Surveillance and research PAEDS is currently conducting surveillance on COVID-19, acute flaccid paralysis, acute childhood encephalitis, influenza, pertussis, varicella and herpes zoster, invasive group A streptococcus, invasive meningococcal disease, Kawasaki disease and Gram-negative blood stream infections. COVID-19 Principal investigator Associate Professor Nigel Crawford The PAEDS network is conducting surveillance of COVID-19 to support the national public health response to the pandemic and is well-placed to prospectively identify children presenting to our hospitals with COVID-19 infection. A novel coronavirus (SARS-CoV-2) that emerged in Wuhan, Hubei Province, China, in late 2019 is a new strain of coronavirus that has caused an evolving pandemic. The disease caused by this virus has been named Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 was initially observed in Wuhan to cause severe pneumonia in adults. Cases have since been identified in many countries, including Australia. Patients with COVID-19 may present with fever, cough, rhinorrhoea and fatigue, with pneumonia and severe acute respiratory distress syndrome (ARDS) occurring in more severe infections. There is still much to learn about COVID-19 in children. Evidence to date shows only a small fraction of confirmed COVID-19 cases are children, and children appear to have relatively low incidence of symptomatic infections and milder disease than adults.1 PAEDS has successfully partnered with FluCAN since 2014 to collect valuable influenza data in hospitalised children. This partnership has expanded to collect enhanced clinical data on all children presenting to our PAEDS sites with COVID-19 to understand the incidence and severity of children requiring hospitalisation for this disease. PAEDS will also be collaborating with other networks, both nationally and internationally, to ensure any increase in severe COVID-19 related outcomes in children are rapidly detected and comprehensively investigated. 1. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30152-1/fulltext PIMS-TS Principal investigator Dr Phil Britton In April 2020, a cluster of severely unwell children with fever and shock were described in the United Kingdom (UK) in association with SARS-CoV-2 infection. No such cases had been reported before this from China. Further cases were identified in the UK, and the condition was labelled Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS). Reports rapidly emerged from other high-burden settings, including New York, Northern Italy and France, of children with fever, shock, rash and abdominal pain, some of whom met diagnostic criteria for Kawasaki disease (KD). Majority of these children had evidence of prior SARS-CoV-2 infection and a minority showed concurrent detection of SARS-CoV-2. The United States Centers for Disease Control has named the syndrome Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C). Recommendations for management of patients with possible PIMS-TS/MIS-C were developed by PAEDS in partnership with specialist clinicians (Inflammatory Vasculitis working group) from Australia and endorsed by the Royal Australasian College of Physicians (RACP). While the overall risk remains extremely low for severe complications of COVID-19 in children in Australia, the PAEDS network is monitoring these rare, but clinically significant, complications of SARS-CoV-2 infection. Case definition of Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS) Clinical Children and adolescents (up to 18 years of age) with fever ≥3 days AND two of the following: rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet) age-specific hypotension or “shock” within first 24 hours of presentation features of myocardial dysfunction, pericarditis, valvulitis or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP) evidence of coagulopathy (by PT, PTT, elevated d-Dimers) acute gastrointestinal problems (diarrhoea, vomiting or abdominal pain). AND elevated markers of inflammation such as ESR, C-reactive protein or procalcitonin. AND exclusion of other infectious causes of inflammation, including bacterial sepsis, staphylococcal or streptococcal toxic shock syndromes. Laboratory AND evidence of SARS-CoV-2 infection (positive RT-PCR), or confirmed contact with a person with SARS-CoV-2 infection (public health defined), or confirmed positive SARS-CoV-2 serology (noting testing may be delayed, particularly serology. If all other criteria are met, collect data pending results). Refer also to the clinical advice statement on PIMS-TS. Acute childhood encephalitis Principal investigator Dr Philip Britton Encephalitis is a complex neurological syndrome caused by inflammation of the brain. Children are among those most severely affected. However, there is limited knowledge about the causes of encephalitis in children worldwide and a cause is not found in up to 70% of cases using routine testing. Australia has unique viruses and other infectious agents that potentially cause encephalitis. There is also increasing awareness of immune-mediated causes of encephalitis, but these have not been systematically studied in children. The Australian Childhood Encephalitis study, led by Professor Cheryl Jones and Dr Philip Britton, aims to describe the causes, clinical features and consequences of this severe disease among Australian children. A 6-month pilot of surveillance for this complex condition began in 2013 at The Children's Hospital at Westmead site only, with roll-out to other states from early 2014. To date, this study has shown considerable success in better understanding acute encephalitis and its causes as well as demonstrating the effectiveness of syndromic surveillance using the PAEDS system in identifying outbreaks related to emerging infectious diseases in children. Acute flaccid paralysis Principal investigator Dr Philip Britton PAEDS has conducted surveillance for acute flaccid paralysis (AFP) since 2007. To retain Australia’s polio-free status it is important that Australia contributes to AFP surveillance including meeting World Health Organization surveillance targets related to case identification, stool collection and case investigation. This work contributes to the goal of global polio eradication. PAEDS sites continue to notify most of the AFP cases that are reported in Australia to the Polio Expert Panel of the Department of Health and provide stool samples to the Victorian Infectious Diseases Reference Laboratory (VIDRL) for testing for enteric pathogens. Together with the Australian Paediatric Surveillance Unit (APSU) and National Enterovirus Reference Laboratory(NERL/VIDRL), PAEDS has helped achieve WHO benchmarks each year since 2007. A recent review of polio surveillance in Australia confirmed the importance of PAEDS surveillance for AFP. Influenza Principal investigator Associate Professor Christopher Blyth Influenza is the most common vaccine preventable disease and a common cause of hospitalisation for children. PAEDS has been conducting surveillance for hospitalised influenza, in collaboration with the inFluenza Complications Alert Network (FluCAN), led by Professor Allen Cheng. Two sites (The Children’s Hospital at Westmead and Perth Children’s Hospital) joined FluCAN in 2014 and additional PAEDS sites joined the network in 2017, with the assistance of NHMRC partnership grant. This research has demonstrated the previously unrecognised burden of influenza in paediatric hospitals, explored risk factors for severe disease, evaluated antiviral and vaccine use and estimated vaccine effectiveness on an annual basis (Blyth et al, Eurosurveillance 2016; Blyth et al, Clinical Infectious Diseases 2019). Young children (<5 years), Aboriginal and Torres Strait Islander children and children with underlying medical conditions remain at significantly increased risk of hospitalised influenza. One in ten children admitted to hospital with influenza are admitted to the intensive care unit. Although most hospitalisations are short (less than 3 days), many children have prolonged hospitalisation. Although uncommon, influenza-associated deaths continue to occur. Despite significant variation between years, vaccination is the most effective prevention strategy we have. PAEDS-FluCAN has demonstrated vaccine effectiveness in young children and children with comorbidities. In addition, the effectiveness of vaccinating pregnant women to prevent infant disease has been demonstrated. Vaccine effectiveness estimates are provided to the national influenza committee to inform strain choice for future annual vaccines. PAEDS-FluCAN has led an advocacy campaign to highlight the need for vaccination in children. Vaccine coverage has increased significantly in recent years, in both children and pregnant women, with the Commonwealth and state governments now providing free influenza vaccination for all children 6 months to 5 years; all children 6 months and older with underlying medical conditions; all Aboriginal and Torres Strait Islander children from 6 months of age; and pregnant women. Pertussis Principal investigator Associate Professor Nick Wood Despite immunisation coverage approaching 93%, pertussis continues to cause significant morbidity and mortality, particularly in very young Australian children. The aims of this surveillance are to determine the burden of disease from hospitalised pertussis, with special emphasis on the duration of hospitalisation, use of intensive care, death and disability. Possible sources of infection and comorbidities to severity of pertussis are examined. The NHMRC-funded Partnership Project (APP1113851) seeks to estimate the effectiveness of pertussis vaccination (either in infancy or maternal) against pertussis hospitalisations and emergency department presentations by comparing pertussis vaccination status in infants with pertussis <6 months of age and test-negative controls. These surveillance data will assist in optimising pertussis prevention strategies. Social research Attitudes about and access to influenza vaccination in Australia: experiences of parents of children hospitalised for acute respiratory infection Influenza vaccination is the most effective tool to prevent influenza disease. However, uptake in children in Australia is low. A social research project was undertaken to understand why is influenza vaccine coverage low and how can it be increased to prevent children from being hospitalised for influenza? Methods included: a systematic review of the known barriers and facilitators of influenza vaccination of children and pregnant women in Australia between 2004 and 2015 qualitative interviews with parents of children hospitalised in two sites in Australia for influenza in 2017 a cross-sectional survey with parents of children who were hospitalised for acute respiratory infection (+/– laboratory-confirmed influenza) in five sites across Australia in 2019. To understand the complexities of behaviour, the Capability-Opportunity-Motivation-Behaviour model was used across the multiple studies. This work highlighted the importance of receiving an influenza vaccination recommendation from a healthcare provider: the lack of such a recommendation was a strong variable associated with lack of influenza vaccination in children who had been hospitalised for acute respiratory infection. The work also highlighted the importance of increasing influenza vaccination opportunities: motivation to vaccinate is low if influenza vaccination is difficult to remember, organise and access. We were able to understand exactly where and how to practically target efforts to change behaviour by systematically mapping out the barriers to influenza vaccination of children in Australia to increase uptake of influenza vaccine. Varicella and herpes zoster Principal investigator Associate Professor Helen Marshall Varicella vaccine was included on the National Immunisation Program in 2005 for all children at age 18 months, with catch-up vaccination via school-based programs. PAEDS has been conducting surveillance for hospitalised varicella since 2007. Information is collected on complications of chickenpox (varicella-zoster virus infection) and children hospitalised with shingles (herpes zoster). An important and unique aspect of this surveillance is that genotyping of the virus is also undertaken. Given that varicella has not been nationally notifiable in Australia, this surveillance has made an important contribution toward demonstrating the impact of the varicella vaccination program on severe disease. In 2013, PAEDS published the first major study (Marshall et al, PIDJ 2013) to show a decline in hospitalised varicella and herpes zoster – estimated at 73% and 40%, respectively – since vaccine program commencement. In addition, all genotypes were ‘wild-type’ virus with no hospitalised cases due to any genotypes associated with the varicella vaccine. Of hospitalised children age-eligible for varicella vaccine, 80% were unimmunised, including all cases requiring intensive care. This reinforces the importance of vaccination. Surveillance for varicella is ongoing. Most recently we identified that while vaccination provided some protection against more severe disease, breakthrough varicella requiring hospitalisation still occurs in some children vaccinated with a one-dose schedule, providing evidence to support consideration of a 2-dose varicella vaccination schedule. Invasive group A streptococcus disease Principal investigator Associate Professor Nigel Crawford The group A streptococcus (GAS) bacteria is a common infective agent in children and adults that causes the widest range of clinical disease in humans of any bacterium. The spectrum of GAS disease can be divided into superficial, invasive, toxin mediated and post-infectious diseases. The most common infections caused by GAS are superficial, pharyngitis and pyoderma, which occur particularly in children. Invasive diseases are less common but have high rates of mortality and long-term morbidity. They include bacteraemia, including toxic shock syndrome, necrotising fasciitis and meningitis. Currently there is no vaccine to prevent invasive group A streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is the major virulence factor of group A streptococcus and is a key vaccine target. There are over 220 variants of this protein described. Surveillance of invasive group A streptococcus (IGAS) disease began as a pilot at The Royal Children’s Hospital in Melbourne in 2015, and was rolled out nationally to all PAEDS sites in 2016. Invasive meningococcal disease Principal investigator Associate Professor Helen Marshall Although meningococcal is an uncommon infection, the consequences of this disease can be death in 5-10% of cases and long-term disability in up to 40% of children. Until 2013, rates of meningococcal disease were decreasing, but since then rates have increased, with around 250 individuals affected annually, the majority of whom are children and adolescents. The increase has been due to a hypervirulent W strain in addition to the B strain and emergence of disease due to the Y strain. Surveillance through PAEDS began in 2016 and provides the opportunity to collect detailed clinical data in a timely manner to inform meningococcal immunisation strategies and measure vaccine effectiveness. As a national MenACWY program for infants has recently been introduced in Australia and for adolescents commencing in April 2019, PAEDS offers the opportunity to assist in monitoring the impact of these programs, particularly in relation to the impact on disease severity. Kawasaki disease Principal investigator Associate Professor Davinder Singh-Grewal. For further information or enquiries email the PAEDS team (Monday – Friday) PAEDS has conducted national surveillance of Kawasaki disease (KD) since January 2019. Kawasaki disease is an enigmatic condition that can be difficult to diagnose. One of the difficulties is the lack of a diagnostic test - doctors diagnose the disease on the basis of clinical criteria (such as the presence of a rash, fever, swollen lymph nodes and red eyes). Unfortunately many other conditions can look just like Kawasaki disease, making it very difficult to decide which children need to be treated with intravenous immunoglobulin (IVIG). One of the long-term goals of this study is to help develop a diagnostic test so that children with Kawasaki disease can be diagnosed and treated earlier. Much of the funding for these studies has been provided by the National Blood Authority. IVIG is a blood product that comes from blood donors. As such it is a highly valuable, and sometimes scarce, resource. It is hoped that this research will help to make more informed decisions about how IVIG is used in the management of Kawasaki disease. Kawasaki disease and Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-COV-2 (PIMS-TS) surveillance is also important in the context of the COVID-19 pandemic. Read more about this here. Refer also to the clinical advice statement on PIMS-TS, developed by the PAEDS network and endorsed by the Royal Australasian College of Physicians (RACP). The statement provides information on what is known about PIMS-TS; similarities between PIMS-TS and Kawasaki disease and Toxic Shock Syndrome; recommendations for management of patients with possible PIMS-TS; and who to contact if clinicians need further information. Gram-negative blood stream infections Principal investigator Dr Adam Irwin Bloodstream infections (BSI) in children are increasingly healthcare-associated and occur in those with complex comorbidities. In these children, Gram-negative organisms cause almost one half of all BSI and are associated with significant mortality. In an era when the threat of antimicrobial resistance is growing, Gram-negative BSI (GNBSI) represent a significant concern. The development and evaluation of new, effective antimicrobials for resistant Gram-negative infections is particularly limited in children. Existing surveillance systems rarely capture paediatric-specific data. We have established prospective surveillance of GNBSI in children in tertiary children’s hospitals throughout Australia. This surveillance is necessary to understand the clinical and molecular epidemiology of GNBSI and multi-drug resistant GNBSI in children. It will augment data collected by the Australian Group on Antimicrobial Resistance Gram-negative Sepsis Outcome Program, and will help to explain transmission dynamics of both susceptible and resistant invasive Gram-negative organisms in Australian children. Recruitment commenced in January 2019. Intussusception Principal investigator Associate Professor Jim Buttery Intussusception is the most common cause of bowel obstruction in infants and young children and was associated with a previous rotavirus vaccine in the USA which was withdrawn in 1999. Timely, active and systematic surveillance of intussusception cases is important and has identified a temporal but low incidence association with the rotavirus vaccines currently available under the National Immunisation Program (since July 2007). Surveillance also aims to describe the epidemiology, aetiology and severity of intussusception. Surveillance of intussusception is currently paused. Febrile seizures Principal investigator Associate Professor Nick Wood Febrile seizures are the most common type of childhood seizures, occurring 1 in 30 children aged 6 months to 6 years. They are associated with a sudden rise in temperature, most often from a viral illness. Certain vaccines, including measles-containing vaccines and some influenza vaccines, have been associated with an increased risk of febrile seizures. A PAEDS study was conducted between May 2013 and June 2014, gathering detailed clinical and epidemiological information on all febrile seizure presentations to 5 PAEDS sites. These data were used to determine the risk of febrile seizures following the introduction of new vaccines on the National Immunisation Program and to compare clinical outcomes of children who experienced a febrile seizure following a vaccination with children who experienced a febrile seizure unrelated to a vaccination event. The results of these studies have been published. In addition, children in this study were invited to participate in an NHMRC-funded longer-term follow-up study, led by Associate Professor Nicholas Wood, examining these children’s developmental outcomes and genetic susceptibility to febrile seizures compared with healthy children.