Vaccine-Preventable Disease Outbreaks among Healthcare Workers: A Scoping Review.

BACKGROUND: Outbreaks of vaccine preventable diseases (VPDs) in health care workers (HCWs) can result in morbidity and mortality and cause significant disruptions to health care services, patients and visitors as well as an added burden on the health system. This scoping review is aimed to describe the epidemiology of VPD outbreaks in HCW, caused by diseases which are prevented by the ten vaccines recommended by World Health Organization (WHO) for HCWs. METHODS: In April 2022 CINAHL, MEDLINE, Global Health and EMBASE were searched for all articles reporting on VPD outbreaks in HCWs since the year 2000. Articles were included regardless of language and study type. Clinical and epidemiological characteristics of VPD outbreaks were described. RESULTS: Our search found 9363 articles, of which 216 met inclusion criteria. Studies describing six of the ten VPDs were found: influenza, measles, varicella, tuberculosis, pertussis and rubella. Most articles (93%) were from high- and upper middle-income countries. While most outbreaks occurred in hospitals, several influenza outbreaks were reported in long term care facilities. Based on available data, vaccination rates amongst HCWs were rarely reported. CONCLUSION: We describe several VPD outbreaks in HCWs from 2000 to April 2022. The review emphasises the need to understand the factors influencing outbreaks in HCWs and highlight importance of vaccination amongst HCWs.

The seroprevalence of antibodies to Japanese encephalitis virus in five New South Wales towns at high risk of infection, 2022: a cross-sectional serosurvey.

OBJECTIVES: To determine the proportion of people in New South Wales towns at high risk of Japanese encephalitis virus (JEV) infections during the 2022 outbreak; to identify risk factors for JEV infection. STUDY DESIGN: Cross-sectional serosurvey study of the seroprevalence of JEV-specific antibodies in NSW. SETTING, PARTICIPANTS: Convenience sample of people (all ages) from five regional NSW towns deemed to be at high risk of JEV infections after first outbreak of Japanese encephalitis in southeastern Australia in early 2022 (Balranald, Corowa, Dubbo, Griffith, Temora), 21 June - 22 July 2022. MAIN OUTCOME MEASURES: Proportion of people seropositive for JEV total antibody, assayed by defined epitope-blocking enzyme-linked immunosorbent assay; prevalence odds ratios for exposure risk factors and protective behaviours. RESULTS: Eighty of 917 eligible participants (559 girls or women, 61%; 42 Aboriginal and Torres Strait Islander people, 4.6%; median age, 52 years [IQR, 37-62 years]) were seropositive for JEV-specific total antibody (8.7%); the median age of seropositive people was 61 years (IQR, 48-70 years). The seropositivity proportion was largest for people aged 65 years or more (30 of 192; weighted proportion, 13.7%) and larger for male than female participants (30 of 358, 10.6% v 50 of 559, 7.5%). Five of 42 samples from Aboriginal and Torres Strait Islander participants were seropositive (12%). We found mixed associations with a range of potential risk factors. CONCLUSION: We found evidence for a substantial number of JEV infections in five regional NSW towns during a single arbovirus season in 2022. Public health responses, including effective surveillance, vaccination against JEV, and mosquito management, are critical for controlling outbreaks. Promoting behaviours that reduce exposure to mosquitoes is a core component of prevention, particularly when the vaccine supply is limited.

How have governments supported citizens stranded abroad due to COVID-19 travel restrictions? A comparative analysis of the financial and health support in eleven countries.

BACKGROUND: In response to the continuing threat of importing novel coronavirus disease (COVID-19), many countries have implemented some form of border restriction. A repercussion of these restrictions has been that some travellers have found themselves stranded abroad unable to return to their country of residence, and in need for government support. Our analysis explores the COVID-19-related information and support options provided by 11 countries to their citizens stranded overseas due to travel restrictions. We also examined the quality (i.e., readability, accessibility, and useability) of the information that was available from selected governments' web-based resources. METHODS: Between June 18 to June 30, 2021, COVID-19-related webpages from 11 countries (Australia, New Zealand, Fiji, Canada, United States of America (USA), United Kingdom (UK), France, Spain, Japan, Singapore, and Thailand) were reviewed and content relating to information and support for citizens stuck overseas analysed. Government assistance-related data from each webpage was extracted and coded for the following themes: travel arrangements, health and wellbeing, finance and accommodation, information needs, and sources. Readability was examined using the Simplified Measure of Gobbledygook (SMOG) and the Flesch Kincaid readability tests; content 'accessibility' was measured using the Web Content Accessibility Guidelines (WCAG) Version 2.1; and content 'usability' assessed using the usability heuristics for website design tool. RESULTS: Ninety-eight webpages from 34 websites were evaluated. No country assessed covered all themes analysed. Most provided information and some level of support regarding repatriation options; border control and re-entry measures; medical assistance; and traveller registration. Only three countries provided information or support for emergency housing while abroad, and six provided some form of mental health support for their citizens. Our analysis of the quality of COVID-19-related information available on a subset of four countries' websites found poor readability and multiple accessibility and usability issues. CONCLUSION: This study uniquely analyses government support for citizens stuck abroad during the COVID-19 pandemic. With large variance in the information and services available across the countries analysed, our results highlight gaps, inconsistencies, and potential inequities in support available, and raise issues pertinent to the quality, accessibility, and usability of information. This study will assist policymakers plan and communicate comprehensive support packages for citizens stuck abroad due to the COVID-19 situation and design future efforts to prepare for global public health emergencies.

Examining Australian public perceptions and behaviors towards a future COVID-19 vaccine.

BACKGROUND: As immunisation program launches have previously demonstrated, it is essential that careful planning occurs now to ensure the readiness of the public for a COVID-19 vaccine. As part of that process, this study aimed to understand the public perceptions regarding a future COVID-19 vaccine in Australia. METHODS: A national cross-sectional online survey of 1420 Australian adults (18 years and older) was undertaken between 18 and 24 March 2020. The statistical analysis of the data included univariate and multivariable logistic regression model analysis. RESULTS: Respondents generally held positive views towards vaccination. Eighty percent (n = 1143) agreed with the statement that getting myself vaccinated for COVID-19 would be a good way to protect myself against infection. Females (n = 614, 83%) were more likely to agree with the statement than males (n = 529, 78%) (aOR = 1.4 (95% CI: 1.1-1.8); P = 0.03), while 91% of those aged 70 years and above agreed compared to 76% of 18-29-year-olds (aOR = 2.3 (95% CI:1.2-4.1); P = 0.008). Agreement was also higher for those with a self-reported chronic disease (aOR = 1.4 (95% CI: 1.1-2.0); P = 0.04) and among those who held private health insurance (aOR = 1.7 (95% CI: 1.3-2.3); P < 0.001). Beyond individual perceptions, 78% stated that their decision to vaccinate would be supported by family and friends. CONCLUSION: This study presents an early indication of public perceptions towards a future COVID-19 vaccine and represents a starting point for mapping vaccine perceptions. To support an effective launch of these new vaccines, governments need to use this time to understand the communities concerns and to identify the strategies that will support engagement.

Hepatitis B virus infection in Nigeria: a systematic review and meta-analysis of data published between 2010 and 2019.

BACKGROUND: Hepatitis B virus (HBV) is an infectious disease of global significance, causing a significant health burden in Africa due to complications associated with infection, such as cirrhosis and liver cancer. In Nigeria, which is considered a high prevalence country, estimates of HBV cases are inconsistent, and therefore additional clarity is required to manage HBV-associated public health challenges. METHODS: A systematic review of the literature (via PubMed, Advanced Google Scholar, African Index Medicus) was conducted to retrieve primary studies published between 1 January 2010 and 31 December 2019, with a random-effects model based on proportions used to estimate the population-based prevalence of HBV in the Nigerian population. RESULTS: The final analyses included 47 studies with 21,702 participants that revealed a pooled prevalence of 9.5%. A prevalence estimate above 8% in a population is classified as high. Sub-group analyses revealed the highest HBV prevalence in rural settings (10.7%). The North West region had the highest prevalence (12.1%) among Nigeria's six geopolitical zones/regions. The estimate of total variation between studies indicated substantial heterogeneity. These variations could be explained by setting and geographical region. The statistical test for Egger's regression showed no evidence of publication bias (p = 0.879). CONCLUSIONS: We present an up-to-date review on the prevalence of HBV in Nigeria, which will provide critical data to optimise and assess the impact of current prevention and control strategies, including disease surveillance and diagnoses, vaccination policies and management for those infected.

Distinct Roles for CD4+ Foxp3+ Regulatory T Cells and IL-10-Mediated Immunoregulatory Mechanisms during Experimental Visceral Leishmaniasis Caused by Leishmania donovani.

The outcome of intracellular parasitic infection can be determined by the immunoregulatory activities of natural regulatory CD4+ Foxp3+ T (Treg) cells and the anti-inflammatory cytokine IL-10. These mechanisms protect tissue but can also suppress antiparasitic CD4+ T cell responses. The specific contribution of these regulatory pathways during human parasitic diseases remains unclear. In this study, we investigated the roles of Treg cells and IL-10 during experimental visceral leishmaniasis caused by Leishmania donovani infection of C57BL/6 mice. We report only a limited contribution of Treg cells in suppressing antiparasitic immunity, but important roles in delaying the development of splenic pathology and restricting leukocyte expansion. We next employed a range of cell-specific, IL-10- and IL-10R-deficient mice and found these Treg cell functions were independent of IL-10. Instead, conventional CD4+ T cells and dendritic cells were the most important cellular sources of IL-10, and the absence of IL-10 in either cell population resulted in greater control of parasite growth but also caused accelerated breakdown in splenic microarchitecture. We also found that T cells, dendritic cells, and other myeloid cells were the main IL-10-responding cells because in the absence of IL-10R expression by these cell populations, there was greater expansion of parasite-specific CD4+ T cell responses associated with improved control of parasite growth. Again, however, there was also an accelerated breakdown in splenic microarchitecture in these animals. Together, these findings identify distinct, cell-specific, immunoregulatory networks established during experimental visceral leishmaniasis that could be manipulated for clinical advantage.

Evaluation of the early warning, alert and response system after Cyclone Winston, Fiji, 2016.

OBJECTIVE: To assess the performance of an early warning, alert and response system (EWARS) developed by the World Health Organization (WHO) - EWARS in a Box - that was used to detect and control disease outbreaks after Cyclone Winston caused destruction in Fiji on 20 February 2016. METHODS: Immediately after the cyclone, Fiji's Ministry of Health and Medical Services, supported by WHO, started to implement EWARS in a Box, which is a smartphone-based, automated, early warning surveillance system for rapid deployment during health emergencies. Both indicator-based and event-based surveillance were employed. The performance of the system between 7 March and 29 May 2016 was evaluated. Users' experience with the system was assessed in interviews using a semi-structured questionnaire and by a cross-sectional survey. The system's performance was assessed using data from the EWARS database. FINDINGS: Indicator-based surveillance recorded 34 113 cases of the nine syndromes under surveillance among 326 861 consultations. Three confirmed outbreaks were detected, and no large outbreak was missed. Users were satisfied with the performance of EWARS and judged it useful for timely monitoring of disease trends and outbreak detection. The system was simple, stable and flexible and could be rapidly deployed during a health emergency. The automated collation, analysis and dissemination of data reduced the burden on surveillance teams, saved human resources, minimized human error and ensured teams could focus on public health responses. CONCLUSION: In Fiji, EWARS in a Box was effective in strengthening disease surveillance during a national emergency and was well regarded by users.

Respiratory syncytial virus-associated hospitalisations in Australia, 2006-2015.

OBJECTIVE: To estimate rates of respiratory syncytial virus (RSV)-associated hospitalisation across the age spectrum, and to identify groups at particular risk of serious RSV-associated disease. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of National Hospital Morbidity Database data for all RSV-associated hospitalisations in Australia, 2006-2015. MAIN OUTCOMES AND MEASURES: RSV-coded hospitalisation rates by age, sex, Indigenous status, jurisdiction, and seasonality (month and year); hospital length of stay; in-hospital deaths. RESULTS: During 2006-2015, there were 63 814 hospitalisations with an RSV-specific principal diagnostic code; 60 551 (94.9%) were of children under 5 years of age. The hospitalisation rate for children under 5 years was 418 per 100 000 population; for children under 6 months of age it was 2224 per 100 000 population; the highest rate was for infants aged 0-2 months (2778 per 100 000 population). RSV-coded hospitalisation rates were higher for adults aged 65 or more than for people aged 5-64 years (incidence rate ratio [IRR], 6.6; 95% CI, 6.2-7.1), and were also higher for Indigenous Australians than other Australians (IRR, 3.3; 95% CI, 3.2-3.5). A total of 138 in-hospital deaths were recorded, including 82 of adults aged 65 years or more (59%). CONCLUSIONS: Prevention strategies targeting infants, such as maternal or early infant vaccination, would probably have the greatest impact in reducing RSV disease rates. Further characterisation of RSV disease epidemiology, particularly in older adults and Indigenous Australians, is needed to inform health care strategies.

Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology.

Tumor necrosis factor (TNF) is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1) cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL) patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.

IL-17A-Producing γδ T Cells Suppress Early Control of Parasite Growth by Monocytes in the Liver.

Intracellular infections, such as those caused by the protozoan parasite Leishmania donovani, a causative agent of visceral leishmaniasis (VL), require a potent host proinflammatory response for control. IL-17 has emerged as an important proinflammatory cytokine required for limiting growth of both extracellular and intracellular pathogens. However, there are conflicting reports on the exact roles for IL-17 during parasitic infections and limited knowledge about cellular sources and the immune pathways it modulates. We examined the role of IL-17 in an experimental model of VL caused by infection of C57BL/6 mice with L. donovani and identified an early suppressive role for IL-17 in the liver that limited control of parasite growth. IL-17-producing γδ T cells recruited to the liver in the first week of infection were the critical source of IL-17 in this model, and CCR2(+) inflammatory monocytes were an important target for the suppressive effects of IL-17. Improved parasite control was independent of NO generation, but associated with maintenance of superoxide dismutase mRNA expression in the absence of IL-17 in the liver. Thus, we have identified a novel inhibitory function for IL-17 in parasitic infection, and our results demonstrate important interactions among γδ T cells, monocytes, and infected macrophages in the liver that can determine the outcome of parasitic infection.

Tissue requirements for establishing long-term CD4+ T cell-mediated immunity following Leishmania donovani infection.

Organ-specific immunity is a feature of many infectious diseases, including visceral leishmaniasis caused by Leishmania donovani. Experimental visceral leishmaniasis in genetically susceptible mice is characterized by an acute, resolving infection in the liver and chronic infection in the spleen. CD4+ T cell responses are critical for the establishment and maintenance of hepatic immunity in this disease model, but their role in chronically infected spleens remains unclear. In this study, we show that dendritic cells are critical for CD4+ T cell activation and expansion in all tissue sites examined. We found that FTY720-mediated blockade of T cell trafficking early in infection prevented Ag-specific CD4+ T cells from appearing in lymph nodes, but not the spleen and liver, suggesting that early CD4+ T cell priming does not occur in liver-draining lymph nodes. Extended treatment with FTY720 over the first month of infection increased parasite burdens, although this associated with blockade of lymphocyte egress from secondary lymphoid tissue, as well as with more generalized splenic lymphopenia. Importantly, we demonstrate that CD4+ T cells are required for the establishment and maintenance of antiparasitic immunity in the liver, as well as for immune surveillance and suppression of parasite outgrowth in chronically infected spleens. Finally, although early CD4+ T cell priming appeared to occur most effectively in the spleen, we unexpectedly revealed that protective CD4+ T cell-mediated hepatic immunity could be generated in the complete absence of all secondary lymphoid tissues.

COVID-19 contact tracing and quarantine policies in the Indo-Pacific Region: A mixed-methods study of experiences of public health professionals.

Contact tracing and quarantine are valuable public health tools to prevent the transmission of SARS-CoV-2 and control the epidemic. Many low-and middle-income countries (LMICs) adopted global contact tracing and quarantine guidelines but were unable to contextualise the guidance into policies and practices that were relevant to their setting. Therefore, we examine contact tracing policies and practices in the Indo-Pacific region and the need to design context-specific policies. We conducted a mixed-methods study, including a cross-sectional online survey followed by key-informant interviews (KIIs). Using convenience snowball sampling, we invited public health professionals primarily involved in COVID-19 pandemic response from the Indo-Pacific region. We undertook descriptive analyses using counts and percentages for survey data and framework analysis for qualitative data. Seventy-seven public health professionals participated in the survey, of whom ten also participated in the KIIs. The study identified significant gaps between policies and the local contexts. Factors that broaden the gaps were limited knowledge of the changing dynamics of COVID-19 transmission, poor leadership, and coordination, little or no formal training on contact tracing, poor understanding of the guideline recommendations, limited resources, community resistance and mistrust, social stigmatisation and fear of being ostracised, and discrimination. This study revealed substantial disparities between policies and local contexts, significantly influencing policy implementation at national, provincial, and district levels across the studied countries. To bridge these gaps, we advocate for national contact tracing and quarantine guidelines explicitly addressing the quarantine needs of specific demographics, including children, pregnant women, prisoners, and individuals affected by social exclusion issues. Furthermore, we propose strengthening contact tracing training programs, urging revised guidelines to account for social, cultural, and infrastructural nuances influencing contact tracing and quarantine implementation. We also recommend engaging local NGOs, faith-based organisations, and local administrations to reinforce community connections and strengthen contact tracing.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

Influence of the COVID-19 pandemic on caregiver beliefs and experiences of routine childhood immunisation in Indonesia.

The COVID-19 pandemic contributed to significant health services declines in South-East Asia including Indonesia, which experienced a decline in routine immunisation of children. This study investigated the influence of the pandemic on the beliefs and experiences of caregivers of children related to routine immunisation. This study involved a cross-sectional survey among 1399 caregivers of children aged 0-24 months in Central Java and West Nusa Tenggara provinces from March-April 2022. Data on beliefs and experiences of childhood immunizations were captured using core items from the WHO/UNICEF Behavioural and Social Drivers of Immunization (BeSD) survey. Bivariate and multivariate logistic regression analyses identified factors associated with uptake of routine immunisations. While nearly all caregivers (95.7%) reported wanting their child to receive all recommended routine immunisations, only 40.3% of children aged 2-24 months were up-to-date with all vaccines for age. Factors associated with up-to-date included higher parental education (aOR: 1.76, 95% CI 1.02-3.05), higher household income (aOR: 1.54, 95% CI 1.09-2.18), and caregivers who found it moderately or very easy to get immunisations (aOR: 2.26/2.22, 95% CI 1.06-4.83/1.06-4.69). Recovery efforts should prioritise responding to the factors associated with immunisation status (e.g., perceived ease of access) and on families experiencing disadvantage (e.g., caregivers with lower education and household income) to ensure protections against future outbreaks that are responsive to the context-specific needs and priorities of districts and communities.

Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection.

LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTßR). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTßR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.

Measuring National Immunization System Performance: A Systematic Assessment of Available Resources.

BACKGROUND: Vaccination coverage is widely used to assess immunization performance but, on its own, provides insufficient information to drive improvements. Assessing the performance of underlying components of immunization systems is less clear, with several monitoring and evaluation (M&E) resources available for use in different operational settings and for different purposes. We studied these resources to understand how immunization system performance is measured. METHODS: We reviewed peer-reviewed and gray literature published since 2000 to identify M&E resources that include national-level indicators measuring the performance of immunization systems or their components (governance, financing, regulation, information systems, vaccine logistics, workforce, service delivery, and demand generation). We summarize indicators by the system components or outcomes measured and describe findings narratively. RESULTS: We identified 20 resources to monitor immunization program objectives and guide national strategic decision-making, encompassing 631 distinct indicators. Indicators for immunization program outcomes comprised the majority (124/631 [19.7%]), largely vaccination coverage (110/124 [88.7%]). Almost all resources (19/20 [95%]) included indicators for vaccine logistics (83/631 [13.2%]), and those for regulation (19/631 [3.0%]) and demand generation (28/631 [4.4%]) were least common. There was heterogeneity in how information systems (92/563 [14.6%]) and workforce (47/631 [7.4%]) were assessed across resources. Indicators for vaccination coverage in adults, data use in decision-making, equity and diversity, effectiveness of safety surveillance, and availability of a public health workforce were notably lacking. CONCLUSIONS: Between the resources identified in this review, we identified considerable variability and gaps in indicators assessing the performance of some immunization system components. Given the multitude of indicators, policymakers may be better served by tailoring evaluation resources to their specific context to gain useful insight into health system performance and improve data use in decision-making for immunization programs.

The development of a machine learning algorithm for early detection of viral hepatitis B infection in Nigerian patients.

Access to Hepatitis B Virus (HBV) testing for people in low-resource settings has long been challenging due to the gold standard, enzyme immunoassay, being prohibitively expensive, and requiring specialised skills and facilities that are not readily available, particularly in remote and isolated laboratories. Routine pathology data in tandem with cutting-edge machine learning shows promising diagnostic potential. In this study, recursive partitioning ("trees") and Support Vector Machines (SVMs) were applied to interrogate patient dataset (n = 916) that comprised results for Hepatitis B Surface Antigen (HBsAg) and routine clinical chemistry and haematology blood tests. These algorithms were used to develop a predictive diagnostic model of HBV infection. Our SVM-based diagnostic model of infection (accuracy = 85.4%, sensitivity = 91%, specificity = 72.6%, precision = 88.2%, F1-score = 0.89, Area Under the Receiver Operating Curve, AUC = 0.90) proved to be highly accurate for discriminating HBsAg positive from negative patients, and thus rivals with immunoassay. Therefore, we propose a predictive model based on routine blood tests as a novel diagnostic for early detection of HBV infection. Early prediction of HBV infection via routine pathology markers and pattern recognition algorithms will offer decision-support to clinicians and enhance early diagnosis, which is critical for optimal clinical management and improved patient outcomes.

Serology study of healthcare workers following a hospital-based outbreak of COVID-19 in North West Tasmania, Australia, 2020.

Introduction: Healthcare facilities are high-risk settings for coronavirus disease 2019 (COVID-19) transmission. Early in the COVID-19 pandemic, the first large healthcare-associated outbreak within Australia occurred in Tasmania. Several operational research studies were conducted amongst workers from the implicated hospital campus, to learn more about COVID-19 transmission. Methods: Healthcare workers (HCWs) from the implicated hospital campus were invited to complete an online survey and participate in a serology study. Blood samples for serological testing were collected at approximately 12 weeks (round one) and eight months (round two) after the outbreak. A descriptive analysis was conducted of participant characteristics, serology results, and longevity of antibodies. Results: There were 261 HCWs in round one, of whom 44 (17%) were polymerase chain reaction (PCR) confirmed outbreak cases; 129 of the 261 (49%) participated in round two, of whom 34 (27%) were outbreak cases. The prevalence of positive antibodies at round one was 15% (n = 38) and at round two was 12% (n = 15). There were 15 participants (12%) who were seropositive in both rounds, with a further 9% (n = 12) of round two participants having equivocal results after previously being seropositive. Six HCWs not identified as cases during the outbreak were seropositive in round one, with three still seropositive in round two. Of those who participated in both rounds, 68% (n = 88) were seronegative at both time points. Discussion: Our findings demonstrate that serological testing after this large healthcare-associated COVID-19 outbreak complemented the findings of earlier diagnostic testing, with evidence of additional infections to those diagnosed when use of PCR testing had been restricted. The results also provide evidence of persisting SARS-CoV-2 antibody response eight months after an outbreak in an unvaccinated population. The high proportion of HCWs who remained seronegative is consistent with low community transmission in Tasmania after this outbreak.

Machine learning prediction models for clinical management of blood-borne viral infections: a systematic review of current applications and future impact.

BACKGROUND: Machine learning (ML) prediction models to support clinical management of blood-borne viral infections are becoming increasingly abundant in medical literature, with a number of competing models being developed for the same outcome or target population. However, evidence on the quality of these ML prediction models are limited. OBJECTIVE: This study aimed to evaluate the development and quality of reporting of ML prediction models that could facilitate timely clinical management of blood-borne viral infections. METHODS: We conducted narrative evidence synthesis following the synthesis without meta-analysis guidelines. We searched PubMed and Cochrane Central Register of Controlled Trials for all studies applying ML models for predicting clinical outcomes associated with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or hepatitis C virus (HCV). RESULTS: We found 33 unique ML prediction models aiming to support clinical decision making. Overall, 12 (36.4%) focused on HBV, 10 (30.3%) on HCV, 10 on HIV (30.3%) and two (6.1%) on co-infection. Among these, six (18.2%) addressed the diagnosis of infection, 16 (48.5%) the prognosis of infection, eight (24.2%) the prediction of treatment response, two (6.1%) progression through a cascade of care, and one (3.03%) focused on the choice of antiretroviral therapy (ART). Nineteen prediction models (57.6%) were developed using data from high-income countries. Evaluation of prediction models was limited to measures of performance. Detailed information on software code accessibility was often missing. Independent validation on new datasets and/or in other institutions was rarely done. CONCLUSION: Promising approaches for ML prediction models in blood-borne viral infections were identified, but the lack of robust validation, interpretability/explainability, and poor quality of reporting hampered their clinical relevance. Our findings highlight important considerations that can inform standard reporting guidelines for ML prediction models in the future (e.g., TRIPOD-AI), and provides critical data to inform robust evaluation of the models.