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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).)

Aim: We aimed to determine the cost and potential cost-savings of delivering a targeted congenital cytomegalovirus (cCMV) screening programme through a universal newborn hearing screening (UNHS) programme to detect cCMV-related hearing loss in infants from Victoria, Australia., Methods: We completed a micro-costing analysis from a health-care perspective using data from a targeted cCMV screening programme piloted between June 2019 and March 2020. The programme involved collection of saliva samples to test for cCMV in infants who: received a 'refer' result on their second newborn hearing screen; were aged 21 days or less; and born at one of four maternity hospitals in Victoria, Australia. All costs to complete targeted cCMV screening were recorded in Australian 2020 dollars. Potential costs and benefits of adding targeted cCMV screening to the pre-existing UNHS programme were compared to when no screening was available up to 18 years to determine the likely cost or cost savings., Results: The cost of adding targeted cCMV screening to Victoria's UNHS is $202 per infant screened. The total cost per positive case identified is $21 456. The overall cost of adding targeted salivary cCMV screening at the point of a second 'refer' result on the UNHS programme in Victoria's four largest hospitals is estimated to be $28 966 for the first year., Conclusion: Targeted screening for cCMV provides families the opportunity to detect and, if appropriate, treat cCMV in the first month of life in line with current recommendations. It falls within the range between cost neutral and cost saving., (© 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).)

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).)

Aim: This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated., Methods: The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019-March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive ('refer') result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of 'referred' infants whose parents completed the salivary CMV screening test ≤21 days of life. Acceptability was measured through parent survey., Results: Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken ≤21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32., Conclusions: Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Pharyngeal high-resolution manometry (HRM) has emerged over the last decade as a valuable assessment tool for oropharyngeal dysphagia. Data analysis thus far has focused primarily on measures of pressure and duration within key anatomic regions. We apply spectral arc length (SPARC), a dimensionless metric for quantifying smoothness felt to indirectly reflect neuromuscular coordination, as a new method of describing manometric curves. We then use it to distinguish swallows from healthy subjects and those with dysphagia related to stroke., Methods: Previously collected pharyngeal HRM data from eight subjects with history of stroke and eight age- and sex-matched controls were reviewed. Receiver operating characteristic (ROC) analysis was used to optimize SPARC inputs. SPARC was then computed for the velopharynx, tongue base, hypopharynx, and upper esophageal sphincter (UES), and the values were compared between the two subject groups., Results: Optimized parameter settings yielded an ROC curve with area under the curve (AUC) of 0.953. Mean SPARC values differed between control and stroke subjects for the velopharynx (t = 3.25, p = 0.0058), tongue base (t = 4.77, p = 0.0003), and hypopharynx (t = 2.87, p = 0.0124). Values were similar for the UES (t = 0.43, p = 0.671)., Conclusions: In this preliminary study, SPARC analysis was applied to distinguish control from post-stroke subjects. Considering alternative methods of analyzing pharyngeal HRM data may provide additional insight into the pathophysiology of dysphagia beyond what can be gleaned from measures of pressure and duration alone., (© 2021 John Wiley & Sons Ltd.)

Background: Parkinson's disease (PD) can cause severe dysphagia, especially later in disease progression. Early identification of swallowing dysfunction may lead to earlier intervention. Pharyngeal high-resolution manometry (HRM) provides complementary information to videofluoroscopy, with advantages of being quantitative and objective. Artificial neural network (ANN) classification can examine non-linear relationships among multiple variables with relatively low bias. We evaluated if ANN techniques could differentiate between patients with PD and healthy controls., Methods: Simultaneous videofluoroscopy and pharyngeal HRM were performed on 31 patients with early to mid-stage PD and 31 age- and sex-matched controls during thin-liquid swallows of 2 cc, 10 cc and comfortable sip volume. We performed multilayer-perceptron analyses on only videofluoroscopic data, only HRM data or a combination of the two. We also evaluated variability-based parameters, representing variability in manometric parameters across multiple swallows. We hypothesized that patients with PD and controls would be classified with at least 80% accuracy, and that combined videofluoroscopic and HRM data would classify participants better than either alone., Key Results: Classification rates were highest with all parameters considered. Maximum classification rate was 82.3 ± 5.2%, recorded for 2 cc swallows. Inclusion of variability-based parameters improved classification rates. Classification rates using only manometric parameters were similar to those using all parameters, and rates were substantially lower for the comfortable sip volumes., Conclusions & Inferences: Results from these classifications highlight the differences between swallowing function in patients with early and mid-stage PD and healthy controls. Early identification of swallowing dysfunction is key to developing preventative swallowing treatments for those with PD., (© 2017 John Wiley & Sons Ltd.)

Aim: The human parechovirus (HPeV) is an increasingly recognised cause of sepsis and central nervous system infection in young infants for which there are limited long-term outcome data. We aimed to assess neurodevelopmental outcome and quality of life in infants following hospitalised HPeV infection., Methods: This cohort study was a 12-month follow-up of infants who were hospitalised with confirmed HPeV infection at the Sydney Children's Hospitals Network during an outbreak in Sydney in 2013. Telephone interviews were conducted with parents/guardians. We administered standardised questionnaires, including: Ages and Stages Questionnaire (ASQ), Liverpool Outcome Score-follow-up, Pediatric Quality of Life Inventory(PedsQL) Infant scales and Short-Form health survey (SF-12)., Results: We followed up 46 of 79 infants (58%) aged between 12 and 16 months who had been hospitalised with HPeV infection; 19% showed significant concern in developmental attainment (ASQ3 score <2 standard deviation below population mean), and 50% showed some concern (<1 standard deviation below mean). ASQ3 developmental outcome was associated with the presence of neurodevelopmental sequelae (lower total Liverpool Outcome Score) and poorer health-related quality of life (HRQOL) in physical functioning (PedsQL physical component score), but not overall HRQOL (total PedsQL score) or parental HRQOL (SF-12 scores). No significant associations were identified between clinical or laboratory features during acute hospitalisation and adverse outcome on ASQ3., Conclusions: A high proportion of infants show developmental concern at 12-month follow-up post-hospitalisation with HPeV infection. Clinical features during hospitalisation were not associated with adverse outcomes at 12 months. These results suggest that careful follow-up of young infants hospitalised with HPeV disease may be warranted., (© 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Aim: An estimated 1.1% of Australian adults are infected with hepatitis C virus (HCV). Many develop chronic liver disease, and some develop liver failure or hepatocellular carcinoma. HCV infection in Australian children is poorly defined. We aimed to determine the reported incidence, clinical and epidemiological features of newly diagnosed HCV infection in Australian children presenting to paediatricians., Methods: We undertook prospective active national surveillance, using the Australian Paediatric Surveillance Unit, of incident HCV cases in children aged <15 years between 1(st) January 2003, and 31(st) December 2007., Results: There were 45 confirmed cases of newly diagnosed HCV infection over five years (<1 per 100,000 children aged <15 years per year). Median age at diagnosis was 2.9 years. Positive maternal HCV serostatus was the most frequent reported risk factor for HCV infection in children (40/45). Three children (all aged > 14), were exposed through their own IV drug use. No children were co-infected with HIV and only one child was co-infected with HBV. All children were asymptomatic at diagnosis, although many had minor elevations in liver transaminases. Many clinicians reported difficulties with follow-up., Conclusions: Childhood HCV infection is uncommon in Australia, although our data likely underestimate the incidence. Only a small number of children aged <18 months was identified, despite known perinatal exposure. Opportunistic investigation of children at risk for HCV, improved education regarding vertical transmission for health care providers, and increased coordination of childhood HCV services are required to improve recognition and management of children with HCV., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Aim: Cytomegalovirus (CMV) is an important cause of congenital infection, which can result in neonatal deaths or contribute to deaths in later childhood. Post-natally acquired CMV is a less common cause of disease and mortality, and only in preterm infants or immunocompromised children. Here we sought to describe CMV as a direct or secondary contributor to childhood mortality in Australia., Method: We searched national mortality data sets between1999 and 2011 for cases <15 years with CMV recorded as an underlying or contributing cause of death., Results: Eighty-three CMV-associated deaths in children <15 years were identified (0.2 cases per 100 000 <15 years; 95% confidence interval 0.16-0.24). Childhood deaths associated with CMV were evenly distributed between males and females, and the majority (n = 57; 68%) occurred in children less than 12 months of age, with 22 cases <1 month of age. Over the 13-year study period, the mortality rate remained stable and CMV resulted in an estimated age-adjusted 5925 years of potential life lost., Conclusions: CMV makes a small but important contribution to childhood mortality in Australia. Most CMV-related deaths occurred in infants <12 months of age. These infant deaths may be an indirect marker of the burden of severe intrauterine CMV disease given the natural history of this infection., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Encephalitis is a complex neurological syndrome caused by inflammation of the brain that occurs with highest incidence in children. It is challenging to diagnose and manage due to the variety of aetiologies and non-specific clinical presentations. We discuss the recent progress in clinical case definitions; review recent, large, prospective epidemiological studies; and describe aetiologies. We emphasise infectious causes relevant to children in Australasia but also consider emerging immune-mediated syndromes responsive to immune therapies. We identify priorities for future research in children, given the potential for climate change and international travel to influence the emergence of infectious agents in our region., (© 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background/hypothesis: Teaching hospitals affiliated with universities are now common sites for research higher degree supervision. We hypothesised that the hospital environment poses unique challenges to supervision compared with the traditional university research institute setting., Aims: This study aimed to identify and rank important supervision issues in a clinical setting from the students' perspective., Methods: Using the Delphi method to explore issues and facilitate consensus, small group discussions were conducted with 10 research doctoral students from a tertiary teaching hospital., Results: We identified supervision issues that are unique to the hospital-based context. These include the demands placed on supervisors combining clinical and supervisory roles, the challenges of academic medical/scientific writing and career issues for students who are already established in their professions. Other issues identified, common to all doctoral students, include differing expectations between students and supervisors (with students wanting support for their career plans, training in research skills and increasing autonomy and responsibility), supervisor access, quality and frequency of meetings, lack of training in writing and dealing with conflicts., Conclusion: Our research identified that postgraduate students of supervisors who combine clinical and supervisory roles report significant issues with supervision, some of which are unique to the clinical setting. Clinician researchers who supervise postgraduate students need to balance clinical and supervisory responsibilities, identify and negotiate student expectations early in candidature and provide career counselling to students who are already highly experienced. Furthermore, clinician supervisors should undertake postgraduate supervisor training programme tailored to the hospital setting to better support their students., (© 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Objective: Home visiting programs for very young children seek to promote their health and development. We conducted a process and outcome evaluation of the Postpartum/Newborn Home Visit (PPNBHV) service in 1 county., Design: A retrospective study of Aiken County Health records of live infant births in 2004 was conducted., Sample: A random sample of 176 infants who were born in 2004 and enrolled in the women, infants, and children's (WIC) program in the same year was selected., Measures: Process measures include timeliness of the home visit, and appropriateness of revisits. Outcome measures include age at WIC enrollment and immunization status at 6/9 months., Results: Of the 176 infants, 76 (43%) received a home visit. Of these, 13 (17%) received the visit within the stipulated time frame. After controlling for potential confounders, infants who received a home visit were 4 times (95% CI 1.92-8.36) as likely to enroll early in the WIC program compared with those who did not., Conclusion: The PPNBHV service may contribute to early enrollment in the WIC program. Improvement in the timeliness of the visits is needed. Program monitoring and evaluation are necessary to ensure adherence, measure outcomes, and provide feedback for continuous quality improvement.

The mother of a baby on the neonatal intensive care unit was found to have untreated open pulmonary tuberculosis. Tuberculin skin testing and chemoprophylaxis was offered to selected mothers and babies, depending on level of exposure. One of 3 mothers sharing a room with the index mother and 2 of 20 mothers whose babies were on the neonatal unit subsequently converted to tuberculin and were given isoniazid chemoprophylaxis. Isoniazid chemoprophylaxis was given to 13 exposed babies, none of whom tuberculin converted. Two babies were treated empirically for tuberculosis.

Breast milk provides a superior source of nutrition and many other health benefits to the newborn infant. However, breastfeeding has also been recognized as a route of transmission to the newborn of some important pathogens that may result in disease. In the present article, up-to-date research and recommendations on the maternal transmission of infectious pathogens in breast milk or by breastfeeding are discussed in the context of local epidemiology and in the setting of an industrialized country.

There has been increasing interest in the possibility that the mother has an important role to play in influencing the development of fetal and infant immune responses to allergens during gestation. This finding, by several groups, of specific immune responses of infants at birth to individual trigger factors associated with an underlying immaturity of cytokine production, is intriguing in the light of the development of subsequent allergic disease. The interactions between mother, placenta and fetus are now forming a focus for ongoing research and may be a potential target for intervention aimed at preventing allergic asthma.

Interleukin-4 (IL-4), like interferon-gamma (IFN-gamma), stimulates monocyte major histocompatibility complex (MHC) class II expression and thus, by increasing antigen presentation, has the potential to increase immune reactivity. In this study, activation of human monocytes by lipopolysaccharide (LPS) prevented concomitant IL-4 stimulation of MHC class II expression. However, this was not a general observation for activated monocytes because although the high levels of MHC class II antigen expressed by monocytes stimulated in vitro with IFN-gamma were not further regulated by IL-4, the stimulatory effects of IL-4 persisted on cells activated with granulocyte macrophage colony-stimulating factor and tumour necrosis factor-alpha for enhanced MHC class II expression. MHC class II expression by monocytes cultured for 7 days with macrophage colony-stimulating factor was regulated by IL-4 and LPS in a manner very similar to that detected for freshly isolated monocytes. The inhibitory effect of LPS was not due to LPS-induced production of IL-10 or regulatory prostanoids. Furthermore, IFN-gamma-increased MHC class II expression was suppressed by LPS, suggesting that the regulation was at the level of MHC class II expression per se. This study suggests that during Gram-negative bacterial infections, IL-4 and IFN-gamma may not be able to signal enhanced MHC class II expression and thus, enhanced immune reactivity.

Air-dried material normally submitted for Diff-Quik (modified Romanowsky stain) was rehydrated in normal saline, then fixed for a short period in formol alcohol, before staining by a modified Papanicolaou technique. Staining was performed by a rapid manual technique (< 2 min) if urgent or routinely on an automatic stainer. Comparisons were made between wet-fixed Papanicolaou-stained specimens and air-dried Papanicolaou-stained material. Air-dried material stained after rehydration showed superior nuclear definition compared with wet-fixed material; the removal of erythrocytes enhanced the staining of the remaining epithelial cells.

The prognosis of babies with symptomatic congenital cytomegalovirus (CMV) infection is worse than for those with asymptomatic CMV, but is difficult to quantify. Babies affected as a result of primary maternal CMV are at greater risk than after reactivation CMV. Chorioretinitis occurs in 10-15% of symptomatic babies and almost always indicates significant mental impairment. Microcephaly occurs in around 50% at birth, but does not always persist, and does not necessarily imply later neurological handicap. Investigative findings that increase the likelihood of handicap include radiographic or computerized tomography scan finding of intracranial calcification and raised cerebrospinal fluid protein. Late deafness is always unpredictable and all babies with congenital CMV infection should have an audiological follow up. The mortality of symptomatic congenital CMV infection is about 30%.

The molecular mechanisms by which human interleukin-4 (IL-4) down-regulates tumour necrosis factor-alpha (TNF-alpha) production by monocytes remain unknown. Other studies of IL-4 action in B lymphocytes and large granular lymphocytes (LGL) suggested that IL-4 may suppress mediator production by augmenting intracellular cyclic AMP (cAMP) levels. However, this study did not find evidence for involvement of a cAMP-dependent signalling pathway for expression of IL-4 activity in monocytes. IL-4 reduced TNF-alpha production by monocytes when IL-4 and lipopolysaccharide (LPS) were added concomitantly, or upon subsequent activation by LPS 16 hr after first exposure to IL-4. The continued presence of IL-4 at the time of LPS stimulation was not necessary; however, the suppressive effects of IL-4 were dependent on protein synthesis. This sustained activity of IL-4 for down-regulation of the production of inflammatory signals may be important for control in vivo of excessively activated monocytes/macrophages, and in therapy.

This study investigated whether enhanced metabolic responsiveness to beta-adrenergic stimulation might explain the liability of the stress-sensitive pig to develop an acidosis during stressful situations. Blood lactate, pH, PCO2 and heart rate response to an intravenous infusion of isoprenaline were examined in three lines of pentobarbitone anaesthetized, atropinized pigs. The lines were Pietrain X Hampshire which had been selected over eight generations for a positive reaction to the halothane test (stress-sensitive); Pietrain X Hampshire which had been selected over eight generations for no reaction to the halothane test (stress-resistant) and British Landrace which had been selected over four generations for a positive halothane reaction (stress-sensitive). The metabolic responses to isoprenaline were greater in the stress-sensitive Pietrain X Hampshire line than the stress-resistant line. The stress-sensitive Landrace pigs, however, had smaller changes in pH and PCO2 in response to isoprenaline than the stress-resistant Pietrain X Hampshire pigs. This inconsistent trend across the three lines led to the conclusion that enhanced beta-adrenergic responsiveness was not the likely cause of stress sensitivity.