Sequential adaptive strategies for sampling rare clustered populations.

A new class of sampling strategies is proposed that can be applied to population-based surveys targeting a rare trait that is unevenly spread over an area of interest. Our proposal is characterised by the ability to tailor the data collection to specific features and challenges of the survey at hand. It is based on integrating an adaptive component into a sequential selection, which aims both to intensify the detection of positive cases, upon exploiting the spatial clustering, and to provide a flexible framework to manage logistics and budget constraints. A class of estimators is also proposed to account for the selection bias, that are proved unbiased for the population mean (prevalence) as well as consistent and asymptotically Normal distributed. Unbiased variance estimation is also provided. A ready-to-implement weighting system is developed for estimation purposes. Two special strategies included in the proposed class are presented, that are based on the Poisson sampling and proved more efficient. The selection of primary sampling units is also illustrated for tuberculosis prevalence surveys, which are recommended in many countries and supported by the World Health Organisation as an emblematic example of the need for an improved sampling design. Simulation results are given in the tuberculosis application to illustrate the strengths and weaknesses of the proposed sequential adaptive sampling strategies with respect to traditional cross-sectional non-informative sampling as currently suggested by World Health Organisation guidelines.

Global Epidemiology of Tuberculosis and Progress Toward Meeting Global Targets - Worldwide, 2018.

Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1), including among persons living with human immunodeficiency virus (HIV) infection (2). A World Health Organization (WHO) initiative, The End Tuberculosis Strategy, set ambitious targets for 2020-2035, including 20% reduction in TB incidence and 35% reduction in the absolute number of TB deaths by 2020 and 90% reduction in TB incidence and 95% reduction in TB deaths by 2035, compared with 2015 (3). This report evaluated global progress toward these targets based on data reported by WHO (1). Annual TB data routinely reported to WHO by 194 member states were used to estimate TB incidence and mortality overall and among persons with HIV infection, TB-preventive treatment (TPT) initiation, and drug-resistant TB for 2018 (1). In 2018, an estimated 10 million persons had incident TB, and 1.5 million TB-related deaths occurred, representing 2% and 5% declines from 2017, respectively. The number of persons with both incident and prevalent TB remained highest in the WHO South-East Asia and African regions. Decreases in the European region were on track to meet 2020 targets. Globally, among persons living with HIV, 862,000 incident TB cases occurred, and 1.8 million persons initiated TPT. Rifampicin-resistant or multidrug-resistant TB occurred among 3.4% of persons with new TB and 18% among persons who were previously treated for TB (overall, among 4.8% of persons with TB). The modest decreases in the number of persons with TB and the number of TB-related deaths were consistent with recent trends, and new and substantial progress was observed in increased TPT initiation among persons living with HIV. However, to meet the global targets for 2035, more intensive efforts are needed by public health partners to decrease TB incidence and deaths and increase the number of persons receiving TB curative and preventive treatment. Innovative approaches to case finding, scale-up of TB preventive treatment, use of newer TB treatment regimens, and prevention and control of HIV will contribute to decreasing TB.

Prevention of tuberculosis in household members: estimates of children eligible for treatment.

OBJECTIVE: To estimate of the number of children younger than 5 years who were household contacts of people with tuberculosis and were eligible for tuberculosis preventive treatment in 2017. METHODS: To estimate the number of eligible children, we obtained national values for the number of notified cases of bacteriologically confirmed pulmonary tuberculosis in 2017, the proportion of the population younger than 5 years in 2017 and average household size from published sources. We obtained global values for the number of active tuberculosis cases per household with an index case and for the prevalence of latent tuberculosis infection among children younger than 5 years who were household contacts of a tuberculosis case through systematic reviews, meta-analysis and Poisson regression models. FINDINGS: The estimated number of children younger than 5 years eligible for tuberculosis preventive treatment in 2017 globally was 1.27 million (95% uncertainty interval, UI: 1.24-1.31), which corresponded to an estimated global coverage of preventive treatment in children of 23% at best. By country, the estimated number ranged from less than one in the Bahamas, Iceland, Luxembourg and Malta to 350 000 (95% UI: 320 000-380 000) in India. Regionally, the highest estimates were for the World Health Organization (WHO) South-East Asia Region (510 000; 95% UI: 450 000-580 000) and the WHO African Region (470 000; 95% UI: 440 000-490 000). CONCLUSION: Tuberculosis preventive treatment in children was underutilized globally in 2017. Treatment should be scaled up to help eliminate the pool of tuberculosis infection and achieve the End TB Strategy targets.

Global Epidemiology of Tuberculosis and Progress Toward Achieving Global Targets - 2017.

Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious disease agent (1) and the leading cause of death among persons living with human immunodeficiency virus (HIV) infection, accounting for approximately 40% of deaths in this population (2). The United Nations' (UN) Sustainable Development Goals (3) and the World Health Organization's (WHO's) End TB Strategy (4) have defined ambitious targets for 2020-2035, including a 35% reduction in the absolute number of TB deaths and a 20% reduction in TB incidence by 2020, compared with 2015 (4). Since 2000, WHO has produced annual TB estimates for all countries (1). Global and regional disease estimates were evaluated for 2017 to determine progress toward meeting targets. In 2017, an estimated 10 million incident cases of TB and 1.57 million TB deaths occurred, representing 1.8% and 3.9% declines, respectively, from 2016. Numbers of TB cases and disease incidence were highest in the WHO South-East Asia and Africa regions, and 9% of cases occurred among persons with HIV infection. Rifampicin-resistant (RR) or multidrug-resistant (MDR) (resistance to at least both isoniazid and rifampicin) TB occurred among 3.6% and 18% of new and previously treated TB cases, respectively (5.6% among all cases). Overall progress in global TB elimination was modest in 2017, consistent with that in recent years (1); intensified efforts to improve TB diagnosis, treatment, and prevention are required to meet global targets for 2020-2035.

The incidence of tuberculosis among adolescents and young adults: a global estimate.

Historical data show that the risk of tuberculosis increases dramatically during adolescence, and young people face unique challenges in terms of case detection and effective treatment. However, little is known about the burden of tuberculosis among young people in the modern era. This study aimed to provide the first estimates of the global and regional incidence of tuberculosis among young people aged 10-24 years.Using the World Health Organization (WHO) database of tuberculosis notifications for 2012, we estimated the burden of tuberculosis among young people by WHO region. Adjustments were made for incomplete age disaggregation and underreporting, using supplementary data from several countries representing diverse tuberculosis epidemics.We estimate that 1.78 million (uncertainty interval (UI) 1.23-3.00 million) young people developed tuberculosis in 2012, accounting for 17% of all new tuberculosis cases globally. Young people in the WHO South East Asian Region (721 000, UI 473 000-1.35 million) and the WHO African Region (534 000, UI 359 000-912 000) experienced the greatest number of tuberculosis episodes.Young people suffer a considerable burden of tuberculosis. Age-specific burden of disease estimation for this age group is complicated by incomplete age disaggregation of tuberculosis data, highlighting the importance of continued surveillance system strengthening.

Incidence and prevalence of bacteriologically confirmed pulmonary tuberculosis among adolescents and young adults: a systematic review.

The burden of tuberculosis (TB) among adolescents and young adults in endemic settings is poorly characterised. This study aimed to review published and unpublished estimates of the incidence and prevalence of bacteriologically confirmed TB among young people aged 10-24 years. We searched PubMed and World Health Organization archives for publications and unpublished data from population-based epidemiologic studies reporting confirmed pulmonary TB among young people, conducted from January 2000 onwards. We identified 27 publications and unpublished data from two national surveys, representing a total of 26 studies in 19 countries. The prevalence of bacteriologically confirmed TB ranged from 45 to 799 per 100 000 in the Asia-Pacific region and from 160 to 462 per 100 000 in African settings. We did not identify any epidemiologic studies of confirmed TB among adolescents living with human immunodeficiency virus (HIV). Many studies were excluded due to absent or inadequately reported age-specific data. Adolescents and young adults living in many endemic settings appear to be at substantial risk of developing active TB. There is a pressing need to improve the routine reporting of age in epidemiologic studies of TB, and to generate high-quality epidemiologic data regarding TB among adolescents living with HIV.

A four-month gatifloxacin-containing regimen for treating tuberculosis.

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 patients) was 3.5 percentage points (95% confidence interval, -0.7 to 7.7). There was heterogeneity across countries (P=0.02 for interaction, with differences in the rate of an unfavorable outcome ranging from -5.4 percentage points in Guinea to 12.3 percentage points in Senegal) and in baseline cavitary status (P=0.04 for interaction) and body-mass index (P=0.10 for interaction). The standard regimen, as compared with the 4-month regimen, was associated with a higher dropout rate during treatment (5.0% vs. 2.7%) and more treatment failures (2.4% vs. 1.7%) but fewer recurrences (7.1% vs. 14.6%). There was no evidence of increased risks of prolongation of the QT interval or dysglycemia with the 4-month regimen. CONCLUSIONS: Noninferiority of the 4-month regimen to the standard regimen with respect to the primary efficacy end point was not shown. (Funded by the Special Program for Research and Training in Tropical Diseases and others; ClinicalTrials.gov number, NCT00216385.).

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.

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.

Effect of intermittent preventive treatment for malaria during infancy on serological responses to measles and other vaccines used in the Expanded Programme on Immunization: results from five randomised controlled trials.

BACKGROUND: Intermittent preventive treatment for malaria during infancy (IPTi) is the administration of a full therapeutic course of antimalarial drugs to infants living in settings where malaria is endemic, at the time of routine vaccination in the first year of life. We investigated whether IPTi with sulfadoxine-pyrimethamine or other antimalarial drug combinations adversely affected serological responses to vaccines used in the Expanded Programme on Immunization (EPI). METHODS: The study was done in a subset of children enrolled in five randomised controlled trials in Navrongo, Ghana; Kilimanjaro, Tanzania; Manhica, Mozambique; Kisumu, Kenya; and Bungoma, Kenya. All infants presenting for the second dose of the diphtheria-tetanus-pertussis vaccination (given at 8-10 weeks of age) were eligible, and analyses included all children who had received measles vaccination (at 9 months of age) and at least one dose of IPTi or placebo. Blood samples were collected before and after vaccination, and antibody titres were measured by plaque reduction neutralisation (measles, yellow fever), microneutralisation (polio serotypes 1 and 3), and ELISA (all other EPI antigens). Laboratory personnel were unaware of the randomisation groups. We compared the proportion of infants in the IPTi and placebo groups who did not attain protective antibody titres after vaccination, using a one-sided significance non-inferiority margin of 5% for measles (the primary endpoint) and 10% for other EPI antigens. FINDINGS: Between September, 2000, and May, 2008, 8416 children were enrolled in the five studies. Paired samples from 2368 children from sites where sulfadoxine-pyrimethamine was compared with placebo were analysed for measles antibodies. 464 children with detectable measles antibody in their sample before vaccination were excluded, leaving 1904 individuals (934 placebo and 970 sulfadoxine-pyrimethamine) in the study. IPTi with sulfadoxine-pyrimethamine did not have a clinically significant effect on immune responses to measles vaccine; 61 of 970 (6·3%) children who received IPTi did not develop a protective antibody response after measles vaccination compared with 60 of 934 (6·4%) who received placebo, a difference of -0·14% (95% CI -2·3 to 2·1). When other antimalarial drugs were used for IPTi the results were much the same. Among 2396 children from whom serological response data for other EPI antigens were available, we identified no evidence of an adverse effect of IPTi with sulfadoxine-pyrimethamine or other antimalarial drugs on the proportion achieving protective antibody concentrations. INTERPRETATION: IPTi with sulfadoxine-pyrimethamine does not affect serological responses to EPI vaccines. This analysis, therefore, supports the WHO recommendation for coadministration of IPTi with sulfadoxine-pyrimethamine to infants at the time of the second and third doses of DTP and measles vaccination, in areas of sub-Saharan Africa with moderate to high malaria transmission and where malaria parasites are sensitive to these drugs. It also suggests that treatment of clinical malaria at or around the time of vaccination does not compromise vaccine responsiveness. FUNDING: Bill & Melinda Gates Foundation.

Multidrug-resistant tuberculosis in children: evidence from global surveillance.

Multidrug-resistant tuberculosis (MDR-TB) can affect persons of any age, but it remains unknown whether children are more or less likely than adults to have MDR-TB. Representative drug resistance surveillance data reported to the World Health Organization between 1994 and 2011 were analysed to test the association between MDR-TB and age group (children aged <15 years versus adults aged ≥ 15 years), using odds ratios derived by logistic regression with robust standard errors. Of 85 countries with data from nationwide surveys or surveillance systems, 35 reported at least one paediatric MDR-TB case. Aggregated data on age and drug susceptibility testing for 323 046 tuberculosis cases notified in these 35 countries were analysed. Odds ratios for MDR-TB in children compared to adults varied widely between countries. In Germany, Namibia, South Africa, the UK and the USA, MDR-TB was positively associated with age <15 years. In the remaining countries no association was established. Despite the limitations intrinsic to the use of surveillance data and to the challenges of diagnosing childhood tuberculosis, our analysis suggests that proportions of MDR-TB in children and adults are similar in many settings. Of particular concern is the association found between age <15 years and MDR-TB in southern African countries with high HIV prevalence.

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.

Prevention, diagnosis, and treatment of tuberculosis in children and mothers: evidence for action for maternal, neonatal, and child health services.

Tuberculosis affected an estimated 8.8 million people and caused 1.4 million deaths globally in 2010, including a half-million women and at least 64 000 children. It also results in nearly 10 million cumulative orphans due to parental deaths. Moreover, it causes 6%-15% of all maternal mortality, which increases to 15%-34% if only indirect causes are considered. Increasingly, more women with tuberculosis are notified than men in settings with a high prevalence of human immunodeficiency virus (HIV), and maternal tuberculosis increases the vertical transmission of HIV. Tuberculosis prevention, diagnosis, and treatment services should be included as key interventions in the integrated management of pregnancy and child health. Tuberculosis screening using a simple clinical algorithm that relies on the absence of current cough, fever, weight loss, and night sweats should be used to identify eligible pregnant women living with HIV for isoniazid preventive therapy or for further investigation for tuberculosis disease as part of services for prevention of vertical HIV transmission. While implementing these simple, low-cost, effective interventions as part of maternal, neonatal, and child health services, the unmet basic and operational tuberculosis research needs of children, pregnant, and breastfeeding women should be addressed. National policy makers, program managers, and international stakeholders (eg, United Nations bodies, donors, and implementers) working on maternal, neonatal, and child health, especially in HIV-prevalent settings, should give due attention and include tuberculosis prevention, diagnosis, and treatment services as part of their core functions and address the public health impacts of tuberculosis in their programs and services.

Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007-2010.

OBJECTIVE: To present a global update of drug-resistant tuberculosis (TB) and explore trends in 1994-2010. METHODS: Data on drug resistance among new and previously treated TB patients, as reported by countries to the World Health Organization, were analysed. Such data are collected through surveys of a representative sample of TB patients or surveillance systems based on routine drug susceptibility testing. Associations between multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection and sex were explored through logistic regression. FINDINGS: In 2007-2010, 80 countries and 8 territories reported surveillance data. MDR-TB among new and previously treated cases was highest in the Russian Federation (Murmansk oblast, 28.9%) and the Republic of Moldova (65.1%), respectively. In three former Soviet Union countries and South Africa, more than 10% of the cases of MDR-TB were extensively drug-resistant. Globally, in 1994 to 2010 multidrug resistance was observed in 3.4% (95% confidence interval, CI: 1.9-5.0) of all new TB cases and in 19.8% (95% CI: 14.4-25.1) of previously treated TB cases. No overall associations between MDR-TB and HIV infection (odds ratio, OR: 1.4; 95% CI: 0.7-3.0) or sex (OR: 1.1; 95% CI: 0.8-1.4) were found. Between 1994 and 2010, MDR-TB rates in the general population increased in Botswana, Peru, the Republic of Korea and declined in Estonia, Latvia and the United States of America. CONCLUSION: The highest global rates of MDR-TB ever reported were documented in 2009 and 2010. Trends in MDR-TB are still unclear in most settings. Better surveillance or survey data are required, especially from Africa and India.

Addressing the Data Gaps on Child and Adolescent Tuberculosis.

The burden of tuberculosis (TB) among children and young adolescents (<15 years old) is estimated at 1.1 million; however, only 400,000 are treated for TB, indicating a large gap between the number who are cared for and the number estimated to have TB. Accurate data on the burden of pediatric TB is essential to guide action. Despite several improvements in estimating the burden of pediatric TB in the last decade, as well as enhanced data collection efforts, several data gaps remain, both at the global level, but also at the national level where surveillance systems and collaborative research are critical. In this article, we describe recent advances in data collection and burden estimates for TB among children and adolescents, and the remaining gaps. While data collection continues to improve, burden estimates must evolve in parallel, both in terms of their frequency and the methods used. Currently, at the global level, there is a focus on age-disaggregation of TB notifications, the collection of data on TB-HIV, multi-drug resistant (MDR)-TB and treatment outcomes, as well as estimates of the disease burden. Additional data from national surveillance systems or research projects on TB meningitis, as well as other forms of extra-pulmonary TB, would be useful. We must capitalize on the current momentum in child and adolescent TB to close the remaining data gaps for these age groups to better understand the epidemic and further reduce morbidity and mortality due to TB.

Prevalence of bacteriologically confirmed pulmonary tuberculosis in South Africa, 2017-19: a multistage, cluster-based, cross-sectional survey.

BACKGROUND: Tuberculosis remains an important clinical and public health issue in South Africa, which has one of the highest tuberculosis burdens in the world. We aimed to estimate the burden of bacteriologically confirmed pulmonary tuberculosis among people aged 15 years or older in South Africa. METHODS: This multistage, cluster-based, cross-sectional survey included eligible residents (age ≥15 years, who had slept in a house for ≥10 nights in the preceding 2 weeks) in 110 clusters nationally (cluster size of 500 people; selected by probability proportional-to-population size sampling). Participants completed face-to-face symptom questionnaires (for cough, weight loss, fever, and night sweats) and manually read digital chest X-ray screening. Screening was recorded as positive if participants had at least one symptom or an abnormal chest X-ray suggestive of tuberculosis, or a combination thereof. Sputum samples from participants who were screen-positive were tested by the Xpert MTB/RIF Ultra assay (first sample) and Mycobacteria Growth Indicator Tube culture (second sample), with optional HIV testing. Participants with a positive Mycobacterium tuberculosis complex culture were considered positive for bacteriologically confirmed pulmonary tuberculosis; when culture was not positive, participants with a positive Xpert MTB/RIF Ultra result with an abnormal chest X-ray suggestive of active tuberculosis and without current or previous tuberculosis were considered positive for bacteriologically confirmed pulmonary tuberculosis. FINDINGS: Between Aug 15, 2017, and July 28, 2019, 68 771 people were enumerated from 110 clusters, with 53 250 eligible to participate in the survey, of whom 35 191 (66·1%) participated. 9066 (25·8%) of 35 191 participants were screen-positive and 234 (0·7%) were identified as having bacteriologically confirmed pulmonary tuberculosis. Overall, the estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 852 cases (95% CI 679-1026) per 100 000 population; the prevalence was highest in people aged 35-44 years (1107 cases [95% CI 703-1511] per 100 000 population) and those aged 65 years or older (1104 cases [680-1528] per 100 000 population). The estimated prevalence was approximately 1·6 times higher in men than in women (1094 cases [95% CI 835-1352] per 100 000 population vs 675 cases [494-855] per 100 000 population). 135 (57·7%) of 234 participants with tuberculosis screened positive by chest X-ray only, 16 (6·8%) by symptoms only, and 82 (35·9%) by both. 55 (28·8%) of 191 participants with tuberculosis with known HIV status were HIV-positive. INTERPRETATION: Pulmonary tuberculosis prevalence in this survey was high, especially in men. Despite the ongoing burden of HIV, many participants with tuberculosis in this survey did not have HIV. As more than half of the participants with tuberculosis had an abnormal chest X-ray without symptoms, prioritising chest X-ray screening could substantially increase case finding. FUNDING: Global Fund, Bill & Melinda Gates Foundation, USAID.

Lives saved by tuberculosis control and prospects for achieving the 2015 global target for reducing tuberculosis mortality.

OBJECTIVE: To assess whether the global target of halving tuberculosis (TB) mortality between 1990 and 2015 can be achieved and to conduct the first global assessment of the lives saved by the DOTS/Stop TB Strategy of the World Health Organization (WHO). METHODS: Mortality from TB since 1990 was estimated for 213 countries using established methods endorsed by WHO. Mortality trends were estimated separately for people with and without human immunodeficiency virus (HIV) infection in accordance with the International classification of diseases. Lives saved by the DOTS/Stop TB Strategy were estimated with respect to the performance of TB control in 1995, the year that DOTS was introduced. FINDINGS: TB mortality among HIV-negative (HIV-) people fell from 30 to 20 per 100,000 population (36%) between 1990 and 2009 and could be halved by 2015. The overall decline (when including HIV-positive [HIV+] people, who comprise 12% of all TB cases) was 19%. Between 1995 and 2009, 49 million TB patients were treated under the DOTS/Stop TB Strategy. This saved 4.6-6.3 million lives, including those of 0.23-0.28 million children and 1.4-1.7 million women of childbearing age. A further 1 million lives could be saved annually by 2015. CONCLUSION: Improvements in TB care and control since 1995 have greatly reduced TB mortality, saved millions of lives and brought within reach the global target of halving TB deaths by 2015 relative to 1990. Intensified efforts to reduce deaths among HIV+ TB cases are needed, especially in sub-Saharan Africa.

Methods for estimating tuberculosis incidence and mortality by age and sex.

AIMS: To develop methods to disaggregate World Health Orgagnization estimates of tuberculosis (TB) incidence and mortality for each country by sex and age. METHODS: For countries where incidence estimates derived from a factor adjustment of notifications and case detection ratio over 0.85, or with <1000 reported TB cases, we disaggregated incidence proportional to notifications. For each other country, a prior was constructed using a hierarchical model of age-stratified prevalence survey data, meta-analysis of sex ratios, and mathematical modelling for children under 15 years. Samples from this prior were used to disaggregate incidence and accepted if incidence exceeded notifications in each age/sex category. Results were inspected and, if implausible, incidence was disaggregated proportional to notifications. Mortality was disaggregated proportional to patterns in vital registration (VR) data in countries with VR data. Where VR data were lacking, a case-fatality ratio (CFR) approach was applied to estimated incidence, with separate CFRs by HIV/ART status, child/adult age groups, and anti-TB treatment status. Uncertainty in all disaggregated country estimates was constructed to be consistent with corresponding overall uncertainty. RESULTS: We generated disaggregated results for 216 countries. For 125 countries, incidence disaggregation was based on notifications. Of the rest, accepted samples from the prior were considered implausible in 4 countries. For 72 countries, mortality disaggregation was based on VR data; the rest were based on the CFR approach. CONCLUSIONS: While multi-stage, this approach is comparatively simple in overall logic. Disaggregated estimates have relatively larger uncertainty and should be used with caution.