Point of care HbA1c level for diabetes mellitus management and its accuracy among tuberculosis patients: a study in four countries.

BACKGROUND: Diabetes mellitus (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA1c) testing among newly diagnosed TB patients to assess POC test accuracy, safety and acceptability in settings in which immediate access to DM services may be difficult. METHODS: We measured POC and accredited laboratory HbA1c (using high-performance liquid chromatography) in 1942 TB patients aged 18 years recruited from Peru, Romania, Indonesia and South Africa. We calculated overall agreement and individual variation (mean ± 2 standard deviations) stratified by country, age, sex, body mass index (BMI), HbA1c level and comorbidities (anaemia, human immunodeficiency virus [HIV]). We used an error grid approach to identify disagreement that could raise significant concerns. RESULTS: Overall mean POC HbA1c values were modestly higher than laboratory HbA1c levels by 0.1% units (95%CI 0.1-0.2); however, there was a substantial discrepancy for those with severe anaemia (1.1% HbA1c, 95%CI 0.7-1.5). For 89.6% of 1942 patients, both values indicated the same DM status (no DM, HbA1c <6.5%) or had acceptable deviation (relative difference <6%). Individual agreement was variable, with POC values up to 1.8% units higher or 1.6% lower. For a minority, use of POC HbA1c alone could result in error leading to potential overtreatment (n = 40, 2.1%) or undertreatment (n = 1, 0.1%). The remainder had moderate disagreement, which was less likely to influence clinical decisions. CONCLUSION: POC HbA1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB patients.

Tuberculosis in children treated with second-line drugs under programmatic conditions in Lima, Peru.

OBJECTIVE: To characterise childhood tuberculosis (TB) treated with second-line drugs (SLDs) in Lima, Peru. DESIGN: Results for the age groups <5 and 5-14 years were compared and treatment outcomes were assessed in cases reported between 2011 and 2015 from six districts of Lima. RESULTS: Of 96 reported cases, 82 were evaluated. Among these, 59% were boys; the median age was 8 years and 32% were aged <5 years. Contact with a TB case was reported in 82% of cases; 90% were treatment-naïve, 98% had pulmonary localisation and 50% underwent the tuberculin skin test (purified protein derivative), with induration 10 mm in 88%. A positive smear was found in 40%, all in the 5-14 years age group, and 46% were culture-positive. Only 26% had confirmed multidrug-resistant TB, 90% of whom were in the 5-14 years age group. SLDs for confirmed or probable drug-resistant TB (DR-TB) were administered to all cases, with a high proportion of success (over 83%), no failures or deaths and a high proportion of loss to follow-up. CONCLUSION: The main indication for SLDs in childhood TB was the empirical treatment of DR-TB due to contact with one or more identified DR-TB patients. Bacteriological confirmation was limited; however, treatment success was adequate.

Rapid drug susceptibility testing and treatment outcomes for multidrug-resistant tuberculosis in Peru.

SETTING: The detection of multidrug-resistant tuberculosis (MDR-TB) using rapid drug susceptibility testing (DST) has increased steadily in recent years in Peru, from 9216 tests in 2010 to 27 021 tests in 2015. Research examining the impact of rapid DST on treatment outcomes is required. OBJECTIVE: To evaluate the association between rapid DST use (nitrate reductase assay, microscopic observation drug susceptibility assay [MODS] and GenoType® MTBDRplus) and treatment outcomes and mortality in MDR-TB patients in Peru. DESIGN: Retrospective cohort study of patients diagnosed with pulmonary MDR-TB between 2010 and 2013 (with treatment outcomes up to December 2015) using the electronic registry of the Peruvian National TB Programme. RESULTS: A total of 2671 MDR-TB patients were included; the median age was 27 years, 2.8% were co-infected with the human immunodeficiency virus. Use of rapid DST was associated with a 40% increase in the adjusted odds of treatment success (aOR 1.40, 95%CI 1.19-1.64) and a 54% reduction in mortality (aOR 0.46, 95%CI 0.33-0.64). Higher treatment success rates were driven by MODS and GenoType® MTBDRplus testing (aORs for unsuccessful outcomes respectively 0.68 and 0.66). CONCLUSION: The use of rapid DST (MODS and MTBDRplus) to diagnose MDR-TB was associated with a reduction in the odds of death and a substantial increase in the odds of treatment success.

Programmatic management of patients with pre-extensively drug-resistant tuberculosis in Peru, 2011-2014.

BACKGROUND: In Peru, a treatment approach for extensively drug-resistant tuberculosis (XDR-TB) incorporating World Health Organization Group 5 drugs and patient-centred care has achieved 65% success. To extend this approach to pre-XDR-TB patients, we evaluated this population separately. OBJECTIVE: To assess programmatic management of pre-XDR-TB. METHOD: Retrospective study using the official national registry from 2011 to 2014. Cases were separately evaluated according to resistance to fluoroquinolones (FQs) (pre-XDR-F) or to second-line injectables (SLIs) (pre-XDR-I). RESULTS: Of 610 pre-XDR-TB patients, 120 (20%) had pre-XDR-F and 490 (80%) had pre-XDR-I. Pre-XDR-F cases were older (34 years vs. 28 years, P < 0.001) and a higher proportion had previously received two or more regimens (70% vs. 38%, P < 0.001). Among the 452 patients who started treatment in 2011-2013, treatment success was 43.3%, 26.5% were lost to follow-up, 12.1% died and 13.7% failed treatment. Success was higher in pre-XDR-I (48.5%) than pre-XDR-F (21.4%) patients. History of previous treatment (OR 2.23, 95%CI 1.52-3.38) and pre-XDR-F (OR 2.39, CI 1.18-4.83) were associated with unsuccessful outcomes. CONCLUSION: Programmatic management of pre-XDR-TB has not been successful, particularly in pre-XDR-F patients, with lower rates of success than those achieved in the same setting for XDR-TB. The strategy used for XDR-TB should be extended to pre-XDR-TB patients in Peru.

MPT64 patch test for the diagnosis of active pulmonary tuberculosis: a randomised controlled trial in Peru.

SETTING: There remains a lack of effective and inexpensive diagnostic tools for active tuberculosis (TB) disease. Testing immune responses to proteins secreted by Mycobacterium tuberculosis, such as MPT64, may be a diagnostic option. OBJECTIVE: To evaluate the sensitivity and specificity of a patch test using MPT64 for the diagnosis of active TB disease. DESIGN: This randomised, double-blind, placebo-controlled, prospective study in Lima, Peru, involved 55 healthy controls and 457 symptomatic individuals referred for routine TB testing by the National TB Control Programme. All subjects underwent a comprehensive diagnostic workup, and received an active patch on one arm and a placebo patch on the opposite arm, which were read after 4 days. RESULTS: Eighty-one (18%) of the symptomatic participants were classified as having definite TB, while an additional 98 (21%) had probable TB. The patch tests performed the same in both groups, with a sensitivity of 27% and specificity of 74%. The area under the receiver operating characteristic curve was 0.495 (95%CI 0.425-0.565). CONCLUSIONS: Contrary to existing literature, the MPT64 patch was not sensitive and specific to detect active TB. Given the potential of the test, understanding possible differences in the protein source or underlying genetic factors should be explored further.

Validation of microscopic observation drug susceptibility testing for rapid, direct rifampicin and isoniazid drug susceptibility testing in patients receiving tuberculosis treatment.

Drug susceptibility testing (DST) is often needed in patients clinically failing tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility tests, such as microscopic observation drug susceptibility (MODS) tests, have been performed in patients not receiving TB treatment. The effect of ongoing TB treatment on the performance of MODS direct DST has not been previously explored, but patients failing such therapy constitute an important target group. The aim of this study was to determine the performance of MODS direct rifampicin and isoniazid DST in patients clinically failing first-line TB treatment, and to compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays; strains were tested for rifampicin and isoniazid susceptibility by the proportion method at the national reference laboratory. Ninety-three samples were culture-positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS plate DST reading (performed on the same day as the sample is classified as culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading of MODS DST plates 1 week after cultures had been determined to be culture-positive improved overall performance marginally-the isoniazid DST concordance was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa 0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS testing provided reliable rifampicin and isoniazid DST results for samples obtained from patients receiving TB therapy. A modified DST reading schedule for such samples, with a final reading 1 week after a MODS culture turns positive, marginally improves the concordance with reference DST.

A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India.

BACKGROUND: The converging epidemics of HIV and tuberculosis (TB) pose one of the greatest public health challenges of our time. Rapid diagnosis of TB is essential in view of its infectious nature, high burden of cases, and emergence of drug resistance. OBJECTIVE: The purpose of this present study was to evaluate the feasibility of implementing the microscopic observation drug susceptibility (MODS) assay, a novel assay for the diagnosis of TB and multi-drug-resistant tuberculosis (MDR-TB) directly from sputum specimens, in the Indian setting. MATERIALS AND METHODS: This study involved a cross-sectional, blinded assessment of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV-negative patients against the radiometric method, BD-BACTEC TB 460 system. RESULTS: Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of the MODS assay in detecting MTB among TB suspected patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono-resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21 days (P<0.001). CONCLUSION: Costing 5 to 10 times lesser than the automated culture methods, the MODS assay has the potential clinical utility as a simple and rapid method. It could be effectively used as an alternative method for diagnosing TB and detection of MDR-TB in a timely and affordable way in resource-limited settings.

Tuberculosis in household contacts of multidrug-resistant tuberculosis patients.

SETTING: The burden of tuberculosis (TB) disease among household contacts of multidrug-resistant TB (MDR-TB) patients is poorly understood and might represent a target for transmission-interrupting interventions. DESIGN: This retrospective cohort study, conducted in Lima, Peru, from June to September 2008, estimated the incidence of TB disease among household contacts of MDR-TB patients in 358 households. RESULTS: Of 2112 household contacts in 80 households (22% of households), 108 (5%) developed TB disease during the study, giving an incidence rate of 2360 per 100 000 contact follow-up years for each of the first 3 years after exposure. Drug susceptibility tests (DST) were available for 50 diseased contacts, of whom 36 (80%) had MDR-TB. Forty-two pairs of index-contact DSTs were available, among which the contact had an identical or less resistant phenotype than the index case in 27 pairs. Multivariate Cox regression demonstrated that male contacts (hazard ratio [HR] 2.8, P < 0.05), with previous TB disease (HR 20.7, P < 0.001) and with associated (non-human immunodeficiency virus) comorbidities (HR 11.2, P < 0.001) were more likely to develop TB. CONCLUSION: The high percentage of diseased household contacts highlights an opportunity for household-level interventions to prevent transmission, whether or not these cases were all attributable to the index case.

Development of an automated MODS plate reader to detect early growth of Mycobacterium tuberculosis.

In this work, an automated microscopic observation drug susceptibility (MODS) plate reader has been developed. The reader automatically handles MODS plates and after autofocussing digital images are acquired of the characteristic microscopic cording structures of Mycobacterium tuberculosis, which are the identification method utilized in the MODS technique to detect tuberculosis and multidrug resistant tuberculosis. In conventional MODS, trained technicians manually move the MODS plate on the stage of an inverted microscope while trying to locate and focus upon the characteristic microscopic cording colonies. In centres with high tuberculosis diagnostic demand, sufficient time may not be available to adequately examine all cultures. An automated reader would reduce labour time and the handling of M. tuberculosis cultures by laboratory personnel. Two hundred MODS culture images (100 from tuberculosis positive and 100 from tuberculosis negative sputum samples confirmed by a standard MODS reading using a commercial microscope) were acquired randomly using the automated MODS plate reader. A specialist analysed these digital images with the help of a personal computer and designated them as M. tuberculosis present or absent. The specialist considered four images insufficiently clear to permit a definitive reading. The readings from the 196 valid images resulted in a 100% agreement with the conventional nonautomated standard reading. The automated MODS plate reader combined with open-source MODS pattern recognition software provides a novel platform for high throughput automated tuberculosis diagnosis.

Missed opportunities for tuberculosis diagnosis.

BACKGROUND: In high tuberculosis (TB) burden, resource-poor countries, sputum smear microscopy remains the mainstay of diagnosis. The low sensitivity of this test means that patients with smear-negative but culture-positive TB pass undetected through the health care system. Such clinical episodes are missed opportunities for diagnosis and interruption of transmission, which might be averted through the application of more sensitive diagnostic tests. OBJECTIVES: To estimate the proportion of incident TB cases that might have been detected earlier than the actual date of diagnosis if a test more sensitive than smear microscopy had been used at an earlier presentation episode. METHOD: Retrospective cohort study in urban Peru, investigating health care facility interactions for symptoms suggestive of TB prior to TB diagnosis through patient interviews and a review of clinical records. RESULTS: Of 212 participants enrolled, 58% had one or more clinical interactions prior to their diagnostic episode. Of those with a prior episode, the median number of episodes was three. The median delay to diagnosis from first presentation was 26 days. CONCLUSION: There are clear missed opportunities for earlier TB diagnosis, delaying treatment initiation and continued spread of Mycobacterium tuberculosis to the community. The implementation of sensitive diagnostic tests appropriate to resource-poor settings should be given high priority.

Reliability of the MODS assay decentralisation process in three health regions in Peru.

OBJECTIVE: To deliver rapid isoniazid (INH) and rifampicin (RMP) drug susceptibility testing (DST) close to the patient, we designed a decentralisation process for the microscopic observation drug susceptibility (MODS) assay in Peru and evaluated its reliability. METHODS: After 2 weeks of training, laboratory staff processed ≥ 120 consecutive sputum samples each in three regional laboratories. Samples were processed in parallel with MODS testing at an expert laboratory. Blinded paired results were independently analysed by the Instituto Nacional de Salud (INS) according to pre-determined criteria: concordance for culture, DST against INH and RMP and diagnosis of multidrug-resistant tuberculosis (MDR-TB) ≥ 95%, McNemar's P > 0.05, kappa index (κ) ≥ 0.75 and contamination 1-4%. Sensitivity and specificity for MDR-TB were calculated. RESULTS: The accreditation process for Callao (126 samples, 79.4% smear-positive), Lima Sur (n = 130, 84%) and Arequipa (n = 126, 80%) took respectively 94, 97 and 173 days. Pre-determined criteria in all regional laboratories were above expected values. The sensitivity and specificity for detecting MDR-TB in regional laboratories were >95%, except for sensitivity in Lima Sur, which was 91.7%. Contamination was 1.0-2.3%. Mean delay to positive MODS results was 9.9-12.9 days. CONCLUSION: Technology transfer of MODS was reliable, effective and fast, enabling the INS to accredit regional laboratories swiftly.

The MIT D-lab electricity-free PortaTherm™ incubator for remote testing with the QuantiFERON®-TB Gold In-Tube assay.

BACKGROUND: Use of the QuantiFERON®-TB Gold In-Tube assay (QFT-GIT) in remote areas is limited by the need to incubate blood samples within 12 h of collection. PortaTherm™ is a portable, electricity-free, phase-change incubator previously used for field collection of microbiological samples. OBJECTIVE: To determine whether the PortaTherm can be used for the reliable incubation of QFT-GIT samples, thus enabling QFT-GIT use in settings distant from laboratory facilities. METHODS: In a prospective comparative study in Peru, blood samples were collected from 50 participants and processed in three parallel QFT-GIT tests per participant; two were incubated in a conventional incubator; the third was incubated in the PortaTherm. RESULTS: All 150 QFT-GIT tests gave definitive results, and for 46 of the 50 participants all three tests were concordant, eight of which were positive. Four participants had one discordant result: two due to discordance of a conventional incubator QFT-GIT result, and two due to discordant PortaTherm QFT-GIT results. CONCLUSION: The QFT-GIT inter-incubator variability between the PortaTherm and conventional incubator was no greater than the intra-incubator variability for the conventional incubator, indicating that the PortaTherm is a suitable tool for incubating QFT-GIT whole blood samples in remote settings where access to a laboratory or electricity is limited.

MODS accreditation process for regional reference laboratories in Peru: validation by GenoType® MTBDRplus.

SETTING: Although considerable effort has been put into the development and evaluation of new diagnostics for tuberculosis (TB) and multidrug-resistant TB (MDR-TB), little attention has thus far been paid to the technical aspects of initiating quality-assured routine service use. For implementation of the microscopic-observation drug susceptibility (MODS) methodology in the Peruvian reference laboratory network, a laboratory accreditation process was devised; MODS results from an expert reference laboratory (Universidad Peruana Cayetano Heredia [UPCH]) were used as the standard against which implementing laboratory MODS results were judged to ensure that, prior to use for patient care, implementing laboratories achieved the same high performance with MODS as previously demonstrated in the research laboratory. OBJECTIVE: To evaluate the validity of MODS-based accreditation and the concordance of MODS drug susceptibility testing (DST) with molecular testing. DESIGN: Head-to-head comparison of MODS DST results from implementing Peruvian regional reference laboratories and the accrediting expert MODS laboratory (UPCH) with GenoType® MTBDRplus DST. RESULTS: The concordance of phenotypic MODS rifampicin (RMP) DST with GenoType MTBDRplus was respectively 97.4%, 97.9% and 97.1% for the two implementing regional laboratories and UPCH, and respectively 94.7%, 95.7% and 94.6% for isoniazid (INH) DST. CONCLUSION: High and consistent levels of MODS/MTBDRplus concordance for INH and RMP DST confirm the validity of the use of rapid methods as reference standards for accreditation.

Tuberculosis transmission risk and infection control in a hospital emergency department in Lima, Peru.

BACKGROUND: Overcrowded emergency departments (EDs) are used by undiagnosed tuberculosis (TB) patients. TB infection control measures are seldom prioritized, making EDs potential foci of unrecognised nosocomial transmission. OBJECTIVE: To quantify TB infection risk among health care workers in an ED in a high TB-burden setting, Lima, Peru, and to evaluate TB infection control measures. METHODS: Consenting ED staff were tested for TB infection at baseline and after 1 year using the QuantiFERON-TB Gold In-Tube (QFT-G). In parallel, sputum for TB culture was requested from patients spending >2 h in the ED, irrespective of presenting complaint. Infection control measures were documented and room ventilation measured. RESULTS: Over 1 year, there were 2246 TB patient-hours of exposure in the ED from 153 different patients. At baseline, 56% of the 70 staff recruited were QFT-G-positive; 27 of 31 baseline-negatives consented to follow-up after 1 year, and eight (30%, all clinical staff) tested positive. Annual incidence of infection was 1730 per 100,000 population. TB infection control measures were sub-optimal, with no patient screening, no isolation rooms, inadequate ventilation and sporadic respirator use. CONCLUSIONS: ED staff were exposed to an unexpectedly large TB burden in the workplace, resulting in a high rate of TB infection. TB infection control should be prioritized in EDs, especially in high-prevalence settings.

Falls, poisonings, burns, and road traffic injuries in urban Peruvian children and adolescents: a community based study.

OBJECTIVES: To identify individual and household characteristics associated with serious falls, poisonings, burns and road traffic injuries (RTIs) for children in Lima, Peru. METHODS: 5061 households consisting of 10,210 children were included in this community based, cross-sectional study in San Juan de Miraflores (SJM), a low income, urban district of Lima, Peru. Households were eligible if there was a consenting adult and at least one resident child aged < or =18 years. A door to door survey was conducted in SJM, collecting childhood injury, demographic, and socioeconomic data. Analysis was done at the individual and household level for injuries severe enough to have required medical consultation. RESULTS: The greatest burden of injury was from falls and RTIs. For individuals, male gender and age were the most important predictors of injuries. Households in which multiple injuries were reported were more likely to be poor (odds ratio (OR) 1.66, 95% CI 1.24 to 2.22) and overcrowded (OR 1.88, 95% CI 1.20 to 2.94). The occurrence of serious falls, poisonings, burns, and pedestrian RTIs significantly increased the likelihood of a second serious injury in the home (adjusted ORs ranged between 1.88 and 2.99). CONCLUSION: All children from households in which an unintentional injury has occurred appear to have an increased likelihood of future injury; such high risk households may be readily identifiable in the clinical setting. Interventions in this environment designed to prevent subsequent injuries merit further investigation.

Reducing the string test intra-gastric downtime for detection of Mycobacterium tuberculosis.

OBJECTIVES: To explore the potential for reducing the procedural duration of the string test for the diagnosis of tuberculosis (TB) using microscopic observation drug susceptibility (MODS) culture. METHODS: Twelve patients already diagnosed with pulmonary TB, four each with sputum smear acid-fast bacilli grade 1+, 2+ and 3+, underwent four consecutive string tests of varying intra-gastric downtime (IGDT) of 30 min, 1, 2 and 4 h. Each retrieved string was cut into three-one oesophageal and two gastric sections. Eluates from one of the gastric sections and the oesophageal section were cultured in MODS after a decontamination procedure; eluate from the other gastric section was cultured in MODS with no decontamination. RESULTS: No significant difference was observed in the retrieval efficacy of Mycobacterium tuberculosis (P = 0.29) or time to positive MODS culture (P = 0.80) among string tests of varying IGDTs. Every patient with a sample that was positive after a 4-h IGDT also had positive culture of a 1-h IGDT sample. A pre-inoculation sample decontamination step significantly reduced culture contamination (P < 0.001). CONCLUSION: In smear-positive patients, reducing the IGDT to 1 h did not affect the M. tuberculosis retrieval efficacy of the string test. Future evaluations in non-expectorating human immunodeficiency virus and paediatric populations should include a 1-h IGDT.

Physician-initiated courtesy MODS testing for TB and MDR-TB diagnosis and patient management.

SETTING: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia (UPCH) and government health centres, Lima, Peru. OBJECTIVE: To evaluate the contribution of unselected (courtesy) microscopic observation drug susceptibility (MODS) testing to the diagnosis and/or drug susceptibility testing (DST) of tuberculosis and their subsequent impact upon patient management. DESIGN: Retrospective database analysis and case note review of MODS culture-positive cases. RESULTS: Mycobacterium tuberculosis was isolated in 28.9% of 225 samples (209 patients); 22.2% of 63 positive cases were multidrug-resistant. In 58 MODS culture-positive cases with follow-up data available, MODS provided culture confirmation of diagnosis, DST or both in 82.8%, before any standard method. In 41.4%, this result should have prompted a modification in patient management. Delays between laboratory result and initiation or change of treatment, where applicable, took on average 42 and 64 days, respectively, of which a delay of respectively 17 and 48 days occurred after the receipt of results by the health facility. CONCLUSION: MODS provides important data for clinical management within a meaningful timeframe and should contribute positively to patient outcomes due to earlier initiation of appropriate therapy. Although clinicians may successfully select patients likely to benefit from MODS, ongoing work is required to identify optimal implementation of the assay and to reduce logistical and health system derived delays.

Tuberculosis skin testing, anergy and protein malnutrition in Peru.

SETTING: Malnutrition and intestinal parasites cause immunosuppression. This may cause false-negative tuberculin skin tests (TST) and failure to identify tuberculosis (TB) infection. OBJECTIVE: To assess factors associated with TST positivity and anergy in disadvantaged communities in Peru. DESIGN: A study of 212 randomly selected adults: 102 in a rural Amazonian village and 110 shanty town residents in urban Lima. RESULTS: Respectively 52% and 53% of urban and rural jungle populations were TST-positive. Using simultaneous tetanus and candida skin tests, 99% had at least one positive skin test. Generalised anergy was therefore rare, despite frequent intestinal parasitic infection, including 34% helminth infection prevalence in the jungle. TST positivity was associated with age (P = 0.001), known TB contact (P = 0.02) and poor household ventilation (P = 0.007). TST positivity was not significantly associated with crowding, reported past TB, single/multiple BCG vaccination, income, intestinal parasites, dietary factors, body mass index or body fat. Individuals with lower anthropometric body protein, as measured by corrected arm muscle area, were less likely to be TST-positive (P = 0.02), implying that protein malnutrition caused tuberculin-specific anergy. CONCLUSION: These results identify the importance of household ventilation for community TB transmission and add to the evidence that protein malnutrition suppresses TB immunity, causing false-negative TST results.