Assessment of Markers of Antimalarial Drug Resistance in Plasmodium falciparum Isolates from Pregnant Women in Lagos, Nigeria.

BACKGROUND: The use of antimalarial drugs for prevention and treatment is a major strategy in the prevention of malaria in pregnancy. Although sulphadoxine-pyrimethamine (SP) is currently recommended for intermittent preventive treatment of malaria during pregnancy in Nigeria, previously used drugs for prophylaxis such as chloroquine (CQ) and pyrimethamine are accessible as they are purchased over the counter. This study describes the markers of absence or presence of resistance to quinoline (Pfcrt and Pfmdr 1) and type 1 antifolate antimalarial medicines (Pfdhfr). METHODS: Plasmodium falciparum-positive dried blood spots from pregnant women attending antenatal clinics for the first time during current pregnancy were investigated for the presence of mutations at codons 72-76 of Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene by real time polymerase chain reaction (PCR) using haplotype-specific probes. PCR followed by sequence analysis was used to identify mutations at codons 86, 184, 1034, 1042 and 1246 of P. falciparum multi-drug resistance-1 (Pfmdr1) gene; and codons 16, 50, 51, 59, 108, 140 and 164 of Pfdhfr gene. RESULTS: Two haplotypes of Pfcrt (n = 54) were observed: CVMNK 13(24.2%) and CVIET 41 (75.9%) of the samples. The SVMNT haplotype was absent in this population. The Pfmdr1 (n = 28) haplotypes were NYSND 15(53.6%), YYSND 5(17.9%), NFSND 6(21.4%) and YFSND 2(7.1%). The Pfdhfr (n = 15) were ACNCSVI 4(26.7%), and ACICNSVI 1(6.7%) and ACIRNVI 10 (66.7%). The rate of occurrence of Pfcrt 76T, Pfdhfr108N, Pfmdr186Y and 184F were 75.9%, 73.3%, 25% and 28.1% respectively. The Pfmdr1 86Y was associated with low parasitaemia (median = 71 parasites/µl, P = 0.024) while Pfcrt 76T was associated with young maternal age (mean 24.1 ± 4.5 years; P = 0.006). The median parasitaemia were similar (P>0.05) in wild and mutant strains of Pfcrt 76, Pfmdr1 184 and Pfdhfr 108. There was no association between gravidity or gestational age of the women and presence of mutations in the Pfcrt, Pfmdr1 or Pfdhfr genes (P>0.05). CONCLUSION: Markers of resistance to chloroquine and pyrimethamine were high, whereas cycloguanil-resistance marker was not present in the studied population. The low level of mutations in the Pfmdr1gene indicates likely efficacy of amodiaquine against malaria in pregnancy.

Scaling up of intermittent preventive treatment of malaria in pregnancy using sulphadoxine-pyrimethamine: prospects and challenges.

Intermittent preventive treatment of malaria during pregnancy with sulphadoxine-pyrimethamine (IPTpSP) is one of the major strategies of malaria control in most African countries where malaria is endemic. The use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy was adopted when proof of its superiority to weekly prophylactic dosing with either chloroquine or pyrimethamine became evident from studies in different malaria endemic countries. The administration of 2 and 3 treatment doses of SP for HIV-negative and HIV-positive pregnant women respectively, given after quickening and at an interval not less than 4 weeks was recommended. The prospects of this control strategy lies on the efficacy of SP, convenient treatment dose and high compliance rate. However, the implementation of this strategy and the efficacy of SP are faced with challenges such as: timing of SP administration, rising levels of parasite resistance to SP in the general population, effect of folate supplementation, adequacy of the recommended doses with regards to malaria endemicity and HIV status, interactions between SP and antiretroviral drugs and low coverage in the bid to scale-up its use. This review highlights the prospects and challenges of scaling up IPTp-SP.