Chloroquine Resistant Plasmodium falciparum in Nigeria: Relationship between pfcrt and pfmdr1 Polymorphisms, In-Vitro Resistance and Treatment Outcome

Folarin, Onikepe A.; Gbotosho, Grace O.; Sowunmi, A.; Olorunsogo, Olufunso O.; Oduola, A. M. J.; Happi, Christian T.

doi:10.2174/1874315300801010074

Cited by 17 publications

(20 citation statements)

References 46 publications

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“…These results are in accordance with previous studies in Kenya (17) and Nigeria (57). However, the 86Y mutation has been associated with a decrease in CQ susceptibility in some works (5).…”

Section: Discussionsupporting

confidence: 93%

“…The N86-K76 and 86Y-K76 haplotypes showed a lower CQ IC 50 , in concordance with previous work in Kenya (17,61). The additional Pfmdr1 86Y mutation significantly increased the in vitro susceptibility to CQ (P ϭ 0.0179) in Pfcrt 76T CQ-resistant parasites from Senegal, while the 86Y-76T haplotype was shown to be associated with in vitro CQ resistance in isolates from Nigeria (57).…”

Section: Discussionsupporting

confidence: 89%

“…The parasites with Pfmdr1 86Y plus Y184 and 86Y plus 184F showed a nonsignificant increase of CQ susceptibility (P ϭ 0.0579). However, univariate analysis showed that there was a significant association between CQ treatment failure and the presence of Pfmdr1 86Y plus Y184 in Nigeria (57).…”

Section: Discussionmentioning

confidence: 90%

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Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Wurtz

Fall

Pascual

et al. 2014

Antimicrob Agents Chemother

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The involvement of Pfmdr1 (Plasmodium falciparum multidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms in Pfmdr1 (N86Y, Y184F, S1034C, N1042D, and D1246Y) and Pfcrt (K76T) and in vitro responses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174 Plasmodium falciparum isolates from Dakar, Senegal. The Pfmdr1 86Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. The Pfmdr1 86Y mutation was significantly associated with increased susceptibility to MDAQ (P ‫؍‬ 0.0023), LMF (P ‫؍‬ 0.0001), DHA (P ‫؍‬ 0.0387), and MQ (P ‫؍‬ 0.00002). The N86Y mutation was not associated with CQ (P ‫؍‬ 0.214) or QN (P ‫؍‬ 0.287) responses. The Pfmdr1 184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P ‫؍‬ 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). The Pfmdr1 86Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P ‫؍‬ 0.0136), LMF (P ‫؍‬ 0.0019), and MQ (P ‫؍‬ 0.0001). The additional Pfmdr1 86Y mutation increased significantly the in vitro susceptibility to MDAQ (P < 0.0001), LMF (P < 0.0001), MQ (P < 0.0001), and QN (P ‫؍‬ 0.0026) in wild-type Pfcrt K76 parasites. The additional Pfmdr1 86Y mutation significantly increased the in vitro susceptibility to CQ (P ‫؍‬ 0.0179) in Pfcrt 76T CQ-resistant parasites.

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“…These results are in accordance with previous studies in Kenya (17) and Nigeria (57). However, the 86Y mutation has been associated with a decrease in CQ susceptibility in some works (5).…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Wurtz

Fall

Pascual

et al. 2014

Antimicrob Agents Chemother

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“…Similar K76T pfcrt genotypes were observed in the parasite genomic DNA extracted from filter-paper blood samples and saliva samples. The high prevalence of the mutant pfcrt 76T allele in both saliva (57%) and blood (60%) specimens is consistent with previous reports [20][21][22] from genomic DNA extracted from blood sample.…”

Section: Discussionsupporting

confidence: 91%

“…Nested PCR with RFLP techniques are frequently used to detect polymorphisms in parasite genes that serve as molecular markers of antimalarial drug resistance. [20][21][22] This approach was used in saliva samples to detect K76T polymorphism on the pfcrt gene that is associated with chloroquine resistance. Similar K76T pfcrt genotypes were observed in the parasite genomic DNA extracted from filter-paper blood samples and saliva samples.…”

Section: Discussionmentioning

confidence: 99%

Rapid Detection of Lactate Dehydrogenase and Genotyping of Plasmodium falciparum in Saliva of Children with Acute Uncomplicated Malaria

Gbotosho

Happi²,

Folarin³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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The diagnosis of malaria in biological fluids other than blood using non-invasive, rapid diagnostic techniques provides a valuable approach in case management and epidemiological studies of malaria. Rapid detection of Plasmodium falciparum lactate dehydrogenase (pLDH) in saliva samples from 130 of 144 children with microscopically confirmed P. falciparum infection was evaluated using Optimal-IT dipsticks. Genotyping of parasites was also performed in saliva and blood samples from a cohort of patients by polymerase chain reaction (PCR). The sensitivity of the dipstick in whole-blood, whole-saliva, or supernatant of spun saliva samples was 97.2%, 77.9%, and 48.4%, respectively. The sensitivity of the dipstick in whole-saliva samples was significantly higher than in supernatant of spun saliva samples (P < 0.0005). Mutant T76 allele was detectable in 60% and 57% of blood and saliva samples, respectively. This finding shows rapid detection of pLDH in patient saliva.

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In vitro amodiaquine resistance and its association with mutations in pfcrt and pfmdr1 genes of Plasmodium falciparum isolates from Nigeria

et al. 2011

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Amodiaquine (AQ) is currently being used as a partner drug in combination with artesunate for treatment of uncomplicated malaria in most endemic countries of Africa. In the absence of molecular markers of artemisinin resistance, molecular markers of resistance to AQ may be useful for monitoring the development and spread of parasites resistance to Artesunate-Amodiaquine combination. This study was designed to assess the potential role of polymorphisms on pfcrt and pfmdr1 genes and parasite in vitro susceptibility for epidemiological surveillance of amodiaquine resistance in Plasmodium falciparum. The modified schizont inhibition assay was used to determine in vitro susceptibility profiles of 98 patients' isolates of Plasmodium falciparum to amodiaquine. Polymorphisms on parasites pfcrt and pfmdr1 genes were determined with nested PCR followed by sequencing. The geometric mean (GM) of AQ 50% inhibitory concentration (IC-50) in the 97 P. falciparum isolates was 20.48nM (95% CI 16.53–25.36nM). Based on the cut-off value for AQ in vitro susceptibility, 87% (84) of the P. falciparum isolates were sensitive to AQ (GM IC-50= 16.32nM; 95%CI 13.3–20.04nM) while 13% were resistant to AQ in vitro (GM IC-50= 88.73nM; 95%CI 69.67–113.0nM). Molecular analysis showed presence of mutant CVIET pfcrt haplotype, mutant pfmdr1Tyr86 allele and the double mutant CVIET pfcrt haplotype+pfmdr1Tyr86 in 72%, 49% and 35% respectively. The GM IC-50 of isolates harboring the wild-type pfcrt CVMNK haplotype+ pfmdr1Asn86 allele (3.93nM; 95%CI 1.82–8.46) was significantly lower (p=0.001) than those isolates harboring the double mutant pfcrtCVIET haplotype+pfmdr1Tyr86 allele (50.40nM; 95%CI 40.17–63.24). Results from this study suggest that polymorphisms in pfcrt and pfmdr1 genes are important for AQ resistance and therefore may be useful for epidemiological surveillance of P. falciparum resistance to AQ.

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Chloroquine Resistant Plasmodium falciparum in Nigeria: Relationship between pfcrt and pfmdr1 Polymorphisms, In-Vitro Resistance and Treatment Outcome

Cited by 17 publications

References 46 publications

Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Role of Pfmdr1 in In Vitro Plasmodium falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin

Rapid Detection of Lactate Dehydrogenase and Genotyping of Plasmodium falciparum in Saliva of Children with Acute Uncomplicated Malaria

In vitro amodiaquine resistance and its association with mutations in pfcrt and pfmdr1 genes of Plasmodium falciparum isolates from Nigeria

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