Etiology of Bacterial Meningitis Among Children < 5 Years Old in Cote d'Ivoire: Findings of Hospital-based Surveillance Before and After Pneumococcal Conjugate Vaccine Introduction

Background: Bacterial meningitis remains a major disease affecting children in Côte d’Ivoire. Thus, with support from the World Health Organization (WHO), Côte d’Ivoire has implemented pediatric bacterial meningitis (PBM) surveillance at 2 sentinel hospitals in Abidjan, targeting the main causes of PBM: Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (meningococcus). Herein we describe the epidemiological characteristics of PBM observed in Côte d’Ivoire during 2010–2016. Methods: Cerebrospinal fluid (CSF) was collected from children aged <5 years admitted to the Abobo General Hospital or University Hospital Center Yopougon with suspected meningitis. Microbiology and polymerase chain reaction (PCR) techniques were used to detect the presence of pathogens in CSF. Where possible, serotyping/grouping was performed to determine the specific causative agents. Results: Overall, 2762 cases of suspected meningitis were reported, with CSF from 39.2% (1083/2762) of patients analyzed at the WHO regional reference laboratory in The Gambia. In total, 82 (3.0% [82/2762]) CSF samples were positive for bacterial meningitis. Pneumococcus was the main pathogen responsible for PBM, accounting for 69.5% (52/82) of positive cases. Pneumococcal conjugate vaccine serotypes 5, 18C, 19F, and 6A/B were identified post–vaccine introduction. Emergence of H. influenzae nontypeable meningitis was observed after H. influenzae type b vaccine introduction. Conclusions: Despite widespread use and high coverage of conjugate vaccines, pneumococcal vaccine serotypes and H. influenzae type b remain associated with bacterial meningitis among children aged <5 years in Côte d’Ivoire. This reinforces the need for enhanced surveillance for vaccine-preventable diseases to determine the prevalence of bacterial meningitis and vaccine impact across the country

Modelling the Protective Efficacy of Alternative Delivery Schedules for Intermittent Preventive Treatment of Malaria in Infants and Children

BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy. METHODS AND FINDINGS: A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone. CONCLUSION: Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria

Site characteristics in Old World settings.

<p>Site characteristics in Old World settings.</p

Agreement on key parameters by OWCL and NWCL clinical researchers.

<p>‘Standardized’ criteria are those as proposed in the reference paper Olliaro et al, 2013⁹; ‘updated’ criteria are those resulting from the consultation.</p

Site characteristics in New World settings.

<p>Site characteristics in New World settings.</p

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

International audienceAbstract Introduction The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. Methods This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. Results From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. Discussion The PREVAC trial is evaluating—placebo-controlled—two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. Trial registration ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016