Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.

Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

Alcohol use, drunkenness and tobacco smoking in rural western Kenya.

OBJECTIVES: To describe the prevalence of smoking and alcohol use and abuse in an impoverished rural region of western Kenya. METHODS: Picked from a population-based longitudinal database of demographic and health census data, 72 292 adults (≥18 years) were asked to self-report their recent (within the past 30 days) and lifetime use of tobacco and alcohol and frequency of recent 'drunkenness'. RESULTS: Overall prevalence of ever smoking was 11.2% (11.0-11.5) and of ever drinking, 20.7% (20.4-21.0). The prevalence of current smoking was 6.3% (6.1-6.5); 5.7% (5.5-5.9) smoked daily. 7.3% (7.1-7.5) reported drinking alcohol within the past 30 days. Of these, 60.3% (58.9-61.6) reported being drunk on half or more of all drinking occasions. The percentage of current smokers rose with the number of drinking days in a month (P < 0.0001). Tobacco and alcohol use increased with decreasing socio-economic status and amongst women in the oldest age group (P < 0.0001). CONCLUSIONS: Tobacco and alcohol use are prevalent in this rural region of Kenya. Abuse of alcohol is common and likely influenced by the availability of cheap, home-manufactured alcohol. Appropriate evidence-based policies to reduce alcohol and tobacco use should be widely implemented and complemented by public health efforts to increase awareness of their harmful effects.

Antiretroviral therapy uptake among adult tuberculosis patients newly diagnosed with HIV in Nyanza Province, Kenya.

SETTING: In 2008, the Kenya tuberculosis (TB) program reported low (31%) antiretroviral therapy (ART) uptake among human immunodeficiency virus (HIV) infected TB patients. OBJECTIVE: To confirm ART coverage and identify factors associated with HIV clinic enrollment and ART initiation among TB patients. DESIGN: Retrospective chart abstraction of adult TB patients newly diagnosed with HIV and eligible for ART at 58 Nyanza Province TB clinics between October 2006 and April 2008. TB data were linked to HIV clinic data at 50 facilities that provided ART. Associations with HIV clinic enrollment and ART were evaluated. RESULTS: Among 1137 ART-eligible TB patient records sampled, 32% documented HIV clinic enrollment and 29% ART. Date fields were largely incomplete; 11% of the patient records included HIV testing dates and ≤1% had dates for cotrimoxazole prophylaxis, HIV clinic enrollment and ART initiation. Adding HIV clinic data increased HIV clinic enrollment and ART documentation to respectively 62% and 44%. Among TB patients in HIV care, female sex, older age group and baseline CD4 documentation were associated with ART initiation. CONCLUSION: Linking data increased documentation of HIV clinic enrollment and ART uptake. Continued efforts are required to improve the documentation of HIV service delivery, especially in TB clinics. Interventions to increase ART uptake are needed for younger patients and men.

What are the most sensitive and specific sign and symptom combinations for influenza in patients hospitalized with acute respiratory illness? Results from western Kenya, January 2007-July 2010.

Influenza causes severe illness and deaths, and global surveillance systems use different clinical case definitions to identify patients for diagnostic testing. We used data collected during January 2007-July 2010 at hospital-based influenza surveillance sites in western Kenya to calculate sensitivity, specificity, positive predictive value, and negative predictive value for eight clinical sign/symptom combinations in hospitalized patients with acute respiratory illnesses, including severe acute respiratory illness (SARI) (persons aged 2-59 months: cough or difficulty breathing with an elevated respiratory rate or a danger sign; persons aged ≥5 years: temperature ≥38 °C, difficulty breathing, and cough or sore throat) and influenza-like illness (ILI) (all ages: temperature ≥38 °C and cough or sore throat). Overall, 4800 persons aged ≥2 months were tested for influenza; 416 (9%) had laboratory-confirmed influenza infections. The symptom combination of cough with fever (subjective or measured ≥38 °C) had high sensitivity [87·0%, 95% confidence interval (CI) 83·3-88·9], and ILI had high specificity (70·0%, 95% CI 68·6-71·3). The case definition combining cough and any fever is a simple, sensitive case definition for influenza in hospitalized persons of all age groups, whereas the ILI case definition is the most specific. The SARI case definition did not maximize sensitivity or specificity.

Risk factors for excess mortality and death in adults with tuberculosis in Western Kenya.

OBJECTIVES: To evaluate excess mortality and risk factors for death during anti-tuberculosis treatment in Western Kenya. METHODS: We abstracted surveillance data and compared mortality rates during anti-tuberculosis treatment with all-cause mortality from a health and demographic surveillance population to obtain standardised mortality ratios (SMRs). Risk factors for excess mortality were obtained using a relative survival model, and for death during treatment using a proportional hazards regression model. RESULTS: The crude mortality rate during anti-tuberculosis treatment was 18.0 (95%CI 16.8-19.2) per 100 person-years. The age and sex SMR was 8.8 (95%CI 8.2-9.4). Excess mortality was greater in human immunodeficiency virus (HIV) positive TB patients (excess hazard ratio [eHR] 2.1, 95%CI 1.5-3.1), and lower in patients who were female or started treatment in a later year. Mortality was high in patients with unknown HIV status (HR 2.9, 95%CI 2.2-3.8) or, if HIV-positive, not on antiretroviral treatment (ART; HR 3.3, 95%CI 2.5-4.5) or not known to be on ART (HR 2.8, 95%CI 2.1-3.7). The attributable fraction of incomplete uptake of HIV testing and ART on mortality was 31% (95%CI 15-45) compared to HIV-positive patients on ART. CONCLUSION: Increasing the uptake of HIV testing and ART would further reduce mortality during anti-tuberculosis treatment by an estimated 31%.

Concordance of programmatic and laboratory-based multidrug-resistant tuberculosis treatment outcomes in Peru.

BACKGROUND: Confirmation of cure for multidrug-resistant tuberculosis (MDR-TB) patients requires laboratory tests for Mycobacterium tuberculosis growth on culture media. Outcome decisions dictate patient management, and inaccuracies place patients at an increased risk of morbidity and mortality, and may contribute to continued transmission of MDR-TB. OBJECTIVE: To examine concordance between programmatic and laboratory-based MDR-TB treatment outcomes. METHODS: The study population included 1658 MDR-TB patients in Peru treated between 1996 and 2002 with both program and laboratory-based outcomes. Laboratory-based outcomes were assigned according to international standards requiring at least five consecutive negative cultures in the last 12 months of treatment to confirm cure. RESULTS: Compared to the global culture-defined standard classification, only 1.1% of treatment successes, but 54.3% of failures, were misclassified programmatically. Overall, 10.4% of patients identified by a clinician as having a successful treatment outcome still had cultures positive for MDR-TB. CONCLUSION: Most patients with successful treatment outcomes by strict culture definitions were also classified by clinicians as having successful outcomes. However, many culture-confirmed failures were missed. In light of delays and incomplete access to culture in MDR-TB programs, efforts should be made to improve the accuracy of programmatically determined treatment outcomes.

Performance of six commercial enzyme immunoassays and two alternative HIV-testing algorithms for the diagnosis of HIV-1 infection in Kisumu, Western Kenya.

Performances of serological parallel and serial testing algorithms were analyzed using a combination of three ELISA and three rapid tests for the confirmation of HIV infection. Each was assessed individually for their sensitivity and specificity on a blinded panel of 769 retrospective sera of known HIV status. Western blot was used as a confirmatory assay for discordant results. Subsequently, one parallel and one serial testing algorithm were assessed on a new panel of 912 HIV-positive and negative samples. Individual evaluation of the ELISAs and rapid tests indicated a sensitivity of 100% for all assays except Uni-Gold with 99.7%. The specificities ranged from 99.1% to 99.4% for rapid assays and from 97.5% to 99.1% for ELISAs. A parallel and serial testing algorithms using Enzygnost and Vironostika, and Determine followed by Uni-Gold respectively, showed 100% sensitivity and specificity. The cost for testing 912 samples was US$4.74 and US$ 1.9 per sample in parallel and serial testing respectively. Parallel or serial testing algorithm yielded a sensitivity and specificity of 100%. This alternative algorithm is reliable and reduces the occurrence of both false negatives and positives. The serial testing algorithm was more cost effective for diagnosing HIV infections in this population.

Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002.

SETTING: Brooklyn Chest Hospital, Western Cape, South Africa. OBJECTIVE: To evaluate the treatment outcome and 2- and 5-year follow-up of patients treated for multidrug-resistant tuberculosis (MDR-TB) with individualized regimens. DESIGN: Retrospective cohort study of all MDR-TB patients starting treatment during 1992-2002. Patients were evaluated every 6 months for 2 years after treatment and at 5 years when possible. RESULTS: Over 11 years, 491 (66%) of 747 MDR-TB patients received treatment with two or more second-line drugs; 239 (49%) were cured or completed treatment, 68 (14%) died, 144 (29%) defaulted from treatment, 27 (5%) failed, 10 (2%) transferred out and 3 (<1%) remained on treatment. Only 176 (36%) were tested for human immunodeficiency virus and 15 were positive. The proportion with a successful MDR-TB treatment outcome declined over time, while the proportion who defaulted remained stable. Among 410 patients who had not transferred out or died, 281 (69%) had 2-year data available: 185 (66%) were cured or completed treatment, 32 (11%) were retreated for TB and 64 (23%) died. CONCLUSIONS: Under program conditions in the West Coast/Winelands District, default rates were high and treatment success rates low. Outreach strategies for MDR-TB treatment should only be implemented if adequate resources are committed to the program.

Using program evaluation to improve the performance of a TB-HIV project in Banteay Meanchey, Cambodia.

SETTING: Cambodia has the highest human immunodeficiency virus (HIV) prevalence (1.9%) and tuberculosis (TB) incidence (508/100000) in Asia. Banteay Meanchey, a province with high HIV prevalence of 1.9%, established a pilot project in 2003 to enhance TB-HIV activities. We evaluated this project to improve performance. METHODS: In March 2005, we analyzed 17 months of data on all persons diagnosed with HIV or TB at 11 participating clinics. We determined barriers to HIV testing and TB screening, modified the program to reduce these barriers and assessed whether our interventions improved testing and screening rates. RESULTS: Among 952 patients newly diagnosed with TB disease, 138 (14%) had known HIV infection at the time of TB diagnosis. Of the 814 TB patients with unknown HIV status, 432 (53%) were HIV tested. Of 1228 persons newly diagnosed with HIV infection, 450 (37%) were screened for TB disease. We found and addressed barriers to HIV testing and TB screening. In the 9 months after the interventions, 240/322 (71%) TB patients were HIV tested, an increase of 34% (P < 0.01); 426/751 (57%) HIV-infected patients were screened for TB, an increase of 54% (P < 0.01). CONCLUSION: Evaluations of TB-HIV collaborative activities can lead to increased TB screening and HIV testing rates.

Successful use of rifampicin for Hispanic foreign-born patients with latent tuberculosis infection.

SETTING: Four months of rifampicin (4R) is recommended for the treatment of latent tuberculosis infection (LTBI), although data regarding its use are limited. The majority of tuberculosis (TB) cases in the USA occur among foreign-born persons. OBJECTIVE: To determine tolerability, hepatotoxicity and completion rates associated with 4R among foreign-born persons. DESIGN: We retrospectively evaluated 4R treatment among a cohort of predominantly Hispanic foreign-born LTBI patients in four Middle-Tennessee public health clinics from February 2000 to February 2004. Patients' charts were reviewed to abstract demographic, social and clinical data. 4R completion rates, new symptoms and hepatotoxicity (serum aminoalanine transferase >or=120U/l with gastrointestinal symptoms or >or=200 regardless of symptoms) were evaluated. RESULTS: Of 749 patients treated, 571 (76%) completed 4R. Among all subjects, Hispanics had a lower risk of non-completion (OR 0.6, 95%CI 0.4-0.7) than non-Hispanics. Among non-Hispanic subjects, the risk of non-completion was higher for Blacks than non-Blacks (adjusted OR 2.6, 95%CI 1.5-4.7), but was lower for foreign-born than non-foreign-born subjects (adjusted OR 0.5, 95%CI 0.2-0.9). During treatment, 85 subjects (11%) developed new symptoms, and hepatotoxicity occurred in three patients. CONCLUSION: With high completion rates and minimal side effects, 4R is a favorable LTBI treatment regimen for Hispanic and other foreign-born patients.

The epidemiology of HIV-associated tuberculosis in rural Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: The World Health Organization recommends human immunodeficiency virus (HIV) testing for all tuberculosis (TB) patients and TB screening for all HIV-infected persons in countries with a TB-HIV syndemic. We sought to determine whether evidence supports implementing these recommendations in South-East Asia. DESIGN: We conducted a cross-sectional survey and retrospective cohort study of patients newly diagnosed with HIV or TB from October 2003 to February 2005 to identify risk factors for HIV infection and TB, and for death during TB treatment. RESULTS: HIV infection was diagnosed in 216/574 (38%) TB patients. TB disease was found in 124/450 (24%) HIV-infected persons. No sub-groups of patients had a low risk of HIV infection or TB. Of 180 TB patients with HIV infection and a recorded treatment outcome, 49 (27%) died compared to 17/357 (5%) without HIV infection (relative risk [RR] 5.2, 95% confidence interval [CI] 3.1-8.7). HIV-infected TB patients with smear-negative pulmonary disease died less frequently than those with smear-positive pulmonary disease (RR 0.39, 95%CI 0.16-0.93). CONCLUSIONS: No sub-groups of patients had low risk for HIV infection or TB, and mortality among HIV-infected TB patients was high. These data justify using the WHO global TB-HIV recommendations in South-East Asia. Urgent interventions are needed to reduce the high mortality rate in HIV-infected TB patients.

Reaching the targets for tuberculosis control: the impact of HIV.

In 1991, the 44th World Health Assembly set two key targets for global tuberculosis (TB) control to be reached by 2000: 70% case detection of acid-fast bacilli smear-positive TB patients under the DOTS strategy recommended by WHO and 85% treatment success of those detected. This paper describes how TB control was scaled up to achieve these targets; it also considers the barriers encountered in reaching the targets, with a particular focus on how HIV infection affects TB control. Strong TB control will be facilitated by scaling-up WHO-recommended TB/HIV collaborative activities and by improving coordination between HIV and TB control programmes; in particular, to ensure control of drug-resistant TB. Required activities include more HIV counselling and testing of TB patients, greater use and acceptance of isoniazid as a preventive treatment in HIV-infected individuals, screening for active TB in HIV-care settings, and provision of universal access to antiretroviral treatment for all HIV-infected individuals eligible for such treatment. Integration of TB and HIV services in all facilities (i.e. in HIV-care settings and in TB clinics), especially at the periphery, is needed to effectively treat those infected with both diseases, to prolong their survival and to maximize limited human resources. Global TB targets can be met, particularly if there is renewed attention to TB/HIV collaborative activities combined with tremendous political commitment and will.

Risk factors associated with default from multidrug-resistant tuberculosis treatment, South Africa, 1999-2001.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment centers in five provinces, South Africa. OBJECTIVES: To estimate the mortality and evaluate risk factors associated with default from MDR-TB treatment. DESIGN: Using registries and a standardized questionnaire, we conducted a case-control study among patients diagnosed and treated for MDR-TB. Cases were defined as patients who began MDR-TB treatment between 1 October 1999 and 30 September 2001 and defaulted from treatment for more than 2 months; controls were defined as patients who began MDR-TB treatment during the same time and were cured, completed or failed. RESULTS: After initial identification and reclassification, 269 cases and 401 controls were confirmed eligible for interview. Further investigation revealed that 74 (27%) cases and 44 (10%) controls had died. Among 96 cases located who consented and were interviewed, 70% had defaulted after receiving at least 6 months of treatment. In a multivariate model, the strongest individual risk factors for default included reporting smoking marijuana or mandrax during treatment, and having an unsatisfactory opinion about the attitude of health care workers. CONCLUSION: Mortality among MDR-TB defaulters was high. Interventions to reduce default from MDR-TB treatment should center on substance abuse treatment, patient education and support and improving provider-patient relationships.

TST reversion in a BCG-revaccinated population of nursing and medical students, São Paulo, Brazil, 1997-2000.

SETTING: A major university in São Paulo, Brazil, where vaccination against tuberculosis (TB) with bacille Calmette-Guerin (BCG) was routinely offered to first-year medical and nursing students. OBJECTIVES: To estimate the probability of negative tuberculin skin test (TST) results over a 4-year period following BCG revaccination, and to evaluate the effect of factors associated with reversion. DESIGN: Students were enrolled in 1997, initially given a two-step TST, and were retested annually or biannually for the duration of the study. Data on TB exposures and potential risk factors for TST negativity and reversion were collected through annual surveys. A linear mixture survival model was used to estimate the probability of negative TST results over time. RESULTS: Of 159 students, an estimated 20% had a negative TST result despite revaccination, and a further 31% reverted to negative over 4 years of follow-up. No cofactors significantly affected the probability of reversion. CONCLUSION: Overall, in the absence of reported exposure to Mycobacterium tuberculosis, 51% of students revaccinated upon entering nursing or medical school would have a negative TST result by the time they begin their internships. In this recently vaccinated population, reversion was common, suggesting that annual TST screening may remain a useful tool.

Improved sensitivity of sputum smear microscopy after processing specimens with C18-carboxypropylbetaine to detect acid-fast bacilli: a study of United States-bound immigrants from Vietnam.

The goal of this study was to evaluate the effect of the specimen-processing method that uses the detergent C18-carboxypropylbetaine (CB-18) on the sensitivity of acid-fast bacillus (AFB) staining. Vietnamese immigrants with abnormal chest radiographs provided up to three sputum specimens, which were examined for acid-fast bacilli by use of direct auramine and Ziehl-Neelsen staining. The remaining sputum was split; half was cultured, and the other half was incubated with CB-18 for 24 h, centrifuged, and examined for AFB by both staining methods. CB-18 processing improved the sensitivity of AFB staining by 20 to 30% (only differences in auramine sensitivity were statistically significant) but reduced specificity by approximately 20% (P < 0.05). These findings have direct utility for overseas migrant tuberculosis screening programs, for which maximizing test sensitivity is a major objective.

Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis.

SETTING: Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist. OBJECTIVE: To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy. DESIGN: Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement. RESULTS: Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs. CONCLUSION: Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.

Capacity building for international tuberculosis control through operations research training.

SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the national, provincial, and even district levels have the basic analytical and epidemiological skills necessary for collecting and analyzing quality data pertaining to national TB control program (NTP) improvements. This includes setting program priorities, operations planning, and implementing and evaluating program activities. OBJECTIVES: To present a model course for building capacity in basic epidemiology and operations research (OR). DESIGN: A combination of didactic lectures and applied field exercises were used to achieve the main objectives of the 6-day OR course. These were to increase the understanding of quantitative and qualitative research concepts, study design, and analytic methods, and to increase awareness of how these methods apply to the epidemiology and control of TB; and to demonstrate the potential uses of OR in answering practical questions on NTP effectiveness. As a final outcome, course participants develop OR proposals that are funded and later implemented. RESULTS: Since 1997, this OR course has been conducted nine times in five countries; 149 key NTP and laboratory staff have been trained in OR methods, and 44 OR protocols have been completed or are underway. CONCLUSION: This low-cost model course can be adapted to a wide range of public health issues.

A multicenter evaluation of tuberculin skin test positivity and conversion among health care workers in Brazilian hospitals.

SETTING: Four general Brazilian hospitals. OBJECTIVE: To assess the occupational risk of Mycobacterium tuberculosis (TB) in participating hospitals. DESIGN: In phase one of this longitudinal study, a cross-sectional survey documented baseline tuberculin skin test (TST) positivity rates. In phase two, TST conversion rates were evaluated in participants with an initial negative two-step TST. TST conversion data were analyzed to determine risk factors for TB infection using an increase of > or = 10 mm compared to baseline TST. RESULTS: The initial TST positivity rate was 63.1%; the follow-up TST conversion rate was 10.7 per 1000 person-months (p-m). Hospital of employment, recent bacille Calmette-Guerin (BCG) vaccination, nosocomial TB exposure, and employment as a nurse were independent risk factors for TST conversion. Hospitals without TB infection control measures had higher conversion rates than those with control measures (16.0 vs. 7.8/ 1000 p-m, P < 0.001). CONCLUSIONS: This study indicates an important occupational risk of infection in health care settings with a high TB incidence. Longitudinal TST studies are a valuable tool to assess the occupational risk of TB, even in BCG-vaccinated populations, and should be used to direct limited resources for infection control.

Substandard tuberculosis drugs on the global market and their simple detection.

SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To maximize the effectiveness of tuberculosis (TB) control efforts, simple, inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH) and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were collected from selected TB programs and pharmacies in Colombia, Estonia, India, Latvia, Russia and Vietnam. Samples were screened using a recently developed thin-layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of normal formulations were further analyzed using confirmatory techniques. Samples outside of 85% to 115% of stated content, and/or containing compounds other than the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40) of all samples, including 13% (4/30) RMP samples, contained <85% of stated content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were substandard. A comparison of TLC with the confirmatory analysis for RMP analysis showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of 100% (24/24). An analysis of INH showed a specificity of 90% (9/10). However, sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial number of anti-tuberculosis drugs from several countries, in particular FDCs, were found to be substandard. Such drugs may contribute to the creation of drug-resistant TB. TLC is an effective, convenient, and inexpensive method for the detection of substandard drugs.