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Aoife Moore,1 Bridget Freyne,2 Clare Nourse3 1Department of General Paediatrics, Children’s Health Queensland, Brisbane, QLD, Australia; 2Department of Paediatric Infectious Diseases, Children’s Health Ireland, Dublin, Ireland; 3Department of Paediatric Infectious Diseases, Children’s Health Queensland, Brisbane, QLD, AustraliaCorrespondence: Aoife Moore, Queensland Children’s Hospital, South Brisbane, QLD, 4101, Tel +61 403 400 190, Email aoife.moore@bigpond.comAbstract: Congenital syphilis (CS), previously considered by many paediatricians as a “historical disease”, has re-emerged as a significant preventable neonatal infection. While low-income countries have the highest burden of disease globally, notifications have increased in many high-income countries (HIC) in recent years. This literature report provides an overview of the current strategies for testing and treating syphilis in pregnancy (SIP) and CS and describes the changing global epidemiology of SIP. National SIP guidelines are reviewed with reference to testing in pregnancy and treatment of CS. The report highlights that there is an ongoing crisis of CS in HICs worldwide and a disproportionate burden is being experienced by vulnerable populations in these countries. Action is needed to address this crisis, and interventions aimed at overcoming social and structural barriers to antenatal care access for vulnerable populations should be prioritised.Keywords: syphilis, pregnancy, congenital, epidemiology

Background: Infectious syphilis among women of reproductive age continues to rise in many countries including Australia, with a resultant increase in congenital syphilis. In response, new guidelines for management of syphilis in pregnancy were published in Queensland, Australia in 2018., Aims: This study evaluates the management of women diagnosed with syphilis in pregnancy in South-East Queensland (SEQ) after release of this guideline., Materials and Methods: This retrospective review of notification data identified women in SEQ who had a positive syphilis serology during pregnancy, without evidence of adequate treatment prior to the pregnancy, between January 2019 and December 2021 inclusive. Maternal demographics and pregnancy details including syphilis staging, testing and management were extracted, with management assessed against the 2018 Queensland syphilis in pregnancy guideline., Results: Of the 42 women identified, 79% were diagnosed in the first or second trimester, 69% had early-stage syphilis at the time of diagnosis and 86% were asymptomatic at the time of diagnosis. All, including the eight (19%) Aboriginal and/or Torres Strait Islander women identified, completed stage-appropriate treatment with penicillin, 83% completed treatment four weeks prior to delivery and 60% achieved a four-fold reduction in rapid plasma reagin at time of delivery., Conclusions: Our findings suggest compliance with syphilis in pregnancy management recommendations has improved in SEQ since release of the 2018 guidelines. However, congenital syphilis rates continue to rise; further initiatives addressing barriers to timely testing and management of syphilis in pregnancy are urgently needed at both healthcare system levels and for individual women., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Variations in neonatal aciclovir prescribing for suspected herpes simplex virus (HSV) disease are well-known, but there are limited data describing aciclovir prescribing in older children., Methods: Medical records of neonates (≤28 days) and children (29 days to 18 years) prescribed intravenous aciclovir for suspected HSV disease (1 January 2019-12 December 2019) in eight Australian and New Zealand hospitals were reviewed. Prescribing indication, HSV testing, aciclovir prescription details, adverse events and discharge diagnosis were recorded., Results: 1426 received empirical aciclovir. For neonates (n = 425), the median duration was 1 day (IQR 1-3), 411/425 underwent HSV investigations and 13/425 had HSV disease (two with disseminated encephalitis, four with encephalitis and seven with skin, eye, mouth disease). Of the 1001 children, 906 were immunocompetent. 136/906 suspected of mucocutaneous disease received aciclovir for a median of 2 days (1-2), 121/136 underwent HSV testing, and 69/136 had proven disease. 770/906 received aciclovir for suspected disseminated disease or encephalitis for a median of 1 day (1-2), 556/770 underwent HSV testing, and 5/770 had disseminated disease or encephalitis. Among 95 immunocompromised children, 53/58 with suspected mucocutaneous disease had HSV testing and this was confirmed in 22. Disseminated disease or encephalitis was suspected in 37/95, HSV testing conducted in 23/37 and detected in one. The median aciclovir duration was 3 (2-7) days for immunocompromised children. Nephrotoxicity occurred in 7/1426 and 24/1426 had an extravasation injury., Conclusion: Frequent and often unnecessary intravenous aciclovir prescribing for suspected HSV encephalitis or disseminated disease occurred in children, as evidenced by incomplete HSV investigations and only 5/770 older children having the diagnosis confirmed., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: There is a recognized unmet need for clinical trials to provide evidence-informed care for infants, children and adolescents. This Special Communication outlines the capacity of 3 distinct trial design strategies, sequential, parallel, and a unified adult-pediatric bayesian adaptive design, to incorporate children into clinical trials and transform this current state of evidence inequity. A unified adult-pediatric whole-of-life clinical trial is demonstrated through the Staphylococcus aureus Network Adaptive Platform (SNAP) trial., Observations: Bayesian methods provide a framework for synthesizing data in the form of a probability model that can be used in the design and analysis of a clinical trial. Three trial design strategies are compared: (1) a sequential adult-pediatric bayesian approach that involves a separate, deferred pediatric trial that incorporates existing adult trial data into the analysis model to potentially reduce the pediatric trial sample size; (2) a parallel adult-pediatric bayesian trial whereby separate pediatric enrollment occurs in a parallel trial, running alongside an adult randomized clinical trial; and (3) a unified adult-pediatric bayesian adaptive design that supports the enrollment of both children and adults simultaneously in a whole-of-life bayesian adaptive randomized clinical trial. The SNAP trial whole-of-life design uses a bayesian hierarchical model that allows information sharing (also known as borrowing) between trial age groups by linking intervention effects of children and adults, thereby improving inference in both groups., Conclusion and Relevance: Bayesian hierarchical models may provide more precision for estimates of safety and efficacy of treatments in trials with heterogenous populations compared to traditional methods of analysis. They facilitate the inclusion of children in clinical trials and a shift from children deemed therapeutic orphans to the vision of no child left behind in clinical trials to ensure evidence for clinical practice exists across the life course. The SNAP trial provides an example of a bayesian adaptive whole-of-life inclusion design that enhances trial population inclusivity and diversity overall, as well as generalizability and translation of findings into clinical practice.

Aim: As herpes simplex virus (HSV) in infancy is not a mandatory notifiable condition in Australia, completeness of ascertainment by the Australian Paediatric Surveillance Unit (APSU) has been difficult to evaluate to date. We evaluated case capture in Queensland (QLD) and Western Australia (WA) using statewide laboratory and clinical data and complementary surveillance data collected via the APSU., Methods: HSV polymerase chain reaction positive results in infants (0-3 months) from 2007 to 2017 were obtained from statewide public pathology providers in QLD and WA. Clinical data were extracted from patient records and compared to APSU reported cases., Results: A total of 94 cases of HSV disease in infancy (70 QLD; 24 WA) were identified from laboratory data sets, compared to 36 cases (26 QLD; 10 WA) reported to the APSU. In total there was 102 unique cases identified; 28 cases were common to both data sets (seven skin eye mouth (SEM) disease, 13 central nervous system (CNS) disease and eight disseminated disease). Active surveillance captured 35% (36/102) of cases overall including 74% (14/19) of CNS, 71% (10/14) of disseminated and 17% (12/69) of SEM disease cases, respectively. Surveillance reported cases had a higher case-fatality rate compared to those not reported (14% vs. 3%, P = 0.038). Neurological sequelae at discharge were comparable between the groups., Conclusion: Active surveillance captures one third of hospitalised HSV cases in QLD and WA, including the majority with severe disease. However, morbidity and mortality remain high. Future studies on HSV will rely on observational studies. Enhanced case ascertainment through combined laboratory and surveillance data is essential for better understanding and improving outcomes., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Infants born to mothers with tuberculosis disease are at increased risk of developing tuberculosis disease themselves. We reviewed published studies and guidelines on the management of these infants to inform the development of a consensus practice guideline. We searched MEDLINE, CINAHL, and Cochrane Library from database inception to Dec 1, 2022, for original studies reporting the management and outcome of infants born to mothers with tuberculosis. Of the 521 published papers identified, only three met inclusion criteria and no evidence-based conclusions could be drawn from these studies, given their narrow scope, variable aims, descriptive nature, inconsistent data collection, and high attrition rates. We also assessed a collection of national and international guidelines to inform a consensus practice guideline developed by an international panel of experts from different epidemiological contexts. The 16 guidelines reviewed had consistent features to inform the expert consultation process. Two management algorithms were developed-one for infants born to mothers considered potentially infectious at the time of delivery and another for mothers not considered infectious at the time of delivery-with different guidance for high and low tuberculosis incidence settings. This systematic review and consensus practice guideline should facilitate more consistent clinical management, support the collection of better data, and encourage the development of more studies to improve evidence-based care., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pancreatic ductal adenocarcinoma is a highly metastatic disease and macrophages support liver metastases. Efferocytosis, or engulfment of apoptotic cells by macrophages, is an essential process in tissue homeostasis and wound healing, but its role in metastasis is less well understood. Here, we found that the colonization of the hepatic metastatic site is accompanied by low-grade tissue injury and that efferocytosis-mediated clearance of parenchymal dead cells promotes macrophage reprogramming and liver metastasis. Mechanistically, progranulin expression in macrophages is necessary for efficient efferocytosis by controlling lysosomal acidification via cystic fibrosis transmembrane conductance regulator and the degradation of lysosomal cargo, resulting in LXRα/RXRα-mediated macrophage conversion and upregulation of arginase 1. Pharmacological blockade of efferocytosis or macrophage-specific genetic depletion of progranulin impairs macrophage conversion, improves CD8 + T cell functions, and reduces liver metastasis. Our findings reveal how hard-wired functions of macrophages in tissue repair contribute to liver metastasis and identify potential targets for prevention of pancreatic ductal adenocarcinoma liver metastasis., (© 2024. The Author(s).)

Objective: The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries., Methods: Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods., Results: The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods., Conclusions: Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed., (© 2024 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Postoperative spinal implant infection following pediatric spinal surgery often presents a management dilemma. We aimed to characterize our experience in this cohort of patients, hoping to provide further insight when approaching these challenging cases., Methods: A retrospective, observational study was performed of all children who underwent spinal surgery from January 2015 to June 2021 in a tertiary pediatric spinal surgery referral center in Queensland, Australia. Records were reviewed to identify cases of postoperative surgical site infection, with particular focus on children with infection directly involving implants. Preoperative prophylaxis, microbiology, clinical course and outcomes were analyzed., Results: A total of 580 children underwent 933 procedures during the study period. The most common pathology requiring surgery was idiopathic scoliosis in 257 children (44.3%) followed by neuromuscular scoliosis in 192 children (33.1%). There were 35 cases of surgical site infection (6.03%), and 9 were implant-associated (1.55%). Infection rate among children with neuromuscular spinal deformity was almost 3-fold higher (11.5%) than idiopathic (3.89%). Methicillin-sensitive Staphylococcus aureus was the most commonly isolated organism (n = 15). Four implant-associated infections were successfully managed with retention of implant; all were diagnosed within 32 days (median = 20 days) and cultured either Staphylococcus aureus or Pseudomonas aeruginosa . Conversely, infections that necessitated implant removal had a more indolent onset (median = 175 days), and more often cultured Cutibacterium acnes and coagulase-negative Staphylococci ., Conclusions: Postoperative spinal implant infection can be treated successfully with hardware retention in select cases. Earlier presentation and recognition appear to be associated with better rates of retention and are linked to certain organisms. Further exploration of specific preventative strategies may be key in preventing devastating late-onset infections., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Australia, like many high-income countries, is experiencing a resurgence of infectious syphilis in pregnancy and congenital syphilis. Evaluations of public health notifications and clinical records suggest that healthcare systems may not be providing optimal care to women and their neonates. This study aims to explore the barriers to optimal management of syphilis in pregnancy and congenital syphilis to identify key areas for improvement., Methods: Between 2021 and 2022, 34 healthcare workers (HCW) practicing in south-east Queensland (SEQ) Australia were recruited to complete semi-structured interviews regarding their perceptions towards management of syphilis in pregnancy and congenital syphilis. Interviews were analysed thematically., Results: Thematic analysis identified four themes related to the management of syphilis in pregnancy. These included poor communication between disciplines, services, and teams from delivery through to management and post-delivery, lack of formal internal and external referral pathways, unclear and often complex maternal and congenital syphilis management procedures, and limited HCW knowledge of infectious syphilis in pregnancy and congenital syphilis., Conclusion: As congenital syphilis numbers continue to rise in SEQ, it is imperative that healthcare systems and HCWs identify and address gaps in the provision of health care.

Background: Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumors at high risk of metastasis would have a significant impact on management., Objective: To develop a robust and validated gene expression profile signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach., Methods: Archival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 nonmetastasizing and 86 metastasizing) were collected retrospectively from four centers. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets., Results: A 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk., Limitations: This was a retrospective 4-center study and larger prospective multicenter studies are now required., Conclusion: The 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC., Competing Interests: Conflict of interest Dr Harwood is honoraria for advisory boards from Sanofi/Regeneron, Almirall, AmLo Biosciences, Incanthera, Leo Pharma, L'Oreal. Other authors have no disclosures., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Increasing rates of syphilis in pregnancy (SiP) in Australia and other high-income countries, has led to the resurgence of congenital syphilis. Suboptimal syphilis screening during pregnancy has been identified as a key contributing factor., Methods: This study aimed to explore, from the perspective of multidisciplinary healthcare providers (HCPs), the barriers to optimal screening during the antenatal care (ANC) pathway. Semi-structured interviews conducted with 34 HCPs across multiple disciplines practising in south-east Queensland (SEQ) were analysed through a process of reflexive thematic analysis., Results: Barriers were found to occur at the system level of ANC, through difficulties in patient engagement in care, limitations in the current model of health care delivery and limitations in the communication pathways across health care disciplines; and at the individual HCP level, through HCP knowledge and awareness of epidemiological changes in syphilis in SEQ, and adequately assessing patient risk., Conclusion: It is imperative that the healthcare systems and HCPs involved in ANC address these barriers to improve screening in order to optimise management of women and prevent congenital syphilis cases in SEQ.

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-deficient CRC. Loss of Apc in the mouse intestine was found to be sufficient to drive expression of one of its enzymes, adenosylhomocysteinase (AHCY), which was also found to be transcriptionally upregulated in human CRC. Targeting of AHCY function impaired growth of APC-deficient organoids in vitro, and prevented the characteristic hyperproliferative/crypt progenitor phenotype driven by acute deletion of Apc in vivo, even in the context of mutant Kras. Finally, pharmacological inhibition of AHCY reduced intestinal tumour burden in Apc Min/+ mice indicating its potential as a metabolic drug target in CRC., (© 2023. The Author(s).)

Specific cell types and, therefore, organs respond differently during aging. This is also true for the hematopoietic system, where it has been demonstrated that hematopoietic stem cells alter a variety of features, such as their metabolism, and accumulate DNA damage, which can lead to clonal outgrowth over time. In addition, profound changes in the bone marrow microenvironment upon aging lead to senescence in certain cell types such as mesenchymal stem cells and result in increased inflammation. This heterogeneity makes it difficult to pinpoint the molecular drivers of organismal aging gained from bulk approaches, such as RNA sequencing. A better understanding of the heterogeneity underlying the aging process in the hematopoietic compartment is, therefore, needed. With the advances of single-cell technologies in recent years, it is now possible to address fundamental questions of aging. In this review, we discuss how single-cell approaches can and indeed are already being used to understand changes observed during aging in the hematopoietic compartment. We will touch on established and novel methods for flow cytometric detection, single-cell culture approaches, and single-cell omics., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Purpose of Review: In light of alarming increases in the incidence of congenital syphilis in many middle and higher income countries across the globe, this review summarizes recent changes in the epidemiology of syphilis, highlights recommended changes to testing in pregnancy and provides an update for the management of syphilis infection in pregnancy (SIP) and of the infant born to a mother with SIP., Recent Findings: The re-emergence of congenital syphilis is a result of increasing infectious syphilis in women of childbearing age, which is in turn a result of increasing syphilis in the general population particularly in Indigenous and marginalized populations. Potential reasons for the increase include changing sexual practices and increased travel and migration, as well as factors that limit healthcare access, particularly access to antenatal care and limited awareness and education amongst mothers and maternity services. A single antenatal test for syphilis is insufficient; more frequent testing in pregnancy is necessary even for women deemed to be low risk. The management of SIP and of the newborn is complex and guidelines should be readily available with clear recommendations., Summary: Congenital syphilis is preventable. The current crisis calls for a global and national multipronged, co-ordinated approach involving public health and hospital systems which includes education of individuals and healthcare workers, availability of updated guidelines for prevention and treatment, prioritization of antenatal testing, assurance of accessible and prompt treatment and appropriate assessment and follow-up of infants., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Herpes simplex CNS infection is a rare but important cause of neurological disability. Long term outcomes after HSV CNS infection in Australia have not yet been fully described. We sought to provide a comprehensive review of HSV CNS infection in children using a retrospective 13-year evaluation of statewide laboratory and clinical records and a parent survey conducted at least one year after the initial infection., Methods: All positive PCR HSV 1 and 2 results from cerebrospinal fluid (CSF) or brain tissue were obtained from Queensland pathology providers for children aged 0-16 years between 1 January 2005 and 31 December 2017. Clinical data were obtained from patient records and longer-term outcomes via parent survey at least 1 year after initial infection., Results: Forty-three children were identified over the 13-year period, 17 (39.5%) neonates and 26 (60.4%) non-neonates. The annual incidence for HSV CNS infection in Queensland children aged ≤16 years was 0.3/100 000 (95% confidence intervals (CIs): 0.2-0.4) with neonates at highest risk (incidence 2.5/100 000 live births, 95% CI: 1.5-3.9). HSV 1 was the predominant serotype in both neonates and non-neonates (9/17, 52.9% neonates and 19/26, 73.1% non-neonates). Seven (16.3%) children died, five (5/17, 29.4% neonates), directly attributable to HSV CNS infection (all neonates). Twenty-five (58.1%) had neurological morbidity at discharge (9/17 neonates (52.9%) vs. 16/26 (61.5%) non-neonates) and 20/27 (74.1%) reported long-term neurological morbidity at follow-up (5/9 neonates (55.6%) vs. 15/18 non-neonates (83.3%)). Seven children (two neonates and four non-neonates) with long-term neurological sequelae had no neurological morbidity identified at discharge., Conclusion: Significant long-term neurologic sequelae were seen in children with HSV CNS infection even in children with no neurological disability identified at discharge from hospital. Careful neurodevelopmental follow-up of all children is recommended., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Objectives: The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration., Methods: A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort., Results: 353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2])., Conclusion: From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management., Competing Interests: Declaration of Competing Interest P.A.B. reports grants from National Health and Medical Research Council, Medical Research Futures Fund and Murdoch Children's Research Institute outside the submitted work and travel funds from the Royal Children's Hospital. S.O. has acted on an advisory board for CSL-Behring. All remaining authors have no reported conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: None declared.

We describe 4 cases of cutaneous leishmaniasis in children in Australia. Treatment is challenging given lack of firm guidelines and limited access to conventional modalities used in endemic countries. Topical paromomycin or oral fluconazole were effective outpatient-based first-line treatments, however, topical paromomycin use was limited by expense to import or compound locally., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood., Methods: ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017-2018)., Results: Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8; 95% confidence interval [CI], 1.6-296.9), multifocal infection (aOR, 22.6; CI, 1.4-498.5), necrotizing pneumonia (aOR, 38.9; CI, 1.7-1754.6), multiorgan dysfunction (aOR, 26.5; CI, 4.1-268.8), and empiric vancomycin (aOR, 15.7; CI, 1.6-434.4); while infectious diseases (ID) consultation (aOR, 0.07; CI .004-.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival; however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1; 95% CI 1.3-8.1)., Conclusions: High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity; therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Syphilis in pregnancy and congenital syphilis (CS) are increasing in Australia. Prevention of adverse outcomes requires adherence to management guidelines., Aims: The aim is to evaluate the management of syphilis in pregnant women and their newborns., Materials and Methods: A retrospective study of public health notifications, clinical records and testing results of women with positive syphilis serology in pregnancy requiring treatment from 2016 to 2018 inclusive across South-East Queensland was conducted. Management was described and compared with contemporary guidelines from the Australasian Society of Infectious Diseases, the Communicable Diseases Network Australia and the United States Centers for Disease Control and Prevention., Results: Of 30 women identified, 22 (73%) had management consistent with the guidelines (stage-appropriate penicillin regimen, appropriate dosing interval and treatment completed greater than 30 days before delivery). Only 14 (47%) women had documentation of partner testing and/or treatment. Of 26 mother-infant pairs with complete data, 16 (62%) had investigations at delivery consistent with recommendations (parallel maternal-infant rapid plasma reagin, infant syphilis immunoglobulin M, placental histopathology +/- syphilis polymerase chain reaction and infant clinical examination). One infant met the criteria for confirmed CS. Five infants received penicillin therapy. Only seven (27%) infants had serological monitoring after discharge., Conclusions: Management can be optimised with timely maternal testing and treatment, comprehensive partner screening and treatment, strict adherence to seven-day penicillin dosing for late latent syphilis and thorough maternal and infant testing after treatment and delivery. If maternal treatment was inadequate in pregnancy, consideration needs to be given to close evaluation and empiric treatment of the infant., (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)