Trends in Tuberculosis Mortality Across India: Improvements Despite the COVID-19 Pandemic

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has had significant health implications across the globe. India is a country that has faced a double burden of COVID-19 and tuberculosis (TB) since 2020. There is a need to understand the impacts of COVID-19 on tuberculosis control programs in India. Therefore, our study aimed to determine the changes in TB mortality across India between 2019 and 2021. Methods: In our study, we described trends in TB and COVID-19 cases reported across India. Next, we compared death totals for TB between 2019, 2020, and 2021 in India at the national and state level. We considered total TB deaths, as well as deaths by TB for tribal populations, and for those living with human immunodeficiency virus (HIV). Percent changes were calculated. Results: In 2020, compared to 2019, there was a 15.4% decrease in TB death totals, with 28 out of India’s 36 states showing a decrease during this time period. While total deaths increased in 2021 compared to 2020, decreases did occur in 2021 compared to 2019. Deaths by TB for individuals living with HIV decreased by 16.0% across India. At a national level, there was a notable rise in TB deaths among tribal populations, though this was not universal across states. Conclusion: While the majority of the world has seen an increase in new TB cases and TB deaths annually since the start of the COVID-19 pandemic, there have instead been decreases in India during this time period. More research is required to understand the factors that have led to this decrease in TB deaths. Furthermore, additional allocation of resources is required to better support vulnerable populations in states where TB death totals have increased, especially among tribal populations.


Introduction
The coronavirus disease 2019 (COVID-19) pandemic has had devastating health consequences on populations all over the world. The pandemic has also been shown to have an impact on the control of other communicable diseases, such as tuberculosis (TB). Previous analysis demonstrated that there was a sharp decline in reporting of TB across high-burden countries since the start of the COVID-19 pandemic [1].
One country with a high burden of TB that has been greatly impacted by COVID-19 is India (Bharat). Currently, India has the highest burden of TB in the world [2]. However, it has been previously demonstrated that the total number of reported cases of TB across India has declined since the start of the COVID-19 pandemic; there were notable decreases in reported TB cases across India in 2020 and 2021 compared to 2019 [3]. While the number of reported cases has sharply declined in India, little is known about the implications of this on mortality. We, therefore, sought to determine the changes in TB death totals across India since the start of the COVID-19 pandemic.

Materials And Methods
For our study, we first compared trends in total TB cases, pulmonary TB cases, and extrapulmonary cases for 2019, 2020 and 2021; alongside this, we compared trends in COVID-19 case and death totals annually since the start of the pandemic. Next, we compared total TB deaths across India in 2019, 2020 and 2021. These comparisons were made at the national level, as well as at the state level for each of India's 36 states. Thereafter, we analyzed changes in TB death totals among tribal populations, and for individuals coinfected with human immunodeficiency virus (HIV). Tribal populations were specifically chosen for our analysis as they have been shown to have a higher burden of TB compared to the general population [4]. Similarly, TB death totals among individuals co-infected with HIV were analyzed as this population has been shown to have significantly higher rates of TB mortality compared to the general population [5,6]. In our study, percent changes were calculated for state and national level data. Data for this study was retrieved from the Government of India's TB Reports for 2020-2023 [7][8][9][10]. The data from these reports are publicly available. The Government of India publishes TB reports annually and provides data at the state and national level regarding TB incidence, prevalence, outcomes, and drug resistance [11]. These reports are published as part of the Indian government's National Tuberculosis Elimination Program (NTEP), which is an initiative that aims to end TB infection in India [11,12] ultimately. As well, COVID-19 case and death data for India was retrieved from Worldometer [13], which is a source that has publicly available data on COVID-19 incidence and mortality for countries across the world.

Results
In 2019, there was a total of 2,404,815 TB cases detected across India, and this decreased by 24.9% in 2020 (1,805,670 cases). While there was a higher number of total TB cases detected in 2021 (2,135,830 cases) compared to 2020, this was 11.2% lower compared to 2019. Pulmonary cases of TB made up 73.4% of cases in 2019 (1,764,416 pulmonary cases), and this decreased to 72% of total cases in 2020 (1,291,986 pulmonary cases) and again constituted 72% of total cases in 2021 (1,528,000 pulmonary cases). A summary of changes in TB case notifications is shown in Table 1

Discussion
Our study has shown that, at a national level, there have been notable decreases in TB death totals across India since the start of the COVID-19 pandemic. Critically, this has occurred despite an increase in total TB deaths worldwide in 2020 and 2021 [14]. The World Health Organization's 2022 Global Tuberculosis Report has indicated that, across the overwhelming majority of high-burden TB countries, there was a rise in TB deaths since the start of COVID-19, and this was partially attributed to a decrease in detection of new cases [15]. While India has seen a steady decline in reported TB cases annually since the start of the COVID-19 pandemic, in consideration of the decline of total deaths due to TB in India, it is plausible that the lower rates of TB case reporting may reflect actual declines in disease incidence. Furthermore, it demonstrates that public health initiatives launched and maintained, as part of the NTEP, may have shown effectiveness in controlling TB. Examples of such initiatives include India's TB preventive treatment regimen roll-out, cash incentive schemes to improve nutrition, and application of family-centric care models for TB [16]. However, it is crucial to denote that there were increases in TB cases and deaths in 2021 compared to 2020, and these corresponded to sharp increases in the COVID-19 burden across India. Ongoing monitoring in upcoming years is necessary to determine if continual progress is made in addressing both of these infectious diseases.
This trend regarding declines in deaths due to TB has also been shown for populations living with HIV in India, both in 2020 and 2021. Amongst tribal populations, while there has been an increase in TB deaths at a national level, this increase was relatively minimal in 2020. However, there was shown to be a sharp increase in tribal population deaths in 2021. Therefore, it is important that TB control programs across India work to ensure that they are appropriately serving tribal populations, who may be at an elevated risk of mortality. A previous study has shown that tribal populations may be more likely to delay health seeking behavior after development of TB symptoms [17]; it is not clear if this can serve as a viable explanation for the increases in TB deaths among tribal populations, or if there are other important factors that also need to be considered. More research is hence required to understand this concerning trend in TB mortality among tribal populations in India.
At the state level, there has been notable variation in TB deaths. While numerous states, such as Uttar Pradesh and Andhra Pradesh, have shown effectiveness in lowering TB death totals during the pandemic, numerous other states have instead shown increases in death tolls. Alarmingly, some Indian states have seen considerable rises in TB deaths among tribal populations and populations living with HIV. Further research is needed to investigate the factors associated with the decreases, and increases, that are unique among subpopulations at the state level.
It is imperative that national and state governments continue to prioritize supporting TB control and prevention programs alongside COVID-19 control efforts. Supporting vulnerable populations in states that have been most negatively impacted will be integral. Public health programs should focus on ensuring that testing facilities are widely available, and that individuals are supported in adhering to treatment regimens. Usage of video-directly observed therapy (vDOT), where treatment adherence is supported and monitored through the usage of video services, has had positive impacts in other contexts [18] and may offer utility in improving overall TB outcomes across India. However, more research is required to better understand how vulnerable populations can best be supported.
Alongside the findings of our work, the limitations need to be considered. It is possible that a high number of TB deaths in India may not have been accounted for due to the COVID-19 pandemic, and therefore may not have been included in the available datasets. Furthermore, our analysis did not account for patients who never received follow-up, or failed treatment (but did not immediately die). Lastly, as our study was an ecological analysis that used data at the national and state level, we cannot make conclusions regarding outcomes in specific towns and cities. Other limitations of ecological analyses that must be considered here are an inability to demonstrate causality [19], and a lack of consideration of potential confounding variables [20]. Regardless of these limitations, our study provides important insights regarding trends in TB mortality across India since the start of the COVID-19 pandemic.

Conclusions
Our study has demonstrated that there have been notable decreases in TB cases and death totals across India since the emergence of COVID-19. This trend has occurred at the national level, though there have been notable exceptions at the state level where death totals have instead increased -this is particularly salient among tribal populations. In consideration of the enormous burden of TB in India, it is imperative that public health programs continue to control the spread of both TB and COVID-19 concurrently.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.