Deborah Lehmann, Nick de Klerk, Marty Firth in collaboration with Michael P Alpers (Centre for International Health, Curtin University of Technology)
In the 1980s pneumococcal polysaccharide vaccine was found to be efficacious in reducing mortality and severe morbidity due to acute lower respiratory infection when given from the age of 6 months onwards to young children in the highlands of Papua New Guinea. An effectiveness study of a 23-valent pneumococcal polysaccharide vaccine was subsequently undertaken between 1991 and 1995 when the vaccine was offered to all children aged 8-23 months attending rural child health clinics. The effectiveness of this vaccine in reducing mortality and hospitalisation for pneumonia has been investigated but the problem of access to vaccination being highly correlated with access to hospitals makes a meaningful analysis problematic. The analysis is continuing, trying to overcome this problem.
This study is funded by the World Health Organization; NHMRC, as part of NHMRC Program Grant number 353514
Deborah Lehmann, Hannah Moore, Judith Willis, Catherine Harrison, Leanne Brown, Leonie Waplington in collaboration with Carolien Giele, Paul van Buynder, Michael Watson (Communicable Disease Control Directorate, WA Department of Health), Tony Keil (Department of Microbiology, Princess Margaret Hospital), Denise Murphy (Public Health Bacteriology Laboratory, Brisbane) and Peter Richmond (School of Paediatrics and Child Health, University of Western Australia) for the VISN Network.
The Vaccine Impact Surveillance Network (VISN) was established in 1996 to collect and analyse information pertaining to vaccine-preventable diseases in WA and to assess the impact of vaccination programs. Invasive Pneumococcal Disease (IPD) is a disease caused by Streptococcus pneumoniae (Pneumococcus) invading a normally sterile site such as blood and cerebrospinal fluid. IPD is a major cause of pneumonia, septicaemia and meningitis and is responsible for approximately 1.6 million deaths annually. IPD primarily affects young children and the elderly, but in Australia, incidence rates across all age groups are high in the Aboriginal population.
Pneumococcal vaccines are specifically designed to cover the serotypes that are most commonly associated with severe IPD. There are currently two types of pneumococcal vaccine; a 23-valent polysaccharide vaccine (Pneumovax, 23vPPV) and a 7-valent conjugate vaccine (Prevenar, 7vPCV). Since 1986, Pneumovax has been available free of charge to Aboriginal adults aged ≥50 years and those with known risk factors aged 15-49 years. Since 2005, Pneumovax has been fully funded by the Federal Government for the elderly and at risk groups. Prevenar was licensed in Australia in 2001 and made available to Aboriginal and other high-risk children (at ages 2, 4, and 6 months) at no cost. Aboriginal children get a booster of Pneumovax at age 18 months. In January 2005 Prevenar became available to all Australian children at no cost.
Although IPD only became notifiable in 2001, VISN has collected epidemiological and microbiological data on all reported IPD cases since 1996. The Communicable Disease Control Directorate (CDCD) at the WA Department of Health took over monitoring IPD from 2008. Throughout 2008, ICHR activity has therefore involved finalising the 1997-2007 data, presenting results at conferences, and preparing publications.
From April 1, 1996 to December 31, 2007, a total of 1913 episodes of IPD were recorded on the VISN database. There has been a substantial decline in 7vPCV-type IPD across all age groups and hence also in adults who are not eligible for vaccination, suggesting a herd immunity effect. However, despite the decline in IPD cases caused by 7vPCV serotypes, there is now a significant increase in IPD due to non-7vPCV serotypes. In particular, we have seen a rise in the incidence due to the non-Prevenar serotype 19A in the non-Aboriginal population and a doubling of IPD rates due to non-7vPCV serotypes in Aboriginal adults aged 30-49 years. Currently there is no register of immunizations in adults. Such a register is needed to assess the impact of adult vaccination programs.
In 2008, two posters were presented at the 6th International Symposium on Pneumococci & Pneumococcal Diseases held in Iceland. One documented the increase in IPD observed within the young Aboriginal adult population whilst the other focused on the recent increase in IPD rates observed in the non-Aboriginal population from 2004-2007. Trends in IPD 1997-2007 were also presented at the PHAA National Immunisation Conference at the Gold Coast. A manuscript documenting these results is now in advanced draft form.
Funded by WA Department of Health through the Collaboration for Applied Research and Evaluation
Deborah Lehmann, Anke Bergmann, Ruth Monck in collaboration with Jacinta Bowman, Tom Riley (Division of Microbiology and Infectious Diseases, PathWest Laboratory Medicine WA). Carolien Giele, Michael Watson, Paul van Buynder (Communicable Disease Control Directorate, WA Department of Health), Amanda Leach, Kim Hare (Menzies School of Health Research, Darwin) , Peter Richmond (School of Paediatrics and Child Health, University of Western Australia), Tony Keil (Department of Microbiology, Princess Margaret Hospital) in collaboration with WA Aboriginal Community Controlled Health Organisations and remote Aboriginal communities in WA
Streptococcus pneumoniae (pneumococcus) can cause middle ear infection and invasive pneumococcal disease (IPD) resulting in meningitis, pneumonia and septicaemia (blood poisoning). The Australian Aboriginal population has among the highest reported IPD rates worldwide.
The existence of 90 different types (serotypes) of pneumococci increases the challenge of prevention. A vaccine (Prevenar) covering the 7 most common serotypes and a booster with another vaccine (Pneumovax) covering 23 serotypes is offered to Aboriginal children and Pneumovax is also offered to adults. Cause for concern is that IPD is now primarily due to serotypes not included in the Prevenar vaccine.
Pneumococci are carried in the back of the nose of healthy as well as sick individuals. Surveillance of pneumococcal carriage offers important complementary information to data on IPD since it can quickly provide a large amount of information on serotypes circulating in the population, thereby informing public health programs. It also gives a conservative estimate of antibiotic resistance of invasive pneumococcal strains. This study aims to monitor pneumococcal carriage by collecting 300 nose swabs annually from Aboriginal adults and 300 from Aboriginal children in metropolitan, urban, rural and remote areas of Western Australia. We also collect ear swabs from children with ear discharge. Other study aims include: i) describing the prevalence of URT carriage of other pathogens identified on primary culture; ii) comparing pneumococcal carriage rates in Aboriginal children aged < 2 years in the Kalgoorlie-Boulder region with those documented in 1999-2005; iii) comparing the distribution of pneumococcal serotypes in the URT with those causing IPD in Aboriginal adults and children annually; iv) storing pernasal swabs for detection of viruses by PCR to describe the prevalence of respiratory viruses; and v) investigating viral-bacterial interactions in the URT.
We recruit Aboriginal children and adults attending health services for routine examination, immunisation or illness, regardless of whether they have chronic illness. Between August and December of 2008, we collected 320 nose swabs and 13 ear swabs in Wiluna, Kalgoorlie and Roebourne. Our collaboration with the Menzies School of Health Research has recently been enhanced by the award of a joint NHMRC project grant.
Funded by WA Department of Health through the Collaboration for Applied Research and Evaluation
Deborah Lehmann, Nick de Klerk, Marty Firth in collaboration with Michael P Alpers (Centre for International Health, Curtin University of Technology)
Following a report of increased risk of death associated with diphtheria tetanus pertussis (DTP) and oral polio vaccination of children living in rural areas of Guinea-Bissau, the World Health Organization Department of Vaccines and Biologicals sought proposals to determine the effects of routine infant immunisation on survival in areas of high mortality. We investigated the impact of routine immunisations on childhood survival in Tari, Southern Highlands Province, Papua New Guinea. Continuous monthly demographic surveillance enabled us to identify births, deaths, migrations, and immunisation status of all children born in Tari between 1989 and 1994. The study determined the effect of DTP, BCG and measles vaccinations on mortality in the first two years of life and found no deleterious effects of infant immunisations. Our findings have been published in an international journal.
There has also been an investigation into some statistical methodology issues concerning longitudinal and observational data sets such as this one. A paper comparing the potential impact of the varying assumptions that different studies have made around the world is in preparation.
Funded by World Health Organization; NHMRC, as part of NHMRC Program Grant number 353514
Deborah Lehmann, Hannah Moore, Nick de Klerk, Peter Jacoby, Heather D’Antoine, Daniel McAullay in collaboration with Peter Richmond (School of Paediatrics and Child Health, University of Western Australia), David Smith (Division of Microbiology and Infectious Diseases, PathWest Laboratory Medicine WA), Tony Keil, Katie Lindsay (PathWest Laboratory Medicine WA, Princess Margaret Hospital).
The primary objective of this PhD project is to describe the aetiology, burden and causal pathways of acute lower respiratory infections (ALRI) in Aboriginal and non-Aboriginal children from a 10-year birth cohort using population linked data. This large data linkage project involves linkages between hospital morbidity data, emergency department data, state-wide laboratory data, cerebral palsy register data, birth defects register data and data from births, deaths and midwives’ notifications and when available, immunisation data from the Australian Childhood Immunisation Register. In 2008 data were received from the Midwives’ Notification System, Birth and Death Register, Hospital Morbidity Database System and the Emergency Department Data Collection. The birth cohort dataset has been formed and consists of 245, 249 singleton live births of which 7.1% are Aboriginal. Episodes of ALRI in hospital from children in the birth cohort have been identified and data cleaning of the emergency department dataset to identify ALRI-related metropolitan emergency department presentations is underway. Preliminary results from this project indicate that 1 in every 4 Aboriginal children and 1 in every 15 non-Aboriginal children under the age of 9 years are admitted to hospital at least once for ALRI. The most common form of ALRI is bronchiolitis which accounted for 11,988 (45.9%) of all ALRI admissions between 1996 and 2005. Negotiations with data custodians of laboratory data continued in 2008 and it is anticipated that laboratory data will be extracted and linked during 2009. In late 2008, we were awarded an NHMRC Project Grant (number 572590) centred on this project. The study will provide the essential baseline data on which to identify, recommend and evaluate appropriate preventive measures for ALRI in Aboriginal and non-Aboriginal children in WA.
As preliminary work for this project, de-identified data on specimens collected between 1997 and 2005 that were sent to the Department of Microbiology at Princess Margaret Hospital were extracted to investigate seasonal and temporal trends of respiratory viruses. This work highlighted the differences in seasonality between respiratory syncytial virus (RSV), influenza viruses, adenovirus and parainfluenza virus types 1 and 3 and in particular, differences in seasonality of influenza viruses between Aboriginal and non-Aboriginal children. This work has been accepted for publication and was presented at local and national conferences including the Public Health Association of Australia’s 11th National Immunisation Conference.
Funded by NHMRC Program Grant
Shane Venables, Deborah Lehmann, Hannah Moore
Diarrhoea is a significant reason for hospitalisation in Australia. This study utilising the total population-based databases from the Maternal and Child Health Research Database is investigating the trends in hospital admissions for diarrhoeal diseases in Western Australian children aged <15 years between 1983 and 2006. One major cause of diarrhoeal disease in children is rotavirus and this virus contributes to approximately 50% of children’s admissions to hospital for diarrhoeal disease. A rotavirus vaccine was introduced in 2007. This study will be useful in providing baseline data on hospitalisations for diarrhoeal disease prior to the introduction of the vaccine.
Funded by NHMRC Program Grant
Deborah Lehmann, Hannah Moore, Kirsten Alpers, Anne McKenzie
In 2007 we commenced planning for an Infectious Diseases Community Reference Group to inform the wider community about research conducted at ICHR around infectious diseases and for community members to provide researchers with their valuable input into research projects. In 2008 the Infectious Diseases Community Reference Group met on four occasions and has had various discussions regarding current projects within the infectious diseases team. The group consists of 8 community members (3 of whom are Indigenous), representatives from the Western Australian Department of Health and The Meningitis Centre, ICHR’s community liaison officer and infectious disease researchers.
Funded by The Meningitis Centre
Deborah Lehmann, Anita van den Biggelaar, Pat Holt in collaboration with Peter Siba, William Saila Pomat, Suparat Phuanukoonnon, John Reeder (Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea), Peter Richmond (School of Paediatrics and Child Health, University of Western Australia), Amanda Leach (Menzies School of Health Research), David Smith (Division of Microbiology and Infectious Disease, PathWest Laboratory Medicine WA).
Throughout the world an estimated one million children die annually from pneumococcal disease, the majority in early infancy. This study is designed to investigate the safety, immunogenicity and priming for immunologic memory of pneumococcal conjugate vaccine (PCV) in Papua New Guinean infants at 1-2-3 months of age and to find out whether neonatal immunisation in the first week of life will provide earlier protective antibody responses. The study is assessing the impact of a 7-valent PCV on early pneumococcal nasopharyngeal colonisation and on the incidence of acute respiratory infections in the first year of life. We are investigating the development of mucosal and T-cell immunity to non-capsular pneumococcal protein antigens and how this may be affected by early onset of colonisation. The study will also assess the impact of neonatal immunisation on humoral and cellular immune responses to concomitant vaccines (diphtheria toxoid, tetanus toxoid and measles) and whether PCV interferes with normal maturation of the immune system.
Enrolment of all 319 study participants was completed in September 2007. By December 2008 all children had completed follow-up to age 15 months and PCV and 23-valent pneumococcal polysaccharide vaccination (PPV). Reactogenicity to PCV was low, but tended to be a little higher in children vaccinated in early infancy than at birth, probably because of their older age and hence more mature immune system. Analysis of cellular immune responses when children were 3 months old demonstrated that neonatal PCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses (accepted for publication in Vaccine in December 2008). Preliminary findings from measurement of pneumococcal serotype-specific antibodies indicate that neonatal and early infant immunisation is safe and immunogenic and that it may delay onset of a first episode of pneumonia in young children.
Ms Jacinta Francis from the Papua New Guinea Institute of Medical Research has submitted her MSc Thesis in which she reports on the maternal and neonatal immune responses to Streptococcus pneumoniae and how these responses relate to early pneumococcal carriage in the nasopharynx. She has now completed her 2 year stay and returned to PNG.
The research team presented six posters on this project at the 6th International Symposium on Pneumococci and Pneumococcal Diseases in Iceland.
At this meeting Dr. Anita van den Biggelaar was awarded the Robert Austrian Research Award of USD25,000 for her work in pneumococcal vaccinology.
In an extension of this project, D Lehmann is co-supervising a post-doctoral research fellow (IA Laing), who is investigating the contribution of human genetic susceptibility to nasal bacterial carriage, development of immune/vaccine responses and the incidence of pneumonia in this population. Dr Laing has an Australian Research Council Ann Woolcock Research Fellowship and genetics studies are supported through a grant from the University of Western Australia Research Grants Scheme 2006. Preliminary results from investigation of associations between genotype and acute lower respiratory infections (ALRIs) suggest that several genetic variants from known immune pathways may play a role in the frequency of ALRIs in children in PNG.
In a small pilot project, multiplex PCR at PathWest Laboratory Medicine WA has been used to identify viruses in the nasopharynx of sick and healthy vaccine trial participants. Influenza viruses, respiratory syncytial virus and adenoviruses were more common during ALRI episodes while coronaviruses and rhinoviruses were more common when children were healthy. We will be examining all nasopharyngeal samples for respiratory viruses.
This study is funded by the NHMRC/ Welcome Trust International Collaborative Research Grant Number 303123
Deborah Lehmann, Peter Jacoby, Wenxing Sun, Christine Jeffries- Stokes, Annette Stokes, Daniel McAullay, Dimity Elsbury, Janine Finucane, Ruth Monck, Fiona Stanley in collaboration with Bega Garnbirringu Health Services Aboriginal Corporation, Ngunytju Tjitji Pirni Inc, Harvey Coates (Senior ENT Surgeon, Princess Margaret Hospital), Thomas V Riley (Department of Microbiology, University of Western Australia), Sharon Weeks (Audiologist, Professional Hearing Services), Allan W Cripps (Griffith University, Queensland), Jennelle Kyd (Central Queensland University, Rockhampton), Jacinta Bowman, Amanda Taylor, David Smith (Division of Microbiology and Infectious Diseases, PathWest Laboratory Medicine WA), Denise Murphy (Public Health Bacteriology Laboratory, Brisbane), Amanda Leach (Menzies School of Health Research, Darwin), Nevada Pingault (University of Western Australia).
Otitis media (OM, middle ear infection) can seriously affect childhood development, school performance and subsequent social and economic well-being. The Kalgoorlie Otitis Media Research Project was established in 1999 to investigate the causal pathways to OM and, specifically, to identify demographic, socio-economic, environmental, microbiological and immunological risk factors for OM in Aboriginal and non-Aboriginal children in order to develop appropriate interventions. We followed 100 Aboriginal and 180 non-Aboriginal children from birth to age two years. Field work was completed in 2004 and data cleaning was completed in April 2005.
The burden of OM remains very high in the Kalgoorlie-Boulder area with a peak prevalence of 72% in Aboriginal children aged 5-9 months and 40% in non-Aboriginal children aged 10-14 months. Furthermore, 29% of Aboriginal children and 5% of non-Aboriginal children have had a perforated ear drum at least once by age 2 years, and 65% of Aboriginal children and 23% of non-Aboriginal children have some degree of hearing loss at age 12-17 months.
Several papers have been published in 2008. One paper details the rationale, methods, population characteristics and ethical considerations. We have reported in the Medical Journal of Australia that exposure to environmental tobacco smoke is associated with an increased risk of developing OM. In a further publication we report that measurement of otoacoustic emissions at a young age using a simple tool can identify those Aboriginal children who are at risk of getting OM later on. We have now been awarded a Healthway grant to evaluate a program of promoting good ear health and regular screening of Aboriginal children in the Goldfields from birth in order to have children hearing when they reach school age. We also described an improved pulsed field gel electrophoresis for molecular typing of Moraxella catarrhalis.
Rhinoviruses and adenoviruses are commonly identified in the upper respiratory tract, more commonly in Aboriginal than non-Aboriginal children and are frequently associated with bacterial carriage. We are preparing a paper that describes the respiratory viruses identified in healthy Aboriginal and non-Aboriginal participants and the simultaneous identification of viruses and bacteria. We have also found that crowding is associated with increased risk of carrying the pneumococcus, nontypeable Haemophilus influenzae or M. catarrhalis in the nasopharynx, which is important since carriage of these bacteria is associated with increased risk of OM. Interestingly, exclusive breastfeeding for the first 6-8 weeks of life protects children from carriage of Staphylococcus.aureus. Finally, independent of environmental factors such as crowding, children who carry pneumococcus, nontypeable Haemophilus influenzae or M. catarrhalis in the nasopharynx at 1-2 months of age are at increased risk of getting OM.
Funded by Healthway; NHMRC Project grant number 212044 and as part of NHMRC Program Grant number 353514, Theme 4: Infection
