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[Adverse events following immunisation in Germany from 1.1.2001 to 31.12.2003].

The German Protection Act against Infection (Infektionsschutzgesetz) came into effect on 1 January 2001. Physicians must report complications after vaccination to local heath authorities according to Article 6 No. 3. . The local heath authorities send notifications to the Paul-Ehrlich-Institut (PEI). Between 1 January 2001 and 31 December 2003, a total of 941 reports from local public health authorities were registered in a central database and assessed. Compared to the number of reports of suspected adverse drug reactions sent to the PEI independently in the same time period by the pharmaceutical companies and the German Drug Commissions (Arzneimittelkommissionen) (n=2.338), underreporting has to be considered. Age distribution in the reports from local public health authorities revealed the following pattern: 33.8% of reports concerned adults (18-59 years old), 25.4% children aged 1-6 years, 16.9% infants, 11.3% adults (>60 years), 8.9% children aged 7-14 years and 1.9% adolescents aged 15-17 years. In 1.8% the age was not reported. The causal relationship was assessed by the PEI as proven in 0.2%, probable in 41.6%, likely in 27.5% and unlikely in 6.6%. In 11.9% assessment was not possible and in 11.8% of the reports follow-up information has been requested. Comparison to the reports from other sources revealed no major difference in respect to quality and content.

Adolescent↗

Inherited disorders of the IL-12-IFN-gamma axis in patients with disseminated BCG infection.

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN-gamma axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN-gamma circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN-gamma receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12Rbeta1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN-gamma circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN-gamma circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.

Adult↗

Optic neuritis complicating measles, mumps, and rubella vaccination.

A 6-year-old boy developed bilateral optic neuritis with decreasing visual acuity 18 days after administration of live attenuated trivalent measles, mumps, and rubella vaccine. The patient was treated with oral corticosteroids. The optic neuritis resolved within several weeks and normal vision returned. An afferent pupillary defect persistent in the more severely involved eye for 14 months following vaccination.

Adult↗

Child mortality after high-titre measles vaccines: prospective study in Senegal.

The use of Edmonston-Zagreb high-titre (EZ-HT) vaccine at age 6 months has been recommended for countries in which measles before the age of 9 months is a substantial cause of death, but little is known about the long-term effects of high-titre live measles vaccines given early in life. In a randomised vaccine trial in a rural area of Senegal, children were randomly assigned at birth to three vaccine groups: EZ-HT at 5 months (n = 336); Schwarz high-titre (SW-HT) at 5 months (n = 321); and placebo at 5 months followed by standard low-titre Schwarz vaccine at 10 months (standard: n = 358). All children were prospectively followed for 24-39 months in a well-established demographic surveillance system. Child mortality after immunisation was significantly higher in the two groups which received high-titre vaccines than in the group given the standard vaccine. The relative risk of death was 1.80 (95% confidence interval [CI] 1.18-2.74; p = 0.007) in the EZ-HT group and 1.51 (0.97-2.34; p = 0.07) in the SW-HT group compared with the standard group. The three vaccine groups were comparable as regards various social, family, and health characteristics, and there was no difference in mortality between children who received the standard vaccine and those who were eligible for the trial but did not take part for various reasons. The higher risk of death in the two high-titre vaccine groups remained significant in multivariate analyses. These findings suggest a need to reconsider the use of high-titre measles vaccines early in life in less developed countries.

Cause of Death↗

The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response.

Encephalitis is a rare, but serious complication from vaccination against smallpox using replication competent strains of vaccinia virus. In this report we describe mutants of vaccinia virus, containing N-terminal deletions of the vaccinia virus interferon resistance gene, E3L, that are attenuated for neuropathogenesis in a mouse model system. These recombinant viruses replicated to high titers in the nasal mucosa after intra-nasal infection of C57BL/6 mice but failed to spread to the lungs or brain. These viruses demonstrated reduced pathogenicity after intra-cranial infection as well, indicating a decrease in neurovirulence. Intra-nasal inoculation or inoculation by scarification with a low dose of recombinant virus containing a deletion of the entire N-terminal domain of E3L protected against challenge with a high dose of wild-type vaccinia virus, suggesting that this replication competent, but attenuated strain of vaccinia virus may have promise as an improved vaccine for protecting against smallpox, and as a vector for inducing mucosal immunity to heterologous pathogenic organisms.

Animals↗

Viral infections after renal transplantation.

Viral infections are a leading cause of posttransplantation morbidity and mortality. A number of recent developments have altered our understanding and management of these disorders. The pathogenetic roles of several viruses, including human herpesviruses 6 and 8, have been newly established. Molecular-based diagnostic tests now make more rapid diagnosis possible. The licensing of new potent antiviral agents offers a wider choice of drugs for viral prophylaxis and treatment. The use of more potent immunosuppressive agents is responsible in part for the increasing incidence of some viral infections, but this varies among drugs, and individual viruses differ in their sensitivity to immunosuppressive agents. This review summarizes the natural history, diagnosis, prevention, and treatment of many common viral infections after renal transplantation.

Antiviral Agents↗

Laboratory diagnosis of smallpox: role of the Virus Reference Laboratory, Colindale, 1947-70.

The Virus Reference Laboratory, Colindale, first embarked on laboratory investigations for smallpox early in 1947. From then, in conjunction with the Department of Bacteriology, University of Liverpool, it provided a complete diagnostic service throughout England and Wales until 1962, after which the service became available regionally until eradication was effected. Up to 1970 it had investigated 2696 specimens from suspected cases of smallpox and had recovered 108 strains of variola and 248 of vaccinia virus. These last were from persons suffering the complications of vaccination. Some outbreaks following smallpox importation are discussed but infection among laboratory staff during this period was not demonstrated.

England↗