After their children, pregnant women are the first victims of malaria. Pregnancy weakens their body’s ability to defend itself against the Plasmodium falciparum parasite. Gestational malaria is responsible for many miscarriages and in utero deaths. It increases the risk of fetal growth retardation, prematurity and low birth weight, all of which make newborn babies more vulnerable. “Pregnancy increases women’s susceptibility to infection and the parasite is able to adapt to lodge in the placenta, explains Valérie Briand, specialist in gestational malaria, director of the Epicenter research department of Médecins sans frontières (MSF) . The mother can then suffer from severe anemia, sometimes fatal. But, above all, the parasite disrupts the placental exchanges of the fetus with the mother. The imperative to advance research into preventive drugs for them is therefore twofold: to protect mothers as well as their unborn babies.
This imperative for innovation is at the heart of the theme chosen by the World Health Organization (WHO) for Malaria Day, Tuesday 25 April: “It’s time to get to zero cases of malaria: invest, innovate , implement “. In Africa, which carries 95% of the world’s malaria burden, one in three pregnancies was exposed to malaria infection (out of an estimated 33.8 million) in 2022, according to the UN agency’s report. Added to this vulnerability is resistance to the drug used for prevention among pregnant women, which is constantly growing, particularly in sub-Saharan Africa.
Several studies are underway to find a molecule that could replace sulfadoxine-pyrimetamine (SP), developed in the 1950s and used for thirty years. The results of a study published on March 25 in the medical journal The Lancet, which raised real hope, illustrate the complexity of this specific prevention.
“Many Complications”
The clinical trial published in The Lancet was conducted by an international team between 2018 and 2019 in Tanzania, Kenya and Malawi, where resistance to SP is high. Nearly 4,700 pregnant women participated in three different intermittent preventive treatment (IPT) protocols. The first group received conventional treatment (SP); the second a newer antimalarial, dihydroartemisinin piperaquine (DP); the third, PD combined with an antibiotic, azithromycin. All the participants benefited from a monthly medical follow-up during which several clinical and blood tests were carried out.
“We expected DP to be so effective against malaria that we could advise the WHO to replace SP with this molecule,” said Christentze Schmiegelow, a researcher at the University of Copenhagen and co-author of this work led by the Liverpool School of Tropical Medicine. The data collected was indeed inspiring. Women on PD had up to half as many malaria infections. In addition, a one-third reduction in infections of the placenta with the parasite responsible for malaria was also observed.
But if the new molecule has lived up to researchers’ expectations against Plasmodium falciparum infections, other data have mixed the results. “African women can face many complications during pregnancy, not just those related to malaria, develops Michael Alifrangis, associate professor at the University of Copenhagen who co-authors this work. However, it is known that sulfadoxine-pyrimetamine has, in addition to its antimalarial properties, an antibacterial effect which can protect against a wide spectrum of infections. Our study therefore evaluated the complications as a whole for each group, and if the new molecule is much more effective against malaria than the old one, it is despite everything in the group treated with SP that we found the least of complications. »
Effects on the fetus
Although the rates of prematurity were similar in the three groups, the proportion of babies with low birth weight was significantly reduced only in the group that received the old molecule, which is very effective in limiting sexually transmitted infections likely to develop. have repercussions on the foetus.
Finally, the complication rates obtained in the third group (PD azithromycin) were no better than in the group that received only PD. Michael Alifrangis points out, however, that the women received only one dose of azithromycin and that the results might have been different with a monthly antibiotic intake.
So should another antibiotic be added to the new molecule? Or combine it with the old, thus combining the benefits against malaria and other infections? In both cases, the much higher cost of the new molecule is still an obstacle to its deployment on the continent.
And the fact of multiplying the taking of drugs could dissuade some women from following the preventive treatment. “The huge advantage of SP is that it is a single dose, unlike PD which must be taken over three consecutive days, which could reduce compliance,” notes Valérie Briand of MSF.
Pregnancy follow-up
While waiting for the drug equation to be resolved, a major axis remains to strengthen the prevention of malaria in pregnant women and their children: improving the monitoring of prenatal consultations for African women, many of whom do not benefit on the continent. Because this is the time when intermittent preventive treatment (IPT) must be offered.
“Despite the progress made in recent years, it is estimated that only one third of women receive at least three doses of IPT during pregnancy, as recommended by the WHO”, assesses Michael Alifrangis. “To overcome this pitfall, testifies Valérie Briand, from MSF, we are carrying out the Integration project. We take advantage of pre-scheduled visits targeting children under 5, to provide their mothers with information, offer them IPT and motivate them to attend antenatal care. »
This pregnancy follow-up is also an opportunity to distribute mosquito nets impregnated with repellent free of charge to future mothers, which remains a very effective way to fight against Anopheles, the transmitter of malaria. In sub-Saharan Africa, according to WHO estimates, four out of ten pregnant women did not sleep under an insecticide-treated mosquito net in 2018.