Guerra-Silveira F , Abad-Franch F , 2013. Sex bias in infectious disease epidemiology: patterns and processes. PLoS One 8: e62390.
Nhamoyebonde S , Leslie A , 2014. Biological differences between the sexes and susceptibility to tuberculosis. J Infect Dis 209 (Suppl 3):S100–S106.
Klein SL , Flanagan KL , 2016. Sex differences in immune responses. Nat Rev Immunol 16: 626–638.
Word Health Organization, 2020. Global TB Report. Geneva, Switzerland: WHO.
Abedi S , Moosazadeh M , Tabrizi R , Afshari M , Nezammahalleh A , Akbari M , 2019. The impact of diabetics and smoking on gender differences of smear positive pulmonary tuberculosis incidence. Indian J Tuberc 66: 353–357.
Watkins RE , Plant AJ , 2006. Does smoking explain sex differences in the global tuberculosis epidemic? Epidemiol Infect 134: 333–339.
Neyrolles O , Quintana-Murci L , 2009. Sexual inequality in tuberculosis. PLoS Med 6: e1000199.
Hamilton JB , Mestler GE , 1969. Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population. J Gerontol 24: 395–411.
Bini EI et al., 2014. The influence of sex steroid hormones in the immunopathology of experimental pulmonary tuberculosis. PLoS One 9: e93831.
Dibbern J , Eggers L , Schneider BE , 2017. Sex differences in the C57BL/6 model of Mycobacterium tuberculosis infection. Sci Rep 7: 10957.
Diarra B et al., 2016. Tuberculosis drug resistance in Bamako, Mali, from 2006 to 2014. BMC Infect Dis 16: 714.
Baya B et al., 2020. Association of Mycobacterium africanum infection with slower disease progression compared with Mycobacterium tuberculosis in Malian patients with tuberculosis. Am J Trop Med Hyg 102: 36–41.
Diarra B et al., 2018. Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali. PLoS One 13: e0208603.
Diarra B et al.2020. Fluorescein diacetate and rapid molecular testing for the early identification of rifampicin resistance in Mali. Int J Tuberculosis Lung Dis 24: 763–769.
Word Health Organization , 2014. Definitions et Cadre pour la Notification de la Tuberculose. Geneva, Switzerland: WHO.
Olaru ID , Heyckendorf J , Grossmann S , Lange C , 2014. Time to culture positivity and sputum smear microscopy during tuberculosis therapy. PLoS One 9: e106075.
Chu Y et al., 2019. Sex disparity in severity of lung lesions in newly identified tuberculosis is age-associated. Front Med 6: 163.
Tan W et al., 2018. Sex influences the association between haemostasis and the extent of lung lesions in tuberculosis. Biol Sex Differ 9: 44.
Feng JY et al., 2012. Gender differences in treatment outcomes of tuberculosis patients in Taiwan: a prospective observational study. Clin Microbiol Infect 18: E331–337.
Ramos JM et al., 2020. Sex differences and HIV status of tuberculosis in adults at a rural hospital in southern Ethiopia: an 18-year retrospective cross-sectional study. Afr Health Sci 20: 605–614.
Kamel MI , Rashed S , Foda N , Mohie A , Loutfy M , 2003. Gender differences in health care utilization and outcome of respiratory tuberculosis in Alexandria. East Mediterranean Health J 9: 741–756.
Belo MT et al., 2010. Tuberculosis and gender in a priority city in the state of Rio de Janeiro, Brazil. J Brasileiro Pneumol 36: 621–625.
Weiss MG et al., 2006. Gender and tuberculosis: cross-site analysis and implications of a multi-country study in Bangladesh, India, Malawi, and Colombia. Geneva, Switzerland: World Health Organization. Available at: https://apps.who.int/iris/handle/10665/69355.
Diallo S et al., 2008. Epidemiologic aspects of pulmonary tuberculosis with positive bacilloscopy in the decade of 1995–2004. Mali Med 23: 25–29.
Keita B , Samake L , Sangare S , 1994. Factors in quitting antituberculous treatment in Bamako (Mali). Rev Mal Respir 11: 579–582.
Fox GJ , Orlova M , Schurr E , 2016. Tuberculosis in newborns: the lessons of the “Lubeck disaster” (1929–1933). PLoS Pathog 12: e1005271.
Bustamante J , 2020. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet 139: 993–1000.
Dalgic N , Tekin D , Kayaalti Z , Cakir E , Soylemezoglu T , Sancar M , 2011. Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis. Dis Markers 31: 33–38.
Davila S et al., 2008. Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis. PLoS Genet 4: e1000218.
Salie M et al., 2015. Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms. Infect Genet Evol 34: 221–229.
Schurz H , Salie M , Tromp G , Hoal EG , Kinnear CJ , Moller M , 2019. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum Genomics 13: 2.
Combo Georges TA et al., 2020. Performance of Xpert MTB/RIF in comparison with light-emitting diode-fluorescence microscopy and culture for detecting tuberculosis in pulmonary and extrapulmonary specimens in Bamako, Mali. Int J Mycobacteriol 9: 397–404.
World Health Organization , 2011. Fluorescent Light-emitting Diode (LED) Microscopy for Diagnosis of Tuberculosis: Policy Statement. Geneva, Switzerland: WHO.
Chidambaram V et al., 2021. Male sex is associated with worse microbiological and clinical outcomes following tuberculosis treatment: a retrospective cohort study, a systematic review of the literature, and meta-analysis. Nephrol Dial Transplant 73: 1580–1588.
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Men and women often respond differently to infectious diseases and their treatments. Tuberculosis (TB) is a life-threatening communicable disease that affects more men than women globally. Whether male sex is an independent risk factor for unfavorable TB outcomes, however, has not been rigorously investigated in an African context, where individuals are likely exposed to different microbial and environmental factors. We analyzed data collected from a cohort study in Mali by focusing on newly diagnosed active pulmonary TB individuals who were treatment naive. We gathered baseline demographic, clinical, and microbiologic characteristics before treatment initiation and also at three time points during treatment. More males than females were affected with TB, as evidenced by a male-to-female ratio of 2.4:1. In addition, at baseline, males had a significantly higher bacterial count and shorter time to culture positivity as compared with females. Male sex was associated with lower smear negativity rate after 2 months of treatment also known as the intensive phase of treatment, but not at later time points. There was no relationship between patients’ sex and mortality from any cause during treatment. This study suggests that sex-based differences in TB outcomes exist, with sex-specific effects on disease outcomes being more pronounced before treatment initiation and during the intensive phase of treatment rather than at later phases of treatment.
These authors contributed equally to this work.
Financial support: Research described in this publication was supported by the Fogarty International Center and the Office of the Director of the National Institutes of Health through the Office of Research on Women’s Health, under Career Development Award K43TW011426 (principal investigator: Dabitao D). The research was also supported by the Institute for Global Health at the Feinberg School of Medicine of the Northwestern University, under the Catalyzer Award (principal investigators: Dabitao D and Murphy RL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and Northwestern University.
Authors’ addresses: Djeneba Dabitao, Amadou Somboro, Ibrahim Sanogo, Bassirou Diarra, Bocar Baya, Moumine Sanogo, Mohamed Tolophoudie, Mamadou Wague, Nadie Coulibaly, Mahamadou Kone, Hawa Baye Drame, Bourahima Kone, Ayouba Diarra, Mamadou D. Coulibaly, Kathryn Saliba-Shaw, Yacouba Toloba, Mahamadou Diakite, Seydou Doumbia, and Souleymane Diallo, University Clinical Research Center, Faculty of Pharmacy and Faculty of Medicine and Odonto-Stomatology, University of Sciences, Techniques, and Technologies of Bamako, Mali, West Africa, E-mails: ddabitao@icermali.org, asomboro@icermali.org, isanogo@icermali.org, bdiarra@icermali.org, bbaya@icermali.org, smoumine@icermali.org, mtolofoudie@icermali.org, mwague@icermali.org, nadie@icermali.org, mahakone@icermali.org, hawa.drame@icermali.org, bkone@icermali.org, adiarra@icemrwaf.org, mdcoulibaly@icermali.org, katy.saliba@nih.gov, toloba71@yahoo.fr, mdiakite@icermali.org, sdoumbi@gmail.com, and solo@icermali.org. Chad J. Achenbach, Division of Infectious Diseases and Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL, E-mail: c-achenbach@northwestern.edu. Jane L. Holl, Biological Sciences Division, University of Chicago, Chicago, IL, E-mail: jholl@neurology@bsd.uchicago.edu. Sabra L. Klein, W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and Graduate Program in Immunology, Johns Hopkins School of Medicine, Baltimore, MD, E-mail: sklein2@jhu.edu. William R. Bishai, Department of Infectious Diseases, Center for Tuberculosis Research, Johns Hopkins School of Medicine, Baltimore, MD, E-mail: wbishai1@jhmi.edu. Robert L. Murphy, Division of Infectious Diseases and Institute for Global Health, Feinberg School of Medicine, Northwestern University, Chicago, IL, and Biological Sciences Division, University of Chicago, Chicago, IL, E-mail: r-murphy@northwestern.edu.
Guerra-Silveira F , Abad-Franch F , 2013. Sex bias in infectious disease epidemiology: patterns and processes. PLoS One 8: e62390.
Nhamoyebonde S , Leslie A , 2014. Biological differences between the sexes and susceptibility to tuberculosis. J Infect Dis 209 (Suppl 3):S100–S106.
Klein SL , Flanagan KL , 2016. Sex differences in immune responses. Nat Rev Immunol 16: 626–638.
Word Health Organization, 2020. Global TB Report. Geneva, Switzerland: WHO.
Abedi S , Moosazadeh M , Tabrizi R , Afshari M , Nezammahalleh A , Akbari M , 2019. The impact of diabetics and smoking on gender differences of smear positive pulmonary tuberculosis incidence. Indian J Tuberc 66: 353–357.
Watkins RE , Plant AJ , 2006. Does smoking explain sex differences in the global tuberculosis epidemic? Epidemiol Infect 134: 333–339.
Neyrolles O , Quintana-Murci L , 2009. Sexual inequality in tuberculosis. PLoS Med 6: e1000199.
Hamilton JB , Mestler GE , 1969. Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population. J Gerontol 24: 395–411.
Bini EI et al., 2014. The influence of sex steroid hormones in the immunopathology of experimental pulmonary tuberculosis. PLoS One 9: e93831.
Dibbern J , Eggers L , Schneider BE , 2017. Sex differences in the C57BL/6 model of Mycobacterium tuberculosis infection. Sci Rep 7: 10957.
Diarra B et al., 2016. Tuberculosis drug resistance in Bamako, Mali, from 2006 to 2014. BMC Infect Dis 16: 714.
Baya B et al., 2020. Association of Mycobacterium africanum infection with slower disease progression compared with Mycobacterium tuberculosis in Malian patients with tuberculosis. Am J Trop Med Hyg 102: 36–41.
Diarra B et al., 2018. Mycobacterium africanum (Lineage 6) shows slower sputum smear conversion on tuberculosis treatment than Mycobacterium tuberculosis (Lineage 4) in Bamako, Mali. PLoS One 13: e0208603.
Diarra B et al.2020. Fluorescein diacetate and rapid molecular testing for the early identification of rifampicin resistance in Mali. Int J Tuberculosis Lung Dis 24: 763–769.
Word Health Organization , 2014. Definitions et Cadre pour la Notification de la Tuberculose. Geneva, Switzerland: WHO.
Olaru ID , Heyckendorf J , Grossmann S , Lange C , 2014. Time to culture positivity and sputum smear microscopy during tuberculosis therapy. PLoS One 9: e106075.
Chu Y et al., 2019. Sex disparity in severity of lung lesions in newly identified tuberculosis is age-associated. Front Med 6: 163.
Tan W et al., 2018. Sex influences the association between haemostasis and the extent of lung lesions in tuberculosis. Biol Sex Differ 9: 44.
Feng JY et al., 2012. Gender differences in treatment outcomes of tuberculosis patients in Taiwan: a prospective observational study. Clin Microbiol Infect 18: E331–337.
Ramos JM et al., 2020. Sex differences and HIV status of tuberculosis in adults at a rural hospital in southern Ethiopia: an 18-year retrospective cross-sectional study. Afr Health Sci 20: 605–614.
Kamel MI , Rashed S , Foda N , Mohie A , Loutfy M , 2003. Gender differences in health care utilization and outcome of respiratory tuberculosis in Alexandria. East Mediterranean Health J 9: 741–756.
Belo MT et al., 2010. Tuberculosis and gender in a priority city in the state of Rio de Janeiro, Brazil. J Brasileiro Pneumol 36: 621–625.
Weiss MG et al., 2006. Gender and tuberculosis: cross-site analysis and implications of a multi-country study in Bangladesh, India, Malawi, and Colombia. Geneva, Switzerland: World Health Organization. Available at: https://apps.who.int/iris/handle/10665/69355.
Diallo S et al., 2008. Epidemiologic aspects of pulmonary tuberculosis with positive bacilloscopy in the decade of 1995–2004. Mali Med 23: 25–29.
Keita B , Samake L , Sangare S , 1994. Factors in quitting antituberculous treatment in Bamako (Mali). Rev Mal Respir 11: 579–582.
Fox GJ , Orlova M , Schurr E , 2016. Tuberculosis in newborns: the lessons of the “Lubeck disaster” (1929–1933). PLoS Pathog 12: e1005271.
Bustamante J , 2020. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet 139: 993–1000.
Dalgic N , Tekin D , Kayaalti Z , Cakir E , Soylemezoglu T , Sancar M , 2011. Relationship between toll-like receptor 8 gene polymorphisms and pediatric pulmonary tuberculosis. Dis Markers 31: 33–38.
Davila S et al., 2008. Genetic association and expression studies indicate a role of toll-like receptor 8 in pulmonary tuberculosis. PLoS Genet 4: e1000218.
Salie M et al., 2015. Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms. Infect Genet Evol 34: 221–229.
Schurz H , Salie M , Tromp G , Hoal EG , Kinnear CJ , Moller M , 2019. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum Genomics 13: 2.
Combo Georges TA et al., 2020. Performance of Xpert MTB/RIF in comparison with light-emitting diode-fluorescence microscopy and culture for detecting tuberculosis in pulmonary and extrapulmonary specimens in Bamako, Mali. Int J Mycobacteriol 9: 397–404.
World Health Organization , 2011. Fluorescent Light-emitting Diode (LED) Microscopy for Diagnosis of Tuberculosis: Policy Statement. Geneva, Switzerland: WHO.
Chidambaram V et al., 2021. Male sex is associated with worse microbiological and clinical outcomes following tuberculosis treatment: a retrospective cohort study, a systematic review of the literature, and meta-analysis. Nephrol Dial Transplant 73: 1580–1588.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 3816 | 2629 | 372 |
Full Text Views | 210 | 29 | 8 |
PDF Downloads | 192 | 29 | 5 |