Acute Flaccid Paralysis in Australian Children from 2007 to 2017.

INTRODUCTION: Acute flaccid paralysis (AFP) surveillance continues globally as part of the World Health Organization's goal to eradicate poliomyelitis. The Australian Paediatric Surveillance Unit (APSU), Paediatric Active Enhanced Disease Surveillance (PAEDS) network, and National Enterovirus Reference Laboratory (NERL) collaborate in AFP surveillance in Australia, capturing and reviewing cases of AFP for all aetiologies in order to exclude poliovirus. We aimed to describe the AFP epidemiology in childhood over an 11 year period. METHODS: Data were reported nationally by paediatricians via prospective APSU surveillance, PAEDS surveillance nurses at five tertiary paediatric hospitals and NERL from 2007 to 2017. Children aged 0-15 years with AFP were included. We combined APSU, PAEDS, and NERL datasets, analysed epidemiological trends, and described clinical features and investigations for major diagnoses. RESULTS: Of 590 AFP-compatible cases, 49% were male; 47% were aged 0-4 years, 9% aged <1 year. Annual incidence of AFP was 1.3 cases per 100,000 children aged <15 years. Lower limb paralysis was the most frequent presenting symptom. The most frequent diagnoses were Guillain-Barre syndrome (GBS; 36%), transverse myelitis (TM; 17%), and acute disseminated encephalomyelitis (ADEM; 15%). No secular trend was seen in frequency of AFP cases nor amongst major diagnoses. Seasonality was observed with ADEM occurring more frequently in winter. We observed periods of increased AFP frequency in 2013 and 2016, coinciding with increased reporting of non-polio anterior horn cell disease (AHCD) and detection of non-polio enterovirus (NPEV). CONCLUSIONS: Estimated incidence of GBS, ADEM, and TM in Australian children was comparable with international rates. There was stable incidence of AFP in Australian children between 2007 and 2017. GBS, ADEM, and TM are the major causes of AFP. We observed clustering of cases associated with NPEV that emphasises a need for ongoing vigilance in surveillance given continue emerging infectious disease threats.

Severity of Rotavirus-Vaccine-Associated Intussusception: Prospective Hospital-Based Surveillance, Australia, 2007-2018.

BACKGROUND: Multiple studies have shown an association between intussusception (IS) and receipt of monovalent or pentavalent rotavirus vaccine (RV) in the previous 21 days. Disease severity is an important consideration for risk-benefit evaluations of RV, but no studies have compared the severity of IS within 21 days of vaccination (vaccine-associated, VA) and later (not temporally-associated, VNA). METHODS: We used active hospital-based surveillance in the Australian Paediatric Active Enhanced Disease Surveillance (PAEDS) network (July 2007 to February 2018) to identify infants ≤9 months of age meeting Brighton level 1 criteria for IS. We used five severity levels: (1) no surgery and length of stay (LOS) ≤1 day, (2) no surgery and LOS ≥2 days, (3) surgery, no bowel resection, (4) bowel resection, and (5) ICU admission. RESULTS: Of 323 eligible cases, 87 (26.9%) were VA and 236 (73.1%) VNA. VA-IS cases (median 21 weeks; 24.1% ≤14 weeks) were significantly younger than VNA-IS cases (median 28 weeks, 7.2% ≤14 weeks). Cases 0-≤14 weeks of age were significantly more likely than cases ≥25 weeks to require bowel resection (relative risk ratio 4.6, 95% CI, 1.48-14.3). This effect was not associated with RV. After adjustment for age and sex, VA-IS was not significantly overrepresented in severity levels 2-5; adjusted RRR of 1.37 (95% CI: 0.61-3.11) for bowel resection in cases 0-≤14 weeks of age. CONCLUSIONS: IS was uncommon but significantly more severe under 14 weeks of age. After adjustment for age and sex, IS severity was not related to RV.

Prospective characterisation of SARS-CoV-2 infections among children presenting to tertiary paediatric hospitals across Australia in 2020: a national cohort study.

OBJECTIVE: To present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation. DESIGN: Prospective, multicentre cohort study. SETTING: Eight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network-Paediatric Active Enhanced Disease (PAEDS). PARTICIPANTS: All children aged <19 years with SARS-CoV-2 infection including COVID-19, Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) and Kawasaki-like disease TS infection (KD-TS) treated at a PAEDS site from 24 March 2020 to 31 December 2020. INTERVENTION: Laboratory-confirmed SARS-CoV-2 infection. MAIN OUTCOME: Incidence of severe disease among children with COVID-19, PIMS-TS and KD-TS. We also compared KD epidemiology before and during the COVID-19 pandemic. RESULTS: Among 386 children with SARS-CoV-2 infection, 381 (98.7%) had COVID-19 (median 6.3 years (IQR 2.1-12.8),53.3% male) and 5 (1.3%) had multisystem inflammatory syndromes (PIMS-TS, n=4; KD-TS, n=1) (median 7.9 years (IQR 7.8-9.8)). Most children with COVID-19 (n=278; 73%) were Australian-born from jurisdictions with highest community transmission. Comorbidities were present in 72 (18.9%); cardiac and respiratory comorbidities were most common (n=32/72;44%). 37 (9.7%) children with COVID-19 were hospitalised, and two (0.5%) required intensive care. Postinfective inflammatory syndromes (PIMS-TS/KD-TS) were uncommon (n=5; 1.3%), all were hospitalised and three (3/5; 60%) required intensive care management. All children recovered and there were no deaths. KD incidence remained stable during the pandemic compared with prepandemic. CONCLUSIONS: Most children with COVID-19 had mild disease. Severe disease was less frequent than reported in high prevalence settings. Preventative strategies, such as vaccination, including children and adolescents, could reduce both the acute and postinfective manifestations of the disease.

Human Parechovirus 3 in Infants: Expanding Our Knowledge of Adverse Outcomes.

BACKGROUND: Human parechovirus particularly genotype 3 (HPeV3) is an emerging infection affecting predominantly young infants. The potential for neurologic sequelae in a vulnerable subset is increasingly apparent. A review of 2 epidemics of human parechovirus (HpeV) infection in 2013 and in 2015 in Queensland, Australia, was undertaken, with an emphasis on identifying adverse neurodevelopmental outcome. METHODS: All hospitalized cases with laboratory-confirmed HPeV infection between October 2013 June 2016 were identified. Clinical, demographic, laboratory and imaging data were collected and correlated with reported developmental outcome. RESULTS: Laboratory-confirmed HPeV infections were identified in 202 patients across 25 hospitals; 86.6% (n = 175) were younger than 3 months 16.3% (n = 33) received intensive care admission. Of 142 cerebrospinal fluid samples which were HPeV polymerase chain reaction positive, all 89 isolates successfully genotyped were HPeV3. Clinical information was available for 145 children; 53.1% (n = 77) had follow-up from a pediatrician, of whom 14% (n = 11) had neurodevelopmental sequelae, ranging from hypotonia and gross motor delay to spastic quadriplegic cerebral palsy and cortical visual impairment. Of 15 children with initially abnormal brain magnetic resonance imaging, 47% (n = 7) had neurodevelopmental concerns, the remainder had normal development at follow-up between 6 and 15 months of age. CONCLUSIONS: This is the largest cohort of HPeV3 cases with clinical data and pediatrician-assessed neurodevelopmental follow-up to date. Developmental concerns were identified in 11 children at early follow-up. Abnormal magnetic resonance imaging during acute infection did not specifically predict poor neurodevelopmental in short-term follow-up. Continued follow-up of infants and further imaging correlation is needed to explore predictors of long-term morbidity.

Severe and Complicated Varicella and Associated Genotypes 10 Years After Introduction of a One-Dose Varicella Vaccine Program.

Background: This national, sentinel prospective study aimed to identify children with severe hospitalized varicella, despite availability of universal 1-dose vaccination since 2005, and determine associations between virus genotypes and disease severity. Methods: Children with varicella or zoster from 5 Paediatric Active Enhanced Disease Surveillance hospitals were enrolled. Lesions were swabbed for genotyping. Associations with disease severity were analyzed using multiple regression. Results: From 2007 to 2015, 327 children with confirmed varicella (n = 238) or zoster (n = 89) were enrolled. Two hundred three (62%) were immunocompetent children; including 5 of 8 children who required intensive care unit management. Eighteen percent (36 of 203) of immunocompetent children had been previously vaccinated. Vaccinated children aged >18 months were less likely to have severe disease (9%; 5 of 56) than unvaccinated children (21%; 21 of 100; P = .05). Three of 126 children who had virus genotyping (2 immunocompromised) had varicella (n = 2) or zoster (n = 2) due to the Oka/vaccine strain. European origin clades predominated and were independently associated with more severe disease (odds ratio = 3.2; 95% confidence interval, 1.1- 9.5; P = .04). Conclusions: Severe hospitalized varicella still occurs with a 1-dose varicella program, although predominantly in unvaccinated children. Most 1-dose vaccine recipients were protected against severe disease. Viral genotyping in complex hospitalized cases is important to assist in monitoring disease due to Oka-vaccine strain.

Febrile seizures following measles and varicella vaccines in young children in Australia.

BACKGROUND: Febrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age. METHODS: All FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11-23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk. RESULTS: There were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5-12 days post receipt of MMR1 at 12 months (RI=1.9 [95% CI: 1.3-2.9]), but not after VV at 18 months (RI=0.6 [95% CI: 0.3-1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11-23 months (95% CI=7-49 cases per 100,000) or 1 per 4167 doses. CONCLUSIONS: Our study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013.