Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density ofμ-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal duringearly postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development.

Neonatal poliomyelitis, which was rare even when poliomyelitis was widespread, has not been reported in the United States since use of live oral poliovirus vaccine (Sabin's vaccine) became widespread. We report a child who became symptomatic with apnea at 18 days of age and who subsequently developed a permanent monoparesis. Serologic and cultural evidence indicated the virus as poliovirus vaccine type. Another infant who received live oral poliovirus vaccine was probably the source of the infecting virus. Recognition that poliovirus infection can still occur in the United States and an understanding of the serologic, cultural, and typing tests required to substantiate this diagnosis are needed so that such patients will be accurately diagnosed.

A 25-day-old infant developed varicella 22 days after her mother received varicella vaccine postpartum. Infection with vaccine-strain varicella-zoster virus was confirmed by genetic analysis. The mother had no postvaccination rash nor did other contacts have rash or recent vaccination. The potential means of transmission to the infant are explored.

BACKGROUND:Vaccinations are preventive measures against serious infections. In relation to the number of vaccinations per year, the incidence of severe complications is extremely low.

PATIENT:Two weeks after vaccinations against hepatitis A, hepatitis B and yellow fever in preparation for a trip to Africa a 21-year-old woman experienced an acute and irreversible loss of vision to 0,05 and nasal visual field defect in the left eye. Whereas vision acuity did not recover the scotoma disappeared within 6 weeks. Cerebrospinal fluid showed a lymphocytic pleocytosis. Oligoglonale bands were absent. Pathological parameters were not presented in the serum. The MRI showed a hyperintense thickening of optic nerve,as well as a hyperintense focus in right temporal side using the T(2)W-Sequence.

CONCLUSION:Only few cases have been reported with neurological complications, such as encephalitis, following vaccinations each of the above mentioned. As no other causes for the inflammation were found, the optic nerve involvement must have been caused by the vaccination. Which of the three vaccinations caused encephalitis can not be classified.

We report the brain magnetic resonance (MR) imaging abnormalities observed at the basal ganglia system of 5 patients (2 female and 3 male), who fulfilled the criteria of parkinsonism. The onset of parkinsonian syndrome ranged from 5 to 52 years old. All patients underwent MR exams with a 1.5T MR equipment. High field T2-weighted sequences disclosed hypersignal bilateral and symmetrically located exclusively at substantia nigra (3 cases), exclusively at globus pallidus (1case) and simultaneously at substantia nigra, globus pallidus and nigro-strital interconnections (1case). For three patients, the diagnose of secondary parkinsonism was supported by clinical data: the first had the onset of the symptoms after the exposure to an herbicide (glyphosate); the second after vaccination against measles; the third after coma due to encephalitis. For the other two patients, the onset of PS was progressive, resembling a typical idiopathic Parkinson's disease (PD) but the findings at the MR dimissed this initial diagnose. In this study, the contribution of neuroimaging was crucial to recognize secondary parkinsonism though the ethiological agents could not be determined in these patients.

Neuroparalytic accidents due to sample type rabies vaccination are still an important problem in our country. We present seven patients with ascending polyneuritis, due to rabies vaccine, treated between 1982-1986, and discuss the importance of the problem.

A relatively high incidence of chronic limb pain, frequently complicated by violent, tremulous involuntary movements, has been noted in Japanese girls following human papillomavirus vaccination. 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 feet, limb pain, and weakness. The skin temperature of the girls with limb symptoms was slightly lower in the fingers and moderately lower in the toes. Digital plethysmograms revealed a reduced peak of the waves, especially in the toes. Limb symptoms of the affected girls were compatible with the diagnostic criteria for complex regional pain syndrome. The Schellong test identified a significant number of patients with orthostatic hypotension and a few with postural orthostatic tachycardia syndrome. Electron-microscopic examinations of the intradermal nerves showed an abnormal pathology in the unmyelinated fibers in two of the three girls examined. The symptoms observed in this study can be explained by abnormal peripheral sympathetic responses. The most common previous diagnosis in the patients was psychosomatic disease. Recently, delayed manifestation of cognitive dysfunction in the post-vaccinated girls has attracted attention. The symptoms include memory loss and difficulty in reading textbooks and/or calculation.

Between April 1982 and June 1983 four children 3 to 24 months of age were referred for evaluation of neurologic abnormalities found to be compatible with vaccine-related poliovirus infection, which had not been suspected by referring physicians. Patients were epidemiologically unrelated residents of Indiana, and none had prior symptoms suggestive of immunodeficiency. All had received poliovirus vaccine orally (first dose in three, fourth dose in one) and a diphtheria-tetanus-pertussis injection in the left anterior thigh within 30 days of symptoms. A vaccine-like strain of poliovirus was isolated from each patient, and each had symptoms (left leg paralysis in three; developmental regression, spasticity, and progressive fatal cerebral atrophy in one) persisting for at least 6 months. Immune function was normal in two with poliovirus type 3 infection, and abnormal (hypogammaglobulinemia, combined immunodeficiency) in two with type 1 and type 2 infection, respectively. The incidence of observed vaccine-related poliovirus infection in Indiana recipients of orally administered poliovirus vaccine was 0.058 per 100,000 per year, significantly greater (P less than 0.001) than predicted.

[n/a]

OBJECTIVE:To examine the risk of neurological and autoimmune disorders of special interest in people vaccinated against pandemic influenza A (H1N1) with Pandemrix (GlaxoSmithKline, Middlesex, UK) compared with unvaccinated people over 8-10 months.

DESIGN:Retrospective cohort study linking individualised data on pandemic vaccinations to an inpatient and specialist database on healthcare utilisation in Stockholm county for follow-up during and after the pandemic period.

SETTING:Stockholm county, Sweden. Population All people registered in Stockholm county on 1 October 2009 and who had lived in this region since 1 January 1998; 1,024,019 were vaccinated against H1N1 and 921,005 remained unvaccinated.

MAIN OUTCOME MEASURES:Neurological and autoimmune diagnoses according to the European Medicines Agency strategy for monitoring of adverse events of special interest defined using ICD-10 codes for Guillain-Barré syndrome, Bell's palsy, multiple sclerosis, polyneuropathy, anaesthesia or hypoaesthesia, paraesthesia, narcolepsy (added), and autoimmune conditions such as rheumatoid arthritis, inflammatory bowel disease, and type 1 diabetes; and short term mortality according to vaccination status.

RESULTS:Excess risks among vaccinated compared with unvaccinated people were of low magnitude for Bell's palsy (hazard ratio 1.25, 95% confidence interval 1.06 to 1.48) and paraesthesia (1.11, 1.00 to 1.23) after adjustment for age, sex, socioeconomic status, and healthcare utilisation. Risks for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis remained unchanged. The risks of paraesthesia and inflammatory bowel disease among those vaccinated in the early phase (within 45 days from 1 October 2009) of the vaccination campaign were significantly increased; the risk being increased within the first six weeks after vaccination. Those vaccinated in the early phase were at a slightly reduced risk of death than those who were unvaccinated (0.94, 0.91 to 0.98), whereas those vaccinated in the late phase had an overall reduced mortality (0.68, 0.64 to 0.71). These associations could be real or explained, partly or entirely, by residual confounding.

CONCLUSIONS:Results for the safety of Pandemrix over 8-10 months of follow-up were reassuring -notably, no change in the risk for Guillain-Barré syndrome, multiple sclerosis, type 1 diabetes, or rheumatoid arthritis. Relative risks were significantly increased for Bell's palsy, paraesthesia, and inflammatory bowel disease after vaccination, predominantly in the early phase of the vaccination campaign. Small numbers of children and adolescents with narcolepsy precluded any meaningful conclusions.

Since the introduction of H1N1 influenza vaccine in the wake of the 2009 H1N1 pandemic, many serious and non-serious vaccine-related adverse events have been reported. The vaccination could induce pain, erythema, tenderness, and induration on injected areas. These symptoms usually disappear in a few days after the vaccination. In this case, we observed a 26-year-old woman with multiple erythematous scaly macules scattered on the extremities and trunk. She was injected with an inactivated split-virus influenza A/H1N1 vaccine without adjuvant (Greenflu-S®, Green Corp.) on her left deltoid area 10 days earlier. The first lesion appeared on the injection site three days after the vaccination, and the following lesions spread to the trunk and extremities after a few days. Histopathological examinations showed neutrophilic collections within the parakeratotic cornified layer, moderate acanthosis, diminished granular layer, elongation and edema of the dermal papillae, and dilated capillaries. The lesions were successfully treated with topical steroids and ultraviolet B phototherapy within three weeks, and there was no relapse for the following fourteen months. We assumed that pandemic vaccination was an important trigger for the onset of guttate psoriasis in this case.

Aluminium (Al) oxyhydroxide (Alhydrogel(®)), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoidorgans and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180days after injection of various doses of Alhydrogel(®) (200, 400 and 800μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel(®) was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200μg Al/kg but not at 400 and 800μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost completely disappeared at 6 months in these animals. We conclude that Alhydrogel(®) injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose, but not to the highest doses, exclusively contained small agglomerates in the bacteria-size range known to favour capture and, presumably, transportation by monocyte-lineage cells. In any event, the view that Alhydrogel(®) neurotoxicity obeys"the dose makes the poison"rule of classical chemical toxicity appears overly simplistic.

Live measles vaccine (MV) may have beneficial off-target/non-specific effects (NSEs) reducing child mortality beyond prevention of measles infection. In contrast, the non-live pentavalent (Diphtheria-Tetanus-Pertussis-H. influenzae Type B-Hepatitis B) vaccine has no beneficial NSEs. The NSEs are strongest for the most recent vaccine. Hence, sequence of vaccination may affect survival. In Guinea-Bissau, we followed 7094 measles-vaccinated children prospectively from first home visit after 9 months (when MV is scheduled) to 5 years of age. We compared survival by sequence of MV and third Pentavalent vaccine (Penta3; scheduled at 3½ months) in Cox proportional-hazards models. Compared with being vaccinated in-sequence (Penta3-then-MV), having received out-of-sequence Penta3-after-MV before the visit was associated with an adjusted Hazard Ratio (aHR) of 1.19 (95%CI: 0.84-1.69); Receiving missing Penta doses on the visit date tended to be associated with higher mortality (aHR = 1.87 (0.96-3.65)) while not receiving missing doses of Penta was not (aHR = 0.93 (0.57-1.54)), test for interaction p = 0.09.

We report the case of a child presenting with nonfebrile seizures 6 and 13 days after the first vaccination with a measles, mumps, rubella, and varicella (MMRV) combination vaccine. Measles virus RNA was detected in the patient's serum, throat, and urine. Genotyping revealed the Schwarz vaccine virus strain.

2-Phenoxyethanol, used as an anesthetic for handling small fish at a salmon hatchery, caused three women to experience headache and symptoms of intoxication during use, followed by diminished sensation and strength of hands and fingers, worse in the preferred hand. Persistent neuropathy did not develop in any of them. After 1 to 2 years of exposure, the women manifested gradual onset of symptoms of cognitive impairment with an inability to work. Neuropsychologic testing verified that all three had focal cognitive impairments that persisted. One also had documented labyrinthine hypofunction, which originated during this exposure. The immediate and delayed effects of 2-phenoxyethanol on the central nervous system resemble those of the other organic solvents.

A patient developed severe ocular vaccinia via autoinoculation after acquiring unrecognized contact-transmitted vaccinia from wrestling with vaccinated members of his unit. This case highlights both the need to reinforce infection-control measures among vaccinees and the need for providers to be familiar with the identification and treatment of cutaneous and ocular vaccinia infection.

BACKGROUND:In 2013-15, Denmark experienced an increase in reported suspected adverse events following vaccination (AEFI) against human papilloma virus (HPV). Dedicated centres ("One Access") were established in order to standardize management of patients who experienced medically unexplained physical symptoms after HPV vaccination. Since One Access was targeted patients with suspected AEFI after HPV vaccination, we used this opportunity to estimate completeness in AEFI reporting to the Danish Medicines Agency (DMA), and explore the topic of AEFI reporting from the perspective of physicians working at the centres to better understand health professionals' reporting behaviour.

METHODS:The study consisted of a quantitative and a qualitative part. In the quantitative analysis, we used the Danish civil registry number to merge a line-list of all One Access patients referred in 2015 with total number of patients who had reported suspected serious AEFI following HPV vaccination to the DMA in the years 2009-2015. We conducted four semi-structured interviews with doctors representing three out of five regions. The Theoretical Domains Framework together with empirical data from two clinical fieldtrips guided the formation of the qualitative study.

RESULTS:Among 1577 One Access patients, only 404 (26%) were reported to the DMA. We found significant regional differences in reporting completeness (p < 0.001) and differences between regions when looking at reporters' backgrounds (healthcare professionals vs non-professionals; p = 0.004). We identified several factors of importance for reporting behaviour amongst physicians, mainly under the domains of Knowledge, Motivation&Goals, and Environmental Context.

CONCLUSIONS:Despite an official aim of homogenous case management, reporting of suspected AEFI was incomplete with large regional differences. The qualitative study corroborated that reporting behaviour was contextual. This observation represents an important caveat in interpreting data from AEFI reporting, in particular when these data are used for research or policymaking.

The human papilloma virus (HPV) vaccines were introduced to reduce the incidence of cervical cancer. The bivalent vaccine is effective against HPV-16, -18, -31, -33 and -45 while the quadrivalent vaccine is effective against HPV-16, 18, 31, 6 and 11 types. The immunisation, recommended for adolescent females, has led to high vaccine coverage in many countries. Along with the introduction of the HPV vaccines, several cases of onset or exacerbations of autoimmune diseases following the vaccine shot have been reported in the literature and pharmacovigilance databases, triggering concerns about its safety. This vaccination programme, however, has been introduced in a population that is at high risk for the onset of autoimmune diseases, making it difficult to assess the role of HPV vaccine in these cases and no conclusive studies have been reported thus far. We have thus analysed and reviewed comprehensively all case reports and studies dealing with either the onset of an autoimmune disease in vaccinated subject or the safety in patients with autoimmune diseases to define the role of the HPV vaccines in these diseases and hence its safety. A solid evidence of causal relationship was provided in few cases in the examined studies, and the risk vs. benefit of vaccination is still to be solved. The on-going vigilance for the safety of this vaccine remains thus of paramount importance.

[n/a]

We report the ophthalmological and laboratory findings of 6 patients who, after influenza vaccination, were affected by oculorespiratory syndrome (ORS), complaining of red eyes, photophobia, blurred vision, palpebral edema, ocular pain and itching, and conjunctival secretions. The conjunctivae were mildly hyperemic with few follicles, but the ophthalmological examination findings were otherwise normal. Patients had lymphopenia and decreased levels of the total hemolytic complement and the third and fourth component of the complement. We conclude that ORS causes conjunctivitis and seems to involve the complement.