Unusual Gram-negative bacteria cause more severe bacterial meningitis than the three classical agents in children

Aim To compare the characteristics, mortality and sequelae at hospital discharge of childhood bacterial meningitis (BM) caused by the three "classical" agents Neisseria meningitidis, Haemophilus influenzae or Streptococcus pneumoniae versus BM due to other aetiology in Finland, Latin America and Angola. Methods This observational study is a secondary analysis of data from five prospective treatment trials on non-neonatal BM in Finland, Latin America and Angola in 1984-2017. Results Of the 1568 cases, 1459 (93%) were caused by the classics, 80 (5%) by other Gram-negative and 29 (2%) by other Gram-positive bacteria. Nonclassical Gram-negative disease was encountered especially in Angola (p < 0.0001). Overall, children in the nonclassical group presented later for treatment and were more often underweight and anaemic (p < 0.001). In multivariate analysis, even if the area was strongest predictor of poor outcome, nonclassical Gram-negative BM increased the odds for death twofold and the odds for death or severe sequelae 2.5-fold. Conclusion BM of a nonclassical aetiology is a particularly severe disease affecting especially Angolan children poorly armoured to fight infections. Since vaccinations are diminishing the role of classical agents, that of nonclassical agents is growing.Peer reviewe

Importance of underweight in childhood bacterial meningitis in Finland, Latin America and Angola

Our objective was to explore the importance of underweight on the course of childhood bacterial meningitis (BM) at different study sites, because prior studies showed discrepant results. Using directly comparable, prospective data from three continents, weight-for-age z-scores (WAZ) were determined by WHO Anthro programs in children with BM in Finland (N = 318), LatAm (N = 580), and Angola (N = 780) and compared with data describing the admission, course, and outcome of BM. WAZ < -1 indicates underweight; either mild (< -1 to -2), moderate (< -2 to -3), or severe (< -3). The mean WAZ (SD) was 0.17 (1.17), -0.42 (1.53), and -1.36 (1.44), and the prevalence of moderate-severe underweight 2.8%, 12.6%, and 31.3%, in Finland, LatAm, and Angola, respectively. In univariate analysis, LatAm and Angola showed an association between lower WAZ and poorer condition on admission, slower recovery, and more deaths. In Finland, infrequent underweight limited meaningful analysis. In multivariate analysis of different variables for increasing the odds of death, severe underweight had lower odds compared to disease severity in Angola, but highest in LatAm. Thus, the apparent discrepancy in underweights ' importance for increasing deaths varied from primary to more secondary according to locally more prominent risks.Peer reviewe

Bacterial Meningitis in Children With Sickle Cell Disease in Angola

Publisher Copyright: Copyright © 2022 The Author(s).Sickle cell disease (SCD) was found in 10% of children with bacterial meningitis (BM) in Luanda, 5-fold more than in the general population. BM children with SCD versus BM children without SCD had higher inflammatory markers, more often had pneumococcal meningitis (71% vs. 39%), and either died (39% vs. 22%) or had a longer hospital stay (15 vs. 11 days).Peer reviewe

Prevalence and significance of anaemia in childhood bacterial meningitis : a secondary analysis of prospectively collected data from clinical trials in Finland, Latin America and Angola

Objectives To describe the prevalence and severity of anaemia and to examine its associations with outcome in children with bacterial meningitis (BM). Design Secondary analysis of descriptive data from five randomised BM treatment trials. Setting Hospitals in Finland, Latin America and Angola. Participants Consecutive children from 2 months to 15 years of age admitted with BM and who had haemoglobin (Hb) measured on admission. Outcome measures Prevalence and degree of anaemia using the WHO criteria, and their associations with recovery with sequelae or death. Results The median Hb was 11.8 g/dL in Finland (N=341), 9.2 g/dL in Latin America (N=597) and 7.6 g/dL in Angola (N=1085). Of the children, 79% had anaemia, which was severe in 29%, moderate in 58% and mild in 13% of cases. Besides study area, having anaemia was independently associated with age 3 days, weight-for-age z-score Conclusion Anaemia, mostly moderate, was common in children with BM, especially in Angola, in underweight children, among those with treatment delay, and in pneumococcal meningitis. Poor outcome was associated with anaemia in all three continents.Peer reviewe

Antibiotics by bolus or infusion for bacterial meningitis? : [Authors’ reply]

Non peer reviewe

Extended Continuous beta-Lactam Infusion With Oral Acetaminophen in Childhood Bacterial Meningitis : A( )Randomized, Double-blind Clinical Trial

Background. In our previous study in Luanda, Angola, initial continuous beta-lactam infusion for 24 hours combined with oral acetaminophen for 48 hours showed promising results as a new treatment for childhood bacterial meningitis. We investigated whether extending this treatment regimen to 4 days would improve the outcomes further. Methods. We conducted a randomized, double-blind, parallel-group study at the same hospital in Luanda. Children aged 2 months to 15 years presenting to hospital with symptoms and signs of bacterial meningitis were randomized to receive, for the first 4 days, a continuous infusion of cefotaxime (250 mg/kg/day) with simultaneous oral acetaminophen (first dose 30 mg/kg, then 20 mg/kg every 6 hours), or cefotaxime conventionally as boluses (62.5 mg/I%, 4 times per day) with placebo orally. All children received also glycerol orally. The primary outcome was mortality by day 7. Results. In all, 375 patients were included in the study between 22 January 2012 and 21 January 2017. As 2 children succumbed before treatment initiation, 187 vs 186 participants remained in the intervention and control groups, respectively. On day 7, 61 of 187 (32.6%) children in the intervention group vs 64 of 186 (34.4%) in the control group had died (risk ratio, 0.95 [95% confidence interval {CI}, .71-1.26]; absolute risk difference, 1.8% [95% CI, -7.8 to 11.4]). At discharge from hospital, the corresponding numbers were 71 of 187 (38.0%) and 75 of 186 (40.3%), respectively. Conclusions. Prolonged continuous beta-lactam infusion combined with oral acetaminophen did not improve the gloomy outcomes of childhood bacterial meningitis in Angola.Peer reviewe

Bone and Joint Infections in Children and Adolescents in Luanda, Angola

We reviewed the characteristics of children hospitalized for bone and joint infections in Luanda, Angola. In a retrospective chart review of 45 patients with childhood osteomyelitis or septic arthritis, 51% of the patients had sickle cell disease, and these patients presented with lower hemoglobin and needed blood transfusion more frequently (p < 0.05). Out of all patients, 64% underwent surgical procedures; a pathological fracture occurred in 31% of the patients

Otorhinolaryngological findings and hearing in HIV-positive and HIV-negative children in a developing country

Peer reviewe

Bone and Joint Infections in Children and Adolescents in Luanda, Angola

We reviewed the characteristics of children hospitalized for bone and joint infections in Luanda, Angola. In a retrospective chart review of 45 patients with childhood osteomyelitis or septic arthritis, 51% of the patients had sickle cell disease, and these patients presented with lower hemoglobin and needed blood transfusion more frequently (p < 0.05). Out of all patients, 64% underwent surgical procedures; a pathological fracture occurred in 31% of the patients

Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children

Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) ofTLR4andTLR9are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPsTLR4rs4986790 (896A > G) andTLR9rs187084 (-1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes inTLR4was significantly higher in patients withHaemophilus influenzaemeningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2-5.4;p= 0.021), whereas the frequency of variant genotypes inTLR9was significantly lower in patients withH. influenzaemeningitis than controls (OR, 0.4; 95% CI, 0.2-0.9;p= 0.036). No such differences were found with other causative pathogens, such asStreptococcus pneumoniaeandNeisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variantTLR4genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52-109.80;p= 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07-131.49;p= 0.044) than those with the wild-typeTLR4genotype. Our study suggests an association betweenH. influenzaemeningitis and genetic variation betweenTLR4andTLR9in Angolan children.Peer reviewe