[Smallpox vaccination 1961-1965 and postvaccinal complications 1946-1966 in the land of North-Rhine-Westphalia].
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Adolescent↗
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Smallpox vaccination and bioterrorism with pox viruses.
Bioterrorist attacks occupy a special place amongst the innumerable potential types of terrorist attack, with the intentional release of pox viruses being especially feared in this connection. Apart from the variola virus, the agent responsible for smallpox in humans, the monkeypox virus and numerous other animal pox viruses pose potential risks for humans and animals. This risk scenario also includes recombinations between the various pox viruses, changes in hosts and genetically engineered manipulations of pox viruses. For over 200 years, the method of choice for combatting smallpox was via vaccination with a reproductive, original vaccinia virus. Worldwide eradication of smallpox at the end of the 1970s and the discontinuation of routine smallpox vaccination in 1980 can be credited to such vaccination. Unfortunately, these vaccinations were associated with a large number of postvaccinal impairments, sometimes resulting in death (e.g. postvaccinal encephalitis). The only way to restrict such postvaccinal complications was to carry out initial vaccination within the first 2 postnatal years. Initial vaccination at a later age led to such a sharp increase in the number of vaccines with complications that vaccination had to be discouraged. The dilemma of the smallpox vaccine stocks stems from the fact that a large portion of these stocks are produced with the same vaccinia strains as before. This is irresponsible, especially as the percentage of immune-suppressed persons in the population, for whom vaccination-related complications pose an especial threat, is increasing. One solution to the dilemma of the smallpox vaccine stocks is the MVA strain. It is harmless, protects humans and animals equally well against smallpox and can be applied parenterally.
Animals↗
[BCG-vaccination in neonates as a cause of osteomyelitis--an argument against BCG-vaccination?].
BCG-osteomyelitis is a rare complication of BCG-vaccination. By means of a case report clinical and immunological findings are discussed. Contrary to the undramatic clinical symptoms the x-ray showed pronounced osteolytic lesions in the sternum. The bacteriological examination demonstrated mycobacteria of BCG-type. Immunological investigations presented normal humoral and cellular immunity. The therapy (curettage, antituberculous drugs) was effective. In spite of this complication the BCG-vaccination is furthermore recommended.
BCG Vaccine↗
Lymphadenopathy after BCG vaccination in a child with chronic granulomatous disease.
We report a 15-month-old boy who developed an ulcer in the left axillary fold following bacillus Calmette-Guerin vaccination. Subsequent immunologic and genetic studies led to the diagnosis of chronic granulomatous disease. His mother had "lupus-like" lesions, described in some carriers of this disease, that were thus related to her son's diagnosis. Although in healthy subjects this vaccination is usually harmless, in instances of impaired immunity it may cause adverse reactions. When a vaccine-related complication occurs, an underlying immunodeficiency should be sought.
BCG Vaccine↗
Poliovirus vaccine strains detected in stool specimens of immunodeficient children in South Africa.
After exposure to the oral poliovirus vaccine (OPV), immunocompetent persons excrete poliovirus (PV) vaccine strains for a limited period. In contrast, immunodeficient individuals remain sometimes chronically infected, and in some cases, PV excretion times as long as 10 years have been reported. During prolonged replication in the human intestine, the PV vaccine strain almost invariably reverts its attenuated character and acquires neurovirulent properties (vaccine-derived PVs, or VDPVs), which resemble wild-type PV strains. The aim of this study was to determine the occurrence of OPV strains in stools of immunodeficient children from a selected area in South Africa, as a first step toward future research on the prevalence and potential health impact of VDPVs. In a period of 1 year, a total of 164 stool samples of HIV-positive children aged 4 months to 8 years were studied for the excretion of OPV strains. In addition, 23 stool samples from healthy immunocompetent children were analyzed after receiving their OPV immunization. By applying a reverse transcription-polymerase chain reaction in combination with a nested PCR, a total of 54 enteroviruses (EVs) were detected in the stool specimens of the immunodeficient children. Using restriction enzyme analysis, 13 PVs were distinguished from 41 nonpolio EVs (NPEVs). A Sabin-specific RT-triplex PCR confirmed the presence of 7 Sabin PV type 1, 4 Sabin PV type 3, and 2 Sabin PV type 2 isolates. The majority of the NPEV group was made up of 7 coxsackievirus B3 (CBV3), 6 echovirus 11 (ECV11), 5 ECV9, and 3 coxsackievirus A6 (CAV6) isolates. According to the results, two of the immunodeficient patients (P023 and P140) who had received their last OPV immunization more than 15 months before (vaccinated at 14 weeks of age) tested positive for Sabin PVs types 3 and 1, respectively. A 5-year-old immunodeficient patient (P052) who had received her last OPV immunization more than 42 months before (vaccinated at 18 months of age) tested positive for Sabin PV type 1. These results suggested that immunodeficient patients vaccinated with OPV might excrete potentially pathogenic VDPVs for a prolonged period. These VDPVs may circulate in the community, resulting in possible infections in the unvaccinated population. Therefore, the information obtained in this study would be essential for strategies aimed at the protection of both immunodeficient as well as immunocompetent individuals against complications of vaccination with OPV.
Child↗
Prevention of cytomegalovirus disease by Towne strain live attenuated vaccine.
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Antibodies, Viral↗
Measles vaccination status, delay in recognizing measles outbreaks and outbreak outcome.
From July to October 1994, Mashonaland East Province in Zimbabwe experienced measles outbreaks in which 2118 cases were reported. According to routine statistics, 69 pc of these patients were previously vaccinated against measles, 22 pc were not vaccinated and 9 pc had an unknown vaccination status. The measles vaccine coverages in the nine districts of this province during the year prior to the outbreak ranged from 58 pc to 87 pc with a provincial average of 72 pc. Three hundred and fifty eight patients who came in contact with health services during one month were investigated further. The prevalence of measles related complications among vaccinated and unvaccinated patients was 18,5 pc and 51,7 pc respectively (X2 = 56,01, p < 0,001; df = 2. While no death occurred among vaccinated patients, the case fatality rate among unvaccinated patients was 27,3 pc (X2 = 45,15, p < 0,001; df = 2). The later an outbreak was recognized the longer it was likely to last and the higher the case fatality rate was (Correlation coefficient = 0,76; 95 pc CI 0,02 - 0,96). It is concluded that the Expanded Programme on Immunization in this area is not a failure and that for outbreak control measures to be effective, they have to be implemented as early as possible, preferably within one week of the onset of an outbreak. District managers should put more emphasis on the use of data by Rural Health Centre staff in order to recognize outbreaks early.
Adolescent↗
Measles encephalitis in early pregnancy and after delivery.
We present two cases of measles encephalitis, one in early pregnancy and one after delivery. In case 1, the patient became unconscious 6 days after the appearance of a rash and was treated with glycerol and immunoglobulin. In case 2, the patient became unconscious 6 days after the appearance of a rash and was also treated with glycerol and immunoglobulin. Both of them recovered without any neurological sequelae. Pregnancy is a risk factor for severe measles complications, and vaccination should be promoted much more in countries with poor measles control, such as Japan.
Adult↗
Ocular complications in the Department of Defense Smallpox Vaccination Program.
OBJECTIVE: The purpose of this case series was to present an overview of the nature and frequency of ocular complications in the Department of Defense (DoD) Smallpox Vaccination Program. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: The authors retrospectively evaluated data collected on individuals with an ophthalmologic complaint after receiving smallpox vaccination or after contact with a recently immunized individual. The vaccinee and contact cases occurred secondary to inoculations given between December 13, 2002 and May 28, 2003 as part of the DoD Smallpox Vaccination Program. METHODS: Data were collected primarily from reports to military headquarters or to the Vaccine Adverse Event Reporting System and individual medical records. MAIN OUTCOME MEASURES: The incidence, types, and timing of ocular complications were evaluated. Diagnostic and treatment considerations also were reviewed. RESULTS: Between December 13, 2002 and May 28, 2003, 450,293 smallpox vaccinations were given. We identified 16 confirmed or probable cases of ocular vaccinia, with an incidence of 3.6 per 100,000 inoculations. Of these cases, 12 (75%) were seen in the vaccinees, and 4 (25%) in close contacts. Of the 12 self-inoculation cases, 7 (58.3%) were seen in individuals receiving the vaccine for the first time (primary vaccination), and 3 (25.0%) were seen in individuals previously vaccinated (revaccination); the vaccination status in 2 cases was unknown. Clinical manifestations included lid pustules, blepharitis, periorbital cellulitis, conjunctivitis, conjunctival ulcers, conjunctival membranes, limbal pustules, corneal infiltrates, and iritis, with onset of symptoms 3 to 24 days after inoculation or contact. Five of 9 tested cases were culture or polymerase chain reaction positive for vaccinia. Treatment for most cases was topical trifluridine 1% (Viroptic; King Pharmaceuticals, Inc., Bristol, TN). Vaccinia immune globulin was used in 1 case. In all patients, recovery occurred without significant visual sequelae. CONCLUSIONS: When compared with historical data on the ocular complications of smallpox vaccination, the incidence of ocular complications during the DoD Smallpox Vaccination program has been low. In addition, the severity of disease seems to be less than during other vaccination periods. These findings perhaps are the result of improved screening of vaccinees, prevaccination counseling, postvaccination wound care, and the suggested efficacy of trifluridine in the treatment of ocular vaccinia.
Acyclovir↗
Epidemiology and prevention of measles in rural south India.
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Child↗
Serious adverse events associated with bacille Calmette-Guérin vaccine in Canada.
BACKGROUND: Targeted Bacille Calmette-Guérin (BCG) vaccination is offered to neonates in some First Nations and Inuit (FNI) communities in Canada. Serious adverse events associated with BCG vaccine prompted a review to assess causality. METHODS: The Immunization Monitoring Program Active (IMPACT), a pediatric hospital-based active surveillance network, reported admissions for BCG-related adverse events between 1993 and April 2002. The Canadian Advisory Committee on Causality Assessment (ACCA) reviewed the reports to assess causality. Data between 1987 and September 2002 from the Vaccine-Associated Adverse Event Surveillance (VAAES) Program, a passive national reporting system, were also reviewed. RESULTS: IMPACT identified 21 pediatric cases; 19 were Canadian-born, and 18 were FNI. Six disseminated BCG cases were identified; 5 were FNI infants who subsequently died. All had immunodeficiencies and concurrent infections. Other adverse events included 2 cases of osteomyelitis, BCG abscesses and lymphadenitis. ACCA reviewed the 21 cases and determined that 14 were very likely associated with the vaccine, including the 6 disseminated BCGs; 5 were probably associated and 1 was possibly associated with the vaccine; 1 was unclassifiable. The VAAES program identified 157 adverse events. No additional serious systemic adverse events (disseminated BCG or osteomyelitis) were identified. CONCLUSIONS: Serious BCG vaccine-associated complications continue to occur in Canada. The numbers of FNI children with disseminated disease was greater than expected from reported rates in the literature.
Adverse Drug Reaction Reporting Systems↗
Influenza-related Deaths in Young Children: Observations From a German Case Series.
BACKGROUND: Seasonal influenza virus infections remain a major public health burden. During the last years, several case reports of severe influenza infections in children have been published. CASES: We report 4 fatal influenza cases in young children (2-6 years old) which occurred in Southwest Germany in the seasons 2022/23 and 2023/24. All 4 children were previously healthy; a forensic autopsy was conducted due to an unknown cause of death. Postmortem samples from the respiratory tract and organ tissues were tested for respiratory viruses via real-time polymerase chain reaction (RT-PCR) and analyzed by whole-genome sequencing. RESULTS: In 1 child, RT-PCR revealed influenza B virus, and 3 children died with influenza A (H1N1)pdm09 infection. No mutations associated with high virulence were detected. In 1 case, influenza A(H1N1)pdm09 could be cultivated in cell culture from brain tissue. CONCLUSIONS: This case series underlines the potential risk of fatal outcomes of influenza infections in children. This should be considered when re-evaluating the vaccination recommendations for healthy children.
Humans↗
Cancer complicating chronic ulcerative and scarifying mucocutaneous disorders.
Skin affected by a burn cancer is scarred, ulcerated, and often appears as erythema ab igne clinically in adjacent skin. The latent period in burn scar malignancy is much longer for SCC than BCC. Malignant melanoma and various sarcomas are reported to arise in burn scars, too. The other extreme on the temperature scale can less often result in enough permanent acral damage that poor wound healing may eventually result in cancer, usually SCC. About 1% of patients with chronic osteomyelitis develop cancer, usually SCC in sinus tracts. As with tumors arising in burn scars and chronic leg ulcers of varied etiology, black patients are disproportionately overrepresented in osteomyelitic malignancy. In nearly all of the patients with radiation-induced skin cancer, concomitant radiodermatitis is present. As with burn scar and osteomyelitic cancer, x-ray related cancer has a long latent period. Similar to burn scar cancer, SCC predominates in osteomyelitis and occurs on the extremities. BCC, when it arises, is more common on the face and neck in burn- and radiation-induced tumors. Multiple tumors are frequent as is recurrence in x-ray malignancy. Mortality is high: one out of three to four patients with burn scar, osteomyelitic, and radiation cancer die of dermatosis-related malignancy. Recently, radioactivity-contaminated gold rings have been implicated in causing SCC. Carcinoma tends to occur in irradiated benign dermatoses whereas sarcomas tend to complicate irradiated malignancies. Stasis ulceration and anogenital fistulae may rarely lead to cancer, SCC in the former and adenocarcinoma in the latter. SCC can rarely develop in four related conditions (acne conglobata, dissecting perifolliculitis of the scalp, hidradenitis suppurativa, and pilonidal sinus) after a lengthy latent period; prognosis is poor with a high metastatic rate. A whole host of chronic cutaneous infections can lead to malignancy occasionally; these include lupus vulgaris, lymphogranuloma veverum, granuloma inguinale, leprosy, actinomycosis, and candidiasis. BCC more than SCC is known to complicate smallpox vaccination sites. Certain erosive and/or scarring dermatoses other than those mentioned above can be unusually affected by secondary malignancy. Discoid lupus erythematosus lesions often subjected to the carcinogenic effects of sunlight can degenerate into SCC in patients with either light or dark skin. In acrodermatis chronica atrophicans, a condition not often seen in the United States, the involved skin, particularly of the lower extremities, is susceptible to SCC, lymphoma, and BCC. Epidermolysis bullosa, especially the recessive dystrophic variant, can be complicated by SCC on affected mucous membrane and acral skin.(ABSTRACT TRUNCATED AT 400 WORDS)
Burns↗
Identification of strain-specific nucleotide sequences in the RA 27/3 rubella virus vaccine.
A polymerase chain reaction-based protocol was developed for determination of the sequence of 1300 nucleotides in the E1 coding region of the genomes of multiple strains of rubella virus. From a collection of sequences of 9 independent strains and isolates, characteristic nucleotides were identified that distinguished the RA 27/3 strain, which is the currently used attenuated vaccine strain. These characteristic nucleotides were maintained in virus recovered from recent vaccinees. Both the assay and the knowledge of these characteristic nucleotides should be of use in determining the origin of virus isolated from individuals who have suspected vaccine-associated complications. The nucleotide sequences of the independent rubella virus strains differed by 0.7%-3.6%. Phylogenetic tree analysis of the sequences indicated the existence of at least three distinct genetic lineages.
Adult↗
Non-HTLV-I associated pleomorphic T-cell lymphoma of the brain mimicking post-vaccinal acute inflammatory demyelination.
Two weeks after vaccination against tick-borne encephalitis (TBE), a 57-year-old female suddenly developed mental confusion and hemiparesis of the left side. Cranial MRI demonstrated extensive bilateral lesions in the fronto-parietal white matter of both hemispheres, suggesting an acute inflammatory demyelinating disease following vaccination. Despite administration of high-dose corticosteroids, the patient died 3 weeks after onset of neurological symptoms. Autopsy revealed diffuse infiltrates of a primary cerebral pleomorphic T-cell lymphoma of medium and large cell type. PCR on brain tissue for HTLV-I and serology for anti-HTLV-I antibodies in CSF and serum were negative; immunocytochemistry on brain tissue did not detect EBV-related antigen. This is the first recorded observation of a diffusely infiltrating primary central nervous system T-cell lymphoma, clinically and radiologically mimicking a fatal acute inflammatory demyelinating complication after vaccination.
Brain Neoplasms↗
Effect of Towne live virus vaccine on cytomegalovirus disease after renal transplant. A controlled trial.
OBJECTIVE: To test the efficacy of vaccination with the Towne live attenuated cytomegalovirus vaccine. DESIGN: A double-blind, randomized, placebo-controlled trial in candidates for renal transplantation. The cytomegalovirus serologic status of both recipients and donors were determined, and the recipients were followed for periods of 6 months to 7 years after transplant. SETTING: A university transplant center. PATIENTS: The analyses were made on 237 patients who were given either vaccine or placebo, received renal transplants, and were followed for at least 6 months. INTERVENTION: Subcutaneous inoculation with Towne live attenuated virus or with placebo. MAIN OUTCOME MEASURES: The presence of cytomegalovirus infection was defined by virus isolation and antibody tests. If infection occurred, a prearranged scoring system for cytomegalovirus disease was used to objectify disease severity. RESULTS: The vaccine was well tolerated, and there were no discernible long-term adverse effects. Recipients who were originally seropositive did not clearly benefit from vaccination. Protective efficacy was analyzed in the group at highest risk for cytomegalovirus disease; recipients who were seronegative at the time of vaccination and who received a kidney from a seropositive donor. Compared with placebo recipients, vaccinated patients in this group had significantly less severe cytomegalovirus disease, with a significant reduction in disease scores (P = 0.03) and 85% decrease in the most severe disease (95% CI, 35% to 96%), although infection rates were similar. Graft survival at 36 months was improved in vaccinated recipients of cadaver kidneys (8 of 16) compared with unvaccinated recipients (4 of 16) (P = 0.04). CONCLUSIONS: Previous vaccination of seronegative renal transplant recipients with live cytomegalovirus results in reduction of disease severity mimicking the action of naturally derived immunity.
Adult↗
RA27/3 rubella vaccine. A four-year follow-up.
RA27/3 rubella vaccine was given to 418 subjects aged 1 to 17 years in 1974, 201 of whom participated in a four-year follow-up study. Two vaccine-associated complications were reported. A 5-year-old boy had transient arthritis of the hip, and a 1-year-old boy had a pigmented macule at the inoculation site. Rubella reinfection was uncommon, occurring at most in three of our subjects. All of the 186 susceptible children seroconverted, and 182 had hemagglutination-inhibiting (HI) titers of 8 or greater at four-year follow-up (geometric mean titer, 30.3). In the four children whose HI titers declined to undetectable levels, both HI and neutralizing (Nt) antibodies had developed immediately postimmunization, and two had Nt titers at follow-up despite loss of HI antibodies. RA27/3 vaccine boosted HI titers in 15 seropositive subjects, but titers returned to preimmunization levels four years later. We concluded that RA27/3 vaccine produced durable immunity with very low rates of rubella reinfection and secondary vaccine failure during the four years since immunization.
Adolescent↗
Distribution of surface protein variants among hyperinvasive meningococci: implications for vaccine design.
The bacterium Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Outer membrane proteins (OMPs) are candidates in the search for comprehensive meningococcal vaccines; however, the formulation of OMP vaccines is complicated by antigenic diversity, which is generated by high levels of genetic reassortment and strong positive selection in the meningococcal antigen genes. The genetic and antigenic diversity of three OMPs (FetA, PorA, and PorB) among a global collection of meningococcal isolates representative of the major hyperinvasive clonal complexes was determined. There was evidence for antigenic structuring among the three OMPs that could not be explained purely by descent. These observations violated the predictions of the clonal and epidemic clonal models of population structure but were in concordance with models of strain structure which propose that host immunity selects for nonoverlapping antigen combinations. The patterns of antigenic variant combinations suggested that an OMP-based vaccine with as few as six PorA and five FetA variant sequences could generate homologous immune responses against all 78 isolates examined.
Alleles↗