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Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), remains fatal for 15–25% of affected children despite the availability of treatment. P. falciparum infects and multiplies in erythrocytes, contributing to anemia, parasite sequestration, and inflammation. An unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to study the complex mechanisms underlying CM. A significant down-regulation of proteins from the ubiquitin–proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) were associated with infected erythrocytes from CM patients. At the plasma level, the samples clustered according to clinical presentation. Significantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger cohort (n = 340). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroblasts and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers. Synopsis: A mass spectrometry-based proteomic screening of both plasma and infected erythrocytes from Beninese children with various clinical manifestations of malaria (Uncomplicated Malaria (UM), Severe Malarial Anemia (SMA), and Cerebral Malaria (CM)) was performed. An increase of TFRC abundance was observed in infected erythrocyte samples from CM patients when compared to UM patients, coupled with a decrease of plasmatic Transferrin levels. 20S proteasome abundance was increased in plasma from children with severe malaria (CM and SMA) compared to UM, suggesting that it could serve as potential biomarker of severe malaria. A deregulated iron metabolism pathway and an increased hemolytic anemia were described in the severe malaria groups. Six P. falciparum proteins involved in red blood cell invasion were quantified specifically in plasma samples from severe malaria cases. A mass spectrometry-based proteomic screening of both plasma and infected erythrocytes from Beninese children with various clinical manifestations of malaria (Uncomplicated malaria (UM), Severe Malarial Anemia (SMA), and Cerebral Malaria (CM)) was performed. [ABSTRACT FROM AUTHOR]

Summary: Background: According to the Developmental Origins of Health and Diseases concept, exposures in the preconception period may be critical. For the first time, we evaluated the effect of preconception poor anthropometric status on infant's growth in sub‐Saharan Africa. Methods: A mother‐child cohort was followed prospectively from preconception to 1 year old in Benin. Maternal anthropometric status was assessed by prepregnancy body mass index (BMI), approximated by BMI at the first antenatal visit before 7 weeks' gestation, and gestational weight gain (GWG). BMI was categorized as underweight, normal, overweight, and obesity according to World Health Organization standards. GWG was categorized as low (<7 kg), mild (7‐12 kg), and high (>12 kg). In infant, stunting and wasting were defined as length‐for‐age and weight‐for‐length z scores less than −2 SD, respectively. We evaluated the association between BMI/GWG and infant's weight and length at birth and during the first year of life, as well as with stunting and wasting at 12 months using mixed linear and logistic regression models. Results: In multivariate, preconceptional underweight was associated with a lower infant's weight at birth and during the first year (−164 g; 95% CI, −307 to −22; and −342 g; 95% CI, −624 to −61, respectively) and with a higher risk of stunting at 12 months (adjusted odds ratio [aOR] = 3.98; 95% CI, 1.01‐15.85). Furthermore, preconceptional obesity and a high GWG were associated with a higher weight and length at birth and during the first year. Conclusion: Underweight and obesity before conception as well as GWG were associated with infant's growth. These results argue for preventive interventions starting as early as the preconception period to support child long‐term health. [ABSTRACT FROM AUTHOR]