Articles
Quantifying the global number of tuberculosis survivors: a modelling study

https://doi.org/10.1016/S1473-3099(20)30919-1Get rights and content

Summary

Background

People who survive tuberculosis face clinical and societal consequences after recovery, including increased risks of recurrent tuberculosis, premature death, reduced lung function, and ongoing stigma. To describe the size of this issue, we aimed to estimate the number of individuals who developed first-episode tuberculosis between 1980 and 2019, the number who survived to 2020, and the number who have been treated within the past 5 years or 2 years.

Methods

In this modelling study, we estimated the number of people who survived treated tuberculosis using country-level WHO data on tuberculosis case notifications, excluding those who died during treatment. We estimated the number of individuals surviving untreated tuberculosis using the difference between WHO country-level incidence estimates and notifications, applying published age-stratified and HIV-stratified case fatality ratios. To estimate survival with time, post-tuberculosis life tables were developed for each country-year by use of UN World Population Prospects 2019 mortality rates and published post-tuberculosis mortality hazard ratios.

Findings

Between 1980 and 2019, we estimate that 363 million people (95% uncertainty interval [UI] 287 million–438 million) developed tuberculosis, of whom 172 million (169 million–174 million) were treated. Individuals who developed tuberculosis between 1980 and 2019 had lived 3480 million life-years (95% UI 3040 million–3920 million) after tuberculosis by 2020, with survivors younger than 15 years at the time of tuberculosis development contributing 12% (95% UI 7–17) of these life-years. We estimate that 155 million tuberculosis survivors (95% UI 138 million–171 million) were alive in 2020, the largest proportion (47% [37–57]) of whom were in the WHO South-East Asia region. Of the tuberculosis survivors who were alive in 2020, we estimate that 18% (95% UI 16–20) were treated in the past 5 years and 8% (7–9) were treated in the past 2 years.

Interpretation

The number of tuberculosis survivors alive in 2020 is more than ten times the estimated annual tuberculosis incidence. Interventions to alleviate respiratory morbidity, screen for and prevent recurrent tuberculosis, and reduce stigma should be immediately prioritised for recently treated tuberculosis survivors.

Funding

UK Medical Research Council, the UK Department for International Development, the National Institute for Health Research, and the European and Developing Countries Clinical Trials Partnership.

Introduction

An estimated 10 million people develop tuberculosis disease annually, with around 70% receiving treatment.1 Although tuberculosis is curable, tuberculosis survivors face clinical and societal consequences even after recovery. Despite this burden, health systems do not generally focus attention on people affected by tuberculosis after treatment completion.2 WHO's reporting requirements for tuberculosis focus on diagnosis and treatment, and their epidemiological estimates and programmatic targets set for countries fall within these areas.1 There are sparse data available that focus on people who have survived tuberculosis disease or the impact that tuberculosis continues to have on their lives.

There is increasing recognition that the effect of tuberculosis extends beyond the tuberculosis episode. Those who survive tuberculosis are not only at increased risk of developing tuberculosis again compared with those who have never had tuberculosis,3 but they also have increased all-cause mortality3, 4 and reduced life expectancy5 irrespective of adequate tuberculosis treatment. Pulmonary tuberculosis is increasingly recognised as an important risk factor for chronic respiratory disease. Persistence of abnormal spirometry (airway obstruction and low forced vital capacity) and chronic or recurrent symptoms beyond cure are well described.6, 7, 8 Even mild and subclinical impairment in forced expiratory volume in 1 s has been shown to be an independent predictor of mortality and cardiovascular disease in addition to hospitalisation due to respiratory issues.9 Reductions in health-related quality of life and exercise tolerance have been noted in individuals following an episode of tuberculosis disease despite successful treatment or cure.10 Although data are scarce, pulmonary tuberculosis early in life could have long-term consequences because the prenatal period and early childhood are the most crucial periods for lung growth and development. Individuals surviving other forms of tuberculosis, particularly tuberculosis meningitis, frequently have ongoing neurological morbidity,11 and many tuberculosis survivors have psychological morbidity associated with their disease and treatment.

Research in context

Evidence before this study

There is increasing recognition that many individuals surviving tuberculosis face substantial morbidity, are at increased risk of developing tuberculosis again, and have higher all-cause mortality than those who have never had tuberculosis. Tuberculosis can also lead to stigma and can impact the finances of the affected individuals beyond the end of treatment. To identify and support these survivors, the first step is to quantify the number alive today that have had tuberculosis. van Kampen and colleagues did a broad systematic scoping review in which they searched for articles published between 1990 and 2018 on post-tuberculosis morbidity, and found a rapidly accelerating literature in this area. Therefore, to supplement this systematic review, we searched PubMed for articles published in English between Jan 1, 2018, and Aug 8, 2020, using the search terms: (((cure* OR sequel* OR recovered OR resolved OR former OR “history of” OR survivor* OR prior OR healed OR previous* OR post-treatment OR “completed treatment” OR “after treatment”) AND (tubercul* OR TB)) OR (post-tuberculosis OR posttuberculosis OR posttubercular OR post-tubercular OR post-TB OR treated tubercul* OR “treated pulmonary TB” OR “treated pulmonary tuberculosis” OR “treated tb”)) AND (“burden” OR number OR “life year” OR prevalen* OR estimate*) AND 2018:2020[dp]. This search yielded 2804 results. We evaluated these search results and the articles included by van Kampen and colleagues in their systematic review for relevance. In 2011, Denning and colleagues used a simple estimation approach to quantify the global burden of chronic pulmonary aspergillosis in tuberculosis survivors over a 5-year period (and subsequently in four particular countries). We found no articles estimating the numbers of tuberculosis survivors around the world, nor the cumulative life-years lived after tuberculosis disease.

Added value of this study

Our analysis estimates that 363 million people developed tuberculosis between 1980 and 2019, of whom 155 million were alive in 2020. A total of 3480 million life-years were lived in this period by people who had developed tuberculosis. We found that 18% of tuberculosis survivors alive in 2020 were diagnosed and treated in the past 5 years, representing a population that is amenable to identification, screening, and potential therapeutic intervention. Almost half of these tuberculosis survivors were treated in the WHO South-East Asia region and 8% were living with HIV at the time they developed tuberculosis.

Implications of all the available evidence

Tuberculosis programmes have generally focused on finding and diagnosing tuberculosis and supporting individuals to the end of treatment. Our data suggest that there is a large population of tuberculosis survivors who are alive today who would benefit from screening for post-tuberculosis consequences and then, if necessary, medical intervention. Many people might also need financial or social support. More research is required in this field to better understand the pathophysiology, spectrum, and burden of post-tuberculosis morbidity and to develop improved therapies that might prevent or treat those with impairment.

The social and economic impact of tuberculosis also persists well beyond the end of treatment. Communities might continue to stigmatise or socially isolate tuberculosis survivors, diminishing marriage prospects for young people or prompting divorce.12, 13 Tuberculosis can drive families deeper into poverty by requiring out-of-pocket expenditure for medical and non-medical costs and by reducing income during tuberculosis treatment.14 The socioeconomic effect of impoverishment on both the individual and the household can last for many successive years, with children being at high risk of malnutrition and discontinued education.15

The first step to addressing the challenges faced by tuberculosis survivors is to determine the number of people affected, their basic demographic characteristics, and where to find them. This information is necessary to help health systems to plan interventions directed at mitigating the lasting effects of tuberculosis on survivors. In this study, we aimed to model the number of individuals globally who developed first-episode tuberculosis between 1980 and 2019, the number who have survived to 2020, and the number who have been treated within the past 5 years or 2 years and might thus be amenable to public health intervention.

Section snippets

Methods

Our analysis considered 190 countries, comprising 99% of the global population for 2020 and 98% of estimated 2018 tuberculosis incidence. We characterised individuals who were alive in 2020 and had survived tuberculosis since 1980, the first year of tuberculosis notification data collated by WHO. An overview of the methodology is presented in figure 1 and more detailed methods are provided in the appendix (pp 3–16). Briefly, the general approach was to merge the number of individuals surviving

Results

We estimate that, between 1980 and 2019, a total of 363 million people (95% uncertainty interval [UI] 287 million–438 million) globally developed new tuberculosis disease, of whom 172 million (169 million–174 million) initiated treatment (table 1). Individuals who developed tuberculosis between 1980 and 2019 had lived 3480 million life-years (95% UI 3040 million–3920 million) after tuberculosis by 2020 (figure 2). Those who developed tuberculosis when they were younger than 15 years contributed

Discussion

To our knowledge, this study provides the first comprehensive estimate of the global number of tuberculosis survivors; we estimate that 155 million individuals who developed tuberculosis between 1980 and 2019 were alive in 2020. This approximation is a conservative estimate of all tuberculosis survivors because some individuals alive today will have developed tuberculosis before 1980. The 27·4 million tuberculosis survivors treated within the past 5 years are a relatively accessible group that

Data sharing

The collated input data from public sources are available at http://doi.org/10.5281/zenodo.3989261. Output data and source code are available at https://github.com/petedodd/post.

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