Assessment of prior infection with histoplasmosis using skin test and serological surveys: a global systematic review

Background Evidence suggests geographic expansion in histoplasmosis, a fungal infection caused by Histoplasma spp. Establishing historical and modern population immunity to histoplasmosis is needed to contextualize future trends, and ensure providers give it diagnostic consideration. Methods To summarize what is known regarding the distribution of histoplasmosis globally, we conducted a systematic review of studies reporting prevalence of lifetime or recent exposure to Histoplasma spp., assessed via skin or serological tests, respectively. Results We included 224 studies, including 171 skin test surveys and 44 serological surveys, spanning 66 countries and all six WHO regions. Prevalence of infection exceeded 10% in studies from the Americas, Southeast Asia, and Africa, with substantial variation across population subgroups. Most studies used non-representative sampling. Conclusions Histoplasmosis likely exists along a global gradient. Surveillance and research efforts must shift to address its broad distribution and ensure timely diagnosis and treatment, especially in areas not traditionally considered endemic.