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Plasmodium malariae Prevalence and csp Gene Diversity, Kenya, 2014 and 2015.

ABSTRACT: In Africa, control programs that target primarily Plasmodium falciparum are inadequate for eliminating malaria. To learn more about prevalence and genetic variability of P. malariae in Africa, we examined blood samples from 663 asymptomatic and 245 symptomatic persons from western Kenya during June-August of 2014 and 2015. P. malariae accounted for 5.3% (35/663) of asymptomatic infections and 3.3% (8/245) of clinical cases. Among asymptomatic persons, 71% (32/45) of P. malariae infections detected by PCR were undetected by microscopy. The low sensitivity of microscopy probably results from the significantly lower parasitemia of P. malariae. Analyses of P. malariae circumsporozoite protein gene sequences revealed high genetic diversity among P. malariae in Africa, but no clear differentiation among geographic populations was observed. Our findings suggest that P. malariae should be included in the malaria elimination strategy in Africa and highlight the need for sensitive and field-applicable methods to identify P. malariae in malaria-endemic areas.

SUBMITTER: Lo E

PROVIDER: S-EPMC5367407 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Plasmodium malariae Prevalence and csp Gene Diversity, Kenya, 2014 and 2015.

Lo Eugenia E Nguyen Kristie K Nguyen Jennifer J Hemming-Schroeder Elizabeth E Xu Jiaobao J Etemesi Harrisone H Githeko Andrew A Yan Guiyun G

Emerging infectious diseases 20170401 4

In Africa, control programs that target primarily Plasmodium falciparum are inadequate for eliminating malaria. To learn more about prevalence and genetic variability of P. malariae in Africa, we examined blood samples from 663 asymptomatic and 245 symptomatic persons from western Kenya during June-August of 2014 and 2015. P. malariae accounted for 5.3% (35/663) of asymptomatic infections and 3.3% (8/245) of clinical cases. Among asymptomatic persons, 71% (32/45) of P. malariae infections detect ...[more]

PMID: 28322694

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Project description:The merozoite surface protein 1 (MSP1) gene encodes the major surface antigen of invasive forms of the Plasmodium erythrocytic stages and is considered a candidate vaccine antigen against malaria. Due to its polymorphisms, MSP1 is also useful for strain discrimination and consists of a good genetic marker. Sequence diversity in MSP1 has been analyzed in field isolates of three human parasites: P. falciparum, P. vivax, and P. ovale. However, the extent of variation in another human parasite, P. malariae, remains unknown. This parasite shows widespread, uneven distribution in tropical and subtropical regions throughout South America, Asia, and Africa. Interestingly, it is genetically indistinguishable from P. brasilianum, a parasite known to infect New World monkeys in Central and South America.Specific fragments (1 to 5) covering 60 % of the MSP1 gene (mainly the putatively polymorphic regions), were amplified by PCR in isolates of P. malariae and P. brasilianum from different geographic origin and hosts. Sequencing of the PCR-amplified products or cloned PCR fragments was performed and the sequences were used to construct a phylogenetic tree by the maximum likelihood method. Data were computed to give insights into the evolutionary and phylogenetic relationships of these parasites.Except for fragment 4, sequences from all other fragments consisted of unpublished sequences. The most polymorphic gene region was fragment 2, and in samples where this region lacks polymorphism, all other regions are also identical. The low variability of the P. malariae msp1 sequences of these isolates and the identification of the same haplotype in those collected many years apart at different locations is compatible with a low transmission rate. We also found greater diversity among P. brasilianum isolates compared with P. malariae ones. Lastly, the sequences were segregated according to their geographic origins and hosts, showing a strong genetic and geographic structure.Our data show that there is a low level of sequence diversity and a possible absence of allelic dimorphism of MSP1 in these parasites as opposed to other Plasmodium species. P. brasilianum strains apparently show greater divergence in comparison to P. malariae, thus P. malariae could derive from P. brasilianum, as it has been proposed.

Project description:BACKGROUND:Genetic diversity of the three important antigenic proteins, namely thrombospondin-related anonymous protein (TRAP), apical membrane antigen 1 (AMA1), and 6-cysteine protein (P48/45), all of which are found in various developmental stages of Plasmodium parasites is crucial for targeted vaccine development. While studies related to the genetic diversity of these proteins are available for Plasmodium falciparum and Plasmodium vivax, barely enough information exists regarding Plasmodium malariae. The present study aims to demonstrate the genetic variations existing among these three genes in P. malariae by analysing their diversity at nucleotide and protein levels. METHODS:Three surface protein genes were isolated from 45 samples collected in Thailand (N = 33), Myanmar (N = 8), and Lao PDR (N = 4), using conventional polymerase chain reaction (PCR) assay. Then, the PCR products were sequenced and analysed using BioEdit, MEGA6, and DnaSP programs. RESULTS:The average pairwise nucleotide diversities (?) of P. malariae trap, ama1, and p48/45 were 0.00169, 0.00413, and 0.00029, respectively. The haplotype diversities (Hd) of P. malariae trap, ama1, and p48/45 were 0.919, 0.946, and 0.130, respectively. Most of the nucleotide substitutions were non-synonymous, which indicated that the genetic variations of these genes were maintained by positive diversifying selection, thus, suggesting their role as a potential target of protective immune response. Amino acid substitutions of P. malariae TRAP, AMA1, and P48/45 could be categorized to 17, 20, and 2 unique amino-acid variants, respectively. For further vaccine development, carboxyl terminal of P48/45 would be a good candidate according to conserved amino acid at low genetic diversity (? = 0.2-0.3). CONCLUSIONS:High mutational diversity was observed in P. malariae trap and ama1 as compared to p48/45 in P. malariae samples isolated from Thailand, Myanmar, and Lao PDR. Taken together, these results suggest that P48/45 might be a good vaccine candidate against P. malariae infection because of its sufficiently low genetic diversity and highly conserved amino acids especially on the carboxyl end.

Project description:BACKGROUND:Severe complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global prevalence and mortality of severe P. malariae infection in humans. METHODS:The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All research articles published on the severity and mortality of P. malariae infection cases in humans were retrieved from three public databases: PubMed, Scopus, and ISI Web of Science. The pooled prevalence estimate and 95% confidence interval (CI) of complications in patients with P. malariae malaria was analysed using the random-effects model provided in Stata software. The pooled odds ratio (OR) and 95% CI of severe malaria for P. malariae infection and Plasmodium falciparum infection were analysed using Review Manager software. RESULTS:Six studies were used to estimate the pooled prevalence of severe P. malariae malaria. Out of 10,520 patients infected with P. malariae, the pooled prevalence estimate of severe P. malariae infection was 3% (95% CI 2-5%), with high heterogeneity (I2: 90.7%). Severe anaemia (3.32%), pulmonary complications (0.46%), and renal impairments (0.24%) were the most common severe complications found in patients with P. malariae infection. The pooled proportion of severe anaemia for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.74, 95% CI 0.22-2.45, I2?=?98%). The pooled proportion of pulmonary complications was comparable between patients with P. malariae infection and those with P. falciparum infection among the four included studies (OR: 1.44; 95% CI 0.17-12.31, I2: 92%). For renal complications, the funnel plot showed that the pooled proportion of renal complications for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.94, 95% CI 0.18-4.93, I2: 91%). The mortality rate of patients with P. malariae infection was 0.17% (18/10,502 cases). CONCLUSIONS:This systematic review demonstrated that approximately two percent of patients with P. malariae infection developed severe complications, with a low mortality rate. Severe anaemia, pulmonary involvement, and renal impairment were the most common complications found in patients with P. malariae infection. Although a low prevalence and low mortality of P. malariae infection have been reported, patients with P. malariae infection need to be investigated for severe anaemia and, if present, treated aggressively to prevent anaemia-related death.

Dataset Information

Plasmodium malariae Prevalence and csp Gene Diversity, Kenya, 2014 and 2015.

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Plasmodium malariae Prevalence and csp Gene Diversity, Kenya, 2014 and 2015.

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