The risks of transmission of acute hepatitis A and B virus infection in an urban centre.

In a large urban centre of a developed nation, 63 household contacts of 20 index cases with acute hepatitis A virus infection and 95 household contacts of 29 index cases with acute hepatitis B virus infection were prospectively followed for 2 years to document the risk of acquiring acute hepatitis from the index case. Twenty-one of 63 (33%) hepatitis A virus household contacts had serologic evidence of previous hepatitis A virus infection on the initial serum sample. Of the remaining 42 susceptible individuals, 22 (52%) were or became IgM anti-HAV positive within 6 months of the diagnosis in the index case. With respect to hepatitis B virus infection, 18/95 (17%) household contacts had serologic evidence of previous hepatitis B virus infection on the initial serum sample. Of the remaining 77 susceptible individuals, four (5%) had or developed serologic evidence of acute hepatitis B virus infection (IgM anti-hepatitis B core antigen positive) during the 2 years of follow up. In three of these four individuals, acquisition of hepatitis B virus was apparent within 6 months of the diagnosis in the index case. The results of this study indicate that in this urban centre, the risk of acquiring acute hepatitis A virus infection from index cases within the household is approximately 10 times greater than that for acute hepatitis B virus infection. These results support the need for continued passive and/or active immunization against hepatitis A and B virus infection in susceptible household contacts.

Molecular epidemiology of Legionella pneumophila infection at a Canadian tertiary care institution.

OBJECTIVE: To characterize the molecular epidemiology of Legionella species infection at one Canadian tertiary care centre. DESIGN: Twenty-eight clinical isolates and 12 environmental isolates obtained over a six-year period were analyzed by restriction fragment length polymorphism (rflp) of chromosomal dna. Isolates included 15 from 12 patients with hospital acquired illness and 13 from nine patients with community acquired infection. RESULTS: One nosocomial strain was Legionella micdadei and one community strain was Legionella pneumophila serotype 6; all others were L pneumophila serotype 1. rflp typing revealed one clone for all cases of a 1985 single-ward outbreak and five of six nonoutbreak L pneumophila nosocomial cases. An rflp pattern identical or highly related to that of the nosocomial clonal type was noted among nine of 12 L pneumophila serotype 1 community isolates. The remaining three isolates had two related rflp patterns distinct from the institutional strain. The nosocomial and community strains were isolated from multiple institutional water samples in the institution. For the environmental isolates, monoclonal antibody typing was more discriminating than rflp typing: seven monoclonal antibody subtypes were distinguished among 12 environmental isolates comprising three distinct rflp patterns. CONCLUSIONS: Despite multiple L pneumophila serotype 1 strains isolated in the authors' institutional water, a single clone of L pneumophila produced most disease. Community acquired disease was caused by a wider variety of strains.

An enzyme-linked immunosorbent assay-based isolation procedure for verotoxigenic Escherichia coli.

A colony enzyme-linked immunosorbent assay using the hydrophobic grid membrane filter format was developed for the isolation of verotoxigenic Escherichia coli from human and food samples. The method utilizes monoclonal antibodies directed against the verotoxins and is sensitive to all verotoxin 1- and/or 2-producing serotypes. E. coli that produced a minimum of 2 x 10(2) and 2 x 10(3) 50% cytotoxic doses per ml of verotoxins 1 and 2, respectively, were detectable. In a method comparison using human stool specimens, this procedure isolated 29% more E. coli O157 than did the standard sorbitol-MacConkey agar procedure, with no false-positive reactions. When applied to meat, 11 of 20 samples positive for verotoxin by polymyxin extraction yielded verotoxigenic E. coli of a variety of serotypes including O157:H7. Four false positives were noted. This procedure provides a sensitive means for the isolation of verotoxigenic E. coli and should facilitate recovery of those serotypes that are otherwise indistinguishable from nonpathogenic strains.

Effects of acetaminophen on adverse effects of influenza vaccination in health care workers.

OBJECTIVE: To evaluate the effects of acetaminophen on the incidence of adverse effects to, and the immunogenicity of, whole-virus influenza vaccine in health care workers. DESIGN: Prospective, randomized, double-blind placebo-controlled trial. SETTING: Health Sciences Centre, an acute care teaching hospital in Winnipeg. PARTICIPANTS: Of 474 hospital personnel who agreed to undergo influenza vaccination during the 1990-91 season 262 volunteered to participate in the study. INTERVENTIONS: A dose of 0.5 mL of inactivated trivalent whole-virus influenza vaccine was injected into the deltoid muscle. Volunteers were randomly assigned to ingest two capsules of acetaminophen in a half dose (162.5 mg per capsule) or a full dose (325 mg per capsule) or two identical placebo capsules. Capsules were to be taken at vaccination and at 4, 8 and 12 hours afterward. Subjects were asked to answer questions regarding six symptoms in a diary for the 3 days after vaccination and to record their ingestion of the study medication. MAIN OUTCOME MEASURES: Incidence of local (sore arm) and systemic (headache, fever, muscle ache, nausea and diarrhea) side effects as well as serum titres of hemagglutination inhibition (HAI) antibody to vaccine antigens before vaccination and 2 weeks and 6 months afterward. RESULTS: A total of 87, 87 and 88 subjects received the half dose, full dose and placebo respectively; 96% returned the diaries, 83% ingested all four doses of medication, and 87% volunteered all blood samples. Compared with the placebo group the incidence of sore arm was 25% to 28% lower in the half-dose and full-dose groups respectively at 24 hours after vaccination, and the rate of nausea was 90% lower in the full-dose group. The HAI titres were similar among the groups at the three test times. CONCLUSIONS: The full dose of acetaminophen significantly reduced the incidence of sore arm and nausea without affecting the antibody response. Acetaminophen use may increase the acceptance of influenza vaccine by health care workers in whom concern about side effects is an impediment to vaccination.

An epidemic of Mycoplasma pneumoniae in Manitoba: A serological report.

OBJECTIVES: To report an epidemic of Mycoplasma pneumoniae in Manitoba and to discuss the limitations of the serodiagnostic tests used. DESIGN: A retrospective analysis of the results of a province-wide serological testing for respiratory infections caused by M pneumoniae, using a complement fixation test and an indirect immunofluorescent antibody test for the detection of immunoglobulin (Ig) M antibodies. MATERIAL: From April 1, 1987, to March 31, 1991, 12,804 sera were tested and a serological diagnosis of recent M pneumoniae infections were established in 509 (3.97%). From April 1 to September 30, 1991, an additional 2088 persons were tested; the 158 (7.5%) recent cases of M pneumoniae were subjected to analysis. RESULTS: Compared with the previous three years, an increase in the number of recent cases of M pneumoniae was first noticed in July 1990 which persisted until September 1991. Of 856 single sera tested, 59 (6.8%) were recent M pneumoniae infections and 56 (96.1%) of these were positive for IgM antibodies. Of the 616 persons who submitted paired sera, 99 (16%) were recent infections, but only 46 (46.4%) had IgM antibodies. Primary infections (ie, positive for IgM antibodies) were detected in 102 (64.5%) and reinfections (ie, positive complement fixation test only) in the remaining 56 persons with recent M pneumoniae infections. Primary infections were detected more frequently in the 'under 16' than in the 'over 16' year age group (75% versus 55.8% of the recent cases of M pneumoniae in each age group). Reinfections were more common in the older age group. Of the 158 recent cases of M pneumoniae, 30.3% had a pneumonia; of these, 21 (55.2%) were under the age of 16 years. DISCUSSION: M pneumoniae is an important cause of morbidity. Serological tests are used for the diagnosis despite their limitations. The detection of IgM antibodies in acute serum establishes a diagnosis of primary M pneumoniae; however, their absence does not exclude M pneumoniae. A second (convalescent) blood test is required to diagnose all primary infections. To diagnose all reinfections, paired sera should be tested by complement fixation. SUMMARY: Manitoba experienced an epidemic of M pneumoniae in 1990-91. Properly selected serological tests can provide a specific and rapid diagnosis.

A pilot study of steroid withdrawal followed by oral acyclovir in the treatment of chronic type B hepatitis.

Ten patients with chronic type B hepatitis were treated for four weeks with a rapidly tapered dose of oral prednisone (initial dose, 40 mg/d) followed by two weeks of no therapy followed by four weeks of oral acyclovir (600 mg/d). Liver biochemistry, HBsAg, HBeAg, DNA-polymerase and HBV-DNA levels in serum were determined prior to, during and for six months following therapy. The mean age +/- SD of the study population was 33 +/- 15 years (range 18-58). Nine of the patients were male. Four patients were Caucasian and six of Southeast Asian origin. Three patients were homosexual, all HIV antibody negative. The mean ALT level prior to treatment was 89 +/- 62 IU/L (range: 30-214). During the six month post-treatment follow-up period, 5/8 (63%) patients became DNA-P negative and 6/10 (60%) HBV-DNA negative. One responder reverted to DNA-P positive (final response, 50%) and another to HBV-DNA positive (final response, 50%) prior to completion of the study. Patients were more likely to become DNA-P or HBV-DNA negative if they had elevated pre-treatment ALT values and low levels of DNA-P and HBV-DNA. HBeAg became undetectable in 3/10 (30%) individuals, one of whom reverted to positive at the end of the follow-up period (final response, 20%). All patients remained HBsAg positive. Mild fatigue, which occurred in four individuals, was the most common side effect. The results of this study suggest that a controlled clinical trial of oral prednisone/acyclovir is warranted in the treatment of adults with chronic type B hepatitis.

Increased risk of early measles in infants of human immunodeficiency virus type 1-seropositive mothers.

An increase in illness due to measles is one of the potential consequences of the human immunodeficiency virus (HIV) epidemic in Africa. During a study of perinatal HIV transmission conducted in Kenya, the risk of acquiring measles before vaccination (9 months of age) was found to be 3.8 times higher in infants born to HIV-seropositive mothers than in control infants (10 [9%] of 109 vs. 5 [3%] of 194 infants; P = .02; odds ratio, 3.8; 95% confidence interval, 1.2-13.2). The majority of infants who developed measles in this study had significant sequelae related to their measles infection. The increased risk of measles appeared to be related to relatively lower anti-measles antibody titers detected in cord blood samples of affected infants born to HIV-seropositive mothers. However, 94% of all infants were susceptible to measles on the basis of ELISA testing at age 6 months regardless of maternal HIV serology. These observations highlight the need for improved measles vaccination strategies in Africa and for studies to delineate the effects of HIV infection on the incidence, presentation, and sequelae of childhood infectious illnesses.

Human immunodeficiency virus as a sexually transmitted disease: Manitoba's HIV unlinked seroprevalence study.

OBJECTIVE: To determine the prevalence of human immunodeficiency virus (HIV)-1 infections. DESIGN: An unlinked seroprevalence study on all 'left over' blood submitted for syphilis testing during three consecutive six month periods (April 1, 1990 to September 30, 1991). After the capture of demographic data, sera to be tested for antibodies were stripped of all personal identifiers and assigned a random number. The study fulfilled Canadian ethical guidelines. PARTICIPANTS: Persons with a valid Manitoba Health Services Commission number were included only once in a study year. Persons were enrolled into one of five categories: infants, injection drug users, pregnant women, persons investigated for sexually transmitted diseases (STD) and routine testing. RESULTS: Of the 50,929 persons tested. 133 (0.26%) were positive, a low prevalence of HIV infections. A significant increase in positivity was noticed in the second study period. While 77.7% of those tested were women, only 10 (0.025%) were positive for HIV. The rate of positivity for pregnant women was 0.72 per 10,000 tested. Of the 11,314 males tested. 123 (1.08%) had antibodies. Most of the positives were males in the STD category residing in Winnipeg; for them, the rate of positivity increased by middle age, while the rate of testing decreased with each decade of age (from age 15 to 44 years). DISCUSSION/RECOMMENDATION: This is the first report from a sentinel laboratory in Canada of an unlinked seroprevalence study in persons with STD. Results suggest an urgent need to target strategies for the control of HIV for persons with STD, particularly males in urban centres, by routine HIV testing for STD patients.

Seroprevalence and demographic characteristics of injection drugs users among individuals at risk for HIV infection in Winnipeg, Manitoba, Canada.

From June 1986 to March 1990, a prospective seroprevalence survey and questionnaire of individuals at risk for HIV infection was conducted with volunteers in Winnipeg. Of 610 individuals enrolled, 146 were injected drug users (IDU). Fifteen IDU were in a methadone treatment program and all were seronegative. Three of 131 remaining IDU were HIV-1 seropositive (2.3%), a rate similar to 2.2% positive (20+ of 927) in diagnostic specimens from IDU tested in the province. Demographics and behaviour of 131 IDU were compared with 335 individuals, of whom 112 were gay/bisexual [24 of whom also had sexually transmitted diseases (STD)] and 223 heterosexuals who had STD. Males enrolled were significantly older than females. Multivariate analysis showed that factors independently associated with IDU were: a younger age, less education, mental health counselling, unemployment, and a history of jaundice or hepatitis. Drugs most commonly used were Ritalin/Talwin, cocaine, and heroin. Over 90% of individuals admitted to sharing needles. In spite of the low seroprevalence of HIV-1 infections, these individuals are important for the potential spread of HIV because of multiple means of acquiring and transmitting HIV and a high rate of needle sharing.

Nosocomial pneumonia in a Canadian tertiary care center: a prospective surveillance study.

OBJECTIVE: To determine the contribution of etiologic agents, including Legionella pneumophila and respiratory viruses to nosocomial pneumonia at a tertiary care center. DESIGN: Prospective surveillance of nosocomial pneumonia with standardized laboratory investigations. SETTING: A 1,100-bed tertiary care center. PATIENTS: All adult inpatients. RESULTS: One hundred and thirty-five Nosocomial pneumonias (5.7/1,000 discharges) were identified. Four (3.0%) were L pneumophila serogroup 1 infections (0.17/1,000 discharges). Legionellosis occurred in non-high-risk patients, and three cases would not have been identified without active surveillance. Viral seroconversion was identified in seven (19%) of 36 cases with specimens available (0.59/1,000 discharges): five influenza B, one influenza A, and one respiratory syncytial virus. IgM serology was positive in one case each for Mycoplasma pneumoniae and Chlamydia species. No geographical clustering was observed for viral infections, and these would not have been identified without active surveillance. Mortality for all nosocomial pneumonia was 25%. Patient factors significantly associated with a poorer outcome included older age, underlying disease, low serum albumin, renal insufficiency, lower platelet count, endotracheal intubation, respiratory failure, bacteremia, and use of antacids. CONCLUSIONS: This prospective surveillance suggested that L pneumophila and viral agents were uncommon causes of nosocomial pneumonia at our institution during this surveillance period.

Manitoba virus, a new rhabdovirus isolated from Culex tarsalis mosquitoes collected in Manitoba, Canada.

A rhabdovirus, Mn 936-77, was isolated from a pool of two Culex tarsalis collected on August 16, 1977, from Morris, Manitoba. Isolate Mn 936-77 was not pathogenic for suckling Swiss white mice inoculated by the intracerebral route. The virus propagated in three vertebrate cell lines (Vero, primary chick embryo, mouse neuroblastoma), but apparently not in Aedes albopictus C6/36 cells. Isolate Mn 936-77 did not react by amplified enzyme-linked immunosorbant assay with 230 viruses of proven or possible arbovirus etiology or by immunofluorescence with 88 members of the family Rhabdoviridae. Isolate Mn 936-77 appears to be a newly discovered virus for which the name Manitoba virus is proposed.

Comparison of immunogenicity of two yeast-derived recombinant hepatitis B vaccines.

A comparison was conducted of the immunogenicity of two yeast recombinant vaccines with different doses [10 micrograms Recombivax-HB (Merck Sharpe & Dohme Ltd) vs. 20 micrograms Engerix-B (Smith Kline Biologicals)]. This was conducted as a randomized, blinded study in healthy preclinical medical students, negative for hepatitis B markers. The geometric mean titres (GMT) showed a wide individual variability for both vaccines, and approximately a two- to threefold greater GMT of anti-HBs in recipients of the 20 micrograms vaccine. However, the 95% confidence interval showed an overlap of the means of the GMT for both vaccine groups, and in this study there was no significant difference in immunogenicity of these two vaccines. At 6-7 months after completion of immunization, antibody levels fell to one-third of the levels of one month post-immunization. A case report of an allergic urticarial reaction to one of the recombinant vaccines is presented.

Impact of human immunodeficiency virus type 1 on tuberculosis in rural Haiti.

We conducted a case-control study to determine the relative and attributable risk of HIV seropositivity for bacillary-positive (smear and/or culture) pulmonary tuberculosis in Haiti. There were 274 patients with tuberculosis and an equal number of control subjects. Antibodies to HIV were present in 67 (24%) patients and eight (3%) control subjects. Odds ratios suggested that the risk of pulmonary tuberculosis was 15.7 times as great (95% confidence interval, 4.8 to 5.0; p less than 0.05) in patients 20 to 39 yr of age who were HIV-seropositive than in HIV-seronegative patients. In contrast, the relative risk in those 40 to 59 yr of age was elevated (3.0 times), though not significantly (lower 95% confidence interval, 0.8). In the 20- to 39-yr age group, 31% of tuberculosis was attributable to HIV infection (95% confidence interval between 23 and 39%). HIV-seropositive and HIV-seronegative patients did not differ with respect to sputum smear positivity. HIV-seronegative patients were twice as likely to be infected with resistant organisms, though this was not significant. We conclude that HIV infection is a major risk factor for pulmonary tuberculosis in young adult residents of Haiti. This, together with the fact that similar proportions of HIV-seropositive and HIV-seronegative patients were potentially infectious, suggests that without vigorous counteraction tuberculosis will become a greater problem for Haiti.

The role of humoral immunity in Cryptosporidium spp. infection. Studies with B cell-depleted mice.

Cryptosporidiosis has become an important infection in man, particularly among very young or immunocompromised individuals. Here, the protective role of antibody responses to Cryptosporidium was examined using a well established murine model of cryptosporidiosis. Although normal neonatal BALB/c mice exhibited good IgM and IgG serum antibody responses, no correlation could be drawn between the intensity of these responses and the severity or duration of cryptosporidiosis. Moreover, B cell-deficient (anti-mu-treated) neonatal BALB/c mice did not differ from untreated or normal rabbit Ig-treated, age-matched controls in the onset, peak, or duration of cryptosporidiosis. The apparent absence of a role for antibody in these self resolving infections was supported by the lack of susceptibility of anti-mu-treated adult BALB/c to attempted infection with doses of Cryptosporidium 10 times the dose required to infect 100% of normal (Ig producing) neonates. The results suggest that the role of specific in vivo antibody responses in the resolution of murine infection with this coccidian parasite is minor and that the likelihood of success for cryptosporidial vaccines aimed solely at enhancing in vivo antibody production may be limited.