Young African Children Research Articles

Inflammation and Elevated Osteopontin in Plasma and CSF in Cerebral Malaria Compared to Plasmodium-Negative Neurological Infections.

Cerebral malaria in young African children is associated with high mortality, and persisting neurological deficits often remain in survivors. Sequestered Plasmodium-infected red blood cells lead to cerebrovascular inflammation and subsequent neuroinflammation. Brain inflammation can play a role in the pathogenesis of neurologic sequelae. Therefore, we assessed a select set of proinflammatory analytes (IP10, IL23, MIP3α, GRO, MCP-1, and osteopontin in both the plasma and cerebrospinal fluid(CSF) of Zambian children with cerebral malaria and compared this with children with neurological symptoms that were negative for Plasmodium falciparum (non-cerebral malaria). Several similarities in plasma and CSF levels were found, as were some striking differences. We confirmed that IP10 levels were higher in the plasma of cerebral malaria patients, but this was not found in CSF. Levels of osteopontin were elevated in both the plasma and CSF of CM patients compared to the non-CM patients. These results show again a highly inflammatory environment in both groups but a different profile for CM when compared to non-cerebral malaria. Osteopontin may play an important role in neurological inflammation in CM and the resulting sequelae. Therefore, osteopontin could be a valid target for further biomarker research and potentially for therapeutic interventions in neuroinflammatory infections.

Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial

A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 μg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 μg RH5.1 at 0 and 1 month and 10 μg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 μg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 μg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 μg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per μg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 μg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 μg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

Using vignettes to understand the social-emotional experiences of three-year-olds in diverse language contexts

In this article, we report on the educational experiences of young Afrikaans mother tongue South African children who are exposed to multilingual learning environments during their preschool years. We carried out phenomenological research using a vignette research design that provided observational, co-experiential data of the lived experiences of three-year-old boys as they engaged with formal and informal learning. We controlled vignette data that had been collected through observations, written teacher validation, and face-to-face interviews against existing literature to provide in-depth insights into the participants' different experiences of and within their learning environments. Findings indicate specific areas in which young children may need additional support in multilingual learning environments, in terms of 1) social-emotional security experienced in the learning environment, 2) intentional development of empathy for peers, 3) independence and initiative taking in informal settings, and 4) interactive communication. Although we focused on a South African context, these findings may inform future interventions to support children in multilingual language environments in their early years.

Early Childhood Violence Exposure Patterns in The Drakenstein Child Health Study (DCHS).

Background: Research has highlighted high rates of exposure to violence among South African youth. However, work to date has been largely cross-sectional, focused on violence exposure during the adolescence period, and has been limited to specific types of violence exposure. We examined violence exposure in South African preschool children between 3 and 6 years of age, capturing both direct and indirect forms of violence, and tested for potential sex differences across the several types of exposures. Methods: Lifetime direct and indirect exposure to domestic and community violence wasmeasured by parental report when children were 3.5 years (N = 530), 4.5 years (N = 749) and 6 years of age (N= 417) in a South African birth cohort located in a peri-urban community. Results: There are three main findings. First, a large proportion of children (72%-75%) were reported as having been exposed to some form of direct or indirect violent experience in their homes or communities from a young age. Second, there was significant polyvictimization, with 49% of the children being exposed to more than one type of violence by age 6. Third, by 4.5 years of age, there was evidence that boys were more likely than girls to be exposed to domestic victimisation (28% vs. 17%) and polyvictimization (38% vs. 28%). Conclusions: These findings highlight the high levels of violence exposure in young South African children, particularly among boys, and the need for prevention at both the community and individual levels.

Evidence Based Optimal Dosing of Intravenous Artesunate in Children with Severe Falciparum Malaria.

The majority of deaths from malaria are in young African children. Parenteral artesunate (ARS) is the first-line treatment for severe falciparum malaria. Since 2015, the World Health Organization has recommended individual doses of 3 mg/kg for children weighing < 20 kg. Recently, the US Food and Drug Administration (FDA) has challenged this recommendation, based on a simulated pediatric population, and argued for a lower dose in younger children (2.4 mg/kg). In this study, we performed population pharmacokinetic (PK) modeling of plasma concentration data from 80 children with severe falciparum malaria in the Democratic Republic of Congo who were given 2.4 mg/kg of ARS intravenously. Bayesian hierarchical modeling and a two-compartment parent drug-metabolite PK model for ARS were used to describe the population PKs of ARS and its main biologically active metabolite dihydroartemisinin. We then generated a virtual population representative of the target population in which the drug is used and simulated the total first-dose exposures. Our study shows that the majority of younger children given the lower 2.4 mg/kg dose of intravenous ARS do not reach the same drug exposures as older children above 20 kg. This finding supports withdrawal of the FDA's recent lower ARS dose recommendation as parenteral ARS is an extremely safe and well-tolerated drug and there is potential for harm from underdosing in this rapidly lethal infection.

African Vernacular Symbols of Black Intersex Children in Sinethemba Ngubane's Installations (2007-2016)

African Vernacular Symbols of Black Intersex Children in Sinethemba Ngubane's Installations (2007-2016)

Severe anaemia, iron deficiency, and susceptibility to invasive bacterial infections.

Severe anaemia and invasive bacterial infections remain important causes of hospitalization and death among young African children. The emergence and spread of antimicrobial resistance demand better understanding of bacteraemia risk factors to inform prevention strategies. Epidemiological studies have reported an association between severe anaemia and bacteraemia. In this review, we explore evidence that severe anaemia is associated with increased risk of invasive bacterial infections in young children. We describe mechanisms of iron dysregulation in severe anaemia that might contribute to increased risk and pathogenesis of invasive bacteria, recent advances in knowledge of how iron deficiency and severe anaemia impair immune responses to bacterial infections and vaccines, and the gaps in our understanding of mechanisms underlying severe anaemia, iron deficiency, and the risk of invasive bacterial infections.

Early Childhood Violence Exposure Patterns in The Drakenstein Child Health Study (DCHS)

Background: Research has highlighted high rates of exposure to violence among South African youth. However, work to date has been largely cross-sectional, focused on violence exposure during the adolescence period, and has been limited to specific types of violence exposure. We examined violence exposure in South African preschool children between 3 and 6 years of age, capturing both direct and indirect forms of violence, and tested for potential sex differences across the several types of exposures. Methods: Lifetime direct and indirect exposure to domestic and community violence was measured by parental report when children were 3.5 years (N = 530), 4.5 years (N = 749) and 6 years of age (N= 417) in a South African birth cohort located in a peri-urban community. Results: There are three main findings. First, a large proportion of children (72%-75%) were reported as having been exposed to some form of direct or indirect violent experience in their homes or communities from a young age. Second, there was significant polyvictimization, with 49% of the children being exposed to more than one type of violence by age 6. Third, by 4.5 years of age, there was evidence that boys were more likely than girls to be exposed to domestic victimisation (28% vs. 17%) and polyvictimization (38% vs. 28%). Conclusions: These findings highlight the high levels of violence exposure in young South African children, particularly among boys, and the need for prevention at both the community and individual levels.

Comparison of Several Prediction Equations Using Skinfold Thickness for Estimating Percentage Body Fat vs. Body Fat Percentage Determined by BIA in 6-8-Year-Old South African Children: The BC-IT Study.

Body composition measurement is useful for assessing percentage body fat (%BF) and medical diagnosis, monitoring disease progression and response to treatment, and is essential in assessing nutritional status, especially in children. However, finding accurate and precise techniques remains a challenge. The study compares %BF determined by bioelectrical impedance analysis (BIA) and calculated from available prediction equations based on skinfolds in young South African children. A cross-sectional study performed on 202 children (83 boys and 119 girls) aged 6-8 years. Height and weight, triceps and subscapular skinfolds were determined according to standard procedures. %BF was determined with BIA and three relevant available equations. SPSS analyzed the data using paired samples tests, linear regression, and Bland-Altman plots. Significant paired mean differences were found for BIA and Slaughter (t201 = 33.896, p < 0.001), Wickramasinghe (t201 = 4.217, p < 0.001), and Dezenberg (t201 = 19.910, p < 0.001). For all of the equations, the standards for evaluating prediction errors (SEE) were above 5. The Bland-Altman plots show relatively large positive and negative deviations from the mean difference lines and trends of systematic under- and over-estimation of %BF across the %BF spectrum. All three equations demonstrated a smaller %BF than the %BF measured by BIA, but the difference was smallest with the Wickramasinghe equation. In comparison, a poor SEE was found in the three %BF predicted equations and %BF derived from BIA. As such, an age-specific %BF equation incorporating criterion methods of deuterium dilution techniques or 'gold-standard' methods is needed to refute these findings. However, in the absence of developed %BF equations or 'gold-standard' methods, the available prediction equations are still desirable.

Fungal diversity in the gut microbiome of young South African children

BackgroundThe fungal microbiome, or mycobiome, is a poorly described component of the gut ecosystem and little is known about its structure and development in children. In South Africa, there have been no culture-independent evaluations of the child gut mycobiota. This study aimed to characterise the gut mycobiota and explore the relationships between fungi and bacteria in the gut microbiome of children from Cape Town communities.MethodsStool samples were collected from children enrolled in the TB-CHAMP clinical trial. Internal transcribed spacer 1 (ITS1) gene sequencing was performed on a total of 115 stool samples using the Illumina MiSeq platform. Differences in fungal diversity and composition in relation to demographic, clinical, and environmental factors were investigated, and correlations between fungi and previously described bacterial populations in the same samples were described.ResultsTaxa from the genera Candida and Saccharomyces were detected in all participants. Differential abundance analysis showed that Candida spp. were significantly more abundant in children younger than 2 years compared to older children. The gut mycobiota was less diverse than the bacterial microbiota of the same participants, consistent with the findings of other human microbiome studies. The variation in richness and evenness of fungi was substantial, even between individuals of the same age. There was significant association between vitamin A supplementation and higher fungal alpha diversity (p = 0.047), and girls were shown to have lower fungal alpha diversity (p = 0.003). Co-occurrence between several bacterial taxa and Candida albicans was observed.ConclusionsThe dominant fungal taxa in our study population were similar to those reported in other paediatric studies; however, it remains difficult to identify the true core gut mycobiota due to the challenges set by the low abundance of gut fungi and the lack of true gut colonising species. The connection between the microbiota, vitamin A supplementation, and growth and immunity warrants exploration, especially in populations at risk for micronutrient deficiencies. While we were able to provide insight into the gut mycobiota of young South African children, further functional studies are necessary to explain the role of the mycobiota and the correlations between bacteria and fungi in human health.

Oral Health Status and Practices, and Anthropometric Measurements of Preschool Children: Protocol for a Multi-African Country Survey.

BackgroundOral diseases are among the most prevalent conditions with significant impact on the growth and development of young children. Data are required to plan effectively for the management of early childhood caries (ECC) and other oral diseases in this age. There are currently very few African countries with updated and nationally representative data on ECC prevalence, and risk indicators and regional data on ECC and other oral diseases are scarce.ObjectiveWe aim to determine the oral health status and practices, dietary intake, and anthropometric measurements of preschool children in several African countries.MethodsA cross-sectional study will be conducted in several African countries using a standardized questionnaire and clinical examination for data collection from healthy preschool children in kindergartens and primary health care facilities. The clinical examination will assess ECC using the decayed, missing due to caries, and filled teeth (dmft) index according to the World Health Organization (WHO) criteria, dental erosion (using the Basic Erosive Wear Examination Index), deciduous molar hypomineralization (using the European Association of Paediatric Dentistry criteria), dental fluorosis (using Dean’s Index), oral hygiene status (using the Oral Hygiene Index Simplified), and oral mucosal lesions. Oral hygiene habits and dental visits will be assessed using the WHO child questionnaire, and dietary intake will be assessed using the Food and Agriculture Organization method. Anthropometric measurements will be obtained following the International Society for the Advancement of Kinanthropometry standard protocol, and the children’s nutritional status will be assessed following the WHO child growth standards. To train and calibrate examiners, educational resources and electronic forms will be used to reach interexaminer and intraexaminer reliability with κ>0.6. Descriptive analysis will determine the prevalence of clinical conditions by age and sex. Bivariate analysis and multivariable regression will assess associations between the clinical conditions and sociodemographic factors, and oral health behaviors.ResultsData collection will begin after approvals and ethical clearance are obtained. The first stage will include 3 countries, namely Egypt, Nigeria, and South Africa, and collaborators from other African countries will join afterward.ConclusionsThis study will lay down the foundations for using validated tools to collect data on the oral health of young children in Africa, allowing researchers from different countries across Africa to collect standardized data on ECC and other oral conditions. This will facilitate comparisons and analysis of risk factors that might be unique to the African continent. The results will provide baseline data on the prevalence of oral diseases and enable planning to address the treatment needs of young African children and design programs to prevent oral diseases in the African continent.International Registered Report Identifier (IRRID)PRR1-10.2196/33552

Perceptions of the South African 24-Hour Movement Guidelines for Birth to 5 Years: A Qualitative Study.

South Africa launched 24-hour movement guidelines for birth to 5years in 2018. Perceptions of these guidelines were assessed as part of the dissemination process with community-based organizations in 2019. Fifteen dissemination workshops were held with community-based organization representatives and a range of stakeholders. Discussions were held with workshop attendees (n = 281) to obtain qualitative feedback on the guidelines and workshop. Six follow-up focus groups (n = 28) were conducted to obtain additional feedback on the guidelines and their dissemination. Discussions and focus groups were thematically analyzed. Participants recognized the importance of the guidelines for the health and development of young South African children. Participants' perceptions of the guidelines were consistently positive. The participants acknowledged the alignment of the guidelines with other South African programs and initiatives, and that they addressed gaps. Screen time and sleep were identified as the behaviors needing particular attention among young South African children. The negative impact of COVID-19 on young children's movement behaviors was acknowledged, especially regarding screen time. These findings provide evidence of stakeholders' positive perceptions of the South African guidelines and support the dissemination and implementation of these guidelines for the promotion of early childhood health and development in South Africa.

Making a good malaria vaccine better

Last month, the World Health Organization (WHO) recommended widespread use of RTS,S/AS01 vaccine to prevent malaria in young African children, noting its 30% reduction in deadly severe malaria. In a recent report, Das et al. describe antibody effector functions that may contribute to RTS,S efficacy and thereby guide vaccine improvements.

Comparison of three galenic forms of lamivudine in young West African children living with Human Immunodeficiency Virus.

Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms were administered: liquid formulation, tablet form and dispersible scored tablet. HIV-infected children <4years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma concentrations were analysed using nonlinear mixed effects modelling approach. One hundred and fifty children (age: 2.5 years (1.9-3.2), weight 11.1 (9.5-12.5) kg (median (IQR)) were included in this study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36 from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630 lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant effect on 3TC pharmacokinetic. This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and dispersible scored tablet) of lamivudine in the target population of young HIV-1-infected children. Galenic form had no significant effect on lamivudine pharmacokinetics.

Association between clinical and environmental factors and the gut microbiota profiles in young South African children

Differences in the microbiota in populations over age and geographical locations complicate cross-study comparisons, and it is therefore essential to describe the baseline or control microbiota in each population. This includes the determination of the influence of demographic, clinical and environmental factors on the microbiota in a setting, and elucidates possible bias introduced by these factors, prior to further investigations. Little is known about the microbiota of children in South Africa after infancy. We provide a detailed description of the gut microbiota profiles of children from urban Cape Town and describe the influences of various clinical and environmental factors in different age groups during the first 5 years of life. Prevotella was the most common genus identified in the participants, and after infancy, the gut bacteria were dominated by Firmicutes and Bacteroidetes. In this setting, children exposed to antibiotics and indoor cooking fires were at the most risk for dysbiosis, showing significant losses in gut bacterial diversity.

Pharmacokinetics of Hydroxyurea Therapy in African Children with Sickle Cell Anemia:Â Noharm Ancillary PK Study

▪Background. Hydroxyurea is an important disease-modifying therapy for sickle cell anemia (SCA). Through induction of fetal hemoglobin and other mechanisms, hydroxyurea reduces the number and severity of vaso-occlusive painful crises and episodes of acute chest syndrome, while also lowering the frequency of transfusions and hospitalizations, and even reducing mortality. In the US, hydroxyurea is recommended widely for both children and adults with SCA, although variation in treatment response is well-recognized. In sub-Saharan Africa, which has the greatest global burden of SCA, hydroxyurea is not used widely, due in part to a lack of data regarding its safety and efficacy. Pharmacokinetics (PK) analysis of hydroxyurea has also not been performed to date in Africa, but would provide important data regarding the variable responses to hydroxyurea treatment in low-resource settings.Objectives. There were three main goals of the NOHARM Ancillary PK Study: (1) to evaluate the feasibility of hydroxyurea sparse sampling PK collection and analysis in a low-resource clinical setting; (2) to determine the PK parameters for a cohort of young African children with SCA receiving hydroxyurea at an average oral daily dose of 20 mg/kg; and (3) to compare the PK parameters of African children collected and analyzed in the NOHARM trial with those of US children with SCA from the earlier HUSTLE study that included African-American children with SCA.Methods. NOHARM (NCT01976416) is a prospective, randomized, placebo-controlled, double-blinded phase 3 trial that is investigating the effects of hydroxyurea on the incidence and severity of malaria in very young children living in Uganda with SCA. After a year of blinded treatment, all participants were offered open-label hydroxyurea at an average oral daily dose of 20 ± 2.5 mg/kg, using either a 5-day or 7-day per week treatment regimen. After written informed consent for the ancillary PK study, hydroxyurea analysis was performed using a published sparse-sampling technique based on Bayesian estimation with collections pre-dose and then at T=15 minutes, 60 minutes, and 180 minutes. These four timed finger-prick sample collections over 3 hours used a volumetric absorptive microsampling device that collects exact 10 uL aliquots. All samples were stored at -80°C until analysis of hydroxyurea by LC-MS/MS (ug/mL) using a stable isotope internal standard, performed at Cincinnati Children's Hospital. Population PK analysis was performed using nonlinear mixed effect modeling (NONMEM 7.2). Allometric scaling was used to correct for differences in size.Results. A total of 100 children were enrolled in the NOHARM ancillary PK study (average age 3.8 ± 0.9 years; 55 males), and 98 of these children had three evaluable post-dose samples. Individual PK profiles were best described by a one-compartment model with first order absorption. The dose-normalized hydroxyurea concentrations in NOHARM were comparable between the 5-day and 7-day dosing regimens and similar to published HUSTLE data for 96 children, except for higher T=180 hydroxyurea concentrations and overall higher hydroxyurea exposure in the NOHARM cohort. The higher blood hydroxyurea concentrations were the result of reduced drug clearance in NOHARM, possibly influenced by younger age. Population PK parameter estimates of oral clearance in the NOHARM and HUSTLE cohorts were 9.8 L/h/70kg versus 12.9 L/h/70kg, respectively (p<0.01).Conclusions. The NOHARM PK study demonstrates the feasibility of collecting timed samples for analysis of hydroxyurea exposure, even in the low-resource setting of Uganda. Using a sparse sampling technique, young children with SCA had individual PK parameters calculated and a population PK model established. The oral drug clearance was lower in NOHARM than HUSTLE, with resulting higher hydroxyurea exposure, perhaps reflecting differences in age, nutrition, glomerular filtration, and genetic modifiers that warrant further investigation. DisclosuresWare:Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Prevalence of Malaria Infections Among Patients in Gimbie Adventist Hospital Western Wollega, Oromia Regional State, Ethiopia

Malaria is a disease caused by protozoan parasites belonging to the genus Plasmodium. The five species of parasite in humans are P. falciparum, P. vivax, P. malariae, P.ovale, and P. knowlesi. It is a major cause of morbidity and mortality worldwide, especially in young African children. Therefore, the objectives of this study were to assess the prevalence of malaria infection and associated factors among patients attending Gimbie Adventist Hospital in West Wollega, Oromia, Ethiopia. First, a retrospective study was carried out for the past ten years (2006-2016) to study the prevalence of malaria in the study area. Second, malaria suspected patients-based cross-sectional study was carried out from March to June, 2017. A random sampling technique was carried out to select representative study participants among the patient’s members. Structured questionnaires (n=130) and blood sample examinations were used for data collection. The data was entered and analyzed using SPSS 20 version. The prevalence of malaria in males was 71(65.7%) and in females were 37(34.3%). The greatest number of malaria cases tested in the age group of 16-30 years old was 52(48.1%). Among 384 Malaria suspected patients who were recruited and ascertained for parasitaemia from the blood sample test, 108 patients were malaria positive. The overall prevalence of malaria infection was 28.1%, of which 58 (53.7%) were positive for P. falciparum and 34 (31.5%) for P. vivax and the remaining 16(14.8%) were mixed (P. falciparum + P. vivax). The Major Plasmodium species identified in this study was P. falciparum (53.7%). Out of the screened patients, 69.2% responded to sleep under the ITNs the previous night. The coverage of IRs was observed to be 12.3% during the study period. The higher prevalence of malaria could be the result of several factors as explained in this study. Therefore, effective malaria control measures should be implemented in order to reduce the prevalence of malaria infection among patients.

Prevalence and predictors of vitamin D deficiency in young African children

BackgroundChildren living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children.MethodsWe measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0–8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses.ResultsMedian age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants.ConclusionsApproximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.

Baseline incidence of meningitis, malaria, mortality and other health outcomes in infants and young sub-Saharan African children prior to the introduction of the RTS,S/AS01E malaria vaccine

BackgroundThe lack of background disease incidence rates in sub-Saharan countries where the RTS,S/AS01E malaria vaccine is being implemented may hamper the assessment of vaccine safety and effectiveness. This study aimed to document baseline incidence rates of meningitis, malaria, mortality, and other health outcomes prior to vaccine introduction through the Malaria Vaccine Implementation Programme.MethodsAn ongoing disease surveillance study is combining prospective cohort event monitoring and hospital-based disease surveillance in three study sites in Ghana and Kenya. An interim analysis was performed on the prospective cohort in which children were enrolled in two age-groups (the 5 to 17 months or 6 to 12 weeks age-group), capturing data in the framework of routine medical practice before the introduction of the malaria vaccine. Incidence and mortality rates were computed with 95% confidential intervals (CI) using an exact method for a Poisson variable.ResultsThis analysis includes 14,329 children; 7248 (50.6%) in the 6 to 12 weeks age-group and 7081 (49.4%) in the 5 to 17 months age-group. In the 5 to 17 months age-group (where the malaria vaccine was planned to be subsequently rolled out) the meningitis, malaria, severe malaria and cerebral malaria incidences were 92 (95% CI 25–236), 47,824 (95% CI 45,411–50,333), 1919 (95% CI 1461–2476) and 33 (95% CI 1–181) per 100,000 person-years, respectively. The all-cause mortality was 969 (95% CI 699–1310) per 100,000 person-years.ConclusionIncidence estimates of multiple health outcomes are being generated to allow before-after vaccine introduction comparisons that will further characterize the benefit-risk profile of the RTS,S/AS01E vaccine.Trial registration: clinicaltrials.gov NCT02374450.

CD47 blockade reduces the pathologic features of experimental cerebral malaria and promotes survival of hosts with Plasmodium infection

CD47 is an antiphagocytic "don't eat me" signal that inhibits programmed cell removal of self. As red blood cells (RBCs) age they lose CD47 expression and become susceptible to programmed cell removal by macrophages. CD47-/- mice infected with Plasmodium yoelii, which exhibits an age-based preference for young RBCs, were previously demonstrated to be highly resistant to malaria infection. Our study sought to test the therapeutic benefit of CD47 blockade on ameliorating the clinical syndromes of experimental cerebral malaria (ECM), using the Plasmodium berghei ANKA (Pb-A) murine model. In vitro we tested the effect of anti-CD47 mAb on Plasmodium-infected RBC phagocytosis and found that anti-CD47 treatment significantly increased clearance of Plasmodium-infected RBCs. Infection of C57BL/6 mice with Pb-A is lethal and mice succumb to the clinical syndromes of CM between days 6 and 10 postinfection. Strikingly, treatment with anti-CD47 resulted in increased survival during the cerebral phase of Pb-A infection. Anti-CD47-treated mice had increased lymphocyte counts in the peripheral blood and increased circulating levels of IFN-γ, TNF-α, and IL-22. Despite increased circulating levels of inflammatory cytokines, anti-CD47-treated mice had reduced pathological features in the brain. Survival of ECM in anti-CD47-treated mice was correlated with reduced cellular accumulation in the cerebral vasculature, improved blood-brain barrier integrity, and reduced cytotoxic activity of infiltrating CD8+ T cells. These results demonstrate the therapeutic benefit of anti-CD47 to reduce morbidity in a lethal model of ECM, which may have implications for preventing mortality in young African children who are the highest casualties of CM.