A randomized double-blind clinical trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine compared with a plasma-derived vaccine.

Eight hundred volunteers from heath care and emergency fields participated in a randomized double-blind clinical trial of a new experimental mammalian cell-derived recombinant DNA hepatitis B vaccine (Betagen) compared with a licensed plasma-derived vaccine (Heptavax-B). Vaccine injections (20 micrograms) were administered intramuscularly at 0, 1, and 6 months, and sera were tested at 0, 1, 2, 3, 6, 7, and 12 months for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen. Data from 745 vaccinees (93.1%), analyzed at the 7th month of follow-up, showed no significant difference in the seroconversion rates for Betagen (94.4%) vs Heptavax-B (97.3%), but the geometric mean titer of antibody was significantly higher for Heptavax-B (11 833 mIU/L) than for Betagen (4628 mIU/mL). The antibody response of Betagen was significantly and independently related to age and sex, while that of Heptavax-B was related to age only. Reported side effects from both vaccines were minor and mild, with approximately one fourth of all vaccinees reporting at least one side effect. Vaccinees, who had a protective level of antibody at the 7th month, were tested for antibodies at the 12th month. Of those in the Betagen-vaccinated group and those in the Heptavax-B-vaccinated group, 99.0% and 100%, respectively, were still protected. There was a proportionately larger decline in the geometric mean titers of antibody to hepatitis B surface antigen for Heptavax-B than for Betagen.

Comparison of three HIV antigen detection kits in sequential sera from a cohort of homosexual men.

HIV antigen detection kits are available from a number of commercial sources. Abbott, Coulter, and Du Pont antigen kits were used to test 661 sera collected sequentially from 65 members of the Toronto Sexual Contact Study (TSCS). The sera had been collected at 3-month intervals over 4 years from nine persistently HIV-seronegative men, 14 seroconverters, and 42 seroprevalent participants. Antigen was not detected in any seronegative men. Two of 14 seroconverters were antigen positive in the specimen immediately preceding seroconversion (by all kits). Antigen was detected in 22 of 56 seropositive participants; of these, 16 of 22 demonstrated the emergence of antigen during observation. Discrepancies were noted in the time of detection of antigen (ranging from 3 months to more than 3 years) in nine participants. Although overall concordance among all kits for all specimens appears high (95.4%), when the bias introduced by testing multiple specimens from the same patient is removed, the lower bound of concordance among all three kits is estimated to be 80%. Similarly, after correction, the upper and lower bound of estimates of sensitivity are Abbott 96, 92%; Coulter 88, 63%; and Du Pont 88, 58%. There are significant differences in the performance characteristics of these commercial products for the detection of HIV antigen in serum.

Ongoing high-risk sexual behaviors in relation recreational drug use in sexual encounters. Analysis of 5 years of data from the Toronto Sexual Contact Study.

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.

Assessment of generalized lymphadenopathy in AIDS research: the degree of clinical agreement.

The degree of clinical agreement amongst different physicians on the presence or absence of generalized lymphadenopathy was assessed in 32 randomly selected participants from a prospective study of male sexual contacts of men with AIDS or an AIDS-related condition (ARC). Three physicians completed the same standard examination that was developed for the main project and conducted the examination of the anatomic regions in the same order on each person, at approximately the same time, and in random order. One physician (Doctor A) was the physician responsible for conducting examinations on the main cohort from which these participants were selected. Intra-observer agreement was assessed by comparing Doctor A's examinations on these participants with those he had recently conducted within a one and a half month period in the main study. Acceptable levels of intra-observer agreement (kappa = 0.72) and interobserver agreement (kappa = 0.66) were demonstrated for the presence or absence of generalized lymphadenopathy for Doctor A and Doctor B, a physician who periodically replaced Doctor A in the main project. Agreement between Doctors A, B, and C, was less satisfactory (kappa of 0.45 and 0.39, respectively). Doctor C was the least experienced with the standardized examination. However, during the progress of this study, agreement between the three doctors improved (kappa values for the latter 16 participants ranged from 0.60 to 0.86) suggesting that experience with the criteria and the standardization of the examination may enhance agreement.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between hepatitis B surface antigen prevalence, per capita alcohol consumption and primary liver cancer death rate in 30 countries.

The relationships between the prevalence of hepatitis B surface antigen (HBsAg), mean annual per capita alcohol consumption and primary liver cancer (PLC) death rates were explored in 30 countries. HBsAg prevalence was associated, significantly, with the logarithm of the primary liver cancer death rate (simple correlation coefficient = 0.44, p less than 0.05). This significant association increased following adjustment for a country's mean annual per capita alcohol consumption (partial correlation coefficient = 0.53, p less than 0.01). A logarithmic linear relationship was also found between per capita alcohol consumption and the primary liver cancer death rate after adjustment for the country's prevalence of HBsAg (partial correlation coefficient = 0.38, p less than 0.05). Results from both correlation and regression analyses showed that prevalence of HBsAg was more significantly associated with PLC death rates than was alcohol consumption. However, these two variables were independently related to the PLC death rate in a stepwise multiple regression model. We could not demonstrate an interaction between the two variables. These findings are consistent with the prevailing view that chronic hepatitis B infection is the major factor in the most common form of primary liver cell cancer, hepatocellular carcinoma. In addition, they support the notion that alcohol consumption contributes significantly and independently, although probably to a lesser extent than hepatitis B, to deaths from that disease.

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Changing trends of cirrhosis mortality in Ontario, Canada, 1911-1986.

Cirrhosis mortality death rates in Ontario for ages 20 and over declined from a high of 9.3 per 100,000 in 1911 to a low of 5.6 per 100,000 in 1919 (p less than 0.001) and after a 17-year period of relative stability, rose steadily to a high of 19.7 per 100,000 in 1975 (p less than 0.0001) and then declined to 13.3 per 100,000 in 1986 (p less than 0.001). Rates were consistently higher for men than for women and the male to female ratio of the rates increased from a low of 1.3 in 1933 to a high of 2.5 in 1986. The rate of increase in the rates for both men and women, and the rate of decline after the mid 1970s was most noted in the younger ages. Differences in trend could not be related to changes in disease classification, method of recording deaths, changes in diagnostic habits such as introduction of needle liver biopsy or to method of standardizing the rates. There was a positive and significant correlation between per capita alcohol consumption and rates of cirrhosis in Ontario from 1932 to 1975. However, while cirrhosis rates declined markedly from 1976 to 1986, alcohol consumption remained stable from 1976 to 1980 and declined only slightly from 1981 to 1986. A possible explanation for lack of correlation between alcohol consumption and the cirrhosis rates from 1976 to 1986 could be that the balance of force favoured recovery i.e. those people who already had cirrhosis who decreased (or stopped) their consumption of alcohol, did not die. Correlations with lagged alcohol consumption could not explain all the changes in the cirrhosis rates. Although cirrhosis rates consistently increased with increasing age from 35 to 85, our results showed that succeeding generations were developing cirrhosis at successively younger ages after the age of 35. Possible explanations for this cohort effect are increased survival from infectious diseases in infancy and childhood, increase in hepatitis B infection, excessive drinking habits being established at younger ages or a change in the pathogenesis of the disease.

Relationship between liver cirrhosis death rate and nutritional factors in 38 countries.

The relationship between liver cirrhosis death rates and certain nutritional factors was studied in 38 countries where mortality statistics were considered to be reliable. A partial correlation analysis showed that several food commodity consumption factors were independently and negatively (p less than 0.01) associated with liver cirrhosis death rates after adjustment for alcohol consumption. These factors were total calories, protein, fat, calcium, vitamin A and vitamin B2. The significant association of protein, vitamin A, vitamin B2 and calcium with the cirrhosis death rates is of importance since they were not intercorrelated with alcohol consumption. Further results showed that animal protein was more significantly related to cirrhosis death rates than vegetable protein. However, in view of certain limitations of this study, the findings do not necessarily reflect causal relationships but rather support the consideration by scientists that protein and vitamin deficiency may have certain effects on liver cirrhosis.

The probability of progression to AIDS in a cohort of male sexual contacts of men with HIV disease.

In a cohort of 249 male sexual contacts of men with AIDS or an AIDS-related condition (ARC), 143 cohort members were seropositive on enrollment and 16 seroconverted during follow-up. A logistic Weibull mixture model was used to estimate the probability of progression to AIDS after HIV infection when infection was assumed to occur during the period of sexual contact with the primary case. Forty cohort members developed AIDS while under study. It appears that at least 50% of men with HIV disease will progress to AIDS and that the best estimate of this probability lies anywhere in the interval 70% to 100%.

An efficacy trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China.

We conducted a randomized, double-blind clinical trial of an experimental mammalian cell-derived DNA hepatitis B vaccine (Betagen, Connaught Laboratories Ltd, Toronto, Canada) to determine its efficacy in infants born to mothers who were carriers of hepatitis B surface antigen (HBsAg). Four groups of 55 infants received injections as follows: (1) a licensed plasma-derived vaccine (Lanzhou, Lanzhou Institute for Biological Products, Lanzhou, People's Republic of China), 20 micrograms; (2) Betagen, 20 micrograms; (3) Betagen, 20 micrograms+hepatitis B immune globulin (HBIG); and (4) Betagen, 10 micrograms+HBIG. Vaccine injections were given at birth and at 1 and 6 months and HBIG was given at birth. The vaccines were compared to a historical placebo control group. The efficacy of Betagen alone was 82.6% compared to 51.0% for the Lanzhou. Efficacy of Betagen increased with the concomitant use of HBIG. No infants who were HBsAg negative at birth and/or were born to hepatitis B e antigen (HBeAg) negative mothers became carriers. The rate of HBsAg in infants receiving Betagen alone, and born to mothers who were HBeAg positive, decreased from 60% at birth to 20% by the ninth month, compared to 62.5% and 50% (respectively) for Lanzhou. The percentage of infants with protective levels of antiHBs was significantly higher for Betagen alone than for Lanzhou, but the geometric mean titre of antiHBs for responders was not significantly different. We have shown that Betagen alone is highly efficacious in preventing the development of hepatitis B in infants born to mothers who are carriers of HBsAg and is also highly effective in reducing the carriage of HBsAg in infants who are HBsAg positive at birth and/or born to HBeAg positive mothers.

PIP: Researchers assigned 220 infants born at 5 participating hospitals in Shanghai, China to receive either a 20mcg of an experimental recombinant DNA hepatitis B vaccine (Betagen), a licensed plasma derived hepatitis B vaccine (Lanzhou), 20 mcg of Betagen and hepatitis B immune globulin (HBIG), or 10mcg of Betagen and HBIG to determine the efficacy of Betagen in infants born to mothers with hepatitis B surface antigen (HBsAg) positive. Since China is a hyperendemic hepatitis B carrier area (in Shanghai, for example, prevalence rate is 57%), China hopes to reduce the carrier state via a low cost, safe, immunogenic, and efficacious recombinant vaccine. 20mcg of Betagen resulted in 82.6% efficacy which was significantly higher than that of Lanzhou (51%). The efficacy increased when HBIG was administered with the 20mcg of Betagen (92%). None of the infants born HBsAg negative and/or born to hepatitis B e antigen (HBeAg) mothers later became carriers. Further the HBsAg positive fell from 60-2-% in 9 months whereas these corresponding figures for those who received only Lanzhou were 62.5% and 50%. Even though the percentage of infants with protective levels of antiHBs stood much higher in those who received only Betagen than for those who received Lanzhou in all the months of follow up, except the 1st, their geometric mean titre of antiHBs was not statistically significant. Since Betagen prompted a quick antibody response which probably helped decrease HBsAg in the serum of those infants already positive for HBsAg at birth, it had an advantage over Lanzhou. In conclusion, Betagen given alone proved to be very efficacious in preventing hepatitis B in infants born to carriers of HBsAg. Further it was effective in reducing carriage of HBsAg in infants born HBsAg positive and/or born to HBeAg positive mothers.

Varied potential risks of HIV infection among prostitutes.

To date, most HIV prevention programs targeting North American prostitutes have focused on individual behaviour change, and in particular, the consistent use of condoms between prostitutes and their clients. The organizational and societal level issues which may influence high risk practices within the working and private spheres have received relatively little attention. In addition, most prevention efforts have been limited to targeting the sub-population of street prostitutes. We outline here three different types of prostitutes (street prostitutes, escorts, and prostitutes who work part time in the service sector, i.e. barmaids and erotic massage therapists) known to work in many North American centres. In doing so, we suggest that potential risks of infection vary according to the type of prostitution, and that prevention programs must recognize the diversity in potential risk practices. Differences in the organization of work and working conditions of varied types of prostitutes may, in particular, influence risk practices while working. Some of the individual, organizational and societal level issues which influence risk practices among different types of prostitutes are presented. Much of the research involving HIV and prostitutes has accessed prostitutes at sites where street prostitutes are over-represented. Other studies are based on potentially baised samples as they have recruited prostitutes from medical clinics. Methodologic problems that influence attempts to obtain a representative sample of the prostitute population are discussed.

The knowledge, attitudes and concerns of hospital staff about AIDS.

Staff from 3 Toronto hospitals were surveyed for knowledge, attitudes and concerns about AIDS. 70% of the 1,366 respondents had direct clinical experience with persons with AIDS. Data were analyzed according to hospital setting and professional group: physicians, nurses, technologists and supervisory staff. No setting difference was observed and although statistically significant differences (at the .001 level) were observed between professional groups, these differences are small and have little practical importance. In general, subjects answered 68% of the knowledge questions correctly. All attitudes and concerns were inversely associated to knowledge (Pearson r range was -.31 to -.20). Multivariate analysis demonstrated that knowledge and concern about contagion are important mediating variables (multiple r = .40) for other attitudes and concerns.

Needle sharing behaviour among injection drug users (IDUs) in treatment in Montreal and Toronto, 1988-1989.

Injection drug users (IDUs) entering treatment programs in Montreal and Toronto were recruited for a study of drug using behaviour and risk of HIV infection. Only those who had injected within 6 months of entering their treatment program were eligible for participation. 183 subjects were recruited in Montreal and 167 in Toronto between November, 1988 and October, 1989. Each participant completed a standardized interviewer-administered questionnaire which focussed on, among other things, drug history and needle sharing behaviour. Approximately three-quarters of respondents in both cities reported sharing needles and syringes within the 6-month period prior to their entry into treatment. Our analysis, which focussed on variables associated with needle sharing revealed that having a sexual partner who injected, trouble obtaining sterile needles and syringes and cocaine injection were significantly and independently associated with needle sharing in a logistic regression model which also controlled for city of recruitment.

Sexual behaviour changes in a cohort of male sexual contacts of men with HIV disease: a three-year overview.

We describe the sexual behaviour reported by 240 seronegative and seropositive homosexual men over a 3-year period. Sexual partners of men with HIV disease were recruited into a prospective study between July 1984 and July 1985 and were monitored every 3 months thereafter. Data on sexual activities were collected through interviewer-administered questionnaires. The cohort experienced a reduction in both the number of sexual partners and the volume of sexual activity. Reductions in the number of partners were early and dramatic. Changes in sexual activities were gradual and consistent in trend. The greatest reduction occurred in high risk activities (receptive and insertive anal intercourse). After 3 years of follow-up, only 10% of the men continue to be exposed to semen through unprotected receptive anal intercourse and 18% through unprotected receptive oral-genital sex. The proportion of men engaging in oral-genital contact and masturbation remained stable over the 3 years. Once informed of their serostatus, both seropositive and seronegative men reduced their high risk behaviour. The decline in rates of STDs and seroconversion confirmed that this cohort had indeed reduced their high risk behaviour.

Partner notification for sexually transmitted diseases: proposed practice guidelines.

Using the results of an analysis of available scientific evidence and a survey of current practice in Canada, as well as expert opinion, these guidelines attempt to consider current partner notification practice in Canada and recommend an approach to determining practice which is flexible enough to address local circumstances. Priority areas for future research were also identified.

A survey of public health partner notification for sexually transmitted diseases in Canada.

OBJECTIVE: To describe the range of practice for sexually transmitted disease (STD) contact tracing/partner notification (PN) by public health agencies in Canada. METHODS: A two-level mailed survey, using two different questionnaires, was conducted from Aug. 1991 to Feb. 1992, directed to: 1) provincial and territorial epidemiologists/directors of STD control, asking about program organization; and 2) 154 local health units/provincially run PN programs, asking about practice patterns of STD partner notification. CONCLUSIONS: In Canada, STD PN by public health agencies is routinely practised in most provinces. PN efforts vary by the STD; less PN effort goes to chlamydia despite a high burden of illness; HIV PN is frequently perceived to be within the responsibility of the physician. For STDs with higher PN effort, the preferred method is provider referral. Targeting is seldom utilized, and there are little available data at a local level monitoring even process measures of effectiveness.