Tuberculosis prevalence relation to COVID-19 mortality in malaria free countries
Keywords:COVID-19, Malaria, SARS-Cov2, TB, Trained immunity
Background: Both malaria and latent tuberculosis (TB) are possible factors related to decreased COVID-19 mortality. Malaria endemicity variable is a possible confounder when conducting a study on the correlation of latent TB prevalence to COVID-19 mortality. Studies regarding latent TB prevalence" according to different studies" did not adjust malaria endemicity as a possible confounder. Many malaria-endemic countries are high TB prevalent. Malaria-free countries could be: high, moderate, or low in TB prevalence. The main aim of this study is to look for the influence of TB prevalence on COVID-19 mortality. TB prevalence reflects latent TB prevalence in the absence of malaria endemicity as a possible confounding factor in TB studies.
Methods: The total chosen countries were sixty-nine non-malaria endemic countries. Countries were classified according to TB prevalence groups into low, moderate, and high prevalent groups. Covid-19 deaths/Million (M) inhabitant were taken as reported on September 2, 2020. "Kendall's-τ Correlation Coefficient", "Kruskal-Wall is test, and Mann-Whitney test were used in statistical analyses.
Results: We found inverse relationships between TB prevalence and COVID-19 deaths/ (M) inhabitant and a highly positive significant correlation coefficient was reported (0.008) in Kendall's-τ correlation coefficient test. Kruskal-Wall is test showed a significant relationship within studied groups. Furthermore, the low TB prevalent group had significant reverse associations with both high and moderate TB prevalent groups in the Mann-Whitney test.
Conclusions: In the absence of possible malaria confounding, TB prevalence in malaria free countries is inversely related to COVID-19 mortality in a highly significant association.
Netea MG, Quintin J, van der Meer JW. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011 May 19; 9(5):355-61.
World Health Organization. Global Tuberculosis Report 2015. Geneva: WHO, 2015. Available at http://www.who.int/tb/publications/global_report/e. Accessed on 23 November 2015.
Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep. 2000;49(6):1-51.
Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol. 1974;99:131-8.
WHO Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. 2018. Available at https://apps.who.int/iris/bitstream/handle. Accessed on 12 January 2021.
Biraro IA, Kimuda S, Egesa M, Cose S, Webb EL, Joloba M, et al. The Use of interferon gamma inducible protein 10 as a potential biomarker in the diagnosis of latent tuberculosis infection in Uganda. PLoS One. 2016;11(1):e0146098.
Marcel A, Paul H, Lalita R. Revisiting the timetable of tuberculosis. BMJ. 2020;27:362:
Marcel BA, Paul H, Lalita. Is mycobacterium tuberculosis infection life long?. BMJ. 2020;367:l5770.
Crevel R, Ottenhoff THM, Jos WM. Innate Immunity to Mycobacterium tuberculosis. Clinical Microbiology Reviews. 2002;15(2):294-309.
Raham TF. TB prevalence influence on covid-19 mortality. Int J Psychosocial Rehab. 2020;24(10):3679- 90.
Singh S, Maurya RP, Singh RK. ′Trained immunity′ from Mycobacterium spp. exposure or BCG vaccination and COVID-19 outcomes. Medrxiv. 2020: 10.1101/2020.07.11.20151308.
Takahashi H. Role of latent tuberculosis infections in reduced COVID-19 mortality: evidence from an instrumental variable method analysis. Medical Hypotheses. 2020:144110214.
Banerjee S, Saha A. Finding tentative causes for the reduced impact of Covid-19 on the health systems of poorer and developing nations: an ecological study of the effect of demographic, climatological and health related factors on the global spread of Covid-19. Medrxiv. 2020.
Singh S. BCG vaccines may not reduce covid-19 mortality rates. Medrxiv. 2020.
Gomes LR, Martins YC, Ferreira-da-Cruz MF, Ribeiro CT. Autoimmunity, phospholipid-reacting antibodies and malaria immunity. Lupus. 2014;23(12):1295-8.
Parodi A, Cozzani E. Coronavirus disease 2019 (COVID 19) and Malaria: Have anti glycoprotein antibodies a role? Med Hypotheses. 2020;143:110036.
Napoli PE, Nioi M. Global spread of coronavirus disease 2019 and malaria: an epidemiological paradox in the early stage of a pandemic. J Clin Med. 2020;9(4):1138.
Guha R, Mathioudaki A, Doumbo S, Doumtabe D, Skinner J, Plasmodium falciparum malaria drives epigenetic reprogramming of human monocytes toward a regulatory phenotype BioRxiv. 2020;10:21-34.
Raham TF. Influence of malaria endemicity and tuberculosis prevalence on COVID-19 mortality. Public Health. 2021;194:33-5.
Raham TF. Malaria elimination date correlation to COVID-19 mortality: New Evidence (November 21, 2020). Available at SSRN: https:// ssrn. com/ abstract=3735069 or http://dx.doi.org/10.2139/ssrn.3735069.
WHO. Countries and territories certified malaria-free by WHO. Available at WHO Countries and territories certified malaria-free by WHO. Accessed on 21 April 2021.
Skelly AC, Dettori JR, Brodt ED. Assessing bias: the importance of considering confounding. Evid Based Spine Care J. 2012;3(1):9-12.
Jager KJ, Zoccali C, MacLeod A, Dekker FW. Confounding: What it is and how to deal with it. Kidney Int. 2008;73(3):256-60.
Sorci G, Faivre B, Morand S. Explaining among-country variation in COVID-19 case fatality rate. Sci Rep. 2020;10:18909
Bhutta ZA, Sommerfeld J, Lassi ZS, Salam RA, Das JK. Global burden, distribution, and interventions for infectious diseases of poverty. Infect Dis Poverty. 2014;3(1):1.
Tuberculosis and malaria in the age of COVID-19. The Lancet Infectious Diseases. 2021;21(1):1-148.
Hamed KH. The distribution of Kendall’s tau for testing the significance of cross-correlation in persistent data. Hydrol Sci J. 2011;56(5):841-53.
Al-Momen H, Raham TF, Daher AM. Tuberculosis versus COVID-19 mortality: a new evidence. Maced J Med Sci. 2020;24:33-9.
Corder, Gregory W, Dale FI. (2009). Nonparametric Statistics for Non-Statisticians. Hoboken: John Wiley and Sons. Pp 99-105.
Wallis K. Use of ranks in one-criterion variance analysis. J Am Statistical Association. 1952;47(260):583-621.
World malaria report 2019. Geneva: World Health Organization; 2019.
Jomana A, Ashraf K, Khalid K. Could "trained immunity" be induced by live attenuated vaccines protect against COVID-19? Review of available evidence. J Infect Developing Countries. 2020;14:957-62.
Ai JW, Ruan QL, Liu QH, Zhang WH. Updates on the risk factors for latent tuberculosis reactivation and their managements. Emerg Microbes Infect. 2016;5(2):e10.
CDC. Deciding When to Treat Latent TB Infection. Available at https:// www. cdc. gov/tb/topic/treatment/decideltbi.htm. Accessed on 8 September 2020.
European Centre for Disease Prevention and Control. Management of latent tuberculosis infection. Available at https://www.ecdc.europa.eu/en/tuberculosis/prevention-and-control/management-latent-tuberculosis-infection. Accessed on 8 November 2020.
McNeil, Donald G. Latent' tuberculosis? It's not that common, experts find. The New York Times.
Abubakar I, Pimpin L, Ariti C, Beynon R, Mangtani P, Sterne JA, et al. Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis. Health Technol Assess. 2013;17(37):371-2.