Meningitis caused by Cryptococcus neoformans var. gattii and var. neoformans in Papua New Guinea

Abstract

Eleven cases of cryptococcal meningitis were diagnosed and biotyped from September 1991 to August 1992 in Papua New Guinea (PNG). Seven isolates were Cryptococcus neoformans var. gattii from paediatric and adult patients, one with diabetes mellitus and 4 were C. neoformans var. neoformans from adults, of whom 2 had human immunodeficiency virus type 1 (HIV-1) infection, and one each had tuberculosis and Plasmodium vivax malaria. Significant clinical findings were headache, fever, meningism, vomiting, photophobia, papilloedema and cranial nerve lesions. Five patients (45.5%) died; 3 of these were adults with var. gattii and 2 were men with both var. neoformans and HIV-1 infections. This prospective tropical study documents the emergence of C. neoformans var. neoformans in patients with HIV-1 infection in a country where previously var. gattii had predominated in the immunocompetent. There has been no earlier report of cryptococcosis in an HIV-1 seropositive patient in PNG. Despite presumed exposure to both varieties of C. neoformans, var. gattii infections had been most frequent. As HIV-1 spreads, the proportion of hosts infected with var. neoformans may rise. The course of meningitis caused by the 2 varieties of C. neoformans may differ, with mortality in the tropics remaining particularly high. In PNG the environmental source of C. neoformans remains elusive.

Cryptococcus gattii Infections

“…Cryptococcosis is uncommon in children, including those with HIV/AIDS (232,282), and the same appears to be the case for C. gattii infection (213,218,232,268), with the possible exception of children in Brazil. An earlier study from PNG showed that exposure to the fungus, as demonstrated by levels of serum IgG antibody directed against C. gattii, was significantly greater in adults, and especially adult males, than in children (209), suggesting that exposure increases with age and that it occurs away from the home environment.…”

“…Importantly, papilledema was present in 15 to 53% of patients in earlier studies (29,211,213) but in only 6% of cases in the U.S. outbreak and in 12.4% of cases in a recent Australian study (130). Optic disc swelling is typically present, with loss of definition of the disc margins.…”

“…The mortality rate was high in early studies of C. gattii meningitis in PNG (22.4 to 43%) (210,211,213) and remains so, especially if diagnosis is delayed (218). In Brazil, the mortality rate has ranged from 18.2 to 50% between studies (219,221,248,256), and in the Northern Territory of Australia, it has been as high as 33% (215).…”

“…In Australia, where C. gattii infection is considered to be endemic, the two species have been distinguished routinely since the early 1990s by using canavanine-glycine-bromothymol blue (CGB) agar (266) (see Diagnostics, below). Earlier small (8 to 49 patients) case series of C. gattii infection were mainly from Australia (25,27,28,99,113,204,267), Papua New Guinea (208)(209)(210)(211)(212)(213), and Brazil (206,219). Incidence data from Brazil are imprecise, but compared to other parts of the world, children appear to be disproportionately affected by C. gattii.…”

“…Importantly, there appear to be differences in clinical presentation and site(s) of infection between disease that occurs sporadically and that seen in the reported case clusters. Studies from Papua New Guinea indicate that CNS infection, particularly meningitis, is typical (208,211,213,218). In Australia and New Zealand, meningoencephalitis and/or cerebral involvement occurred in 74% of patients with culture-confirmed C. gattii infection in the 1990s (29), while in a contemporary study, in which most patients underwent cerebral computerized tomography (CT) and magnetic resonance imaging (MRI), CNS infection was diagnosed in 85% of 86 patients; overall, 76% of patients had meningitis and 52% had brain infection, including cerebral cryptococcomas (130).…”