A 4-year-old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with arecall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.

OBJECTIVE:To investigate the causes of neurological manifestations in girls immunized with the human papillomavirus (HPV) vaccine.

METHODS:During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study.

RESULTS:The age at initial vaccination ranged from 11 to 17 years, and the average incubation period after the first dose of the vaccine was 5.47±5.00 months. Frequent manifestations included headaches, general fatigue, coldness of the legs, limb pain and weakness. The skin temperature examined in 28 girls with limb symptoms exhibited a slight decrease in the fingers (30.4±2.6 °C) and a moderate decrease in the toes (27.1±3.7 °C). Digital plethysmograms revealed a reduced height of the waves, especially in the toes. The limb symptoms of four girls were compatible with the Japanese clinical diagnostic criteria for complex regional pain syndrome (CRPS), while those in the other 14 girls were consistent with foreign diagnostic criteria for CRPS. The Schellong test identified eight patients with orthostatic hypotension and four patients with postural orthostatic tachycardia syndrome. The girls with orthostatic intolerance and CRPS commonly experienced transient violent tremors and persistent asthenia. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined.

CONCLUSION:The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the studied girls was psychosomatic disease. The social problems of the study participants remained unresolved in that the severely disabled girls stopped going to school.

Studies in Gothenburg, Sweden, reported an exceptionally high rate of persistent itching nodules at the site of injection of aluminium containing vaccines, usually with positive epicutaneous tests to aluminium. When a new booster diphtheria-tetanus vaccine was introduced we performed a prospective cluster randomised active surveillance in 25,232 10-year-olds. Parental reports 6 months after vaccination with Duplex or diTeBooster were collected for 22,365 (88%) pupils in 851 schools. We identified 3-6 children per 10,000 with a local itching nodule persisting for at least 2 months. There were no significant differences between the vaccine groups. Contact allergy to aluminium was not detected. The findings support the use of the vaccine presently available in the Swedish vaccination program. Continued surveillance of persistent itching nodules and aluminium contact allergy is, however, warranted for vaccines containing pertussis toxoid and aluminium.

Whooping cough or pertussis is a highly infectious respiratory disease in humans caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been associated with the recent resurgence of pertussis in developed countries including Australia despite high vaccination coverage where B. pertussis strains that do not express pertactin (Prn), a key antigenic component of the ACV, have emerged and become prevalent. In this study, we used an in vivo competition assay in mice immunised with ACV and in naïve (control) mice to compare the proportion of colonisation with recent clinical Prn positive and Prn negative B. pertussis strains from Australia. The Prn negative strain colonised the respiratory tract more effectively than the Prn positive strain in immunised mice, out-competing the Prn positive strain by day 3 of infection. However, in control mice, the Prn positive strain out-competed the Prn negative strain. Our findings of greater ability of Prn negative strains to colonise ACV-immunised mice are consistent with reports of selective advantage for these strains in ACV-immunised humans.

We tested 46 fully vaccinated children in two day-care centers in Israel who were exposed to a fatal case of pertussis infection. Only two of five children who tested positive for Bordetella pertussis met the World Health Organization's case definition for pertussis. Vaccinated children may be asymptomatic reservoirs for infection.

OBJECTIVES:We sought to investigate roles that Merck&Co Inc played in state human papillomavirus (HPV) immunization policymaking, to elicit key stakeholders' perceptions of the appropriateness of these activities, and to explore implications for relationships between health policymakers and industry.

METHODS:We used a series of state case studies combining data from key informant interviews with analysis of media reports and archival materials. We interviewed 73 key informants in 6 states that were actively engaged in HPV vaccine policy deliberations.

RESULTS:Merck promoted school-entry mandate legislation by serving as an information resource, lobbying legislators, drafting legislation, mobilizing female legislators and physician organizations, conducting consumer marketing campaigns, and filling gaps in access to the vaccine. Legislators relied heavily on Merck for scientific information. Most stakeholders found lobbying by vaccine manufacturers acceptable in principle, but perceived that Merck had acted too aggressively and nontransparently in this case.

CONCLUSIONS:Although policymakers acknowledge the utility of manufacturers' involvement in vaccination policymaking, industry lobbying that is overly aggressive, not fully transparent, or not divorced from financial contributions to lawmakers risks undermining the prospects for legislation to foster uptake of new vaccines.

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We report a case of Guillain-Barré syndrome in a previously healthy child who received a hepatitis A vaccination (HAVRIX) 5 days before onset of symptoms. No other precipitating factor could be identified. The relevant literature is reviewed and discussed.

Abstract Since the introduction of the H1N1 influenza vaccine in the wake of the 2009 H1N1 influenza pandemic, many serious and nonserious adverse events related to the vaccine have been reported. We describe a 59-year-old African-American man with severe chronic heart failure and chronic obstructive pulmonary disease who experienced a new-onset, generalized tonic-clonic seizure less than 1 hour after receiving the H1N1 vaccine. He had never experienced any reactions to previous seasonal influenza vaccines. His medical history, physical examination, and targeted investigations revealed no evidence of other potential etiologies for his seizure. After this event, the patient, who was discharged without anticonvulsant therapy, remained seizure free for the next 10 months. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship (score of 4) between the patient's seizure and the receipt of the H1N1 vaccine. This is the first case report, to our knowledge, to suggest a possible association between the H1N1 influenza vaccine and seizure. The mechanism of the association is unclear. Further case series may clarify the nature of the association.

Guillain-Barre syndrome is a rare but fatal autoimmune disease. The exact cause of Guillain-Barre syndrome is still unknown. The most common known etiology of Guillain-Barre syndrome is infectious disease notably caused by. A very small fraction of people can develop Guillain-Barre syndrome due to vaccines and vaccinations like a meningococcal vaccine, poliovirus vaccine, influenza vaccine, and rabies vaccine. Of all these, rabies is fatal invariably. It can be preventable if diagnosed early and post-exposure treatment is followed according to the World Health Organization guidelines. Older formulations of rabies vaccines are cultured in the neural tissues and have been found to have an increased risk of Guillain-Barre syndrome. Although less immunogenic older formulations of rabies vaccines are more commonly used in Asian and South American countries due to their cost-effective nature. There is little to no data available on the incidence of Guillain-Barre syndrome due to vaccinations in Pakistan. Most of the cases of Guillain-Barre syndrome due to vaccination are either undiagnosed or misdiagnosed. In this case report, we are presenting a case of vaccine-associated Guillain-Barre syndrome due to neural tissue anti-rabies vaccine in a young girl, who presented with lower limb weakness, inability to pass urine and abdominal pain.

We describe a case of a 15-month-old female child admitted to our hospital because of fever, rash, neurological signs (oscillation between states of irritability and drowsiness), palpebral edema and drooping eyelid, appeared 10 days after the vaccination for measles, mumps and rubella. Brain MRI images showed multiple bilateral hyperintense lesions in the white matter typical of acute disseminated encephalomyelitis (ADEM), an autoimmune demyelinating disorder with inflammatory lesions of the central nervous system, due to viral antigens or vaccines. In the mean time, because of patient's vague phenotypic manifestations, suggestive of a genetic defect, array comparative genomic hybridization was carried out which showed the presence of a microdeletion 22q11.21, linked to the DiGeorge syndrome. Our case suggests that pediatric cases of post-vaccination ADEM, in which neurological signs persist, should be investigated for genetic phenotypical features, in order to exclude the presence of a genetic syndrome or disease.

BACKGROUND:In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States.

OBJECTIVE:To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.

METHODS:We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990-July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV.

RESULTS:VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination.

CONCLUSIONS:This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies.

The intussusception is one of the most frequent causes of occlusive syndrome in infants and in children. (1) The mesenteric lymphadenopathy, wich is very rare post rotavirus vaccination, can cause intussusception, (2-5) especially in genetically predisposed individuals. (6) There is an association between intussusception and some classes of genotype. (7-9) Two infants aged 3 months, vaccinated against rotavirus. After about a week, one of the 2 identical infants presented inconsolable crying, vomiting, loose stools mixed with blood, and was diagnosed with bowel obstruction with intussusception. He was operated in urgency. After a few hours, his brother presented vomiting, and was admitted to our Hospital for suspected intussusception. The controls carried out have confirmed the presence of intussusception that was treated early, before the onset of severe symptoms. The incidence of post rotavirus vaccine intussusception is very low. The determining factor hypothetically might be linked to the presence of a genotype that exposes infants to a greater risk of developing mesenteric lymphadenitis and intussusception. In our case, the diagnosis of intussusception occurred in a twin, which allowed us to recognize early symptoms which accused the brother and schedule the surgery with less urgency. Our experience may want to sensitize families and pediatricians to report cases of intussusception given a theoretical familiar association. The study of the genotype could be decisive for or not to exclude the presence of a risk of invagination, thus avoiding vaccination.

CONTEXT: In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years.

OBJECTIVE: To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV.

DESIGN, SETTING, AND PARTICIPANTS: Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting.

MAIN OUTCOME MEASURES: Numbers of reported AEFIs, reporting rates (reports per 100,000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates.

RESULTS: VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100,000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barré syndrome; 0.1 for anaphylaxis and death; 0.04 for transverse myelitis and pancreatitis; and 0.009 for motor neuron disease. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods.

CONCLUSIONS: Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system in which a change from the supine position to an upright position causes an abnormally large increase in heart rate or tachycardia (30 bpm within 10 min of standing or head-up tilt). This response is accompanied by a decrease in blood flow to the brain and hence a spectrum of symptoms associated with cerebral hypoperfusion. Many of these POTS-related symptoms are also observed in chronic anxiety and panic disorders, and therefore POTS is frequently under- and misdiagnosed.

We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud's syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

We describe a young woman who developed POTS with positive serum anti-NMDA receptor antibodies and no evidence of encephalitis after vaccination with HPV vaccine, Cervarix. Her symptoms improved significantly with immunomodulatory therapy and re-occurred after immunomodulatory therapy was stopped, suggesting an autoimmune etiology of POTS after vaccination.

BACKGROUND AND PURPOSE:Postural tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system that may have an autoimmune etiology.

METHODS:Six patients who developed new onset POTS 6 days to 2 months following human papillomavirus vaccination are reported.

RESULTS:Three patients also had neurocardiogenic syncope, and three patients were diagnosed with possible small fiber neuropathy. Symptoms in all patients improved over 3 years with pharmacotherapy and non-pharmacological measures but residual symptoms persisted. Molecular mimicry with formation of cross-reacting autoantibodies to the potential targets of the autonomic ganglia, neurons, cardiac proteins or vascular receptors is considered as a possible pathogenesis of new onset POTS after immunization.

CONCLUSION:Correct diagnosis of POTS and awareness that POTS may occur after vaccination in young women is essential for prompt and effective management of this condition.

A 5-year-old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. A CT scan of the head and EEG did not disclose any abnormality. An MRI performed 3 months after the event, however, showed clear-cut evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The response to levodopa was good, but adverse reactions appeared early. The child is now 7 years old. Bromocriptine, deprenyl, and levodopa have produced a remarkable improvement of the parkinsonian features.

BACKGROUND:Although postvaccination Guillain-Barré syndrome is commonly reported, there have only been 2 previously reported cases of postvaccination Miller Fisher syndrome, and none in association with the novel influenza A(H1N1) vaccine.

OBJECTIVE:To describe a case of Miller Fisher syndrome following receipt of the seasonal influenza and novel influenza A(H1N1) vaccine.

DESIGN:Case report and literature review.

SETTING:Vancouver General Hospital. Patient  A 77-year-old Chinese woman.

RESULTS:The patient presented with ophthalmoplegia, ataxia, areflexia, and a sensory neuropathy within 2 weeks of immunization. Findings of parainfectious evaluation were unremarkable. Treatment with 2 courses of intravenous immunoglobulin led to clinical improvement. Her presentation and natural history of disease were similar to the 2 previously published cases.

CONCLUSIONS:We present the third case of postvaccination Miller Fisher syndrome in the literature and the first associated with the novel influenza A(H1N1) vaccine.