Malaria during pregnancy: providing evidence to support optimal antimalarial drug dosing

Malaria during pregnancy can have detrimental consequences to the health of both the mother and the child. It can result in still birth, miscarriage, severe anaemia, or haemorrhage in the mother and is linked to learning and developmental difficulties in the baby as it develops. Each year, malaria infection during pregnancy is associated with 10,000 maternal deaths and accounts for up to 200,000 infant deaths in Africa alone.

As part of the Roll Back Malaria Partnership (RBM) impact series, a collaboration between the RBM and multiple research partners in the Malaria in Pregnancy Consortium, have published a new report highlighting the impact of prevention and control strategies for maternal, new-born and child health. The report highlights the outcomes from the roll-out of two preventive measures, intermittent preventive antimalarial treatment during pregnancy (IPTp) and provision of insecticide-treated mosquito nets (ITNs) for pregnant women. The summary confirms that these measures are associated with an 18% reduction in the risk of neonatal mortality. Despite these encouraging results, the report also suggests that many challenges remain in the drive to increase significantly the coverage and access to malaria prevention and control tools. 

Treating patients with malaria during pregnancy also presents many challenges for clinicians and patients. The potential for complex risks and life-threatening complications in the mother or unborn child often exclude pregnant women from clinical drug trials. Paradoxically, this reality causes a knowledge gap in drug efficacy  in the same patient populations that carry this large proportion of the disease burden.

Pregnancy can alter the disposition, or pharmacokinetics, of a drug in the body, changing the drug exposure and thus possibly affecting treatment success. For these reasons, dosing recommendations for a non-pregnant adult do not necessarily reflect the dosing needs of pregnant woman. Pharmacokinetic modelling has become a powerful way of understanding the best way to treat and dose pregnant women.

The WWARN Pharmacology Group are currently using mathematical and statistical techniques, known as population pharmacokinetic modelling, to perform a comparison of drug exposures in non-pregnant adults, pregnant women, and infants to better understand how different factors such as weight, age, and pregnancy affect the pharmacokinetics of antimalarial drugs. The team plan to use information gathered from this method to determine optimal antimalarial drug dosing, specifically focusing on improving our understanding of antimalarial dosing in pregnant women. The results from this work should provide further evidence that will strengthen our overall understanding of malaria in pregnancy.

“The pharmacokinetic differences between pregnant and non-pregnant women, such as differences in enzyme activity, during antimalarial treatment mean that many pregnant women may not be receiving the optimal dose of antimalarial medicines required,” says Dr Joel Tarning, Head of Pharmacometrics at WWARN. “We are now trying to uncover how big a problem this is, while also trying to establish the optimal dosing regimen for pregnant women through modelling.”

The WWARN Study Groups are analysing data sets to assess potential dose optimisation for the antimalarial drugs piperaquine, lumefantrine, amodiaquine and sulfadoxine-pyrimethamine. Pooling data sets from a wide range of studies to increase sample sizes allows the groups to determine treatment trends within specific sub-populations like pregnant women and small children. This evidence can be used by decision-makers to update and strengthen malaria treatment guidelines.

“We plan to use standard adult exposure as a reference and propose dose adjustments in children or pregnant women to achieve the same levels of exposure,” says Dr Paolo Denti, Head of the Pharmacometrics Unit at the University of Cape Town. “We anticipate that our ongoing analysis will shed light on treatment dosing for pregnant women and small children. Our work reinforces the need for more evidence on malaria in pregnancy and complements the call to action highlighted in the ‘The contribution of malaria control to maternal and new-born health’ publication by RBM.”

Download the report Roll Back Malaria: Progress and Impact Series – The contribution of malaria control to maternal and new-born health

This report was developed by researchers at the Liverpool School of Tropical Medicine with contributions from the Department of Reproductive Health at the World Health Organization (WHO), Tulane University, Jhpiego, an affiliate of Johns Hopkins University), the Malaria Control and Evaluation Partnership