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

Gama, Bianca Ervatti; Pereira-Carvalho, Guilhermina A L; Kosi, Florbela J I Lutucuta; Oliveira, Natália K Almeida de; Fortes, Filomeno; Rosenthal, Philip J.; Rosário, Virgílio Estólio do; Daniel-Ribeiro, Cláudio Tadeu; Ferreira-da-Cruz, Maria de Fátima

doi:10.1186/1475-2875-10-248

Cited by 9 publications

(12 citation statements)

References 26 publications

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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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“…Overall, in that study, 25% of the isolates collected from different localities in the country presented the triple pfdhfr mutant alleles. In another study on isolates collected in Luanda [ 25 ], 31 of 61 (51%) samples were triple pfdhfr mutants, and 25 of 61 (41%) and 4 of 61 (6.6%) isolates were Ile-51/Asn-108 and Arg-59/Asn-108 double mutants, respectively. In the northern province of Uige, the majority (40 of 66, 61%) of clinical isolates were double Ile-51/Asn-108 pfdhfr mutants, followed by triple mutants (23 of 66, 35%) and the alternative double Arg-59/Asn-108 mutant (n = 1) and wild-type (n = 2) [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, in Luanda, SGKAA was also the most frequent haplotype (18 of 30, 60%), followed by AGKAA (7 of 30, 23%) and the wild-type SAKAA (2 of 30, 7%) [ 25 ]. SGEAA and SGEGA haplotypes were found in 3 isolates in that study.…”

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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“…A study in Cameroon reported that codon 108 (S108N) has increased inexorably from 48% in 1994-1995, 71% in 1997-1998, and 93% in 2000 -2001. 32 The triple mutations, S108N, N51I, and C59R were evident in 100%, 93%, and 57% of isolates, respectively, in recent surveys in Angola 33 and in Tanzania, 100%, 100%, 100%, and 100% of isolates for 59R, 108N, 436S/437G, and 540E, respectively, in 2007 from a low transmission area. 34 Data from Uganda also showed within 99%, near 99%, and 57-94% of isolates respectively for the 108, 51, and 59 mutations.…”

Section: Discussionmentioning

confidence: 99%

Surveillance of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine-Pyrimethamine 5 Years after the Change of Malaria Treatment Policy in Ghana

Duah

Quashie²,

Abuaku³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. In 2005, sulphadoxine-pyrimethamine (SP) became the drug of choice for intermittent preventive treatment of Plasmodium falciparum malaria in pregnancy (IPTp) in Ghana. Reports suggest the use of SP by others to treat uncomplicated malaria. Because of the increased use of SP, the prevalence of mutations in the genes, dihydrofolate reductase (dhfr), and dihydropteroate synthetase (dhps), linked to SP resistance in P. falciparum were determined. Blood samples from 945 children with uncomplicated malaria collected at nine sites from 2003 to 2010 were analyzed using polymerase chain reaction and restriction fragment length polymorphism. Prevalence of the dhfr triple and dhfr plus dhps quadruple mutations showed significant increase in trend from 2003 to 2010 (χ 2 = 18.78, P 0.001, χ 2 = 15.11, P 0.001, respectively). For dhps double mutant G437 + E540 the prevalence was low (1.12%) caused by the very low prevalence of E540. Our findings show the wide use of SP in Ghana and therefore its use for IPTp needs to be closely monitored.

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

Cited by 9 publications

References 26 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 epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola

Surveillance of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine-Pyrimethamine 5 Years after the Change of Malaria Treatment Policy in Ghana

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