Clinical characteristics of hospitalised children with acute post-streptococcal glomerulonephritis in the Top End of Australia.

AIMS: Despite the declining incidence of acute post-streptococcal glomerulonephritis (APSGN) in Australia, there is still a significant burden of disease amongst Aboriginal and Torres Strait Islander people in the Northern Territory. Childhood APSGN has been highlighted as a predictor of chronic kidney disease in this population. We aimed to describe clinical characteristics and outcomes of hospitalised children with APSGN in the Northern Territory. METHODS: Single-centre, retrospective cohort study of children (<18 years) with APSGN admitted to a tertiary hospital in the Top End of the Northern Territory between January 2012 and December 2017. Cases were confirmed using the Centre for Disease Control case definition guidelines. Data were extracted from the case notes and electronic medical records. RESULTS: There were 96 cases of APSGN with median age of 7.1 years (interquartile range (IQR) 6.7-11.4). Majority were Aboriginal and Torres Strait Islander (90.6%) and from rural and remote areas (82.3%). Preceding skin infections were identified in 65.5% and sore throat in 27.1%. Severe complications included hypertensive emergencies (37.4%), acute kidney injury (43.8%) and nephrotic-range proteinuria (57.7%). All children improved from their acute illness with supportive medical therapy; however, only 55 out of 96 (57.3%) children were followed up within 12 months of their acute illness. CONCLUSIONS: APSGN disproportionately affects Aboriginal and Torres Strait Islander children and highlights the need for continued and improved public health response. There is room for significant improvement in the medium- and long-term follow-up of affected children.

Burden of Group A Streptococcal Pharyngitis, Rheumatic Fever, and Rheumatic Heart Disease in India: A Systematic Review and Meta-Analysis.

OBJECTIVE: To estimate the burden of group A streptococcal pharyngitis (GAS) pharyngitis, rheumatic fever (RF), and rheumatic heart disease (RHD) in India using existing data sources, as well as to recognize the most serious gaps in GAS disease burden data. METHODS: Four electronic databases-PubMed, Scopus, Embase, and Web of Science were searched using a comprehensive search strategy. Data were identified primarily from observational studies including school surveys, community-based and hospital-based studies. The standard methodological procedures as per Cochrane guidelines were used. Eligible studies were pooled for estimating prevalence, incidence, and case fatality rate using R software version 3.3.3. The protocol was registered with PROSPERO; registration number CRD42018075742. RESULTS: The pooled prevalence of GAS pharyngitis among asymptomatic children and pharyngitis cases aged 5 to 15 y was estimated as 2.79 percent [95% Confidence interval (CI): 1.58-4.89] and 13 percent (95% CI: 3.18-41.97), respectively. The prevalence rate of rheumatic fever was found to be 0.04% (95% CI: 0.01-0.17). The pooled prevalence rate of RHD among children aged 5-15 y using clinical auscultation and echocardiography was estimated as 0.36 percent (95% CI: 0.02-7.52) and 0.28 percent (95% CI: 0.08-1.03), respectively. CONCLUSION: The study emphasizes the importance of developing a population-based surveillance framework to track patterns, management strategies, and outcomes in order to develop informed recommendations for launching contextual measures to regulate RF and RHD.

Estimation of country-level incidence of early-onset invasive Group B Streptococcus disease in infants using Bayesian methods.

Neonatal invasive disease caused by Group B Streptococcus (GBS) is responsible for much acute mortality and long-term morbidity. To guide development of better prevention strategies, including maternal vaccines that protect neonates against GBS, it is necessary to estimate the burden of this condition globally and in different regions. Here, we present a Bayesian model that estimates country-specific invasive GBS (iGBS) disease incidence in children aged 0 to 6 days. The model combines different types of epidemiological data, each of which has its own limitations: GBS colonization prevalence in pregnant women, risk of iGBS disease in children born to GBS-colonized mothers and direct estimates of iGBS disease incidence where available. In our analysis, we present country-specific maternal GBS colonization prevalence after adjustment for GBS detection assay used in epidemiological studies. We then integrate these results with other epidemiological data and estimate country-level incidence of iGBS disease including in countries with no studies that directly estimate incidence. We are able to simultaneously estimate two key epidemiological quantities: the country-specific incidence of early-onset iGBS disease, and the risk of iGBS disease in babies born to GBS-colonized women. Overall, we believe our method will contribute to a more comprehensive quantification of the global burden of this disease, inform cost-effectiveness assessments of potential maternal GBS vaccines and identify key areas where data are necessary.

Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study.

BACKGROUND: Group B Streptococcus (GBS) disease is a leading cause of neonatal death, but its long-term effects have not been studied after early childhood. The aim of this study was to assess long-term mortality, neurodevelopmental impairments (NDIs), and economic outcomes after infant invasive GBS (iGBS) disease up to adolescence in Denmark and the Netherlands. METHODS: For this cohort study, children with iGBS disease were identified in Denmark and the Netherlands using national medical and administrative databases and culture results that confirmed their diagnoses. Exposed children were defined as having a history of iGBS disease (sepsis, meningitis, or pneumonia) by the age of 89 days. For each exposed child, ten unexposed children were randomly selected and matched by sex, year and month of birth, and gestational age. Mortality data were analysed with the use of Cox proportional hazards models. NDI data up to adolescence were captured from discharge diagnoses in the National Patient Registry (Denmark) and special educational support records (the Netherlands). Health care use and household income were also compared between the exposed and unexposed cohorts. FINDINGS: 2258 children-1561 in Denmark (born from Jan 1, 1997 to Dec 31, 2017) and 697 in the Netherlands (born from Jan 1, 2000 to Dec 31, 2017)-were identified to have iGBS disease and followed up for a median of 14 years (IQR 7-18) in Denmark and 9 years (6-11) in the Netherlands. 366 children had meningitis, 1763 had sepsis, and 129 had pneumonia (in Denmark only). These children were matched with 22 462 children with no history of iGBS disease. iGBS meningitis was associated with an increased mortality at age 5 years (adjusted hazard ratio 4·08 [95% CI 1·78-9·35] for Denmark and 6·73 [3·76-12·06] for the Netherlands). Any iGBS disease was associated with an increased risk of NDI at 10 years of age, both in Denmark (risk ratio 1·77 [95% CI 1·44-2·18]) and the Netherlands (2·28 [1·64-3·17]). A history of iGBS disease was associated with more frequent outpatient clinic visits (incidence rate ratio 1·93 [95% CI 1·79-2·09], p<0·0001) and hospital admissions (1·33 [1·27-1·38], p<0·0001) in children 5 years or younger. No differences in household income were observed between the exposed and unexposed cohorts. INTERPRETATION: iGBS disease, especially meningitis, was associated with increased mortality and a higher risk of NDIs in later childhood. This previously unquantified burden underlines the case for a maternal GBS vaccine, and the need to track and provide care for affected survivors of iGBS disease. FUNDING: The Bill & Melinda Gates Foundation. TRANSLATIONS: For the Dutch and Danish translations of the abstract see Supplementary Materials section.

Rheumatic heart disease in Indigenous young peoples.

Indigenous children and young peoples live with an inequitable burden of acute rheumatic fever and rheumatic heart disease. In this Review, we focus on the epidemiological burden and lived experience of these conditions for Indigenous young peoples in Australia, New Zealand, and Canada. We outline the direct and indirect drivers of rheumatic heart disease risk and their mitigation. Specifically, we identify the opportunities and limitations of predominantly biomedical approaches to the primary, secondary, and tertiary prevention of disease among Indigenous peoples. We explain why these biomedical approaches must be coupled with decolonising approaches to address the underlying cause of disease. Initiatives underway to reduce acute rheumatic fever and rheumatic heart disease in Australia, New Zealand, and Canada are reviewed to identify how an Indigenous rights-based approach could contribute to elimination of rheumatic heart disease and global disease control goals.

ENT involvement and orobuccal movements' disorders in Pandas patients: assessment and rehabilitations tools.

OBJECTIVE: PANDAS are known as the spectrum of autoimmune pathologies related to a previous or current infection by group A beta-hemolytic streptococcus (SBEGA), dealing with several neuropsychiatric manifestations that mainly affect pediatric age. The main features consist of behavioral disease or movement disease characterized by acute-onset, presenting especially through infant period or adolescence. Specific manifestations, occurring during the progression of the disease, are the presence of otorhinolaryngologic symptoms (ENT) and orofacial movement disorders associated with temporomandibular joint pain. PATIENTS AND METHODS: We enrolled 130 children (5-15 years) with a clinical diagnosis of PANDAS between 2012 and 2018. Participants were assessed using ENT specific parameters, PSG to examine respiratory disorders and conventional audiological evaluation. Descriptive and comparative statistical analyses were performed with a control group of 51 healthy patients. RESULTS: The prevalence of ENT symptoms associated was significantly detected in 88 patients of 130 in Group A (relative frequency (%) 67.6; p=0.041) and in 51 patients of 130 in the control Group B (relative frequency (%) 39.2; p=0.063). In relation to prevalence of SDB, 54 subjects have presented nocturnal respiratory obstructive symptoms from mild to severe (relative frequency (%) 61.3; p=0.033) vs. 20 patients of Group B (relative frequency (%) 39.2; p=0.055). The obstructive severity average type was correlated to the consensual adenotonsillar development (size 3-4), (relative frequency (%) 45.4; p=0.047). The audiological deficits found were mostly of transmissive type with OME correlated and linked to the presence of occasional episodes of AOM. The four PANDAS patients who presented orobuccal dystonia (relative frequency (%) 4.54; p=0.091) achieved an improvement of the algic symptoms through the exercises of self-rehabilitation. CONCLUSIONS: Findings from our study show that respiratory diseases, characterizing a group of patients with pandas, are the direct consequences of the malformed or hypertrophic condition and suggesting in these conditions surgical therapy as an approaching tool.

Burden of disease and economic impact of human Streptococcus suis infection in Viet Nam.

BACKGROUND: Streptococcus suis is a zoonotic disease mainly affecting men of working age and can result in death or long-term sequelae, including severe hearing loss and vestibular dysfunction. We aimed to quantify the burden of disease and economic impact of this infection in Viet Nam. METHODS: The annual disease incidence for the period 2011-2014 was estimated based on surveillance data using a multiple imputation approach. We calculated disease burden in disability-adjusted life years (DALYs) and economic costs using an incidence-based approach from a patient's perspective and including direct and indirect impacts of S. suis infection and its long-term sequelae. RESULTS: The estimated annual incidence rate was 0.318, 0.324, 0.255 and 0.249 cases per 100 000 population in 2011, 2012, 2013 and 2014, respectively. The corresponding DALYs lost were 1832, 1866, 1467 and 1437. The mean direct cost per episode was US$1635 (95% confidence interval 1352-1923). The annual direct cost was US$370 000-500 000 and the indirect cost was US$2.27-2.88 million in this time period. CONCLUSIONS: This study showed a large disease burden and high economic impact of S. suis infection and provides important data for disease monitoring and control.

[CURRENT TRENDS IN THE PREVENTION, DIAGNOSIS AND TREATMENT OF RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE (REVIEW)].

The purpose of the work is to analyze the evolution of the clinical course, diagnosis, treatment and prevention of acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD), antibiotic therapy of streptococcal infection, using modern analysis of modern literature and our own observations. Diagnostic criteria for the disease were revised. Improving the capabilities of echocardiography can improve the prognosis of the disease through the early use of treatment and prevention. The level of ORL / RHD correlates with the economic development of countries. Mutation of the etiological factor of rheumatism - ß-HSA, the formation of antibiotic resistance, increased migration, tourist activity in countries with high morbidity due to ß-HSA can lead to new outbreaks of this infection. Prevention ARF/RHD is multistage. Thus, using the experience of healthcare in different countries, new approaches to prevention can improve disease control.

Post-streptococcal glomerulonephritis: Some reduction in a disease of disparities.

AIM: A retrospective Auckland-wide (total population approximately 1.4 million) study of hospital admissions from 2007 to 2015 was conducted to assess trends in admissions for acute post-streptococcal glomerulonephritis (APSGN) in children aged 0-14 years. METHODS: International Statistical Classification of Diseases (ICD10) discharge codes were used to identify potential cases of APSGN, and electronic clinical records and laboratory data were compared with established case definitions for definite or probable APSGN. RESULTS: A total of 430 cases of APSGN were identified (definite n = 337, probable n = 93), with a mean annual incidence of 15.2/100 000 (95% confidence interval (CI) 14.9-15.6). Incidence (0-14 years) was 17 times higher in Pacific peoples (50.2/100 000, 95% CI 48.6-51.8) and almost 7 times higher in Maori (19.6/100 000, 95% CI 18.6-20.7) than European/other populations (2.9/100 000, 95% CI 2.7-3.1). Multivariate analysis found ethnicity, deprivation, male gender, age (peak 3-8 years) and season (summer/autumn) to be associated with admission risk. Admission rates showed a significant change of -9.0% (95% CI -10.4, 7.4%) per year, with 2011 being an exception. Low C3 complement, hypertension, elevated streptococcal titres, oedema and heavy proteinuria were present in 94, 65, 67, 52 and 49% of cases, respectively. Relying on ICD10 codes without further review of clinical notes would result in an overcount of cases by 25%. CONCLUSIONS: There is severe disparity in APSGN admission rates, with a disproportionate burden of disease for Pacific and Maori children and those living in deprived circumstances. Rates trended downward from 2007 to 2015.

Increasing Access to High Value Care: Preventing Complications in Common Disorders.

Most infantile hemangiomas (IHs), the most common vascular tumors of childhood, evolve without complications; however 10% to 12% require specialty referral for treatment. To emphasize the complications of late referral, we present a case of necrotizing infection within a segmental IH leading to sepsis. Early evaluation by a pediatric dermatologist could have prevented this life-threatening and disfiguring complication. We discuss how teledermatology would enable rapid triage of such critical cases in underserved areas, increasing access to high-value care and optimizing outcomes for our most vulnerable patients.

Clinical Mimics: An Emergency Medicine-Focused Review of Streptococcal Pharyngitis Mimics.

BACKGROUND: Pharyngitis is a common disease in the emergency department (ED). Despite a relatively low incidence of complications, there are many dangerous conditions that can mimic this disease and are essential for the emergency physician to consider. OBJECTIVE: This article provides a review of the evaluation and management of group A ß-hemolytic Streptococcal (GABHS) pharyngitis, as well as important medical conditions that can mimic this disease. DISCUSSION: GABHS pharyngitis often presents with fever, sore throat, tonsillar exudates, and anterior cervical lymphadenopathy. History and physical examination are insufficient for the diagnosis. The Centor criteria or McIsaac score can help risk stratify patients for subsequent testing or treatment. Antibiotics may reduce symptom duration and suppurative complications, but the effect is small. Rheumatic fever is uncommon in developed countries, and shared decision making is recommended if antibiotics are used for this indication. Oral analgesics and topical anesthetics are important for symptom management. Physicians should consider alternate diagnoses that may mimic GABHS pharyngitis, which can include epiglottitis, infectious mononucleosis, Kawasaki disease, acute retroviral syndrome, Lemierre's syndrome, Ludwig's angina, peritonsillar abscess, retropharyngeal abscess, and viral pharyngitis. A focused history and physical examination can help differentiate these conditions. CONCLUSIONS: GABHS may present similarly to other benign and potentially deadly diseases. Diagnosis and treatment of pharyngitis should be based on clinical evaluation. Consideration of pharyngitis mimics is important in the evaluation and management of ED patients.

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination.

Accuracy of a rapid real-time polymerase chain reaction assay for diagnosis of group B Streptococcus colonization in a cohort of HIV-infected pregnant women.

OBJECTIVE: There are limited data regarding Xpert performance to detect Group B Streptococcus (GBS) in HIV-infected pregnant women. We evaluated the accuracy of a rapid real-time polymerase chain reaction (PCR) test in a cohort of HIV-infected women. METHODS: At 35-37 weeks of pregnancy, a pair of combined rectovaginal swabs were collected for two GBS assays in a cohort of sequentially included HIV-infected women in Rio de Janeiro: (1) culture; and (2) real-time PCR assay [GeneXpert GBS (Cepheid, Sunnyvale, CA)]. Using culture as the reference, sensitivity, specificity, positive and negative-likelihood ratios were estimated. RESULTS: From June 2012 to February 2015, 337 pregnant women met inclusion criteria. One woman was later excluded, due to failure to obtain a result in the index test; 336 were included in the analyses. The GBS colonization rate was 19.04%. Sensitivity and specificity of the GeneXpert GBS assay were 85.94% (95% CI: 75.38-92.42) and 94.85% (95% CI: 91.55-96.91), respectively. Positive and negative predictive values were 79.71% (95% CI: 68.78-87.51) and 96.63% (95% CI: 93.72-98.22), respectively. CONCLUSIONS: GeneXpert GBS is an acceptable test for the identification of GBS colonization in HIV-infected pregnant women and represents a reasonable option to detect GBS colonization in settings where culture is not feasible.

A personal 35 year perspective on Gilles de la Tourette syndrome: assessment, investigations, and management.

After having examined the definition, clinical phenomenology, comorbidity, psychopathology, and phenotypes in the first paper of this Series, here I discuss the assessment, including neuropsychology, and the effects of Gilles de la Tourette syndrome with studies showing that the quality of life of patients with Tourette's syndrome is reduced and that there is a substantial burden on the family. In this paper, I review my local and collaborative studies investigating causal factors (including genetic vulnerability, prenatal and perinatal difficulties, and neuro-immunological factors). I also present my studies on neuro-imaging, electro-encephalograms, and other special investigations, which are helpful in their own right or to exclude other conditions. Finally, I also review our studies on treatment including medications, transcranial magnetic stimulation, biofeedback, target-specific botulinum toxin injections, biofeedback and, in severe refractory adults, psychosurgery and deep brain stimulation. This Review summarises and highlights selected main findings from my clinic (initially The National Hospital for Neurology and Neurosurgery Queen Square and University College London, UK, and, subsequently, at St George's Hospital, London, UK), and several collaborations since 1980. As in Part 1 of this Series, I address the main controversies in the fields and the research of other groups, and I make suggestions for future research.

Late cardiac assessment in children diagnosed with post-streptococcal reactive arthritis: a long term study.

OBJECTIVES: Unlike rheumatic fever (RF), the association of post-streptococcal reactive arthritis (PSRA) and carditis is controversial. The American Heart Association recommends anti-streptococcal prophylaxis for PSRA for one year, repeating echocardiogram and discontinuation of prophylaxis if normal. In this study the possibility of late cardiac involvement was investigated in a cohort of children with PSRA. METHODS: Children diagnosed with PSRA and followed at the Paediatric Rheumatology Units at two medical centres in Israel had echocardiography carried out by a paediatric cardiologist, at least 1 year following diagnosis. RESULTS: 146 patients with PSRA met the study criteria. Of these, 69 had undergone echocardiography 1-6.9 years (mean 3.6 years ± 1.5 years) after diagnosis. All had normal major parameters. Twenty (29.0%) patients had minimal cardiac findings, including 5 (7.2%) mild mitral insufficiency, 12 (17.4%) minimal mitral insufficiency, 2 (2.9%) mild tricuspid insufficiency and one patient (1.4%) had very mild, aortic insufficiency. Of the 77 patients who did not have echocardiography, 31 were randomly excluded from the initial study list, 26 refused to undergo echocardiography, and 20 were lost to follow-up. All were asymptomatic according to their medical record or telephone questionnaire. There were no significant differences in clinical or demographic data between those with or without echocardiography. CONCLUSIONS: No late cardiac involvement was found in our paediatric PSRA patients. Therefore, different approaches to antibiotic prophylaxis for PSRA and ARF are probably suggested. A prospective, controlled study is needed to definitively assess the necessity of prophylaxis in PSRA.

A cost-effective strategy for primary prevention of acute rheumatic fever and rheumatic heart disease in children with pharyngitis.

Primary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in children depends on prompt and effective diagnosis and treatment of pharyngitis at the primary level of care. Cost-effectiveness modeling shows that the most cost-effective strategy for primary prevention in South Africa (SA) is to use a simple symptomatic clinical decision rule (CDR) to diagnose pharyngitis in children presenting at the primary level of care and then to treat them with a single dose of intramuscular penicillin. Treat All and CDR2+ strategies are affordable and simple and miss few cases of streptococcal pharyngitis at the primary level of care. The CDR2+ strategy is the most cost-effective for primary prevention of ARF and RHD in urban SA and should complement primordial and secondary prevention efforts.

Cost-effectiveness analysis of rheumatic heart disease prevention strategies.

Rheumatic heart disease (RHD), secondary to group A streptococcal infection is endemic in the developing as well as parts of the developed world with significant costs to the patient, and to the healthcare system. We briefly review the prevalence and cost of RHD in developed and developing nations. We subsequently develop a Markov model to evaluate the cost-effectiveness of three strategies (vs standard no prevention) for preventing RHD in a developing world country: primary prophylaxis (throat swab to detect and subsequently treat group A streptococci as needed); primary prophylaxis (antibiotic prophylaxis for all) with benzathine penicillin G once monthly to all patients (ages 5-21 years) regardless of evidence of infection; and secondary prophylaxis with monthly only to those with echocardiographic evidence of early RHD. Our model suggests that echocardiographic screening and secondary prophylaxis is the best strategy although the strategies change depending on parameters used.

Prospective population-based study on the burden of disease from post-streptococcal glomerulonephritis of hospitalised children in New Zealand: epidemiology, clinical features and complications.

AIM: A nationwide 24-month study was conducted (2007-2009), via the New Zealand Paediatric Surveillance Unit to define epidemiology and clinical features of acute poststreptococcal glomerulonephritis (APSGN) in children hospitalised with the illness. METHODS: Paediatricians (n = 215) were requested to report new hospitalised cases fulfilling a case definition of definite (haematuria with low C3 and high streptococcal titres or biopsy proven APSGN) or probable (haematuria with low C3 or high streptococcal titres). RESULTS: A total of 176 cases were identified (definite: n = 138, probable: n = 38) with 63% residing in the Auckland metropolitan region. Sixty-seven percent were in the most deprived quintile. Annual incidence (0-14 years) was 9.7/100,000 (Pacific 45.5, Maori 15.7, European/other 2.6 and Asian 2.1/100,000). Annual incidence was highest in the South Auckland Metropolitan region (31/100,000), Central Auckland 14.9, West/North Auckland metropolitan region 5.9 and for the remainder of New Zealand 5.5/100,000. Age-specific incidence was highest in age 5-9 years (15.1/100,000). Reduced serum complement C3, gross haematuria, hypertension, impairment of renal function and heavy proteinuria were present in 93%, 87%, 72%, 67% and 44% of patients, respectively. Severe hypertension was closely associated with either symptoms of an acute encephalopathy or congestive heart failure. CONCLUSIONS: New Zealand children carry a significant disease burden of hospitalised APSGN with socio-economically deprived; Pacific and Maori children are being over-represented. Significant short-term complications were observed in hospitalised children with APSGN. Persistently very low rates in European/other suggest a preventable disease.