health consideration.

Gwenyth O. Lee, Germán Comina, Gustavo Hernandez-Cordova, Nehal Naik, Oscar Gayoso, Eduardo Ticona, Jorge Coronel, Carlton A. Evans, Mirko Zimic, Valerie A. Paz-Soldan, Robert H. Gilman, Richard Oberhelman.

PLoS ONE 15(6): e0231167

Cough is a characteristic symptom of tuberculosis, is the main cause of transmission, and is
used to assess treatment response. We aimed to identify the best measure of cough severity
and characterize changes during initial tuberculosis therapy. We conducted a prospective
cohort of recently diagnosed ambulatory adult patients with pulmonary tuberculosis in two tertiary hospitals in Lima, Peru. Pre-treatment and five times during the first two months of treatment, a vibrometer was used to capture 4-hour recordings of involuntary cough. A total of 358
recordings from 69 participants were analyzed using a computer algorithm. Total time spent
coughing (seconds per hour) was a better predictor of microbiologic indicators of disease
severity and treatment response than the frequency of cough episodes or cough power.
Patients with prior tuberculosis tended to cough more than patients without prior tuberculosis,
and patients with tuberculosis and diabetes coughed more than patients without diabetes comorbidity. Cough characteristics were similar regardless of HIV co-infection and for drug-susceptible versus drug-resistant tuberculosis. Tuberculosis treatment response may be meaningfully assessed by objectively monitoring the time spent coughing. This measure demonstrated
that cough was increased in patients with TB recurrence or co-morbid diabetes, but not
because of drug resistance or HIV co-infection.

Taryn Clark, Manuela Verastegui, Freddy Tinajeros, Maritza Calderon, Rony Colanzi, and Robert H. Gilman.

Am. J. Trop. Med. Hyg., 103(6), 2020, pp. 2581–2583

Capacity building in public health is an urgent global priority. Recently, there has been an increasing
emphasis on South–South and triangular cooperation. We describe our experience with a public health training collaboration between Peru and Bolivia, with Peru providing capacity building and expertise to Bolivia, while receiving supportive funding and training from the United States. This collaboration has led to a groundswell of research on clinically significant diseases, outreach to more than 800 scientists, several dozen publications, and the start of four institutional review boards. South–South and South–South–North collaborations should publish their experiences, and Northern
funding organizations should consider funding such collaborations.

Jessica D. Brewer, Julianna Shinnick, Karina Román, Maria P. Santos, Valerie A. Paz-Soldan, Alison M. Buttenheim.

Global Health: Science and Practice 2020, volume 8, number 4

Childhood anemia remains a significant driver of morbidity in low- and middle-income countries, including Peru. To identify behavioral challenges to using micronutrient powder (MNP) that is
given to supplement children’s diets and prevent anemia, we applied a behavioral design approach to interviews and focus groups with 129 caregivers in Arequipa, Peru. We examined 3 key points in the decision-making process: accessing MNP through the health system; forming intentions to use MNP; and MNP use at the time of child feeding. Using the NUDGE (Narrow, Understand, Discover, Generate, Evaluate) approach, we identified the following behavioral barriers and facilitators:
(1) caregivers’ experiences with health care providers shaped their motivation to access MNP; (2) caregivers felt accessing MNP at clinics was inconvenient and created hassle factors; (3) caregivers’ mental models about anemia prevention shaped MNP intentions and use; (4) caregivers’ salient negative experiences could have caused them to stop giving MNP; (5) caregivers forgot to
give MNP if they did not have cues to remind them but could be prompted with salient cues; and (6) caregivers were affected by emotional, cognitive, and attentional factors during feeding that
were difficult to anticipate. Our results, based on a behavioral design approach, suggest opportunities to adapt current messaging, counseling, and education around MNP use. Adaptations include
providing culturally relevant messages, leveraging caregivers’ emotional and cognitive states, and encouraging small but impactful changes to feeding routines to address barriers to MNP use.

Josh M. Colston, Abu S. G. Faruque, M. Jahangir Hossain, Debasish Saha, Suman Kanungo, Inácio Mandomando, M. Imran Nisar, Anita K. M. Zaidi, Richard Omore, Robert F. Breiman, Samba O. Sow, Anna Roose, Myron M. Levine, Karen L. Kotloff, Tahmeed Ahmed, Pascal Bessong, Zulfiqar Bhutta , Estomih Mduma, Pablo Penatero Yori, Prakash Sunder Shrestha, Maribel P. Olortegui, Gagandeep Kang, Aldo A. M. Lima, Jean Humphrey, Andrew Prendergast, Francesca Schiaffino, Benjamin F. Zaitchik and Margaret N. Kosek.

Int. J. Environ. Res. Public Health 2020, 17, 8078

Abstract: Diarrheal disease remains a major cause of childhood mortality and morbidity causing
poor health and economic outcomes. In low-resource settings, young children are exposed to
numerous risk factors for enteric pathogen transmission within their dwellings, though the relative
importance of different transmission pathways varies by pathogen species. The objective of this
analysis was to model associations between five household-level risk factors—water, sanitation,
flooring, caregiver education, and crowding—and infection status for endemic enteric pathogens in
children in five surveillance studies. Data were combined from 22 sites in which a total of 58,000
stool samples were tested for 16 specific enteropathogens using qPCR. Risk ratios for pathogen- and
taxon-specific infection status were modeled using generalized linear models along with hazard
ratios for all-cause diarrhea in proportional hazard models, with the five household-level variables
as primary exposures adjusting for covariates. Improved drinking water sources conferred a 17%
reduction in diarrhea risk; however, the direction of its association with particular pathogens was
inconsistent. Improved sanitation was associated with a 9% reduction in diarrhea risk with protective
effects across pathogen species and taxa of around 10–20% risk reduction. A 9% reduction in diarrhea
risk was observed in subjects with covered floors, which were also associated with decreases in
risk for zoonotic enteropathogens. Caregiver education and household crowding showed more
modest, inconclusive results. Combining data from diverse sites, this analysis quantified associations
between five household-level exposures on risk of specific enteric infections, effects which differed by
pathogen species but were broadly consistent with hypothesized transmission mechanisms. Such
estimates may be used within expanded water, sanitation, and hygiene (WASH) programs to target
interventions to the particular pathogen profiles of individual communities and prioritize resources.

Francesca Schiaffino, Dixner Rengifo Trigoso, Josh M. Colston, Maribel Paredes Olortegui, Wagner V. Shapiama Lopez, Paul F. Garcia Bardales, Nora Pisanic, Meghan F. Davis, Pablo Penataro Yori, and Margaret N. Kosek.

Am. J. Trop. Med. Hyg., 104(1), 2021, pp. 372–381

Abstract. Using previously validated microbial source tracking markers, we detected and quantified fecal contamination from avian species and avian exposure, dogs, and humans on household cooking tables and floors. The association among contamination, infrastructure, and socioeconomic covariates was assessed using simple and multiple ordinal logistic regressions. The presence of Campylobacter spp. in surface samples was linked to avian markers. Using molecular methods, animal feces were detected in 75.0% and human feces in 20.2% of 104 households. Floors were more contaminated than tables as detected by the avian marker Av4143, dog marker Bactcan, and human marker Bachum. Wood tables were consistently more contaminated than non-wood surfaces, specifically with the mitochondrial avian markers ND5 and CytB, fecal marker Av4143, and canine marker Bactcan. Final multivariable models with socioeconomic and infrastructure characteristics included as covariates indicate that detection of avian feces and avian exposure was associated with the presence of chickens, maternal age, and length of tenancy, whereas detection of human markers was associated with unimproved water source. Detection of Campylobacter in surface samples was associated with the avian fecal marker Av4143. We highlight the critical need to detect and measure the burden of animal
fecal waste when evaluating household water, hygiene, and sanitation interventions, and the possibility of decreasing risk of exposure through the modification of surfaces to permit more effective household disinfection practices. Animals may be a more important source of household fecal contamination than humans in many low-resource settings, although interventions have historically focused almost exclusively on managing human waste.

Aizhamal Tabyshova, MD; John R. Hurst, MD, PhD; Joan B. Soriano, MD, PhD; William Checkley, MD, PhD; Erick Wan-Chun Huang, MD; Antigona C. Trofor, MD, PhD; Oscar Flores-Flores, MD; Patricia Alupo, MD; Gonzalo Gianella, MD; Tarana Ferdous, MPH; David Meharg, MPH; Jennifer Alison, PhD; Jaime Correia de Sousa, MD, PhD; Maarten J. Postma, PhD; Niels H. Chavannes, MD, PhD; and Job F. M. van Boven, PharmD, PhD.

CHEST 2021; 159(2):575-584

BACKGROUND: Guidelines are critical for facilitating cost-effective COPD care. Development
and implementation in low-and middle-income countries (LMICs) is challenging. To guide
future strategy, an overview of current global COPD guidelines is required.
RESEARCH QUESTION: We systematically reviewed national COPD guidelines, focusing on
worldwide availability and identification of potential development, content, context, and
quality gaps that may hamper effective implementation.
STUDY DESIGN AND METHODS: Scoping review of national COPD management guidelines. We
assessed: (1) global guideline coverage; (2) guideline information (authors, target audience,
dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socioeconomic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline
standards. LMICs guidelines were compared with those from high-income countries (HICs).
RESULTS: Of the 61 national COPD guidelines identified, 30 were from LMICs. Guidelines did
not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs
were without national guidelines. Compared with HICs, LMIC guidelines targeted fewer
health-care professional groups and less often addressed case finding and co-morbidities. More
than 90% of all guidelines included smoking cessation advice. Air pollution reduction strategies
were less frequently mentioned in both LMICs (47%) and HICs (42%). LMIC guidelines fulfilled
on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05).
LMICs scored significantly lower compared with HICs regarding conflicts of interest management,
updates, articulation of recommendations, and funding transparency (all, P < .05).

Matthew J Saunders, Tom Wingfield, Sumona Datta, Rosario Montoya, Eric Ramos, Matthew R Baldwin, Marco A Tovar, Benjamin E W Evans, Robert H Gilman, Carlton A Evans.

Lancet Infect Dis 2020; 20: 110–22

The epidemiological impact and cost-effectiveness of social protection and biomedical interventions for tuberculosis-affected households might be improved by risk stratification. We therefore derived and externally validated a household-level risk score to predict tuberculosis among contacts of patients with tuberculosis.

In this prospective cohort study, we recruited tuberculosis-affected households from 15 desert shanty
towns in Ventanilla and 17 urban communities in Callao, Lima, Peru. Tuberculosis-affected households included index patients with a new diagnosis of tuberculosis and their contacts who reported being in the same house as the index patient for more than 6 h per week in the 2 weeks preceding index patient diagnosis. Tuberculosis-affected households were not included if the index patient had no eligible contacts or lived alone.

We followed contacts until 2018 and defined household tuberculosis, the primary outcome, as any contact having any form of tuberculosis within 3 years. We used logistic regression to identify characteristics of index patients, contacts, and households that were predictive of household tuberculosis, and used these to derive and externally validate a household-level score.

Andrew Nicholson, Suzanne L Pollard, John J Lima, Pharm, Karina Romero, Carla Tarazona-Meza, Gary Malpartida-Guzmán, Edward Mougey, Nadia N Hansel, William Checkley, and GASP Study Investigators.

Respir Med. 2017 Dec;133:29-35.

The relationship between folate status and asthma-related outcomes has not been carefully examined in low- and middle-income countries where folate deficiency is common.

Ancillary analysis of an unmatched case-control study in which we analyzed serum folate concentrations in 412 children with asthma and 342 controls living in peri-urban communities in Lima, Peru. We examined baseline associations between folate and asthma, atopy, total serum IgE, pulmonary function, and fractional exhaled nitric oxide. We then followed children with asthma longitudinally for 6-9 months and assessed associations between folate and odds of uncontrolled asthma (defined as Asthma Control Test score ≤ 19) and of ≥1 emergency visits during follow-up.

Serum folate concentrations were inversely associated with asthma, but this effect was stronger in children without atopy. Among children with asthma, lower serum folate concentrations were associated with higher risk of uncontrolled asthma.

Josh M. Colston, Pablo Peñataro Yori, Lawrence H. Moulton, Maribel Paredes Olortegui, Peter S. Kosek, Dixner Rengifo Trigoso, Mery Siguas Salas, Francesca Schiaffino, Ruthly François, Fahmina Fardus-Reid, Jonathan R. Swann, Margaret N. Kosek.

PLoS Negl Trop Dis. 2019 Nov 15;13(11):e0007851.

Environmental enteric dysfunction (EED) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EED reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker’s association with linear growth in infancy and early childhood. 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects’ length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the best-fitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker’s adjusted effect on growth. Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score-a coefficient value of 0.50 (0.24, 0.75) for each log2 increase in plasma transferrin concentration. Other biomarkers with large effect size estimates included adiponectin, arginine, growth hormone, proline and serum amyloid P-component. The selected subset explained up to 23.0% of the variability in LAZ-score. Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EED. There is a need to systematically express the strength of association of biomarkers with linear growth or other outcomes to compare results across studies.

Md Ahshanul Haque, James A. Platts-Mills, Estomih Mduma, Ladaporn Bodhidatta, Pascal Bessong, Sadia Shakoor, Gagandeep Kang, Margaret N. Kosek, Aldo A. M. Lima, Sanjaya K. Shrestha, Md. Ashraful Alam , Alexandre Havt, Amidou Samie, Richard L. Guerrant, Dennis Lang, Mustafa Mahfuz, Zulfqar A. Bhutta, Eric R. Houpt & Tahmeed Ahmed.

Sci Rep. 2019 Nov 20;9(1):17124

Campylobacter species infections have been associated with malnutrition and intestinal inflammation among children in low-resource settings. However, it remains unclear whether that association is specific to Campylobacter jejuni/coli. The aim of this study was to assess the association between both all Campylobacter species infections and Campylobacter jejuni/coli infections on growth and enteric inflammation in children aged 1-24 months. We analyzed data from 1715 children followed from birth until 24 months of age in the MAL-ED birth cohort study, including detection of Campylobacter species by enzyme immunoassay and Campylobacter jejuni/coli by quantitative PCR in stool samples. Myeloperoxidase (MPO) concentration in stool, used as a quantitative index of enteric inflammation, was measured. The incidence rate per 100 child-months of infections with Campylobacter jejuni/coli and Campylobacter species during 1-24 month follow up were 17.7 and 29.6 respectively. Female sex of child, shorter duration of exclusive breastfeeding, lower maternal age, mother having less than 3 living children, maternal educational level of <6 years, lack of routine treatment of drinking water, and unimproved sanitation were associated with Campylobacter jejuni/coli infection. The cumulative burden of both Campylobacter jejuni/coli infections and Campylobacter species were associated with poor growth and increased intestinal inflammation.

Schiaffino, F., Lee, G. O., Paredes-Olortegui, M., Cabrera, L., Peñataro-Yori, P., Gilman, R. H., Kosek, M. N.

Am J Perinatol. 2019 Oct;36(12):1264-1270.

Bacillus Calmette-Guerin (BCG) scar formation is considered a visual marker of vaccination and cell-mediated immune response. This study characterized the association between pregnancy and birth characteristics with BCG scar formation.

Pregnant women were enrolled prospectively. Infants were followed up for the first 6 months of life, and the diameter of the BCG scar was recorded. Marginal models were fitted to assess the association of BCG scar diameter with pregnancy and birth characteristics using linear regressions with generalized estimating equations.

The immune reaction to the BCG vaccination is affected by gestational age at birth and systemic inflammatory episodes during pregnancy.

Mayta, H., Romero, Y., Pando, A., Verastegui, M., Tinajeros, F., Bozo, R., Henderson-Frost, J., Colanzi, R., Flores, J., Lerner, R., Bern, C., Gilman, R.; Chagas Working Group in Perú and Bolivia.

PLoS Negl Trop Dis. 2019 Jan 11;13(1)

The detection of Trypanosoma cruzi genetic material in clinical samples is considered an important diagnostic tool for Chagas disease. We have previously demonstrated that PCR using clot samples yields greater sensitivity than either buffy coat or whole blood samples. However, phenol-chloroform DNA extraction from clot samples is difficult and toxic. The objective of the present study was to improve and develop a more sensitive method to recover parasite DNA from clot samples for the diagnosis of Chagas disease.

Carrillo-Larco RM, Miranda JJ, Gilman RH, Checkley W, Smeeth L, Bernabe-Ortiz A, Cronicas Cohort Study Group.

J Diabetes Res. 2018 Dec 16.

Prognostic thresholds to identify new type 2 diabetes mellitus (T2DM) cases using the HOMA-IR have not been defined. We studied the HOMA-IR performance to identify incident T2DM cases and to assess if the thresholds varied according to urbanization and altitude in Peru.

Using the HOMA-IR to identify incident T2DM cases seems to yield moderate accuracy. The HOMA-IR could help improve identifying people at high risk of T2DM.

Correa M, Zimic M, Barrientos F, Barrientos R, Román-Gonzalez A, Pajuelo MJ, Anticona C, Mayta H, Alva A, Solis-Vasquez L, Figueroa DA, Chavez MA, Lavarello R, Castañeda B, Paz-Soldán VA, Checkley W, Gilman RH, Oberhelman R.

PloS one, 13(12), e0206410. doi:10.1371/journal.pone.0206410

Pneumonia is one of the major causes of child mortality, yet with a timely diagnosis, it is usually curable with antibiotic therapy. In many developing regions, diagnosing pneumonia remains a challenge, due to shortages of medical resources. Lung ultrasound has proved to be a useful tool to detect lung consolidation as evidence of pneumonia. However, diagnosis of pneumonia by ultrasound has limitations: it is operator-dependent, and it needs to be carried out and interpreted by trained personnel. Pattern recognition and image analysis is a potential tool to enable automatic diagnosis of pneumonia consolidation without requiring an expert analyst.

Shibabaw A, Gelaw B, Kelley HV, Tesfaye E, Balada-Llasat JM, Evans CA, Torrelles JB, Wang SH, Tessema B.

Int J Infect Dis. 2019 Nov 2.

Appropriate-technology tests are needed for Mycobacterium tuberculosis drug-susceptibility testing (DST) in resource-constrained settings. We evaluated the MDR/XDRTB colour plate thin-layer agar test (TB-CX) for M. tuberculosis DST by directly testing sputum at University of Gondar Hospital.

The TB-CX was simple and rapid for M. tuberculosis DST. Discordant DST results may have resulted from sub-optimal storage and different isoniazid concentrations used in TB-CX versus the reference standard test.

Mekonnen B, Mihret A, Getahun M, Hailu T, Sidiki S, V Kelley H, Scordo JM, Hunt WG, Pan X, Balada-Llasat JM, Gebreyes W, Evans CA, Aseffa A, Torrelles JB, Wang SH, Abebe T.

PLoS One. 2019 May 28;14(5):e0215679.

Timely diagnosis of tuberculosis (TB) is limited in Ethiopia. We evaluated the performance of a low technology, thin layer agar, Mycobacterium tuberculosis (M.tb) culture color plate (TB-CX) test with concurrent drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) directly from sputum specimens. Patients undergoing examination for TB and multidrug-resistant (MDR)-TB were enrolled in Addis Ababa, Ethiopia from March 2016 to February 2017. All subjects received a GeneXpert MTB/RIF PCR test. TB-CX test results were compared to reference Löwenstein-Jensen (LJ) culture for M.tb detection and DST for susceptibility to INH and RIF. Kappa statistic was applied to test agreement between results for TB-CX test and the reference methods, a cut-off Kappa value of 0.75 was considered as high level of agreements. A total of 137 participants were analyzed: 88 (64%) were new TB cases, 49 (36%) were re-treatment cases. The TB-CX test detected M.tb and DST in an average of 13 days compared to 50 days for the conventional DST result. The sensitivity and specificity of the TB-CX test for detecting M.tb were 94% and 98%, respectively (concordance, 96%; kappa 0.91). The sensitivity of the TB-CX test to detect drug resistance to INH, RIF, and MDR-TB was 91%, 100%, and 90% respectively. The specificity of the TB-CX test for detecting INH, RIF, and MDR-TB was 94%, 40%, and 94% respectively. Overall agreement between TB-CX test and LJ DST for detection of MDR-TB was 93%. The TB-CX test showed strong agreement with the GeneXpert test for detecting M.tb (89%, kappa 0.76) but low agreement for the detection of RIF resistance (57%, kappa 0.28). The TB-CX test was found to be a good alternative method for screening of TB and selective drug resistant-TB in a timely and cost-efficient manner.

Sumona Datta, Keren Alvarado, Robert H. Gilman, Teresa Valencia, Christian Aparicio, Eric S. Ramos, Rosario Montoya, Carlton A. Evans.

PLoS One. 2019; 14(4): e0214131.

Assessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings.

George, C., Sima, L., Jahuira, M., Mihalic, J., Cabrera, L., Danz, D., Checkley, W., Gilman, R.,

Bull World Health Organ. 2014 Aug 1; 92(8)

In several districts of Peru, drinking water shows widespread arsenic contamination, exceeding the WHO arsenic guideline. This poses a public health threat requiring further investigation and action. For groundwater samples, the EQ kit performed well relative to the WHO arsenic limit and therefore could provide a vital tool for water arsenic surveillance.

Weldon, C., Riley-Powell, A., Aguerre, I., Celis Nacimento R., Morrison, A., Oberhelman, R., Paz-Soldan, V.

PLoS Negl Trop Dis. 2018 Aug 30;12(8)

The aim of this study was to explore the knowledge, attitudes, and preventative practices related to Zika virus and its transmission among women of childbearing age in Iquitos, Peru. Six focus group discussions with 46 women of ages 20-35 from an Iquitos district with confirmed Zika cases were conducted to explore: 1) knowledge of Zika transmission, its symptoms, and treatment, 2) attitudes regarding Zika, including perceptions of risk for and severity of Zika, and 3) preventative practices, including awareness of health promotion activities.

François, R., Peñataro, P., Rouhani, S., Siguas, M., Paredes, M., Rengifo, D., Pisanic, N., Burga, R., Meza, R., Meza, G., Gregory, M., Houpt, E., Platts-Mills, J., and Kosek, M.,

PLoS Negl Trop Dis. 2018 Feb; 12(2): e0006200.

Campylobacter is one of the main causes of gastroenteritis worldwide. Most of the current knowledge about the epidemiology of this food-borne infection concerns two species, C. coli and C. jejuni. Recent studies conducted in developing countries and using novel diagnostic techniques have generated evidence of the increasing burden and importance of other Campylobacter species, i.e. non-C. coli/jejuni. We performed a nested case-control study to compare the prevalence of C. coli/jejuni and other Campylobacterin children with clinical dysentery and severe diarrhea as well as without diarrhea to better understand the clinical importance of infections with Campylobacter species other than C. coli/jejuni.

Carrillo-Larco, R., Saavedra-Garcia, L., Miranda, J., Sacksteder, K., Diez-Canseco, F., Gilman, R., Bernabe-Ortiz, A.

Nutrients. 2018 Feb 22;10(2).

Despite the negative effects of high sodium and low potassium consumption on cardiovascular health, their consumption has not been quantified in sites undergoing urbanization. We aimed to determine the sodium and potassium consumption in a semi-urban area in Peru with a cross-sectional study. Public health actions ought to be implemented in areas undergoing urbanization to improve sodium and potassium consumption at the population level.

Lee, G., Surkan, P., Zelner, J., Paredes M., Peñataro P., Ambikapathi, R., Caulfield, L., Gilman, R., and Kosek, M.,

SSM Popul Health. 2018 Apr; 4: 254–262.

Food insecurity is a major global public health issue. Social capital has been identified as central to maintaining food security across a wide range of low- and middle-income country contexts, but few studies have examined this relationship through sociocentric network analysis.

We investigated relationships between household- and community-level social connectedness, household food security, and household income; and tested the hypothesis that social connectedness modified the relationship between income and food security.

López, J., Loader, M., Smith, D., Pastorius, D., Bravard, M., Caviedes, L., Romero, K., Clark, T., Checkley, W., Ticona, E., Friedland, J., Gilman, R.

Am J Trop Med Hyg. 2018 Jun;98(6)

To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.

Bonadonna, L., Saunders, M., Zegarra, R., Evans, C., Alegria-Flores, K., Guio, H.

PLoS One. 2017 Sep 25;12(9):e0185018.

Early detection and diagnosis of tuberculosis remain major global priorities for tuberculosis control. Few studies have used a qualitative approach to investigate the social determinants contributing to diagnostic delay and none have compared data collected from individual, community, and health-system levels. We aimed to characterize the social determinants that contribute to diagnostic delay among persons diagnosed with tuberculosis living in resource-constrained settings.

Negherbon, J., Romero, K., Williams, D., Guerrero-Preston, R., Hartung, T., Scott, A., Breysse, P., Checkley, W., Hansel, N.

Front Pharmacol. 2017 Mar 30;8

This study sought to investigate if acute phase immune responses of whole blood from Peruvian children with controlled and uncontrolled asthma differed from children without asthma, following exposure to traffic-related particulate matter (TRPM). TRPM, including particulate matter from diesel combustion, has been shown to stimulate acute airway inflammation in individuals with and without asthma. For this study, a whole blood assay (WBA) was used to test peripheral whole blood samples from 27 children with asthma, and 12 without asthma.

Carrillo-Larco, R., Miranda, J., Gilman, R., Medina-Lezama, J., Chirinos-Pacheco, J., Muñoz-Retamozo, P., Smeeth, L., Checkley, W., Bernabe-Ortiz, A., and CRONICAS Cohort Study Group

BMC Nephrol. 2017; 18: 343.

Chronic Kidney Disease (CKD) represents a great burden for the patient and the health system, particularly if diagnosed at late stages. Consequently, tools to identify patients at high risk of having CKD are needed, particularly in limited-resources settings where laboratory facilities are scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD using data from four settings in Peru: a complete risk score including all associated risk factors and another excluding laboratory-based variables.

Málaga-Machaca, E., Romero-Ramirez, A., Gilman, R., Astupiña-Figueroa, S., Angulo, N., Florentini, A., Lovon-Luque, C., Gonza, R., Del Carpio-Sanz, A., Cabello, I., Camargo, R., Recuenco, F., Barrueta-Soria, L., Verastegui, M., Calderon, M., Mayta, H.

PLoS Negl Trop Dis. 2017 Nov 9;11(11)

Abstract

BACKGROUND:

Detection of Trypanosoma cruzi antigens in clinical samples is considered an important diagnostic tool for Chagas disease. The production and use of polyclonal antibodies may contribute to an increase in the sensitivity of immunodiagnosis of Chagas disease.

METHODOLOGY/PRINCIPAL FINDINGS:

Polyclonal antibodies were raised in alpacas, rabbits, and hens immunized with trypomastigote excreted-secreted antigen, membrane proteins, trypomastigote lysate antigen and recombinant 1F8 to produce polyclonal antibodies. Western blot analysis was performed to determine specificity of the developed antibodies. An antigen capture ELISA of circulating antigens in serum, plasma and urine samples was developed using IgY polyclonal antibodies against T. cruzi membrane antigens (capture antibody) and IgG from alpaca raised against TESA. A total of 33 serum, 23 plasma and 9 urine samples were analyzed using the developed test. Among serum samples, compared to serology, the antigen capture ELISA tested positive in 55% of samples. All plasma samples from serology positive subjects were positive in the antigen capture ELISA. All urine positive samples had corresponding plasma samples that were also positive when tested by the antigen capture ELISA.

CONCLUSIONS:

Polyclonal antibodies are useful for detection of circulating antigens in both the plasma and urine of infected individuals. Detection of antigens is direct evidence of the presence of the parasite, and could be a better surrogate of current infection status.

Hollada, J., Williams, K., Miele, C., Danz, D., Harvey, S., Checkley, W.

Int J Environ Res Public Health. 2017 Feb 13;14(2)

Abstract

Many households in low- and middle-income countries cook with inefficient biomass-burning stoves, which cause high levels of household air pollution and threaten long-term health. Although clean stoves and fuels are available, uptake and consistent use has been low. Using observations and in-depth interviews, we assessed the attitudes, preferences, and beliefs about traditional versus liquefied petroleum gas (LPG) stoves in rural Puno, Peru. A total of 31 in-depth interviews were conducted with primary cooks and their families, health workers, community leaders, and improved stove contractors. Six in-home observations of meal preparation were also conducted. Six major barriers to consistent use of clean stoves were identified: (1) perceived differences in food taste and nutrition by stove type; (2) cooking niches filled by different stoves; (3) social norms related to cooking practices; (4) safety concerns; (5) comparative costs of using different stoves; and (6) lack of awareness and concern about long-term health risks. These findings suggest that to successfully reduce household air pollution, clean cooking programs and policies must consider the many factors influencing adoption beyond health, such as cost, taste, fears, and cultural traditions. These factors could be incorporated into community-based and national efforts to scale-up sustained and exclusive adoption of clean cooking.

KEYWORDS:

biomass; clean cooking adoption; clean fuel; exclusive use; household air pollution; improved cookstoves; liquefied petroleum gas (LPG)

Harvey, S., Lam, Y., Martin, N., and Paredes M.

Malaria Journal 2017 16:265

Abstract

Background

Increased insecticide-treated net (ITN) use over the last decade has contributed to dramatic declines in malaria transmission and mortality, yet residual transmission persists even where ITN coverage exceeds 80%. This article presents observational data suggesting that complex human net use patterns, including multiple entries to and exits from ITNs by multiple occupants throughout the night, might be a contributing factor.

Methods

The study included dusk-to-dawn observations of bed net use in 60 households in the Peruvian Amazon. Observers recorded number of net occupants and the time and number of times each occupant entered and exited each net. The study team then tabulated time of first entry, total times each net was lifted, and, where possible, minutes spent outside by each occupant.

Results

The sample included 446 individuals and 171 observed sleeping spaces with nets. Household size ranged from 2 to 24 occupants; occupants per net ranged from 1 to 5. Nets were lifted a mean 6.1 times per night (SD 4.35, range 1–22). Observers captured substantial detail about time of and reasons for net entry and exit as well as length of time and activities undertaken outside.

Conclusions

These findings suggest that the ITN use patterns observed in this study may contribute to residual transmission. As a result, respondents to net use surveys may truthfully report that they slept under a net the previous night but may not have received the anticipated protection. More research is warranted to explore the impact of this phenomenon. Concurrent entomological data would help assess the magnitude of the effect.

Lee, G., McCormick, B., Seidman, J., Kosek, M., Haque, R., Olortegui, M., Lima, A., Bhutta, Z., Kang, G., Samie, A., Amour, C., Mason, C., Ahmed, T., Yori, P., Oliveira, D., Alam, D., Babji, S., Bessong, P., Mduma, E., Shrestha, S., Ambikapathi, R., Lang, D., Gottlieb, M., Guerrant, R., Caulfield, L.; For The Mal-Ed Network Investigators.

Am J Trop Med Hyg. 2017 Jul;97(1)

Abstract

The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.

Datta, S., Saunders, M., Tovar, M., and Evans, C.

PLoS Med. 2017 Oct; 14(10): e1002406.

Tuberculosis (TB) is a preventable and curable disease, but it kills more people than any other infection. Many people with TB are never diagnosed, and those who are diagnosed are often ill and contagious for many weeks or months before a diagnosis is made. Barriers to TB diagnosis are well described, often including poverty; stigma; marginalization; indolent, nonspecific symptoms; and poorly performing diagnostic tests. However, despite their central role in TB diagnosis, healthcare providers have been the subject of surprisingly little research [1].

This week in PLOS Medicine, Sylvia and colleagues report findings with important implications for TB elimination [1]. They trained and sent simulated “standardized patients,” also known as “mystery clients,” to healthcare providers at village clinics, township health centers, and county hospitals in China and found that the care provided in 274 consultations differed greatly from TB recommendations. The standardized patients reported classical TB symptoms, but only 15% of the providers mentioned TB, and only 41% of the providers tested or referred patients as recommended for TB. These differences between policy and practice were especially marked in the village clinics where most care was provided, and simulations suggested that a proposed system of managed referral with gatekeeping at the level of the village clinic would further reduce correct management, all of which makes for uncomfortable reading.

Rogawski, E., Guerrant, R., Havt, A., Lima, I., Medeiros, P., Seidman, J., McCormick, B., Babji, S., Hariraju, D., Bodhidatta, L., Shrestha, J., Anania, J., Maro, A., Samie, A., Yori, P., Qureshi, S., Mahfuz, M., Bessong, P., Kosek, M., Ahmed, T., Bhutta, Z., Lang, D., Gottlieb, M., Houpt, E., Lima, A.; MAL-ED Network Investigators

PLoS Negl Trop Dis. 2017 Jul 24;11(7)

Abstract

BACKGROUND:

Enteroaggregative E. coli (EAEC) have been associated with mildly inflammatory diarrhea in outbreaks and in travelers and have been increasingly recognized as enteric pathogens in young children with and without overt diarrhea. We examined the risk factors for EAEC infections and their associations with environmental enteropathy biomarkers and growth outcomes over the first two years of life in eight low-resource settings of the MAL-ED study.

METHODS:

EAEC infections were detected by PCR gene probes for aatA and aaiC virulence traits in 27,094 non-diarrheal surveillance stools and 7,692 diarrheal stools from 2,092 children in the MAL-ED birth cohort. We identified risk factors for EAEC and estimated the associations of EAEC with diarrhea, enteropathy biomarker concentrations, and both short-term (one to three months) and long-term (to two years of age) growth.

RESULTS:

Overall, 9,581 samples (27.5%) were positive for EAEC, and almost all children had at least one detection (94.8%) by two years of age. Exclusive breastfeeding, higher enrollment weight, and macrolide use within the preceding 15 days were protective. Although not associated with diarrhea, EAEC infections were weakly associated with biomarkers of intestinal inflammation and more strongly with reduced length at two years of age (LAZ difference associated with high frequency of EAEC detections: -0.30, 95% CI: -0.44, -0.16).

CONCLUSIONS:

Asymptomatic EAEC infections were common early in life and were associated with linear growth shortfalls. Associations with intestinal inflammation were small in magnitude, but suggest a pathway for the growth impact. Increasing the duration of exclusive breastfeeding may help prevent these potentially inflammatory infections and reduce the long-term impact of early exposure to EAEC.

Fandiño-Del-Rio, M., Goodman, D., Kephart, J., Miele, C., Williams, K., Moazzami, M., Fung, E., Koehler, K., Davila-Roman, V., Lee, K., Nangia, S., Harvey, S., Steenland, K., Gonzales, G., Checkley, W.; Cardiopulmonary outcomes and Household Air Pollution trial (CHAP) Trial Investigators.

Trials. 2017 Nov 3;18(1)

Abstract

BACKGROUND:

Biomass fuel smoke is a leading risk factor for the burden of disease worldwide. International campaigns are promoting the widespread adoption of liquefied petroleum gas (LPG) in resource-limited settings. However, it is unclear if the introduction and use of LPG stoves, in settings where biomass fuels are used daily, reduces pollution concentration exposure, improves health outcomes, or how cultural and social barriers influence the exclusive adoption of LPG stoves.

METHODS:

We will conduct a randomized controlled, field intervention trial of LPG stoves and fuel distribution in rural Puno, Peru, in which we will enroll 180 female participants aged 25-64 years and follow them for 2 years. After enrollment, we will collect information on sociodemographic characteristics, household characteristics, and cooking practices. During the first year of the study, LPG stoves and fuel tanks will be delivered to the homes of 90 intervention participants. During the second year, participants in the intervention arm will keep their LPG stoves, but the gas supply will stop. Control participants will receive LPG stoves and vouchers to obtain free fuel from distributors at the beginning of the second year, but gas will not be delivered. Starting at baseline, we will collect longitudinal measurements of respiratory symptoms, pulmonary function, blood pressure, endothelial function, carotid artery intima-media thickness, 24-h dietary recalls, exhaled carbon monoxide, quality-of-life indicators, and stove-use behaviors. Environmental exposure assessments will occur six times over the 2-year follow-up period, consisting of 48-h personal exposure and kitchen concentration measurements of fine particulate matter and carbon monoxide, and 48-h kitchen concentrations of nitrogen dioxide for a subset of 100 participants.

DISCUSSION:

Findings from this study will allow us to better understand behavioral patterns, environmental exposures, and cardiovascular and pulmonary outcomes resulting from the adoption of LPG stoves. If this trial indicates that LPG stoves are a feasible and effective way to reduce household air pollution and improve health, it will provide important information to support widespread adoption of LPG fuel as a strategy to reduce the global burden of disease.

TRIAL REGISTRATION:

ClinicalTrials.gov, ID: NCT02994680 , Cardiopulmonary Outcomes and Household Air Pollution (CHAP) Trial. Registered on 28 November 2016.

KEYWORDS:

Behavior change; Biomass fuel; Cardiopulmonary outcomes; Cookstove; Exclusive adoption; Household air pollution; Indoor air pollution; LPG; Personal exposure

McCormick, B., Lee, G., Seidman, J., Haque, R., Mondal, D., Quetz, J., Lima, A., Babji, S., Kang, G., Shrestha, S., Mason, C., Qureshi, S., Bhutta, Z., Paredes, M., Peñataro P., Samie, A., Bessong, P., Amour, C., Mduma, E., Patil, c., Guerrant, R., Lang, D., Gottlieb, M., Caulfield, L., and Kosek, M., for the MAL-ED Network

Am J Trop Med Hyg. 2017 Feb 8; 96(2)

Abstract

Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child’s life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0–24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.

Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child’s life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0–24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.

McCloskey, M., Tarazona-Meza, C., Jones-Smith, J., Miele, C., Gilman, R., Bernabe-Ortiz, A., Miranda, A., and Checkley, W.

International Journal of Behavioral Nutrition and Physical Activity 2017 14:90

https://doi.org/10.1186/s12966-017-0545-4

Abstract

Background

Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru.

Methods

We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers.

Results

Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03).

Conclusions

Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region.

Keywords

Nutrition transition, 24-h recall, Urbanization, Overweight, Low- and middle income countries, Chronic diseases.

Rudgard, W., Evans, C., Sweeney, S., Wingfield, T., Lönnroth, K., Barreira, D., Boccia, D.

PLoS Med. 2017 Nov 7;14(11):e1002418.

Abstract

BACKGROUND:

Illness-related costs for patients with tuberculosis (TB) ≥20% of pre-illness annual household income predict adverse treatment outcomes and have been termed «catastrophic.» Social protection initiatives, including cash transfers, are endorsed to help prevent catastrophic costs. With this aim, cash transfers may either be provided to defray TB-related costs of households with a confirmed TB diagnosis (termed a «TB-specific» approach); or to increase income of households with high TB risk to strengthen their economic resilience (termed a «TB-sensitive» approach). The impact of cash transfers provided with each of these approaches might vary. We undertook an economic modelling study from the patient perspective to compare the potential of these 2 cash transfer approaches to prevent catastrophic costs.

METHODS AND FINDINGS:

Model inputs for 7 low- and middle-income countries (Brazil, Colombia, Ecuador, Ghana, Mexico, Tanzania, and Yemen) were retrieved by literature review and included countries’ mean patient TB-related costs, mean household income, mean cash transfers, and estimated TB-specific and TB-sensitive target populations. Analyses were completed for drug-susceptible (DS) TB-related costs in all 7 out of 7 countries, and additionally for drug-resistant (DR) TB-related costs in 1 of the 7 countries with available data. All cost data were reported in 2013 international dollars ($). The target population for TB-specific cash transfers was poor households with a confirmed TB diagnosis, and for TB-sensitive cash transfers was poor households already targeted by countries’ established poverty-reduction cash transfer programme. Cash transfers offered in countries, unrelated to TB, ranged from $217 to $1,091/year/household. Before cash transfers, DS TB-related costs were catastrophic in 6 out of 7 countries. If cash transfers were provided with a TB-specific approach, alone they would be insufficient to prevent DS TB catastrophic costs in 4 out of 6 countries, and when increased enough to prevent DS TB catastrophic costs would require a budget between $3.8 million (95% CI: $3.8 million-$3.8 million) and $75 million (95% CI: $50 million-$100 million) per country. If instead cash transfers were provided with a TB-sensitive approach, alone they would be insufficient to prevent DS TB-related catastrophic costs in any of the 6 countries, and when increased enough to prevent DS TB catastrophic costs would require a budget between $298 million (95% CI: $219 million-$378 million) and $165,367 million (95% CI: $134,085 million-$196,425 million) per country. DR TB-related costs were catastrophic before and after TB-specific or TB-sensitive cash transfers in 1 out of 1 countries. Sensitivity analyses showed our findings to be robust to imputation of missing TB-related cost components, and use of 10% or 30% instead of 20% as the threshold for measuring catastrophic costs. Key limitations were using national average data and not considering other health and social benefits of cash transfers.

CONCLUSIONS:

A TB-sensitive cash transfer approach to increase all poor households’ income may have broad benefits by reducing poverty, but is unlikely to be as effective or affordable for preventing TB catastrophic costs as a TB-specific cash transfer approach to defray TB-related costs only in poor households with a confirmed TB diagnosis. Preventing DR TB-related catastrophic costs will require considerable additional investment whether a TB-sensitive or a TB-specific cash transfer approach is used.

Datta, S., Shah, L., Gilman, R., Evans, C.

Lancet Glob Health. 2017 Aug;5(8)

Abstract

BACKGROUND:

The performance of laboratory tests to diagnose pulmonary tuberculosis is dependent on the quality of the sputum sample tested. The relative merits of sputum collection methods to improve tuberculosis diagnosis are poorly characterised. We therefore aimed to investigate the effects of sputum collection methods on tuberculosis diagnosis.

METHODS:

We did a systematic review and meta-analysis to investigate whether non-invasive sputum collection methods in people aged at least 12 years improve the diagnostic performance of laboratory testing for pulmonary tuberculosis. We searched PubMed, Google Scholar, ProQuest, Web of Science, CINAHL, and Embase up to April 14, 2017, to identify relevant experimental, case-control, or cohort studies. We analysed data by pairwise meta-analyses with a random-effects model and by network meta-analysis. All diagnostic performance data were calculated at the sputum-sample level, except where authors only reported data at the individual patient-level. Heterogeneity was assessed, with potential causes identified by logistic meta-regression.

FINDINGS:

We identified 23 eligible studies published between 1959 and 2017, involving 8967 participants who provided 19 252 sputum samples. Brief, on-demand spot sputum collection was the main reference standard. Pooled sputum collection increased tuberculosis diagnosis by microscopy (odds ratio [OR] 1·6, 95% CI 1·3-1·9, p<0·0001) or culture (1·7, 1·2-2·4, p=0·01). Providing instructions to the patient before sputum collection, during observed collection, or together with physiotherapy assistance increased diagnostic performance by microscopy (OR 1·6, 95% CI 1·3-2·0, p<0·0001). Collecting early morning sputum did not significantly increase diagnostic performance of microscopy (OR 1·5, 95% CI 0·9-2·6, p=0·2) or culture (1·4, 0·9-2·4, p=0·2). Network meta-analysis confirmed these findings, and revealed that both pooled and instructed spot sputum collections were similarly effective techniques for increasing the diagnostic performance of microscopy.

INTERPRETATION:

Tuberculosis diagnoses were substantially increased by either pooled collection or by providing instruction on how to produce a sputum sample taken at any time of the day. Both interventions had a similar effect to that reported for the introduction of new, expensive laboratory tests, and therefore warrant further exploration in the drive to end the global tuberculosis epidemic.

FUNDING:

Wellcome Trust, Joint Global Health Trials consortium, Innovation For Health and Development, and Bill & Melinda Gates Foundation.

Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Kosek M.; MAL-ED Network Investigators.

EBioMedicine. 2017 Apr;18:109-117

Abstract

BACKGROUND:

Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries.

METHODS:

Non-diarrheal stool samples (N=22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N=6363) and plasma alpha-1-acid glycoprotein (AGP) (N=2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0-2years of age.

FINDINGS:

Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated.

INTERPRETATION:

The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation.

FUNDING:

Bill & Melinda Gates Foundation.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Child growth; Child health; Enteropathogen; Enteropathy; Stunting; Undernutrition

Pollard, S., Lima, J., Romero, K., Tarazona-Meza, C., Mougey, E., Tomaino, K., Malpartida-Guzmán, G., Hansel, N., Checkley, W.; GASP Study Investigators.

Asthma Res Pract. 2017 Jun 2;3:5.

Abstract

BACKGROUND:

Prior evidence suggests that vitamin D deficiency may increase the risk of asthma and atopy and impair pulmonary function in children.

METHODS:

In this cross-sectional analysis nested in a case-control study, we analyzed serum 25(OH)D concentrations in 413 children with asthma and 471 children without asthma living in two geographically adjacent study communities (Pampas and Villa El Salvador). We measured total and antigen-specific IgE levels, pulmonary function, asthma control, and exhaled nitric oxide.

RESULTS:

Mean 25(OH)D concentrations were 25.2 ng/mL (SD 10.1) in children with asthma and 26.1 ng/mL (SD 13.7) in children without asthma (p = 0.28). Vitamin D deficiency (25(OH)D < 20 ng/ml) was more common in Pampas than in Villa El Salvador (52.7% vs. 10.5%; p < 0.001). In the overall study population, a 10 ng/ml decrease in serum 25(OH)D concentrations was not significantly associated with odds of asthma (OR 1.09, 95% CI: 0.94 to 1.25). However, vitamin D deficiency was associated with a 1.6-fold increase in odds of asthma in the overall cohort (95% CI: 1.14 to 2.25). After stratifying by site, a 10 ng/mL decrease in serum 25(OH)D concentrations was associated with 18% higher odds of having asthma in Pampas (OR = 1.18, 95% CI 1.02 to 1.38), whereas there was no significant association between 25(OH)D concentrations and asthma in Villa El Salvador (OR = 0.95, 95% CI 0.87 to 1.05). Combined data from these geographically adjacent populations suggests a possible threshold for the relationship between 25(OH)D levels and asthma at approximately 27.5 ng/ml. Serum 25(OH)D concentrations were not clearly associated with asthma control, total serum IgE, atopy, or airway inflammation.

CONCLUSION:

Serum 25(OH)D concentrations were inversely associated with asthma in one study community with a high prevalence of deficiency. Studies are needed to investigate a possible threshold 25(OH)D concentration after which higher vitamin D levels show no further benefit for asthma.

KEYWORDS:

25(OH)D; Asthma; Nutrition; Pediatric asthma; Urbanization; Vitamin D

Carrillo-Larco, R., Bernabe-Ortiz, A., Sacksteder, K., Diez-Canseco, F., Cárdenas, M., Gilman, R., and Miranda, J.,

Glob Health Epidemiol Genom. 2017; 2: e12.

Abstract

Sleep difficulties and short sleep duration have been associated with hypertension. Though body mass index (BMI) may be a mediator variable, the mediation effect has not been defined. We aimed to assess the association between sleep duration and sleep difficulties with hypertension, to determine if BMI is a mediator variable, and to quantify the mediation effect. We conducted a mediation analysis and calculated prevalence ratios with 95% confidence intervals. The exposure variables were sleep duration and sleep difficulties, and the outcome was hypertension. Sleep difficulties were statistically significantly associated with a 43% higher prevalence of hypertension in multivariable analyses; results were not statistically significant for sleep duration. In these analyses, and in sex-specific subgroup analyses, we found no strong evidence that BMI mediated the association between sleep indices and risk of hypertension. Our findings suggest that BMI does not appear to mediate the association between sleep patterns and hypertension. These results highlight the need to further study the mechanisms underlying the relationship between sleep patterns and cardiovascular risk factors.

Key words: Body mass index, hypertension, obesity, sleep apnea, sleep disorders

Sleep difficulties and short sleep duration have been associated with hypertension. Though body mass index (BMI) may be a mediator variable, the mediation effect has not been defined. We aimed to assess the association between sleep duration and sleep difficulties with hypertension, to determine if BMI is a mediator variable, and to quantify the mediation effect. We conducted a mediation analysis and calculated prevalence ratios with 95% confidence intervals. The exposure variables were sleep duration and sleep difficulties, and the outcome was hypertension. Sleep difficulties were statistically significantly associated with a 43% higher prevalence of hypertension in multivariable analyses; results were not statistically significant for sleep duration. In these analyses, and in sex-specific subgroup analyses, we found no strong evidence that BMI mediated the association between sleep indices and risk of hypertension. Our findings suggest that BMI does not appear to mediate the association between sleep patterns and hypertension. These results highlight the need to further study the mechanisms underlying the relationship between sleep patterns and cardiovascular risk factors.

Key words: Body mass index, hypertension, obesity, sleep apnea, sleep disorders

Lee, G., Pan, W., Peñataro, P., Paredes, M., Tilley, D., Gregory, M., Oberhelman, R., Burga, R., Chavez, C., Kosek, M.

PLoS Negl Trop Dis. 2013;7(1):e2036.

Although diarrheal illnesses are recognized as both a cause and effect of undernutrition, evidence for the effect of specific enteropathogens on early childhood growth remains limited. We estimated the effects of undernutrition as a risk factor for campylobacteriosis, as well as associations between symptomatic and asymptomatic Campylobacter infections and growth.

Romero, K., Robinson, C., Baumann, L., Gilman, R., Hamilton, R., Hansel, N., Checkley, W.

Respiratory Research2013 14:48

Abstract

Background

The fractional exhaled nitric oxide (FeNO) is a quantitative, noninvasive and safe measure of airways inflammation that may complement the assessment of asthma. Elevations of FeNO have recently been found to correlate with allergic sensitization. Therefore, FeNO may be a useful predictor of atopy in the general population. We sought to determine the diagnostic accuracy of FeNO in predicting atopy in a population-based study.

Methods

We conducted a cross-sectional study in an age- and sex- stratified random sample of 13 to 15 year-olds in two communities in Peru. We asked participants about asthma symptoms, environmental exposures and sociodemographics, and underwent spirometry, assessment of FeNO and an allergy skin test. We used multivariable logistic regression to model the odds of atopy as a function of FeNO, and calculated area-under-the-curves (AUC) to determine the diagnostic accuracy of FeNO as a predictor of atopy.

Results

Of 1441 recruited participants, 1119 (83%) completed all evaluations. Mean FeNO was 17.6 ppb (SD=0.6) in atopics and 11.6 ppb (SD=0.8) in non-atopics (p<0.001). In multivariable analyses, a FeNO>20 ppb was associated with an increase in the odds of atopy in non-asthmatics (OR=5.3, 95% CI 3.3 to 8.5) and asthmatics (OR=16.2, 95% CI 3.4 to 77.5). A FeNO>20 ppb was the best predictor for atopy with an AUC of 68% (95% CI 64% to 69%). Stratified by asthma, the AUC was 65% (95% CI 61% to 69%) in non-asthmatics and 82% (95% CI 71% to 91%) in asthmatics.

Conclusions

FeNO had limited accuracy to identify atopy among the general population; however, it may be a useful indicator of atopic phenotype among asthmatics.

Keywords

Allergic sensitization, Asthma, Exhaled nitric, Allergic rhinitis.

Chuquiyauri, R., Peñataro, P., Brouwer, K., Fasabi, M., Calderon, M., Torres, S., Gilman, R., Kosek, M., Vinetz, J.

Am J Trop Med Hyg. 2013 Aug;89(2)

Abstract

To determine the magnitude of Plasmodium vivax relapsing malaria in rural Amazonia, we carried out a study in four sites in northeastern Peru. Polymerase chain reaction-restriction fragment length polymorphism of PvMSP-3α and tandem repeat (TR) markers were compared for their ability to distinguish relapse versus reinfection. Of 1,507 subjects with P. vivax malaria, 354 developed > 1 episode during the study; 97 of 354 (27.5%) were defined as relapse using Pvmsp-3α alone. The addition of TR polymorphism analysis significantly reduced the number of definitively defined relapses to 26 of 354 (7.4%) (P < 0.05). Multivariate logistic regression modeling showed that the probability of having > 1 infection was associated with the following: subjects in Mazan (odds ratio [OR] = 2.56; 95% confidence interval [CI] 1.87, 3.51), 15-44 years of age (OR = 1.49; 95% CI 1.03, 2.15), traveling for job purposes (OR = 1.45; 95%CI 1.03, 2.06), and travel within past month (OR = 1.46; 95% CI 1.0, 2.14). The high discriminatory capacity of the molecular tools shown here is useful for understanding the micro-geography of malaria transmission.

Diniz, P., Morton, B., Tngrian, M., Kachani, M., Barrón, E., Gavidia, C., Gilman, R., Angulo, N., Brenner, E., Lerner, R., Chomel, B.

PLoS Negl Trop Dis. 2013 Sep 5;7(9)

Abstract

Bartonella species are emerging infectious organisms transmitted by arthropods capable of causing long-lasting infection in mammalian hosts. Among over 30 species described from four continents to date, 15 are known to infect humans, with eight of these capable of infecting dogs as well. B. bacilliformis is the only species described infecting humans in Peru; however, several other Bartonella species were detected in small mammals, bats, ticks, and fleas in that country. The objective of this study was to determine the serological and/or molecular prevalence of Bartonella species in asymptomatic dogs in Peru in order to indirectly evaluate the potential for human exposure to zoonotic Bartonella species. A convenient sample of 219 healthy dogs was obtained from five cities and three villages in Peru. EDTA-blood samples were collected from 205 dogs, whereas serum samples were available from 108 dogs. The EDTA-blood samples were screened by PCR followed by nucleotide sequencing for species identification. Antibodies against B. vinsonii berkhoffii and B. rochalimae were detected by IFA (cut-off of 1∶64). Bartonella DNA was detected in 21 of the 205 dogs (10%). Fifteen dogs were infected with B. rochalimae, while six dogs were infected with B. v. berkhoffii genotype III. Seropositivity for B. rochalimae was detected in 67 dogs (62%), and for B. v. berkhoffii in 43 (40%) of the 108 dogs. Reciprocal titers ≥1∶256 for B. rochalimae were detected in 19% of dogs, and for B. v. berkhoffii in 6.5% of dogs. This study identifies for the first time a population of dogs exposed to or infected with zoonotic Bartonella species, suggesting that domestic dogs may be the natural reservoir of these zoonotic organisms. Since dogs are epidemiological sentinels, Peruvian humans may be exposed to infections with B. rochalimae or B. v. berkhoffii.

Parker, B., Paredes, M., Peñataro, P., Escobedo, K., Florin, D., Rengifo, S., Cardenas, R., Capcha, L., Rodriguez, H., Pan, W., Banda, C., Vinetz, J., Kosek, M.

Malar J. 2013 May 31;12

Abstract

BACKGROUND:

Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru. Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infective bites per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas. Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen.

METHODS:

To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers. Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes. Slide surveillance was performed for humans encountered in the zone.

RESULTS:

In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax VK210 or P. vivax VK247). Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night. Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however, 88% of the individuals found to be positive were asymptomatic at the time of sampling.

CONCLUSIONS:

The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru. The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control strategies.

Kosek, M., Yori, P., Gilman, R., Calderon, M., Zimic, M., Chuquiyauri, R., Jeri, C., Pinedo-Cancino, V., Matthias, M., Llanos-Cuentas, A., Vinetz, J..

Am J Trop Med Hyg. 2012 Apr;86(4)

Abstract

Molecular tools to distinguish strains of Plasmodium vivax are important for studying the epidemiology of malaria transmission. Two sets of markers-tandem repeat (TR) polymorphisms and MSP3α-were used to study Plasmodium vivax in patients in the Peruvian Amazon region of Iquitos. Of 110 patients, 90 distinct haplotypes were distinguished using 9 TR markers. An MSP3α polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using HhaI and AluI revealed 8 and 9 profiles, respectively, and 36 profiles when analyzed in combination. Combining TR and PCR-RFLP markers, 101 distinct molecular profiles were distinguished among these 110 patients. Nine TR markers arrayed along a 100 kB stretch of a P. vivax chromosome containing the gene for circumsporozoite protein showed non-linear linkage disequilibrium (I(SA) = 0.03, P = 0.001). These findings demonstrate the potential use of TR markers for molecular epidemiology studies.

Li, N., Xiao, L., Cama, V., Ortega, Y., Gilman, R., Guo, M., and Feng, Y.,

Emerg Infect Dis. 2013 Oct; 19(10)

Little is known about the emergence and spread of virulent subtypes of Cryptosporidium hominis, the predominant species responsible for human cryptosporidiosis. We conducted sequence analyses of 32 genetic loci of 53 C. hominis specimens isolated from a longitudinally followed cohort of children living in a small community. We identified by linkage disequilibrium and recombination analyses only limited genetic recombination, which occurred exclusively within the 60-kDa glycoprotein gene subtype IbA10G2, a predominant subtype for outbreaks in industrialized nations and a virulent subtype in the study community. Intensive transmission of virulent subtype IbA10G2 in the study area might have resulted in genetic recombination with other subtypes. Moreover, we identified selection for IbA10G2 at a 129-kb region around the 60-kDa glycoprotein gene in chromosome 6. These findings improve our understanding of the origin and evolution of C. hominis subtypes and the spread of virulent subtypes.

Kosek, M., Haque, R., Lima, A., Babji, S., Shrestha, S., Qureshi, S., Amidou, S., Mduma, E., Lee, G., Yori, P., Guerrant, R., Bhutta, Z., Mason, C., Kang, G., Kabir, M., Amour, C., Bessong, P., Turab, A., Seidman, J., Olortegui, M., Quetz, J., Lang, D., Gratz, J., Miller, M., Gottlieb, M.

Am J Trop Med Hyg. 2013 Feb;88(2)

Abstract

Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood.

Julian, T., MacDonald, L., Guo, Y., Marks, S., Kosek, M., Yori, P., Rengifo S., and Schwab, K.,

Am J Trop Med Hyg. 2013 Nov 6; 89(5)

Abstract

Surface-mediated disease transmission is understudied in developing countries, particularly in light of the evidence that surface concentrations of fecal bacteria typically exceed concentrations in developed countries by 10- to 100-fold. In this study, we examined fecal indicator bacterial contamination of dinner plates at 21 households in four peri-urban communities in the Peruvian Amazon. We also used surveys to estimate household use of and demand for surface disinfectants at 280 households. Despite detecting total coliform, enterococci, and Escherichia coli on 86%, 43%, and 24% of plates sampled, respectively, less than one-third of households were regularly using bleach to disinfect surfaces. Among non-users of bleach, only 3.2% of respondents reported a new demand for bleach, defined as a high likelihood of using bleach within the next year. This study highlights the potential for marketing approaches to increase use of and demand for surface disinfectants to improve domestic hygiene.

Surface-mediated disease transmission is understudied in developing countries, particularly in light of the evidence that surface concentrations of fecal bacteria typically exceed concentrations in developed countries by 10- to 100-fold. In this study, we examined fecal indicator bacterial contamination of dinner plates at 21 households in four peri-urban communities in the Peruvian Amazon. We also used surveys to estimate household use of and demand for surface disinfectants at 280 households. Despite detecting total coliform, enterococci, and Escherichia coli on 86%, 43%, and 24% of plates sampled, respectively, less than one-third of households were regularly using bleach to disinfect surfaces. Among non-users of bleach, only 3.2% of respondents reported a new demand for bleach, defined as a high likelihood of using bleach within the next year. This study highlights the potential for marketing approaches to increase use of and demand for surface disinfectants to improve domestic hygiene.

Klasen, E., Miranda, J., Khatry, S., Menya, D., Gilman, R., Tielsch, J., Kennedy, C., Dreibelbis, R., Naithani, N., Kimaiyo, S., Chiang, M., Carter, E., Sherman, Ch., Breysse, P., Checkley, W., Huaman, A., Levano, M., Haustein, D., Rhodes, E., Grajeda, L., Levy, S., LeClerq, S., Wise, R., Mosol, P., Ogaro, F., Apaka, C., Baliddawa, J.

https://doi.org/10.1186/1745-6215-14-327

Abstract

Background

Exposure to biomass fuel smoke is one of the leading risk factors for disease burden worldwide. International campaigns are currently promoting the widespread adoption of improved cookstoves in resource-limited settings, yet little is known about the cultural and social barriers to successful improved cookstove adoption and how these barriers affect environmental exposures and health outcomes.

Design

We plan to conduct a one-year crossover, feasibility intervention trial in three resource-limited settings (Kenya, Nepal and Peru). We will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site (total 120 to 138).

Methods

At baseline, we will collect information on sociodemographic characteristics and cooking practices, and measure respiratory health and blood pressure for all participating women. An initial observational period of four months while households use their traditional, open-fire design cookstoves will take place prior to randomization. All participants will then be randomized to receive one of two types of improved, ventilated cookstoves with a chimney: a commercially-constructed cookstove (Envirofit G3300/G3355) or a locally-constructed cookstove. After four months of observation, participants will crossover and receive the other improved cookstove design and be followed for another four months. During each of the three four-month study periods, we will collect monthly information on self-reported respiratory symptoms, cooking practices, compliance with cookstove use (intervention periods only), and measure peak expiratory flow, forced expiratory volume at 1 second, exhaled carbon monoxide and blood pressure. We will also measure pulmonary function testing in the women participants and 24-hour kitchen particulate matter and carbon monoxide levels at least once per period.

Discussion

Findings from this study will help us better understand the behavioral, biological, and environmental changes that occur with a cookstove intervention. If this trial indicates that reducing indoor air pollution is feasible and effective in resource-limited settings like Peru, Kenya and Nepal, trials and programs to modify the open burning of biomass fuels by installation of low-cost ventilated cookstoves could significantly reduce the burden of illness and death worldwide.

Keywords

Adoption, Behavior change, Biomass fuel, DLCO, Improved cookstove, Indoor air pollution, Spirometry, Ventilated cookstove.

Kosek, M., Yori, P., Gilman, R., Vela, H., Olortegui, M., Chavez, C., Calderon, M., Bao, J., Hall, E., Maves, R., Burga, R., Sanchez, G.

Am J Trop Med Hyg. 2012 Jun;86(6)

Abstract

To evaluate the performance of enterobacterial repetitive intergenic sequence-based polymerase chain reaction (ERIC-PCR) typing versus the current standard for the typing of Shigella pulsed gel electrophoresis (PFGE), we typed 116 Shigella isolates from a village in an endemic setting over a 20-month period using both methods. PFGE identified 37 pulse types and had a discrimination index of 0.925 (95% confidence interval = 0.830-1.00), whereas ERIC-PCR identified 42 types and had a discrimination index of 0.961 (95% confidence interval = 0.886-1.00). PFGE and ERIC-PCR showed a 90.4% correlation in the designation of isolates as clonal or non-clonal in pairwise comparisons. Both systems were highly reproducible and provided highly similar and supplementary data compared with serotyping regarding the transmission dynamics of shigellosis in this community. ERIC-PCR is considerably more rapid and inexpensive than PFGE and may have a complementary role to PFGE for initial investigations of hypothesized outbreaks in resource-limited settings.

Eisen, S., Pealing, L., Aldridge, R., Siedner, M., Necochea, A., Leybell, I., Valencia, T., Herrera, B., Wiles, S., Friedland, J., Gilman, R., and Evans, C.,

Pai, M., Editor

PLoS One. 2013; 8(9): e74220

Abstract

Background

Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity.

Methods

Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants’ whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants’ whole blood versus positive-control culture broth and versus negative-control plasma.

Results

Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents.

Conclusions

An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or residence at high altitude was associated with decreased mycobacterial growth in whole blood relative to controls, consistent with altitude-related augmentation of antimycobacterial cellular immunity.

Martinez L, Arman A, Haveman N, Lundgren A, Cabrera L, Evans CA, Pelly TF, Saito M, Callacondo D, Oberhelman R, Collazo G, Carnero AM, Gilman RH.

Am J Trop Med Hyg. 2013 Sep;89(3):507-15.

A cross-sectional, community-based study was performed in 2012 with 428 residents of periurban shantytowns in Lima, Peru to study risk factors for and changes in latent tuberculosis infection in age-stratified groups compared with our data from the same region in 1990 (N = 219) and 2005 (N = 103). Tuberculin skin test positivity in these communities was highly prevalent at 52% overall, increased with age (P < 0.01) and was similar to 2005 (53%) and 1990 (48%). From 1990 to 2012, the prevalence of tuberculin positivity decreased in 5-14 and 15-24 year old groups (to 17% and 34%, respectively, both P < 0.05). However, this may be explained by cessation of Bacille Calmette-Guérin revaccination during this period, because Bacille Calmette-Guérin revaccination doubled tuberculin positivity. Over the same 22-year period, tuberculin positivity in the ≥ 25 year old group remained high (71%, P = 0.3), suggesting that prevalent latent tuberculosis infection persists in the adult population despite improving medical care and socioeconomic development in this region.

Castro-Sesquen YE, Gilman RH, Paico H, Yauri V, Angulo N, Ccopa F, Bern C.

PLoS Negl Trop Dis. 2013;7(2):e1996.

We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase.

Rath BA, von Kleist M, Castillo ME, Kolevic L, Caballero P, Soto-Castellares G, Amedee AM, Robinson JE, Katzenstein DK, Van Dyke RB, Oberhelman RA.

BMC Infect Dis. 2013 Jan 2;13:1.

The impact of extended use of ART in developing countries has been enormous. A thorough understanding of all factors contributing to the success of antiretroviral therapy is required. The current study aims to investigate the value of cross-sectional drug resistance monitoring using DNA and RNA oligonucleotide ligation assays (OLA) in treatment cohorts in low-resource settings. The study was conducted in the first cohort of children gaining access to structured ART in Peru.

Román K, Castillo R, Gilman RH, Calderón M, Vivar A, Céspedes M, Smits HL, Meléndez P, Gotuzzo E, Guerra H, Maves RC, Matthias MA, Vinetz JM, Saito M.

Am J Trop Med Hyg. 2013 Mar;88(3):552-8.

Brucella melitensis is highly infectious for humans and can be transmitted to humans in a number of epidemiological contexts. Within the context of an ongoing brucellosis surveillance project, an outbreak at a Peruvian police officer cafeteria was discovered, which led to active surveillance (serology, blood culture) for additional cases among 49 police officers who had also eaten there. This investigation indicates the importance of case tracking and active surveillance for brucellosis in the context of potential common source exposure.

Robinson CL, Baumann LM, Gilman RH, Romero K, Combe JM, Cabrera L, Hansel NN, Barnes K, Gonzalvez G, Wise RA, Breysse PN, Checkley W.

BMJ Open. 2012 Feb 22;2(1):e000421.

According to a large-scale international survey, Peru has one of the highest prevalences of asthma worldwide; however, data from this survey were limited to participants from urban Lima. The authors sought to characterise the epidemiology of asthma in Peru in two regions with disparate degrees of urbanisation. In this manuscript, the authors summarise the study design and implementation.

This study will contribute to the characterisation of a variety of risk factors for asthma, including urbanisation, total IgE levels, vitamin D levels and candidate genes, in a resource-poor setting. The authors present data to support high quality of survey, allergic, spirometric and genetic data collected in our study.

Pereira L, Zamudio R, Soares-Souza G, Herrera P, Cabrera L, Hooper CC, Cok J, Combe JM, Vargas G, Prado WA, Schneider S, Kehdy F, Rodrigues MR, Chanock SJ, Berg DE, Gilman RH, Tarazona-Santos E.

PLoS One. 2012;7(8):e41200.

Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors.

The high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.

Bernabe-Ortiz A, Benziger CP, Gilman RH, Smeeth L, Miranda JJ.

PLoS One. 2012;7(4):e35127.

Although men and women have similar risk factors for cardiovascular disease, many social behaviors in developing countries differ by sex. Rural-to-urban migrants have different cardiovascular risk profiles than rural or urban dwellers. The objective of this study was to evaluate the sex differences with specific cardiovascular risk factors in rural-to-urban migrants.

Our results suggest that interventions for CVD in Peru should be sex-specific and address the unique health needs of migrant populations living in urban shantytowns since the risk factors for obesity and metabolic syndrome differ between males and females.

Miranda, J., Bernabé-Ortiz, A., Diez-Canseco, F., Málaga, G., Cárdenas, M., Carrillo-Larco, R., Lazo-Porras, M., Moscoso-Porras, M., Pesantes, M., Ponce, V., Araya, R., Beran, D., Busse, P., Boggio, O., Checkley, W., García, P., Huicho, L., León-Velarde, F., Lescano, A., Mohr, D., Pan, W., Peiris, D., Perel, P., Rabadán-Diehl, C., Rivera-Chira, M., Sacksteder, K., Smeeth, L., Trujillo, A., Wells, J., Yan, L., García, H., and Gilman R.

Global Health. 2016; 12: 29

Human capital requires opportunities to develop and capacity to overcome challenges, together with an enabling environment that fosters critical and disruptive innovation. Exploring such features is necessary to establish the foundation of solid long-term partnerships. In this paper we describe the experience of the CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Herediain Lima, Peru, as a case study for fostering meaningful and sustainable partnerships for international collaborative research.

Proaño, A., Bravard, M., Tracey, B., López, J., Comina, G., Zimic, M., Corone,l J., Lee, G., Caviedes, L., Cabrera, J., Salas, A., Ticona, E., Kirwan, D., Friedland, J., Evans, C., Moore, D., Gilman, R.; Tuberculosis Working Group in Peru.

BMJ Open. 2016 Apr 22;6(4)

Abstract

INTRODUCTION:

Cough is a key symptom of tuberculosis (TB) as well as the main cause of transmission. However, a recent literature review found that cough frequency (number of coughs per hour) in patients with TB has only been studied once, in 1969. The main aim of this study is to describe cough frequency patterns before and after the start of TB treatment and to determine baseline factors that affect cough frequency in these patients. Secondarily, we will evaluate the correlation between cough frequency and TB microbiological resolution.

METHODS:

This study will select participants with culture confirmed TB from 2 tertiary hospitals in Lima, Peru. We estimated that a sample size of 107 patients was sufficient to detect clinically significant changes in cough frequency. Participants will initially be evaluated through questionnaires, radiology, microscopic observation drug susceptibility broth TB-culture, auramine smear microscopy and cough recordings. This cohort will be followed for the initial 60 days of anti-TB treatment, and throughout the study several microbiological samples as well as 24 h recordings will be collected. We will describe the variability of cough episodes and determine its association with baseline laboratory parameters of pulmonary TB. In addition, we will analyse the reduction of cough frequency in predicting TB cure, adjusted for potential confounders.

ETHICS AND DISSEMINATION:

Ethical approval has been obtained from the ethics committees at each participating hospital in Lima, Peru, Asociación Benéfica PRISMA in Lima, Peru, the Universidad Peruana Cayetano Heredia in Lima, Peru and Johns Hopkins University in Baltimore, USA. We aim to publish and disseminate our findings in peer-reviewed journals. We also expect to create and maintain an online repository for TB cough sounds as well as the statistical analysis employed.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

KEYWORDS:

Cough; Monitoring

Kosek M, Mduma E, Kosek P, Lee G, Svensen E, Pan W, Olortegui M, Bream J, Patil C, Asayag C, Sanchez G, Caulfield L, Gratz J, Yori P.

Am J Trop Med Hyg. 2016 Oct 5;95(4)

Abstract

Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine-tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11-0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03-0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 μM was associated with a 1.63 (95% CI = 1.13-2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines.

Grajeda, L.^†, Ivanescu, A.^†, Saito, M., Crainiceanu, C., Jaganath, D., Gilman, R., Crabtree, J., Kelleher, D., Cabrera, L., Cama, V., and Checkley, W.

^†Contributed equally

Emerging Themes in Epidemiology 2016 13:1

Abstract

Background

Childhood growth is a cornerstone of pediatric research. Statistical models need to consider individual trajectories to adequately describe growth outcomes. Specifically, well-defined longitudinal models are essential to characterize both population and subject-specific growth. Linear mixed-effect models with cubic regression splines can account for the nonlinearity of growth curves and provide reasonable estimators of population and subject-specific growth, velocity and acceleration.

Methods

We provide a stepwise approach that builds from simple to complex models, and account for the intrinsic complexity of the data. We start with standard cubic splines regression models and build up to a model that includes subject-specific random intercepts and slopes and residual autocorrelation. We then compared cubic regression splines vis-à-vis linear piecewise splines, and with varying number of knots and positions. Statistical code is provided to ensure reproducibility and improve dissemination of methods. Models are applied to longitudinal height measurements in a cohort of 215 Peruvian children followed from birth until their fourth year of life.

Results

Unexplained variability, as measured by the variance of the regression model, was reduced from 7.34 when using ordinary least squares to 0.81 (p < 0.001) when using a linear mixed-effect models with random slopes and a first order continuous autoregressive error term. There was substantial heterogeneity in both the intercept (p < 0.001) and slopes (p < 0.001) of the individual growth trajectories. We also identified important serial correlation within the structure of the data (ρ = 0.66; 95 % CI 0.64 to 0.68; p < 0.001), which we modeled with a first order continuous autoregressive error term as evidenced by the variogram of the residuals and by a lack of association among residuals. The final model provides a parametric linear regression equation for both estimation and prediction of population- and individual-level growth in height. We show that cubic regression splines are superior to linear regression splines for the case of a small number of knots in both estimation and prediction with the full linear mixed effect model (AIC 19,352 vs. 19,598, respectively). While the regression parameters are more complex to interpret in the former, we argue that inference for any problem depends more on the estimated curve or differences in curves rather than the coefficients. Moreover, use of cubic regression splines provides biological meaningful growth velocity and acceleration curves despite increased complexity in coefficient interpretation.

Conclusions

Through this stepwise approach, we provide a set of tools to model longitudinal childhood data for non-statisticians using linear mixed-effect models.

Keywords

Longitudinal studies, Body Height, Child development, Growth, Linear Models

Antiporta, D., Smeeth, L., Gilman, R., Miranda, J.

Public Health Nutr. 2016 May;19(7)

Abstract

OBJECTIVE:

To evaluate the association between length of residence in an urban area and obesity among Peruvian rural-to-urban migrants.

DESIGN:

Cross-sectional database analysis of the migrant group from the PERU MIGRANT Study (2007). Exposure was length of urban residence, analysed as both a continuous (10-year units) and a categorical variable. Four skinfold site measurements (biceps, triceps, subscapular and suprailiac) were used to calculate body fat percentage and obesity (body fat percentage >25% males, >33% females). We used Poisson generalized linear models to estimate adjusted prevalence ratios and 95 % confidence intervals. Multicollinearity between age and length of urban residence was assessed using conditional numbers and correlation tests.

SETTING:

A peri-urban shantytown in the south of Lima, Peru.

SUBJECTS:

Rural-to-urban migrants (n 526) living in Lima.

RESULTS:

Multivariable analyses showed that for each 10-year unit increase in residence in an urban area, rural-to-urban migrants had, on average, a 12 % (95 % CI 6, 18 %) higher prevalence of obesity. This association was also present when length of urban residence was analysed in categories. Sensitivity analyses, conducted with non-migrant groups, showed no evidence of an association between 10-year age units and obesity in rural (P=0·159) or urban populations (P=0·078). High correlation and a large conditional number between age and length of urban residence were found, suggesting a strong collinearity between both variables.

CONCLUSIONS:

Longer lengths of urban residence are related to increased obesity in rural-to-urban migrant populations; therefore, interventions to prevent obesity in urban areas may benefit from targeting migrant groups.

KEYWORDS:

Migration; Nutritional epidemiology; Obesity; Peru; Rural-to-urban; Skinfold

Chile, N., Clark, T., Arana, Y., Ortega, Y., Palma, S., Mejia, A., Angulo, N., Kosek, J., Kosek, M., Gomez-Puerta, L., Garcia, H., Gavidia, C., Gilman, R., Verastegui, M., and Cysticercosis Working Group in Peru

Brehm, K., Editor

PLoS Negl Trop Dis. 2016 Feb; 10(2)

Abstract

Background

The transitional period between the oncosphere and the cysticercus of Taenia solium is the postoncospheral (PO) form, which has not yet been completely characterized. The aim of this work was to standardize a method to obtain T. solium PO forms by in vitro cultivation. We studied the morphology of the PO form and compared the expression of antigenic proteins among the PO form, oncosphere, and cysticerci stages.

Methodology/Principal Findings

T. solium activated oncospheres were co-cultured with ten cell lines to obtain PO forms, which we studied at three stages of development–days 15, 30, and 60. A high percentage (32%) of PO forms was obtained using HCT-8 cells in comparison to the other cell lines. The morphology was observed by bright field, scanning, and transmission electron microscopy. Morphology of the PO form changed over time, with the six hooks commonly seen in the oncosphere stage disappearing in the PO forms, and vesicles and microtriches observed in the tegument. The PO forms grew as they aged, reaching a diameter of 2.5 mm at 60 days of culture. 15–30 day PO forms developed into mature cysticerci when inoculated into rats. Antigenic proteins expressed in the PO forms are also expressed by the oncosphere and cysticerci stages, with more cysticerci antigenic proteins expressed as the PO forms ages.

Conclusions/Significance

This is the first report of an in vitro production method of T. solium PO forms. The changes observed in protein expression may be useful in identifying new targets for vaccine development. In vitro culture of PO form will aid in understanding the host-parasite relationship, since the structural changes of the developing PO forms may reflect the parasite’s immunoprotective mechanisms. A wider application of this method could significantly reduce the use of animals, and thus the costs and time required for further experimental investigations.

Lazo-Porras, M., Bernabe-Ortiz, A., Sacksteder, K., Gilman, R., Malaga, G., Armstrong, D., and Miranda, J.

Trials. 2016; 17: 206. Published online 2016 Apr 19.

Abstract

Background

Diabetic foot neuropathy (DFN) is one of the most important complications of diabetes mellitus; its early diagnosis and intervention can prevent foot ulcers and the need for amputation. Thermometry, measuring the temperature of the feet, is a promising emerging modality for diabetic foot ulcer prevention. However, patient compliance with at-home monitoring is concerning. Delivering messages to remind patients to perform thermometry and foot care might be helpful to guarantee regular foot monitoring. This trial was designed to compare the incidence of diabetic foot ulcers (DFUs) between participants who receive thermometry alone and those who receive thermometry as well as mHealth (SMS and voice messaging) over a year-long study period.

Methods/design

This is an evaluator-blinded, randomized, 12-month trial. Individuals with a diagnosis of type 2 diabetes mellitus, aged between 18–80 years, having a present dorsalis pedis pulse in both feet, are in risk group 2 or 3 using the diabetic foot risk classification system (as specified by the International Working Group on the Diabetic Foot), have an operating cell phone or a caregiver with an operating cell phone, and have the ability to provide informed consent will be eligible to participate in the study. Recruitment will be performed in diabetes outpatient clinics at two Ministry of Health tertiary hospitals in Lima, Peru.

Interventions: participants in both groups will receive education about foot care at the beginning of the study and they will be provided with a thermometry device (TempStat™). TempStat™ is a tool that captures a thermal image of the feet, which, depending on the temperature of the feet, shows different colors. In this study, if a participant notes a single yellow image or variance between one foot and the contralateral foot, they will be prompted to notify a nurse to evaluate their activity within the previous 2 weeks and make appropriate recommendations. In addition to thermometry, participants in the intervention arm will receive an mHealth component in the form of SMS and voice messages as reminders to use the thermometry device, and instructions to promote foot care.

Outcomes: the primary outcome is foot ulceration, evaluated by a trained nurse, occurring at any point during the study.

Discussion

This study has two principal contributions towards the prevention of DFU. First, the introduction of messages to promote self-management of diabetes foot care as well as using reminders as a strategy to improve adherence to daily home-based measurements. Secondly, the implementation of a thermometry-based strategy complemented by SMS and voice messages in an LMIC setting, with wider implications for scalability.

Trial registration

This study is registered in ClinicalTrials.gov: Identifier NCT02373592.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1333-1) contains supplementary material, which is available to authorized users.

Keywords: Diabetic neuropathies, Thermometry, Diabetes mellitus, Type 2 ulcer, mHealth

Ticona, E., Huaroto, L., Kirwan, D., Chumpitaz, M., Munayco, C., Maguiña, M., Tovar, M., Evans, C., Escombe, R., Gilman, R.

Am J Trop Med Hyg. 2016 Dec 7;95(6)

Abstract

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000-56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug-susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB-coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective.

© The American Society of Tropical Medicine and Hygiene.

Lee, G., Paredes, M., Salmón-Mulanovich, G., Peñataro, P., Kosek, M.

BMC Int Health Hum Rights. 2016 Oct 12;16(1)

Abstract

BACKGROUND:

Informal settlements are common throughout the developing world. In Peru, land occupations, commonly «invasions» in Spanish, are a means by which the extremely poor attempt to obtain access to land. Here, we examine difference in child health between two communities in the Peruvian Amazon, one well-established and one newly formed by ‘invasion’, as captured incidentally by a prospective epidemiological cohort study.

METHODS:

Between 2002 and 2006 a study designed to describe the epidemiology of pediatric enteric infections and child growth in a community-based setting enrolled 442 children in Santa Clara de Nanay, a community adjacent to the city of Iquitos, in Loreto, Peru. In early 2003, a land occupation, commonly called an «invasion» in Spanish, was organized by members of the Santa Clara community, and approximately 20 % of participating study families began occupying privately owned agricultural land adjacent to Santa Clara, thus forming the new community of La Union.

RESULTS:

Parents in families that chose to invade reported less education than parents in families that chose not to. Children in the new community experienced a higher incidence of diarrheal disease and non-specific fevers, although fewer helminth infections, than children who remained in the established community. At the time of the invasion, there were no differences in anthropometric status between the two groups; however children in the new community experienced greater progressive growth faltering over the course of the longitudinal study.

CONCLUSIONS:

Growth faltering in early childhood represents an enduring loss of human potential. Therefore, our data suggests the human cost of land invasion may be disproportionately borne by the youngest individuals. Innovative policy strategies may be needed to protect this vulnerable group.

KEYWORDS:

Child health; Height-for-age; Informal settlement; Natural experiment; Peru

Bernabe-Ortiz, A., Smeeth, L., Gilman, R., Sanchez-Abanto, J., Checkley, W., Miranda, J., and CRONICAS Cohort Study Group

Received 16 June 2016; Accepted 27 July 2016

Abstract

Objective. To develop and validate a risk score for detecting cases of undiagnosed diabetes in a resource-constrained country. Methods. Two population-based studies in Peruvian population aged ≥35 years were used in the analysis: the ENINBSC survey () and the CRONICAS Cohort Study (). Fasting plasma glucose ≥7.0 mmol/L was used to diagnose diabetes in both studies. Coefficients for risk score were derived from the ENINBSC data and then the performance was validated using both baseline and follow-up data of the CRONICAS Cohort Study. Results. The prevalence of undiagnosed diabetes was 2.0% in the ENINBSC survey and 2.9% in the CRONICAS Cohort Study. Predictors of undiagnosed diabetes were age, diabetes in first-degree relatives, and waist circumference. Score values ranged from 0 to 4, with an optimal cutoff ≥2 and had a moderate performance when applied in the CRONICAS baseline data (AUC = 0.68; 95% CI: 0.62–0.73; sensitivity 70%; specificity 59%). When predicting incident cases, the AUC was 0.66 (95% CI: 0.61–0.71), with a sensitivity of 69% and specificity of 59%. Conclusions. A simple nonblood based risk score based on age, diabetes in first-degree relatives, and waist circumference can be used as a simple screening tool for undiagnosed and incident cases of diabetes in Peru.

Dudley, M., Sheen, P., Gilman, R., Ticona, E., Friedland, J., Kirwan, D., Caviedes, L., Rodriguez, R., Cabrera, L., Coronel, J., Grandjean, L., Moore, D., Evans, C., Huaroto, L., Chávez-Pérez, V., Zimic, M.

Am J Trop Med Hyg. 2016 Dec 7;95(6)

Abstract

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures.

© The American Society of Tropical Medicine and Hygiene.

McAtee, CL., Webman, R., Gilman, RH., Mejia, C., Bern, C., Apaza, S., Espetia, S., Pajuelo, M., Saito, M., Challappa, R., Soria, R., Ribera, JP., Lozano, D., Torrico, F.

Am J Trop Med Hyg. 2016 Jan;94(1)

Abstract

The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5-24 months without AGE were recruited from an urban hospital serving Bolivia’s third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P[8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P[4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus.

© The American Society of Tropical Medicine and Hygiene.

Wingfield, T., Tovar, MA., Huff, D., Boccia, D., Saunders, MJ., Datta, S., Montoya, R., Ramos, E., Lewis, JJ., Gilman, RH., Evans, C.

Clin Med (Lond). 2016 Dec;16(Suppl 6)

Abstract

Poverty drives tuberculosis (TB) rates but the approach to TB control has been disproportionately biomedical. In 2015, the World Health Organization’s End TB Strategy explicitly identified the need to address the social determinants of TB through socio-economic interventions. However, evidence concerning poverty reduction and cost mitigation strategies is limited. The research described in this article, based on the 2016 Royal College of Physicians Linacre Lecture, aimed to address this knowledge gap. The research was divided into two phases: the first phase was an analysis of a cohort study identifying TB-related costs of TB-affected households and creating a clinically relevant threshold above which those costs became catastrophic; the second was the design, implementation and evaluation of a household randomised controlled evaluation of socio-economic support to improve access to preventive therapy, increase TB cure, and mitigate the effects of catastrophic costs. The first phase showed TB remains a disease of people living in poverty – ‘free’ TB care was unaffordable for impoverished TB-affected households and incurring catastrophic costs was associated with as many adverse TB treatment outcomes (including death, failure of treatment, lost to follow-up and TB recurrence) as multidrug resistant (MDR) TB. The second phase showed that, in TB-affected households receiving socio-economic support, household contacts were more likely to start and adhere to TB preventive therapy, TB patients were more likely to be cured and households were less likely to incur catastrophic costs. In impoverished Peruvian shantytowns, poverty remains inextricably linked with TB and incurring catastrophic costs predicted adverse TB treatment outcome. A novel socio-economic support intervention increased TB preventive therapy uptake, improved TB treatment success and reduced catastrophic costs. The impact of the intervention on TB control is currently being evaluated by the Community Randomized Evaluation of a Socio-economic Intervention to Prevent TB (CRESIPT) study.

© Royal College of Physicians 2016. All rights reserved.

KEYWORDS:

End TB Strategy; TB; catastrophic costs; conditional cash transfers; poverty; social determinants; social protection; socio-economic support

Levy MZ, Small DS, Vilhena DA, Bowman NM, Kawai V, Cornejo del Carpio JG, Cordova-Benzaquen E, Gilman RH, Bern C, Plotkin JB.

PLoS Comput Biol. 2011 Sep;7(9):e1002146.

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease.

Bowman NM1, Kawai V, Gilman RH, Bocangel C, Galdos-Cardenas G, Cabrera L, Levy MZ, Cornejo del Carpio JG, Delgado F, Rosenthal L, Pinedo-Cancino VV, Steurer F, Seitz AE, Maguire JH, Bern C.

Am J Trop Med Hyg. 2011 Jan;84(1):85-90.

Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20-30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections.

Miranda JJ, Bernabe-Ortiz A, Stanojevic S, Malaga G, Gilman RH, Smeeth L.

PLoS One. 2011 Mar 25;6(3):e18069.

This study shows that the use of A1C as diagnostic criteria for type 2 diabetes mellitus identifies people of different characteristics than fasting glucose. In the PERU MIGRANT population using A1C to define diabetes tripled the prevalence; the increase was more marked among poorer and rural populations. More than half the newly diagnosed people with diabetes using A1C had normal fasting glucose.

Zevallos K, Vergara KC, Vergara A, Vidal C, Garcia HH, Evans CA.

Am J Trop Med Hyg. 2010 Aug;83(2):319-25.

The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species.

Zaman MJ, Loret de Mola C, Gilman RH, Smeeth L, Miranda JJ.

BMC Cardiovasc Disord. 2010 Oct 8;10:50.

Rural-to-urban migration in low- and middle-income countries causes an increase in individual cardiovascular risk. Cost-effective interventions at early stages of the natural history of coronary disease such as angina may stem an epidemic of premature coronary deaths in these countries. However, there are few data on the prevalence of angina in developing countries, whilst the understanding the aetiology of angina is complicated by the difficulty in measuring it across differing populations.

Platts-Mills, JA., Babji, S., Bodhidatta, L., Gratz, J., Haque, R., Havt, A., McCormick, BJ., McGrath, M., Olortegui, MP., Samie, A., Shakoor, S., Mondal, D., Lima, IF., Hariraju, D., Rayamajhi, BB., Qureshi, S., Kabir, F., Yori, PP., Mufamadi, B., Amour, C., Carreon, JD., Richard, SA., Lang, D., Bessong, P., Mduma, E., Ahmed, T., Lima, AA., Mason, CJ., Zaidi, AK., Bhutta, ZA., Kosek, M., Guerrant, RL., Gottlieb, M., Miller, M., Kang, G., Houpt, ER.; MAL-ED Network Investigators.

Lancet Glob Health. 2015 Sep;3(9)

Abstract

BACKGROUND:

Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.

METHODS:

We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through twice-weekly home visits by fieldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1-12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specific burdens of diarrhoea.

FINDINGS:

Between November 26, 2009, and February 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0-24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0-7·1), rotavirus (4·8%, 4·5-5·0), Campylobacter spp (3·5%, 0·4-6·3), astrovirus (2·7%, 2·2-3·1), and Cryptosporidium spp (2·0%, 1·3-2·6) exhibited the highest attributable burdens of diarrhoea in the first year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1-12·1), norovirus GII (5·4%, 2·1-7·8), rotavirus (4·9%, 4·4-5·2), astrovirus (4·2%, 3·5-4·7), and Shigella spp (4·0%, 3·6-4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fifth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII.

INTERPRETATION:

There was substantial heterogeneity in pathogen-specific burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These findings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the effect of such interventions on total diarrhoeal incidence at the community level might be limited.

Copyright © 2015 Platts-Mills et al. Open access article published under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.

Kalter HD, Gilman RH, Moulton LH, Cullotta AR, Cabrera L, Velapatiño B.

Am J Trop Med Hyg. 2010 May;82(5):879-88.

Few studies have examined the influence of individual-, household-, and community-scale risk factors on carriage of resistant commensal bacteria. We determined children’s medical, agricultural, and environmental exposures by household, pharmacy, and health facility surveys and Escherichia coli cultures of children, mothers’ hands, household animals, and market chickens in Peru.

Ramos E, Schumacher SG, Siedner M, Herrera B, Quino W, Alvarado J, Montoya R, Grandjean L, Martin L, Sherman JM, Gilman RH, Evans CA.

Am J Trop Med Hyg. 2010 Oct;83(4):896-901.

Optimal tuberculosis testing usually involves sputum centrifugation followed by broth culture. However, centrifuges are biohazardous and scarce in the resource-limited settings where most tuberculosis occurs. To optimize tuberculosis testing for these settings, centrifugation of 111 decontaminated sputum samples was compared with syringe-aspiration through polycarbonate membrane-filters that were then cultured in broth. This combination of filtration and colorimetric growth-detection gave similar results to sputum centrifugation followed by culture microscopy regarding mean colony counts (43 versus 48; P = 0.6), contamination rates (0.9% versus 1.8%; P = 0.3), and sensitivity (94% versus 95%; P = 0.7), suggesting equivalency of the two methods. By obviating centrifugation and repeated microscopic screening of cultures, this approach may constitute a more appropriate technology for rapid and sensitive tuberculosis diagnosis in basic laboratories.

Liang L, Leng D, Burk C, Nakajima-Sasaki R, Kayala MA, Atluri VL, Pablo J, Unal B, Ficht TA, Gotuzzo E, Saito M, Morrow WJ, Liang X, Baldi P, Gilman RH, Vinetz JM, Tsolis RM, Felgner PL.

PLoS Negl Trop Dis. 2010 May 4;4(5):e673.

Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients.

Kersulyte D, Kalia A, Gilman RH, Mendez M, Herrera P, Cabrera L, Velapatiño B, Balqui J, Paredes Puente de la Vega F, Rodriguez Ulloa CA, Cok J, Hooper CC, Dailide G, Tamma S, Berg DE.

PLoS One. 2010 Nov 29;5(11):e15076.

The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes.

Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry.

Onifade DA, Bayer AM, Montoya R, Haro M, Alva J, Franco J, Sosa R, Valiente B, Valera E, Ford CM, Acosta CD, Evans CA.

BMC Public Health. 2010 Jun 29;10:381.

This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns.

We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health.

Gavidia CM, Gonzalez AE, Barron EA, Ninaquispe B, Llamosas M, Verastegui MR, Robinson C, Gilman RH.

PLoS Negl Trop Dis. 2010 Feb 23;4(2):e616.

Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep. We demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE. Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.

Ong, CW., Elkington, PT., Brilha, S., Ugarte,-Gil C., Tome-Esteban, MT., Tezera, LB., Pabisiak, PJ., Moores, RC., Sathyamoorthy, T., Patel, V., Gilman, RH., Porter, JC., Friedland, JS..

PLoS Pathog. 2015 May 21;11(5)

Abstract

Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.

Benziger, CP., Bernabé-Ortiz, A., Gilman, RH., Checkley, W., Smeeth, L., Málaga, G., Miranda, JJ.; CRONICAS Cohort Study group.

PLoS One. 2015 Nov 23;10(11)

Abstract

OBJECTIVE:

We aimed to characterize metabolic status by body mass index (BMI) status.

METHODS:

The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru’s capital, costal urban, highly urbanized), urban and rural Puno (both high-altitude), and Tumbes (costal semirural). Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2), and as metabolically healthy (0-1 metabolic abnormality) or metabolically unhealthy (≥2 abnormalities). Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance.

RESULTS:

A total of 3088 (age 55.6±12.6 years, 51.3% females) had all measurements. Of these, 890 (28.8%), 1361 (44.1%) and 837 (27.1%) were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001). Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile.

CONCLUSIONS:

Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose.

Moreno, M., Saavedra, MP., Bickersmith, SA., Lainhart, W., Tong, C., Alava, F., Vinetz, JM., Conn, JE..

Malar J. 2015 Jul 30;14

Abstract

BACKGROUND:

Malaria transmission in the peri-Iquitos region of Amazonian Peru has been designated as seasonal and hypo-endemic with recently described hyper-endemic hotspots. Despite relatively recent distribution of long-lasting insecticidal bed nets (LLINs), malaria in Amazonian Peru persists and increased substantially in 2014 compared to previous years. Anopheles darlingi, identified as the main malaria vector, is known for its variable behaviour depending on locality and environment.

METHODS:

To evaluate vector biology metrics in relation to seasonality and malaria transmission, mosquito collections were carried out in three localities in the peri-Iquitos region, Loreto, Peru in 2011-2012. Human landing catch (HLC) collection method, Shannon (SHA) and CDC trap types were compared for effectiveness in a neotropical setting. Abundance, human biting rate and entomological inoculation rate (EIR) were measured to provide an updated view of transmission patterns post-LLIN distribution.

RESULTS:

HLC collected significantly more anopheline mosquitoes than SHA and CDC light traps. Anopheles darlingi was the most prevalent species in all three villages (84% overall). Biting patterns varied depending on trap type, season and village. EIR varied temporally (monthly) and spatially and the highest (2.52) occurred during the 2012 malaria outbreak in Cahuide. Unexpectedly there was a high infection rate (1.47 and 1.75) outside the normal malaria transmission season, coincident with a second local outbreak in Cahuide. The first identification of Anopheles dunhami and Anopheles oswaldoi C in Peru, using molecular markers, is also reported in this study.

CONCLUSION:

These data underscore the importance of HLC as the most meaningful collection method for measuring vector biology indices in this region. The highest monthly EIR provides additional evidence of seasonal transmission in riverine localities correlated with high river levels, and An. darlingi as the only contributor to transmission. The trend of an increase in outdoor-biting together with early-evening infected mosquitoes may undermine the effectiveness of LLINs as a primary malaria intervention.

Denney, JA., Capanni, F., Herrera, P., Dulanto, A., Roldan, R., Paz, E., Jaymez, AA., Chirinos, EE., Portugal, J., Quispe, R., Brower, RG., Checkley, W.; INTENSIVOS Cohort Study.

BMJ Open. 2015 Jan 16;5(1)

Abstract

INTRODUCTION:

Mechanical ventilation is a cornerstone in the management of critically ill patients worldwide; however, less is known about the clinical management of mechanically ventilated patients in low and middle income countries where limitation of resources including equipment, staff and access to medical information may play an important role in defining patient-centred outcomes. We present the design of a prospective, longitudinal study of mechanically ventilated patients in Peru that aims to describe a large cohort of mechanically ventilated patients and identify practices that, if modified, could result in improved patient-centred outcomes and lower costs.

METHODS AND ANALYSIS:

Five Peruvian intensive care units (ICUs) and the Medical ICU at the Johns Hopkins Hospital were selected for this study. Eligible patients were those who underwent at least 24 h of invasive mechanical ventilation within the first 48 h of admission into the ICU. Information on ventilator settings, clinical management and treatment were collected daily for up to 28 days or until the patient was discharged from the unit. Vital status was assessed at 90 days post enrolment. A subset of participants who survived until hospital discharge were asked to participate in an ancillary study to assess vital status, and physical and mental health at 6, 12, 24 and 60 months after hospitalisation, Primary outcomes include 90-day mortality, time on mechanical ventilation, hospital and ICU lengths of stay, and prevalence of acute respiratory distress syndrome. In subsequent analyses, we aim to identify interventions and standardised care strategies that can be tailored to resource-limited settings and that result in improved patient-centred outcomes and lower costs.

ETHICS AND DISSEMINATION:

We obtained ethics approval from each of the four participating hospitals in Lima, Peru, and at the Johns Hopkins School of Medicine, Baltimore, USA. Results will be disseminated as several separate publications in different international journals.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

KEYWORDS:

EPIDEMIOLOGY

Ballard, SB., Reaves, EJ., Luna, CG., Silva, ME., Rocha, C., Heitzinger, K., Saito, M., Apaza, S., Espetia, S., Blazes, DL., Tilley, DH., Guzmán, RC., Gilman, RH., Bausch, DG.

PLoS One. 2015 Jul 10;10(7)

Abstract

BACKGROUND:

Successful vaccination strategies against norovirus will require understanding the burden of disease and relevant genotypes in populations. However, few data are available from cohort studies of adults living in low- and middle-income countries (LMIC).

MATERIALS AND METHODS:

We conducted a nested case-control study within a Peruvian military cohort to characterize the burden of norovirus infection, predominant genotypes, and associated symptoms from 2004 through 2011. Randomly selected case and control stools were tested for norovirus, bacteria, and parasites. The odds ratio of the association between norovirus infection and diarrhea was estimated using multiple logistic regression and co-infection adjusted attributable fractions were calculated.

RESULTS:

Of the 3,818 cohort study participants, 624 developed diarrhea. Overall and norovirus-associated diarrhea incidence rates were 42.3 and 6.0 per 100 person-years, respectively. The most prevalent norovirus genogroup was GII (72.5%, 29/40), which was associated with diarrhea (AOR 3.4, 95% CI: 1.3-8.7, P = 0.012). The co-infection adjusted GII attributable fraction was 6.4%.

DISCUSSION:

Norovirus was a frequent cause of diarrhea in an adult population followed longitudinally in an LMIC setting. Vaccine strategies should consider targeting adults in endemic settings and special populations that could serve as community transmission sources.

Patil, CL., Turab, A., Ambikapathi, R., Nesamvuni, C., Chandyo, RK., Bose, A., Islam, MM., Ahmed, AM., Olortegui, MP., de Moraes, ML., Caulfield, LE.; MAL-ED network.

J Health Popul Nutr. 2015 May 1;34

Abstract

We report the infant feeding experiences in the first month of life for 2,053 infants participating in «Malnutrition and Enteric Infections: Consequences for Child Health and Development» (MAL-ED). Eight sites (in Bangladesh, India, Nepal, Pakistan, Brazil, Peru, South Africa, Tanzania), each followed a cohort of children from birth (by day 17), collecting detailed information on infant feeding practices, diet and illness episodes. Mothers were queried twice weekly regarding health status, breastfeeding and the introduction (or no) of non-breast milk liquids and foods. Here, our goal is to describe the early infant feeding practices in the cohort and evaluate factors associated with termination of exclusive breastfeeding in the first month of life. With data from enrollment to a visit at 28-33 days of life, we characterized exclusive, predominant or partial breastfeeding (using a median of 6-9 visits per child across the sites). Only 6 of 2,053 infants were never breastfed. By one month, the prevalences of exclusive breastfeeding were < 60% in 6 of 8 sites, and of partial breastfeeding (or no) were > 20% in 6 of 8 sites. Logistic regression revealed that prelacteal feeding (given to 4-63% of infants) increased the likelihood of partial breastfeeding (Odds Ratio (OR): 1.48 (95% confidence interval (CI): 1.04, 2.10), as did the withholding of colostrum (2-16% of infants) (OR: 1.63:1.01, 2.62), and being a first-time mother (OR: 1.38:1.10, 1.75). Our results reveal diversity across these sites, but an overall trend of early transition away from exclusive breastfeeding in the first month of life. Interventions which introduce or reinforce the WHO/UNICEF Ten Steps for Successful Breastfeeding are needed in these sites to improve breastfeeding initiation, to reinforce exclusive breastfeeding and delay introduction of non-breast milk foods and/or liquids.

Quispe, R., Bazo-Alvarez, J., Burroughs, M., Poterico, J., Gilman, R, Checkley, W., Bernabé-Ortiz, A., Huffman, M., Miranda, J.

J Am Heart Assoc. 2015 Aug; 4(8)

Background

Short-term risk assessment tools for prediction of cardiovascular disease events are widely recommended in clinical practice and are used largely for single time-point estimations; however, persons with low predicted short-term risk may have higher risks across longer time horizons.

Methods and Results

We estimated short-term and lifetime cardiovascular disease risk in a pooled population from 2 studies of Peruvian populations. Short-term risk was estimated using the atherosclerotic cardiovascular disease Pooled Cohort Risk Equations. Lifetime risk was evaluated using the algorithm derived from the Framingham Heart Study cohort. Using previously published thresholds, participants were classified into 3 categories: low short-term and low lifetime risk, low short-term and high lifetime risk, and high short-term predicted risk. We also compared the distribution of these risk profiles across educational level, wealth index, and place of residence. We included 2844 participants (50% men, mean age 55.9 years [SD 10.2 years]) in the analysis. Approximately 1 of every 3 participants (34% [95% CI 33 to 36]) had a high short-term estimated cardiovascular disease risk. Among those with a low short-term predicted risk, more than half (54% [95% CI 52 to 56]) had a high lifetime predicted risk. Short-term and lifetime predicted risks were higher for participants with lower versus higher wealth indexes and educational levels and for those living in urban versus rural areas (P<0.01). These results were consistent by sex.

Conclusions

These findings highlight potential shortcomings of using short-term risk tools for primary prevention strategies because a substantial proportion of Peruvian adults were classified as low short-term risk but high lifetime risk. Vulnerable adults, such as those from low socioeconomic status and those living in urban areas, may need greater attention regarding cardiovascular preventive strategies.

Keywords: cardiovascular risk, lifetime cardiovascular risk, Pooled Cohort Risk Equations, risk estimation tools, short-term cardiovascular risk

Background

Short-term risk assessment tools for prediction of cardiovascular disease events are widely recommended in clinical practice and are used largely for single time-point estimations; however, persons with low predicted short-term risk may have higher risks across longer time horizons.

Methods and Results

We estimated short-term and lifetime cardiovascular disease risk in a pooled population from 2 studies of Peruvian populations. Short-term risk was estimated using the atherosclerotic cardiovascular disease Pooled Cohort Risk Equations. Lifetime risk was evaluated using the algorithm derived from the Framingham Heart Study cohort. Using previously published thresholds, participants were classified into 3 categories: low short-term and low lifetime risk, low short-term and high lifetime risk, and high short-term predicted risk. We also compared the distribution of these risk profiles across educational level, wealth index, and place of residence. We included 2844 participants (50% men, mean age 55.9 years [SD 10.2 years]) in the analysis. Approximately 1 of every 3 participants (34% [95% CI 33 to 36]) had a high short-term estimated cardiovascular disease risk. Among those with a low short-term predicted risk, more than half (54% [95% CI 52 to 56]) had a high lifetime predicted risk. Short-term and lifetime predicted risks were higher for participants with lower versus higher wealth indexes and educational levels and for those living in urban versus rural areas (P<0.01). These results were consistent by sex.

Conclusions

These findings highlight potential shortcomings of using short-term risk tools for primary prevention strategies because a substantial proportion of Peruvian adults were classified as low short-term risk but high lifetime risk. Vulnerable adults, such as those from low socioeconomic status and those living in urban areas, may need greater attention regarding cardiovascular preventive strategies.

Keywords: cardiovascular risk, lifetime cardiovascular risk, Pooled Cohort Risk Equations, risk estimation tools, short-term cardiovascular risk

Rothstein JD, Leontsini E, Olortegui MP, Yori PP, Surkan PJ, Kosek M.

Am J Trop Med Hyg. 2015 Sep;93(3)

Abstract

The gap between the efficacy and the effectiveness of household water treatment in reducing diarrhea-related morbidity indicates the need for a better understanding of the determinants of long-term behavior change. To explore the barriers to drinking water chlorination in the Peruvian Amazon, where diarrhea is endemic among under-5 children, we conducted qualitative research with 23 caregivers from peri-urban communities of Iquitos, Peru. Our inquiry drew on the Transtheoretical Model of behavior change and the Integrated Behavioral Model for Water, Sanitation, and Hygiene to identify the most relevant contextual, psychosocial, and technological determinants of initial action and long-term adoption of chlorination. Our findings suggest that the decision to try out this practice resulted from the combined effect of knowledge of chlorination benefits and product availability and affordability. Progress from action to adoption was influenced by caretakers’ understanding of dosage, the packaging of chlorine products, knowledge and skills for multipurpose laundry bleach, the taste of treated water, and reinforcement. This analysis suggests that a focus on these determinants and the household domain may help to improve the sustainability of future intervention efforts.

Wingfield, T., Boccia, D., Tovar, MA., Huff, D., Montoya, R., Lewis, JJ., Gilman, RH., Evans, CA..

BMC Public Health. 2015 Aug 21;15

Abstract

BACKGROUND:

Cash transfers are key interventions in the World Health Organisation’s post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

METHODS:

Newly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings). To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders.

RESULTS:

Over 7 months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %) were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved optimally and 79/964 (8 %) sub-optimally. Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer; and the project being perceived as patient-centred and empowering. Challenges included: participant confidence being eroded through cash transfer delays, hidden account-charges and stigma; access to the initial bank-provider being limited; and conditions requiring participation of all TB-affected household members (e.g. community meetings) being hard to achieve. Refinements were made to improve project acceptability and future impact: the initial bank-provider was changed; conditional and unconditional cash transfers were combined; cash transfer sums were increased to a locally-appropriate, evidence-based amount; and cash transfer size varied according to patient household size to maximally reduce mitigation of TB-related costs and be more responsive to household needs.

CONCLUSIONS:

A novel TB-specific socioeconomic intervention including conditional cash transfers has been designed, implemented, refined and is ready for impact assessment, including by the CRESIPT project. The lessons learnt during this research will inform policy-makers and decision-makers for future implementation of related interventions.

Francis, ER., Kuo, CC., Bernabe-Ortiz, A., Nessel, L., Gilman, RH., Checkley, W., Miranda, JJ., Feldman, HI., CRONICAS Cohort Study Group.

BMC Nephrol. 2015 Jul 24;16

Abstract

BACKGROUND:

The silent progression of chronic kidney diseases (CKD) and its association with other chronic diseases, and high treatment costs make it a great public health concern worldwide. The population burden of CKD in Peru has yet to be fully described.

METHODS:

We completed a cross sectional study of CKD prevalence among 404 participants (total study population median age 54.8 years, 50.2 % male) from two sites, highly-urbanized Lima and less urbanized Tumbes, who were enrolled in the population-based CRONICAS Cohort Study of cardiopulmonary health in Peru. Factors potentially associated with the presence of CKD were explored using Poisson regression, a statistical methodology used to determine prevalence ratios.

RESULTS:

In total, 68 participants (16.8 %, 95 % CI 13.5-20.9 %) met criteria for CKD: 60 (14.9%) with proteinuria, four (1%) with eGFR < 60 mL/min/1.73 m2 , and four (1%) with both. CKD prevalence was higher in Lima (20.7 %, 95 % CI 15.8-27.1) than Tumbes (12.9 %, 95 % CI 9.0-18.5). Among participants with CKD, the prevalence of diabetes and hypertension was 19.1 % and 42.7 %, respectively. After multivariable adjustment, CKD was associated with older age, female sex, greater wealth tertile (although all wealth strata were below the poverty line), residence in Lima, and presence of diabetes and hypertension.

CONCLUSIONS:

The high prevalence rates of CKD identified in Lima and Tumbes are similar to estimates from high-income settings. These findings highlight the need to identify occult CKD and implement strategies to prevent disease progression and secondary morbidity.

Hidron AI, Gilman RH, Justiniano J, Blackstock AJ, Lafuente C, Selum W, Calderon M, Verastegui M, Ferrufino L, Valencia E, Tornheim JA, O’Neal S, Comer R, Galdos-Cardenas G, Bern C; Chagas Disease Working Group in Peru and Bolivia.

PLoS Negl Trop Dis. 2010 May 18;4(5):e688.

Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common. The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz, Bolivia. Data included risk factors for T. cruzi infection, medical history, physical examination, electrocardiogram, echocardiogram, and contact 9 months after initial data collection to ascertain mortality.

Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease.

Ganoza CA, Matthias MA, Saito M, Cespedes M, Gotuzzo E, Vinetz JM.

PLoS Negl Trop Dis. 2010 Feb 23;4(2):e612.

Renal carriage and shedding of leptospires is characteristic of carrier or maintenance animal hosts. Sporadic reports indicate that after infection, humans may excrete leptospires for extended periods. We hypothesized that, like mammalian reservoir hosts, humans develop asymptomatic leptospiruria in settings of high disease transmission such as the Peruvian Amazon.

Asymptomatic renal colonization of leptospires in a region of high disease transmission is common, including among people without serological or clinical evidence of recent infection. Both pathogenic and intermediate Leptospira can persist as renal colonization in humans. The pathogenic significance of this finding remains to be explored but is of fundamental biological significance.

Underhill, LJ., Bose, S., Williams, DL., Romero, KM., Malpartida, G., Breysse, PN., Klasen, EM., Combe, JM., Checkley, W., Hansel, NN..

Int J Environ Res Public Health. 2015 Oct 26;12(10)

Abstract

The influence of traffic-related air pollution on indoor residential exposure is not well characterized in homes with high natural ventilation in low-income countries. Additionally, domestic allergen exposure is unknown in such populations. We conducted a pilot study of 25 homes in peri-urban Lima, Peru to estimate the effects of roadway proximity and season on residential concentrations. Indoor and outdoor concentrations of particulate matter (PM₂.₅), nitrogen dioxide (NO₂), and black carbon (BC) were measured during two seasons, and allergens were measured in bedroom dust. Allergen levels were highest for dust mite and mouse allergens, with concentrations above clinically relevant thresholds in over a quarter and half of all homes, respectively. Mean indoor and outdoor pollutant concentrations were similar (PM₂.₅: 20.0 vs. 16.9 μg/m³, BC: 7.6 vs. 8.1 μg/m³, NO₂: 7.3 vs. 7.5 ppb), and tended to be higher in the summer compared to the winter. Road proximity was significantly correlated with overall concentrations of outdoor PM₂.₅ (rs = -0.42, p = 0.01) and NO₂ (rs = -0.36, p = 0.03), and outdoor BC concentrations in the winter (rs = -0.51, p = 0.03). Our results suggest that outdoor-sourced pollutants significantly influence indoor air quality in peri-urban Peruvian communities, and homes closer to roadways are particularly vulnerable.

KEYWORDS:

air pollution; allergens; asthma; black carbon; childhood; indoor environment; low-income and vulnerable populations; nitrogen dioxide; particulate matter; traffic

Saavedra-Garcia, L., Bernabe-Ortiz, A., Gilman, RH., Diez-Canseco, F., Cárdenas, MK., Sacksteder, KA., Miranda, JJ.

PLoS One. 2015 Jul 30;10(7)

In resourced-constrained settings, daily cooking practices are still the norm. Replacing sodium in regular salt to produce potassium-enriched salts are potential alternative routes to reduce sodium intake, paired with the benefit associated with potassium intake. This change would likely have effects on palatability and taste of prepared foods, yet a threshold to discriminate sensorial changes can be determined. The main goal of this study was to assess if the use of potassium-enriched salt substitutes lead to perceived differences in taste utilizing a sensory discrimination test.

Oberhelman, RA., Soto-Castellares, G., Gilman, RH., Castillo, ME., Kolevic, L., Delpino, T., Saito, M., Salazar-Lindo, E., Negron, E., Montenegro, S., Laguna-Torres, VA., Maurtua-Neumann, P., Datta, S., Evans, CA.

PLoS One. 2015 Apr 30;10(4)

Diagnosing tuberculosis in children is challenging because specimens are difficult to obtain and contain low tuberculosis concentrations, especially with HIV-coinfection. Few studies included well-controls so test specificities are poorly defined. We studied tuberculosis diagnosis in 525 children with and without HIV-infection.

Tuero, I., Palma, S., Cabeza, F., Saleemi, S., Rodriguez, S., Gonzales, I., Mayta, H., Mahanty, S., Garcia, H. H., Gilman, R. H., Cysticercosis Working Group in Perú.

PLoS Negl Trop Dis. 2015 Oct 27;9(10)

The ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.

Escombe AR, Moore DA, Gilman RH, Navincopa M, Ticona E, Mitchell B, Noakes C, Martínez C, Sheen P, Ramirez R, Quino W, Gonzalez A, Friedland JS, Evans CA.

PLoS Med. 2009 Mar 17;6(3):e43.

Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings.

Miranda JJ, Gilman RH, García HH, Smeeth L.

BMC Cardiovasc Disord. 2009 Jun 8;9:23.

The PERU MIGRANT (PEru’s Rural to Urban MIGRANTs) study was designed to investigate the magnitude of differences between rural-to-urban migrant and non-migrant groups in specific CVD risk factors. For this, three groups were selected: Rural, people who have always have lived in a rural environment; Rural-urban, people who migrated from rural to urban areas; and, Urban, people who have always lived in a urban environment. This paper describes the PERU MIGRANT study design together with a critical analysis of the potential for bias and confounding in migrant studies, and strategies for reducing these problems. A discussion of the potential advantages provided by the case of migration in Peru to the field of migration and health is also presented.

Lescano AG, Garcia HH, Gilman RH, Gavidia CM, Tsang V, Rodriguez S, Moulton LH, Villaran MV, Montano SM, Gonzalez AE, Cysticercosis Working Group in Peru.

PLoS Negl Trop Dis 3(1): e371.

Cysticercosis is a parasitic disease caused by the tapeworm Taenia solium, common in areas with limited sanitation or with migration from these populations. The adult parasite is hosted in the human intestine and releases large numbers of eggs with the feces. Human beings sometimes ingest eggs due to poor hygiene, and then eggs sometimes lodge on the brain and after a few years can cause intense headaches and seizures. During a study in seven rural communities in Peru, individuals exposed to T. solium eggs were often tightly clustered at the homes or immediate surrounding of the carriers of the adult parasite. However, no aggregation of cases of seizures was found near carriers. It appears that seizures do not cluster around carriers because several years pass between exposure to T. solium eggs and the onset of seizures. During these years the adult parasite has probably died or people had moved within or even outside their communities. Therefore, only a partial understanding of the epidemiology of cysticercosis is gained by studying seizures cases.

Gálvez-Buccollini JA, DeLea S, Herrera PM, Gilman RH, Paz-Soldan V.

BMC Public Health. 2009 Jan 19;9:23. doi: 10.1186/1471-2458-9-23.

The study participants were 393 men and 400 women between 18 and 30 years of age, from a shantytown in Lima, Peru. Among men, age of sexual debut was lower, number of lifetime sexual partners was higher, and there were higher risk types of sexual partners, compared to women. Though consistent condom use with casual partners was low in both groups, reported condom use at last intercourse was higher among men than women. Also, a lifetime history of illicit drug consumption decreased the probability of condom use at last sexual intercourse by half. Among men, the use of illicit drugs doubled the probability of intercourse with a casual partner during the last year and tripled the probability of reported STI symptoms.

Vittor AY, Pan W, Gilman RH, Tielsch J, Glass G, Shields T, Sánchez-Lozano W, Pinedo VV, Salas-Cobos E, Flores S, Patz JA.

Am J Trop Med Hyg. 2009 Jul;81(1):5-12.

This study examined the larval breeding habitat of a major South American malaria vector, Anopheles darlingi, in areas with varying degrees of ecologic alteration in the Peruvian Amazon. Water bodies were repeatedly sampled across 112 km of transects along the Iquitos-Nauta road in ecologically varied areas. Field data and satellite imagery were used to determine the landscape composition surrounding each site. Seventeen species of Anopheles larvae were collected. Anopheles darlingi larvae were present in 87 of 844 sites (10.3%). Sites with A. darlingi larvae had an average of 24.1% forest cover, compared with 41.0% for sites without A. darlingi (P < 0.0001). Multivariate analysis identified seasonality, algae, water body size, presence of human populations, and the amount of forest and secondary growth as significant determinants of A. darlingi presence. We conclude that deforestation and associated ecologic alterations are conducive to A. darlingi larval presence, and thereby increase malaria risk.

Gehmert S, Velapatiño B, Herrera P, Balqui J, Santivañez L, Cok J, Vargas G, Combe J, Passaro DJ, Wen S, Meyer F, Berg DE, Gilman RH.

Am J Trop Med Hyg. 2009 Nov;81(5):804-10.

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru.

Kersulyte D, Lee W, Subramaniam D, Anant S, Herrera P, Cabrera L, Balqui J, Barabas O, Kalia A, Gilman RH, Berg DE.

PLoSONE 4(9): e6859.

Genes present in only certain strains of a bacterial species can strongly affect cellular phenotypes and evolutionary potentials. One segment that seemed particularly rich in strain-specific genes was found by comparing the first two sequenced Helicobacter pylori genomes (strains 26695 and J99) and was named a “plasticity zone”.

Gálvez-Buccollini JA, Paz-Soldán VA, Herrera PM, DeLea S, Gilman RH.

Rev Panam Salud Publica. 2009 Jun;25(6):499-505.

This study aimed to estimate the effect of sex-related alcohol expectancies (SRAE) on hazardous drinking prevalence and examine gender differences in reporting SRAE. Trained research assistants administered part of a questionnaire to 393 men and 400 women between 18 and 30 years old from a peri-urban shantytown in Lima, Peru. The remaining questions were self-administered. Two measuring instruments-one testing for hazardous drinking and one for SRAE-were used. Multivariate data analysis was performed using logistic regression.In conclusion, in a shantytown in Lima, SRAE is associated with hazardous drinking among men, but not among women, and reporting of SRAE differs by gender.

Ford C, Bayer A, Gilman RH, Onifade D, Acosta C, Cabrera L, Vidal C, Evans CA

Am J Trop Med Hyg. 2009 Dec; 81(6): 1097–1102.

This study aimed to determine the psychosocial factors associated with delayed test-seeking among tuberculosis patients. The duration of symptoms before seeking medical care was assessed by interview for 108 newly diagnosed pulmonary tuberculosis patients in the city of Iquitos in the Peruvian Amazon, which has high tuberculosis incidence. Beliefs associated with test-seeking behavior and delay was assessed in these patients. The median delay from symptom onset to seeking diagnostic testing was 61 days (inter-quartile range 30–91 days). The belief that tuberculosis is curable was associated with a 100% longer test-seeking delay; the perception that tuberculosis was common was associated with a 57% longer delay; male gender was associated with a 48% longer delay; and education less than complete secondary schooling was associated with a 44% longer delay. In conclusion, current health promotion activities that emphasize tuberculosis curability and high prevalence may paradoxically increase test-seeking delay and therefore require prospective evaluation.

Bayer AM, Hunter GC, Gilman RH, Cornejo Del Carpio JG, Naquira C, Bern C, Levy MZ.

PLoS Negl Trop Dis. 2009 Dec 15;3(12)

Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission. This was a qualitative study that employed focus group discussions and in-depth interviews. Five focus groups and 50 in-depth interviews were carried out with 94 community members from three shantytowns and two traditional towns near Arequipa, Peru. Focus groups utilized participatory methodologies to explore the community’s mobility patterns and the historical and current presence of triatomine vectors. In-depth interviews based on event history calendars explored participants’ migration patterns and experience with Chagas disease and vectors.

Escombe AR, Moore DA, Gilman RH, Pan W, Navincopa M, Ticona E, Martínez C, Caviedes L, Sheen P, Gonzalez A, Noakes CJ, Friedland JS, Evans CA.

PLoS Med. 2008 Sep 30;5(9):e188.

The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB. A small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.

Fitzwater S, Calderon M, Lafuente C, Galdos-Cardenas G, Ferrufino L, Verastegui M, Gilman RH, Bern C; Chagas Disease Working Group in Peru and Bolivia.

Am J Trop Med Hyg. 2008 Nov;79(5):768-70.

Trypanosoma cruzi polymerase chain reaction (PCR) is widely used, but sensitivity varies widely. We compared PCR using 121/122 primers targeting kinetoplast minicircle DNA in whole blood, buffy coat, and clot from Bolivian women. Sensitivity was significantly higher in clot (60.1%) than buffy coat (46.5%) or whole blood (40%). The use of clot could simplify specimen collection while improving sensitivity.

Donroe J, Tincopa M, Gilman RH, Brugge D, Moore DA.

PLoS One. 2008 Sep 10;3(9):e3166.

This research investigated personal and environmental risk factors for child pedestrian RTIs relevant to an urban, developing world setting. This is a case control study of personal and environmental risk factors for child pedestrian RTIs in San Juan de Miraflores, Lima, Perú. The analysis of personal risk factors included 100 cases of serious pedestrian RTIs and 200 age and gender matched controls. Demographic, socioeconomic, and injury data were collected. The environmental risk factor study evaluated vehicle and pedestrian movement and infrastructure at the sites in which 40 of the above case RTIs occurred and 80 control sites. Reducing traffic volumes and speeds, limiting the number of street vendors on a given stretch of road, and improving lane demarcation should be evaluated as components of child pedestrian RTI interventions in poorer countries.

Watts, N., Pajuelo, m., Clark, t., Loader, M., Verastegui, M., Sterling, C., Friedland, J., Garcia, H., Gilman, R., and for the Cysticercosis Working Group in Peru

PLoS One. 2014; 9(12)

T. solium tapeworm infection is endemic in much of Peru, but there are scarce data on the prevalence in many rural highland communities where it is likely to be hyper-endemic. Peace Corps Volunteers live and work in these communities; however, to our knowledge, they have not been used to facilitate public health research.

This study recorded high T. solium tapeworm prevalence, and identified hyper-endemic rural communities. It demonstrates that synergy between researchers and Peace Corps Volunteers can be an effective means to conducting large-scale, community-based studies in remote areas of Peru.

Martin, DL., Marks, M., Galdos-Cardenas, G., Gilman, RH., Goodhew, B., Ferrufino, L., Halperin, A., Sanchez, G., Verastegui, M., Escalante, P., Naquira, C., Levy, MZ., Bern, C..

Am J Trop Med Hyg. 2014 Jun;90(6)

Abstract

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major cause of morbidity and mortality in Central and South America. Geographic variations in the sensitivity of serologic diagnostic assays to T. cruzi may reflect differences in T. cruzi exposure. We measured parasite-specific T-cell responses among seropositive individuals in two populations from South America with widely varying antibody titers against T. cruzi. Antibody titers among seropositive individuals were significantly lower in Arequipa, Peru compared with Santa Cruz, Bolivia. Similarly, the proportion of seropositive individuals with positive T-cell responses was lower in Peru than Bolivia, resulting in overall lower frequencies of interferon-γ (IFNγ)-secreting cells from Peruvian samples. However, the magnitude of the IFNγ response was similar among the IFNγ responders in both locations. These data indicate that immunological discrepancies based on geographic region are reflected in T-cell responses as well as antibody responses.

© The American Society of Tropical Medicine and Hygiene.

Psaki, S., Seidman, J., Miller, M., Gottlieb, M., Bhutta, Z., Ahmed, T., Ahmed, A., Bessong, P., John, SM., Kang, G., Kosek, M., Lima, A., Shrestha, P., Svensen, E., Checkley, W.; MAL-ED Network Investigators.

Popul Health Metr. 2014 Mar 21;12(1)

Abstract

BACKGROUND:

There is no standardized approach to comparing socioeconomic status (SES) across multiple sites in epidemiological studies. This is particularly problematic when cross-country comparisons are of interest. We sought to develop a simple measure of SES that would perform well across diverse, resource-limited settings.

METHODS:

A cross-sectional study was conducted with 800 children aged 24 to 60 months across eight resource-limited settings. Parents were asked to respond to a household SES questionnaire, and the height of each child was measured. A statistical analysis was done in two phases. First, the best approach for selecting and weighting household assets as a proxy for wealth was identified. We compared four approaches to measuring wealth: maternal education, principal components analysis, Multidimensional Poverty Index, and a novel variable selection approach based on the use of random forests. Second, the selected wealth measure was combined with other relevant variables to form a more complete measure of household SES. We used child height-for-age Z-score (HAZ) as the outcome of interest.

RESULTS:

Mean age of study children was 41 months, 52% were boys, and 42% were stunted. Using cross-validation, we found that random forests yielded the lowest prediction error when selecting assets as a measure of household wealth. The final SES index included access to improved water and sanitation, eight selected assets, maternal education, and household income (the WAMI index). A 25% difference in the WAMI index was positively associated with a difference of 0.38 standard deviations in HAZ (95% CI 0.22 to 0.55).

CONCLUSIONS:

Statistical learning methods such as random forests provide an alternative to principal components analysis in the development of SES scores. Results from this multicountry study demonstrate the validity of a simplified SES index. With further validation, this simplified index may provide a standard approach for SES adjustment across resource-limited settings.

Chavez, M., Shams, N., Ellington, L., Naithani, N., Gilman, R., Steinhoff, M., Santosham, M., Black, R., Price, C., Gross, M., Checkley, W.

Respir Res. 2014 Apr 23

Abstract

BACKGROUND:

Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults.

METHODS:

We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I2 statistics.

RESULTS:

Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz micro-convex transducer and one used a 5-9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99).

CONCLUSIONS:

Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.

Bernabe-Ortiz, A., Diez-Canseco, F., Gilman, R., Cárdenas, M., Sacksteder, K., Miranda, J.

Trials. 2014 Mar 25;15:93

Abstract

BACKGROUND:

Controlling hypertension rates and maintaining normal blood pressure, particularly in resource-constrained settings, represent ongoing challenges of effective and affordable implementation in health care. One of the strategies being largely advocated to improve high blood pressure calls for salt reduction strategies. This study aims to estimate the impact of a population-level intervention based on sodium reduction and potassium increase – in practice, introducing a low-sodium, high-potassium salt substitute – on adult blood pressure levels.

METHODS/DESIGN:

The proposed implementation research study includes two components: Phase 1, an exploratory component, and Phase 2, an intervention component. The exploratory component involves a triangle taste test and a formative research study designed to gain an understanding of the best implementation methods. Phase 2 involves a pragmatic stepped wedge trial design where the intervention will be progressively implemented in several clusters starting the intervention randomly at different times. In addition, we will evaluate the implementation strategy using a cost-effectiveness analysis.

DISCUSSION:

This is the first project in a Latin-American setting to implement a salt substitution intervention at the population level to tackle high blood pressure. Data generated and lessons learnt from this study will provide a strong platform to address potential interventions applicable to other similar low- and middle-income settings.

Lee, G., Paredes, M., Rengifo, S., Ambikapathi, R., Peñataro, P., Kosek, M., Caulfield, LE.

Rev Panam Salud Publica. 2014 Sep;36(3)

OBJECTIVE:

To characterize feeding practices in a community in the Peruvian Amazon and to consider how this information could be used to strengthen programs and policies designed to improve nutrition and reduce child malnutrition in vulnerable communities.

METHODS:

Data from three structured questionnaires were combined to produce a comprehensive depiction of feeding in a sample of 246 infants from birth through 8 months of life in the community of Santa Clara de Nanay near Iquitos, Peru. Breastfeeding initiation practices, exclusive breastfeeding in the first 180 days of life, the introduction of solids, and complementary feeding practices from 6-8 months, were described and related to maternal, infant, and household characteristics, including food insecurity.

RESULTS:

The median duration of exclusive breastfeeding was 19 days. However, over the first 180 days of life, children were exclusively breastfed on 46.1% of days. Overall, 68.3% of infants received some semi-solid or solid food between 0-6 months and all had received semi-solids by the end of 8 months of age. The proportion of infants consuming a minimally acceptable (frequent and diverse) complementary diet was 2.9%, 7.9%, and 16.1% at 6, 7, and 8 months respectively.

CONCLUSIONS:

Although breastfeeding is nearly universal, promotion programs are needed in Santa Clara to 1) delay the introduction of plain water, other non-breast milk liquids, and semi-solid foods; 2) extend the period of exclusive breastfeeding; and 3) increase food diversity and the frequency of feeding during the period of complementary feeding. These results can be used to guide programs and policies to improve nutrition and reduce child malnutrition.

Rev. perú. med. exp. salud publica vol.31 no.3 Lima jul./set. 2014

Rodríguez, L., Alva, A., Coronel, J., Caviedes, L., Mendoza-Ticona, A., Gilman, R., Sheen, P., Zimic, M.

ABSTRACT

Objectives. To implement a system for remote diagnosis of tuberculosis and multidrug resistance (MDR) using the Microscopic-Observation Drug Susceptibility Assay (MODS) method in the Mycobacteria Laboratory, Trujillo Center of Excellence in Tuberculosis (CENEX-Trujillo). The system included a variant of an algorithm for recognition of Mycobacterium tuberculosis recently reported from digital images of MODS cultures of sputum samples. Materials and methods. The recognition algorithm was optimized using a retraining statistical model based on digital images of MODS cultures from CENEX-Trujillo. Images of 50 positive MODS cultures of patients with suspected multidrug-resistant tuberculosis were obtained between January and October 2012 in the CENEX-Trujillo. Results. The sensitivity and specificity to recognize strings of tuberculosis were 92.04% and 94.93% respectively using objects. The sensitivity and specificity to determine a positive tuberculosis field were 95.4% and 98.07% respectively using pictures. Conclusions. The results demonstrated the feasibility of the implementation of telediagnostics in remote locations, which may contribute to the early detection of multidrug-resistant tuberculosis by MODS method.

Key words: Multiple organ failure; Mycobacterium tuberculosis; Tuberculosis, multidrug-resistant (source: MeSH/NLM).

Wingfield, T., Boccia, D., Tovar, M., Gavino, A., Zevallos, K., Montoya, R., Lönnroth, K., Evans, CA..

PLoS Med. 2014 Jul 15;11(7)

Abstract

Sterling, R., Checkley, W., Gilman, R., Cabrera, L., Sterling, C., Bern, C., Miranda, J.,

PeerJ. 2014; 2: e381.

Abstract

Scliar, MO., Gouveia, MH., Benazzo, A., Ghirotto, S., Fagundes, NJ., Leal, TP., Magalhães, WC., Pereira, L., Rodrigues, MR., Soares-Souza, GB., Cabrera, L., Berg, DE., Gilman, RH., Bertorelle, G., Tarazona-Santos, E.

BMC Evol Biol. 2014 Sep 30;14:174

Abstract

Bayer, A., Danysh, H., Garvich, M., Gonzálvez, G., Checkley, W., Alvarez, M., Gilman, R.

Disasters. 2014 Apr; 38(2)

During the 1997–98 El Niño Southern Oscillation (ENSO), Tumbes, Peru received 16 times the annual average rainfall. We explored how Tumbes residents perceived the ENSO’s impact on basic necessities, transport, healthcare, jobs and migration. Residents needed more time to rebuild housing, recover agriculture, livestock and income stability, and return to eating sufficient animal protein. Although large-scale assistance minimized the ENSO’s effects, residents needed more timely support. Residents’ perspectives on their risks to flooding should be considered to generate effective assistance.

Matson R, Rios CT, Chavez CB, Gilman RH, Florin D, Sifuentes VL, Greffa RC, Yori PP, Fernandez R, Portocarrero DV, Vinetz JM, Kosek M.

Am J Trop Med Hyg. 2008 Mar;78(3):492-8.

We evaluated a PCR-RFLP of the ribosomal internal transcribed spacer 2 region (ITS2) to distinguish species of Anopheles commonly reported in the Amazon and validated this method using reared F1 offspring. The following species of Anopheles were used for molecular analysis: An. (Nys.) benarrochi, An. (Nys.) darlingi, An. (Nys.) nuneztovari, An. (Nys.) konderi, An. (Nys.) rangeli, and An. (Nys.) triannulatus sensu lato (s.l.). In addition, three species of the subgenus Anopheles, An. (Ano.) forattini, An. (Ano.) mattogrossensis, and An. (Ano.) peryassui were included for testing. Each of the nine species tested yielded diagnostic banding patterns. The PCR-RFLP method was successful in identifying all life stages including exuviae with small fractions of the sample. The assay is rapid and can be applied as an unbiased confirmatory method for identification of morphologic variants, disputed samples, imperfectly preserved specimens, and life stages from which taxonomic keys do not allow for definitive species determination.

Levy MZ, Quíspe-Machaca VR, Ylla-Velasquez JL, Waller LA, Richards JM, Rath B, Borrini-Mayori K, del Carpio JG, Cordova-Benzaquen E, McKenzie FE, Wirtz RA, Maguire JH, Gilman RH, Bern C.

Am J Trop Med Hyg. 2008 Oct;79(4):528-34.

We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

Santivañez SJ, Gutierrez AM, Rosenzvit MC, Muzulin PM, Rodriguez ML, Vasquez JC, Rodriguez S, Gonzalez AE, Gilman RH, Garcia HH; Cysticercosis Working Group in Peru.

Am J Trop Med Hyg. 2008 Jul;79(1):89-92.

A molecular PCR study using DNA from 21 hydatid cysts was performed to determine which strain type is responsible for human infection in Peru. The mitochondrial cytochrome c oxidase subunit 1 (CO1) gene was amplified in 20 out of 21 samples, revealing that all but 1 sample (19/20, 95%) belonged to the common sheep strain (G1). The remaining samples belonged to the camel strain (G6). The G1 genotype was most frequently found in human cases of cystic hydatid disease (CHD) in Peru. Local control measures should focus primarily on decreasing dog and sheep infection rather than intermediate reservoirs.

Asayag CR, Garay CR, Sanchez GM, Angeles CC, Baca CJ, Evans C, Yori PP, Kosek M.

Am J Trop Med Hyg. 2008 Oct;79(4):473.

Wolf H, Mendez M, Gilman RH, Sheen P, Soto G, Velarde AK, Zimic M, Escombe AR, Montenegro S, Oberhelman RA, Evans CA.

Am J Trop Med Hyg. 2008 Dec;79(6):893-8.

Pediatric pulmonary tuberculosis diagnosis is difficult because young children are unable to expectorate sputum samples. Testing stool for tuberculosis DNA from swallowed sputum may diagnose pulmonary tuberculosis. Hospitalized children with suspected tuberculosis had stool, nasopharyngeal, and gastric aspirates cultured that confirmed pulmonary tuberculosis in 16/236 patients. Twenty-eight stored stools from these 16 children were used to evaluate stool polymerase chain reaction (PCR) for tuberculosis diagnosis compared with 28 stool samples from 23 healthy control children. Two DNA extraction techniques were used: fast-DNA mechanical homogenization and Chelex-resin chemical extraction. DNA was tested for tuberculosis DNA with a hemi-nested IS6110 PCR. PCR after Fast-DNA processing was positive for 6/16 culture-proven tuberculosis patients versus 5/16 after Chelex extraction (sensitivity 38% and 31%, respectively). All controls were negative (specificity 100%). If sensitivity can be increased, stool PCR would be a rapid, non-invasive, and relatively bio-secure initial test for children with suspected pulmonary tuberculosis.

Cama VA, Bern C, Roberts J, Cabrera L, Sterling CR, Ortega Y, Gilman RH, Xiao L.

Emerg Infect Dis. 2008 Oct;14(10):1567-74.

To determine whether clinical manifestations are associated with genotypes or subtypes of Cryptosporidium spp., we studied a 4-year longitudinal birth cohort of 533 children in Peru. A total of 156 infection episodes were found in 109 children. Data from first infections showed that C. hominis was associated with diarrhea, nausea, vomiting, general malaise, and increased oocyst shedding intensity and duration. In contrast, C. parvum, C. meleagridis, C. canis, and C. felis were associated with diarrhea only. C. hominis subtype families were identified (Ia, Ib, Id, and Ie); all were associated with diarrhea. Ib was also associated with nausea, vomiting, and general malaise. All C. parvum specimens belonged to subtype family IIc. Analysis of risk factors did not show associations with specific Cryptosporidium spp. genotypes or subtypes. These findings strongly suggest that Cryptosporidium spp. and subtypes are linked to different clinical manifestations in children.

Lee, G., Peñataro, P., Paredes, M., Caulfield, L., Sack, D., Fischer-Walker, C., Black, R., Kosek, M.

BMJ Open. 2014; 4(6)

Caffrey D, Miranda JJ, Gilman RH, Davila-Roman VG, Cabrera L, Dowling R, Stewart T, Bernabe-Ortiz A, Wise R, Leon-Velarde F, Checkley W; CRONICAS Cohort Study Group.

Extrem Physiol Med. 2014 Feb 1;3(1):3.

We sought to determine if adult residents living at high altitude have developed sufficient adaptation to a hypoxic environment to match the functional capacity of a similar population at sea level. To test this hypothesis, we compared the 6-min walk test distance (6MWD) in 334 residents living at sea level vs. at high altitud.

The 6-min walk test predicted a lowered functional capacity among Andean high altitude vs. sea level natives at their altitude of residence, which could be explained by an incomplete adaptation or a protective mechanism favoring neuro- and cardioprotection over psychomotor activity.

Mendoza-Núñez M, Mulder M, Franco MP, Maas KS, Castañeda ML, Bonifacio N, Chacaltana J, Yagui E, Gilman RH, Espinosa B, Blazes D, Hall E, Abdoel TH, Smits HL; Brucellosis Working Group in Callao.

Am J Trop Med Hyg. 2008 Apr;78(4):595-8.

During home visits and using a point-of-care test for brucellosis, we screened the household members of adult patients found to have brucellosis by investigation at the Hospital Nacional Daniel Alcides Carrión in Callao, Peru. A total of 206 household members of 43 patients were screened, and 15 (7.3%) household members in 10 (23.3%) households tested seropositive. Brucellosis was diagnosed in 14 of them, all but 4 presenting with acute or subacute uncomplicated disease. Regardless of attempts to control brucellosis in Peru, the disease continues to be reasonably common among household members of brucellosis patients. Household members presumably remain the single most important identifiable risk group in an urban setting, and screening them provides an effective means for their early diagnosis. Although contact with livestock was rare, the consumption of unpasteurized dairy products was reported by almost all patients with brucellosis, their household members, and hospitalized non-brucellosis patients.

Aponte JC, Estevez Y, Gilman RH, Lewis WH, Rojas R, Sauvain M, Vaisberg AJ, Hammond GB.

Planta Med. 2008 Mar;74(4):407-10.

A pharmacological screening of the ethanol extract and fractions of Blepharodon nitidum led to the isolation of fourteen compounds, two of which, 24-hydroperoxycycloart-25-en-3beta-ol and 25-hydroperoxycycloart-23-en-3beta-ol, exhibited in vitro anti- Mycobacterium tuberculosis and antileishmanial activities, as well as significant cytotoxic activity against a panel of human tumor cell lines.

Rao VB, Pelly TF, Gilman RH, Cabrera L, Delgado J, Soto G, Friedland JS, Escombe AR, Black RE, Evans CA.

Emerg Infect Dis. 2007 Jul;13(7):1101-4.

In 50 healthy Peruvian shantytown residents, zinc cream applied to tuberculosis skin-test sites caused a 32% increase in induration compared with placebo cream. Persons with lower plasma zinc had smaller skin-test reactions and greater augmentation with zinc cream. Zinc deficiency caused false-negative skin-test results, and topical zinc supplementation augmented antimycobacterial immune responses enough to improve diagnosis.

Levy MZ, Kawai V, Bowman NM, Waller LA, Cabrera L, Pinedo-Cancino VV, Seitz AE, Steurer FJ, Cornejo del Carpio JG, Cordova-Benzaquen E, Maguire JH, Gilman RH, Bern C.

PLoS Negl Trop Dis. 2007 Dec 26;1(3):e103.

Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy. Methods and findings: We performed a serological survey in children 2-18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4-7.9]) children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child’s risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child’s house. Receiver operator characteristic (ROC) plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children. Conclusions: We found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings.

Lescano AG, Garcia HH, Gilman RH, Guezala MC, Tsang VC, Gavidia CM, Rodriguez S, Moulton LH, Green JA, Gonzalez AE; Cysticercosis Working Group in Peru.

Am J Trop Med Hyg. 2007 Feb;76(2):376-83.

We estimated the Taenia solium swine cysticercosis risk gradient surrounding tapeworm carriers in seven rural communities in Peru. At baseline, the prevalences of taeniasis by microscopy and swine cysticercosis by serology were 1.2% (11 of 898) and 30.8% (280 of 908), respectively. The four-month cumulative seroincidence was 9.8% (30 of 307). The unadjusted swine seroprevalence and seroincidence rates increased exponentially by 12.0% (95% confidence [CI] = 9.7-14.3%) and 32.8% (95% CI = 25.0-41.0%), respectively when distance to carriers decreased by half. Swine seroprevalence was 18.4% at > 500 meters from a carrier, 36.5% between 51 and 500 meters, and 68.9% within 50 meters (P < 0.001). Swine seroincidence also displayed a strong gradient near tapeworm carriers (3.8%, 12.2%, and 44.0%; P < 0.001). Within 50 meters, swine seroprevalence appeared unaffected if the owners harbored tapeworms, although pigs owned by a tapeworm carrier had a four times higher seroincidence compared with other pigs (P = 0.005). In rural areas, swine cysticercosis occurs in high-risk hotspots around carriers where control interventions could be delivered.

Escombe AR, Oeser CC, Gilman RH, Navincopa M, Ticona E, Pan W, Martinez C, Chacaltana J, Rodriguez R, Moore DA, Friedland JS, Evans CA.

PLoS Med. 2007 Feb;4(2):e68.

The study was carried out in eight hospitals in Lima, Peru; five were hospitals of ‘‘oldfashioned’’ design built pre-1950, and three of ‘‘modern’’ design, built 1970–1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells- Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p , 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p , 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p , 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open.

Oswald WE, Lescano AG, Bern C, Calderon MM, Cabrera L, Gilman RH.

Am. J. Trop. Med. Hyg., 77(4), 2007, pp. 699–704

We assessed fecal contamination of drinking water in households in 2 peri-urban communities of Lima, Peru. We measured Escherichia coli counts in municipal source water and, within households, water from principal storage containers, stored boiled drinking water, and water in a serving cup. Source water was microbiologically clean, but 26 (28%) of 93 samples of water stored for cooking had fecal contamination. Twenty-seven (30%) of 91 stored boiled drinking water samples grew E. coli. Boiled water was more frequently contaminated when served in a drinking cup than when stored (P < 0.01). Post-source contamination increased successively through the steps of usage from source water to the point of consumption. Boiling failed to ensure safe drinking water at the point of consumption because of easily contaminated containers and poor domestic hygiene. Hygiene education, better point-of-use treatment and storage options, and in-house water connections are urgently needed.

Maas KS, Méndez M, Zavaleta M, Manrique J, Franco MP, Mulder M, Bonifacio N, Castañeda ML, Chacaltana J, Yagui E, Gilman RH, Guillen A, Blazes DL, Espinosa B, Hall E, Abdoel TH, Smits HL.

Am. J. Trop. Med. Hyg., 76(4), 2007, pp. 698–702

Polymerase chain reaction (PCR) was applied to confirm the diagnosis of brucellosis and to study its clearance in response to the standard treatment regimen with doxycycline and rifampin at hospitals in Callao and Lima, Peru. The PCR confirmed the diagnosis in 23 (91.7%) patients with brucellosis including 12 culture-confirmed cases. For patients treated at the hospital in Callao, PCR was positive for all samples collected during and at the conclusion of treatment and for 76.9% of follow-up samples collected on average 15.9 weeks after completion of treatment. For patients treated at the hospital in Lima, PCR tests were positive for 81.8% of samples collected during treatment, for 33.3% of samples collected at the conclusion of treatment, and for ≥ 50% of samples collected at first, second, and third post-treatment follow-up. Thus, Brucella DNA may persist in the serum weeks to months after completion of the standard treatment regimen.

Saunders MJ, Wingfield T, Tovar MA, Baldwin MR, Datta S, Zevallos K, Montoya R, Valencia TR, Friedland JS, Moulton LH, Gilman RH, Evans CA.

Lancet Infect Dis. 2017 Nov;17(11):1190-1199

Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases.

In February 2014, the Malaria Elimination Working Group, in partnership with the Peruvian Ministry of Health (MoH), hosted its first international conference on malaria elimination in Iquitos, Peru. The main outcome was consensus that implementing a malaria elimination project in the Amazon region is achievable, but would require: 1) a comprehensive strategic plan, 2) the altering of current programmaticguidelines from control toward elimination by including symptomatic as well as asymptomatic individuals for antimalarial therapy and transmission-blocking interventions, and 3) the prioritization of community-based active case detection with proper rapid diagnostic tests to interrupt transmission.

In Cusco, Peru, and South America in general, there is a dearth of travelers’ diarrhea (TD) data concerning the clinical features associated with enteropathogen-specific infections and destination-specific risk behaviors. Understanding these factors would allow travel medicine providers to tailor interventions to patients’ risk profiles and travel destination.