|Year : 2021 | Volume
| Issue : 4 | Page : 307-310
Adult Bacille Calmette-Guérin vaccination during the pandemic of COVID-19 in India
BM Shrinivasa1, Padmapriyadarsini Chandrasekaran1, Joshua Chadwick1, Manoj V Murekhar2
1 Department of Clinical Research, ICMR- National Institute of Research in Tuberculosis, Chennai, Tamil Nadu, India
2 Department of Clinical Research, ICMR- National Institute of Epidemiology, Chennai, Tamil Nadu, India
|Date of Submission||23-Mar-2021|
|Date of Acceptance||09-Aug-2021|
|Date of Web Publication||17-Nov-2021|
Dr. B M Shrinivasa
Department of Clinical Research, ICMR- National Institute of Research in Tuberculosis, Chetpet, Chennai - 600 100, Tamil Nadu
Source of Support: None, Conflict of Interest: None
The pandemic of coronavirus disease 2019 (COVID-19) has impacted many health service systems including tuberculosis (TB) control in India. As of October 19, 2020, India has the second highest number of COVID cases globally, amounting to 7.55 million reported COVID-19 cases and 114,640 deaths. Indian Council of Medical Research's Bacille Calmette-Guérin vaccine study among elderly individuals in COVID-19 hotspots involves the following strategy such as COVID screening by antibody testing and real-time reverse-transcriptase-polymerized chain reaction, TB screening by symptom and chest X-ray, and those who are tested positive will be linked to the national tuberculosis elimination programme for the management, this could be a sustainable new strategy in combating the two pandemic diseases, especially in India with high TB and COVID-19 disease burden. To ensure no one is left behind, the paradigm shift of screening for TB and COVID should be in place to sustain the progress made toward TB elimination.
Keywords: Bacille Calmette-Guérin, coronavirus disease 2019, national tuberculosis elimination programme, ICMR-NIRT, tuberculosis
|How to cite this article:|
Shrinivasa B M, Chandrasekaran P, Chadwick J, Murekhar MV. Adult Bacille Calmette-Guérin vaccination during the pandemic of COVID-19 in India. Int J Health Allied Sci 2021;10:307-10
|How to cite this URL:|
Shrinivasa B M, Chandrasekaran P, Chadwick J, Murekhar MV. Adult Bacille Calmette-Guérin vaccination during the pandemic of COVID-19 in India. Int J Health Allied Sci [serial online] 2021 [cited 2022 Jan 25];10:307-10. Available from: https://www.ijhas.in/text.asp?2021/10/4/307/330556
| Introduction|| |
The pandemic of coronavirus disease 2019 (COVID-19) has impacted many health service systems including tuberculosis (TB) control in India and has given a newer dimension to public health management. India has the second highest number of COVID cases globally, amounting to 7.55 million reported COVID-19 cases and 114,640 deaths.,, India ranks the highest in terms of global COVID-19 recoveries with a recovery rate of more than 75%.
COVID-19 pandemic has adversely impacted the TB control activities in India. As reported by Central TB Division Nikshay portal, the diagnosis of new TB cases has decreased by 78% in April, 2020 compared to April, 2019. India accounts for one-third of the global drug-resistant TB. The stop TB partnership's modelling analysis to document the impact of COVID on TB indicate that the annual TB incidence is likely to increase to 6.3 million cases, in addition to existing TB cases and about 1.4 million TB deaths by 2025. The findings also indicate that the progress made in recent 5 years toward TB elimination would be lost because of COVID pandemic. To recover the gains made over the last many years, it is important to have measures such as active screening, early and prompt initiation of treatment, and preventive measures including vaccination in place to reduce the accumulated pool of undiagnosed patients with TB or COVID-19.
| Similarities between Tuberculosis and Coronavirus Disease 2019|| |
Primarily, TB and COVID-19 can manifest with respiratory symptoms, and management of TB and COVID-19 co-infection is challenging during this pandemic. TB affects all age groups and the risk for its transmission is high in congested living and over-crowded conditions. This is further aggravated during the lockdown period when the infected and symptomatic individuals are unable to reach the diagnostic center and have to stay indoors thus spreading the disease to others in the household.
The available data on the COVID-19 mortality indicates that the elderly individuals and those with preexisting chronic conditions are at high risk of fatality;,, furthermore, people with TB or underlying lung condition are more likely to suffer from post-COVID sequelae, also long-term sequelae for pulmonary TB is well-known which further underscores the importance of early diagnosis and treatment of both conditions.
| Bacille Calmette-Guérin as a Protecting Factor against Coronavirus Disease 2019|| |
The rationale for use of the Bacille Calmette-Guérin vaccine (BCG) vaccine against COVID-19 is due to its nonspecific effects (NSEs) on the immune system. The NSEs protection of BCG is initiated through epigenetic mechanisms by potentiating innate immune. These changes lead to lymphocyte activation and enhancement of innate immunity which act as a protective effect against viral infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., This trained immunity acts as a protective factor against variety of infections including bacterial, viral, and parasites.
Miller et al. reported that countries with universal BCG policies had fewer deaths when compared to countries without universal policies of BCG., Furthermore, Ozdemir et al. have also found that there was decrease in morbidity and mortality due to COVID-19 among BCG vaccinated when compared to BCG nonvaccinated people. BCG vaccination may offer protective effect against viral infection and is likely to reduce cytokine storm after SARS-COV-2 exposure, resulting in mitigating the impact of severe COVID-19 infection and early recovery.
| Bacille Calmette-Guérin Vaccination and Tuberculosis|| |
The history of BCG vaccination in India goes back to 1948, when the first BCG vaccine laboratory was set up in Guindy, Chennai, in an effort to find the evidence for protective effects of BCG which was the basis on which BCG was universalized for new born immunization to prevent severe form of TB, from then on the BCG vaccination program is integrated in national TB control and scaled up to cover entire geographic areas through primary health center (PHC) network. The current documented evidence from Japan shows the negative correlation between severity of COVID disease and the BCG vaccination status of the general population.
| Adverse Effects of Bacille Calmette-Guérin|| |
The reported adverse events (AEs) for BCG both for infant vaccination and for bladder cancer therapy have been well-documented. In the case of BCG vaccination against TB, the solicited AE of pustule formation at the injection site is the most common and faulty technique of administration, i.e., subcutaneous than intradermal being the common reason. According to food drug and administration, the severe and rare AEs of BCG TB vaccination include suppurative lymphadenitis, BCG osteitis and disseminated TB as the most serious complication.,, The notable factors about the BCG vaccination and the reported AE from the existing evidence indicate that most AEs are manageable at the sub-center or PHC level which translates to the point that these are mostly mild or moderate in grade.
| Available Capacity for Implementation and Time to Upscale|| |
One of the national public health programs which is dynamic and frequently updated to keep in line with the newer development is the national tuberculosis elimination programme (NTEP) (previously known as the Revised National TB Control Programme). This program has percolated to the grass-root level in the Indian public health system in the form of designated microscopic centers. The system is placed for quality diagnostics and patient care. The commitment of the Government of India toward TB elimination can be measured from the increased budgetary outlay of the 2020 budget allocation for TB.
Furthermore, with the vaccine available at each gross root unit, PHC in the case of Indian public health system, it adds to the advantage of an easy point of delivery. In routine vaccination programs, the existing human resource available at PHC can be trained to administer and manage solicited AEs which gives an added advantage in the implementation of the BCG vaccination at a large scale in short time duration. The absolute contraindication for BCG vaccination is active TB and the target for NTEP is to diagnose and treat all cases of TB and this method of screening for two high burden diseases may achieve two goals with one action, thereby, catching up for the opportunity missed in the recent months.
Government of India's top priority to ensure continuity of essential health services including TB services during the COVID pandemic. Access to TB services was ensured besides COVID response in order prevent the additional TB deaths. Lessons learned from West Africa during the Ebola outbreak that the combined additional deaths due to HIV, TB, and malaria (indirect consequence) was more when compared to deaths directly caused by Ebola.
As NTEP ensures that there is no disruption in TB services despite COVID-19 pandemic, both TB and COVID-19 should remain as top priority. Observational studies suggest that the BCG vaccine offering protection against severe COVID-19 besides the mixed findings from observational studies,, Existing evidence from the animal models found that BCG vaccine offers protection against several respiratory tract infections along with TB and reduces about 70% of mortality and morbidity, As elderly individuals and those with preexisting conditions are at increased risk of severe disease and adverse outcomes for both diseases, combined strategy of screening for both TB and COVID-19 will address the threat of both the conditions. To determine the extent of protection from BCG vaccination, especially among the clinically vulnerable population, the result of the ongoing trials would inform us further on whether the BCG vaccine can offer nonspecific protection to fill the gap until a COVID-19 specific vaccine is developed.
| Conclusion and Way Forward|| |
A number of clinical trials involving the BCG vaccine are underway [Table 1] for the prevention of COVID. Indian Council of Medical Research's BCG vaccine trial among elderly individuals in COVID-19 hotspots areas initiated to assess the efficacy in reducing morbidity and mortality' aims at screening for COVID and active TB among the vulnerable elderly population [Figure 1]. As the trial includes the combination of screening for TB and COVID 19 in addition to BCG vaccination, this could be a sustainable new strategy in combating the two pandemic diseases, especially in a country like India with a high TB and COVID-19 disease burden. This strategy will add to case notification and early diagnosis of TB. Thus ensuring that no one is left behind, the paradigm shift of screening for TB and COVID should be in place to sustain the progress made over the Indian government's goal of “TB harega desh jeetega” (”TB will lose, the nation will win”).
|Table 1: Ongoing clinical trials evaluating the protective role of Bacille Calmette-Guérin vaccine against coronavirus disease-2019 in India|
Click here to view
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
#IndiaFightsCorona COVID-19 in India, Corona Virus Tracker | mygov.in n.d. Available from: https://www.mygov.in/Covid-19
. [Last accessed on 2020 Oct 19].
Leung C. Risk factors for predicting mortality in elderly patients with COVID-19: A review of clinical data in China. Mech Ageing Dev 2020;188:111255.
Asfahan S, Deokar K, Dutt N, Niwas R, Jain P, Agarwal M. Extrapolation of mortality in COVID-19: Exploring the role of age, sex, co-morbidities and health-care related occupation. Monaldi Arch Chest Dis 2020;90:313-7.
Ioannidis JP, Axfors C, Contopoulos-ioannidis DG. Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters. Environ Res 2020;188:109890.
Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: A systematic review. Int J Infect Dis 2015;32:138-46.
Zumla A, Marais BJ, Mchugh TD, Maeurer M, Kapata N, Ntoumi F, et al
. COVID-19 and tuberculosis-threats and opportunities. Int J Tuberc Lung Dis 2020;24:757-60.
BCG Vaccines 1 Report on BCG Vaccine use for Protection Against Mycobacterial Infections Including Tuberculosis, Leprosy, and Other Nontuberculous Mycobacteria (NTM) Infections Prepared by the SAGE Working Group on BCG Vaccines and WHO Secretariat; 2017.
Arts RJ, Moorlag SJ, Novakovic B, Li Y, Wang SY, Oosting M, et al.
BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe 2018;23:89-100.e5.
Moorlag SJ, Arts RJ, van Crevel R, Netea MG. Non-specific effects of BCG vaccine on viral infections. Clin Microbiol Infect 2019;25:1473-8.
Usher NT, Chang S, Howard RS, Martinez A, Harrison LH, Santosham M, et al
. Association of BCG vaccination in childhood with subsequent cancer diagnoses: A 60-year follow-up of a clinical trial. JAMA Netw Open 2019;2:e1912014.
Miller CL, Morris J, Pollock TM. PHLS inquiry into current BCG vaccination policy. Br Med J (Clin Res Ed) 1984;288:564.
Otu A, Ebenso B, Labonte R, Yaya S. Tackling COVID-19: Can the African continent play the long game? J Glob Health 2020;10:010339.
Ozdemir C, Kucuksezer UC, Tamay ZU. Is BCG vaccination affecting the spread and severity of COVID-19? Allergy 2020;75:1824-7.
Mohapatra PR, Mishra B, Behera B. BCG vaccination induced protection from COVID-19. Indian J Tuberc 2020;68:119-24.
Trial of BCG vaccines in south India for tuberculosis prevention: First report. Tuberculosis Prevention Trial. Bull Int Union Tuberc 1980;55:14-22.
Miller A, Reandelar MJ, Fasciglione K, Roumenova V, Li Y, Otazu G. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: An epidemiological study. MedRxiv 2020; [doi. 10.1101/2020.03.24.20042937].
Xie J, Codd C, Mo K, He Y. Differential adverse event profiles associated with BCG as a preventive tuberculosis vaccine or therapeutic bladder cancer vaccine identified by comparative ontology-based VAERS and literature meta-analysis. PLoS One 2016;11:e0164792.
Mostaan S, Yazdanpanah B, Moukhah R, Hozouri HR, Rostami M, Khorashadizadeh M, et al
. Adverse effects of BCG vaccine 1173 P2 in Iran: A meta-analysis. Adv Biomed Res 2016;5:99. doi: 10.4103/2277-9175.183659. PMID: 27376038; PMCID: PMC4918213.
] [Full text]
Konwloh PK, Cambell CL, Ade S, Bhat P, Harries AD, Wilkinson E, et al
. Influence of Ebola on tuberculosis case finding and treatment outcomes in Liberia. Public Heal Action 2017;7:62-9.
Wingfield T, Cuevas LE, MacPherson P, Millington KA, Squire SB. Tackling two pandemics: A plea on world tuberculosis day. Lancet Respir Med 2020;8:536-8. [doi: 10.1016/S2213-2600(20)30151-X].
Berg MK, Yu Q, Salvador CE, Melani I, Kitayama S. Mandated bacillus calmette-guérin (BCG) vaccination predicts flattened curves for the spread of COVID-19. Sci Adv 2020;6:eabc1463.
Escobar LE, Molina-Cruz A, Barillas-Mury C. BCG vaccine protection from severe coronavirus disease 2019 (COVID-19). Proc Natl Acad Sci U S A 2020;117:17720-6.
Gopalaswamy R, Ganesan N, Velmurugan K, Aravindhan V, Subbian S. The strange case of BCG and COVID-19: The verdict is still up in the air. Vaccines (Basel) 2020;8:E612.
Rajarshi K, Chatterjee A, Ray S. BCG vaccination strategy implemented to reduce the impact of COVID-19: Hype or hope? Med Drug Discov 2020;7:100049.
Doesschate TT, Moorlag SJ, van der Vaart TW, Taks E, Debisarun P, Oever JT, et al
. Two Randomized controlled trials of bacillus calmette-guérin vaccination to reduce absenteeism among health care workers and hospital admission by elderly persons during the COVID-19 pandemic: A structured summary of the study protocols for two randomised controlled trials. Trials 2020;21:481.