A COMPARISON OF SULFADOXINE-PYRIMETHAMINE WITH CHLOROQUINE AND PYRIMETHAMINE FOR PREVENTION OF MALARIA IN PREGNANT NIGERIAN WOMEN IBRAHIM U. TUKUR, TOM D. THACHER,* ATIENE S. SAGAY, AND JEREMIAH K. A. MADAKI Departments of Family Medicine, and Obstetrics and Gynaecology, Jos University Teaching Hospital, Jos, Nigeria Abstract. Few studies have documented the effectiveness in west Africa of intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine (SP) in pregnancy. Pregnant Nigerian women were assigned to receive either SP given twice or presumptive chloroquine (CQ) treatment followed by weekly pyrimethamine (CQ + P); 250 were enrolled in each group. Of those completing follow-up, 4 (1.8%) in the SP group and 22 (9.8%) in the CQ + P groups had a febrile illness (P  0.005). None in the SP group but 11 (4.9%) in the CQ + P group had peripheral parasitemia prior to or during delivery (P  0.002). Two (1.2%) in the SP group and 9 (5.0%) in the CQ + P group were anemic at delivery (P  0.04). There were six low birth weight infants in the SP group and eight in the CQ + P group (P  0.21). Intermittent preventive treatment with SP is superior to CQ + P for prevention of malaria and anemia in pregnant women in Nigeria. INTRODUCTION Because the placenta is a site of preferential parasite se- questration and development, pregnant women have in- creased susceptibility to Plasmodium falciparum infection, with more frequent episodes of malaria and higher density of parasitemia than non-pregnant women. 1 This increased sus- ceptibility is particularly evident in the first pregnancy and appears to decrease with subsequent pregnancies. Malaria in- fection during pregnancy increases the risk of maternal ane- mia, maternal mortality, abortion, prematurity, intrauterine growth retardation, intrauterine death, and low birth weight. 2–4 Low birth weight is the greatest risk factor for neonatal mortality. In Nigeria, malaria accounts for up to 11% of maternal deaths. 5 Malaria is one of the few conditions that cause low birth weight that is amenable to intervention during pregnancy. Given the adverse effects of malarial in- fection during pregnancy, pregnant women residing in ma- laria-endemic regions have been targeted for antimalarial prophylaxis. 6 Intermittent preventive treatment (IPT) for malaria with sulfadoxine-pyrimethamine (SP) has been recommended for pregnant women living in malaria-endemic areas where P. falciparum is resistant to chloroquine (CQ) and sensitive to SP. 7–9 Intermittent preventive treatment with SP has been rapidly adopted in west Africa, despite the paucity of infor- mation on its effectiveness in the region. 10 Use of SP for IPT has been most extensively evaluated in east Africa. However, similar data are lacking from west Africa, where antimalarial drug resistance is not as widespread and infection with human immunodeficiency virus (HIV) is less prevalent. 11 Infection with HIV appears to interfere with the maintenance of ma- larial immunity acquired during infection in the first preg- nancy, 12,13 and heavy placental malaria infection increases the risk of perinatal mother-to-child transmission of HIV. 14 Emergence of CQ resistance in Nigeria 15,16 and problems of compliance have limited the effectiveness of weekly chemoprophylaxis with CQ. Weekly pyrimethamine is still widely used in antenatal clinics throughout Nigeria. 17 Pre- sumptive treatment with CQ followed by weekly pyrimeth- amine (CQ + P) was standard practice at the time this study was conducted. Chemoprophylaxis with CQ during preg- nancy may have a protective effect, even in certain areas where chloroquine-resistant P. falciparum is endemic and residents have partial immunity. 18 A recent report of the Dis- ease Control Priorities Project estimated that IPT with CQ was more cost-effective than with SP. 19 No study has demonstrated the superiority of IPT with SP over CQ + P in pregnant women in Nigeria, the most popu- lated nation in Africa. We conducted a controlled trial to compare presumptive CQ treatment followed by weekly pyrimethamine (CQ + P) with IPT with SP. METHODS We hypothesized that SP would be more effective than CQ + P in preventing malaria in pregnancy among Nigerian women. The primary outcomes were episodes of acute un- complicated or severe malaria during pregnancy, infants born with congenital malaria parasitemia, and infants with low birth weight. Enrollment. The study was conducted from April to De- cember 2002 in Jos, Nigeria, an urban center located in north- central Nigeria. Malaria is endemic and transmission occurs throughout the year with greater transmission during the rainy season from May to October. Consequently, most adults have partial immunity to malaria. We offered enrollment to pregnant women who came to Jos University Teaching Hospital for antenatal care between 12 and 28 weeks of gestation and who intended to deliver at the teaching hospital. Women were excluded from the study if they were currently using malaria prophylaxis, had a history of allergies to sulfa drugs or intolerance to CQ, or had sickle cell disease. The ethical committee of Jos University Teach- ing Hospital reviewed and approved the study, and written informed consent was obtained from all subjects. Women were alternately assigned to receive CQ + P or SP. Women in the CQ + P group were presumptively treated with CQ, 600 mg base on days one and two, followed by 300 mg base on day 3. This was followed by weekly pyrimethamine, * Address correspondence to Tom D. Thacher, Department of Fam- ily Medicine, Jos University Teaching Hospital, Jos, Nigeria. E-mail: tom@thachers.org Am. J. Trop. Med. Hyg., 76(6), 2007, pp. 1019–1023 Copyright © 2007 by The American Society of Tropical Medicine and Hygiene 1019