lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

The Effect of BCG on Mortality Beyond Infancy: 30-Year Follow-Up of a Double-Blind Randomised Placebo-Controlled Trial of BCG Re-Vaccination in Malawi

18 Pages Posted: 16 Oct 2020

See all articles by Judith R. Glynn

Judith R. Glynn

London School of Hygiene and Tropical Medicine - Department of Infectious Disease Epidemiology; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine

Albert Dube

Malawi Epidemiology Intervention Research Unit

Katherine Fielding

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine

Amelia C. Crampin

Malawi Epidemiology and Intervention Research Unit (MEIRU); London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health

Karonga Prevention Trial Group

Independent

Chifundo Kanjala

London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health

Paul Fine

London School of Hygiene & Tropical Medicine

More...

Abstract

Background: Trials of BCG to prevent COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of BCG’s beneficial non-specific effects come largely from data on mortality in infants, and from in vitro and animal studies. We assess all-cause mortality following a large BCG re-vaccination trial in Malawi. 

Methods: A population-based double-blind randomised trial comparing BCG re-vaccination vs placebo to prevent tuberculosis and leprosy was initiated in Karonga District, Malawi, in 1986-9, in individuals aged 3 months to 75 years. Active follow-up was carried out in northern areas of the district in 1991-94 and in a southern area in 2002-2018 covering 15.8% (7389 individuals) and 12.0% (5616 individuals) of the trial population respectively. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality rates.

Findings: There was no difference in mortality rate between the BCG and placebo group in either follow-up, overall or by age group. Mortality rates in the northern areas were 6.6/1000 person years at risk (pyar), 95% confidence interval 5.5-7.8, and 7.0/1000pyar (5.9-8.2) for those who received BCG and placebo, respectively. In the southern area they were 6.3/1000 pyar, (5.5-7.1), and 5.9/1000 pyar, (5.2-6.8), respectively. 

Interpretation: We found no evidence of any beneficial effect of BCG re-vaccination 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, may obscure any benefits. 

Funding Statement: The original trial was funded by primarily by the British Leprosy Relief Association (LEPRA), with assistance from the International Federation of Anti-Leprosy Organizations (ILEP), and the Immunology of Leprosy component of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (IMMLEP/TDR), with support of the Malawian Ministry of Health. The later follow-up was funded by The Wellcome Trust There was no specific funding for this analysis.

Declaration of Interests: We declare no competing interests.

Ethics Approval Statement: The trial protocol was approved in 1985 by the Health Sciences Research Committee of the Malawi Ministry of Health, the Standing Committee on Research in Human Subjects of WHO, and the Ethics Committee of the London School of Hygiene & Tropical Medicine. Follow-up of the population has been approved in the context of other studies by the Health Sciences Research Committee of the Malawi Ministry of Health and the Ethics Committee of the London School of Hygiene & Tropical Medicine.

Keywords: BCG, non-specific effects, re-vaccination, Mortality, COVID-19, randomised controlled trial

Suggested Citation

Glynn, Judith R. and Dube, Albert and Fielding, Katherine and Crampin, Amelia C. and Group, Karonga Prevention Trial and Kanjala, Chifundo and Fine, Paul, The Effect of BCG on Mortality Beyond Infancy: 30-Year Follow-Up of a Double-Blind Randomised Placebo-Controlled Trial of BCG Re-Vaccination in Malawi. Available at SSRN: https://ssrn.com/abstract=3684476 or http://dx.doi.org/10.2139/ssrn.3684476

Judith R. Glynn (Contact Author)

London School of Hygiene and Tropical Medicine - Department of Infectious Disease Epidemiology

London
United Kingdom

Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine ( email )

Albert Dube

Malawi Epidemiology Intervention Research Unit ( email )

Katherine Fielding

Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine

Keppel Street
London, WC1E 7HT
United Kingdom

Amelia C. Crampin

Malawi Epidemiology and Intervention Research Unit (MEIRU)

London
United Kingdom

London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health ( email )

London, WC1E 7HT
United Kingdom

Chifundo Kanjala

London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health ( email )

London, WC1E 7HT
United Kingdom

Paul Fine

London School of Hygiene & Tropical Medicine ( email )

Keppel Street
London, WC1E 7HT
United Kingdom

Click here to go to TheLancet.com

Paper statistics

Abstract Views
275
Downloads
18
PlumX Metrics