ALLELIC DIVERSITY AT THE MEROZOITE SURFACE PROTEIN-1 (MSP-1) LOCUS INNATURAL PLASMODIUM-FALCIPARUM POPULATIONS - A BRIEF OVERVIEW

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 extensiv e polymorphism, which may compromise its use in sub-unit vaccines. Her e we compare the patterns of allelic diversity at the MSP-1 locus in w ild isolates from three epidemiologically distinct malaria-endemic are as: the hypoendemic southwestern Brazilian Amazon (n = 54), the mesoen demic southern Vietnam (n = 238) and the holoendemic northern Tanzania (n = 79). Fragments of the variable blocks 2, 4a, 4b and 6 or 10 of t his 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 identifi ed in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of gene tically mixed infections (isolates with parasites carrying more than o ne 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 onl y 61% of the typed parasite populations from Vietnam. Non-random assoc iations were found between allelic types in blocks 4a and 6 among Viet namese isolates, the same pattern being observed in independent studie s performed in 1994, 1995 and 1996. These results suggest that MSP-1 i s under selective pressure in the local parasite population. Neverthel ess, the finding that similar MSP-1 type frequencies were found in 199 4 and 1996 argues against the prominence of short-term frequency-depen dent immune selections of MSP-1 polymorphisms. Non-random associations between MSP-1 allelic types, however, were not detected among isolate s from Brazil and Tanzania. A preliminary analysis of the distribution of MSP-1 gene types per host among isolates from Tanzania, but not am ong those from Brazil and Vietnam, shows significant deviations from t hat expected under the null hypothesis of independent distribution of parasites carrying different gene types in the human hosts. Some epide miological consequences of these findings are discussed.