Finding new ways to combat pregnancy-associated malaria
Malarial infections during pregnancy can be a particular problem in sub-Saharan Africa, where the disease remains a widespread hazard to human health. Such infections can bring serious complications during pregnancy, including stillbirth, premature birth and low birth-weight, as well as severe risks to the mother's health.
The European Union (EU)-funded research project STOPPAM sought to find new ways to counter this problem of pregnancy-associated malaria (PAM). Through a clinical investigation carried out in the two countries of Tanzania (eastern Africa) and Benin (western Africa), STOPPAM project team attempted to quantify the effects of PAM and to identify a suitable candidate-vaccine for further development.
“We set out to investigate the most harmful characteristics of malaria infections in pregnant mothers,” says STOPPAM project coordinator, Dr Philippe Deloron of the French Institute of Research for Development (IRD). “Our objective was to develop a clinical and pathological overview of what happens with the disease during pregnancy and to study patient responses to potential future vaccines,” he adds.
Malaria has been a health problem in sub-Saharan Africa for many years and it remains so. Increasing levels of drug-resistance among mosquito populations are challenging official prevention strategies, and there are fears that this resistance to existing drugs could rise to the point where clinicians would no longer possess an effective course of treatment for the disease.
Governments, public-health agencies and drug companies around the world are therefore seeking to develop new and effective vaccines for the disease.
The partner organisations that came together under the STOPPAM project all had a history of high-class, internationally-recognised research in malaria, pooling their knowledge to try and come up with a potential new vaccine.
The research team studied a large group of women – pregnant mothers who were at risk from malaria – at clinics in each country. One thousand women living in Korogwe District, North-East Tanzania were followed from their first antenatal booking until delivery. At Comé, in Benin, 1,037 women were included in the study.
The mothers were screened for malaria infection, anaemia, hypertensive disorders and signs of foetal/infant problems at regular visits during their term to the maternity clinic, as well as upon delivery. Ultrasound investigations were performed, and blood, plasma and placenta samples collected for laboratory analysis. Two hundred children born to the mothers participating in the study were also followed up for one year.
For STOPPAM team one of the challenges was the greater than expected variation in malarial infection rates between Benin and Tanzania. Infection rates in Benin were as expected, but in Tanzania the team found much less malarial transmission than expected. Mosquito numbers during the project's three-year term had mysteriously declined at the same rate in areas treated with insecticide as in those not treated.
One of the key developments that emerged during the project was the importance of early detection of infections: finding the infection within the first three months of pregnancy. “This insight is of real importance for public health,” explains Dr Deloron. “In most tropical countries, pregnancy is generally only detected in month five. In addition, treatment is generally not given before week 20, leaving several months unprotected from infection,” he says. As a consequence, a successful new anti-PAM vaccine would have to treat teenage girls of child-bearing age in order to be effective, rather than waiting until pregnancy is confirmed.
By the end of the project the STOPPAM team had successfully identified a likely candidate vaccine for further development, DBL1-ID1-DBL2. The potential for this new drug in combating PAM is currently being analysed in a new FP7 research project called PLACMALVAC.
Much of the clinical and pathological data resulting from the project has been published via leading medical journals, with over a dozen papers in publications such as PLoS One and Malaria Journal.