Evaluation of a single-sample serological technique for diagnosing pertussis in unvaccinated children.

This study was performed to evaluate the sensitivity of immunoglobulin (Ig)G and IgA antibodies to pertussis toxin and filamentous hemagglutinin in diagnosing pertussis from a single serum sample. The pertussis group was defined according to the World Health Organization pertussis case definition. The control group coughed for 21 days or more but had no microbiological or serological evidence of Bordetella infection. Both cohorts were divided into infants (< 12 months of age), toddlers (1-4 years) and school children (5-10 years). There were 525 subjects in the pertussis group and 321 in the control group, with an even distribution of genders. IgG and IgA antibodies to pertussis toxin and filamentous hemagglutinin were measured in a standardized enzyme immunoassay. Antibody levels beyond the 95 percentile of the control cohort were regarded as indicative of recent contact, setting the specificity level at 0.95. Acute serum samples drawn between 1 week and 3 weeks after the onset of coughing showed a low sensitivity (2-19%) for diagnosing pertussis. In convalescent samples taken 5-10 weeks after the onset of symptoms, detection of IgG anti-pertussis toxin was the best single test, with a sensitivity of 61%, 65%, and 74% in infants, toddlers and school children, respectively. A combination of IgG anti-pertussis toxin and IgA anti-filamentous hemagglutinin using age-specific reference values had a sensitivity of 81-89% in diagnosing pertussis from a single serum sample taken 5-10 weeks after the beginning of symptoms.

Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group.

BACKGROUND: The risk of acquiring Lyme disease is high in areas in which the disease is endemic, and the development of a safe and effective vaccine is therefore important. METHODS: We conducted a multicenter, double-blind, randomized trial involving 10,936 subjects who lived in areas of the United States in which Lyme disease is endemic. Participants received an injection of either recombinant Borrelia burgdorferi outer-surface lipoprotein A (OspA) with adjuvant or placebo at enrollment and 1 and 12 months later. In cases of suspected Lyme disease, culture of skin lesions, polymerase-chain-reaction testing, or serologic testing was done. Serologic testing was performed 12 and 20 months after study entry to detect asymptomatic infections. RESULTS: In the first year, after two injections, 22 subjects in the vaccine group and 43 in the placebo group contracted definite Lyme disease (P=0.009); vaccine efficacy was 49 percent (95 percent confidence interval, 15 to 69 percent). In the second year, after the third injection, 16 vaccine recipients and 66 placebo recipients contracted definite Lyme disease (P<0.001); vaccine efficacy was 76 percent (95 percent confidence interval, 58 to 86 percent). The efficacy of the vaccine in preventing asymptomatic infection was 83 percent in the first year and 100 percent in the second year. Injection of the vaccine was associated with mild-to-moderate local or systemic reactions lasting a median of three days. CONCLUSIONS: Three injections of vaccine prevented most definite cases of Lyme disease or asymptomatic B. burgdorferi infection.

Factors influencing the spread of pertussis in households.

UNLABELLED: The objective of this study was to compare the spread of pertussis in children and adults being secondary contacts after household exposure. The study was nested in an efficacy trial of an acellular pertussis vaccine. The spread of the disease was also monitored with respect to gender and antibiotic therapy. A total of 453 index cases, of which 133 were monitored for adult disease, fulfilled the WHO definition of pertussis. They had contacts to 173 unvaccinated children aged 6-47 months, and a total of 101 adults with pertussis were followed. Detection of the bacteria, or a significant increase of specific antibodies confirmed the diagnosis. Secondary spread of the disease was assumed, when a household member coughed for 7 days or more and had laboratory evidence for pertussis. Crude attack rates (AR) were 69% in children and 31% in adults (P < 0.05). AR in children were independent of gender but more women than men (P=0.02) were affected in those households where the index case was a child. Erythromycin treatment of the index case reduced the AR in exposed toddlers from 80% to 57% (P=0.06), and in exposed adults from 40% to 21% (P=0.2). Erythromycin therapy in contacts did not alter the clinical course of the disease significantly. CONCLUSIONS: In a household study of pertussis, 69% of children and 31% of adults (more women than men) contracted the disease. Erythromycin reduced the number of infections in household contacts, but did not alter the clinical course in those who contracted pertussis.

Safety and efficacy of acellular pertussis vaccines: the Mainz study and other recent studies.

Following concerns about the safety and reactogenicity profile of diphtheria, tetanus and whole cell pertussis vaccines (DTwP), new and less reactogenic alternatives were developed over the last two decades. The new diphtheria, tetanus and acellular pertussis vaccines (DTaP) no longer consist of the whole bacterial cell but of either extracts or of a few highly purified components. While it soon became clear that DTaP vaccines are significantly less reactogenic than DTwP vaccines, their efficacy was disputed and remained unproven. First studies and epidemiological data from Japan suggested vaccine efficacy rates (VE) of about 80%; however, the first blinded clinical trial from Sweden documented a much lower VE. Worldwide, seven large DTaP efficacy trials have recently been completed. Our own efforts included a large safety trial with 22505 vaccinees and, nested in this setting, a prospective household contact study. Typical WHO-defined pertussis developed in 7 of 112 DTaP vaccinated children following household exposure as compared to 96 cases in 173 children not vaccinated against pertussis. Thus, vaccine efficacy was calculated to be 88.7% (95% CI 76.6 to 94.6). The median duration of spasmodic cough in the few children vaccinated with DTaP who did start coughing was 17 days as compared to 35 days in unvaccinated children. No waning of protection was observed. None of the confounding variables analyzed influenced study results in favour of DTaP. Following administration of more than 67000 DTaP doses, 153 serious adverse events were reported. Eight events were considered possibly related and five were considered related to the study vaccine. According to additional study results from the other trials it can be concluded that DTaP vaccines, like DTwP vaccines, are safe and effective. The choice between DTwP and DTaP should be based on acceptance of the reactogenicity profile, coverage rates achieved, costs and other factors in each individual country.

Factors influencing the analysis of secondary prevention of pertussis.

The aim of this study was to evaluate factors that influenced the spread of pertussis in secondary contacts after household exposure. The data were acquired during a prospective household-contact study into the efficacy of an acellular vaccine. The spread of the disease was monitored with respect to various case definitions of pertussis, socio-economic factors, household composition, and antibiotic therapy. A total of 453 index cases had contact with 173 unvaccinated children aged from 6 to 47 months. Depending on the clinical case definition, the attack rates (AR) in children with a laboratory-confirmed Bordetella infection increased from 55% for the WHO definition to 69%, when a less stringent definition was used. AR in children were independent of age and gender. The social status of the family had no significant influence on the AR in children. Erythromycin treatment of the index case reduced the AR from 64% to 51% (p = 0.08). These factors should be taken into consideration when studies into the secondary prevention of pertussis by acellular vaccines are initiated.