Immunization with a whole cell vaccine reduces pneumococcal nasopharyngeal density and shedding, and middle ear infection in mice.

Pneumococcal Conjugate Vaccines (PCVs) have substantially reduced the burden of disease caused by Streptococcus pneumoniae (the pneumococcus). However, protection is limited to vaccine serotypes, and when administered to children who are colonized with pneumococci at the time of vaccination, immune responses to the vaccine are blunted. Here, we investigate the potential of a killed whole cell pneumococcal vaccine (WCV) to reduce existing pneumococcal carriage and mucosal disease when given therapeutically to infant mice colonized with pneumococci. We show that a single dose of WCV reduced pneumococcal carriage density in an antibody-dependent manner. Therapeutic vaccination induced robust immune responses to pneumococcal surface antigens CbpA, PspA (family 1) and PiaA. In a co-infection model of otitis media, a single dose of WCV reduced pneumococcal middle ear infection. Lastly, in a two-dose model, therapeutic administration of WCV reduced nasal shedding of pneumococci. Taken together, our data demonstrate that WCV administered in colonized mice reduced pneumococcal density in the nasopharynx and the middle ear, and decreased shedding. WCVs would be beneficial in low and middle-income settings where pneumococcal carriage in children is high.

Predictors of antibody persistence to the 7-valent pneumococcal conjugate vaccine in healthy Fijian infants at 12 months of age.

Little is known about the predictors of antibody persistence to pneumococcal conjugate vaccines (PCV) in the context of reduced dose schedules. In Fiji, an RCT investigated 0, 1, 2 and 3 dose schedules of 7-valent PCV administered at 6, 10 and 14 weeks of age in 364 healthy infants. This study was a post-hoc analysis of the predictors of poor antibody persistence at 12 months, prior to a booster, using univariable and multivariable analyses. The strongest predictors of poor antibody persistence as measured by serotype-specific immunoglobulin G (IgG) and opsonophagocytosis (OI) assays were being of Indigenous Fijian ethnicity (IgG: adjusted odds ratio (aOR) 3.43, p < 0.001; OI: aOR 1.96, p = 0.013) and receipt of fewer than 3 doses of PCV. These findings may help to identify which children may be at an increased risk of pneumococcal disease in the context of reduced dose primary series PCV schedules.

Using pneumococcal carriage studies to monitor vaccine impact in low- and middle-income countries.

Pneumococcal disease is a leading cause of childhood mortality, globally. The pneumococcal conjugate vaccine (PCV) has been introduced to many countries worldwide. However there are few studies evaluating PCV impacts in low- and middle-income countries (LMIC) because measuring the impact of PCV on pneumococcal disease in LMICs is challenging. We review the role of pneumococcal carriage studies for the evaluation of PCVs in LMICs and discuss optimal methods for conducting these studies. Fifteen carriage studies from 13 LMICs quantified the effects of PCV on carriage, and identified replacement carriage serotypes in the post-PCV era. Ten studies reported on the indirect effects of PCV on carriage. Results can be used to inform cost-effectiveness evaluations, guide policy decisions on dosing and product, and monitor equity in program implementation. Critically, we highlight gaps in our understanding of serotype replacement disease in LMICs and identify priorities for research to address this gap.

The spectrum of hypoxaemia in children admitted to hospital in The Gambia, West Africa.

OBJECTIVE: Hypoxia predicts mortality in children with acute lower respiratory infections (ALRIs). We investigated the prevalence and predictive value of hypoxia in ALRI and other acute infectious diseases. METHODS: We studied the spectrum of hypoxaemia in 4,047 children admitted to a tertiary hospital in The Gambia. Oxygen saturation was measured shortly after admission. Severe hypoxaemia was defined as an oxygen saturation below 90%. RESULTS: 5.8% of all admissions had severe hypoxaemia. Prevalence of hypoxaemia varied between disease groups: it was 11.7% in ALRI cases, 16.5% in neonates; 2.9% in malaria cases overall but 6.5% in cerebral malaria patients; and 2.7% in children with meningitis. Hypoxaemia predicted a poor outcome; the odds ratio for death among paediatric admissions overall was 7.45 [95% confidence intervals (CI) 5.40-10.29]. Surprisingly, it was lowest for children with ALRI [OR 3.53 (95% CI 1.13-10.59)], and higher for those with malaria 9.90 [95% CI 4.39-22.35]. CONCLUSION: Hypoxaemia is common among Gambian children admitted to hospital and it is often associated with a poor outcome. A similar situation is likely in many other developing countries. Thus, equipment for measuring oxygen saturation, and facilities and equipment for effective oxygen delivery need to be made available in developing countries.