Improving the management of medical emergency team calls due to suspected infections: A before-after study.

Objective: To introduce a management guideline for sepsis-related MET calls to increase lactate and blood culture acquisition, as well as prescription of appropriate antibiotics. Design: Prospective before (Jun-Aug 2018) and after (Oct-Dec 2018) study was designed. Setting: A public university linked hospital in Melbourne, Australia. Participants: Adult patients with MET calls related to sepsis/infection were included. Main outcome measures: The primary outcome measure was the proportion of MET calls during which both a blood culture and lactate level were ordered. Secondary outcomes included the frequency with which new antimicrobials were commenced by the MET, and the presence and class of administered antimicrobials. Results: There were 985 and 955 MET calls in the baseline and after periods, respectively. Patient features, MET triggers, limitations of treatment and disposition after the MET call were similar in both groups. Compliance with the acquisition of lactates (p = 0.101), respectively. There was a slight reduction in compliance with lactate acquisition in the after period (97% vs 99%; p = 0.06). In contrast, there was a significant increase in acquisition of blood cultures in the after period (69% vs 78%; p = 0.035). Conclusions: Introducing a sepsis management guideline and enhanced linkage with an AMS program increased blood culture acquisition and decreased broad spectrum antimicrobial use but didn't change in-hospital mortality.

Locally acquired lymphocytic choriomeningitis virus infections in South-East Queensland: an outbreak of a pathogen rarely described in Australia.

Lymphocytic choriomeningitis virus (LCMV) is a zoonotic virus that can cause clinically significant illnesses in humans. Although cases of LCMV infection are well described globally, and there is evidence that the virus is present in Australian rodent populations, there has been only one case of domestically acquired LCMV infection published previously. Here, we describe a cluster of LCMV infections in South-East Queensland identified in early 2021, and the diagnostic testing processes implemented. This identifies LCMV as an under-recognised human pathogen in Australia.

Critical care nurses' perceptions of essential elements for an intensive care liaison or critical care outreach nurse curriculum.

BACKGROUND: For over a decade, patients experiencing clinical deterioration have been attended to by specialised nurses, the most senior of which are intensive care unit liaison nurses (ICU LNs) or critical care outreach nurses. These roles have evolved without consistent and formal recognised educational preparation. To continue to advance patient safety, an understanding of the educational requirements for these vital roles is required. AIM: The aim of this study was to ascertain nurses' perceptions of the curriculum required to perform the roles of ICU LNs or critical care outreach nurses within an acute care sector rapid response system. METHODS: An exploratory descriptive study was conducted at an international rapid response system conference in 2016 following ethics approval. Using convenience sampling, extended response surveys were completed by nurses with rapid response system leadership experience and roles. Data were analysed using content analysis according to a priori themes of theoretical knowledge, skills, and attributes. RESULTS: Seventy-seven registered nurses volunteered to take part in the study, forming 14 groups, each with four to seven members. Participants identified key concepts for desired theoretical knowledge, practical skills, and personal attributes. Professional behaviours were more frequently emphasised than theoretical knowledge or practical skills, suggesting personal attributes were highly valued in these leadership roles. CONCLUSIONS: A curriculum designed to prepare patient safety leadership roles of the ICU LN or critical care outreach nurse has been identified. These findings can inform the development of postgraduate courses and training requirements, along with position descriptions and expectations of employers regarding the skill set expected in these leadership roles.

A Case of Japanese Encephalitis with a Fatal Outcome in an Australian Who Traveled from Bali in 2019.

A severe case of Japanese encephalitis virus (JEV) infection, resulting in fatality, occurred in an unvaccinated Australian male traveler from Bali, Indonesia, in 2019. During hospitalisation in Australia, patient cerebrospinal fluid (CSF) yielded JEV-specific IgM antibodies and RNA, and an isolate of the virus. Ongoing transmission of JEV in Bali underscores this pathogen as a public health risk and the importance of appropriate health, vaccination and mosquito avoidance advice to prospective travelers to the region.

COVID-19 in a complex obstetric patient with cystic fibrosis.

We report the first case of COVID-19 in a pregnant patient with cystic fibrosis. We describe the diagnosis, clinical course and management of the patient and their family with regards to clinical, social and infection control measures around delivery. This case highlights the importance of the cooperation of multidisciplinary teams to achieve good clinical outcomes in complex patients with COVID-19.

A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus.

Flaviviruses such as dengue, yellow fever, Zika, West Nile, and Japanese encephalitis virus present substantial global health burdens. New vaccines are being sought to address safety and manufacturing issues associated with current live attenuated vaccines. Here, we describe a new insect-specific flavivirus, Binjari virus, which was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of the aforementioned pathogenic vertebrate-infecting flaviviruses (VIFs). Chimeric BinJ/VIF-prME viruses remained replication defective in vertebrate cells but replicated with high efficiency in mosquito cells. Cryo-electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental VIFs. Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 109.5 cell culture infectious dose/ml or ≈7 mg/liter. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR-/- mouse models). BinJ/VIF-prME viruses thus represent a versatile, noninfectious (for vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.

Erratum: Pyke, A.T. et al. On the Home Front: Specialized Reference Testing for Dengue in the Australasian Region. Trop. Med. Infect. Dis. 2018, 3, 75.

The authors wish to make the following correction to Table 1 of this paper [...].

Differences in the characteristics, treatment, and outcomes of patient groups reviewed by intensive care liaison nurses in Australia: A multicentre prospective study.

BACKGROUND: There is a lack of knowledge about tasks intensive care unit liaison nurses (ICU LNs) perform during patient review, despite this role operating in at least 31 acute care hospitals in Australia. OBJECTIVES: To evaluate the tasks that ICU LNs perform during patient review in the following referral subcategories: review after ICU discharge, rapid response team (RRT) review, and ward referral. METHODS: A 2-month prospective observational study using standardised case report forms to collect data on patients reviewed by ICU LNs in 20 Australian hospitals was conducted. RESULTS: From 3799 patients screened, 3542 were included, among whom 1933 (54.6%) were men, and the mean (standard deviation) age was 63 (19.4) years. The admitting units were surgical 1765 (49.8%) and medical 1696 (47.9%), and the breakdown of referral types were routine review after ICU discharge (1732; 47.9%), RRT review (1208; 34.1%), and ward referral (602; 17.0%). Patients subject to ward and RRT reviews were older, more likely to be medical admissions with less favourable vital signs on the initial review, and less likely to have repeat reviews. Of note, ward reviews were more likely to receive palliative care. Intensive care liaison nurse-initiated medication prescription and investigation ordering was uncommon. The most common interventions included consultation with medical staff, bedside education, adjusting oxygen flow and patient position, and directing the change in frequency of vital sign measurement. In-hospital mortality was lower in patients reviewed after ICU discharge (2.3%), compared with those after RRT review (2.8%) and ward referral (4.4%). CONCLUSIONS: Most patients were reviewed after ICU discharge or in the context of the RRT. RRT and ward patients were less physiologically stable and more likely to die in hospital. The most common interventions performed by the ICU LN were nontechnical skills including clinical education, consultation with medical staff, and changes to vital sign frequency. Finally, the most common medication therapies administered related to intravenous therapy and electrolyte administration.

On the Home Front: Specialised Reference Testing for Dengue in the Australasian Region.

Reference laboratories are vital for disease control and interpreting the complexities and impact of emerging pathogens. The role of these centralized facilities extends beyond routine screening capabilities to provide rapid, specific, and accurate diagnoses, advanced data analysis, consultation services, and sophisticated disease surveillance and monitoring. Within the Australasian region, the Public Health Virology Laboratory (PHV), Forensic and Scientific Services, Department of Health, Queensland Government, Australia, and the Institute of Environmental Science and Research Limited (ESR), New Zealand (NZ) perform specialised reference testing and surveillance for dengue viruses (DENVs) and other emerging arthropod-borne viruses (arboviruses), including chikungunya virus (CHIKV) and Zika virus (ZIKV). With a focus on DENV, we review the reference testing performed by PHV (2005 to 2017) and ESR (2008 to 2017). We also describe how the evolution and expansion of reference-based methodologies and the adoption of new technologies have provided the critical elements of preparedness and early detection that complement frontline public health control efforts and limit the spread of arboviruses within Australasia.

Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay.

Zika virus (ZIKV) has spread widely in the Pacific and recently throughout the Americas. Unless detected by RT-PCR, confirming an acute ZIKV infection can be challenging. We developed and validated a multiplexed flavivirus immunoglobulin M (IgM) microsphere immunoassay (flaviMIA) which can differentiate ZIKV-specific IgM from that due to other flavivirus infections in humans. The flaviMIA bound 12 inactivated flavivirus antigens, including those from ZIKV and yellow fever virus (YFV), to distinct anti-flavivirus antibody coupled beads. These beads were used to interrogate sera from patients with suspected ZIKV infection following travel to relevant countries. FlaviMIA results were validated by comparison to the ZIKV plaque reduction neutralization test (PRNT). The results highlight the complexity of serological ZIKV diagnosis, particularly in patients previously exposed to or vaccinated against other flaviviruses. We confirmed 99 patients with ZIKV infection by a combination of RT-PCR and serology. Importantly, ZIKV antibodies could be discriminated from those ascribed to other flavivirus infections. Serological results were sometimes confounded by the presence of pre-existing antibodies attributed to previous flavivirus infection or vaccination. Where RT-PCR results were negative, testing of appropriately timed paired sera was necessary to demonstrate seroconversion or differentiation of recent from past infection with or exposure to ZIKV.

Assessment of Local Mosquito Species Incriminates Aedes aegypti as the Potential Vector of Zika Virus in Australia.

BACKGROUND: Within the last 10 years Zika virus (ZIKV) has caused unprecedented epidemics of human disease in the nations and territories of the western Pacific and South America, and continues to escalate in both endemic and non-endemic regions. We evaluated the vector competence of Australian mosquitoes for ZIKV to assess their potential role in virus transmission. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes were exposed to infectious blood meals containing the prototype African ZIKV strain. After 14 days incubation at 28°C and high relative humidity, infection, dissemination and transmission rates were assessed. Infection in Culex annulirostris and Cx. sitiens could not be detected. 8% of Cx. quinquefasciatus were infected, but the virus did not disseminate in this species. Despite having infection rates > 50%, Aedes notoscriptus and Ae. vigilax did not transmit ZIKV. In contrast, Ae. aegypti had infection and transmission rates of 57% and 27%, respectively. In susceptibility trials, the virus dose required to infect 50% (ID50) of Ae. aegypti was106.4 tissue culture infectious dose50 (TCID50)/mL. Additionally, a threshold viral load within the mosquito of at least 105.1 TCID50 equivalents/mL had to be reached before virus transmission occurred. CONCLUSIONS/SIGNIFICANCE: We confirmed Ae. aegypti to be the most likely mosquito vector of ZIKV in Australia, although the restricted distribution of this species will limit the receptive zone to northern Queensland where this species occurs. Importantly, the role in ZIKV transmission of Culex and other Aedes spp. tested will be negligible. Despite being the implicated vector, the relatively high ID50 and need for a high titer disseminated infection in Ae. aegypti suggest that high mosquito population densities will be required to facilitate epidemic ZIKV transmission among the currently immunologically naïve human population in Australia.

Highly divergent dengue virus type 1 genotype sets a new distance record.

Dengue viruses (DENVs) are the leading cause of mosquito-borne viral disease of humans. They exist in both endemic and sylvatic ecotypes. In 2014, a viremic patient who had recently visited the rainforests of Brunei returned to Australia displaying symptoms consistent with DENV infection. A unique DENV strain was subsequently isolated from the patient, which we propose belongs to a new genotype within DENV serotype 1 (DENV-1). Bayesian evolutionary phylogenetic analysis suggests that the putative sylvatic DENV-1 Brunei 2014 (Brun2014) is the most divergent DENV-1 yet recorded and increases the time to the most recent common ancestor (MRCA) for DENV-1 from ≈120 years to ≈315 years. DENV-1 classification of the Brun2014 strain was further supported by monoclonal antibody serotyping data. Phenotypic characterization demonstrated that Brun2014 replication rates in mosquito cells and infection rates in Aedes aegypti mosquitoes were not significantly different from an epidemic DENV-1 strain. Given its ability to cause human illness and infect Ae. aegypti, potential urban spillover and clinical disease from further Brun2014 transmission cannot be discounted.

Characteristics and outcomes of patients reviewed by intensive care unit liaison nurses in Australia: a prospective multicentre study.

BACKGROUND: Intensive care unit liaison nurse (ICU LN) services are one strategy to manage deteriorating hospital patients. Studies on the characteristics and outcomes of patients reviewed by ICU LNs have been from single centres and surveys. OBJECTIVES AND METHODS: To conduct a 20-hospital, prospective observational study on the characteristics and outcomes of patients reviewed by Australian ICU LNs over 2 months. PARTICIPANTS AND OUTCOME MEASURES: All patients screened by ICU LNs over the study period were included. Details included the source of initial review, patient demographics and initial physiological parameters, case load, interventions and patient outcome. RESULTS: Only two hospitals provided a 24-hour, 7-day service, and in 14 hospitals, an ICU LN participated in the rapid response team (RRT). There were 3799 patients screened (54.6% men, mean age 62.9 years [SD, 19.4 years]), of whom 1330 (35%) had no interventions (were screened only). The remaining 2469 patients received interventions; 978 (39.6%) were reviewed once, and 1491 (60.4%) were reviewed multiple times. The three commonest reasons for screening patients were after ICU discharge (1734 [45.6%]), as part of the RRT review (914 [24.1%]), or for a ward patient review meeting with a "worried" criterion (412 [10.8%]). Patients who did not receive interventions were younger, more likely to be surgical patients, less likely to have dementia, less likely to be seen during an RRT review, had more favourable vital signs and were less likely to be discharged to a nursing home or die in hospital. The commonest interventions included ordering a diagnostic test, administration of medication, initiating an interprofessional referral and increasing limitations of therapy. The inhospital mortality was 10.2% overall, and 4.6% in patients who were screened but did not receive any interventions. Several predictors of inhospital mortality were identified. CONCLUSIONS: Most ICU LN reviews occur after ICU discharge or in association with an RRT review. The inhospital mortality of ICU LN-reviewed patients is high (about 10%). ICU LNs effectively screen patients and often participate in end-of-life care planning.

The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition.

Chikungunya virus (CHIKV) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs) previously generated towards the capsid protein (CP) of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1-35 and 140-210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP.

Imported zika virus infection from the cook islands into australia, 2014.

A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM antibody seroconversions were detected between paired acute and convalescent phase sera using recombinant Zika virus serology assays. This is the first known imported case of Zika virus infection into northern Queensland where the potential mosquito vector Aedes aegypti is present and only the second such reported case diagnosed within Australia.

Characteristics and outcomes of patients subject to intensive care nurse consultant review in a teaching hospital.

OBJECTIVE: To describe the evolution of our Intensive Care Nurse Consultant (ICNC) service, the characteristics and outcomes of the patients reviewed, and interventions performed. DESIGN, SETTING AND PARTICIPANTS: Retrospective observational study in a tertiary referral university-affiliated teaching hospital among all patients reviewed by the ICNC service between September 2007 and December 2009. MAIN OUTCOME MEASURES: Number and characteristics of patients reviewed, source of referral, interventions performed, inhospital mortality and hospital length of stay. RESULTS: Since August 2006, operating hours have increased and provision has been made for senior ICU nurses to undertake 6-month developmental allocations to the role. The name of the service was changed and a weekly report was commenced to capture patient referral source, and subsequent ICU medical referral. Additional changes included provision of an administration day, and use of an ICU discharge scoring tool. A total of 3118 (2278 post-ICU and 840 non-ICU) care episodes were provided by the ICNC service between September 2007 and December 2009. Median patient age was 64 years, inhospital mortality was about 9% and most reviews occurred in surgical patients and after ICU discharge. Most new ward referrals came from an ICU doctor or ward nurse, with few referrals from ward doctors. Communication with ward nurses was more common than with ward doctors. A common recommendation involved fluid and electrolyte management. In-hospital mortality was higher among patients entering the service after review by a medical emergency team or de-novo referral than in patients after ICU discharge. CONCLUSIONS: Most interventions are relatively simple, and the ICNC role may be augmented by limited rights to prescribe electrolyte replacement. The effect of the intervention on patient outcomes and the reproducibility of our findings in other hospitals remain to be determined.

Implications of dengue outbreaks for blood supply, Australia.

Dengue outbreaks have increased in size and frequency in Australia, and transfusion-transmitted dengue poses a risk to transfusion safety. Using whole blood samples collected during the large 2008-2009 dengue epidemic, we estimated the risk for a dengue-infectious blood donation as ≈1 in 7,146 (range 2,218-50,021).