Four artemisinin-based treatments in African pregnant women with malaria

A. A. Pekyi, H. Ampromfi, M. Tinto, M. C. Traor Coulibaly, I. Tahita, V. Val, L. Mwapasa, G. Kalilani-Phiri, M. Kalanda, R. Madanitsa, T. Ravinetto, P Mutabingwa, H. Gbekor, G. Tagbor, J. Antwi, M. Menten, Y. De Crop, C. Claeys, Caroline Schurmans, K. Van OvermeirK Thriemer, U. Van Geertruyden, M. Dalessandro, Michael Nambozi, S. Mulenga, J. B B Hachizovu, J. Kabuya

    Research output: Contribution to journalArticle

    Abstract

    BACKGROUND: Information regarding the safety and efficacy of artemisinin combination treatments for malaria in pregnant women is limited, particularly among women who live in sub-Saharan Africa.

    METHODS: We conducted a multicenter, randomized, open-label trial of treatments for malaria in pregnant women in four African countries. A total of 3428 pregnant women in the second or third trimester who had falciparum malaria (at any parasite density and regardless of symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points were the polymerase-chainreaction (PCR)-adjusted cure rates (i.e., cure of the original infection; new infections during follow-up were not considered to be treatment failures) at day 63 and safety outcomes.

    RESULTS: The PCR-Adjusted cure rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin- piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-Adjusted cure rates in the intention-To-Treat analysis were 94.2%, 96.9%, 98.0%, and 95.5%, respectively. There was no significant difference among the amodiaquine-artesunate group, dihydroartemisinin- piperaquine group, and the mefloquine-artesunate group. The cure rate in the artemether-lumefantrine group was significantly lower than that in the other three groups, although the absolute difference was within the 5-percentage-point margin for equivalence. The unadjusted cure rates, used as a measure of the post-Treatment prophylactic effect, were significantly lower in the artemether-lumefantrine group (52.5%) than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference in the rate of serious adverse events and in birth outcomes was found among the treatment groups. Drug-related adverse events such as asthenia, poor appetite, dizziness, nausea, and vomiting occurred significantly more frequently in the mefloquine-artesunate group (50.6%) and the amodiaquine- artesunate group (48.5%) than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether-lumefantrine group (11.5%) (P<0.001 for comparison among the four groups).

    CONCLUSIONS: Artemether-lumefantrine was associated with the fewest adverse effects and with acceptable cure rates but provided the shortest post-Treatment prophylaxis, whereas dihydroartemisinin- piperaquine had the best efficacy and an acceptable safety profile. (Funded by the European and Developing Countries Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.)

    Original languageEnglish
    Pages (from-to)913-927
    Number of pages15
    JournalNew England Journal of Medicine
    Volume374
    Issue number10
    DOIs
    Publication statusPublished - 10 Mar 2016

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    Pekyi, A. A., Ampromfi, H., Tinto, M., Traor Coulibaly, M. C., Tahita, I., Val, V., Mwapasa, L., Kalilani-Phiri, G., Kalanda, M., Madanitsa, R., Ravinetto, T., Mutabingwa, P., Gbekor, H., Tagbor, G., Antwi, J., Menten, M., De Crop, Y., Claeys, C., Schurmans, C., ... Kabuya, J. (2016). Four artemisinin-based treatments in African pregnant women with malaria. New England Journal of Medicine, 374(10), 913-927. https://doi.org/10.1056/NEJMoa1508606