Genetic diversity in the major merozoite surface antigen of Plasmodium falciparum: high prevalence of a third polymorphic form detected in strains derived from malaria patients

Kimura, Emı́lia A.; Mattei, Denise; Santi, Sílvia Maria Di; Scherf, Artur

doi:10.1016/0378-1119(90)90162-k

Cited by 88 publications

(46 citation statements)

References 20 publications

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“…Due to the continuous nature of size variation of the amplified fragments of the two genes, alleles with similar sizes, within 20-basepair (bp) differences, were grouped into discrete bins around an estimated average size. 13 In addition, three sequence classes of the amplified block 2 of the MSP-1 gene, denoted K1, MAD20, and RO33, 14 and two of block 3 of the MSP-2, denoted IC1 and FC27, were identified by sequence-specific probes hybridized to Southern blots of the PCR-amplified fragments. 15 In addition, a probe was used that recognizes alleles of the FC27 form of MSP-2 that lacks the 12 amino acid repeat 16 denoted SUD (5Ј-GTTCA-AGTTCTGGCAATGCA-3Ј).…”

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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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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“…18 Analysis by RFLP. The product from the second round PCR amplification was digested with the restriction enzymes Bgl II, Ssp I, Taq I, and Afl II following the manufacturer's (New England Biolabs, Beverly, MA) instructions.…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Natural polymorphism in the thrombospondin-related adhesive protein of Plasmodium falciparum.

Robson

Dolo

Hackford

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. 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.The thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum was first described in 1988. 1 The gene derives its name from the deduced protein sequence that contains two amino acid motifs found in the adhesive host glycoprotein thrombospondin. 2 One of these motifs is based on the amino acid sequence Glu-Trp-Ser-ProCys-Ser-Val-Thr-Cys-Gly-Lys-Gly-Thr-Arg-Ser-Arg-LysArg, which has been demonstrated to allow TRAP to bind to sulfatide. 3 The protein is present in sporozoites and erythrocytic-stage parasites. 4, 5 Antibodies against TRAP inhibit sporozoite invasion. 3 Recent data demonstrate that TRAP is expressed in mature, salivary gland sporozoites but not in hemocoel sporozoites, suggesting that TRAP may be one of the unidentified accessory molecules required for infection of the vertebrate host. 6 Data from a longitudinal and prospective study showed that the immune response to TRAP is long-lived in adults and older children but short-lived in young children. 7 There were seasonal fluctuations of the levels of specific antibodies, as well as age-dependent quantitative differences. 7 These data, together with that for the TRAP homolog sporozoite surface protein 2 (SSP2) from P. yoelii, suggesting that adoptive transfer of a CD8 ϩ cytotoxic T cell clone recognizing SSP2 gave complete protection against P. yoelii infection, suggest that TRAP would be an important component of a multi-subunit malaria vaccine. 8 Further evidence for this has been the identification of a cytotoxic T lymphocyte response to certain conserved epitopes in TRAP. 9,10 A major problem in the design of any malaria vaccine is which antigens to choose and which variants of these antigens are relevant. We have previously shown that TRAP is ...

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“…The clonal diversity of natural P. vivax infections in humans remained unexplored until the early 1990s. At that time, advances in molecular methods -particularly with the implementation of poly- merase chain reaction (PCR)-based protocols to amplify parasite DNA -allowed for the genotyping of malaria parasite samples obtained directly from patient blood without a preceding in vitro culture step (Kimura et al 1990). Over the following years, these techniques revealed that multiple-clone (also known as mixed-strain) P. vivax infections are very common in areas with quite variable levels of malaria transmission.…”

mentioning

confidence: 99%

A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

Havryliuk

Ferreira

2009

Mem. Inst. Oswaldo Cruz

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Genetic diversity in the major merozoite surface antigen of Plasmodium falciparum: high prevalence of a third polymorphic form detected in strains derived from malaria patients

Cited by 88 publications

References 20 publications

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

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

Natural polymorphism in the thrombospondin-related adhesive protein of Plasmodium falciparum.

A closer look at multiple-clone Plasmodium vivax infections: detection methods, prevalence and consequences

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