Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine

Abstract

BackgroundIn Nigeria, despite the change in National malaria drug policy to artemisinin combination therapy (ACT) in 2005 due to widespread chloroquine resistance, chloroquine (CQ) is still widely used in the treatment of malaria because it is cheap, affordable and accessible. The use of ACT for the management of uncomplicated malaria is currently being promoted. The employment of genetic markers to track circulating chloroquine-resistant parasites are useful in elucidating likely poor efficacy of chloroquine, especially in settings where it is not recommended for the treatment of uncomplicated falciparum malaria. This study determined the prevalence of pfcrt haplotypes and point mutations in pfmdr1 genes four years after the change in antimalarial treatment policy from CQ to the ACTs in Lagos, a commercial city in South-West, Nigeria.MethodsThis was a cross sectional study on uncomplicated malaria in children less than 12 years that presented with fever and other symptoms suggestive of malaria. Parasite DNA was extracted from 119 patients out of 251 children who were positive for Plasmodium falciparum by microscopy and amplified. The occurrence of haplotypes was investigated in pfcrt gene using probe-based qPCR and single nucleotide polymorphisms in pfmdr1 gene using nested PCR.ResultsOne hundred and nine (109) of the 119 children with P falciparum infection (91.6%) harbourd parasites with the mutant pfcrt haplotype (CVIET). Out of this, 4.2% comprised a mixture of genotypes encoding CVMNK and CVIET, while 4.2% had the wild type (CVMNK). Furthermore, the frequency of point mutations in pfmdr1 was 62.2% and 69.0% for codons Y86 and F184 respectively. There were no mutations at codons 1034, 1042 and 1246 of the Pfmdr1 genes.ConclusionThe high frequency of the CQ-resistant haplotypes (CVIET) and mutations in Pfmdr1 associated with CQ resistance in P. falciparum among these children suggest that CQ-resistant parasites are still in circulation. Continuous use of chloroquine may continue to increase the level of mutations in pfcrt and pfmdr1genes. There is need to strengthen current case management efforts at promoting ACT use as well as urgently restricting access to chloroquine by the National drug regulatory agency, National Agency for Food Drug Administration and Control (NAFDAC).Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2069472010142303

Is Nigeria winning the battle against malaria? Prevalence, risk factors and KAP assessment among Hausa communities in Kano State

“…This behaviour did not different with malaria fever, wherein people began treatment with analgesics and then anti-malarial drugs if symptoms persisted. The same behaviour has been reported elsewhere in Nigeria [ 85 , 93 – 95 ], and from other parts of Africa [ 96 , 97 ]. Intriguingly, a previous study in Oyo state, Southwest Nigeria, showed that approximately 90 % of suspected malaria cases were self-treated first at home with traditional herbs or drugs purchased from medicine stores [ 85 ].…”

“…Similarly, the choice of going to hospital on time depends on the level of education, as non-educated respondents are more likely to patronize unauthorized practitioners or buy medication from street vendors. This practice, combined with the poor quality of anti-malarial drugs in Africa, has led to the emergence and wide distribution of chloroquine-resistant malaria among the population [ 95 , 99 ]. Therefore, policymakers should recognize that proper training of medical and paramedical personnel in malaria treatment and management must include those “shop operators,” as they are associated most closely with the population, and attitudes about the efficacy of treatment with their remedies cannot be altered immediately.…”

Plasmodium Falciparum Multidrug Resistance Gene-1 N86Y-Y184F-D1246Y Polymorphisms in Northern Nigeria: Implications for the Continued Use of Artemether-Lumefantrine in the Region

“…The pfmdr1 D1246Y mutation affects P. falciparum susceptibility to various antimalarials including QN, MFQ, (HF), CQ and ART, with the latter two drugs affected in a strain speci c manner [14,42]. The observed low prevalence of mutant pfmdr1 1246Y alleles compared to the wild type in this study is consistent with reports from Southern Nigeria [38] as well as other West and East African countries that adopted AL as a front-line antimalarial therapy for uncomplicated malaria [1,36]. Countries in Central Africa have observed an unsteady increase in the prevalence of the pfmdr1 D1246 allele, possibly due to the selective pressure of AS-AQ [2,6].…”

Return of chloroquine sensitivity to Africa? Surveillance of African Plasmodium falciparum chloroquine resistance through malaria imported to China

“…On the whole, the frequency of the CQ-resistant pfcrt 76T has decreased through time, although CQ sensitivity recovery trends show regional variability. Table 3 summarizes the changes in the prevalence of pfcrt 76T–carrying isolates after cessation of CQ use in five African countries, including Angola [ 28 , 29 ], Congo [ 29 – 31 ], Equatorial Guinea [ 29 , 32 – 34 ], Ghana [ 29 , 35 – 37 ] and Nigeria [ 29 , 38 , 39 ] (countries contributing ≥20 isolates in the present study). The prevalence of pfcrt 76T–carrying isolates generally reduces through time, except in Equatorial Guinea, which shows large variation within a similar period [ 29 , 32 ].…”