Histoplasmosis Caused by Histoplasma capsulatum var. duboisii: A Comprehensive Review of Cases from 1993 to 2019

Background: Histoplasmosis caused by Histoplasma capsulatum var. duboisii (Hcd) is a rare, but probably underestimated, endemic infection described in intertropical Africa. Therefore, the epidemiology of the infection remains unclear, and there is no consensus on therapeutic management. Methods: Using a comprehensive search on different Internet databases, we collected case reports of Hcd infection published from 1993 to 2019. Epidemiological and clinical charts and therapeutic strategies were analyzed. Results: We found 94 well-documented cases of Hcd infection, and 30.1% of the patients were under 18 years old. Symptoms occurred in some patients several decades after leaving the endemic area. Cutaneous/subcutaneous lesions, bone infections, and lymphadenopathies, both isolated and combined, were the most frequent presentations. The human immunodeficiency virus (HIV) coinfection rate was at 20.8%, with fever, lymphadenopathies, and an absence of bone infection being the differentiating elements from patients living without HIV. The rate of disseminated forms (60.6% in our review) significantly increased as compared to studies published before 1993, but without correlation with HIV infection. The global mortality rate was at 23.4% by the end of follow-up. The outcome was not correlated with the antifungal drug prescribed, nor with HIV serologic status, but was correlated with the initiation of an antifungal therapy. Conclusions: Hcd histoplasmosis is a severe fungal infection for which the precise mode of acquisition remains to be determined. There is a need for affordable and more specific diagnostic tools. Itraconazole and amphotericin B are the best therapeutic alternatives and should be available in all low-income countries of the endemic area.