Malaria and pregnancy

Malaria in pregnancy is the most common yet preventable cause of maternal and perinatal morbidity and mortality in sub-Saharan Africa. Around 125 million pregnancies are at risk of malaria every year, and up to 200,000 babies die as a result.1

In the absence of an effective and safe vaccine, the best available option to help counter these dismal statistics is Intermittent Preventative Therapy in Pregnant Women (IPTp). The idea is that pregnant women receive a curative dose of an antimalarial drug during the second and third trimester when attending an antenatal clinic – regardless of whether the mother-to-be has malaria symptoms. Treatment must be administered on at least two occasions during the pregnancy. A drug with a long-half life is used so that not only is any existing malaria infection treated but also some underlying protection from future infection or re-infection remains for some time  following the clinic visit.

The efficacy of IPTp regimens in reducing neonatal mortality has been demonstrated in a number of trials.2 On this basis, in 2004 the World Health Organization (WHO) recommended the use of sulfadoxine-pyrimethamine (SP) as IPTp in areas of high and medium malaria transmission.3

Nevertheless, while several African countries have recently adopted SP as the standard IPTp regimen, the emergence and spread of SP resistance, especially in East and Southern Africa, has become a cause for concern. As such, there is an urgent need to develop new and effective IPTp regimens.

Developing new medicines for pregnant women presents a huge ethical challenge. In this vulnerable group, safety is of paramount importance, but difficult to test. One of the things we can do, however, is develop new combinations of medicines that are individually known to be safe in pregnancy.

In partnership with Pfizer and London School of Hygiene and Tropical Medicine (LSHTM) MMV is developing a fixed-dose combination tablet of azithromycin and chloroquine (AZCQ) for IPTp. Each individual drug in AZCQ has demonstrated adequate safety in children and pregnant women over a number of years. The combination is synergistic against chloroquine-resistant strains of Plasmodium falciparum and has already shown efficacy in the treatment of symptomatic malaria in sub-Saharan Africa.4 Furthermore, the efficacy of azithromycin in treating and preventing sexually transmitted diseases should provide additional benefit in improving pregnancy outcomes.

AZCQ’s clinical development programme consists of one large multi-country pivotal Phase III study in East, Southern and West Africa to compare AZCQ IPTp with SP IPTp in terms of impact on reducing the incidence of adverse pregnancy outcomes. The study is planned to begin in the third quarter of 2010.

1.    Dellicour S et al. Quantifying the Number of Pregnancies at Risk of Malaria in 2007: A Demographic Study. PLoS Med 7(1): e1000221 (2010)
2.    Parise ME et al. Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg. 59(5):813-22 (1998).
3.    WHO: A Strategic Framework for Malaria Prevention and Control during Pregnancy in the Africa Region.
4.    Nakornchai S, Konthiang P. Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro. Acta Trop. 100(3):185-91. (2006).