The merozoite surface protein-1 (MSP-1) locus
of Plasmodium falciparum codes for a major asexual
blood-stage antigen currently proposed as a major malaria vaccine
candidate. The protein, however, shows extensive polymorphism,
which may compromise its use in sub-unit vaccines. Here we
compare the patterns of allelic diversity at the MSP-1
locus in wild isolates from three epidemiologically distinct
malaria-endemic areas: the hypoendemic southwestern Brazilian
Amazon (n = 54), the mesoendemic southern Vietnam (n = 238) and
the holoendemic northern Tanzania (n = 79). Fragments of the
variable blocks 2, 4a, 4b and 6 or 10 of this single-copy gene
were amplified by the polymerase chain reaction, and 24
MSP-1 gene types were defined as unique combinations of
allelic types in each variable block. Ten different MSP-1
types were identified in Brazil, 23 in Vietnam and 13 in
Tanzania. The proportion of genetically mixed infections
(isolates with parasites carrying more than one MSP-1
version) ranged from 39% in Brazil to 44% in Vietnam and 60% in
Tanzania. The vast majority (90%) of the typed parasite
populations from Brazil and Tanzania belonged to the same seven
most frequent MSP-1 gene types. In contrast, these seven
gene types corresponded to only 61% of the typed parasite
populations from Vietnam. Non-random associations were found
between allelic types in blocks 4a and 6 among Vietnamese
isolates, the same pattern being observed in independent studies
performed in 1994, 1995 and 1996. These results suggest that
MSP-1 is under selective pressure in the local parasite
population. Nevertheless, the finding that similar MSP-1
type frequencies were found in 1994 and 1996 argues against
the prominence of short-term frequency-dependent immune selection
of MSP-1 polymorphisms. Non-random associations between
MSP-1 allelic types, however, were not detected among
isolates from Brazil and Tanzania. A preliminary analysis of the
distribution of MSP-1 gene types per host among isolates
from Tanzania, but not among those from Brazil and Vietnam, shows
significant deviation from that expected under the null
hypothesis of independent distribution of parasites carrying
different gene types in the human hosts. Some epidemiological
consequences of these findings are discussed.
