The incidence of Histoplasmosis and Cryptococcal antigenemia among patients attending a Large HIV Clinic in Trinidad

Histoplasmosis and cryptococcosis are important co-infections 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 [14] and it has also been found on the bark, leaves, plant debris and wood of Eucalyptus trees (Pfeiffer and Ellis, 1990, Bedi et al, 2020, [13]). It has been recently recognized by the World Health Organization [33] as a critical priority fungal pathogen [32]. 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 (Rajasingham et al, 2017). The first case of AIDS diagnosed in Trinidad and Tobago in 1983 was in a patient with cryptococcal meningitis [4]. The WHO HIV guidelines recommend cryptococcal antigenemia screening in patients with CD4+ counts < 100 cells/mm3 who are not on ART and proactive anti-fungal treatment among those who are cryptococcal antigen positive to prevent invasive disease [16].

The dimorphic fungus Histoplasma capsulatum is endemic in Latin America and the Caribbean causing life-threatening disseminated histoplasmosis in PLHIV (Cano Torres et al, 2016), it has been recognized as a high priority fungal pathogen by the WHO [32]. 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 [22] but similar to a study in Nigeria which had a prevalence of 7.7% among 988 HIV patients with advanced disease [24]. In Trinidad, H. capsulatum has been isolated in soil with bat droppings [1,15] and population exposure based on a skin test survey was approximately 60% [17]. Histoplasmosis has been reported in patients diagnosed with AIDS [3,5]. A study conducted in 2021 [11] 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 [11].

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 [12]. UNAIDS estimates that of the 11,000 PLHIV in Trinidad and Tobago, 65% of these persons are on ART [30].

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 [2], 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 [21]. Histopathology is observer dependent and also has a low sensitivity [19]. 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 [28]; 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% [29] 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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