Structural diversity in the Plasmodium falciparum merozoite surface antigen 2.

Smythe, Jason A.; Coppel, Ross L.; Day, Karen P.; Martin, Rodger K.; Oduola, A. M. J.; Kemp, David J.; Anders, Robin F.

doi:10.1073/pnas.88.5.1751

Cited by 163 publications

(124 citation statements)

References 24 publications

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“…In this study we applied PCR-RFLP for the MSP2 (Merozoite Surface Protein 2) locus, coding for a polymorphic plasmodial membrane protein, to unequivocally identify recrudescent or new infections after drug treatment. MSP2 amplification and distinct restriction patterns in conjunction with extensive sequence information allow the discrimination of almost all different genotypes found (Thomas et al 1990;Smythe et al 1991;Felger et al 1993Felger et al , 1997.…”

Section: A Irion Et Al Distinction Of Recrudescences From New Infecmentioning

confidence: 99%

Distinction of recrudescences from new infections by pcr‐rflp analysis in a comparative trial of cgp 56 697 and chloroquine in Tanzanian children.

Irion

Felger

Abdulla

et al. 1998

Tropical Med Int Health

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SummaryOBJECTIVE To test the efficacy of a new compound drug (CGP 56 697) against acute, uncomplicated falciparum malaria. METHOD Reappearing parasites were analysed by PCR-RFLP within a randomized controlled trial. 130 patients received chloroquine and 130 patients were treated with CGP 56 697. Samples from 96 patients with parasitological failure were tested by PCR-RFLP for MSP2 of Plasmodium falciparum. Seven days after treatment 32 patients of the chloroquine control group with reappearing parasites were tested by PCR and one infection was unequivocally determined as a new infection. After 7 days, in the CGP 56 697 group, 6 samples were tested in which one new infection was identified. Similar observations were made one and three weeks later in both groups. RESULTS Although a high multiplicity of infections on admission was observed, there was no significant correlation between multiplicity and either recrudescence or new infection. Patients in both treatment groups with subsequent recrudescent parasites had higher initial mean parasite densities than patients who cleared. Those of the patients with recrudescent parasites who were treated with CGP 56 697 had higher initial parasite densities than those treated with chloroquine. The rate of re-infection increased with time as expected in holoendemic areas and appeared to be higher in chloroquine patients. Generally, CGP 56 697 showed a superior clearance rate, successfully cleared higher parasite densities and suppressed new infections over a longer period of time. CONCLUSION The PCR analysis confirmed that reinfections beyond day 7 are significant in areas highly endemic for malaria and showed the necessity of excluding these when estimating 14 day clearance rates. Provided new infections are excluded, the 28-day clearance rate can also be used to determine the efficacy of antimalarial drugs in highly endemic areas, and adds to our knowledge of drug resistance and dynamics of infections in people living in such areas. keywords malaria, Plasmodium falciparum, drug treatment, resistance, polymerase chain reaction, artemether, benflumetol correspondence Hans-Peter Beck, Swiss Tropical Institute,

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Section: A Irion Et Al Distinction Of Recrudescences From New Infecmentioning

confidence: 99%

Distinction of recrudescences from new infections by pcr‐rflp analysis in a comparative trial of cgp 56 697 and chloroquine in Tanzanian children.

Irion

Felger

Abdulla

et al. 1998

Tropical Med Int Health

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“…The PCR amplification of each gene was then carried out using six pairs of primers, one pair for the initial round of the PCR and one pair for the nested PCR to enhance the sensitivity of detection of subpatent infections. 9,10 The primers amplified respectively a polymorphic region (block 2) of MSP-1, 11 most of MSP-2, 12 and the central region of the GLURP gene. 8 To characterize alleles of these genes, the PCR-amplified fragments were separated by electrophoresis on 1.6% agarose gels, their sizes were calculated, and they were then transferred onto nylon membrane by Southern blotting.…”

Section: Methodsmentioning

confidence: 99%

Characteristics of Plasmodium falciparum parasites that survive the lengthy dry season in eastern Sudan where malaria transmission is markedly seasonal.

et al. 1998

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Abstract. We have examined 83 inhabitants of Asar village in eastern Sudan, where malaria transmission lasts approximately 2-3 months each year, for the presence of Plasmodium falciparum during the prolonged dry season. All patients were treated with a standard dose of chloroquine following the first diagnosis, then examined by microscopy and the polymerase chain reaction (PCR) every two weeks for the first two months and subsequently once each month for the next 15 months throughout the dry season until the following transmission season. The PCR primers used amplified polymorphic regions of the merozoite surface protein-1 (MSP-1), MSP-2, and glutamate-rich protein genes. Results show that subpatent and asymptomatic parasitemias persisted in some patients for several months throughout the dry season, often as genetically complex infections. Different genotypes could coexist together in a single infection and the proportions of each could fluctuate dramatically during this period. However, in some individuals, single genotypes appeared to persist for several months. Reappearance of clinical symptoms among patients with chronic infections was often associated with appearance of new alleles, indicating reinfections with parasites of novel genotypes.In the poor savannah area of eastern Sudan, the malaria transmission season is short and confined to approximately three rainy months of the year. In this region, the epidemiology of malaria is consistent with that of a hypoendemic area, where transmission occurs only following rains. A brief expansion of the mosquito population at this time leads to malaria outbreaks in October and November each year. However, during the long dry season from January to June, apart from a few clinical reports, very little is known about parasite reservoirs, or whether mosquitoes continue to transmit the parasite. A previous entomologic study suggested that the main mosquito vector, Anopheles arabiensis, retracts to scanty breeding sites where it can survive the dry season with continuous feeding activity but an incomplete reproductive cycle. 1 Nothing is known about how the long dry season influences the dynamics and the structure of the parasite populations in this region.During the past seven years, we have carried out regular surveys of the Plasmodium falciparum population in October-November in Asar village in eastern Sudan. 2,3 The principal findings have been that 1) a considerable amount of allelic polymorphism exists among the genes of parasites infecting patients at this time of the year, 2) no two patients are infected with identical parasite clones, and 3) most patients are infected with a mixture of parasite clones. A great diversity was found even among parasites that caused the very early malaria cases in the transmission season. 3 Such a level of diversity suggests that the parasites that appear at this time of the year may belong to a large parasite reservoir existing prior to the beginning of the rainy season. A recent study in a neighboring village has shown that sub-pa...

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“…Nonetheless, the pattern of allele polymorphism in Msp2 is consistent with the IGR model. Similar to CSP, the MSP-2 protein is characterized by N-and C-termini with 43 and 74 residues, respectively 26 . Bracketed within these conserved segments is the highly variable repeat region.…”

Section: Merozoite and Sporozoite Surface Antigensmentioning

confidence: 99%