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Victoria, Australia, has been experiencing an intensifying outbreak of Buruli ulcer (1). The mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, has been contested. The first evidence that [...]

Alphavirus infections are transmitted by mosquitoes, but the mode of transmission for Mycobacterium ulcerans, which causes Buruli ulcer, is contested. Using notification data for Victoria, Australia, during 2017–2022, adjusted for incubation period, we show close alignment between alphavirus and Buruli ulcer seasons, supporting the hypothesis of mosquito transmission of M. ulcerans.

Haemophilus influenzae is a human respiratory pathogen and inhabits the human respiratory tract as its only niche. Despite this, the molecular mechanisms that allow H. influenzae to establish persistent infections of human epithelia are not well understood. Here, we have investigated how H. influenzae adapts to the host environment and triggers the host immune response using a human primary cell-based infection model that closely resembles human nasal epithelia (NHNE). Physiological assays combined with dualRNAseq revealed that NHNE from five healthy donors all responded to H. influenzae infection with an initial, 'unproductive' inflammatory response that included a strong hypoxia signature but did not produce pro-inflammatory cytokines. Subsequently, an apparent tolerance to large extracellular and intraepithelial burdens of H. influenzae developed, with NHNE transcriptional profiles resembling the pre-infection state. This occurred in parallel with the development of intraepithelial bacterial populations, and appears to involve interruption of NFκB signalling. This is the first time that large-scale, persistence-promoting immunomodulatory effects of H. influenzae during infection have been observed, and we were able to demonstrate that only infections with live, but not heat-killed H. influenzae led to immunomodulation and reduced expression of NFκB-controlled cytokines such as IL-1β, IL-36γ and TNFα. Interestingly, NHNE were able to re-activate pro-inflammatory responses towards the end of the 14-day infection, resulting in release of IL-8 and TNFα. In addition to providing first molecular insights into mechanisms enabling persistence of H. influenzae in the host, our data further indicate the presence of infection stage-specific gene expression modules, highlighting fundamental similarities between immune responses in NHNE and canonical immune cells, which merit further investigation.

Growth in online higher education offerings has been significant in recent years, with many Australian Universities launching programs to extend into new markets and meet the student demand for greater flexibility in delivery modes. Further, it is well understood that good support is an essential component to student success, satisfaction and retention. Despite this, orientation, including non-academic support, is often overlooked in online education systems. Therefore, the current study aimed to develop an orientation program to increase student preparedness and facilitate ongoing support, in addition to developing evidence-based best-practice strategies to support academic's when developing new online courses.

Course and subject development teams are increasingly seen in the tertiary online teaching environment and they face a unique set of challenges. The purpose of this study was to synthesise and share learnings of 12 academics involved in the development of subjects with an external partner for a new multidisciplinary online health science course at an Australian university, in order to improve ongoing development within the course and inform new course development. In this case study, thematic analysis of focus group discussions and qualitative survey data identified five key themes related to the development process: time management, setting expectations, communication, the development team, and ownership. Barriers to productive subject development included unrealistic timelines, unclear lines of communication, unmet or unrealistic expectations and lack of recognition of team members' expertise, and lack of support for genuine collaboration. Team-based development of an online course has the potential to be a rewarding experience for academics. In order for the benefits to be realised, approaches to development underpinned by a community-centred framework, observing core values such as collaboration, shared sense of purpose and expectations, would address a number of the issues identified in this study.

Background: Despite recent evidence demonstrating iron and folate supplementation reduces the risk of low birth weight and preterm births, synthesis of the evidence is not sufficient to understand their impacts in Africa. Method: MEDLINE, PsycINFO, Embase, Scopus, CHINAL, Web of Science, Cochrane databases, and Google Scholar were searched for the published and grey literature. Either iron-only, folate-only, or iron–folic acid (IFA) oral supplementation during pregnancy was the primary exposure/intervention. The focus of this review was low birth weight and preterm births in the African region. Qualitative synthesis, meta-analysis, and subgroup analysis were employed. Results: In the qualitative synthesis (n = 4), IFA supplementation showed a positive impact on reducing preterm birth. Additionally, the meta-analysis showed that IFA and iron-only supplementation reduced the odds of low birth weight by 63% (OR 0.37; 95% CI: 0.29, 0.48) and 68% (OR 0.32; 95% CI: 0.21 to 0.50), respectively. Conclusion: Both iron-only and IFA supplementation are effective in reducing the risk of low birth weight in Africa. There is also promising evidence suggesting a potential reduction in preterm births. Consequently, further research is needed, particularly targeting high-risk groups such as women residing in rural areas with limited support and low levels of literacy.

Background: Buruli ulcer (BU) is a neglected tropical disease caused by infection of subcutaneous tissue with Mycobacterium ulcerans. BU is commonly reported across rural regions of Central and West Africa but has been increasing dramatically in temperate southeast Australia around the major metropolitan city of Melbourne, with most disease transmission occurring in the summer months. Previous research has shown that Australian native possums are reservoirs of M. ulcerans and that they shed the bacteria in their fecal material (excreta). Field surveys show that locales where possums harbor M. ulcerans overlap with human cases of BU, raising the possibility of using possum excreta surveys to predict the risk of disease occurrence in humans. Methods: We thus established a highly structured 12 month possum excreta surveillance program across an area of 350 km2 in the Mornington Peninsula area 70 km south of Melbourne, Australia. The primary objective of our study was to assess using statistical modeling if M. ulcerans surveillance of possum excreta provided useful information for predicting future human BU case locations. Results: Over two sampling campaigns in summer and winter, we collected 2,282 possum excreta specimens of which 11% were PCR positive for M. ulcerans-specific DNA. Using the spatial scanning statistical tool SaTScan, we observed non-random, co-correlated clustering of both M. ulcerans positive possum excreta and human BU cases. We next trained a statistical model with the Mornington Peninsula excreta survey data to predict the future likelihood of human BU cases occurring in the region. By observing where human BU cases subsequently occurred, we show that the excreta model performance was superior to a null model trained using the previous year’s human BU case incidence data (AUC 0.66 vs 0.55). We then used data unseen by the excreta-informed model from a new survey of 661 possum excreta specimens in Geelong, a geographically separate BU endemic area to the southwest of Melbourne, to prospectively predict the location of human BU cases in that region. As for the Mornington Peninsula, the excreta-based BU prediction model outperformed the null model (AUC 0.75 vs 0.50) and pinpointed specific locations in Geelong where interventions could be deployed to interrupt disease spread. Conclusions: This study highlights the One Health nature of BU by confirming a quantitative relationship between possum excreta shedding of M. ulcerans and humans developing BU. The excreta survey-informed modeling we have described will be a powerful tool for the efficient targeting of public health responses to stop BU. Funding: This research was supported by the National Health and Medical Research Council of Australia and the Victorian Government Department of Health (GNT1152807 and GNT1196396).

Background: Despite recent evidence demonstrating iron and folate supplementation reduces the risk of low birth weight and preterm births, synthesis of the evidence is not sufficient to understand their impacts in Africa. Method: MEDLINE, PsycINFO, Embase, Scopus, CHINAL, Web of Science, Cochrane databases, and Google Scholar were searched for the published and grey literature. Either iron-only, folate-only, or iron–folic acid (IFA) oral supplementation during pregnancy was the primary exposure/intervention. The focus of this review was low birth weight and preterm births in the African region. Qualitative synthesis, meta-analysis, and subgroup analysis were employed. Results: In the qualitative synthesis (n = 4), IFA supplementation showed a positive impact on reducing preterm birth. Additionally, the meta-analysis showed that IFA and iron-only supplementation reduced the odds of low birth weight by 63% (OR 0.37; 95% CI: 0.29, 0.48) and 68% (OR 0.32; 95% CI: 0.21 to 0.50), respectively. Conclusion: Both iron-only and IFA supplementation are effective in reducing the risk of low birth weight in Africa. There is also promising evidence suggesting a potential reduction in preterm births. Consequently, further research is needed, particularly targeting high-risk groups such as women residing in rural areas with limited support and low levels of literacy. [ABSTRACT FROM AUTHOR]

Haemophilus influenzae is a human respiratory pathogen and inhabits the human respiratory tract as its only niche. Despite this, the molecular mechanisms that allow H. influenzae to establish persistent infections of human epithelia are not well understood. Here, we have investigated how H. influenzae adapts to the host environment and triggers the host immune response using a human primary cell-based infection model that closely resembles human nasal epithelia (NHNE). Physiological assays combined with dualRNAseq revealed that NHNE from five healthy donors all responded to H. influenzae infection with an initial, 'unproductive' inflammatory response that included a strong hypoxia signature but did not produce pro-inflammatory cytokines. Subsequently, an apparent tolerance to large extracellular and intraepithelial burdens of H. influenzae developed, with NHNE transcriptional profiles resembling the pre-infection state. This occurred in parallel with the development of intraepithelial bacterial populations, and appears to involve interruption of NFκB signalling. This is the first time that large-scale, persistence-promoting immunomodulatory effects of H. influenzae during infection have been observed, and we were able to demonstrate that only infections with live, but not heat-killed H. influenzae led to immunomodulation and reduced expression of NFκB-controlled cytokines such as IL-1β, IL-36γ and TNFα. Interestingly, NHNE were able to re-activate pro-inflammatory responses towards the end of the 14-day infection, resulting in release of IL-8 and TNFα. In addition to providing first molecular insights into mechanisms enabling persistence of H. influenzae in the host, our data further indicate the presence of infection stage-specific gene expression modules, highlighting fundamental similarities between immune responses in NHNE and canonical immune cells, which merit further investigation. Author summary: Respiratory tract infections are highly debilitating, and Haemophilus influenzae is a bacterial pathogen that is associated with persistent acute and chronic respiratory tract infections particularly in vulnerable parts of the population. Persistent infections rely on close molecular interactions between the human respiratory cells and the bacterial pathogen, and here we have investigated changes in host and bacterial cells during persistent, long-term infections with H. influenzae. We were able to show for the first time that H. influenzae infections can induce a tolerance to the presence of bacteria in human respiratory epithelia. This tolerance included reduced immune responses, and required live bacteria to be established, which indicates that H. influenzae likely produce specific effector molecules that interrupt immune system signalling. This is the first time that such interactions have been documented for H. influenzae, and suggests that future treatments for H. influenzae infections could include those that strengthen the human immune responses. [ABSTRACT FROM AUTHOR]

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection. Non-technical author summary: In this paper, we progress our research towards establishing a controlled human infection model (CHIM) of Buruli ulcer, caused by Mycobacterium ulcerans. It is crucial that the challenge agent used for such experiments is thoroughly characterised; not only is this important to ensure standardisation between participants, but also to reinforce their safety. Using established criteria, we systematically demonstrate why the isolate M. ulcerans JKD8049 may be a suitable challenge strain. This strain is non-genetically modified, susceptible to antibiotics, can be cultured in relatively simple media, and can be filtered and preserved as individual bacteria to ensure accurate dosing of participants. Even after repeatedly culturing the organism for months, it remains genetically stable, so significant mutations are not expected to develop during manufacture. After preserving the isolate at -80°C, it can be revived and diluted for human inoculation at very low doses. Importantly, it produces the toxin mycolactone, so it is expected to recreate typical Buruli ulcer disease in participants, which will be important to properly test vaccines and other therapeutics. We also demonstrate a set of principles to ensure the produced batch is free from contamination. [ABSTRACT FROM AUTHOR]

Fundamental to effective Legionnaires’ disease outbreak control is the ability to rapidly identify the environmental source(s) of the causative agent, Legionella pneumophila. Genomics has revolutionized pathogen surveillance, but L. pneumophila has a complex ecology and population structure that can limit source inference based on standard core genome phylogenetics. Here, we present a powerful machine learning approach that assigns the geographical source of Legionnaires’ disease outbreaks more accurately than current core genome comparisons. Models were developed upon 534 L. pneumophila genome sequences, including 149 genomes linked to 20 previously reported Legionnaires’ disease outbreaks through detailed case investigations. Our classification models were developed in a cross-validation framework using only environmental L. pneumophila genomes. Assignments of clinical isolate geographic origins demonstrated high predictive sensitivity and specificity of the models, with no false positives or false negatives for 13 out of 20 outbreak groups, despite the presence of within-outbreak polyclonal population structure. Analysis of the same 534-genome panel with a conventional phylogenomic tree and a core genome multi-locus sequence type allelic distance-based classification approach revealed that our machine learning method had the highest overall classification performance—agreement with epidemiological information. Our multivariate statistical learning approach maximizes the use of genomic variation data and is thus well-suited for supporting Legionnaires’ disease outbreak investigations. IMPORTANCE Identifying the sources of Legionnaires’ disease outbreaks is crucial for effective control. Current genomic methods, while useful, often fall short due to the complex ecology and population structure of Legionella pneumophila, the causative agent. Our study introduces a high-performing machine learning approach for more accurate geographical source attribution of Legionnaires’ disease outbreaks. Developed using cross-validation on environmental L. pneumophila genomes, our models demonstrate excellent predictive sensitivity and specificity. Importantly, this new approach outperforms traditional methods like phylogenomic trees and core genome multi-locus sequence typing, proving more efficient at leveraging genomic variation data to infer outbreak sources. Our machine learning algorithms, harnessing both core and accessory genomic variation, offer significant promise in public health settings. By enabling rapid and precise source identification in Legionnaires’ disease outbreaks, such approaches have the potential to expedite intervention efforts and curtail disease transmission. [ABSTRACT FROM AUTHOR]

Buruli ulcer (BU) is a chronic and destructive infection of the skin and soft tissues caused by Mycobacterium ulcerans. Recently, population flows have triggered the appearance of several sporadic cases of BU in non-endemic countries. This represents a significant diagnostic challenge for clinicians and microbiologists. We describe the first case of BU imported to Spain. The patient was a Spanish woman who had stayed 5 months in the jungle of Peru. Keywords: Whole genome sequencing, Buruli ulcer, Mycobacterium ulcerans

Objective: The review presents a systematic analysis of literature investigating the association between migraine and suicidal behaviors.Introduction: Migraine is a common neurological disorder. The prevalence of migraines increases with age from adolescence to adulthood in both sexes, and results in a substantial loss of productivity due to missing days of school or work and need for bed rest. Literature prior to 2015 suggests that migraine is a predictor of suicide. Given the worldwide public health interest in suicide prevention, we examined the literature collected from diverse, predominantly non-European, populations post-2015.Methods: The databases used in this systematic review included: Medline, PsycINFO, EMBASE (Ovid), Science Direct (Elsevier), Cochrane, and PubMed for all available years of publication from January 2015 onwards. The review included participants aged 16 and over who had been diagnosed with migraines with the following outcome variables: any suicidality, both fatal and non-fatal; suicidal ideation; and suicidal behavior.Results: The database searches yielded a total of 542 citations. Following title and abstract screening, 460 articles were excluded and a total of 21 citations were evaluated. After full-text review and excluding a further 11 non-eligible studies, a total of 10 studies were eligible for inclusion in the systematic review.Conclusions: Current existing research highlights the important association between the increased risk of suicidal behaviors in the clinical and general population among chronic migraineurs with/without aura worldwide. Future studies are needed to facilitate the development of clinical guidelines for risk assessment, targeted interventions, and evidence-based treatment of migraine to reduce the risk of suicide among this vulnerable population.

Abstract Background Vancomycin-resistant Enterococcus faecium (VRE) is a leading cause of hospital-acquired infections. New, presumably better-adapted strains of VRE appear unpredictably; it is uncertain how they spread despite improved infection control. We aimed to investigate the relatedness of a novel sequence type (ST) of vanB E. faecium - ST796 - very near its time of origin from hospitals in three Australian states and New Zealand. Methods Following near-simultaneous outbreaks of ST796 in multiple institutions, we gathered then tested colonization and bloodstream infection isolates’ antimicrobial resistance (AMR) phenotypes, and phylogenomic relationships using whole genome sequencing (WGS). Patient meta-data was explored to trace the spread of ST796. Results A novel clone of vanB E. faecium (ST796) was first detected at one Australian hospital in late 2011, then in two New Zealand hospitals linked by inter-hospital transfers from separate Melbourne hospitals. ST796 also appeared in hospitals in South Australia and New South Wales and was responsible for at least one major colonization outbreak in a Neonatal Intensive Care Unit without identifiable links between centers. No exceptional AMR was detected in the isolates. While WGS analysis showed very limited diversity at the core genome, consistent with recent emergence of the clone, clustering by institution was observed. Conclusions Evolution of new E. faecium clones, followed by recognized or unrecognized movement of colonized individuals then rapid intra-institutional cross-transmission best explain the multi-center, multistate and international outbreak we observed.

We conducted epidemiologic and genetic analyses of family clusters of Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found that the incidence of M. ulcerans disease in family members was increased. However, the risk for exposure appeared short-term and not related to human-human transmission.

We have previously shown that secondary infections of Buruli ulcer wounds were frequently caused by Staphylococcus aureus. To gain understanding into possible routes of secondary infection, we characterized S. aureus isolates from patient lesions and surrounding environments across two Ghanaian health centres. One hundred and one S. aureus isolates were isolated from wounds (n=93, 92.1%) and the hospital environment (n=8, 7.9%) and characterized by the spa gene, mecA and the Panton–Valentine leucocidin toxin followed by spa sequencing and whole genome sequencing of a subset of 49 isolates. Spa typing and sequencing of the spa gene from 91 isolates identified 29 different spa types with t355 (ST152), t186 (ST88), and t346 dominating. Although many distinct strains were isolated from both health centres, genotype clustering was identified within centres. In addition, we identified a cluster consisting of isolates from a healthcare worker, patients dressed that same day and forceps used for dressing, pointing to possible healthcare-associated transmission. These clusters were confirmed by phylogenomic analysis. Twenty-four (22.8%) isolates were identified as methicillin-resistant S. aureus and lukFS genes encoding Panton–Valentine leucocidin were identified in 67 (63.8%) of the isolates. Phenotype screening showed widespread resistance to tetracycline, erythromycin, rifampicin, amikacin and streptomycin. Genomics confirmed the widespread presence of antibiotic resistance genes to β-lactams, chloramphenicol, trimethoprim, quinolone, streptomycin and tetracycline. Our findings indicate that the healthcare environment probably contributes to the superinfection of Buruli ulcer wounds and calls for improved training in wound management and infection control techniques.

Mycobacterium ulcerans is a slow-growing organism that causes necrotizing infections of skin and soft tissue, often requiring reconstructive surgery and resulting in long-term disability (1,2). Prevailing opinion is that humans [...]

The commercial whale watching industry in Sri Lanka, like the tourism industry generally, is experiencing rapid growth in visitor numbers. The challenge for the government is to ensure the sector is managed sustainably which, in-part, requires an understanding of tour participants, their needs and experiences. In order to address this need, a study using the perceived-performance model was undertaken in Mirissa and Galle to examine the profile of whale watching tourists, their tour experiences and spending patterns. In late-2012 and early-2013 a questionnaire constructed in English and Sinhala and containing 28 questions was administered to participants after their tour in both Mirissa and Galle. Study participants indicated that they were overwhelmingly satisfied with all aspects of their tour. Additional the findings indicated that undertaking a whale watching tour was an important influence on their decision to visit Mirissa/Galle and contributed significantly to their enjoyment of their visit to the towns. The results also indicated the economic importance of whale watching to Mirissa and Galle.