Plasmodium falciparum malaria in pregnancy predisposes to maternal and foetal morbidity. In 1993 Malawi adopted intermittent presumptive therapy with sulfadoxine-pyrimethamine (SP) as malaria prophylaxis for all pregnant women. To assess operational effectiveness of SP, we examined (in 1997-99) the relationship between number of doses of SP prescribed in antenatal clinic and indicators of malaria infection and morbidity at delivery, including peripheral and placental parasitaemia, maternal and neonatal anaemia, and birthweight. Among Malawian women delivering in a large urban hospital, SP prescription was associated with a decrease in placental malaria prevalence (from 31.9% with no SP prescription to 22.8% with > or = 2 doses SP) and density, decreased prevalence of low birthweight (from 23% in women not receiving SP to 10.3% in women given > or = 2 doses), and higher maternal haemoglobin concentrations. These effects were most marked in first and second pregnancies, in which malaria prevalence was highest. Maternal and cord blood malaria prevalence and mean cord blood haemoglobin concentrations did not differ with SP usage. Implementation of the SP administration policy was incomplete: 24% of women were not prescribed any SP, and only 30% were prescribed at least 2 doses as recommended. Intermittent presumptive treatment with SP is having a positive impact on some, but not all indicators of malaria infection and morbidity in Malawi. Improved implementation and continued surveillance are essential.
Background
Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial.
Methods
Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus–uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted.
Results
Among 1222 parasitemic pregnant women, overall polymerase chain reaction–uncorrected and –corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69–.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67–.97; P = .02).
Conclusions
The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.
Placental malaria infection is associated with an increase in peripheral and placental HIV-1 viral load, which might increase the risk of mother-to-child transmission of HIV.
Maternal syphilis is associated with IU and IP/PP HIV MTCT. Screening and early treatment of maternal syphilis during pregnancy may reduce pediatric HIV infections.
Abstract. Malaria and anemia are common in pregnant African women. We screened 4,764 Malawian women at first antenatal visits for malaria and anemia. A total of 42.7% had a malaria infection, which was more common and of higher density in primigravidae (prevalence ϭ 47.3%, geometric mean ϭ 332 parasites/l) and teenagers (49.8%, 390/1) than in multigravidae (40.4%, 214/l) or older women (40.6%, 227/l). However, 35% of gravida 3ϩ women were parasitemic. A total of 57.2% of the women was anemic (hemoglobin Ͻ 11 g/dl), with moderate anemia (7.0-8.9 g/dl) in 14.9% and severe anemia (Ͻ 7 g/dl) in 3.2%. Prevalences of malaria and anemia were highest in the rainy season. Women with moderate/severe anemia had higher parasite prevalences and densities than women with mild/no anemia. Logistic regression showed that age, season, and trimester of presentation were significantly associated with the prevalence of malaria, but gravidity was not. In this urban setting, age and season are more important than gravidity as predictors of malaria at first antenatal visit, and parasitemia is frequent in women of all gravidities.
BackgroundThe World Health Organization recommends insecticidal bednets and intermittent preventive treatment to reduce malaria in pregnancy. Longitudinal data of malaria prevalence and pregnancy outcomes are valuable in gauging the impact of these antimalarial interventions.Methodology/Principal FindingsWe recruited 8,131 women delivering in a single Malawian hospital over 9 years. We recorded demographic data, antenatal prescription of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine and bed net use, and examined finger-prick blood for malaria parasites and hemoglobin concentration. In 4,712 women, we examined placental blood for malaria parasites and recorded the infant's birth weight. Peripheral and placental parasitemia prevalence declined from 23.5% to 5.0% and from 25.2% to 6.8% respectively. Smaller declines in prevalence of low birth weight and anemia were observed. Coverage of intermittent preventive treatment and bednets increased. Number of sulfadoxine-pyrimethamine doses received correlated inversely with placental parasitemia (Odds Ratio (95% CI): 0.79 (0.68, 0.91)), maternal anemia (0.81, (0.73, 0.90)) and low birth weight from 1997–2001 (0.63 (0.53, 0.75)), but not from 2002–2006. Bednet use protected from peripheral parasitemia (0.47, (0.37, 0.60)) and placental parasitemia (0.41, (0.31, 0.54)) and low birth weight (0.75 (0.59, 0.95)) but not anemia throughout the study. Compared to women without nets who did not receive 2-dose sulfadoxine-pyrimethamine, women using nets and receiving 2-dose sulfadoxine-pyrimethamine were less likely to have parasitemia or low birth weight babies. Women receiving 2-dose sulfadoxine-pyrimethamine alone had little evidence of protection whereas bednets alone gave intermediate protection.Conclusions/SignificanceIncreased bednet coverage explains changes in parasitemia and birth weight among pregnant women better than sulfadoxine-pyrimethamine use. High bed net coverage, and sulfadoxine-pyrimethamine resistance, may be contributing to its apparent loss of effectiveness.
IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.
We conducted a prevalence study of mutations in Plasmodium falciparum that are associated with antifolate resistance in Blantyre, Malawi. The dihydrofolate reductase 164-Leu mutation, which confers resistance to both pyrimethamine and chlorproguanil, was found in 4.7% of the samples. Previously unreported mutations in dihydropteroate synthase were also found.
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