Most cases of cryptococcal meningitis in HIV-uninfected patients in Vietnam are due to a distinct amplified fragment length polymorphism-defined cluster of Cryptococcus neoformans var. grubii VN1

Abstract

Cryptococcal disease most commonly occurs in patients with an underlying immune deficit, most commonly HIV infection, and is due to Cryptococcus neoformans var. grubii. Occasionally disease due to this variety occurs in apparently immunocompetent patients. The relationship between strains infecting immunosuppressed and immunocompetent patients is not clear. Amplified fragment length polymorphism (AFLP) analysis was used to characterize the relationship between strains infecting HIV-infected and uninfected patients. Isolates from 51 HIV-uninfected patients and 100 HIV-infected patients with cryptococcal meningitis were compared. C. neoformans var. grubii VNI was responsible for infections in 73% of HIV-uninfected and 100% of HIV-infected patients. AFLP analysis defined two distinct clusters, VNIγ and VNIδ. The majority (84%) of isolates from HIV-uninfected patients were VNIγ, compared with only 38% of isolates from HIV-infected patients (odds ratio, 8.30; 95% confidence interval [CI], 3.04 to 26.6; P < 0.0001). In HIV-uninfected patients, underlying disease was less frequent in those with VNIγ infections. Two clusters of C. neoformans var. grubii VN1 are responsible for the majority of cases of cryptococcal meningitis in Vietnam. The distribution of these clusters differs according to the immune status of the host.

Fig. 1.

Representative PCR-RFLP profiles of the URA5 genes of 45 Cryptococcus isolates. Typical molecular types: lane 1, C. neoformans var. grubii VNI; lane 2, C. gattii VG1; lane 16, C. gattii VG2.

Fig. 2.

(a) AFLP-derived neighbor-joining tree obtained using the GT/GT primer set for Vietnamese C. neoformans var. grubii clinical isolates. Gray bars, isolates from HIV-uninfected patients; white bars, C. neoformans controls; black bars, C. gattii controls. Circles represent well-supported clusters; the numbers are the cophenetic correlation values (%). (b) AFLP-derived neighbor-joining tree obtained using the AC/G primer set for Vietnamese C. neoformans var. grubii clinical isolates Gray bars, isolates from HIV-uninfected patients; white bars, C. neoformans controls; black bars, C. gattii controls. Circles represent well-supported clusters, the numbers are the cophenetic correlation values (%).