Pneumococcal disease in Australia.

The proceedings of the Pneumococcal Disease in Australia Workshop, held on 26-27 March 1999 are presented in this report. The world-wide epidemiology of the pneumococcus, with its predilection for the very young and the very old, differs between the developing and the developed world, and between indigenous and non-indigenous populations. Sources of data on pneumococcal disease in each of the Australian States, clinical aspects of invasive and non-invasive disease, and the role of the public health laboratory in surveillance of serotypes and antimicrobial sensitivity, both nationally and over time, were discussed at the Workshop. Polysaccharide pneumococcal vaccines are recommended for those over 65 years of age and for at-risk groups, but are supplied free of charge only in Victoria and for indigenous Australians over 50 years of age. Children will require conjugate vaccines, which are likely to be licensed in the United States of America early in 2000. In Australia indigenous children, especially in rural areas, will be the priority group for conjugate vaccines.

Factors influencing vaccination uptake. Workshop report. Current Australian research on the behavioural, social and demographic factors influencing immunisation, Royal Alexandra Hospital for Children, Sydney, March 1998.

Current Australian research on factors influencing vaccination was discussed at a workshop held at the Royal Alexandra Hospital for Children, Sydney, in March 1998, sponsored by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases (NCIRS). The application of decision making theory to vaccination behaviour, the expectations and experiences of mothers, and reasons why parents fail to vaccinate their children were considered. Mothers' perceptions of the risks of vaccines, preferences of parents and providers for the mode of vaccine delivery, and community and social factors were all found to be part of the framework within which vaccination is accepted in Australia. Consumer considerations, media influences and overseas comparisons were discussed.

The epidemiology of rubella and congenital rubella in Australia, 1992 to 1997.

Selective rubella vaccination of schoolgirls commenced in 1971 and was followed by a significant reduction in congenital rubella. Infant vaccination with MMR was introduced in 1989 to interrupt circulation of the virus in young children, and in 1994/95 the adolescent school based rubella vaccination program was changed to MMR for both boys and girls. This report reviews the epidemiology of rubella and congenital rubella between 1992 and 1997 using reports to the National Notifiable Diseases Surveillance System (NNDSS) and the Australian Paediatric Surveillance Unit (APSU). Notification rates for rubella exceeded 20 per 100,000 in 1992, 1993 and 1995 and declined to 7.2 per 100,000 in 1997. Sixty-one per cent of notifications occurred between September and December and 68% occurred in males. The incidence rate in males aged 15-22 years peaked at 152.6 per 100,000 in 1995 reflecting the lack of immunisation in this cohort. From 1993 to 1997, 19 children were reported with congenital rubella syndrome, representing 1 in 67,000 live births. Of these, 17 had multiple defects (4 died) and 2 had deafness only. There were also 5 infants with congenital rubella infection but no defects. Australia's rate of congenital rubella syndrome exceeded that of the United Kingdom and the United States of America but this may be partly attributable to differences in reporting practices. The impact of changing the second dose of MMR vaccine to 4 years of age in 1998 will require careful monitoring.

Varicella-zoster virus infection in Australia.

OBJECTIVE: To determine the epidemiology of varicella-zoster virus (VZV) infection in Australia using currently available data sources. DESIGN: Analysis of national death data (23 years), congenital and neonatal cases (one year) and attendances at sentinel general practices (two years); hospital admissions in NSW and SA (six years); serological studies in 1995 involving antenatal clinics in Sydney and Brisbane and child-care centre staff and refugees in Sydney; and case-ascertainment in 1995 in South Western Sydney among public hospital staff, child-care centre staff and the community. RESULTS: In Australia, there have been an average of 3.5 deaths from chickenpox (mostly children) and 11 from herpes zoster (mostly older people) each year since 1980. The crude death rate for chickenpox has declined (p > 0.05). In 1995, there were 14 cases of neonatal and two of congenital varicella. Average annual admission rates for NSW and SA showed 1,200 hospital bed-days used for chickenpox, more than 20% with complications, and more than 7,300 bed days for zoster; annually more than 880 in-patient admissions were complicated by VZV. Most people encounter the virus in their first 15 years, but some remain susceptible into their 20s; 25% of cases and 37% of hospital admissions for chickenpox occur in people > or = 15 years of age. CONCLUSION: VZV infection involves people of all ages. It causes substantial morbidity and mortality, particularly at the extremes of life. The death rate from chickenpox but not zoster has fallen since the introduction of acyclovir in the 1980s. Surveillance of VZV infection must be given priority once vaccines become available, to monitor changes in morbidity and mortality.

Measles control in Australia. Report of the Measles Control in Australia Workshop, 5 November 1997.

The proceedings of the Measles Control in Australia Workshop held on 5 November 1998 are presented in this report. Prompted by the possibility of a global elimination campaign in the near future the Workshop considered the factors involved in elimination of measles from Australia. Epidemiology, surveillance, laboratory diagnosis methods, mathematical modelling, and the cost and logistics were all addressed. Mass vaccination for all 2-18 year olds, and a routine 2-dose regimen with scheduled doses at 12 months and school entry were recommended. Intensified surveillance, based on a sensitive case definition and laboratory confirmation (measles specific IgM) of suspected cases was identified as a crucial component of the campaign. The continuation of high vaccination coverage for each of the two doses would be essential to maintain elimination once established.

Update on immunization.

By 1995, measles, mumps, and rubella were eliminated from Finland, acellular vaccines for pertussis were showing great promise, and the global eradication of poliomyelitis by the year 2000 looked possible. The meningococcus was replacing Haemophilus influenzae type b as the main cause of childhood meningitis, and 75 countries were vaccinating their children against hepatitis B. The United States recommended varicella vaccination for children, effective vaccines were available for hepatitis A, and new vaccines for rotavirus and cholera were being tested; malaria and HIV offer a continuing challenge.

Interaction of 68-kDa TAR RNA-binding protein and other cellular proteins with prion protein-RNA stem-loop.

The RNA stem-loop structure of the trans-activating region TAR sequence of human immunodeficiency virus-1 mRNA is the binding site for a number of host cell proteins. A virtually identical set of proteins from HeLa nuclear extracts was found to bind to the predicted RNA hairpin element of prion protein (PrP) mRNA, as demonstrated in UV cross-linking/RNase protection and Northwestern assays. We show that the cellular TAR loop-binding protein, p68, is among those proteins which associate with PrP RNA. Competition experiments with various TAR RNA mutants revealed that binding of partially purified p68 to PrP RNA stem-loop occurs sequence-specifically. The 100-kDa 2-5A synthetase which is involved in the cellular antiviral defense was able to bind to PrP mRNA stem-loop in Northwestern blots with cytosolic proteins from HeLa cells treated with interferon. However, the PrP RNA failed to activate this enzyme in vitro, in contrast to TAR RNA.

A pilot study of a computerized assessment (AGE-PC) for the elderly in general practice.

A pilot project was undertaken in Liverpool UK, to investigate whether data useful for both general practice and public health purposes could be collected by primary care personnel using a computerized semi-structured interview (AGE-PC) for assessment of patients aged 75 and over. A high degree of variation between practices was found in the proportion of elderly assessed with AGE-PC largely related to motivation to undertake assessments and methods employed to approach patients. Considerable differences between and within practices were evident in staff attitudes to the need for detailed formal assessments and the use of computers. Several aspects of the AGE-PC package itself were identified as requiring modification including streamlining data transfer methods, adding facilities for analysis and giving users a degree of choice over content of the assessment. This technique does offer a potentially efficient means of collecting very detailed standardized data for intra- or inter-practice analysis while at the same time generating a comprehensive report for individual patients. However, in the context of the over-75 assessments it was too time-consuming. Possible future strategies are discussed such as using an initial screening stage with a self-report questionnaire to reduce numbers needing full assessment and the use of the package for the community care assessments. The pilot project highlighted some of the potential advantages and disadvantages of collecting data from primary health care for public health purposes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures.

Rat cortical cells were incubated with the Scrapie prion protein, PrionSc. At concentrations of 3 ng/ml of PrionSc and higher, the viability of the cells decreased significantly after a 12-h incubation period. Simultaneously, the degree of DNA fragmentation increased. In control experiments with antibodies against PrionSc, PrionSc lost its deleterious effect on neurons. PrionSc did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as memantine (1-amino-3,5-dimethyl-adamantane) (Mem), its analogue 1-N-methylamino-3,5-dimethyl-adamantane as well as (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) prevented the effect of PrionSc. Production of PrionSc in the Scrapie prion-infected subclone of N2 a cells (ScN2 a cells) was not affected by memantine. We conclude that antagonists of the NMDA receptor-channel complex (i) abolish the PrionSc-induced neuronal injury in vitro, and (ii) display no influence on the synthesis and/or the processing of PrionSc.

Stage-specific Monoclonal Antibodies to the Potato Cyst Nematode Globodera pallida Stone (Behrens).

Using standard hybridoma technology and hierarchical screening, monoclonal antibodies (MAbs) were obtained with specific reactivity against two developmental stages of Globodera pallida. The procedure was based on enzyme-linked immunosorbent assay (ELISA) with homogenates prepared from second-stage juveniles, young adult females, and potato roots. Hybridomas were formed by fusing myelomas with splenocytes derived from mice immunized with either infective juveniles or females of G. pallida. About 600 hybridoma lines were screened from the fusion involving the mouse immunized with juveniles. Two MAbs (LJMAbl &2) were identified with high reactivity toward second-stage juveniles but no reactivity with either potato roots or females of G. pallida. A total of 630 cell lines was screened from the corresponding fusion involving the spleen of a mouse receiving immunogens from adult female nematodes. One MAb (LFMAbl) was obtained with the required specificity against only adult female G. pallida. This work extends the application of monoclonal antibodies in nematology from valuable probes for research and species identification to recognition of developmental stages. These specific MAbs have potential value in plant breeding programs for screening for resistant lines unable to support nematode development.

Human immunodeficiency virus: novel enzyme-linked immunoassays for quantitation of envelope glycoprotein 120.

Two novel enzyme-linked immunoassays (ELISA) for the quantitation of human immunodeficiency virus type 1 (HIV-1) coded glycoprotein with an Mr 120 (gp120) are described. These are based on the highly specific interaction between gp120 and the mannose-specific lectins from Narcissus pseudonarcissus (NPL) and Galanthus nivalis (GNL). Two systems were developed: (1) an HIV-protein ELISA using HIV-protein (also containing HIV-gp120) for the solid phase and NPL as a detector and (2) a lectin-ELISA using the NPL bound to the solid phase and GNL as detector. The HIV-protein ELISA was validated for quantitation of gp120 within the range 3 to 600 ng/ml; the lectin-ELISA for concentrations between 0.6 and 20000 ng gp120/ml. Serum components did not interfere with the binding of gp120 to the lectins. The ELISAs were used for the quantitation of gp120 in HIV-infected CEM cells in vitro. It was found that gp120 appeared in the medium earlier after infection than HIV-p24 and reverse transcriptase, suggesting that gp120 is released as free glycoprotein. Moreover, the ELISAs were also applied successfully for the detection of compounds that bind to gp120 and for the identification of antibodies directed against the highly pathogenic mannan portion of gp120. These ELISAs are considered to be suitable also for the detection of gp120 in the serum of HIV-infected individuals.

Sulphoevernan, a polyanionic polysaccharide, and the narcissus lectin potently inhibit human immunodeficiency virus infection by binding to viral envelope protein.

Sulphoevernan is a sulphated alpha-1----3, 1----4 polyglucan (Mr 20,000) with a helical structure. This compound effectively inhibits both human immunodeficiency virus type 1 (HIV-1) and type 2 infection of cells in vitro at concentrations around 0.5 micrograms/ml. Moreover, the compound completely inhibits HIV-1-induced syncytium formation at a concentration of 1 microgram/ml. Competition experiments with 35S-labelled sulphoevernan revealed that the mannose-specific lectin from Narcissus pseudonarcissus prevented binding of sulphoevernan to HIV-1, whereas the antibody OKT4A did not reduce the amount of sulphoevernan bound to MT-2 cells. These data indicate that the non-cytotoxic polymer sulphoevernan binds to the virus rather than to the host cell. In vivo studies, using Rauscher leukaemia virus in NMRI mice, revealed that, at a daily dose of 20 mg/kg, the animals were protected against virus-induced increases in spleen weight. From these in vitro and in vivo data we conclude that sulphoevernan has potential in the treatment of acquired immunodeficiency syndrome.

Reproduction of Globodera rostochiensis on Transformed Roots of Solanum tuberosum cv. Desiree.

Transformed roots of the susceptible potato Solanum tuberosum L. cv. Desiree were inoculated with second-stage juveniles (J2) of Globodera rostochiensis pathotype Rol. Adult males emerged after 3-4 weeks and matings with females occurred. After 8 weeks gentle pressure on the eggs of maturing females released the J2 which were viable. Because this technique enables the production of vigorously growing roots with numerous laterals, it may be suitable for obtaining a high yield of sterile potato cyst nematodes.

Continuing education: a survey among general practitioners.

A survey of perceptions of continuing education--content, methods and current provision--was undertaken among all established general practitioners in one health region of the UK using a postal questionnaire. Interviews were conducted with a small random sample of respondents and with a larger sample of non-respondents to the questionnaire. Data from the questionnaire and interviews demonstrated overall a wide diversity of content and methods of continuing education perceived as appropriate, with duration of experience and involvement in undergraduate teaching or postgraduate training as significant determinants. The findings are used to review, critically, current provision of continuing education for general practice and to suggest ways in which future provision might reflect the range of educational need perceived by doctors.

Congenital limb reduction deformities and use of oral contraceptives.

A study of congenital limb deficiencies in two Australian states indicated that use of an oral contraceptive during pregnancy by the mother was associated with an increased risk of limb defect in the child. The study included mothers of 155 children born with absence or reduction of the major long bones during a 12-year period from 1970 onward; 274 mothers with births of normal infants, matched for date of birth and area of residence, made up the control group. Compared with control infants, the case infants were more likely to have been conceived while the mother was using an oral contraceptive, especially when the deformity was a transverse or amputation type. It is too early in our state of knowledge of teratogenic mechanisms to exclude the possible existence of a biologic mechanism that would explain this statistical association.

PIP: A study of congenital limb deficiencies in 2 Australian states indicate that use of an oral contraceptive during pregnancy by the mother was associated with an increased risk of limb defect in the child. The study included mothers of 155 children born with absence or reduction of the major long bones during a 12-year period from 1970 onward; 274 mothers with births of normal infants, matched for date of birth and area of residence, made up the control group. Detailed results are presented, including a multivariate analysis that incorporated as potential confounders maternal age, sex of infant, parity of mother, staus of father's occupation, and a number of pregnancy factors. Each mother was interviewed an average of 405 years after the birth of the child. Compared with control infants, the case infants were more likely to have been conceived while the mother was using an oral contraceptive, particularly when the deformity was a transverse or amputation type. Knowledge of teratogenic mechanisms is not advanced enough to enable exclusion of the possible existence of a biologic mechanism that would explain this statistical assocation. Low socioeconomic status judged by an unskilled occupation of the father, sex of the child (male), vaginal bleeding at any time during pregnancy, and a febrile illness in the 1st trimester were significant at the 0.05 level, while smoking during pregnancy, hormonal therapy, maternal age, and parity were mot.