Anna M Stadelman1,2,3, Kenneth Ssebambulidde3, Lillian Tugume3, Katelyn A Pastick2,3, Kathy Huppler Hullsiek4, Sarah Lofgren2, Edwin Nuwagira5, Emily E Evans5, Darlisha A Williams2,3, Conrad Muzoora5, David B Meya2,3,6, Radha Rajasingham2,7, Joshua Rhein2,3, David R Boulware2,7. 1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. 2. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA. 3. Infectious Diseases Institute, Makerere University, Kampala, Uganda. 4. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA. 5. Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda. 6. Department of Medicine, Faculty of Health Sciences, Makerere University, Kampala, Uganda. 7. Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, MN, USA.
Abstract
The role of biological sex on clinical outcomes and the pathogenesis of AIDS-related opportunistic infections is unknown. We assessed baseline biomarkers and outcomes between 577 men and 400 women in HIV-related cryptococcal meningitis cohorts in Uganda and South Africa from 2010 to 2017. We compared 10-week mortality by sex via Cox proportional hazards models. The 10-week mortality for women was 50% (198/400) and 43% (247/577) for men. Women had higher risk of death in an unadjusted model (Hazard Ratio (HR) = 1.20; 95%CI, 1.00-1.45; P = .05). Women maintained a higher risk when adjusting for quantitative CSF culture, altered mental status, CSF pleocytosis, age, and antiretroviral status (HR = 1.31; 95%CI, 1.07-1.59; P < .01). However, after adjusting for hemoglobin, the risk of death did not differ between women and men (HR = 1.17; 95%CI, 0.94-1.45; P = .17). Moderate to severe anemia (hemoglobin < 8.5 g/dL) was present among 16% (55/355) of women and 10% (55/532) of men (P = .02). Of the 373 participants with CSF biomarkers, men had higher median pro- and anti-inflammatory, monocyte/macrophage differentiation, maturation, and migration, immune exhaustion, and cytotoxicity cytokines than women (P < .05). We identified biological sex as proxy for anemia, a potentially modifiable risk factor for cryptococcal meningitis mortality. Immune response may contribute to the multifaceted underlying mechanisms for the discrepancy in mortality based on sex. LAY SUMMARY: We examined the role of biological sex in cryptococcal meningitis mortality in a large cohort. Our findings reveal significant differences in inflammatory markers by biological sex. Women have significantly higher mortality due to cryptococcal meningitis that is attributable to anemia at baseline.
The role of biological sex on clinical outcomes and the pathogenesis of AIDS-related opportunistic infections is unknown. We assessed baseline biomarkers and outcomes between 577 men and 400 women in HIV-related cryptococcal meningitis cohorts in Uganda and South Africa from 2010 to 2017. We compared 10-week mortality by sex via Cox proportional hazards models. The 10-week mortality for women was 50% (198/400) and 43% (247/577) for men. Women had higher risk of death in an unadjusted model (Hazard Ratio (HR) = 1.20; 95%CI, 1.00-1.45; P = .05). Women maintained a higher risk when adjusting for quantitative CSF culture, altered mental status, CSF pleocytosis, age, and antiretroviral status (HR = 1.31; 95%CI, 1.07-1.59; P < .01). However, after adjusting for hemoglobin, the risk of death did not differ between women and men (HR = 1.17; 95%CI, 0.94-1.45; P = .17). Moderate to severe anemia (hemoglobin < 8.5 g/dL) was present among 16% (55/355) of women and 10% (55/532) of men (P = .02). Of the 373 participants with CSF biomarkers, men had higher median pro- and anti-inflammatory, monocyte/macrophage differentiation, maturation, and migration, immune exhaustion, and cytotoxicity cytokines than women (P < .05). We identified biological sex as proxy for anemia, a potentially modifiable risk factor for cryptococcal meningitis mortality. Immune response may contribute to the multifaceted underlying mechanisms for the discrepancy in mortality based on sex. LAY SUMMARY: We examined the role of biological sex in cryptococcal meningitis mortality in a large cohort. Our findings reveal significant differences in inflammatory markers by biological sex. Women have significantly higher mortality due to cryptococcal meningitis that is attributable to anemia at baseline.
Authors: Radha Rajasingham; Rachel M Smith; Benjamin J Park; Joseph N Jarvis; Nelesh P Govender; Tom M Chiller; David W Denning; Angela Loyse; David R Boulware Journal: Lancet Infect Dis Date: 2017-05-05 Impact factor: 25.071
Authors: Asha R Kallianpur; Quan Wang; Peilin Jia; Todd Hulgan; Zhongming Zhao; Scott L Letendre; Ronald J Ellis; Robert K Heaton; Donald R Franklin; Jill Barnholtz-Sloan; Ann C Collier; Christina M Marra; David B Clifford; Benjamin B Gelman; Justin C McArthur; Susan Morgello; David M Simpson; J A McCutchan; Igor Grant Journal: J Infect Dis Date: 2015-12-21 Impact factor: 5.226
Authors: Radha Rajasingham; Joshua Rhein; Kate Klammer; Abdu Musubire; Henry Nabeta; Andrew Akampurira; Eric C Mossel; Darlisha A Williams; Dave J Boxrud; Mary B Crabtree; Barry R Miller; Melissa A Rolfes; Supatida Tengsupakul; Alfred O Andama; David B Meya; David R Boulware Journal: Am J Trop Med Hyg Date: 2014-11-10 Impact factor: 2.345