Treatment Africa and Asia

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

Project Coordinators:         

Prof Umberto D'Alessandro (LSHTM), Dr Theonest K Mutabingwa (Hubert Kairuki Memorial University, Tanzania)

Site Principal Investigators: 

Prof Halidou Tinto (Research Institute of Health Sciences (IRSS), Burkina Faso); Dr Harry Tagbor (Kwame Nkrumah University of Science and Technology (KNUST), Ghana); Drs  Linda Kalilani and Gertrude Kalanda (College of Medicine, Malawi); Dr Modest Mulenga (Tropical Diseases Research Centre (TDRC), Zambia)

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.

Study design

A non-inferiority, multi-centre, randomized, open label trial comparing the fixed dose combinations of artemether-lumefantrine; amodiaquine-artesunate; mefloquine–artesunate and dihydroartemisinin-piperaquine for the treatment of malaria in the second and third trimesters of pregnancy, conducted in four sites across Africa (Burkina Faso, Ghana, Malawi and Zambia). Overall 3428 women were enrolled across the four sites in the largest trial of its kind to date.

Results and Conclusion

The cure rates for all four drugs were high (>95%). There was no significant difference in serious adverse events and birth outcomes found between treatment arms. 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. Based on these safety and efficacy data, dihydroartemisinin-piperaquine seems the most suitable treatment for uncomplicated malaria in pregnancy.

Impact of the research

The trial results were presented and discussed at a meeting of the WHO Evidence Review Group (ERG) on Malaria in Pregnancy held in Geneva in 2015 (WHO Malaria Policy Advisory Committee (2016). Malar J 15(1): 117). The findings provide reassurance on WHO’s adoption of dihydroartemisinin-piperaquine as a safe and efficacious antimalarial for the treatment of malaria in the second and third trimesters of pregnancy.  

Guidelines for the treatment of malaria (3rd edition)

Publications

Group, P. S., et al. (2016). "Four Artemisinin-Based Treatments in African Pregnant Women with Malaria." N Engl J Med 374(10): 913-927.

Valea, I., et al. (2014). "Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso." J Antimicrob Chemother 69(9): 2499-2507.

Tahita, M. C., et al. (2015). "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 14: 251.

Nambozi, M., et al. (2015). "Safe and efficacious artemisinin-based combination treatments for African pregnant women with malaria: a multicentre randomized control trial." Reprod Health 12: 5.

D'Alessandro, U., et al. (2018). "Treatment of uncomplicated and severe malaria during pregnancy." Lancet Infect Dis 18(4): e133-e146.

Nosten, F., et al. (2007). "Case management of malaria in pregnancy." Lancet Infect Dis 7(2): 118-125