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Why is WHO failing women with falciparum malaria in the first trimester of pregnancy?

From The Lancet Correspondence. In the opening to the 2019 World Malaria Report, entitled Leaving no one behind in the march to a malaria free world, the WHO’s Director-General notes that the scourge of malaria continues to strike hardest against pregnant women and children in Africa.

Health care workers sharing information about malaria to locals © 2020 MORU. Photographer: Mehul Dhorda.
Women being recruited for a malaria study in Kinshasa

WHO’s Director-General reports that “some 11 million pregnant women in sub- Saharan Africa were infected with malaria and, consequently, nearly 900 000 children were born with a low birthweight.” Furthermore, he notes that “Malaria in pregnancy compromises the mother’s health and puts her at greater risk of death. It impacts the health of the fetus, leading to prematurity and low birthweight, major contributors to neonatal and infant mortality.”1

In sub-Saharan Africa, Plasmodium falciparum is responsible for an estimated 50,000 maternal deaths and 200,000 stillbirths each year, in addition to substantial adverse neonatal morbidity (preterm birth and small-for-gestational-age) predisposing to death in infancy and non-communicable diseases in later life.2 This intolerable carnage is preventable.

Artemisinin combination treatments (ACTs) are first-line treatments for falciparum malaria throughout the world, and they are recommended by WHO as the treatment of choice for women in the second and third trimesters of pregnancy, but puzzlingly they are still not recommended by WHO in the first trimester. Concerns over the use of artemisinin derivatives in the first trimester have been systematically addressed.2,3 In 2015 an Evidence Review Group convened by the WHO’s Global Malaria Programme (WHO GMP) reported a detailed review of all available data and recommended that the clear benefits exceeded any potential risks and that ACTs should be used to treat uncomplicated falciparum malaria in the first trimester.

The WHO GMP’s own malaria policy advisory group then recommended “review of the WHO Guidelines for the treatment of malaria to consider the timely inclusion of ACT as a first-line therapeutic option for uncomplicated falciparum malaria”,4 a process WHO GMP initiated through its Treatment Guidelines Committee in 2017. Yet today, well over 4 years after the original recommendation, WHO still recommends quinine, a drug for which there are few data on safety in the first trimester. Quinine is poorly tolerated, poorly adhered to, and therefore less effective than ACTs.2,3 Hospitals, antenatal clinics, and malaria control programmes all have to retain quinine for this one unnecessary indication.5

Why is WHO leaving behind women in the first trimester of pregnancy? Nothing has justified this more than 4-year delay. We urge WHO to heed the advice of the Evidence Review Group and revise its outdated recommendations on the treatment of malaria in early pregnancy as a matter of urgency.

- Rose McGready, François Nosten, Karen I Barnes, Olugbenga Mokuolu, Nicholas J White

 

Declaration of interests’ statement

KB, OM and NW were all members of the  WHO Technical Expert Group on Malaria Chemotherapy

 

Shoklo Malaria Research Unit (RM, FN) and Mahidol–Oxford Tropical Medicine Research Unit (RM, FN, NJW), Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK (RM, FN, NJW);

Division of Clinical Pharmacology and SAMRC Collaborating Centre for Optimising Antimalarial Therapy, Department of Medicine, University of Cape Town, Cape Town, South Africa (KIB); and Department of Paediatrics and Child Health, University of Ilorin Teaching Hospital, Ilorin, Nigeria (OM)

 

1 WHO. World Malaria Report 2019. 2019. https://www.who.int/publications-detail/ world-malaria-report-2019 (accessed Jan 22, 2020).

2 Saito M, Gilder ME, McGready R, Nosten F. Antimalarial drugs for treating and preventing malaria in pregnant and lactating women. Expert Opin Drug Saf 2018; 17: 1129–44.

3 Dellicour S, Sevene E, McGready R, et al. First-trimester artemisinin derivatives and quinine treatments and the risk of adverse pregnancy outcomes in Africa and Asia: A meta-analysis of observational studies. PLoS Med 2017; 14: e1002290.

4 WHO Malaria Policy Advisory Committee and Secretariat. Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of eighth biannual meeting (September 2015). Malaria J 2016; 15: e117

5 Rao VB, Jensen TO, Jimenez BC, et al. Malaria in pregnancy: a call for a safe, efficient, and patient-centred approach to first-trimester treatment. Lancet Glob Health 2018; 6: e607–08.

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