Streptococcal Infections In Children Research Articles

Microglia as a Target of Immunomodulation in Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections (PANDAS)

PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections, is a neuropsychiatric condition characterized by the abrupt onset of diverse neuropsychiatric manifestations following streptococcal infections in children. It's believed to involve immune dysregulation and autoimmune targeting of the brain basal ganglia. However, the precise mechanisms remain unclear. Hypothesis: considering the role of microglia in neuroinflammation, evidence for their activation in PET imaging of PANDAS patients, and increased number of CD68+/Iba1+ activated microglia in mice inoculated with group A Streptococcus (GAS), we hypothesized that as a consequence of disrupted blood-brain barrier (BBB), circulating factors modulate microglial functions towards a pro-inflammatory phenotype. Methods: Untargeted metabolomics was performed with sera from 10 children with PANDAS and 12 healthy controls. Human iPSC-derived microglia were generated and exposed to 5% serum from PANDAS patients or healthy controls in the presence or absence of Polymyxin B (PMB; endotoxin scavenger) and assessed for nitric oxide (NOx) production, immunophenotyped with flow cytometry (TMEM119, TREM2, CD68, and Iba-1) and bulk RNA-seq analysis. Results: Significant differences in serum metabolomic profile of PANDAS cases were observed, particularly in pathways associated with amino acid, fatty acid, lipid, steroid, and oxidative stress-related pathways. Treatment of iPSC-derived or primary human microglia with PANDAS serum led to a significant increase in NOx production, which was blunted by approx. 30% by PMB. Immunophenotyping revealed a significant reduction in homeostatic markers TMEM119 and TREM2, and expansion of CD68+ and Iba-1+ microglia associated with inflammatory response. Regulation of TMEM119 and TREM2 was endotoxin-independent, while PMB partially blunted the increase in CD68 and Iba-1. RNAseq revealed dramatic effects of PANDAS sera on microglial gene expression pattern, with upregulated genes associated with C-type lectin receptor, TLR, TNF, and NFk-B signaling pathways among others. Conclusion: The results suggest that as a result of BBB disruption in PANDAS, associated systemic inflammatory mediators modulate the phenotype and function of the brain microglia, a mechanism that likely contributes to neuroinflammation and the observed symptoms. The observed contribution of endotoxin may also suggest a dysfunction of intestinal barrier which may compound the systemic immune responses in PANDAS. Arizona Department of Health Services RFGA2022-010-23 (PK) & ADHS17-00007403 (SR, MD); The Alex Manfull Fund (PK). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Fulminant invasive group A streptococcal infection in children

Group A streptococcal infections dominate among invasive streptococcal infections, with the major causative agent, Streptococcus pyogenes, being quite stable in the environment and bearing a large number of chromosome encoded pathogenicity factors or transmitted by horizontal transfer through bacteriophages. Different genetic variants of S. pyogenes can have a different set of pathogenicity factors able to change during pathogen evolution and determine virulence level for specific isolate. With a short incubation period, the disease can proceed with developing invasive infection and toxic shock syndrome with unfavorable outcome within 7 days from disease onset. The purpose of this article is to increase the doctors’ alertness to early recognition and diagnosis, which directly affects adequate treatment in a timely manner and disease outcome. The data on streptococcal morbidity in Russia and worldwide, review of laboratory diagnostic methods and pathogen genetic typing are presented. The maximum number of cases of streptococcal septicemia in Russia was registered in 2022, which accounted for 69% of all cases during the 2014–2022 observation period. The article also describes two clinical cases of fulminant invasive group A streptococcal infection in children with symptoms of acute respiratory viral infections at the onset of the disease. The results of various laboratory diagnostics methods verifying the diagnosis are presented. The genetic characterization of microbial isolates was performed by deep DNA sequencing. In the biological material from patients (including autopsy in one case), S. pyogenes sequence type ST-28, serotypes emm-1.25 and emm-1.0 were identified. The increasing importance of invasive streptococcal infection for health care in Russia and other countries may be associated with a possible change in dominating S. pyogenes genetic variants. In this regard, the study on circulating S. pyogenes genotypes on an ongoing basis as part of surveillance of streptococcal infection and development of vaccine for specific prevention are required.

Invasive group A streptococcal infections in children and adolescents in Denmark during 2022–23 compared with 2016–17 to 2021–22: a nationwide, multicentre, population-based cohort study

A historic increase in paediatric invasive group A streptococcal (iGAS) infections was reported globally in 2022. iGAS infections can lead to severe manifestations (eg, pleural empyema, necrotising fasciitis, toxic shock syndrome, osteomyelitis, septic arthritis, and meningitis). We aimed to compare the incidence and severity of iGAS infections overall, for distinct clinical phenotypes, and for GAS emm variants in Denmark in 2022-23 with reference to the previous six seasons (ie, 2016-17, 2017-18, 2018-19, 2019-20, 2020-21, and 2021-22). In this nationwide, multicentre, population-based cohort study, we included all children and adolescents in Denmark aged 0-17 years with a positive culture of GAS or GAS confirmed through PCR-based methods from otherwise sterile sites in 2022-23 and the previous six seasons from 2016-17 to 2021-22. For all seven seasons, data were obtained from week 21 to week 20 of the next year. Patients at all 18 paediatric hospital departments in Denmark were identified through the Danish Microbiology Database, in which iGAS isolates from sterile sites are prospectively registered, including emm typing. We obtained electronic medical health records for each patient admitted with a diagnosis of iGAS. We calculated the incidence of iGAS per 1 000 000 inhabitants aged 0-17 years in each season from week 21 to week 20 of the next year and the risk ratios (RRs) for incidence of iGAS, distinct disease manifestations, and emm variants in 2022-23 versus the three pre-COVID-19 seasons in 2016-17, 2017-18, and 2018-19 using Fisher's exact test and Pearson's χ2 test. Among the Danish population of 1 152 000 children and adolescents aged 0-17 years, 174 with iGAS disease were included. 76 children and adolescents with iGAS during 2022-23 were identified; 31 (41%) of 76 were female and 45 (59%) were male. 98 children and adolescents with iGAS during 2016-17 to 2021-22 were identified; 41 (42%) of 98 were female and 57 (58%) were male. There was an increase in incidence of iGAS from mean 22·6 (95% CI 14·7-33·1) per 1 000 000 children and adolescents during 2016-17 to 2018-19 to 66·0 (52·0-82·6) per 1 000 000 during 2023-23 (RR 2·9, 95% CI 1·9-4·6; p<0·0001). During the COVID-19 pandemic in 2019-20, 2020-21, and 2021-22, the mean incidence of iGAS was 6·1 (95% CI 2·4-12·5) per 1 000 000 children and adolescents. In 2022-23, there was a 9·5-fold increase in emm-12 (95% CI 2·2-40·8; p=0·0002) and a 2·7-fold increase in emm-1 (1·3-5·5; p=0·0037). The most common clinical manifestations of iGAS in 2022-23 were soft-tissue infections, which increased by 4·5-fold (1·9-10·9; p=0·0003), and complicated pneumonia with parapneumonic effusion, which increased by 4·0-fold (1·4-11·4; p=0·0059), both compared with the three pre-COVID-19 seasons. Overall, there was no increased severity of iGAS in 2022-23 compared with the previous six seasons as measured by median duration of hospital stay (8 days, IQR 4-14 vs 9 days, 5-15; p=0·39), paediatric intensive care unit (PICU) admission (17 [22%] of 76 vs 17 [17%] of 98; p=0·53), duration of stay in PICU (4 days, IQR 2-10 vs 4 days, 2-11; p=0·84), or mortality (three [4%] of 76 vs three [3%] of 98; p=1·00). In 2022-23, there was a 3·6-fold (95% CI 1·8-7·3; p=0·0001) increase in children with a preceding upper respiratory tract infection and a 4·6-fold (1·5-14·1; p=0·0034) increase in children with a preceding varicella-zoster infection, both compared with the three pre-COVID-19 seasons. In Denmark, the incidence of paediatric iGAS increased in 2022-23 compared with the three pre-COVID-19 seasons of 2016-17, 2017-18, and 2018-19. However, the course of iGAS disease in children and adolescents in 2022-23 was not more severe than in previous seasons. The high morbidity across all seasons highlights iGAS as a major invasive bacterial infection in children and adolescents. Innovation Fund Denmark.

Unexpected Increase in Invasive Group A Streptococcal Infections in Children After Respiratory Viruses Outbreak in France: A 15-Year Time-Series Analysis.

In a 15-year pediatric time-series analysis, we showed a rise of invasive Group A streptococcal (iGAS) infections since October 2022, mainly involving pleural empyema, simultaneously to a respiratory virus outbreak. Physicians should be aware of this increased risk of pediatric iGAS infections, especially in settings with intense respiratory viruses' circulation.

Increase in Invasive Group a Streptococcal Infections in Children in the Netherlands, A Survey Among 7 Hospitals in 2022.

Following an increase in notifiable invasive group A streptococcal (iGAS) infections in the Netherlands, we conducted a survey among 7 hospitals. Pediatric iGAS case numbers were 2-fold higher between July 2021 and June 2022 versus pre-COVID-19. A sharp increase occurred early 2022, most pronounced in <5 years old and for diagnoses empyema and necrotizing fasciitis. This recent pediatric iGAS surge warrants investigation and vigilance.

Roadmap to incorporating group A Streptococcus molecular point-of-care testing for remote Australia: a key activity to eliminate rheumatic heart disease.

Roadmap to incorporating group A Streptococcus molecular point-of-care testing for remote Australia: a key activity to eliminate rheumatic heart disease.

Pediatric Autoimmune Neuropsychiatric Disorders Associated With Group A Streptococci: Etiopathology and Diagnostic Challenges.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) have attracted a lot of interest and discussion since it was originally characterized in 1998. The role of streptococcal infection in children with abrupt-onset obsessive-compulsive disorder (OCD) and new-onset tics, the natural history of this entity, and the role of symptomatic and disease-modifying therapies, such as antibiotics, immunotherapy, and psychoactive drugs, are still unresolved issues. Alternative therapies for acute-onset OCD have been developed based on this postulated pathophysiology, including antibiotics and immunomodulatory therapy. The literature on PANDAS therapy is varied but there is no clinical consensus on the treatment of choice.While there is no convincing evidence for the autoimmune rationale for PANDAS, given the increased attention to this entity and the apparent growth in usage of this diagnostic category, it is critical to address concerns about the condition's diagnosis, treatment, and pathogenesis.We conducted a multi-language literature search on Medline, Cochrane, Embase, and Google Scholar for a period spanning until October 2021. The following search strings and Medical Subject Heading (MeSH) terms were used: “PANDAS,” “Group A Streptococcus,” “OCD,” and “tics.” We explored the literature on PANDAS in terms of its epidemiology, pathophysiology, the role of group A streptococcal infection, associated complications, and prophylactic and treatment modalities.We examined current working definitions of PANDAS, analyzed differential diagnoses, and published pieces of evidence for therapies associated with this entity, with a view to proposing a therapeutic strategy for children with acute symptoms that meet PANDAS criteria, in this review article.

VEGETATIVE REACTIVITY OF CHILDREN WITH STREPTOCOCCAL TONSILITIS ON THE BACKGROUND OF HERPES VIRAL INFECTION

Streptococcal infection in children, its complications and adverse long-term consequences remain an urgent problem in pediatrics. Scientists continue to search for factors that shape the course of the disease. One of them is the timely and adequate response of the autonomic nervous system, which provides both short-term and long-term strategic adaptation of the organism. Violations of this adaptation can lead to the presence of comorbid conditions, which are increasingly common. The share of children is growing. infected with the herpes virus group, including human herpes virus type 6 (HHV-6).&#x0D; &#x0D; The aim of the work was to study the state of vegetative reactivity (VR) of children with streptococcal tonsillitis on the background of HHV-6 infection. In 68 children aged 4 - 15 years with tonsillitis of streptococcal etiology of moderate severity, vegetative reactivity was determined by cardiointervalography (CIG) followed by analysis of heart rate variability (CP) depending on the presence or absence of concomitant HHV-6 type of infection. The studies were performed in the acute period of the disease and in the period of early convalescence. The control group consisted of 20 healthy children, similar in age and sex. Static processing of the obtained results was performed using Excel and Statistica 6.0 using parametric and non-parametric research methods.&#x0D; &#x0D; Results.&#x0D; In the acute period of streptococcal tonsillitis in children of both groups there was a decrease in the humoral component in the regulation of the system and the level of activity of the parasympathetic ANS, as evidenced by a decrease in Mo and ΔX, independent of background, p&gt; 0.05. There was an activation of the influence of the sympathetic link of the VNS, increased the degree of centralization of heart rate control in all patients, and this was confirmed by an increase in AMO and IN. Prior to the convalescence period, CIG parameters were restored only in patients without concomitant VGL-6 infection, and the interrelationships of the sympathetic and parasympathetic links of the VNS were restructured with increasing role of the latter. In patients with concomitant VGL-6 infection, the values ​​of ΔX and IN differed significantly from the control group, p˂0.05. Thus, in children with streptococcal tonsillitis on the background of HHV-6 infection, there was a decrease in the level of functioning of the sympathetic VNS, but complete recovery did not occur, indicating instability of adaptation processes, depletion of the parasympathetic VNS, which hides the possibility of failure of adaptation, recurrence of the disease and / or chronicity, the development of secondary disorders of the cardiovascular system.&#x0D; Conclusions.&#x0D; The acute period of streptococcal tonsillitis is accompanied by stress of the sympathetic VNS, the severity of which does not depend on the presence of concomitant herpes virus infection. In the period of convalescence of streptococcal tonsillitis in the presence of children with HHV-6 infection there is no complete recovery of autonomic reactivity, among which the most informative are ΔX and IN.

Post streptococcal myalgia: a subdiagnosed disorder- a case report

Post streptococcal myalgia (PSM) is an underrecognized non-infectious sequela of streptococcal infection in children. The authors report a case of PSM in a previously healthy 11-year-old girl admitted due to probable Streptococcal toxic shock syndrome (STSS) secondary to complicated periorbital cellulitis. Ten days after discharge, following steroid weaning for adverse drug reaction, she presented with low fevers associated with a painful swollen right forearm, with elevated inflammatory markers and normal muscle enzymes. MRI excluded infectious complications and showed simple myositis. PMS was suspected and the patient was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) with progressive clinical and laboratory improvement. The clinical complaints were resolved 3 months later, without sequelae or recurrence. The diagnosis of PSM should be considered in children presenting with acute myalgia and evidence of recent streptococcal infection

Group A Streptococcal Infections in Children.

Invasive group A streptococcal disease (iGAS) can have varied clinical presentations in children, are responsible for prolonged hospital stays and can cause mortality and long-term morbidity in children. Over the last decade, there has been an increase in the incidence of iGAS infections in the UK and worldwide. This has renewed the focus on early diagnosis, management and prevention of this disease. The aim of this study was to review the varied clinical presentations and management of children with iGAS infections. We reviewed the data of children admitted to our tertiary Children's Hospital who had positive isolation of Group A Streptococcus( GAS) from sterile site cultures over the last 8 years. We reviewed their clinical presentations and management including treatment given (antibiotics and duration), outcome and follow up. A total of 57 children had iGAS during the study period. The incidence of iGAS was 6-7 cases per year during the study period, except for 2015 when we had 11 cases. The mean length of stay of children admitted with iGAS was 11 days (range 2- 35 days). 21.1% children were admitted to intensive care during their hospital stay. Fever was the most common presenting symptom. Pneumonia with or without empyema was the most common Diagnosis. Initial antibiotic management was varied with ceftriaxone the most commonly used antibiotic in 30% of the cases. 50% of children had their antimicrobial therapy optimised to IV benzylpenicillin after the confirmed isolation of GAS. 7 Children were re-admitted for further treatment and needed a further course of antibiotics. 4 children (7%) died due to iGAS infection. Our study highlighted the varied symptomatology and management practices in children with iGAS and showed that early diagnosis and prompt initiation of appropriate antibiotics for iGAS can help in the resolution of symptoms and good outcomes.

PANDAS/PANS in childhood: Controversies and evidence.

Since first defined in 1998, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) and its later, broader iteration, paediatric acute-onset neuropsychiatric syndrome (PANS), have garnered significant attention and controversy. The role of streptococcal infection in children with explosive onset obsessive-compulsive disorder and new onset tics, the natural history of this entity, and the role of symptomatic and disease-modifying therapies, including antibiotics, immunotherapy, and psychoactive drugs, are all issues that have yet to be definitively addressed. While definitive proof of the autoimmune hypothesis of PANDAS is lacking, given the heightened attention to this entity and apparent rise in use of this diagnostic category, addressing questions around diagnosis, treatment, and etiology is imperative. In this paper, we review current working definitions of PANDAS/PANS, discuss published evidence for interventions related to this entity, and propose a clinical approach to children presenting with acute symptoms satisfying criteria for PANDAS/PANS.

Altered cerebral glucose metabolism normalized in a patient with a pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS)-like condition following treatment with plasmapheresis: a case report

BackgroundPediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS) is a specific autoimmune response to group-A streptococcal infections in children and adolescents with a sudden onset of obsessive-compulsive disorders or tic-like symptoms. Cerebral metabolic changes of patients have not yet been observed.Case presentationWe present a case of an 18-year old male with a PANDAS-like condition after developing tic-like symptoms and involuntary movements three weeks after cardiac surgery. The patient had suffered from pharyngotonsillitis before the symptoms started. The anti-streptolysin O (ASO) titer was elevated (805 kU/l). Antibiotic therapy did not improve his condition. Intravenous immunoglobulins and high-dose cortisone therapy had minor beneficial effects on his involuntary movements. 18F-Fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) demonstrated pronounced hypermetabolism of the basal ganglia and cortical hypometabolism. The patient was treated with five cycles of plasmapheresis. A marked clinical improvement was observed after four months. Cerebral metabolic alterations had completely normalized.ConclusionsThis is the first report of cerebral metabolic changes observed on FDG-PET/CT in a patient with a PANDAS-like condition with a normalization following immunomodulatory treatment. Cerebral FDG-PET/CT might be a promising tool in the diagnosis of PANDAS.

Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital.

Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant.Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records.A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia.Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure.The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia.

Invasive Group A Streptococcal Infections in Children: A Nationwide Survey in Finland.

The incidence of invasive group A streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nationwide survey to assess the population-based incidence rates and outcomes of children with iGAS infections. We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emm types or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet. We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006-2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients were severe soft-tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain was the most typical symptom for soft-tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate was 2%. The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.

Đặc điểm dịch tễ và di truyền của liên cầu khuẩn gây tan máu β lưu hành ở trẻ em tỉnh Quảng Trị

This study was carried out in 200 children aged 7 ÷ 11 in Gio Chau Primary School, Gio Linh District, Quang Tri Province. The results showed that the rate of ß - hemolytic streptococcal infection was 25.5%, including strains of group A (17,5%) and group G (8,0%). The streptococcal infection in children is not related to their sex but to their parents’ occupation. The types of emm 4.0, emm 12.0, emm 44.0, emm 58.0, emm 104.0 and emm 109.1 were found among 30/35 S. Pyogenes strains. For group G streptococcus 12 S. anginosus and 2 S. dysgalactiae subsp. Equisimilis strains were classified.

Increased incidence of invasive group A beta hemolytic streptococcal infections in children

Group A beta hemolytic streptococci (GAS) can cause a wide range of mild infections but they are associated with severe infections with high morbidity and mortality rates. Risk factors for invasive GAS infections in children include antecedent varicella zoster infection. There is an increasing incidence of invasive GAS infection caused by clonal strains leading to outbreaks in the last decade. We describe four pediatric patients with severe conditions caused by GAS, leading to intensive care support in two patients. Two of the patients had antecedent varicella infection. A single clone of group A streptococcus was responsible in all children. Routine varicella vaccination is not currently part of the health programs of many countries, including The Netherlands. One benefit of universal varicella vaccination would be the prevention of some cases of pediatric invasive GAS disease, leading to a decrease in hospitalization, morbidity and mortality rates.

Clinical Perineal Streptococcal Infection in Children: Epidemiologic Features, Low Symptomatic Recurrence Rate after Treatment, and Risk Factors for Recurrence

To evaluate the epidemiology of perineal streptococcal infection and recurrence rates following amoxicillin treatment. We used laboratory logs in a single pediatric practice to identify patients 0-18 years of age with perineal cultures positive for group A Streptococcus (GAS) and reviewed their medical charts. We described epidemiologic features, determined recurrence rates following antibiotic treatment, and performed a case-control study to identify possible risk factors for recurrence in patients treated with amoxicillin. We found a perineal streptococcal infection rate of 4.6 per 10,000 patient encounters and a recurrence rate in 157 patients with perineal streptococcal infection of 12.4% after amoxicillin. In male patients, the predominant site of involvement was the perianal region (86%), and for female patients, the perivaginal area (62%). Nearly 80% of patients were 2-7 years of age (range 18 days-12.5 years). Perineal streptococcal infection and GAS pharyngitis followed a similar seasonal pattern of occurrence with 65% of perineal streptococcal infection occurring October through March. In patients with perineal streptococcal infection, 95% had a concomitant pharyngeal culture positive for GAS. Best predictive factors for recurrence after amoxicillin were longer duration of symptoms prior to diagnosis and having a sibling with perineal streptococcal infection at some time before or after the initial episode. Following treatment with amoxicillin, we found a low recurrence rate of 12.4%. Amoxicillin can be expected to be reliable first-line therapy for perineal streptococcal infection.

Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: a systematic review and prospective multicentre external validation study.

Several clinical prediction rules for diagnosing group A streptococcal infection in children with pharyngitis are available. We aimed to compare the diagnostic accuracy of rules-based selective testing strategies in a prospective cohort of children with pharyngitis. We identified clinical prediction rules through a systematic search of MEDLINE and Embase (1975-2014), which we then validated in a prospective cohort involving French children who presented with pharyngitis during a 1-year period (2010-2011). We diagnosed infection with group A streptococcus using two throat swabs: one obtained for a rapid antigen detection test (StreptAtest, Dectrapharm) and one obtained for culture (reference standard). We validated rules-based selective testing strategies as follows: low risk of group A streptococcal infection, no further testing or antibiotic therapy needed; intermediate risk of infection, rapid antigen detection for all patients and antibiotic therapy for those with a positive test result; and high risk of infection, empiric antibiotic treatment. We identified 8 clinical prediction rules, 6 of which could be prospectively validated. Sensitivity and specificity of rules-based selective testing strategies ranged from 66% (95% confidence interval [CI] 61-72) to 94% (95% CI 92-97) and from 40% (95% CI 35-45) to 88% (95% CI 85-91), respectively. Use of rapid antigen detection testing following the clinical prediction rule ranged from 24% (95% CI 21-27) to 86% (95% CI 84-89). None of the rules-based selective testing strategies achieved our diagnostic accuracy target (sensitivity and specificity>85%). Rules-based selective testing strategies did not show sufficient diagnostic accuracy in this study population. The relevance of clinical prediction rules for determining which children with pharyngitis should undergo a rapid antigen detection test remains questionable.

The curious case of the "inseparable child".

Streptococcal infections in children rarely lead to neuropsychiatric manifestations referred to as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. The common sequelae include tics, Tourette's syndrome or obsessive-compulsive disorder. Rare presentations may include separation anxiety disorder, body dysmorphic disorder and attention deficit hyperactivity disorder. We present a case of a 10-year-old child that presented primarily with abrupt onset of separation anxiety without any other neuropsychiatric manifestations such as tics or obsessive-compulsive symptoms. Streptococcal infections may present with varied neuropsychiatric manifestations in the pediatric age group and one needs to be more vigilant in cases that have an abrupt onset and unusual presentation. A high index of suspicion is important to diagnose such cases and provide them with a timely treatment.

Group A streptococcal infections in children

With the advent of antimicrobials during World War II, and a natural decline that began before then, dread diseases began to assume a less important role, especially in industrialised countries. By the 1970s, acute rheumatic fever and acute glomerulonephritis were rarely seen, even though acute streptococcal infections continued to occur with their usual frequency and severity. In the 1980s, attention was once again focused on infections caused by group A streptococcus and its sequelae. The most common infections caused by group A streptococcus are pharyngitis and pyoderma, which occur in children particularly.