Design: Single centre, randomised, double blind, dose-response study.

Setting: Research vaccine evaluation centre at a teaching hospital.

Subjects: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component.

Intervention: Each subject was randomly allocated two doses of 5, 10, 20, or 40 micro-g of a new hepatitis B vaccine two months apart.

Main outcome measures: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody titre >10 IU/l and >100 IU/l respectively against an international antibody standard.

Results: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micro-g of vaccine, 19 given 10 micro-g, 16 given 20 micro-g, and 20 given 40 micro-g seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out.

Conclusion: A single dose of 20 micro-g of the vaccine was as effective as two doses of either 40 micro-g or 20 micro-g of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.

Academic Unit of Travel Medicine and Vaccines,
Royal Free Hospital School of Medicine,
London NW3 2PF
Jane N Zuckerman, head

Department of Primary Care and Population Sciences,
Royal Free Hospital School of Medicine,
London NW3 2PF
Caroline Sabin, lecturer in medical statistics and epidemiology

Medeva Scientific and Regulatory Affairs,
Evans House,
Regent Park,
Leatherhead,
Surrey KT22 7PQ
Fiona M Craig, project manager
A Williams, director of clinical development

WHO Collaborating Centre for Reference and Research on Viral Diseases,
Royal Free Hospital School of Medicine,
London NW3 2PF
Arie J Zuckerman, professor of medical microbiology

Correspondence to: Dr J N Zuckerman.

Design: Meta-analysis of randomised controlled trials that compared routine antibiotic prophylaxis with no antibiotic treatment or selective treatment of pneumonia or sepsis.

Subjects: Six trials of children admitted to hospital with measles: five in Glasgow, London, or New York between 1939 and 1954; and one in India in 1967.

Main outcome measures: Incidence of pneumonia or sepsis, and mortality.

Results: All but one of the trials were unblinded, and randomisation was either not described or was by alternate allocation. In four studies, the incidence of pneumonia or sepsis in the control group was similar to that in the antibiotic prophylaxis group; in the other two studies, the incidence of pneumonia or sepsis was unusually high in the control group so these children had a higher complication rate than the antibiotic group. Four of the 764 children given antibiotics died compared with one of the 637 controls (exact odds ratio 4.0, mid-P corrected 95% confidence interval 0.5 to 101.6).

Conclusion: The quality of the trials reviewed was poor, and they provide weak evidence for giving antibiotics to all children with measles. Available evidence suggests that, when mortality from measles is high, all children with measles should be treated with vitamin A but antibiotics should be given only if a child has clinical signs of pneumonia or other evidence of sepsis.

Intensive Care Unit,
Royal Children's Hospital,
Parkville,
Victoria 3052,
Australia
Frank Shann, professor of critical care medicine

Design: Cross sectional survey.

Setting: Bhopal, India.

Subjects: Random sample of 454 adults stratified by distance of residence from the Union Carbide plant.

Main outcome measures: Self reported respiratory symptoms; indices of lung function measured by simple spirometry and adjusted for age, sex, and height according to Indian derived regression equations.

Results: Respiratory symptoms were significantly more common and lung function (percentage predicted forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of vital capacity (FEF_25-75), and FEV₁/FVC ratio) was reduced among those reporting exposure to the gas leak. The frequency of symptoms fell as exposure decreased (as estimated by distance lived from the plant), and lung function measurements displayed similar trends. These findings were not wholly accounted for by confounding by smoking or literacy, a measure of socioeconomic status. Lung function measurements were consistently lower in those reporting symptoms.

Conclusion: Our results suggest that persistent small airways obstruction among survivors of the 1984 disaster may be attributed to gas exposure.

Department of Occupational and Environmental Medicine,
Imperial College (National Heart and Lung Institute),
London SW3 6LR
P Cullinan, senior lecturer

Department of Epidemiology and Public Health,
University of Newcastle upon Tyne,
Newcastle upon Tyne NE2 4HH
S Acquilla, lecturer

Agency for Toxic Substances and Disease Registry,
E-31,
1600 Clifton Road,
Atlanta 30333,
Georgia,
USA
V Ramana Dhara, visiting scientist

Design: Prospective, longitudinal assessment of the state of the middle ear by otoscopy and tympanometry at monthly intervals from birth to 3 years.

Setting: Domiciliary visits to family homes.

Subjects: 95 full term infants born between August 1991 and November 1993.

Main outcome measures: Observed and simulated data (Monte Carlo) for the duration of single episodes of otitis media with effusion.

Results: 17 of the children had unilateral or bilateral otitis media with effusion for more than half of their first three years of life. Thirty three of the 95 children had tympanograms suggestive of otitis media with effusion at more than a third of observations; the remaining 62 had such tympanograms at less than a third of observations. The data of each group were described by a first order Markov model, yielding a mean duration of unilateral effusion episodes of 5-6 weeks in both groups; the mean duration of bilateral effusion was 6 and 10 weeks in the low and high incidence groups, respectively. However, the main difference between the groups was the time spent between episodes of effusion: effusion free periods were, on average, three times longer in the children who experienced less otitis media with effusion.

Conclusion: Children who are susceptible to otitis media with effusion tend to have more separate episodes of effusion rather than an increased overall duration of episodes. Such children are primarily distinguished by the likelihood with which they acquire the disease than by their ability to recover from it.

University Laboratory of Physiology,
Oxford OX1 3PT
Sarah C Hogan, audiological scientist
Kenneth J Stratford, senior research scientist
David R Moore, reader in physiology