Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis.

BACKGROUND: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions. METHODS: We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results. FINDINGS: We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations. INTERPRETATION: The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission. FUNDING: Mr Willem Bakhuys Roozeboom Foundation.

Applicability of artificial intelligence-based computer-aided detection (AI-CAD) for pulmonary tuberculosis to community-based active case finding.

BACKGROUND: Artificial intelligence-based computer-aided detection (AI-CAD) for tuberculosis (TB) has become commercially available and several studies have been conducted to evaluate the performance of AI-CAD for pulmonary tuberculosis (TB) in clinical settings. However, little is known about its applicability to community-based active case-finding (ACF) for TB. METHODS: We analysed an anonymized data set obtained from a community-based ACF in Cambodia, targeting persons aged 55 years or over, persons with any TB symptoms, such as chronic cough, and persons at risk of TB, including household contacts. All of the participants in the ACF were screened by chest radiography (CXR) by Cambodian doctors, followed by Xpert test when they were eligible for sputum examination. Interpretation by an experienced chest physician and abnormality scoring by a newly developed AI-CAD were retrospectively conducted for the CXR images. With a reference of Xpert-positive TB or human interpretations, receiver operating characteristic (ROC) curves were drawn to evaluate the AI-CAD performance by area under the ROC curve (AUROC). In addition, its applicability to community-based ACFs in Cambodia was examined. RESULTS: TB scores of the AI-CAD were significantly associated with the CXR classifications as indicated by the severity of TB disease, and its AUROC as the bacteriological reference was 0.86 (95% confidence interval 0.83-0.89). Using a threshold for triage purposes, the human reading and bacteriological examination needed fell to 21% and 15%, respectively, detecting 95% of Xpert-positive TB in ACF. For screening purposes, we could detect 98% of Xpert-positive TB cases. CONCLUSIONS: AI-CAD is applicable to community-based ACF in high TB burden settings, where experienced human readers for CXR images are scarce. The use of AI-CAD in developing countries has the potential to expand CXR screening in community-based ACFs, with a substantial decrease in the workload on human readers and laboratory labour. Further studies are needed to generalize the results to other countries by increasing the sample size and comparing the AI-CAD performance with that of more human readers.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

Ending TB in South-East Asia: flagship priority and response transformation.

Over the decades, the global tuberculosis (TB) response has evolved from sanatoria-based treatment to DOTS (Directly Observed Therapy Shortcourse) strategy and the more recent End TB Strategy. The WHO South-East Asia Region, which accounted for 45% of new TB patients and 50% of deaths globally in 2021, is pivotal to the global fight against TB. "Accelerate Efforts to End TB" by 2030 was adopted as a South-East Asia Regional Flagship Priority (RFP) in 2017. This article illustrates intensified and transformed approaches to address the disease burden following the adoption of RFP and new challenges that emerged during the COVID-19 pandemic. TB case notifications improved by 25% and treatment success rates improved by 6% between 2016 and 2019 due to interventions ranging from galvanising political commitments to empowering and engaging communities. Cumulative TB programme budget allocations in 2022 reached US$ 1.4 billion, about two and a half times the budget in 2016. An ambitious Regional Strategic Plan towards ending TB, 2021-2025, identifies priority interventions that will need investments of up to US$ 3 billion a year to fully implement them. Moving forward, countries in the Region need to leverage RFP and take up intensified, people-centred, holistic interventions for prevention, diagnosis, treatment and care of TB with commensurate investments and cross-ministerial and multi-sectoral coordination.

Subclinical Tuberculosis Disease-A Review and Analysis of Prevalence Surveys to Inform Definitions, Burden, Associations, and Screening Methodology.

While it is known that a substantial proportion of individuals with tuberculosis disease (TB) present subclinically, usually defined as bacteriologically-confirmed but negative on symptom screening, considerable knowledge gaps remain. Our aim was to review data from TB prevalence population surveys and generate a consistent definition and framework for subclinical TB, enabling us to estimate the proportion of TB that is subclinical, explore associations with overall burden and program indicators, and evaluate the performance of screening strategies. We extracted data from all publicly available prevalence surveys conducted since 1990. Between 36.1% and 79.7% (median, 50.4%) of prevalent bacteriologically confirmed TB was subclinical. No association was found between prevalence of subclinical and all bacteriologically confirmed TB, patient diagnostic rate, or country-level HIV prevalence (P values, .32, .4, and .34, respectively). Chest Xray detected 89% (range, 73%-98%) of bacteriologically confirmed TB, highlighting the potential of optimizing current TB case-finding policies.

The Prevalence of Tuberculosis in Zambia: Results from the First National TB Prevalence Survey, 2013-2014.

BACKGROUND: Tuberculosis in Zambia is a major public health problem, however the country does not have reliable baseline data on the TB prevalence for impact measurement; therefore it was among the priority countries identified by the World Health Organization to conduct a national TB prevalence survey. OBJECTIVE: To estimate the prevalence of tuberculosis among the adult Zambian population aged 15 years and above, in 2013-2014. METHODS: A cross-sectional population-based survey was conducted in 66 clusters across all the 10 provinces of Zambia. Eligible participants aged 15 years and above were screened for TB symptoms, had a chest x-ray (CXR) performed and were offered an HIV test. Participants with TB symptoms and/or CXR abnormality underwent an in-depth interview and submitted one spot- and one morning sputum sample for smear microscopy and liquid culture. Digital data collection methods were used throughout the process. RESULTS: Of the 98,458 individuals who were enumerated, 54,830 (55.7%) were eligible to participate, and 46,099 (84.1%) participated. Of those who participated, 45,633/46,099 (99%) were screened by both symptom assessment and chest x-ray, while 466/46,099 (1.01%) were screened by interview only. 6,708 (14.6%) were eligible to submit sputum and 6,154/6,708 (91.7%) of them submitted at least one specimen for examination. MTB cases identified were 265/6,123 (4.3%). The estimated national adult prevalence of smear, culture and bacteriologically confirmed TB was 319/100,000 (232-406/100,000); 568/100,000 (440-697/100,000); and 638/100,000 (502-774/100,000) population, respectively. The risk of having TB was five times higher in the HIV positive than HIV negative individuals. The TB prevalence for all forms was estimated to be 455 /100,000 population for all age groups. CONCLUSION: The prevalence of tuberculosis in Zambia was higher than previously estimated. Innovative approaches are required to accelerate the control of TB.

The first national tuberculosis prevalence survey of Lao PDR (2010-2011).

OBJECTIVE: The objective of the study was to measure the prevalence of bacteriologically confirmed pulmonary tuberculosis (TB) in Lao PDR in 2010-2011. METHOD: A nationwide, multistage cluster-sampled cross-sectional survey was undertaken in 2010-2011. All consenting participants ≥15 years were screened for pulmonary TB with chest X-ray and symptom questionnaire. Two sputum specimens for bacteriological examination by microscopy and culture were collected from those who screened positive. Prevalence was estimated using multiple imputation and inverse probability weighting methods. RESULTS: Of 39 212 eligible participants from 50 clusters, 6290 participants provided at least one sputum sample for smear and culture. There were 237 bacteriologically confirmed pulmonary TB cases, 107 of which were smear-positive. Chest X-ray screening alone identified 230 (97.0%) cases compared with 118 (49.8%) by symptom screening alone. The estimated prevalence of smear-positive and bacteriologically confirmed TB in those ≥15 years was 278 per 100 000 (95%C.I. 199-356) and 595 per 100 000 (95%C.I. 457-733), respectively. Prevalence significantly increased with age and was higher in men than women. CONCLUSIONS: The prevalence of TB in Lao PDR is almost twice as high than previous estimates, with the greatest burden in the older population. Case detection efforts remain the primary goal of the national TB programme with case notifications being very low in comparison with the estimated number of prevalent cases. The survey observed major limitations with the diagnostic strategy of passive (symptom based) case finding that uses only direct smear microscopy for confirmation.

National tuberculosis prevalence surveys in Asia, 1990-2012: an overview of results and lessons learned.

OBJECTIVE AND METHODS: In many countries, national tuberculosis (TB) prevalence surveys are the only way to reliably measure the burden of TB disease and monitor trends. They can also provide evidence about the current performance of TB care and control and how this could be improved. We developed an inventory of Asian surveys from 1953 to 2012 and then compiled and analysed a standard set of data for all national surveys implemented between 1990 (the baseline year for 2015 global TB targets) and 2012. RESULTS: There were 21 surveys in 12 countries between 1990 and 2012; published results were available for 18. The participation rate was at least 80% and often much higher except for two surveys in Thailand. The prevalence of bacteriologically-positive TB disease among adults aged ≥15 years varied widely among countries (1.2 per 1000 population in China in 2010 to 15 per 1000 population in Cambodia in 2002), but age and sex distribution patterns were consistent with a progressive increase in rates of disease by age, and men accounting for 66-75% of prevalent cases. A high proportion of cases (40-79% across all surveys) did not report TB symptoms that met screening criteria (generally cough of 2-3 weeks or more, and blood in the sputum) and were only detected due to chest X-ray screening of all survey participants; this proportion increased over time in countries with repeat survey data. The ratio of prevalent cases to cases notified to national TB programmes was typically around two, but was as high as three in Lao PDR and Pakistan even after the internationally recommended TB control strategy had been implemented nationwide for several years. Four countries (China, Cambodia, the Republic of Korea and the Philippines demonstrated declines in smear or culture-positive pulmonary TB prevalence of approximately 50% over 10 years. CONCLUSIONS: National TB prevalence surveys in Asia show that large reductions in the prevalence of TB disease can be achieved within a decade, that men bear much more of the burden than women and that the epidemic is ageing. Comparisons among countries show that more can be achieved in TB control in some countries with existing strategies and technologies. However, with many prevalent cases not reporting classic TB symptoms, all countries face the challenge of defining and implementing strategies that will result in earlier detection and treatment of cases.

Choosing algorithms for TB screening: a modelling study to compare yield, predictive value and diagnostic burden.

BACKGROUND: To inform the choice of an appropriate screening and diagnostic algorithm for tuberculosis (TB) screening initiatives in different epidemiological settings, we compare algorithms composed of currently available methods. METHODS: Of twelve algorithms composed of screening for symptoms (prolonged cough or any TB symptom) and/or chest radiography abnormalities, and either sputum-smear microscopy (SSM) or Xpert MTB/RIF (XP) as confirmatory test we model algorithm outcomes and summarize the yield, number needed to screen (NNS) and positive predictive value (PPV) for different levels of TB prevalence. RESULTS: Screening for prolonged cough has low yield, 22% if confirmatory testing is by SSM and 32% if XP, and a high NNS, exceeding 1000 if TB prevalence is ≤0.5%. Due to low specificity the PPV of screening for any TB symptom followed by SSM is less than 50%, even if TB prevalence is 2%. CXR screening for TB abnormalities followed by XP has the highest case detection (87%) and lowest NNS, but is resource intensive. CXR as a second screen for symptom screen positives improves efficiency. CONCLUSIONS: The ideal algorithm does not exist. The choice will be setting specific, for which this study provides guidance. Generally an algorithm composed of CXR screening followed by confirmatory testing with XP can achieve the lowest NNS and highest PPV, and is the least amenable to setting-specific variation. However resource requirements for tests and equipment may be prohibitive in some settings and a reason to opt for symptom screening and SSM. To better inform disease control programs we need empirical data to confirm the modeled yield, cost-effectiveness studies, transmission models and a better screening test.

Cross-sectional studies of tuberculosis prevalence in Cambodia between 2002 and 2011.

OBJECTIVE: To measure trends in the pulmonary tuberculosis burden between 2002 and 2011 and to assess the impact of the DOTS (directly observed treatment, short-course) strategy in Cambodia. METHODS: Cambodia's first population-based nationwide tuberculosis survey, based on multistage cluster sampling, was conducted in 2002. The second tuberculosis survey, encompassing 62 clusters, followed in 2011. Participants aged 15 years or older were screened for active pulmonary tuberculosis with chest radiography and/or for tuberculosis symptoms. For diagnostic confirmation, sputum smear and culture were conducted on those whose screening results were positive. FINDINGS: Of the 40,423 eligible subjects, 37,417 (92.6%) participated in the survey; 103 smear-positive cases and 211 smear-negative, culture-positive cases were identified. The weighted prevalences of smear-positive tuberculosis and bacteriologically-positive tuberculosis were 271 (95% confidence interval, CI: 212-348) and 831 (95% CI: 707-977) per 100,000 population, respectively. Tuberculosis prevalence was higher in men than women and increased with age. A 38% decline in smear-positive tuberculosis (P = 0.0085) was observed with respect to the 2002 survey, after participants were matched by demographic and geographical characteristics. The prevalence of symptomatic, smear-positive tuberculosis decreased by 56% (P = 0.001), whereas the prevalence of asymptomatic, smear-positive tuberculosis decreased by only 7% (P = 0.7249). CONCLUSION: The tuberculosis burden in Cambodia has declined significantly, most probably because of the decentralization of DOTS to health centres. To further reduce the tuberculosis burden in Cambodia, tuberculosis control should be strengthened and should focus on identifying cases without symptoms and in the middle-aged and elderly population.

Analysis of tuberculosis prevalence surveys: new guidance on best-practice methods.

BACKGROUND: An unprecedented number of nationwide tuberculosis (TB) prevalence surveys will be implemented between 2010 and 2015, to better estimate the burden of disease caused by TB and assess whether global targets for TB control set for 2015 are achieved. It is crucial that results are analysed using best-practice methods. OBJECTIVE: To provide new theoretical and practical guidance on best-practice methods for the analysis of TB prevalence surveys, including analyses at the individual as well as cluster level and correction for biases arising from missing data. ANALYTIC METHODS: TB prevalence surveys have a cluster sample survey design; typically 50-100 clusters are selected, with 400-1000 eligible individuals in each cluster. The strategy recommended by the World Health Organization (WHO) for diagnosing pulmonary TB in a nationwide survey is symptom and chest X-ray screening, followed by smear microscopy and culture examinations for those with an abnormal X-ray and/or TB symptoms. Three possible methods of analysis are described and explained. Method 1 is restricted to participants, and individuals with missing data on smear and/or culture results are excluded. Method 2 includes all eligible individuals irrespective of participation, through multiple missing value imputation. Method 3 is restricted to participants, with multiple missing value imputation for individuals with missing smear and/or culture results, and inverse probability weighting to represent all eligible individuals. The results for each method are then compared and illustrated using data from the 2007 national TB prevalence survey in the Philippines. Simulation studies are used to investigate the performance of each method. KEY FINDINGS: A cluster-level analysis, and Methods 1 and 2, gave similar prevalence estimates (660 per 100,000 aged ≥ 10 years old), with a higher estimate using Method 3 (680 per 100,000). Simulation studies for each of 4 plausible scenarios show that Method 3 performs best, with Method 1 systematically underestimating TB prevalence by around 10%. CONCLUSION: Both cluster-level and individual-level analyses should be conducted, and individual-level analyses should be conducted both with and without multiple missing value imputation. Method 3 is the safest approach to correct the bias introduced by missing data and provides the single best estimate of TB prevalence at the population level.

Equity and the Sun Quality Health Private Provider Social Franchise: comparative analysis of patient survey data and a nationally representative TB prevalence survey.

INTRODUCTION: Since 2004, the Sun Quality Health (SQH) franchise network has provided TB care in Myanmar through a network of established private medical clinics. This study compares the wealth distribution of the TB patients to non-TB patients to determine if TB is most common among the poor, and compares the wealth of all TB patients to SQH TB patients to assess whether the franchise achieves its goal of serving the poor. METHODS: The study uses data from two sources: 1) Myanmar's first nationally representative TB prevalence study conducted in 2009, and 2) client exit interviews from TB patients from SQH clinics. In total, 1,114 TB-positive individuals were included in the study, including 739 from the national sample and 375 from the SQH sample. RESULTS: TB patients at SQH clinics were poorer than TB-positive individuals in the overall population, though not at a statistically significant level (p > 0.05). After stratification we found that in urban areas, TB patients at SQH clinics were more likely to be in the poorest quartile compared to general TB positive population (16.8% vs. 8.6%, respectively; p < 0.05). In rural areas, there was no statistically significant difference between the wealth distribution of SQH clinic patients and general TB positive individuals (p > 0.05). CONCLUSION: Franchised clinics in Myanmar are reaching poor populations of TB patients in urban areas; more efforts are needed in order to reach the most vulnerable in rural areas.

[National surveys of the prevalence of tuberculosis disease--overview, progress and lessons learnt].

This is a summary of an invited lecture at the 88th annual assembly of the Japanese Society for Tuberculosis on 28 March 2013. The lecture was carried out in Japanese. The WHO's Global Task Force on TB Impact Measurement was established in June 2006 to produce a robust, rigorous and widely-endorsed assessment of whether the 2015 targets for reductions in TB incidence, prevalence and mortality are achieved at global and regional levels and in individual countries; to regularly report on progress towards these targets in the years leading up to 2015; and strengthen national capacity in monitoring and evaluation of TB control. Three major and inter-related areas of work were defined and working groups were established to cover each of these areas, Surveillance, Prevalence surveys, and Estimates of TB burden, in 2007. x-ray screening and culture diagnosis between 2007 and today (March 2013). At least six countries are expected to launch a survey in 2013, and seven are already in a pipeline to launch one in 2014. These surveys provide an unbiased estimation of disease burden that is often higher than it was thought when the survey was planned especially in Asian countries. Surveys are also providing a rich source of data to inform programme policy and strategy: In this lecture, lessons learnt from surveys in China, Cambodia and Myanmar were discussed to show impact of DOTS as well as its limitations and challenges caused by rapidly ageing populations in Asia. An overall synthesis of the main implications of the results from recent prevalence surveys implemented in Asia and Africa for post-2015 global TB policy and strategy is also in the pipeline. The summary results and implications will be widely disseminated from 2014 when the results of the surveys in African countries are finalized.

Stopping tuberculosis in the 21st century: goals and strategies.

The Stop TB Strategy and the Global Plan to Stop TB were launched in 2006 to achieve the tuberculosis (TB)-related Millennium Development Goals and the Stop TB Partnership targets, and to address new challenges such as that of HIV-associated TB and multi-drug-resistant TB. This paper reviews the historical and recent progress in TB control to show what has changed since the introduction of directly observed therapy (DOTS) in the mid-1990s, why we needed the new strategy and what the global agenda is today. Major progress was seen in most countries in the last two decades. Globally, the estimated rates of TB prevalence and mortality are declining, but not quickly enough to reach the 2015 Stop TB Partnership targets of halving TB prevalence and death rates compared with 1990. In 2007, it was estimated that more than one-third of TB patients were not detected or properly treated under proper conditions. Enhancing case detection, while maintaining high treatment success rates, is essential to achieve the 2015 targets. The ultimate goal of TB control is the elimination of the disease as a public health problem. The Stop TB Partnership aims at eliminating TB by 2050 by reaching a global incidence of disease of less than one case per million population. This target will not be achieved unless TB control efforts are further intensified and effective and affordable new technologies to prevent both disease and infection are developed and rapidly introduced in all countries worldwide.

Decentralized DOTS shortens delay to TB treatment significantly in Cambodia.

SETTING: Rural districts in Cambodia with and without decentralized health center based DOTS program. OBJECTIVE: To compare delays to treatment and behavior of patients up to diagnosis, between the pilot districts where DOTS is decentralized through the health centers, and the control districts where DOTS is provided through hospitals. DESIGN: A cross sectional study with structured questionnaire interviews to all new smear-positive TB patients aged 15 years or older who were registered in the study sites from May 1st to July 31st in 2002. RESULTS: The total delay in the pilot districts was significantly shorter than that in the control districts (median 58 days vs. 232 days, p < 0.01). The median doctors' delay within TB service in the pilot districts was 10 days and that in the control was 6 days. The period between first consultation to any health care provider and first visit to a TB service center, subsequent contact delay, was longer than any other type of delay and significantly different (24 days in pilot vs. 185 days in control, p < 0.01). The distance and travel costs to a TB service center were the factors associated with delay in seeking diagnosis of tuberculosis. No other variables had any significant association with the delay. CONCLUSION: Decentralizing DOTS to primary care health centers is highly effective in reducing the delay to TB treatment in Cambodia.