Although antischistosomal properties of peroxides were studied in recent years, systematic structure-activity relationships have not been conducted. We evaluated the antischistosomal potential of 64 peroxides belonging to bridged 1,2,4,5-tetraoxanes, alphaperoxides, and tricyclic monoperoxides. Thirty-nine compounds presented IC₅₀ values <15 μM on newly transformed schistosomula. Active drugs featured phenyl-, adamantane-, or alkyl residues at the methylene bridge. Lower susceptibility was documented on adult schistosomes, with most hit compounds being tricyclic monoperoxides (IC₅₀: 7.7-13.4 μM). A bridged 1,2,4,5-tetraoxane characterized by an adamantane residue showed the highest activity (IC₅₀: 0.3 μM) on adult Schistosoma mansoni . Studies with hemin and heme supplemented medium indicated that antischistosomal activation of peroxides is not necessarily triggered by iron porphyrins. Two compounds (tricyclic monoperoxide; bridged 1,2,4,5-tetraoxane) revealed high worm burden reductions in the chronic (WBR: 75.4-82.8%) but only moderate activity in the juvenile (WBR: 18.9-43.1%) S. mansoni mouse model. Our results might serve as starting point for the preparation and evaluation of related derivatives.

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a 9-month cluster-randomized controlled trial conducted in south-central Côte d’Ivoire. 378 children aged 12–36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (ID; PF < 30 μg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44–66%, and 57–76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on ID with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).

The study was conducted to assess infection intensity and morbidity due to Schistosoma mansoni in schoolchildren on Ukerewe Island in Lake Victoria, Tanzania, East Africa. Three hundred and sixty pupils who have never been treated previously were enrolled (180 males/180 females, age 6-17 years [median 10 years]) in three different schools of the island. Double stool samples were collected from each pupil and egg excretion was classified according to WHO recommendations. Ultrasound investigations were performed in accordance with the WHO Niamey-Belo-Horizonte protocol. Male (112/180, 62.2%) and female (104/180; 57.7%) pupils were infected (difference, not significant [n.s.]). In the positive 216 cases, egg excretion varied from 1 to 2,440 eggs per gramme stool (epg) [median 165 epg]. There were 69/216 (31.9%) who had a low grade, 105/216 (53.2%) had a moderate and 42/216 (14.8%) had a heavy infection. There was no significant difference between male and female sex nor with regard to age groups. There were 354/360 children who underwent sonography: 321 (90.7%) had splenomegaly, 316 (89.3%) showed a left lobe and 109 (30.9%) had a right lobe hepatomegaly. Overt signs of portal fibrosis (PF) were present in 19 children (5.4%) out of whom 11 presented with echogenic thickening of peripheral portal and 8 with thickening of central portal branches. Non-specific portal wall changes were seen in 6 children (1.7%). Association of PF to quantitative egg excretion was not seen (median in PF, 172 epg vs. median in non PF, 168 epg; difference, n.s.). Portal vein dilatation was seen in 101/354 (28.5%) cases. In Ukerewe, the prevalence of S. mansoni infection and infection intensity in children is high, yet overt hepatic morbidity is low as compared to other endemic foci. Non-specific ultrasonographic abnormalities including hepatosplenomegaly and portal vein dilatation were seen frequently but the fraction attributable to schistosomiasis is difficult to assess.

BackgroundInsecticides targeting adult mosquitoes are the main way of controlling malaria. They work not only by killing mosquitoes, but also by repelling and irritating them. Indeed their repellent action gives valuable personal protection against biting mosquitoes. In the context of malaria control this personal protection is especially relevant when mosquitoes are infectious, whereas to protect the community we would prefer that the mosquitoes that are not yet infectious are killed (so, not repelled) by the insecticide. As the infectious stage of malaria parasites increases the motivation of mosquitoes to bite, we predicted that it would also change their behavioural response to insecticides.ResultsWith two systems, a laboratory isolate of the rodent malaria Plasmodium berghei infecting Anopheles gambiae and several isolates of P. falciparum obtained from schoolchildren in Tanzania that infected Anopheles arabiensis, we found that mosquitoes harbouring the infectious stage (the sporozoites) of the parasite were less repelled by permethrin-treated nets than uninfected ones.ConclusionsOur results suggest that, at least in the laboratory, malaria infection decreases the personal protection offered by insecticide-treated nets at the stage where the personal protection is most valuable. Further studies must investigate whether these results hold true in the field and whether the less effective personal protection can be balanced by increased community protection.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2846-0) contains supplementary material, which is available to authorized users.