Nigel W. Crawford

International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

BACKGROUND The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. METHODS The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. RESULTS We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach. CONCLUSIONS This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines.

Rotavirus vaccine induced diarrhea in a child with severe combined immune deficiency.

To the Editor: The first case report on a patient who developed Churg-Strauss syndrome (CSS) after therapy with omalizumab, the anti-IgE recombinant humanized mAb, was described by Winchester et al in 2006. Later, several similar cases were reported in the medical literature; the authors suggested a possible role for anti-IgE treatment in the emergence of CSS and recommended careful monitoring of emerging symptoms of this vasculitis in patients treated with omalizumab. In contrast, Giavina Bianchi et al presented the case of a patient with CSS with uncontrolled asthma that improved with omalizumab treatment without increase of CSS clinical severity. The authors hypothesized that steroid tapering during omalizumab therapy could have caused CSS clinical appearance. Here we describe the case of a 42-year-old Caucasian man with a 5 year history of asthma. One year after asthma onset, blood hypereosinophilia became evident (1600/mL), and the patient J ALLERGY CLIN IMMUNOL

Identification of Strains of RotaTeq Rotavirus Vaccine in Infants With Gastroenteritis Following Routine Vaccination

BACKGROUND RotaTeq vaccine was introduced into the Australian National Immunisation Program in 2007. This study identified and characterised rotavirus strains excreted by infants who presented with symptoms of gastroenteritis following recent RotaTeq vaccination. METHODS Fecal samples (N = 61) from children who developed gastroenteritis following recent RotaTeq vaccination were forwarded to the Australian Rotavirus Surveillance Program (ARSP). RotaTeq-positive samples were genotyped and regions of the VP3, VP4, VP6, and VP7 genes were sequenced. Also, 460 rotavirus-positive ARSP routine surveillance samples were analyzed by dot-blot Northern hybridization to detect RotaTeq vaccine-derived strains circulating in the community. RESULTS Thirteen of the 61 samples collected from infants developing gastroenteritis after RotaTeq vaccination contained vaccine-derived (vd) rotavirus strains. Of these, 4 contained a vdG1P[8] strain derived by reassortment between the G1P[5] and G6P[8] parental vaccine strains. Northern hybridization analysis of 460 surveillance samples identified 3 samples that contained RotaTeq vaccine-derived strains, including 2 vdG1P[8] reassortant vaccine strains. CONCLUSIONS During replication and excretion of RotaTeq vaccine, reassortment of parental strains can occur. Shedding of RotaTeq vaccine strains in 7 of 13 infants was associated with underlying medical conditions that may have altered their immune function. The benefits of vaccination outweigh any small risk of vaccine-associated gastroenteritis.

Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study

Objective To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007. Design Retrospective cohort study. Setting Two tertiary paediatric allergy centres in Victoria and South Australia, Australia. Participants 35 schoolgirls aged 12 to 18.9 years with suspected hypersensitivity reactions to the quadrivalent human papillomavirus vaccine. Main outcome measures Clinical review and skin prick and intradermal testing with the quadrivalent vaccine and subsequent challenge with the vaccine. Results 35 schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine were notified to the specialised immunisation services in 2007, after more than 380 000 doses had been administered in schools. Of these 35 schoolgirls, 25 agreed to further evaluation. Twenty three (92%) experienced reactions after the first dose. Thirteen (52%) experienced urticaria or angio-oedema, and of these, two experienced anaphylaxis. Thirteen had generalised rash, one with angio-oedema. The median time to reaction was 90 minutes. Nineteen (76%) underwent skin testing with the quadrivalent vaccine: all were skin prick test negative and one was intradermal test positive. Eighteen (72%) were subsequently challenged with the quadrivalent vaccine and three (12%) elected to receive the bivalent vaccine. Seventeen tolerated the challenge and one reported limited urticaria four hours after the vaccine had been administered. Only three of the 25 schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine. Conclusion True hypersensitivity to the quadrivalent human papillomavirus vaccine in Australian schoolgirls was uncommon and most tolerated subsequent doses.

Parechovirus Encephalitis and Neurodevelopmental Outcomes.

OBJECTIVE: We aimed to describe the clinical features and outcome of human parechovirus (HPeV) encephalitis cases identified by the Australian Childhood Encephalitis (ACE) study. METHODS: Infants with suspected encephalitis were prospectively identified in 5 hospitals through the (ACE) study. Cases of confirmed HPeV infection had comprehensive demographic, clinical, laboratory, imaging, and outcome at discharge data reviewed by an expert panel and were categorized by using predetermined case definitions. Twelve months after discharge, neurodevelopment was assessed by using the Ages and Stages Questionnaire (ASQ). RESULTS: We identified thirteen cases of suspected encephalitis with HPeV infection between May 2013 and December 2014. Nine infants had confirmed encephalitis; median age was 13 days, including a twin pair. All had HPeV detected in cerebrospinal fluid with absent pleocytosis. Most were girls (7), admitted to ICU (8), and had seizures (8). Many were born preterm (5). Seven patients had white matter diffusion restriction on MRI; 3 with normal cranial ultrasounds. At discharge, 3 of 9 were assessed to have sequelae; however, at 12 months’ follow-up, by using the ASQ, 5 of 8 infants showed neurodevelopmental sequelae: 3 severe (2 cerebral palsy, 1 central visual impairment). A further 2 showed concern in gross motor development. CONCLUSIONS: Children with HPeV encephalitis were predominantly young, female infants with seizures and diffusion restriction on MRI. Cranial ultrasound is inadequately sensitive. HPeV encephalitis is associated with neurodevelopmental sequelae despite reassuring short-term outcomes. Given the absent cerebrospinal fluid pleocytosis and need for specific testing, HPeV could be missed as a cause of neonatal encephalopathy and subsequent cerebral palsy.

Survivors of childhood cancer: An Australian audit of vaccination status after treatment

Survivors of childhood and adolescent cancer are at risk of vaccine preventable diseases and are recommended to receive booster vaccinations post‐chemotherapy. The aim of this study was to describe the compliance of post‐chemotherapy revaccination of childhood cancer survivors relative to current Australian guidelines.

Complex regional pain syndrome following immunisation

Complex regional pain syndrome type 1 (CRPS-1) is a clinical syndrome that affects one or more extremities and is characterised by persistent pain disproportionate to any inciting event, and at least one sign of autonomic dysfunction in the affected limb(s). The pathogenesis of this syndrome is poorly understood, but its onset is often precipitated by a physical injury, such as minor trauma, fracture, infection or a surgical procedure. In the literature, there are reports of CRPS-1 following immunisation with rubella and hepatitis B vaccines. Here we present a case series of CRPS-1 following immunisation in adolescents, with either diphtheria-tetanus-acellular pertussis (1 case), or human papillomavirus vaccines (4 cases). Enhanced awareness of this syndrome and its potential to occur following immunisation in the paediatric population is vital to the prompt and effective management of this condition.

Active surveillance for adverse events following immunization

Comprehensive surveillance of adverse events following immunization (AEFI) is required to detect potential serious adverse events that may not be identified in prelicensure vaccine trials. Surveillance systems have traditionally been passive, relying upon spontaneous reporting, but increasingly active surveillance and supplemental strategies are being incorporated into vaccine safety programs. These include active screening for targeted conditions of interest (e.g., hospitalization), monitoring of new data sources and real-time methodologies to detect changes in vaccine safety data in these sources. The role of improved causality assessment in AEFI surveillance is discussed, with its important role in determining whether a temporal association may have occurred by chance alone. Strong local vaccine safety networks are required to support national immunization programs, with recent progress in developing a framework for low- and middle-income countries. Global collaboration is increasingly required to address challenges in active AEFI surveillance, particularly for rare serious adverse events.

Optimizing immunization in pediatric special risk groups

This article analyzes the current recommended practices and evidence in the immunization of pediatric ‘special risk groups’. Special risk group patients are at higher risk of vaccine-preventable diseases and hence require additional strategies to maximize protection against these diseases. The special risk groups include those with an underlying chronic disease, some of whom are on immunosuppressive therapy to treat that condition. The article uses four special risk groups (acute lymphoblastic leukemia; preterm birth; juvenile idiopathic arthritis; and inflammatory bowel disease), to highlight the management considerations and potential vaccination strategies. The risks, benefits and timing of vaccination in the setting of immunosuppression require detailed discussion with treating clinicians, in particular the use of live-attenuated vaccines. The immunogenicity of vaccines in these special risk groups helps provide the evidence base for their immunization guidelines. Protection can include ‘cocooning’ (i.e., ensuring appropriate immunizations within the immediate family; e.g., varicella, influenza and pertussis vaccination). Improving timeliness and minimizing missed opportunities to vaccinate individuals with these special risk conditions will also optimize protection from vaccine-preventable diseases.

Genetic characterization of a novel G3P[14] rotavirus strain causing gastroenteritis in 12 year old Australian child.

A genotype G3P[14] rotavirus strain was identified in a 12year old child presenting to the Emergency Department of the Royal Childrens Hospital, Melbourne, with gastroenteritis. G3P[14] strains have been previously identified in rabbits in Japan, China, the USA and Italy and a single lapine-like strain from a child in Belgium. Full genome sequence analysis of RVA/Human-wt/AUS/RCH272/2012/G3P[14] (RCH272) revealed that the strain contained the novel genome constellation G3-P[14]-I2-R3-C3-M3-A9-N2-T6-E2-H3. The genome was genetically divergent to previously characterized lapine viruses and the genes were distantly related to a range of human bovine-like strains and animal strains of bovine, bat and canine/feline characteristics. The VP4, VP6, NSP2, NSP3, NSP4 and NSP5 genes of RCH272 clustered within bovine lineages in the phylogenetic analysis and shared moderate genetic similarity with an Australian bovine-like human strain RVA/Human-tc/AUS/MG6/1993/G6P[14]. Bayesian coalescent analysis suggested these genes of RCH272 and RVA/Human-tc/AUS/MG6/1993/G6P[14] were derived from a population of relatively homogenous bovine-like ancestral strains circulating between 1943 and 1989. The VP7, VP1, VP2 and NSP1 genes shared moderate genetic similarity with the Chinese strain RVA/Bat-tc/CHN/MSLH14/2011/G3P[3] and the VP3 gene clustered within a lineage comprised of canine and feline strains. This strain may represent the direct transmission from an unknown host species or be derived via multiple reassortment events between strains originating from various species. The patient lived in a household containing domesticated cats and dogs and in close proximity to a colony of Gray-headed Flying-foxes. However, without screening numerous animal populations it is not possible to determine the origins of this strain.