Reliability and validity of measures used to elicit health expectations, values, tradeoffs and intentions to be immunized for hepatitis B.

We evaluated measures eliciting health expectations, health values, health tradeoffs and intentions to take hepatitis B (HepB) vaccine among health science and technology students. We tested 23 students two weeks apart and then surveyed a cross-section of 373 students in 6 health disciplines. In a subsequent prospective study, 863 students were tested, invited to be immunized, and followed to observe who presented for immunization. The test-retest reliability coefficients exceeded 0.80 for all but the health value measures. All but the health values measures discriminated between those with strong and weak intentions to be immunized. Expectation measures discriminated among disciplines with different risks of exposure to blood and body fluids. The intention, health tradeoff and expectation measures discriminated between those who did and did not present themselves for immunization. We conclude that all but the health values measures met acceptable standards of reliability and validity. Health value tradeoff measures are more discriminating than health value measures.

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

OBJECTIVE: To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. METHODS: 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. RESULTS: Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). CONCLUSION: In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

An outbreak of influenza A in a neonatal intensive care unit.

OBJECTIVES: Investigation of an outbreak of influenza A in a neonatal intensive care unit (NICU) with examination of risk factors for infection and outcomes. DESIGN: Retrospective cohort study of infants admitted to the unit during the outbreak period. Prospective survey of NICU staff and mothers of infants in the cohort study. SETTING: Level III nursery in a university-affiliated tertiary referral center. RESULTS: Nineteen infants in the NICU were infected with influenza A There were six symptomatic cases and one death who had evidence of virus-associated hemophagocytic syndrome at autopsy. Amantadine prophylaxis was offered to the NICU staff, and amantadine therapy was given to five of the six symptomatic infants. Mechanical ventilation, gestational age, birth weight, Clinical Risk Index for Babies score, and twin pregnancy were associated with acquisition of influenza A on univariate analysis. Mechanical ventilation (odds ratio [OR], 6.2; P=.02) and twin pregnancy (OR, 7.0; P=.04) remained as significant risk factors for infection on multiple logistic regression analysis. Only 15% of respondents to the NICU staff survey were vaccinated against influenza. There was no association between a history of an influenza-like illness during pregnancy and acquisition of influenza A by infants of mothers who responded to the maternal survey (OR, 0.91; P=1.0). CONCLUSIONS: Influenza A is an important pathogen in the neonatal population and is readily transmissible in the NICU setting.

Steady state pharmacokinetics of mefloquine in long-term travellers.

Mefloquine is an antimalarial drug with a 3-week elimination half-life, which has led to concerns that toxic accumulation may occur during weekly administration for long-term malaria chemoprophylaxis. Despite the endorsement of weekly mefloquine by the World Health Organization and the United States Centers for Disease Control, mefloquine pharmacokinetics have been incompletely studied in subjects taking the drug once weekly for more than 4 weeks. Our objective was to study plasma mefloquine concentrations in travelers taking mefloquine 250 mg once weekly for 3 months. Multiple mefloquine concentrations were measured by high pressure liquid chromatography following the 1st, 2nd and 10th to 13th of 13 weekly doses of 250 mg mefloquine taken by 15 Canadian travellers (median age 23 years; 6 male, 14 white). Steady state was achieved in all subjects by or before the 10th dose. Mefloquine pharmacokinetic values were comparable to those previously reported by other investigators. In 7 subjects, 2 peaks of mefloquine and metabolite concentration followed ingestion, suggesting redistribution of mefloquine. Mefloquine concentration 14 d after the last dose was 74% of the level 7 d after the last dose. In conclusion, pharmacokinetic values determined by this study support mefloquine weekly dosing for long-term malaria chemoprophylaxis; toxic accumulation does not occur and weekly dosing is associated with significantly higher trough levels than 14 d dosing.

Stereoselective pharmacokinetics of mefloquine in healthy Caucasians after multiple doses.

Mefloquine (MQ) is a chiral antimalarial agent effective against chloroquine-resistant Plasmodium falciparum. It is commercially available as a racemic mixture of the (+) and (-) enantiomers for oral administration. The pharmacokinetics of the (+) and (-) enantiomers of MQ were studied in eight healthy volunteers after administration of a first oral dose of 250 mg of racemic MQ and at steady state after 13 repeated doses of 250 mg given at 1-week intervals. Plasma samples were collected, and concentrations of each enantiomer were determined using a previously described achiral-chiral double column-switching liquid chromatographic method. At each time point, higher plasma concentrations values were found for the (-) enantiomer (p < 0.001). At steady state, Cmax values of (-)-MQ were higher than those of (+)-MQ (1.42 +/- 0.19 versus 0.26 +/- 0.05 mg/L; p < 0.001). Similarly, the plasma concentrations 7 days after the final dose were higher for (-)-MQ (1.01 +/- 0.26 versus 0.11 +/- 0.04 mg/L; p < 0.001). AUC values at steady state were also higher for (-)-MQ (197.3 +/- 36.7 versus 30.1 +/- 8.9 mg/L x h; p < 0.001). The terminal half-life values (T1/2beta) were longer for (-)-MQ (430.4 +/- 225.2 versus 172.8 +/- 56.5 h; p < 0.001). This study shows that the pharmacokinetics of MQ is highly stereoselective.

Factors influencing the acceptance of hepatitis B vaccine by students in health disciplines in Ottawa.

Few students in health care disciplines are immunized against hepatitis B. In order to determine the immunization prevalence and identify the factors influencing the intentions of students to accept hepatitis B vaccine, we administered a questionnaire to 435 university and community college students in health care disciplines in Ottawa where there was no hepatitis B immunization program. We found that only 14% of the students had been immunized. There was significant variability among student groups in their perceptions of the risk of acquiring hepatitis B, beliefs about the efficacy of the vaccine, and their willingness to pay for it. The need for a low-cost vaccine was demonstrated by the fact that only 35% of students would pay the wholesale price of the vaccine ($100), but 94% said they would pay $15.

High prevalence of occult hepatitis B among immigrant students in Canada: A case for universal immunization of young adults.

The prevalence and demographic characteristics of positive hepatitis B (HBV) serology were determined among post secondary health care students in Ottawa. Ontario. HBV seropositivity was defined as the presence of HBV surface antigen (HBsAg) or antibodies to HBV core or surface antigens by radioimmunoassay. HBsAg-positive students were advised to visit their family doctors; the health measures that resulted were observed. Among 600 students born in North America, the proportion of HBV seropositive and HBsAg-positive were 0.8 and 0.2%, respectively. Among the 63 students born outside Europe or North America. 22.2% were HBV seropositive (odds ratio 29.7. confidence interval 10.1 to 97.5) and 7.9% were HBsAg-positive (odds ratio 54.2, confidence interval 5.9 to 2568.3). Of the seven HBsAg-positive students, none had known their HBV status - five visited their doctors, two of whom sought and immunized susceptible household contacts. This survey supports the view that many sexually active young adults integrating into Canadian society from immigrant families are unknowingly HBsAg-positive, and when their HBV status is identified to them and their doctors, appropriate measures for the protection of close contacts are often overlooked. Physician education about the management of HBV carriers should be improved and consideration given to the universal HBV immunization of young adults.

Early onset neonatal septicaemia in a level II nursery.

A prospective study of 486 high risk neonates admitted to a level II nursery in a relatively poor and rural area of Malaysia was carried out to determine the incidence, the spectrum of micro-organisms and predisposing factors in relation to early onset septicaemia. The incidence of proven or probable septicaemia was 57.61 per 1000 high risk newborns over 1.5 kg. The case fatality was 10.71 per cent. Coagulase negative staphylococci, Streptococcus Group B and Klebsiella species were the most commonly isolated organisms. Meconium staining of liquor was the most common risk factor for admission to the nursery, and prematurity was the most significant risk factor for early neonatal infection (P < 0.005) followed by small for gestational age (P < 0.04). Although the incidence of septicaemia was quite high in the level II nursery, the mortality rate was comparable to established figures.

Mantoux tests. Performing, interpreting, and acting upon them.

Interpreting and acting upon results of the tuberculin skin test (Mantoux test) can be confusing because the test is inherently ambiguous and published recommendations for investigation and prevention of tuberculosis are complex. This article presents a step-by-step guide to enable family physicians to make effective use of the Mantoux test.

Prospective study of antibiotic prescribing for children.

OBJECTIVES: To observe the frequency with which children in outpatient primary care settings are prescribed antibiotics and to investigate why these antibiotics are prescribed. To compare the prescribing behaviour of family doctors, primary care pediatricians, and urgent care physicians and to determine where refinements in management are most needed to reduce the number of antibiotic prescriptions appropriately. DESIGN: Prospective study using a data entry form with mostly closed-ended questions. SETTING: Ten primary care offices in urban south-central and eastern Ontario: five family practices, three pediatric practices, and two urgent care centres (UCC). PARTICIPANTS: Every child younger than 16 years visiting these offices during a 3-week period in February and March 1997. MAIN OUTCOME MEASURES: Frequency, clinical indications, and nature of the antibiotics prescribed. RESULTS: There were 4344 observed visits. Of 1706 antibiotic prescriptions, 1481 were for 10 days, and 1577 (92%) were for acute respiratory infections, 920 (53%) specifically for acute otitis media (AOM). Full courses of antibiotics were given immediately (i.e., without test results) to 321 (76%) of 425 children with pharyngitis. Antibiotics were prescribed for 145 (90%) of 163 children with bronchitis. Urgent care physicians were significantly more likely than pediatricians or family physicians to prescribe immediate antibiotics and to disregard guidelines when choosing antibiotics for uncomplicated AOM. CONCLUSIONS: Three diagnoses accounted for 82% of antibiotic prescriptions: AOM, pharyngitis, and bronchitis. Physicians should be more selective when deciding whether, and for how long, to prescribe antibiotics for those three common conditions. Substantial reductions in antibiotic use will require changes in how physicians manage suspected AOM, the most common indication for antibiotics.

Misidentification of toxigenic Corynebacterium diphtheriae as a Corynebacterium species with low virulence in a child with endocarditis.

A 6-year-old boy presented to a university hospital in Malaysia with infective endocarditis complicating cyanotic congenital heart disease. Blood cultures showed a gram-positive, aerobic, coryneform-like bacillus identified by the hospital laboratory as Corynebacterium xerosis, but a reference laboratory identified the organism as a toxigenic strain of Corynebacterium diphtheriae. The two laboratories concurred on all biochemical test results except for sucrose fermentation.

Susceptibility of Campylobacter jejuni to strain-specific bactericidal activity in sera of infected patients.

Campylobacter jejuni is a common cause of inflammatory enteritis, which in normal hosts is usually self-limited and resolves without antibiotic therapy. C. jejuni bacteremia is very rare. We examined sera for bactericidal activity that might be important in limiting the extent of C. jejuni infection in man. We studied the ability of nonimmune sera and homologous and heterologous immune sera from infected patients to kill different fresh case isolates of C. jejuni in vitro. The reduction of the log10 concentration of viable C. jejuni (log10 killing) by fresh sera from nonimmune donors was only 0.2. Log10 killing by homologous acute sera varied from 0 to 3.8 (mean, 1.8). Convalescent sera showed remarkable log10 killing of only homologous C. jejuni, with values of 2.7 to 4.4 (mean, 3.7). The bactericidal effects of acute and convalescent sera were abrogated by heat and EDTA chelation, indicating mediation by complement. The role of classical complement pathway activation was supported by chelating sera with magnesium EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid] and by reconstitution experiments with heat-inactivated sera, C2-deficient serum, and purified C2. The requirement of specific antibody for the serum bactericidal effect was indicated by the loss of bactericidal activity when immune sera were absorbed with homologous but not heterologous whole C. jejuni isolates. The presence of specific antibodies was further documented by agglutination of only homologous C. jejuni suspensions by heat-inactivated immune sera. Studies with polymorphonuclear leukocytes suggested that ingestion and killing of two C. jejuni strains were modest and variable in the presence of heat-inactivated homologous serum. In summary, the data document a potent serum bactericidal effect that develops rapidly and specifically during C. jejuni enteritis and may be an important factor in host defense against C. jejuni.

Cor pulmonale: an unusual presentation of tropical eosinophilia.

Tropical pulmonary eosinophilia (TPE) is considered to be a variant of human filarial infection. The pulmonary manifestations of TPE have been well described. Extra-pulmonary features of the disease, although not commonly seen, have been reported previously. A 9-year-old Malay girl with a history of recurrent cough and wheezing was admitted because of cardiac failure. Physical examination revealed a very sick girl with tachypnoea, central cyanosis, finger clubbing, elevated jugular venous pulse, generalized crackles and rhonchi in the chest, a loud second heart sound and hepatosplenomegaly. A chest radiograph showed cardiomegaly and right pleural effusion. Laboratory investigations revealed hypochromic, microcytic anaemia with persistent blood eosinophilia (absolute eosinophil counts varied from 1.9 to 5.5 x 10(9)/1). The ELISA test for antifilarial IgG antibodies was strongly positive. She responded promptly to treatment with diethylcarbamazine. In summary, this is a patient with TPE who presented with cor pulmonale, probably due to late-stage interstitial pulmonary fibrosis. In order to prevent the long term morbidity of cardiorespiratory disability, the early signs of TPE should be recognized and the infection treated.

Susceptibility pattern of Streptococcus pneumoniae among pre-school children in Kota Bharu, Malaysia.

Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of pneumonia, meningitis, and otitis media, with the highest incidence among young children and the elderly. S. pneumoniae was once routinely susceptible to penicillin, but since the mid-1980s the incidence of resistance to penicillin and other antimicrobial agents has been increasing all over the world. To optimize empirical regimens and initial therapy for S. pneumoniae infections, clinical healthcare providers must be informed about the prevalence and pattern of drug resistance among the isolates in their communities. No such data are available for the Malaysian population. Therefore, this study was designed to determine the antibiotic susceptibility pattern of S. pneumoniae among colonized pre-school children in Kota Bharu, Malaysia. Pharyngeal swabs were collected from children 1 month to 6 years of age. S. pneumoniae isolates were identified according to the standard and tested for penicillin resistance with a 1-microgram oxacillin disk by the Kirby-Bauer disk diffusion methods. Of 355 nasopharyngeal specimens obtained from kindergarten students, in-patients and pediatric clinics over a period of 1 year, S. pneumoniae was isolated from 36 (10 per cent). All isolates, except one, were susceptible to penicillin. The resistant isolates was susceptible to erythromycin, chloramphenicol and cephalosporins.

Economical, simple method for production of the gaseous environment required for cultivation of Campylobacter jejuni.

Campylobacter jejuni is an enteric pathogen recognized worldwide as a cause of diarrhea. Its isolation from stool samples requires a microaerophilic environment that heretofore has been expensive and cumbersome to create. An economical, portable, and simple method is described which involves the production of appropriate concentrations of oxygen and carbon dioxide. Inside a plastic bag are placed two cups, one containing fine steel wool (grade 0) previously soaked in a 2.5% aqueous solution of copper sulfate and the other containing an Alka-Seltzer tablet in tap water. As suggested by Jurgensen et al. (Rev. Bras. Pat. Clin. 18:58-63, 1982), we used the effervescent antacid to generate CO2. By plate counts, we found this method to be as reliable in the cultivation of 20 isolates of C. jejuni in pure and mixed fecal culture as the reference gas method (85% N2, 10% CO2, and 5% O2). Analyses of the gas mixture inside the bag after up to 24 h of incubation confirmed the creation of an atmosphere of reduced O2 and increased CO2 concentrations. This method is eminently suitable for field situations in which more costly supplies are not available.

Low-cost hepatitis B vaccine improves uptake among self-paying health-care students.

Advisory committees recommend hepatitis B (HBV) immunization for professional and student health-care workers. However, the currently licensed vaccines are expensive, and previous surveys have shown that few students (14%) have been immunized in Canada. A low-cost immunization program was offered to health-care students in order to determine whether the effectiveness of HBV immunization could be improved by substantially reducing the vaccine cost to recipients. The immunogenicity, side effects, and 3-dose completion rate of a low-cost Korean HBV vaccine were compared with a similar U.S.-made vaccine. A total of 922 postsecondary students enrolled in 6 health-care disciplines in Ottawa, Canada were surveyed for hepatitis-B immunization status. Nonimmunized students were subsequently offered HBV vaccine at total cost of $15 (Canadian), randomly allocated to receive 3 intramuscular doses of either Korean or U.S.-made plasma-derived HBV vaccine in a double-blind fashion, surveyed about side effects, and tested for hepatitis B surface antibody seroconversion. Only 12% of the 922 surveyed students had been previously immunized when vaccine was obtainable only at high cost. However, 66% of those not immunized participated in the vaccine trial and paid the $15 fee. Hepatitis-B surface antibody seroconversion (greater than or equal to 10 sample ratio units by radioimmunoassay) occurred in 291/311 (93.6%) and 299/310 (96.5%) of recipients of 3 doses of the Korean and U.S. vaccines, respectively (P = 0.10). There were no meaningful differences in vaccine adverse effects, and 92.6% of recipients of either vaccine completed 3 doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of a unique cytotoxin by Campylobacter jejuni.

Campylobacter jejuni is an important diarrheal pathogen worldwide; the mechanisms by which it causes disease remain unclear. Because of its association with inflammatory diarrhea, we postulated that C. jejuni might produce a cytotoxin similar to that produced by Shigella sp., enterohemorrhagic Escherichia coli O157, or Clostridium difficile. Filtrates of 12 polymyxin-treated isolates of C. jejuni were placed on HeLa cells (sensitive to Shiga toxin cytotoxicity) and Chinese hamster ovary (CHO) cells. Of 12 isolates of C. jejuni tested, 5 killed 50% of the cells at greater than or equal to 1:4 dilutions of filtered suspensions of 10(9) bacteria per ml; killing was similar in HeLa and CHO cells (the CHO cells being insensitive to Shiga cytotoxin). One isolate produced a titer of 1:32 to 1:128. The relative potency in HeLa cells was comparable to that of E. coli strains that produce intermediate amounts of Shiga-like toxin. The other seven strains showed no cytotoxic effect, nor did the control diluents, polymyxin B, or supernatants of C. jejuni not treated with polymyxin B. Sonication also released active cytotoxin, but slightly less well than did polymyxin. The cytotoxic effect was dose dependent. Concentration of the C. jejuni in suspension by 10-fold before treatment with polymyxin B resulted in a 10-fold increase in the 50% cytotoxic dose. The cytotoxin effect was not neutralized by Shiga toxin immune serum against either Shiga-like toxin I or II or by anti-Clostridium difficile antiserum. The C jejuni cytotoxin was partially labile to trypsin (0.25%) and to heating to greater than or equal to 60 degrees C. Cytotoxicity was retained in Scientific Products dialysis tubing D1615-1 (Mr cutoff, 12,000 to 14,000). Some isolates of C. jejuni release a substance lethal to HeLa or CHO cells in vitro that is distinct from Shiga-like or Clostridium difficile toxin. This cytotoxin may contribute to the colonic mucosal invasive process that characterizes C. jejuni enteritis.