Molecular determinants of sulfadoxine-pyrimethamine resistance in
Plasmodium falciparum in Nigeria and the regional emergence of dhps
Mary C. Oguike
Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United
Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria
Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Enugu Campus, Enugu, Nigeria
Department of Child Health, University of Benin Teaching Hospital, Benin City, Nigeria
Department of Paediatrics, Specialist Hospital Maiduguri, Borno State, Nigeria
Malaria Consortium, Regional Ofﬁce for Africa, Kampala, Uganda
Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
Malaria Consortium, London, United Kingdom
Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United
Received 12 March 2016
Accepted 12 August 2016
Available online 29 September 2016
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 conse-
quently 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 un-
complicated 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 N igeria 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 þ 436A þ 437Gþ581Gþ613S 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
-strand. Con sequently, 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
© 2016 The Authors. Published by Elsevie r Ltd on behalf of Australian Society for Parasitology. This is an
open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
* Corresponding author. Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
E-mail address: firstname.lastname@example.org (M.C. Oguike).
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International Journal for Parasitology:
Drugs and Drug Resistance
journal homepage: www.elsevier.com/locate/ijpddr
2211-3207/© 2016 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY license (http://
International Journal for Parasitology: Drugs and Drug Resistance 6 (2016) 220e229