13. Otros

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

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

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.