Community-acquired invasive Staphylococcus aureus: Uncovering disparities and the burden of disease in Auckland children.

AIM: Staphylococcus aureus (SA) causes serious invasive disease in children. Large studies have measured the incidence of SA bacteraemia, but there is less information on the total burden of community-acquired invasive SA (iSA) in children. METHODS: A retrospective, cross-sectional analysis of Auckland resident children aged 0-14 years who were hospitalised with iSA between 2011 and 2015 was performed. Laboratory databases and SA-related international classification of diseases 10 discharge codes were searched to identify community-onset cases with SA isolated from a normally sterile site. Clinical records and coroner's reports were reviewed to determine clinical syndromes and exclude nosocomial infections. RESULTS: A total of 295 children with iSA were identified. The average annual incidence of iSA was 18.6 per 100 000 - for Pacific populations 44.3 per 100 000, Maori 24.3 per 100 000 and New Zealand European and other 8.8 per 100 000; 68% had bacteraemia. The incidence of iSA for Pacific infants was 10 times greater than non-Maori/non-Pacific (113.4/100 000 population vs. 11.8/100 000). Multivariate analysis found a higher risk of admission in Pacific children, males and those living in areas of high deprivation. Thirty-two patients (10.8%) were admitted to the intensive care unit; risk was higher in infants, Pacific children and those with respiratory infection (Relative Risk (RR) 12.2, 95% confidence interval (CI) 5.7-26.4) and multifocal (RR 6.9, 95% CI 3.4-13.8) and endovascular disease (RR 8.9, 95% CI 3.9-20.6). All deaths (n = 7) had respiratory infections, and four were patients <1 year of age. CONCLUSIONS: Studies investigating SA bacteraemia alone significantly underestimate the total burden of iSA disease. There are marked ethnic and socio-economic disparities in iSA disease among Auckland children. Pacific infants are at the highest risk.

Post-streptococcal glomerulonephritis: Some reduction in a disease of disparities.

AIM: A retrospective Auckland-wide (total population approximately 1.4 million) study of hospital admissions from 2007 to 2015 was conducted to assess trends in admissions for acute post-streptococcal glomerulonephritis (APSGN) in children aged 0-14 years. METHODS: International Statistical Classification of Diseases (ICD10) discharge codes were used to identify potential cases of APSGN, and electronic clinical records and laboratory data were compared with established case definitions for definite or probable APSGN. RESULTS: A total of 430 cases of APSGN were identified (definite n = 337, probable n = 93), with a mean annual incidence of 15.2/100 000 (95% confidence interval (CI) 14.9-15.6). Incidence (0-14 years) was 17 times higher in Pacific peoples (50.2/100 000, 95% CI 48.6-51.8) and almost 7 times higher in Maori (19.6/100 000, 95% CI 18.6-20.7) than European/other populations (2.9/100 000, 95% CI 2.7-3.1). Multivariate analysis found ethnicity, deprivation, male gender, age (peak 3-8 years) and season (summer/autumn) to be associated with admission risk. Admission rates showed a significant change of -9.0% (95% CI -10.4, 7.4%) per year, with 2011 being an exception. Low C3 complement, hypertension, elevated streptococcal titres, oedema and heavy proteinuria were present in 94, 65, 67, 52 and 49% of cases, respectively. Relying on ICD10 codes without further review of clinical notes would result in an overcount of cases by 25%. CONCLUSIONS: There is severe disparity in APSGN admission rates, with a disproportionate burden of disease for Pacific and Maori children and those living in deprived circumstances. Rates trended downward from 2007 to 2015.

Fast tracking the vaccine licensure process to control an epidemic of serogroup B meningococcal disease in New Zealand.

Epidemics of serogroup B meningococcal disease are rare. Strain-specific outer membrane vesicle vaccines, which are not marketed, are the only current tool for control. A correlate of protection is ill defined, but published data suggest that measured serum bactericidal antibody levels parallel efficacy. Even infants can mount a strain-specific antibody response to a strain-specific vaccine. New Zealand's epidemic (1991-2007; peak rate [in 2001], 17.4 cases per 100,000 persons) was dominated by a single strain. After a 5-year search (1996-2001) for a manufacturer for a strain-specific outer membrane vesicle vaccine, a fast-tracked research program (2002-2004) determined the safety and immunogenicity of vaccine in infants (2 age groups: 6-10 weeks and 6-8 months), children (age, 16-24 months), and school-aged children (age, 8-12 years) after an adult trial. The vaccine was reactogenic, compared with control vaccines (meningococcal C conjugate and routine infant vaccines), but retention was high. Three vaccine doses produced antibody levels (measured by serum bactericidal assay) that were considered to be adequate for public health intervention. However, in young infants, a fourth dose was required to achieve levels equivalent to those achieved by other age groups. Provisional licensure by New Zealand's MedSafe was based on serological criteria strengthened by bridged safety data from studies of the parent outer membrane vesicle vaccine, independent assessment of manufacturing quality, and a clear plan for safety monitoring and effectiveness evaluation after licensure.