Malaria is a cause of iron deficiency in African children.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria, as an instrumental variable in Mendelian randomization analyses.

Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria.

Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites, we identify P.

Impact of maternally derived antibodies to Plasmodium falciparum Schizont Egress Antigen-1 on the endogenous production of anti-PfSEA-1 in offspring.

Background: We evaluated whether maternally-derived antibodies to a malarial vaccine candidate, Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), in cord blood interfered with the development of infant anti-PfSEA-1 antibodies in response to natural exposure.

Methods: We followed 630 Tanzanian infants who were measured their antibodies against PfSEA-1 (aa 810-1023; PfSEA-1A) at birth and 6, 12, 18, and 24 months of age, and examined the changes in anti-PfSEA-1A antibody levels in response to parasitemia, and evaluated whether maternally-derived anti-PfSEA-1A antibodies in cord blood modified infant anti-PfSEA-1A immune responses.

Results: Infants who experienced parasitemia during the first 6 months of life had significantly higher anti-PfSEA-1A antibodies at 6 and 12 months of age compared to uninfected infants.

Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.

Background: In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive.

Methods: We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania.

Developing a novel risk prediction model for severe malarial anemia.

As a pilot study to investigate whether personalized medicine approaches could have value for the reduction of malaria-related mortality in young children, we evaluated questionnaire and biomarker data collected from the Mother Offspring Malaria Study Project birth cohort (Muheza, Tanzania, 2002-2006) at the time of delivery as potential prognostic markers for pediatric severe malarial anemia. Severe malarial anemia, defined here as a infection accompanied by hemoglobin levels below 50 g/L, is a key manifestation of life-threatening malaria in high transmission regions. For this study sample, a prediction model incorporating cord blood levels of interleukin-1β provided the strongest discrimination of severe malarial anemia risk with a C-index of 0.

A Malaria-Resistant Phenotype with Immunological Correlates in a Tanzanian Birth Cohort Exposed to Intense Malaria Transmission.

AbstractMalaria incidence is highly heterogeneous even in areas of high transmission, although no conclusive evidence exists that innate or naturally acquired resistance can prevent infection over an extended period of time. This longitudinal study examined immunoparasitological evidence for a malaria-resistant phenotype in which children do not develop malaria despite an extended period of exposure to parasites. Within a birth cohort followed from 2002 to 2006 in Muheza, Tanzania, an area of intense transmission, children ( = 687) provided blood smears biweekly during infancy and monthly thereafter.

Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study.

Hepcidin, the master regulator of bioavailable iron, is a key mediator of anemia and also plays a central role in host defense against infection. We hypothesized that measuring hepcidin levels in cord blood could provide an early indication of interindividual differences in iron regulation with quantifiable implications for anemia, malaria, and mortality-related risk. Hepcidin concentrations were measured in cord plasma from a birth cohort (N = 710), which was followed for up to 4 years in a region of perennial malaria transmission in Muheza, Tanzania (2002-2006).

Preparing for future efficacy trials of severe malaria vaccines.

Severe malaria is a major cause of mortality in children, but comprises only a small proportion of Plasmodium falciparum infections in naturally exposed populations. The evaluation of vaccines that prevent severe falciparum disease will require clinical trials whose primary efficacy endpoint will be severe malaria risk during follow-up. Here, we show that such trials are feasible with fewer than 1000 participants in areas with intense malaria transmission during the age interval when severe malaria incidence peaks.

Fetal origins of malarial disease: cord blood cytokines as risk markers for pediatric severe malarial anemia.

Background: Severe malarial anemia (SMA) remains a major cause of pediatric illness and mortality in Sub-Saharan Africa. Here we test the hypothesis that prenatal exposures, reflected by soluble inflammatory mediators in cord blood, can condition an individual's susceptibility to SMA.

Methods: In a Tanzanian birth cohort (n = 743), we measured cord blood concentrations of tumor necrosis factor (TNF), TNF receptors I and II (TNF-RI and TNF-RII), interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-10, and interferon gamma (IFN-γ).

Parasite burden and severity of malaria in Tanzanian children.

Background: Severe Plasmodium falciparum malaria is a major cause of death in children. The contribution of the parasite burden to the pathogenesis of severe malaria has been controversial.

Methods: We documented P.

Cytokine profiles at birth predict malaria severity during infancy.

Background: Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood.

Methods And Findings: Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6 and IL-10) were measured at birth (cord blood; N=783) and during subsequent routine follow-up visits (peripheral blood) for children enrolled between 2002 and 2006 into a birth cohort in Muheza, Tanzania.

Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia.

Background: Levels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. It remains unclear whether CrP changes seen during malaria contribute to the development of anaemia, or result from an altered RBC age distribution due to suppressive effects of malaria on erythropoiesis.

Methods: A cross sectional study was conducted in the north-east coast of Tanzania to investigate whether the changes in glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins (CD55 and CD59) contributes to malaria anaemia.

Azithromycin plus artesunate versus artemether-lumefantrine for treatment of uncomplicated malaria in Tanzanian children: a randomized, controlled trial.

Background: Acute febrile illness is the most common cause of outpatient attendance and mortality for children in Africa. Malaria and bacterial disease are difficult to differentiate with limited diagnostic facilities. Combinations of antibiotics and antimalarials are potentially attractive for treatment of the syndrome.