Systematic review of household transmission of Strep A: A potential site for prevention that has eluded attention.

BACKGROUND: Despite being the sixth most common infectious disease globally, transmission of Streptococcus pyogenes (Strep A) within the household remains an understudied driver of infection. We undertook a systematic review to better understand the transmission of Strep A between people within the home while highlighting opportunities for prevention. METHODS: A search strategy was applied to five databases between September 2022 and March 2023. Results were limited to those published between January 2000 and March 2023. Texts were reviewed by two authors and the following data extracted: article details (title, author, year), study type, transmission year, country, participant age/s, infection status, molecular testing, and transmission mode. Funding was provided by the Australian National Health and Medical Research Council (NHMRC, grant number GNT2010716). RESULTS: The final analysis comprised 28 texts. Only seven studies (25.0%) provided sufficient detail to identify the Strep A transmission mode. These were contact (4), vehicle (bedding; clothing; other fabric, and medical equipment, [2]), and contact with animals (1). All others were classified as household (specific mode unascertainable). Most articles reported outbreaks involving invasive Strep A infections. CONCLUSIONS: There is limited literature regarding household transmission of Strep A. Understanding transmission in this setting remains imperative to guide control methods.

Low rates of complications and ß-lactam resistance in viridans group streptococci bloodstream infection among cancer patients receiving chemotherapy.

BACKGROUND: Viridans group streptococci (VGS) bloodstream infection (BSI) frequently occurs in cancer patients receiving chemotherapy, and is associated with infective endocarditis (IE) in up to 20% of cases in the general population. OBJECTIVES: In cancer patients receiving chemotherapy with VGS BSI, we aimed to: (i) determine the incidence of infective complications including IE, (ii) assess the utility of echocardiography in this patient population, (iii) determine the duration and type of antimicrobial therapy received for monomicrobial infections, and (iv) determine the evolution of antimicrobial resistance. METHODS: VGS BSIs (excluding Streptococcus pneumoniae and Streptococcus pseudopneumoniae) in cancer patients receiving chemotherapy were identified from a statewide public pathology database between 2013 and 2022 at our tertiary centre. Medical records were accessed for clinical, microbiological and radiological data. RESULTS: Of 581 patient episodes screened, 183 episodes involving 171 patients met inclusion criteria. Of these, 51% were bone marrow transplantation (BMT) patients, 40% were non-BMT haematology patients, and 8% were solid organ malignancy patients. The median age was 55 years, and 96% were neutropenic at the time of blood culture collection. A transthoracic echocardiogram was performed for 71% of episodes, and one patient met modified Duke's criteria for definite IE, although this diagnosis was not suspected on clinical grounds. Other complications were uncommon. Benzylpenicillin resistance was rare (2.9%) and did not change over time. Most episodes (75%) were treated with piperacillin/tazobactam. For monomicrobial BSIs, the median antibiotic duration was 5 days (IQR 2-7) post-neutropenia resolution. CONCLUSIONS: Infective complications and antimicrobial resistance are rare in cancer patients with VGS BSI. This may provide a safe opportunity to limit both investigations (e.g. echocardiogram) and prolonged exposure to broad-spectrum antimicrobials.

Human T-cell leukaemia virus type 1 and Adult T-cell leukaemia/lymphoma in Queensland, Australia: a retrospective cross-sectional study.

OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.

OBJECTIVE: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. DESIGN: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RESULTS: Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. CONCLUSIONS: These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.

Peer-delivered point-of-care testing for Chlamydia trachomatis and Neisseria gonorrhoeae within an urban community setting: a cross-sectional analysis.

Background The advent of fully automated nucleic acid amplification test (NAAT) technology brings new public health opportunities to provide Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) point-of-care testing (POCT) in non-traditional settings. METHODS: This pilot study evaluated the integration of the CT/NG Xpert diagnostic assay into an urban peer-led community setting providing HIV and syphilis POCT. A comprehensive protocol of testing, result notification, referral and follow up, managed by peer test facilitators, was undertaken. RESULTS: Over 67 weeks, there were 4523 occasions of CT/NG testing using urine, oropharyngeal and anorectal samples with 25.7% (803) of the 3123 unique participants returning for repeat testing. The prevalence of CT and NG was 9.5% and 5.4% respectively. Where CT and or NG infection was detected, 98.4% (604/614) of participants were successfully notified of detected infection and referred for treatment. Evaluation Survey responses (11.4%, 516/4523) indicated a substantial proportion of respondents (27.1%, 140/516) 'would not have tested anywhere else'. Of note, 17.8% (92/516) of participants reported no previous CT/NG test and an additional 17.8% (92/516) reported testing more than 12 months ago. A total of 95.9% (495/516) of participants 'Strongly agreed' or 'Agreed' to being satisfied with the service. CONCLUSION: The project successfully demonstrated an acceptable and feasible model for a peer-delivered community-led service to provide targeted molecular CT/NG POCT. This model offers capacity to move beyond the traditional pathology and STI testing services and establish community-led models that build trust and increase testing rates for key populations of epidemiological significance.

Reduced sensitivity from pooled urine, pharyngeal and rectal specimens when using a molecular assay for the detection of chlamydia and gonorrhoea near the point of care.

Background The aim of this study was to compare the performance of pooled self-collected urogenital, pharyngeal and anorectal specimens to that of individual specimen results for the molecular detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) near the point of care (POC) for diagnostic sensitivity. METHODS: Clients (mostly men who have sex with men) attending an urban community testing service and three sex-on-premises venues in Brisbane, Australia, were offered CT and NG testing by trained lay providers. Participants provided three self-collected specimens (urine, pharyngeal and rectal) for testing by GeneXpert (Cepheid, Sunnyvale, CA, USA). If any of the individual specimens from a participant were positive, all three specimens were pooled and retested. RESULTS: Of the 388 participants who provided three individual anatomical specimens, 76 (19.6%) were found to be positive for CT and/or NG at one or more sites. The pooling approach failed to detect five CT rectal and four NG pharyngeal infections. The overall performance (sensitivity) of the pooling approach compared with individual specimen testing and Cohen's κ were 90.0% and 0.86 respectively for CT and 89.7% and 0.89 respectively for NG. CONCLUSIONS: Reduced sensitivity was observed when using pooled specimens for the detection of CT and NG using GeneXpert near the POC, similar to results reported in laboratory-based CT and NG pooling studies. These data suggest specimen pooling is feasible near to the POC, potentially saving time and costs when screening at-risk populations for CT and NG. Our data also suggest a reduction in pooled urine could improve overall test sensitivity.

Integrated HIV self-testing (HIVST) service delivery in Queensland for policy and service development: study protocol.

This study aims to pilot and evaluate an integrated model for HIV self-testing (HIVST) service delivery in a peer-led Queensland community setting to increase access to HIVST, particularly for men who have sex with men (MSM) living in regional, remote and rural areas. It seeks to provide evidence that would overcome some of the key objections previously raised to HIVST. Recruitment strategies have been designed to engage hard to reach MSM populations in testing. Awareness of the trial will be generated through advertising on social media platforms, including dating applications, word of mouth and HIV related websites. Participants will access an HIVST online ordering system hosted by a HIV community organisation. This system: (1) enables on-line informed consent; 2) gives clients the choice to accept verbal pre-test information from a trained peer test facilitator or not; and (3) allows for ordering of the HIVST kit after completion of an online survey (with demographic information and testing history etc.). Clients receive the kits via the post; and at 2 weeks receive a follow-up phone-call and SMS link to a post-test survey. If the test is non-reactive, clients can opt for test reminders. If reactive, referral to clinical services, peer navigation and support systems are provided. This study addresses important gaps in understanding of acceptable and feasible methods to integrate HIVST into an existing peer-led testing service and into the broader suite of HIV testing options and services. The findings will inform the actions needed to enhance access to HIVST for MSM wishing to use this technology in Australia and elsewhere, especially those who have never tested and infrequent testers.

Subcutaneous cholera toxin exposure induces potent CD103⁺ dermal dendritic cell activation and migration.

CD103⁺ dermal dendritic cells (dDCs) are a recently described DC subset of the skin shown to be the principal migratory DCs capable of efficiently cross-presenting antigens and activating CD8⁺ T cells. Harnessing their activity would promote vaccine efficacy, but it has been unclear how this can be achieved. We tested a panel of adjuvants for their ability to affect dDCs. In comparison to the other adjuvants tested, the capacity of cholera toxin (CT) to induce the migration of dDCs was unique. Within 24 h of CT injection, large numbers of highly activated dDCs (including CD103⁺ dDCs) migrated to the draining lymph nodes and cross-presented coinjected antigens, potently activating naïve CD8⁺ T cells. Peptide vaccines adjuvanted with CT induced T-cell responses uniquely characterized by dynamic cytokine responses including the production of IL-2, and such vaccines were protective in situations reliant on CD8⁺ T-cell responses, including liver-stage Plasmodium challenge, or tumor challenge. This study is the first to examine the effects of adjuvants on CD103⁺ dDCs and identifies CT as a prototypical adjuvant for the activation of CD103⁺ dDCs, opening the way to development of vaccines and adjuvants that specifically target dDCs and generate effective CD8⁺ T-cell responses.

Community-Led Health Initiatives for Torres Straits Island Communities in a Changing Climate: Implementing Core Values for Mitigation and Adaptation.

First Nations Peoples have a long history of living in Australia's changing climate and a deep knowledge of their traditional estate ('Country'). However, human-induced climate change raises unforeseen risks to the health of First Nations Peoples-especially in remotely located communities. This includes the Torres Strait Islands, where a local leader asked our Torres Strait Islander co-author, 'We know that you will return to your Country-unlike previous researchers. So how can you help with climate change?' In response, this research describes four core values focused on supporting First Nations Peoples' health and wellbeing: co-design, appropriate governance, support for self-determination, and respectfully incorporating Indigenous Knowledges into health-protective climate initiatives. Supporting the health and wellbeing of Torres Strait Islanders to continue living in the remote Torres Strait Islands in a changing climate can enable long-term care for Country, maintenance of culture, and a sense of identity for First Nations Peoples. Ensuring these core values are implemented can support the health of present and future generations and will likely be applicable to other First Nations communities.

Climate change and infectious diseases in Australia's Torres Strait Islands.

OBJECTIVE: This research seeks to identify climate-sensitive infectious diseases of concern with a present and future likelihood of increased occurrence in the geographically vulnerable Torres Strait Islands, Australia. The objective is to contribute evidence to the need for adequate climate change responses. METHODS: Case data of infectious diseases with proven, potential and speculative climate sensitivity were compiled. RESULTS: Five climate-sensitive diseases in the Torres Strait and Cape York region were identified as of concern: tuberculosis, dengue, Ross River virus, melioidosis and nontuberculous mycobacterial infection. The region constitutes 0.52% of Queensland's population but has a disproportionately high proportion of the state's cases: 20.4% of melioidosis, 2.4% of tuberculosis and 2.1% of dengue. CONCLUSIONS: The Indigenous Torres Strait Islander peoples intend to remain living on their traditional country long-term, yet climate change brings risks of both direct and indirect human health impacts. Implications for public health: Climate-sensitive infections pose a disproportionate burden and ongoing risk to Torres Strait Islander peoples. Addressing the causes of climate change is the responsibility of various agencies in parallel with direct action to minimise or prevent infections. All efforts should privilege Torres Strait Islander peoples' voices to self-determine response actions.

Online HIV Self-Testing (HIVST) Dissemination by an Australian Community Peer HIV Organisation: A Scalable Way to Increase Access to Testing, Particularly for Suboptimal Testers.

HIV self-testing (HIVST) introduces opportunities for screening in non-conventional settings, and addresses known testing barriers. This study involved the development and evaluation of a free online HIVST dissemination service hosted by a peer-led, community-based organisation with on-site, peer-facilitated HIV testing, and established referral and support programs for people newly diagnosed with HIV to determine whether this model was feasible and acceptable for engaging MSM, particularly among infrequent and naive HIV-testers, or those living in remote and rural areas. Between December 2016 and April 2018, 927 kits were ordered by 794 individuals, the majority of whom were men who have sex with men (MSM) (62%; 494), having condomless sex (50%; 392), or living outside a major city (38%; 305). Very few (5%; 39) sought the available pre-test peer contact, despite 45% (353) being naive HIV-testers. This study demonstrates that online HIVST dissemination is acceptable and feasible for engaging at-risk suboptimal testers, including those unwilling to test elsewhere (19%; 47/225). With half (50%; 403) unwilling to buy a kit, our study suggests that HIVST will need to be subsidized (cost-neutral to users) to enhance population coverage and access.

Meropenem-induced liver injury and beta-lactam cross-reactivity.

A 63-year-old man admitted to hospital for the management of a frontal lobe abscess developed elevated liver enzymes within 48 hours of receiving meropenem. Liver enzymes reached a maximum at 5 days postadministration of meropenem, with alanine aminotransferase 1160 U/L, aspartate aminotransferase 787 U/L, alkaline phosphatase 297 U/L and gamma-glutamyltransferase 252 U/L. Meropenem was ceased and liver function normalised. Meropenem was administered for a second time later in the patient's admission and again the patient developed rapidly increasing liver enzymes, with a mixed hepatocellular/cholestatic pattern. Other possible causes of liver injury were excluded following extensive investigations, and the patient's liver enzymes continued to normalise following meropenem discontinuation. The patient was asymptomatic during the admission and was transferred to a rehabilitation facility. This case demonstrates that meropenem can cause severe liver injury and that early recognition of drug-induced liver injury is important.

Antimalarial activity of sera from subjects taking HIV protease inhibitors.

Synergy between HIV and malaria is being increasingly recognized. We examined the antimalarial activity of sera from subjects receiving chloroquine, no drugs or HAART. Sera from subjects taking ritonavir-boosted saquinavir or lopinavir significantly inhibited parasite growth (median of 55 and 69% inhibition, respectively). These results indicate that patients on protease inhibitors may be afforded some protection from malaria. The clinical relevance of these observations will require confirmation in controlled studies in malaria-endemic regions.

Fungal infections of the central nervous system: A review of fungal pathogens and treatment.

Multiple factors influence the outcome of fungal infection of the central nervous system (CNS). The host and the pathogen in concert with drug delivery across the blood-brain barrier and drug activity are key factors in outcome. Drug costs can be prohibitively expensive. Drug toxicity with standard antifungal agents such as amphotericin B (infusion rate toxicity) can be reduced using simple techniques such as slower infusion and appropriate saline loading. Continuous infusion can allow relatively large doses of amphotericin B (up to 2 mg/kg/day, remaining below 0.08 mg/kg/hour) to be given with toxicity profiles comparable to expensive lipid formulations of amphotericin B. Dedicated peripherally inserted central catheters can remain in situ for weeks to months and are safe and relatively inexpensive. Correction of metabolic pathology in the case of mucormycosis and resolution of neutropenia are essential to effective treatment of filamentous fungal infections such as Mucor, Aspergillus and Scedosporium. The pharmacology and pharmacokinetics of the current major antifungal agents used to treat fungal infections of the CNS are reviewed. Tables that provide information about achievable CNS drug levels, antifungal susceptibilities and the likelihood of intrinsic drug resistance of significant fungal pathogens have been included to help the clinician with therapy. Treatment recommendations for Cryptococcal and Candida meningitis and for rhinocerebral infection with Mucor and Aspergillus have been included.

Epidemic syphilis exhibits diverse manifestations.

There are recent reports of a sustained increase in the incidence of syphilis around the world, including in the Australian cities of Sydney and Melbourne.