Hugues Bogaerts

Symptoms and complications of pertussis in adults

SummaryThere is increasing evidence that pertussis occurs frequently in adults, but there is limited information on the clinical course of this disease beyond childhood. A household contact study on the efficacy of an acellular pertussis vaccine was used to study the symptoms of pertussis in adults. Among 257 patients with pertussis identified in 121 families during a two-year period in one study center with a low whole-cell pertussis-vaccine uptake, 79 (30.7%) were adults, aged 19–83 years (mean age: 36 years) with a 1:1.8 male to female ratio. Ninety-one percent of the adults suffered from coughing (mean duration: 54 days), and in 80% this cough lasted ≥ 21 days. Whoops were rare (8%), whereas cough followed by vomiting and/or choking (53%) and cough disturbing sleep (52%) were common. This is the first report to describe sweating attacks as symptom of pertussis (14%). Pharyngeal symptoms (37%), influenza-like symptoms (30%), sneezing attacks (22%), hoarseness (18%), sinus pain (16%) and headaches (14%) were also observed. Various complications were seen in 23% of the patients. In order to minimize the spread of the organism, micro-biological diagnostics should be vigorously applied to all symptomatic contacts of a patient with pertussis but also to all patients with long lasting cough — irrespective of age.ZusammenfassungWährend viele Berichte belegen, daß Pertussis eine häufige Krankheit auch im Erwachsenenalter ist, gibt es nur wenige Studien zum klinischen Verlauf der Krankheit jenseits der Kindheit. Im Rahmen einer Haushalt-kontaktstudie zum Nachweis der Wirksamkeit einer azellulären Pertussis-Vakzine wurden in einem Studienzentrum mit bekannt niedriger Pertussis-Durchimpfungsrate Erwachsene mit Keuchhusten identifiziert und Symptome erfragt. Innerhalb von 2 Jahren wurden 257 Patienten mit Pertussis in 121 Familien gefunden. Davon waren 79 Erwachsene (30,7%) im Alter zwischen 19 und 83 Jahren (Durchschnittsalter: 36 Jahre). Das Verhältnis männlich zu weiblich betrug 1:1,8. Husten wurde von 91% der Erwachsenen angegeben (durch-schnittliche Dauer: 54 Tage). Er dauerte in 80% der Fälle ≥ 21 Tage an. Inspiratorischer Stridor war selten (8%), dagegen war der Husten häufig von Erbrechen und/oder Würgreiz gefolgt (53%) oder störte den Schlaf der Patienten (52%). Dies ist die erste Studic, in der anfallsweise auftretender Schweißausbruch als Symptom bei Pertussis beschrieben wird (14%). Über pharyngeale Symtome, (37%), Influenza-ähnliche Symptome (30%), Niesanfälle (22%), Heiserkeit (18%), schmerzhafte Sinus (16%) und Kopfschmerzen (14%) wurde ebenfalls berichtet. Komplikationen wurden bei 23% der erwachsenen Patienten beobachtet. Unabhängig vom Alter sollte die mikrobiologische Diagnostik bei allen symptomatischen Kontaktpersonen eines Patienten mit Pertussis und ebenso bei jedem Patienten mit lang anhaltendem Husten konsequent durchgeführt werden, damit die weitere Ausbreitung des Erregers zu einem möglichst frühen Zeitpunkt verhindert werden kann.

Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations

Abstract With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, ≥95% of vaccinees had anti-Hib antibody concentrations ≥0.15 μg/ml and there was a marked booster response (>100-fold) in all groups. Conclusions Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity.

Reactogenicity and immunogenicity of a booster dose of a combined diphtheria, tetanus, and tricomponent acellular pertussis vaccine at fourteen to twenty-eight months of age

OBJECTIVES The primary objective was to assess the nature and incidence of adverse events after a fourth dose of a tricomponent acellular pertussis-diphtheriatetanus vaccine given in the second year of life after primary vaccination with the same vaccine at 3, 4, and 5 months of age. A secondary objective was to analyze the immunogeniecity of the booster vaccination. DESIGN Of the 5361 children enrolled (aged 14 to 28 months), adverse reactions were specifically solicited from the first 1863 enrollees for the first 4 days after vaccination and then were unsolicited for the remainder of the 4 weeks of follow-up (group 1). In the next 3498 subjects, safety and reactogenicify were entirely unsolicited for this 4-week period (group 2). Immunogenicity was analyzed by means of prebooster and postbooster serum antibody titers for all vaccine components in a random subgroup of 197 children from group 1. RESULTS Soliciting symptoms elicited reports of at least one symptom in 1314 of 1809 children in group 1 (72.6%), including 993 (54.9%) with local and 885 (48.9%) with general symptoms during the first 4 days after vaccination. When symptoms were gathered in an unsolicited fashion, only 580 of 3498 children in group 2 (16.6%) had a reported symptom during this time, consisting of 344 (9.8%) local and 319 (9.1%) general symptoms, respectively. An unsolicited symptom, areactive edematous swelling of the whole thigh, occurred in 62 children (1.1%), with 45 and 17 reports in groups 1 and 2, respectively. The vast majority of all reported symptoms were mild to moderate, and all children recovered without sequelae. Fourteen serious adverse events were reported, but none was considered to be related to the vaccination. Immunogenicity analysis showed a vaccine response to pertussis toxin in 99.5% of subjects, to filamentous hemagglutinin in 98.5%, and to pertactin (69 kd outer membrane protein) in 99%. All subjects had postvaccination antibody titers of 0.1 IU/ml or greater against diphtheria and tetanus toxoids.

Evaluation of a Single-Sample Serological Technique for Diagnosing Pertussis in Unvaccinated Children

Abstract 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.

Factors influencing the spread of pertussis in households.

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.ConclusionsIn 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.

Immunogenicity and reactogenicity of a bicomponent and a tricomponent acellular pertussis-diphtheria-tetanus (DTaP) vaccine in primary immunization and as second year booster: A double-blind, randomized trial

Abstract Objectives: To compare the immunogenicities and reactogenicities of bicomponent (B) (pertussis toxoid, filamentous hemagglutinin) and tricomponent (T) (pertussis toxoid, filamentous hemagglutinin, pertactin) acellular pertussis vaccines when coadministered with diphtheria and tetanus toxoids in primary (3, 4, and 5 mo) and booster (15–19 mo) vaccinations. Design and Methods: A randomized, double-blind study involving 175 children aged 12 to 18 weeks. Reactogenicity was based on diary cards, immunogenicity assessed by ELISA measurements of serum IgG antibodies. Results: There were no clinically relevant differences in local (B = 34.5; T=31.3%) and general (B = 43.9; T=41.8%) reactogenicities between the two vaccines during the primary vaccinations. Booster doses caused significantly more adverse reactions than primary vaccination, but local (B = 77.6; T=66.2%) and general (B = 64.2; T=60.8%) reaction rates remained similar for the two vaccines. Both vaccines had almost identical immunogenicities with respect to the corresponding antigens and elicited seropositive antibody titers in 100% of the recipients of vaccines against diphtheria, tetanus, and the respective pertussis antigens 1 month after primary and booster vaccinations. Conclusions: The tricomponent vaccine was no more reactogenic than the bicomponent vaccine and at least as immunogenic for the respective antigens. Because tricomponent vaccine reliably induces antibodies to an additional antigen involved in immunoprotection, it may be preferable for use in primary as well as booster vaccination.