Varicella vaccination in Australia.

Varicella zoster virus (VZV) causes both chickenpox and herpes zoster and is responsible for a significant disease burden, including hospitalizations and deaths, in Australian children and adults. Varicella vaccine has been available in Australia for 5 years; however, from November 2005, it will be funded for use in all susceptible children at 18 months and 10-13 years of age under the National Immunisation Program. Experience with universal varicella vaccination of children in the USA over the last 10 years has shown that the vaccine is safe and highly effective in reducing varicella-related disease. This review summarizes the epidemiology of VZV-related disease in Australia, the use of varicella vaccine and the international experience with vaccine efficacy and safety. The potential impact of varicella vaccination on the incidence of herpes zoster is also discussed.

Use of hospitalization and pharmaceutical prescribing data to compare the prevaccination burden of varicella and herpes zoster in Australia.

The aims of the study were to compare the burden of varicella and herpes zoster in Australia. No national surveillance exists for varicella or herpes zoster. We used hospital morbidity data from 1993-9 and pharmaceutical prescribing data from 1995-9. In the financial year 1998/99, there were 4718 hospitalizations for zoster compared to 1991 for varicella. For varicella the mean age of patients was 15 years compared to 69 years for zoster. The mean length of stay in hospital was 4.2 days for varicella and 12.7 days for zoster. Varicella accounted for 8396 (3726 with principal diagnosis varicella) bed days compared to 26 266 (5382 with principal diagnosis of zoster) for zoster. The in-hospital case-fatality rate was 0.4% for varicella and 1% for zoster. In 1999, 59 200 community-based cases of zoster were treated with antivirals. We estimate that 157 266 cases of zoster occurred in the community in 1999, a rate of 830 per 100 000 population. Herpes zoster has a higher burden of disease than varicella, and must be a component of disease surveillance in order to determine the full impact of vaccination on the epidemiology of varicella zoster virus (VZV).

Hepatitis A vaccination options for Australia.

The epidemiology of hepatitis A is changing, with an increasing proportion of the population becoming susceptible to infection. The burden of hepatitis A is comparable to that of other vaccine-preventable diseases for which new vaccines are available. Options for vaccination include selective programmes for high-risk groups, which could involve screening prior to vaccination, or universal programmes for infants and/or adolescents. Selective programmes have been shown to be highly cost-effective if well implemented, but there is evidence that they might be poorly implemented. If a universal vaccination programme were considered for Australia, an infant programme, with doses at 18 months and 2 years, possibly with an additional adolescent programme, would be the recommended option. Universal hepatitis A vaccination for infants and/or adolescents is of comparable cost-effectiveness compared with other preventive strategies, but needs to be considered in the context of competing vaccination options.

The seroepidemiology and transmission dynamics of varicella in Australia.

To enhance our understanding of the epidemiology and transmission dynamics of varicella in the pre-vaccine era we performed a serosurvey using opportunistically collected sera submitted to diagnostic laboratories across Australia during 1997-1999. A representative sample by state and sex of 2027 sera from persons aged 1-49 years was tested using an enzyme immunoassay method. The average age of infection and age-specific forces of infection (the probability that a susceptible individual acquires infection) were calculated using published methodologies. Seropositivity increased with age, with 83% of sera positive by ages 10-14 years. The highest force of infection was in the 5-9 years age group (0.195 per susceptible year) followed by the 0-4 years age group (0.139 per susceptible year) and the average age of infection was 8.15 years. These results provide valuable baseline information to measure the impact of vaccination and indicate that vaccination should be aimed at children less than 5 years of age, although further modelling using the serosurvey data is warranted.

National study of adverse reactions after vaccination with bacille Calmette-Guérin.

Few large prospective studies of adverse reactions after bacille Calmette-Guérin (BCG) vaccination are available. In a prospective national study of such adverse reactions among 918 subjects (aged 1 day to 54 years) over a 14-month period, 45 vaccinees (5%) reported 53 adverse reactions (23 injection-site abscesses, 14 severe local reactions, 10 cases of lymphadenitis, and 6 other reactions). Only 1% of vaccinees required medical attention. Reactions, particularly lymphadenitis, were significantly less common in infants <6 months old (but not in subjects aged > or =6 months) vaccinated by trained (vs. untrained) providers (relative risk [RR], 0.24; 95% confidence interval [CI], 0.09-0.68). Injection-site abscesses (RR, 2.96; 95% CI, 1.11-7.90) and severe local reactions (RR, 4.93; 95% CI, 1.11-21.90) were significantly more common in older vaccinees. Local reactions were more frequently reported by adult females than by adult males (RR, 7.18; 95% CI, 1.59-32.45). Adverse reactions were not significantly associated with any currently available vaccine batch, previous receipt of BCG vaccine, or concomitant administration of other vaccines.

Concurrent ifosfamide-based chemotherapy and irradiation. Analysis of treatment-related toxicity in 43 patients with sarcoma.

BACKGROUND: The current study was performed to evaluate the toxicity profile of therapeutic doses of ifosfamide (IFX) given concurrently with full-dose external beam radiotherapy (EBRT) in patients with soft tissue and bone sarcomas. METHODS: The medical records of 43 consecutive patients with soft tissue or bone sarcomas who were treated with concurrent IFX and EBRT were reviewed. RESULTS: The median patient age was 20 years. Histologies were rhabdomyosarcoma (n = 16 patients), Ewing sarcoma (n = 10 patients), malignant fibrous histiocytoma (n = 9 patients), and other soft tissue sarcomas (n = 8 patients). Thirty-one patients (72%) had localized disease, and 12 patients (28%) had synchronous local and distant disease. Treatment consisted of EBRT (median dose, 50.4 gray [Gy]) with concomitant IFX (median dose per cycle, 10.2 g/m(2)). All patients with Ewing sarcoma or rhabdomyosarcoma received additional concurrent chemotherapy. Twenty-six patients (60%) received two or more cycles of IFX, and 17 patients (40%) were treated with one cycle of IFX and EBRT. The incidences of World Health Organization Grade 3 and Grade 4 toxicities were 29% (21 of 73 cycles) and 22% (16 of 73 cycles), respectively. Grade 4 systemic toxicities included leukopenia (n = 14 patients), neurotoxicity (suicidal ideation; n = 1 patient), and diarrhea (n = 1 patient). Confluent moist desquamation (Grade 3) occurred in nine patients in the treatment field; no patient experienced Grade 4 local toxicity. Among 14 patients who were treated preoperatively, 2 patients (14%) had a pathologic complete response, and 6 patients (43%) had a pathologic near-complete response (> or = 90% necrosis). CONCLUSIONS: Local and systemic toxicities after the administration of therapeutic doses of IFX with concomitant EBRT appear comparable to those observed with either treatment alone. These results support the design of prospective studies evaluating concurrent ifosfamide and radiation therapy for patients with sarcomas.

Impact of the Australian Measles Control Campaign on immunity to measles and rubella.

To evaluate the impact of the 1998 Australian Measles Control Campaign on immunity to measles and rubella, 4400 opportunistically-collected sera, submitted to diagnostic laboratories across Australia from subjects aged 1-49 years, and 3000 from subjects aged 1-18 years, were tested before and after the campaign, respectively. The proportion of individuals aged 1-18 years who were immune to measles rose from 85% before, to 90% after, the campaign (P < 0.001). The greatest increase was in preschool (7%, P < 0.001) and primary school (10%, P < 0.001) children, who were actively targeted by the campaign. Rubella immunity in 1-18 year-olds rose from 83% to 91% (P < 0.0001), again with significant increases in preschool (4%, P = 0.002) and primary school (16%, P < 0.001) children. 94% of individuals aged 19-49 years were immune to rubella. These serosurveys confirm other evidence of the effectiveness of the Australian Measles Control Campaign and demonstrate the value of serosurveillance using opportunistically collected sera.

The Australian Measles Control Campaign, 1998.

The 1998 Australian Measles Control Campaign had as its aim improved immunization coverage among children aged 1-12 years and, in the longer term, prevention of measles epidemics. The campaign included mass school-based measles-mumps-rubella vaccination of children aged 5-12 years and a catch-up programme for preschool children. More than 1.33 million children aged 5-12 years were vaccinated at school: serological monitoring showed that 94% of such children were protected after the campaign, whereas only 84% had been protected previously. Among preschool children aged 1-3.5 years the corresponding levels of protection were 89% and 82%. During the six months following the campaign there was a marked reduction in the number of measles cases among children in targeted age groups.

Comparative immunogenicity and safety of two dosing schedules of a combined hepatitis A and B vaccine in healthy adolescent volunteers: an open, randomised study.

An open, randomised study was undertaken to demonstrate the equivalence in immunogenicity and to determine the reactogenicity and safety of two dosing schedules (0, 6 or 0, 12 month) of an adult formulation of a combined hepatitis A and B vaccine containing 720 EL.U. of inactivated hepatitis A antigen and 20 microg of hepatitis B surface antigen (Twinrix, SmithKline Beecham Biologicals, Belgium) in 240 healthy volunteers aged 12-15 years. The vaccine was well tolerated when administered using either vaccination schedule. At month 7, 98.1% of subjects completing the 0, 6 month vaccination schedule were seroprotected against hepatitis B (anti-hepatitis B surface antigen (anti-HBs) > or =10 mIU/ml) and 100% were seropositive for anti-hepatitis A virus (anti-HAV) antibodies (i.e., > or =33 mIU/ml). The corresponding geometric mean titres (GMTs) were 2791 mIU/ml for anti-HBs and 5992 mIU/ml for anti-HAV antibodies. At month 13, 97% of subjects assigned to the 0, 12 month vaccination schedule were protected against hepatitis B and 99% were seropositive for anti-HAV antibodies. The corresponding GMTs were 4340 and 8472 mIU/ml, respectively. A combined response (i.e., subjects, who were seropositive for anti-HAV antibodies and seroprotected for anti-HBs antibodies) was achieved in 98% of subjects vaccinated according to the 0, 6 month interval and in 96% of subjects vaccinated using the 0, 12 month schedule. The reactogenicity of both vaccination schedules was also equivalent. The results thus show that the combined hepatitis A and B vaccine can be administered using flexible vaccination intervals, which make it suitable for use in large-scale hepatitis immunisation programmes.

Phase II clinical investigation of gemcitabine in advanced soft tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation.

PURPOSE: To evaluate the efficacy, toxicity, and optimal dose rate of gemcitabine in adult patients with advanced soft tissue sarcomas (STS) by comparing levels of gemcitabine triphosphate (GTP) in peripheral-blood mononuclear cells (PBMCs) of patients receiving two different dose rates. PATIENTS AND METHODS: Fifty-six assessable patients with STS (17 gastrointestinal [GI] leiomyosarcomas and 39 other histologies) were treated on a two-arm phase II study. Gemcitabine was given at 1 g/m2 as a 30-minute infusion weekly for up to 7 weeks followed by 1 week of rest and reassessment of tumor. Subsequent cycles were given at 1 g/m2 weekly for 3 weeks followed by 1 week of rest. Nine patients underwent cellular pharmacologic studies at two different dose rates (1 g/m2 over a standard 30-minute infusion on week 1 and over pharmacologically based infusion of 150 minutes on week 2) to evaluate GTP levels in PBMCs. RESULTS: Seven partial responses were noted among 39 patients, for an overall response rate of 18% (95% confidence interval, 7% to 29%). Median duration of response was 3.5 months (range, 2 to 13 months). Four of 10 patients with non-GI leiomyosarcomas achieved a partial response. No objective responses were noted in 17 patients with GI leiomyosarcomas. One patient had a mixed response. Median time to progression for all patients (both arms) was 3 months; median survival was 13.9 months. Treatment was generally well tolerated. Comparison of cellular pharmacology demonstrated a significant 1.4-fold increase in the concentration of GTP with the 150-minute infusion. CONCLUSION: Given the limited therapeutic armamentarium for STS, the activity of gemcitabine is encouraging. Its potential for combination therapy in the salvage setting should be studied with pharmacologically guided fixed dose-rate infusion.

Hepatitis A epidemiology in Australia: national seroprevalence and notifications.

OBJECTIVES: To determine hepatitis A seroprevalence and notification rates in Australia in order to inform vaccination policy. DESIGN: Seroprevalence was determined by cross-sectional survey of opportunistically collected sera; notifications were extracted from the National Notifiable Diseases Surveillance System. PARTICIPANTS: 3,043 serum samples collected in 1998 were obtained from 46 laboratories around Australia. Sample size in each age group was based on expected seroprevalence, and States and Territories were sampled proportionally to their population size. Males and females were equally represented. Notifications were extracted for cases with onset between 1 January 1991 and 31 December 1998. MAIN OUTCOME MEASURES: Seroprevalence and notifications were analysed by age, sex and State/Territory. RESULTS: 41.1% of serum samples were seropositive for hepatitis A (95% CI, 39.4%-42.9%) (population-weighted seroprevalence, 38.3%). Seroprevalence was significantly associated with increasing age (P<0.001), but did not differ between the sexes (male:female ratio, 1.04:1; 95% CI, 0.95-1.14). However, significantly more notifications were recorded for males than females (male:female ratio, 1.65:1; 95% CI, 1.60-1.70). The Northern Territory had the highest seroprevalence (68.8%; 95% CI, 52.7%-84.8%) and annual notification rates (48.7 per 100,000 population; 95% CI, 45.0-52.4 per 100,000). CONCLUSIONS: These data show that about half the Australian population has not been exposed to hepatitis A and is therefore susceptible to infection. However, any decision on national routine childhood hepatitis A vaccination requires a cost-benefit analysis. Routine vaccination of high-incidence communities remains controversial.

A short history of vaccination in Australia.

It is almost 50 years since infant vaccination for diphtheria, pertussis and tetanus became routine in Australia. Since then, the incidence of vaccine-preventable diseases has declined dramatically. We have used existing records and the recollections of experts to compile a history of vaccination in Australia, focusing on vaccines in the current childhood schedule.

A randomized trial of two acellular pertussis vaccines (dTpa and pa) and a licensed diphtheria-tetanus vaccine (Td) in adults.

A single blinded randomized controlled trial to compare the reactogenicity and immunogenicity of adult formulated dTpa and monovalent pa vaccines with a licensed Td vaccine. Five hundred and forty-eight healthy adults aged 19-70 years received a single injection of dTpa or separate injections of pa or Td (with the alternate vaccine 1 month later). Local and systemic reactions were monitored for 15 days after each vaccination. Serum antibody levels were measured immediately prior to and 1 month after vaccination. Antibody levels were measured 12 months after vaccination in 100 subjects. There was no difference in the total frequency of symptoms and signs between subjects receiving any of the three vaccines. There was a significantly lower incidence of local reactions following pa (60%) than dTpa (80%, P=0.002) or Td (93%, P=0.0008). The incidence of clinically significant (Grade 2 or 3) swelling (> or =20 mm) was higher for Td (20%, P=0.002) than for dTpa (11%) or for pa (2%), however, there were no other significant differences in the incidence of Grade 2 or 3 reactions between the vaccines. A high anti-pertussis seroconversion rate (>97%) against all the studied pertussis antigens was seen 1 month after vaccination with dTpa and pa. A total of 96 and 99% of subjects receiving dTpa and Td, respectively, had anti-diphtheria titres > or =0.01 IU/ml, and all but one subject had anti-tetanus titres > or =0.1 IU/ml after 1 month. Twelve months after vaccination the majority (90-100%) of the subjects were still seropositive for each antigen and although GMTs had decreased they were substantially higher than pre-vaccination levels. The dTpa vaccine was well tolerated and capable of eliciting an immune response against all the antigens in a broad spectrum of the adult population and could potentially replace Td for routine boosters in adults.

Impact of neoadjuvant chemotherapy on postoperative morbidity in soft tissue sarcomas.

PURPOSE: The purpose of this study was to test the hypothesis that neoadjuvant chemotherapy (NeoCT) does not increase morbidity in patients undergoing radical surgery for soft tissue sarcomas. PATIENTS AND METHODS: The records of 309 patients who presented to The University of Texas M.D. Anderson Cancer Center for definitive surgical management of primary soft tissue sarcomas were retrospectively reviewed. One hundred five patients who received NeoCT were compared with 204 patients who had surgery first (Surg). Patients had extremity sarcomas (71 NeoCT patients and 130 Surg patients) or retroperitoneal/visceral sarcomas (34 NeoCT and 74 Surg). RESULTS: NeoCT patients had larger tumors (median, 12 v 8 cm), more frequently had high-grade tumors (90% v 64%), and were younger (median age 47 v 55 years). The incidence of surgical complications was not different for NeoCT patients than for Surg patients, both in those with extremity sarcomas (34% v 41%) and in those with retroperitoneal/visceral sarcomas (29% v 34%). The most common complications were wound infections and other wound complications. Preoperative radiation therapy, autologous flap coverage, and extremity tumors were associated with increased wound complications. No significant differences in length of hospital stay, rate of readmission, or rate of reoperation for complications were found between the NeoCT and Surg groups. One of the three postoperative deaths in our series occurred in the NeoCT group. CONCLUSION: In this retrospective review, there was no evidence that NeoCT increased postoperative morbidity in patients with soft tissue sarcomas. Prospective, randomized studies are needed to confirm these results.

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.