Improving the accuracy of ACIR data and increasing vaccination rates.

Immunisation at the earliest appropriate age and high levels of vaccine coverage at milestone ages are important in preventing the spread of vaccine-preventable diseases. At the Central Coast Public Health Unit, the authors sought to determine if follow-up of children said by the Australian Childhood Immunisation Register (ACIR) to be overdue for vaccination improved both of these factors. In a quality improvement activity, monthly ACIR lists of overdue Central Coast children aged 9 to 10 months of age were examined. The study alternated three months of intervention with three months of no intervention. The intervention was designed to find evidence of vaccination, first from the last known provider, and then if this was unsuccessful, from the parent. If no information was available, a letter was sent to the parents. If the child was indeed vaccinated, the register was updated. If the child was missing any vaccinations, the parent(s) were encouraged to complete the schedule. On reviewing routinely-published quarterly ACIR data at three-monthly intervals for 24 months after the intervention (or non-intervention), timeliness of vaccination improved in the intervention cohort. Central Coast fully vaccinated rates diverged from NSW rates during the study. In addition, the ACIR quarters that contained two out of three months of intervention rather than one out of three months of intervention had the highest rates of fully vaccinated children. The authors concluded that the intervention improved both timeliness of vaccination and the proportion of fully vaccinated children.

Overexpression of neprilysin reduces alzheimer amyloid-beta42 (Abeta42)-induced neuron loss and intraneuronal Abeta42 deposits but causes a reduction in cAMP-responsive element-binding protein-mediated transcription, age-dependent axon pathology, and premature death in Drosophila.

The amyloid-beta42 (Abeta42) peptide has been suggested to play a causative role in Alzheimer disease (AD). Neprilysin (NEP) is one of the rate-limiting Abeta-degrading enzymes, and its enhancement ameliorates extracellular amyloid pathology, synaptic dysfunction, and memory defects in mouse models of Abeta amyloidosis. In addition to the extracellular Abeta, intraneuronal Abeta42 may contribute to AD pathogenesis. However, the protective effects of neuronal NEP expression on intraneuronal Abeta42 accumulation and neurodegeneration remain elusive. In contrast, sustained NEP activation may be detrimental because NEP can degrade many physiological peptides, but its consequences in the brain are not fully understood. Using transgenic Drosophila expressing human NEP and Abeta42, we demonstrated that NEP efficiently suppressed the formation of intraneuronal Abeta42 deposits and Abeta42-induced neuron loss. However, neuronal NEP overexpression reduced cAMP-responsive element-binding protein-mediated transcription, caused age-dependent axon degeneration, and shortened the life span of the flies. Interestingly, the mRNA levels of endogenous fly NEP genes and phosphoramidon-sensitive NEP activity declined during aging in fly brains, as observed in mammals. Taken together, these data suggest both the protective and detrimental effects of chronically high NEP activity in the brain. Down-regulation of NEP activity in aging brains may be an evolutionarily conserved phenomenon, which could predispose humans to developing late-onset AD.

Abeta42 mutants with different aggregation profiles induce distinct pathologies in Drosophila.

Aggregation of the amyloid-beta-42 (Abeta42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc) and an artificial mutation (Abeta42art) that is known to suppress aggregation and toxicity of Abeta42 in vitro. In the Drosophila brain, Abeta42Arc formed more oligomers and deposits than did wild type Abeta42, while Abeta42art formed fewer oligomers and deposits. The severity of locomotor dysfunction and premature death positively correlated with the aggregation tendencies of Abeta peptides. Surprisingly, however, Abeta42art caused earlier onset of memory defects than Abeta42. More remarkably, each Abeta induced qualitatively different pathologies. Abeta42Arc caused greater neuron loss than did Abeta42, while Abeta42art flies showed the strongest neurite degeneration. This pattern of degeneration coincides with the distribution of Thioflavin S-stained Abeta aggregates: Abeta42Arc formed large deposits in the cell body, Abeta42art accumulated preferentially in the neurites, while Abeta42 accumulated in both locations. Our results demonstrate that manipulation of the aggregation propensity of Abeta42 does not simply change the level of toxicity, but can also result in qualitative shifts in the pathology induced in vivo.

Septicaemia secondary to Vibrio vulnificus cellulitis.

Vibrio vulnificus is a naturally occurring, salt-water bacteria found in estuarine and coastal waters worldwide. It prefers low salinity and warm water temperatures for optimum growth. Infection from Vibrio vulnificus is uncommon, although it has been reported from many locations (e.g. southern United States of America, Israel, Republic of Korea, Japan, Taiwan, Spain, Turkey). It can be serious and life threatening, causing septicaemia and wound infections. This paper reports a case of septicaemia secondary to Vibrio vulnificus cellulitis in an elderly woman. The infection was acquired after wading in a coastal lagoon with a pre-existing superficial leg wound.

Tremor syndrome associated with a fungal toxin: sequelae of food contamination.

We report on an elderly couple who presented with a syndrome that included severe generalised tremor and incoordination after eating soup from a damaged can. Black mould contaminating the can was subcultured and the fungus Penicillium crustosum was identified. This fungus usually produces a potent neurotoxin called penitrem A. The couple displayed symptoms consistent with penitrem A ingestion, all of which resolved fully. Penitrem A intoxication has been well documented in animals, but not in humans.