Genetic diversity of Plasmodium falciparum infections in mild and severe malaria of children from Kampala, Uganda

Abstract

Diversity in parasite virulence is one of the factors that contribute to the clinical outcome of malaria infections. The association between the severity of Plasmodium falciparum malaria and the number of distinct parasite populations infecting the host (multiplicity of infection) or polymorphism within any of the specific antigen genes was investigated. The study included 164 children presenting with mild and severe malaria from central Uganda where malaria is meso-endemic. The polymorphic regions of the circumsporozoite protein (csp), merozoite surface proteins 1 and 2 (msp1 and msp2), and glutamate-rich protein (glurp) were genotyped by polymerase chain reaction methods and fragment analysis by gel electrophoresis. In a subset of samples fragment analysis was also performed by fluorescent PCR genotyping followed by capillary electrophoresis. The multiplicity of infection (MOI), determined as the highest number of alleles detected within any of the four genetic loci, was significantly higher in severe than in mild malaria cases (mean 3.7 and 3.0, respectively, P = 0.002). No particular genotype or allelic family of msp1 or msp2 was associated with severity of malaria, and nor did the genotyping method reveal any significant difference in MOI when only assessed by msp2 genotyping. Severity of malaria was not linked to the predominance of any particular msp1 or msp2 allelic types, independent of methods used for genotyping. Monitoring the dynamics of multiple clone infections in relation to disease outcome, host immune status and genetic factors will provide more insight into parasite virulence mechanisms.

Diversity and Multiplicity of P. falciparum infections among asymptomatic school children in Mbita, Western Kenya

“…The 79.69% prevalence of polyclonal infections found in the study population is consistent with results from other studies carried out in malaria endemic and high transmission intensity regions where multi-clonal infection rates varied from 50% to 100%, respectively [62][63][64][65][66][67] . The overall mean MOI of 3.39 in the study population found in our study corroborates with other studies in high malaria transmission areas in Africa like Kenya (2.83) 68 , Gambia (2.1), Senegal (2.2), Guinea Bissau (2.6), Guinea (4.0) 54 , Tanzania (3.5) 62 , Uganda (3.0-3.7) 65 and Madagascar (3.72-3.73) 66 but higher than results from low malaria transmission regions like Djibouti (1.0-1.4), Dakar (1.0-1.5), Niamey (1.0-1.8) 67 and Sudan 69 . The high MOI found in this study maybe due to the boosted parasite specific immunity in people residing in high malaria transmission regions and the study population as children were reported to carry higher MOI infections compared to adults 38,70 .…”

Plasmodium falciparum Genetic Diversity in Bangladesh Does Not Suggest a Hypoendemic Population Structure

“…[7][8][9][10][11][12][13][14][15][16][17] Since treatment with drugs of malaria patients is an integral part of malaria control and prevention strategy and the selected markers can be used as drug efficacy markers, knowing the baseline population structure of circulating parasites in an endemic country will aid in monitoring change in transmission pattern as well as efficacy of drugs that are in use. In this study, pretreatment patients were enrolled and genotyped to know parasite population structure and provide a baseline data for future reference.…”

“…5 Genetic diversity of the parasite arises during adjustment with different environmental and immunological factors such as drugs, host immune systems, and transmission intensity, and it contributes to the parasite's virulence. 6,7 Several P. falciparum genes have been found to show extensive genetic polymorphism. This phenomenon has been exploited for assessing the genetic diversity and population dynamics.…”

“…High polymorphism in merozoite surface protein 1 (msp1), merozoite surface protein 2 (msp2), and glutamaterich protein (glurp) genes have been shown in genetic diversity studies in different malaria-endemic countries from Asia to Africa. [7][8][9][10][11][12][13][14][15][16][17] Large allelic polymorphism has been reported in the block 2 of the msp1, the central repetitive domain of the msp2, and region II of the glurp. In msp1, three distinct allelic families have been described: K1, MAD20, and RO33 while in msp2, two allelic families, FC27 and 3D7/IC, have been described.…”

“…In msp1, three distinct allelic families have been described: K1, MAD20, and RO33 while in msp2, two allelic families, FC27 and 3D7/IC, have been described. 8,13,18 These markers have been used to distinguish recrudescence from new infections in various drug trial studies 7,11,12 including studies from CHT areas of Bangladesh. 19,20 Though, msp1, msp2, and glurp have been used in a limited approach in drug resistance studies, the parasite population genetic profile has not been assessed systematically in Bangladesh yet.…”