Why severe Plasmodium falciparum malaria occurs in only a small percentage
of patients is unclear. The possibility that specific parasite characterist
ics contribute to severity has been investigated in French Guiana, a hypoen
demic area, where parasite diversity is low and all patients with severe ca
ses are referred to a single intensive care unit. Parasite genotyping in ge
ographically and temporally matched patients with mild and severe disease s
howed that the association of a specific msp-1 allele (B-K1) with a specifi
c var gene (var-D) was overrepresented among patients with severe versus mi
ld disease (47% vs. 3%, respectively; P < .001). Moreover, this genotype co
mbination was consistently observed in the most severe clinical cases. Reve
rse-transcription polymerase chain reaction demonstrated programmed express
ion of var-D in vivo, which is consistent with its potential implication in
severe disease. These results provide field evidence of an association of
severe malaria with specific genetic characteristics of parasites and open
the way for intervention strategies targeting key virulence factors of para
sites.