Kristine Macartney

Intussusception Risk and Disease Prevention Associated With Rotavirus Vaccines in Australia's National Immunization Program

BACKGROUND Estimates of the risk of intussusception (IS) associated with currently licensed rotavirus vaccines (RV1 [Rotarix; GSK] and RV5 [RotaTeq; Merck]) diverge. Contemporaneous introduction of both vaccines in Australia enabled a population-based assessment of risk. METHODS Confirmed cases of IS in infants aged 1 to <12 months were identified from national hospitalization databases, supplemented by active hospital-based surveillance, from July 2007 through June 2010. Vaccination histories were verified by the Australian Childhood Immunisation Register, which was also used to identify age-matched controls. Self-controlled case series and case-control methods were used to assess the risk of IS associated with both vaccines in prespecified periods after vaccination. The estimated burden of vaccine-attributable IS was compared with estimated reductions in gastroenteritis hospitalizations. RESULTS Based on 306 confirmed cases of IS, the relative incidence of IS in the 1-7-day period after the first vaccine dose, was 6.8 (95% confidence interval, 2.4-19.0; P < .001) for RV1, and 9.9 (95% confidence interval, 3.7-26.4; P < .001) for RV5. There was a smaller increased risk 1-7 days after the second dose of each vaccine. The case-control analysis gave similar results. We estimate an excess of 14 IS cases and >6500 fewer gastroenteritis hospitalizations in young children annually in Australia after vaccine introduction. CONCLUSIONS We found a similarly increased risk of IS after both vaccines, but the balance of benefits and risks at population level was highly favorable, a finding likely to extend to other settings despite varying incidence of IS and potentially higher morbidity and mortality from both gastroenteritis and IS.

Decline in rotavirus hospitalisations following introduction of Australia's national rotavirus immunisation programme

Aim:  To determine the impact of rotavirus immunisation on rotavirus hospitalisations in young children.

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.

Changes in hospitalisations for acute gastroenteritis in Australia after the national rotavirus vaccination program.

Objective: To evaluate the impact of the Australian rotavirus vaccination program on both rotavirus and all‐cause acute gastroenteritis (AGE) hospitalisations and to compare outcomes in Indigenous and non‐Indigenous people.

Duration of Protection After First Dose of Acellular Pertussis Vaccine in Infants

OBJECTIVE: Data on the effectiveness of the diphtheria–tetanus–acellular pertussis (DTaP) vaccine in the first 4 years of life are sparse. We evaluated the vaccine effectiveness (VE) of 1 and 2 doses of DTaP before 6 months of age and of 3 doses from 6 months of age in Australia, where, since 2003, a fourth dose is not given until 4 years. METHODS: We matched reported pertussis cases aged 2 to 47 months between January 2005 and December 2009 to controls from a population-based immunization register by date of birth and region of residence. VE by number of doses and age group was calculated as (1 – odds ratio) × 100%. RESULTS: VE against hospitalization increased from 55.3% (95% confidence interval [CI], 42.7%–65.1%) for 1 dose before 4 months of age to 83.0% (95% CI, 70.2%–90.3%) for 2 doses before 6 months. The VE of 3 doses of DTaP against all reported pertussis was 83.5% (95% CI, 79.1%–87.8%) between 6 and 11 months, declining to 70.7% (95% CI, 64.5%–75.8%) between 2 and 3 years of age and 59.2% (95% CI, 51.0%–66.0%) between 3 and 4 years of age. CONCLUSIONS: DTaP provided good protection against pertussis in the first year of life from the first dose. Without a booster dose, the effectiveness of 3 doses waned more rapidly from 2 to 4 years of age than previously documented for children >6 years of age who had received 5 doses.

Population-wide vaccination against human papillomavirus in adolescent boys: Australia as a case study

Female-only vaccination programmes for human papillomavirus (HPV) have been introduced in many countries aimed at the prevention of cervical cancer in women. One HPV vaccine is registered for male vaccination, but boys, men, or both, are not yet included in nationally funded HPV vaccination programmes. In this Review we discuss the different considerations relevant to the introduction of population-wide HPV vaccination of boys in Australia, which was the first country to publicly fund HPV vaccination of girls. Several factors need to be taken into account during decision making around the introduction of population-based vaccination programmes, such as local disease burden, vaccine efficacy, vaccine safety, and cost-effectiveness. Social and ethical factors are also important. Although evidence for men is increasing in these areas, uncertainties need to be kept in mind. The features discussed in this Review are likely to be applicable, with caveats, to policy making in other developed countries.

SEVERE ENCEPHALOPATHY WITH SWINE ORIGIN INFLUENZA A H1N1 INFECTION IN CHILDHOOD: CASE REPORTS

The potential for severe respiratory complications associated with swine origin influenza A H1N1 is well documented.1 Australia has seen a dramatic increase in the number of cases of H1N1 infection. H1N1 currently is responsible for >50% of all influenza cases in the Australian 2009 winter. Recently 4 children were reported with neurologic complications associated with swine origin influenza A H1N1.2 We report 2 previously well children who presented to our institution over a 2-week period with serious neurologic complications and focal changes on MRI associated with H1N1 2009 influenza infection. ### Case reports. Case 1 was a previously healthy 5-year-old girl who presented with 3 days of fever, right occipital headache, confusion, and drowsiness. She was febrile (38.5°C), agitated, and had a left hemiplegia. A brain MRI showed high signal and swelling of the right parieto-occipital cortex on T2-weighted images with diffusion restriction in the underlying subcortical white matter (figure, A). A nasopharyngeal swab specimen was positive for influenza A by direct immunofluorescence (IF), which was identified as influenza H1N1 of swine origin by real-time PCR.3 CSF RT-PCR was negative for H1N1 influenza virus. Treatment was started with oseltamivir within 24 hours of admission. She subsequently developed focal status epilepticus (clonic jerking of left hand and face) with right posterior spike and wave activity on EEG. …

Immunisation attitudes, knowledge and practices of health professionals in regional NSW

Objective: This study investigated the immunisation knowledge, attitudes and practices among health professionals in two regional Area Health Services of NSW with low and high immunisation rates. It also compared these factors between the areas and between the health professional groups.

Varicella and herpes zoster hospitalizations before and after implementation of one-dose varicella vaccination in Australia: an ecological study

OBJECTIVE To examine trends in varicella and herpes zoster (HZ) hospitalization following the availability and subsequent National Immunization Programme funding of one-dose varicella vaccination in Australia. METHODS Varicella vaccination coverage for children born between 2001 and 2009 was obtained from the Australian Childhood Immunization Register. Principal or any coded varicella or HZ hospitalizations were retrieved from the national hospital morbidity database from 1998 to 2010. Trends in hospitalization rates in different age groups and indigenous status were assessed. Incidence rate ratios (IRR) were calculated between periods before and after implementation of immunization programme funding. FINDINGS In the first year of the funded immunization programme, varicella vaccine coverage reached 75% in children aged 24 months and more than 80% in children aged 60 months. Compared with the pre-vaccine period, varicella hospitalization rates during the funded programme were significantly lower for age groups younger than 40 years; with the greatest reduction in children aged 18-59 months (IRR: 0.25; 95% confidence interval, CI: 0.22-0.29). Indigenous children had a higher varicella hospitalization rate compared with non-indigenous children before vaccine implementation (IRR: 1.9; 95% CI: 1.4-2.7), but afterwards reached equivalence (IRR: 1.1; 95% CI: 0.7-1.6). The age-standardized HZ hospitalization rate declined between the periods (IRR: 0.95; 95% CI: 0.92-0.97). CONCLUSION Rapid attainment of high coverage reduced varicella hospitalizations in the targeted age group, particularly for indigenous children, but also in non-targeted age groups, with no increase in HZ hospitalizations. This suggests high one-dose varicella vaccine coverage can have a substantial impact on severe disease.

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.