Philip LaRussa

Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination.

BACKGROUNDnAdverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination.nnnMETHODSnCenters for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined.nnnRESULTSn212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as possibly related (33%), 108 as unlikely related (51%), and 20 as unrelated (9%) to H1N1 vaccination; none were classified as probable or definite and 12 were unclassifiable (6%).nnnCONCLUSIONnThe absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment.

Causality assessment of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS).

UNLABELLEDnAdverse events following immunization (AEFI) reported to the national Vaccine Adverse Event Reporting System (VAERS) represent true causally related events, as well as events that are temporally, but not necessarily causally related to vaccine.nnnOBJECTIVEnWe sought to determine if the causal relationships between the vaccine and the AEFI reported to VAERS could be assessed through expert review.nnnDESIGNnA stratified random sample of 100 VAERS reports received in 2004 contained 13 fatal cases, 19 cases with non-fatal disabilities, 39 other serious non-fatal cases and 29 non-serious cases. Experts knowledgeable about vaccines and clinical outcomes, reviewed each VAERS report and available medical records.nnnMAIN OUTCOME MEASURESnModified World Health Organization criteria were used to classify the causal relationship between vaccines and AEFI as definite, probable, possible, unlikely or unrelated. Five independent reviewers evaluated each report. If they did not reach a majority agreement on causality after initial review, the report was discussed on a telephone conference to achieve agreement.nnnRESULTSn108 AEFIs were identified in the selected 100 VAERS reports. After initial review majority agreement was achieved for 83% of the AEFI and 17% required further discussion. In the end, only 3 (3%) of the AEFI were classified as definitely causally related to vaccine received. Of the remaining AEFI 22 (20%) were classified as probably and 22 (20%) were classified as possibly related to vaccine received; a majority (53%) were classified as either unlikely or unrelated to a vaccine received.nnnCONCLUSIONSnUsing VAERS reports and additional documentation, causality could be assessed by expert review in the majority of VAERS reports. Assessment of VAERS reports identified that causality was thought to be probable or definite in less than one quarter of reports, and these were dominated by local reactions, allergic reactions, or symptoms known to be associated with the vaccine administered.

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

BACKGROUNDnHypersensitivity disorders following vaccinations are a cause for concern.nnnOBJECTIVEnTo determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines.nnnDESIGNnA systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines.nnnSETTING/PATIENTSnUS Civilian reports following vaccine received from October 1, 2009 through May 31, 2010.nnnMEASUREMENTSnAge, 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.nnnRESULTSnOf 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.nnnLIMITATIONSnUnderreporting, 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.nnnCONCLUSIONSnAdult 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.

Case Report of Subcutaneous Nodules and Sterile Abscesses Due to Delayed Type Hypersensitivity to Aluminum-Containing Vaccines

Routine childhood immunizations have resulted in great reductions in vaccine-preventable infectious diseases. Vaccine-related adverse events, albeit rare, can be of significant consequence. Although anaphylaxis, or type I hypersensitivity, is recognized as a potential reaction after vaccination, delayed type hypersensitivity or type IV reactions are less so. We present a case of persistent subcutaneous nodules and sterile abscesses in the setting of delayed type hypersensitivity to aluminum, confirmed by patch testing and recurrence on re-exposure. We review sources of aluminum in common immunizations, principles for treatment, and strategies for management of future vaccinations for this patient.

Vaccination of adolescents with chronic medical conditions: Special considerations and strategies for enhancing uptake

Adolescents with chronic medical conditions (CMCs), a growing population worldwide, possess a wide array of preventive health care needs. Vaccination is strongly recommended for the vast majority of these adolescents given their increased risk of vaccine preventable infection and associated complications. Not only should they receive routine vaccines, but some also require additional vaccines. Despite these guidelines, evidence suggests that adolescents with CMCs often fail to receive needed vaccines. Many factors contribute to this under-immunization, including lack of knowledge among parents and providers and suboptimal coordination of primary and subspecialty care. This review describes current vaccination recommendations for these adolescents as well as recent data related to infection risk, vaccine efficacy and safety, vaccination coverage, and the unique multilevel factors impacting uptake in this population. It also discusses strategies for improving coverage levels and reducing missed vaccination opportunities, with a particular focus on technology-based interventions.

Community ‐and hospital laboratory‐based surveillance for respiratory viruses

Traditional surveillance for respiratory viruses relies on symptom detection and laboratory detection during medically attended encounters for acute respiratory infection/influenza‐like illness (ARI/ILI). Ecological momentary reporting using text messages is a novel method for surveillance. This study compares respiratory viral activity detected through longitudinal community‐based surveillance using text message responses for sample acquisition and testing to respiratory viral activity obtained from hospital laboratory data from the same community. We demonstrate a significant correlation between community‐ and hospital laboratory‐based surveillance for most respiratory viruses, although the relative proportions of viruses detected in the community and hospital differed significantly.

Factors associated with willingness to participate in a vaccine clinical trial among elderly Hispanic patients

A population specific understanding of barriers and facilitators to participation in clinical trials could improve recruitment of elderly and minority populations. We investigated how prior exposure to clinical trials and incentives were associated with likelihood of participation in a vaccine clinical trial through a questionnaire administered to 200 elderly patients in an academic general internal medicine clinic. Wilcoxon signed rank sum test compared likelihood of participation with and without monetary incentives. Logistic regression evaluated characteristics associated with intent to participate in an influenza vaccine trial, adjusted for age, gender, language, and education history. When asked about likelihood of participation if there was monetary compensation, there was a 12.2% absolute increase in those reporting that they would not participate, with a significant difference in the distribution of likelihood before and after mentioning a monetary incentive (Wilcoxon signed rank test, p = 0.001). Those with previous knowledge of clinical trials (54.4%) were more likely to report they would participate vs. those without prior knowledge (OR 2.5, 95% CI [1.2, 5.2]). The study highlights the importance of pre-testing recruitment materials and incentives in key group populations prior to implementing clinical trials.

Influenza B virus infection and Stevens–Johnson syndrome

A 2‐year‐old boy with influenza B infection and rapidly worsening targetoid skin lesions with mucosal involvement was diagnosed with Stevens–Johnson syndrome (SJS) and treated with oseltamivir and intravenous immunoglobulin, with resolution of illness. Subsequent quadrivalent inactivated influenza vaccine was well tolerated. This case highlights the rarity of SJS in the setting of influenza B infection and addresses the safety of administering subsequent influenza vaccines to such individuals.

Respiratory Pathogens in Children 1 Month to 5 Years of Age Presenting With Undifferentiated Acute Respiratory Distress in 2 District-Level Hospitals in Ghana

Abstract Ghanaian children (2176) aged <5 years who presented with undifferentiated acute respiratory distress were tested for respiratory pathogens using a BioFire FilmArray polymerase chain reaction assay. Rhinovirus and/or enterovirus was detected in 36% of the assays, respiratory syncytial virus in 11%, and parainfluenza in 7%. Respiratory syncytial virus and metapneumovirus were detected more frequently in the rainy season than in the dry season.

Epidemiology and Clinical Features of Human Coronaviruses in the Pediatric Population

Abstract Background The epidemiology and clinical features of human coronaviruses (HCoVs) in children are not fully characterized. Methods A retrospective study of children with HCoV detected by reverse-transcriptase polymerase chain reaction (RT-PCR) was performed for a community cohort and a children’s hospital in the same community from January 2013 to December 2014. The RT-PCR assay detected HCoV 229E, HKU1, NL63, and OC43 in nasal swabs from symptomatic children ≤18 years. Factors associated with increased severity of illness in hospitalized children were assessed by multivariable logistic regression. Results Human coronavirus was detected in 261 children, 49 and 212 from the community and hospital, respectively. The distribution of HCoV types and seasonal trends were similar in the community and hospital. Community cases were older than hospitalized cases (median age, 4.4 versus 1.7 years, respectively; P < .01), and a minority of community cases (26.5%) sought medical attention. Among the hospitalized children with HCoV detected, 39 (18.4%) received respiratory support and 24 (11.3%) were admitted to the pediatric intensive care unit (PICU). Age <2 years (odds ratio [OR] = 5.0; 95% confidence interval [CI], 1.9–13.1) and cardiovascular (OR = 3.9; 95% CI, 1.6–9.5), genetic/congenital (OR = 2.8; 95% CI, 1.1–7.0), and respiratory chronic complex conditions ([CCCs] OR = 4.5; 95% CI, 1.7–12.0) were associated with receiving respiratory support. Genetic/congenital (OR = 2.8; 95% CI, 1.1–7.4) CCCs were associated with PICU admission. Severity of illness was similar among hospitalized children with different HCoV types. Conclusions Children in the community with HCoV detected generally had mild illness as demonstrated by few medically attended cases. In hospitalized children, young age and CCCs, but not HCoV type, were associated with increased severity of illness.