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H L Bock

Publications and source records attributed to H L Bock.

At least 37 records · Page 2Linked to original sources

Long-term persistence of anti-HAV antibodies following active immunization with hepatitis A vaccine.

Seventy-one anti-hepatitis A virus (HAV) negative volunteers were immunized against hepatitis A. An inactivated hepatitis A vaccine (HAVRIX, SmithKline Beecham), derived from tissue cell cultures, at single doses of 720 ELISA units was used following a schedule of vaccinations at month 0.1 and 6. The vaccines were tested for the presence of HAV antibodies 1 month after each vaccination and then after 2, 3, 4 and 5 years. The annual decrease of anti-HAV titres was 25%. Five years after vaccination a protective antibody titre, varying between 20 and 5200 mIU ml-1, could be demonstrated in all 47 retested volunteers with a geometric mean titre (GMT) of 442 mIU ml-1. Levels of anti-HAV-antibodies following active immunization were significantly higher in female volunteers. This could be consistently demonstrated throughout the observation period. Based on these data the antibody persistence was calculated over time. GMTs at protective levels higher than 20 mIU ml-1 can be expected to persist for at least 15 years.

Adult↗

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.

Child, Preschool↗

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.

Clinical Trials as Topic↗

Immunogenicity of a recombinant hepatitis B vaccine in adults.

OBJECTIVES: To evaluate the immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in health care staff under routine use and unselected conditions and to investigate factors that influence the response to vaccination. METHODS: This prospective postmarketing surveillance study was performed in unselected health care staff and their relatives (age range, 12-60 years) at 58 hospitals. Overall, 880 subjects were administered a 20-microgram dose of a vaccine at 0, 1, and 6 months according to the prescribing information and under routine hospital practice, and they were tested for antibody to hepatitis B surface antigen after the third dose at the hospitals routine laboratory. The principal outcome measures were antibody to hepatitis B surface antigen titers that were expressed as the seroprotection rate (SPR) (SPR [given as a percentage], > or = 10 mlU/ mL), spontaneously reported adverse events, and geometric mean titers (in milli-international units per milliliter). RESULTS: The compliance to the 3-dose schedule under routine hospital practice was 98.1%. The immune response was good in all age groups, and the overall SPR was 97.8% at 1 month after the third dose in field conditions with unselected health care workers. The SPR in vaccinees (age range, 40-59 years) was close to 95%. Age (P < .001), smoking (> or = 10 cigarettes per day) (P < .001), Broca index (> 110%) (P < .001), antibody to hepatitis B surface antigen testing (> 8 weeks after the last dose) (P = .03), chronic underlying disease (P = .04), and male gender (P = .04) were factors associated with lower geometric mean titers in routine vaccine use. No serious adverse events were reported. CONCLUSION: The large immune response that was elicited by this hepatitis B vaccine in adults under daily routine field conditions reflected reality, with a high SPR also found in elderly and other persons with risk factors associated with a lower immune response.

Adolescent↗

Efficacy of acellular pertussis vaccine in early childhood after household exposure.

OBJECTIVE: To evaluate the efficacy of a three-dose primary vaccination with a diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical" pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of Bordetella pertussis infection by culture or serology. DESIGN: Passive monitoring for suspected first household (index) cases of typical pertussis in six areas in Germany comprising 22,505 children vaccinated with study vaccine at 3, 4, and 5 months of age. Blinded, prospective follow-up of household contacts of index cases for incidence and progression of pertussis. SETTING: Six areas in Germany with a high incidence of pertussis. SUBJECTS: Four hundred fifty-three households with index cases comprising 360 evaluable contacts eligible for analysis of vaccine efficacy. MAIN OUTCOME MEASURE: Vaccine efficacy from attack rates of pertussis in household contacts classified by vaccination status. RESULTS: Of the 173 nonvaccinated household contacts, 96 developed typical pertussis, compared with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6% to 94.6%). Protection did not wane until at least the time recommended for booster vaccination. None of the analyzed potential confounding factors--age, socioeconomic status, erythromycin treatment, household composition, center effect, and selection bias--influenced study results in favor of the vaccine. CONCLUSIONS: Under conditions of intense household exposure, primary vaccination with acellular vaccine protected against pertussis until at least the time recommended for booster vaccination. The vaccine can be expected to be equally or more effective in settings with lower infectious pressure.

Bordetella pertussis↗

Immunogenicity of an inactivated hepatitis A vaccine administered according to two different schedules and the interference of other "travellers" vaccines with the immune response.

A total of 2036 persons consulting vaccination centers in Germany were vaccinated with an inactivated hepatitis A vaccine (containing 720 ELISA units of antigen) either according to the standard schedule (two vaccinations given 4 weeks apart) or to an abbreviated schedule (two vaccinations given 2 weeks apart) in a controlled clinical study. The abbreviated schedule induced a similar rate of seroconversion and geometric mean antibody titre as compared to the standard schedule. The incidence of reactions reported after vaccination was similar in both groups. When other "travellers" vaccines were given simultaneously neither the immunogenicity nor the reactogenicity of the hepatitis A vaccine were influenced. These findings have considerable practical importance in the prevention of hepatitis A in travellers.

Adolescent↗

Acellular pertussis vaccines: the rationale for an efficacy trial in Germany.

After concern about the safety of diphtheria-tetanus toxoid-whole cell pertussis vaccines (DTPw), the recommendation to vaccinate children with DTPw was withdrawn in 1974 in the former West Germany. This led pertussis cases to increase to an estimated 100,000 annually. Despite renewal of the vaccination recommendation in 1991, vaccine use remained low. The German health care structure assures regular contact between most children and pediatricians. This enabled the conduct of a large efficacy trial with a diphtheria-tetanus toxoid-acellular pertussis (DTPa) vaccine. Because a placebo-controlled trial was not ethically possible, a prospective household contact study with a blinded clinical follow-up was done. Possible study participants were screened by their pediatrician, who also initiated diagnostic procedures. Clinical follow-up was done by another locally based but independent and blinded physician. Vaccine efficacy was calculated to be 89% (95% confidence interval, 76.6%-94.6%). None of the identified confounding factors biased results in favor of the DTPa vaccine.

Clinical Trials as Topic↗

Immunogenicity and reactogenicity of a combined hepatitis A/B candidate vaccine: first results.

We evaluated immunogenicity and reactogenicity of an inactivated, combined hepatitis A/B candidate vaccine in 50 seronegative volunteers. Each volunteer received a total of three doses of vaccine (720 EIU HAV and 20 micrograms HBs antigen) according to a 0, 1 and 6 month vaccination schedule. One month after the first injection, the seroconversion rate was 90% (45/50) for anti-HAV and 28% (14/50) for anti-HBs, respectively. After the booster dose, at month 7, the seroconversion rate was as high as 100% (49/49) for anti-HAV and 94% (46/49) for anti-HBs. The geometric mean titres increased with each dose of vaccine administered. Mild, and mostly local side effects were reported in 54% of the volunteers after the first injection and in less than 10% after the third injection. Our results show that this inactivated, candidate hepatitis A/B vaccine is highly immunogenic and well-tolerated.

Adult↗

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.

Adult↗

[Immunogenicity and tolerance of a combined hepatitis A/B vaccine. Preliminary results with a candidate vaccine].

AIM OF STUDY: Active immunization against hepatitis A having been undertaken in Germany since January 1993, a multicentre study was conducted to test, for the first time, immunogenicity of and tolerance to a candidate vaccine against hepatitis A and B. SUBJECTS AND METHODS: 50 healthy volunteers aged 18-40 years, negative for antibodies against hepatitis A (HAV) and B (HBs), received three intramuscular injections of the candidate vaccine (720 EIU of strain HM 175 and 20 micrograms recombinant HBsAg) in a total volume of 1 ml, on day 1 and then, one month and 6 months later. RESULTS: Four weeks after the first injection the seroprotection rate (percentage of subjects with protective antibody titres) was 90% for HAV and 28% for HBs. The second injection produced seroconversion rates of 98% and 50%, respectively, and after the third one of 100% and 98%. All reported side effects were minor, of short duration and decreased after each injection. After the first injection, effects at the site of injection occurred in 50% of subjects, decreasing to 6% after the third one. The only systemic side effect, headache, occurred in only 4% of subjects and only after the first injection. CONCLUSION: The test vaccine against hepatitis A and B proved to be highly immunogenic, safe and well tolerated.

Adolescent↗

Immunogenicity and safety of an inactivated hepatitis A vaccine in anti-HIV positive and negative homosexual men.

The immunogenicity, reactogenicity, and safety of an inactivated hepatitis A vaccine were assessed in anti-HIV positive homosexual men. Fourteen anti-HIV positive (group 1) and 20 anti-HIV negative (group 2) men received vaccine (containing 720 ELISA units of hepatitis A antigen per dose) intramuscularly at 0, 1, and 6 months. Twelve unvaccinated anti-HIV positive men (group 3) were included as controls to evaluate disease progression. Seroconversion (anti-hepatitis V virus (HAV) > or = 20 mlU/ml) was higher in group 2 than group 1 at months 2 (100% vs. 73%) and 7 (100% vs. 77%). Group 2 had higher antibody titres than group 1 at months 1 (201 vs. 92 mlU/ml) and 7 (1,687 vs. 636 mlU/ml). The decline in CD4+ cells between months 0 and 7 was similar in groups 1 and 3 (6.4% vs. 16.2%), showing no evidence for harmful effect of the vaccine on the course of HIV infection. This hepatitis A vaccine appears safe, well tolerated, but less immunogenic in HIV positive homosexual men.

Acquired Immunodeficiency Syndrome↗

Therapeutic effects of antivenom supplemented by antithrombin III in rats experimentally envenomated with Russell's viper (Daboia russelli siamensis) venom.

The effects of equine antivenom and antithrombin III (AT-III) on the coagulopathy induced by Russell's viper venom (RVV, Daboia russelli siamensis) were investigated in the rat. After taking blood samples from the femoral vein for determination of simple blood clotting time and AT-III activity, all anaesthetized rats received an intramuscular injection of venom (2 micrograms/g). Treatment (antivenom or AT-III or both) was given intravenously through another femoral vein 30 min after venom injection. All untreated rats (n = 7) developed AT-III depletion (< 70%) [mean (S.D.)] 70 (36) min, and incoagulable blood 85 (53) min after venom injection. Supplementation with AT-III (either 0.25 U/g or 0.5 U/g) had no effect on the RVV induced coagulopathy (n = 20). Treatment with antivenom alone (10 micrograms/g) reduced the incidence of abnormal clotting significantly (8/15, 53%) (P = 0.03). When antivenom was given in combination with AT-III (0.5 U/g), abnormal clotting was prevented in all but one animal (1/15, 7%) (P = 0.007). AT-III activity declined progressively in all rats which developed non-clotting blood. These results suggest that coagulopathy in Russell's viper envenoming is associated with activation of coagulation and consumption of AT-III. Antivenom can prevent coagulopathy, but its neutralizing activity is augmented significantly by AT-III supplementation.

Animals↗

Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway.

The mechanisms involved in the activation of the coagulation cascade in severe falciparum malaria were studied in 22 adult patients (19 male, three female) aged 18-45 (mean +/- SD 31 +/- 11) years. Of these, nine had multiple vital organ dysfunction, and bleeding occurred in four patients, two of whom died. During acute illness the reduction in plasma antithrombin III (AT III) concentrations and elevation in thrombin-AT III complexes were associated with significant reductions in factor XII and prekallikrein activities, and an increase in the C1 inhibitor antigen/activity ratio. Serial plasminogen activity remained within the normal range in all patients while protein C activity was significantly reduced. All patients had markedly elevated plasma polymorphonuclear leucocyte elastase (PMN-elastase) levels with mild depletion of alpha-2 macroglobulin but normal concentrations of alpha-1 antitrypsin. There was no correlation between PMN-elastase concentrations and any of the coagulation parameters or concentrations of proteinase inhibitors. These results suggest that the intrinsic pathway of the clotting cascade is activated in severe malaria. This may cause activation of the complement system and release of bradykinin and PMN-elastase and could contribute to the pathogenesis of severe malaria.

Adolescent↗

[Active immunization against hepatitis A. Comparison of various immunization schedules].

Three different immunization schedules were compared in 144 young, healthy adults (81 men, 63 women; mean age 28.5 years). They were randomly assigned to one of three groups: group 1, immunization shots on day 0 and day 14 (n = 47), group 2, on day 0 and day 28 (n = 50), and group 3, on day 0, 14 and 28 (n = 47). All participants had a booster shot after one year. The seroconversion rate was 40-46% after first shot, 95-100% after the second one; all were anti-HAV positive after the booster injection. All subjects had specific antibodies in a mean concentration of > 400 IU/l two weeks after the second shot. In almost all subjects antibodies were demonstrable up to the 12th month after the first immunization (> 20 IU/l). Mean antibody concentration during the interval between the second and third immunization after basal immunization on day 0 and 14 or 0 and 28, respectively, was comparable. Three initial immunizations 14 days apart did not achieve much higher anti-HAV levels. The vaccine was equally well tolerated in all three groups. Thus basal immunization shortened to two injections two weeks apart presents a good alternative to the standard scheme of two injections four weeks apart. Three injections two weeks apart bring no demonstrable advantage.

Adult↗

[Halofantrine in the treatment of imported malaria in nonimmune travelers].

The efficacy (criteria: cure rate, time to resolution of fever or absence of parasites) and safety (criteria: clinical side effects, altered laboratory parameters) of halofantrin were investigated in a multi-centre study of 96 non-immune patients (71 men, 25 women, mean age 34.3 [21-62] years) with malaria imported from regions of high resistance into Germany or Switzerland. The initial 63 patients received one-day treatment (three doses of 500 mg halofantrin), while the last 33 patients received an additional course of treatment one week later. Treatment was curative in all patients in the second group, but relapses occurred in five of the 41 patients (12.2%) with falciparum malaria who received one-day therapy. Fever resolved after a mean of 45 hours and parasites were absent after a mean of 66 hours. There were small increases in transaminase values (most probably because of the infection) in five patients, but all became normal again within a few days. Halofantrin is a safe drug and is suitable for both therapy and stand-by therapy of resistant Plasmodium infections. Treatment should be repeated after 7 days.

Adolescent↗

Influence of vaccination schedules and host factors on antibody response following hepatitis B vaccination.

In a prospective multicentre trial, the influence of schedule, compliance, age, sex and weight on the antibody response to hepatitis B vaccination was investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n = 143) and 0, 1, 2, 12 months (group 2; n = 141) was performed in months 3, 7 and 12. In addition, the antibody response was compared one month after the third and one and six months after the last vaccination. Seroprotection rates (anti-HBs greater than 10 IU/l) and antibody titres, given as geometric means (GMTs), were higher in group 1 at month 12 as well as one month after completion of three immunizations. More vaccinees of group 2, however, showed seroprotection at month 3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and six months after the last vaccine dose. Determination of parallel corrected correlation factors demonstrated that age was the most important single factor, followed by body weight and sex. However, no more than 3% of the variation in the GMT can be explained by the influence of age. Due to decreased compliance with the four-dose schedule with a drop-out rate of approximately 10% of the vaccinees, the total percentage of initial vaccinees who in the end developed protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12 months schedule as more rapid protection is obtained and the higher antibody levels after the booster vaccination at month 12 provide longer protection. However, vaccinees whose compliance might be questionable over a period of 12 months, should be selected for the vaccination 0, 1, 6 months schedule as compliance is at a higher level over this period and advantage can be taken of the booster effect of the third dose given in month 6.

Adolescent↗