Longer follow-up needed for malaria treatment in pregnant women

New research published in Open Forum Infectious Diseases has found that a longer follow-up is required to assess antimalarial drug efficacy in pregnant women. This was found across all drugs assessed in low malaria transmission settings. The report’s authors have called for guidelines specifically for pregnant women and further investigation of optimal follow-up periods in high malaria transmission settings.

Credit: Paul Arps CC by 2.0
Credit: Paul Arps CC by 2.0

Antimalarial treatment follow-up is crucial for monitoring the effectiveness of drugs to inform policies on treatment guidelines and track the emergence or spread of resistance, which is a global problem. The World Health Organization currently recommends a follow-up period of between 28 and 42 days depending on the drug used. Although these guidelines exclude pregnant women, they are often modified and extended for pregnant women – however, the optimal follow-up period is likely to be different in this group due to placental sequestration (where infected red blood cells accumulate in the placenta causing adverse effects on mother and fetus), altered immunity and physiological changes that take place during pregnancy.

The optimal follow-up needs to be long enough to capture the majority of events that can occur post-treatment, for example, recurrence of infection (known as recrudescence), to ensure that the statistical analysis and conclusions are as accurate as possible.

The authors set out to determine the optimal duration of treatment follow-up in pregnant women and the factors affecting recrudescence. Accelerating failure time models (a computational statistical method) were used to analyse data from studies conducted at the Shoklo Malaria Research Unit on the Thailand-Myanmar border between 1994–2010 where malaria care is integrated into routine antenatal care services. Recrudescence was analysed for different antimalarial drugs.

It was found that a 28-day follow-up could be missing more than 30% of recrudescent events (for the drug quinine) while 11% were predicted to be missed even for 42-day follow-up (artemether-lumefantrine). Longer follow-up periods such as 53 days (artemether-lumefantrine) or 72 days (dihydroartemisinin-piperaquine) are predicted to be needed to capture 95% of recrudescences. The author’s reasoned that as 53 to 72 days is just under a trimester, it may not be too burdensome to carry out in antenatal care settings.

Dr Makoto Saito, lead author on the study says “Pregnant women are vulnerable to infectious diseases but hugely understudied. Simple extrapolation of what is best for non-pregnant populations may not be always best for pregnant women. They need special attention, and research and clinical practice should be tailored for pregnant women.”

While existing data is limited and malaria transmission at the Thailand-Myanmar border is low and unstable, results indicated that the current length of follow-up recommended for non-pregnant populations is insufficient for pregnant women, and that further studies are needed in high transmission areas. Follow-ups that are too short may be underestimating the rate of recrudescence and therefore overestimating how effective treatments are. The accurate analysis of treatment is vital to protect current and future expectant mothers, a group particularly vulnerable to malaria infection.

Read the paper: Optimal duration of follow-up for assessing antimalarial efficacy in pregnancy: a retrospective analysis of a cohort followed up until delivery on the Thailand-Myanmar border. Open Forum Infectious Diseases. Volume 6, Issue 7, July 2019.

Find out more about the Shoklo Malaria Research Unit