Genetic diversity and genetic relatedness in Plasmodium falciparum parasite population in individuals with uncomplicated malaria based on microsatellite typing in Eastern and Western regions of Uganda, 2019–2020

Malaria Journal

Christiane Prosser¹  Rhoda Namubiru²  Charles Karamagi²  Joan K. Nakayaga²  Sam Nsobya³  Moses R. Kamya³  Adoke Yeka³  Joaniter I. Nankabirwa³  Agaba B. Bosco⁴  Chae Seung Lim⁵  Emmanuel Arinaitwe⁶  John Kissa⁷  Karen Anderson⁸  Karryn Gresty⁸  David Smith⁸  Qin Cheng⁸  Paul Mbaka⁹ 

[1] Australian Defence Force Malaria and Infectious Disease Institute, Brisbane, Australia;College of Health Sciences, Makerere University, Kampala, Uganda;College of Health Sciences, Makerere University, Kampala, Uganda;Infectious Diseases Research Collaboration, Kampala, Uganda;College of Health Sciences, Makerere University, Kampala, Uganda;National Malaria Control Division, Kampala, Uganda;Department of Laboratory Medicine, College of Health Sciences, Korea University, Seoul, South Korea;Infectious Diseases Research Collaboration, Kampala, Uganda;National Health Information Division, Ministry of Health, Kampala, Uganda;QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;Australian Defence Force Malaria and Infectious Disease Institute, Brisbane, Australia;World Health Organization Country Office, Kampala, Uganda;

关键词: Malaria;    Rapid diagnostic tests;    Genetic diversity;    Multiplicity of infection;    Multiclonal infections;    Parasite relatedness;    Pfhrp2;    Microsatellite markers;   

DOI  :  10.1186/s12936-021-03763-6

来源: Springer

【 摘 要 】

BackgroundGenetic diversity and parasite relatedness are essential parameters for assessing impact of interventions and understanding transmission dynamics of malaria parasites, however data on its status in Plasmodium falciparum populations in Uganda is limited. Microsatellite markers and DNA sequencing were used to determine diversity and molecular characterization of P. falciparum parasite populations in Uganda.MethodsA total of 147 P. falciparum genomic DNA samples collected from cross-sectional surveys in symptomatic individuals of 2–10 years were characterized by genotyping of seven highly polymorphic neutral microsatellite markers (n = 85) and genetic sequencing of the Histidine Rich Protein 2 (pfhrp2) gene (n = 62). ArcGIS was used to map the geographical distribution of isolates while statistical testing was done using Student's t-test or Wilcoxon's rank-sum test and Fisher’s exact test as appropriate at P ≤ 0.05.ResultsOverall, 75.5% (95% CI 61.1–85.8) and 24.5% (95% CI14.2–38.9) of parasites examined were of multiclonal (mixed genotype) and single clone infections, respectively. Multiclonal infections occurred more frequently in the Eastern region 73.7% (95% CI 48.8–89.1), P < 0.05. Overall, multiplicity of infection (MOI) was 1.9 (95% CI 1.7–2.1), P = 0.01 that was similar between age groups (1.8 vs 1.9), P = 0.60 and regions (1.9 vs 1.8), P = 0.43 for the < 5 and ≥ 5 years and Eastern and Western regions, respectively. Genomic sequencing of the pfhrp2 exon2 revealed a high level of genetic diversity reflected in 96.8% (60/62) unique sequence types. Repeat type AHHAAAHHATD and HRP2 sequence Type C were more frequent in RDT−/PCR + samples (1.9% vs 1.5%) and (13% vs 8%), P < 0.05 respectively. Genetic relatedness analysis revealed small clusters of gene deleted parasites in Uganda, but no clustering with Eritrean parasites.ConclusionHigh level of genetic diversity of P. falciparum parasites reflected in the frequency of multiclonal infections, multiplicity of infection and variability of the pfhrp2 gene observed in this study is consistent with the high malaria transmission intensity in these settings. Parasite genetic analysis suggested spontaneous emergence and clonal expansion of pfhrp2 deleted parasites that require close monitoring to inform national malaria diagnosis and case management policies.

【 授权许可】

CC BY