Treatment Africa

Safe and efficacious artemisinin-based combination treatments for African pregnant women with malaria

Project Coordinator:          Umberto D'Alessandro

European Partners:            

Feiko ter Kuile and Jenny Hill (UK), Raffaella Ravinetto, Jean Pierre Van geertruyden, Joris Menten (Belgium), Henk Schallig and Peter De Vries (The Netherlands), Vera Ecser (Austria)

Site PIs:

Halidou Tinto (Burkina Faso); Harry Tagbor (Ghana); Linda Kalilani (Malawi); Modest Mulenga (Zambia), Steven Rulisa (Rwanda), TK Mutabingwa (Tanzania)


Objective:

The project aims were to identify two treatment regimens that are at least 95% effective as first-line treatment of uncomplicated malaria in second and third trimester pregnancy, and one regimen for the second line (rescue) treatment.

Method

Designed as a non-inferiority, multi-centre, randomized, open label trial it was conducted in four sites across Africa (Burkina Faso, Ghana, Malawi and Zambia) and comparing the fixed dose combinations of artemether-lumefantrine (AL); amodiaquine-artesunate (AQ-AS); mefloquine–artesunate (MQ-AS) and dihydroartemisinin-piperaquine (DQ-PPQ). Pregnant women attending the antenatal clinic at 16 weeks of gestation or above will be screened for P. falciparum malaria infection and, following informed consent, were randomised to one of the above treatments.

Each pregnant woman were actively followed for 63 days post treatment and then monthly until delivery. The newborn was examined for congenital abnormalities. Both the mother and the newborn were reassessed between four and six weeks after delivery for any adverse event. Blood samples for population pharmacokinetics were collected at established times, allowing the analysis of the relationship between drugs levels and response to treatment.

Overall 3428 women were enrolled across the sites.

Results

The PCR adjusted cure rates for all four drugs were high. There was no significant difference in serious adverse events and birth outcomes found between treatment arms. Based on safety and efficacy DHP seems the most suitable treatment for uncomplicated malaria in pregnancy.

 

Publications

PREGACT Study Group, D.Pekyi, A.A. Ampromfi, H. Tinto, M.Traoré-Coulibaly, M.C. Tahita, I. Valéa, 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. Van Overmeir, K. Thriemer, J.-P. Van Geertruyden, U. D’Alessandro, M. Nambozi, M. Mulenga, S. Hachizovu, J.-B.B. Kabuya, and J. Mulenga.  Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. N Engl J Med 2016;374:913-27. DOI: 10.1056/NEJMoa1508606 

Nambozi M, Mulenga M, Halidou T, et al.  Safe and efficacious artemisinin-based combination treatments for African pregnant women with malaria: a multicentre randomized control trial. Reproductive Health.2015, 12:5 DOI: 10.1186/1742-4755-12-5.

Tahita MC, Tinto H, Yarga S, Kazienga A, Traore Coulibaly M, Valea I, Van Overmeir C, Rosanas-Urgell A, Ouedraogo JB, Guiguemde RT, van Geertruyden JP, Erhart A, D'Alessandro U.  Ex vivo anti-malarial drug susceptibility of Plasmodium falciparum isolates from pregnant women in an area of highly seasonal transmission in Burkina Faso. Malar J. 2015 Jun 20;14:251. doi: 10.1186/s12936-015-0769-1. 

Valea, I, Tinto, H, Traore-Coulibaly, M, Toe, L. C, Lindegardh, N, Tarning, J, Van Geertruyden, J. P, D'Alessandro, U. Davies, G. R, Ward, S. A. Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso.  J Antimicrob Chemother. 2014 Sep;69(9):2499-507.