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1.
Lancet Infect Dis ; 21(11): 1590-1597, 2021 11.
Article in English | MEDLINE | ID: covidwho-1561435

ABSTRACT

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.


Subject(s)
BCG Vaccine/administration & dosage , Immunization, Secondary/statistics & numerical data , Mortality , Vaccination/methods , Adolescent , Adult , Aged , BCG Vaccine/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , Child , Child, Preschool , Double-Blind Method , Female , Follow-Up Studies , Humans , Immunogenicity, Vaccine , Leprosy/immunology , Leprosy/mortality , Leprosy/prevention & control , Malawi/epidemiology , Male , Middle Aged , Mycobacterium leprae/immunology , SARS-CoV-2/immunology , Treatment Outcome , Tuberculosis/immunology , Tuberculosis/mortality , Tuberculosis/prevention & control , Vaccination/statistics & numerical data , Young Adult
2.
Int J Dermatol ; 61(6): 733-738, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1537821

ABSTRACT

Leprosy, also known as Hansen's disease, is an age-old chronic granulomatous infection characterized by prominent cutaneous and neurologic findings. Long known to be caused by Mycobacterium leprae, a new etiologic species was identified and linked in 2008, Mycobacterium lepromatosis. The BCG vaccine with highly variable efficacy may soon be replaced by the first leprosy-specific subunit vaccine LepVax, which has recently moved forward in human trials. Recent evidence supporting theories of zoonotic transmission from armadillos and the less-discussed Eurasian red squirrels has emerged. Knowledge on genetic polymorphisms that may increase leprosy susceptibility, such as the newly uncovered mitochondrial ribosomal protein S5 (MRPS5) polymorphism in the Chinese population, has provided a fresh perspective and direction. Further, we will delineate the latest information on leprosy, including the possible effects of leprosy coinfection with COVID-19, HIV, and HTLV-1, and the shift to newer leprosy therapies and treatment regimens.


Subject(s)
COVID-19 , Leprosy , Animals , Armadillos/microbiology , Humans , Leprosy/epidemiology , Leprosy/microbiology , Mycobacterium leprae/genetics
3.
Vaccine ; 38(48): 7629-7637, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-879777

ABSTRACT

This work demonstrates the presence of immune regulatory cells in the cervical lymph nodes draining Bacillus Calmette-Guérin (BCG) vaccinated site on the dorsum of the ear in guinea pigs. It is shown that whole cervical lymph node cells did not proliferate in vitro in the presence of soluble mycobacterial antigens (PPD or leprosin) despite being responsive to whole mycobacteria. Besides, T cells from these lymph nodes separated as a non-adherent fraction on a nylon wool column, proliferated to PPD in the presence of autologous antigen presenting cells. Interestingly, addition of as low as 20% nylon wool adherent cells to these, sharply decreased the proliferation by 83%. Looking into what cells in the adherent fraction suppressed the proliferation, it was found that neither the T cell nor the macrophage enriched cell fractions of this population individually showed suppressive effect, indicating that their co-presence was necessary for the suppression. Since BCG induced granulomas resolve much faster than granulomas induced by other mycobacteria such as Mycobacterium leprae the present experimental findings add to the existing evidence that intradermal BCG vaccination influences subsequent immune responses in the host and may further stress upon its beneficial role seen in Covid-19 patients.


Subject(s)
Antigens, Bacterial/pharmacology , BCG Vaccine/pharmacology , Granuloma/immunology , Lymph Nodes/immunology , T-Lymphocytes/immunology , Animals , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/microbiology , COVID-19 , Cell Adhesion , Cell Proliferation , Coronavirus Infections/prevention & control , Ear , Female , Granuloma/microbiology , Guinea Pigs , Humans , Injections, Intradermal , Lymph Nodes/microbiology , Macrophages/drug effects , Macrophages/immunology , Macrophages/microbiology , Male , Mycobacterium bovis/immunology , Mycobacterium leprae/immunology , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Remission, Spontaneous , T-Lymphocytes/classification , T-Lymphocytes/drug effects , T-Lymphocytes/microbiology
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