A prospective descriptive study of cryptococcal meningitis in HIV uninfected patients in Vietnam - high prevalence of Cryptococcus neoformans var grubii in the absence of underlying disease

Tran Th Chau, Nguyen H Mai, Nguyen H Phu, Ho D Nghia, Ly V Chuong, Dinh X Sinh, Van A Duong, Pham T Diep, James I Campbell, Stephen Baker, Tran T Hien, David G Lalloo, Jeremy J Farrar, Jeremy N Day, Tran Th Chau, Nguyen H Mai, Nguyen H Phu, Ho D Nghia, Ly V Chuong, Dinh X Sinh, Van A Duong, Pham T Diep, James I Campbell, Stephen Baker, Tran T Hien, David G Lalloo, Jeremy J Farrar, Jeremy N Day

Abstract

Background: Most cases of cryptococcal meningitis occur in patients with HIV infection: the course and outcome of disease in the apparently immunocompetent is much more poorly understood. We describe a cohort of HIV uninfected Vietnamese patients with cryptococcal meningitis in whom underlying disease is uncommon, and relate presenting features of patients and the characteristics of the infecting species to outcome.

Methods: A prospective descriptive study of HIV negative patients with cryptococcal meningitis based at the Hospital for Tropical Diseases, Ho Chi Minh City. All patients had comprehensive clinical assessment at baseline, were cared for by a dedicated study team, and were followed up for 2 years. Clinical presentation was compared by infecting isolate and outcome.

Results: 57 patients were studied. Cryptococcus neoformans var grubii molecular type VN1 caused 70% of infections; C. gattii accounted for the rest. Most patients did not have underlying disease (81%), and the rate of underlying disease did not differ by infecting species. 11 patients died while in-patients (19.3%). Independent predictors of death were age > or = 60 years and a history of convulsions (odds ratios and 95% confidence intervals 8.7 (1 - 76), and 16.1 (1.6 - 161) respectively). Residual visual impairment was common, affecting 25 of 46 survivors (54.3%). Infecting species did not influence clinical phenotype or outcome. The minimum inhibitory concentrations of flucytosine and amphotericin B were significantly higher for C. neoformans var grubii compared with C. gattii (p < 0.001 and p = 0.01 respectively).

Conclusion: In HIV uninfected individuals in Vietnam, cryptococcal meningitis occurs predominantly in people with no clear predisposing factor and is most commonly due to C. neoformans var grubii. The rates of mortality and visual loss are high and independent of infecting species. There are detectable differences in susceptibility to commonly used antifungal drugs between species, but the clinical significance of this is not clear.

Figures

Figure 1
Figure 1
Representative PCR-RFLP profiles of the URA5 gene of 20 Cryptococcus isolates and 8 control strains A - H. Footnote: A = VN1, B = VN2, C = VN3, D = VN4, E = VG1, F = VG2, G = VG3, H = VG4 * denotes examples of detected molecular groups.

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