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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.

The relationship of anemia as a risk factor for child mortality was analyzed by using cross-sectional, longitudinal and case-control studies, and randomized trials. Five methods of estimation were adopted: 1) the proportion of child deaths attributable to anemia; 2) the proportion of anemic children who die in hospital studies; 3) the population-attributable risk of child mortality due to anemia; 4) survival analyses of mortality in anemic children; and 5) cause-specific anemia-related child mortality. Most of the data available were hospital based. For children aged 0-5 y the percentage of deaths due to anemia was comparable for reports from highly malarious areas in Africa (Sierra Leone 11.2%, Zaire 12.2%, Kenya 14.3%). Ten values available for hemoglobin values <50 g/L showed a variation in case fatality from 2 to 29.3%. The data suggested little if any dose-response relating increasing hemoglobin level (whether by mean value or selected cut-off values) with decreasing mortality. Although mortality was increased in anemic children with hemoglobin <50 g/L, the evidence for increased risk with less severe anemia was inconclusive. The wide variation for mortality with hemoglobin <50 g/L is related to methodological variation and places severe limits on causal inference; in view of this, it is premature to generate projections on population-attributable risk. A preliminary survival analysis of an infant cohort from Malawi indicated that if the hemoglobin decreases by 10 g/L at age 6 mo, the risk of dying becomes 1.72 times higher. Evidence from a number of studies suggests that mortality due to malarial severe anemia is greater than that due to iron-deficiency anemia. Data are scarce on anemia and child mortality from non-malarious regions. Primary prevention of iron-deficiency anemia and malaria in young children could have substantive effects on reducing child mortality from severe anemia in children living in malarious areas.

Aim-To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer. Methods-One hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunsorbent assay (ELISA). Results-Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively. No eVect was seen with tetanus toxoid antibody transfer. Conclusion-The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population.

Summaryobjectives To examine in pregnant women the relationship between HIV infection and malaria prevalence and to determine, in relation to HIV infection, the effectiveness of sulphadoxine-pyrimethamine in clearing P. falciparum infection.method Descriptive cross-sectional analysis of P. falciparum prevalence in pregnant women at first antenatal visit and of women at delivery who had received two sulphadoxine-pyrimethamine treatments for malaria. HIV status was assessed in 621 women who attended for antenatal care and for delivery at two rural hospitals in southern Malawi in 1993-94. Information was collected on maternal age, parity and gestational age. Prevalence of P. falciparum was measured at first antenatal visit and delivery. Women were given two routine treatment doses of sulphadoxine-pyrimethamine (SP), at first antenatal visit and between 28 and 34 weeks gestation, conforming to Malawi government policy on antimalarial control during pregnancy.results Prevalence of HIV infection was 25.6% and all infections were HIV type-1. In primigravidae malaria prevalence at recruitment was 56.3% in HIV-infected and 36.5% in HIV-uninfected women (P ϭ 0.04). The corresponding figures for multigravidae were 23.8% and 11.0%, respectively (P Ͻ 0.01). HIVinfected primigravidae had increased malaria prevalence at all gestational ages. Peak parasite prevalence occurred earlier in gestation in HIV-infected primigravidae (16-19 weeks if HIV-infected; 20-23 weeks if HIV-uninfected). The relative risk for parasitaemia in HIV-infected compared to HIV-uninfected women was significantly increased in three of five parity groups, including the two highest ones (parity Ͼ3), indicating parity-specific immunity to malaria was impaired. Malaria prevalence at delivery remained high in HIV-infected women despite prior routine treatment with sulphadoxine-pyrimethamine in pregnancy. There was no significant difference in parasite prevalence at delivery between women who did or did not use sulphadoxine-pyrimethamine.conclusions HIV infection is associated with a significant increase in malaria prevalence in pregnant women of all parities with the effect apparent from early in gestation. Two treatment doses of sulphadoxine-pyrimethamine were inadequate to clear parasitaemia in many women by the time of delivery and this occurred independently of HIV status and despite high sensitivity to SP in this area. There is a need to undertake longitudinal studies to determine the incidence of P. falciparum infection in HIV-infected and uninfected pregnant women and to reassess the frequency and timing of sulphadoxine-pyrimethamine treatment doses in these women. Late pregnancy re-infections with P. falciparum probably explain the high parasite prevalence at delivery following sulphadoxinepyrimethamine treatment at 28-34 weeks gestation. keywords pregnancy, malaria, HIV, antimalarial control, sulphadoxine-pyrimethamine correspondence Professor B.J. Brabin,

In this review we examine the available information on the safety of antimalarials in pregnancy, from both animal and human studies. The antimalarials that can be used in pregnancy include (1) chloroquine, (2) amodiaquine, (3) quinine, (4) azithromycin, (5) sulfadoxine-pyrimethamine, (6) mefloquine, (7) dapsone-chlorproguanil, (8) artemisinin derivatives, (9) atovaquone-proguanil and (10) lumefantrine. Antimalarial drugs that should not be used in pregnancy including (1) halofantrine, (2) tetracycline/doxycycline, and (3) primaquine. There are few studies in humans on the pharmacokinetics, safety and efficacy of antimalarials in pregnancy. This is because pregnant women are systematically excluded from clinical trials. The absence of adequate safety data, especially in the first trimester, is an important obstacle to developing treatment strategies. The pharmacokinetics of most antimalarial drugs are also modified in pregnancy and dosages will need to be adapted. Other factors, including HIV status, drug interactions with antiretrovirals, the influence of haematinics and host genetic polymorphisms may influence safety and efficacy. For these reasons there is an urgent need to assess the safety and efficacy of antimalarial treatments in pregnancy, including artemisinin based combination therapies.

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Objectives: The objective of this study was to compare growth, morbidity incidence and risk factors for undernutrition between infants receiving complementary feeding early, before 3 months of age, with those receiving complementary foods after 3 months in a poor rural Malawian community. Methods: A cohort of babies was enrolled at birth for follow-up to 12 months of age. Weight, length, morbidity and feeding patterns were recorded at 4 weekly intervals from birth to 52 weeks. Results: Mean age at introduction of water was 2.5 months (range 0-11.8), complementary foods 3.4 months (range, 1.0-10.7) and solids 4.5 months (range 1.2-13.8). Over 40% of infants had received complementary foods by 2 months and 65% by 3 months. The proportion of exclusively breast-fed infants, which included those receiving supplemental water, was 13% at 4 months, 6.3% at 5 months and 1.5% at 6 months. Infants with early complementary feeding had lower weight for age at 3 and 6 months (Po0.05), and at 9 months (P ¼ 0.07) and at 2 months they were approximately 200 g lighter. Early complementary feeding was significantly associated with increased risk for respiratory infection (Po0.05), and marginally increased risk for eye infection and episodes of malaria. Maternal illiteracy was associated with early complementary feeding (OR ¼ 2.1, 95% CI 1.3, 3.2), while later complementary feeding was associated with reduced infant morbidity and improved growth. Conclusion: Breast-feeding promotion programmes should target illiterate women. Greater emphasis is required to improve complementary feeding practices.