Abstract
Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts ≤200/μl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10–12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9–20.3) for cryptococcal infection and 10.9% (95% CI 6.1–17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p<0.001). The 13 Cryptococcus strains obtained at baseline were all Cryptococcus neoformans var. grubii, genotypes VNI-αA (3 isolates), VNII-αA (4 isolates) or hybrid VNI/VNII-αAAα (6 isolates), suggesting high diversity. Two strains acquired fluconazole resistance after four and five months of exposure, respectively. The prevalence of cryptococcosis is high in Madagascar and this serious condition is life-threatening in HIV-infected patients. These findings will be used to raise the awareness of national authorities to strengthen the national HIV/AIDS control program.
Highlights
Cryptococcal meningoencephalitis (CM) is a common opportunistic infection in developing countries, including those of sub-Saharan Africa
The study was conducted in the main hospitals of two geographically distant cities, one located at Antananarivo in the central highlands and the other at Toamasina on the east coast
The prevalence of cryptococcal infection was higher than previously reported global prevalence values, and most of the patients developed CM
Summary
Cryptococcal meningoencephalitis (CM) is a common opportunistic infection in developing countries, including those of sub-Saharan Africa. It mostly affects severely immunocompromised HIV-infected patients. With an estimated 625,000 deaths annually [1] and a global burden of almost a million cases per year [2], cryptococcal infection is one of the most devastating infectious diseases in sub-Saharan Africa and worldwide. A recent update of the global burden of HIV-associated cryptococcal meningoencephalitis (CM) reported an annual incidence of 162,500 cases in sub-Saharan Africa, accounting for 73% of the estimated number of cases globally and 135,500 deaths [3]. Most cryptococcal infections in HIV-infected patients are caused by the Cryptococcus neoformans (Cn) species complex, which includes two varieties and five molecular types: VNI, VNII and VNB Central nervous system invasion occurs principally in immunocompromised individuals, including people living with HIV [8], and results in CM, the most common and severe clinical form of cryptococcal infection [9]
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