Malaria in Pregnancy – MMV Makes Renewed Efforts To Protect This High-Risk Group
Pregnant women remain one of the groups at highest risk of complications from malaria infection.

Reducing new cases of malaria among pregnant women remains one of the key challenges on the road to malaria elimination – a goal that was celebrated last week, on World Malaria Day, 25 April.

Although malaria deaths fell by nearly a quarter between 2010 and 2018, pregnant women remain among the groups most at risk from the parasitic disease.

In response, MMV has recently ramped up a longstanding programme (first initiated in 2014) dedicated to fighting malaria in pregnancy, naming it the Malaria in Mothers and Babies (MiMBa) initiative.

MiMBa for short, the acronym is aptly named after the Swahili word for “pregnancy.”

Every year, malaria in pregnancy causes some 10,000 maternal deaths, mostly in sub-Saharan Africa.

In areas where malaria is widespread, it is estimated that at least 25% of pregnant women are infected with malaria. And more than 11 million pregnant women were infected in sub-Saharan Africa in 2018 alone – putting a third of all future mothers in that region at risk.

During pregnancy, the disease can also cause maternal anaemia, premature labor, and low birth weight in babies – some 872,000 babies alone were born with low birth weight in 38 sub-Saharan African countries in 2018. This puts newborns, as well, at much higher risk of early death in the first 12 months of life, according to the latest WHO World Malaria Report.

“Protecting pregnant women from malaria has been a key concern of the malaria community for many years, though today in the context of a burgeoning COVID-19 pandemic the stakes are even higher,” said Dr David Reddy, MMV’s CEO. “We need to move quickly to ensure pregnant women and others at risk of malaria can access the tools they need to protect them today, particularly because access to healthcare facilities will be compromised during the COVID-19 outbreak. Beyond this immediate need, we must continue to develop the new tools they will need for the future”.

A key tool to protect pregnant women – Intermittent Preventive Treatment

A key tool to protect pregnant women from malaria in areas with moderate-to-high malaria transmission in Africa is intermittent preventive treatment of malaria during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), which is a cost-effective intervention.

A minimum of three doses of SP from the second trimester onwards prevents maternal and foetal anaemia, reduces maternal malaria episodes, and decreases the risk of low birth weight.

“IPTp has been shown to reduce negative pregnancy outcomes and if well implemented, with good coverage, these interventions can drastically reduce the malaria prevalence in these specific populations,” said MMV Director of Access & Product Management, Dr André-Marie Tchouatieu.

Intermittent treatment with sulfadoxine-pyrimethamine (SP) can help prevent malaria during pregnancy.
Scaling Up Access to IPTp

However, right now, a complete three-dose course of IPTp only reaches about 31% of the pregnant women that need the treatment, according to the latest WHO data. This year the RBM Malaria in Pregnancy Working Group, which includes MMV, has launched the Speed-up Scale-up campaign to rally a larger community of stakeholders to bring IPTp-SP to all eligible women who need it in sub-Saharan Africa.

The challenge on the ground, Dr Tchouatieu said, is to “bring these interventions as close as possible to the affected communities.”

He explained that IPTp has so far been delivered primarily in health facilities, during antenatal care (ANC) visits. However, these ANC visits typically cost women money, while malaria preventive drugs are often freely provided.

Since pregnant women often skimp on ANC visits due to limited resources, they miss out on the opportunity to get the three doses of anti-malarial preventive treatment.

As part of a Jhpiego-led consortium, MMV and other partners are exploring ways to complement the existing delivery method for IPTp by bringing treatments more directly into the communities and homes of women who need them. Under the UNITAID-funded TIPTOP project, the consortium is exploring whether community-based delivery of IPTp-SP could successfully complement ANC-based delivery.

“We are exploring how to involve community health volunteers to both deliver IPTp and encourage women to attend ANC visits,” said Dr Tchouatieu. Results from the recently wrapped primary phase of the project showed that in four pilot countries – Nigeria, the Democratic Republic of the Congo, Mozambique, and Madagascar – coverage of the second and third doses of IPTp went up along with attendance at a fourth and fifth ANC visit.

WHO currently recommends at least six ANC visits in order for pregnant women to be screened for other pregnancy-related health problems. Ideally, says Dr Tchouatieu, recommendations on IPTp might also be expanded to a monthly administration to cover women more completely during the last two trimesters of pregnancy.

Malaria – A Particular Risk in the First Pregnancy    

Malaria is a particular risk to women and their foetus during their first pregnancy. In moderate and high transmission settings such as parts of sub-Saharan Africa, women tend to naturally have a higher level of immunity to malaria due to the constant exposure to the disease; but that immunity may be depressed during pregnancy.

“There is a breakdown of acquired immunity [to malaria] that occurs in pregnancy, especially in the first pregnancy,” said Dr Tchouatieu.

That may also explain the comparatively higher rate of malaria mortality seen in teenage girls and young women in some settings, where teenage pregnancy is more common. According to WHO, malaria remained one of the top 5 killers of adolescent girls 10 to 14 years old, and maternal conditions were the leading cause of death in young women age 15 to 19 around the world in 2016.  In subsequent pregnancies, on the other hand, immunity appears to be less impacted.

Many young women also carry asymptomatic infections, Dr Tchouatieu adds. This can lead to chronic anaemia, which is caused by a low level of parasitic activity that destroys red blood cells. Women who were previously asymptomatic or slightly anaemic may develop stronger symptoms during pregnancy, and even progress to severe disease.

In addition, during pregnancy, the malaria parasites may be attracted to a new, abundant source of healthy red blood cells – the placenta. The parasites infect the placenta, a condition known as placental parasitaemia, interfering with the circulation of nutrients between the mother and foetus, leading to low birth weight, still births, or even miscarriages.

In areas of unstable malaria transmission, such as Asia and Latin America, as well as in low transmission areas of Africa, where populations have a lower level of  acquired malaria immunity, the risks of developing severe disease upon being infected by malaria can be even higher for pregnant women, said Dr Tchouatieu.

Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is effective in reducing maternal malaria episodes, and may help prevent low birth weight in babies.
IPTp – Part of a Wider MiMBa Strategy

Supporting the scale up of IPTp is just one part of a wider MiMBa strategy whose ambition is to improve equity and inclusion of the needs of future mothers, mothers and their babies in malaria drug development – MMV and its partners also want to accelerate the discovery, development, and monitoring of new antimalarial options – optimized for pregnant women and lactating mothers.

As other elements of the MiMBa initiative, MMV also aims to:

  1. Fill the gaps on existing compounds to inform on their use in pregnant women and neonates;
  2. Develop new antimalarial medicines to address the needs of pregnant women and neonates;
  3. Strengthen the capture of safety data from use of antimalarials in endemic countries during pregnancy;
  4. Advocate for changes in drug development that promote the proper inclusion of pregnant women into clinical studies, with the aim of generating data to support earlier access to innovative medicines for this population.

While the current IPTp strategy is important, it can only be administered from the second trimester onward. So, development of a new treatment that could also be safely administered to prevent malaria in the first trimester of pregnancy, would represent a breakthrough.

“The face for malaria is female. The disease disproportionately affects pregnant women resulting in severe illness, deaths, loss of productivity and missed professional development opportunities,” says Joy Phumaphi, the Executive Secretary of the African Leaders Malaria Alliance, speaking at a meeting last year. “We must ensure sufficient resources are available to remove barriers to treatment and prevention, including the fast tracking of new commodities and interventions.

Image Credits: Elizabeth Poll/MMV, Karel Prinsloo-Jhpiego .