Malaria in pregnancy

By Petra Mens
Biomedical Research, Royal Tropical Institute

The department Biomedical Research, Unit Parasitology, has several research lines in “malaria in pregnancy”.

2012-2016
Community-based scheduled screening and treatment of malaria in pregnancy for improved maternal and infant health: a cluster-randomized trial COSMIC (European Union FP7 grant) www.cosmicmalaria.eu
Preventive treatment with Sulphadoxine-Pyrimethamine can substantially reduce the effects of malaria in pregnancy. This medicine should be taken at every Antenatal care visit starting from the 2nd trimester and should be given at least 1 month apart. This corresponds to at least 3 doses during pregnancy However, as a result of low antenatal care attendance in many countries this strategy is not completely effective. An alternative to protect the women and her child is early detection and treatment. This can be done by rapid diagnostic tests (an approach called scheduled screening and treatment). However as women fail to attend the ANCs regulary other means of devlivering tests and treatments to the women are needed. This study looks at wether Community Health Workers working in the community of the pregnant women can deliver the tests and treatment on regular basis and asseses the health impact of this intervention. Next to this socio-economic fectors, health system factors and health economic factors are being investigated in order to come to a complete picture before policy recommendations will be done.

Development of diagnostic tools for malaria that can be used in pregnancy (FIND)
2008-2011
Malaria in pregnancy is difficult to diagnose, especially in endemic countries. Often the disease is asymptomatic in mothers who are regularly exposed to malaria and do not show the characteristic symptoms that can be seen in non pregnant persons. One of the reasons is that malaria “hides” in the placenta that is rich of blood and can there do its damage. If the parasite is happy in the placenta it is rarely found in the blood stream of the mother. This makes diagnosis very difficult since most forms of health centers the women go to use a drop of blood for microscopical examination and it is not possible to examine the placenta before the baby is born. Diagnostic tests that make use of the antigens (specific particles of the parasite that are different from the human body, circulate in the bloodstream and are recognized by the human immune system) can be used as an alternative for diagnostics. There are already some of these tests available for diagnostic use but these are not used on regular basis. The Parasitology Unit of Biomedical research is developing new diagnostic tools based on antigen detection that are sensitive and also reliable for diagnostics in pregnant women.
This study has resulted in better insight in the performance of rapid tests and other tests for the detection of malaria and has identified new targets for the development of diagnostic tests

Publications that have arisen through this project:

• PhD thesis : J.H. Kattenberg  (Supervisor: Prof. P.A. Kager, Co –supervisors: Dr. P.F. Mens; Dr. H. D.F.H. Schallig) Diagnosis of Malaria in Pregnancy, Evaluation, New developments and Implications
• Kattenberg J.H., Tahita M, Versteeg I., Tinto H, Traore-Coulibaly M, d’Alessandro U., Schallig H.D.F.H., Mens P.F. (2012) Evaluation of antigen detection tests, microscopy and PCR for the diagnosis of malaria in peripheral blood in asymptomatic pregnant women in Nanoro, Burkina Faso. American Journal of Tropical Medicine & Hygiene 87:251-6
• Kattenberg J.H., Tahita M, Versteeg I., Tinto H, Traore-Coulibaly M, Schallig H.D.F.H., Mens P.F. (2012) Antigen persistence of rapid diagnostic tests in pregnant women in Nanoro, Burkina Faso and the implications for the diagnosis of malaria in pregnancy. Tropical Medicine and International Health 5:550-557
• Kattenberg J.H., Versteeg I., Migchelsen S.M., I.J. Gonzales, M.D. Perkins., Mens P.F., Schallig H.D.F.H. (2012) New developments in diagnostics: Monoclonal Antibodies against Plasmodium Dihydrofolate Reductase- Thymidylate Synthase, Heme Detoxification Protein and Glutamate Rich Protein. Mabs 4:120-126
• Kattenberg J.H., Ochondo E.A., Boer K.R., Schallig H.D.F.H. Mens. P.F. Leeflang  M.M.G (2011) Systematic review and meta-analysis: Rapid diagnostic tests versus placental histology, peripheral and placental blood microscopy and PCR for malaria in pregnant women. Malaria Journal 10:321

Malaria in pregnancy in Rwanda (INTERACT Project H)
2006-2012
Rwanda is a country in Africa that also suffers from malaria. In this project a Rwandese PhD student, trained in gynecology, that is supervised by the Parasitology Unit, together with the Academic Medical Centre, Amsterdam, The Netherlands , is studying several aspects of Malaria in pregnancy. In Rwanda the artemisinin based combination drug Coartem is given to all people who are infected with malaria. This is a unique situation since the effects of the drug in pregnancy is not widely studied. Here we study the effects of the drug in 1000 pregnant women in a so called “post marketing surveillance” and compare the pregnancy outcome (the baby) with 1000 women that did not take Coartem during pregnancy. The babies are thoroughly examined directly after delivery and followed up until the age of 9 months.
In addition the effects of the malaria in utero (when the baby is still in the womb) are studied in a smaller group of 100 women. The baby is monitored by ultrasound and a CTG (recording of the hart tones of the baby). The women are compared with a control group of healthy women and women who have fever that is not caused by malaria.
Another aspect of this project is the effects of malaria on the birth weight in Rwanda It is known that malaria has an effect on the birth weight in countries where very high levels of  malaria is present. In Rwanda there has been a decline in malaria over the past years and the amount of malaria differs greatly in the different regions of the country. A study in the birth registers and national malaria data showed that malaria does not have the same effect on pregnancy outcome in Rwanda as is found in other African countries.

PhD student Stephen Rulisa expects to defend his thesis on malaria in pregnancy in Rwanda in 2013

Publications that have arisen form this project are:

• Rulisa S., Kaligirwa N., Agaba S., Karangayire P., Karangwa JB, Vyankandondera J., Mens P.F., de Vries P.J. (2012) Fetal and maternal hemodynamics in acute malaria: persistent maternal tachycardia after recovery from malaria. International Journal of Gynecology and Obstetrics 119: 66-69
• Rulisa S., Kaligirwa N., Agaba S., Karema C., Mens P.F., de Vries P.J. (2012) Pharmacovigilance of artemether-lumefantrine in pregnant women followed up till delivery in Rwanda. Malaria Journal  11:225
• Rulisa S., Mens P.F., Karema C., Schallig H.D.F.H., Kaligirwa N., Vyankandondera J., de Vries P.J. (2009) Malaria has no effect on birth weight in Rwanda. Malaria Journal 8:194

Malaria in pregnancy in Nigeria (Malaria no More)
2008-2010
Many pregnant women in countries where malaria exists do not know of the dangers of the disease. Most of them know the disease since they experienced it often but do not know the additional effects of malaria during their pregnancy. This is also true for the women in Nigeria. In this project the Parasitology Unit collaborated with the University of Benin City in Edo State, Nigeria to investigate the knowledge, behavior and subsequent actions of pregnant women with respect to malaria. This was done with validated questionnaires. In the second phase of the study groups of women were educated on the dangers of malaria in pregnancy and were trained to become peer educators, The effects of this method of education was evaluated by doing a second round of questionnaires. Although the study showed that peer education was an effective method to increase the level of education on malaria in pregnancy in the area it did not lead to direct behavioural changes. The study showed that targeted interventions should not only look at education but also invest in active behavioral change. 

• Mens P.F. Scheelbeek P., Altabbi H, Enato E.O. (2011) Peer education: The effects on knowledge, of pregnancy related malaria and preventive practice in women of reproductive age in Edo-State, Nigeria. BMC Public Health 11:e610
• Enato, E.F.O, Mens, PF., Okhamafe, A.O., Okpere, E.E., Schallig, H.D.F.H. & Pogoson, E. (2009). Plasmodium falciparum malaria in pregnancy: Prevalence of peripheral parasitaemia, anaemia, and malaria care seeking behaviour among pregnant women attending antenatal clinic in Edo State, Nigeria. Journal of Obstetrics and Gynaecology 29:301-306

Other publications from KIT-BR on Malaria in Pregnancy

• Mens P.F, Bojtor E.C., Schallig H.D.F.H. (2010) Molecular interactions in the placenta during malaria infection. Review. European Journal of Obstetrics & Gynecology and Reproductive Biology  152:126-132