The Impact of Maternal Depression and Parent-Child Interactions on Risk of Parasitic Infections in Early Childhood: A Prospective Cohort in Benin.

OBJECTIVES: Maternal depression occurs in 13-20% of women from low-income countries, which is associated with negative child health outcomes, including diarrheal disease. However, few studies have investigated its impact on child risk of infectious disease. We studied the impacts of maternal depressive symptoms and parent-child interactions, independently, on the risk of Plasmodium falciparum malaria and soil-transmitted helminth infection in Beninese children. METHODS: Our population included mothers and children enrolled in a clinical trial during pregnancy (MiPPAD) in Benin. The Edinburgh Postnatal Depression Scale (EPDS) assessed maternal depressive symptoms and the home observation measurement of the environment (HOME) assessed parent-child interactions. Blood and stool sample analyses diagnosed child malaria and helminth infection at 12, 18, and 24 months. Negative binomial and Poisson regression models with robust variance tested associations. RESULTS: Of the 302 mother-child pairs, 39 (12.9%) mothers had depressive symptoms. Median number of malaria episodes per child was 3 (0-14) and 29.1% children had at least one helminth infection. Higher EPDS scores were associated with lower HOME scores; relative risk (RR) 0.97 (95% confidence interval (CI) 0.95, 0.99), particularly with lower acceptance, involvement, and variety subscales; RR 0.92 (95% CI 0.85, 0.99), RR 0.82 (95% CI 0.77, 0.88), RR 0.93 (95% CI 0.88, 0.99), respectively. However, neither exposure was associated with risk of parasitic infection in children. CONCLUSIONS FOR PRACTICE: Maternal depressive symptoms are associated with poor parent-child interactions, particularly acceptance of behavior, involvement with children, and variety of interactions, but these exposures do not independently impact risk of parasitic infection in children.

Possible effect of maternal safe food preparation behavior on child malnutrition in Benin, Africa.

BACKGROUND: In many developing countries, faulty complementary feeding practises and frequently contaminated foods are contributing factors to child malnutrition. The aims of this study were to evaluate the nutrition status of, and clarify the maternal safe food preparation behaviors associated with malnutrition in, children aged <5 years in Cotonou, Benin. METHODS: This study targeted 300 mother-child pairs visiting the University Hospital of Mother and Child Cotonou Lagoon. Mothers were interviewed using a structured questionnaire. Child height/length and weight measurements were determined and Z-scores were calculated using the 2006 World Health Organization Child Growth Standards. Children with Z-score < -2 were considered to have stunting or be underweight. On logistic regression analysis, significant variables on bivariate analysis, the associations of which were clarified in previous studies, were established as independent variables. Approximately 80% of the children who participated in this study were aged < 1 year. Being underweight was analyzed as a dependent variable. RESULTS: Regarding nutrition status, 11.0% of the children had stunting and 14.7% were underweight. On logistic regression analysis, underweight was correlated significantly with birthweight. As a remarkable point, food refrigeration was statistically significant. Food refrigeration can possibly be regarded as a maternal safe food preparation behavior. CONCLUSIONS: Maternal safe food preparation behaviors can prevent child malnutrition, even after considering biological and socioeconomic factors.

Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria.

BACKGROUND: Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis. METHODS: Children presenting with CM (n = 70) due to P. falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients' cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysed by univariate analysis using the nonparametric Mann‒Whitney U test and Pearson's Chi2 test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors. RESULTS: Univariate analysis revealed higher plasma levels of tumour necrosis factor (TNF), interleukin-1beta (IL-1ß), IL-10, IL-8, C-X-C motif chemokine ligand 9 (CXCL9), granzyme B, and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite (PGEM) in children who died compared to those who survived CM (Mann-Whitney U-test, P-values between 0.03 and < 0.0001). The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM (adjusted odd ratio = 14.2, P-value = 0.002). Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, C-C motif chemokine ligand 17 (CCL17), CCL22, and urinary 15-F2t-isoprostane. CONCLUSIONS: The main risk factor of death during CM was thus elevated plasma levels of IL-8 at inclusion. Follow-up of patients until D30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation, endothelium activation and damage, inflammatory and oxidative response. These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

Seroepidemiology of toxoplasmosis in pregnant women and detection of infection acquired during pregnancy in Cotonou, Benin.

Assessing the prevalence of toxoplasmosis in pregnant women and the associated risk factors is the first step in defining policy for the prevention of congenital toxoplasmosis in a given population. An epidemiological study was conducted during prenatal consultations at the CHU-MEL of Cotonou (Benin) between September 2018 and April 2021 and recruited 549 pregnant women to determine the seroprevalence and potential factors associated with Toxoplasma gondii infection. Toxoplasma gondii IgG/IgM antibodies were detected using an enzyme-linked fluorescence assay (ELFA) technique, an IgG avidity test and an IgG/IgM comparative Western blot to diagnose the maternal toxoplasmosis serological status, the possibility of an infection acquired during pregnancy and congenital infection, respectively. Concomitantly, the participants answered a questionnaire investigating potential risk factors. Toxoplasmosis seroprevalence was estimated at 44.4% (95% CI 40.3-48.6) and the factors significantly associated with T. gondii seropositivity were: age over 30 years, multigravid women and contact with cats. The possibility of an infection acquired during the periconceptional period or the first trimester of pregnancy concerned six women [1.1% (95% CI 0.5-2.0)]. However, due to the low rate of serological controls in seronegative women, a significant proportion of women first tested during the 3rd trimester of pregnancy, and an insufficient sample size, the incidence of primary infection during pregnancy could not be determined. No cases of congenital transmission occurred in the newborns from the suspected cases of primary infection.

Title: Séroépidémiologie de la toxoplasmose chez la femme enceinte et détection de l'infection contractée pendant la grossesse à Cotonou, Bénin. Abstract: L'évaluation de la prévalence de la toxoplasmose chez la femme enceinte et des facteurs de risque associés est la première étape pour définir une politique de prévention de la toxoplasmose congénitale dans une population donnée. Une étude épidémiologique a été menée lors des consultations prénatales au CHU-MEL de Cotonou (Bénin) entre septembre 2018 et avril 2021 et a recruté 549 femmes enceintes pour déterminer la séroprévalence et les facteurs potentiels associés à l'infection à Toxoplasma gondii. Les anticorps IgG / IgM de T. gondii ont été détectés à l'aide d'une technique ELFA, du test d'avidité IgG et du Western blot comparatif IgG / IgM pour diagnostiquer respectivement le statut sérologique de la toxoplasmose maternelle, la possibilité d'une infection acquise pendant la grossesse et l'infection congénitale. Parallèlement, les participants ont répondu à un questionnaire portant sur les facteurs de risque potentiels. La séroprévalence de la toxoplasmose a été estimée à 44,4 % (IC 95 % 40,3­48,6) et les facteurs significativement associés à la séropositivité pour T. gondii étaient l'âge supérieur à 30 ans, la multigravidité et les contacts avec les chats. La possibilité d'une infection acquise pendant la période périconceptionnelle ou le premier trimestre de la grossesse concernait six femmes [1,1 % (IC 95 % 0,5­2,0)]. Cependant, en raison du faible taux de contrôles sérologiques chez les femmes séronégatives, d'une proportion importante de femmes testées pour la première fois au cours du 3ème trimestre de la grossesse et d'une taille d'échantillon insuffisante, l'incidence de la primo-infection pendant la grossesse n'a pas pu être déterminée. Aucun des enfants nés des six femmes suspectes de primo-infection en cours de grossesse n'a présenté d'infection congénitale.

Lead Exposure in Infancy and Subsequent Growth in Beninese Children.

Studies suggest that elevated postnatal blood lead levels (BLLs) are negatively associated with child growth. This study aimed to investigate the associations of childhood BLLs at age one year and growth outcomes at age six years (n = 661) in a cohort of children in Allada, Benin. The growth outcomes studied are weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ), BMI-for-age Z-score (BMIZ), weight-for-height Z-score (WHZ), head circumference (HC), growth velocities, underweight, stunting, and wasting. Multivariable regression models examined the associations between BLLs and growth outcomes, with adjustment for potential confounders. The geometric mean BLLs was 59.3 µg/L and 82% of children had BLLs >35 µg/L at the age of 12.8 months. After adjusting for confounding factors, no overall association was found between BLL quartiles and HAZ, WAZ, BMIZ, WHZ, growth velocities, wasting, and underweight. However, boys in the highest quartile had a 1.02 cm lower HC (95% CI: [−1.81, −0.24]) as compared to the lowest quartile. Furthermore, an increased odds of being stunted was observed in children in the highest quartile of exposure compared to the first (OR: 2.43; 95% CI: [1.11−5.33]) which remained statistically significant only among girls in sex-specific strata. Blood lead was found to be associated with an increased risk of childhood stunting and a lower head circumference in a resource-limited setting.

Non-traumatic coma in young children in Benin: are viral and bacterial infections gaining ground on cerebral malaria?

BACKGROUND: While malaria morbidity and mortality have declined since 2000, viral central nervous system infections appear to be an important, underestimated cause of coma in malaria-endemic Eastern Africa. We aimed to describe the etiology of non-traumatic comas in young children in Benin, as well as their management and early outcomes, and to identify factors associated with death. METHODS: From March to November 2018, we enrolled all HIV-negative children aged between 2 and 6 years, with a Blantyre Coma Score ≤ 2, in this prospective observational study. Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol, including blood cultures, malaria diagnostics, and cerebrospinal fluid analysis using multiplex PCR. To determine factors associated with death, univariate and multivariate analyses were performed. RESULTS: From 3244 admissions, 84 children were included: malaria was diagnosed in 78, eight of whom had a viral or bacterial co-infection. Six children had a non-malarial infection or no identified cause. The mortality rate was 29.8% (25/84), with 20 children dying in the first 24 h. Co-infected children appeared to have a poorer prognosis. Of the 76 children who consulted a healthcare professional before admission, only 5 were prescribed adequate antimalarial oral therapy. Predictors of early death were jaundice or increased bilirubin [odd ratio (OR)= 8.6; 95% confidential interval (CI): 2.03-36.1] and lactate > 5 mmol/L (OR = 5.1; 95% CI: 1.49-17.30). Antibiotic use before admission (OR = 0.1; 95% CI: 0.02-0.85) and vaccination against yellow fever (OR = 0.2, 95% CI: 0.05-0.79) protected against mortality. CONCLUSIONS: Infections were found in all children who died, and cerebral malaria was by far the most common cause of non-traumatic coma. Missed opportunities to receive early effective antimalarial treatment were common. Other central nervous system infections must be considered in their management. Some factors that proved to be protective against early death were unexpected.

Prospective multicentre study of host response signatures in neonatal sepsis in Sub Saharan Africa.

Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. While the role of host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating new biomarkers targeting host response in regions where sepsis burden is high and medico-economic resources are scarce. The objective of the study is to evaluate diagnostic and prognostic accuracy of biomarkers of neonatal sepsis in Sub Saharan Africa. This prospective multicentre study included newborn infants delivered in the Abomey-Calavi region in South Benin and their follow-up from birth to 3 months of age. Accuracy of transcriptional (CD74, CX3CR1), proteic (PCT, IL-6, IL-10, IP-10) biomarkers and clinical characteristics to diagnose and prognose neonatal sepsis were measured. At delivery, cord blood from all consecutive newborns were sampled and analysed, and infants were followed for a 12 weeks' period. Five hundred and eighty-one newborns were enrolled. One hundred and seventy-two newborns developed neonatal sepsis (29.6%) and death occurred in forty-nine infants (8.4%). Although PCT, IL-6 and IP-10 levels were independently associated with sepsis diagnosis, diagnostic accuracy of clinical variables combinations was similar to combinations with biomarkers and superior to biomarkers alone. Nonetheless, CD74, being the only biomarkers independently associated with mortality, showed elevated prognosis accuracy (AUC > 0.9) either alone or in combination with other biomarkers (eg. CD74/IP-10) or clinical criterion (eg. Apgar 1, birth weight). These results suggest that cord blood PCT had a low accuracy for diagnosing early onset neonatal sepsis in Sub Saharan African neonates, while association of clinical criterion showed to be more accurate than any biomarkers taken independently. At birth, CD74, either associated with IP-10 or clinical criterion, had the best accuracy in prognosing sepsis mortality.Trial registration Clinicaltrial.gov registration number: NCT03780712. Registered 19 December 2018. Retrospectively registered.

Follow-Up of Elevated Blood Lead Levels and Sources in a Cohort of Children in Benin.

Lead exposure is associated with poor cognitive development in children. Very few studies in sub-Saharan Africa (SSA) have studied blood lead levels (BLLs) and non-gasoline sources of exposure in children. Data from a birth cohort in Benin (2011-2013) suggested that 58% of 1-year-old children had BLLs > 50 ug/L. We aimed to investigate the prevalence of elevated BLLs (>50 µg/L and >100 µg /L) among 425 of these children at 6 years of age in 2016-2018 and to compare BLLs between age 1 and 6 years, and study sources of lead at age 6 years. BLLs were analysed by inductively coupled plasma mass spectrometry. Multiple linear regression and quantile regressions were used to study potential sources of lead. The prevalence of BLLs > 50 µg/L in children was 59.5% (Geometric Mean (GM) 56.4 µg/L, 95% CI: 54.1-58.7) at 6 years of age compared to 54.8% (GM 56.5 µg/L, 95% CI: 53.4-59.6) at 1 year of age. The prevalence of children with BLLs > 100 µg/L decreased from 14.4% at 1 year of age to 8.2% at 6 years of age. After adjustment for all other covariates, consumption of peanuts more than once per month was significantly associated with a 22.0% (95% CI: 4.6, 42.5) increment in BLLs at age 6 years compared with no consumption. Consumption of bushmeat killed by lead bullets at age 6 years was associated with an increase in the higher percentiles of BLLs (P75) compared with the absence of this source. Other potential sources of lead associated with BLLs with marginal significance were consumption of rice, paternal occupational exposure, and the presence of activity with the potential use of lead. This prospective cohort confirms the persistently high prevalence of elevated BLLs in children residing in a rural region in the south of Benin, as well as the presence of multiple and continuous sources of lead. These results highlight the need for prevention programs to reduce and eliminate lead exposure in children.

Identification of Plasmodium falciparum and host factors associated with cerebral malaria: description of the protocol for a prospective, case-control study in Benin (NeuroCM).

INTRODUCTION: In 2016, an estimated 216 million cases and 445 000 deaths of malaria occurred worldwide, in 91 countries. In Benin, malaria causes 26.8% of consultation and hospitalisation motif in the general population and 20.9% in children under 5 years old.The goal of the NeuroCM project is to identify the causative factors of neuroinflammation in the context of cerebral malaria. There are currently very few systematic data from West Africa on the aetiologies and management of non-malarial non-traumatic coma in small children, and NeuroCM will help to fill this gap. We postulate that an accurate understanding of molecular and cellular mechanisms involved in neuroinflammation may help to define efficient strategies to prevent and manage cerebral malaria. METHODS AND ANALYSIS: This is a prospective, case-control study comparing cerebral malaria to uncomplicated malaria and non-malarial non-traumatic coma. This study takes place in Benin, precisely in Cotonou for children with coma and in Sô-Ava district for children with uncomplicated malaria. We aim to include 300 children aged between 24 and 71 months and divided in three different clinical groups during 12 months (from December 2017 to November 2018) with a 21 to 28 days follow-up for coma. Study data, including clinical, biological and research results will be collected and managed using CSOnline-Ennov Clinical. ETHICS AND DISSEMINATION: Ethics approval for the NeuroCM study has been obtained from Comité National d'Ethique pour la Recherche en santé of Benin (n°67/MS/DC/SGM/DRFMT/CNERS/SA; 10/17/2017). NeuroCM study has also been approved by Comité consultatif de déontologie et d'éthique of Institut de Recherche pour le Développement (IRD; 10/24/2017). The study results will be disseminated through the direct consultations with the WHO's Multilateral Initiative on Malaria (TDR-MIM) and Roll Back Malaria programme, through scientific meetings and peer-reviewed publications in scientific or medical journals, and through guidelines and booklets.