Trends in Parasitology
Volume 20, Issue 9, September 2004, Pages 425-432
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Malaria in pregnancy and the endemicity spectrum: what can we learn?

https://doi.org/10.1016/j.pt.2004.06.007Get rights and content

The increased susceptibility of pregnant women to malaria infection has long been recognized, but the magnitude of the disease burden in this particular group, together with the pathophysiology of maternal malaria and the specific difficulties in treatment, have only recently been the focus of research. Most research on maternal malaria has derived from sub-Saharan Africa where transmission is high, whereas most of the studies on the treatment of malaria and the effect of non-falciparum species has been conducted in low-transmission areas of Asia. In this paper, we attempt to improve our understanding of the disease and its mechanisms from observed differences and similarities between contrasting areas of transmission, and to identify priorities for future research.

Section snippets

Plasmodium falciparum

In all endemic areas, women are at higher risk of malaria and are more susceptible to infection when pregnant than either before or after pregnancy, or when compared with adult males [4]. Pregnant women are more likely to be bitten by important malaria vectors [5]. Pregnant women with malaria in high-transmission areas are less often symptomatic than those in low-transmission areas [6] and, in a study from Asia, women who lived their childhood in a malaria-endemic area were at reduced risk of

Therapy and prophylaxis

For decades, chloroquine prophylaxis was recommended during pregnancy. When P. falciparum was fully sensitive to the drug, a pregnant woman with good adherence to this regimen would be free of parasites during her pregnancy. This is no longer achievable because of the spread of chloroquine resistance. In Thailand, where chloroquine resistance emerged first, aggressive case detection and management were substituted. Infected pregnant women were treated with sulfadoxine–pyrimethamine [SP] or

Placental malaria

When discussing differences in the pathological and immunological features of malaria in pregnancy in areas of high- and low-transmission, several issues must be considered. Pre-existing immunity to malaria may be considerably lower in areas of low transmission, and P. vivax is also endemic in many areas where transmission is low (e.g. India, South America, parts of Southeast Asia) and in some areas of high transmission (e.g. Papua New Guinea and Vanuatu). Inter-species interactions must be

Placental pathology

Most studies of the placental pathology of P. falciparum have been in African women. Characteristic features of placental pathology include the accumulation of parasite-infected erythrocytes, deposition of malaria pigment (haemozoin), fibrinoid deposits, areas of necrosis and inflammatory cell infiltrates (for a recent review on placental malaria see Ref. [41]). Pigmented macrophage infiltrates in the intervillous space are frequently observed in Africa 42, 43, and are associated with anaemia.

Placental malaria and pregnancy outcome

LBW is a composite of FGR and PTD. Placental histology and pathogenesis differ between these groups 29, 48. Dense placental monocyte infiltrates (termed massive chronic intervillositis [43]) are most common in primigravidae, and have been associated with LBW caused by FGR 8, 29. Massive chronic intervillositis frequently occurs with acute infections in African primigravidae but is rare in Thailand, where it is also associated with first pregnancy [47]. Further studies from Asia and Oceania will

Parasite characteristics and mechanisms of placental infection/sequestration

Plasmodium falciparum-infected erythrocytes (IEs) can undergo antigenic variation, by switching expression of variant surface antigens (VSAs), which thereby facilitates immune evasion. In addition, IEs can adhere to endothelial and vascular cells, mediating sequestration of parasites in various organs [53]. In pregnancy, a combination of selection for adhesion in the placenta and immune selective pressure appears to drive the emergence of novel parasite phenotypes. In settings of different

Immune responses

Antibodies to CSA-binding IEs and novel VSAs expressed by placental parasites are acquired in association with exposure to malaria in pregnancy 54, 55, 56, 58, 64. Results from one study suggest that the acquisition of antibodies that inhibit CSA adhesion relate to transmission intensity, comparing women in Thailand and Kenya [54]. Differences in methods and parasite isolates used make it difficult to draw direct comparisons between different studies. The proportion of pregnant women at term in

Concluding comments

This paper is an attempt to understand malaria in pregnancy more clearly (or at least to identify the important questions), by comparing the disease at the two extremes of the endemicity spectrum. However, the exercise has numerous limitations. The difference in endemicity is not the sole factor influencing the relationship between the (pregnant) host and the parasite: ethnicity, economic development, HIV incidence and parasite-related factors are all important. There is a great shortage of

Acknowledgements

The authors are grateful to B. Cooke for his encouragements to write this review. F.N. is a Wellcome Career Fellow in Clinical Tropical Medicine. S.J.R. is supported by a Senior Overseas Fellowship from the Wellcome Trust, and by the National Health and Medical Research Council of Australia. J.G.B. is supported by a National Health and Medical Research Council Training Award.

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