Malaria in pregnancy

By Petra Mens
Approximately one fourth of the world population is at risk of contracting malaria and every year more than 2 million people, mainly young children in sub-Sahara Africa, die due to the complications of malaria. However, not only children are the victim of malaria; also pregnant women in developing countries are a risk group which is threatened by the disease. More than 90% of malaria infections occur in sub-Saharan Africa. There, approximately 30 million women per year become pregnant. Plasmodium falciparum, the most serious form of malaria, is an risk factor in seriously illness is of the pregnant woman, early birth, serious sickness of the child and infant mortality. In areas with stable malaria transmission (e.g. sub-Saharan Africa), P. falciparum infection during pregnancy is estimated to cause as many as 10,000 maternal deaths each year, contributes to approximately 2 – 15% of maternal anemia, 8 – 14% of low birth weight infants (an important contributor to infant mortality), and 3 – 8% of all infant deaths.

Although malaria in pregnancy is often asymptomatic (the patient is infected but does not feel ill or has the typical symptoms of malaria), it nevertheless is the cause of unfavorable pregnancy outcomes both in the mother and in her child. The outcomes of the invasion of the placenta by the malaria parasites, even at low infection rates, leads to ill health for the mother, may cause abortion of the fetus, premature labour, small-for-date babies, low birth weight  and post-neonatal infant mortality. The association between maternal malaria and neonatal or infant mortality is not completely clear, but it is evident that chronic malaria during pregnancy causes low birth weight.

Prevention and/or treatment of malaria in pregnancy are major public health challenges and essential components of the obstetrician and antenatal care in endemic areas, but these require special considerations during pregnancy. In particular, only few anti-malaria drugs can be used in this target group and there are some problems with the malaria parasite becoming resistant to these medicines.

Prophylaxis (giving medication to protect pregnant women and the unborn child against malaria without evidence that they are really sick) during pregnancy with anti-malarial drugs has shown that it reduces malaria in the blood and in the placenta of the mother, it has a favourable impact on anaemia of the mother and on the birth weight of the baby. This applies mainly for the first and second pregnancy. This approach is called intermittent preventive treatment or IPT, but is not widely applied yet in many countries where malaria is abundant. This can be caused due to ignorance of the expecting mothers concerning the risk of malaria during pregnancy and/or lack of access to and or knowledge within the medical care. This unfortunately leads to the fact that not everyone takes correct preventive measures (like IPT and sleeping under a bed net). KIT is working on a project to improve IPTp uptake and ANC attendance in combination with scheduled screening of women by a rapid test and treatment if positive in their own communities by community health workers. See http://www.cosmicmalaria.eu/

An additional problem is the proper treatment of the women when they are infected with malaria. Any medicine in pregnancy should in general be given when it is proven to be safe for the unborn child. For anti-malarials this still poses many problems since not all drugs can be given safely  pregnancy. This problem is exacerbated due to the fact that the malaria parasites are or are becoming resistant to several available drugs, which frustrates the treatment of symptomatic malaria.

The increase of anti-malarial drug resistance over the last decades demands continuous research to improve existing treatment and to develop new drugs. Pregnant women and children are the target groups of current global malaria control efforts. However, the antimalarial drugs which are considered safe during pregnancy, chloroquine, quinine and sulfadoxine-pyrimethamine, become increasingly ineffective. The increased inefficacy of these the common affordable anti-malarials prompted many countries to recently shift their treatment guidelines to other, more expensive, medicines , most often combination regimens that contain an artemisinin derivative drug.

In Africa, the most commonly used artemisinin-based treatment (ACT) is Coartem,  a combination of artemisinin derivative arthemether with an other component called lumefantrine. The introduction of this drug combination drug in national drug policies, including malaria in pregnancy, went faster than drug registration, so that off label prescription is common. Pre-clinical investigations repeatedly showed that artemisinin-based drugs are potentially neurotoxic, and that in high dosages they may also have toxic effects on the unborn child. ACT is currently recommended for drug resistant P. falciparum malaria but usage in the first trimester of pregnancy was recently excluded. The general opinion though is that toxic effects of therapeutic dosages in humans have not been documented yet and that the risks are small and outweighed by the benefits of the artemisinin drugs in the second and third trimester of pregnancy. Recent studies have shown that Coartem can be used safely and effectively in the second trimester of pregnancy for treatment of P. falciparum malaria.

These aspects: treatment, education of pregnant women and effects of different drugs on the unborn child are topics in several research projects of KIT-BR (see KITs involvement).
Biomedical Research, Royal Tropical Institute.

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