High prevalence and mortality due to Histoplasma capsulatum in the Brazilian Amazon: An autopsy study

PLoS Negl Trop Dis. 2021 Apr 5;15(4):e0009286. doi: 10.1371/journal.pntd.0009286. eCollection 2021 Apr.

Abstract

Background: Histoplasmosis is acquired by inhalation of spores of the dimorphic fungus Histoplasma spp. Although this pathogen is distributed worldwide, it is more prevalent in the Americas. However, the real burden of histoplasmosis remains undefined in many endemic regions.

Methodology: We conducted a series of 61 autopsies to individuals who died in a hospital in the Brazilian Amazon focused on infectious diseases. We performed a detailed histological and microbiological evaluation with genetic characterization of Histoplasma strains with the aim to evaluate the contribution of histoplasmosis to morbidity and mortality. Additionally, we assessed the clinicopathological correlation.

Principal findings: Evidence of Histoplasma infection was detected in 21 patients (34%). Eight cases were disseminated infections, all of them occurred in HIV-positive patients. Six cases were localized histoplasmosis, limited to the lungs. In seven patients Histoplasma DNA was detected by PCR in patients with no histological lesions. Histoplasma infection was detected in 38% of HIV-positive patients and was a major contributor to death in 22% of them. Lungs, liver and spleen were affected in all cases of disseminated histoplasmosis. Phylogenetic analysis of the strains suggested a high diversity of Histoplasma species circulating in the Brazilian Amazon. Histoplasmosis was clinically missed in 75% of the disseminated infections.

Conclusions: The high incidence of histoplasmosis, the low index of clinical suspicion, and the severity of the disseminated disease highlight the need of proactively implementing sensitive routine screening methods for this pathogen in endemic areas. Antifungal prophylaxis against Histoplasma should be encouraged in the severely immunocompromised HIV patients in these areas. In conclusion, substantial mortality is associated with disseminated histoplasmosis among HIV-positive patients in the Brazilian Amazon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / microbiology*
  • AIDS-Related Opportunistic Infections / mortality
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autopsy
  • Brazil / epidemiology
  • Female
  • Histoplasma / classification*
  • Histoplasma / genetics*
  • Histoplasmosis / microbiology*
  • Histoplasmosis / mortality
  • Histoplasmosis / pathology
  • Humans
  • Male
  • Middle Aged
  • Phylogeny
  • Prevalence
  • Young Adult

Grants and funding

This work was supported by the Bill & Melinda Gates Foundation [grant numbers OPP1067522 to QB, OPP1128001 to JO], and by the Instituto de Salud Carlos III [grant number PI12/00757 to CM], and the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) of Generalitat de Catalunya [grant number 2017SGR794 to M.J.M.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.