Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy.For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371.We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49–1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47–1·17), stillbirth (aHR=0·71, 0·32–1·57), and major congenital anomalies (aHR=0·60, 0·13–2·87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36–0·92).We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Background Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability.Methods In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662.Results Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5% vs 3 . 0%, p=0 . 1). Two versus 13 (0 . 03% vs 0 . 22%, p=0 . 0020) were permanently disabled; total dead or disabled: 156 versus 190 (2 . 6% vs 3.2%, p=0 . 0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% Cl 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesurate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0 . 0013).Interpretation If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability.Funding UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Poundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).

Emergency contraception (EC) refers to methods that women can use to prevent pregnancy after unprotected sexual intercourse, method failure, or incorrect use. There is growing worldwide acceptance and promotion of EC as a measure to reduce the level of unwanted pregnancies and, hence, unsafe abortions. The potential effect of EC in this regard could be most evident in sub-Saharan Africa. In Ghana, the Ministry of Health has since 1996 included EC in its reproductive health service policy and standards. The Planned Parenthood Association of Ghana is the only agency involved in the promotion of EC in the country. Very little is known about societal perception of EC. We undertook a study to assess knowledge and attitude toward EC among a sample of students at the University of Ghana. We used a two-page, self-administered questionnaire in a cross-sectional study among students chosen by random sampling. The aspects of EC assessed included level of knowledge, extent of use, common traditional methods of emergency contraception, as well as socially and culturally acceptable ways to promote EC in Ghana. We also assessed how the availability of EC could influence the use of condoms among male respondents. Less than half (43.2%) of the 194 respondents (88 males and 106 females) had heard of modern emergency contraceptive methods. Postinor-2, a dedicated emergency contraceptive product, which was already on the Ghanaian market, was known to 1.5% of respondents. Only 11.3% of respondents indicated correctly the recommended time within which emergency contraceptive pills (ECPs) are to be taken after unprotected sex. Taking concentrated sugar solutions, having an enema, and douching were commonly used traditional methods of EC. More than half (55.0%) of the male respondents indicated that they would either "certainly" or "probably" reduce how often they used condoms once they knew that EC was available. Almost all (97.4%) the respondents wanted to learn more about EC. The indications from this study are that the promotion of EC in Ghana is desired and must be encouraged. The fact that EC does not offer protection against sexually transmitted infections should always be emphasized.