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1.
Proc Biol Sci ; 288(1943): 20201635, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33467995

RESUMO

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.

2.
Clin Infect Dis ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32936877

RESUMO

While it is known that a substantial proportion of individuals with tuberculosis disease (TB) present subclinically, usually defined as bacteriologically-confirmed but negative on symptom screening, considerable knowledge gaps remain. Our aim was to review data from TB prevalence population surveys and generate a consistent definition and framework for subclinical TB, thus enabling an estimate of the proportion of TB that is subclinical, explore associations with overall burden and programme indicators, and performance of screening strategies. We extracted data from all publicly available prevalence surveys conducted since 1990. Between 36.1-79.7% (median 50.4%) of prevalent bacteriologically-confirmed TB was subclinical. No association was found between prevalence of subclinical and all bacteriologically confirmed TB, patient diagnostic rate or country-level HIV prevalence (p-values, 0.32, 0.4, 0.34, respectively). Chest X-ray detected 89% (range 73-98%) of bacteriologically-confirmed TB disease, highlighting the potential of optimizing current TB case-finding policies.

3.
Eur Respir J ; 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855219

RESUMO

Previous analyses suggest children with tuberculosis (TB) are no more or no less likely to have multidrug- or rifampicin-resistant TB (MDR/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 (OR) of MDR/RR-TB among children (<15 years) with TB, compared to the odds of MDR/RR-TB among adults (≥15 years) with TB.In most settings (45/55 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. Meanwhile, in Western Europe in general, and the UK, Poland, Finland and Luxembourg in particular, MDR/RR-TB is positively associated with age <15. Sixteen countries had sufficient data to compare over time between 2000-2011 and 2012-2018, with evidence for decreases in the OR in children compared to adults in Germany, Kazakhstan and the USA.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. Further, the OR 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.

6.
Clin Infect Dis ; 70(10): 2111-2118, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31246254

RESUMO

BACKGROUND: The risk of progression to tuberculosis (TB) disease is greatest soon after infection, yet disease may occur many years or decades later. However, rates of TB reactivation long after infection remain poorly quantified. Australia has a low incidence of TB and most cases occur among migrants. We explored how TB rates in Australian migrants varied with time from migration, age, and gender. METHODS: We combined TB notifications in census years 2006, 2011, and 2016 with time- and country-specific estimates of latent TB prevalences in migrant cohorts to quantify postmigration reactivation rates. RESULTS: During the census years, 3246 TB cases occurred among an estimated 2 084 000 migrants with latent TB. There were consistent trends in postmigration reactivation rates, which appeared to be dependent on both time from migration and age. Rates were lower in cohorts with increasing time, until at least 20 years from migration, and on this background there also appeared to be increasing rates during youth (15-24 years of age) and in those aged 70 years and above. Within 5 years of migration, annual reactivation rates were approximately 400 per 100 000 (uncertainty interval [UI] 320-480), dropping to 170 (UI 130-220) from 5 to 10 years and 110 (UI 70-160) from 10 to 20 years, then sustaining at 60-70 per 100 000 up to 60 years from migration. Rates varied depending on age at migration. CONCLUSIONS: Postmigration reactivation rates appeared to show dependency on both time from migration and age. This approach to quantifying reactivation risks will enable evaluations of the potential impacts of TB control and elimination strategies.

7.
Lancet Infect Dis ; 19(8): 903-912, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31281059

RESUMO

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.


Assuntos
Carga Global da Doença/estatística & dados numéricos , Carga Global da Doença/tendências , Tuberculose Latente/epidemiologia , Modelos Teóricos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Saúde Global , Humanos , Lactente , Tuberculose Latente/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Vigilância da População , Prevalência , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
10.
Clin Infect Dis ; 68(11): 1919-1925, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-30239605

RESUMO

BACKGROUND: People with pulmonary tuberculosis are at risk of developing chronic respiratory disorders due to residual lung damage. To date, the scope of the problem in high-burden tuberculosis countries is relatively unknown. METHODS: Chronic respiratory symptoms (cough and phlegm lasting >2 weeks) and radiological lung abnormalities were compared between adults with and without a history of tuberculosis among the general population of Uganda. Multivariable regression models were used to estimate odds ratios (ORs) with adjustment for age, gender, smoking, education, setting, and region. Random effects models accounted for village clustering effect. RESULTS: Of 45293 invited people from 70 villages, 41154 (90.9%) participated in the survey. A total of 798 had a history of tuberculosis and, among them, 16% had respiratory symptoms and 41% X-ray abnormalities. Adjusted ORs showed strong evidence for individuals with a history of tuberculosis having increased risk of respiratory symptoms (OR, 4.02; 95% confidence interval [CI], 3.25-4.96) and X-ray abnormalities (OR, 17.52; 95% CI, 14.76-20.79), attributing 6% and 24% of the respective population risks. CONCLUSIONS: In Uganda, a history of tuberculosis was a strong predictor of respiratory symptoms and lung abnormalities, before older age and smoking. Eliminating tuberculosis disease could reduce the prevalence of chronic respiratory symptoms as much as eliminating smoking.


Assuntos
Pneumopatias/microbiologia , Pulmão/anormalidades , Tuberculose/complicações , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Doença Crônica , Estudos Transversais , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Radiografia , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologia , Uganda/epidemiologia , Adulto Jovem
11.
Clin Infect Dis ; 68(1): 150-156, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982375

RESUMO

To find the millions of missed tuberculosis (TB) cases, national TB programs are under pressure to expand TB disease screening and to target populations with lower disease prevalence. Together with imperfect performance and application of existing diagnostic tools, including empirical diagnosis, broader screening risks placing individuals without TB on prolonged treatment. These false-positive diagnoses have profound consequences for TB patients and prevention efforts, yet are usually overlooked in policy decision making. In this article we describe the pathways to a false-positive TB diagnosis, including trade-offs involved in the development and application of diagnostic algorithms. We then consider the wide range of potential consequences for individuals, households, health systems, and reliability of surveillance data. Finally, we suggest practical steps that the TB community can take to reduce the frequency and potential harms of false-positive TB diagnosis and to more explicitly assess the trade-offs involved in the screening and diagnostic process.


Assuntos
Erros de Diagnóstico , Testes Diagnósticos de Rotina/métodos , Programas de Rastreamento/métodos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Humanos
12.
Clin Infect Dis ; 69(1): 159-166, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-30383204

RESUMO

Although less well-recognized than for other infectious diseases, heterogeneity is a defining feature of tuberculosis (TB) epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment, and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask heterogeneity in transmission. Reliance on notified cases may lead to misidentification of the most affected groups, as case detection is often poorest where prevalence is highest. Assuming that average rates apply across diverse groups and ignoring the effects of cohort selection may result in misunderstanding of the epidemic and the anticipated effects of control measures. Given this substantial heterogeneity, interventions targeting high-risk groups based on location, social determinants, or comorbidities could improve efficiency, but raise ethical and equity considerations.


Assuntos
Interações Hospedeiro-Patógeno , Tuberculose/epidemiologia , Comorbidade , Humanos , Prevalência , Fatores de Risco , Tuberculose/transmissão
14.
Eur Respir J ; 52(6)2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30361251

RESUMO

Migration is a key driver of tuberculosis (TB) in many low-incidence settings, with the majority of TB cases attributed to reactivation of latent TB (LTBI) acquired overseas. A greater understanding of LTBI risk in heterogeneous migrant populations would aid health planning. We aimed to estimate the LTBI prevalence and distribution among locally born and overseas-born Australians.Annual risks of TB infection estimates were applied to population cohorts (by country of birth, year of arrival and age) in Australian census data in 2006, 2011 and 2016.Both the absolute number and proportion of Australian residents with LTBI increased from 4.6% (interquartile range (IQR) 4.2-5.2%) in 2006 to 5.1% (IQR 4.7-5.5%) in 2016, due to the increasing proportion of the population born overseas (23.8% in 2006 to 28.3% in 2016). Of all residents estimated to have LTBI in 2016; 93.2% were overseas born, 21.6% were aged <35 years and 34.4% had migrated to Australia since 2007.The overall prevalence of LTBI in Australia is low. Some residents, particularly migrants from high-incidence settings, may have considerably higher risk of LTBI, and these findings allow for tailored public health interventions to reduce the risk and impact of future TB disease.


Assuntos
Tuberculose Latente/epidemiologia , Prevalência , Saúde Pública , Adolescente , Adulto , Idoso , Antituberculosos/uso terapêutico , Austrália/epidemiologia , Criança , Pré-Escolar , Controle de Doenças Transmissíveis , Coleta de Dados , Emigração e Imigração , Humanos , Incidência , Lactente , Recém-Nascido , Tuberculose Latente/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco , Migrantes , Adulto Jovem
15.
BMC Genomics ; 19(1): 613, 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30107785

RESUMO

BACKGROUND: Mixed, polyclonal Mycobacterium tuberculosis infection occurs in natural populations. Developing an effective method for detecting such cases is important in measuring the success of treatment and reconstruction of transmission between patients. Using whole genome sequence (WGS) data, we assess two methods for detecting mixed infection: (i) a combination of the number of heterozygous sites and the proportion of heterozygous sites to total SNPs, and (ii) Bayesian model-based clustering of allele frequencies from sequencing reads at heterozygous sites. RESULTS: In silico and in vitro artificially mixed and known pure M. tuberculosis samples were analysed to determine the specificity and sensitivity of each method. We found that both approaches were effective in distinguishing between pure strains and mixed infection where there was relatively high (> 10%) proportion of a minor strain in the mixture. A large dataset of clinical isolates (n = 1963) from the Karonga Prevention Study in Northern Malawi was tested to examine correlations with patient characteristics and outcomes with mixed infection. The frequency of mixed infection in the population was found to be around 10%, with an association with year of diagnosis, but no association with age, sex, HIV status or previous tuberculosis. CONCLUSIONS: Mixed Mycobacterium tuberculosis infection was identified in silico using whole genome sequence data. The methods presented here can be applied to population-wide analyses of tuberculosis to estimate the frequency of mixed infection, and to identify individual cases of mixed infections. These cases are important when considering the evolution and transmission of the disease, and in patient treatment.


Assuntos
Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Análise de Sequência de DNA/métodos , Tuberculose/diagnóstico , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Teorema de Bayes , DNA Bacteriano , Feminino , Genoma Bacteriano , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Tuberculose/microbiologia , Adulto Jovem
16.
BMC Infect Dis ; 18(1): 340, 2018 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-30031378

RESUMO

BACKGROUND: Increasing case notifications is one of the top programmatic priorities of National TB Control Programmes (NTPs). To find more cases, NTPs often need to consider expanding TB case-detection activities to populations with increasingly low prevalence of disease. Together with low-specificity diagnostic algorithms, these strategies can lead to an increasingly high number of false positive diagnoses, which has important adverse consequences. METHODS: We apply TIME, a widely-used country-level model, to quantify the expected impact of different case-finding strategies under two scenarios. In the first scenario, we compare the impact of implementing two different diagnostic algorithms (higher sensitivity only versus higher sensitivity and specificity) to reach programmatic screening targets. In the second scenario, we examine the impact of expanding coverage to a population with a lower prevalence of disease. Finally, we explore the implications of modelling without taking into consideration the screening of healthy individuals. Outcomes considered were changes in notifications, the ratio of additional false positive to true positive diagnoses, the positive predictive value (PPV), and incidence. RESULTS: In scenario 1, algorithm A of prolonged cough and GeneXpert yielded fewer additional notifications compared to algorithm B of any symptom and smear microscopy (n = 4.0 K vs 13.8 K), relative to baseline between 2017 and 2025. However, algorithm A resulted in an increase in PPV, averting 2.4 K false positive notifications thus resulting in a more efficient impact on incidence. Scenario 2 demonstrated an absolute decrease of 11% in the PPV as intensified case finding activities expanded into low-prevalence populations without improving diagnostic accuracy, yielding an additional 23 K false positive diagnoses for an additional 1.3 K true positive diagnoses between 2017 and 2025. Modelling the second scenario without taking into account screening amongst healthy individuals overestimated the impact on cases averted by a factor of 6. CONCLUSION: Our findings show that total notifications can be a misleading indicator for TB programme performance, and should be interpreted carefully. When evaluating potential case-finding strategies, NTPs should consider the specificity of diagnostic algorithms and the risk of increasing false-positive diagnoses. Similarly, modelling the impact of case-finding strategies without taking into account potential adverse consequences can overestimate impact and lead to poor strategic decision-making.


Assuntos
Reações Falso-Positivas , Modelos Estatísticos , Tuberculose , Algoritmos , Humanos , Programas de Rastreamento , Prevalência , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Tuberculose/epidemiologia
17.
Am J Epidemiol ; 187(11): 2431-2438, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29955827

RESUMO

Globally, men have a higher epidemiologic burden of tuberculosis (incidence, prevalence, mortality) than women do, possibly due to differences in disease incidence, treatment initiation, self-cure, and/or untreated-tuberculosis mortality rates. Using a simple, sex-stratified compartmental model, we employed a Bayesian approach to explore which factors most likely explain men's higher burden. We applied the model to smear-positive pulmonary tuberculosis in Vietnam (2006-2007) and Malawi (2013-2014). Posterior estimates were consistent with sex-specific prevalence and notifications in both countries. Results supported higher incidence in men and showed that both sexes faced longer durations of untreated disease than estimated by self-reports. Prior untreated disease durations were revised upward 8- to 24-fold, to 2.2 (95% credible interval: 1.7, 2.9) years for men in Vietnam and 2.8 (1.8, 4.1) years for men in Malawi, approximately a year longer than for women in each country. Results imply that substantial sex differences in tuberculosis burden are almost solely attributable to men's disadvantages in disease incidence and untreated disease duration. The latter, for which self-reports provide a poor proxy, implies inadequate coverage of case-finding strategies. These results highlight an urgent need for better understanding of gender-related barriers faced by men and support the systematic targeting of men for screening.


Assuntos
Antituberculosos/uso terapêutico , Teorema de Bayes , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Antituberculosos/administração & dosagem , Feminino , Saúde Global , Humanos , Incidência , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Tempo para o Tratamento , Tuberculose Pulmonar/mortalidade , Vietnã/epidemiologia , Adulto Jovem
18.
Lancet Glob Health ; 6(5): e514-e522, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29580761

RESUMO

BACKGROUND: The End TB Strategy and the Sustainable Development Goals (SDGs) are intimately linked by their common targets and approaches. SDG 1 aims to end extreme poverty and expand social protection coverage by 2030. Achievement of SDG 1 is likely to affect the tuberculosis epidemic through a range of pathways. We estimate the reduction in global tuberculosis incidence that could be obtained by reaching SDG 1. METHODS: We developed a conceptual framework linking key indicators of SDG 1 progress to tuberculosis incidence via well described risk factor pathways and populated it with data from the SDG data repository and the WHO tuberculosis database for 192 countries. Correlations and mediation analyses informed the strength of the association between the SDG 1 subtargets and tuberculosis incidence, resulting in a simplified framework for modelling. The simplified framework linked key indicators for SDG 1 directly to tuberculosis incidence. We applied an exponential decay model based on linear associations between SDG 1 indicators and tuberculosis incidence to estimate tuberculosis incidence in 2035. FINDINGS: Ending extreme poverty resulted in a reduction in global incidence of tuberculosis of 33·4% (95% credible interval 15·5-44·5) by 2035 and expanding social protection coverage resulted in a reduction in incidence of 76·1% (45·2-89·9) by 2035; both pathways together resulted in a reduction in incidence of 84·3% (54·7-94·9). INTERPRETATION: Full achievement of SDG 1 could have a substantial effect on the global burden of tuberculosis. Cross-sectoral approaches that promote poverty reduction and social protection expansion will be crucial complements to health interventions, accelerating progress towards the End TB targets. FUNDING: World Health Organization.


Assuntos
Saúde Global/estatística & dados numéricos , Pobreza/prevenção & controle , Política Pública , Tuberculose/prevenção & controle , Objetivos , Humanos , Incidência , Modelos Estatísticos , Tuberculose/epidemiologia
20.
Lancet Glob Health ; 5(11): e1123-e1132, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29025634

RESUMO

BACKGROUND: The economic burden on households affected by tuberculosis through costs to patients can be catastrophic. WHO's End TB Strategy recognises and aims to eliminate these potentially devastating economic effects. We assessed whether aggressive expansion of tuberculosis services might reduce catastrophic costs. METHODS: We estimated the reduction in tuberculosis-related catastrophic costs with an aggressive expansion of tuberculosis services in India and South Africa from 2016 to 2035, in line with the End TB Strategy. Using modelled incidence and mortality for tuberculosis and patient-incurred cost estimates, we investigated three intervention scenarios: improved treatment of drug-sensitive tuberculosis; improved treatment of multidrug-resistant tuberculosis; and expansion of access to tuberculosis care through intensified case finding (South Africa only). We defined tuberculosis-related catastrophic costs as the sum of direct medical, direct non-medical, and indirect costs to patients exceeding 20% of total annual household income. Intervention effects were quantified as changes in the number of households incurring catastrophic costs and were assessed by quintiles of household income. FINDINGS: In India and South Africa, improvements in treatment for drug-sensitive and multidrug-resistant tuberculosis could reduce the number of households incurring tuberculosis-related catastrophic costs by 6-19%. The benefits would be greatest for the poorest households. In South Africa, expanded access to care could decrease household tuberculosis-related catastrophic costs by 5-20%, but gains would be seen largely after 5-10 years. INTERPRETATION: Aggressive expansion of tuberculosis services in India and South Africa could lessen, although not eliminate, the catastrophic financial burden on affected households. FUNDING: Bill & Melinda Gates Foundation.


Assuntos
Custos de Cuidados de Saúde , Tuberculose/economia , Tuberculose/prevenção & controle , Doença Catastrófica/economia , Humanos , Índia , Modelos Teóricos , África do Sul
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