Rebecca J. Rockett

• PostDoc Position at Westmead Hospital

Background Despite successful vaccination programs, many countries are experiencing a marked rise in pertussis cases since 2024, compounded by the emergence of macrolide-resistant Bordetella pertussis (MRBP). Here, we report the clinical, laboratory, and genomic features of MRBP isolated from a child with severe pertussis. Case Summary An 11-week-...

Simultaneous genomic sequencing of multiple respiratory pathogens from clinical samples can provide real-time data on viral evolution, co-circulation and co-infection during seasonal epidemics. Influenza is a major global respiratory pathogen, with a mature genomic epidemiology framework, that has yet to be integrated with genomic surveillance of o...

Bordetella pertussis continues to circulate globally despite wide-spread vaccination, with an emergent international epidemic in 2024. The resurgence of disease is confounded by the emergence of pertactin-deficient, macrolide-resistant B. pertussis (MRBP) strains in Asia and Europe, which are under-recognised using traditional diagnostic and survei...

Computational multi-scale pandemic modelling remains a major and timely challenge. Here we identify specific requirements for a new class of pandemic models operating across three scales: (1) rapid pathogen evolution, punctuated by emergence of new variants, (2) human interactions within a heterogeneous population, and (3) public health responses w...

Background Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to m...

Recurrent waves which are often observed during long pandemics typically form as a result of several interrelated dynamics including public health interventions, population mobility and behaviour, varying disease transmissibility due to pathogen mutations, and changes in host immunity due to recency of vaccination or previous infections. Complex no...

In response to the emergence of the monkeypox virus (MPXV) in Australia in May 2022, we developed and evaluated indirect immunofluorescence assays (IFA) for MPXV and Vaccinia virus (VACV) IgG and IgM antibodies using serum samples from patients with nucleic acid amplification test (NAAT)‐confirmed mpox and uninfected unvaccinated controls. Addition...

Constantly evolving viral populations affect the specificity of primers and the quality of genomic surveillance. This study presents a framework for the continuous optimization of sequencing efficiency for public health surveillance based on the ongoing evolution of the COVID-19 pandemic. SARS-CoV-2 genomic clustering capacity based on three amplif...

Genomic sequencing has emerged as a powerful tool to enhance early pathogen detection and characterization with implications for public health and clinical decision making. Although widely available in developed countries, the application of pathogen genomics among low-resource, high-disease burden settings remains at an early stage. In these conte...

Aims To explore viral evolution during in vitro neutralisation using next generation sequencing, and to determine whether sera from individuals immunised with two doses of the Pfizer-BioNTech vaccine (BNT162b2) are as effective at neutralising the SARS-CoV-2 variant of concern (VOC) Delta (B 1.617.2) compared to the earlier lineages Beta (B.1.351)...

Constantly evolving viral populations affect the specificity of primers and quality of genomic surveillance. This study presents a framework for continuous optimisation of sequencing efficiency for public health surveillance based on the ongoing evolution of the COVID-19 pandemic. SARS-CoV-2 genomic clustering capacity based on three amplification...

Modelling evolution of foodborne pathogens is crucial for mitigation and prevention of outbreaks. We apply network-theoretic and information-theoretic methods to trace evolutionary pathways of Salmonella Typhimurium in New South Wales, Australia, by studying whole genome sequencing surveillance data over a five-year period which included several ou...

The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition...

A major outbreak of the globally significant Salmonella Enteritidis foodborne pathogen was identified within a large clinical data set by a program of routine WGS of clinical presentations of salmonellosis in New South Wales, Australia. Pangenome analysis helped to quantify and isolate prophage content within the accessory partition of the pangenom...

Genomic surveillance of SARS-CoV-2 has been essential to inform public health response to outbreaks. The high incidence of infection has resulted in a smaller proportion of cases undergoing whole genome sequencing due to finite resources. We present a framework for estimating the impact of reduced depths of genomic surveillance on the resolution of...

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired over 30 mutations in the spike protein (with 15 in the receptor-binding domain), raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an aut...

In order to rapidly differentiate sublineages BA.1 and BA.2 of the SARS-CoV-2 variant of concern Omicron, we developed a real-time reverse-transcriptase polymerase chain reaction to target the discriminatory spike protein deletion at amino acid position 69–70 (S:del69–70). Compared to the gold standard of whole genome sequencing, the candidate assa...

The unprecedented emergence of Japanese encephalitis (JE) in mainland Australia represents an outbreak of high clinical and public health significance. JE is a zoonosis spread by mosquitoes and is one of the most important causes of endemic viral encephalitis in South-East Asia and the Indian subcontinent. While occasional cases of human Japanese e...

The emergence of resistance to antiviral drugs increasingly used to treat SARS-CoV-2 infections has been recognised as a significant threat to COVID-19 control. In addition, some SARS-CoV-2 variants of concern appear to be intrinsically resistant to several classes of these antiviral agents. Therefore, there is a critical need for rapid recognition...

Co-infections with different variants of SARS-CoV-2 are a key precursor to recombination events that are likely to drive SARS-CoV-2 evolution. Rapid identification of such co-infections is required to determine their frequency in the community, particularly in populations at-risk of severe COVID-19, which have already been identified as incubators...

Background Low frequency intrahost single nucleotide variants (iSNVs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been increasingly recognised as predictive indicators of positive selection. Particularly as growing numbers of SARS-CoV-2 variants of interest (VOI) and concern (VOC) emerge. However, the dynamics of subgenomic...

We identified the co-infection of the SARS-CoV-2 Omicron and Delta variants in two epidemiologically unrelated patients with chronic kidney disease requiring haemodialysis. Both SARS-CoV-2 variants were co-circulating locally at the time of detection. Amplicon- and probe-based sequencing using short- and long-read technologies identified and quanti...

Objectives To enhance monitoring of high-burden foodborne pathogens, there is opportunity to combine pangenome data with network analysis. Methods Salmonella enterica subspecies Enterica serovar Enteritidis isolates were referred to the New South Wales (NSW) Enteric Reference Laboratory between August 2015 and December 2019 (1033 isolates in total...

Whole-genome sequencing of viral isolates is critical for informing transmission patterns and for the ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory diff...

Objectives: To enhance monitoring of high-burden foodborne pathogens, there is opportunity to combine pangenome data with network analysis. Methods: Salmonella enterica subspecies Enterica serovar Enteritidis isolates were referred to the New South Wales (NSW) Enteric Reference Laboratory between August 2015 and December 2019 (1033 isolates in tota...

Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable...

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired 15 mutations in the receptor binding domain of the spike protein, raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, m...

Objective To adapt ‘fishplots’ to describe real-time evolution of SARS-CoV-2 genomic clusters. Results This novel analysis adapted the fishplot to depict the size and duration of circulating genomic clusters over time in New South Wales, Australia. It illuminated the effectiveness of interventions on the emergence, spread and eventual elimination...

Background: Low frequency intrahost single nucleotide variants (iSNVs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been increasingly recognised as predictive indicators of positive selection. Particularly as growing numbers of SARS-CoV-2 variants of interest (VOI) and concern (VOC) emerge. However, the dynamics of subgenomi...

SARS-CoV-2 genomic surveillance has been vital in understanding the spread of COVID-19, the emergence of viral escape mutants and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low frequency variants, important in uncovering infection transmission chains. We syst...

Objectives: To describe local operational aspects of the coronavirus disease 2019 (COVID-19) response during the first three waves of outbreaks in New South Wales (NSW), Australia, which began in January, July and December 2020. Type of program or service: Public health outbreak response. Methods: Narrative with epidemiological linking and genomi...

Whole-genome sequencing of viral isolates is critical for informing transmission patterns and ongoing evolution of pathogens, especially during a pandemic. However, when genomes have low variability in the early stages of a pandemic, the impact of technical and/or sequencing errors increases. We quantitatively assessed inter-laboratory differences...

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants,...

Objective: To adapt ‘fishplots’ to describe SARS-CoV-2 genomic cluster evolution. Results: This novel analysis adapted the fishplot to depict the size and duration of circulating genomic clusters over time in New South Wales, Australia. It illuminated the effectiveness of interventions on the emergence, spread and eventual elimination of clusters a...

Objective: To explore the factors associated with the transmission of SARS-CoV-2 to patrons of a restaurant. Methods: A retrospective cohort design was undertaken, with spatial examination and genomic sequencing of cases. The cohort included all patrons who attended the restaurant on Saturday 25 July 2020. A case was identified as a person who test...

SARS-CoV-2 genomic surveillance has been vital in understanding the spread of COVID-19, the emergence of viral escape mutants and variants of concern. However, low viral loads in clinical specimens affect variant calling for phylogenetic analyses and detection of low frequency variants, important in uncovering infection transmission chains. We syst...

Virulence arresting drugs (VAD) are an expanding class of antimicrobial treatment that act to “disarm” rather than kill bacteria. Despite an increasing number of VAD being registered for clinical use, uptake is hampered by the lack of methods that can identify patients who are most likely to benefit from these new agents. The application of pathoge...

An outbreak of severe acute respiratory syndrome coronavirus 2 infection occurred among church attendees after an infectious chorister sang at multiple services. We detected 12 secondary case-patients. Video recordings of the services showed that case-patients were seated in the same section, >15 m from the primary case-patient, without close physi...

Whooping cough, or pertussis, is a highly transmissible respiratory infection caused by Bordetella pertussis . Due to the high burden of pertussis, vaccine programmes were introduced internationally and in Australia since the 1950s. This has resulted in a significant decrease of pertussis infections. However, since the 1990s the number of pertussis...

A second cluster of COVID-19 cases imported from Europe occured in Vietnam from early March 2020. We describe 44 SARS-CoV-2 RT-PCR positive patients (cycle threshold value <30) admitted to the National Hospital for Tropical Diseases in Hanoi between March 6 and April 15 2020. Whole SARS-CoV-2 genomes from these patients were sequenced using Illumin...

Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health laboratory activities. Here, we announce a BioProject (PRJNA556438) dedicated to sharing complete genomes chosen to represent a range of pathogenic bacteria with regional importance to Australia and the Southwest Pacific...

In January 2020, a novel betacoronavirus (family Coronaviridae), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the etiological agent of a cluster of pneumonia cases occurring in Wuhan City, Hubei Province, China1,2. The disease arising from SARS-CoV-2 infection, coronavirus disease 2019 (COVID-19), subsequent...

Salmonella is a highly diverse genus consisting of over 2600 serovars responsible for high-burden food- and water-borne gastroenteritis worldwide. Sensitivity and specificity of PCR-based culture-independent diagnostic testing (CIDT) systems for Salmonella , which depend on a highly conserved gene target, can be affected by single nucleotide polymo...

Community transmission of the new coronavirus SARS-CoV-2 is a major public health concern that remains difficult to assess. We present a genomic survey of SARS-CoV-2 from a during the first 10 weeks of COVID-19 activity in New South Wales, Australia. Transmission events were monitored prospectively during the critical period of implementation of na...

The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea, and Iran. Phylogenetic analyses of whole-genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epide...

Introduction There is limited data on the analytical performance of commercial nucleic acid tests (NATs) for laboratory confirmation of COVID-19 infection. Methods Nasopharyngeal, combined nose and throat swabs, nasopharyngeal aspirates and sputum was collected from persons with suspected SARS-CoV-2 infection, serial dilutions of SARS-CoV-2 viral...

The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea and Iran. Phylogenetic analyses of whole genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidem...

Bordetella pertussis, the aetiological agent of whooping cough, is re-emerging globally despite widespread vaccination. B. pertussis is highly infectious and, prior to vaccination programmes, was the leading cause of infant mortality. The WHO estimated that over 600 000 deaths are prevented annually by pertussis vaccination, but B. pertussis infect...

BK polyomavirus (BKPyV) is an important pathogen in transplant recipients. We report four draft BKPyV genomes, three of BKPyV genotype I (subtype I-b2) (AUS-105, AUS-106, and AUS-108) and one of genotype II (AUS-107). These draft genomes were identified in longitudinal urine samples collected from a single hematopoietic stem cell transplant recipie...

JC polyomavirus (JCPyV) may cause clinical syndromes such as progressive multifocal leukoencephalopathy in immunocompromised patients. Here, we report seven complete genome sequences of JCPyV genotype 7A, generated directly from urine samples from Vietnamese renal transplant recipients by using rolling-circle amplification and next-generation seque...

Salmonella is a highly diverse genus consisting of over 2600 serovars responsible for high-burden food- and water-borne gastroenteritis worldwide. Sensitivity and specificity of PCR-based culture-independent diagnostic testing (CIDT) systems for Salmonella , which depend on a highly conserved gene target, can be affected by single nucleotide polymo...

Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health lab activities. Here, we present complete genomes of pathogen strains of regional importance to the Southwest Pacific and Australia. These enrich the catalogue of globally available complete genomes for public health whi...

Whole genome sequencing (WGS) plays an increasing role in communicable disease control through high-resolution outbreak tracing, laboratory surveillance and diagnostics. However, WGS has traditionally relied on microbial culture in order to obtain pathogen specific DNA for sequencing. This has severely limited the application of whole genome sequen...

The decline in invasive pneumococcal disease (IPD), following the introduction of the 7-valent pneumococcal conjugate vaccination (PCV-7), was tempered by emergence of non-vaccine serotypes, particularly 19A. In Australia, three years after PCV-7 was replaced by PCV-13, containing 19A and 19F antigens, serogroup 19 was still a prominent cause of IP...

Multidrug- and colistin-resistant Salmonella enterica serotype 4,[5],12:i:- sequence type 34 is present in Europe and Asia. Using genomic surveillance, we determined that this sequence type is also endemic to Australia. Our findings highlight the public health benefits of genome sequencing-guided surveillance for monitoring the spread of multidrug-...

Publicly available Salmonella sequence type 34 genomes used in study of multidrug-resistant Salmonella sequence type 34, New South Wales, Australia, 2016–2017.

The city of Sydney, Australia, experienced a persistent outbreak of Legionella pneumophila serogroup 1 (Lp1) pneumonia in 2016. To elucidate the source and guide public health actions, the genomes of clinical and environmental Lp1 isolates recovered over 7 weeks were examined. A total of 48 isolates from human cases and cooling towers were sequence...

Candida glabrata can rapidly acquire mutations that result in drug resistance, especially to azoles and echinocandins. Identification of genetic mutations is essential, as resistance detected in vitro can often be correlated with clinical failure. We examined the feasibility of using whole genome sequencing (WGS) for genome-wide analysis of antifun...

BK polyomavirus (BKPyV) is a non-enveloped, circular dsDNA virus with a genome of approximately 5100 base pairs. It can be divided into four major genotypes, but the effects of different genotypes on clinical disease are uncertain. Primary BKPyV infection is generally acquired asymptomatically in childhood. It establishes low-level persistence in m...

The city of Sydney, Australia, experienced a persistent outbreak of Legionella pneumophila serogroup 1 (Lp1) pneumonia in 2016. To elucidate the source and bring the outbreak to a close we examined the genomes of clinical and environmental Lp1 isolates recovered over 7 weeks. A total of 48 isolates from patients and cooling towers were sequenced an...

Effective progression of candidate antimalarials is dependent on optimal dosing in clinical studies, which is determined by a sound understanding of pharmacokinetics and pharmacodynamics (PK/PD). Recently, two important translational models for antimalarials have been developed: the NOD/SCID/IL2Rγ –/– (NSG) model whereby mice are engrafted with non...

Background: Piperaquine, co-formulated with dihydroartemisin is a component of a widely used Artemisinin Combination Therapy. There is a paucity of data on its antimalarial activity as a single agent, data that would inform selection of new co-formulations. Methods: We undertook a study in healthy subjects using the induced blood stage malaria (...

A large number of human polyomaviruses have been discovered in the last seven years. However, little is known about the clinical impact on vulnerable immunosuppressed patient populations. Blood, urine and respiratory swabs collected from a prospective, longitudinal adult kidney transplant cohort (n=167) generally pre-operatively, at day 4, months 1...

We investigated the presence of 4 human polyomaviruses (PyVs) (WU, KI, Merkel cell, and Malawi) in respiratory specimens from a community-based birth cohort. These viruses typically were acquired when children were ≈1 year of age. We provide evidence that WU, KI, and Malawi, but not Merkel cell PyVs, might have a role in respiratory infections.

Technical Appendix. Supplementary methods for detection of human polyomaviruses in the first 18 months of life.

The polyomavirus family is rapidly expanding with twelve new human viruses identified since 2007. A significant number of the new human polyomaviruses (HPyV) has been found on the skin. Whether these viruses share biological properties and should be grouped together is unknown. Here we investigated the serological behavior of cutaneous HPyVs in a g...

Background: Major impediments to development of vaccines and drugs for Plasmodium vivax malaria are the inability to culture this species and the extreme difficulty in undertaking clinical research by experimental infection. Methods: A parasite bank was collected from a 49-year-old woman with P. vivax infection, characterized, and used in an exp...

Eight novel human polyomaviruses have been discovered since 2007. Prevalence rates and tissue tropism for the most recent members HPyV 6, 7, 9, TSPyV and MWPyV are largely unknown. We used real-time PCR to determine the presence of HPyV 6, 7, 9, TSPyV and MWPyV in feces (n = 263), urine (n = 189), blood (n = 161), respiratory swabs (n = 1385) and c...

BK virus (BKV) is an ubiquitous human polyomavirus that establishes latency in urothelium. BKV is known to re-activate in immunosuppressed individuals, and is an increasingly important cause of nephropathy and graft loss in kidney transplant recipients. Animal studies have demonstrated BKV has a potential role as a tumor virus. However, its role in...

Despite a recent decline in the burden of malaria worldwide, it continues to cause significant morbidity and mortality. Many new antimalarials are in development, however there are a number of issues that continue to make their assessment problematic. To address this, a human challenge model was developed where healthy subjects are inoculated with...

Background: Pregnane X, encoded by the gene NR112, is a nuclear receptor whose primary role is to promote the detoxification and clearance of drugs and other foreign compounds from the body. Aim: The aim of this study was to analyze associations between NR1I2 polymorphisms, immunosuppressant drug exposure, and clinical outcomes in adult kidney t...

Several different viruses have been proposed to play a role in breast carcinogenesis. The aim of this study was to investigate the prevalence of a subset of viruses in breast cancer tissue. We investigated the prevalence of 12 DNA viruses: EBV and CMV from the Herpesviridae family and SV40, BKV, JCV, MCV, WUV, KIV, LPV, HPyV6, HPyV7, and TSV from t...

PCR-derived parasite counts in study subjects. Parasite counts at time of treatment commencement are underlined. ND = not detected. Samples that yielded positive PCR results with parasite counts below 64/mL provided qualitative information only and were censored for the purpose of calculating parasite clearance kinetics. (DOCX)

Trial protocol. (PDF)

Parasite Reduction Ratios (PRR) in previous studies of artemether – lumefantrine and atovaquone -proguanil, where the starting parasitemia and parasite clearance times were reported. To calculate the PRR it was assumed that the threshold of detection of parasites on a thick film was 20 parasites per microlitre. (DOCX)

CONSORT checklist. (DOC)

Amended trial protocol. (PDF)