Heterogeneity of Clinical Presentations and Paraclinical Explorations to Diagnose Disseminated Histoplasmosis in Patients with Advanced HIV: 34 Years of Experience in French Guiana

Abstract

We aimed to describe the ways patients with disseminated histoplasmosis—a multifaceted and often lethal disease—present themselves and are explored. A retrospective, observational, multicentric study spanned the period between 1 January 1981 and 1 October 2014. Principal component analysis was performed for the sampling sites and for the clinical signs and symptoms. The factor loadings of the principal components were selected for eigenvalues > 1. The most frequent signs and symptoms were an alteration of the WHO general performance status, fever, digestive tract, respiratory signs and symptoms and lymphadenopathies. The most common sites sampled were bone marrow, respiratory tract, blood, lymph node and liver biopsies, with significant variations in the number of sites from which samples were taken to try to identify the pathogen. The principal component analysis clinical signs and symptoms leading to the diagnosis showed four main lines of variation. The factor loadings of the four main components were compatible with four broad types of clinical presentations and four types of exploration strategies. Extracting simple algorithms was difficult, emphasizing the importance of clinical expertise when diagnosis depends on obtaining a sample where Histoplasma can be seen or grown. Histoplasma antigen detection tests will help simplifying the algorithms.

HIV-Associated Disseminated Histoplasmosis and Rare Adrenal Involvement: Evidence of Absence or Absence of Evidence

“…Overall, these numbers are far from the 10% reports among living patients and 80-90% among histoplasmosis autopsy series. Our retrospective analysis was a significant limitation, and all patients were not explored in the same manner depending on their clinical presentation (for example, cases with diarrhea benefitted from colonoscopy whereas those with enlarged superficial lymphadenopathies were more likely to have lymph node aspiration or biopsy) or the availability of different diagnostic tools at the time of their diagnosis, possible sources of information bias ( Nacher et al, 2020 ). In French Guiana, fungal culture was first implemented in 1998, liposomal amphotericin B became available in 2003, and, perhaps more importantly for the capacity to detect adrenal enlargement, over time the use of thoraco-abdomino-pelvic CT-scan became increasingly frequent.…”

Advanced HIV disease: A review of diagnostic and prophylactic strategies

“…Mathematical models suggest that among PWH in Latin America, mortality from histoplasmosis may be higher than from TB [ 60 ]. In persons with AHD, histoplasmosis is frequently disseminated, presenting as a multisystem febrile illness (similar to TB), and carries ≥20% mortality [ 61 ]. Unfortunately, histoplasmosis is often not diagnosed until autopsy, as it is either: (1) not considered outside of traditionally endemic areas, (2) considered less likely than TB or (3) not considered due to lack of diagnostics or antifungal therapeutics [ 62 ].…”

Forty Years of HIV Research in French Guiana: Comprehend to Combat

“…Disseminated histoplasmosis is proteiform [ 56 ], and it may be severe, moderately severe or mild, with fuzzy boundaries between categories. The histoplasmosis cohort allowed us to determine prognostic factors for early death [ 57 ], with a recent update and prognostic score [ 58 ] to help determine what induction antifungal treatment should be given, itraconazole or liposomal amphotericin b; the cohort also allowed us to describe the various presentations [ 59 , 60 , 61 , 62 , 63 , 64 ], the proportion of severe forms and its relation with common clinical presentations [ 44 , 59 , 65 , 66 ].…”

“…However, recent work emphasized the huge genetic variation in Histoplasma capsulatum, with four different phylogenetic species isolated within French Guiana, three of which had never been described before [68]. The fact that principal component analyses on the histoplasma cohort data identified four main components [60] begs the question whether the four phylogenetic species have anything to do with this.…”