Estimating the Global and Regional Burden of Streptococcus pneumoniae Meningitis in Children: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. OBJECTIVE: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. METHODS: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. RESULTS: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. CONCLUSIONS: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. TRIAL REGISTRATION: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50678.

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.

BACKGROUND: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. METHODS: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). FINDINGS: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). INTERPRETATION: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. FUNDING: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Hospital acquired infections in a private paediatric hospital in Kenya: a retrospective cross-sectional study.

Introduction: Hospital acquired infections (HAI) or infections acquired in a hospital setting significantly increase morbidity and mortality, prolong hospital stay and increase healthcare costs. Factors like malnutrition and irrational use of antibiotics in a resource limited setting contribute to poor outcome in children. Thus a retrospective cross-sectional study was undertaken to study the different types of HAI in children, the different organisms causing them and their sensitivity to different antimicrobials so as to inform appropriate empirical antimicrobial therapy initiation and thus prevent antimicrobial resistance in the region. Methods: children aged one day to eighteen years, admitted to the hospital for at least 48 hours, during the period of January 2015 to December 2016, with positive laboratory findings on clinical specimens and clinical features in keeping with HAI were included. Results: the total number of HAI were fifty-two infections in forty-one cases of which, twenty-five cases were culture proven bacterial HAI. Six cases had more than one HAI. The point prevalence of culture positive bacterial HAI in this study was 2.62% (95%CI: 3.8-6.7). The gastrointestinal infections (53%), blood stream infections (21%), lower respiratory tract infections (11%) were the commonest hospital acquired infections. Klebsiella Pneumoniae was the most common bacteria causing HAI with 61.53% of multidrug resistance strains. Conclusion: gastrointestinal infections were the commonest HAI followed by blood stream infections. The commonest bacteria causing HAI was Klebsiella pneumoniae. The multidrug resistant organisms were Klebsiella Pneumoniae, Enterobacter Cloacae and Acinetobacter baumannii mainly resistant to third and fourth generation cephalosporins and carbapenems.

Estimating the global and regional burden of meningitis in children caused by Haemophilus influenzae type b: A systematic review and meta-analysis.

Background: Haemophilus influenzae Type B (Hib) meningitis caused significant public health concern for children. Recent assessment in 2015 suggests vaccination has virtually eliminated invasive Hib diseases. However, many countries launched their programs after 2010, and few are yet to establish routine Hib immunisations. We therefore aimed to update the most recent global burden of Hib meningitis before the impact of COVID-19 pandemic, from 2010 to 2020, in order to aid future public health policies on disease management and prevention. Methods: Epidemiological data regarding Hib meningitis in children <5 years old were systematically searched and evaluated from PubMed and Scopus in August, 2020. We included studies published between 2010 and 2019 that reported incidence, prevalence, mortality, or case-fatality-ratio (CFR), and confirmation of meningitis by cerebrospinal fluid culture, with a minimum one year study period and ten cases. Each data was stratified by one study-year. Median study-year was used if information was not available. Quality of all studies were assessed using our adapted assessment criteria from Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from National Heart, Lung and Blood Institute (NHLBI). We constructed and visually inspected a funnel plot of standard error by the incidence rate and performed an Egger's regression test to statistically assess publication bias. To ascertain incidence and CFR, we performed generalised linear mixed models on crude individual study estimates. Heterogeneity was assessed using I-squared statistics whilst further exploring heterogeneity by performing subgroup analysis. Results: 33 studies were identified. Pooled incidence of global Hib meningitis in children was 1.13 per 100 000-child-years (95% confidence interval (CI) = 0.80-1.59). Southeast Asian Region (SEAR) of World Health Organisation (WHO) region reported the highest incidence, and European Region (EUR) the lowest. Considering regions with three or more data, Western Pacific Region (WPR) had the highest incidence rate of 5.22 (95% CI = 3.12-8.72). Post-vaccination incidence (0.67 cases per 100 000-child-years, 95% CI = 0.48-0.94) was dramatically lower than Pre-vaccination incidence (4.84 cases per 100 000-child-years, 95% CI = 2.95-7.96). Pooled CFR in our meta-analysis was 11.21% (95% CI = 7.01-17.45). Eastern Mediterranean Region (EMR) had the highest CFR (26.92, 95% CI = 13.41-46.71) while EUR had the lowest (4.13, 95% CI = 1.73-9.54). However, considering regions with three or more data, African Region (AFR) had the highest CFR at 21.79% (95% CI = 13.65-32.92). Before the coronavirus disease 2019 (COVID-19) impact, the estimation for global Hib meningitis cases in 2020 is 7645 and 857 deaths. Conclusions: Global burden of Hib meningitis has markedly decreased, and most regions have implemented vaccination programs. Extrapolating population-at-risk from studies has possibly led to an underestimation. Continuous surveillance is necessary to monitor vaccination impact, resurgence, vaccine failures, strain variance, COVID-19 impact, and to track improvement of regional and global Hib meningitis mortality.

Spirometry Abnormalities and Its Associated Factors Among Primary School Children in a Nigerian City.

BACKGROUND: There is paucity of data on objectively measured lung function abnormalities in Nigerian children using diagnostic testing methods such as spirometry. Such assessments could prompt early diagnosis and therapeutic interventions. METHODS: This was a cross sectional study among children aged 6 to 12 years in South-Eastern Nigeria. We selected participants from one school using a multistage stratified random sampling technique. A structured respiratory questionnaire was administered to obtain necessary data. The lung functions of the children were measured by spirometry. We used Lower Limits of Normal (LLN) based on GLI reference equations for African-American and mixed ethnicities to define abnormal spirometry. We studied the association between the exposures and lung function using logistic regression/chi-squared tests. RESULTS: A total of 145 children performed acceptable and repeatable tests. There were 73 males (50.3%), mean age of 9.13 years (+1.5) and age range 6 to 12 years. Frequency of respiratory symptoms was cough- 64 (44.1%) and wheeze in 19 (13.1%). Using GLI for African-Americans, fifty-five (37.9%) children had abnormal spirometryobstructive pattern in 40 (27.6%) and restrictive pattern in 15 (10.3%). The two references showed significant differences in interpretation of abnormality (χ2 = 72.86; P < .001). Respiratory symptom-wheeze was an independent determinant of abnormal lung function in this population.(OR = 0.31; 95%CI: 0.10-0.94; P = .04). CONCLUSION: There is a high burden of respiratory symptoms and abnormal spirometry among these children. The need for objective evaluation of lung function especially for children with respiratory symptoms is evident.

Global burden of active smoking among people living with HIV on antiretroviral therapy: a systematic review and meta-analysis.

BACKGROUND: Although the high burden of both active smoking and human immunodeficiency virus (HIV) is clearly known, the relationship between them is still not well characterized. Therefore, we estimated the global prevalence of active smoking in people living with HIV (PLHIV) on antiretroviral therapy (ART) and investigated the association between exposure to active smoking and risk for suboptimal adherence to ART. Main text: We searched PubMed, Embase, and Web of Science to identify articles published until September 19, 2019. Eligible studies reported the prevalence of active smoking in PLHIV on ART or investigated the association between active smoking and ART adherence; or enough data to compute these estimates. We used a random-effects model to pool data and quantified heterogeneity (I2). The global prevalence of active smoking was 36.1% (95% CI: 33.7-37.2; 329 prevalence data; 462 104 participants) with substantial heterogeneity. The prevalence increased with level of country income; from 10.1% (95% CI: 6.8-14.1) in low-income to 45.2% (95% CI: 42.7-47.7) in high-income countries; P < 0.0001. With regards to the Joint United Nations Programme on HIV/AIDS (UNAIDS) regions, the prevalence was higher in West and Central Europe and North America 45.4% (42.7-48.1) and lowest in the two UNAIDS regions of sub-Saharan Africa: Eastern and Southern Africa 10.7% (95% CI: 7.8-14.0) and West and Central Africa 4.4% (2.9-6.3); P < 0.0001. Globally, we estimated that there were 4 110 669 PLHIV on ART who were active smokers, among which the highest number was from Eastern and Southern Africa (35.9%) followed by Asia and the Pacific (25.9%). Active smoking was significantly associated with suboptimal ART adherence: pooled odds ratio 1.57 (95% CI: 1.37-1.80; I2 = 56.8%; 19 studies; 48 450 participants); even after considering adjusted estimates: 1.67 (95% CI: 1.39-2.01; I2 = 53.0%; 14 studies). CONCLUSIONS: This study suggests a high prevalence of active smoking in PLHIV on ART and an association between active smoking and ART suboptimal adherence. As such, healthcare providers and policy makers should focus on adopting and implementing tobacco harm reduction strategies in HIV care, especially in sub-Saharan Africa known as epicenter of HIV pandemic with highest number of active tobacco smoking among PLHIV on ART.

The Effect of Nebivolol on Office Blood Pressure of Blacks Residing in Sub-Saharan Africa (A Pilot Study).

Introduction: There is substantial clinical evidence that monotherapy with beta-blockers are less effective in reducing blood pressure among hypertensive Black patients compared to Whites. The highly selective beta-1 agents like nebivolol and bisoprolol have, however, been reported to be effective in reducing blood pressure in African Americans. However, results in African Americans cannot be extrapolated to native Africans because of genetic admixture and gene-environment interaction. There is, therefore, the need for us to generate data that are applicable to Africans residing in sub-Saharan Africa. We therefore decided to evaluate the efficacy and tolerability of highly selective beta-1 agent nebivolol in hypertensive Black patients residing in sub-Saharan Africa. Materials and Methods: The nebivolol study was a multicenter, prospective, observational program among hypertensive patients with 4- and 8-week follow up which was conducted in 5 cities in Nigeria of Abuja, Calabar, Enugu, Oghara, and Port Harcourt. Dosages of nebivolol used in keeping with local prescribing information were 5 and 10 mg once daily each. The effectiveness of treatment was assessed by change from baseline in mean office systolic and diastolic blood pressures, and the proportion of patients achieving the therapeutic goal of <140/90 mmHg. Safety and tolerability of this medication were also assessed. Results: We report the results of the 140 patients studied. The mean age and body mass index were 46.9 ± 7.3 years and 22.3 ± 5.8 kg/m2, respectively, and 57.1% were female. Nebivolol reduced SBP and DBP by 7.6 and 6.6 mmHg, respectively, in 4 weeks, and by 11.1 and 8.0 mm Hg, respectively, in 8 weeks. Blood pressure control was achieved in 54.8% of the patients in 4 weeks and increased to 60.4% in 8 weeks. There was no change in metabolic profile between randomization and at 8 weeks, and erectile dysfunction occurred in 1.3% of the study population. Conclusions: Nebivolol 5 and 10 mg appear efficacious in Nigerian Africans with no negative metabolic effect and minimal side effect profile. Clinical Trial Registration: www.ClinicalTrials.gov, Study Identification: NCT03598673.

Comparison of motorcycle taxi driver's respiratory health using an air quality standard for carbon monoxide in ambient air: a pilot survey in Benin.

INTRODUCTION: Ambient air quality standards are not designed to protect people occupationally exposed to outdoor air pollution on a routine basis. This study aimed to assess the effect of exceeding the US ambient air quality standard for carbon monoxide (CO) on motorcycle taxi drivers respiratory health. METHODS: A cross-sectional study of 85 current motorcycle taxi drivers with at least 5 years of job tenure in Cotonou (Benin) was conducted. Personal CO was measured with a portable CO data logger for 8 hours per day during working hours. A questionnaire on respiratory symptoms was administered to participants and spirometry was performed. Participants were divided into two groups, those with exposure to CO >9 ppm and ≤9 ppm, according to the US Environmental Protection Agency (EPA) National Ambient Air Quality Standard which is an 8-hour average of 9ppm. 8 and 10 ppm were also used an exposure limit. Analysis was done using these two groups. RESULTS: Socio-demographic characteristics were well balanced between the two study groups. The drivers with a CO exposure of more than 9ppm had non-significantly more respiratory symptoms (OR=1.67; 95%CI:0.26,10.74), lower FVC and FEV1 compared to the less exposed group but they have a significant lower PEF (-10%, p=0.02). When we used an exposure limit of 8 or 10 ppm the results were not statistically different. CONCLUSION: Drivers with a CO exposure >9 ppm tend to have more respiratory problems. More research is needed to reinforce this result in order to improve air quality standards to protect workers occupationally exposed to outdoor air pollution.