Antimicrobials in the management of invasive meningococcal disease.
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Biomedical subjects
Publications and source records attributed to D Lennon.
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The 192-kb linear DNA genome of vaccinia virus has covalently closed hairpin termini that are extremely AT rich and contain 12 extrahelical bases. Vaccinia virus telomeres have previously been implicated in the initiation of viral genome replication; therefore, we sought to determine whether the telomeres form specific protein-DNA complexes. Using an electrophoretic mobility shift assay, we found that extracts prepared from virions and from the cytoplasm of infected cells contain telomere binding activity. Four shifted complexes were detected using hairpin probes representing the viral termini, two of which represent an interaction with the "flip" isoform and two with the "flop" isoform. All of the specificity for protein binding lies within the terminal 65-bp hairpin sequence. Viral hairpins lacking extrahelical bases cannot form the shifted complexes, suggesting that DNA structure is crucial for complex formation. Using an affinity purification protocol, we purified the proteins responsible for hairpin-protein complex formation. The vaccinia virus I1 protein was identified as being necessary and sufficient for the formation of the upper doublet of shifted complexes, and the vaccinia virus I6 protein was shown to form the lower doublet of shifted complexes. Competition and challenge experiments confirmed that the previously uncharacterized I6 protein binds tightly and with great specificity to the hairpin form of the viral telomeric sequence. Incubation of viral hairpins with extracts from infected cells also generates a smaller DNA fragment that is likely to reflect specific nicking at the apex of the hairpin; we show that the vaccinia virus K4 protein is necessary and sufficient for this reaction. We hypothesize that these telomere binding proteins may play a role in the initiation of vaccinia virus genome replication and/or genome encapsidation.
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AIMS: The present study examined the effectiveness of three modes of communication designed to increase high school students' knowledge about throat infections and rheumatic fever in a high risk area. METHODS: The study was part of an evaluation of a rheumatic fever prevention programme that has established 27 school-based 'sore throat' clinics in South Auckland. The rationale for the clinics was explained to students through: assemblies conducted by public health nurses, written information sheets and classroom lessons. The effectiveness of each communication mode was assessed by comparing the knowledge of students from eight classes at an intervention school with eight classes at a control school before and after the intervention school students received the teaching. RESULTS: Students at the intervention school showed a significant improvement in knowledge compared to students at the control school. The assembly presentations by health professionals were more effective in informing students than information sheets or classroom lessons. CONCLUSIONS: This study suggests that presentations by health professionals are an effective method of teaching basic health information to students in these South Auckand secondary schools. Classroom teachers need to be provided with appropriate resources, if they are to provide effective instruction. Written information sheets should not be relied on.
BACKGROUND: New Zealand is in its ninth year of a serogroup B meningococcal disease epidemic with annual rates of up to 16.9 cases per 100,000. The highest incidence is in Maori and Pacific Island children in the Auckland region. We conducted a case-control study to identify potentially modifiable risk factors for this disease. METHODS: A case-control study of 202 cases of confirmed and probable meningococcal disease in Auckland children younger than 8 years of age recruited from May, 1997, to March, 1999, was undertaken. Controls (313) were recruited door-to-door by a cluster sampling method based on starting points randomly distributed in the Auckland region. They were frequency matched with the expected distribution of age and ethnicity in the meningococcal disease cases. RESULTS: With the use of a multivariate model and controlling for age, ethnicity, season and socioeconomic factors, risk of disease was strongly associated with overcrowding as measured by the number of adolescent and adult (10 years or older) household members per room [odds ratio (OR), 10.7; 95% confidence interval (CI), 3.9 to 29.5]. This would result in a doubling of risk with the addition of 2 adolescents or adults to a 6-room house. Risk of disease was also associated with analgesic use by the child, which was thought to be a marker of recent illness (OR 2.4, CI 1.5 to 4.0); number of days at substantial social gatherings (10 or more people for > 4 h; OR 1.8, CI 1.2 to 2.6); number of smokers in the household (OR 1.4, CI 1.0 to 1.8); sharing an item of food, drink or a pacifier (OR 1.6, CI 1.0 to 2.7); and preceding symptoms of a respiratory infection (cough, "cold or flu," runny nose, sneezing) in a household member (OR 1.5, CI 1.0 to 2.5). CONCLUSION: Some of these identified risk factors for meningococcal disease are modifiable. Measures to reduce overcrowding could have a marked effect on reducing the incidence of this disease in Auckland children.
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AIMS: To assess two years of meningococcal disease in the Auckland area, the outcomes and management issues, and the specific socio-geographic groups that are affected. METHODS: Using the nationally agreed case definition, a retrospective chart review was undertaken. Case finding was through the National surveillance system at ESR, backed by hospital laboratory and coroner case findings. RESULTS: There were 106 cases of meningococcal disease, both adult and paediatric, from July 1992 to June 1994. Group B (n=61), was predominant throughout this period especially in the winter months. There were two main age groups most affected. The first, and most striking, was in Maori and New Zealand Pacific Island children younger than five years, with rates of 52.6 and 54.2/100,000 respectively. The second peak was in European, and to a lesser extent Maori, 15-24 year-olds, (rates 11.7 and 8.5/100,000, respectively). The annual incidence was 5.6/100,000 with an overall case fatality rate of 6.6%, (n=7). South Auckland had the greatest proportion of cases with 42/106. Two-thirds of the cases were referred for hospital admission by a general practitioner. From both general practitioner and self-referred groups, two-thirds had a petechial/purpuric rash on arrival at hospital. For general practitioner referred cases, 24 received parenteral antibiotics on referral, and from these cases there was one death, (1/24). Those not treated with antibiotics (general practitioner or self-referred) had a mortality of 2/41. There were 31 cases of paediatric meningococcal meningitis. Nineteen cases had dexamethasone in appropriate dose and timing; no hearing loss occurred in the 17 cases that survived (0/17), compared to 2/12 not treated with dexamethasone. This compares to a published rate of 5-7%. CONCLUSIONS: Meningococcal disease, predominantly serogroup B, is of high incidence in Auckland. The highest rates of disease are occurring in the under five-year-olds, where an effective group B vaccine is awaited. The benefit of dexamethasone is suggestive. There was no clear benefit in outcome by pre-treatment with parenteral antibiotics for paediatric meningococcal disease though no suggestive detrimental effect either.
BACKGROUND: Rotavirus illness is associated with significant morbidity and mortality worldwide. We have examined trends in diarrheal disease in New Zealand children to determine the disease burden attributable to rotavirus and to estimate the proportion of hospitalizations preventable by vaccination. METHODS: Hospital admissions data and laboratory records for 1994 to 1996, were obtained for children 0 to 4 years at four sites (serving -60% of the New Zealand population). Rotavirus disease burden was estimated using combined admissions and laboratory data. Severity of disease was estimated in a sample of 150 hospitalizations for rotavirus diarrhea, and the proportion of vaccine-preventable admissions was extrapolated. Mortality attributed to diarrheal causes was determined from national records for 1974 to 1993. RESULTS: Between 1994 and 1996, 4436 children <5 years of age were hospitalized with diarrhea (1047/100000 children per year). Admissions associated with rotavirus were estimated at 1522 to 1535 (315 to 362/100000 annually). Infants between 6 and 17 months were most commonly affected (42% of all cases). More male children than female children were hospitalized (P < 0.001) and mean length of stay was calculated as 1.51 days (SD 2.35). Disease severity scoring revealed that 61.3 and 38.0% of admissions reviewed were severe and very severe, respectively. Deaths from diarrheal causes numbered 138 among children 0 to 4 years old for the 20-year period 1974 to 1993, with 18 deaths occurring between 1984 and 1993 (10 years). CONCLUSION: Current vaccines control severe disease, suggesting that 72% of cases reviewed would be eligible for prevention. A full cost effectiveness analysis is required to demonstrate anticipated benefits of vaccination.
PREVENTION: The appropriate use of varicella vaccine, effective in the prevention of chickenpox, has been considered by a Ministry of Health Working Party in 1996 and 1997, including discussion at a workshop held in Wellington, 26-27 June 1996. The introduction of varicella vaccine into the routine childhood immunisation schedule was not supported at this stage. The use of the only varicella vaccine for which the Minister of Health has given consent for distribution in New Zealand, Varilrix (SmithKline Beecham Limited), in healthy children aged nine months to 13 years inclusive, was supported. Consent has not been given for the use of Varilrix in immunocompromised people or in adults. This report discusses other groups that could be candidates for vaccination, such as children with deteriorating renal function and susceptible health care workers who regularly come into contact with especially vulnerable patients. In these cases, the vaccine would need to be administered on a named patient basis. The use of Varilrix in immunocompromised people was not supported. SURVEILLANCE: Enhanced surveillance of chickenpox and zoster are required in New Zealand. Adverse reactions to Varilrix should be carefully monitored. OUTBREAK CONTROL: There are insufficient data at present to support the use of Varilrix in outbreak control. The frequency, cost and current management of nosocomial outbreaks should be ascertained. This information may also assist in the decision whether to incorporate a varicella vaccine into the routine childhood immunisation schedule in the future.
Bloom syndrome (BS) is more frequent in the Ashkenazic Jewish population than in any other. There the predominant mutation, referred to as "blmAsh," is a 6-bp deletion and 7-bp insertion at nucleotide position 2281 in the BLM cDNA. Using a convenient PCR assay, we have identified blmAsh on 58 of 60 chromosomes transmitted by Ashkenazic parents to persons with BS. In contrast, in 91 unrelated non-Ashkenazic persons with BS whom we examined, blmAsh was identified only in 5, these coming from Spanish-speaking Christian families from the southwestern United States, Mexico, or El Salvador. These data, along with haplotype analyses, show that blmAsh was independently established through a founder effect in Ashkenazic Jews and in immigrants to formerly Spanish colonies. This striking observation underscores the complexity of Jewish history and demonstrates the importance of migration and genetic drift in the formation of human populations.
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AIMS: To determine the microbiology of chronic otitis media with effusion in a group of Auckland children. To determine the antimicrobial sensitivities of isolated bacterial pathogens to commonly used antibiotics for this condition. METHODS: A descriptive study recruiting subjects from otherwise well children with chronic otitis media with effusion having insertion of ventilation tubes at Starship Children's Health, Auckland. Tympanocentesis was performed, the middle ear aspirate cultured and antimicrobial sensitivities obtained. RESULTS: Sixty seven children (11mo to 8yr) with chronic otitis media with effusion had tympanocentesis of 105 ears. 38/105 (36%) of the middle ear aspirate cultures were positive. Forty nine organisms were isolated with 10 ears having two or more different bacteria identified. Isolated were 17 Haemophilus influenzae (16 nontype b and 1 type b), 13 Moraxella catarrhalis, nine Streptococcus pneumoniae and 10 'others'. All S pneumoniae(9/9), most H influenzae(14/17) and no M catarrhalis(0/13) were sensitive to amoxycillin. More than 80% of subjects had either a sterile effusion or an organism sensitive to amoxycillin or cotrimoxazole. CONCLUSIONS: Middle ear effusions were culture positive in a third of cases of chronic otitis media with effusion. The commonest organisms were H influenzae nontype b, M catarrhalis and S pneumoniae. This is similar to reports from other countries. Sensitivity data obtained supports the continued recommendation of amoxycillin or cotrimoxazole as first line therapy for the antimicrobial treatment of this condition.