BACKGROUND:Evans' syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia purpura and autoimmune hemolytic anemia with a positive direct antiglobulin test in the absence of known underlying etiology.

OBJECTIVES:We present a case of Evans' syndrome following influenza vaccination.

CASE REPORT:A 50-year-old man with no prior medical history developed Evans' syndrome 4 days after receiving influenza immunization. The patient improved following treatment with oral prednisone and intravenous immunoglobulin.

CONCLUSION:Influenza vaccine is one of the most commonly used vaccines worldwide, with millions of people being vaccinated annually. Despite its wide use, only sparse information has been published concerning any hematological effects of this vaccine. The rarity of such effects supports the safety of using this vaccine.

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BACKGROUND:The 2014-2015 influenza season was distinguished by an epidemic of antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013-2014. We report 2014-2015 vaccine effectiveness (VE) from Canada and explore contributing agent-host factors.

METHODS:VE against laboratory-confirmed influenza was derived using a test-negative design among outpatients with influenza-like illness. Sequencing identified amino acid mutations at key antigenic sites of the viral hemagglutinin protein.

RESULTS:Overall, 815/1930 (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%) influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577; 99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460 (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations F159Y (a cluster-transition position) and K160T (a predicted gain of glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2) was -17% (95% confidence interval [CI], -50% to 9%) overall with clade-specific VE of -13% (95% CI, -51% to 15%) for clade 3C.2a but 52% (95% CI, -17% to 80%) for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients vaccinated in 2014-2015 only, significantly lower at -32% (95% CI, -75% to 0%) if also vaccinated in 2013-2014 and -54% (95% CI, -108% to -14%) if vaccinated each year since 2012-2013. VE against clade-mismatched B(Yamagata) viruses was 42% (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination compared to A(H3N2).

CONCLUSIONS:Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014-2015.

BACKGROUND This study evaluated the hypothesis that the 1999 recommendation by the American Academy of Pediatrics (AAP) and US Public Health Service (PHS) to reduce exposure to mercury (Hg) from Thimerosal in US vaccines would be associated with a reduction in the long-term risk of being diagnosed with autism.

MATERIAL AND METHODS A two-phase assessment utilizing a case (n=73) -control (n=11,783) study in the Vaccine Adverse Event Reporting System (VAERS) database (for hypothesis generating) and a more rigorous, independent matched case (n=40) -control (n=40) study (hypothesis testing) was undertaken.

RESULTS Analysis of the VAERS database using logistic regression revealed that the odds ratio (OR) for being an autism case in the VAERS database significantly decreased with a more recent year of vaccination in comparison to controls (OR=0.65) from 1998 to 2003. Sex-separated analyses revealed similar significant effects for males (OR=0.62) and females (OR=0.71). Analyses of the matched case-control data revealed, using the t-test statistic, that the mean date of birth among cases diagnosed with an autism spectrum disorder (ASD) (2000.5±1.2) was significantly more in the past than in controls (2001.1±1.3). Logistic regression also revealed that the OR for being diagnosed with ASD significantly decreased with a more recent date of birth in comparison to controls (OR=0.67) from 1998-2003. CONCLUSIONS This study reveals that the risk of autism during from the late1990s to early 2000s in the US significantly decreased with reductions in Hg exposure from Thimerosal-containing childhood vaccines, but future studies should examine this phenomenon in other US populations. Vaccine programs have significantly reduced the morbidity and mortality associated with infectious disease, but Thimerosal should be removed from all vaccines.

A 22-year-old woman with no significant medical history developed acute left shoulder pain and severe restrictions in range of motion after a seasonal influenza vaccine injection. Imaging by MRI, approximately 8 weeks after the injection, and by ultrasound, approximately 9.5 weeks after the injection demonstrated contusions on the humerus, injury of the supraspinatus, and effusion in the subacromial bursa. Her reaction was reported to the Vaccine Adverse Event Reporting System as a case of shoulder injury related to vaccine administration, likely due to injection of the influenza vaccine into the subacromial bursa. This case serves as a catalyst for discussion regarding vaccination technique and the potential to prevent complications arising from vaccine overpenetration.

Acute disseminated encephalomyelitis is an inflammatory demyelinating disease of the central nervous system that has been associated with influenza immunization, but only a few cases related to vaccination for influenza have been reported. Acute disseminated encephalomyelitis developed in a 42-year-old woman within 3 weeks of receiving the seasonal influenza vaccine. She had 80% recovery after 3 months of treatment with methylprednisolone. Although cases of acute disseminated encephalomyelitis after vaccination for influenza are rare, enough of them have occurred that critical care nurses should be aware of the possibility. Early treatment can prevent serious residual signs and symptoms; therefore, correct and quick diagnosis is important. Medical history obtained from patients with central nervous system problems should include history of recent vaccinations.

Here, we describe a case of acute disseminated encephalomyelitis (ADEM) that occurred during a plausible risk interval following inactivated influenza vaccination in a previously healthy 27-year-old man from Manaus, Brazil. He was treated with intravenous methylprednisolone and immunoglobulin. One-month follow-up revealed resolution of the brain lesions, but not of the spinal cord lesions. No recurrence or progression of the main neurological symptoms was observed. After two years of monitoring, the patient continues to experience weak lower limbs and urinary retention. Thus, we recommend that ADEM should be considered in a patient presenting with neurological symptoms after influenza vaccination.

We present a case of callosal disconnection syndrome as a rare manifestation of acute disseminated encephalomyelitis (ADEM). A dextral 48-year-old Japanese woman received trivalent inactivated influenza vaccine in mid-November 2011. Twenty days later, she was found to be in a daze. Subsequently, she developed abnormal behavior and gait disturbance, and she was disoriented regarding time and place. Nystagmus and abnormal ocular movements were absent. Upper limb power was normal, whereas her lower limbs were mildly weak. Tendon reflexes were normally evoked without pathological reflexes. There was no sensory impairment. Serum CRP levels were slightly elevated; other routine laboratory tests, thyroid functions, and vitamin B1 levels were within the normal range. Cerebrospinal fluid examination revealed that it was acellular with a protein level of 54 mg/dl and high myelin basic protein level. Fluid-attenuated inversion recovery MR images revealed a large hyperintense lesion in the corpus callosum, but the lower part of the splenium was spared. Flow voids were observed in the pericallosal arteries. She was diagnosed with post-vaccination ADEM and vigorously treated with an intravenous infusion of methylprednisolone (1 g/day for 6 days) and immunoglobulin (1.2 g/kg). Gait disturbance and disorientation rapidly improved; however, tactile anomia, ideomotor apraxia, ideational apraxia, and agraphia of the left hand were present one month after onset. She had no aphasia or alexia.Interestingly, the patient's left unilateral agraphia was more prominent in kana than kanji (an article in Japanese text) for polysyllabic words, whereas she could write kana characters to dictation. Changes in the sequential order of kana characters within a word were observed. These findings were similar to those observed in pure agraphia associated with lesions in the posterior part of the left middle frontal gyrus. Thus, an interhemispheric mechanism is probably involved in the selection and arrangement of kana characters to form words.

Although such occurrences are rare, it should be recognized that certain vaccines might trigger serious neurological immune phenomena such as Guillain-Barre syndrome, seizures, cranial neuropathy, and acute disseminated encephalomyelitis (ADEM). Here we report on an elderly woman with ADEM following seasonal influenza vaccination who recovered after plasma exchange.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory, usually monophasic, immune mediate, demyelinating disease of the central nervous system which involves the white matter. ADEM is more frequent in children and usually occurs after viral infections, but may follow vaccinations, bacterial infections, or may occur without previous events. Only 5% of cases of ADEM are preceded by vaccination within one month prior to symptoms onset. The diagnosis of ADEM requires both multifocal involvement and encephalopathy and specific demyelinating lesions of white matter. Overall prognosis of ADEM patients is often favorable, with full recovery reported in 23% to 100% of patients from pediatric cohorts, and more severe outcome in adult patients. We describe the first case of ADEM occurred few days after administration of virosomal seasonal influenza vaccine. The patient, a 59-year-old caucasic man with unremarkable past medical history presented at admission decreased alertness, 10 days after flu vaccination. During the 2 days following hospitalization, his clinical conditions deteriorated with drowsiness and fever until coma. The magnetic resonance imaging of the brain showed multiple and symmetrical white matter lesions in both cerebellar and cerebral hemispheres, suggesting demyelinating disease with inflammatory activity, compatible with ADEM. The patient was treated with high dose of steroids and intravenous immunoglobulin with relevant sequelae and severe neurological outcomes.

We report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) after pandemic influenza (H1N1) vaccination. A 57-year-old man, who had been diagnosed with IPF in September 2008, was admitted to our hospital in December 2009 because of aggravation of dyspnea and fever two days after H1N1 vaccination. Chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities. We diagnosed AE-IPF. Corticosteroid and cyclophosphamide were effective. Although the efficacy of influenza vaccination in patients with chronic lung diseases is well established, physicians should keep in mind that influenza vaccination has the potential to cause AE-IPF.

Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

Descriptions in the literature of magnetic resonance imaging (MRI) findings in post-vaccination myelitis are scarce. Described here is a case of acute transverse myelitis that occurred after administration of an influenza vaccination. T1-weighted MRIs showed diffuse, fusiform spinal cord enlargement, extending from C-3 to rostral thoracic levels. Intramedullary lesions containing increased T2 signal were found in the areas of cord enlargement. The involvement on MRI was profound, extending far rostral to the level of the discrete clinical myelopathy. The lesions did not enhance after contrast administration. The patient had a complete long-term recovery of neurological function. This represents the first report of MRI findings in acute transverse myelitis after influenza vaccination.

H1N1 vaccination is currently safe, and only rare acceptable side-effects have been reported. Here we describe for the first time a serious adverse event, i.e., acute transverse myelitis, following H1N1 vaccination in China. After the standard treatment with methylprednislone, the patient recovered completely.

Australia was alerted to a possible increase in allergy-related adverse events following immunisation (AEFI) with 2015 seasonal trivalent influenza vaccines (TIV) by the Victorian state vaccine safety service, SAEFVIC. We describe SAEFVIC's initial investigation and upon conclusion of the 2015 influenza vaccination programme, to define the signal event and implications for vaccine programmes. Allergy-related AEFI were defined as anaphylaxis, angioedema, urticaria or generalised allergic reaction. Investigations compared 2015 TIV AEFI reports to previous years as proportions and reporting risk (RR) per 100,000, stratified by influenza vaccine brand. The initial investigation showed an increased proportion of allergy-related AEFI compared with 2014 (25% vs 12%), predominantly in adults, with insufficient clinical severity to alter the programme risk-benefit. While overall TIV AEFI RR in 2015 was similar to previous years (RR: 1.07, 95% confidence interval (CI): 0.88-1.29), we identified a near-doubling RR for allergy-related AEFI in 2015 (RR: 1.78, 95% CI: 1.14-- 2.80) from 2011 to 2014 with no difference by vaccine brand or severity increase identified. This increase in generalised allergy-related AEFI, across all used vaccine brands, supports evidence of variable reactogenicity arising from influenza vaccine strain variations. This investigation underlines the importance of effective seasonal influenza vaccine pharmacovigilance.

Allergic alveolitis as a side effect of vaccination is very rare. We report a life-threatening complication in a female patient after influenza vaccination. The causative antigen was the influenza virus itself. Our Patient has suffered from exogen-allergic alveolitis for 12 years. Because of the guidelines of regular administration of influenza vaccination in patients with chronic pulmonary disease further research in patients with known exogen-allergic alveolitis is vitally important for the pharmaceutical drug safety.

Kawasaki disease (KD) is a childhood vascular disorder of unknown etiology. Concerns have recently been raised regarding vaccinations as a potential risk factor for KD. In addition, various forms of vasculitis have been reported as adverse events following administration after various vaccines. Patients exhibiting post vaccination KD have previously been described; however, thus far, to the best of our knowledge, only one patient exhibiting post influenza vaccination KD has been reported in Japan. The present study describes a case of KD 24 h after immunization with influenza in an infant (age, 18 months) following 6 days of high fever, a body rash that had persisted for 2 days and nonsuppurative bilateral conjunctivitis. To the best of the authors' knowledge, this is the first reported case in Korea and the present study reviews various recent studies regarding vasculitis following vaccination and the causal association between them.

BACKGROUND:Allergic reactions to the influenza vaccine are uncommon and usually associated with sensitivity to egg or gelatin. The aim of this study was to report the case of anaphylaxis to the influenza vaccine.

METHODS:Allergy percutaneous skin testing, serum specific IgE testing and IgE immunoblotting were performed to the influenza vaccine, egg, and gelatin.

RESULTS:Percutaneous skin testing to the influenza vaccine and gelatin were positive and egg (white, whole, and yolk) was negative. Immunocap serum-specific IgE testing to egg (white, whole, and yolk) and gelatin were negative (<0.35 kU/l). IgE immunoblots were performed with 2 cord blood serums and the patient's serum at a 1:20 dilution against 10 microg of the Fluzone influenza vaccine. The patient's IgE immunoblot showed a protein band at 100 kDa which is similar to the molecular weight of gelatin protein, a 68-kDa protein which is similar to the molecular weight of hemagglutinin protein from the influenza vaccine, and a 45-kDa protein band that is similar to the molecular weight of ovalbumin protein from chicken embryo/egg.

CONCLUSION:Based on clinical symptoms, skin testing, Immunocap testing and immunoblot evaluation, we feel that our patient is allergic to the infectious agent in the influenza vaccine as well as gelatin and ovalbumin in egg.

Importance:Maternal infections and fever during pregnancy are associated with increased risk for autism spectrum disorders (ASDs). To our knowledge, no study has investigated the association between influenza vaccination during pregnancy and ASD.

Objective:To investigate the association between influenza infection and vaccination during pregnancy and ASD risk.

Design, Setting, and Participants:This cohort study included 196 929 children born at Kaiser Permanente Northern California from January 1, 2000 to December 31, 2010, at a gestational age of at least 24 weeks.

Exposures:Data on maternal influenza infection and vaccination from conception date to delivery date, obtained from Kaiser Permanente Northern California inpatient and outpatient databases. Influenza infection was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification codes or positive influenza laboratory test results.

Main Outcomes and Measures:Clinical diagnoses of ASDs identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes 299.0, 299.8, or 299.9 recorded in Kaiser Permanente Northern California electronic medical records on at least 2 occasions any time from birth through June 2015.

Results:Within this cohort of 196 929 children, influenza was diagnosed in 1400 (0.7%) mothers and 45 231 (23%) received an influenza vaccination during pregnancy. The mean (SD) ages of vaccinated and unvaccinated women were 31.6 (5.2) and 30.4 (5.6) years, respectively. A total number of 3101 (1.6%) children were diagnosed with ASD. After adjusting for covariates, we found that maternal influenza infection (adjusted hazard ratio, 1.04; 95% CI, 0.68-1.58) or influenza vaccination (adjusted hazard ratio, 1.10; 95% CI, 1.00-1.21) anytime during pregnancy was not associated with increased ASD risk. In trimester-specific analyses, first-trimester influenza vaccination was the only period associated with increased ASD risk (adjusted hazard ratio, 1.20; 95% CI, 1.04-1.39). However, this association could be due to chance (P = 0.1) if Bonferroni corrected for the multiplicity of hypotheses tested (n = 8). Maternal influenza vaccination in the second or third trimester was not associated with increased ASD risk.

Conclusions and Relevance:There was no association between maternal influenza infection anytime during pregnancy and increased ASD risk. There was a suggestion of increased ASD risk among children whose mothers received an influenza vaccination in their first trimester, but the association was not statistically significant after adjusting for multiple comparisons, indicating that the finding could be due to chance. These findings do not call for changes in vaccine policy or practice, but do suggest the need for additional studies on maternal influenza vaccination and autism.

INTRODUCTION:Inactivated influenza vaccine is recommended in any stage of pregnancy, but evidence of safety in early pregnancy is limited, including for vaccines containing A/H1N1pdm2009 (pH1N1) antigen. We sought to determine if receipt of vaccine containing pH1N1 was associated with spontaneous abortion (SAB).

METHODS:We conducted a case-control study over two influenza seasons (2010-11, 2011-12) in the Vaccine Safety Datalink. Cases had SAB and controls had live births or stillbirths and were matched on site, date of last menstrual period, and age. Of 919 potential cases identified using diagnosis codes, 485 were eligible and confirmed by medical record review. Exposure was defined as vaccination with inactivated influenza vaccine before the SAB date; the primary exposure window was the 1-28days before the SAB.

RESULTS:The overall adjusted odds ratio (aOR) was 2.0 (95% CI, 1.1-3.6) for vaccine receipt in the 28-day exposure window; there was no association in other exposure windows. In season-specific analyses, the aOR in the 1-28days was 3.7 (95% CI 1.4-9.4) in 2010-11 and 1.4 (95% CI 0.6-3.3) in 2011-12. The association was modified by influenza vaccination in the prior season (post hoc analysis). Among women who received pH1N1-containing vaccine in the previous influenza season, the aOR in the 1-28days was 7.7 (95% CI 2.2-27.3); the aOR was 1.3 (95% CI 0.7-2.7) among women not vaccinated in the previous season. This effect modification was observed in each season.

CONCLUSION:SAB was associated with influenza vaccination in the preceding 28days. The association was significant only among women vaccinated in the previous influenza season with pH1N1-containing vaccine. This study does not and cannot establish a causal relationship between repeated influenza vaccination and SAB, but further research is warranted.