| dc.description.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, | en_US |
