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01.12.2012 | Review | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy

Malaria Journal > Ausgabe 1/2012
Christine Manyando, Kassoum Kayentao, Umberto D’Alessandro, Henrietta U Okafor, Elizabeth Juma, Kamal Hamed
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-141) contains supplementary material, which is available to authorized users.

Competing interests

CM, KK, HUO and EJ have no competing interests. UDA has received research funding from Sigma Tau and Sanofi-Aventis. He has also received travel grants from Sigma Tau and Novartis. KH is an employee of Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.

Authors’ contributions

All authors met International Committee of Medical Journal Editors criteria for authorship. All authors contributed to the development of the outline, revised the manuscript critically, and read and approved the final manuscript.


Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL) in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the WHO recommendation to treat uncomplicated falciparum malaria with quinine plus clindamycin in early pregnancy and ACT in later pregnancy.
Additional file 1: Ovid search strategy. Ovid was used to search the EMBASE, MEDLINE, BIOSIS (included In-Process and Other Non-indexed Citations, Daily Update) and Cochrane (included Cochrane Database of Systematic Reviews, APC Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessment, NHS Economic Evaluation Database) databases between 1948 and 2011. Six queries were performed using the search terms shown. *Search for the term shown with or without any number of additional letters; ?Search for the term shown with or without one additional letter. (DOC 40 KB)
Additional file 2: Results of literature search: Number of references identified for each query and database. EMBASE, MEDLINE, BIOSIS and Cochrane were searched on 16 December, 2011. Malaria in Pregnancy consortium library, and WHO ICTRP were searched on 8 December, 2011 and TrialTrove was searched on 14 December, 2011. ICTRP, International Clinical Trials Registry Platform. (DOC 37 KB)
Additional file 3: 400 unique references recovered in the literature search. (DOC 386 KB)
Additional file 4: Publications reporting on the safety, efficacy and pharmacokinetics of artemether and artemether-lumefantrine in pregnancy, including the number of exposures during pregnancy. Sixteen articles were identified by the literature search, all reporting on pregnancies exposed to artemether or artemether-lumefantrine. The number of pregnancies exposed to artemether or artemether-lumefantrine are reported, and it is noted where exposures have been previously reported. AL, artemether-lumefantrine; AE, adverse events; SAE, serious adverse events; SP, sulphadoxine-pyrimethamine; ACT, artemisinin-based combination therapies; National treatment policy is quinine throughout pregnancy [ 5557]; National treatment policy is quinine in the first trimester and ACT in the second and third trimesters of pregnancy [ 55, 58, 59]; §National treatment policy is quinine in the first trimester and SP in the second and third trimesters of pregnancy; Benin, Burkina Faso, Cameroon, DRC, Gabon, Mozambique, Mali, Thailand, Ghana, Kenya, Malawi, Nigeria, Sudan, Tanzania, Uganda, Zambia, §[ 26, 55, 5759]; #McGready et al., 2001 [ 17] includes all of the artemether exposures reported across three publications. To avoid duplication of pregnancy exposures the other two reports have not been included [ 18, 19]; Included women with a pregnancy in the last 12 months that lasted until at least the third trimester. Current pregnancies were excluded; ††Mali, Mozambique, Thailand, Kenya, Nigeria, Sudan, Tanzania, Zambia §[ 26, 55, 57, 59]; ‡‡National treatment policy is quinine/AL [ 60]. Wang, 1989 [ 20], Sowunmi et al., 1998 [ 15], McGready et al., 2001 [ 17], Adam et al., 2004 [ 16], McGready et al., 2006 [ 21], Dellicour et al., 2007 [ 14], McGready et al., 2008 [ 22], Kaye et al., 2008 [ 23], Orton et al., 2008 [ 61], Adam et al., 2009 [ 24], Tarning et al., 2009 [ 37], Piola et al., 2010 [ 25], Manyando et al., 2010 [ 26], McGready et al., 2011 [ 29], Sangaré et al., 2011 [ 27], Wilby and Ensom, 2011 [ 30]. (DOC 58 KB)
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