Abstract
There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north.Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing.The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common.All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015.
Highlights
Malaria is a major public health challenge in sub-Saharan Africa
Point mutations in dhps and dhfr genes were evaluated in 1000 malaria-positive (PCR-confirmed) filter paper blood spots obtained from pregnant women and children in the southern and northern parts of Nigeria between 2003 and 2015
In Enugu (Component A), of the 233 samples evaluated from day0, 7, 14, 21, 28, 42, maternal and placental blood spots, 145 samples were left for dhps and 139 for dhfr analyses after filtering off the duplicates by sample IDs
Summary
Malaria is a major public health challenge in sub-Saharan Africa. In 2015, there was an estimated 214 million cases and 438,000 deaths due to malaria globally with Nigeria accounting for 25% of these (WHO, 2015). WHO recommended IPTp-SP as a strategy for prevention of malaria in pregnancy in 2001 but IPTp-SP was only adopted in 2005 as national policy in Nigeria (WHO, 2000; FMOH, 2005). The implementation of this strategy is being faced with challenges such as timing of SP administration (Onoka et al, 2012), knowledge and practices of the population (Onwujekwe et al, 2012; Diala et al, 2013) and rising levels of parasite resistance to SP in the general population (Happi et al, 2005; Mockenhaupt et al, 2008). SMC has been fully deployed in Katsina and Jigawa states of northern Nigeria
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