Tuberculosis, COVID-19, and the End Tuberculosis strategy in India

The COVID-19 pandemic caused by the novel corona virus, Severe Acute Respiratory Syndrome corona virus 2 (SARS-CoV-2), has affected 188 countries of the world with 10,450,628 reported cases and 510,632 deaths as of July 1, 2020, and the same figure for India, which has the 4th highest number of cases, are 568,092 and 17,400, respectively.[1] Many countries and societies are impacted by the disease in an unprecedented scale. Many countries implemented lockdowns and quarantines to curtail the spread of the virus, and a large number of global populations are still under these restrictions. These restrictive measures, such as physical distancing, and restrictions on gatherings, and travel, have led to many adverse impacts on societies, economies, and health-care delivery systems. All countries of the world are struggling to maintain their health care systems to cope under such extraordinary conditions. In addition to affecting medical care of various diseases, whether therapeutic or preventive, COVID-19 has bad prognosis if associated with certain disease conditions such as cardiovascular disease, chronic respiratory diseases (COPD and bronchial asthma), diabetes mellitus, hypertension, chronic kidney diseases, and cancer. However, the association and effect of COVID-19 vis-a-vis tuberculosis (TB) on each other is not clearly understood and experience on COVID-19 in TB patients is limited. There are many similarities and differences between the two diseases. Some limited and preliminary observations suggest that TB infection is likely to increases susceptibility to SARS-CoV-2, and increases COVID-19 severity, but this requires validation in larger studies.[23] If it is so it will have a major impact in India as one third of its population is infected with TB. There are striking similarities between the two. Both cause major infection-related morbidity and mortality. While COVID-19 had caused over 0.5 million deaths so far over a period of 6 months, TB was the leading cause of mortality from an infectious disease worldwide in 2018, causing 1.2 million deaths.[4] The number of new cases of TB globally was nearly 10 million but COVID-19 cases have already crossed that figure within 6 months of its origin. In India, COVID-19 mortality is above 17,000 over a period of 3 months out of the over 5.6 lakh infections over this period. On the other hand, in India in 2019, 24.1 lakh TB cases were reported and there was a mortality of nearly 79,000 in that year.[5] The other similarities are that both COVID-19 and TB present with respiratory symptoms with small differences. Diagnosis and treatment of TB, or TB and COVID-19 co-infection, are likely to be compromised during the COVID-19 pandemic. Older age and associated co-morbidities are at increased risk of severe disease and adverse outcomes in both diseases. Both diseases have considerable social impact such as stigma, discrimination, and isolation in addition to the economic impact because of loss of productivity and catastrophic costs to individuals and households. There are some important differences between the two also. While TB is a slow pandemic and has affected mankind for over 7000 years the coronavirus (SARS-CoV-2) causing COVID-19 is just new and has occurred only recently with rapid spread worldwide causing a pandemic. TB has been labeled as a pandemic many times over the past three centuries, whereas this is the first COVID-19 pandemic. Children are often less severely affected by COVID-19, whereas 1.1 million children had TB disease in 2018, of whom 200,000 died[4] and in India about 342,000 incident cases of pediatric TB are estimated to occur every year accounting for 31% of the global burden and 13% of the overall TB burden in the country.[5] The association between poverty and COVID-19 is unclear. TB will be associated with the poverty, in which poorer people have a higher likelihood of infection, disease, and adverse outcomes. Moreover, unemployed populations including contract workers will experience increases risk of TB. While most of the cases and deaths from TB occur in low- and middle-income countries (LMICs), COVID-19 occurred more in the developed countries following China and most deaths occurred in the USA.[1] COVID-19 has mobilized more global and human resources in a few months than TB has in decades. However, the number of COVID-19 cases and mortality might increase in future as now India is the fourth highest number country in the world with Brazil having the second highest number.[1] Even with these similarities and dissimilarities, there are many unknown relationships. The clinical and epidemiological interactions of COVID-19 with TB (with or without HIV) will be highly complex. The transmission of TB might rise because of increased respiratory symptoms associated with COVID-19, or it may even decline due to COVID-19-related self-isolation, use of masks and quarantine. Millions of people treated for TB that have residual, long-term lung damage who are likely to be at a higher risk of severe disease and death from COVID-19. Because of extreme pressures on health systems, exacerbated by COVID-19, people with TB are likely to face decreased access to diagnostic and treatment services, which might also result in adverse outcomes.[6] Both TB and COVID-19 spread by close contact between people, although the exact mode of transmission differs, explaining some differences in infection control measures to mitigate the two conditions. TB bacilli remain suspended in the air in droplet nuclei for several hours after a TB patient coughs, sneezes, shouts, or sings, and people who inhale them; the size of these droplet nuclei is a key factor determining their infectiousness. Their concentration decreases with ventilation and exposure to direct sunlight. On the other hand, COVID-19 transmission has primarily been attributed to the direct breathing of droplets expelled by someone with the disease (people may be infectious before clinical features become apparent). Droplets produced by coughing, sneezing, exhaling and speaking may land on objects and surfaces, and contacts can get infected with covid-19 by touching them and then touching their eyes, nose or mouth. Handwashing is thus important in the control of COVID-19. Hospital procedures that generate aerosols predispose to infection of both conditions and should only be conducted within recommended safeguards. While the reproduction number (R0) is 2.2 for COVID-19; the same for TB is (R0) higher for TB like it was 4.3 in China (2012); and 3.55 in Southern India (2004–2006).[7] Although clinical course and outcome of COVID-19 is well reported from different parts of the world,[8910111213141516171819] including commentaries, perspectives and reviews, information is scanty about the clinical course of such co-infections. Global and national experience with concomitant TB and COVID-19 is extremely limited. Mycobacterium tuberculosis was not detected in a recent analysis of 1217 consecutive respiratory specimens collected from COVID-19 patients.[20] It is possible that synergistic co-infection of viral respiratory infections and TB will impede the host's immune responses; and therefore, their harmful synergism may contribute to more severe clinical evolution although COVID-19 pandemic is likely to affect TB in many ways in many countries. One recent study of 49 cases claimed to be the first-ever global cohort of current or former TB patients (post-TB treatment sequel) with COVID-19, was recruited by the Global Tuberculosis Network (GTN) from 8 countries and 3 continents.[21] Analysis on the outcome was not done. Most patients (53.0%) had TB before COVID-19, 28.5% had COVID-19 first and 18.3% had both diseases diagnosed within the same week. Forty-two (85.7%) patients had active TB with a median age of 45.5 years (28.0–63.0) and 7 (14.3%) had post-TB treatment sequel; the patients with TB sequel were cured 8.2 (2.7–44.3) years earlier. Overall, 26/49 (53.1%) patients were migrants, 15/48 (31.3%) unemployed, and 2/48 (4.1%) health-care workers (medical doctor and radiology technician). Forty-six (93.9%) patients had confirmed SARS-CoV-2 infection and 3 other patients (6.1%) had chest high resolution computerized tomography (HRCT) highly suggestive of COVID-19 related pneumonia (bilateral ground glass opacities). Forty-eight patients had pulmonary TB (one caused by Mycobacterium bovis). From this preliminary analysis the authors concluded that in about 40% of cases COVID-19 appeared during anti-TB treatment and limited or no protection against COVID-19 might have favored SARS-CoV-2 infection (which affected two health-care workers); since diagnosis of TB and COVID-19 was done simultaneously or within 7 days in some patients, differential diagnosis challenges will be there, which suggested that clinical assessments to investigate COVID-19 (e.g., clinical picture and HRCT) facilitated the identification of (a probably preexisting) TB. Any contribution of COVID-19 to TB pathogenesis cannot be excluded or confirmed. Although the diagnosis of COVID-19 preceded that of TB in 14 patients, larger studies are needed to understand any role played by SARS-CoV-2 in the progression of TB infection to disease. Given that up to a quarter of the population in some regions of the work is latently infected, SARS-CoV-2 infection might boost the development of active TB in the coming months. As individuals with latent TB infection followed up over time were not included in the study, it was not possible to report on the potential contribution of COVID-19 toward the development of active disease. Probably, an overlap of signs/symptoms of COVID-19 and TB occurred and COVID-19 was diagnosed earlier because of a higher index of suspicion while TB may have been there since before. Or, differently, COVID brought to clinical valuation/diagnostic assessment TB patients at an earlier stage of disease before the occurrence of TB-related symptoms. In some cases, COVID-19 occurred in patients with TB sequelae. They were older than patients under anti-TB treatment and presented higher (although not statistically significant) mortality. The presence of comorbidities was present in these cases (4 Chronic Obstructive Pulmonary Disease; 1 HIV co-infection plus liver and kidney diseases, hypertension, and cancer present in different combinations). Studies with larger numbers are necessary to further understand the role played by TB sequel. The impact on the health-care system (e.g., days of admission and intensive care unit beds) was relevant in this study. The information on BCG (Bacillus Calmette–Guérin) vaccination was modest (30 patients with information, 19 previously vaccinated in all 8 countries) and no significant elements can be provided to the ongoing debate on its protective role. At present, there was no data on drug-drug interactions.[21] Another study data from 49 consecutive cases in 8 countries and 20 hospitalized patients with TB and COVID-19 showed that 8 out of 69 (11.6%) patients died. Most of them were young migrants. It was noted that mortality was more in elderly patients with comorbidities; TB was not a major determinant of mortality and migrants had lower mortality due to younger age and lower number of comorbidities. However, the authors postulated that in settings where advanced forms of TB frequently occur and are caused by drug-resistant (DR) strains of M. tuberculosis, higher mortality rates can be expected in young individuals.[22] Another small series of 20 TB patients[23] diagnosed with COVID-19 co-infection from North Italy, 12 (60%) were males and the median age was 39 (27–47) years: Foreign-born (85%) individuals were younger than Italian nationals. Overall, 50% of patients had a body mass index BMI <18.5 kg/m2 at admission and eight had comorbidities but none had HIV co-infection. Three patients reported having been vaccinated with Bacillus Calmette–Guérin (BCG). Even if there is scarcity of data about the interaction and coexistence of both the diseases, one can draw conclusions or may expect similar outcomes from experience gained from other viral diseases occurring in the pat and their impact on TB. Recently, the issue was examined by Crisan-Dabija et al.[24] and the on the effect of the three human coronaviruses known to cause fatal respiratory diseases like the SARS-CoV (now known as SARS-CoV-1) that led to a global epidemic in 2002; the middle-east respiratory syndrome CoV which was discovered in 2012 and still affects people from 27 countries, and most recently, the novel CoV (SARS-CoV-2) and the influenza pandemic of 1918–1919. The authors noted that these epidemics have a negative impact on TB patients; transmission prevention was crucial for containing the epidemics and in order to decrease the opportunity of SARS-CoV-2 spreading amongst TB cases, hospital treatment for TB patients should be limited to severe cases. Immunopathogenesis of these viral illnesses also will affect course of TB;[24] diagnostic confusions. Similar observations are also made by the A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), GTN and members of ESCMID Study Group for Mycobacterial Infections (ESGMYC)[19] and others.[25] Similarly, Ebola virus disease in 2013–2015 in Liberia, West Africa had major negative effects in the form of significant decreases in diagnoses of smear-positive pulmonary TB, the declines in HIV testing and antiretroviral therapy (ART) uptake and poor treatment success.[26] COVID-19 had upset the major public health care system throughout the world. Prevention and treatment services for noncommunicable diseases (NCDs) are affected severely since the pandemic began. According to a WHO completed by 155 countries during a 3-week period in May, confirmed that the impact is global, but that low-income countries are most affected. There have been partial or complete disrupted in many countries. More than half (53%) of the countries surveyed have partially or completely disrupted services for hypertension treatment; 49% for treatment for diabetes and diabetes-related complications; 42% for cancer treatment; and 31% for cardiovascular emergencies. Rehabilitation services have been disrupted in almost two-thirds (63%) of countries, even though rehabilitation is key to a healthy recovery following severe illness from COVID-19. In almost, all (94%) health in the of are and to COVID-19. The of public was also in more than 50% of countries. The most for or services were of a decrease in public and a of because health workers had been to One of the for services was a of and other in about of countries. Many countries had for care which may or may not be the TB is the infectious diseases, more than each of TB and COVID-19 is a of one the There are many similarities and some differences between the two as earlier. As the COVID-19 pandemic has many other health there are ways in which this will impact and public health In the same the COVID-19 will and with TB control and it is important as TB is still the leading cause of death due to a infectious disease There is likely to be for the and to be diagnosed TB patients, more so in where TB is and health services are not well TB control will be under severe due to of loss of with increased of COVID-19 due to of for TB related to of TB care of of patients and contacts with for COVID related work because of in the of health-care is to to a in of TB care and poor outcomes. is an for the and societies for that the pandemic has the possible impact on key health that will close According to a report in 2020, there has been a significant decline in the made under the during the period in There was a decline of to 2 in the made under the health in the since the was The report the about access to due to the of the to the COVID-19 India reported million cases in accounting for of the burden to the report of the TB Tuberculosis of India is the public health in the world to the TB in the India has and had an of TB by years of the Global The to the TB with to TB deaths by and to new cases by to that was in and to that no is with catastrophic due to these the India, developed the to these there are many challenges and to these and to on such in was as the as the Tuberculosis A is under to these so that the be by the However, the COVID 19 pandemic the various TB control were in as it many other of health-care delivery in many countries including India at the highest the TB an system the is a key to the and are the key in the TB COVID-19 pandemic in India has affected the TB 1 the TB there is a in the although the was as a result of In to the ongoing pandemic the of India the health and like use of for COVID testing were These led to important on the of the TB of reported cases by in the 3 following a was to an of cases during the of was to a of including in the data the national TB system to health services, of health and a in TB testing and TB in by in with the number of cases detected in Similarly, recently by in in although the national TB in Brazil reported no recent in at the national According to the global TB was decreased by an of over a period of 3 months to the of before the will to a TB deaths (a 13% the to million TB deaths in 2020, the global of TB mortality of the year TB in with and out a analysis to the potential impact of the on TB in countries that included India, and According to the if there is a with 2 months then for India, there will be an of cases detected between and which is an increase of about and an of TB related deaths of during years which is an of There will be similar increase in number of cases and deaths in and also If there is a and a of services, the world an million cases of TB between and and an million TB deaths during that same period. India will get an new cases of and deaths during this period. The also that the global to the COVID-19 pandemic is having on TB services, with lockdowns and on and prevention services expected to increase the number of TB cases and deaths over the years leading to loss of during the past the impact of the COVID-19 pandemic on TB, and to of TB patients and to get the country on in the all national including India to measures that the of TB and prevention services during the period and a to and TB and has on the of all countries with high TB to the of the TB in the time of COVID-19, to measures that who are most and to protection against economic stigma, and the to the human and resources needed for of TB services the COVID-19 that this is an unprecedented the TB and the WHO are for national TB and their and The also is in the form of during this Some in India TB and COVID as many workers to their following has led to of TB of for these migrants and other will to them more to TB. of the population in India in and in will risk for both TB and of all COVID-19 patients will care including As the number of COVID cases is in India, many cases with TB will be an issue both for the of number of and more to TB cases on the spread of COVID-19 to people on infection control for populations and to care for the will both the diseases. of health-care workers is an important issue and by all should be to TB care as It will a from all from and national to the and health care One of the important effects of COVID-19 is about the of infection control including use of face and social which are to be and after the COVID-19 pandemic that will TB control also. TB treatment should not be TB treatment for or and for TB treatment and treatment of TB disease should be the COVID-19 It is that TB services are not disrupted during the The TB the and as well as has for the to work during the COVID-19 to be by people with TB to their risk for COVID-19 social with to remain at and contact with people as as possible including other for COVID-19. with TB should far to TB and health-care and be provided with to can complete their treatment at at health-care on the of use of protective and for to the spread of COVID-19 in TB All people with TB should and a while a TB and be for COVID-19 an should by all with that with TB on treatment should have a number that can contact if have any about their treatment or other that their TB The to for to be with TB who also have HIV and who are not on should be on on the same as TB with and TB The to TB patients to necessary and economic It is also necessary that TB care are well and use protection The should to treatment for drug-resistant TB which is systems are in for of effects and hospital It is of to maintain TB by and of and in The national and should population because these populations are at risk of TB, because of or because of other that result in to health the of the COVID-19 health as well as social should and and economic are to be to maintain health and to against and Although India to TB by the present COVID-19 and its direct and effects on TB with and economic on the new pandemic result in a in However, if the to on measures as above to this which the be if the not measures, the country may have to its TB of