Population Health and Biology

Prof. Alyssa Barry

Dr Kirsty McCann

Genomic analysis of remaining Plasmodium falciparum infections throughout Cambodia will improve our understanding on persisting pockets of high malaria risk, asymptomatic infections and the emergence and spread of multi-drug resistance. This research is essential to implement appropriate treatment plans to reach the national goal of malaria elimination by 2025. The whole genome of 29 P. falciparum isolates were sequenced that were collected from patients with clinical malaria residing in the Kaev Seima District in the Mondulkiri Province, Cambodia. Through whole genome sequencing we identified high-quality genotypes to investigate P. falciparum population structure in Mondulkiri Province compared with 1) MalariaGen Pf3kv5 collected data of neighbouring countries, 2) structure between Cambodian provinces and 3) within Mondulkiri Province. We filtered the dataset to identify known drug resistant genes including crt, mdr1, dhfr, dhps and kelch13. We identified variants associated with resistance to multiple antimalarials within these Cambodian isolates with high levels of IBD driving population structure. Most Cambodian isolate genomes contained markers associated with resistance against Sulfadoxine Pyrimethamine, Chloroquine Amodiaquine Quinine and Artemisinin treatments.

Deakin University

Burnet Institute

Institut Pasteaur Cambodia

Walter and Eliza Hall Institute (WEHI)

Dr Benoit Witkowski

Dr Amelie Vantaux

Prof. Leanne Robinson

Prof. Ivo Mueller

Dr John Stenos

Prof Stephen R. Graves

The aim of this project is to develop an endogenous vaccine that will protect goats from the C. burnetii pathogen.  Initially the agent was isolated from the endemic farm and then amplified at the ACDP.  Following inactivation it will be used to vaccinate the goats.  The vaccine needs to be approved and licensed by the Australian Pesticides and Veterinary Medicines Authority.  This regulatory process requires the vaccine to be manufactured under GMP conditions. Once we have vaccinated the animals we will gauge the efficacy of the delivery by monitoring both, animals and their immediate environment for the presence of C. burnetii.

Prof Peter Irwin

Dr Amanda Barbosa

Prof Stephen R. Graves

Centre for Biosecurity and One Health, Harry Butler Institute, Murdoch University.  Emergency Department, Northern Beaches Hospital, Sydney.  School of Medicine, Macquarie University, Sydney.

Sydney Medical School, Sydney University. School of Medicine, University of Western Australia. College of Science, Health, Education and Engineering, Murdoch University

This is a four-year longitudinal study of patients with tick bite that aims to provide a scientifically valid, evidence-based understanding of the cause(s) of debilitating symptom complexes attributed to ticks (DSCATT). With current uncertainty about the aetiology of DSCATT, our proposal will encompass clinical, psychological, and laboratory testing of tick bite patients, and matched controls, to better define the illness and to determine if infectious organism(s) are contributing to the symptom complexes. Utilising routine pathology, immune profiling, phenomics and advanced molecular testing on samples collected at the time of tick bite, together with psychological profiling, and at subsequent occasions up to 12 months, we will determine if persistent and/or recurrent infection with microbes found in Australian ticks are directly associated with clinical, psychological and/or laboratory markers.

This study, funded by the NHMRC, builds upon our recognised research and is informed by our team of experienced clinicians and medical scientists with expertise in vector-borne diseases, microbiology, epidemiology, immunology, and molecular biology. We are uniquely placed to analyse samples collected from people bitten by ticks (n=900), and from controls (n=1,800) living in the same geographical locations.

Michelle Long, Wenna Lee,Jill M. Austen, Mike Cunneen, Andrew Ratchford, Brian Burns, Prasad Kumarasinghe, Rym Ben-Othman, Tobias R. Kollmann ,Cameron R. Stewart, Miles Beaman, Rhys Parry, Roy Hall, Ala Tabor, Justine O’Donovan, Helen M. Faddy, Marjorie Collins, Allen C. Cheng, Charlotte L. Oskam and Una M. Ryan

Amanda Barbosa et al. The Troublesome Ticks Research Protocol: Developing a Comprehensive, Multidiscipline Research Plan for Investigating Human Tick-Associated Disease in Australia.  Pathogens 2022, 11(11), 1290; https://doi.org/10.3390/pathogens11111290

Dr Stephen R. Graves

Dr John Stenos

This project involves growing the phase 1 (virulent) bacterium Coxiella burnetii in axenic medium and extracting the O-polysaccharide of the bacterial lipopolysaccharide cell wall. The purified polysaccharide is then conjugated to tetanus toxoid to convert it into a vaccine. The vaccine is tested in guinea pigs, as this infection model mimics acute Q fever infection in humans. Guinea pigs are monitored for fever and loss of weight after challenge infection with C. burnetii. To date the vaccine seems to protect guinea pigs from fever and loss of weight. The long term objective is to test the new vaccine in humans as a phase 1 trial.

Graves et al (2022) “An O-specific polysaccharide/tetanus toxoid conjugate vaccine induces protection in guinea pigs against virulent challenge with Coxiella burnetii.” Vaccines, 10, 1393.

Dr John Stenos

Dr Tshokey Tshokey

Prof Stephen R. Graves

World Health Organisation, MORU Tropical Health Network, Thailand,

Swiss Tropical and Public Health Institute, Switzerland

There is a current opportunity at WHO to develop activities on severe bacterial diseases which have been forgotten thus far, such as leptospirosis, melioidosis and rickettsioses. This is related to the One Health initiative. As the focal point for these diseases, we have been asked to review the rickettsial burden and propose action points to the WHO. Once the review has been finalised WHO approved centres of rickettsial excellence will be established worldwide in order to achieve the goal of the initiative.  The primary interest is on the epidemic manifestations of these diseases and that they constitute a significant differential diagnosis of epidemic disease with outcomes aimed at developing activities on the prevention and control of rickettsial diseases.

Eric Gerard Georges Bertherat, Matthew Robinson, Stuart Blacksell, Nicholas Day, Daniel Paris, Kartika Saraswati