The incidence of histoplasmosis and cryptococcal antigenemia among patients attending a large HIV clinic in Trinidad

Histoplasmosis and cryptococcosis are important coinfections among persons living with HIV (PLHIV) and are significant causes of severe life-threatening illnesses and mortality in these patients. Cryptococcus neoformans is a fungus that is most frequently found in bird droppings (mainly pigeons) and soil [1] and it has also been found on the bark, leaves, plant debris and wood of Eucalyptus trees (Pfeiffer and Ellis, 1990 [2], Bedi et al, 2020 [3], [4]). It has been recently recognized by the World Health Organization [5] as a critical priority fungal pathogen [6]. It is the most common cause of meningitis in PLHIV and this tends to occur in patients with CD4+ counts less than 100 cells/mm3 especially among those not on antiretroviral therapy (ART), those failing ART and those who defaulted from care and are lost to follow up [7]. The first case of AIDS diagnosed in Trinidad and Tobago in 1983 was in a patient with cryptococcal meningitis [8]. The WHO HIV guidelines recommend cryptococcal antigenemia screening in patients with CD4+ counts < 100 cells/mm3 who are not on ART and proactive antifungal treatment among those who are cryptococcal antigen positive to prevent invasive disease [9].

The dimorphic fungus Histoplasma capsulatum is endemic in Latin America and the Caribbean causing life-threatening disseminated histoplasmosis in PLHIV [10], it has been recognized as a high priority fungal pathogen by the WHO [6]. A recent screening study performed among 6366 HIV patients in Guatemala, has shown that the histoplasmosis incidence was 7.4%, which was almost double that estimated in previous studies [11] but similar to a study in Nigeria which had a prevalence of 7.7% among 988 HIV patients with advanced disease [12]. In Trinidad, H. capsulatum has been isolated in soil with bat droppings [13,14] and population exposure based on a skin test survey was approximately 60% [15]. Histoplasmosis has been reported in patients diagnosed with AIDS [16,17]. A study conducted in 2021 [18] estimated that annually, of the 11,000 PLHIV in Trinidad and Tobago (UNAIDS), there were 88 cases of disseminated histoplasmosis with an annual incidence of 6.3 per 100,000 person-years and 40 cases of cryptococcal meningitis with an incidence of 2.9 per 100,000 person-years [18].

Trinidad and Tobago (T&T) are the southernmost islands of the Caribbean chain and comprise a single nation and has a population of approximately 1,403,374 persons (2021 mid-year estimate). Antiretroviral therapy (ART) supported by the government became available in 2002 [19]. UNAIDS estimates that of the 11,000 PLHIV in Trinidad and Tobago, 65% of these persons are on ART [20].

The gold standard for the diagnosis of histoplasmosis is isolation of the fungus by culture of clinical specimens or histopathologic examination of tissue sample for the characteristic intracellular yeasts [21], both procedures requiring invasive sampling methods which may not be readily available in resource limited countries. Weeks are required to grow the fungus in standard media culture which requires a Biosafety Level 3 Laboratory and the sensitivity of culture is low [22]. Histopathology is observer dependent and also has a low sensitivity [23]. The gold standard for the diagnosis of cryptococcal meningitis is culture of the cerebrospinal fluid (CSF) which may take up to 1-2 weeks for definitive diagnosis and requires trained laboratory personnel [24]; thus this technique is not available in many resource limited countries. Cryptococcal antigen (CrAg) detection tests provide rapid and accurate methods of diagnosis in PLHIV. A systematic review and meta-analysis of the serum CrAg screening in cryptococcal meningitis reported a sensitivity of 99.7% and a specificity of 94.1% [25] and using these, the incidence of cryptococcosis in PLHIV was quantified [26].

The aim of the study was to determine the incidence of histoplasmosis and cryptococcal antigenemia among PLHIV attending the Medical Research Foundation (MRFTT), a large HIV clinic in Trinidad.

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