Barbara Pahud

Varicella Zoster Disease of the Central Nervous System: Epidemiological, Clinical, and Laboratory Features 10 Years after the Introduction of the Varicella Vaccine

BACKGROUND Since the introduction of live attenuated varicella zoster virus (VZV) vaccine in 1995 there has been a significant reduction in varicella incidence and its associated complications, but the impact on VZV-associated central nervous system (CNS) disease has not been assessed. METHODS In this descriptive study we evaluated patients referred to the California Encephalitis Project from 1998 to 2009 with VZV PCR-positive cerebrospinal fluid (CSF). Epidemiological, clinical, and laboratory data were collected using a standardized case form. Specimens were genotyped using multi-single nucleotide polymorphism (SNP) analysis. RESULTS Twenty-six specimens were genotyped from patients 12-85 years of age (median, 46 years). Clinical presentations included meningitis (50%), encephalitis (42%), and acute disseminated encephalomyelitis (ADEM) (8%). Only 11 patients (42%) had a concomitant herpes zoster rash. Genotype analysis identified 20 European Group (Clade1, Clade 3) strains; 4 Asian (Clade 2) strains, and 2 Mosaic Group (Clade 4, Clade VI) strains. One specimen was recognized as vaccine strain by identifying vaccine-associated SNPs. CONCLUSIONS VZV continues to be associated with CNS disease, with meningitis being the most frequent clinical presentation. CNS VZV disease often presented without accompanying zoster rash. Sequencing data revealed multiple genotypes, including 1 vaccine strain detected in the CSF of a young patient with meningitis.

Narcolepsy as an adverse event following immunization: case definition and guidelines for data collection, analysis and presentation.

rancesca Poli a,2, Sebastiaan Overeemb,∗,2, Gert Jan Lammersc,2, Giuseppe Plazzia,2, ichel Lecendreuxd,2, Claudio L. Bassetti e,1,2, Yves Dauvilliers f,1,2, Daniel Keeneg,1,2, amin Khatamih,1,2, Yulin Li i,j,1,2, Geert Mayerk,1,2, Hanna Nohynekl,1,2, Barbara Pahudm,1,2, eresa Paivan,1,2, Markku Partineno,1,2, Thomas E. Scammellp,1,2, Tom Shimabukuroq,1,2, iriam Sturkenboomr,1,2, Kristy van Dinthers,1,2, Max Wiznitzer t,1,2, Jan Bonhoeffer i,j,2

Vasculitis as an adverse event following immunization - Systematic literature review.

BACKGROUND Several types of vasculitis have been observed and reported in temporal association with the administration of various vaccines. A systematic review of current evidence is lacking. OBJECTIVE This systematic literature review aimed to assess available evidence and current reporting practice of vasculitides as adverse events following immunization (AEFI). METHODS We reviewed the literature from 1st January 1994 to 30th June 2014. This review comprises randomized controlled trials, observational studies, case series, case reports, reviews and comments regardless of vaccine and target population. RESULTS The initial search resulted in the identification of 6656 articles. Of these, 157 articles were assessed for eligibility and 75 studies were considered for analysis, including 6 retrospective/observational studies, 2 randomized controlled trials, 7 reviews, 11 case series, 46 case reports and 3 comments. Most of the larger, higher quality studies found no causal association between vaccination and subsequent development of vasculitis, including several studies on Kawasaki disease and Henoch-Schönlein purpura (IgA vasculitis). Smaller case series reported a few cases of vasculitis following BCG and vaccines against influenza and hepatitis. Only 24% of the articles reported using a case definition of vasculitis. CONCLUSIONS Existing literature does not allow establishing a causative link between vaccination and vasculitides. Further investigations were strengthened by the use of standardized case definitions and methods for data collection, analysis and presentation to improve data comparability and interpretation of vasculitis cases following immunization.

Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004–2009

BACKGROUND In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical Immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). METHODS Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. RESULTS CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of the cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. CONCLUSIONS The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations.

Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: reports to VAERS.

BACKGROUND Hypersensitivity disorders following vaccinations are a cause for concern. OBJECTIVE To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. DESIGN A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. SETTING/PATIENTS US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. MEASUREMENTS Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. RESULTS Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. LIMITATIONS Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. CONCLUSIONS Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity reactions.

Apophysomyces trapeziformis infection associated with a tornado-related injury.

This report defines the role of Apophysomyces as an aggressive fungal pathogen seen after a tornado injury. Clinical and laboratory manifestations of infections after environmentally contaminated wounds incurred during a tornado are outlined, emphasizing mechanism of injury, comorbidities, and diagnostic and treatment challenges. Therapy with systemic antifungal therapy and aggressive serial tissue debridement was successful in achieving cure.

Lack of association between childhood immunizations and encephalitis in California, 1998-2008.

OBJECTIVE A number of new and combination vaccines have been introduced for children in the past two decades. Encephalitis cases occurring within defined time windows following administration of pertussis- or measles-containing vaccines are eligible for compensation by the Vaccine Injury Compensation Program. Due to increased parental concerns about vaccine safety and potential neurologic adverse events following immunization with new and multiple vaccines administered at the same visit, our aim was to determine whether immunizations are associated with an increased risk of encephalitis within defined risk windows. METHODS We reviewed immunization records from 246 pediatric encephalitis cases referred to the California Encephalitis Project between July 1998 and December 2008. We included data on 110 cases who had been immunized in the year prior to the onset of encephalitis (observation period) and had complete immunization records. We used the case-centered method to test whether cases were more likely to have developed encephalitis in defined risk windows-42, 30 and 21 days after any vaccination, 3 days after pertussis-containing vaccines and 5-15 days after measles-virus containing vaccines-compared with the rest of the observation period. RESULTS All vaccines recommended in the current immunization schedule were represented in our sample. No increased risk of encephalitis was seen following administration of pertussis-containing vaccines, measles-containing vaccines or any number of vaccines administered in a single visit (vaccine episode); the odds ratios and 95% confidence intervals for encephalitis after a vaccine episode were: 1.0 (0.6-1.8) in a 42-day risk window, 0.9 (0.5-1.6) in a 30-day risk window and 1.2 (0.7-2.2) in a 21-day risk window. CONCLUSION No association between receipt of currently recommended immunizations and subsequent development of encephalitis was observed in this study.

Clinical Course of Enterovirus D68 in Hospitalized Children

BACKGROUND Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. METHODS A retrospective chart review was performed of children admitted to Childrens Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records. Patients with EV-D68 were compared with children presenting simultaneously with other EV/RV. RESULTS Of 542 eligible specimens, children with EV-D68 were significantly older than children with other EV/RV (4.6 vs. 2.2 years, P < 0.001). Children with EV-D68 were more likely to have a history of asthma (38.6% vs. 30.0%, P = 0.04) or recurrent wheezing (22.1% vs. 14.8%, P = 0.04). EV-D68-positive children more commonly received supplemental oxygen (86.7% vs. 65.0%, P < 0.001), albuterol (91.2% vs. 65.5%, P < 0.001) and corticosteroids (82.9% vs. 58.6%, P < 0.001). Age ≥5 years was an independent risk factor for intensive care unit management in EV-D68-infected children. Children with a history of asthma or recurrent wheezing and EV-D68 received supplemental oxygen (92.7% vs. 82.4%, P = 0.007) and magnesium (42.7% vs. 29.7%, P = 0.03) at higher rates and more continuous albuterol (3 vs. 2 hours, P = 0.03) than those with other EV/RV. CONCLUSIONS EV-D68 causes severe disease in the pediatric population, particularly in children with a history of asthma or recurrent wheezing. EV-D68-positive children are more likely to require therapy for refractory bronchospasm and may need intensive care unit- level care.Background: Enterovirus D68 (EV-D68) has been sporadically reported as a cause of respiratory tract infections. In 2014, an international outbreak of EV-D68 occurred and caused severe respiratory disease in the pediatric population. Methods: A retrospective chart review was performed of children admitted to Children’s Mercy Hospital from August 1, 2014, to September 15, 2014, with positive multiplex polymerase chain reaction testing for EV/rhinovirus (RV). Specimens were subsequently tested for EV-D68, and clinical data were obtained from the medical records. Patients with EV-D68 were compared with children presenting simultaneously with other EV/RV. Results: Of 542 eligible specimens, children with EV-D68 were significantly older than children with other EV/RV (4.6 vs. 2.2 years, P < 0.001). Children with EV-D68 were more likely to have a history of asthma (38.6% vs. 30.0%, P = 0.04) or recurrent wheezing (22.1% vs. 14.8%, P = 0.04). EV-D68–positive children more commonly received supplemental oxygen (86.7% vs. 65.0%, P < 0.001), albuterol (91.2% vs. 65.5%, P < 0.001) and corticosteroids (82.9% vs. 58.6%, P < 0.001). Age ≥5 years was an independent risk factor for intensive care unit management in EV-D68–infected children. Children with a history of asthma or recurrent wheezing and EV-D68 received supplemental oxygen (92.7% vs. 82.4%, P = 0.007) and magnesium (42.7% vs. 29.7%, P = 0.03) at higher rates and more continuous albuterol (3 vs. 2 hours, P = 0.03) than those with other EV/RV. Conclusions: EV-D68 causes severe disease in the pediatric population, particularly in children with a history of asthma or recurrent wheezing. EV-D68–positive children are more likely to require therapy for refractory bronchospasm and may need intensive care unit– level care.

Kawasaki disease and immunisation: Standardised case definition & guidelines for data collection, analysis

http://dx.doi.org/10.1016/j.vaccine.2016.09.025 0264-410X/ 2016 Published by Elsevier Ltd. Abbreviations: ADR, adverse drug reaction; AHA, American Heart Association; ALT, alanine transaminase; AST, aspartate transaminase; BCG, Bacillus Calmette (vaccine); CAAs, coronary artery aneurysms; CMRA, cardiac magnetic resonance angiography; CRP, C-reactive protein; DTP, diphtheria, tetanus, pertussis diphtheriatetanus, acellular pertussis; EBV, Epstein Barr Virus; ESR, erythrocyte sedimentation rate; GGT, gamma glutamyl transferase; HHV, human herpes vi Haemophilus influenza type b; HPF, high powered field; HSP, heat shock protein; IVIG, intravenous gamma globulin; JMoH, Japanese Ministry of Health; KD, Kawasaki LAD, left anterior descending; LV, left ventricular; MRI, magnetic resonance imaging; MSCT, multi, slice computed tomography; PAN, polyarteritis nodosa; PCV, pneum conjugate vaccine; PCR, polymerase chain reaction; RCA, right coronary artery; RMSF, Rocky Mountain Spotted Fever; RTPE,, recurrent toxin, mediated perineal er sJIA, systemic juvenile idiopathic arthritis; SPECT, single photon emission computed tomography; TSS, toxic shock syndrome; TST, tuberculin skin test; WBC, wh cells. ⇑ Corresponding author at: The Brighton Collaboration Foundation, c/o Universitäts-Kinderspital beider Basel, Spitalstrasse 33, 4056 Basel, Switzerland. E-mail address: contact@brightoncollaboration.org (J. Bonhoeffer). 1 Brighton Collaboration homepage: http://www.brightoncollaboration.org.

Clinical assessment of serious adverse events in children receiving 2009 H1N1 vaccination.

Background: Monovalent 2009 H1N1 influenza vaccines were licensed and administered in the United States during the H1N1 influenza pandemic between 2009 and 2013. Methods: Vaccine Adverse Event Reporting System received reports of adverse events following immunization (AEFI) after H1N1 vaccination. Selected reports were referred to the Centers for Disease Control and Prevention’s Clinical Immunization Safety Assessment network for additional review. We assessed causality using modified World Health Organization criteria. Results: There were 3,928 reports of AEFI in children younger than age 18 years after 2009 H1N1 vaccination received by January 31, 2010. Of these, 214 (5.4%) were classified as serious nonfatal and 109 were referred to Clinical Immunization Safety Assessment for further evaluation. Ninety-nine (91%) had sufficient initial information to begin investigation and are described here. The mean age was 8 years (range, 6 months–17 years) and 38% were female. Median number of days between vaccination and symptom onset was 2 (range, −11 days to +41 days). Receipt of inactivated, live attenuated, or unknown type of 2009 H1N1 vaccines was reported by 68, 26 and 5 cases, respectively. Serious AEFI were categorized as neurologic events in 47 cases, as hypersensitivity in 15 cases and as respiratory events in 10 cases. At the time of evaluation, recovery was described as complete (61), partial (16), no improvement (1), or unknown (21). Causality assessment yielded the following likelihood of association with 2009 H1N1 vaccination: 8 definitely; 8 probably; 21 possibly; 43 unlikely; 17 unrelated; and 2 unclassifiable. Conclusions: Most AEFI in children evaluated were not causally related to vaccine and resolved without sequelae. Detailed clinical assessment of individual serious AEFI can provide reassurance of vaccine safety.