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In sub-Saharan Africa, human immunodeficiency virus (HIV) and malaria are among the leading causes of morbidity during pregnancy. We reviewed available information collected since the first report 15 years ago that HIV impaired the ability of pregnant women to control malaria parasitemia. Results from 11 studies showed that HIV-infected women experienced consistently more peripheral and placental malaria (summary relative risk = 1.58 and 1.66, respectively), higher parasite densities, and more febrile illnesses, severe anemia, and adverse birth outcomes than HIV-uninfected women, particularly in multigravidae. Thus, HIV alters the typical gravidity-specific pattern of malaria risk by shifting the burden from primarily primigravidae and secundigravidae to all pregnant women. The proportional increase of malaria during pregnancy attributable to HIV was estimated to be 5.5% and 18.8% for populations with HIV prevalences of 10% and 40%, respectively. Maternal malaria was associated with a two-fold higher HIV-1 viral concentrations. Three studies investigating whether placental malaria increased mother-to-child HIV-1 transmission showed conflicting results, possibly reflecting a complex balance between placental malarial immune responses and stimulation of HIV-1 viral replication. Further investigations of interactions between antiretroviral drugs, prophylaxis with cotrimoxazole, and antimalarial drugs in pregnant women are urgently needed. Although much has been learned in the past 15 years about the interaction between malaria and HIV-1 during pregnancy, many issues still require further information to improve our understanding. There is a clear need to strengthen the deployment of existing malaria and HIV prevention and intervention measures for pregnant women.
Received January 12, 2004. Accepted for publication February 27, 2004.
Acknowledgments: We thank the many colleagues that contributed to these ideas, discussion, and field studies. We are particularly grateful to the following colleagues for providing details or unpublished results for this review: Dr. Steven Meshnick (University of North Carolina, Chapel Hill, NC); Dr. Victor Mwapasa (College of Medicine, Blantyre, Malawi and University of Michigan, Ann Arbor, MI); and Dr. Ingrid Inion and Professor Marleen Temmerman (University of Ghent, Ghent, Belgium).
Financial support: Feiko O. ter Kuile is grateful to Roll Back Malaria/World Health Organization and the Centers for Disease Control and Prevention for support as part of a collaboration between the Liver-pool School of Tropical Medicine and the Malaria Branch of the Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Francine H. Verhoeff was supported by funds from PREgnancy Malaria and Anemia European Union (PREMA-EU), which received financial support from the European Commission Research Directorate Fifth Framework Program (contract no PREMA-EU-ICA4-CT4-2001-10012). Stephen J. Rogerson is supported by the Wellcome Trust, United Kingdom, through an Overseas Senior Research Fellowship. Anne M. van Eijk is supported by the Oak Ridge Institute for Science and Education, Tennessee.
Disclaimer: Use of trade names is for identification only and does not imply endorsement by U.S. Public Health Service or Department of Health and Human Services.
Authors’ addresses: Feiko O. ter Kuile and Francine H. Verhoeff, Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, United Kingdom, E-mail: terkuile{at}liv.ac.uk. Monica E. Parise, Venkatachalam Udhayakumar, Robert D. Newman, and Richard W. Steketee, Malaria Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Mail-stop F-22, 4770 Buford Highway, Chamblee, Atlanta GA 30341. Anne M. van Eijk, Kenya Medical Research Institute, Vector Biology and Control Research Centre, PO Box 1578, Kisumu, Kenya. Stephen J. Rogerson, Department of Medicine (Royal Melbourne Hospital/Western Hospital), University of Melbourne, Post Office, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
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