Encephalitis in Australian children: contemporary trends in hospitalisation.

OBJECTIVE: The clinical epidemiology of childhood encephalitis in Australia is inadequately understood. We aimed to describe recent trends in childhood encephalitis-related hospitalisation. STUDY DESIGN: We identified encephalitis-related hospital admissions (2000-2012) in national datasets among children ≤14 years using ICD encephalitis codes. We calculated hospitalisation rates and analysed trends by year, age, gender, location, indigenous status and aetiology. RESULTS: Rates of childhood encephalitis hospitalisations significantly declined over an 11-year period (2000-2012; average hospitalisation rate 3.2/100 000). Varicella encephalitis hospitalisations decreased significantly, associated with high levels of varicella vaccine coverage since 2006. Acute disseminated encephalomyelitis (ADEM) was the most common 'specified' cause of encephalitis hospitalisation (15%-17%), and its rate has significantly increased. The highest hospitalisation rates occurred in the <1 year age group (5.8/100 000) and varied by location (highest in Northern Territory). The majority (58.9%) of hospitalised encephalitis had no cause identified; this proportion was highest in the <1 year age group (77%). The most common specified infectious causes included: herpes simplex virus, enterovirus, bacterial meningoencephalitis and varicella. When aggregated, the proportion of childhood encephalitis coded as viral was 21.2%. CONCLUSION: Hospitalisation of childhood encephalitis has slightly decreased in Australia. High rates of childhood immunisation have been associated with a reduction of varicella-associated encephalitis in Australian children. ADEM, an immune-mediated encephalitis, is the most common recognised cause of encephalitis in children. Young children (<1 year) have the highest admission rates. The high proportion of 'unspecified' encephalitis deaths and hospitalisations is an ongoing challenge.

Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients.

In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach.

Varicella zoster disease of the central nervous system: epidemiological, clinical, and laboratory features 10 years after the introduction of the varicella vaccine.

BACKGROUND: Since the introduction of live attenuated varicella zoster virus (VZV) vaccine in 1995 there has been a significant reduction in varicella incidence and its associated complications, but the impact on VZV-associated central nervous system (CNS) disease has not been assessed. METHODS: In this descriptive study we evaluated patients referred to the California Encephalitis Project from 1998 to 2009 with VZV PCR-positive cerebrospinal fluid (CSF). Epidemiological, clinical, and laboratory data were collected using a standardized case form. Specimens were genotyped using multi-single nucleotide polymorphism (SNP) analysis. RESULTS: Twenty-six specimens were genotyped from patients 12-85 years of age (median, 46 years). Clinical presentations included meningitis (50%), encephalitis (42%), and acute disseminated encephalomyelitis (ADEM) (8%). Only 11 patients (42%) had a concomitant herpes zoster rash. Genotype analysis identified 20 European Group (Clade1, Clade 3) strains; 4 Asian (Clade 2) strains, and 2 Mosaic Group (Clade 4, Clade VI) strains. One specimen was recognized as vaccine strain by identifying vaccine-associated SNPs. CONCLUSIONS: VZV continues to be associated with CNS disease, with meningitis being the most frequent clinical presentation. CNS VZV disease often presented without accompanying zoster rash. Sequencing data revealed multiple genotypes, including 1 vaccine strain detected in the CSF of a young patient with meningitis.