A randomized trial reported by Alassane Dicko and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes by insecticide-treated bednets provides substantial protection from malaria.
BackgroundMaternal malaria is a tropical scourge associated with poor pregnancy outcomes. Women become resistant to Plasmodium falciparum pregnancy malaria as they acquire antibodies to the variant surface antigen VAR2CSA, a leading vaccine candidate. Because malaria infection may increase VAR2CSA antibody levels and thereby confound analyses of immune protection, gravidity-dependent changes in antibody levels during and after infection, and the effect of VAR2CSA antibodies on pregnancy outcomes were evaluated.MethodsPregnant women enrolled in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali provided plasma samples at enrollment, gestational week 30–32, and delivery. Antibody levels to VAR2CSA domains were measured using a multiplex bead-based assay.ResultsAntibody levels to VAR2CSA were higher in multigravidae than primigravidae. Malaria infection was associated with increased antibody levels to VAR2CSA domains. In primigravidae but not in secundigravidae or multigravidae, antibodies levels sharply declined after an infection. A relationship between any VAR2CSA antibody specificity and protection from adverse pregnancy outcomes was not detected.ConclusionsDuring malaria infection, primigravidae acquire short-lived antibodies. The lack of an association between VAR2CSA domain antibody reactivity and improved pregnancy outcomes suggests that the recombinant proteins may not present native epitopes targeted by protective antibodies.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2258-9) contains supplementary material, which is available to authorized users.
Background
In malaria-endemic areas, pregnant women and especially first-time mothers are more susceptible to Plasmodium falciparum. Malaria diagnosis is often missed during pregnancy, since many women with placental malaria remain asymptomatic or have submicroscopic parasitemia, masking the association between malaria and pregnancy outcomes Severe maternal anemia and low birthweight deliveries are well-established sequelae, but few studies have confirmed the relationship between malaria infection and severe outcomes like perinatal mortality in high transmission zones.
Methods
Pregnant women of any gestational age enrolled at antenatal clinic into a longitudinal cohort study in Ouelessebougou, Mali, an area of high seasonal malaria transmission. Follow-up visits included scheduled and unscheduled visits throughout pregnancy. Blood smear microscopy and PCR analysis were employed to detect both microscopic and submicroscopic infections, respectively. Intermittent preventative treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) was documented and prompt treatment regardless of symptoms given upon malaria diagnosis.
Results
Of the 1850 women followed through delivery, 72.6% of women received 2 or more IPTp-SP doses, 67.2% of women experienced at least one infection between enrollment up to and including delivery. Malaria infection increased the risks of stillbirth (adjusted-hazard ratio (aHR) 3.87, 95%CI 1.18-12.71) and preterm delivery (aHR 2.41, 95%CI 1.35-4.29) in primigravidae, and early neonatal death (death within 7 days) in secundigravidae and multigravidae (HR 6.30, 95%CI 1.41-28.15).
Conclusions
Malaria treatment after diagnosis, alongside IPTp-SP, is insufficient to prevent malaria-related stillbirth, early neonatal death and PTD. While IPTp-SP was beneficial in Mali during the study period, new tools are needed to improve pregnancy outcomes.
BackgroundIntermittent preventive treatment of malaria in children (IPTc) is a promising strategy for malaria control. A study conducted in Mali in 2008 showed that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe malaria and malaria infection by >80% in children under 5 years of age. Here we report the results of a follow-on study undertaken to establish whether children who had received IPTc would be at increased risk of malaria during the subsequent malaria transmission season.MethodsMorbidity from malaria and the prevalence of malaria parasitaemia and anaemia were measured in children who had previously received IPTc with SP and AQ using similar surveillance methods to those employed during the previous intervention period.Results1396 of 1508 children (93%) who had previously received IPTc and 1406 of 1508 children (93%) who had previously received placebos were followed up during the high malaria transmission season of the year following the intervention. Incidence rates of clinical malaria during the post-intervention transmission season (July –November 2009) were 1.87 (95% CI 1.76 –1.99) and 1.73 (95% CI; 1.62–1.85) episodes per child year in the previous intervention and placebo groups respectively; incidence rate ratio (IRR) 1.09 (95% CI 0.99 –1.21) (P = 0.08). The prevalence of malaria infection was similar in the two groups, 7.4% versus 7.5%, prevalence ratio (PR) of 0.99 (95% CI 0.73–1.33) (P = 0.95). At the end of post-intervention malaria transmission season, the prevalence of anaemia, defined as a haemoglobin concentration<11g/dL, was similar in the two groups (56.2% versus 55.6%; PR = 1.01 [95% CI 0.91 – 1.12]) (P = 0.84).ConclusionIPTc with SP+AQ was not associated with an increase in incidence of malaria episodes, prevalence of malaria infection or anaemia in the subsequent malaria transmission season.Trial RegistrationClinicalTrials.gov NCT00738946
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