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.

Marked decline of sudden mass fatality events in New Zealand 1900 to 2015: the basic epidemiology.

OBJECTIVE: To describe the basic epidemiology of sudden mass fatality events for the 1900 to 2015 period in New Zealand (NZ). METHODS: Official lists and internet searches were used to identify the events. Events were categorised, rates calculated and time trends analysed. RESULTS: A total of 56 sudden mass fatality events with 10 or more fatalities between 1900 and 2015 in NZ were identified. There were 1,896 deaths in total, with the worst event being the Hawke's Bay earthquake (258 deaths). Events were classified as transportation-related (64%), natural causes (11%), industrial (9%), war (9%) and infrastructure (5%). There were marked declines in the rate of events per person-years of exposure and the associated mortality rate (both p<0.0001). Knowledge gaps were identified around: i) the basic epidemiology, e.g. non-fatal injuries and numbers of survivors; ii) the role of subsequent official inquiries in guiding preventive measures; and iii) the likely cost-effectiveness of measures to prevent harm from such events. CONCLUSIONS: The occurrence and health burden of sudden mass fatality events have markedly declined in NZ over time. Implications for public health: There remains large scope for addressing the knowledge gaps in the basic epidemiology and societal responses to these events to guide primary prevention and appropriate disaster response.

Prolonged Type 1 Metabotropic Glutamate Receptor Dependent Synaptic Signaling Contributes to Spino-Cerebellar Ataxia Type 1.

UNLABELLED: Type 1 metabotropic glutamate receptor (mGluR1)-dependent signaling at parallel fiber to Purkinje neuron synapses is critical for cerebellar function. In a mouse model of human spino-cerebellar ataxia type 1 (early SCA1, 12 weeks) we find prolonged parallel fiber mGluR1-dependent synaptic currents and calcium signaling. Acute treatment with a low dose of the potent and specific activity-dependent mGluR1-negative allosteric modulator JNJ16259685 shortened the prolonged mGluR1 currents and rescued the moderate ataxia. Our results provide exciting new momentum for developing mGluR1-based pharmacology to treat ataxia. SIGNIFICANCE STATEMENT: Ataxia is a progressive and devastating degenerative movement disorder commonly associated with loss of cerebellar function and with no known cure. In the early stages of a mouse model of human spinocerebellar ataxia type 1, SCA1, where mice exhibit only moderate motor impairment, we detect excess "gain of function" of metabotropic glutamate receptor signaling at an important cerebellar synapse. Because careful control of this type of signaling is critical for cerebellar function in mice and humans, we sought to remove the excess signaling with a powerful, readily available pharmacological modulator. Remarkably, this pharmacological treatment acutely restored normal motor function in the ataxic mice. Our results pave the way for exploring a new avenue for early treatment of human ataxias.