Hepatitis B and the dental profession: response to hepatitis B vaccine in Canadian dental personnel. A study by the Canadian Red Cross Collaborative Group.

Reports from North America and Western Europe based on the prevalence of hepatitis B virus markers and frequency of hepatitis B in dentists indicate that this professional group is at increased risk of HBV infection. We gave hepatitis B vaccine (Merck Sharp and Dohme) to 251 dental students and faculty/staff members at faculties of dentistry in three Canadian universities. Participants received three 20 micrograms doses of vaccine, at 0, 1 and 5.5 months. Anti-HBs was detected in 42.9 per cent of persons after the first dose of vaccine, in 96.8 per cent after the second dose and in 99.6 per cent after the third dose. A follow-up of 150 persons 22 months after the first dose of vaccine indicated that high or medium levels of anti-HBs were maintained in nearly 87 per cent of the participants and only six per cent had no detectable antibody. Female vaccinees in each age group developed anti-HBs more promptly, and more of them were in the high antibody-response range in comparison to male participants. There were no unacceptable reactions to the vaccine. Our favourable experience with this vaccine would support recommendations for its routine use among dental professionals in Canada and other countries where this group is at increased risk of HBV infection.

Impact of measles in Canada.

The reported incidence of measles in Canada in 1981 was reduced 97% from the average annual rates during the prevaccine period, 1949-1958. Throughout recent years the age-specific incidence of reported cases of measles has remained highest in the group five to nine years of age, but there has been a definite increase in the proportion of cases of measles in persons greater than 10 years of age. During the extensive measles epidemic in Alberta in 1979, a high proportion of the reported cases occurred in adolescents and young adults previously vaccinated with killed vaccine, and the majority of these developed atypical measles syndrome. In Canada, from five to 36 patients per 100,000 population have required hospitalization annually for complications due to measles over the past 16 years. Measles-related deaths have declined in a pattern similar to that for reported incidence. Despite favorable trends in the control of measles in Canada, the social and economic impacts of this disease remain substantial and warrant a nationwide effort to eliminate indigenous infection.

The HBsAg-Positive Patient: Implications and a Guide to Management.

Following infection with hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) is detectable in the serum before liver function tests become abnormal and before development of clinical features of hepatitis; HBsAg tests usually become negative shortly after illness subsides. Screening individuals such as volunteer blood donors for HBsAg occasionally reveals apparently healthy people who are persistent carriers of HBsAg; the majority have no laboratory evidence of hepatitis whereas others have biochemical or histologic findings of chronic liver disease.

Interferon in the cerebrospinal fluid of children with central nervous system disorders.

Interferon was detected in the cerebrospinal fluid (CSF) of 26 of 51 children with aseptic meningitis, two of 44 with bacterial meningitis, and four of 118 with miscellaneous conditions including encephalitis, convulsive disorders and leukemia with neurological involvement. The geometric mean titre of interferon in mumps meningitis was seven to eight times higher than that in enteroviral meningitis; however, levels of interferon were not related to the concentration of leukocytes in CSF from these patients. Interferon titres were relatively greater at the height of the febrile response in children with mumps meningitis or enteroviral meningitis. There was no association between the presence of interferon in the CSF and the isolation of mumps virus or an enterovirus from the same specimen. Patients frequently developed homologous antibody one to three days after signs of aseptic meningitis, obscuring the relationship of interferon production to clinical improvement.

Interferon: a changing picture.

Concepts regarding the nature and function of interferon have undergone considerable modification since its initial description in 1957. A low-molecular-weight protein, interferon has been produced by a variety of host cells following exposure not only to most viruses but also to bacterial cells and endotoxins, rickettsiae, nucleotides and a polyanionic polysaccharide (Statolon). Interferon production and activity require de novo synthesis of cellular RNA and protein, although interferon induced in vivo by endotoxins appears to involve release from a preformed state.The pathogenesis of primary viral infections may be determined largely by non-immune defence mechanisms. Interferon, detectable in the host's serum and associated with leukocytes during the course of viral illness, may make an important contribution to recovery. Low toxicity, weak antigenicity and wide range of antiviral activity make interferon an attractive therapeutic possibility. Stimulation of inherent interferon-producing mechanisms by administration of relatively innocuous agents may prove beneficial in humans.

Contrasting effects of rabbit and human platelets on chikungunya virus infectivity.

Chikungunya virus infectivity was markedly stabilized in the presence of washed suspensions of human platelets but rapidly disappeared in similar preparations of rabbit platelets. Supernatant fluids collected from human platelets had some stabilizing effect on chikungunya virus over a 6-day incubation period at 37 degrees C. Rabbit platelet supernatant fluid had no virus-stabilizing effect, nor did it demonstrate any capacity to inactivate virus as compared to whole rabbit platelet preparations. Thin-section election microscopy demonstrated that chikungunya virus formed an associated with human platelets by becoming entrapped in platelet aggregates; during this process some of the platelets appeared to have undergone degranulation and lysis. Rabbit platelets exposed to chikungunya virus for 24 h demonstrated a considerable amount of platelet degranulation and lysis but virus was not visualized either in association with platelet membranes or within phagocytic vacuoles in the platelet cytoplasm. Human platelets, which appear to be more stable under these incubation conditions, may protect chikungunya virus infectivity from heat inactivation by surrounding viruses with large platelet aggregates whereas rabbit platelets, which appear to be more fragile, do not afford this type of protection. Thus, chikungunya virus in the presence of rabbit platelets may become inactivated by heat or may become bound irreversibly to membranes in such a fashion that infectivity assay and electron microscopy techniques may prove to be too insensitive for detection of virus.

Comparative seroepidemiology of cytomegalovirus infection in the Canadian Arctic and an urban center.

We conducted a seroepidemiologic study of cytomegalovirus (CMV) infection among 9,928 Inuit (Eskimo), Dene (Indian) and non-native inhabitants of the Northwest Territories (NWT) of Canada between April 1983 and March 1985. 4,184 inhabitants of Edmonton, a large predominantly white urban center served as controls. Sera were screened for antibody to CMV by enzyme-linked immunosorbent assay (ELISA). The prevalence rates of CMV antibody increased with age in all ethnic groups. By the age of two years 69.2 percent of Dene, 63.5 percent of Inuit, 33.3 percent of non-native and 22.9 percent of Edmonton children had CMV antibody. Over the age of five years Inuit children had higher rates of CMV antibody than Dene children (P less than .05) reflecting differences in infant adoption, breastfeeding practices and patterns of child care in the two native groups. By the age of 15 to 19 years 81.1 percent of Dene and 88.5 percent of Inuit women had CMV antibody compared to 48.8 percent of non-native and 50.9 percent of Edmonton women (P less than .05). Native children had higher prevalence rates than non-native children living in the NWT (P less than .05). Compared to similarly aged Edmonton residents, non-native children in the NWT 2 to 4 years and 5 to 9 years of age had a higher prevalence of CMV antibody (P less than .05). We observed a higher prevalence rate of CMV antibody among non-native children (10-14 years) and young women (15-19 years) living in predominantly native communities compared to those living in predominantly non-native communities in the NWT (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of responses to influenza A/New Jersey/76-A/Victoria/75 virus vaccine administered intradermally or subcutaneously to adults with chronic respiratory disease.

Serum HAI (hemagglutination inhibition) antibody responses were compared in two groups of 70 age-matched patients (age range, 17 to 82 years) who were vaccinated with bivalent influenza A/New Jersey/76-A/Victoria/75 whole-virus vaccine. The group that was vaccinated intradermally received 40 chick cell-agglutinating units of each viral antigen in 0.1 ml, and the group that was vaccinated subcutaneously received 200 chick cell-agglutinating units of each antigen in 0.5 ml. The serum HAI antibody response to A/New Jersey/76 antigen was significantly higher in the group that was vaccinated subcutaneously; this difference was particularly evident in patients less than or equal to 50 years old. The serologic response to A/Victoria/75 antigen did not differ significantly between the two groups. Levels of antibody before vaccination indicated previous widespread exposure of patients to influenza A/Victoria/75 virus, but not to influenza A/New Jersey/76 virus. Such differences in prior immunologic experience with a particular strain of influenza virus probably determine whether the intradermal route of vaccination is as effective as, or inferior to, the subcutaneous route.

Relationship between tuberculin reactivity and hepatitis B virus infection in the Northwest Territories.

Of 370 NWT Inuit or Dene who were HBsAg-positive, only 31 had HBeAg. Persons who were PPD negative were 6.2 times more likely to be HBeAg-positive than those who were PPD positive, but this inverse association applied only to those 30 years of age. We further analyzed a group of 3,378 Inuit whose status was known for HBV serologic markers and PPD reactivity. Overall, a significantly greater proportion (76.2%) of HBsAg positives were PPD reactive in comparison to those positive for anti-HBs (67.2%) or who had no HBV markers (43.2%). For persons 30 years of age who were positive for HBsAg or anti-HBs there was no significant difference between the proportions with PPD reactivity but a significantly smaller proportion of PPD reactivity was found in the no marker group. Among persons 30 years of age, the proportions of those who were PPD reactive were statistically equivalent across all three HBV marker groups. We conclude that patterns of HBV infection in NWT are random with respect to tuberculin reactivity resulting from either exposure to M. tuberculosis or administration of BCG vaccine.

Extension of the epidemiology of hepatitis B in circumpolar regions through a comprehensive serologic study in the Northwest Territories of Canada.

We conducted a seroepidemiologic study of hepatitis B virus (HBV) infection among 14,198 Inuit (Eskimo), Dene (Indian), and non-native inhabitants of the Northwest Territories (NWT, total 1982 population 47,053) between April 1983 and March 1985. Participants represented almost all of the NWT communities and included approximately half of the total indigenous population. Sera were screened for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface antigen (anti-HBs) by radioimmunoassay. A total of 428 persons (3.0%) were positive for HBsAg; their mean age was 41.5 years and 68.7% were greater than 30 years old. Anti-HBs was detected concomitantly in 153 (35.7%) of these persons and present as a single marker in 2,943 sera (20.7%). Overall prevalence rates for HBsAg were marginally higher among Inuit than Dene (3.9% and 2.9%, respectively; P less than 0.05), as were rates for anti-HBs (24.5% and 21.5%, respectively; P less than 0.01). Marker rates among the 2,776 participants of other ethnic groups, predominantly whites, were distinctly lower (HBsAg 0.3%, anti-HBs 8.5%) than among Inuit or Dene populations (P less than 0.01). The prevalence of HBsAg and anti-HBs increased with each decade of life in all five geographic regions, but there were marked differences among the regions as well as among communities within regions. The greatest concentration of HBV markers was in the Baffin Region (36.0% positive for HBsAg or anti-HBs). Hepatitis B e antigen (HBeAg) was detected in only 37 of 421 persons (8.8%) positive for HBsAg; most were less than or equal to 20 years old and were clustered in a few communities with the highest HBV marker rates.

Haemolytic uraemic syndrome: evidence of multiple viral infections in a cluster of ten cases.

During July 1979, ten patients were admitted to the hospital with bloody diarrhoea followed by manifestations of haemolytic uraemic syndrome (HUS): acute microangiopathic haemolytic anaemia, intravascular coagulopathy, and impaired renal function. Ages ranged from 13 months to 58 yr, with only two patients more than 5 yr old. In a household that included seven children born to three sisters who married three brothers, six children required hospitalization for bloody diarrhoea and four developed HUS; the father of one case and the maternal grandmother also developed bloody diarrhoea. Echovirus type 11 was isolated from the pharyngeal secretions or faeces of all members of the household with bloody diarrhoea, with the exception of the grandmother. Picornavirus-like particles were seen by direct electron microscopy (E/M) in faeces from four other HUS patients and an adenovirus in one, but these viruses failed to replicate in cell cultures. Parvovirus-like particles were seen by E/M in faeces from six patients. Serological examination indicated recent infection with one or more enteroviruses (echovirus 11, coxsackieviruses A4, B2, B4) in nine cases. Combined viral studies revealed presumptive evidence of recent infection with two or more viruses in all of the patients with HUS. Stools were negative for bacterial pathogens including campylobacter, salmonella, shigella, and yersinia organisms. Only one of nine patients tested had circulating immune complexes. Our data support the concept that the pathology seen in HUS may be due to a Shwartzman-type reaction provoked by concurrent infection with two or more viral agents.

Congenital cytomegalovirus infection in an urban Canadian community.

congenital cytomegalovirus (CMV) infection was diagnosed in 64 (0.42%) of 15,212 infants born in Hamilton, Ontario, Canada, during a period of 44 consecutive months. Urine specimens collected within 48 hr of birth were screened for CMV by inoculation into cell cultures. Only four infants had clinical or laboratory findings in the first week of life that suggested cytomegalic inclusion disease; CMV infection was mild or inapparent in the remainder. Fourteen CMV-positive infants (21.9%) had birth weights of less than or equal to 2,500 g, including eight of 11 premature infants (less than or equal to 37 weeks of gestation). Only five CMV-positive infants were small for gestational age. Overall, there were no significant differences between CMV-positive and CMV-negative infants in mean gestational age or mean measurements of weight and head circumference at birth. Mothers of CMV-positive infants were predominantly younger, primiparous women of lower educational and economic status, and the number who were unmarried was about threefold greater than among mothers of uninfected infants.

Viral infections of Toronto children during 1965. I. Enteroviral disease.

Enteroviruses were isolated from feces and/or cerebrospinal fluid of 29 of 43 Toronto children who contracted aseptic meningitis, pleurodynia, abdominal pain or febrile upsets between June and October, 1965. Coxsackie A9 virus was the dominant agent in aseptic meningitis and Coxsackie B1 virus in pleurodynia and other syndromes. Sero-logical evidence of recent Coxsackie B1 and Echo 6 infection was obtained in two additional patients with aseptic meningitis who did not yield virus, and elevated Coxsackie B1 antibody titres were found in one patient with pericarditis. A newborn infant died with myocarditis due to Coxsackie B1 virus following infection of the mother during the immediate antenatal period. Paired sera collected only two to four days apart from patients with enteroviral syndromes or mumps meningoencephalitis frequently showed four-fold or greater increases of antibody levels.

Mumps and enteroviral meningitis in Toronto, 1966.

Of 52 children admitted to hospital for apparently typical mumps meningitis in 1966, 50 had their cerebrospinal fluid (CSF) examined. In only 17 was the mumps virus isolated from the CSF. Mumps antihemagglutinin conversions or increments were detected in 32 subjects including 10 whose CSF yielded virus. Antibody conversions were found in 16 patients and fourfold increments in another nine whose serum pairs were collected only one to four days apart. Initial sera from 20 patients were obtained three days or less after the onset of meningitis. Antibody increments were frequently noted about one day after defervescence and clinical improvement. Interferon was detected in CSF from two of eight patients, both of whom yielded virus. Enteroviruses were isolated from CSF and/or feces in seven of 15 cases of aseptic meningitis which occurred between July and October. Six patients including three virus excretors showed enteroviral neutralizing antibody increments during convalescence. The dominant enteroviral serotype was coxsackievirus A9.

The outcome in children with congenital cytomegalovirus infection. A longitudinal follow-up study.

Infants with congenital cytomegalovirus (CMV) infection were identified through urine cultures of 15,212 consecutive neonates and studied prospectively to determine whether their neurodevelopmental and audiologic status was different from that of matched uninfected control subjects. Of 64 children with congenital CMV infection, three died, 11 could not be located for follow-up, one had quadriplegic cerebral palsy, and seven had varying degrees of sensorineural hearing loss. All matched control subjects were normal neurologically, and none of them had sensorineural hearing impairment. The Stanford-Binet test revealed scores within the normal range, at 3 and 5 years of age, for both children with CMV infection and matched control subjects, as did the preschool assessment (Wide Range Achievement Test) in children older than 5 years. However, in children with CMV infection, the home environment was less stimulating, discipline and punishment were more readily implemented, and behavioral problems were significantly greater than in the matched control subjects.

Guide to the management of rubella problems.

Despite the availability of rubella vaccine the incidence of the congenital rubella syndrome has been increasing in certain regions of Canada. Perhaps this is not surprising in view of the known irregular cyclic activity of rubella virus in a community and the fact that the percentage of seropositive women of childbearing age has not changed appreciable since the vaccine was introduced. Clearly vaccine is not being administered to sufficient numbers of women at risk. Until a much higher percentage of women of childbearing age possess rubella antibody, the costly problem of congenital rubella syndrome is likely to be with us. Common rubella problems relate to four categories: the exposed pregnant woman, laboratory diagnosis, the infant with suspected congenital rubella and the vaccine. One of the most common questions about the vaccine is the following: Can recently vaccinated individuals disseminate vaccine and infect seronegative contact? The answer is No.