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Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups. SARS-CoV-2 infection can cause COVID-19, which is usually a mild disease in children. However, severe illness requiring intensive care management can occur, particularly in younger children and those with chronic disease. The immune system likely plays an important role in susceptibility to severe disease, but few studies have examined the immune response in infants with severe COVID-19. Here, we provide an in-depth analysis of the clinical features and immune response over time in a 5-month-old infant with congenital heart disease and severe COVID-19. Robust immune responses were observed up to 3 months following infection, providing evidence of durable and long-lived immunity against SARS-CoV-2. These findings provide important insights into the immune responses of a young infant with severe COVID-19 and might help inform future research into therapeutic targets. Wurzel et al. describe the kinetics of the immune response in relation to clinical and virological features in a 5-month old infant with congenital heart disease and severe COVID-19. The immune response was characterised by an elevated inflammatory response in the acute phase of infection, followed by Th2 skewing and prolonged T cell activation.

AIM: To describe the epidemiology of respiratory viruses in children before and during the 2020 SARS-CoV-2 pandemic and the relationship to public health measures instituted by the Victorian government. METHODS: Retrospective audit of respiratory viruses at a tertiary paediatric hospital in Melbourne from January 2015 up to week 47, 2020 in children under 18 years of age. The proportion of positive cases in weeks 1-47 in 2015-2019 (period 1) were compared to weeks 1-47, 2020 (period 2), and reviewed in the context of public health restrictions in Victoria. RESULTS: An annual average of 4636 tests were performed in period 1 compared to 3659 tests in period 2. Proportions of positive influenza A virus, influenza B virus, respiratory syncytial virus (RSV) and human parainfluenza virus were significantly reduced in period 2 compared to period 1: 77.3, 89.4, 68.6 and 66.9% reductions, respectively (all P < 0.001). From week 12-47, 2020, 28 893 SARS-CoV-2 tests were performed with a 0.64% positivity rate. Influenza viruses were not detected after week 17, RSV was not detected after week 35. CONCLUSIONS: Strict public health measures and border closures were successful in eliminating community transmission of SARS-CoV-2 in Melbourne. This was associated with a significant reduction in other respiratory virus infections in children. Identifying sustainable and effective ongoing public health interventions to reduce transmission of RSV and influenza could result in reduced morbidity and mortality in children and requires further research.

Aim Donor selection for milk banks is essential to ensure the safety and nutritional quality of the donor milk, and to ensure that the prospective donor and her breastfeeding infant do not come to harm through donating. Australian Red Cross Lifeblood Milk went through a robust process to develop a set of criteria for the selection and screening of potential breast milk donors, which included development of a Donor Questionnaire (DQ), supported by a formal set of Guidelines for the Selection of Milk Donors. Key screening questions from the DQ were made available to prospective donors to self-screen prior to the formal assessment process. The aim of this study was to review the outcomes of milk donor screening at Lifeblood Milk. Methods We reviewed the outcomes of our donor screening process over the first 12-months (July 2018-June 2019) of operations. Results A total of 50 out of 327 donors who responded to the self-screening questions were not able to proceed further; 201 donors were formally screened using the DQ and Guidelines for the Selection of Milk Donors, with 9 of 201 deferred based on their responses. An additional two donors were deferred (failed phlebotomy (n = 1) and reactive infectious disease serology (n = 1)), with 190 of 201 (95%) of prospective donors accepted after screening. Conclusions Our experience highlighted international differences in practice between milk banks and lack of strong research to inform milk donor selection. Making a set of key screening questions available to donors for self-screening resulted in a high acceptance rate (95%) for donors who began the formal screening process. Further work is needed to better understand the impact of deferral on prospective milk donors.

Background Household studies are crucial for understanding the transmission of SARS-CoV-2 infection, which may be underestimated from PCR testing of respiratory samples alone. We aim to combine assessment of household mitigation measures; nasopharyngeal, saliva and stool PCR testing; along with mucosal and systemic SARS-CoV-2 specific antibodies, to comprehensively characterise SARS-CoV-2 infection and transmission in households. Methods Between March and September 2020, we obtained samples from 92 participants in 26 households in Melbourne, Australia, in a 4-week period following onset of infection with ancestral SARS-CoV-2 variants. Results The secondary attack rate was 36% (24/66) when using nasopharyngeal swab (NPS) PCR positivity alone. However, when respiratory and non-respiratory samples were combined with antibody responses in blood and saliva, the secondary attack rate was 76% (50/66). SARS-CoV-2 viral load of the index case and household isolation measures were key factors that determine secondary transmission. In 27% (7/26) of households, all family members tested positive by NPS for SARS-CoV-2 and were characterised by lower respiratory Ct-values than low transmission families (Median 22.62 vs 32.91; IQR 17.06 to 28.67 vs 30.37 to 34.24). High transmission families were associated with enhanced plasma antibody responses to multiple SARS-CoV-2 antigens and the presence of neutralising antibodies. Three distinguishing saliva SARS-CoV-2 antibody features were identified according to age (IgA1 to Spike 1, IgA1 to nucleocapsid protein (NP), suggesting that adults and children generate distinct mucosal antibody responses during the acute phase of infection. Conclusion Utilising respiratory and non-respiratory PCR testing, along with measurement of SARS-CoV-2 specific local and systemic antibodies, provides a more accurate assessment of infection within households and highlights some of the immunological differences in response between children and adults.

Australian Red Cross Lifeblood supplies pasteurised donor human milk (PDHM) to more than 30 partner hospitals across Australia. Preterm infants who receive PDHM are a highly vulnerable population but formal biovigilance programs are rare in human milk banking. Lifeblood Milk performs ongoing surveillance for both donor and recipient adverse events. This study aimed to formally review adverse events reported to Lifeblood Milk since 2018.Milk donor infectious diseases testing outcomes and donor adverse events (DAEs) are prospectively recorded at Lifeblood. Infant recipient adverse events are contractually reported back to Lifeblood Milk by hospitals and assessed according to severity and likelihood of relationship to PDHM administration. Donor and recipient adverse events over a 3.5-year period (July 2018 to December 2021) were reviewed.There were three DAEs (3/976 = 0.31%) related to phlebotomy; these included two vasovagal reactions and one phlebotomy site haematoma. Eight (8/976 = 0.81%) additional donors had biological false reactive (BFR) infectious diseases serology results. There were 10 reported suspected adverse events in recipients. Six were infection-related; other events included milk curd obstruction, high urinary iodine levels, sudden cardiac death and nasogastric tube obstruction. All reported suspected adverse events in recipients were classified as unlikely to be related, or definitely not related, to PDHM administration.Milk donor adverse events were rare but biological false reactive serology results were not uncommon. There were no recipient adverse events considered causally related to pasteurised donor human milk, which is generally a low-risk biological product. Ongoing biovigilance remains essential.

The immune response in children with SARS-CoV-2 infection is not well understood.To compare seroconversion in nonhospitalized children and adults with mild SARS-CoV-2 infection and identify factors that are associated with seroconversion.This household cohort study of SARS-CoV-2 infection collected weekly nasopharyngeal and throat swabs and blood samples during the acute (median, 7 days for children and 12 days for adults [IQR, 4-13] days) and convalescent (median, 41 [IQR, 31-49] days) periods after polymerase chain reaction (PCR) diagnosis for analysis. Participants were recruited at The Royal Children's Hospital, Melbourne, Australia, from May 10 to October 28, 2020. Participants included patients who had a SARS-CoV-2-positive nasopharyngeal or oropharyngeal swab specimen using PCR analysis.SARS-CoV-2 immunoglobulin G (IgG) and cellular (T cell and B cell) responses in children and adults. Seroconversion was defined by seropositivity in all 3 (an in-house enzyme-linked immunosorbent assay [ELISA] and 2 commercial assays: a SARS-CoV-2 S1/S2 IgG assay and a SARS-CoV-2 antibody ELISA) serological assays.Among 108 participants with SARS-CoV-2-positive PCR findings, 57 were children (35 boys [61.4%]; median age, 4 [IQR, 2-10] years) and 51 were adults (28 women [54.9%]; median age, 37 [IQR, 34-45] years). Using the 3 established serological assays, a lower proportion of children had seroconversion to IgG compared with adults (20 of 54 [37.0%] vs 32 of 42 [76.2%]; P .001). This result was not associated with viral load, which was similar in children and adults (mean [SD] cycle threshold [Ct] value, 28.58 [6.83] vs 24.14 [8.47]; P = .09). In addition, age and sex were not associated with seroconversion within children (median age, 4 [IQR, 2-14] years for both seropositive and seronegative groups; seroconversion by sex, 10 of 21 girls [47.6%] vs 10 of 33 boys [30.3%]) or adults (median ages, 37 years for seropositive and 40 years for seronegative adults [IQR, 34-39 years]; seroconversion by sex, 18 of 24 women [75.0%] vs 14 of 18 men [77.8%]) (P.05 for all comparisons between seronegative and seropositive groups). Symptomatic adults had 3-fold higher SARS-CoV-2 IgG levels than asymptomatic adults (median, 227.5 [IQR, 133.7-521.6] vs 75.3 [IQR, 36.9-113.6] IU/mL), whereas no differences were observed in children regardless of symptoms. Moreover, differences in cellular immune responses were observed in adults compared with children with seroconversion.The findings of this cohort study suggest that among patients with mild COVID-19, children may be less likely to have seroconversion than adults despite similar viral loads. This finding has implications for future protection after SARS-CoV-2 infection in children and for interpretation of serosurveys that involve children. Further research to understand why seroconversion and development of symptoms are potentially less likely in children after SARS-CoV-2 infection and to compare vaccine responses may be of clinical and scientific importance.

ObjectiveShorter courses of intravenous antibiotics for young infants with urinary tract infection (UTI) have myriad advantages. As practice shifts toward shorter intravenous treatment courses, this study aimed to determine the safety of early intravenous-to-oral antibiotic switch and identify risk factors for bacteraemia with UTI.MethodsRetrospective audit of infants aged ≤90 days with a positive urine culture at a quaternary paediatric hospital over 4 years (2016–2020). Data were collected from the hospital electronic medical record and laboratory information system. Short-course intravenous antibiotic duration was defined as ResultsAmong 427 infants with non-bacteraemic UTI, 257 (60.2%) were treated for 30 days, afebrile and those without bacteraemia or cerebrospinal fluid pleocytosis. Treatment failure (30-day UTI recurrence) occurred in 6/451 (1.3%) infants. All had non-bacteraemic UTI and one received ConclusionShort-course intravenous antibiotics for

ImportanceThe immune response in children with SARS-CoV-2 infection is not well understood.ObjectiveTo compare seroconversion in children and adults with non-hospitalized (mild) SARS-CoV-2 infection and to understand the factors that influence this.DesignParticipants were part of a household cohort study of SARS-CoV-2 infection. Weekly nasopharyngeal/throat swabs and blood samples were collected during the acute and convalescent period following PCR diagnosis for analysis.SettingParticipants were recruited at the Royal Children’s Hospital, Melbourne, Australia between May and October 2020.ParticipantsThose who had a SARS-CoV-2 PCR-positive nasal/throat swab.Main outcomes and measuresSARS-CoV-2 antibody and cellular responses in children and adults. Seroconversion was defined by seropositivity in all three serological assays.ResultsAmong 108 SARS-CoV-2 PCR-positive participants, 57 were children (median age: 4, IQR 2-10) and 51 were adults (median age: 37, IQR 34-45). Using three established serological assays, a lower proportion of children seroconverted compared with adults [20/54 (37.0%) vs 32/42 (76.2%); (pConclusion and RelevanceIn this non-hospitalized cohort with mild COVID-19, children were less likely to seroconvert than adults despite similar viral loads. This has implications for future protection following COVID-19 infection in children and for interpretation of serosurveys that involve children. Further research to understand why children are less likely to seroconvert and develop symptoms following SARS-CoV-2 infection, and comparison with vaccine responses may be of clinical and scientific importance.Key pointsQuestionWhat proportion of children with non-hospitalized (mild) SARS-CoV-2 infection seroconvert compared to adults?FindingsIn this cohort study conducted in 2020, we found the proportion of children who seroconverted to SARS-CoV-2 was half that in adults despite similar viral load.MeaningSerology is a less reliable marker of prior SARS-CoV-2 infection in children. SARS-CoV-2-infected children who do not seroconvert may be susceptible to reinfection. Our findings support strategies to protect children against COVID-19 including vaccination.

Objective To compare the concordance and acceptability of saliva testing with standard‐of‐care oropharyngeal and bilateral deep nasal swab testing for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in children and in general practice. Design Prospective multicentre diagnostic validation study. Setting Royal Children’s Hospital, and two general practices (cohealth, West Melbourne; Cirqit Health, Altona North) in Melbourne, July–October 2020. Participants 1050 people who provided paired saliva and oropharyngeal‐nasal swabs for SARS‐CoV‐2 testing. Main outcome measures Numbers of cases in which SARS‐CoV‐2 was detected in either specimen type by real‐time polymerase chain reaction; concordance of results for paired specimens; positive percent agreement (PPA) for virus detection, by specimen type. Results SARS‐CoV‐2 was detected in 54 of 1050 people with assessable specimens (5%), including 19 cases (35%) in which both specimens were positive. The overall PPA was 72% (95% CI, 58–84%) for saliva and 63% (95% CI, 49–76%) for oropharyngeal‐nasal swabs. For the 35 positive specimens from people aged 10 years or more, PPA was 86% (95% CI, 70–95%) for saliva and 63% (95% CI, 45–79%) for oropharyngeal‐nasal swabs. Adding saliva testing to standard‐of‐care oropharyngeal‐nasal swab testing increased overall case detection by 59% (95% CI, 29–95%). Providing saliva was preferred to an oropharyngeal‐nasal swab by most participants (75%), including 141 of 153 children under 10 years of age (92%). Conclusion In children over 10 years of age and adults, saliva testing alone may be suitable for SARS‐CoV‐2 detection, while for children under 10, saliva testing may be suitable as an adjunct to oropharyngeal‐nasal swab testing for increasing case detection.

Objectives The high diagnostic accuracy indices for saliva SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) reported in adults has not been demonstrated in children and adequately powered studies focused on the paediatric population are lacking. This study was carried out to determine the diagnostic accuracy of saliva for SARS-CoV-2 RT-PCR in ambulatory children. Methods From 1st-23rd October 2020, we recruited a population-based sample of children presenting for COVID-19 screening in Dubai, United Arab Emirates. Each child provided paired nasopharyngeal (NP) swab and saliva for SARS-CoV-2 RT-PCR N, E and RdRp genes detection. Results Paired NP swab and saliva samples were obtained from 476 children with mean (±SD) age of 10.8 years (±3.9) and 58.1% were male (n/N=277/476). Nine participants were sampled twice, hence 485 pairs of NP swab/saliva were tested. Viral detection in at least one specimen type was reported in 17.9% (n/N=87/485), with similar detection in NP swab (16.7%; n/N=81/485) and saliva (15.9%; n/N=77/485). Sensitivity and specificity of saliva RT-PCR was 87.7% (95% CI 78.5%-93.9%) and 98.5% (95% CI 96.8%-99.5%). The positive and negative predictive values were 92.2% (95% CI 84.2%-96.3%) and 97.6% (95% CI 95.7%-98.6%) with Kappa coefficient 0.879 (95% CI 0.821-0.937). Concordance of findings between NP swab and saliva did not differ by age (p=0.67) or gender (p=0.29). Cycle threshold (Ct) values were significantly higher in NP swab/saliva pairs with discordant findings compared to those with both specimens positive. Conclusion In light of these findings, we recommend saliva as a diagnostic specimen for COVID-19 screening in children.

If maternal milk is unavailable, the World Health Organization recommends that the first alternative should be pasteurised donor human milk (DHM). Human milk banks (HMBs) screen and recruit milk donors, and DHM principally feeds very low birth weight babies, reducing the risk of complications and supporting maternal breastfeeding where used alongside optimal lactation support. The COVID‐19 pandemic has presented a range of challenges to HMBs worldwide. This study aimed to understand the impacts of the pandemic on HMB services and develop initial guidance regarding risk limitation. A Virtual Collaborative Network (VCN) comprising over 80 HMB leaders from 36 countries was formed in March 2020 and included academics and nongovernmental organisations. Individual milk banks, national networks and regional associations submitted data regarding the number of HMBs, volume of DHM produced and number of recipients in each global region. Estimates were calculated in the context of missing or incomplete data. Through open‐ended questioning, the experiences of milk banks from each country in the first 2 months of the pandemic were collected and major themes identified. According to data collected from 446 individual HMBs, more than 800,000 infants receive DHM worldwide each year. Seven pandemic‐related specific vulnerabilities to service provision were identified, including sufficient donors, prescreening disruption, DHM availability, logistics, communication, safe handling and contingency planning, which were highly context‐dependent. The VCN now plans a formal consensus approach to the optimal response of HMBs to new pathogens using crowdsourced data, enabling the benchmarking of future strategies to support DHM access and neonatal health in future emergencies.

Aim: As the COVID-19 pandemic evolves, human milk banks world-wide continue to provide donor human milk to vulnerable infants who lack access to mother's own milk. Under these circumstances, ensuring the safety of donor human milk is paramount, as the risk of vertical transmission of SARS-CoV-2 is not fully understood. Here, we investigate the inactivation of SARS-CoV-2 in human milk by pasteurisation and the stability of SARS-CoV-2 in human milk under cold storage. Methods: SARS-CoV-2 was experimentally inoculated into human milk samples from healthy donors or into a control medium. Triplicates of each sample were layered onto uninfected cells after Holder pasteurisation (63°C for 30 min), heating to 56°C for 30 min, or after 48 h of storage at 4°C or −30°C. Infectious titres of virus were determined at 72 h post-infection by endpoint titration. Results: Following heating to 63°C or 56°C for 30 min, replication competent (i.e. live) SARS-CoV-2 was undetected in both human milk and the control medium. Cold storage of SARS-CoV-2 in human milk (either at 4°C or −30°C) did not significantly impact infectious viral load over a 48 h period. Conclusion: SARS-CoV-2 is effectively inactivated by Holder pasteurisation, suggesting that existing milk bank processes will effectively mitigate the risk of transmission of SARS-COV-2 to vulnerable infants through pasteurised donor human milk. The demonstrated stability of SARS-CoV-2 in refrigerated or frozen human milk may assist in the development of guidelines around safe expressing and storing of milk from COVID-19 infected mothers.

As the COVID-19 pandemic evolves, human milk banks worldwide continue to provide donor human milk to vulnerable infants who lack access to mother’s own milk. Under these circumstances, ensuring the safety of donor human milk is paramount, as the risk of vertical transmission of SARS-CoV-2 is not well understood. Here, we investigate the inactivation of SARS-CoV-2 in human milk by pasteurisation, and the stability of SARS-CoV-2 in human milk under cold storage (freezing or refrigeration). Following heating to 63°C or 56°C for 30 minutes, SARS-CoV-2 replication competent (i.e. live) virus was undetected in both human milk and the control medium. Cold storage of SARS-CoV-2 in human milk (either at 4°C or - 30°C) did not significantly impact infectious viral load over a 48 hour period. Our findings demonstrate that SARS-CoV-2 can be effectively inactivated by Holder pasteurisation, and confirm that existing milk bank processes will effectively mitigate the risk of transmission of SARS-COV-2 to vulnerable infants through pasteurised donor human milk.

Objectives New tests are needed to overcome the limitations of existing immunodiagnostic tests for tuberculosis (TB) infection, including their inability to differentiate between active TB and latent TB infection (LTBI). This review aimed to identify the most promising cytokine biomarkers for use as stage-specific markers of TB infection. Methods A systematic review was done using electronic databases to identify studies that have investigated Mycobacterium tuberculosis (MTB)-specific cytokine responses as diagnostic tools to differentiate between LTBI and active TB. Results The 56 studies included in this systematic review measured the MTB-specific responses of 100 cytokines, the most frequently studied of which were IFN-γ, IL-2, TNF-α, IP-10, IL-10 and IL-13. Ten studies assessed combinations of cytokines, most commonly IL-2 and IFN-γ. For most cytokines, findings were heterogenous between studies. The variation in results likely relates to differences in the study design and laboratory methods, as well as participant and environmental factors. Conclusions Although several cytokines show promise as stage-specific markers of TB infection, this review highlights the need for further well-designed studies, in both adult and paediatric populations, to establish which cytokine(s) will be of most use in a new generation of immunodiagnostic tests.

Objective Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. Methods 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α, IFN-γ, IP-10 and MIP-1β) responses, measured by Luminex multiplex immunoassay. Results The background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected individuals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. Conclusion Mycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected individual, and potentially between LTBI and active tuberculosis.

Summary There is increasing demand for access to rapid microbiological testing, with a view to improving clinical outcomes. The possibility of rapid testing has been facilitated by development of cartridge-based random access molecular technologies that are now widely available. Whether the expense of cartridge-based assays is justified in terms of clinical or laboratory cost savings is controversial. This prospective study evaluated the impact of the Biofire FilmArray Respiratory Panel (‘FilmArray’), a cartridge-based random access molecular test, compared with standard batched molecular testing using an ‘in-house’ respiratory polymerase chain reaction (PCR) on laboratory and health service outcomes for adult patients at a tertiary-level adult hospital in Melbourne, Australia. Laboratory result turnaround time was significantly reduced with the FilmArray (median 4.4 h) compared to a standard validated in-house respiratory PCR assay (median 21.6 h, p < 0.0001) and there was a significant increase in diagnostic yield with the Filmarray (71/124, 57.3%) compared to in-house PCR (79/200; 39.5%; p = 0.002). Despite improved result turnaround time and increased diagnostic yield from testing, there was no corresponding reduction in hospital length of stay or use of isolation beds. Although cartridge-based molecular testing reduced turnaround time to result for respiratory pathogen testing, it did not impact on health service outcomes such as hospital length of stay. Further work is warranted to determine whether cartridge-based tests at the point of care can improve clinical and health service impacts.

Background This study aimed to document changes in serological response before and after treatment of Schistosoma infection in resettled refugee children from endemic countries in Australia. Current Australian guidelines recommend serological screening for Schistosoma infection in children and adults from endemic countries. Data on the utility of follow-up serology after treatment is limited. Methods We undertook a retrospective audit of Schistosoma serology in refugee-background children presenting to a specialist paediatric refugee health clinic in Melbourne, Australia, between January 2005 and December 2014. Patients were included with positive Schistosoma serology, documented treatment with praziquantel; clinical and serological followup data after treatment, and no return to endemic areas. Results Fifty-one refugee-background children were included. Overall, 40/51 (78.4%) children had serology that decreased after treatment, 25/51 (49.0%) had a greater than twofold decrease and 22/51 (43.1%) reverted to negative serology. Six (11.8%) children showed an increasing serology titre and 5/51 (9.8%) had unchanged serology after treatment. Conclusions This is the first study describing the changes in Schistosoma serological titres following treatment in immigrant children in a non-endemic country. We observed a majority downward trend in antibody titres after praziquantel treatment, suggesting follow-up serological testing may be useful in children to monitor treatment response.

BACKGROUND AND OBJECTIVES Donor syphilis testing began in the 1940s amidst widespread transfusion-transmitted syphilis (TTS). Since then, the introduction of penicillin, pre-donation screening questionnaires and improved storage conditions have contributed to reducing transmission risk. Consequently, universal testing may no longer be cost-effective. This study analysed alternative options for donor syphilis testing to determine the optimal strategy. MATERIALS AND METHODS A model was developed using conservative parameter estimates for factors affecting TTS and 2009-2015 Australian donations to calculate risk outcomes (TTS infections, tertiary syphilis in recipients and transfusion-associated congenital syphilis) and cost-effectiveness of alternative testing strategies. The strategies modelled were as follows: universal testing, targeted-testing of high-risk groups (males ≤50 years old and first-time donors) and no testing. RESULTS The estimated risk of TTS is one in 49·5 million transfusions for universal testing, one in 6 million for targeted-testing of males ≤50 years old, one in 4 million for targeted-testing of first-time donors and one in 2·8 million for no testing. For all strategies, the risk of tertiary and congenital syphilis is

The ability to monitor response to therapy for tuberculosis (TB) and confirm adequate treatment would be a major advance. The low reversion rate of interferon-gamma based assays means that they are unlikely to be useful for monitoring therapy. Several exploratory studies have evaluated the diagnostic potential of cytokine biomarkers other than interferon-gamma for monitoring anti-tuberculous therapy. A systematic review of these studies was performed to identify the most promising candidate biomarkers. TNF-α, IL-2, IL-6, IL-10 and IL-12 were the most extensively investigated cytokines. There was significant heterogeneity between studies in relation to study design and laboratory methodology, complicating direct comparisons. There was marked variation between studies in the observed changes during treatment for many of the biomarkers. Further longitudinal studies in sufficiently large patient cohorts with rigorous methodology are needed to determine the true potential of individual cytokine biomarkers, or combinations, for monitoring TB treatment.

Summary Introduction The ability to monitor and confirm adequate treatment of latent TB infection (LTBI) would be a major advance. The potential immunomodulatory effects of anti-tuberculous drugs and steroids need to be considered in assessing the utility of cytokine-based assays for this purpose. Methods We determined whether anti-tuberculous antibiotics or dexamethasone affect the production of IFN-γ and other potential cytokine biomarkers (TNF-α, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β) in the QuantiFERON-TB Gold In-Tube (QFT-IT) assay. Blood from ten adults with LTBI was added to one standard set of QFT-IT tubes and five further sets containing therapeutic concentrations of either isoniazid, rifampicin, isoniazid and rifampicin, ciprofloxacin or dexamethasone. Resulting supernatants were analysed by ELISA (QFT-IT assay IFN-γ) and xMAP- Luminex assays (all cytokines). Results Anti-tuberculous antibiotics had only a limited effect on categorical QFT-IT assay results and the production of cytokines. In contrast, dexamethasone resulted in a change in categorical results from positive to negative in four of ten patients, and caused a marked reduction in IL-13 and IL-1ra responses. Conclusion Substantial changes in TB-antigen-induced IFN-γ and other cytokine responses during treatment likely primarily reflect host immunological changes rather than immunomodulatory effects of anti-tuberculous antibiotics. Results from cytokine-based assays in patients on corticosteroids should be interpreted with caution.

This study aimed to determine whether there are seasonal changes in the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays, an interferon-gamma release assay widely used for the diagnosis of tuberculosis infection. Results of 31,932 QFT-GIT assays performed at a large independent, accredited diagnostic service provider in London, UK over a 4.5-year-period were analysed. The proportion of positive results was significantly lower in autumn (14.8%) than in spring (16.0%; p = 0.0366) and summer (17.5%; p < 0.0001), but similar to winter (15.2%; p = 0.4711). The proportion of indeterminate results was significantly higher in autumn (8.2%) than in spring (6.2%; p < 0.0001), summer (4.8%; p < 0.0001), and winter (6.2%; p < 0.0001). The highest proportions of indeterminate results were observed in October (8.4%) and November (8.8%), the lowest in June (4.5%). Our data show that significant seasonal variation occurs in the performance of QFT-GIT assays in a temperate climate setting. Potential underlying mechanisms, including host and environmental factors, are discussed.

Background We aimed to assess antimicrobial stewardship (AMS) resources and activities for children in hospitals throughout Australia, to identify gaps in services. Methods Every public hospital in Australia with paediatric beds was identified via the Australian Institute of Health and Welfare. The director of pharmacy or most senior paediatrician was asked to complete an online evaluation in 2017 regarding their AMS resources and activities. For analysis, tertiary (7) and major metropolitan hospitals (50) were combined (metropolitan) and compared with hospitals in regional (42) and rural towns (7) combined (rural). Results We identified 106 hospitals and received 106 (100%) responses. Paediatric bed numbers ranged from 3 to 360. In metropolitan hospitals, 17 (35%) had a paediatric AMS team or representation, compared with 5 (9%) for rural (P = 0.001) There was an AMS pharmacist in 42 (86%) metropolitan hospitals compared with 37 (65%) rural (P = 0.1) although the majority of these were not paediatric. Fifty-one (48%) hospitals had locally adapted empirical antibiotic prescribing guidelines (metropolitan 28 (57%) vs. rural 23 (40%)(P = 0.06)), although fewer had specialty-specific guidelines (figure). One hundred two (96%) hospitals had restrictions on broad-spectrum antimicrobials, but formal approval systems were fewer: metropolitan 44 (90%) vs. rural 35 (66%) (P = 0.004)). Auditing methods differed but were mostly ad hoc, with results fed back in an untargeted way with only 22 (34%) providing direct physician feedback. There was a paucity of AMS education: only 25 (24%) provided education for senior medical staff, and 24 (23%) had no education for any staff (metropolitan 8 (17%) vs. rural 16 (29%)(P = 0.1)). The commonest perceived barriers to successful AMS for all hospitals were lack of dedicated infectious diseases and microbiology services (64 (60%)), lack of dedicated pharmacy resources (62 (59%)), and a lack of education for clinicians in antibiotic use (53 (50%)). Conclusion Australian hospitals have implemented some AMS activities for children, but most lack resources—this was much more evident in regional/rural than metropolitan hospitals. Barriers to successful AMS include a lack of infectious diseases and pharmacy resources and education, which need to be addressed in workforce planning. Disclosures All authors: No reported disclosures.

We read with interest the recent article by Wergeland et al., reporting that serum interferon-gamma inducible protein 10 (IP-10) may be a useful biomarker for differentiating between active tuberculosis (TB) and latent TB infection (LTBI), as well as for monitoring the effectiveness of anti-tuberculous therapy.1 However, a key limitation of this study was the absence of a 'sick control' group of patients with respiratory tract infections. Prompted by this finding, we analysed data from our ongoing study investigating novel biomarkers of active and latent TB.

Australia is a diverse society: 26% of the population were born overseas, a further 20% have at least one parent born overseas and 19% speak a language other than English at home. Paediatricians are frequently involved in the assessment and management of non-English-speaking-background children with developmental delay, disability or learning issues. Despite the diversity of our patient population, information on how children learn additional or later languages is remarkably absent in paediatric training. An understanding of second language acquisition is essential to provide appropriate advice to this patient group. It takes a long time (5 years or more) for any student to develop academic competency in a second language, even a student who has received adequate prior schooling in their first language. Refugee students are doubly disadvantaged as they frequently have limited or interrupted prior schooling, and many are unable to read and write in their first language. We review the evidence on second language acquisition during childhood, describe support for English language learners within the Australian education system, consider refugee-background students as a special risk group and address common misconceptions about how children learn English as an additional language.

The impact of immunosuppression on interferon-γ release assays and novel cytokine biomarkers of TB infection, mycobacteria-specific IL-2, IP-10 and TNF-α responses was investigated in an ex vivo model. Cytokine responses in standard QuantiFERON-TB Gold in-Tube (QFT-GIT) assays were compared with duplicate assays containing dexamethasone or infliximab. Dexamethasone converted QFT-GIT results from positive to negative in 30% of participants. Antigen-stimulated interferon-γ, IL-2 and TNF-α responses were markedly reduced, but IP-10 responses were preserved. Infliximab caused QFT-GIT result conversion in up to 30% of participants and substantial reductions in all cytokine responses. Therefore, corticosteroids and anti-TNF-α agents significantly impair interferon-γ release assay performance. IP-10 may be a more robust TB biomarker than interferon-γ in patients receiving corticosteroids.

Central venous catheters are essential for treatment of cancer and hematologic disorders in children. Central line-associated bloodstream infection (CLABSI) is the most common important complication and can lead to serious sequelae. Conventional antibiotic treatment is often unsuccessful. Ethanol lock therapy (ELT) has been shown to prevent CLABSI in various patient groups and might also be beneficial as adjunctive treatment for active infection. Efficacy and safety have not been adequately studied in the pediatric hematology/oncology population. Catheter occlusion and intraluminal clots have been reported. Routine use of ELT should not be recommended in this population until more data are available.

Surgical site infections are a common complication of obstetric and gynaecological surgeries; up to 10% of gynaecological patients undergoing an operative procedure will develop a surgical site infection. In surgeries with high rates of post-operative infection, antibiotic prophylaxis (using an antibiotic with an appropriate microbiological spectrum and administered in a timely manner) can play a major role in improving outcomes. This review examines the medical literature to assess the indications and appropriate antibiotic choices for prophylaxis to prevent surgical site infection in obstetric and gynaecological surgery. For some procedures, such as caesarean section, surgical termination of pregnancy and hysterectomy, antibiotic prophylaxis is clearly indicated. For other procedures, such as insertion of an intrauterine device, medical termination of pregnancy and laparoscopy, antibiotic prophylaxis is usually not required. For several other procedures where the evidence for antibiotic prophylaxis is unclear or inadequate, we discuss the current evidence for and against prophylaxis. Guidelines for infective endocarditic prophylaxis with surgery are also discussed.

There have been significant reductions in early-onset neonatal group B streptococcus (GBS) disease following implementation of maternal intrapartum antibiotic prophylaxis (IAP) policies. Nevertheless, GBS remains a leading cause of neonatal sepsis in Australia and New Zealand resulting in considerable morbidity and mortality, particularly among preterm infants. In the United States, the universal screening-based approach for identifying women for IAP results in apparently lower rates of early-onset neonatal GBS infection than risk-based assessment. In addition, IAP has altered the profile of newborn infants who develop early-onset disease. Many affected infants lack the typical intrapartum risk factors for GBS infection, are born to mothers with a negative GBS screen or represent missed opportunities for prevention. Clinicians should remain alert for signs of sepsis in any newborn infant. We provide an update of GBS preventative management strategies in the perinatal period taking into account recent United States, Australian and New Zealand guidelines.

Background: Intrapartum chemoprophylaxis for group B streptococcus (GBS) carriers reduces the risk of early-onset neonatal GBS infection. For women with β-lactam allergy, either erythromycin or clindamycin are administered. Recent reports worldwide suggest that GBS resistance to these antibiotics is increasing. Aims: To compare erythromycin and clindamycin resistance phenotypes in invasive neonatal GBS isolates across New Zealand and Australia over the past two decades and to determine whether regional variation in resistance patterns exist. Method: Invasive neonatal GBS isolates were collected from laboratories across New Zealand (n = 107) and Australia (n = 74) over two time periods (1992-1994 and 2002-2004 in New Zealand; 1982-2001 and 2002-2006 in Australia) and subjected to standard antibiotic susceptibility testing. A nested sub-study in New Zealand examined antibiotic susceptibilities of 112 maternal colonising GBS isolates during 2003-2004. Results: Erythromycin resistance among invasive neonatal GBS isolates increased across both countries over the past decade, with similar rates of resistance in New Zealand (9%) and Australia (6%) in recent years. New Zealand erythromycin-resistant GBS isolates commonly displayed cross-resistance to clindamycin. Also, there were significantly higher rates of isolated clindamycin resistance in GBS isolates from New Zealand than Australia (P = 0.034). Maternal GBS isolates from New Zealand showed similar resistance patterns to neonatal isolates. Conclusion: Erythromycin and clindamycin resistance among invasive neonatal GBS isolates has emerged in both New Zealand and Australia over the past decade and is consistent with global trends in GBS resistance patterns. Although regional variations exist, these findings should be considered when implementing intrapartum GBS prevention strategies. © 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology

Aim: The World Medical Association Declaration of Helsinki states that the use of a placebo in a clinical trial can only be justified ethically when no proven active treatment is available as a comparison. Despite this, placebos remain a popular choice as controls in clinical trials. Recent literature reviews have suggested that reliance on placebos may, in part, be because of methodological misconceptions about the need for placebos to control for the ‘placebo effect’. This study aimed to assess doctors' understanding of the requirements for placebo use in clinical trials. Methods: Two hundred doctors working in tertiary hospitals in Melbourne, Australia were surveyed in regards to their understanding of the role of the placebo and placebo effects in clinical trials. There was a 72% response rate. Doctors were specifically asked if a placebo was required in a randomised clinical trial, in preference to another form of control, to control for the ‘placebo effect’. Results: The majority of respondents (62%) incorrectly believed that placebos are essential to control for the ‘placebo effect’ in a randomised clinical trial. Conclusions: Misconceptions about the methodological requirement for placebos in randomised controlled trials may influence researcher decisions to use placebo controls in unethical situations.

The significance of Ureaplasma species as pathogens in neonatal meningitis remains contentious. Using an illustrative case of a premature infant with Ureaplasma parvum meningitis, confirmed by cerebrospinal fluid cultures and both specific and 16s rDNA polymerase chain reaction, we discuss the epidemiology of Ureaplasma species, the difficulties involved in diagnosis and establishing pathogenicity, and the challenges in defining appropriate treatment.