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Treatment and prevention of malaria
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
David A Warrell, William M Watkins, Peter A Winstanley
Sulfadoxine-pyrimethamine plus artesunate This is an important concept for Africa, where sulfadoxine-pyrimethamine is beginning to fail in areas of chloroquine-resistant falciparum malaria. It is hoped that sulfadoxine-pyrimethamine ACT will reduce the rate of emergence of sulfadoxine-pyrimethamine resistance, and so prolong the useful therapeutic life of sulfadoxine-pyrimethamine, which is currently the last of the available, affordable treatments for uncomplicated malaria in this continent.
Sulfonamides
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Natasha E. Holmes, M. Lindsay Grayson
A systematic review concluded that a two-dose regimen of IPTp with sulfadoxine–pyrimethamine continues to provide benefit (with reduction of placental malaria, low birth weight, and anemia) to semi-immune, HIV-negative pregnant women in their first or second pregnancy (Kalanda et al., 2006; Ter Kuile et al., 2007). This benefit occurred even in areas where sulfadoxine–pyrimethamine resistance is well established (Tan et al., 2014) and fails to cure one in four malaria infections in symptomatic children by day 14. Rates of the triple DHFR mutation were low in Burkina Faso, indicating that Fansidar is still an efficacious therapy for IPTp there (Tahita et al., 2015). However, even 6 years after the withdrawal of Fansidar for first-line therapy of malaria in Tanzania, resistance mutations to Fansidar remain highly prevalent and could undermine the potential success of IPTp in improving pregnancy outcomes (Baraka et al., 2015; Lucchi et al., 2015). In a large multinational study in sub-Saharan African HIV-negative women, IPTp failure rates ranged from 21% in high-resistance areas to 1.1% in low-resistance areas; despite this resistance, increased maternal hemoglobin and increased infant birth weight were still observed (Desai et al., 2016). In a meta-analysis of randomized and quasirandomized trials, Fansidar did not reduce the incidence of low birth weight in regions where the DHPS 540E mutation frequency exceeded 50% (Muanda et al., 2015). A recent large three-group randomized controlled trial conducted in Kenya, where Fansidar resistance is prevalent, compared intermittent screening and treatment in pregnancy (ISTp) with dihydroartemisinin–piperaquine, IPTp with dihydroartemisinin–piperaquine, or IPTp with Fansidar (Desai et al., 2015). ISTp rather than either IPTp strategy was associated with higher incidence of malaria infection and clinical malaria, although use of dihydroartemisinin–piperaquine was associated with lower rates of malaria infection at delivery compared with Fansidar. However, in areas where sulfadoxine–pyrimethamine resistance is low, such as Gambia, Mali, Burkina Faso, and Ghana, ISTp was noninferior to IPTp to Fansidar in a different randomized trial (Tagbor et al., 2015).
Infection-related stillbirth: an update on current knowledge and strategies for prevention
Published in Expert Review of Anti-infective Therapy, 2021
Samia Aleem, Zulfiqar A. Bhutta
IPT with sulfadoxine-pyrimethamine (SP) during pregnancy is recommended year-round with a 3 dose regimen in areas that are malaria endemic, starting in the second trimester [14]. This recommendation is based on a systematic review and meta-analysis of trials that compared regimens containing three or more doses for IPT, versus the previous standard of two doses [15]. Seven trials comprising 6281 pregnancies in sub-Saharan Africa were included in the study, which found that IPT with 3 or more doses of SP was associated with a higher birth weight and a lower risk of low birth weight compared to 2 doses [15]. This study however did not assess the effect on rates of stillbirth. A Cochrane review from 2014 which included 17 chemoprevention trials, enrolling 20,256 pregnant women found that malaria chemoprevention reduced the risk of antenatal parasitemia by nearly 61%, and reduced low birthweight by nearly 27% [16]. Notably, no effect was seen on perinatal mortality, spontaneous abortions, or stillbirths; these analyses, however, were underpowered to detect clinically significant differences [16].
Pharmacotherapy for the prevention of malaria in pregnant women: currently available drugs and challenges
Published in Expert Opinion on Pharmacotherapy, 2018
Brioni R. Moore, Timothy M. E. Davis
Both sulfadoxine and pyrimethamine are well absorbed and reach peak plasma concentrations approximately 4 h after administration (range 2–6 h) [67]. Both drugs are highly (>87%) protein bound, resulting in prolonged clearance with a mean elimination t1/2 of 169 h and 111 h for sulfadoxine and pyrimethamine, respectively [67]. However, there has been significant differences in pharmacokinetic parameters between studies in pregnancy [20,68–70]. A recent pharmacokinetic study of IPTp-SP concluded that pregnancy resulted in a three-fold increased clearance of sulfadoxine but an 18% decrease in the clearance of, and thus greater exposure to, pyrimethamine [68,70]. The unexpected sulfadoxine result was in the context of studies showing increased (Mali, Mozambique, Zambia [69]), similar (Sudan, Kenya [69,71];) or reduced (PNG, Uganda [19,70,72];) exposure. However, the studies showing reduced clearance in pregnancy utilized lactating women as controls. The expression of CYP enzymes can be upregulated during breastfeeding and so pyrimethamine clearance may be relatively high with the result that pregnancy may be wrongly interpreted as showing a reduced clearance [73].
Protective effects of some Nigerian indigenous antimalarial plants on placental malaria related pathological damages and pregnancy outcomes in murine model
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Ayodele S. Babalola, Olufunmilayo A. Idowu, Kehinde O. Ademolu, J. Olukunle, A. Rahman Samson
A total of 110 mice (each weighing between 23.0 g and 23.2 g) were randomly divided into 22 groups of 5 pregnant mice each. Eleven out of the pregnant groups were infected at low inoculum at gestation day (GD) 6. Treatment started at GD 9 and lasted for 6 days; nine (9) groups were given plant extracts. A group was treated with Sulphadoxine-pyrimethamine (Positive control) while a group was not treated (Negative control). Remaining non-infected groups were subjected to the same treatment (Table 1). On GD 18, three out of five mice in each group euthanized by cervical dislocation. The placenta(s) were harvested for histopathological studies. The remaining animals were allowed to litter for studies on pregnancy outcome.