Species and genotype diversity of Plasmodium in malaria patients from Gabon analysed by next generation sequencing

Lalremruata, Albert; Jeyaraj, Sankarganesh; Engleitner, Thomas; Joanny, Fanny; Lang, Annika; Bélard, Sabine; Mombo-Ngoma, Ghyslain; Ramharter, Michael; Kremsner, Peter G.; Mordmüller, Benjamin; Held, Jana

doi:10.1186/s12936-017-2044-0

Cited by 57 publications

(53 citation statements)

References 36 publications

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“…mixture of the parasites within the host, 24,25 may have enabled more comprehensive detection of pfhrp2 sequences present in those samples. Although comparative analysis of the sequences showed that no two sequences were the same between our study and previous studies, the prevalence and frequency of each of the 12 Baker repeat types, common between these two groups, were comparable.…”

Section: Discussionmentioning

confidence: 99%

“…The pfhrp2 gene sequences were translated into protein sequences and 24 amino acid repeat types (1-24) were classified as described by Baker et al 9,10 Of these 24 amino acid repeat types (called Baker repeats), 20 (repeats [1][2][3][4][5][6][7][8][9][10][11][12][13][14][19][20][21][22][23][24] are present in pfhrp2, whereas four (repeats 15-18) are present in the pfhrp2 paralog gene pfhrp3. 9 Because RDT-based diagnosis was not performed on these samples, 14 both scenarios of the predictive model, based on the number of type 2 × type 7 repeats, were used to predict the sensitivity of an RDT detecting PfHRP2: (a) an isolate would be detectable at £ 250 parasites/μL if the number of repeat types is > 43 10 and (b) an isolate would be detectable at ³ 200 parasites/μL regardless of the number of repeat types.…”

Section: Introductionmentioning

confidence: 99%

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Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

Willie

Zimmerman

Mehlotra

2018

The American Journal of Tropical Medicine and Hygiene

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Histidine-rich protein 2 of (PfHRP2) forms the basis of many current malaria rapid diagnostic tests (RDTs). It is concerning that there are parasites that lack part or all of the gene, and thus do not express the PfHRP2 protein; such parasites are not identifiable by PfHRP2-detecting RDTs. Very limited information is available regarding genetic variation in Papua New Guinea (PNG). In the present study, this gene variation was evaluated using 169 samples previously collected from the Wosera area in East Sepik Province of PNG. Molecular diagnosis of these samples showed that 81% were infected, and was present in 91% of those infected samples. One hundred and twenty samples were amplified for exon-2, from which 12 randomly selected amplicons were sequenced, yielding 18 sequences, all of which were unique. Baker repeat type 2 × type 7 numbers ranged from 0 to 108. Epitope mapping analysis revealed that three major epitopes, DAHHAHHA, AHHAADAHHA, and AHHAADAHH, were present in high prevalence and frequencies. These major epitopes have been shown to be recognized by the monoclonal antibodies 3A4 and PTL-3 (DAHHAHHA), C1-13 (AHHAADAHHA), and S2-5 and C2-3 (AHHAADAHH). This study provides further information on the high genetic variation of and its unclear relationship with prediction of RDT detection sensitivity, and identifies major epitopes in this gene from PNG. These results could be relevant and useful to understand the genetic diversity of this gene and the performance of current and future RDTs in this malarious region of the world.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

Willie

Zimmerman

Mehlotra

2018

The American Journal of Tropical Medicine and Hygiene

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“…Plasmodium falciparum was identified by microscopic examination of Giemsa-stained slides. Furthermore, the presence of other Plasmodium species were checked by sequencing of two conserved regions of the Plasmodium parasite mitochondrial genome [24]. This procedure was done to confirm that the samples were only P. falciparum.…”

Section: Plasmodium Species Confirmationmentioning

confidence: 99%

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

Mohamed

Hussien

Mohamed

et al. 2020

Malar J

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Background: Plasmodium falciparum malaria is a public health problem worldwide. Malaria treatment policy has faced periodic changes due to emergence of drug resistant parasites. In Sudan chloroquine has been replaced by artesunate and sulfadoxine/pyrimethamine (AS/SP) in 2005 and to artemether-lumefantrine (AL) in 2017, due to the development of drug resistance. Different molecular markers have been used to monitor the status of drug resistant P. falciparum. This study aimed to determine the frequency of malaria drug resistance molecular markers in Southeast Sudan. Methods:The samples of this study were day zero dried blood spot samples collected from efficacy studies in the Blue Nile State from November 2015 to January 2016. A total of 130 samples were amplified and sequenced using illumina Miseq platform. The molecular markers included were Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfk13, exonuclease and artemisinin resistant (ART-R) genetic background (Pfmdr2, ferroredoxine, Pfcrt and Pfarps10). Results:Resistance markers for chloroquine were detected in 25.8% of the samples as mutant haplotype Pfcrt 72-76 CVIET and 21.7% Pfmdr1 86Y. Pfdhfr mutations were detected in codons 51, 59 and 108. The ICNI double-mutant haplotype was the most prevalent (69%). Pfdhps mutations were detected in codons 436, 437, 540, 581 and 613. The SGEGA triple-mutant haplotype was the most prevalent (43%). In Pfdhfr/Pfdhps combined mutation, quintuple mutation ICNI/SGEGA is the most frequent one (29%). Six of the seven treatment failure samples had quintuple mutation and the seventh was quadruple. This was significantly higher from the adequately responsive group (P < 0.01). Pfk13 novel mutations were found in 7 (8.8%) samples, which were not linked to artemisinin resistance. Mutations in ART-R genetic background genes ranged from zero to 7%. Exonuclease mutation was not detected.

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“…Several studies involving sophisticated molecular detection methods have revealed more accurate picture of P. malariae infection indicating much higher prevalence of the disease than previously expected in many regions of the world [ 3 – 5 ]. Moreover, P. malariae infection often displays low parasitaemia and can occur as mixed infection involving P. falciparum or P. vivax [ 6 ]. Similarly, P. malariae infection can remain asymptomatic for longer period of time and lead to increase in mortality by causing chronic nephrotic syndrome [ 7 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity of three surface protein genes in Plasmodium malariae from three Asian countries

Srisutham

Saralamba

Sriprawat

et al. 2018

Malar J

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BackgroundGenetic 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.MethodsThree 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.ResultsThe average pairwise nucleotide diversities (π) 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 (π = 0.2–0.3).ConclusionsHigh 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.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2176-x) contains supplementary material, which is available to authorized users.

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Species and genotype diversity of Plasmodium in malaria patients from Gabon analysed by next generation sequencing

Cited by 57 publications

References 36 publications

Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

Plasmodium falciparum Histidine-Rich Protein 2 Gene Variation in a Malaria-Endemic Area of Papua New Guinea

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

Genetic diversity of three surface protein genes in Plasmodium malariae from three Asian countries

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