Evaluation of prevalence's of pfdhfr and pfdhps mutations in Angola

Fortes, Filomeno; Dimbu, Rafael; Figueiredo, Paula; Neto, Zoraima; Rosário, Virgílio Estólio do; Lopes, Dinora

doi:10.1186/1475-2875-10-22

Cited by 18 publications

(21 citation statements)

References 45 publications

(46 reference statements)

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“…Double-or triple-mutant haplotypes were the most common for the pfdhfr gene, especially I 51 R 59 N 108 and I 51 N 108 . pfdhfr 51I was the second most prevalent, similar to the previous studies in Angola (40)(41)(42)(43). pfdhfr 164L was only found in one isolate and presented in association with I 51 R 59 N 108 , which was rare in Africa and could be detected occasionally together with 108N ϩ 51I and/or 59R (44).…”

Section: Discussionsupporting

confidence: 87%

Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

Zhou

Yang

et al. 2019

Antimicrob Agents Chemother

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Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR using Sanger sequencing. The prevalences of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164, and pfdhps S436A437A476K540A581 were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of the K13 gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.

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Section: Discussionsupporting

confidence: 87%

Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

Zhou

Yang

et al. 2019

Antimicrob Agents Chemother

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“…The results showed a complex mixture of pfdhfr/pfdhps haplotypes in Luanda as already reported in other six provinces of Angola [ 25 , 26 ]. The 164L mutation was not disclosed, corroborating the findings of other nearby African countries [ 27 - 29 ].…”

Section: Discussionsupporting

confidence: 85%

Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola

Gama

Pereira-Carvalho

Kosi

et al. 2011

Malar J

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BackgroundPlasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola.MethodsPlasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes.ResultsThe most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples).ConclusionThis study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola.

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“…In a study on 21 isolates collected in Huambo, a neighbouring province to the east of Benguela province, all carried the mutant Asn-108 pfdhfr allele, and the double mutant haplotype Ile-51/Asn-108 was the most prevalent [ 24 ]. Overall, in that study, 25% of the isolates collected from different localities in the country presented the triple pfdhfr mutant alleles.…”

Section: Resultsmentioning

confidence: 99%

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Ngane

Djaman

Culeux

et al. 2015

Malar J

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BackgroundThe malaria situation has been worsening in Angola, partly due to armed conflict until the recent past and drug-resistant Plasmodium falciparum. Malaria transmission is heterogeneous within the country, and data on drug-resistant malaria in different parts of the country are incomplete. The aim of the present study was to evaluate resistance to 4-aminoquinolines and antifolate drugs in P. falciparum isolates collected in Benguela province, central Angola, using molecular markers.MethodsFingerprick capillary blood was collected from asymptomatic children aged less than 15 years old during a household survey in and around Balombo town in 2010–2011. Samples were screened for P. falciparum by nested PCR. Molecular markers (P. falciparum dihydrofolate reductase [pfdhfr], P. falciparum dihydropteroate synthase [pfdhps], P. falciparum chloroquine resistance transporter [pfcrt], and P. falciparum multidrug-resistance gene 1 [pfmdr1]) were sequenced to determine the key codons associated with drug resistance.ResultsA total of 60 blood samples were positive for P. falciparum. Most isolates with successful PCR amplification had mutant pfdhfr alleles, with either double mutant AICNI (69%) or triple mutant AIRNI (21%) haplotypes. A16V, S108T, and I164L substitutions were not found. Many of the isolates were carriers of either SGKAA (60%) or AGKAA (27%) pfdhps haplotype. K540E substitution was absent. There were only two pfcrt haplotypes: wild-type CVMNK (11%) and mutant CVIET (89%). Wild-type pfmdr1 NYSND haplotype was found in 19% of the isolates, whereas single mutant pfmdr1 YYSND and NFSND haplotypes occurred in 48% and 11%, respectively. Double mutant pfmdr1 haplotypes (YFSND and YYSNY) occurred rarely.ConclusionsThe results suggest that the high prevalence of mutant pfcrt CVIET haplotype is in agreement with low clinical efficacy of chloroquine observed in earlier studies and that the double pfdhfr mutant AICNI and single pfdhps mutant SGKAA are currently the predominant haplotypes associated with antifolate resistance in Benguela province. The hallmark of clinical resistance observed in East Africa, i.e. triple pfdhfr mutant haplotype (AIRNI) and double pfdhps mutant haplotype (SGEAA), was absent. These molecular findings need to be further evaluated in parallel with clinical studies, in particular with the efficacy of intermittent preventive treatment using sulphadoxine-pyrimethamine in pregnant women and artesunate-amodiaquine for uncomplicated malaria.

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Evaluation of prevalence's of pfdhfr and pfdhps mutations in Angola

Cited by 18 publications

References 45 publications

Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

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