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Workshop on neurologic complications of pertussis and pertussis vaccination.

A multidisciplinary workshop held from September 29 to October 1, 1989, at Airlie House, Warrenton, Virginia, considered the neurologic complications of whooping cough and pertussis vaccine. Pertussis mortality in the U.S. in 2-3/1000 cases. Seizures occur in 1.9% of cases, and encephalopathy in 0.3%. Reviewing all data, it appears likely that a combination of one or more bacterial toxins, asphyxia, CO2 retention and loss of cerebral vascular autoregulation is responsible for neurologic symptoms. The timing of the encephalopathy suggests that it results from increased lysis of bacteria, and release of endotoxin. The encephalopathy is not confined to the paroxysmal phase. In evaluating side-reactions to the vaccine, the following must be kept in mind: 1. Vaccines are not standardized between manufacturers. 2. For a given manufacturer, vaccines are not standard from one batch to the next. 3. Unless the vaccine is properly prepared and refrigerated, its potency and reactivity varies with shelf life. In fact, the whole question of vaccine detoxification has never been systematically investigated. Listed in order of increasing severity, observed adverse reactions include irritability, persistent, unusually high pitched crying, somnolence, seizures, a shock-like "hypotensive, hyporesponsive" state, and an encephalopathy. Since the neurologic picture is not specific for pertussis vaccination, its temporal relationship to the vaccination is the critical variable for determining causation. Although the majority of seizures following pertussis vaccination are associated with fever, it was the consensus of the neurologists attending the workshop, that these do not represent febrile convulsions, but are non-benign convulsions. The incidence of post-vaccine encephalopathy is difficult to ascertain.(ABSTRACT TRUNCATED AT 250 WORDS)

Diphtheria-Tetanus-Pertussis Vaccine↗

Enhanced antibody response to rabies virus in patients with neurologic complications following brain tissue-derived rabies vaccination.

Sera from 26 patients with major neurologic complications, 19 patients with minor complications and 23 patients with no complications induced by Semple rabies vaccine were assayed for neutralizing antibody to rabies virus. Seroconversion to the protective level (greater than or equal to 0.5 IU/ml) was found in 21 of 22 patients (95%) with major complications, and in 7 of 19 (37%) with minor complications, occurring during the first 14 days of vaccination. This was in contrast to 42% (5/12) seroconversion in uncomplicated recipients after 14 daily injections. After initiation of dexamethasone treatment, 13 of 18 patients with major complications showed a diminution in their rabies antibody levels on day 4 or 7.

Antibodies, Viral↗

Case report: A presumptive case of vaccinia myocarditis.

A 26-year-old male medical technician who received the smallpox (vaccinia) vaccination developed a clinical case of myocarditis 11 days after vaccination. The medical literature has little information on this complication of vaccination. The individual was admitted for evaluation and pain control. At discharge, he appeared to have had no long-term effects and has returned to duty.

Adult↗

Influenza vaccination among veterans with spinal cord injury: Part 1. A survey of attitudes and behavior.

BACKGROUND/OBJECTIVE: Persons with spinal cord injury and disorders (SCID) are at increased risk of developing influenza, pneumonia, and ensuing complications. Influenza vaccine has been shown to be effective, yet vaccination rates have been low in this population. To improve these rates, barriers and facilitators to receiving influenza vaccine in this population were identified. METHODS: A cross-sectional telephone survey was conducted with a convenience sample of patients at 13 Department of Veterans Affairs (VA) Spinal Cord Injury (SCI) Centers between September and November 2000. Survey questions assessed perceptions regarding the influenza vaccine. RESULTS: Participants interviewed (N = 377) had a mean age of 58.6 years and were predominantly male and white. Most had had received the influenza vaccine at some time in the past; however, 35% had not received it in the previous year. The most common reason reported for not being vaccinated was the belief that it was not important. Those who knew the best time to be vaccinated were more likely to have been vaccinated the previous year (OR = 3.57, 95%, CI: 2.12-6.01). Other predictors of vaccination included being married, being aged 65 and older, and being aware that the vaccine was a good way to prevent some pulmonary problems that can result from influenza. CONCLUSIONS: Barriers to vaccination include poor understanding of the seriousness of influenza and of the vulnerability of someone with SCID to respiratory complications. Availability of the influenza vaccine at VA facilities and knowledge of when to be vaccinated were facilitators. Providers should use every opportunity to vaccinate patients and provide education about the value of influenza vaccination and when to be vaccinated.

Adult↗

Zanamivir: a review of its use in influenza.

UNLABELLED: Zanamivir is a novel inhibitor of the enzyme neuraminidase, a surface glycoprotein essential for the replication of type A and B influenza viruses. Statistically significant reductions in median time to alleviation of major symptoms of influenza were reported in phase II and III studies of zanamivir. Benefit was seen with early treatment (within 30 or 36 hours of onset of illness) in phase II trials. Median times to alleviation of major (or 'clinically significant') symptoms were reduced by 1 to 2.5 days after treatment with zanamivir 10 mg twice daily by oral inhalation for 5 days in 3 phase III studies. Benefit of zanamivir treatment in terms of time to return to normal activities and reductions in consumption of paracetamol (acetaminophen), and reductions in the level of interference of influenza with sleep, work, leisure and recreational activities, were reported. Reductions relative to placebo of 2.5 to 3.25 days were observed in median time to alleviation of major symptoms in high-risk patients. Available data also indicate potential of zanamivir in the prophylaxis of influenza. A statistically significant reduction in the incidence of influenza A was reported with zanamivir 10 mg by oral inhalation once daily for 4 weeks in a double-blind study in 1107 persons in 2 university communities. Prophylactic benefit of zanamivir in influenza A and B outbreaks has also been suggested by data from a nursing home community. Adverse event profiles in patients receiving zanamivir therapeutically or prophylactically appear similar to those in patients receiving placebo. The most commonly reported adverse events in therapeutic trials have been nasal signs and symptoms, diarrhoea, nausea, headache, bronchitis and cough. CONCLUSIONS: Prompt treatment with zanamivir in patients with naturally acquired influenza is associated with significant reductions in duration of symptomatic illness, accelerated return to normal levels of activity and reduced consumption of antibiotics for influenza-related complications. While vaccination in selected populations remains the seasonal intervention of choice for prophylaxis, the efficacy, good tolerability and lack of resistance seen with zanamivir are likely to make the drug a valuable treatment option, particularly in individuals not covered or inadequately protected by vaccination, and in those at high risk of influenza-related complications. Confirmation of the prophylactic efficacy of zanamivir would indicate a major potential role for the drug in this setting, especially in persons for whom vaccination is not suitable or fully effective, in closed communities (e.g. nursing homes) and in individuals at high risk.

Antiviral Agents↗

Improvement of inactivated influenza virus vaccines.

Inactivated influenza virus vaccines (IVVs) are used for prevention of influenza and its complications. Present vaccines are immunogenic, of low reactogenicity, and protective, but protection has varied between 0% and 100%. Increasing the dose of hemagglutinin and neuraminidase antigens with purified proteins significantly increased serum and nasal antibody responses; however, trials with newer adjuvants have not shown increased serum antibody to levels comparable with those in earlier studies using oil emulsion adjuvants. IgA antibody responses in respiratory secretions were enhanced by the respiratory administration of IVVs, but IVVs by the oral route yielded varying results. IVVs appeared less effective for pandemic influenza in 1968 than in 1957. Since IVVs will be the major preventative measure for pandemic influenza in most countries, they need to be improved to provide better protection against pandemic and interpandemic influenza. Increasing the doses of hemagglutinin and neuraminidase, using adjuvants or immunomodulators, and administering IVVs by the mucosal route could improve the performance of these vaccines.

Adjuvants, Immunologic↗

Serological method using recombinant S2 protein to differentiate equine infectious anemia virus (EIAV)-infected and EIAV-vaccinated horses.

We recently reported a highly protective attenuated live virus vaccine for equine infectious anemia virus (EIAV) based on a proviral construct (EIAVUKDeltaS2) with a genetically engineered mutation in the viral S2 gene that eliminates expression of this accessory protein. While the EIAVUKDeltaS2 vaccine provides protection from detectable infection by experimental challenge with highly virulent virus, the potential for commercial application of this vaccine is complicated by the fact that horses inoculated with the EIAVUKDeltaS2 vaccine strain become seropositive in various reference diagnostic assays based on detection of antibodies to virion core or envelope proteins. To address this issue, we describe here the development and optimization of a new serologic EIAV diagnostic enzyme-linked immunosorbent assay (ELISA) to detect serum antibodies to the EIAV S2 protein that are produced in infected horses but not in horses inoculated with the EIAVUKDeltaS2 vaccine virus. The test S2 protein antigen was developed using the S2 gene sequence from the EIAVUK strain of virus and a series of modifications to facilitate production and purification of the diagnostic antigen, designated HS2G. Using this HS2G as antigen, we describe the development of an affinity ELISA that provides a sensitive and specific detection of S2-specific serum antibodies in experimentally and field-infected horses (22 of 24), without detectable reactivity with immune serum from uninfected (12 of 12) or vaccinated (29 of 29) horses. These data indicate that the S2-based diagnostic ELISA has the potential to accurately differentiate horses infected with EIAV from horses inoculated with an attenuated EIAV vaccine strain with a mutant S2 gene.

Animals↗

[Epidemiologic data for tetanus prophylaxis. Assessment of the need for vaccination].

OBJECTIVE: In spite of the low morbidity secondary to tetanus, the high fatality rate (about 50%) requires effective and extensive protection of the population by vaccination. Since documentation is often lacking, booster tetanus vaccination is frequently applied in cases of minor injury. This leads to vaccination associated complications such as hyperergic reactions. The more intense the vaccination-associated side effects are, the less revaccination is possible. We investigated the tetanus immune status of a selected Austrian population. MATERIALS AND METHODS: Tetanus antitoxin antibodies were measured with ELISA (Immunozym Tetanus, Immuno AG) in serum samples from 218 subjects who were hospitalised in a dermatology unit. In addition, patient history and data concerning vaccination were collected. RESULTS: Based on the assumption that an antitoxin level of 0.1 IU/ml provides sufficient protection, 63% of the subjects were found to be adequately protected. 56% showed high antibody concentrations above 0.5 IU/ml. However, the data also revealed no protection by vaccination in 37% of the subjects. Data obtained by case history or vaccination certificates could not serve as a discrimination factor for applying revaccination or not. CONCLUSION: We strongly recommend better documentation of tetanus vaccination. In some cases, a search for tetanus antibodies before applying booster tetanus vaccination might be necessary.

Adult↗

The Immunization Monitoring Program Active (IMPACT) prospective five year study of Canadian children hospitalized for chickenpox or an associated complication.

BACKGROUND: Varicella vaccine was approved for use in Canada in 1998. A major goal of universal varicella vaccine programs is to reduce severe infection and associated complications. Baseline data are essential against which to judge the effectiveness of routine childhood immunization. OBJECTIVE: To describe morbidity and mortality among children hospitalized for chickenpox. Methods. From January 1, 1991, to March 31, 1996, chickenpox admissions to 11 pediatric referral centers were actively identified. Patient and illness characteristics were compared for 3 subgroups defined by prior health: healthy; unhealthy but immunocompetent; immunocompromised. RESULTS: Of 861 cases 488 (56.7%) were healthy, 75(8.7%) were unhealthy and 298 (34.6%) were immunocompromised. The immunocompromised children differed from healthy/unhealthy cases in mean age (6.4 vs. 4.0/4.6 years, respectively, P < 0.0001); median interval from rash onset to admission (2 vs. 5/5 days, P < 0.0001); complication rate (20% vs. 90%/79%; P = 0.001); and rate of acyclovir therapy (98% vs. 24%/39%; P = 0.001). Unhealthy vs. healthy cases had a higher frequency (P < 0.01) of intensive care (13.3% vs. 4.7%), ventilation (9.3% vs. 2.0%) and death (4% vs. 0.2%). CONCLUSION: These data provide a baseline for morbidity/mortality resulting from chickenpox before varicella vaccine use in Canada.

Adolescent↗

Therapeutic options for diseases due to potential viral agents of bioterrorism.

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

Antiviral Agents↗

[Prognostic significance of the NBT test in patients with ichterohaemorrhagic leptospirosis].

The values of spontaneous NBT test significantly rise at the peak of leptospirosis in patients with an uncomplicated course of the disease (p < 0.05). Low values of the spontaneous NBT test with stimulation with Staphylococcus in patients with grave leptospirosis predict the development of life-threatening complications. Leptospirosis vaccine reduced the elevated values of the NBT in leptospirosis. The depressing effect of leptospirosis vaccine is indicative of a high risk of development of late complications.

Adolescent↗

[BCG vaccination in low risk tuberculosis; first experiences after the suspension of BCG vaccination of newborns in Czechoslovakia].

With the steadily declining risk of tuberculosis infection in CSR the question arose whether vaccination of infants remains worthwhile considering not only resources spent but also complications to vaccination vis-a-vis benefits derived. A prospective study has been designed in which BCG vaccination of newborns is discontinued in an area with 30,000 newborns yearly. In the period from April 1, 1986 to January 31, 1988 there were not vaccinated 43,428 children (84.8% of the newborns). The collaboration of mothers was good. The one year old non-vaccinated children were tested with 2 TU PPD RT 23 with Tween 80. The distribution of positive tuberculin reactions appears unimodal, relatively large reactions being absent. 8 children had reactions with 6 or more mm induration. That corresponds to a risk of infection of 0.04%. The project continues in the research area and might be extended to another area.

BCG Vaccine↗