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Infectious Diseases and Microbiology Research

The Department conducts research into various aspects of clinical infectious diseases and microbiology with a focus on healthcare-associated infections and pathogen genomics.

Multidrug-resistant bacteria, and the hospital acquired infections they cause, are one of the most significant future threats to human health both in Australia and globally. Effective antibiotics are essential for the safe provision of life-saving interventions such as solid organ and bone marrow transplantation, cancer chemotherapy and surgery. These interventions are now under threat, due to rapidly expanding antimicrobial resistance and a lack of novel antimicrobial drug classes.

A major focus of the Department's research is understanding how these multidrug-resistant bacteria spread across the community and the hospital and how they adapt to specific niches, using state-of-the-art molecular epidemiological methods. This research is accomplished by patient screening, surveillance and use of whole genome sequencing for high-consequence and high-prevalence micro-organisms. The Department participates in national surveillance programs for bacterial resistance, reporting to the Australian Group for Antimicrobial Resistance (AGAR), OrgTrx and CARalerts.

The Department has led the state in developing highly specialised and locally optimised in-house bioinformatics pipelines and automated reporting systems. This has facilitated studies which have provided important insights into the transmission dynamics of healthcare-associated pathogens, particularly vancomycin-resistant enterococcus (VRE) and carbapenem-resistant Enterobacterales (CPE), and more recently SARS-CoV-2. Research findings have been rapidly translated into the implementation of targeted measures to optimise control of these multi-drug resistant organisms as well as COVID-19.

Other areas of research involve immunocompromised individuals. The Department participates in mycology studies which have examined fungal resistance rates. These findings have enabled refinement of local antifungal prophylaxis strategies for the numerous immunosuppressed hosts cared for at Royal Prince Alfred Hospital including liver, renal and allogeneic transplant recipients. HIV drug resistance surveillance is another area of interest of the Department, through involvement in the implementation of a state-wide HIV drug resistance database and participation in national surveillance reports. Optimising care for patients in other specialised services has also become a focus of the Department, through the individualised prescribing of antimicrobials, in particular using therapeutic drug monitoring for patients on extracorporeal membrane oxygenation (ECMO) or with cystic fibrosis.

Selected Grants

Amount awarded Grant and project details
$2,971,764 Medical Research Future Fund (MRFF) Clinical Trials Activity, 2023-2025
Modulating stem cell differentiation in individuals with high risk clonal haematopoiesis: the MOSAIC trial.
RPA Investigator: Dharan N (CIL)
$1,993,166 Medical Research Future Fund (MRFF) International Clinical Trials Collaboration, 2023-2025
Strategies and treatments for respiratory infections and viral emergencies (STRIVE).
RPA Investigator: Dharan N (CIB)
$655,150 NHMRC Investigator Grant, 2022-2025
The impact of chronic viral infections on molecular ageing processes and associated clinical outcomes.
RPA Investigator: Dharan N (CIA)
$75,000 UNSW Sydney Triple I SPHERE Seed Grant, 2022
Immune dysregulation and the risk of clonal haematopoiesis in chronic HIV infection.
Investigator: Dharan N (CIA)

Our Publications

2022

ACTIV-3/TICO Study Group, Rogers AJ, Wentworth D, Phillips A, Shaw-Saliba K, Dewar RL, Aggarwal NR, Babiker AG, Chang W, Dharan NJ, Davey VJ, Higgs ES, Gerry N, Ginde AA, Hayanga JWA, Highbarger H, Highbarger JL, Jain MK, Kan V, Kim K, Lallemand P, Leshnower BG, Lutaakome JK, Matthews G, Mourad A, Mylonakis E, Natarajan V, Padilla ML, Pandit LM, Paredes R, Pett S, Ramachandruni S, Rehman MT, Sherman BT, Files DC, Brown SM, Matthay MA, Thompson BT, Neaton JD, Lane HC, Lundgren JD. The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19. Ann Intern Med. 2022 Oct;175(10):1401-1410. doi: 10.7326/M22-0924. Epub 2022 Aug 30. PMID: 36037469; PMCID: PMC9447373.
Boan P, Marinelli T, Opdam H. Solid organ transplantation from donors with COVID-19 infection. 2022. Transplantation (PMID: 35238852).
Brito AF, Semenova E, Dudas G, Hassler GW, Kalinich CC, Kraemer MUG, Ho J, Tegally H, Githinji G, Agoti CN, Matkin LE, Whittaker C; Bulgarian SARS-CoV-2 sequencing group; Communicable Diseases Genomics Network (Australia and New Zealand); COVID-19 Impact Project; Danish Covid-19 Genome Consortium; Fiocruz COVID-19 Genomic Surveillance Network; GISAID core curation team; Network for Genomic Surveillance in South Africa (NGS-SA); Swiss SARS-CoV-2 Sequencing Consortium; Howden BP, Sintchenko V, Zuckerman NS, Mor O, Blankenship HM, de Oliveira T, Lin RTP, Siqueira MM, Resende PC, Vasconcelos ATR, Spilki FR, Aguiar RS, Alexiev I, Ivanov IN, Philipova I, Carrington CVF, Sahadeo NSD, Branda B, Gurry C, Maurer-Stroh S, Naidoo D, von Eije KJ, Perkins MD, van Kerkhove M, Hill SC, Sabino EC, Pybus OG, Dye C, Bhatt S, Flaxman S, Suchard MA, Grubaugh ND, Baele G, Faria NR. Global disparities in SARS-CoV-2 genomic surveillance. Nat Commun. 2022. Nov 16;13(1):7003. doi: 10.1038/s41467-022-33713-y.
Chan C, Fraser D, Vaccher S, Yeung B, Jin F, Amin J, Dharan NJ, Carr A, Ooi C,, Vaughan M, Holden J, Power C, Grulich A, Bavinton B, for the MI-EPIC research group. Overcoming barriers to HIV pre-exposure prophylaxis (PrEP) coverage in Australia among Medicare ineligible people at risk of HIV: Results from the MI-EPIC clinical trial. Sexual Health. 2022 Jan;18(6):453-459. PMID: 3489542; doi:10.1071/SH21096.
Dharan NJ, Jin F, Vaccher S, Bavinton B, Yeung B, Guy R, Carr A, Zablotska I, Amin J, Read P, Templeton DJ, Oii C, Martin SJ, Ryder N, Smith DE, McNulty A, Brown K, Price K, Holden J, Grulich AE, for the Expanded PrEP Implementation in Communities in New South Wales (EPIC-NSW) research group. Characteristics of HIV seroconversions in a large prospective implementation cohort study of oral HIV pre-exposure prophylaxis in men who have sex with men (EPIC-NSW). Clinical Infectious Diseases 2022 Aug 19:ciac660. doi: 10.1093/cid/ciac660. Epub ahead of print. PMID: 35982613.
Ferreira VH, Solera JT, Hu Q, Hall VG, Arbol BG, Hardy WR, Samson R, Marinelli T, Ierullo M, Virk AK, Kurtesi A, Mavandadejad F, Majchrzak-Kita B, Kulasingam V, Gingras AC, Kumar D, Humar A. Homotypic and heterotypic immune responses to Omicron variant in immunocompromised patients in diverse clinical settings. 2022. Nature Communications. (PMID: 35927279).
Foster CSP, Madden M, Chan R, Agapiou D, Bull RA, Rawlinson WD, Van Hal SJ. SARS-CoV-2 N-gene mutation leading to Xpert Xpress SARS-CoV-2 assay instability. Pathology. 2022 Jun;54(4):499-501. doi: 10.1016/j.pathol.2022.02.001. Epub 2022 Apr 16.
Foster CSP, Stelzer-Braid S, Deveson IW, Bull RA, Yeang M, Au JP, Ruiz Silva M, van Hal SJ, Rockett RJ, Sintchenko V, Kim KW, Rawlinson WD. Assessment of Inter-Laboratory Differences in SARS-CoV-2 Consensus Genome Assemblies between Public Health Laboratories in Australia. Viruses. 2022 Jan 19;14(2):185. doi: 10.3390/v14020185.
Gardiner A, Volovets A, Haber P, JoH, Visser S, Yozghatlian V, Taylor N, Nolan S, Dentice R, Malouf M, Marinelli T, Sivam D. ELX/TEZ/IVA use in cystic fibrosis liver disease: is the perspective of improved lung function worth the risk? 2022. Journal of Cystic Fibrosis (PMID: 35760705).
Hall VG, Al-Alahmadi G, Solera JT, Marinelli T, Cardinal H, Prasad R, De Serres S, Isaac D, Mainra R, Lamarche C, Sapir-Piccade R, Humar A, Kumar D. Outcomes of SARS-CoV-2 Infection in Unvaccinated Compared with Vaccinated Solid Organ Transplant Recipients: A multicentre, Matched Case-Control Study. 2022. Transplantation. (PMID: 35502801).
Hall VG, Solera J, Alahmadi G, Marinelli T, Cardinal H, Poirier C, Huard G, Prasad GVR, Manira R, Lamarche C, Sapir-Pichhadze R, Gilmour S, Humar A, Kumar D. Severity of COVID-19 in Solid Organ Transplant Recipients in Canada 2020-2021: A Prospective, Multicentre Cohort Study. 2022. Canadian Medical Association Journal (doi.org/10.1503/cmaj.220620).
Jacob R. Liu K, Marinelli T. Successful liver transplantation for hepatitis B-related acute liver failure in a patient with active COVID-19. 2022. Transplant Infectious Diseases (PMID: 35751133).
Kazmer ST, Hartel G, Robinson H, Richards RS, Yan K, van Hal SJ, Chan R, Hind A, Bradley D, Zieschang F, Rawle DJ, Le TT, Reid DW, Suhrbier A, Hill MM.  Pathophysiological Response to SARS-CoV-2 Infection Detected by Infrared Spectroscopy Enables Rapid and Robust Saliva Screening for COVID-19. Biomedicines. 2022 Feb 1;10(2):351. doi: 10.3390/biomedicines10020351.
Keighley C, Gall M, van Hal SJ, Halliday CL, Chai LYA, Chew KL, Biswas C, Slavin MA, Meyer W, Sintchenko V, Chen SCA. Whole Genome Sequencing Shows Genetic Diversity, as Well as Clonal Complex and Gene Polymorphisms Associated with Fluconazole Non-Susceptible Isolates of Candida tropicalis. J Fungi (Basel). 2022 Aug 23;8(9):896. doi: 10.3390/jof8090896.
Kim KW, Wang X, Adhikari A, Yeang M, Jenkins F, Naing Z, Walker GJ, Foster CSP, Stelzer-Braid S, Deveson I, Craig ME, Tedla N, Bull RA, Martinello M, Pinto AN, Chan R, Turville S, Rawlinson WD, van Hal S. Persistent high-level shedding of cultivable SARS-CoV-2 Delta virus 33 days after onset of COVID-19 in a hospitalized patient with pneumonia. J Med Virol. 2022 Sep;94(9):4043-4046. doi: 10.1002/jmv.27832. Epub 2022 May 14.
Li J, Lau C, Anderson N, Burrows F, Mirdad F, Carlos L, Pitman A, Muthiah K, Darley DR, Andresen D, Macdonald P, Marriott D, Dharan NJ. Multispecies outbreak of Nocardia infections in heart transplant recipients and associations with local climate conditions in New South Wales, Australia between January 2018 and August 2019. Emerging Infectious Diseases 2022 Nov;28(11):2155-2164. doi: 10.3201/eid2811.220262.
Marinelli T, Davoudi S, Foroutan F, Orchanian-Cheff, A, Husain S. Antifungal prophylaxis in adult lung transplant recipients: uncertainty despite 30 years of experience. A systematic review of the literature and network meta-analysis. 2022. Transplant Infectious Diseases (PMID: 35388588).
Marinelli T, Dolan L, Jenkins F, Lee A, Davis RJ, Crawford S, Nield, B, Ronnachit A, van Hal S. The role of real-time, on-site whole genome sequencing in guiding management of hospital outbreaks of SARS-CoV-2. 2022. Infection Control and Hospital Epidemiology (PMID: 36082784).
Marinelli T, Pennington KM, Hamandi B, Donahoe L, Rotstein C, Martinu T, Husain S. Epidemiology of candidemia in lung transplant recipients and risk factors for candidemia in the early post-transplant period in the absence of universal antifungal prophylaxis. 2022. Transplant Infectious Diseases (PMID: 35182095).
Marinelli T, Van Hal S. The evolving landscape of diagnostics for invasive fungal infections in lung transplant recipients. 2022. Current Fungal Infection Reports. (doi.org/10.1007/s12281-022-00433-1).
Nicholas C. Kortt NC, Santhakumar C, Davis RJ, Strasser SI, McCaughan GW, Liu K, Majumdar A. Prevalence and outcomes of Clostridioides difficile infection in liver transplant recipients. Transpl Infect Dis. 2022; 24:e13758. https://doi.org/10.1111/tid.13758.
Nield B. Nirmatrelvir Use during the Omicron Surge. N Engl J Med. 2022 Dec 29;387(26):2479-2480. doi: 10.1056/NEJMc2213868. PMID: 36577107.
Sandaradura I, Alffenaar JW, Cotta MO, Daveson K, Day RO, Van Hal S, Lau C, Marriott DJE, Penm J, Roberts JA, Tabah A, Williams P, Imani S.Emerging therapeutic drug monitoring of anti-infective agents in Australian hospitals: Availability, performance and barriers to implementation. Br J Clin Pharmacol. 2022 Feb;88(2):669-679. doi: 10.1111/bcp.14995. Epub 2021 Jul 31.
Shivasabesan G, Logan B, Brennan X, Lau C, Vaze A, Bennet M, Gorrie N, Mirdad F, Deveza R, Mo Koo C, McCluskey P, Macdonald P, Marriott D, Muthiah K, Dharan N. Disseminated Aspergillus lentulus infection in a heart transplant recipient: a case report. Clinical Infectious Diseases. 2022 Mar 11;ciac205. doi: 10.1093/cid/ciac205.
Stelzer-Braid S, Yeang M, Britton PN, Kim KW, Varadhan H, Andrews PI, Briest R, Branley J, Balgahom R, Burrell R, Gehrig N, Newcombe J, Kesson A, Kok J, Maley M, Van Hal S, MacIntyre CR, Craig ME, Ferson MJ, Rawlinson WD. Circulation of enterovirus D68 (EV-D68) causing respiratory illness in New South Wales, Australia, between August 2018 and November 2019. Pathology. 2022 Oct;54(6):784-789. doi: 10.1016/j.pathol.2022.03.007. Epub 2022 Jun 15.
Tong SYC, Mora J, Bowen AC, Cheng MP, Daneman N, Goodman AL, Heriot GS, Lee TC, Lewis RJ, Lye DC, Mahar RK, Marsh J, McGlothlin A, McQuilten Z, Morpeth SC, Paterson DL, Price DJ, Roberts JA, Robinson JO, van Hal SJ, Walls G, Webb SA, Whiteway L, Yahav D, Davis JS; Staphylococcus aureus Network Adaptive Platform (SNAP) Study Group.. The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe. Clin Infect Dis. 2022 Nov 30;75(11):2027-2034. doi: 10.1093/cid/ciac476.
van Hal SJ, Willems RJL, Gouliouris T, Ballard SA, Coque TM, Hammerum AM, Hegstad K, Pinholt M, Howden BP, Malhotra-Kumar S, Werner G, Yanagihara K, Earl AM, Raven KE, Corander J, Bowden R; Enterococcal Study Group.  The interplay between community and hospital Enterococcus faecium clones within health-care settings: a genomic analysis. Lancet Microbe. 2022 Feb;3(2):e133-e141. doi: 10.1016/S2666-5247(21)00236-6.

Our Presentations

2022

Davis, RJ. Improving environmental sustainability of microbiology laboratory processes. Pathology Update, Sydney, March 2022
Hernandez Cordero AI (presenter), Yang CX, Yang J, MacIsaac J, Lin D, Kobor M, Tedaldi E, Ekenberg C, Dharan N, Man SFP, Sin DD, Kunisaki K, Leung JM. Genetic architecture of the epigenome reveals new associations for lung function in HIV. American Thoracic Society Annual Meeting May 2022.   
Marinelli, T. Candida colonization and ECMO are associated with early invasive candidiasis in lung transplant recipients. Transplant Society of Australia and New Zealand Annual Scientific Meeting. Adelaide. June 2022
Marinelli. T. Prevention of invasive candidiasis in the ICU. International Conference on Antimicrobial Chemotherapy Agents. Perth. November 2022