Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial.

BACKGROUND: Children account for a substantial proportion of cases and deaths during Ebola virus disease outbreaks. We aimed to evaluate the safety and immunogenicity of a booster dose of the Ad26.ZEBOV vaccine in children who had been vaccinated with a two-dose regimen comprising Ad26.ZEBOV as dose one and MVA-BN-Filo as dose two. METHODS: We conducted an open-label, non-randomised, phase 2 trial at one clinic in Kambia Town, Sierra Leone. Healthy children, excluding pregnant or breastfeeding girls, who had received the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen in a previous study, and were aged 1-11 years at the time of their first vaccine dose, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) and were followed up for 28 days. Primary outcomes were safety (measured by adverse events) and immunogenicity (measured by Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration) of the booster vaccine dose. Safety was assessed in all participants who received the booster vaccination; immunogenicity was assessed in all participants who received the booster vaccination, had at least one evaluable sample after the booster, and had no major protocol deviations that could have influenced the immune response. This trial is registered with ClinicalTrials.gov, NCT04711356. FINDINGS: Between July 8 and Aug 18, 2021, 58 children were assessed for eligibility and 50 (27 aged 4-7 years and 23 aged 9-15 years) were enrolled and received an Ad26.ZEBOV booster vaccination, more than 3 years after receiving dose one of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen. The booster was well tolerated. The most common solicited local adverse event during the 7 days after vaccination was injection site pain, reported in 18 (36%, 95% CI 23-51) of 50 participants. The most common solicited systemic adverse event during the 7 days after vaccination was headache, reported in 11 (22%, 12-36) of 50 participants. Malaria was the most common unsolicited adverse event during the 28 days after vaccination, reported in 25 (50%, 36-64) of 50 participants. No serious adverse events were observed during the study period. 7 days after vaccination, the Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration was 28 561 ELISA units per mL (95% CI 20 255-40 272), which was 44 times higher than the geometric mean concentration before the booster dose. 21 days after vaccination, the geometric mean concentration reached 64 690 ELISA units per mL (95% CI 48 356-86 541), which was 101 times higher than the geometric mean concentration before the booster dose. INTERPRETATION: A booster dose of Ad26.ZEBOV in children who had received the two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen more than 3 years earlier was well tolerated and induced a rapid and robust increase in binding antibodies against Ebola virus. These findings could inform Ebola vaccination strategies in paediatric populations. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Serum Micronutrients as related to Childhood Pneumonia Severity and Outcome in a Nigerian Health Facility.

INTRODUCTION: Micronutrients are essential minerals and vitamins needed for optimal health. There are however conflicting reports about the roles of micronutrients in severity and outcomes of childhood pneumonia. This study aims to determine the socio-demographic and serum micronutrients - Zinc (Zn), Selenium (Se), Vitamins (Vit) A, C and E status of Nigerian children with or without pneumonia and relate these to pneumonia severity and outcome. METHODOLOGY: Children aged two months to 14 years with severe and non-severe pneumonia were recruited with age and sex-matched controls over 12 month period in a Nigerian tertiary health centre. Relevant history and serum micronutrients were compared in the two groups and related to pneumonia severity and length of hospitalisation (LOH). RESULTS: One hundred and forty-four children (72 for each group) were recruited with median (IQR) age 1.6 (0.6 - 4.0) years and fifty-six (38.8%) had severe pneumonia. Pneumonia incidence was associated with undernutrition, inappropriate immunisation and Zn deficiency (p < 0.05). Hypovitaminosis A [60.8(22.2)µg/dl vs. 89.5(34.7)µg/dl; p < 0.001], low serum Zn [71.6(32.5)µg/dl vs. 92.6(24.6)µg/dl; p=0.019] and indoor air pollution (IAP) were associated with pneumonia severity. However, only IAP (OR = 4.529; 95%CI 1.187-17.284; p=0.027) and Zn deficiency (OR=6.144; 95%CI 1.157-32.617; p=0.033) independently predicted severe pneumonia. No significant correlation between serum micronutrients and LOH. CONCLUSIONS: Exposure to IAP and low serum micronutrients particularly Zn and Vit A were associated with pneumonia incidence and severity in Nigerian children. Routine micronutrient supplementation may assist to reduce the burden of childhood pneumonia in developing countries.

Clinical presentations and management of COVID-19 infected children seen in a district health facility in Kambia, northern Sierra Leone.

Studies reporting the clinical presentations of COVID-19 in children in sub-Saharan Africa are few, especially from resource-constrained countries. This case series reports the demographic and clinical characteristics and laboratory findings of confirmed cases of COVID-19 in children seen at a district hospital in Sierra Leone. This is a report of nine COVID-19 paediatric cases managed at a secondary level hospital in Kambia District, Northern Sierra Leone. Each child was detected by contact tracing after an infected adult was identified by the COVID-19 response team. The clinical symptoms at presentation, clinical courses, and treatments instituted and patient outcomes are discussed in the context of the facilities available at a typical West African district hospital. Nine out of 30 individuals with confirmed COVID-19 infection who presented to the hospital from 24 April to 20 September 2020 and who were admitted to the isolation center of the hospital were in the paediatric age group. The mean age (SD) and median (IQR) of the children were 69.0 ± 51.7months and 84.0 (10.5, 108.0) months, respectively; five (55.6%) were males. The children were asymptomatic or only had mild illnesses and none required intranasal oxygen or ventilatory support. In the five symptomatic children, the most common symptoms were fever (40%) and cough (40%). All children had normal haemoglobin, platelet and white blood cell (WBC) count. Four children had a positive malaria test and were treated with a complete course of anti-malaria medications. No child received steroid or had specific anti-COVID-19 treatment. All children stayed in the isolation center for 14 days and were re-tested for COVID-19 two weeks after initial diagnosis. No complications have been reported in any of them since discharge. The proportion of children among COVID-19 infected cases seen in a rural community in Sierra Leone was 30%. Fever was the most common symptom and malaria was confirmed in 40% of the infected children. This has significant implication on the diagnosis of COVID-19 in malaria-endemic settings and on how best to manage children who present with fever during the COVID-19 pandemic.

Carpopedal spasm in a 4 year old boy with persisted vomiting and dyselectrolytemia in Wesley Guild Hospital Ilesa.

Carpopedal spasm have various causes ranging from dsyselecrolytemia, syndromic, metabolic or endocrine causes. Any of these could cause a decrease in ionized calcium and tetany. Excessive vomiting leading to alkalosis, hypokaleamia and decreased ionised calcium should be kept in mind for early etiological diagnosis of carpopedal spasm. We report a case of 4-year-old boy presenting with a history of recurrent painful spasm and flexion of bilateral hands following excessive vomiting and electrolyte derangement.