Tilman A. Ruff

At-birth immunisation against hepatitis B using a novel pre-filled immunisation device stored outside the cold chain

We evaluated the immunogenicity of hepatitis B (HB) vaccine in UniJect, a pre-filled, non-reusable injection device, stored at tropical temperatures for up to one month and used to give the first dose of HB vaccine to newborns. Infants in Tabanan district, Bali, Indonesia, were given their first dose of HB vaccine with UniJect stored out of the cold chain, UniJect stored in the cold chain; or standard syringe, needle and multidose vial stored in the cold chain. Subsequent doses were given by usual means and blood samples drawn 4-6 weeks after the third dose. No significant differences were found in seroconversion rates or geometric mean titres of HB surface antibody between the three groups.

The effectiveness of the infant hepatitis B immunisation program in Fiji, Kiribati, Tonga and Vanuatu

The aims of this project were: (1) to determine the extent to which infant hepatitis B immunisation is preventing chronic hepatitis B infection in children living in a sample of Pacific Island countries; and (2) to identify factors associated with the successful prevention of hepatitis B infection in these populations. A regional hepatitis B immunisation project which supplied hepatitis B vaccine to 10 Pacific Island countries began in 1995. Seroepidemiological surveys were conducted in Fiji, Kiribati, Tonga and Vanuatu in early 1998. These included immunised pre-school children and their biological mothers, and a historical control group of unimmunised students. Prevalence rates for hepatitis B surface antigen (HBsAg) in the populations of students, mothers and their pre-school children were respectively: Fiji: 6.9, 6.6, 0.7%; Kiribati: 27.4, 15.1, 3.8%; Tonga: 11.1, 18.6, 3.8%; Vanuatu: 16.3, 12.3, 3.0%; and for all four countries: 13.2, 12.5, 2.6%. Compared to the historical control group of students, the pre-school population had a much lower probability of HBsAg positivity (relative risk [RR]=0.19 [95%CI: 0.12-0.31]). Statistically significant differences in risk were apparent for all the countries: Fiji: RR=0.10; Kiribati: RR=0.14; Tonga: RR=0.34; Vanuatu: RR=0.19. This is equivalent to an overall program effectiveness of 81% (95%CI: 69-88%) in reducing chronic carriage. Also, the overall protective effectiveness against vertical hepatitis B transmission resulting in HBsAg positivity among children exposed to HBeAg positive and negative carrier mothers, was estimated to be 70%. By age 6 months, when all children should have had three vaccine doses, completed immunisation rates ranged from 22 (Fiji) to 84% (Vanuatu). Coverage of the first dose being given within 2 days of birth varied from 43% in Kiribati to 92% in Tonga. In conclusion hepatitis B immunisation of infants in these four countries is having a substantial beneficial effect in preventing chronic hepatitis B infection. Nevertheless, there is significant scope for further improving the timeliness of immunisation.

Ciguatera: Ecological, clinical, and socioeconomic perspectives

Ciguatera fish poisoning, found throughout the world in warm waters, is the most common type of marine biotoxin ingestion. A polymorphous disease caused by toxins produced by coral reef dinoflagellate(s) and which concentrate up the food chain, ciguatera poses important health, nutritional, economic, and social problems for inhabitants of endemic areas. Despite considerable recent study and progress, the ecology and pathophysiology of the disease remain relatively little understood. Areas in which progress has been made include identification of the causative organisms and toxins and, to a lesser extent, treatment of affected persons. It has become clear that a variety of disturbances of the ecology of coral reefs may be associated with outbreaks of ciguatera. This paper reviews broadly the current knowledge of ciguatera, particularly the ecological, clinical, and socioeconomic aspects.

Antibody persistence six years after two doses of combined hepatitis A and B vaccine.

Persistent immunity to hepatitis A and hepatitis B antibodies six years after vaccination of adolescents (aged 12-15 years) with a combined hepatitis A and B (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed. Yearly (Year-2-6) serum samples were tested for anti-HAV and anti-HBs using EIA. Subjects with anti-HBs concentrations <10 mIU/mL (14/23) at Year-5 or Year-6, received an additional HBV vaccine dose approximately 12 months after Year-6. Blood samples were collected pre-booster and 1 month post-booster to assess booster response. 240 subjects were vaccinated in the study; at Year-6, data were available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9% (39/42; 0, 12 month) of subjects had anti-HBs concentrations > or = 10 mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations > or = 100 mIU/mL. All seroconverted subjects who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced number of doses and similar long-term persistence of immunity make the 0, 6 month and 0, 12 month schedule preferable for immunization against HAV/HBV in this population.

A pilot study of the quality of informed consent materials for Aboriginal participants in clinical trials

Objective: To pilot informed consent materials developed for Aboriginal parents in a vaccine trial, and evaluate their design and the informed consent process. Methods: Cross sectional quantitative and qualitative survey of 20 Aboriginal and 20 non-Aboriginal women in Alice Springs. Information about the proposed research was presented to Aboriginal participants by an Aboriginal researcher, using purpose designed verbal, visual, and written materials. Non-Aboriginal participants received standard materials developed by the sponsor. Questionnaires were used to evaluate recall and understanding immediately and five days later. Qualitative analysis of Aboriginal participants’ interviews was performed. Results: There were no differences between the groups in understanding of diseases prevented by the vaccine, the potential risks of participating, or the voluntary nature of participation. Most Aboriginal participants had difficulty with the concept of a “licensed” versus “unlicensed” vaccine. The non-Aboriginal group had a good understanding of this. Aboriginal participants identified the use of the flipchart, along with a presentation by a doctor and Aboriginal health worker, as preferred delivery modes. Group presentations were preferred rather than one-on-one discussions. The use of the questionnaire posed considerable methodological difficulties. Conclusions: A one-off oral presentation to Aboriginal participants is unlikely to produce “informed consent”. Key but unfamiliar concepts require identification and particularly considered presentation.

Hepatitis B Vaccination

Hepatitis B is one of the world’s most common and serious infectious diseases, with around 350 million chronic carriers worldwide. Many carriers will die of chronic liver disease, cirrhosis or hepatocellular carcinoma. An estimated 1 million people worldwide die of hepatitis B each year. Safe and effective vaccines against hepatitis B became commercially available in the early 1980s. Initially in limited supply and very expensive, hepatitis B vaccines are now readily available and very much closer in price to other infant vaccines. Strategies for immunisation of selected high risk groups alone have not been shown to be effective in controlling hepatitis B infection, even in developed countries with a low incidence of infection. In 1992, the World Health Assembly recommended that all countries with high levels of hepatitis B prevalence should implement universal infant hepatitis B immunisation programs by 1995, and that all other countries should do so by 1997. An increasing number of countries are adopting policies of universal immunisation, usually infant immunisation integrated with the routine immunisation schedule. In some countries, supplemental or catch-up immunisation of older children or adolescents is also being carried out. Important practical issues in relation to hepatitis B immunisation are: (a) vaccine and service delivery costs; (b) the place of prevaccination screening and post-vaccination serological testing; (c) vaccine and host factors that can reduce the immunological response to vaccination; (d) the management of non-responders; and (e) the duration of protection. The key obstacles to achieve universal childhood immunisation are political will and the lack of committed resources. Combination vaccines incorporating hepatitis B, particularly diphtheria/tetanus/pertussis/hepatitis B, are likely to facilitate the universal vaccination that is necessary for global control of this important disease.

Vaccine research and development

The number of vaccines available since the time of Jenner has increased exponentially, particularly in the last decade. Of the 10 largest infectious disease causes of mortality,1 vaccines are available for four: (i) measles, (ii) hepatitis B, (iii) pertussis and (iv) tetanus. With lower efficacy, vaccines are also available for the major cause of pneumonia deaths – pneumococcus – and tuberculosis (TB). Vaccines against the remaining diseases are under development, including: (i) TB (improved), (ii) diarrhoeal diseases (especially rotavirus), (iii) malaria, (iv) HIV/ AIDS and (v) dengue. Fuelled by modern understandings of immunology and molecular biology, and by extraordinary potential for disease control and eradication, an unprecedented range of vaccines and vaccine candidates are spread across the development pipelines of vaccine manufacturers and their commercial and academic partners. Ensuring that available vaccines equitably reach all those who need them is another monumental challenge.

Biological weapons preparedness: the role of physicians

The real risk posed by biological weapons was demonstrated with the distribution of anthrax spores via the USA postal service in 2001. This review outlines the central roles of physicians in optimizing biopreparedness in Australia, including maintaining awareness of the risk, promptly recognizing an event, notifying appropriate authorities upon suspicion of an event, and instituting appropriate management. Management aspects covered include appropriate diagnostic tests, infection control procedures, and empirical therapy of agents considered possible biological weapons. The critical role of physicians as public health advocates working to prevent the use of biological weapons is also outlined. (Intern Med J 2003; 33: 242−253)

Immunisation strategies for viral diseases in developing countries

In just under a quarter of a century, the Expanded Programme on Immunisation has been associated with an increase in infant immunisation coverage from around 5% to 80%, and the prevention of at least 3 million deaths annually, at very low cost. The global target of poliomyelitis eradication by the year 2000 appears feasible. Measles is the next likely target for eradication via immunisation, through ‘catch‐up’, ‘keep up’ and ‘follow‐up’ strategies which have proven highly effective in the Americas.

Proliferation dangers associated with nuclear medicine: getting weapons-grade uranium out of radiopharmaceutical production

Abstract Abolishing the threat of nuclear war requires the outlawing of nuclear weapons and dismantling current nuclear weapon stockpiles, but also depends on eliminating access to fissile material (nuclear weapon fuel). The near-universal use of weapons-grade, highly enriched uranium (HEU) to produce radiopharmaceuticals is a significant proliferation hazard. Health professionals have a strategic opportunity and obligation to progress the elimination of medically-related commerce in HEU, closing one of the most vulnerable pathways to the much-feared ‘terrorist bomb’.