Lifetime burden of disease due to incident tuberculosis: a global reappraisal including post-tuberculosis sequelae.

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. FUNDING: National Institutes of Health.

Burden of non-communicable diseases from infectious causes in 2017: a modelling study.

BACKGROUND: Non-communicable diseases (NCDs) cause a large burden of disease globally. Some infectious diseases cause an increased risk of developing specific NCDs. Although the NCD burden from some infectious causes has been quantified, in this study, we aimed to more comprehensively quantify the global burden of NCDs from infectious causes. METHODS: In this modelling study, we identified NCDs with established infectious risk factors and infectious diseases with long-term non-communicable sequelae, and did narrative reviews between April 11, 2018, and June 10, 2020, to obtain relative risks (RRs) or population attributable fractions (PAFs) from studies quantifying the contribution of infectious causes to NCDs. To determine infection-attributable burden for the year 2017, we applied estimates of PAFs to estimates of disease burden from the Global Burden of Disease Study (GBD) 2017 for pairs of infectious causes and NCDs, or used estimates of attributable burden directly from GBD 2017. Morbidity and mortality burden from these conditions was summarised with age-standardised rates of disability-adjusted life-years (DALYs), for geographical regions as defined by the GBD. Estimates of NCD burden attributable to infectious causes were compared with attributable burden for the groups of risk factors with the highest PAFs from GBD 2017. FINDINGS: Globally, we quantified 130 million DALYs from NCDs attributable to infection, comprising 8·4% of all NCD DALYs. The infection-NCD pairs with the largest burden were gastric cancer due to H pylori (14·6 million DALYs), cirrhosis and other chronic liver diseases due to hepatitis B virus (12·2 million) and hepatitis C virus (10·4 million), liver cancer due to hepatitis B virus (9·4 million), rheumatic heart disease due to streptococcal infection (9·4 million), and cervical cancer due to HPV (8·0 million). Age-standardised rates of infection-attributable NCD burden were highest in Oceania (3564 DALYs per 100 000 of the population) and central sub-Saharan Africa (2988 DALYs per 100 000) followed by the other sub-Saharan African regions, and lowest in Australia and New Zealand (803 DALYs per 100 000) followed by other high-income regions. In sub-Saharan Africa, the proportion of crude NCD burden attributable to infectious causes was 11·7%, which was higher than the proportion of burden attributable to each of several common risk factors of NCDs (tobacco, alcohol use, high systolic blood pressure, dietary risks, high fasting plasma glucose, air pollution, and high LDL cholesterol). In other broad regions, infectious causes ranked between fifth and eighth in terms of crude attributable proportions among the nine risks compared. The age-standardised attributable proportion for infectious risks remained highest in sub-Saharan Africa of the broad regions, but age-standardisation caused infectious risks to fall below dietary risks, high systolic blood pressure, and fasting plasma glucose in ranked attributable proportions within the region. INTERPRETATION: Infectious conditions cause substantial NCD burden with clear regional variation, and estimates of this burden are likely to increase as evidence that can be used for quantification expands. To comprehensively avert NCD burden, particularly in low-income and middle-income countries, the availability, coverage, and quality of cost-effective interventions for key infectious conditions need to be strengthened. Efforts to promote universal health coverage must address infectious risks leading to NCDs, particularly in populations with high rates of these infectious conditions, to reduce existing regional disparities in rates of NCD burden. FUNDING: Leona M and Harry B Helmsley Charitable Trust.

Better than a pound of cure: preventing the development of multidrug-resistant tuberculosis.

Diagnostic and treatment delays contribute to increased death and disability among the 490,000 adults and children who develop multidrug-resistant (MDR) tuberculosis every year. Since the treatment of MDR tuberculosis is complex, costly and often toxic, tuberculosis control programs should prioritize strategies to prevent drug-resistant tuberculosis. Opportunities to limit transmission and prevent disease progression in close contacts of MDR tuberculosis cases are often neglected. Effective MDR tuberculosis preventive strategies could minimize the costs for patients and healthcare systems. This review characterizes the biological basis for the development of MDR tuberculosis, outlines the evidence for strategies to reduce transmission and highlights programmatic approaches to the management of patients infected with drug-resistant strains of Mycobacterium tuberculosis.

Decentralized care for multidrug-resistant tuberculosis: a systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches. METHODS: We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization's portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses. FINDINGS: Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01-1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38-1.13), for death RR: 1.01 (95% CI: 0.67-1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48-2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models. CONCLUSION: Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings.