Search results

Background Many individuals who survive tuberculosis disease face ongoing disability and elevated mortality risks. However, the impact of post-tuberculosis sequelae is generally omitted from policy analyses and disease burden estimates. We therefore estimated the global burden of tuberculosis, inclusive of post-tuberculosis morbidity and mortality. Methods We constructed a hypothetical cohort of individuals developing tuberculosis in 2019, including pulmonary and extrapulmonary disease. We simulated lifetime health outcomes for this cohort, stratified by country, age, sex, HIV status, and treatment status. We used disability-adjusted life-years (DALYs) to summarise fatal and non-fatal health losses attributable to tuberculosis, during the disease episode and afterwards. We estimated post-tuberculosis mortality and morbidity based on the decreased lung function caused by pulmonary tuberculosis disease. Findings Globally, we estimated 122 (95% uncertainty interval [UI] 98–151) million DALYs due to incident tuberculosis disease in 2019, with 58 (38–83) million DALYs attributed to post-tuberculosis sequelae, representing 47% (95% UI 37–57) of the total burden estimate. The increase in burden from post-tuberculosis varied substantially across countries and regions, driven largely by differences in estimated case fatality for the disease episode. We estimated 12·1 DALYs (95% UI 10·0–14·9) per incident tuberculosis case, of which 6·3 DALYs (5·6–7·0) were from the disease episode and 5·8 DALYs (3·8–8·3) were from post-tuberculosis. Per-case post-tuberculosis burden estimates were greater for younger individuals, and in countries with high incidence rates. The burden of post-tuberculosis was spread over the remaining lifetime of tuberculosis survivors, with almost a third of total DALYs (28%, 95% UI 23–34) accruing 15 or more years after incident tuberculosis. Interpretation Post-tuberculosis sequelae add substantially to the overall disease burden caused by tuberculosis. This hitherto unquantified burden has been omitted from most previous policy analyses. Future policy analyses and burden estimates should take better account of post-tuberculosis, to avoid the potential misallocation of funding, political attention, and research effort resulting from continued neglect of this issue.

Background Tuberculosis causes more deaths than any other infectious disease globally. Bacillus Calmette‐Guérin (BCG) is the only available vaccine, but protection is incomplete and variable. The modified Vaccinia Ankara virus expressing antigen 85A (MVA85A) is a viral vector vaccine produced to prevent tuberculosis. Objectives To assess and summarize the effects of the MVA85A vaccine boosting BCG in humans. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and four other databases. We searched the WHO ICTRP and ClinicalTrials.gov. All searches were run up to 10 May 2018. Selection criteria We evaluated randomized controlled trials of MVA85A vaccine given with BCG in people regardless of age or HIV status. Data collection and analysis Two review authors independently assessed the eligibility and risk of bias of trials, and extracted and analyzed data. The primary outcome was active tuberculosis disease. We summarized dichotomous outcomes using risk ratios (RR) and risk differences (RD), with 95% confidence intervals (CI). Where appropriate, we combined data in meta‐analyses. Where meta‐analysis was inappropriate, we summarized results narratively. Main results The search identified six studies relating to four Phase 2 randomized controlled trials enrolling 3838 participants. Funding was by government bodies, charities, and philanthropic donors. Five studies included infants, one of them infants born to HIV‐positive mothers. One study included adults living with HIV. All trials included authors from Oxford University who led the laboratory development of the vaccine. Participants received intradermal MVA85A after BCG in some studies, and before selective deferred BCG in HIV‐exposed infants. The largest trial in 2797 African children was well conducted with low risk of bias for most parameters. Risk of bias was uncertain for selective reporting because there were no precise case definition endpoints for active tuberculosis published prior to the trial analysis. MVA85A added to BCG compared to BCG alone probably has no effect on the risk of developing microbiologically confirmed tuberculosis (RR 0.97, 95% CI 0.58 to 1.62; 3439 participants, 2 trials; moderate‐certainty evidence), or the risk of starting on tuberculosis treatment (RR 1.10, 95% CI 0.92 to 1.33; 3687 participants, 3 trials; moderate‐certainty evidence). MVA85A probably has no effect on the risk of developing latent tuberculosis (RR 1.01, 95% CI 0.85 to 1.21; 3831 participants, 4 trials; moderate‐certainty evidence). Vaccinating people with MVA85A in addition to BCG did not cause life‐threatening serious adverse effects (RD 0.00, 95% CI –0.00 to 0.00; 3692 participants, 3 trials; high‐certainty evidence). Vaccination with MVA85A is probably associated with an increased risk of local skin adverse effects (3187 participants, 3 trials; moderate‐certainty evidence), but not systemic adverse effect related to vaccination (144 participants, 1 trial; low‐certainty evidence). This safety profile is consistent with Phase 1 studies which outlined a transient, superficial reaction local to the injection site and mild short‐lived symptoms such as malaise and fever. Authors' conclusions MVA85A delivered by intradermal injection in addition to BCG is safe but not effective in reducing the risk of developing tuberculosis.

Background Tuberculosis (TB) is a leading cause of death from a single infectious agent, despite being largely curable and preventable. In 2019 an estimated 2.9 million of the 10 million people who fell ill with TB were not diagnosed or reported to the World Health Organization. The Political Declaration adopted by the United Nations General Assembly in September 2018 commits, amongst others, to diagnosing and treating 40 million people with TB by 2022. In order to achieve this ambitious target, there is an urgent need to deploy strategies to improve diagnosis and initiation of care for people with TB. One of them is systematic screening for TB disease, which is included in the End TB Strategy as a central component of its first pillar to ensure early diagnosis for all with TB. To help facilitate the implementation of TB screening at the country level, WHO published guidelines on screening for TB in 2013. Since then, there have been important new studies evaluating the impact of screening interventions on both individual-level and community-level outcomes related to TB, as well as new research evaluating innovative tools for screening for TB among important populations at high risk for TB disease. Overview In view of these new developments and upon demand by countries for more guidance, WHO convened a Guideline Development Group (GDG) in 2020 to examine the evidence and prepare WHO consolidated guidelines on tuberculosis. Module 2: Screening - Systematic screening for tuberculosis disease. As a result of this process a set of 17 new and updated recommendations for the screening of TB disease have been developed. These recommendations identify contacts of TB patients, people living with HIV, people exposed to silica, prisoners and other key populations to be prioritized for TB screening. The new guidance also recommends different tools for screening, namely symptom screening, chest radiography, computer-aided detection software, molecular WHO-approved rapid diagnostic tests, and C-reactive protein. The new recommendations are being released as part of a modular series of WHO guidance on TB and are accompanied by a complementary implementation guide.

Introduction: Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. Methods: We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. Results: Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. Conclusion: Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.

Objective To compare predeparture tuberculosis (TB) screening policies, including screening criteria and screening tests, and visa requirements for prospective migrants to high-income countries that have low to intermediate TB incidence and high immigration. Study design Systematic review of policy documents. Methods We systematically identified high-income, high net-migration countries with an estimated TB incidence of <30 per 100,000. After initial selection, this yielded 15 countries which potentially had TB screening policies. We performed a systematic search of governmental and official visa services' websites for these countries to identify visa information and policy documents for prospective migrants. Results were summarized, tabulated, and compared. Results Programs to screen for active TB were identified in all 15 countries, but screening criteria and screening tests varied substantially between countries. Prospective migrants' country of origin represented an initial assessment criterion which generally focused on elevated TB incidence based on World Health Organization data but also focused on the countries of origin that sent the most migrants, and this varied between destination countries. Specific categories of migrants represented a second assessment criterion that focused on duration of stay and reasons for migration; the focus of which showed variation between the destination countries. Specific screening tests including medical examination and chest X-rays were used as the final stage of assessment, and there were differences between which tests were used between the destination countries. Conclusions Current approaches to migrant TB screening are inconsistent in their approach and implementation. While this variation might reflect adaptation to local public health situations, it could also indicate uncertainty concerning optimal strategies. Comparative research studies are needed to define the most effective and efficient methods for TB screening of migrants.

Background: Tuberculosis elimination strategies in Brazil might neglect adolescents and young adults aged 10-24 years, hampering tuberculosis control. However, little is known about factors associated with tuberculosis treatment outcomes in this underserved group. In this study, we aimed to investigate social and health factors associated with unfavourable treatment outcomes in young people with tuberculosis in Brazil. Methods: A national retrospective cohort study was done using data from Sistema de Informação de Agravos de Notificação (SINAN), the national tuberculosis registry in Brazil. People aged 10-24 years (young people) with tuberculosis registered in SINAN between Jan 1, 2015, and Dec 31, 2018, were included. Unfavourable outcomes were defined as loss to follow-up, treatment failure, and death. Favourable outcome was defined as treatment success. Multiple logistic regression models estimated the association between social and health factors and tuberculosis treatment outcomes. Findings: 67 360 young people with tuberculosis were notified to SINAN, and we included 41 870 young people in our study. 7024 (17%) of the 41 870 included individuals had unfavourable treatment outcomes. Young people who received government cash transfers were less likely to have an unfavourable outcome (adjusted odds ratio 0·83, 95% CI 0·70-0·99). Homelessness (3·03, 2·07-4·42), HIV (2·89, 2·45-3·40), and illicit drug use (2·22, 1·93-2·55) were the main factors associated with unfavourable treatment outcome. Interpretation: In this national cohort of young people with tuberculosis in Brazil, tuberculosis treatment success rates were lower than WHO End TB Strategy targets, with almost a fifth of participants experiencing unfavourable treatment outcomes. Homelessness, HIV, and illicit drug use were the main factors associated with unfavourable outcome. In Brazil, strategies are required to support this underserved group to ensure favourable tuberculosis treatment outcomes.

Summary Objective To measure patient expenditure on additional drugs and tests in public services where tuberculosis (TB) drugs are supplied for free. Methods Questionnaire survey of patients currently on treatment in eight TB dispensaries in two provinces; in depth interviews with providers at the facilities. Results Liver protection drugs (141/163) were prescribed for 86% of patients, 93% had one or more tests in the last month, and 23% were on treatment past the World Health Organization-recommended treatment duration. All but two patients were charged for something in cash at each visit: on average 287 Chinese Yuan (40 US dollars) in the previous month. For patients below the poverty line, drug and test expenditure was 1.85 times their average household monthly income. Average charges varied little between income categories. In terms of anti-TB drugs prescribed, 17.8% of regimens were inadequate by international standards. Providers reported they prescribe liver protection drugs to avoid medical negligence, and they believed they were effective; and the government subsidy for providing TB treatment was simply not enough. Conclusions Despite an ostensibly fully subsidised TB programme in China, patients are charged substantive amounts irrespective of income. Research is needed to confirm these practices are widespread but this needs to be coupled with financing strategies to tackle it.

Setting A high proportion of notified tuberculosis cases in the Philippines are clinically diagnosed (63%) as opposed to bacteriologically confirmed. Better understanding of this phenomenon is required to improve tuberculosis control. Objectives To determine the percentage of smear negative presumptive tuberculosis patients that would be diagnosed by GeneXpert; compare clinical characteristics of patients diagnosed as tuberculosis cases; and review the impact that the current single government physician and a reconstituted Tuberculosis Diagnostic committee (expert panel) may have on tuberculosis over-diagnosis. Design This a cross-sectional study of 152 patients 15–85 years old with two negative Direct Sputum Smear Microscopy results, with abnormal chest X-ray who underwent GeneXpert testing and review by an expert panel. Results Thirty-two percent (48/152) of the sample were Xpert positive and 93% (97/104) of GeneXpert negatives were clinically diagnosed by a single physician. Typical symptoms and X-ray findings were higher in bacteriologically confirmed tuberculosis. When compared to the GeneXpert results the Expert panel's sensitivity for active tuberculosis was high (97.5%, 39/40), specificity was low (40.2%, 35/87). Conclusion Using the GeneXpert would increase the level of bacteriologically confirmed tuberculosis substantially among presumptive tuberculosis. An expert panel will greatly reduce over-diagnosis usually seen when a decision is made by a single physician.

Background: To achieve the WHO End TB Strategy targets, it is necessary to detect and treat more people with active TB early. Scale–up of active case finding (ACF) may be one strategy to achieve that goal. Given human resource constraints in the health systems of most high TB burden countries, volunteer community health workers (CHW) have been widely used to economically scale up TB ACF. However, more evidence is needed on the most cost-effective compensation models for these CHWs and their potential impact on case finding to inform optimal scale-up policies. Methods: We conducted a two-year, controlled intervention study in 12 districts of Ho Chi Minh City, Viet Nam. We engaged CHWs as salaried employees (3 districts) or incentivized volunteers (3 districts) to conduct ACF among contacts of people with TB and urban priority groups. Eligible persons were asked to attend health services for radiographic screening and rapid molecular diagnosis or smear microscopy. Individuals diagnosed with TB were linked to appropriate care. Six districts providing routine NTP care served as control area. We evaluated additional cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF by human resource model on TB case notifications. Results: We verbally screened 321,020 persons in the community, of whom 70,439 were eligible for testing and 1138 of them started TB treatment. ACF activities resulted in a + 15.9% [95% CI: + 15.0%, + 16.7%] rise in All Forms TB notifications in the intervention areas compared to control areas. The ITS analyses detected significant positive post-intervention trend differences in All Forms TB notification rates between the intervention and control areas (p = 0.001), as well as between the employee and volunteer human resource models (p = 0.021). Conclusions: Both salaried and volunteer CHW human resource models demonstrated additionality in case notifications compared to routine case finding by the government TB program. The salaried employee CHW model achieved a greater impact on notifications and should be prioritized for scale-up, given sufficient resources.

Background Mycobacterium Tuberculosis (TB) poses a substantial burden in sub-Saharan Africa and is the leading cause of death amongst infectious diseases. Randomised controlled trials (RCTs) are regarded as the gold standard for evaluating the effectiveness of interventions. We aimed to describe published TB treatment trials conducted in Africa. Methods This is a cross-sectional study of published TB trials conducted in at least one African country. In November 2019, we searched three databases using the validated Africa search filter and Cochrane's sensitive trial string. Published RCTs conducted in at least one African country were included for analysis. Records were screened for eligibility. Co-reviewers assisted with duplicate data extraction. Extracted data included: the country where studies were conducted, publication dates, ethics statement, trial registration number, participant's age range. We used Cochrane's Risk of Bias criteria to assess methodological quality. Results We identified 10,495 records; 175 trials were eligible for inclusion. RCTs were published between 1952 and 2019. The median sample size was 206 participants (interquartile range: 73–657). Most trials were conducted in South Africa (n = 83) and were drug therapy trials (n = 130). First authors were from 30 countries globally. South Africa had the most first authors (n = 55); followed by the United States of America (USA) (n = 28) and Great Britain (n = 14) with fewer other African countries contributing to the first author tally. Children under 13 years of age eligible to participate in the trials made up 17/175 trials (9.71%). International governments (n = 29) were the most prevalent funders. Ninety-four trials provided CONSORT flow diagrams. Methodological quality such as allocation concealment and blinding were poorly reported or unclear in most trials. Conclusions By mapping African TB trials, we were able to identify potential research gaps. Many of the global north's researchers were found to be the lead authors in these African trials. Few trials tested behavioural interventions compared to drugs, and far fewer tested interventions on children compared to adults to improve TB outcomes. Lastly, funders and researchers should ensure better methodological quality reporting of trials.

BACKGROUND Vietnam has a high burden of undetected tuberculosis (TB). The Vietnamese National TB Strategic Plan highlights active case-finding (ACF) as one strategy to find people with TB who are currently unreached by the existing government health services. The IMPACT TB (Implementing proven community-based active TB case-finding intervention) project was implemented across six districts of Ho Chi Minh City, 2017-2019. We aimed to explore the facilitators and barriers for ACF implementation during the IMPACT TB project to understand how and why the intervention achieved high yields. METHODS This was an exploratory qualitative study based on 39 semi-structured key-informant interviews with TB patients who were diagnosed through ACF, employees and volunteers who implemented ACF, and leaders from district, national, or international institutions and organizations in Vietnam. Thematic analysis was applied, using an implementation science framework by Grol and Wensing. RESULTS We generated three main themes: (1) the studied ACF model used in Vietnam provided a conducive social and organizational context for ACF implementation with areas for improvement, including communication and awareness-raising, preparation and logistics, data systems and processes, and incentives; (2) employees and volunteers capitalized on their strengths to facilitate ACF implementation, e.g., experience, skills, and communication; and (3) employees and volunteers were in a position to address patient-level barriers to ACF implementation, e.g., stigma, discrimination, and mistrust. These themes covered a variety of facilitators and barriers, which we divided into 17 categories. All categories were mentioned by employees and volunteers, except the category of having a network that facilitates ACF implementation, which was only mentioned by volunteers. This study also highlighted examples and ideas of how to address facilitators and barriers. CONCLUSIONS IMPACT TB provided a favorable social and organizational context for ACF implementation. Individual employees and volunteers still determined the success of the project, as they had to be able to capitalize on their own strengths and address patient-level barriers. Volunteers especially used their networks to facilitate ACF. Knowledge of both facilitators and barriers, and how to address them can inform the planning and implementation ACF in Vietnam and similar contexts across low- and middle-income countries worldwide.

Background Tuberculosis (TB) remains the most common cause of infectious disease deaths worldwide. What is perhaps less appreciated is that the caseload of tuberculosis patients in South Asia is staggering.South Asia has almost 40% of the global TB burden with 4,028,165 cases in 2015. This region also has a disproportionate share of TB deaths (681,975 deaths, 38% of the global burden). Worldwide just 12.5% of TB cases are in HIV positive individuals, but much research and investment has focused on HIV-associated TB. Only 3.5% of patients with tuberculosis in South Asia have HIV co-infection. Not surprisingly with such a huge burden of disease, this region has an estimated 184,336 multi drug resistant (MDR) cases among notified TB cases which accounts for a third of global MDR burden. Crucially, at least 70% of the estimated MDR cases remain untreated in this region and MDR treatment success ranged from only 46% for India to 88% for Sri Lanka in the 2012 cohort that received treatment. This region represents many of the drivers of the modern TB epidemic: rapid urbanization and high density populations with dramatically rising incidence of diabetes, a burgeoning and largely unregulated private sector with escalating drug resistance and high air pollution both outdoor and household. Conclusion From bacterial biochemistry to policy implementation, we suggest ways in which South Asia can seize the opportunity lead global TB elimination by demonstrating feasibility in some of the world's most densely populated cities and remotest reaches of the Himalayas. Clearly political will is essential, but we cannot defeat TB without understanding how to eliminate it in South Asia.

BACKGROUND Active case-finding (ACF), also referred to as community-based tuberculosis screening, is a component of the World Health Organization's End TB Strategy. ACF has potential benefits but also harms, which need to be carefully assessed when developing and implementing ACF policies. While empirical evidence on the benefits of ACF is still weak, evidence on the harms is even weaker. This study aimed to explore experts' views on the benefits and harms of ACF for people with presumptive TB and communities. METHODS This was an exploratory study. Semi-structured interviews were conducted with a purposive sample of 39 experts from international, non-governmental/non-profit organizations, funders, government institutions, international societies, think tanks, universities and research institutions worldwide. Framework analysis was applied. RESULTS Findings elaborated perceived benefits of ACF, including reaching vulnerable populations, reducing patient costs, helping raise awareness for tuberculosis among individuals and engaging communities, and reducing tuberculosis transmission. Perceived harms included increasing stigma and discrimination, causing false-positive diagnoses, as well as triggering other unintended consequences related to screening for tuberculosis patients, such as deportation of migrants once confirmed to have tuberculosis. Most of the perceived benefits of ACF could be linked to its objective of finding and treating persons with tuberculosis early (theme 1), while ACF was also perceived as a "double-edged sword" and could cause harms, if inappropriately designed and implemented (theme 2). The analysis underlined the importance of considering the benefits and harms of ACF throughout the screening pathway. The study provides new insights into the perceived benefits and harms of ACF from the perspectives of experts in the field. CONCLUSION This study highlights gaps in the evidence base surrounding ACF and can stimulate further research, debate and analysis regarding the benefits and harms of ACF to inform contextual optimization of design and implementation of ACF strategies.

Under-detection and -reporting in the private sector constitute a major barrier in Viet Nam's fight to end tuberculosis (TB). Effective private-sector engagement requires innovative approaches. We established an intermediary agency that incentivized private providers in two districts of Ho Chi Minh City to refer persons with presumptive TB and share data of unreported TB treatment from July 2017 to March 2019. We subsidized chest x-ray screening and Xpert MTB/RIF testing, and supported test logistics, recording, and reporting. Among 393 participating private providers, 32.1% (126/393) referred at least one symptomatic person, and 3.6% (14/393) reported TB patients treated in their practice. In total, the study identified 1203 people with TB through private provider engagement. Of these, 7.6% (91/1203) were referred for treatment in government facilities. The referrals led to a post-intervention increase of +8.5% in All Forms TB notifications in the intervention districts. The remaining 92.4% (1112/1203) of identified people with TB elected private-sector treatment and were not notified to the NTP. Had this private TB treatment been included in official notifications, the increase in All Forms TB notifications would have been +68.3%. Our evaluation showed that an intermediary agency model can potentially engage private providers in Viet Nam to notify many people with TB who are not being captured by the current system. This could have a substantial impact on transparency into disease burden and contribute significantly to the progress towards ending TB.

ABSTRACT Objective To explore antecedents, components and influencing factors on active case- finding (ACF) policy development and implementation. Design Scoping review, searching MEDLINE, Web of Science, the Cochrane Database of Systematic Reviews and the World Health Organization (WHO) Library from January 1968 to January 2018. We excluded studies focusing on latent tuberculosis (TB) infection, passive case- finding, childhood TB and studies about effectiveness, yield, accuracy and impact without descriptions of how this evidence has/could influence ACF policy or implementation. We included any type of study written in English, and conducted frequency and thematic analyses. Results Seventy- three articles fulfilled our eligibility criteria. Most (67%) were published after 2010. The studies were conducted in all WHO regions, but primarily in Africa (22%), Europe (23%) and the Western- Pacific region (12%). Forty- one percent of the studies were classified as quantitative, followed by reviews (22%) and qualitative studies (12%). Most articles focused on ACF for tuberculosis contacts (25%) or migrants (32%). Fourteen percent of the articles described community- based screening of high- risk populations. Fifty- nine percent of studies reported influencing factors for ACF implementation; mostly linked to the health system (eg, resources) and the community/individual (eg, social determinants of health). Only two articles highlighted factors influencing ACF policy development (eg, politics). Six articles described WHO's ACF- related recommendations as important antecedent for ACF. Key components of successful ACF implementation include health system capacity, mechanisms for integration, education and collaboration for ACF. Conclusion We identified some main themes regarding the antecedents, components and influencing factors for ACF policy development and implementation. While we know much about facilitators and barriers for ACF policy implementation, we know less about how to strengthen those facilitators and how to overcome those barriers. A major knowledge gap remains when it comes to understanding which contextual factors influence ACF policy development. Research is required to understand, inform and improve ACF policy development and implementation.