Hans L. Bock

Pertussis in adults: frequency of transmission after household exposure

Although pertussis in adults is well documented, opinions differ about incidence of adult disease and about the role of adults as reservoirs of infection. We made use of a prospective household contact study of an acellular pertussis vaccine to collect data about pertussis in adults. All members of families with an index case of pertussis were monitored for respiratory symptoms, and pertussis was confirmed by laboratory tests. In 122 households, 104 children (85%) and 18 adults (15%) were the source of pertussis. These households consisted of 265 adults (aged 19-83 years), in 84 of whom (31%) pertussis was confirmed. Of these 84, 81% had respiratory symptoms for 21 days or more. The spread of pertussis was independent of whether a child (74/104) or an adult (14/18) was the index case. Most adult index cases had no pertussis recall (odds ratio 11.8). The overall attack rate in adult contacts was 0.267 and was independent of the social status and the size of the family and of a pertussis recall, although it differed significantly between women and men (p < 0.05). Erythromycin treatment of the index case reduced the attack rate significantly (p < 0.05). Patients whose first pertussis episode dated back more than 20 years had similar symptoms and attack rates to patients without a recall. We conclude that adults are often involved in the spread of pertussis, and that they can be susceptible to reinfection 20 years after a first pertussis episode.

Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: Randomised, double-blind, controlled study

This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 (Rotarix) during the first 2 years of life in Asian infants from high-income countries. Healthy infants were enrolled to receive 2 doses of RIX4414 (N=5,359) or placebo (N=5,349). From 2 weeks post-dose 2 to 2 years of age, vaccine efficacy was 96.1% (95%CI:85.1%; 99.5%) against severe rotavirus gastroenteritis, 100% (95%CI:80.8%; 100%) against wild-type G1P[8] and 93.6% (95%CI:74.7%; 99.3%) against circulating non-G1 rotavirus types. No intussusception cases were reported within 31 days post-vaccination. RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population.

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.

Successful co-administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age.

Co-administration of oral live-attenuated human rotavirus vaccine RIX4414 (Rotarix) and oral polio vaccine (OPV) was assessed. Healthy infants were randomised to receive 2-doses of either: RIX4414 or placebo co-administered with OPV (12 and 16 weeks of age); or RIX4414 or placebo given 15 days after OPV. After vaccination, 56.5-66.7% of RIX4414 and 18.6% of placebo recipients had seroconverted for rotavirus IgA. No significant differences between RIX4414 groups with or without OPV co-administration were observed. No statistically significant differences were observed between groups for polio seroprotection rates. RIX4414 vaccine was immunogenic when co-administered with OPV and did not interfere with OPV seroprotection rates.

Immunogenicity and tolerability of an AS03A-adjuvanted prepandemic influenza vaccine: A phase III study in a large population of Asian adults

The immunogenicity and lot-to-lot consistency of an AS03-adjuvanted H5N1 vaccine were evaluated in 1206 Asian adults, randomised to receive two doses of adjuvanted (3.75 microg haemagglutinin) or diluent-mixed vaccines, 21 days apart. Post-Dose 2, 96.0% of vaccinees in the H5N1-AS03 group demonstrated a four-fold increase in neutralising antibody titres against the vaccine strain A/Vietnam/1194/2004 and 91.4% against strain A/Indonesia/05/2005. Haemagglutination-inhibiting antibodies (titre > or = 1:40) against A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains were observed in 94.3% and 50.2% of subjects, respectively. Lot-to-lot consistency of the AS03-adjuvanted vaccine combinations was demonstrated. The AS03-adjuvanted vaccine was well tolerated, induced a high frequency of immune responses to the vaccine strain, allowed antigen sparing and promoted cross-clade immunity. These characteristics make it suitable for presumptive use if an H5N1 pandemic were considered to be imminent.

Persistence of antibodies and immune memory to hepatitis B vaccine 20 years after infant vaccination in Thailand

Booster vaccination against hepatitis B (HBV) is not currently recommended, although debate continues on the duration of protection after priming. We assessed antibody persistence and immune memory to hepatitis B 20 years after priming with a recombinant HBV-vaccine during infancy. Infants were vaccinated at birth, 1, 2 and 12 months of age. A subset received a booster dose at Year 5. Antibody persistence was measured approximately yearly until Year 20. Immune memory was assessed by administration of HBV booster dose. At Year 20, anti-HBs seroprotection rates and GMCs tended to be higher in Year 5 boosted than unboosted recipients (83.9% versus 60.5%). After the Year 20 booster dose, anti-HBs anamnestic responses were within the same range 95.8% of subjects in both groups. Primary and booster vaccination with HBV-vaccine in infants induces sustained seroprotection and immune memory against hepatitis B for up to 20 years. Higher persisting seroprotection rates in subjects boosted at Year 5 did not translate into apparent differences in immune memory in a high endemic country.

Booster immunization of low- and non-responders after a standard three dose hepatitis B vaccine schedule—results of a post-marketing surveillance

Seventy-nine low-responders and 83 non-responders after a previous three-dose hepatitis B (HB) vaccine course at 0.1, and 6 months were enrolled to receive additional 20 micrograms recombinant HB vaccine doses every 2 months until all had anti-HBs levels > or = 100 mIU ml-1. After the first booster, 65.4% had anti-HBs levels > or = 100 mIU ml-1, 17.9% were low-responders (10-99 mIU ml-1), and 16.7% remained non-responders (< 10 mIU ml-1). All complying non-responders developed anti-HBs levels > or = 100 mIU ml-1 after the third booster at the latest, whereas all low-responders reached this level after the second booster. Although body mass index affected the response to the first hepatitis B booster, when full compliance to regular revaccination was ensured, all non- and low-responders eventually reached sufficient anti-HBs levels.

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.

Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414) in Indian infants.

Aim: This study was undertaken to assess the immunogenicity, reactogenicity and safety of two doses of an oral live-attenuated human rotavirus vaccine, strain RIX4414 (Rotarix™) in an Indian setting. Patients and Methods: Healthy infants (N=363), approximately 8 weeks of age were enrolled to receive two doses of RIX4414 vaccine (n=182) or placebo (n=181) separated by one month. To assess the immune response, blood samples were taken before vaccination and one month post-dose 2 of RIX4414/placebo. Solicited symptoms were collected for 8-days post each dose and safety data was collected throughout the study. Results: The seroconversion rate observed one month post-dose 2 in the RIX4414 group 58.3% [95% CI: 48.7; 67.4] was significantly higher when compared to the placebo group 6.3%; [95% CI: 2.5; 12.5]. The reactogenicity and safety profile was similar for both groups. Conclusions: Two doses of RIX4414 (Rotarix™) were immunogenic, had a good safety profile and were well-tolerated when administered to healthy Indian infants.