Evaluation of Plasmodium Falciparum Resistance to Sulfadoxine- Pyrimethamine in Human Immunodeficiency Virus(HIV) Infected and Non-Infected Pregnant Women in A Malaria-Endemic Region of Western Kenya

Abstract

Malaria and Human immunodeficiency virus (HIV) co-infection in pregnancy is a major cause of anaemia, low birth weight (LBW) abortion and infant mortality in malaria-endemic countries of sub-Saharan Africa. Intermittent preventive therapy (IPTp) with Sulfadoxinepyrimethamine (SP) is recommended by the World Health Organization ((WHO) for malaria control during pregnancy. However, widespread resistance of Plasmodium falciparum to SP is a threat to the IPTp strategy. Therefore, there is an urgent need to evaluate the extent of parasite resistance to SP, specifically in pregnant women. The overall objective of this study was to evaluate P. falciparum resistance to SP in HIV -infected and non-infected pregnant women using real-time PCR. Samples used in this study were obtained from 94 women enrolled in a retrospective study conducted in Siaya and Bondo district hospitals in western Kenya, to investigate the effectiveness of daily cotrimoxazole (CTX) in preventing malaria during pregnancy. The enrolled women were categorized into four treatment arms on the basis of the drug used during pregnancy: SP, cotrimoxazole (CTX), SP and CTX and neither SP nor CTX. After delivery, peripheral and placental blood was collected and thick and thin smears made and stained with 10% Giemsa stain for P. Jalciparum detection using a light microscope. Unigold" and Determine" rapid tests were used for HIV testing. Parasite-positive peripheral and placental dried blood spots, obtained at delivery, were analyzed for the presence of specific mutations in the P. Jalciparum dihydrofolate reductase (Pf/dhfr) and dihydropteorate synthase (Pjldhps) genes associated with SP resistance using real-time PCR. Prevalence and profiles of . Pf/dhfr and Pjldhps mutations were compared using the chi-square test cl, PSO.050). Overall, there was high prevalence (>50%) of Pjldhfr and Pjldhps mutant codons (Pjldhfrl08N, 511, 59R, and Pjldhps 437G, 540E) in both peripheral and placental samples in all treatment arms. There was no significant difference in the profiles of Pjldhfr (SP, P=0.934; CTX, P=O.l89; SP and CTX, P=0.407; neither SP nor CTX, P=0.477) and Pf/dhps (SP, P=0.655; CTX, P=0.705; SP and CT., P=0.513; neither SP nor CTX, P=0.646) mutant codons between peripheral and placental samples. The prevalence of the quintuple mutant (Pjldhfr Asn-l08/1le-511Arg- 591Pjldhps Gly-437/Glu-540) associated with in vivo SP treatment failure was high in all the treatment arms (>50%) and was comparable in both peripheral and placental samples in the different arms (SP, P=0.350; CTX, P=0.083; SP and CTX, P=l.OOO; neither SP nor CTX, P=0.362). However, in HIV -positive women in the CTX treatment arm, the prevalence of the quintuple mutant was significantly higher in placental samples (90.9%) than in peripheral samples (50%) (P=0.033). This study revealed that there is very high prevalence of PjldhJr and Pjldhps resistance markers. Therefore, there is need for in vivo trials to evaluate SP efficacy in pregnant women in western Kenya. In addition, these findings can inform the design of field surveillance and monitoring of SP resistance in pregnant women resident in malaria-endemic regions,