Plasmodium falciparum merozoite protein-1 genetic diversity and multiplicity of infection in isolates from Congolese children consulting in a pediatric hospital in Brazzaville

Gueye, Nerly Shirère Gampio; Ntoumi, Francine; Vouvoungui, Christevy; Kobawila, Simon Charles; Nkombo, Michael; Mouanga, Alain Maxime; Deibert, Julia; Koukouikila-Koussounda, Félix

doi:10.1016/j.actatropica.2018.04.012

Cited by 20 publications

(22 citation statements)

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“…One possible mechanism for parasite tolerance could be through clonal selection in immune adults which has been reported by Ntoumi et al [58], who have showed that the number of genotypes and allelic families per positive sample is signi cantly reduced around the age of 15 years in endemic areas. The present study showed that submicroscopic P. falciparum infection was associated with a low COI (2.4) con rming those obtained by A-Elbasit et al (COI=1.0 with msp-2 marker) and Gueye et al (COI=1.4 and 1.7 for less than 5 years old and over 5 years old, respectively, with msp-1 marker) [62,63]. Among the two types of antigens tested, the crude antigen was more sensitive than the MSP-3 recombinant antigen [33].…”

Section: Discussionsupporting

confidence: 92%

Immune tolerance to asymptomatic submicroscopic Plasmodium falciparum infections in adults living in malaria endemic areas

Diouf

Diop

Dièye

et al. 2020

Preprint

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Background Combined malaria control interventions have reduced mortality rate, number of clinical cases and parasite prevalence across Africa between 2000 and 2015. As a consequence, Plasmodium infections have become mostly asymptomatic and often sub-microscopic in many endemic areas. The present study aims to evaluate the contribution of asymptomatic sub-microscopic P. falciparum carriage on antibody responses against malaria antigens. Methods A total of 353 samples from a cross-sectional sampling conducted in Ndiop (Senegal) in 2016 were tested by qPCR and microscopy to determine parasite prevalence. Plasmodium falciparum positive samples were genotyped using msp-2 marker. The IgG seroprevalence against crude schizont antigen of a local P. falciparum strain, tested by ELISA, was compared to parasite prevalence. An age-matched, under 10 years, 10-15 and over 15 years cohort of 110 positive and negative qPCR samples were used to determine the impact of sub-microscopic carriage on IgG and IgM antibody responses against schizont extract and MSP3 recombinant antigen. Results The microscopic diagnosis was negative for all thick smears defining a study cohort of submicroscopic asymptomatic individuals with an overall parasite prevalence of 22.37% (79/353) by qPCR. Submicroscopic infections were associated with significant lower IgG responses in qPCR positive samples for individuals over 15 years of age, for both crude schizont (p=0.021) and MSP3 recombinant antigen (p=0.035). IgM responses were significantly higher (p=0.034) in children under 10 years, showing their susceptibility to primary infection. Above 15 years of age, a significant difference was found between parasite prevalence of 9.3% (33/353) and IgG seroprevalence of 23.8% (84/353) (p=0.01). The overall genetic diversity detected is characterized by a complexity of infection (COI) and a number of genotypes of 2.4 and 17, respectively.Conclusion Asymptomatic submicroscopic P. falciparum carriage is prevalent in the study area and is associated with immune tolerance to parasites in adults. The difference between parasite prevalence and IgG seroprevalence results from long-lived IgG in adults point out attention for elders in endemic areas as a stable parasite reservoir. In this context, mass molecular detection followed by treatment could be a valuable method for achieving elimination.

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Section: Discussionsupporting

confidence: 92%

Immune tolerance to asymptomatic submicroscopic Plasmodium falciparum infections in adults living in malaria endemic areas

Diouf

Diop

Dièye

et al. 2020

Preprint

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“…However, its extensive polymorphic nature suggests that continuous survey of the genetic polymorphism from a wide range of field isolates is necessary. To date, a considerable amount of studies on MSP-1 42 have been carried out on P. falciparum [ 42 , 43 ] and P. vivax [ 24 , 25 , 44 ] but there is a paucity of information on the structure, function or genetic variation in MSP-1 in P. knowlesi . Recent studies by Cheong et al [ 20 , 45 ] demonstrated the high immunogenicity of MSP-1 42 and its ability to elicit protective immunity in P. knowlesi .…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphism and natural selection in the C-terminal 42 kDa region of merozoite surface protein-1 (MSP-1) among Plasmodium knowlesi samples from Malaysia

et al. 2018

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BackgroundThe merozoite surface protein-1 (MSP-1) gene encodes for a leading malaria vaccine candidate antigen. However, its extensive polymorphic nature represents a major obstacle to the development of a protective vaccine. Previously, a pilot study was carried out to explore the sequence variation of the C-terminal 42 kDa fragment within P. knowlesi MSP-1 gene (PkMSP-142) based on 12 clinical samples; however, further study on an adequate sample size is vital in estimating the genetic diversity of the parasite population.MethodsIn the present study, we included a larger sample size of P. knowlesi (83 samples) covering eight states of Malaysia to determine the genetic polymorphism, natural selection and haplotype groups of the gene fragment coding PkMSP-142. The region flanking PkMSP-142 was amplified by PCR and directly sequenced. Genetic diversity, haplotype diversity, population genetic differentiation and natural selection were determined in order to study the polymorphic characteristic of PkMSP-142.ResultsA high level of genetic diversity (Hd = 0.970 ± 0.007; л = 0.01079 ± 0.00033) was observed among the 83 P. knowlesi samples, confirming the extensive genetic polymorphism exhibited among the P. knowlesi population found in Malaysia. A total of 18 distinct haplotypes with 17 amino acid changes were identified, whereby 15 were new haplotypes. High population differentiation values were observed within samples from Peninsular Malaysia and Malaysian Borneo. The 42 kDa fragments of P. knowlesi from Malaysian Borneo were found to be acting on balancing selection whilst purifying selection was suggested to act on isolates from Peninsular Malaysia. The separation of PkMSP-142 haplotypes into two main groups based on geographical separation has further supported the existence of two distinct P. knowlesi lineages.ConclusionsA high level of genetic diversity was observed among PkMSP-142 in Malaysia, whereby most of the polymorphisms were found within the 33 kDa region. Taken together, these data will be useful in order to understand the nature of P. knowlesi population in Malaysia as well as the design and development of a MSP-142 based knowlesi malaria vaccine.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3234-5) contains supplementary material, which is available to authorized users.

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“…Total genomic DNA was isolated using QIAamp DNA Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Amplification of P. falciparum merozoite surface protein 2 gene (Pfmsp2)was used to determine P. falciparum multiplicity of infection (MOI) as described previously [25].Nested-PCR and restriction fragment length polymorphism (PCR-RFLP) were used to genotype Pfmd1 N86Y as described previously [26]. In brief, Pfmdr1primary and nested PCRs were conducted by adding 2µl DNA template into a PCR master mix (50µl) containing 1X PCR buffer2.8mM MgCl 2 , 200µM dNTPs,5pM of each primer,1UTaq DNA polymerase.…”

Section: Pfmdr1 Genotypingmentioning

confidence: 99%

Molecular surveillance of the Pfmdr1 N86Y allele in P. falciparum isolates from Brazzaville, Republic of Congo

Dossou-Yovo¹,

Ntoumi²,

Koukouikila-Koussounda³

et al. 2019

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Background: Regular surveillance of artemisinin−based combination therapy tolerance or resistance molecular makers is vital for effective malaria treatment, control and eradication programmes. P. falciparum multiple drug resistance-1 gene (Pfmdr1) N86Y mutation is associated with reduced susceptibility to lumefantrine. This study assessed the prevalence of Pfmdr1 N86Y in Brazzaville, Republic of Congo.Methods: A total 1001 of P. falciparum−infected blood samples obtained from asymptomatic malaria pregnant women having a normal child delivery at the Madibou Integrated Health Center were analysed.Pfmdr1 N86Y genotyping was conducted using PCR-Restriction fragment length polymorphism (RFLP).Results: The wild type Pfmdr1 N86 allele was predominant (>68 %) in this study whereas a few isolates carrying the either the mutant allele (Pfmdr1 86Y) alone or both alleles (mixed genotype).The dominance of the wildtype allele (pfmdr1 N86) indicates the plausible decline P. falciparum susceptibility to lumefantrine.Conclusion: This study gives an update on the prevalence of Pfmdr1 N86Y alleles in Brazzaville, Republic of Congo. It also raises concern on the imminent emergence of resistance against artemether−lumefantrine in this setting. Our study underscores the importance to regular artemether −lumefantrine efficacy monitoring to inform malaria control programme of the Republic of Congo.The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the funding agency. Author's contributionsLR D-Y performed all the lab analyses, FKK supervised the lab work, JCV was responsible of statistical 8 analysis, AA and AL participated in the interpretation of the results, DN and TPV reviewed and edited the manuscript. FN supervised the overall work. All authors approved the final manuscript. All the authors contributed in drafting the paper.

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Plasmodium falciparum merozoite protein-1 genetic diversity and multiplicity of infection in isolates from Congolese children consulting in a pediatric hospital in Brazzaville

Cited by 20 publications

References 33 publications

Immune tolerance to asymptomatic submicroscopic Plasmodium falciparum infections in adults living in malaria endemic areas

Immune tolerance to asymptomatic submicroscopic Plasmodium falciparum infections in adults living in malaria endemic areas

Genetic polymorphism and natural selection in the C-terminal 42 kDa region of merozoite surface protein-1 (MSP-1) among Plasmodium knowlesi samples from Malaysia

Molecular surveillance of the Pfmdr1 N86Y allele in P. falciparum isolates from Brazzaville, Republic of Congo

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