Fatal Cryptococcus gattii genotype AFLP5 infection in an immunocompetent Cuban patient

Abstract

We describe the first clinical case of cryptococcosis due C. gattii in a Cuban immunocompetent patient who had a traveling history two years before to Central America. Molecular characterization of the isolate showed it to be genotype AFLP5 of which MLST sequences clustered with clinical and environmental strains from Colombia. The patient died one year after the diagnosis despite a prolonged treatment with (liposomal) amphotericin B, fluconazole, voriconazole and gamma interferon.

Cryptococcus and Cryptococcosis in Cuba. A minireview

“…Because (i) up to now, there is no evidence suggesting environmental presence of C. gattii in Cuba; (ii) it has been demonstrated that the time interval between exposure to C. gattii and the development of the disease is highly variable; (iii) both cases had a history of travel to C. gattii endemic regions; and (iv) AFLP and phylogenetic analysis showed that the strain from the cheetah was genotype AFLP4, nearly identical to a strain isolated from an unknown source in Kenya, and that the human isolate was genotype AFLP5 also closely related with strains from Colombia, we suppose that both human and animal patients from Cuba, were infected outside Cuba and that they had a dormant infection at arrival to the country.…”

“…There is evidence for three main ways of crossing the blood-brain barrier: the paracellular mechanism whereby cryptococcal yeasts sequestered in cerebral capillaries, change capsule structures and cell size damaging the endothelium of small capillaries in the brain tissue; the transcellular route by which the fungal cells cross the capillary endothelium by direct transcytosis, and a 'Trojan horse' whereby cryptococci enter the CNS after macrophage ingestion. 42,45,58 Because (i) up to now, there is no evidence suggesting environmental presence of C. gattii in Cuba 28 ; (ii) it has been demonstrated that the time interval between exposure to C. gattii and the development of the disease is highly variable [59][60][61] ; (iii) both cases had a history of travel to C. gattii endemic regions; and (iv) AFLP and phylogenetic analysis showed that the strain from the cheetah was genotype AFLP4, nearly identical to a strain isolated from an unknown source in Kenya, 15 and that the human isolate was genotype AFLP5 also closely related with strains from Colombia, 16 we suppose that both human and animal patients from Cuba, were infected outside Cuba and that they had a dormant infection at arrival to the country.…”

“…12,13 Till now only two cases of infections due to C. gattii have been reported in Cuba: one from a HIV-negative patient and the other one from a cheetah at the National Zoo in Havana. [14][15][16] Characterisation of the other Cuban Cryptococcus isolates from clinical and environmental samples (pigeons droppings) by conventional, serological (Iatron Laboratories, Tokyo, Japan) and molecular methods using high-resolution techniques (AFLP, sequencing D1/D2 and ITS1/5.8S/ITS2 fragments and conventional PCR using STE12alphaand STE12a-specific primers) allowed confirmation of the dominance of C. neoformans var. grubii mating-type MATa in this country, 17 which matches with the current international literature.…”

Molecular epidemiology and in vitro antifungal susceptibility testing of 108 clinical Cryptococcus neoformans sensu lato and Cryptococcus gattii sensu lato isolates from Denmark

“…The nuclear loci CAP59 , GPD1 , IGS1, LAC1 , PLB1 , SOD1 and URA5 were amplified and sequenced as described before . Obtained sequences were concatenated and compared to available sequences . Phylogenetic analysis on the concatenated dataset was carried out using the software package mega v6.6 .…”

Fatal Cryptococcus gattii genotype AFLP6/VGII infection in a HIV‐negative patient: case report and a literature review

“…Table 1 summarise clinical reports since 1998 to 2012 published in the literature. 12,18,19,34,35,36,37,38,39,40 Given the severity of infections caused by Cryptococcus gattii and the possible neurological sequelae, which affect not only immunocompromised patients but also healthy individuals, laboratories require adequation to provide early diagnosis of cryptococcosis in Brazil. Moreover, the importance of performing molecular typing of C. gattii species cannot be overemphasised considering findings in the literature that confirm the existence of differences in in vitro susceptibility profiles.…”