Management of the infant born to a mother with tuberculosis: a systematic review and consensus practice guideline.

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.

Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

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.

Implant-associated Infection After Pediatric Spine Deformity Surgery: Is Removal of Hardware Indicated?

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.

Barriers to optimal management of syphilis in pregnancy and congenital syphilis in south-east Queensland: a qualitative investigation.

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.

Syphilis in pregnancy: a qualitative investigation of healthcare provider perspectives on barriers to syphilis screening during pregnancy in south-east Queensland.

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.

New trends in congenital syphilis: epidemiology, testing in pregnancy, and management.

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.

Epidemiology and long-term neurological sequelae of childhood herpes simplex CNS infection.

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.

Whole genome sequencing and molecular epidemiology of paediatric Staphylococcus aureus bacteraemia.

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.

Treatment of Cutaneous Leishmaniasis in a Nonendemic Country: A Case Series of Children in Australia.

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.

Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome.

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.

Addressing the crisis of congenital syphilis: Key findings from an evaluation of the management of syphilis in pregnancy and the newborn in South-East Queensland.

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.

The role of Kingella kingae in pre-school aged children with bone and joint infections.

OBJECTIVES: The Pre-school Osteoarticular Infection (POI) study aimed to describe the burden of disease, epidemiology, microbiology and treatment of acute osteoarticular infections (OAI) and the role of Kingella kingae in these infections. METHODS: Information about children 3-60 months of age who were hospitalized with an OAI to 11 different hospitals across Australia and New Zealand between January 2012 and December 2016 was collected retrospectively. RESULTS: A total of 907 cases (73%) were included. Blood cultures grew a likely pathogen in only 18% (140/781). The peak age of presentation was 12 to 24 months (466/907, 51%) and Kingella kingae was the most frequently detected microorganism in this age group (60/466, 13%). In the majority of cases, no microorganism was detected (517/907, 57%). Addition of PCR to culture increased detection rates of K. kingae. However, PCR was performed infrequently (63/907, 7%). CONCLUSIONS: This large multi-national study highlights the need for more widespread use of molecular diagnostic techniques for accurate microbiological diagnosis of OAI in pre-school aged children. The data from this study supports the hypothesis that a substantial proportion of pre-school aged children with OAI and no organism identified may in fact have undiagnosed K. kingae infection. Improved detection of Kingella cases is likely to reduce the average length of antimicrobial treatment.

Infective Endocarditis in Children in Queensland, Australia: Epidemiology, Clinical Features and Outcome.

BACKGROUND: Infective endocarditis (IE) is a rare entity in children associated with significant morbidity and mortality. To optimize management, it is important to understand local epidemiology, risk factors, clinical features and outcome. These are investigated in this retrospective 10-year study of endocarditis in children in Queensland. METHODS: Children <18 years with IE were identified from the state-wide pediatric cardiology center (Mater Children's Hospital, 2009-2014; Queensland Children's Hospital, 2014-2018) through International Classification of Diseases codes and local cardiology database. Clinical records were assessed by a clinician and echocardiograms by a cardiologist. Incidence was calculated using Australian Bureau of Statistics Queensland Estimated Resident Population data, 2019. RESULTS: Fifty-one children were identified, with an overall estimated incidence of 0.84 per 100,000 per year; 0.69 per 100,000 in 2009-2013 and 0.99 per 100,000 in 2014-2018, respectively. Twenty-four (47.1%) children were male and 10 (19.6%) were identified as Aboriginal or Torres Strait Islander peoples. Underlying cardiac conditions were present in 29 (56.9%): 25 congenital heart disease, 3 rheumatic heart disease and 1 cardiomyopathy. A causative pathogen was identified in 46 (90.2%) children with Staphylococcus aureus most common. Thirty-six (70.6%) met criteria for "Definite IE" as per modified Duke criteria, with the remainder "Possible IE." Surgery was required in 26 (51%). Median duration of antibiotics was 42 (interquartile range = 32-51) days and hospitalization 49 (interquartile range = 34-75) days. One child died due to IE. CONCLUSIONS: IE in children in Queensland is increasing in incidence and is higher than the reported incidence in New Zealand and the United States. Congenital heart disease is the most common risk factor and S. aureus is the commonest responsible organism. Aboriginal or Torres Strait Islander children are over-represented. Mortality remains low.

Herpes Simplex Virus Infection in Infants: 13 Year Evaluation (2005-2017) of Laboratory Confirmed Cases in Queensland, Australia.

BACKGROUND: National neonatal surveillance for herpes simplex virus (HSV) disease suggests that the incidence of HSV disease may be higher in Queensland (QLD) than in other Australian States. We sought to investigate the incidence via a retrospective 13-year evaluation of statewide laboratory data, autopsy data and linked clinical records of infants with laboratory confirmed infection. METHODS: All positive polymerase chain reaction HSV 1 and 2 results were obtained for infants 0-3 months of age from January 1, 2005 to December 31, 2017. Clinical data were obtained from patient records and parent questionnaires were used to evaluate long-term sequelae. RESULTS: One hundred seventy-two infants with HSV positive polymerase chain reaction results: 121 (70.3%) with HSV 1. Of 104 (60.5%) infants with signs of HSV disease, 76 (73.1%) were neonates (≤28 days of age) [incidence 9.6 (95% confidence interval, 7.0-11.5) per 100,000 live births] and 28 (26.9%) were young infants (29-90 days of age) [3.6 (95% confidence interval, 2.4-5.4) per 100,000 live births]. The annual incidence of neonatal HSV disease increased significantly in Queensland over the study period (P < 0.01). Of the 76 neonates with HSV disease, 58 (76.3%) presented with the skin, eye, mouth (SEM) disease, 17 (22.4%) with HSV encephalitis and 11 (14.5%) had disseminated disease. Young infants presented with HSV skin, eye, mouth disease (21, 75.0%) or HSV encephalitis (6, 21.4%). Death occurred in 12/104 (11.5%) infants (all neonates) with 10 attributable to HSV disease. CONCLUSION: The incidence of neonatal HSV disease in QLD is almost 3 times the national reported incidence. Further research is being undertaken to explore reasons for this change and implications for practice.

Anti-NMDA-receptor Encephalitis in an Adolescent With HIV Infection and Review of the Literature.

Anti-N-Methyl-D-Aspartate-receptor encephalitis is the most common antibody-mediated autoimmune encephalopathy. A HIV-infected African boy presented with subacute psychosis as manifestation of anti-N-Methyl-D-Aspartate-receptor encephalitis. Intravenous immunoglobulin and corticosteroids induced complete remission. Although this is the first pediatric case described, 5 adult cases have been reported. The role of HIV in the etiology of this autoimmune condition requires further exploration.

Two cases of neuroangiostrongyliasis: A rare disease because rarely considered or rarely diagnosed?

AIM: The rat lungworm, Angiostrongylus cantonensis, is well established in eastern Australia, where it is the almost exclusive cause of human eosinophilic meningoencephalitis (EME). While neuroangiostrongyliasis can result in severe morbidity or death, its diagnosis requires a high index of clinical suspicion among medical practitioners. Prevention requires a high level of public awareness. METHODS: We report two cases of EME in children from Queensland and summarise all reported Australian cases from the literature. We discuss the pathogenesis of neuroangiostrongyliasis, with particular reference to the timing of prophylaxis and treatment. RESULTS: A 5-year-old girl developed severe headache, eosinophilic meningitis and abnormal neuroimaging following a holiday to Bali. A 10-year-old boy with Rubinstein-Taybi syndrome, marked developmental delay and pica developed EME following ingestion of a snail, resulting in long-term morbidity. From 1971 to 2018, 28 Australian cases have been reported, with acquisition restricted to Southeast Queensland and New South Wales. Ages ranged from 10 months to 45 years; most were male and most likely acquired infection from consuming unwashed lettuce or vegetables. The mortality rate was 18%; most fatalities occurred in children <1 year old. Long-term neurological deficit was reported in 14% of cases and a full recovery in 57% of cases. CONCLUSIONS: Heightened medical and public awareness of the parasite is required to prevent infection and subsequent disease. A better understanding of the efficacy of prophylactic anthelmintic following ingestion or handling of molluscs and further studies of epidemiology of this parasite will inform and facilitate public health recommendations.