An online mapping database of molecular markers of drug resistance in Plasmodium falciparum: the ACT Partner Drug Molecular Surveyor

Otienoburu, Sabina Dahlström; Suay, Ignacio; Garcia, Steven; Thomas, Nigel V.; Srisutham, Suttipat; Björkman, Anders; Humphreys, Georgina S

doi:10.1186/s12936-019-2645-x

Cited by 21 publications

(27 citation statements)

References 31 publications

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“…This finding is quite in contrast to longitudinal studies in areas that used other ACTs as first-line treatment. P. falciparum genotypes associated with tolerance/resistance to the ACT partner drugs lumefantrine (18,39), sulfadoxine/pyrimethamine (40,41) and piperaquine (12) have all been shown to consistently increase over time, after respective ACT use.…”

Section: Discussionmentioning

confidence: 99%

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar

Msellem¹,

Morris²,

Soe³

et al. 2020

Emerg. Infect. Dis.

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A rtemisinin-based combination therapy (ACT) has been first-line treatment for uncomplicated Plasmodium falciparum malaria globally for the past 10-15 years and has contributed greatly to a reduction of malaria illnesses and deaths during 2005-2015 (1,2). However, artemisinin resistance emerged in Cambodia during 2008, where it then spread and even developed de novo throughout the Great Mekong Region (3,4). Possible resistance has been reported from eastern India (5) and, Guyana in South America (6) but not yet from Africa (4). However, ACT resistance represents a continuous threat in contexts such as Zanzibar, where numerous longdistance visitors represent a special risk for imported artemisinin-resistant malaria parasites. Chloroquine resistance entered eastern Africa most probably from India in late 1970s (7). In addition, selection of resistance/tolerance to the slowly eliminated long-acting partner drugs in ACT (e.g., amodiaquine) is expected, especially in highly malaria-endemic areas of Africa (8-10), which could result in relatively reduced ACT cure rates and reduced protection against artemisinin resistance (11). Currently, however, complete ACT resistance has developed and spread only in Asia (e.g., Cambodia) (12). In Zanzibar, malaria transmission has been reduced substantially after new and reinforced malaria tools and interventions, including ACT for uncomplicated malaria (2), were implemented. The reduced parasite biomass on the islands of Zanzibar has resulted in an expected selection (bottleneck) of the parasite populations (2,13), which under strong drug exposure might select for drug resistance. The firstline ACT in Zanzibar has been artesunate/amodiaquine (ASAQ) since 2003, plus recently added single, low-dose primaquine. Artemether/lumefantrine was used as second-line treatment when ACT was first used, followed by quinine when treatment guidelines were revised in 2009 (2). Free access throughout the health systems has resulted in sustained high population coverage and compliance to ASAQ (2,14,15). The partner drug amodiaquine is relatively short-lived (half-life 2-8 hours) and is primarily metabolized to

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Section: Discussionmentioning

confidence: 99%

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar

Msellem¹,

Morris²,

Soe³

et al. 2020

Emerg. Infect. Dis.

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“…For partner drugs in the national treatment regimens AL and AS/AQ, increased risk of treatment failure and decreased susceptibility to lumefantrine in vitro are associated with N86, 184F, D1246, K76 alleles of Pfmdr-1 [11, 13, 14]. AQ resistance is associated with Pfmdr-1 alleles 86Y, Y184 and 1246Y; P. falciparum chloroquine resistance gene ( Pfcrt ) alleles 76T and SVMNT while CQ resistance is associated with 86Y and 76T alleles of Pfmdr-1 and Pfcrt genes respectively [13, 15]. Over the years, changes in malaria treatment practices have resulted in changes in the above markers of resistance.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of Pfmdr-1 N86 and D1246 genotypes detected among febrile malaria outpatients attending Lira Regional Referral Hospital, Northern Uganda

et al. 2019

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Objective To determine the prevalence of Plasmodium falciparum multi-drug resistant gene-1 ( Pfmdr-1 ) N86Y and D1246Y genotypes among febrile malaria outpatients attending Lira Regional Referral Hospital, Uganda. Results Overall, 92.3% (n = 48/52) and 90% (n = 45/50) of the parasites detected carried the wild type alleles 1246D and N86, respectively. Only 7.7% (n = 4/52) and 10% (n = 5/50) of these P. falciparum isolates carried the Pfmdr-1 mutant alleles 1246Y and 86Y, respectively. Our results show high prevalence of wild type alleles N86 and D1246 in P. falciparum isolates from Lira Regional Referral Hospital, which could translate to a decreased sensitivity to artemether-lumefantrine. Continued monitoring of prevalence of single nucleotide polymorphisms is warranted to timely inform malaria treatment policies and guidelines.

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“…k13 was fully genotyped in almost all samples, whilst crt had more missing data due to the introduced homopolymer. With increasing information on the variant frequency in target populations however, missing genotypes can be imputed 37 and flow cell chemistry has improved to allow more accurate sequencing of homopolymers. Despite missing data for some samples, a large number of PNG isolates from different time points were successfully genotyped for all genes.…”

Section: Discussionmentioning

confidence: 99%

Real time, field-deployable whole genome sequencing of malaria parasites using nanopore technology

Razook

Mehra

Gilchrist

et al. 2020

Preprint

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Malaria parasite genomes have been generated predominantly using short read sequencing technology which can be slow, requires advanced laboratory training and does not adequately interrogate complex genomic regions that harbour important malaria virulence determinants. The portable Oxford Nanopore Technologies MinION platform generates long reads in real time and may overcome these limitations. We present compelling evidence that Nanopore sequencing delivers valuable additional information for malaria parasites with comparable data fidelity for single nucleotide variant (SNV) calls, compared to standard Illumina whole genome sequencing. We demonstrate this through sequencing of pure Plasmodium falciparum DNA, mock infections and natural isolates. Nanopore has low error rates for haploid SNV genotyping and identifies structural variants (SVs) not detected with short reads. Nanopore genomes are directly comparable to publically available genomes and produce high quality end to end chromosome assemblies. Nanopore sequencing will expedite genomic surveillance of malaria and provide new insights into parasite genome biology.

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An online mapping database of molecular markers of drug resistance in Plasmodium falciparum: the ACT Partner Drug Molecular Surveyor

Cited by 21 publications

References 31 publications

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar

Increased Sensitivity of Plasmodium falciparum to Artesunate/Amodiaquine Despite 14 Years as First-Line Malaria Treatment, Zanzibar

High prevalence of Pfmdr-1 N86 and D1246 genotypes detected among febrile malaria outpatients attending Lira Regional Referral Hospital, Northern Uganda

Real time, field-deployable whole genome sequencing of malaria parasites using nanopore technology

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