Background: An increasing body of evidence supports associations between inflammation and mental health difficulties, but the onset and directionality of these relationships are unclear.Methods: Data sources: Barwon Infant Study (BIS; n = 500 4-year-olds) and Longitudinal Study of Australian Children (LSAC; n = 1099 10-13-year-olds).Measures: Strengths and Difficulties Questionnaire emotional symptoms at 4, 10-11 and 12-13 years, and circulating levels of two inflammatory biomarkers, high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), at 4 and 11-12 years. Analysis: Adjusted quantile regression models examining cross-sectional associations between emotional symptoms and inflammation in 4 year-olds (BIS), and cross-lagged associations in 10-13-year-olds (LSAC).Results: We identified a small association between higher emotional symptoms at 10-11 years and higher GlycA levels a year later (standardised coefficient 13 = 0.09; 95%CI: 0.02 to 0.15). Sex-stratified analyses revealed this association was stronger for boys (13 = 0.13; 95%CI: 0.04 to 0.21) than girls (13 = 0.01; 95%CI:-0.09 to 0.11). These associations were not observed for hsCRP. There was little evidence of an association between higher GlycA or hsCRP at 11-12 years and emotional symptoms a year later, or cross-sectional associations between emotional symptoms and hsCRP or GlycA at 4 years.Limitations: A single time-point of biomarker collection in late childhood precluded adjustment for baseline inflammatory biomarkers.

Journal of Paediatrics and Child HealthVolume 59, Issue 10 p. 1175-1177 Case Report Simultaneous diagnosis of primary adrenal insufficiency and Type 1 diabetes mellitus Tahlia Espenschied, Tahlia Espenschied Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, AustraliaSearch for more papers by this authorRobyn Lawford, Robyn Lawford Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, AustraliaSearch for more papers by this authorMargaret Zacharin, Margaret Zacharin Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia Department of Endocrinology, Royal Children's Hospital, Parkville, Victoria, AustraliaSearch for more papers by this authorLawrence EK Gray, Corresponding Author Lawrence EK Gray [email protected] Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia Correspondence: Dr Lawrence Gray, Women's and Children's Services, Barwon Health, University Hospital, Ryrie Street Geelong, Vic., Australia. email:[email protected]Search for more papers by this author Tahlia Espenschied, Tahlia Espenschied Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, AustraliaSearch for more papers by this authorRobyn Lawford, Robyn Lawford Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, AustraliaSearch for more papers by this authorMargaret Zacharin, Margaret Zacharin Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia Department of Endocrinology, Royal Children's Hospital, Parkville, Victoria, AustraliaSearch for more papers by this authorLawrence EK Gray, Corresponding Author Lawrence EK Gray [email protected] Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia Correspondence: Dr Lawrence Gray, Women's and Children's Services, Barwon Health, University Hospital, Ryrie Street Geelong, Vic., Australia. email:[email protected]Search for more papers by this author First published: 28 August 2023 https://doi.org/10.1111/jpc.16482 Conflict of interest: None declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Cooke DW, Plotnick L. Type 1 diabetes mellitus in pediatrics. Pediatr. Rev. 2008; 29: 374–384. 2Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881–1893. 3Bornstein SR, Allolio B, Arlt W et al. Diagnosis and treatment of primary adrenal insufficiency: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metabol. 2016; 101: 364–389. 4Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: Autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr. Rev. 2002; 23: 327–364. 5Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N. Engl. J. Med. 2004; 350: 2068–2079. 6Betterle C, Lazzarotto F, Presotto F. Autoimmune polyglandular syndrome type 2: The tip of an iceberg? Clin. Exp. Immunol. 2004; 137: 225–233. 7Elbelt U, Hahner S, Allolio B. Altered insulin requirement in patients with type 1 diabetes and primary adrenal insufficiency receiving standard glucocorticoid replacement therapy. Eur. J. Endocrinol. 2009; 160: 919–924. 8Chantzichristos D, Eliasson B, Johannsson G. Disease burden and treatment challenges in patients with both Addison's disease and type 1 diabetes mellitus. Eur. J. Endocrinol. 2020; 183: R1–R11. Volume59, Issue10October 2023Pages 1175-1177 ReferencesRelatedInformation

Background: The mechanisms underlying the protective effect of older siblings on allergic disease remain unclear but may relate to the infant gut microbiota.Objective: We sought to investigate whether having older siblings decreases the risk of IgE-mediated food allergy by accelerating the maturation of the infant gut microbiota. Methods: In a birth cohort assembled using an unselected antenatal sampling frame (n = 1074), fecal samples were collected at 1 month, 6 months, and 1 year, and food allergy status at 1 year was determined by skin prick test and in-hospital food challenge. We used 16S rRNA gene amplicon sequencing to derive amplicon sequence variants. Among a random subcohort (n = 323), microbiota-by-age z scores at each time point were calculated using fecal amplicon sequence variants to represent the gut microbiota maturation over the first year of life.Results: A greater number of siblings was associated with a higher microbiota-by-age z score at age 1 year (b = 0.15 per an additional sibling; 95% CI, 0.05-0.24; P = .003), which was in turn associated with decreased odds of food allergy (odds ratio, 0.45; 95% CI, 0.33-0.61; P < .001). Microbiota-by-age z scores mediated 63% of the protective effect of siblings. Analogous associations were not observed at younger ages.Conclusions: The protective effect of older siblings on the risk of developing IgE-mediated food allergy during infancy is substantially mediated by advanced maturation of the gut microbiota at age 1 year.

Early childhood is characterised by repeated infectious exposures that result in inflammatory responses by the innate immune system. In addition, this inflammatory response to infection is thought to contribute to the epidemiological evidence linking childhood infection and adult non-communicable diseases. Consequently, the relationship between innate immune responses and inflammation during early life may inform prevention of NCDs later in life. In adults, non-genetic host factors such as age, sex, and obesity, strongly impact cytokine production and circulating mediators, but data in children are lacking. Here, we assessed cytokine responses and inflammatory markers in a population of healthy preschool children (mean age 4.2 years). We studied associations between cytokines, plasma inflammatory markers and non-genetic host factors, such as sex, age, adiposity, season, and immune cell composition. Similar to adults, boys had a higher inflammatory response than girls, with IL-12p70 and IL-10 upregulated following TLR stimulation. Adiposity and winter season were associated with increased circulating inflammatory markers but not cytokine production. The inflammatory markers GlycA and hsCRP were positively associated with production of a number of cytokines and may therefore reflect innate immune function and inflammatory potential. This dataset will be informative for future prospective studies relating immune parameters to preclinical childhood NCD phenotypes.

Environmental factors can accelerate telomere length (TL) attrition. Shortened TL is linked to attention deficit/hyperactivity disorder (ADHD) symptoms in school-aged children. The onset of ADHD occurs as early as preschool-age, but the TL-ADHD association in younger children is unknown. We investigated associations between infant TL and ADHD symptoms in children and assessed environmental factors as potential confounders and/or mediators of this association. Relative TL was measured by quantitative polymerase chain reaction in cord and 12-month blood in the birth cohort study, the Barwon Infant Study. Early life environmental factors collected antenatally to two years were used to measure confounding. ADHD symptoms at age two years were evaluated by the Child Behavior Checklist Attention Problems (AP) and the Attention Deficit/Hyperactivity Problems (ADHP). Associations between early life environmental factors on TL or ADHD symptoms were assessed using multivariable regression models adjusted for relevant factors. Telomere length at 12 months (TL12), but not at birth, was inversely associated with AP (β = −0.56; 95% CI (−1.13, 0.006); p = 0.05) and ADHP (β = −0.66; 95% CI (−1.11, −0.21); p = 0.004). Infant secondhand smoke exposure at one month was independently associated with shorter TL12 and also higher ADHD symptoms. Further work is needed to elucidate the mechanisms that influence TL attrition and early neurodevelopment.

Background Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally. Objective We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age. Methods A birth cohort (n = 1074) with information on prenatal and postnatal early life factors. Both naive Treg (nTreg) and activated Treg (aTreg) cell populations (as a proportion of CD4(+) T cells) were available in 463 infants at birth (cord blood), 600 at 6 months, and 675 at 12 months. 191 infants had serial measures. Measures of allergic status at 12 months were polysensitization (sensitization to 2 or more allergens), clinically proven food allergy, atopic eczema, and atopic wheeze. Results Infants born to larger households (3 or more residents) had higher longitudinal nTreg proportions over the first postnatal year with a mean difference (MD) of 0.67 (95% CI 0.30-1.04)%. Higher nTreg proportions at birth were associated with a reduced risk of infant allergic outcomes. Childcare attendance and breastfeeding were associated with higher longitudinal nTreg proportions (MD 0.48 (95% CI 0.08-0.80)%. Conclusion Multiple prenatal and postnatal microbial factors are associated with nTreg and aTreg development. Larger household size was associated with higher nTreg at birth which in turn was associated with reduced allergic sensitization and disease at 12 months of age.

Environmental exposures during pregnancy that alter both the maternal gut microbiome and the infant's risk of allergic disease and asthma include a traditional farm environment and consumption of unpasteurized cow's milk, antibiotic use, dietary fiber, and psychosocial stress. Multiple mechanisms acting in concert may underpin these associations and prime the infant to acquire immune competence and homeostasis following exposure to the extrauterine environment. Cellular and metabolic products of the maternal gut microbiome can promote the expression of microbial pattern recognition receptors, as well as thymic and bone marrow hematopoiesis relevant to regulatory immunity. At birth, transmission of maternally derived bacteria likely leverages this in utero programming to accelerate postnatal transition from a TH2- to TH1- and TH17-dominant immune phenotype and maturation of regulatory immune mechanisms, which in turn reduce the child's risk of allergic disease and asthma. Although our understanding of these phenomena is rapidly evolving, the field is relatively nascent, and we are yet to translate existing knowledge into interventions that substantially reduce disease risk in humans. Here, we review evidence that the maternal gut microbiome impacts the offspring's risk of allergic disease and asthma, discuss challenges and future directions for the field, and propose the hypothesis that maternal carriage of Prevotella copri during pregnancy decreases the offspring's risk of allergic disease via production of succinate, which in turn promotes bone marrow myelopoiesis of dendritic cell precursors in the fetus.

A bstract Chronic respiratory diseases are often difficult to cure and are likely to originate early in life. Therefore, early identification of such diseases is of interest for early prevention. We explored the potential to predict these almost from birth; using data at 1 month of age, we attempted to predict disease occurrence 4 years later in life. Our data came from the Barwon Infant Study; after cleaning and processing, we had measurements on 41 variables from 401 participants. We considered three respiratory diseases: asthma, wheeze and hay fever. As predictors, we used a variety of information that would be available in a clinical setting. Of particular interest to our investigation was whether lung function measurements (newly available at such an early age) would helpfully improve predictive accuracy. We also investigated whether maternal smoking (previously associated with respiratory illnesses) is a helpful predictor. Our methods included logistic regression as the main model, multiple imputation to deal with missing values, stepwise selection and LASSO to select variables, and cross-validation to assess performance. We measured predictive performance using AUC (area under the receiver operating characteristic curve), sensitivity and specificity. Broadly, we found that the best models had only modest predictive power for each disease. For example, for asthma we achieved an AUC of 0.67, a sensitivity of 68% and a corresponding specificity of 63%. Performance for the other two diseases was similar. We also found that our lung function measurements did not improve predictive performance; some-what surprisingly, this was also true for maternal smoking. The most useful predictors included, among others, family history of these diseases and variables relating to the size of the infants. Given the modest performance of these models, our findings suggest that very early prediction of respiratory illnesses is still a challenging task.

In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella , a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort ( n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri . Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri .

Aim To determine the incidence, risk factors and health service utilisation for infection in the first 12 months of life in a population‐derived Australian pre‐birth cohort. Methods The Barwon Infant Study is a population‐derived pre‐birth cohort with antenatal recruitment ( n = 1074) based in Geelong, Victoria, Australia. Infection data were collected by parent report, and general practitioner and hospital records at 1, 3, 6, 9 and 12 months of age. We calculated the incidence of infection, attendance at a health service with infection and used multiple negative binomial regression to investigate the effects of a range of exposures on incidence of infection. Results In the first 12 months of life, infections of the upper and lower respiratory tract (henceforth ‘respiratory infections’), conjunctivitis and gastroenteritis occurred at a rate of 0.35, 0.04 and 0.04 episodes per child‐month, respectively. A total of 482 (72.4%) infants attended a general practitioner with an infection and 69 (10.4%) infants attended the emergency department. Maternal antibiotic exposure in pregnancy and having older siblings were associated with respiratory infection. Childcare attendance by 12 months of age was associated with respiratory infections and gastroenteritis. Breastfeeding, even if less than 4 weeks in total, was associated with reduced respiratory infection. Conclusion Infection, especially of the respiratory tract, is a common cause of morbidity in Australian infants. Several potentially modifiable risk factors were identified, particularly for respiratory infections. Most infections were managed by general practitioners and 1 in 10 infants attended an emergency department with infection in the first year of life.

Aim The burden of wheezing illnesses in Australian infants has not been documented since the success of initiatives to reduce maternal cigarette smoking. We aimed to determine the incidence of wheeze and related health-care utilisation during the first year of life among a contemporary Australian birth cohort. Methods A birth cohort of 1074 infants was assembled between 2010 and 2013. Parents completed questionnaires periodically. Several non-exclusive infant respiratory disease phenotypes were defined, including any wheeze, wheeze with shortness of breath and recurrent wheeze. Skin prick testing was performed to determine atopic wheeze. Health-care utilisation for respiratory disease was determined from questionnaires and hospital medical records. Results Retention to 1 year was 840/1074 (83%). The incidence of any wheeze was 51.8% (95% confidence interval (CI) 48.3-55.2%), wheeze with shortness of breath 20.6% (95% CI 17.9-23.5), recurrent wheeze 19.4% (95% CI 16.8-22.2) and atopic wheeze 6% (95% CI 4.6-7.8). Respiratory illness resulted in primary health-care utilisation in 82.2% (95% CI 79.3-84.8) of participants and hospital presentation in 8.8% (95% CI 7.2-10.6). Maternal smoking during pregnancy was uncommon (15.7%) and was not associated with wheeze or health resource utilisation. Male gender, familial atopy and asthma and smaller household size were associated with a higher incidence of wheeze. Conclusions The incidence of wheezing illness among Australian infants remains high despite relatively low rates of maternal smoking during pregnancy. The majority of the health-care burden is borne by primary health-care services. Further research is required to inform novel prevention strategies.

BACKGROUND:In previous studies, deficits in regulatory T-cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy.METHODS:In a birth cohort (n = 1074), the proportion of nTreg in the CD4+ T-cell compartment was measured by flow cytometry at birth (n = 463), 6 (n = 600) and 12 (n = 675) months. IgE-mediated food allergy was determined by food challenge at 1 year. Associations between perinatal factors (gestation, labour, sex, birth size), nTreg at each time point and food allergy at 1 year were examined by linear regression.RESULTS:A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour-associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy.CONCLUSION:The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.

Gut bacteria from the genus Prevotella are found in high abundance in faeces of non-industrialised communities but low abundance in industrialised, Westernised communities. Prevotella copri is one of the principal Prevotella species within the human gut. As it has been associated with developmental health and disease states, we sought to (i) develop a real-time polymerase chain reaction (PCR) to rapidly determine P. copri abundance and (ii) investigate its abundance in a large group of Australian pregnant mothers.The Barwon Infant Study is a pre-birth cohort study (n = 1074). Faecal samples were collected from mothers at 36 weeks gestation. Primers with a probe specific to the V3 region of P. copri 16S rRNA gene were designed and optimised for real-time PCR. Universal 16S rRNA gene primers amplified pan-bacterial DNA in parallel. Relative abundance of P. copri was calculated using a 2-ΔCt method.Relative abundance of P. copri by PCR was observed in 165/605 (27.3%) women. The distribution was distinctly bimodal, defining women with substantial (n = 115/165, 69.7%) versus very low P. copri expression (n = 50/165, 30.3%). In addition, abundance of P. copri by PCR correlated with 16S rRNA gene MiSeq sequencing data (r2 = 0.67, P < 0.0001, n = 61).We have developed a rapid and cost-effective technique for identifying the relative abundance of P. copri using real-time PCR. The expression of P. copri was evident in only a quarter of the mothers, and either at substantial or very low levels. PCR detection of P. copri may facilitate assessment of this species in large, longitudinal studies across multiple populations and in various clinical settings.

This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria. Part 3 focuses on the interplay between diet, gut bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial composition, with dietary microbiota-accessible carbohydrates (MACs) selecting short-chain fatty acid (SCFA)-producing bacteria. Current evidence from mouse models indicates an association between increased maternal dietary MACs, SCFA exposure during pregnancy, and reduced offspring asthma that is, at least in part, mediated by the induction of regulatory T lymphocytes in the fetal lung. Part 4 discusses considerations for future studies investigating maternal diet-by-microbiome determinants of offspring asthma including the challenge of measuring dietary MAC intake; limitations of the existing measures of the gut microbiome composition and metabolic activity; measures of SCFA exposure; and the complexities of childhood respiratory health assessment.

Selecting “healthy” preschool aged children for reference ranges is not clear. Relaxing the strict exclusion criteria has been shown to have no significant effect on spirometry Z-scores when compared to healthy children (Lum, S et al. ERJ 2015;45: 1576-1581). We investigated the effect of health status in pre-schoolers on reference ranges for respiratory impedance (Zrs) using a modified forced oscillation technique (FOT). 585 children (4.3 ±. 68 years) were classified into health groups from the ISAAC questionnaire. Zrs was measured with FOT between 4-26 Hz and mean resistance (R) and compliance (C) were obtained by model fitting. Prediction models were determined by mixed effect modelling and Z-scores compared between healthy children and the health groups. Data were obtained in 88% of children. Compared to healthy children (n=295), R and C Z-scores were significantly increased in asthmatics (n=70) [0.25 ±1.03 (mean±SD) vs -0.01 ±0.99 hPa.s/L, p=0.05] and [-0.20(-1.08;0.43) vs 0.08(-0.51;0.74)hPa.s/L, p=0.03]. Presence of a respiratory tract infection within 4 weeks of testing (n=67) significantly increased R (-0.35±1.11 vs -0.01±0.99, p=0.01). R and C in those preterm (n=35), with early life wheeze (n=49) or who wheezed in the last 12 months (n=71) but not asthmatic were no different to healthy children [(p=0.50, p=0.24), (p=0.91, p=0.91), (p=0.21, p=0.12)]. Our data suggest that children with asthma or a current respiratory infection should not be included in reference equations but the usually strict inclusion criteria, excluding children born pre-term or with a history of wheeze can be relaxed for FOT. This more inclusive approach results in larger, more robust reference ranges.

To investigate the relationship between a family history of allergic disease and infant respiratory health. The Barwon Infant Study (BIS) is a population-derived birth cohort (n = 1074) conducted in regional South-East Australia, designed to investigate the early life origins of non-communicable diseases. At enrolment, a family history of allergic disease (hay fever, eczema or asthma) in a first-degree relative of the child was recorded. A validated respiratory questionnaire was administered to parents at 1, 3, 6, 9 and 12 months of child's age to determine symptoms and primary health resource utilisation (HRU) for a respiratory condition. Hospital medical records were reviewed for respiratory-related emergency department presentations in the first year of life. There was a positive association identified between a family history of a first-degree relative with allergic disease and parent-reported wheeze (Hazard Ratio (HR) 1.50; 95% CI 1.16-1.94; P = 0.002), parent-reported wheeze with associated shortness of breath (SOB) (HR 2.4; 95% CI 1.39-4.14; p = 0.002), primary healthcare utilisation for a respiratory condition (HR 4.36; 95% CI 1.60-11.88; p = 0.004) and hospital presentations for a respiratory condition (HR 1.24; 95% CI 1.00-1.54; p = 0.005) (Figure below, broken line = family history of atopy, solid line = non-atopic family history).

Journal of Paediatrics and Child HealthVolume 52, Issue 6 p. 672-675 Instructive Case Congenital adrenal hyperplasia (CAH) or Wolff–Parkinson–White (WPW): The difficulties of diagnosing a shocked neonate Lawrence EK Gray, Corresponding Author Lawrence EK Gray lekgrayresearch@gmail.com University Hospital, Barwon Health, Geelong, Victoria, 3220 Australia University Hospital, Barwon Health, PO Box 281, Geelong, Victoria, 3220 AustraliaCorrespondence: Dr Lawrence EK Gray, Children's Services, University Hospital, Barwon Health, PO Box 281, Geelong, Vic. 3220, Australia; email: lekgrayresearch@gmail.comSearch for more papers by this authorPeter Vuillermin, Peter Vuillermin University Hospital, Barwon Health, Geelong, Victoria, 3220 Australia University Hospital, Barwon Health, PO Box 281, Geelong, Victoria, 3220 AustraliaSearch for more papers by this author Lawrence EK Gray, Corresponding Author Lawrence EK Gray lekgrayresearch@gmail.com University Hospital, Barwon Health, Geelong, Victoria, 3220 Australia University Hospital, Barwon Health, PO Box 281, Geelong, Victoria, 3220 AustraliaCorrespondence: Dr Lawrence EK Gray, Children's Services, University Hospital, Barwon Health, PO Box 281, Geelong, Vic. 3220, Australia; email: lekgrayresearch@gmail.comSearch for more papers by this authorPeter Vuillermin, Peter Vuillermin University Hospital, Barwon Health, Geelong, Victoria, 3220 Australia University Hospital, Barwon Health, PO Box 281, Geelong, Victoria, 3220 AustraliaSearch for more papers by this author First published: 22 June 2016 https://doi.org/10.1111/jpc.13201Citations: 2 Conflict of interest: None declared. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume52, Issue6June 2016Pages 672-675 RelatedInformation

Primary amoebic meningoencephalitis (PAM) is a fulminant, diffuse haemorrhagic meningoencephalitis caused by Naegleria fowleri, with an almost invariably fatal outcome. In Australia and the developed world, PAM remains a rare disease, although it is very likely that large numbers of cases go undetected in developing countries. N. fowleri is a thermophilic, free-living amoeba with a worldwide distribution. It is acquired when contaminated fresh water is flushed into the nose and penetrates the central nervous system via the cribriform plate. Clinical features are similar to those of bacterial meningitis, but it does not respond to standard therapy and rapid progression to death occurs in most cases. Some survivors have been reported; these patients received early treatment with amphotericin B in combination with a variety of other medications. Our review describes the local and worldwide experience of this disease and its clinical features, and discusses the associated diagnostic challenges. We hope that by detailing the local response to a recent case, and the outcomes of our public health campaign, we can improve the knowledge of this rare disease for doctors working in rural and remote Australia.