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Murray Valley encephalitis virus (MVEV) is the most serious of the endemic arboviruses in Australia. It was responsible for six known large outbreaks of encephalitis in south-eastern Australia in the 1900s, with the last comprising 58 cases in 1974. Since then MVEV clinical cases have been largely confined to the western and central parts of northern Australia. In 2011, high-level MVEV activity occurred in south-eastern Australia for the first time since 1974, accompanied by unusually heavy seasonal MVEV activity in northern Australia. This resulted in 17 confirmed cases of MVEV disease across Australia. Record wet season rainfall was recorded in many areas of Australia in the summer and autumn of 2011. This was associated with significant flooding and increased numbers of the mosquito vector and subsequent MVEV activity. This paper documents the outbreak and adds to our knowledge about disease outcomes, epidemiology of disease and the link between the MVEV activity and environmental factors. Clinical and demographic information from the 17 reported cases was obtained. Cases or family members were interviewed about their activities and location during the incubation period. In contrast to outbreaks prior to 2000, the majority of cases were non-Aboriginal adults, and almost half (40%) of the cases acquired MVEV outside their area of residence. All but two cases occurred in areas of known MVEV activity. This outbreak continues to reflect a change in the demographic pattern of human cases of encephalitic MVEV over the last 20 years. In northern Australia, this is associated with the increasing numbers of non-Aboriginal workers and tourists living and travelling in endemic and epidemic areas, and also identifies an association with activities that lead to high mosquito exposure. This outbreak demonstrates that there is an ongoing risk of MVEV encephalitis to the heavily populated areas of south-eastern Australia. [ABSTRACT FROM AUTHOR]

Australia is currently canine rabies free. However, communities located on the northern coastline–such as the Northern Peninsula Area (NPA), Queensland–are at risk of an incursion due to their large populations of susceptible free-roaming dogs and proximity to rabies-infected Indonesian islands. A rabies-spread model was used to simulate potential outbreaks and evaluate various disease control strategies. A heterogeneous contact structure previously described in the population of interest–explorer dogs, roamer dogs and stay-at-home dogs–was incorporated into the model using six spatial kernels describing contacts between dog roaming categories. Twenty-seven vaccination strategies were investigated based on a complete block design of 50%, 70% and 90% coverage for each of the three roaming categories to simulate various targeted vaccination strategies. The 27 strategies were implemented in four population structures in which the proportion of dogs in each category varied–explorer dominant, roamer dominant, stay-at-home dominant and a field population (based on field estimates of population structure). The overall vaccination coverage varied depending on the subpopulation targeted for vaccination and the population structure modelled. A total of 108 scenarios were simulated 2000 times and the model outputs (outbreak size and duration) were compared to Strategy 14 (a standard recommended overall 70% vaccination coverage). In general, targeting explorer dogs–and to a lesser extent roamer dogs–produced similar outbreaks to Strategy 14 but with a lower overall vaccination coverage. Similarly, strategies that targeted stay-at-home dogs required a higher vaccination coverage to produce significantly smaller and shorter outbreaks. This study provides some theoretical evidence that targeting subpopulations of dogs for vaccination based on their roaming behaviours (and therefore risk of rabies transmission) could be more efficient than blanket 70% vaccination campaigns. Such information can be used in preparedness planning to help improve control of a potential rabies incursion in Australia. [ABSTRACT FROM AUTHOR]

The 2018 outbreak of Nipah virus in Kerala, India, highlights the need for global surveillance of henipaviruses in bats, which are the reservoir hosts for this and other viruses. Nipah virus, an emerging paramyxovirus in the genus Henipavirus, causes severe disease and stuttering chains of transmission in humans and is considered a potential pandemic threat. In May 2018, an outbreak of Nipah virus began in Kerala, > 1800 km from the sites of previous outbreaks in eastern India in 2001 and 2007. Twenty-three people were infected and 21 people died (16 deaths and 18 cases were laboratory confirmed). Initial surveillance focused on insectivorous bats (Megaderma spasma), whereas follow-up surveys within Kerala found evidence of Nipah virus in fruit bats (Pteropus medius). P. medius is the confirmed host in Bangladesh and is now a confirmed host in India. However, other bat species may also serve as reservoir hosts of henipaviruses. To inform surveillance of Nipah virus in bats, we reviewed and analyzed the published records of Nipah virus surveillance globally. We applied a trait-based machine learning approach to a subset of species that occur in Asia, Australia, and Oceana. In addition to seven species in Kerala that were previously identified as Nipah virus seropositive, we identified at least four bat species that, on the basis of trait similarity with known Nipah virus-seropositive species, have a relatively high likelihood of exposure to Nipah or Nipah-like viruses in India. These machine-learning approaches provide the first step in the sequence of studies required to assess the risk of Nipah virus spillover in India. Nipah virus surveillance not only within Kerala but also elsewhere in India would benefit from a research pipeline that included surveys of known and predicted reservoirs for serological evidence of past infection with Nipah virus (or cross reacting henipaviruses). Serosurveys should then be followed by longitudinal spatial and temporal studies to detect shedding and isolate virus from species with evidence of infection. Ecological studies will then be required to understand the dynamics governing prevalence and shedding in bats and the contacts that could pose a risk to public health. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei causes melioidosis, a common source of pneumonia and sepsis in Southeast Asia and Northern Australia that results in high mortality rates. A caprine melioidosis model of aerosol infection that leads to a systemic infection has the potential to characterize the humoral immune response. This could help identify immunogenic proteins for new diagnostics and vaccine candidates. Outbred goats may more accurately mimic human infection, in contrast to the inbred mouse models used to date. B. pseudomallei infection was delivered as an intratracheal aerosol. Antigenic protein profiling was generated from the infecting strain MSHR511. Humoral immune responses were analyzed by ELISA and western blot, and the antigenic proteins were identified by mass spectrometry. Throughout the course of the infection the assay results demonstrated a much greater humoral response with IgG antibodies, in both breadth and quantity, compared to IgM antibodies. Pre-infection sera showed multiple immunogenic proteins already reactive for IgG (7–20) and IgM (0–12) in most of the goats despite no previous exposure to B. pseudomallei. After infection, the number of IgG reactive proteins showed a marked increase as the disease progressed. Early stage infection (day 7) showed immune reaction to chaperone proteins (GroEL, EF-Tu, and DnaK). These three proteins were detected in all serum samples after infection, with GroEL immunogenically dominant. Seven common reactive antigens were selected for further analysis using ELISA. The heat shock protein GroEL1 elicited the strongest goat antibody immune response compared to the other six antigens. Most of the six antigens showed the peak IgM reactivity at day 14, whereas the IgG reactivity increased further as the disease progressed. An overall MSHR511 proteomic comparison between the goat model and human sera showed that many immune reactive proteins are common between humans and goats with melioidosis. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is increasing in incidence in Victoria, Australia. To improve understanding of disease transmission, we aimed to map the location of BU lesions on the human body. Methods: Using notification data and clinical records review, we conducted a retrospective observational study of patients diagnosed with BU in Victoria from 1998–2015. We created electronic density maps of lesion locations using spatial analysis software and compared lesion distribution by age, gender, presence of multiple lesions and month of infection. Findings: We examined 579 patients with 649 lesions; 32 (5.5%) patients had multiple lesions. Lesions were predominantly located on lower (70.0%) and upper (27.1%) limbs, and showed a non-random distribution with strong predilection for the ankles, elbows and calves. When stratified by gender, upper limb lesions were more common (OR 1·97, 95% CI 1·38–2·82, p<0·001) while lower limb lesions were less common in men than in women (OR 0·48, 95% CI 0·34–0·68, p<0·001). Patients aged ≥ 65 years (OR 3·13, 95% CI 1·52–6·43, p = 0·001) and those with a lesion on the ankle (OR 2·49, 95% CI 1·14–5·43, p = 0·02) were more likely to have multiple lesions. Most infections (71.3%) were likely acquired in the warmer 6 months of the year. Interpretation: Comparison with published work in Cameroon, Africa, showed similar lesion distribution and suggests the mode of M. ulcerans transmission may be the same across the globe. Our findings also aid clinical diagnosis and provide quantitative background information for further research investigating disease transmission. [ABSTRACT FROM AUTHOR]

Background: Globally, trachoma is the leading cause of infectious blindness and Australia is the only developed country with endemic trachoma. It is found in remote Indigenous communities burdened with poverty, overcrowding and poor hygiene. Lack of culturally appropriate health promotion, a small trachoma workforce and lack of awareness and support for trachoma elimination in general, were early barriers. Methods: A cross-sectional pre-post study using a convenience sample, was conducted in clinics, schools and community work-settings from 63 of the 82 remote Aboriginal communities identified as being at risk of trachoma in the Northern Territory (NT). The study assessed the effect of a multi-component health promotion strategy aimed at increasing knowledge, attitude and practice amongst health, education and community support settings staff. Data were collected between 2010 and 2012. The health promotion initiatives were introduced in communities in staggered delivery over a one-year period; 272 participants were surveyed at baseline and 261 at follow-up. Results: Trachoma related knowledge, attitudes and practice increased across all settings and for all primary outcome measures. Across all settings, there was a significant increase in the proportion of participants reporting the most important thing to do if a child has a ‘dirty’ face is to ‘wash it every time its dirty’ (61.6% cf 69.7%; X2p = 0.047), a significant reduction in the proportion of respondents answering ‘no’ to the question “Is it normal for kids to have dirty faces in your community’ (40.5% cf 29.6%; X2p = 0.009) and a significant increase in reported capacity to teach others about trachoma prevention (70.8% cf 83.3%; X2p <0.001). Conclusion: Health promotion was associated with increased trachoma knowledge, attitude and practice amongst health, education and community support staff working with children and in remote NT communities. In the early stages of the trachoma health promotion program, this increased trachoma awareness and improved local workforce capacity and support for trachoma elimination in three health promotion settings in remote communities in the NT. [ABSTRACT FROM AUTHOR]

Modelling disease dynamics is most useful when data are limited. We present a spatial transmission model for the spread of canine rabies in the currently rabies-free wild dog population of Australia. The introduction of a sub-clinically infected dog from Indonesia is a distinct possibility, as is the spillover infection of wild dogs. Ranges for parameters were estimated from the literature and expert opinion, or set to span an order of magnitude. Rabies was judged to have spread spatially if a new infectious case appeared 120 km from the index case. We found 21% of initial value settings resulted in canine rabies spreading 120km, and on doing so at a median speed of 67 km/year. Parameters governing dog movements and behaviour, around which there is a paucity of knowledge, explained most of the variance in model outcomes. Dog density, especially when interactions with other parameters were included, explained some of the variance in whether rabies spread 120km, but dog demography (mean lifespan and mean replacement period) had minimal impact. These results provide a clear research direction if Australia is to improve its preparedness for rabies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Australia is the only high income country with persisting endemic trachoma. A national control program involving mass drug administration with oral azithromycin, in place since 2006, has some characteristics which differ from programs in low income settings, particularly in regard to the use of a wider range of treatment strategies, and more regular assessments of community prevalence. We aimed to examine the association between treatment strategies and trachoma prevalence. Methods: Through the national surveillance program, annual data from 2007–2013 were collected on trachoma prevalence and treatment with oral azithromycin in children aged 5–9 years from three Australian regions with endemic trachoma. Communities were classified for each year according to one of four trachoma treatment strategies implemented (no treatment, active cases only, household and community-wide). We estimated the change in trachoma prevalence between sequential pairs of years and across multiple years according to treatment strategy using random-effects meta-analyses. Findings: Over the study period, 182 unique remote Aboriginal communities had 881 annual records of both trachoma prevalence and treatment. From the analysis of pairs of years, the greatest annual fall in trachoma prevalence was in communities implementing community-wide strategies, with yearly absolute reductions ranging from -8% (95%CI -17% to 1%) to -31% (-26% to -37%); these communities also had the highest baseline trachoma prevalence (15.4%-43.9%). Restricting analyses to communities with moderate trachoma prevalence (5–19%) at initial measurement, and comparing community trachoma prevalence from the first to the last year of available data for the community, both community-wide and more targeted treatment strategies were associated with similar absolute reductions (-11% [-8% to -13%] and -7% [-5% to -10%] respectively). Results were similar stratified by region. Interpretation: Consistent with previous research, community-wide administration of azithromycin reduces trachoma prevalence. Our observation that less intensive treatment with a ‘household’ strategy in moderate prevalence communities (5-<20%) is associated with similar reductions in prevalence over time, will require confirmation in other settings if it is to be used as a basis for changes in control strategies. [ABSTRACT FROM AUTHOR]

Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE2) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE2 promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE2-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens. [ABSTRACT FROM AUTHOR]