Constructing an ethical framework for priority allocation of pandemic vaccines.

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.

Priority allocation of pandemic influenza vaccines in Australia - Recommendations of 3 community juries.

BACKGROUND: Pandemic planning has historically been oriented to respond to an influenza virus, with vaccination strategy being a key focus. As the current COVID-19 pandemic plays out, the Australian government is closely monitoring progress towards development of SARS-CoV2 vaccines as a definitive intervention. However, as in any pandemic, initial supply will likely be exceeded by demand due to limited manufacturing output. METHODS: We convened community juries in three Australian locations in 2019 to assess public acceptability and perceived legitimacy of influenza pandemic vaccination distribution strategies. Preparatory work included literature reviews on pandemic vaccine allocation strategies and on vaccine allocation ethics, and simulation modelling studies. We assumed vaccine would be provided to predefined priority groups. Jurors were then asked to recommend one of two strategies for distributing remaining early doses of vaccine: directly vaccinate people at higher risk of adverse outcomes from influenza; or indirectly protect the general population by vaccinating primary school students, who are most likely to spread infection. RESULTS: Thirty-four participants of diverse backgrounds and ages were recruited through random digit dialling and topic-blinded social media advertising. Juries heard evidence and arguments supporting different vaccine distribution strategies, and questioned expert presenters. All three community juries supported prioritising school children for influenza vaccination (aiming for indirect protection), one by 10-2 majority and two by consensus. Justifications included that indirect protection benefits more people and is likely to be more publicly acceptable. CONCLUSIONS: In the context of an influenza pandemic, informed citizens were not opposed to prioritising groups at higher risks of adverse outcomes, but if resources and epidemiological conditions allow, achieving population benefits should be a strategic priority. These insights may inform future SARS-CoV-2 vaccination strategies.

Q fever seroprevalence in Australia suggests one in twenty people have been exposed.

Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1-79 years in 2012-2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%-6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%-6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%-8.0%). More males were seropositive (6.9%; 95% CI 5.2%-8.6%) than females (4.2%; 95% CI 2.9%-5.5%) with peak seroprevalence at 50-59 years (9.2%; 95% CI 5.2%-13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.

Synovial fluid leukocyte cell count before versus after administration of antibiotics in patients with septic arthritis of a native joint.

BACKGROUND: Antibiotics have been shown to affect the accuracy of cultures; so antibiotics are held prior to obtaining cultures intra-operatively. No study has evaluated the effects of antibiotics on synovial fluid leukocyte cell count. The purpose of the current study is to compare the leukocyte cell count of native joints with septic arthritis when antibiotics have been given before aspiration and when no antibiotics have been given prior to aspiration. METHODS: This study was performed at a community hospital and a level 1 urban trauma hospital after IRB approval from both institutions from July 2007 to July 2017. Inclusion criteria comprised of a diagnosis of septic arthritis with positive cultures and a recorded arthrocentesis with cell count performed. Patients with septic arthritis were identified using ICD-9 codes 711.00-711.99 and ICD-10 codes M00 - M02. A retrospective chart review was performed and data was collected. Patients were placed into one of two groups. Group 1 received no antibiotics for two weeks prior to arthrocentesis, group 2 received antibiotics within 24 h prior to arthrocentesis. Demographic information, cell count number and differential, and blood lab values were collected. Timing data was also collected on timing of admission, antibiotics, joint irrigation, and discharge from the inpatient setting. RESULTS: There were 81 patients meeting final inclusion criteria. The average cell count for the group which received antibiotics (n = 30) was 40,408 ± 29,433 while the average cell count for the group receiving no antibiotics (n = 51) was 93,824 ± 73,875 (p < .0001). The average length of stay was not significantly different between the antibiotic group versus no antibiotic group (14.0 days vs 12.1 days p = .4). The time from admission to arthrocentesis and admission to washout was longer for the antibiotic group versus no antibiotic group (p = .004 and p = .002, respectively). CONCLUSION: When antibiotics are given prior to arthrocentesis of a septic joint, there is an associated lower synovial fluid leukocyte count compared to when no antibiotics are given prior. LEVEL OF EVIDENCE: Level III.

Equine chlamydiosis-An emerging infectious disease requiring a one health surveillance approach.

Psittacosis is a rare but potentially fatal zoonosis caused by Chlamydia psittaci, an organism that is typically associated with bird contact. However C. psittaci is capable of infecting other non-avian hosts, such as horses, sheep, cattle and goats. Stud staff and veterinarians have significant exposure to parturient animals and reproductive materials in their routine work. To investigate the zoonotic potential associated with the emergence of C. psittaci as an abortifacient agent in horses, we established a programme of joint human and animal surveillance in a sentinel horse-breeding region in Australia. This programme comprised cross-notification of equine cases to public health agencies, and active follow-up of known human contacts, including stud workers, foaling staff, veterinarians and laboratory staff. We identified no confirmed cases of acute psittacosis despite intensive surveillance and testing of heavily exposed contacts; however, further work in the area is needed.

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.

Pregnant women's intention to take up a post-partum pertussis vaccine, and their willingness to take up the vaccine while pregnant: a cross sectional survey.

INTRODUCTION: Post-partum vaccination of new mothers is currently recommended in Australia to reduce pertussis infection in infants. Internationally, vaccination recommendations now include pregnant women in some countries. Understanding the awareness of pertussis vaccination recommendations among pregnant women, and their willingness to have the vaccine while pregnant is important for informing vaccine program implementation. OBJECTIVE: To determine awareness and intentions toward current recommendations for post-partum pertussis vaccination among Australian pregnant women, and their willingness to accept pertussis vaccine during pregnancy, should it be recommended in Australia in the future. DESIGN: Quantitative self-administered survey, using a non-random stratified sampling plan based on representative proportions by age, parity and region of residence. PARTICIPANTS AND SETTING: Pregnant women receiving antenatal care through three large, demographically diverse referral hospitals in metropolitan, urban and rural New South Wales, Australia. RESULTS: The response rate was 815/939 (87%). Most women (80%) reported willingness to have the pertussis vaccine during pregnancy, should it be recommended. Thirty four per cent of women intended to receive a pertussis vaccine post-partum, 17% had received it previously, while 45% had never heard of pertussis vaccine, had not thought about it, or were undecided about having it. Compared with those who had not received a recommendation to have the vaccine post-partum, women who had received a recommendation were 7 times more likely (95% CI 4-14) to report intention to have the vaccine. CONCLUSIONS: Health care provider recommendation is paramount to raising awareness of pertussis vaccination recommendations among pregnant women. Women's willingness to have the vaccine while pregnant is encouraging, and indicates the potential for high pertussis vaccine coverage among pregnant women, should it be recommended in Australia.

Prevention and surveillance of public health risks during extended mass gatherings in rural areas: the experience of the Tamworth Country Music Festival, Australia.

OBJECTIVE: To describe and evaluate the public health response to the Tamworth Country Music Festival, an annual extended mass gathering in rural New South Wales, Australia; and to propose a framework for responding to similar rural mass gatherings. STUDY DESIGN: Process evaluation by direct observation, archival analysis and focus group discussion. METHODS: The various components of the public health response to the 2011 Tamworth Country Music Festival were actively recorded. An archival review of documentation from 2007 to 2010 was performed to provide context. A focus group was also conducted to discuss the evolution of the public health response and the consequences of public health involvement. RESULTS: Public health risks increased with increasing duration of the rural mass gathering. Major events held within the rural mass gathering further strained resources. The prevention, preparedness, response and recovery principles provided a useful framework for public health actions. Particular risks included inadequately trained food preparation volunteers functioning in poorly equipped temporary facilities, heat-related ailments and arboviral disease. CONCLUSION: Extended mass gatherings in rural areas pose particular public health challenges; surge capacity is limited and local infrastructure may be overwhelmed in the event of an acute incident or outbreak. There is value in proactive public health surveillance and monitoring. Annual mass gatherings provide opportunities for continual systems improvement. Early multi-agency planning can identify key risks and identify opportunities for partnership. Special consideration is required for major events within mass gatherings.

TB questions, East Kwaio answers: community-based participatory research in a remote area of Solomon Islands.

INTRODUCTION: East Kwaio is a remote region on the island of Malaita, Solomon Islands. Atoifi Adventist Hospital (the Hospital) is the only hospital and tuberculosis (TB) services provider in the region. If people come to the Hospital with TB, they are usually admitted for the two-month intensive phase of treatment as there are no community-based TB services. Most people walk or travel by canoe to the Hospital as there are no roads. East Kwaio is known to have high rates of TB; however, it has a low case detection rate and low treatment completion. The aims of this study were to explore why people with TB, especially from the mountain areas, present to the Hospital so late in their illness or do not present at all. The study was part of a larger project to strengthen the research capacity of local health workers and community leaders, supported by visiting researchers from Australia. METHODS: Semi-structured interviews with TB patients, a focus group of key informants and direct interaction with a community with a history of TB were used to explore reasons why people present to the Hospital late in their TB illness. RESULTS: Four interviews and a focus group of 12 key informants were conducted and a mountain hamlet with a history of TB was visited. The results represent the data from the interviews and the focus group. The time delay in presenting to the Hospital from when participants first became unwell ranged between two and three years. In the mountain hamlet, two additional people with probable TB were seen who had not presented to the Hospital during illnesses of five and nine months. Reasons for delays included: seeking care from traditional healers; the challenge of accessing health services due to distance, cost and cultural issues different from the Hospital's worldview; social isolation when in hospital; and being old so not having long to live. Delays in diagnosis of people with TB will increase the risk of transmission to family and through hamlets and villages. This study has led to plans being developed to build a more culturally appropriate TB ward and community treatment program. CONCLUSIONS: The study has identified TB questions that need East Kwaio answers. It has shown that a small project can inform the development of important changes to TB services, such as the redevelopment and relocation of the TB ward. To enable TB control, the local health services need to develop an understanding of, and appropriately engage with, traditional beliefs that influence how people interact with Hospital TB treatment and management. This is the case even if the beliefs are based on a worldview different than that of the health service providers. Ongoing operational research is required into TB diagnosis and treatment services and the many factors that contribute to the high TB burden in this remote area.

Blood, guts and knife cuts: reducing the risk of swine brucellosis in feral pig hunters in north-west New South Wales, Australia.

INTRODUCTION: Humans who have close contact with livestock, wild or feral animals can risk acquiring zoonotic infections such as brucellosis, Q fever, and leptospirosis. Human infection with Brucella suis (swine brucellosis) usually follows occupational or recreational exposure to infected animals. Worldwide, many cases of human infection follow contact with infected feral pigs. In Australia there is a growing market for the export of 'wild boar' and a considerable number of people are involved in feral pig hunting. However, feral pig hunters are often hard to reach with health strategies. According to Australian authorities the most important means of preventing disease in humans includes covering cuts; wearing gloves; washing hands; and avoiding blood when coming into contact with feral pigs. There has not been an evaluation of the acceptability of these recommended risk-reduction strategies in the settings where feral pig hunting and evisceration occurs. METHODS: Semi-structured interviews and small focus groups were conducted with feral pig hunters in north-west New South Wales (NSW), Australia, to explore their hunting experiences and views on the brucellosis prevention strategies. Interview and focus group notes were thematically analysed. RESULTS: There was a range of experiences of feral pig hunting, from a very professional approach to a purely recreational approach. The main domains that emerged from participants' experiences during their most recent feral pig hunting activity and their reflections on current swine brucellosis risk reduction strategies were: 'you've gotta be tough to be a feral pig hunter'; 'most of the suggested strategies won't work as they are'; 'reducing risk in the scrub'; and 'how to let pig hunters know'. The recreational nature and prevailing macho perspective of participants demand a pragmatic approach to risk reduction if it is going to prove acceptable to feral pig hunters. The 'you've gotta be tough to be a feral pig hunter' context of the activity and the reality that many feral pig hunters participate with little preparation and a 'just keep going' approach, may counteract currently recommended risk-reduction strategies. The alternate strategies that emerged from the interviews need to be tested in the real activity, especially evisceration 'in the scrub' (at the site of slaughter). But the following ideas were grounded in the participants' experiences: take more time and watch your hands when making cuts; have good lighting; take care when cutting near a sow's uterus; use latex gloves to cover cuts on hands. CONCLUSIONS: Swine brucellosis is a zoonosis of concern for feral pig hunters in many parts of Australia, including north-west NSW. Many of the current strategies to reduce the risk of brucellosis did not appear appropriate or acceptable to the feral pig hunters interviewed. More acceptable strategies when eviscerating, such as taking more time, watching hands when cutting, ensuring good lighting, being careful in the vicinity of the uterus and using a latex glove to cover cuts and abrasions on hands need to be field tested. Further development of the food safety regulations is required to also support zoonosis risk reduction strategies.

Preventing Q fever endocarditis: a review of cardiac assessment in hospitalised Q fever patients.

INTRODUCTION: Acute Q fever is an important zoonotic disease in some parts of rural Australia. Q Fever can lead to chronic disease such as endocarditis, this complication occurring more commonly in patients with underlying heart valve pathology or an impaired immune system. Untreated Q fever endocarditis has a high mortality rate, but even with appropriate therapy, 10% of patients will die. Cardiac assessment can identify patients at risk. The aim of this review was to examine recorded cardiac assessment of hospitalised Q fever patients within the regional area of Hunter New England (HNE), New South Wales (NSW). METHODS: Medical records of patients with Q fever admitted to hospitals in HNE during the period 2005-2009 were identified through the NSW Notifiable Diseases Database and the NSW Inpatient Statistics Collection. A standardised medical record review tool was used to undertake the review. RESULTS: Eighty-nine records were reviewed. Over 50% of patients were admitted to a district hospital staffed by local GPs. Cardiac assessment was not routinely documented and for 91% there was no record of a cardiac history being taken. Approximately 25% had no record of a cardiac physical examination and only 6 cases had a record of a complete cardiac examination. CONCLUSION: Q Fever remains an important disease in some parts of rural Australia. Q Fever endocarditis is a serious sequel to acute Q fever and underlying heart valve pathology. Due to its indolent progression and poor outcome when diagnosis is delayed, a thorough cardiac assessment of all patients with suspected or confirmed Q fever is important. The level of documentation of cardiac assessment for Q fever patients is of concern because it may indicate cardiac assessments were not performed. General practitioners, especially in rural and regional areas, are encouraged to conduct cardiac assessments for all patients with acute Q fever to identify patients at risk of developing Q fever endocarditis.

Steroid myopathy in patients with acute graft-versus-host disease treated with high-dose steroid therapy.

High-dose steroids are the first line of treatment for acute graft-versus-host disease (aGVHD). Steroid myopathy is a debilitating steroid-induced complication that significantly impairs a patient's performance status. To determine the frequency and severity of steroid myopathy and other steroid related complications in patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) who developed grade >or=2 aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT), we performed a retrospective analysis. Patients were included in the analysis if they had a diagnosis of AML/MDS, underwent an allogeneic HSCT between January 1996 and December 2001 and developed grade >or=2 aGVHD that was treated with 2 mg/kg of methylprednisolone and survived at least 100 days post transplant. A total of 70 patients fulfilled our inclusion criteria. Steroid myopathy was identified in 29 (41%) patients. Steroid myopathy was generally of moderate severity with severe debilitating steroid myopathy seen in only 3% of patients. We concluded that steroid myopathy is a common complication of high-dose steroid therapy after allogeneic HSCT in AML/MDS. Interventions aimed at preventing and treating this complication are warranted and need to be explored in prospective clinical trials.

Galanin regulates spatial memory but not visual recognition memory or synaptic plasticity in perirhinal cortex.

It has previously been shown that the neuropeptide galanin plays a role in the age-dependent regulation of hippocampal synaptic plasticity and spatial memory. Here, we further extend these studies by demonstrating that galanin knockout mice also have deficits in an object-in-place spatial memory task. In contrast however, there is no deficit in single item object recognition memory, a memory that depends on perirhinal cortex. Furthermore, in perirhinal cortex slices there are no differences in activity-dependent long-term potentiation or depotentiation, nor in muscarinic receptor-dependent long-term depression between galanin knockout mice and wild-type litter-mates. Therefore, these results suggest that galanin has a differential role in hippocampal-dependent and perirhinal cortex-dependent memory.

Activation of muscarinic receptors induces protein synthesis-dependent long-lasting depression in the perirhinal cortex.

There is strong evidence that decrements in neuronal activation in perirhinal cortex when a novel stimulus is repeated provide a neural substrate of visual recognition memory. There is also strong evidence that muscarinic acetylcholine (ACh) receptors are involved in learning and memory. However, the mechanisms underlying neuronal decrements in the perirhinal cortex and the basis of ACh involvement in learning and memory are not understood. In an in vitro preparation of rat perirhinal cortex we now demonstrate that activation of ACh receptors by carbachol (CCh) produces long-lasting depression (LLD) of synaptic transmission that is dependent on muscarinic M1 receptor activation. Crucially, the induction of this form of LLD requires neither N-methyl-D-aspartate receptor activation nor synaptic stimulation. CCh-induced LLD was not blocked by the protein kinase C inhibitors staurosporine or BIM, or by the protein phosphatase inhibitor okadaic acid. However, each of cyclopiazonic acid (an agent that depletes intracellular calcium stores) and anisomycin (an inhibitor of protein synthesis) significantly reduced the magnitude of CCh-induced LLD. These mechanisms triggered by muscarinic receptor activation could play a role in the induction and/or expression of certain forms of activity-dependent long-term depression in perirhinal cortex. An understanding of CCh-induced LLD may thus provide clues to the mechanisms underlying lasting neuronal decrements that occur in the perirhinal cortex and hence for neural substrates of visual recognition memory.

Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole.

OBJECTIVE: To investigate the effects of the immune modulators levamisole and loxoribine in a rat model of endometriosis. DESIGN: Prospective, placebo-controlled study. SETTING: Hospital-based research facility. ANIMAL(S): Nineteen rats with experimentally induced endometriosis. INTERVENTION(S): Rats were treated with three weekly intraperitoneal injections of levamisole (2 mg per rat; n = 6), loxoribine (1 mg per rat; n = 6), or saline (control; n = 7) and killed 8 weeks after treatment. MAIN OUTCOME MEASURE(S): Histologic and immunohistochemical analysis of endometriotic explants. RESULT(S): The loxoribine-treated group showed marked regression of both epithelial and stromal components. Epithelial regression was noted in the control group, but the epithelium was strikingly preserved in the levamisole group. There were significantly greater numbers of dendritic cells in the explants of animals treated with loxoribine and levamisole. The number of natural killer cells was significantly reduced in loxoribine-treated explants. CONCLUSION(S): Loxoribine, a potent immunomodulatory drug, appeared to cause regression in both stromal and epithelium components in a rat model of endometriosis. Further, specific cell-mediated immune responses in this model of endometriosis were elucidated.