Search

Background The COVID-19 pandemic resulted in extreme strain on health systems including the health workforce, essential health services and vaccination coverage. We examined disruptions to immunisation and maternal and child health (MCH) services, concerns of personal well-being and delivery of healthcare during the pandemic as well as factors associated with self-reported trauma or burnout among healthcare providers (HCPs).Methods In March–April 2022, we conducted a cross-sectional survey among HCPs in two provinces of Indonesia. HCPs involved in COVID-19 or routine immunisation and MCH services were randomly selected from district/city health office registration lists. We descriptively analysed service disruptions experienced by HCPs as well as trauma, burnout and concerns of personal well-being and delivery of healthcare during the pandemic. Multivariate logistic regression analyses were undertaken to identify factors associated with trauma or burnout.Results We recruited 604 HCPs. Mobilisation of staff from routine health services to COVID-19 response duties was a key reason for service disruptions (87.9%). Strategies such as community outreach and task shifting were implemented to overcome disruptions. Trauma or burnout during the pandemic was reported by 64.1% HCPs, with 23.5% reporting worse mental or emotional health.Factors associated with trauma or burnout included delivery of COVID-19 immunisation (adjusted OR (aOR) 2.54, 95% CI 1.08 to 5.94); and delivery of both COVID-19 immunisation and routine immunisation compared with no involvement in vaccination programmes (aOR 2.42, 95% CI 1.06 to 5.52); poor treatment in the workplace (aOR 2.26, 95% CI 1.51 to 3.38) and lower confidence to respond to patient queries on COVID-19 immunisation (aOR 1.51, 95% CI 1.03 to 2.22).Conclusion HCPs experienced service disruptions, trauma and burnout and implemented strategies to minimise disruptions to service delivery and improve patient experiences. Our study highlights the need to ensure that workforce resilience and strategies to protect and support HCPs are considered for pandemic planning, preparedness and management.

Increasing countries' access to data can improve immunisation coverage through evidence-based decision-making. However, data collection and reporting is resource-intensive, so needs to be pragmatic, especially in low-and-middle-income countries. We aimed to identify which indicators are most important for measuring, and improving, national immunisation performance in Pacific Island Countries (PICs). We conducted an expert elicitation study, asking 13 experts involved in delivering immunisation programs, decision-makers, health information specialists, and global development partners across PICs to rate 41 indicators based on their knowledge of the feasibility and relevance of each indicator. We also asked experts their preferences for indicators to be retained or removed from a list of indicators for PICs. Experts participated in two rating rounds, with a discussion on the reasons for ratings before the second round. We calculated mean scores for feasibility and relevance, and ranked indicators based on experts' preferences and mean scores. We used framework analysis to identify reasons for selecting indicators. Experts agreed that certain indicators were essential to measure (e.g. data use in program planning and measles vaccination coverage), but preferences varied for most indicators. Preferences to include indicators in a set of indicators for PICs moderately correlated with scores for relevance (r = 0.68) and feasibility (r = 0.56). In discussions, experts highlighted usefulness for decision-making and ease of data collection, reporting and interpretation as the main reasons driving indicator selection. Country-specific factors such as health system factors, roles and influence of various immunisation actors, and macro-level factors (namely population size, distribution and mobility) affected relevance and feasibility, leading us to conclude that a single set of indicators for all PICs is inappropriate. Rather than having a strict set of indicators that all countries must measure and report against, performance indicators should be flexible, country-specific, and selected in consultation with immunisation actors who collect and use the data.

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.

Abstract 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.

Access to accurate information during a crisis is essential. However, while the amount of information circulating during the COVID-19 pandemic has increased exponentially, finding trustworthy resources has been difficult for many, including those affected by international travel restrictions. In this study, we examined the information-seeking behaviors of individuals seeking to travel internationally during the COVID-19 pandemic. We also explored perceptions regarding the value of resources in supporting understanding of COVID-19 travel restriction-related information. Two online cross-sectional surveys targeting four groups were conducted. The groups targeted were: (1) citizens and permanent residents stranded abroad; (2) individuals separated from their partners; (3) individuals separated from immediate families; and (4) temporary visa holders unable to migrate or cross international borders. In total, we analyzed 2,417 completed responses, and a further 296 responses where at least 75% of questions were completed. Findings suggest that social media groups (78.4%, 1,924/2,453), specifically Facebook (86.6%, 2,115/2,422) were the most useful or most used information resource for these groups. Some significant information seeking behavior differences across age and gender were also found. Our study highlights the diversity in information needs of people impacted by COVID-19 travel restrictions and the range of preferred channels through which information is sought. Further, it highlights which challenges hold legitimacy in their target audiences' eyes and which do not. Policymakers may use these results to help formulate more nuanced, consumer-tailored—and hence likely more acceptable, trusted, and impactful—communication strategies as part of future public health emergencies.

Introduction Group A Streptococcus (GAS) causes pharyngitis (sore throat) and impetigo (skin sores) GAS pharyngitis triggers rheumatic fever (RF) with epidemiological evidence supporting that GAS impetigo may also trigger RF in Australian Aboriginal children. Understanding the concurrent burden of these superficial GAS infections is critical to RF prevention. This pilot study aimed to trial tools for concurrent surveillance of sore throats and skins sore for contemporary studies of RF pathogenesis including development of a sore throat checklist for Aboriginal families and pharynx photography. Methods Yarning circle conversations and semi-structured interviews were performed with Aboriginal caregivers and used to develop the language and composition of a sore throat checklist. The sore throat story checklist was combined with established methods of GAS pharyngitis and impetigo surveillance (examination, bacteriological culture, rapid antigen detection and serological tests) and new technologies (photography) and used for a pilot cross-sectional surveillance study of Aboriginal children attending their health clinic for a routine appointment. Feasibility, acceptability, and study costs were compiled. Results Ten Aboriginal caregivers participated in the sore-throat yarning circles; a checklist was derived from predominant symptoms and their common descriptors. Over two days, 21 Aboriginal children were approached for the pilot surveillance study, of whom 17 were recruited; median age was 9 years [IQR 5.5–13.5], 65% were female. One child declined throat swabbing and three declined finger pricks; all other surveillance elements were completed by each child indicating high acceptability of surveillance assessments. Mean time for screening assessment was 19 minutes per child. Transport of clinical specimens enabled gold standard microbiological and serological testing for GAS. Retrospective examination of sore throat photography concorded with assessments performed on the day. Conclusion Yarning circle conversations were effective in deriving culturally appropriate sore throat questionnaires for GAS pharyngitis surveillance. New and established tools were feasible, practical and acceptable to participants and enable surveillance to determine the burden of superficial GAS infections in communities at high risk of RF. Surveillance of GAS pharyngitis and impetgio in remote Australia informs primary RF prevention with potential global translation.

Objectives: Resistance to third-generation cephalosporins in Escherichia coli bacteremia is on the rise in Australia. Currently, laboratory definitions of multidrug-resistant organisms determine infection control responses. The incidence of particular extended-spectrum β-lactamase (ESBL) E. coli phenotype, with nonsusceptibility to both ciprofloxacin and trimethoprim-sulfamethoxazole, is increasing in the Australian Capital Territory, Australia. The increase was noted primarily through antimicrobial stewardship clinical care rather than standard infection control or microbiology processes. Clinically, patients are left with limited or no oral therapeutic options for treatment. Despite not necessarily meeting the laboratory definition of a multidrug-resistant organism, this phenotype is likely to be just as transmissible as other healthcare-associated pathogens. We sought to determine whether laboratory definitions of multidrug-resistant organisms adequately inform infection control responses. Methods: Using laboratory data from Australian Capital Territory (ACT) Pathology, we identified all ESBL E. coli bloodstream isolate episodes from 2016 to 2020. We then reviewed the antibiotic sensitivities of each isolate to identify isolates with nonsusceptibility to both ciprofloxacin and trimethoprim-sulfamethoxazole. We then compared these isolates with the multidrug-resistant organism definition used by ACT Pathology. Results: In total, 152 isolates were reviewed. ACT Pathology classified 35 (23.0%) of these isolates as a multidrug-resistant organisms. We identified 80 (52.6%) isolates with nonsusceptibility to both ciprofloxacin and trimethoprim-sulfamethoxazole. Of these 80 isolates, only 24 (30.0%) met the ACT Pathology definition of a multidrug-resistant organism. Conclusions: Multidrug-resistant organism definitions should encompass a broad range of healthcare considerations. When the laboratory defines what is important, it may not include the complete spectrum of clinical care concerns. To help combat the rise of multidrug-resistant organisms, definitions for organisms of resistance and transmissibility significance should be developed in conjunction with microbiology, infection control, and antimicrobial stewardship.

Background: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted 7 rounds of mass drug administration (MDA) between 2000 and 2006. The territory passed transmission assessment surveys (TASs) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Abs) may have provided a timelier indication of LF resurgence in American Samoa. Methods: We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, and Bm33 Ags at each TAS. Pearson chi-square test and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. Results: Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% confidence interval [CI] 1.2–512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33, or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0–24.5). Conclusion: Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in surveillance after MDA and decision making should be further investigated in other settings.

Abstract 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.

Abstract 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.

Abstract 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

BackgroundAmerican Samoa completed seven rounds of mass drug administration from 2000-2006 as part of the Global Programme to Eliminate Lymphatic Filariasis (LF). However, resurgence was confirmed in 2016 through WHO-recommended school-based transmission assessment survey and a community-based survey. This paper uses data from the 2016 community survey to compare different spatial and non-spatial methods to characterise clustering and hotspots of LF.MethodNon-spatial clustering of infection markers (antigen [Ag], microfilaraemia [Mf], and antibodies (Ab [Wb123, Bm14, Bm33]) was assessed using intra-cluster correlation coefficients (ICC) at household and village levels. Spatial dependence, clustering and hotspots were examined using semivariograms, Kulldorf's scan statistic and Getis-Ord Gi* statistics based on locations of surveyed households.ResultsThe survey included 2671 persons (750 households, 730 unique locations in 30 villages). ICCs were higher at household (0.20-0.69) than village levels (0.10-0.30) for all infection markers. Semivariograms identified significant spatial dependency for all markers (range 207-562 metres). Using Kulldorff's scan statistic, significant spatial clustering was observed in two previously known locations of ongoing transmission: for all markers in Fagali'i and all Abs in Vaitogi. Getis-Ord Gi* statistic identified hotspots of all markers in Fagali'i, Vaitogi, and Pago Pago-Anua areas. A hotspot of Ag and Wb123 Ab was identified around the villages of Nua-Seetaga-Asili. Bm14 and Bm33 Ab hotspots were seen in Maleimi and Vaitogi-Ili'ili-Tafuna.ConclusionOur study demonstrated the utility of different non-spatial and spatial methods for investigating clustering and hotspots, the benefits of using multiple infection markers, and the value of triangulating results between methods.

The COVID-19 pandemic has reiterated the interdependence of health security and health systems, and the need for resilient health systems to prevent large-scale impacts of infectious disease outbreaks and other acute public health events. Three years into the COVID-19 pandemic has led to discussions on how to "build back better", making it important to identify lessons to strengthen health systems and prevent future shocks from health security threats. Limited data exist on effective implementable initiatives, especially for the Pacific region. We explored the perceptions of a selection of experts with field experience in the Pacific region to identify and prioritise areas for future health system investments that strengthen health security. We conducted a qualitative cross-sectional study, collecting data using four focus group discussions. We analysed the data using a content analysis of notes recorded from each of the sessions. There were 24 participants, representing 15 research and academic institutions, nongovernment agencies, UN agencies and government as well as independent consultants. All were health sector stakeholders with field experience in the Pacific region and expertise in either health systems or health security. The analysis revealed four areas to prioritise future efforts, namely workforce development, risk communication, public health surveillance and laboratory capacity. A fifth theme, localisation, was identified as a cross cutting theme that should be applied to implementation of other identified priority areas. These findings provide a starting point to apply in practice this relatively new concept, of targeted health systems strengthening for health security development, in the Pacific. Evaluation of these initiatives will strengthen knowledge on the value of integrating these two concepts.

BackgroundThe impact of COVID-19 international travel restrictions has to date, not been fully explored, and with the ongoing threat that new variants could potentially restrict movement further, it is important to consider the impacts that travel restrictions have on community members. This study aimed to evaluate the psychological and financial impact of COVID-19 travel restrictions on those separated from their partners or immediate families, as well as temporary visa holders who were unable to migrate.MethodsBetween 4 November 2021 to 1 December 2021, we executed a cross-sectional online survey targeting three specific groups; (1) those stranded from their partners; (2) those stranded from immediate families; and (3) temporary visa holders unable to migrate or cross international borders. We collected data on respondents' demographic profile; the nature of COVID-19-related travel impacts; depression, anxiety, and stress levels (using the validated DASS-21); and finally, data on respondents financial, employment and accommodation situation.Results1363 respondents located globally completed the survey. 71.2% reported financial stress, 76.8% ([Formula: see text], SD = 5.94) reported moderate-to-extremely severe depression, 51.6% ([Formula: see text], SD = 5.49) moderate-to-extremely severe anxiety, and 62.6% ([Formula: see text], SD = 5.55) moderate-to-extremely severe stress levels. Statistically significant factors associated with moderate-to-extremely severe depression, anxiety, and stress included being female, chronic illness, and experiencing financial stress. Employment during COVID-19 -specifically essential services workers or unemployed-was associated with higher levels of anxiety and stress, with only essential workers being a predictor of higher stress severity. Factors that provided psychological protection included being older and having children.ConclusionThis study is one of the first to explore the impact COVID-19-related international travel restrictions have had on the financial status and psychological health of affected individuals. It highlights the significant human cost associated with the restrictions and identifies psychologically vulnerable populations. These results will help the design of targeted health and social policy responses.

Since the start of the COVID-19 pandemic there has been a global call for sex/gender-disaggregated data to be made available, which has uncovered important findings about COVID-19 testing, incidence, severity, hospitalisations, and deaths. This mini review scopes the evidence base for efficacy, effectiveness, and safety of COVID-19 vaccines from both experimental and observational research, and asks whether (1) women and men were equally recruited and represented in vaccine research, (2) the outcomes of studies were presented or analysed by sex and/or gender, and (3) there is evidence of sex and/or gender differences in outcomes. Following a PubMed search, 41 articles were eligible for inclusion, including seven randomised controlled trials (RCTs), 11 cohort studies, eight cross-sectional surveys, eight routine surveillance studies, and seven case series. Overall, the RCTs contained equal representation of women and men; however, the observational studies contained a higher percentage of women. Of 10 studies with efficacy data, only three (30%) presented sex/gender-disaggregated results. Safety data was included in 35 studies and only 12 (34%) of these presented data by sex/gender. For those that did present disaggregated data, overall, the majority of participants reporting adverse events were women. There is a paucity of reporting and analysis of COVID-19 vaccine data by sex/gender. Research should be designed in a gender-sensitive way to present and, where possible analyse, data by sex/gender to ensure that there is a robust and specific evidence base of efficacy and safety data to assist in building public confidence and promote high vaccine coverage.

Accurate and current information has been highlighted across the globe as a critical requirement for the COVID-19 pandemic response. To address this need, many interactive dashboards providing a range of different information about COVID-19 have been developed. A similar tool in Australia containing current information about COVID-19 could assist general practitioners and public health responders in their pandemic response efforts. The COVID-19 Real-time Information System for Preparedness and Epidemic Response (CRISPER) has been developed to provide accurate and spatially explicit real-time information for COVID-19 cases, deaths, testing and contact tracing locations in Australia. Developed based on feedback from key users and stakeholders, the system comprises three main components: (1) a data engine; (2) data visualization and interactive mapping tools; and (3) an automated alert system. This system provides integrated data from multiple sources in one platform which optimizes information sharing with public health responders, primary health care practitioners and the general public.

Abstract Benzathine penicillin G (BPG) is used as first‐line treatment for most forms of syphilis and as secondary prophylaxis against rheumatic heart disease (RHD). Perceptions that poor quality of BPG is linked to reported adverse effects and therapeutic failure may impact syphilis and RHD control programs. Clinical networks and web‐based advertising were used to obtain vials of BPG from a wide range of countries. The quality of BPG was assessed using a high performance liquid chromatography assay capable of detecting relevant impurities and degradation products. Tests for water content, presence of heavy metals and physical characteristics of BPG, including particle size analysis and optical microscopy, also were conducted. Thirty‐five batches of BPG were sourced from 16 countries across 4 WHO regions. All batches passed the US Pharmacopeia requirements for BPG injection (content), with no evidence of breakdown products or other detected contaminants. Water content and heavy metal analysis (n = 11) indicated adherence to regulatory standards and Good Manufacturing Practice. Particle size analysis (n = 20) found two batches with aggregated particles (>400 µm) that were dispersed following sonication. Current batches of BPG were of satisfactory pharmaceutical quality but aggregated particles were found in a modest proportion of samples. Future studies should focus on the physical characteristics of BPG which may contribute to variations in plasma penicillin concentrations an observed needle blockages in clinical practice. Pharmacopeial monographs could be revised to include standards on particle size and crystal morphology of BPG.

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to

Summary: Type I interferons (IFNs) play critical roles in anti-viral and anti-tumor immunity. However, they also suppress protective immune responses in some infectious diseases. Here, we identify type I IFNs as major upstream regulators of CD4+ T cells from visceral leishmaniasis (VL) patients. Furthermore, we report that mice deficient in type I IFN signaling have significantly improved control of Leishmania donovani, a causative agent of human VL, associated with enhanced IFNγ but reduced IL-10 production by parasite-specific CD4+ T cells. Importantly, we identify a small-molecule inhibitor that can be used to block type I IFN signaling during established infection and acts synergistically with conventional anti-parasitic drugs to improve parasite clearance and enhance anti-parasitic CD4+ T cell responses in mice and humans. Thus, manipulation of type I IFN signaling is a promising strategy for improving disease outcome in VL patients. : CD4+ T cells are critical for control of intracellular parasites such as Leishmania donovani. Kumar et al. show that type I interferons (IFNs) suppress Th1 cells and promote IL-10-producing CD4+ T cells during visceral leishmaniasis (VL). Thus, manipulation of type I IFN signaling may improve disease outcome in VL patients. Keywords: type I interferons, visceral leishmaniasis, CD4+ T cells

BackgroundSince the emergence of SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in late 2019, communities have been required to rapidly adopt community mitigation strategies rarely used before, or only in limited settings. This study aimed to examine the attitudes and beliefs of Australian adults towards the COVID-19 pandemic, and willingness and capacity to engage with these mitigation measures. In addition, we aimed to explore the psychosocial and demographic factors that are associated with adoption of recommended hygiene-related and avoidance-related behaviors.MethodsA national cross-sectional online survey of 1420 Australian adults (18 years and older) was undertaken between the 18 and 24 March 2020. The statistical analysis of the data included univariate and multivariate logistic regression analysis.FindingsThe survey of 1420 respondents found 50% (710) of respondents felt COVID-19 would 'somewhat' affect their health if infected and 19% perceived their level of risk as high or very high. 84·9% had performed ≥1 of the three recommended hygiene-related behaviors and 93·4% performed ≥1 of six avoidance-related behaviors over the last one month. Adopting avoidance behaviors was associated with trust in government/authorities (aOR: 6.0, 95% CI 2.6-11·0), higher perceived rating of effectiveness of behaviors (aOR: 4·0, 95% CI: 1·8-8·7), higher levels of perceived ability to adopt social distancing strategies (aOR: 5.0, 95% CI: 1·5-9.3), higher trust in government (aOR: 6.0, 95% CI: 2.6-11.0) and higher level of concern if self-isolated (aOR: 1.8, 95% CI: 1.1-3.0).InterpretationIn the last two months, members of the public have been inundated with messages about hygiene and social (physical) distancing. However, our results indicate that a continued focus on supporting community understanding of the rationale for these strategies, as well as instilling community confidence in their ability to adopt or sustain the recommendations is needed.

Introduction: Influenza-associated severe acute respiratory infections (SARI) are a major contributor to global morbidity and mortality. In response to a cluster of SARI cases and deaths in pregnant women, with two deceased cases testing positive for influenza A(H1N1)pdm09, an investigation was initiated to determine whether there was an increase of paediatric SARI cases admitted to divisional hospital intensive care units in Fiji in may 2016 compared to May 2013–2015. Methods: Retrospective case finding was conducted at the paediatric intensive care units (PICUs) in Fiji’s three divisional hospitals. Data were collected from 1 January 2013 to 26 May 2016. Cases were identified using a list of clinical diagnoses compatible with SARI. Results: A total of 632 cases of paediatric SARI with complete details were identified. The median age of cases was 6 months (Interquartile range: 2–14 months). Children aged less than 5 years had a higher rate of paediatric SARI requiring admission to a divisional hospital PICU in May 2016 compared to May 2013–2015 (Incidence rate ratio: 1.7 [95% CI: 1.1–2.6]). This increase was not observed in children aged 5–14 years. The case-fatality ratio was not significantly different in 2016 compared to previous years. Conclusion: The investigation enabled targeted public health response measures, including enhanced SARI surveillance at divisional hospitals and an emergency influenza vaccination campaign in the Northern Division.

Circulating filarial antigen (Ag) prevalence, measured using rapid point-of-care tests, is the standard indicator used for monitoring and surveillance in the Global Program to Eliminate Lymphatic Filariasis. In 2015, the immunochromatographic test (ICT) was replaced with the filariasis test strip (FTS), which has higher reported sensitivity. Despite differences in sensitivity, no changes in recommended surveillance targets were made when the FTS was introduced. In 2016, we conducted lymphatic filariasis surveys in American Samoa using FTS, which found higher Ag prevalence than previous surveys that used ICT. To determine whether the increase was real, we assessed the concordance between FTS and ICT results by paired testing of heparinised blood from 179 individuals (63% FTS-positive). ICT had 93.8% sensitivity and 100% specificity for identifying FTS-positive persons, and sensitivity was not associated with age, gender, or presence of microfilariae. Based on these findings, if ICT had been used in the 2016 surveys, the results and interpretation would have been similar to those reported using FTS. American Samoa would have failed Transmission Assessment Survey (TAS) of Grade 1 and 2 children with either test, and community prevalence would not have been significantly different (4.1%, 95% CI, 3.3–4.9% with FTS vs. predicted 3.8%, 95%, CI: 3.1–4.6% with ICT).

The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.

INTRODUCTION:Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration (MDA) from 2000-2006. The World Health Organization recommends systematic post-MDA surveillance using Transmission Assessment Surveys (TAS) for epidemiological assessment of recent LF transmission. We compared the effectiveness of two survey designs for post-MDA surveillance: a school-based survey of children aged 6-7 years, and a community-based survey targeting people aged ≥8 years. METHODS:In 2016, we conducted a systematic school-based TAS in all elementary schools (N = 29) and a cluster survey in 28 villages on the two main islands of American Samoa. We collected information on demographics and risk factors for infection using electronic questionnaires, and recorded geo-locations of schools and households. Blood samples were collected to test for circulating filarial antigen (CFA) using the Alere Filariasis Test Strip. For those who tested positive, we prepared slides for microscopic examination of microfilaria and provided treatment. Descriptive statistics were performed for questionnaire variables. Data were weighted and adjusted to account for sampling design and sex for both surveys, and for age in the community survey. RESULTS:The school-based TAS (n = 1143) identified nine antigen-positive children and found an overall adjusted CFA prevalence of 0.7% (95% CI: 0.3-1.8). Of the nine positive children, we identified one microfilariaemic 7-year-old child. The community-based survey (n = 2507, 711 households) identified 102 antigen-positive people, and estimated an overall adjusted CFA prevalence of 6.2% (95% CI: 4.5-8.6). Adjusted village-level prevalence ranged from 0-47.1%. CFA prevalence increased with age and was higher in males. Of 86 antigen-positive community members from whom slides were prepared, 22 (25.6%) were microfilaraemic. School-based TAS had limited sensitivity (range 0-23.8%) and negative predictive value (range 25-83.3%) but had high specificity (range 83.3-100%) and positive predictive value (range 0-100%) for identifying villages with ongoing transmission. CONCLUSIONS:American Samoa failed the school-based TAS in 2016, and the community-based survey identified higher than expected numbers of antigen-positive people. School-based TAS was logistically simpler and enabled sampling of a larger proportion of the target population, but the results did not provide a good indication of the overall CFA prevalence in older age groups and was not sensitive at identifying foci of ongoing transmission. The community-based survey, although operationally more challenging, identified antigen-positive individuals of all ages, and foci of high antigen prevalence. Both surveys confirmed recrudescence of LF transmission.

Many infectious diseases are characterized by the development of immunoregulatory pathways that contribute to pathogen persistence and associated disease symptoms. In diseases caused by intracellular parasites, such as visceral leishmaniasis (VL), various immune modulators have the capacity to negatively impact protective CD4+ T cell functions. Galectin-1 is widely expressed on immune cells and has previously been shown to suppress inflammatory responses and promote the development of CD4+ T cells with immunoregulatory characteristics. Here, we investigated the role of galectin-1 in experimental VL caused by infection of C57BL/6 mice with Leishmania donovani. Mice lacking galectin-1 expression exhibited enhanced tissue-specific control of parasite growth in the liver, associated with an augmented Th1 cell response. However, unlike reports in other experimental models, we found little role for galectin-1 in the generation of IL-10-producing Th1 (Tr1) cells, and instead report that galectin-1 suppressed hepatic Th1 cell development. Furthermore, we found relatively early effects of galectin-1 deficiency on parasite growth, suggesting involvement of innate immune cells. However, experiments investigating the impact of galectin-1 deficiency on dendritic cells indicated that they were not responsible for the phenotypes observed in galectin-1-deficient mice. Instead, studies examining galectin-1 expression by CD4+ T cells supported a T cell intrinsic role for galectin-1 in the suppression of hepatic Th1 cell development during experimental VL. Together, our findings provide new information on the roles of galectin-1 during parasitic infection and indicate an important role for this molecule in tissue-specific Th1 cell development, but not CD4+ T cell IL-10 production.

Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNγ production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different immune modulation strategies.

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.

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 (LTβR). 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-LTβR 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.