title: Burden of malaria in pregnancy in Mali and impact of dosing frequency and antimalarial drug resistance on the effectiveness of intermittent preventive therapy in pregnancy in Africa
Creators: name: Kayentao, Kassoum
Publisher: name: University of Liverpool Repository
Year: 2014

description: For many centuries, malaria has remained the most common parasitic disease in sub-Saharan Africa potentially placing 32 million pregnancies at risk each year. Malaria in pregnancy (MiP) in malaria endemic Africa is mostly asymptomatic or paucisymptomatic, yet associated with maternal anaemia and intra-uterine growth retardation resulting in low birth weight (LBW) which is an important risk factor for infant mortality (chapter 1). In Mali, several observational studies have determined the risk and consequences of malaria in pregnancy. However, national estimates of the burden of MiP and its potential impact are lacking. This thesis describes the results of a series of surveys conducted in different malaria transmission settings countrywide from 2005 to 2010, to quantify the burden and consequences of MiP in Mali (chapter 2). Results demonstrate that the risk of malaria infection at delivery was generally high ([average prevalence 11.6%]) and showed marked diversity between regions and transmission settings. Coverage of intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) and impregnated treated bednets (ITNs) was low (30.4% and 60.7%) and indicated important miss opportunities for the control of PAM. To prevent the disease and its consequences in pregnancy, the World Health Organization recommends IPTp using SP and use of an ITN. For IPTp, the recommended regimen consists of at least 2 doses of SP given during the second and third trimesters for HIV negative women and at least 3 doses for HIV-positive women not receiving cotrimoxazole. However, there are concerns that the 2-dose regimen, which provides at most 12 weeks of prophylaxis, leaves many women unprotected for as much as half of the 20-26 pregnancy weeks after quickening. Re-infection with the 2-dose regimen is common, especially during the transmission seasons and amongst women who complete their last dose early in the third trimester. A trial was therefore conducted to compare the standard 2-dose regimen versus 3 doses using SP, hypothesizing that the third dose may add significant benefit over the 2-dose regimen in preventing placental malaria and other birth outcomes (chapter 3). The study concluded that IPTp-SP with 3-doses was superior to the standard 2-dose regimen and resulted in better birth outcomes. The results of this trial were then combined with 6 similar trials as part of a meta-analysis assessing if 3 or more doses of IPTp-SP are more effective than the current standard 2-dose regimen. The pooled results suggested a marked benefit of adding extra SP doses over the standard 2-dose regimen in both regions of high and low SP resistance as measured by the prevalence of dihydropteroate synthase K540E mutations (chapter 4). Although studies from western Africa favour the use of IPTp-SP, SP resistance is now a serious threat to the longevity of IPTp with SP in parts of eastern and southern Africa where the quintuple dihydofolate reductase (N51I, C59L, S108N) /dhps (A437G, K540E) mutation is saturated in many places. In order to get a better understanding of the impact of SP resistance on IPTp effectiveness, this thesis also determined the in vivo response of parasites in asymptomatic parasitaemic pregnant women who received IPTp-SP and the effectiveness of IPTp-SP on birth parameters in West-Africa (chapter 5 &amp; 6) Overall, the study concluded that SP resistance in Mali and Burkina Faso is low and that the IPT-SP is associated with clinically relevant improvements in birth outcomes in Mali.