Complications from falciparum malaria are responsible for over one million infant deaths annually. There is as yet no clinically protective vaccine that has been developed against human malaria parasites. While several studies have demonstrated the inhibitory properties of human sera against Plasmodium falciparum, there is no reported investigation that has examined the protective effects of human breastmilk against the malaria parasite. This study demonstrates the presence of significant antibody titers to ring, trophozoite, schizont and gametocyte stages of P. falciparum in 144 Nigerian maternal milk samples and also in paired maternal and infant sera. The study also demonstrates significant in vitro growth inhibition of P. falciparum by maternal and infant sera, but most notably by breastmilk samples and breastmilk constituents, such as lactoferrin and sIgA. The results therefore suggest a protective in vivo role for breastmilk in the possible modulation of malaria frequency, severity and complications.

Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high, at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patient clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO), and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate the host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.

BACKGROUND:Previous analyses derived the relative risk (RR) of dying as a result of low weight-for-age and calculated the proportion of child deaths worldwide attributable to underweight.

OBJECTIVES:The objectives were to examine whether the risk of dying because of underweight varies by cause of death and to estimate the fraction of deaths by cause attributable to underweight.

DESIGN:Data were obtained from investigators of 10 cohort studies with both weight-for-age category (<-3 SDs, -3 to<-2 SDs, -2 to<-1 SD, and>-1 SD) and cause of death information. All 10 studies contributed information on weight-for-age and risk of diarrhea, pneumonia, and all-cause mortality; however, only 6 studies contributed information on deaths because of measles, and only 3 studies contributed information on deaths because of malaria or fever. With use of weighted random effects models, we related the log mortality rate by cause and anthropometric status in each study to derive cause-specific RRs of dying because of undernutrition. Prevalences of each weight-for-age category were obtained from analyses of 310 national nutrition surveys. With use of the RR and prevalence information, we then calculated the fraction of deaths by cause attributable to undernutrition.

RESULTS:The RR of mortality because of low weight-for-age was elevated for each cause of death and for all-cause mortality. Overall, 52.5% of all deaths in young children were attributable to undernutrition, varying from 44.8% for deaths because of measles to 60.7% for deaths because of diarrhea.

CONCLUSION:A significant proportion of deaths in young children worldwide is attributable to low weight-for-age, and efforts to reduce malnutrition should be a policy priority.