Economic impact of tuberculosis mortality in 120 countries and the cost of not achieving the Sustainable Development Goals tuberculosis targets: a full-income analysis.

BACKGROUND: The tuberculosis targets for the UN Sustainable Development Goals (SDGs) call for a 90% reduction in tuberculosis deaths by 2030, compared with 2015, but meeting this target now seems highly improbable. To assess the economic impact of not meeting the target until 2045, we estimated full-income losses in 120 countries, including those due to excess deaths resulting from COVID-19-related disruptions to tuberculosis services, for the period 2020-50. METHODS: Annual mortality risk changes at each age in each year from 2020 to 2050 were estimated for 120 countries. This risk change was then converted to full-income risk by calculating a population-level mortality risk change and multiplying it by the value of a statistical life-year in each country and year. As a comparator, we assumed that current rates of tuberculosis continue to decline through the period of analysis. We calculated the full-income losses, and mean life expectancy losses per person, at birth and at age 35 years, under scenarios in which the SDG targets are met in 2030 and in 2045. We defined the cost of inaction as the difference in full-income losses and tuberculosis mortality between these two scenarios. FINDINGS: From 2020 to 2050, based on the current annual decrease in tuberculosis deaths of 2%, 31·8 million tuberculosis deaths (95% uncertainty interval 25·2 million-39·5 million) are estimated to occur, corresponding to an economic loss of US$17·5 trillion (14·9 trillion-20·4 trillion). If the SDG tuberculosis mortality target is met in 2030, 23·8 million tuberculosis deaths (18·9 million-29·5 million) and $13·1 trillion (11·2 trillion-15·3 trillion) in economic losses can be avoided. If the target is met in 2045, 18·1 million tuberculosis deaths (14·3 million-22·4 million) and $10·2 trillion (8·7 trillion-11·8 trillion) can be avoided. The cost of inaction of not meeting the SDG tuberculosis mortality target until 2045 (vs 2030) is, therefore, 5·7 million tuberculosis deaths (5·1 million-8·1 million) and $3·0 trillion (2·5 trillion-3·5 trillion) in economic losses. COVID-19-related disruptions add $290·3 billion (260·2 billion-570·1 billion) to this cost. INTERPRETATION: Failure to achieve the SDG tuberculosis mortality target by 2030 will lead to profound economic and health losses. The effects of delay will be greatest in sub-Saharan Africa. Affected countries, donor nations, and the private sector should redouble efforts to finance tuberculosis programmes and research because the economic dividend of such strategies is likely to be substantial. FUNDING: None.

The effect of BCG revaccination on all-cause mortality beyond infancy: 30-year follow-up of a population-based, double-blind, randomised placebo-controlled trial in Malawi.

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust.

Sociodemographic Characteristics, Comorbidities, and Mortality Among Persons Diagnosed With Tuberculosis and COVID-19 in Close Succession in California, 2020.

Importance: Tuberculosis (TB) and COVID-19 are respiratory diseases that disproportionately occur among medically underserved populations; little is known about their epidemiologic intersection. Objective: To characterize persons diagnosed with TB and COVID-19 in California. Design, Setting, and Participants: This cross-sectional analysis of population-based public health surveillance data assessed the sociodemographic, clinical, and epidemiologic characteristics of California residents who were diagnosed with TB (including cases diagnosed and reported between September 3, 2019, and December 31, 2020) and COVID-19 (including confirmed cases based on positive results on polymerase chain reaction tests and probable cases based on positive results on antigen assays reported through February 2, 2021) in close succession compared with those who were diagnosed with TB before the COVID-19 pandemic (between January 1, 2017, and December 31, 2019) or diagnosed with COVID-19 alone (through February 2, 2021). This analysis included 3 402 713 California residents with COVID-19 alone, 6280 with TB before the pandemic, and 91 with confirmed or probable COVID-19 diagnosed within 120 days of a TB diagnosis (ie, TB/COVID-19). Exposures: Sociodemographic characteristics, medical risk factors, factors associated with TB severity, and health equity index. Main Outcomes and Measures: Frequency of reported successive TB and COVID-19 (TB/COVID-19) diagnoses within 120 days, frequency of deaths, and age-adjusted mortality rates. Results: Among the 91 persons with TB/COVID-19, the median age was 58.0 years (range, 3.0-95.0 years; IQR, 41.0-73.0 years); 52 persons (57.1%) were male; 81 (89.0%) were born outside the US; and 28 (30.8%) were Asian or Pacific Islander, 4 (4.4%) were Black, 55 (60.4%) were Hispanic or Latino, 4 (4.4%) were White. The frequency of reported COVID-19 among those who received a TB diagnosis between September 3, 2019, and December 31, 2020, was 225 of 2210 persons (10.2%), which was similar to that of the general population (3 402 804 of 39 538 223 persons [8.6%]). Compared with persons with TB before the pandemic, those with TB/COVID-19 were more likely to be Hispanic or Latino (2285 of 6279 persons [36.4%; 95% CI, 35.2%-37.6%] vs 55 of 91 persons [60.4%; 95% CI, 49.6%-70.5%], respectively; P < .001), reside in low health equity census tracts (1984 of 6027 persons [32.9%; 95% CI, 31.7%-34.1%] vs 40 of 89 persons [44.9%; 95% CI, 34.4%-55.9%]; P = .003), live in the US longer before receiving a TB diagnosis (median, 19.7 years [IQR, 7.2-32.3 years] vs 23.1 years [IQR, 15.2-31.5 years]; P = .03), and have diabetes (1734 of 6280 persons [27.6%; 95% CI, 26.5%-28.7%] vs 42 of 91 persons [46.2%; 95% CI, 35.6%-56.9%]; P < .001). The frequency of deaths among those with TB/COVID-19 successively diagnosed within 30 days (8 of 34 persons [23.5%; 95% CI, 10.8%-41.2%]) was more than twice that of persons with TB before the pandemic (631 of 5545 persons [11.4%; 95% CI, 10.6%-12.2%]; P = .05) and 20 times that of persons with COVID-19 alone (42 171 of 3 402 713 persons [1.2%; 95% CI, 1.2%-1.3%]; P < .001). Persons with TB/COVID-19 who died were older (median, 81.0 years; IQR, 75.0-85.0 years) than those who survived (median, 54.0 years; IQR, 37.5-68.5 years; P < .001). The age-adjusted mortality rate remained higher among persons with TB/COVID-19 (74.2 deaths per 1000 persons; 95% CI, 26.2-122.1 deaths per 1000 persons) compared with either disease alone (TB before the pandemic: 56.3 deaths per 1000 persons [95% CI, 51.2-61.4 deaths per 1000 persons]; COVID-19 only: 17.1 deaths per 1000 persons [95% CI, 16.9-17.2 deaths per 1000 persons]). Conclusions and Relevance: In this cross-sectional analysis, TB/COVID-19 was disproportionately diagnosed among California residents who were Hispanic or Latino, had diabetes, or were living in low health equity census tracts. These results suggest that tuberculosis and COVID-19 occurring together may be associated with increases in mortality compared with either disease alone, especially among older adults. Addressing health inequities and integrating prevention efforts could avert the occurrence of concurrent COVID-19 and TB and potentially reduce deaths.

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.

Universal health coverage and tuberculosis care in India in the times of Covid-19: Aligning Ayushman Bharat (National Health Assurance Scheme) to improve case detection, reduce deaths and catastrophic health expenditure.

India has the largest global burden of new cases of tuberculosis (TB) and deaths due to TB. These occur predominantly in the poor who suffer catastrophic costs during diagnosis and treatment. The National Tuberculosis Elimination Programme has ambitious goals of 80% reduction of incidence of TB, 90% reduction in mortality due to TB by 2025 and 0% occurrence of catastrophic costs to households affected by TB by 2020. The Covid-19 pandemic and the resulting disruption to TB services are expected to worsen the situation. There are gaps in case finding at the peripheral level and access to care at the higher level for patients with TB. An estimated 32% patients with active TB do not access diagnostic services, while catastrophic costs associated with hospitalization are a barrier to access for seriously ill patients. Deaths due to TB in India occur largely at home and not in medical facilities, and are preventable with appropriate inpatient care. The Ayushman Bharat scheme with its Health and Wellness Centres (HWCs) and coverage for inpatient care under the Pradhan Mantri Jan Arogya Yojana (PM-JAY) can facilitate, the achievement of the goals of TB elimination. The HWCs provide an opportunity to close the case-finding gap as first point of contact by enabling sputum transport services to the designated microscopy centres. This will facilitate case detection, reduce diagnostic delays, and decrease community transmission and the incidence of TB. The benefit package of PM-JAY can cover patients with pulmonary TB, inpatient evaluation for other forms of TB, enhance the allocation for treatment and cover management of comorbid conditions such as severe undernutrition, anaemia, HIV and diabetes.

Corticosteroids for COVID-19 Therapy: Potential Implications on Tuberculosis.

On 11 March 2020, the World Health Organization announced the Corona Virus Disease-2019 (COVID-19) as a global pandemic, which originated in China. At the host level, COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), affects the respiratory system, with the clinical symptoms ranging from mild to severe or critical illness that often requires hospitalization and oxygen support. There is no specific therapy for COVID-19, as is the case for any common viral disease except drugs to reduce the viral load and alleviate the inflammatory symptoms. Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), also primarily affects the lungs and has clinical signs similar to pulmonary SARS-CoV-2 infection. Active TB is a leading killer among infectious diseases and adds to the burden of the COVID-19 pandemic worldwide. In immunocompetent individuals, primary Mtb infection can also lead to a non-progressive, asymptomatic latency. However, latent Mtb infection (LTBI) can reactivate symptomatic TB disease upon host immune-suppressing conditions. Importantly, the diagnosis and treatment of TB are hampered and admixed with COVID-19 control measures. The US-Center for Disease Control (US-CDC) recommends using antiviral drugs, Remdesivir or corticosteroid (CST), such as dexamethasone either alone or in-combination with specific recommendations for COVID-19 patients requiring hospitalization or oxygen support. However, CSTs can cause immunosuppression, besides their anti-inflammatory properties. The altered host immunity during COVID-19, combined with CST therapy, poses a significant risk for new secondary infections and/or reactivation of existing quiescent infections, such as LTBI. This review highlights CST therapy recommendations for COVID-19, various types and mechanisms of action of CSTs, the deadly combination of two respiratory infectious diseases COVID-19 and TB. It also discusses the importance of screening for LTBI to prevent TB reactivation during corticosteroid therapy for COVID-19.

Tuberculosis and COVID-19 Co-infection: An Updated Review.

Coronavirus disease (COVID 19) has involved millions of people all over the world. Tuberculosis (TB) continues to affect millions of people every year with high mortality. There is limited literature on the occurrence of COVID 19 in patients with TB. We reviewed the available data on various clinical details, management, and outcome among patients with COVID-19 and TB. 8 studies reported a total of 80 patients with this coinfection. These patients were reported from ten different countries, with Italy reporting the largest number of cases. Migrant, males constituted a major proportion of cases. Most reported patients were symptomatic. Fever, dry cough, and dyspnea were the most commonly reported symptoms. Bilateral ground glass opacities were more common in COVID 19 infection and cavitary lesions were more common in patients with TB. Most reported TB patients had been found to have mycobacterium tuberculosis from sputum culture in the background of pulmonary TB. Most patients of TB were treated with multidrug regimen antitubercular therapy. In all 8 studies, COVID 19 was treated as per the local protocol. Mortality was reported in more than 10% of patients. Mortality was higher in elderly patients (> 70 years) and amongst patient with multiple medical comorbidities.

Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.

BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.

Previous and active tuberculosis increases risk of death and prolongs recovery in patients with COVID-19.

BACKGROUND: There is a growing literature on the association of SARS-CoV-2 and other chronic conditions, such as noncommunicable diseases. However, little is known about the impact of coinfection with tuberculosis. We aimed to compare the risk of death and recovery, as well as time-to-death and time-to-recovery, in COVID-19 patients with and without tuberculosis. METHODS: We created a 4:1 propensity score matched sample of COVID-19 patients without and with tuberculosis, using COVID-19 surveillance data in the Philippines. We conducted a longitudinal cohort analysis of matched COVID-19 patients as of May 17, 2020, following them until June 15, 2020. The primary analysis estimated the risk ratios of death and recovery in patients with and without tuberculosis. Kaplan-Meier curves described time-to-death and time-to-recovery stratified by tuberculosis status, and differences in survival were assessed using the Wilcoxon test. RESULTS: The risk of death in COVID-19 patients with tuberculosis was 2.17 times higher than in those without (95% CI: 1.40-3.37). The risk of recovery in COVID-19 patients with tuberculosis was 25% lower than in those without (RR = 0.75,05% CI 0.63-0.91). Similarly, time-to-death was significantly shorter (p = .0031) and time-to-recovery significantly longer in patients with tuberculosis (p = .0046). CONCLUSIONS: Our findings show that coinfection with tuberculosis increased morbidity and mortality in COVID-19 patients. Our findings highlight the need to prioritize routine and testing services for tuberculosis, although health systems are disrupted by the heavy burden of the SARS-CoV-2 pandemic.