Malaria prevention in north-eastern Tanzania: patterns of expenditure and determinants of demand at the household level.

Objective. This study aims to provide a better understanding of the amounts spent on different malaria prevention products and the determinants of these expenditures. Methods. 1,601 households were interviewed about their expenditure on malaria mosquito nets in the past five years, net re-treatments in the past six months and other expenditures prevention in the past two weeks. Simple random sampling was used to select villages and streets while convenience sampling was used to select households. Expenditure was compared across bed nets, aerosols, coils, indoor spraying, using smoke, drinking herbs and cleaning outside environment. Findings. 68% of households owned at least one bed net and 27% had treated their nets in the past six months. 29% were unable to afford a net. Every fortnight, households spent an average of US $0.18 on nets and their treatment, constituting about 47% of total prevention expenditure. Sprays, repellents and coils made up 50% of total fortnightly expenditure (US$0.21). Factors positively related to expenditure were household wealth, years of education of household head, household head being married and rainy season. Poor quality roads and living in a rural area had a negative impact on expenditure. Conclusion. Expenditure on bed nets and on alternative malaria prevention products was comparable. Poor households living in rural areas spend significantly less on all forms of malaria prevention compared to their richer counterparts. Breaking the cycle between malaria and poverty is one of the biggest challenges facing malaria control programmes in Africa.

Determinants of bed net use in The Gambia: implications for malaria control

Malaria is still one of the biggest health threats in the developing world, with an estimated 300 million episodes per year and one million deaths, most of which are in sub-Saharan Africa. Although the efficacy and cost-effectiveness of treated bed nets has been widely reported, little is known about the range, strength, or interaction between different factors that influence their demand at the household level. This study modeled the determinants of bed net ownership as well as the factors that influence the number of bed nets purchased. Data was collected from 1,700 randomly selected households in the Farafenni region of The Gambia. Interviews were also held with 129 community spokespersons to explore the extent to which community level factors such as the quality of roads and access to market centers also influence demand for bed nets. The results of each model of demand and their policy implications are discussed.

Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria

Cerebral malaria is characterized by cytoadhesion of Plasmodium falciparum–infected red blood cells (Pf-iRBCs) to endothelial cells in the brain, disruption of the blood-brain barrier, and cerebral microhemorrhages. No available antimalarial drugs specifically target the endothelial disruptions underlying this complication, which is responsible for the majority of malaria-associated deaths. Here, we have demonstrated that ruptured Pf-iRBCs induce activation of β-catenin, leading to disruption of inter–endothelial cell junctions in human brain microvascular endothelial cells (HBMECs). Inhibition of β-catenin–induced TCF/LEF transcription in the nucleus of HBMECs prevented the disruption of endothelial junctions, confirming that β-catenin is a key mediator of P. falciparum adverse effects on endothelial integrity. Blockade of the angiotensin II type 1 receptor (AT1) or stimulation of the type 2 receptor (AT2) abrogated Pf-iRBC–induced activation of β-catenin and prevented the disruption of HBMEC monolayers. In a mouse model of cerebral malaria, modulation of angiotensin II receptors produced similar effects, leading to protection against cerebral malaria, reduced cerebral hemorrhages, and increased survival. In contrast, AT2-deficient mice were more susceptible to cerebral malaria. The interrelation of the β-catenin and the angiotensin II signaling pathways opens immediate host-targeted therapeutic possibilities for cerebral malaria and other diseases in which brain endothelial integrity is compromised.