Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

Human immune responses to vaccines in the first year of life: biological, socio-economic and ethical issues - a viewpoint.

Human newborns are vulnerable to infectious diseases that account for majority of the morbidity and mortality, particularly in first year of life. Vaccines have become the most effective public health intervention strategy to curtail the prevalence of these infectious diseases. Although vaccines against a number of diseases exist, there are no vaccines against many other diseases that commonly affect children. The adequate assessment of immune responses to vaccines is an important step in the development of vaccines. However, a number of biological and "non-medical" socio-economic and ethical factors could influence either the administration and/or evaluation of vaccines in infants. Recognition and understanding of these determinants are crucial in planning interventions and for logical interpretations of results.

Invasive Bacteria Isolates from Children with Severe Infections in a Nigerian Hospital

Background: Little information is available about the aetiology and epidemiology of serious bacterial infections in Nigeria. This study determined bacterial isolates from blood and cerebrospinal fluid (CSF) of children presenting in the emergency room of a teaching hospital in Nigeria. Method: From October 2005 to December 2006; children aged two to 60 months presenting with signs of acute systemic infections were recruited. Blood culture and CSF specimens were collected and processed using standard microbiological protocols. Data were analysed using SPSS version 11 software. Results: Two hundred and two blood and 69 CSF samples were cultured. Fifty-five (27) of the blood cultures yielded Gram-negative bacilli and Gram-positive cocci in almost equal proportions. The most common isolates from the blood cultures were Staphylococcus aureus; 26 (12.9) and atypical coliforms; 13 (6.5). Others are Klebsiella spp; 3 (1.5); Klebsiella pneumonia; 2 (1.0); Escherichia coli; 3 (1.5); Enterobacter agglomerans; 2 (1.1); Proteus mirabilis; 2(1); Pseudomonas spp; 2 (1.0); Haemophilus influenza; 1 (1.0); and Coagulase-negative Staphylococcus; 1 (1.0). Fourteen out of 67 (20.9) of the CSF samples yielded bacterial isolates: Streptococcus pneumonia; 3 (4.5); Haemophilus influenza; 8 (11.9); Hemophilus spp; 1 (1.5); E. Coli; 1 (1.5); and atypical coliform; 1 (1.5). Gram-negative coliform isolates were predominantly resistant to penicillin based antibiotics and co-trimoxazole but sensitive to third-generation cephalosporins and quinolones. A high percentage of S. aureus isolates were multi-drug resistant. Conclusions: Bacterial infections contribute to the significant morbidity among children in our environment. S. aureus was more frequently isolated in sepsis while H. influenzae appears to play a major role in meningitis. Appropriate use of antibiotics is needed to manage affected children effectively. We also recommend improved vaccine coverage of children under the age of five years) of the blood cultures yielded Gram-negative bacilli and Gram-positive cocci in almost equal proportions. The most common isolates from the blood cultures were Staphylococcus aureus; 26 (12.9) and atypical coliforms; 13 (6.5). Others are Klebsiella spp; 3 (1.5); Klebsiella pneumonia; 2 (1.0); Escherichia coli; 3 (1.5); Enterobacter agglomerans; 2 (1.1); Proteus mirabilis; 2(1); Pseudomonas spp; 2 (1.0); Haemophilus influenza; 1 (1.0); and Coagulase-negative Staphylococcus; 1 (1.0). Fourteen out of 67 (20.9) of the CSF samples yielded bacterial isolates: Streptococcus pneumonia; 3 (4.5); Haemophilus influenza; 8 (11.9); Hemophilus spp; 1 (1.5); E. Coli; 1 (1.5); and atypical coliform; 1 (1.5). Gram-negative coliform isolates were predominantly resistant to penicillin based antibiotics and co-trimoxazole but sensitive to third-generation cephalosporins and quinolones. A high percentage of S. aureus isolates were multi-drug resistant.Conclusions: Bacterial infections contribute to the significant morbidity among children in our environment. S. aureus was more frequently isolated in sepsis while H. influenzae appears to play a major role in meningitis. Appropriate use of antibiotics is needed to manage affected children effectively. We also recommend improved vaccine coverage of children under the age of five years