Monitoring vaccine reactions in Australia.
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Biomedical subjects
Publications and source records attributed to Nicholas Wood.
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In most of Australia, general practitioners manage routine childhood vaccination schedules. However, paediatricians have an important role and need to have a thorough understanding of vaccination, particularly as it interfaces with other medical care. This is challenging as the Australian Standard Vaccination Schedule has undergone some substantial changes over the past 4 years, with the addition of meningococcal C conjugate, 7 valent pneumococcal conjugate, varicella and inactivated polio vaccines. Paediatricians are frequently the first port of call for advice on vaccination schedules for children with special needs, in relation to either vaccine efficacy or the risk of side effects. Categories include children with a range of chronic diseases, immunosuppression, premature infants and immigrant children. Advice about specific vaccines such as varicella, inactivated polio, influenza or multivalent vaccines and revaccination after adverse events is also often sought. The aim of this article is to update paediatricians on vaccination recommendations and relevant reference sources. The first part of this article discusses groups with special vaccination requirements. The second part discusses the use of individual vaccines in these children.
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Extremely long (>150) CAG repeats are often used to create models of polyglutamine diseases yet are very rare in humans where they manifest as pediatric multisystem syndromes of little specificity. Here, we describe an infant with 180 CAG repeats in the spinocerebellar ataxia type 7 gene and focus on systemic ataxin-7 aggregation. This was found in many organs, including the cardiovascular system. In the brain, the hippocampus emerged as a principal site of ataxin-7 aggregation without cell loss. We note differential ubiquitination of aggregates and discuss how this may relate to selective vulnerability.
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Since the advent of widespread testing for the presence of the DYT1 gene mutation, the range of phenotypes that have been associated with this genetic abnormality has expanded. We report on 5 DYT1 gene-positive patients with unusual phenotypes. Two of them had late presentation, one of these after peripheral injury. Three additional patients had late progression of symptoms, onset after exposure to haloperidol, and severe bulbar involvement, respectively. The clinical heterogeneity of this condition raises problems for clinicians in selecting appropriate patients for diagnostic testing. Also, because of the low phenotypic penetrance of DYT1 dystonia, the discovery of the DYT1 mutation in a patient with an atypical clinical syndrome may not necessarily suggest a causal relationship. We have, therefore, analysed all published clinical studies of DYT1 dystonia to guide clinical decision making concerning DYT1 gene testing based on current information.
We previously have described a group of patients with gluten sensitivity presenting with ataxia (gluten ataxia) and suggested that this disease entity may account for a large number of patients with sporadic idiopathic ataxia. We have therefore investigated the prevalence of gluten sensitivity amongst a large cohort of patients with sporadic and familial ataxia and looked at possible genetic predisposition to gluten sensitivity amongst these groups. Two hundred and twenty-four patients with various causes of ataxia from North Trent (59 familial and/or positive testing for spinocerebellar ataxias 1, 2, 3, 6 and 7, and Friedreich's ataxia, 132 sporadic idiopathic and 33 clinically probable cerebellar variant of multiple system atrophy MSA-C) and 44 patients with sporadic idiopathic ataxia from The Institute of Neurology, London, were screened for the presence of antigliadin antibodies. A total of 1200 volunteers were screened as normal controls. The prevalence of antigliadin antibodies in the familial group was eight out of 59 (14%), 54 out of 132 (41%) in the sporadic idiopathic group, five out of 33 (15%) in the MSA-C group and 149 out of 1200 (12%) in the normal controls. The prevalence in the sporadic idiopathic group from London was 14 out of 44 (32%). The difference in prevalence between the idiopathic sporadic groups and the other groups was highly significant (P < 0.0001 and P < 0.003, respectively). The clinical characteristics of 68 patients with gluten ataxia were as follows: the mean age at onset of the ataxia was 48 years (range 14-81 years) with a mean duration of the ataxia of 9.7 years (range 1-40 years). Ocular signs were observed in 84% and dysarthria in 66%. Upper limb ataxia was evident in 75%, lower limb ataxia in 90% and gait ataxia in 100% of patients. Gastrointestinal symptoms were present in only 13%. MRI revealed atrophy of the cerebellum in 79% and white matter hyperintensities in 19%. Forty-five percent of patients had neurophysiological evidence of a sensorimotor axonal neuropathy. Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia. Antigliadin antibody testing is essential at first presentation of patients with sporadic ataxia.
The Adverse Drug Reactions Advisory Committee (ADRAC) database collates notifications of adverse events following immunisation (AEFI) from across Australia. The data were analysed for vaccines received between 1 January 2000 and 30 September 2002. Dose-based AEFI reporting rates were calculated using denominator data from the Australian Childhood Immunisation Register and annual national influenza vaccination coverage surveys. The majority of the 2,409 AEFI records analysed described non-serious events, principally injection site reactions; 10.5 per cent (n = 253) described AEFIs with outcomes defined as 'serious'. Ten deaths were recorded but only one, following yellow fever vaccine, was causally related to immunisation. The average annual population-based reporting rate was 4.5 per 100,000 population. Vaccine dose-based AEFI reporting rates were 2.2 per 100,000 doses of influenza vaccine for adults aged 40 years and over and 14.6 per 100,000 doses of all scheduled vaccines for children aged less than 7 years. The most frequently reported type of adverse event was injection site reaction following receipt of an acellular pertussis-containing vaccine, particularly among children in the age groups scheduled to receive their fourth or fifth doses of the vaccine (overall reporting rate 67 per 100,000 doses). The data highlight the safety of vaccines in Australia, and illustrate both the utility of available immunisation coverage data to estimate dose-based AEFI reporting rates and the value of the ADRAC database as a surveillance tool for monitoring AEFIs nationally.
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