Epidemiological evidence for dormant Cryptococcus neoformans infection

Abstract

To date, the time of acquisition of a Cryptococcus neoformans infectious strain has never been studied. We selected a primer, (GACA)(4), and a probe, CNRE-1, that by randomly amplified polymorphic DNA (RAPD) analysis and restriction fragment length polymorphism (RFLP), respectively, regrouped strains from control samples of C. neoformans var. grubii environmental isolates according to their geographical origins. The two typing techniques were then used to analyze 103 isolates from 29 patients diagnosed with cryptococcosis in France. Nine of the 29 patients lived in Africa a median of 110 months prior to moving to France; 17 of the patients originated from Europe. Results showed a statistically significant clustering of isolate subtypes from patients originating from Africa compared to those from Europe. We conclude that the patients had acquired the C. neoformans infectious strain long before their clinical diagnoses were made.

FIG. 1

Schematic representation of and dendogram generated from the Dice coefficient complement computed from the CNRE-1 patterns of environmental isolates from Japan (J), France (F), the United States (US), and Africa (AF).

FIG. 2

Representative RAPD profiles of C. neoformans isolates generated with the (GACA)₄ primer. Profile identifications are indicated as roman numerals (I through VI). Profiles V and VI were obtained only with environmental isolates. Molecular size standards were obtained with the 1-kb ladder (Gibco BRL, Gaithersburg, Md.).

FIG. 3

Schematic representation of and dendogram generated from the Dice coefficient complement computed from the CNRE-1 patterns of 29 clinical isolates. African strains (in boldface) are regrouped in clusters A and B (boxed in this figure). DRC, Democratic Republic of Congo.