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Multiple studies have shown an association between intussusception (IS) and receipt of monovalent or pentavalent rotavirus vaccine (RV) in the previous 21 days. Disease severity is an important consideration for risk-benefit evaluations of RV, but no studies have compared the severity of IS within 21 days of vaccination (vaccine-associated, VA) and later (not temporally-associated, VNA).We used active hospital-based surveillance in the Australian Paediatric Active Enhanced Disease Surveillance (PAEDS) network (July 2007 to February 2018) to identify infants ≤9 months of age meeting Brighton level 1 criteria for IS. We used five severity levels: (1) no surgery and length of stay (LOS) ≤1 day, (2) no surgery and LOS ≥2 days, (3) surgery, no bowel resection, (4) bowel resection, and (5) ICU admission.Of 323 eligible cases, 87 (26.9%) were VA and 236 (73.1%) VNA. VA-IS cases (median 21 weeks; 24.1% ≤14 weeks) were significantly younger than VNA-IS cases (median 28 weeks, 7.2% ≤14 weeks). Cases 0-≤14 weeks of age were significantly more likely than cases ≥25 weeks to require bowel resection (relative risk ratio 4.6, 95% CI, 1.48-14.3). This effect was not associated with RV. After adjustment for age and sex, VA-IS was not significantly overrepresented in severity levels 2-5; adjusted RRR of 1.37 (95% CI: 0.61-3.11) for bowel resection in cases 0-≤14 weeks of age.IS was uncommon but significantly more severe under 14 weeks of age. After adjustment for age and sex, IS severity was not related to RV.

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.

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.

Over 80% of residents in the Australian Capital Territory were fully vaccinated within 10 weeks of a SARS-CoV-2 Delta variant outbreak. Of the outbreak’s 1,545 cases, 10% were breakthrough infections. The incidence of infections among fully- and partially-vaccinated people was 98.5% and 90% lower, respectively, than for unvaccinated people.

Over 892 million people in 48 countries are at risk of infection by nematodes that cause lymphatic filariasis. As part of the Global Programme to Eliminate Lymphatic Filariasis, mass drug administration is distributed to communities until surveillance indicates infection rates are below target prevalence thresholds. In some countries, including American Samoa, lymphatic filariasis transmission persists despite years of mass drug administration and/or has resurged after cessation. Nothing is known about the population genetics of Wuchereria bancrofti worms in Polynesia, or whether local transmission is persisting and/or increasing due to inadequate mass drug administration coverage, expansion from residual hotspots, reintroduction from elsewhere, or a combination. We extracted DNA from microfilariae on blood slides collected during prevalence surveys in 2014 and 2016, comprising 31 pools of five microfilariae from 22 persons living in eight villages. We sequenced 1104 bp across three mitochondrial markers (ND4, COI, CYTB). We quantified parasite genetic differentiation using variant calls and estimated haplotypes using principal components analysis, F-statistics, and haplotype networks. Of the variants called, all but eight were shared across the main island of Tutuila, and three of those were from a previously described hotspot village, Fagali’i. Genotypic data did not support population genetic structure among regions or villages in 2016, although differences were observed between worms collected in Fagali’i in 2014 and those from 2016. Because estimated haplotype frequency varied between villages, these statistics suggested genetic differentiation, but were not consistent among villages. Finally, haplotype networks demonstrated American Samoan sequence clusters were related to previously published sequences from Papua New Guinea. These are, to our knowledge, the first reports of W. bancrofti genetic variation in Polynesia. The resurgent parasites circulating on the main island of American Samoa represent a single population. This study is the first step towards investigating how parasite population structure might inform strategies to manage resurgence and elimination of lymphatic filariasis.

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 The 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. Methods Between 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. Results 1363 respondents located globally completed the survey. 71.2% reported financial stress, 76.8% (x¯=11.57, SD = 5.94) reported moderate-to-extremely severe depression, 51.6% (x¯=6.80, SD = 5.49) moderate-to-extremely severe anxiety, and 62.6% (x¯=11.52, 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. Conclusion This 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.

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.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.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).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.

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.

BackgroundHepatitis 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.MethodsA 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.ResultsThe 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).ConclusionsWe 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.

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.

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.

Background: American 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 a community-based survey and a WHO-recommended school-based transmission assessment survey (TAS). This paper uses data from the 2016 community survey to compare different spatial and non-spatial methods to characterise clustering and hotspots of LF.Method: Non-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 explored using semivariograms, Kulldorf’s scan statistic and Getis-Ord Gi* statistics at locations of surveyed households.Results: The 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 Kuldorff’s scan statistic, significant 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-Afao. Bm14 and Bm33 Ab hotspots were seen in Maleimi and Vaitogi-Ili’ili-Tafuna.Conclusion:Our 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.Funding Statement: This work received financial support from the Coalition for Operational Research on Neglected Tropical Diseases (COR-NTD), which is funded at The Task Force for Global Health primarily by the Bill & Melinda Gates Foundation, by UK aid from the British government, and by the United States Agency for International Development through its Neglected Tropical Diseases Program. CLL was funded by an Australian National Health and Medical Research Council Fellowship (1109035). The funders had no role in interpretation of results, decision to publish, or preparation of the manuscript. MS is funded by a fellowship from the Westpac Scholars Trust.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This study was approved by the American Samoa Institutional Review Board and the Human Research Ethics Committee at the Australian National University (protocol number 2016/482).

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 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.

The current prophylactic treatment to prevent rheumatic heart disease requires four-weekly intramuscular injection of a suspension of the poorly soluble benzathine salt form of penicillin G (BPG) often for more than 10 years. In seeking to reduce the frequency of administration to improve adherence, biodegradable polymer matrices have been investigated. Poly(lactide-co-glycolide) (PLGA)-based in situ forming precursor systems containing N-methyl-2-pyrrolidone as solvent and PLGA-based monolithic implants for surgical implantation containing BPG were developed. Long-term release studies indicated low and plateaued release of penicillin G, but continual favourable release profiles for the benzathine counterion, indicating degradation of the polymer and generation of acidic microenvironment being detrimental to penicillin stability. In order to avoid the issue of the acidic product, poly(caprolactone)(PCL) implants were also investigated, with favourable penicillin G release behaviour being achieved, and slow release over 180 days. However, when taking into account the mass of polymer, and the total dose of drug calculated from literature pharmacokinetic parameters for penicillin G, we concluded that an implant size of over 7 g would still be required. This may preclude clinical deployment of a polymer matrix type delivery system for this indication in children and adolescents. Therefore, we have learned that biodegradable PLGA-type systems are not suitable for development of sustained release BPG treatments and that although the PCL system provides favourable release behaviour, the total size of the implant may still present a hurdle for future development.

IntroductionThe Global Polio Eradication Initiative uses polio supplementary immunisation activities (SIAs) as a strategy to increase vaccine coverage and cease poliovirus transmission. Impact of polio SIAs on immunisation systems is frequently debated. We reviewed the impact of polio SIAs on routine immunisation and health systems during the modern era of polio eradication.MethodsWe searched nine databases for studies reporting on polio SIAs and immunisation coverage, financial investment, workforce and health services delivery. We conducted a narrative synthesis of evidence. Records prior to 1994, animal, modelling or case studies data were excluded.Results20/1637 unique records were included. Data on vaccine coverage were included in 70% (14/20) studies, workforce in 65% (13/20) and health services delivery in 85% (17/20). SIAs positively contributed to vaccination uptake of non-polio vaccines in seven studies, neutral in three and negative in one. Some polio SIAs contributed to workforce strengthening through training and capacity building. Polio SIAs were accompanied with increased social mobilisation and community awareness building confidence in vaccination programmes. Included studies were programmatic in nature and contained variable data, thus could not be justly critically appraised.ConclusionPolio SIAs are successful at increasing polio vaccine coverage, but the resources and infrastructures were not always utilised for delivery of non-polio vaccines and integration into routine service delivery. We found a gap in standardised tools to evaluate SIAs, which can then inform service integration. Our study provides data to inform SIAs evaluations, and provides important considerations for COVID-19 vaccine roll-out to strengthen health systems.PROSPERO registration numberCRD42020152195.

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).

This study was designed to determine the sensitivity and reproducibility of recovering anti-streptolysin O titres (ASOT) from dried blood spot (DBS) samples, a methodologic subcomponent of the penicillin pharmacokinetic studies in children receiving secondary prophylaxis with intramuscular benzathine penicillin for acute rheumatic fever.

In 2005, the National Immunisation Program implemented a varicella vaccine for children aged 18 months, and in 2016, a herpes zoster (HZ) vaccine for adults aged 70-79 years. This epidemiological review analyses national trends in varicella and HZ for the years 1998-2015 to examine the impact of a funded varicella vaccine and provide a baseline for monitoring the impact of a funded HZ vaccine.Varicella and HZ notifications (2002-2015), hospitalisations (1999-2013) and deaths (1998-2013) were sourced. We stratified analyses by age, sex and Indigenous status, and estimated rates and incidence rate ratios.Funded varicella vaccine led to a rapid decline in varicella notifications, hospitalisations and deaths. During the post-varicella vaccine period, hospitalisations declined in all age groups40 years, with greatest reduction of 84% in children aged 18-59 months. Annual HZ hospitalisation rate was 10.8 per 100,000. HZ hospitalisation rates increased with age and were highest in persons aged =75 years (87.6 per 100,000). Post-herpetic neuralgia (PHN) was diagnosed in 32.5% HZ hospitalisations with highest hospitalisation rate in persons aged =75 years (32.1 per 100,000). Varicella and HZ hospitalisation rates were significantly higher among Indigenous Australians. Twenty one deaths were coded as due to varicella and 340 deaths were coded as due to HZ in persons aged40 years and =40 years, respectively.The national varicella immunisation program substantially reduced varicella associated morbidity and mortality. Burden of HZ and PHN in Australia is substantial. Following the introduction of a funded HZ vaccine, timely and high quality surveillance will be crucial to assess the impact of the national HZ immunisation program.

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, Author summary Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito bites. Globally, tens of millions are infected, with many disfigured and disabled by severe damage to their lymphatic systems, such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through mass drug administration (MDA), and to control illness and suffering in affected persons. The World Health Organization recommends conducting Transmission Assessment Surveys (TAS) in school children aged 6 to 7 years to determine if infection rates have dropped to levels where disease transmission is no longer sustainable. From 2000–2006, American Samoa conducted MDA and made significant progress towards eliminating LF. However, despite passing TAS in 2011/2012 and 2015, surveys in 2016 showed evidence of resurgence. This study aimed to investigate the prevalence of anti-filarial antibodies in American Samoa in 2016; identify risk factors for testing positive for antigen, microfilaria and antibodies; and compare the efficiency of different sampling strategies for identifying persons who test positive. The sampling strategies that we compared included testing of 6–7 year-old children, population representative surveys of older age groups, and targeted surveys of high-risk groups such as older people, household members of infected children identified through TAS, and known hotspots. Based on our findings, we recommended that in addition to TAS, strategies that target high-risk populations and hotspots would strengthen surveillance and help countries achieve their goals of LF elimination.

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.

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.

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.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.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.In Fiji, EWARS in a Box was effective in strengthening disease surveillance during a national emergency and was well regarded by users.Évaluer les performances du système d'alerte et d'intervention rapides conçu par l'Organisation mondiale de la Santé (OMS) baptisé « Immédiatement après le passage du cyclone, le ministère de la Santé et des Services médicaux, avec l'aide de l'OMS, a déployé le systèmeLa surveillance effectuée sur la base des indicateurs a donné lieu au signalement de 34 113 cas correspondant à la définition des neuf syndromes surveillés, sur un total de 326 861 consultations. Trois flambées épidémiques confirmées ont été détectées et aucune flambée majeure n'a échappé à la surveillance. Les utilisateurs se sont dits satisfaits des performances du systèmeÀ Fidji, le systèmeEvaluar el funcionamiento de un sistema de alerta temprana, alerta y respuesta (EWARS, por sus siglas en inglés) desarrollado por la Organización Mundial de la Salud (OMS), EWARS in a Box, que se utilizó para detectar y controlar los brotes de enfermedades después de que el ciclón Winston causara destrucción en Fiji el 20 de febrero de 2016.Inmediatamente después del ciclón, el Ministerio de Salud y Servicios Médicos de Fiji, con el apoyo de la OMS, comenzó a aplicar el sistema EWARS in a Box, que es un sistema de vigilancia de alerta temprana automatizado y basado en teléfonos inteligentes para un despliegue rápido durante las emergencias sanitarias. Se recurrió tanto a la vigilancia basada en indicadores como en eventos. Se evaluó el funcionamiento del sistema entre el 7 de marzo y el 29 de mayo de 2016. La experiencia de los usuarios con el sistema se evaluó en entrevistas mediante un cuestionario semiestructurado y una encuesta transversal. El rendimiento del sistema se evaluó utilizando datos de la base de datos EWARS.La vigilancia basada en indicadores registró 34.113 casos de los nueve síndromes bajo vigilancia, entre 326.861 consultas. Se detectaron tres brotes confirmados y ningún brote serio fue detectado. Los usuarios se mostraron satisfechos con el rendimiento del EWARS y lo consideraron útil para el seguimiento oportuno de las tendencias de enfermedades y la detección de brotes. El sistema era sencillo, estable y flexible y podía desplegarse rápidamente durante una emergencia sanitaria. La recopilación, el análisis y la difusión automatizados de datos redujo la carga de los equipos de vigilancia, ahorró recursos humanos, minimizó los errores humanos y garantizó que los equipos pudieran centrarse en las respuestas de sanidad pública.En Fiji, EWARS in a Box fue efectivo en el fortalecimiento de la vigilancia de enfermedades durante una emergencia nacional y fue bien considerado por los usuarios.تقييم أداء نظام الإنذار المبكر والإنذار والاستجابة (EWARS)، الذي طورته منظمة الصحة العالمية (EWARS in a Box)، والذي تم استخدامه لاكتشاف ومكافحة تفشي الأمراض بعد ما تسبب فيه إعصار وينستون من تدمير في فيجي، في 20 فبراير/شباط 2016.بعد وقوع الإعصار مباشرة، بدأت وزارة الصحة والخدمات الطبية في فيجي، بدعم من منظمة الصحة العالمية، في تنفيذ نظام EWARS in a Box، وهو نظام آلي للمراقبة والإنذار المبكر يعتمد على الهاتف الذكي، وذلك من أجل الانتشار السريع أثناء الطوارئ الصحية. تم استخدام كل من المراقبة المستندة إلى المؤشر والمستندة على الحدث. تم تقييم أداء النظام بين 7 مارس/آذار و29 مايو/أيار 2016. تم تقييم تجربة المستخدمين مع النظام في مقابلات شخصية باستخدام استبيان شبه منظم ومسح مقطعي. تم تقييم أداء النظام باستخدام بيانات من قاعدة بيانات EWARS.سجلت المراقبة المستندة إلى المؤشر 34113 حالة من المتلازمات التسع تحت المراقبة بين 326861 استشارة. تم الكشف عن ثلاث حالات تفشي مؤكدة، ولم يتم تفويت أي تفش كبير. أعرب المستخدمون عن ارتياحهم لأداء نظام EWARS واعتبروا أنه مفيد لرصد اتجاهات الأمراض والكشف عن التفشي في الوقت المناسب. كان النظام بسيطًا ومستقرًا ومرنًا ويمكن نشره بسرعة أثناء الطوارئ الصحية. وقد أدى الجمع الآلي وتحليل البيانات ونشرها إلى تقليل العبء الواقع على فرق المراقبة، والموارد البشرية المحفوظة، والحد الأدنى من الأخطاء البشرية ، كما ضمنت للفرق أن تركز على استجابات الصحة العامة.كان نظام EWARS in a Box في فيجي فعالاً في تعزيز مراقبة الأمراض خلال حالات الطوارئ الوطنية، وكان محل تقدير من المستخدمين.旨在评估世界卫生组织开发的早期预警、警报和响应系统 (EWARS in a Box) 的性能，其被用于检测和控制 2016 年 2 月 20 日温斯顿飓风在斐济大规模破坏后的疾病爆发。.飓风侵袭后，斐济卫生和医疗服务部在世界卫生组织的支持下，开始实施早期预警、警报和响应系统 (EWARS in a Box)，这是一个基于智能手机、自动化的早期预警监控系统，可用于卫生紧急状态下的快速部署。采用基于指标和基于事件的监测方法。对 2016 年 3 月 7 日至 5 月 29 日期间的系统性能进行了评估。在访谈中，我们使用半结构式问卷和横断面调查，评估使用该系统用户的用户体验。使用早期预警、警报和响应系统 (EWARS) 数据库的数据来评估系统性能。.基于指标的监测记录了在 326861 次咨询中，9 种综合症状，共 34113 个病例得以监测。已检测到三次证实的突发疾病，没有错失任何大规模的疾病爆发。用户对早期预警、警报和响应系统 (EWARS) 的性能表示满意，认为其有助于及时监测疾病趋势和疾病爆发。该系统简单、稳定、灵活，可在卫生紧急状态下快速进行部署。数据的自动整理、分析和传播能减轻监测小组的负担，节省人力资源，最大限度地减少人为错误，确保监测小组能够专注于公共卫生响应。.在斐济，早期预警、警报和响应系统 (EWARS in a Box) 能有效加强国家卫生紧急状态下的疾病监测，并受到用户的好评。.Оценка качества работы системы раннего предупреждения, оповещения и реагирования (early warning, alert and response system, EWARS), разработанной Всемирной организацией здравоохранения (ВОЗ), в пакетном варианте, которая использовалась для выявления и контроля вспышек заболеваний после разрушений, вызванных циклоном «Уинстон» на островах Фиджи 20 февраля 2016 года.Незамедлительно после циклона Министерство здравоохранения и медицинского обслуживания Фиджи при поддержке ВОЗ стало внедрять пакетный вариант EWARS, представляющий собой автоматическую систему мониторинга раннего предупреждения на базе смартфонов, предназначенную для быстрого развертывания в ситуациях внезапной угрозы здоровью населения. Мониторинг осуществлялся на основе индикаторов и событий. Оценка работы системы проводилась в период с 7 марта по 29 мая 2016 года. Опыт эксплуатации системы оценивался в ходе собеседований с использованием частично структурированных анкет и в ходе перекрестного опроса. Качество работы системы оценивалось с использованием информации, хранимой в базе данных EWARS.Мониторинг на основе индикаторов позволил выявить 34 113 случаев девяти наблюдаемых синдромов в ходе 326 861 консультации. Были обнаружены и подтверждены три вспышки, и ни одна крупная вспышка не была упущена. Пользователи были довольны качеством работы системы EWARS и нашли ее полезной для своевременного мониторинга динамики распространения и выявления вспышек заболеваний. Система оказалась простой, стабильной и гибкой, и в случае чрезвычайных ситуаций в сфере здравоохранения ее можно быстро задействовать. Автоматическая сводка, анализ и распространение данных позволили разгрузить группы осуществления мониторинга, сэкономить людские ресурсы, свести к минимуму человеческие ошибки и сосредоточиться ликвидаторам на ответных мерах в системе здравоохранения.На островах Фиджи пакетная система EWARS позволила эффективно укрепить систему мониторинга заболеваний в ходе национального природного бедствия и получила хорошую оценку пользователей.

The current prophylactic treatment to prevent rheumatic heart disease requires four-weekly intramuscular injection of a suspension of the poorly soluble benzathine salt form of penicillin G (BPG) often for more than 10 years. In seeking to reduce the frequency of administration to improve adherence, biodegradable polymer matrices have been investigated. Poly(lactide-co-glycolide) (PLGA)-based in situ forming precursor systems containing N-methyl-2-pyrrolidone as solvent and PLGA-based monolithic implants for surgical implantation containing BPG were developed. Long-term release studies indicated low and plateaued release of penicillin G, but continual favourable release profiles for the benzathine counterion, indicating degradation of the polymer and generation of acidic microenvironment being detrimental to penicillin stability. In order to avoid the issue of the acidic product, poly(caprolactone)(PCL) implants were also investigated, with favourable penicillin G release behaviour being achieved, and slow release over 180 days. However, when taking into account the mass of polymer, and the total dose of drug calculated from literature pharmacokinetic parameters for penicillin G, we concluded that an implant size of over 7 g would still be required. This may preclude clinical deployment of a polymer matrix type delivery system for this indication in children and adolescents. Therefore, we have learned that biodegradable PLGA-type systems are not suitable for development of sustained release BPG treatments and that although the PCL system provides favourable release behaviour, the total size of the implant may still present a hurdle for future development.

The outcome of intracellular parasitic infection can be determined by the immunoregulatory activities of natural regulatory CD4

Objectives Innate lymphoid cells (ILCs) share many characteristics with CD4+ T cells, and group 1 ILCs share a requirement for T‐bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs during Plasmodium infection. Methods We quantified group 1 ILCs in peripheral blood collected from subjects infected with with Plasmodium falciparum 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of Pc AS‐infected mice. We used genetically‐modified mouse models, as well as cell‐depletion methods in mice to characterise the role of group 1 ILCs during Pc AS infection. Results In a controlled human malaria infection study, we found that the frequencies of circulating ILC1s and NK cells decreased as infection progressed but recovered after volunteers were treated with antiparasitic drug. A similar observation was made for liver and splenic ILC1s in P. chabaudi chabaudi AS (Pc AS)‐infected mice. The decrease in mouse liver ILC1 frequencies was associated with increased apoptosis. We also identified a population of cells within the liver and spleen that expressed both ILC1 and NK cell markers, indicative of plasticity between these two cell lineages. Studies using genetic and cell‐depletion approaches indicated that group 1 ILCs have a limited role in antiparasitic immunity during Pc AS infection in mice. Discussion Our results are consistent with a previous study indicating a limited role for natural killer (NK) cells during Plasmodium chabaudi infection in mice. Additionally, a recent study reported the redundancy of ILCs in humans with competent B and T cells. Nonetheless, our results do not rule out a role for group 1 ILCs in human malaria in endemic settings given that blood stage infection was initiated intravenously in our experimental models, and thus bypassed the liver stage of infection, which may influence the immune response during the blood stage. Conclusion Our results show that ILC1s are lost early during mouse and human malaria, and this observation may help to explain the limited role for these cells in controlling blood stage 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.

Rheumatic fever is caused by an abnormal immune reaction to group A streptococcal infection. Secondary prophylaxis with antibiotics is recommended for people after their initial episode of rheumatic fever to prevent recurrent group A streptococcal infections, recurrences of rheumatic fever and progression to rheumatic heart disease. This secondary prophylaxis must be maintained for at least a decade after the last episode of rheumatic fever. Benzathine penicillin G is the first line antibiotic for secondary prophylaxis, delivered intramuscularly every 2 to 4 weeks. However, adherence to recommended secondary prophylaxis regimens is a global challenge. This paper outlines a consultation with global experts in rheumatic heart disease on the characteristics of benzathine penicillin G formulations which could be changed to improve adherence with secondary prophylaxis. Characteristics included dose interval, pain, administration mechanism, cold chain independence and cost. A sample target product profile for reformulated benzathine penicillin G is presented.

Group A Streptococcus (GAS) infections are a significant global cause of morbidity and mortality. GAS diseases disproportionally affect those living in conditions characterized by poverty and social injustice, in both developing countries and in marginalized populations of industrialized nations. In Australia and New Zealand, GAS-associated Acute Rheumatic Fever (ARF) is a major cause of health inequality disproportionally affecting indigenous children. Recognition of these inequalities by the governments of Australia and New Zealand has resulted in the formation of a Trans-Tasman Coalition to Advance New Vaccines for group A Streptococcus (CANVAS). This review provides an update on the current status of GAS vaccine development, and describes global efforts by CANVAS and others to accelerate the development of GAS vaccines.

Jürgen B. Bulitta's name was misspelled in the original version of the article. It is correct as reflected here. The original article has been revised.

The mononuclear phagocyte system (MPS), comprising monocytes, macrophages, and dendritic cells (DCs), plays an important role in the control of disease, but can also contribute to the establishment of persistent infections. Monocytes are derived from progenitors in the bone marrow. Once in circulation, they migrate into the tissues, differentiate into macrophages, and phagocytose microbes under inflammatory conditions. However, recent work shows they not only act as phagocytes, but are also precursors for particular types of DCs, inflammatory macrophages, and tissue macrophages. The role of monocytes during inflammation in models of bacterial and viral infections, cancer, atherosclerosis, and autoimmunity has been widely studied and reported. In this review we focus on the less understood role of monocytes in protozoan infections.

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., Author Summary Visceral leishmaniasis (VL) is a potentially fatal human disease caused by the intracellular protozoan parasites Leishmania donovani and L. infantum (chagasi). Parasites infect macrophages throughout the viscera, though the spleen and liver are the major sites of disease. VL is responsible for significant morbidity and mortality in the developing world, particularly in India, Sudan, Nepal, Bangladesh and Brazil. Because of the intrusive techniques required to analyse tissue in VL patients, our current understanding of the host immune response during VL largely derives from studies performed in genetically susceptible mice. We have discovered that mice which are unable to produce a cytokine called LIGHT have poor control of L. donovani infection in the liver, compared with wild-type control animals. In addition, we demonstrated that LIGHT has distinct roles during VL, depending on which of its two major cell-bound receptors it engages. Finally, we identified an antibody that stimulates the lymphotoxin β receptor (one of the LIGHT receptors), that can stimulate anti-parasitic activity during an established infection, thereby identifying this receptor as a therapeutic target during disease.

SUMMARYSkin infections are highly prevalent in many Australian Aboriginal communities. This study aimed to determine the prevalence of group A streptococcus (GAS) andStaphylococcus aureusin skin sores of Indigenous people living in an urban setting. We undertook a cross-sectional study of 173 children and youths attending the Wuchopperen Clinic (Cairns) for treatment of skin infections. Participants were interviewed using a structured questionnaire, and a skin lesion swab obtained. The median age was 5·3 years, with 42% identifying themselves as Torres Strait Islanders and 34% as Aboriginal. Impetigo (65%) was the most frequent diagnosis reported followed by scabies (19%); 79% of the lesions had erythema and 70% had exudate. Of 118 lesions, 114 were positive for pathogenic bacteria, with GAS isolated in 84 cases andS. aureusin 92; both these species were recovered from 63 lesions. Significant diversity ofemm-types of GAS was associated with skin lesions in Indigenous patients (22emm-types identified). Fifteen of the 92S. aureusisolates were suggestive of being community-acquired on the basis of antimicrobial susceptibility profile and nine of these strains were co-cultured from nine lesions. These results have implications for future changes of antibiotic policies for the treatment of skin infections in this population.

In the Review article ‘The diverse roles of monocytes in inflammation caused by protozoan parasitic diseases’ by Meru Sheel and Christian R. Engwerda, which was published in the August 2012 issue of Trends in Parasitology, the authors incorrectly cited Ref [46]: Mukhopadhyay, R. et al. (2011) Characterisation of antimony resistant Leishmania donovani isolates: biochemical and biophysical studies and interaction with host cells. Int. J. Parasitol. 41, 1311–1321. This reference should be replaced with:46 Mukhopadhyay, D. et al. (2011) Miltefosine effectively modulates the cytokine milieu in Indian post kala-azar dermal leishmaniasis. J. Infect. Dis. 204, 1427–36The authors apologize for the oversight.