The Marshall Centre for Infectious Diseases Research and Training

Arbovirus Surveillance Unit

Dr Cheryl Johnasen, Professor Geoffrey Shellam, Dr David Smith

Arboviruses are transmitted between and replicate in arthropod vectors and susceptible vertebrate hosts. The flaviviruses Murray Valley encephalitis virus (MVEV) and Kunjin virus (KUNV) and the alphaviruses Ross River virus (RRV) and Barmah Forest virus (BFV) are mosquito-borne arboviruses can cause outbreaks of human disease in Australia. The Arbovirus Surveillance and Research Laboratory (ASRL) at The University of Western Australia is funded by the Western Australian Department of Health (DOH) to monitor activity of these and other medically important arboviruses in Western Australia. The goals of the ASRL are to:

1. provide advance warning of arboviruses and vector mosquito activity;

2. increase the understanding of the ecology and epidemiology of arboviruses of public health importance and their inter-relationships between vectors, vertebrate hosts, the environment and human activities, to predict and be prepared for future outbreaks of human disease; and

3. increase the speed, accuracy and sensitivity of the program.

The program provides the WA DOH and Local Government Authorities with early warning of the need to undertake vector management measures and issue media releases warning the public to take self-protective measures. It also provides accurate information to maximise the effect of current mosquito management programs, assists with the development of new control strategies, and directs strategies for public education and management of natural, rural and urban environments. Ultimately, the aim of the program is to reduce the risk and incidence of mosquito-borne diseases in Western Australia.

Bacterial Pathogens of the Intestine

Dr Harry Sakellaris

The major aims of our research are to understand the pathogenesis of diarrhoeal diseases caused by enterotoxigenic E. coli (ETEC) and Shigella spp. The World Health Organisation estimates that these two bacteria are responsible for almost half of the 4-6 million deaths caused by diarrhoeal disease every year.

ETEC diarrhoea is a major public health burden in developing countries lacking the infrastructure to provide clean water supplies. The development of cheap and effective vaccines for ETEC is a strategy that has been encouraged and facilitated by the World Health Organisation. However, recent vaccine trials using whole, killed bacteria to stimulate immunity have failed to protect against ETEC infections in 80% of individuals who developed “vaccine-preventable” diarrhoea. Alternative strategies are required to prevent ETEC infections but we are hampered by our incomplete understanding of ETEC pathogenesis. The major focus of our research on ETEC involves:

• Identifying novel ETEC virulence genes.
• Elucidating the mechanisms by which ETEC colonises host.
• Identifying conserved surface proteins in ETEC that be may be suitable for the development of broadly effective vaccines.

The virulence of Shigella spp. is influenced by a number of laterally acquired genetic elements including pathogenicity islands (PAIs). The she PAI carries encodes three autotransporter proteins, with established or putative roles in bacterial virulence. The main aim of our current work in this area is to analyse the structure-function relationships of these proteins and to determine how they contribute to disease development.

Cytomegalovirus

Professor Geoff Shellam, Dr Alec Redwood, Dr Lee Smith, Dr Megan Lloyd

Cytomegaloviruses are large, double-stranded DNA viruses, which persist for the lifetime of the infected host. These viruses have co-evolved with their hosts, and thus most vertebrate species appear to have their own, species-specific cytomegalovirus.

The research of the Cytomegalovirus Research Group focuses on murine cytomegalovirus, which is the most widely used model for human CMV infection. Our research involves detailed studies of specific gene function, analysis of the effects of genetic variation on virus immune evasion, and genomic analyses of wild strains of MCMV. Of particular interest are the putative interactions (complementation, competition or recombination) between multiple viral strains infecting the same host.

We also use murine CMV as a vector for delivery of foreign proteins into the murine host, resulting in long-lived and specific immune responses against the recombinant antigen. One such system, utilizing murine CMV expressing murine fertility proteins, can be used to induce infertility in mice.

Environmental pathogens

Dr Tim Inglis

This group is currently working on environmental drivers of melioidosis; a tropical bacterial infection present in northern Australia and Southeast Asia. They have recently joined a multinational metagenome project that uses comparative genomics to understand the evolutionary origins of bacterial virulence. In other developments, the group is improving rapid identification and genotyping methods for bacterial infections, with special emphasis on deployable laboratory capability.

Helicobacter pylori

Professor Barry Marshall, Dr Mohammed Benghezal, Dr Alma Fulurija, Dr Tobias Schoep, Dr Helen Windsor

In 1997 Professor Barry Marshall established the Helicobacter pylori Research Laboratory at the QEII Medical Centre to study this organism which infects half of the world’s population and is the proven cause of peptic ulcer and most gastric cancer. Research has been carried out on improving diagnostic methods, on prevalence within the Australian population and within family groups. At present a study is underway to determine whether a person can be reinfected with their own strain of H. pylori. Increasing levels of resistance to the antibiotics routinely used to eradicate H. pylori, has meant that approximately 15% of patients are not cured of their infections with standard ‘over-the-counter’ drug combinations. Such patients are referred to Prof Marshall and, after isolation of their H. pylori strain, they receive a ‘tailor-made’ combination of antibiotics prescribed specifically to eradicate their strain of H. pylori.
Since 2005 work has been carried out on a new vaccine and drug delivery system called the “Helicobacter pylori Platform Technology” via the new biotechnology start-up company “Ondek “ funded by Western Australian and international investors and supplemented by an Ausindustry commercial ready grant from Federal government. The Ondek vaccine system will utilize the unique characteristics of a genetically modified H. pylori bacterium which will act as a live vaccine vector.

Influenza Surveillance Unit

Dr David Smith

Influenza surveillance has been carried out since 1999, initially only during the winter season but now throughout the year. This is conducted in collaboration with the Communicable Disease Control Directorate (CDCD) of the Western Australian Department of Health. Weekly data on influenza-like illnesses presenting at Sentinel General Practitioners is collected, and testing is carried out on a subset of those patients. Data on routine laboratory detection of influenza at PathWest at the QE2 Medical Centre and PathWest at the Women's and Children's Health Service is also collected. PathWest at the QE2 Medical Centre is one of the Australian National Influenza Centres and collects and forwards influenza isolates to the World Health Organization Collaborating Centre in Melbourne. A number of applied research activities are carried out in conjunction with the influenza surveillance. These include new technologies for detection and characterisation, molecular surveillance of other respiratory viruses, estimating impact of influenza, and programs for identifying new respiratory pathogens.

Neisseria

Dr Charlene Kahler, Dr Lea-Ann Kirkham

Neisseria meningitidis and N. gonorrhoeae are two closely related obligate human pathogens. N. meningitidis is the causative agent of epidemic meningococcal meningitis and septic shock. It colonizes mucosal surfaces of the nasopharynx and in susceptible individuals, the bacterium becomes systemic resulting in fatal bacteremia. Vaccines have been developed based on the polysaccharide capsules to prevent community spread and therefore are an effective means of reducing meningococcal disease. However, serotype B remains prevalent since there is no vaccine against this organism.
Neisseria gonorrhoeae on the other hand, is the causative agent of the sexually transmitted disease (STD) gonorrhoea. Globally approximately 20-60 million new cases are reported per annum (WHO). In males, gonococcal infection is generally acute and resolves rapidly with treatment. However, in women the infection remains asymptomatic and without treatment progresses to pelvic inflammatory disease (PID) resulting in infertility in approximately one third of patients. Unlike meningococci, this organism is increasingly resistant to antibiotics with a recent report of the emergence of a “superbug” resistant to all antibiotics. Because the cell surface proteins expressed by this organism are highly antigenically variable, no successful vaccine strategies have been developed to prevent infections.
Dr Kahler’s group is interested in three different facets of these important human pathogens:

a. Understanding the biosynthesis pathway and regulatory networks controlling the production of the primary toxin produced by meningococci, the endotoxin.

b. Examining the regulatory networks within meningococci that are triggered during attachment to the human nasopharynx.

c. The role of stress proteins in the survival of gonococci during intracellular growth in human urethral and cervical cells.