Applied epidemiology of infectious diseases in Australia

My placement for the Master of Philosophy in Applied Epidemiology (MAE) degree was with the Zoonoses, Foodborne and Emerging Infectious Diseases section (ZoFE), within the Office of Health Protection, Australian Government Department of Health. This placement has allowed me to apply the skills and knowledge of the epidemiology of infectious diseases acquired throughout my degree. I focused on the following four core projects. My review of the National Enhanced Listeriosis Surveillance System (NELSS) found that it had been invaluable in listeriosis surveillance in Australia since 2010. It has been used not only to detect clusters and outbreaks but has also assisted in the identification and investigation of possible sources of these outbreaks. NELSS is viewed as valuable with a high level of acceptability by the users of the system, despite limitations including a lack of understanding of system capabilities, duplication of data entry and the system not storing all available data. This review highlights the effectiveness of enhanced surveillance for a foodborne disease, though improvements are needed. In 2013 I was part of a team that investigated an outbreak of foodborne gastroenteritis linked to a buffet meal served at a Canberra restaurant. The cohort study and environmental and laboratory investigations suggested that a breakdown in cleanliness, temperature control and food handling practices resulted in contamination of the buffet food. Our investigation resulted in public health actions, such as repairs to the kitchen of the implicated restaurant, staff training and the development of food business management plans, to limit the potential for such an outbreak to occur in the future. As there is no reliable treatment for Australian Bat lyssavirus (ABLV) or rabies virus infection upon the onset of symptoms, treatment must occur as either pre or post-exposure prophylaxis. The National Human Rabies Immunoglobulin Database records information of people who have received Human Rabies Immunoglobulin (HRIg) in Australia as part of post-exposure prophylaxis treatment. Between 1 January 2010 and 31 December 2013, 3,003 individuals received HRIg for potential exposures to ABLV or rabies virus. A third received HRIg due to potential exposures to ABLV occurring in Australia. The current messaging for the risks of ABLV infection from bats in Australia should be reviewed and revised to ensure that it is appropriately targeted and effective. Two thirds of people received HRIg for potential exposures to the rabies virus overseas. Most occurred in Indonesia and most due to exposure to monkeys. We need to continue to warn of the risk of potential exposure to rabies virus when travelling overseas, particularly to Indonesia. Q fever is a zoonosis that has a wide range of reservoirs in Australia. In humans the disease can manifest as either acute febrile illness or chronic illness that may affect the heart or liver. The Australian Government funded the National Q fever Management Program (NQFMP) from 2000 to 2006, which provided screening and vaccination for target high risk groups. We found notified Q fever cases were predominately male, aged 40 to 59 years, who resided in Queensland or New South Wales. Interestingly the age of notified Q fever cases and the proportion of cases that were female both increased over time. It may be time to re-evaluate the at-risk groups recommended for Q fever vaccination as per the Australian Immunisation Handbook. Additionally, there may be a place for an agreed and consistent enhanced dataset for collection at the jurisdictional level or at the national level to better understand the epidemiology of Q fever in Australia

An outbreak of Bacillus cereus toxin-mediated emetic and diarrhoeal syndromes at a restaurant in Canberra, Australia 2018

A cluster of gastrointestinal illness was detected following receipt of a complaint of becoming ill after a multi-course dinner at a restaurant in Canberra, Australian Capital Territory (ACT), Australia. The complaint led to an investigation by ACT Health. Food samples retained by the restaurant for microbiological analysis returned an unsatisfactory level of Bacillus cereus in beef (19,000 colony forming units/gram [cfu/g]) and a satisfactory level in arancini (50 cfu/g). These positive samples underwent whole genome sequencing and genes encoding diarrhoeal toxins were detected with no laboratory evidence of the emetic toxin. No stool specimens were collected. A cohort study was undertaken and 80% (33/41) of patrons took part in a structured interview. There was no significant difference in age or sex between those ill and not ill. Due to universal exposure most foods were unable to be statistically analysed and no significant results were found from the food history. The ill cohort diverged into two distinct groups based on incubation period and symptoms suggesting this outbreak involved B. cereus intoxication with both diarrhoeal and potentially emetic toxins. Some hygiene practices during food preparation were noted to be inadequate and heating and cooling procedures were unverified when questioned. A combination of the incubation periods and symptom profile, food laboratory evidence, and genomic sequencing of the B. cereus diarrhoeal gene suggest a probable aetiology of B. cereus intoxication. Public health action included the restaurant rectifying hygiene practices and documenting heating/cooling procedures

Trends and risk factors for human Q fever in Australia, 1991-2014

Australian abattoir workers, farmers, veterinarians and people handling animal birthing products or slaughtering animals continue to be at high risk of Q fever despite an effective vaccine being available. National Notifiable Diseases Surveillance System data were analysed for the period 1991–2014, along with enhanced risk factor data from notified cases in the states of New South Wales and Queensland, to examine changes in the epidemiology of Q fever in Australia. The national Q fever notification rate reduced by 20% [incident rate ratio (IRR) 0·82] following the end of the National Q fever Management Program in 2006, and has increased since 2009 (IRR 1·01–1·34). Highest rates were in males aged 40–59 years (5·9/100 000) and 87% of Q fever cases occurred in New South Wales and Queensland. The age of Q fever cases and proportion of females increased over the study period. Based on the enhanced risk factor data, the most frequently listed occupation for Q fever cases involved contact with livestock, followed by ‘no known risk’ occupations. More complete and comparable enhanced risk factor data, at the State/Territory and national levels, would aid in further understanding of the epidemiology of Q fever

Exercise training reduces the acute physiological severity of post-menopausal hot flushes.

A hot-flush is characterised by feelings of intense heat, profuse elevations in cutaneous vasodilation and sweating, and reduced brain blood flow. Exercise training reduces self-reported hot-flush severity, but underpinning physiological data are lacking. We hypothesised that exercise training attenuates the changes in cutaneous vasodilation, sweat rate and cerebral blood flow during a hot flush. In a preference trial, 18 symptomatic post-menopausal women underwent a passive heat stress to induce hot-flushes at baseline and follow-up. Fourteen participants opted for a 16-week moderate intensity supervised exercise intervention, while 7 participants opted for control. Sweat rate, cutaneous vasodilation, blood pressure, heart rate and middle cerebral artery velocity (MCAv) were measured during the hot-flushes. Data were binned into eight equal segments, each representing 12.5% of hot flush duration. Weekly self-reported frequency and severity of hot flushes were also recorded at baseline and follow-up. Following training, mean hot-flush sweat rate decreased by 0.04 mg·cm2 ·min-1 at the chest (95% CI: 0.02-0.06, P = 0.01) and by 0.03 mg·cm2 ·min-1 (0.02-0.05, P = 0.03) at the forearm, compared with negligible changes in control. Training also mediated reductions in cutaneous vasodilation by 9% (6-12) at the chest and by 7% (4-9) at forearm (P≤0.05). Training attenuated hot flush MCAv by 3.4 cm/s (0.7-5.1, P = 0.04) compared with negligible changes in control. Exercise training reduced the self-reported severity of hot-flush by 109 arbitrary units (80-121, P<0.001). These data indicate that exercise training leads to parallel reductions in hot-flush severity and within-flush changes in cutaneous vasodilation, sweating and cerebral blood flo

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies