RESUMO
New tuberculosis (TB) drugs with little existing antimicrobial resistance enable a pan-TB treatment regimen, intended for universal use without prior drug-susceptibility testing. However, widespread use of such a regimen could contribute to an increasing prevalence of antimicrobial resistance, potentially rendering the pan-TB regimen ineffective or driving clinically problematic patterns of resistance. We developed a model of multiple sequential TB patient cohorts to compare treatment outcomes between continued use of current standards of care (guided by rifampin-susceptibility testing) and a hypothetical pan-TB approach. A pan-TB regimen that met current target profiles was likely to initially outperform the standard of care; however, a rising prevalence of transmitted resistance to component drugs could make underperformance likely among subsequent cohorts. Although the pan-TB approach led to an increased prevalence of resistance to novel drugs, it was unlikely to cause accumulation of concurrent resistance to novel drugs and current first-line drugs.
Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Humanos , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Farmacorresistência Bacteriana , Resultado do Tratamento , Rifampina/uso terapêutico , Rifampina/farmacologiaRESUMO
BACKGROUND: The COVID-19 pandemic disrupted tuberculosis (TB) health services, including treatment support and access to drugs, as patients were not able to access health facilities. While the effect of this disruption on treatment outcomes has been studied in isolated treatment centres, cities and provinces, the impact of the pandemic on TB treatment outcomes at a country and regional level has not been evaluated. METHODS: We used treatment outcomes for new and relapse TB cases reported to the World Health Organization (WHO) from 49 high TB, TB/HIV and drug-resistant TB burden countries from 2012 to 2019. We developed multinomial logistic regression models for trends in TB treatment success, failure, death and loss to follow up. We predicted TB treatment outcomes for 2020 and 2021, comparing these to observations, by computing ratios between observed and predicted probabilities. We aggregated these risk ratios (RR) for six WHO-defined regions using random-effects meta-analysis. RESULTS: Across 49 countries and four TB treatment outcomes, 17 (out of 196) country-outcome pairs in 2020 and 21 in 2021 had evidence of systematic differences between observed and predicted TB treatment outcome probabilities. Regionally, only four (out of 24) region-outcome pairs had evidence of systematic differences in 2020 and four in 2021, where the European region accounted for four of these in total. Globally, there was evidence of systematic differences in treatment failure in both 2020 (RR: 1.14, 95%CI: 1.01-1.28, p = 0.0381) and 2021 (RR: 1.36, 95%CI: 1.03-1.78, p = 0.0277), deaths in 2020 (RR: 1.08, 95%CI: 1.03-1.13, p = 0.0010) and losses to follow up in 2020 (RR: 0.91, 95%CI: 0.86-0.97, p = 0.0059). CONCLUSIONS: While for some countries and regions there were significant differences between observed and predicted treatment outcomes probabilities, there was insufficient evidence globally to identify systematic differences between observed and expected TB treatment outcome probabilities because of COVID-19-associated disruptions in general. However, larger numbers of treatment failures and deaths on treatment than expected were observed globally, suggesting a need for further investigation.
Assuntos
COVID-19 , Tuberculose , Humanos , COVID-19/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Resultado do Tratamento , Antituberculosos/uso terapêutico , Pandemias , SARS-CoV-2 , Saúde GlobalRESUMO
KEY MESSAGE: We summarise modelling studies of the most economically important cassava diseases and arthropods, highlighting research gaps where modelling can contribute to the better management of these in the areas of surveillance, control, and host-pest dynamics understanding the effects of climate change and future challenges in modelling. For over 30 years, experimental and theoretical studies have sought to better understand the epidemiology of cassava diseases and arthropods that affect production and lead to considerable yield loss, to detect and control them more effectively. In this review, we consider the contribution of modelling studies to that understanding. We summarise studies of the most economically important cassava pests, including cassava mosaic disease, cassava brown streak disease, the cassava mealybug, and the cassava green mite. We focus on conceptual models of system dynamics rather than statistical methods. Through our analysis we identified areas where modelling has contributed and areas where modelling can improve and further contribute. Firstly, we identify research challenges in the modelling developed for the surveillance, detection and control of cassava pests, and propose approaches to overcome these. We then look at the contributions that modelling has accomplished in the understanding of the interaction and dynamics of cassava and its' pests, highlighting success stories and areas where improvement is needed. Thirdly, we look at the possibility that novel modelling applications can achieve to provide insights into the impacts and uncertainties of climate change. Finally, we identify research gaps, challenges, and opportunities where modelling can develop and contribute for the management of cassava pests, highlighting the recent advances in understanding molecular mechanisms of plant defence.
Assuntos
Manihot , Controle de Pragas , Doenças das PlantasRESUMO
BACKGROUND: Tuberculosis remains a major public health priority and is the second leading cause of mortality from infectious disease worldwide. TB case detection rates are unacceptably low for men, the elderly and children. Disruptions in TB services due to the COVID-19 pandemic may have exacerbated these and other inequalities. METHODS: We modelled trends in age- and sex- disaggregated case notifications for all forms of new and relapse TB reported to the World Health Organization for 45 high TB, TB/HIV and MDR-TB burden countries from 2013 to 2019. We compared trend predicted notifications to observed notifications in 2020 to estimate the number of people with TB likely to have missed or delayed diagnosis. We estimated the risk ratio (RR) of missed or delayed TB diagnosis for children (aged < 15 years) or the elderly (aged ≥ 65 years) compared to adults (aged 15-64 years) and women compared to men (both aged ≥ 15 years) using a random-effects meta-analysis. RESULTS: An estimated 195,449 children (95% confidence interval, CI: 189,673-201,562, 37.8% of an expected 517,168), 1,126,133 adults (CI: 1,107,146-1,145,704, 21.8% of an expected 5,170,592) and 235,402 elderly (CI: 228,108-243,202, 28.5% of an expected 826,563) had a missed or delayed TB diagnosis in 2020. This included 511,546 women (CI: 499,623-523,869, 22.7%, of an expected 2,250,097) and 863,916 men (CI: 847,591-880,515, 23.0% of an expected 3,763,363). There was no evidence globally that the risk of having TB diagnosis missed or delayed was different for children and adults (RR: 1.09, CI: 0.41-2.91), the elderly and adults (RR: 1.40, CI: 0.62-3.16) or men and women (RR: 0.59, CI: 0.25-1.42). However, there was evidence of disparities in risk by age and/or sex in some WHO regions and in most countries. CONCLUSIONS: There is no evidence at an aggregate global level of any difference by age or sex in the risk of disruption to TB diagnosis as a result of the COVID-19 pandemic. However, in many countries, disruptions in TB services have been greater for some groups than others. It is important to recognise these context-specific inequalities when prioritising key populations for catch-up campaigns.
Assuntos
COVID-19 , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Criança , Adulto , Masculino , Feminino , Humanos , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Pandemias , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Organização Mundial da SaúdeRESUMO
Previous analyses suggest that children with tuberculosis (TB) are no more or no less likely to have multidrug (MDR)- or rifampicin-resistant (RR)-TB than adults. However, the availability of new data, particularly for high MDR/RR-TB burden countries, suggest updates of country-specific estimates are warranted.We used data from population-representative surveys and surveillance collected between 2000 and 2018 to compare the odds ratio of MDR/RR-TB among children (aged <15 years) with TB, compared to the odds of MDR/RR-TB among adults (aged ≥15 years) with TB.In most settings (45 out of 55 countries), and globally as a whole, there is no evidence that age is associated with odds of MDR/RR-TB. However, in some settings, such as former Soviet Union countries in general, and Georgia, Kazakhstan, Lithuania, Tajikistan and Uzbekistan in particular, as well as Peru, MDR/RR-TB is positively associated with age ≥15 years. Meanwhile, in Western Europe in general, and the United Kingdom, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15 years. 16 countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the odds ratio in children compared to adults in Germany, Kazakhstan and the United States of America.Our results support findings that in most settings a child with TB is as likely as an adult with TB to have MDR/RR-TB. However, setting-specific heterogeneity requires further investigation. Furthermore, the odds ratio for MDR/RR-TB in children compared to adults is generally either stable or decreasing. There are important gaps in detection, recording and reporting of drug resistance among paediatric TB cases, limiting our understanding of transmission risks and measures needed to combat the global TB epidemic.
Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Adolescente , Adulto , Antituberculosos/uso terapêutico , Criança , Europa (Continente) , Finlândia , Alemanha , Humanos , Peru , Polônia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Reino UnidoRESUMO
BACKGROUND: Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. METHODS: We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027-2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. RESULTS: By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69-72) and 72% (UI: 70-74), and the PSI vaccine by 31% (UI: 30-32) and 44% (UI: 42-47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8-1.1) and 1.1 million (UI: 0.9-1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. CONCLUSIONS: Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.
Assuntos
Antituberculosos/uso terapêutico , Análise Custo-Benefício/métodos , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/epidemiologia , Antituberculosos/farmacologia , China , Humanos , Índia , Vacinas contra a Tuberculose/farmacologiaRESUMO
Background: it is widely assumed that individuals with Mycobacterium tuberculosis (Mtb) infection remain at lifelong risk of tuberculosis (TB) disease. However, there is substantial evidence that self-clearance of Mtb infection can occur. We infer a curve of self-clearance by time since infection and explore its implications for TB epidemiology. Methods and findings: data for self-clearance were inferred using post-mortem and tuberculin-skin-test reversion studies. A cohort model allowing for self-clearance was fitted in a Bayesian framework before estimating the lifetime risk of TB disease and the population infected with Mtb in India, China and Japan in 2019. We estimated that 24.4% (17.8-32.6%, 95% uncertainty interval (UI)) of individuals self-clear within 10 years of infection, and 73.1% (64.6-81.7%) over a lifetime. The lifetime risk of TB disease was 17.0% (10.9-22.5%), compared to 12.6% (10.1-15.0%) assuming lifelong infection. The population at risk of TB disease in India, China and Japan was 35-80% (95% UI) smaller in the self-clearance scenario. Conclusions: the population with a viable Mtb infection may be markedly smaller than generally assumed, with such individuals at greater risk of TB disease. The ability to identify these individuals could dramatically improve the targeting of preventive programmes and inform TB vaccine development, bringing TB elimination within reach of feasibility.
Assuntos
Mycobacterium tuberculosis , Tuberculose , Teorema de Bayes , China/epidemiologia , Humanos , Índia/epidemiologia , Japão/epidemiologia , Tuberculose/epidemiologiaRESUMO
Males are at an increased risk of tuberculosis (TB) disease compared to females. Additionally, several risk factors for multidrug-resistant (MDR) or rifampicin-resistant (RR) TB disease are more common in males, hence male TB patients may have a higher relative risk of MDR/RR-TB than female TB patients.We used sex-disaggregated data of TB patients reported to the World Health Organization for 106 countries to calculate male-to-female (M:F) risk ratios of having MDR/RR-TB.There was no evidence of either sex being more at risk of MDR/RR-TB in 81% (86 out of 106) of countries, with an overall random-effects weighted M:F risk ratio of 1.04 (95% CI 0.97-1.11). In 12% (13 out of 106) of countries there was evidence that males were more at risk, while in 7% (seven out of 106), females were more at risk. The risk of having TB that was MDR/RR increased for males compared to females as MDR/RR-TB incidence increased, and was higher for males than females in the former Soviet Union, where the risk ratio was 1.16 (1.06-1.28). Conversely, the risk increased for females compared to males as gross domestic product purchase power parity increased, and was higher for females than males in countries where the majority of TB burden was found in the foreign-born population, where the risk ratio was 0.84 (0.75-0.94).In general, the risk of MDR/RR-TB, among those with TB, is the same for males as for females. However, males in higher MDR/RR-TB burden countries, particularly the former Soviet Union, face an increased risk that their infection is MDR/RR-TB, highlighting the need for a sex-differentiated approach to TB case-finding and care.
Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Antituberculosos/uso terapêutico , Feminino , Humanos , Masculino , Razão de Chances , Rifampina , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Organização Mundial da SaúdeAssuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Rifampina/uso terapêutico , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Isoniazida/uso terapêutico , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Farmacorresistência BacterianaAssuntos
COVID-19 , Tuberculose , Humanos , SARS-CoV-2 , Tuberculose/epidemiologia , Tuberculose/prevenção & controleAssuntos
Antituberculosos/uso terapêutico , Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , COVID-19 , Comorbidade , Infecções por Coronavirus/prevenção & controle , Efeitos Psicossociais da Doença , Feminino , Saúde Global , Humanos , Incidência , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Medição de Risco , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Parasitic species are likely to have a significant effect on the stability of ecosystems. However, little is known of the nature of this effect, with debate over whether it is positive or negative. In previous work it was observed that a mixture of interaction types increases the local stability of a network. Following this, we investigate the consequences for species persistence of replacing host species with parasitic species. We consider systems with varying mixtures of mutualistic and antagonistic interactions, showing that the effect of parasitic interactions on a system depends on both the interaction types present and the levels of parasitism considered. Higher levels of mutualism make a system vulnerable to destabilisation on the addition of parasite species. However, for systems with antagonistic interactions, persistence in the system decreases primarily due to the failure of parasite species to persist. This increases with increasing proportions of parasite species, leading to a peak number of parasite species able to persist. Increasing parasite species richness does not have as significant an effect on host species richness as we might expect; although parasites have an important role to play in ecological networks, their effect on persistence is seen primarily through their own self-limitation.
Assuntos
Biodiversidade , Cadeia Alimentar , Parasitos/fisiologia , Animais , Interações Hospedeiro-Parasita , Humanos , Modelos Biológicos , Dinâmica Populacional , Especificidade da EspécieRESUMO
BACKGROUND: A pan-tuberculosis regimen that could be initiated without knowledge of drug susceptibility has been proposed as an objective of tuberculosis regimen development. We modelled the health and economic benefits of such a regimen and analysed which of its features contribute most to impact and savings. METHODS: We constructed a mathematical model of tuberculosis treatment parameterised with data from the published literature specific to three countries with a high tuberculosis burden (India, the Philippines, and South Africa). Our model simulated cohorts of newly diagnosed tuberculosis patients, including drug susceptibility testing if performed, regimen assignment, discontinuation, adherence, costs, and resulting outcomes of durable cure (microbiological cure without relapse), need for retreatment, or death. We compared a pan-tuberculosis regimen meeting the WHO 2023 target regimen profile against the standard of care of separate rifampicin-susceptible and rifampicin-resistant regimens. We estimated incremental cures; averted deaths, secondary cases, and costs; and prices below which a pan-tuberculosis regimen would be cost saving. We also assessed scenarios intended to describe which mechanisms of benefit from a pan-tuberculosis regimen (including improved characteristics compared with the current rifampicin-susceptible and rifampicin-resistant regimens and improved regimen assignment and retention in care for patients with rifampicin-resistant tuberculosis) would be most impactful. Results are presented as a range of means across countries with the most extreme 95% uncertainty intervals (UIs) from the three UI ranges. FINDINGS: Compared with the standard of care, a pan-tuberculosis regimen could increase the proportion of patients durably cured after an initial treatment attempt from 69-71% (95% UI 57-80) to 75-76% (68-83), preventing 30-32% of the deaths (20-43) and 17-20% of the transmission (9-29) that occur after initial tuberculosis diagnosis. Considering savings to the health system and patients during and after the initial treatment attempt, the regimen could reduce non-drug costs by 32-42% (22-49) and would be cost saving at prices below US$170-340 (130-510). A rifamycin-containing regimen that otherwise met pan-tuberculosis targets yielded only slightly less impact, indicating that most of the benefits from a pan-tuberculosis regimen resulted from its improvements upon the rifampicin-susceptible standard of care. Eliminating non-adherence and treatment discontinuation, for example via a long-acting injectable regimen, increased health impact and savings. INTERPRETATION: In countries with a high tuberculosis burden, a shorter, highly efficacious, safe, and tolerable regimen to treat all tuberculosis could yield substantial health improvements and savings. FUNDING: Bill & Melinda Gates Foundation.
RESUMO
We read with great interest the recent paper by Lo et al., who argue that there is an urgent need to ensure the quality of modelling evidence used to support international and national guideline development. Here we outline efforts by the Tuberculosis Modelling and Analysis Consortium, together with the World Health Organization Global Task Force on Tuberculosis Impact Measurement, to develop material to improve the quality and transparency of country-level tuberculosis modelling to inform decision-making.
RESUMO
Food web structure of free-living species is an important determinant of parasite species richness. Downwardly asymmetric predator-prey interactions (where there are more prey than predator species) have been shown, both theoretically and empirically, to harbour more trophically transmitted parasite species than expected due to chance. Here, we demonstrate that this could be due to the increase in the basic reproductive ratio that the addition of non-host prey species to a system creates. However, we note that the basic reproductive ratio is only increased by those prey that stabilise oscillations in a predator-prey system, and is decreased by those that do not.
Assuntos
Cadeia Alimentar , Modelos Biológicos , Animais , Biodiversidade , Ecossistema , Humanos , Conceitos Matemáticos , Parasitos/patogenicidade , Parasitos/fisiologia , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/transmissão , Dinâmica PopulacionalRESUMO
Both ecological and evolutionary timescales are of importance when considering an ecological system; population dynamics affect the evolution of species traits, and vice versa. Recently, these two timescales have been used to explain structural patterns in host-parasite networks, where the evolution of the manner in which species balance the use of their resources in interactions with each other was examined.One of these patterns was nestedness, in which the set of parasite species within a particular host forms a subset of those within a more species-rich host. Patterns of both nestedness and anti-nestedness have been observed significantly more often than expected due to chance in host-parasite networks. In contrast, mutualistic networks tend to display a significant degree of nestedness, but are rarely anti-nested. Within networks with different interaction types, therefore, there appears to be a feature promoting non-random structural patterns, such as nestedness and anti-nestedness, depending on the interaction types involved.Here, we invoke the co-evolution of species trait-values when allocating resources to interactions to explain the structural pattern of nestedness in a mutualistic community. We look at a bipartite, multi-species system, in which the strength of an interaction between two species is determined by the resources that each species invests in that relationship. We then analyze the evolution of these interactions using adaptive dynamics.We found that the evolution of these interactions, reflecting the trade-off of resources, could be used to accurately predict that nestedness occurs significantly more often than expect due to chance alone in a mutualistic network. This complements previous results applying the same concept to an antagonistic network. We conclude that population dynamics and resource trade-offs could be important promoters of structural patterns in ecological networks of different types.
Assuntos
Modelos Biológicos , Simbiose , Animais , Evolução Biológica , Biologia Computacional , Ecossistema , Conceitos Matemáticos , Fenômenos Fisiológicos Vegetais , Dinâmica PopulacionalRESUMO
Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges.
Assuntos
Antibacterianos , Tratamento Farmacológico da COVID-19 , COVID-19 , Procedimentos Clínicos , Farmacorresistência Bacteriana/fisiologia , Saúde Global/tendências , Antibacterianos/provisão & distribuição , Antibacterianos/uso terapêutico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Procedimentos Clínicos/organização & administração , Procedimentos Clínicos/tendências , Humanos , SARS-CoV-2RESUMO
BACKGROUND: To end the global tuberculosis epidemic, latent tuberculosis infection needs to be addressed. All standard treatments for latent tuberculosis contain drugs to which multidrug-resistant (MDR) Mycobacterium tuberculosis is resistant. We aimed to estimate the global burden of multidrug-resistant latent tuberculosis infection to inform tuberculosis elimination policy. METHODS: By fitting a flexible statistical model to tuberculosis drug resistance surveillance and survey data collated by WHO, we estimated national trends in the proportion of new tuberculosis cases that were caused by MDR strains. We used these data as a proxy for the proportion of new infections caused by MDR M tuberculosis and multiplied trends in annual risk of infection from previous estimates of the burden of latent tuberculosis to generate trends in the annual risk of infection with MDR M tuberculosis. These estimates were used in a cohort model to estimate changes in the global and national prevalence of latent infection with MDR M tuberculosis. We also estimated recent infection levels (ie, in 2013 and 2014) and made predictions for the future burden of MDR tuberculosis in 2035 and 2050. FINDINGS: 19·1 million (95% uncertainty interval [UI] 16·4 million-21·7 million) people were latently infected with MDR tuberculosis in 2014-a global prevalence of 0·3% (95% UI 0·2-0·3). MDR strains accounted for 1·2% (95% UI 1·0-1·4) of the total latent tuberculosis burden overall, but for 2·9% (95% UI 2·6-3·1) of the burden among children younger than 15 years (risk ratio for those younger than 15 years vs those aged 15 years or older 2·65 [95% UI 2·11-3·25]). Recent latent infection with MDR M tuberculosis meant that 1·9 million (95% UI 1·7 million-2·3 million) people globally were at high risk of active MDR tuberculosis in 2015. INTERPRETATION: We estimate that three in every 1000 people globally carry latent MDR tuberculosis infection, and prevalence is around ten times higher among those younger than 15 years. If current trends continue, the proportion of latent tuberculosis caused by MDR strains will increase, which will pose serious challenges for management of latent tuberculosis-a cornerstone of tuberculosis elimination strategies. FUNDING: UK Medical Research Council, Bill & Melinda Gates Foundation, and European Research Council.