The ethics of xenotransplantation: a survey of student attitudes.

Xenotransplantation is a burgeoning technology that could provide a solution to the shortage of organs and tissue for transplantation. It does, however, raise many moral and ethical dilemmas. The aim of this study was to evaluate undergraduate university students' knowledge and opinions on the controversial practice. Choice of science or arts subjects and gender were also assessed to establish if they were influencing factors. A total of 100 students, 50 science students and 50 arts students, answered a questionnaire. Seventy-seven percent of the students had heard of xenotransplantation, 66% believed it would be beneficial to society and only 45% believed it to be ethically and morally acceptable. The medical need for organs was highlighted as the most important argument in favour, and the risk of infection was revealed to be the most important argument against xenotransplantation. The students would significantly prefer a human to non-human animal organ, and did not believe the genetic modification of animals for transplantation was ethically acceptable. This study, in general, did not find that knowledge and acceptance of xenotransplantation was associated with subject background (i.e., science or arts courses) or gender.

Partial uptake of varicella vaccine and the epidemiological effect on varicella disease in 11 day-care centers in North Carolina.

BACKGROUND: The increasing use of varicella vaccine in children attending day care has rapidly decreased the incidence of wild-type varicella disease. The herd immunity noted is significant and will have an effect on the epidemiology of natural varicella. OBJECTIVE: To monitor the change in varicella incidence in day-care attendees after the licensure of varicella vaccine. DESIGN: A prospective observational cohort study design. SETTING: Eleven private day-care centers and preschools in North Carolina participated in the study from January 1, 1995, through December 31, 1999. PARTICIPANTS: All children in the 11 centers were eligible for participation. Some participated more actively, supplying information on a regular basis. Others participated passively. Day-care personnel provided information about all cases of varicella. INTERVENTIONS: None. MAIN OUTCOME VARIABLES: The change in the incidence of varicella disease was documented as the use of varicella vaccine increased. RESULTS: Varicella vaccine coverage increased substantially from 4.4% in 1995 to 63.1% in December 1999. The vaccination rate accelerated dramatically in 1996 and 1997, leveled off in 1998, and rose again in 1999. Cumulative varicella incidence decreased from 16.74 cases per 1000 person-months in July 1996 to 1.53 cases per 1000 person-months in December 1999 in unvaccinated children. CONCLUSIONS: The varicella vaccination rate continued to increase slowly in the day-care population after an initial rapid uptake. The decrease in varicella disease is greater than the increase in varicella vaccination. This herd effect is welcome and even apparent in the unvaccinated children younger than 1 year.

Varicella vaccination in children.

Varicella vaccines have been developed, studied, tested and used since the early 1970s, first in Japan and subsequently in Europe, the US, Asia and South and Central America. Varicella vaccination was first used to immunise Japanese children in cancer remission, as wild-type varicella disease is often fatal in immunocompromised individuals. Since then, it has been licensed for use in healthy children as well. There are 3 manufacturers of the vaccine: Biken (Japan), Merck and Co. (US) and SmithKline Beecham (Belgium). The Biken vaccine has been approved for use in Japan since 1986 (although it was developed and used for research purposes from 1974). The Merck and Co. vaccine was approved in the US in March 1995 and the SmithKline Beecham vaccine was first licensed for use in immunocompromised children in 1984 and for healthy children in Sweden in October 1994. All 3 vaccines are derived from the Oka (Japanese) strain obtained from an immunologically normal 3-year-old Japanese boy named Oka with wild-type disease. Aventis-Pasteur has also purchased the rights to the Oka strain but no published literature is available for review. Use of the varicella vaccine has been controversial because many argue that: (i) the disease is mild and not worth preventing; (ii) the long term immunity provided by the vaccine is unknown; and (iii) the average age of those with the disease will increase if the vaccine is used and hence there will be more complications in older patients and, therefore, more costs. Because of some outbreaks of secondary bacterial infections after varicella in children in US day care centres, vaccination of healthy children is required in some states. It will be interesting to see whether other countries adopt a similar recommendation as more families have 2 working parents. The financial benefit of the vaccine (keeping parents at work) may encourage more use of the vaccine and a subsequent recommendation for immunisation schedules.

Postlicensure study of varicella vaccine effectiveness in a day-care setting.

BACKGROUND: Varicella vaccine has been licensed for use in the United States since the spring of 1995. The acceptance of the vaccine and its effect on varicella incidence in children is important. AIM: To document the effectiveness of the varicella vaccine in children attending day care in 11 centers in North Carolina. METHODS: A dynamic cohort study design was used in 11 day-care centers in North Carolina. Multiple cross-sectional evaluations were performed and children were noted to be vaccinated or not and diseased or not. Vaccine effectiveness was estimated by comparing the varicella attack rate in the vaccinated with the varicella attack rate in the unvaccinated. Person time was used as the denominator for all calculations. RESULTS: During the study period February 1, 1996, to September 1, 1997, 134 cases of varicella occurred in the unvaccinated and 11 cases occurred in the vaccinated children. The attack rates in the vaccinated and unvaccinated were 2.49 and 14.66, respectively, for an overall vaccine effectiveness of 83% for mild/moderate disease. CONCLUSIONS: In the day-care setting varicella vaccine demonstrated benefit in preventing and modifying wild-type varicella disease.

Concurrent administration of inactivated hepatitis A vaccine with immune globulin in healthy adults.

301 healthy adult volunteers were randomized to one of three treatment groups: inactivated hepatitis A vaccine alone; inactivated hepatitis A vaccine with immune globulin (Ig) concurrently; or Ig alone. The first two treatment groups received a second dose of hepatitis A vaccine at week 24. Anti-HAV was measured 4, 8, 12, 24 and 28 weeks after the primary immunization. When comparing subjects receiving inactivated hepatitis A vaccine alone to those receiving vaccine and Ig, the seropositivity rates were not significantly different at 4, 8, 12 and 28 weeks, but at week 24 the seropositivity rate was lower in the group receiving both vaccine and Ig compared to the group receiving vaccine alone (92.0% compared to 97.0%). At weeks 8, 12 and 24 the geometric mean titers (GMTs) were significantly lower for subjects receiving both vaccine and Ig. The GMTs were not significantly different after the second dose of vaccine. At all time points, the lower serum antibody concentrations observed in subjects receiving both inactivated hepatitis A vaccine and Ig were nevertheless substantially higher than the cutoff for assay seropositivity and much higher than after Ig alone; these differences are therefore clinically insignificant.

Modified varicella-like syndrome.

After incidental exposure to natural varicella, up to 18% of vaccinees reported a breakthrough infection known as modified varicella-like syndrome (MVLS) over up to 10 years of postvaccination follow-up, compared with natural varicella occurring in similarly aged unvaccinated children at the rate of 9% per year. Children with MVLS are frequently asymptomatic, and their disease is characterized by having fewer lesions, less fever, and lasting fewer days than natural varicella. When a case of MVLS occurs there are few secondary cases, suggesting that it is infrequently transmitted. Sequelae such as secondary bacterial infection, cerebellar ataxia, encephalitis, and pneumonia occur infrequently.

A case-control study examining risk factors for invasive Haemophilus influenzae type b disease in Victoria, Australia 1988-90.

OBJECTIVE: To determine whether day-care attendance was a risk factor for Haemophilus influenzae type b (Hib) disease, particularly for epiglottitis. METHODOLOGY: A case-control analysis of risk factors for invasive Hib disease was performed in Victoria, Australia between February 1988 and February 1990 prior to the introduction of immunization for Hib. A total of 210 cases and 367 day surgery hospital controls were enrolled prospectively. Data were collected by questionnaire at the time of admission. RESULTS: Logistic regression analysis showed that risk factors for meningitis were day-care attendance, household crowding and recent illness in a sibling. Risk factors for epiglottitis were day-care attendance and mother's birthplace in Australia or New Zealand. CONCLUSIONS: This study confirms that day-care attendance is a risk factor for Hib epiglottitis as well as meningitis. In addition, the mother's birthplace in Australia or New Zealand is a risk factor for epiglottitis in these data. The reason for this latter observation is unclear.

Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care.

OBJECTIVE: To determine if the use of influenza vaccine in children in day care decreases the incidence of otitis media during the influenza season. DESIGN: Prospective cohort study. SETTING: Eight day-care centers in North Carolina. PARTICIPANTS: One hundred eighty-six children aged 6 to 30 months. INTERVENTION: Half the participants received trivalent subvirion influenza virus vaccine. MEASUREMENTS: Acute otitis media (AOM) and serous otitis media (SOM) were assessed biweekly from mid-November 1993 to mid-March 1994 by visual and tympanometric examinations performed by "blinded" observers. The winter season was divided into three periods-before, during, and after influenza season--and the number of children with AOM or SOM during each period was determined. Unadjusted and adjusted odds ratios (ORs) were computed, while controlling for race and sex using logistic regression methods. RESULTS: Influenza vaccine was protective against AOM (OR = 0.69, 95% CI, 0.49-0.98) during the influenza season. Although there may have been some protection against SOM (OR = 0.75, 95% CI, 0.54-1.02) statistical significance was not achieved. Myringotomy tubes were also significantly protective against AOM and SOM during all three time periods, with ORs between 0.34 and 0.52, but the greatest protection was seen during the influenza period. CONCLUSIONS: Influenza vaccination of 6- to 30-month-old children in day care was associated with a decreased incidence of otitis media during the influenza season. Myringotomy tubes protected against AOM and SOM during all 16 weeks monitored.

Over five-year follow-up of Oka/Merck varicella vaccine recipients in 465 infants and adolescents.

A total of 465 healthy infants and adolescents ages 12 months to 17 years without a known history of varicella or recent exposure to varicella-zoster virus VZV were immunized with live attenuated Oka/Merck varicella vaccine from November, 1984, through April, 1989. The vaccine administered was from 1 of 7 production lots containing from 950 to 3265 plaque-forming units and was well-tolerated with few side effects. The seroconversion rate for seronegative subjects was 94.6% (403 of 426). This varied by lot from 85% (950 plaque-forming units) to 100% (3010 and 3265 plaque-forming units). Breakthrough disease after exposure to varicella in seroconverters during 5 to 10 years of follow-up was 18.6% (75 of 403). The breakthrough disease was characterized by a maculopapular rash with a median of 35 lesions, most of which were macules. Breakthrough disease lasted a median of 5 days and the median temperature was 99 degrees F; 65.3% (49 of 75) of subjects were afebrile and 2.7% (2 of 75) of subjects had temperatures of > 102.9 degrees F. Varicella vaccine provides excellent (94.6%) seroconversion, and most children who developed breakthrough disease (18.6%) experienced a modified, milder form of illness than has been observed with natural varicella in unvaccinated subjects.

Maternal acceptance of voluntary human immunodeficiency virus antibody testing during the newborn period with the Guthrie card.

In order to provide the opportunity for women delivering newborns to have human immunodeficiency virus (HIV) testing we piloted a hospital-based voluntary HIV testing program during the newborn period using the Guthrie card. During the study period 789 women were offered newborn HIV antibody testing. Test acceptance during the newborn period (61.0%) was comparable to that reported for the prenatal period (60.6%). Overall 77.4% of women were tested in the newborn period or reported being tested in the prenatal period. Prenatal test acceptance best predicted newborn HIV test acceptance (odds ratio, 3.37; 95% confidence interval, 2.40 to 4.74). When compared to HIV testing during the newborn period prenatal HIV testing is preferable because it enables the recognition of HIV infection early during pregnancy and allows the mother the option to elect zidovudine therapy and potentially prevent infection in her newborn. However, when prenatal HIV testing is not routinely made available or cannot be assured, women should be offered the opportunity to be tested during the newborn period.

Clinical manifestations and outcome of Haemophilus influenzae type b disease.

OBJECTIVE: To document clinical manifestations, laboratory findings and outcome of childhood Haemophilus influenzae type b (Hib) infections. METHODOLOGY: Medical records of 235 children with Hib disease admitted to hospital during a 2 year period were reviewed; additional information was obtained by questionnaire and follow up 6 weeks after discharge. RESULTS: Three-quarters of patients presented with either meningitis or epiglottitis. Children with epiglottitis were older, had shorter illnesses and were less likely to have had antibiotics before admission than those with meningitis; 38% of the latter had been given some antibiotic therapy, with no apparent effect on the outcome. Fever persisted for 7 days or more in 23% of patients with meningitis. Death from meningitis occurred in 3.8% of patients and was due to fulminating disease. CONCLUSIONS: These data will assist in recognition and appropriate management of Hib disease as the clinical manifestations become less familiar following the introduction of immunization. Specific laboratory diagnosis is required for accurate surveillance, which should be maintained in order to ensure high immunization rates.

Cost of treatment and prevention of Haemophilus influenzae type b disease. An international perspective.

On the basis of immunogenicity and protective efficacy studies, 4 Haemophilus influenzae type b (Hib) conjugate vaccines have been licensed for administration to infants and children. Population based studies of Hib disease from Australia, Chile, Finland, Gambia, Israel, Switzerland, UK and US show that the relative and absolute incidence of Hib disease varies significantly. These differences in Hib epidemiology, and associated sequelae and hospital costs affect the cost-benefit analysis of preventive vaccination, necessitating unique calculations for each country. Published papers on the cost of Hib disease and the cost-benefit relationship of Hib vaccination have been based primarily on reports from the US, but more recently also on studies from Australia, Finland, Israel, Switzerland, UK, Sweden and Chile. All studies to date have produced favourable cost-benefit ratios. The implementation of Hib vaccination has led to the virtual disappearance of Hib disease in some of these countries. The lessons gained from these analyses are instructive not only for better understanding of the epidemiology of Hib disease, but also as a template for assessing the cost-benefit ratio of the implementation of preventive vaccination for other diseases.