Antimalarial drug resistance is a major impediment to malaria chemotherapy in sub-Saharan Africa  largely because Plasmodium falciparum rapidly develops resistance to drugs . Resistance to antimalarial drugs occurs through drug-selection of spontaneous mutations in P. falciparum that confer tolerance to the drug . The selection and spread of drug resistant P. falciparum is facilitated by the rapid genome replication rate and by a relatively high mutation rate per generation of the parasite [4, 5]. The speed of selection of mutants within parasite populations depends upon the pharmacokinetics of the drug itself and its degree of usage within a given host population . For many antimalarial drugs, molecular markers of parasite resistance are known. Surveillance of these markers in parasite populations can act as a proxy measure of the efficacy of drugs within that population, and can act as early warning signals of the emergence of resistance into new regions. Frequent and thorough molecular surveys of the prevalence of mutations associated with drug resistance can, therefore, inform regional drug policies.
Single nucleotide polymorphisms (SNPs) in the P. falciparum multidrug resistance gene (pfmdr1) have been shown to modulate the susceptibility of the parasite to the long acting partner drug in ACTs  but are not associated with resistance to Artemisinin based Combination Therapies (ACTs). Artemether-lumefantrine (AL) and Artesunate-amodiaquine (AS-AQ) are two ACTs commonly used in sub-Saharan Africa to treat uncomplicated malaria, but until now, there is no clear evidence of treatment failure from their use in the region. However, some genetic studies involving pfmdr1 have suggested opposing selective pressures following separate use of the drugs, in which parasites harboring N86, 184F, D1246 pfmdr1 genotypes predominate in African countries that recommend AL as first line antimalarial drug whilst those carrying 86Y, Y184 and 1246Y pfmdr1 genotypes predominated in African countries that use AS-AQ as frontline antimalarial therapy .
African P. falciparum isolates may carry the resistant allele of pfcrt encoding the amino acids CVIET at codons 72–76 as well as a variety of polymorphic pfmdr1 alleles which have originated and spread within the African continent [8, 9, 10]. The pfmdr1 gene is a structural homologue of the mammalian multidrug resistance gene encoding a P-glycoprotein homologue-1 (Pgh1) multi-drug resistant transporter  and is expressed into a PfMDR1 transporter located in the P. falciparum food vacuole.
Mutations in PfMDR1 are associated with reduced influx of diverse antimalarial drugs reducing their intracellular accumulation [12, 13]. Single nucleotide polymorphisms (SNPs) in pfmdr1 are associated with resistance to aminoquinolines [14, 15]. Several codons in pfmdr1 have been putatively linked with changes in the parasite’s susceptibility to antimalarial drugs, but codons N86Y, Y184F and D1246Y are uniquely associated with changes in sensitivity to lumefantrine (LUM) and amodiaquine (AQ) in sub-Saharan Africa . While the pfmdr1 86Y allele was strongly associated with chloroquine (CQ) and amodiaquine (AQ) resistance [17, 18], 1246Y alleles were shown to confer resistance to quinine (QN) and possess the capacity to increase the parasite susceptibility to mefloquine (MQ), halofantrine (HF) and artemisinin (ART) [19, 20]. In the study of Reed et al. , the sensitivity of CQS D10 parasites to CQ was not affected by transfection of the parasites with pfmdr1 D1246Y mutation, but reduced by half, due to replacement of the mutation with a wild-type D10 pfmdr1 sequence on a different genetic background of the parasite (CQR 7G8).
The mutant pfmdr1 86Y and 1246Y alleles have also been linked to reduced sensitivity to AQ, whereas the wild-type pfmdr1 N86 and D1246 alleles are linked to reduced susceptibility against LUM [22, 23]. In Africa, the common use of AL and AS-AQ in the treatment of uncomplicated malaria has been linked with the emergence of pfmdr1 N86Y, Y184F and D1246Y SNPs , and the prevalence of these mutations are frequently used for evaluating changes in sensitivity to LUM and AQ partners in ACTs . Several studies have shown that parasites carrying a combination of pfmdr1 N86, 184F, and D1246 (the “NFD” haplotype) display decreased susceptibility to AL and that treatment with AL can select for such a haplotype [25, 26].
Nigeria accounts for 25% of global cases of malaria and an estimated 50% of the country’s population suffer at least one episode of malaria every year while under-five children experience an average of 2 – 4 attacks in a year . P. falciparum is stably and perennially transmitted in all parts of the country , with transmission increased during the wet season compared to the dry [29, 30]. North-West and North–East Nigeria have so far been identified as hotspots of malaria in relation to the southern parts of the country due primarily to climatic and environmental conditions . The North-West region of the country suffers a much higher P. falciparum transmission rate than the other regions including North-East Nigeria .
The frontline drug for malaria chemotherapy in the country was chloroquine until 2005 when it was withdrawn as a result of resistance . Subsequently, the artemether-lumefantrine was recommended as the only first-line drug for the treatment of uncomplicated malaria in the regions. Unfortunately, several reports investigating molecular markers of antimalarial resistance have suggested a massive reduction of parasite susceptibility to LUM component of AL [19, 24, 34-35]. In Uganda, Dokomajilar et al.  showed a high prevalence of pfmdr1 N86, 184F, and D1246 alleles after treatment with AL, where the pattern persists even in patients that presented with clinical failure. Few years after, Mbogo et al.  genotyped 982 archived samples collected during 2003 - 2012 for pfmdr1 polymorphisms and reported a dramatic reduction in pfmdr1 86Y and 1246Y alleles over time. Similarly, the relationship between presence of mutations involving pfmdr1 86, 184 and 1246 codons and success of ultralow-dose mefloquine treatment was investigated in Gabon, where Mawili-Mboumba et al.  observed a low prevalence of pfmdr1 N86 allele but the prevalence of 184F and D1246 alleles was above 80% each. In Tanzania, Humphreys et al.  observed a high prevalence of pfmdr1 86Y, Y184 and 1246Y in patients who failed treatment with AQ, but observed the opposite in those who failed AL treatment. The prevalence of pfmdr1 polymorphisms in Nigeria was majorly reported from the Southern region, where a positive association between pfmdr1 N86, F184 and D1246 alleles and clinical failure was observed . In contrast, a prevalence of 62.2% and 69.0% for pfmdr1 86Y and F184 allele, respectively, was also reported from the region  which was recently followed by another survey where the pfmdr1 86Y and 1246Y alleles had prevalence of 24% and 18.6%, respectively .Yet, there is no valid baseline data involving pfmdr1 SNPs in both North-West and North–East Nigeria since the withdrawal of CQ and adoption of AL in Northern Nigeria. In this study, the distributions of the pfmdr1 N86Y, Y184F and D1246Y SNPs across the North-West and-East Nigeria were investigated.