Plasmodium falciparum: Genetic diversity and complexity of infections in an isolated village in western Thailand

Tanabe, Kazuyuki; Zollner, Gabriela; Vaughan, Jefferson A.; Sattabongkot, Jetsumon; Khuntirat, Benjawan; Honma, Hajime; Mita, Toshihiro; Tsuboi, Takafumi; Coleman, Russell E.

doi:10.1016/j.parint.2013.09.011

Cited by 12 publications

(15 citation statements)

References 47 publications

(79 reference statements)

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“…In contrast with Africa where the SGA motif is present in 57.5% of all K1 - like alleles sampled, only three (1.8%) of the K1 - like alleles detected in Asia have an SGA motif in the tripeptide repeat, and these three are identical sequences from a single site in Bangladesh. This is consistent with previous data noting a high frequency of alleles containing the SAQSGA motif in Africa [ 3 ], but their absence in a Southeast Asian population [ 29 ], and interestingly this motif has previously been reported in a single allele from Northeast India [ 28 ], close to Bangladesh. Previously described rare K1 - like msp1 block 2 variants encoding SAT or SAP tripeptides [ 30 ] were not seen in any sequences.…”

Section: Resultssupporting

confidence: 93%

“…The existing diversity of msp1 block 2 alleles has been previously characterized in population samples by polymerase chain reaction (PCR) amplification followed by chain termination sequencing spanning the whole of block 2 [ 3 , 4 , 6 , 26 – 29 ], or pyro-sequencing which produces reads of up to 300 base pairs (bp) that are long enough to span most individual msp1 block 2 sequences [ 30 ]. The msp1 block 2 genotypes can also be characterized at a lower level of resolution using allele type-specific PCR methods [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data

Aspeling-Jones¹,

Conway²

2018

Malar J

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BackgroundWithin Plasmodium falciparum merozoite surface protein 1 (MSP1), the N-terminal block 2 region is a highly polymorphic target of naturally acquired antibody responses. The antigenic diversity is determined by complex repeat sequences as well as non-repeat sequences, grouping into three major allelic types that appear to be maintained within populations by natural selection. Within these major types, many distinct allelic sequences have been described in different studies, but the extent and significance of the diversity remains unresolved.MethodsTo survey the diversity more extensively, block 2 allelic sequences in the msp1 gene were characterized in 2400 P. falciparum infection isolates with whole genome short read sequence data available from the Pf3K project, and compared with the data from previous studies.ResultsMapping the short read sequence data in the 2400 isolates to a reference library of msp1 block 2 allelic sequences yielded 3815 allele scores at the level of major allelic family types, with 46% of isolates containing two or more of these major types. Overall frequencies were similar to those previously reported in other samples with different methods, the K1-like allelic type being most common in Africa, MAD20-like most common in Southeast Asia, and RO33-like being the third most abundant type in each continent. The rare MR type, formed by recombination between MAD20-like and RO33-like alleles, was only seen in Africa and very rarely in the Indian subcontinent but not in Southeast Asia. A combination of mapped short read assembly approaches enabled 1522 complete msp1 block 2 sequences to be determined, among which there were 363 different allele sequences, of which 246 have not been described previously. In these data, the K1-like msp1 block 2 alleles are most diverse and encode 225 distinct amino acid sequences, compared with 123 different MAD20-like, 9 RO33-like and 6 MR type sequences. Within each of the major types, the different allelic sequences show highly skewed geographical distributions, with most of the more common sequences being detected in either Africa or Asia, but not in both.ConclusionsAllelic sequences of this extremely polymorphic locus have been derived from whole genome short read sequence data by mapping to a reference library followed by assembly of mapped reads. The catalogue of sequence variation has been greatly expanded, so that there are now more than 500 different msp1 block 2 allelic sequences described. This provides an extensive reference for molecular epidemiological genotyping and sequencing studies, and potentially for design of a multi-allelic vaccine.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2475-2) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data

Aspeling-Jones¹,

Conway²

2018

Malar J

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“…falciparum infections is not associated with clinical symptoms or severity of malaria cases. In particular, groups of severe and mild malaria cases have been compared independently in The Gambia [ 22 ], Senegal [ 52 ], Gabon [ 23 ], Côte d'Ivoire [ 12 ], and Thailand [ 53 ] with each study showing that the numbers of genotypes per infection were similar between groups. These observations are consistent with our findings in P .…”

Section: Discussionmentioning

confidence: 99%

Multiplicity of Infection and Disease Severity in Plasmodium vivax

et al. 2016

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BackgroundMultiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared.Methodology/Principal FindingsAs part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections.ConclusionThe association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired immunity and exposure may have on multiclonal infections and their association with disease severity.

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“…Detailed molecular studies on the polymorphism of the P. falciparum AMA -1 gene have been conducted in various endemic areas worldwide, including the Middle East and South Asia [ 23 – 28 ], Oceania [ 29 – 31 ], Africa [ 31 – 39 ], and South America [ 40 – 41 ]. Whereas the majority of the AMA -1 sequences spanned the regions of domain I or the ectodomain (domains I-III) of the gene, there are currently only limited datasets in which the full-length sequences of the AMA -1 gene are reported [ 31 , 40 , 42 ]. In addition, there is only limited AMA -1 sequence data from P. falciparum populations in Southeast Asia, including the Thailand-Myanmar border and none from the Thailand-Cambodia and Thailand-Laos borders, where the multidrug resistant parasites are often detected and the vaccines will be needed most [ 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

Unraveling Haplotype Diversity of the Apical Membrane Antigen-1 Gene in Plasmodium falciparum Populations in Thailand

et al. 2018

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Development of an effective vaccine is critically needed for the prevention of malaria. One of the key antigens for malaria vaccines is the apical membrane antigen 1 (AMA-1) of the human malaria parasite Plasmodium falciparum, the surface protein for erythrocyte invasion of the parasite. The gene encoding AMA-1 has been sequenced from populations of P. falciparum worldwide, but the haplotype diversity of the gene in P. falciparum populations in the Greater Mekong Subregion (GMS), including Thailand, remains to be characterized. In the present study, the AMA-1 gene was PCR amplified and sequenced from the genomic DNA of 65 P. falciparum isolates from 5 endemic areas in Thailand. The nearly full-length 1,848 nucleotide sequence of AMA-1 was subjected to molecular analyses, including nucleotide sequence diversity, haplotype diversity and deduced amino acid sequence diversity and neutrality tests. Phylogenetic analysis and pairwise population differentiation (Fst indices) were performed to infer the population structure. The analyses identified 60 single nucleotide polymorphic loci, predominately located in domain I of AMA-1. A total of 31 unique AMA-1 haplotypes were identified, which included 11 novel ones. The phylogenetic tree of the AMA-1 haplotypes revealed multiple clades of AMA-1, each of which contained parasites of multiple geographical origins, consistent with the Fst indices indicating genetic homogeneity or gene flow among geographically distinct populations of P. falciparum in Thailand’s borders with Myanmar, Laos and Cambodia. In summary, the study revealed novel haplotypes and population structure needed for the further advancement of AMA-1-based malaria vaccines in the GMS.

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Plasmodium falciparum: Genetic diversity and complexity of infections in an isolated village in western Thailand

Cited by 12 publications

References 47 publications

An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data

An expanded global inventory of allelic variation in the most extremely polymorphic region of Plasmodium falciparum merozoite surface protein 1 provided by short read sequence data

Multiplicity of Infection and Disease Severity in Plasmodium vivax

Unraveling Haplotype Diversity of the Apical Membrane Antigen-1 Gene in Plasmodium falciparum Populations in Thailand

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