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.

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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

BACKGROUND:

Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed «catastrophic» but are poorly defined. We studied TB-affected households’ hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs.

METHODS AND FINDINGS:

From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2-4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household’s annual income. In poorer households, costs were lower but constituted a higher proportion of the household’s annual income: 27% (95% CI = 20%-43%) in the least-poor houses versus 48% (95% CI = 36%-50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%-61%] versus 38% [95% CI = 34%-41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7-15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3-3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00-1.01], p = 0.02), and catastrophic costs (OR = 1.7 [95% CI = 1.1-2.6], p = 0.01). The adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18% (95% CI = 6.9%-28%), similar to that of MDR TB (20% [95% CI = 14%-25%]). Sensitivity analyses demonstrated that existing catastrophic costs thresholds (≥10% or ≥15% of household annual income) were not associated with adverse outcome in our setting. Study limitations included not measuring certain «dis-saving» variables (including selling household items) and gathering only 6 mo of costs-specific follow-up data for MDR TB patients.

CONCLUSIONS:

Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring higher relative costs was associated with adverse TB outcome. The population attributable fraction indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse outcomes. Thus TB is a socioeconomic as well as infectious problem, and TB control interventions should address both the economic and clinical aspects of this disease. Please see later in the article for the Editors’ Summary.

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.

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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.

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