We are pleased to announce the award of our NHMRC-funded Partnership Project (APP1113851). This project is aimed at improving immunisation programs to most effectively and equitably prevent illness and death due to the two most prevalent vaccine preventable diseases in Australian children, influenza and pertussis.
Morbidity from influenza and pertussis remains a significant challenge. An average of 2,700 children are hospitalised from these diseases each year. Deaths also continue to occur from influenza and pertussis, even in previously healthy children and babies.
We will be undertaking a novel and systematic examination of how factors related to both the effectiveness and the uptake of vaccination contribute to controlling influenza and pertussis in Australian children.
This project expands upon our national partnership of major paediatric hospitals in Australia: the Paediatric Active Enhanced Disease Surveillance (PAEDS) network. We have established PAEDS sites in the major paediatric hospitals in five states (NSW, Western Australia, South Australia, Queensland and Victoria), and will be adding a sixth site in Darwin in the Northern Territory. With total funding comprising of fifty-per cent support from the NHMRC and fifty-per cent from our funding partners, who are all relevant State and Territory and the Australian Government Departments of Health, our collaboration is well placed to conduct this cutting edge program-relevant research.
Our nationally representative team is comprised of immunisation and public health experts, epidemiologists and social scientists. Over the coming three years we will undertake a range of studies, including:
a) identifying in whom breakthrough disease occurs despite immunisation and why, and we will estimate vaccine effectiveness of new programs;
b) identify reasons for under or no-vaccination at the individual, community, system and policy levels; and
c) determine factors or gaps in immunisation policy and practice that can be changed to improve prevention of disease from influenza and pertussis in children.
Associate Professor Kristine Macartney
Dr Christopher Blyth
Associate Professor Helen Marshall
Associate Professor Julie Leask
Professor Peter McIntyre
Professor Elizabeth Elliott
Dr Thomas Snelling
Associate Professor Julia Clark
Associate Professor Jim Buttery
Associate Professor Nicholas Wood
Dr Philip Britton
Professor Allen Cheng
Dr Nigel Crawford
Associate Professor Michael Gold
Professor Peter Richmond
Dr Joshua Francis
Associate Professor Stephen Lambert
Professor Paul Effler
Dr Kerrie Wiley
Emeritus Professor Lesley Barclay
Dr Alan Leeb
Jocelynne Mcrae (University of Sydney)
Samantha Carlson (University of Sydney)
Gemma Saravanos (University of Sydney)
James Bao (University of Sydney)
The Sydney Children’s Hospitals Network (The Children’s Hospital at Westmead) (NSW)
The University of Sydney (NSW)
Princess Margaret Hospital (WA)
Telethon Kids Institute (WA)
The University of Western Australia (WA)
Women and Children’s Hospital (SA)
The University of Adelaide (SA)
Queensland Children's Hospital (formerly Lady Cilento Children’s Hospital) (QLD)
The University of Queensland (QLD)
Royal Children’s Hospital (VIC)
Murdoch Children’s Research Institute (VIC)
Monash University (VIC)
Royal Darwin Hospital (NT)
Flinders University (NT)
Australian Government Department of Health
NSW Ministry of Health
The Sydney Children’s Hospitals Network (The Children’s Hospital at Westmead) (NSW)
Western Australia Department of Health
South Australia Department for Health and Ageing
Queensland Department of Health
Department of Health and Human Services, Victoria
Northern Territory Department of Health
Professor Kristine Macartney – email@example.com
Surveillance is ongoing for the three conditions monitored by PAEDS since 2007 – acute flaccid paralysis (AFP), intussusception and varicella/herpes zoster. Since then, additional conditions have been added to ongoing surveillance, including – pertussis (2012), acute childhood encephalitis (2013), influenza (2014), invasive meningococcal disease, invasive group A streptococcus disease (GAS; 2016) and Kawasaki disease, Gram-negative blood stream infections (2019).
In previous years, PAEDS has also studied important conditions such as pandemic influenza in 2009 and Guillain-Barré syndrome following pandemic influenza vaccine. Surveillance of febrile seizures (2013-2014) was also conducted following introduction of the new vaccines to the National Immunisation Program.
Pertussis is one of the most common vaccine-preventable diseases seen in Australia, with a recent large outbreak experienced nationally from 2008 to 2011, and again more recently in 2015. Pertussis is particularly severe in young infants, not yet fully immunised in whom many complications, and sometimes death, occur. PAEDS conducts surveillance for hospitalised pertussis in Australia, with special emphasis on disease severity, the need for intensive care, death and disability.
This work also aims to examine the contribution of co-infections and other co-morbidities, and disease transmission in households (by checking the immunisation history of patients, family members and ‘coughing contacts’).
These factors will also be correlated with the genetic sub-types identified in Bordetella pertussis positive cultures. Recruitment commenced in January 2012.
Febrile seizures typically occur in children from 6 months to 6 years of age and can be triggered by a sudden fever from any cause – most often from a viral illness. About 1 in 30 children of this age will have a febrile seizure, with recurrent seizures occurring in approximately one-third of children.
New vaccines recently added to the National Immunisation Program (the 13-valent pneumococcal conjugate vaccine and the combined measles-mumps-rubella-varicella vaccine) have been associated with somewhat high rates of fever, and therefore potentially a risk of febrile seizure occurring.
This PAEDS study will gather enhanced clinical and epidemiological information on febrile seizures and will determine if there is an increased risk of febrile seizures with these new vaccines. It will also describe the clinical and revaccination outcomes of children who have experienced a febrile seizure.
In addition, in four PAEDS sites, children who experience febrile seizures can enrol in an NHMRC funded study led by Dr Nicholas Wood from NCIRS, to look at genetic susceptibility to seizures and long term developmental outcomes. PAEDS surveillance for febrile seizures was conducted in 2013-2014.
Surveillance for acute flaccid paralysis (AFP) has been conducted by PAEDS since 2007. To retain Australia's polio free status, it is important that Australia contributes to AFP surveillance, including meet World Health Organization surveillance targets related to case identification, stool collection and case investigation. This work contributes to the goal of global polio eradication (http://polioeradication.org/).
PAEDS centres 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; http://www.apsu.org.au/) and National Enterovirus Reference Laboratory(NERL/VIDRL; http://www.vidrl.org.au/laboratories/poliovirus-reference/), 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.
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.
From 2014, two PAEDS sites – The Children’s Hospital at Westmead (Sydney) and Princess Margaret Hospital (Perth) – have participated in active hospital-based surveillance for influenza with FluCAN (the Influenza Complications Alert Network). FluCAN is a rapid alert system for severe respiratory illness that commenced in 2009 and maintains a real-time sentinel hospital surveillance system for acute respiratory disease requiring hospitalisation. It currently operates across approximately 15 hospitals and has mainly assessed influenza in adult patients. Given the high burden of influenza in children, this collaboration between PAEDS and FluCAN promises to provide much needed, enhanced data on the complications of influenza in children, as well as assess vaccine effectiveness in this age group.
PAEDS has conducted surveillance for intussusception (IS) since 2007 when rotavirus vaccines (a potential trigger for IS) were introduced in Australia. PAEDS investigators were the first worldwide to publish data on the risk of IS associated with these new vaccines (Buttery et al. Vaccine 2011). This risk remains very low, however, in comparison with the benefits seen from rotavirus vaccination in Australia and worldwide.
Our PAEDS study was key in informing advice from the World Health Organization and other key expert bodies worldwide regarding the use of rotavirus vaccines. In 2012, a study commissioned by the Therapeutic Goods Administration (TGA) extended the analysis done by PAEDS. This study (Carlin et al. CID 2013), using data collected by many Australian states and territories in addition to PAEDS data, estimated that there would be approximately 6 additional cases of IS among every 100,000 infants vaccinated, or 14 additional cases per year in Australia.
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.
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.
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.
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 kindly 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. Recruitment commenced in January 2019.
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.