Improving malaria treatment during pregnancy

Dr Rukhsana Ahmed, Postdoctoral Research Associate in Clinical Epidemiology, Liverpool School of Tropical Medicine, UK

Due to a shortage of safety data on pregnant women for most of the currently recommended malaria treatments, there are limited treatment options for this vulnerable population, particularly in the first trimester.

During the first trimester of pregnancy, quinine in combination with clindamycin remains the recommended drug,1 due to a historic lack of safety evidence regarding the use of ACT in this delicate period of foetal development.Recent expert guidance, based on newly accumulated safety data showing that treatment with artemisinin in the first trimester is not associated with an increased risk of miscarriage or stillbirth compared with quinine,3 has led the World Health Organization (WHO) to consider recommending ACT as a first-line therapeutic option for uncomplicated malaria during all trimesters of pregnancy.4

While there is comparatively rich data on the safety of artemether-lumefantrine (one of the most widely used ACTs) in treating pregnant women in the first trimester of pregnancy, there is much less data today demonstrating comparable safety with dihydroartemisinin-piperaquine (DHA-PQP) and other ACTs. To address this gap, MMV is supporting a study in Indonesia with the Liverpool School of Tropical Medicine in conjunction with the Timika Research Facility, Indonesia, to gather significantly more data – retrospectively and prospectively – on the safety of DHA-PQP during all trimesters of pregnancy.

Dr Rukhsana Ahmed, Postdoctoral Research Associate in Clinical Epidemiology, Liverpool School of Tropical Medicine, UK, and Principal Investigator of the Indonesian safety study talks about her experience of working on this important research.

1. What are the risks for pregnant women with malaria infection?

The risks depend on several factors, such as the epidemiology of malaria in the country, the parasite species, the level of malaria transmission in the country and whether it is seasonal or perennial. In high-transmission areas, most women develop partial immunity by the time they reach reproductive age. In low-transmission areas, however, young women do not develop immunity, and are therefore prone to malaria infections, leading to possible preterm or low-birth-weight babies, or even stillbirths. For those with chronic infections, both mother and infant are at risk of developing severe anaemia. It can affect the foetus in utero through to birth and even into childhood.

2. What are the challenges with the current options for protection and treatment of pregnant women?

The currently recommended regimen for intermittent preventive treatment in pregnancy (IPTp) is sulfadoxine-pyrimethamine (SP) in eligible African countries, but there is no such IPTp recommendation for malaria-endemic countries outside of Africa. When we screen and treat in Indonesia at the first antenatal visit, the drug of choice is an ACT, which is to be used only during the second and third trimesters. We therefore need a drug suitable for use during the first trimester as well as options that could be considered for IPTp.

3. Why is DHA-PQP being studied in pregnant women in Indonesia?

Indonesia was one of the first countries to introduce a national policy, in 2006, for the use of DHA-PQP for the treatment of malaria in adults and pregnant women in their second and third trimester. Many women could thus have been inadvertently exposed to this drug early in their first trimester while being unaware of their pregnancy. As such, a wealth of data regarding the effect of the use of DHA-PQP during the first trimester must exist.

4. How is this study being conducted?

There are two components to our study: retrospective and prospective. The retrospective part started in October 2017. For this, we access data between 2006 and 2017 from two main hospitals, and gather data relating to pregnant women who received DHA-PQP in their first trimester, either inadvertently or as a drug of choice. We then compare data on pregnancy outcomes and risks of congenital anomalies in these women with data from women who received quinine in their first trimester.

The prospective component of the study began in January 2018. For this, we enrol women in early pregnancy and treat them with DHA-PQP if they have confirmed malaria. These women are closely monitored until delivery, for pregnancy outcomes. One of the reasons for this close monitoring is that in the retrospective arm, despite having 10 years of data, we may not find sufficient data on women who had early miscarriages as they might not have gone to the hospital. We may also have missed women who had stillbirths, as home delivery is common in rural settings.

5. What is it like working with MMV on this project?

This is our first collaborative project with MMV. MMV has been very supportive of innovative work in the field of malaria and has shown a lot of interest in this project. We look forward to sharing the findings of this study, which will be particularly beneficial for pregnant women living in areas of malaria transmission.

  1. World Health Organization. Guidelines for the treatment of malaria. Third Edition (2015)
  2. Clark RL. “Embryotoxicity of the artemesinin antimalarials and potential consequences of use in women in the first trimester”. Reprod Toxicol; 28(3):285–296 (2009).
  3. Moore KA et al. “Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study”. Lancet Infect Dis; 16(5):576–583 (2016).
  4. World Health Organization. Intermittent screening and treatment in pregnancy and the safety of ACTs in the first trimester. Recommendations. (2015)