Clinical observations have long suggested that women are protected against paracoccidioidomycosis. 17β-estradiol, the main female estrogen, inhibits conidia-to-yeast transformation (C-to-Y), which is required for the infection establishment. However, experiments in murine models have yielded conflicting results, suggesting that C-to-Y inhibition, alone, fails to explain the female-associated protection and that sexual hormones may also act by modulating the host’s immune responses. Therefore, this issue remains unsolved. Strikingly, no studies have compared the severity of paracoccidioidomycosis between men and women. This retrospective case-control study compared 36 women with 72 age-matched men for clinical–demographic, laboratory, and chest imaging findings. Overall, paracoccidioidomycosis in women presented the main features described in the acute/subacute and chronic forms seen in men. Women also showed similar demographic features and clinical–laboratory and imaging severity scores as men. We additionally reviewed 58 paracoccidioidin skin test surveys undertaken by volunteers from endemic areas. Data accumulated from 10.873 tests showed that females and males are infected with similar magnitudes (21.9% vs. 25.2%) and that reactivity steadily increased with age, peaking after the age of 60. We discuss the paradox of similar infection rates but much lower disease prevalence in women, considering the current pathogenetic views of paracoccidioidomycosis, and we raise alternative hypotheses to account for this paradox.
Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. Three hundred eighty-four patients were included; the median age was 39 years and 283 (73.7%) were men. Hosts were 304 (79.2%) HIV-positive, 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplanted (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). Two hundred and seventy-one (70.6%) patients were discharged home and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional AMB mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Patients with CNS cryptococcosis had lower mortality (83/313, 26.5%) when compared with the other categories (P = 0.017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death [odds ratio (OR), 1.03; 95% Confidence Interval (CI), 1.01 to 1.05; P = 0.008 and OR, 1.84; 95% CI, 1.01 to 3.53; P = 0.048, respectively]. Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.
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