Towards elimination of chronic viral hepatitis in French Polynesia: results from a national population-based survey.

Background: In French Polynesia, hepatitis B virus (HBV) infection appears as a major risk factor for hepatocellular carcinoma (HCC), which detection rate in the Austral archipelago is among the highest in the world. Through a nationally representative cross-sectional survey of the adult population, this study aimed at assessing the prevalence of HBV, but also hepatitis C virus (HCV), and hepatitis delta virus (HDV). Methods: A total of 1942 blood samples from participants aged 18-69 years were tested for anti-HBc, anti-HBs, HBsAg, anti-HCV IgG, and HDV RNA. Complete genome sequencing of detected HBV strains was performed. Findings: Among participants, 315/1834, 582/1834, 33/1834, 0/1857, and 0/33 tested positive for anti-HBc, anti-HBs, HBsAg, anti-HCV IgG, and HDV RNA, respectively. The population prevalence of HBsAg was estimated at 1.0% (95% CI: 0.6-1.7). All HBsAg carriers were born in French Polynesia before vaccination at birth became mandatory. In multivariate analyses, identified factors associated with HBsAg carriage included: the archipelago of residence (p < 0.0001), age (p < 0.0001), and education level (p = 0.0077). HBV genotypes B, C, and F were detected. Interpretation: French Polynesia has a low endemicity level of HBV and its population may be considered at low risk for HCV and HDV infection. However, prevalence of HBsAg was found concerning in Austral (3.8%; 95% CI: 1.9-7.5) and Marquesas (6.5%; 95% CI: 3.8-11) archipelagoes. In the Austral archipelago, the presence of genotype C may account for the elevated rate of HCC. Our findings warrant more efforts to improve access to detection, prevention and care to people born before the systematic vaccination policy application, and residing in higher-risk areas, to achieve HBV elimination in French Polynesia. Funding: Research Delegation of French Polynesia.

Transmission modeling to infer tuberculosis incidence prevalence and mortality in settings with generalized HIV epidemics.

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore develop a novel age-structured TB transmission model incorporating evolving demographic, HIV and antiretroviral therapy effects, and calibrate to TB prevalence and notification data from 12 African countries. We use Bayesian methods to include uncertainty for all TB model parameters, and estimate age-specific annual risks of TB infection, finding up to 16.0%/year in adults, and the proportion of TB incidence from recent (re)infection, finding a mean across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.

25 years of surveillance of drug-resistant tuberculosis: achievements, challenges, and way forward.

Tuberculosis is second only to COVID-19 as a cause of death from a single infectious agent. In 2020, almost 10 million people were estimated to have developed tuberculosis and it caused 1·5 million deaths. Around a quarter of deaths caused by antimicrobial resistance are due to rifampicin-resistant tuberculosis. Antimicrobial resistance surveillance systems for many bacterial pathogens are still in the early stages of implementation in many countries, and do not yet allow for the estimation of disease burden at the national level. In this Personal View, we present the achievements, challenges, and way forward for the oldest and largest global antimicrobial resistance surveillance system. Hosted by WHO since 1994, the Global Project on Anti-Tuberculosis Drug Resistance Surveillance has served as a platform for the evaluation of the trends in anti-tuberculosis drug resistance for over 25 years at country, regional, and global levels. With an estimated 465 000 incident cases of multidrug-resistant and rifampicin-resistant tuberculosis in 2019, drug-resistant tuberculosis remains a public health crisis. The COVID-19 pandemic has reversed years of progress in providing essential tuberculosis services and reducing disease burden. The number of people diagnosed with drug-resistant tuberculosis has dropped by 22% since before the pandemic, and the number of patients provided with treatment for drug-resistant tuberculosis has dropped by 15%. Now more than ever, closing gaps in the detection of drug-resistant tuberculosis requires investment in research and development of new diagnostic tools and their rollout, expansion of sample transport systems, and the implementation of data connectivity solutions.

A call for standardised age-disaggregated health data.

The 2030 Sustainable Development Goals agenda calls for health data to be disaggregated by age. However, age groupings used to record and report health data vary greatly, hindering the harmonisation, comparability, and usefulness of these data, within and across countries. This variability has become especially evident during the COVID-19 pandemic, when there was an urgent need for rapid cross-country analyses of epidemiological patterns by age to direct public health action, but such analyses were limited by the lack of standard age categories. In this Personal View, we propose a recommended set of age groupings to address this issue. These groupings are informed by age-specific patterns of morbidity, mortality, and health risks, and by opportunities for prevention and disease intervention. We recommend age groupings of 5 years for all health data, except for those younger than 5 years, during which time there are rapid biological and physiological changes that justify a finer disaggregation. Although the focus of this Personal View is on the standardisation of the analysis and display of age groups, we also outline the challenges faced in collecting data on exact age, especially for health facilities and surveillance data. The proposed age disaggregation should facilitate targeted, age-specific policies and actions for health care and disease management.

Epidemiology of Tuberculosis and Progress Toward Meeting Global Targets - Worldwide, 2019.

Although tuberculosis (TB) is curable and preventable, in 2019, TB remained the leading cause of death from a single infectious agent worldwide and the leading cause of death among persons living with HIV infection (1). The World Health Organization's (WHO's) End TB Strategy set ambitious targets for 2020, including a 20% reduction in TB incidence and a 35% reduction in the number of TB deaths compared with 2015, as well as zero TB-affected households facing catastrophic costs (defined as costs exceeding 20% of annual household income) (2). In addition, during the 2018 United Nations High-Level Meeting on TB (UNHLM-TB), all member states committed to setting 2018-2022 targets that included provision of TB treatment to 40 million persons and TB preventive treatment (TPT) to 30 million persons, including 6 million persons living with HIV infection and 24 million household contacts of patients with confirmed TB (4 million aged <5 years and 20 million aged ≥5 years) (3,4). Annual data reported to WHO by 215 countries and territories, supplemented by surveys assessing TB prevalence and patient costs in some countries, were used to estimate TB incidence, the number of persons accessing TB curative and preventive treatment, and the percentage of TB-affected households facing catastrophic costs (1). Globally, TB illness developed in an estimated 10 million persons in 2019, representing a decline in incidence of 2.3% from 2018 and 9% since 2015. An estimated 1.4 million TB-related deaths occurred, a decline of 7% from 2018 and 14% since 2015. Although progress has been made, the world is not on track to achieve the 2020 End TB Strategy incidence and mortality targets (1). Efforts to expand access to TB curative and preventive treatment need to be substantially amplified for UNHLM-TB 2022 targets to be met.

Bayesian evidence synthesis to estimate subnational TB incidence: An application in Brazil.

BACKGROUND: Evidence on local disease burden and the completeness of case detection represent important information for TB control programs. We present a new method for estimating subnational TB incidence and the fraction of individuals with incident TB who are diagnosed and treated in Brazil. METHODS: We compiled data on TB notifications and TB-related mortality in Brazil and specified an analytic model approximating incidence as the number of individuals exiting untreated active disease (sum of treatment initiation, death before treatment, and self-cure). We employed a Bayesian inference approach to synthesize data and adjust for known sources of bias. We estimated TB incidence and the fraction of cases treated, for each Brazilian state and the Federal District over 2008-2017. FINDINGS: For 2017, TB incidence was estimated as 41.5 (95 % interval: 40.7, 42.5) per 100 000 nationally, and ranged from 11.7-88.3 per 100 000 across states. The fraction of cases treated was estimated as 91.9 % (89.6 %, 93.7 %) nationally and ranged 86.0 %-94.8 % across states, with an estimated 6.9 (5.3, 9.2) thousand cases going untreated in 2017. Over 2008-2017, incidence declined at an average annual rate of 1.4 % (1.1 %, 1.9 %) nationally, and -1.1%-4.2 % across states. Over this period there was a 0.5 % (0.2 %, 0.9 %) average annual increase in the fraction of incident TB cases treated. INTERPRETATION: Time-series estimates of TB burden and the fraction of cases treated can be derived from routinely-collected data and used to understand variation in TB outcomes and trends.

Decline of Tuberculosis Burden in Vietnam Measured by Consecutive National Surveys, 2007-2017.

Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%-55.4%), from 199 (95% CI 160-248) cases/100,000 adults in 2007 to 125 (95% CI 98-159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%-69.7%), from 99 (95% CI 78-125) cases/100,000 adults to 46 (95% CI 32-68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.

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.

Monitoring the status of selected health related sustainable development goals: methods and projections to 2030.

Background: Monitoring Sustainable Development Goal indicators (SDGs) and their targets plays an important role in understanding and advocating for improved health outcomes for all countries. We present the United Nations (UN) Inter-agency groups' efforts to support countries to report on SDG health indicators, project progress towards 2030 targets and build country accountability for action. Objective: We highlight common principles and practices of each Inter-agency group and the progress made towards SDG 3 targets using seven health indicators as examples. The indicators used provide examples of best practice for modelling estimates and projections using standard methods, transparent data collection and country consultations. Methods: Practices common to the UN agencies include multi-UN agency participation, expert groups to advise on estimation methods, transparent publication of methods and data inputs, use of UN-derived population estimates, country consultations, and a common reporting platform to present results. Our seven examples illustrate how estimates, using mostly Bayesian models, make use of country data to track progress towards SDG targets for 2030. Results: Progress has been made over the past decade. However, none of the seven indicators are on track to achieve their respective SDG targets by 2030. Accelerated efforts are needed, especially in low- and middle-income countries, to reduce the burden of maternal, child, communicable and noncommunicable disease mortality, and to provide access to modern methods of family planning to all women. Conclusion: Our analysis shows the benefit of UN interagency monitoring which prioritizes transparent country data sources, UN population estimates and life tables, and rigorous but replicable modelling methods. Countries are supported to build capacity for data collection, analysis and reporting. Through these monitoring efforts we support countries to tackle even the most intransient health issues, including the pandemic caused by SARS-CoV-2 that is reversing the hard-earned gains of all countries.

Correction: The second national tuberculosis prevalence survey in Vietnam.

[This corrects the article DOI: 10.1371/journal.pone.0232142.].

The second national tuberculosis prevalence survey in Vietnam.

INTRODUCTION: Tuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second national TB prevalence survey was conducted in 2017-2018 to assess the current burden of TB disease in the country. METHOD: Eighty-two clusters were selected using a multistage cluster sampling design. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF G4, BACTEC MGIT960 liquid culture and Löwenstein-Jensen solid culture. Bacteriologically confirmed TB cases were defined by an expert panel following a standard decision tree. RESULT: Of 87,207 eligible residents, 61,763 (70.8%) participated, and 4,738 (7.7%) screened positive for TB. Among these, 221 participants were defined as bacteriologically confirmed TB cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 322 (95% CI: 260-399) per 100,000, and the male-to-female ratio was 4.0 (2.8-5.8, p<0.001). In-depth interviews with the participants with TB disease showed that only 57.9% (95% CI: 51.3-64.3%) reported cough for 2 weeks or more and 32.1% (26.3-38.6%) did not report any symptom consistent with TB, while their chest X-ray results showed that 97.7% (95% CI: 94.6-99.1) had abnormal chest X-ray images suggesting TB. CONCLUSION: With highly sensitive diagnostics applied, this survey showed that the TB burden in Vietnam remains high. Half of the TB cases were not picked up by general symptom-based screening and were identified by chest X-ray only. Our results indicate that improving TB diagnostic capacity and access to care, along with reducing TB stigma, need to be top priorities for TB control and elimination in Vietnam.

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.

Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data.

BACKGROUND: The surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%-4.4%) of new TB patients and 18% (95% CI 7.6%-31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns. METHODS AND FINDINGS: Aggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003-2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%-8.4%) among new TB patients and 11.4% (95% CI 9.4%-13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 countries (Azerbaijan, Bangladesh, Belarus, Pakistan, the Philippines, and South Africa). There were no cases of resistance to both pyrazinamide and levofloxacin among Hr-TB patients, except for the Philippines (1.8%, 95% CI 0.2-6.4) and Belarus (5.3%, 95% CI 0.1-26.0). Sequencing data for all genomic regions involved in isoniazid resistance were available for 4,563 patients. Among the 1,174 isolates that were resistant by either phenotypic testing or sequencing, 78.6% (95% CI 76.1%-80.9%) had resistance-conferring mutations in the katG gene and 14.6% (95% CI 12.7%-16.8%) in both katG and the inhA promoter region. For 6.8% (95% CI 5.4%-8.4%) of patients, mutations occurred in the inhA promoter alone, for whom an increased dose of isoniazid may be considered. The main limitations of this study are that most analyses were performed at the national rather than individual patient level and that the quality of laboratory testing may vary between countries. CONCLUSIONS: In this study, the prevalence of Hr-TB among TB patients was higher than the prevalence of rifampicin resistance globally. Many patients with Hr-TB would be missed by current diagnostic algorithms driven by rifampicin testing, highlighting the need for new rapid molecular technologies to ensure access to appropriate treatment and care. The low prevalence of resistance to pyrazinamide and fluoroquinolones among patients with Hr-TB provides further justification for the recommended modified treatment regimen.

Guidance for the Evaluation of Tuberculosis Diagnostics That Meet the World Health Organization (WHO) Target Product Profiles: An Introduction to WHO Process and Study Design Principles.

Existing high-priority target product profiles (TPPs) of the World Health Organization (WHO) establish important needs for tuberculosis (TB) diagnostic development. Building on this earlier work, this guidance series aims to provide study guidance for performing accuracy studies of novel diagnostic products that may meet the 4 high-priority WHO TPPs and thus enable adequate evidence generation to inform a WHO evidence review process. Diagnostic accuracy studies represent a fundamental step in the validation of all tests. Unfortunately, such studies often have limitations in design, execution, and reporting, leading to low certainty of the evidence about true test performance, which can delay or impede policy and scale-up decisions. This introductory paper outlines the following: (1) the purpose of this series of papers on study guidance; (2) WHO evidence needs and process for the development of policy guidelines for new TB diagnostic tests; and (3) study design considerations, ie, general diagnostic study considerations, intended use of test and role in the clinical pathway, choice of population and setting, index-test specific issues, suitable reference standard and comparators, study flow and specimen issues, and finally key issues beyond accuracy that should be considered. The other 4 papers in this series will provide more detailed guidance for each of the 4 WHO high-priority TPPs. By increasing the clarity around the clinical evaluation needs for tests that have the potential to meet the TPP specifications, we hope to support harmonized evidence generation and enable the WHO review process towards meeting the WHO End TB Strategy targets for reducing the incidence and mortality associated with 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.

Global Epidemiology of Tuberculosis.

Tuberculosis (TB) was the underlying cause of 1.3 million deaths among human immunodeficiency virus (HIV)-negative people in 2016, exceeding the global number of HIV/acquired immune deficiency syndrome (AIDS) deaths. In addition, TB was a contributing cause of 374,000 HIV deaths. Despite the success of chemotherapy over the past seven decades, TB is the top infectious killer globally. In 2016, 10.4 million new cases arose, a number that has remained stable since the beginning of the 21th century, frustrating public health experts tasked to design and implement interventions to reduce the burden of TB disease worldwide. Ambitious targets for reductions in the epidemiological burden of TB have been set within the context of the Sustainable Development Goals (SDGs) and the End TB Strategy. Achieving these targets is the focus of national and international efforts, and demonstrating whether or not they are achieved is of major importance to guide future and sustainable investments. This article reviews epidemiological facts about TB, trends in the magnitude of the burden of TB and factors contributing to it, and the effectiveness of the public health response.