ABSTRACT
Parasite genotyping by the polymerase chain reaction was used to distinguish recrudescent from newly acquired Plasmodium falciparum infections in a Karen population resident on the northwestern border of Thailand where malaria transmission is low (one infection/person/year). Plasmodium falciparum infections were genotyped for allelic variation in three polymorphic antigen loci, merozoite surface proteins-1 and -2 (MSP-1 and -2) and glutamaterich protein (GLURP), before and after antimalarial drug treatment. Population genotype frequencies were measured to provide the baseline information to calculate the probability of a new infection with a different or the same genotype to the initial pretreatment isolate. Overall, 38% of the infections detected following treatment had an identical genotype before and up to 121 days after treatment. These post-treatment genotypes were considered recrudescent because of the low (< 5%) probability of repeated occurrence by chance in the same patient. This approach allows studies of antimalarial drug treatment to be conducted in areas of low transmission since recrudescences can be distinguished confidently from newly acquired infections.
Subject(s)
Malaria, Falciparum/parasitology , Plasmodium falciparum/genetics , Alleles , Animals , Antigens, Protozoan/genetics , DNA, Protozoan/analysis , DNA, Protozoan/chemistry , Drug Resistance, Multiple , Gene Frequency , Genetic Markers , Genetic Variation , Genotype , Humans , Malaria, Falciparum/drug therapy , Malaria, Falciparum/epidemiology , Plasmodium falciparum/classification , Plasmodium falciparum/drug effects , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Recurrence , Thailand/epidemiologyABSTRACT
Genetic analysis of the number of Plasmodium falciparum genotypes per infected person in regions of holoendemic and hyperendemic malaria suggest that in areas of lower transmission intensity, significantly fewer parasite genotypes per infected person should be found. A predominance of single clone infections in the human population could generate the controversial clonal population structure proposed for P. falciparum by Tibayrenc and others. Characterization of P. falciparum from individuals on the Thai-Burmese border, an area of hypoendemic transmission, revealed a higher number of genotypes per infected person than that predicted. Possible reasons for this observation are discussed, with particular attention paid to human migration and multidrug resistance.
Subject(s)
Genetic Variation , Malaria, Falciparum/parasitology , Plasmodium falciparum/genetics , Adolescent , Adult , Alleles , Animals , Child , Child, Preschool , DNA, Viral/analysis , DNA, Viral/chemistry , Gene Frequency , Genetic Linkage , Genotype , Humans , Incidence , Malaria, Falciparum/epidemiology , Malaria, Falciparum/transmission , Merozoite Surface Protein 1 , Plasmodium falciparum/classification , Protein Precursors/genetics , Protozoan Proteins/genetics , Thailand/epidemiologyABSTRACT
We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines.
