Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study).

BACKGROUND: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients' characteristics, and determine ICU mortality associated factors. METHODS: We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate. RESULTS: Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality. CONCLUSION: The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.

Postinfectious Inflammation, Autoimmunity, and Obsessive-Compulsive Disorder: Sydenham Chorea, Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection, and Pediatric Acute-Onset Neuropsychiatric Disorder.

Postinfectious neuroinflammation has been implicated in multiple models of acute-onset obsessive-compulsive disorder including Sydenham chorea (SC), pediatric acute-onset neuropsychiatric syndrome (PANS), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). These conditions are associated with a range of autoantibodies which are thought to be triggered by infections, most notably group A streptococci (GAS). Based on animal models using huma sera, these autoantibodies are thought to cross-react with neural antigens in the basal ganglia and modulate neuronal activity and behavior. As is true for many childhood neuroinflammatory diseases and rheumatological diseases, SC, PANS, and PANDAS lack clinically available, rigorous diagnostic biomarkers and randomized clinical trials. In this review article, we outline the accumulating evidence supporting the role neuroinflammation plays in these disorders. We describe work with animal models including patient-derived anti-neuronal autoantibodies, and we outline imaging studies that show alterations in the basal ganglia. In addition, we present research on metabolites, which are helpful in deciphering functional phenotypes, and on the implication of sleep in these disorders. Finally, we encourage future researchers to collaborate across medical specialties (e.g., pediatrics, psychiatry, rheumatology, immunology, and infectious disease) in order to further research on clinical syndromes presenting with neuropsychiatric manifestations.

Self-collection of samples for group B streptococcus testing during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Sample self-collection for reproductive tract infection diagnosis has been found to offer greater convenience, privacy, autonomy, and expanded access to testing in non-pregnant adults. This review aimed to determine whether sample self-collection is as accurate as provider-collection for detection of group B streptococcus colonisation in pregnancy and whether a strategy of self-collection compared to provider-collection might improve maternal and neonatal health outcomes. METHODS: We searched CINAHL Plus, Medline, EMBASE, Maternity and Infant Care Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews in June 2022. Eligible studies compared self-collected and provider-collected samples taken from the same participants or participants randomised to either self-collection or provider-collection for reproductive tract infection testing using the same test and testing method in pregnant individuals. We included trials and observational studies. Reviewers assessed risk of bias using the QUADAS-2 checklist and independently extracted data. Sensitivity and specificity for group B streptococcus colonisation of self-collected compared to provider-collected samples were pooled using a bivariate, random-effects, meta-analytic model. This review was registered with PROSPERO (CRD42023396573). RESULTS: The search identified 5909 references, of which eleven diagnostic accuracy group B streptococcus studies were included (n = 3269 participants). No studies assessed the effects of self-collection in pregnancy on health outcomes. All studies had high or unclear risk of bias. Pooled sensitivities of self-collected samples for group B streptococcus detection were 82% (95% CI: 66-91%; I2 = 68.85%) in four trials (n = 1226) and 91% (95% CI: 83-96%; I2 = 37.38%) in seven non-randomised studies (n = 2043). Pooled specificities were 99% (95% CI: 98-99%; I2 = 12.08%) and 97% (95% CI: 94-99%; I2 = 72.50%), respectively. CONCLUSIONS: Self-collected samples for group B streptococcus detection in pregnancy had high specificity compared to provider-collection, but lower sensitivity, particularly for included trials. Studies investigating the effect of self-collection on health outcomes, and further higher quality trials comparing accuracy of self-collection to provider-collection, are required.

Enhancement of chlorhexidine activity against planktonic and biofilm forms of oral streptococci by two Croton spp. essential oils from the Caatinga biome.

This work investigates the ability of two Croton spp. essential oils (EO) to enhance chlorhexidine (CHX) activity against oral streptococci. EO's chemical composition of Croton argyrophyllus and C. pluriglandulosus was determined by GC-MS/FID. The microbial growth kinetics and minimum inhibitory concentration (MIC) of EOs and CHX were determined, followed by their synergism against S. mutans UA159 and ATCC 25175, S. salivarius ATCC 7073 and S. sp. ATCC 15300. The microplate-based method was used to determine the EO/CHX activity against 24-h-old biofilms. The major compounds were α-pinene (54.74%) and bicyclogermacrene (16.08%) for EOAr and 1,8-cineole (17.41%), methyleugenol (16.06%) and elemicin (15.99%) for EOPg. Both EO had MIC around 16,000 µg/mL. EOs/CHX presented a synergistic effect against most strains (FICi from 0.133 to 0.375), and OE/CHX-treated biofilms showed a reduction in biomass and cell viability compared to CHX, only (p < 0.01). Thus, the EOs works as natural adjuvants for CHX.

Recurrent, non-traumatic, non-exertional rhabdomyolysis after immunologic stimuli in a healthy adolescent female: a case report.

BACKGROUND: Dysferlinopathy refers to a heterogenous group of autosomal recessive disorders that affect a skeletal muscle protein called dysferlin. These mutations are associated with limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, asymptomatic hyperCKemia, and distal myopathy with anterior tibial onset. CASE PRESENTATION: A 16 year old female presented with myalgia, weakness and dark urine one week after her second BNT162b2 mRNA (Pfizer) vaccine. Initial serum creatine kinase (CK) was measured at 153,000 IU/L, eventually up-trending to over 200,000 IU/L. However, stable renal function precluded hemodialysis allowing discharge after 10 days of intravenous (IV) hydration and alkaline diuresis. Just two years prior to the current presentation, the patient was hospitalized following Group A Streptococcal pharyngitis infection complicated by rhabdomyolysis. She presented with fatigue, lower extremity weakness, and dark oliguria with CK measuring 984,800 IU/L. IV hydration was attempted however hemodialysis was ultimately required throughout her 24-day hospital stay. Her episode was presumed to be idiopathic and no further work-up was performed at that time. During the patient's current hospitalization, she reported similar symptomology (myalgias and weakness) following her first quadrivalent Gardasil vaccine at age 11. No hospitalization was required at that time. A comprehensive workup was now initiated while the patient was being treated for her suspected second or third non-exertional, non-traumatic rhabdomyolysis. Rheumatologic, metabolic, infectious, and endocrinologic workup were all unremarkable. Patient eventually had whole exome sequencing performed which revealed a heterozygous pathogenic variant in the DYSF gene (DYSF c.2643 + 1G > A) encoding dysferlin. No clinically significant sequelae occurred thus far. CONCLUSIONS: While there have been reports of symptomatic heterozygote carriers of dysferlinopathies, to our knowledge none have been associated with recurrent rhabdomyolysis after immunogenic stimuli. This unique case presentation highlights the importance of a multi-disciplinary care team, the utility of modern whole-exome gene sequencing, and the future challenges of balancing vaccine risk vs benefit.

Improving Intrapartum Group B Streptococcus Prophylaxis in Patients with a Reported Penicillin or Cephalosporin Allergy: A Quality Improvement Project.

OBJECTIVE: To evaluate the impact of a standardized allergy-guided approach to Group B Streptococcus (GBS) prophylaxis in pregnant women with reported penicillin or cephalosporin allergy. METHODS: This interrupted time-series analysis included obstetric patients requiring GBS prophylaxis who reported penicillin or cephalosporin allergies. Patients were divided into baseline (April 1, 2019 to July 21, 2020) and intervention (July 22, 2020 to July 31, 2021) groups. The primary outcome was prophylaxis appropriateness, based on antibiotic type, nature of reaction, and cross-reactivity risk. Secondary outcomes included type of prophylaxis received and antibiotic-related adverse events. RESULTS: The study included 88 patients in the baseline period and 52 patients in the intervention period. Appropriate prophylaxis increased from 47% (41/88) to 85% (44/52), with the segmented regression model confirming a statistically significant increase over time (incidence rate ratio 1.57; 95% CI 1.02-2.43, P = 0.04, slope coefficient 1.06/month; 95% CI 1.01-1.10, P = 0.01). Penicillin and cefazolin use increased from 61% (54/88) to 87% (45/52) in the intervention period (P = 0.002), and no hypersensitivity reactions occurred during this period. CONCLUSIONS: Implementation of standardized allergy-guided prophylaxis safely improved appropriate ß-lactam antibiotic use in obstetric patients requiring GBS prophylaxis who reported penicillin and cephalosporin allergies.

Epidemiology and Clinical Characteristics of Henoch-Schönlein Purpura Associated with Streptococcal Infection in 217 Children in Hubei Province, China.

Objectives The objectives of present study were to analyze the association of the streptococcal infection with childhood Henoch-Schönlein purpura (HSP) in China. Methods: We performed a case-control study over a period of five years to evaluate the epidemiology and clinical characteristics of group A ß-hemolytic streptococcal (GABHS) triggered HSP. Results: 1. The frequency of GABHS-triggered HSP was 15.1%, while that of GABHS infection developing HSP in children was 4.7%. 2.The epidemiological characteristics of HSP with streptococcal infection were similar to those of HSP alone. 3. The GABHS-triggered HSP cases had a significantly higher frequency of renal involvement than the noninfectious group. 4. IgA and IgG were significantly increased in the streptococcal infection group than in the noninfectious group, while the levels of C3 and C4 decreased significantly. Conclusions: GABHS infection is the most frequent agent in HSP children, and may aggravate the immune dysfunction and prolong the course of HSP.

Oral cavity swabbing for diagnosis of group a Streptococcus: a prospective study.

BACKGROUND: Throat pain is a common complaint in the ambulatory setting. Diagnosis of group A Streptococcus is made with a culture, molecular test or a rapid antigen detection test from the tonsils or the posterior pharyngeal wall, while other areas of the oral cavity are considered unacceptable. The purpose of the study is to compare cultures from the tonsils or posterior pharyngeal wall (throat) with cultures from the oral cavity (mouth). METHODS: A prospective study conducted in ambulatory care. Eleven family physicians collected 2 swabs (throat and mouth) from 200 consecutive patients who complaint about throat pain. Inclusion criteria were throat pain and Centor Criteria > 2. Exclusion criteria were tonsillectomy and age (< 3 or > 65 years old). Participants were later divided into two groups - pediatrics (3-18 years old) and adults (19-65 year old). Sensitivity and specificity of mouth culture were calculated, with throat culture considered the reference gold standard. RESULTS: Between November 2017 and March 2019, 200 swabs were collected (101 adults and 99 children). In the adult group sensitivity of mouth culture was 72.1% (95% Confidence Interval [CI] 59.9-82.3%) and specificity was 100% (95% CI 92.7-89.4%-100%). In the pediatric group sensitivity of mouth culture was 78.3% (95% CI 65.8-87.9%) and specificity was 100% (95% CI 92.5-100%). CONCLUSION: Our study demonstrated higher sensitivity of mouth culture for GAS than previously published. This finding suggests that areas of the oral cavity that were considered as unacceptable sites for culture of GAS pharyngitis may be considered as acceptable swabbing sites. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov, ID NCT03137823. Registered 3 May 2017.

How could we suspect life-threatening perinatal group A streptococcal infection?

AIM: Perinatal group A streptococcal infection is a rare but life-threatening condition. Few reports have focused on its clinical characteristics and how to prevent deterioration. We report our experience with two antenatal fatal cases and reviewed 96 cases in the literature to assess the clinical characteristics of group A streptococcal infection. METHODS: English-language clinical reports of antenatal and postnatal group A streptococcal infection in 1974-2019 were retrieved and examined. Relationships between clinical characteristics and maternal outcomes were assessed. RESULTS: Univariate analysis revealed that antenatal group A streptococcal infection was significantly associated with an age of ≤19 or ≥ 35 years, cesarean section, sore throat as an initial symptom, positive throat culture, maternal death and fetal death. Multivariate analysis revealed that antenatal onset (odds ratio = 7.922, 95% confidence interval = 1.297-48.374; P = 0.025) and a quick sepsis-related organ-failure assessment score (qSOFA; low blood pressure, high respiratory rate or altered mental status) of ≥2 (odds ratio = 6.166, 95% confidence interval = 1.066-35.670; P = 0.042) were significantly related to maternal death. CONCLUSION: Per our findings, antenatal group A streptococcal infection was significantly associated with maternal and fetal death. Further, the antenatal infection was revealed as a more critical risk factor. We suggest that the presence of any sign related to the qSOFA is a potential clue suspecting perinatal group A streptococcal infection in primary obstetric facilities.

Preventing Early-Onset Group B Streptococcus neonatal infection and reducing antibiotic exposure using a rapid PCR test in term prelabour rupture of membranes.

BACKGROUND: How best to target intrapartum antibiotic prophylaxis (IAP) to minimise both Early-Onset Group B Streptococcus (EOGBS) neonatal infection and maternal/fetal antibiotic exposure is uncertain, with both routine-screening and risk-factor approaches available. AIMS: This retrospective cohort study was undertaken to examine the outcomes of a hybrid risk-and-screen approach to EOGBS prevention using GBS polymerase chain reaction (PCR). The target population was women with term prelabour rupture of membranes (TermPROM) having the risk factor of prolonged rupture of membranes (ROM) ≥18 h. MATERIALS AND METHODS: Non-labouring TermPROM women had rapid GBS PCR testing at presentation. GBS screen-positive women proceeded to induction of labour and received IAP. GBS screen-negative women were allowed home to await spontaneous labour and not given IAP regardless of duration of ROM, unless other risk factors developed. For all other women, the risk-factor approach was followed. RESULTS: From 2009 to 2018, there were 20 cases of culture-positive EOGBS, a rate of 0.36/1000 live births (95% CI 0.22-0.56/1000), comparable to other recent reports. Over 2010-2018 when laboratory data were available, 1120 TermPROM women with ROM ≥18 h avoided antibiotics because they were GBS PCR-negative (2.3% of all births, 3.6% of vaginal births) while 338 TermPROM women with ROM <18 h received targeted antibiotics for being GBS-positive. No cases of EOGBS occurred in TermPROM women, those with ROM ≥18 h, or due to protocol-compliance failure. CONCLUSIONS: A hybrid approach involving risk-factor-based IAP and intrapartum GBS PCR screening of non-labouring TermPROM women delivers acceptably low rates of EOGBS while minimising and better targeting antibiotic exposure.

Emerging serotype III sequence type 17 group B streptococcus invasive infection in infants: the clinical characteristics and impacts on outcomes.

BACKGROUND: Group B Streptococcus (GBS) is an important pathogen that causes high mortality and morbidity in young infants. However, data on clinical manifestations between different GBS serotypes and correlation with molecular epidemiology are largely incomplete. The aim of this study was to determine the serotype distribution, antimicrobial resistance, clinical features and molecular characteristics of invasive GBS isolates recovered from Taiwanese infants. METHODS: From 2003 to 2017, 182 non-duplicate GBS isolates that caused invasive disease in infants less than one year of age underwent serotyping, multilocus sequence typing (MLST) and antibiotic susceptibility testing. The clinical features of these infants with GBS disease were also reviewed. RESULTS: Of the 182 patients with invasive GBS disease, 41 (22.5%) were early-onset disease, 121 (66.5%) were late-onset disease and 20 (11.0%) were late late-onset disease (> 90 days of age). All these patients were treated with effective antibiotics on time. Among them, 51 (28.0%) had meningitis, 29 (16.0%) had neurological complications, 12 (6.6%) died during hospitalization, and 15 (8.8%) out of 170 patients who survived had long-term neurological sequelae at discharge. Serotype III GBS strains accounted for 64.8%, followed by serotype Ia (18.1%) and Ib (8.2%). MLST analysis revealed 11 different sequence types among the 182 isolates and ST-17 was the most dominant sequence type (56.6%). The correlation between serotype III and ST17 was evident, as ST17 accounted for 87.3% of all serotype III isolates. There was an obvious increasing trend of type III/ST-17 GBS that caused invasive disease in infants. All isolates were susceptible to penicillin, cefotaxime, and vancomycin, while 68.1 and 65.9% were resistant to erythromycin and clindamycin, respectively. CONCLUSIONS: Despite timely and appropriate antibiotic treatment, a significant proportion of invasive GBS disease still inevitably causes adverse outcomes. Further study to explore preventive strategies and development of serotype-based vaccines will be necessary in the future.

European Multicentre Tics in Children Studies (EMTICS): protocol for two cohort studies to assess risk factors for tic onset and exacerbation in children and adolescents.

Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive-compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3-10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3-16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host's immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders.

Epidemiology and Pathophysiology of Childhood Narcolepsy.

It is now recognized that there are two types of narcolepsy. Narcolepsy type I or Narcolepsy with cataplexy is caused by the loss of hypocretin or orexin neurons. Narcolepsy type II or narcolepsy without cataplexy has normal hypocretin and the etiology is unknown. Hypocretin is a neuropeptide produced by neurons in the lateral hypothalamus. Both genetic and environmental factors play a crucial role in the pathogenesis of narcolepsy. Most patients with narcolepsy type I and half of patients with narcolepsy type II carry HLA-DQB1*0602. HLA-DQB1*0602 forms a heterodimer with HLA-DQA1*0102 and may act as an antigen presenter to the T cell receptors, resulting in narcolepsy susceptibility. In addition, narcolepsy has been shown to be linked to polymorphisms in other non-HLA genes that may affect immune regulatory function, leading to speculation that autoimmune processes may play a crucial role in the loss of hypocretin neurons. Infections have been proposed as a potential trigger for the autoimmune-mediated mechanism. Several recent studies have shown increased cases of narcolepsy, especially in children and adolescents in relation with H1N1 influenza. The increased cases in Europe seems to be related to a specific type of H1N1 influenza vaccination (Pandemrix), while the increased cases in China are related to influenza infection. The data from the Pediatric Working Group of the Sleep Research Network have shown similar increases of early onset narcolepsy in the United States.

Fulminant group A streptococcal infection without gangrene in the extremities: Analysis of five autopsy cases.

Five autopsy cases of fulminant group A streptococcal infection without gangrene in the extremities are presented. Clinical course of the fulminant illness was short (2-4 days). One pathological autopsy case was aged (86-years-old), and hemorrhagic cystitis was observed. The other four forensic autopsy cases were young (24-38 years-old) with the mean age of 32, and the primary infective lesions were located in the postpartum endometrium, tonsil and bronchus (2 cases). Systemic coccal dissemination with poor neutrophilic reaction was seen in two of five cases. Bilateral renal cortical necrosis was noted in three cases (including two with bacterial embolism). Hemophagocytosis, probably resulting from hypercytokinemia, was characteristic in three cases without bacterial embolism. Gram-positive cocci colonizing the hemorrhagic and necrotizing lesions were consistently immunoreactive for streptococcal antigens and Strep A (a carbohydrate antigen on group A streptococci). Neutrophilic reaction was mild in the primary infected foci. Clinicians should note that fulminant streptococcal infection (streptococcal toxic shock syndrome) in young and immunocompetent patients may not be associated with gangrene in the extremities. Autopsy prosecutors (diagnostic and forensic pathologists) must recognize the difficulty in making an appropriate autopsy diagnosis, particularly when bacterial embolism is not associated.

The usefulness of determination of the procalcitonin (PCT) concentration in GBS piositive pregnant womens blood serum for anticipations of infections in newborns

Group-B streptococci (GBS) are commensal bacteria of the human body. They may, however, pose a serious life hazard to pregnant women. During labour, newborns of GBS-positive mothers run the risk of infections that may eventually lead to severe complications, sepsis or even death. For this reason, it is very important to find new diagnostic markers that will enable fast and effective diagnostics and control of the disease process. The level of procalcitonin emerges as a promising diagnostic parameter. AIM. Analysis of the impact of the procalcitonin (PCT) level in GBS-positive pregnant women on the possibility of complications and infections in mothers and newborns MATERIAL AND METHODS. The study group consisted of 115 GBS-positive pregnant women. For each mother-to-be, the CRP and the PCT concentration levels were determined. The clinical state of 117 newborns (2 twin pregnancies) was also assessed. After delivery, the CRP concentration level was determined in the newborns. The examinations had a retrospective character. RESULTS. 30 women showed a raised concentration of CRP and 13 ­ of PCT. No correlation was found between the two diagnostic markers. Similarly, no relation was found between a raised concentration of PCT and the occurrence of a bacterial infection or other complications in the parturient. A raised concentration of procalcitonin in the mother did not translate into the development of an infection in the newborn, either. CONCLUSIONS. The results of the study indicate that there is no correlation between a raised concentration of PCT in GBS-positive pregnant women and a raised CRP level. Abnormal PCT levels in the women covered by the study did not involve a higher frequency of the occurrence of complications or bacterial infections either in the mothers or in the newborns.

Reduced incidence of neonatal early-onset group B streptococcal infection after promulgation of guidelines for risk-based intrapartum antibiotic prophylaxis in Sweden: analysis of a national population-based cohort.

INTRODUCTION: This study aimed to investigate the incidence of neonatal early-onset group B streptococcal (GBS) infection in Sweden after promulgation of guidelines (2008) for risk factor-based intrapartum antibiotic prophylaxis, and evaluate the presence of risk factors and obstetric management in mothers. MATERIAL AND METHODS: National registers were searched for infants with early-onset GBS infection during 2006-2011. Medical records of cases and case mothers were abstracted. Verified cases of sepsis/meningitis and cases with clinical sepsis/pneumonia were documented, as well as risk factors in case mothers and timeliness of intrapartum antibiotic prophylaxis administration. RESULTS: There were 227 cases with verified infection, with an incidence of 0.34‰ of live births during the whole period. There was a significant decrease after promulgation of guidelines, from 0.40 to 0.30‰ [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.57-0.99]. A significant decrease in the number of cases with clinical GBS sepsis/pneumonia was also observed. In parturients with one or more risk factors, the incidence of any GBS infection was reduced by approximately 50% (OR 0.47, 95% CI 0.35-0.64), although there were many cases where the opportunity for timely administration of intrapartum antibiotic prophylaxis was missed. In infants of mothers without risk factor(s) there was no reduction in early-onset GBS morbidity. The mortality in verified cases was 4.8% (95% CI 2.1-7.6). CONCLUSIONS: The introduction of national guidelines for risk-based intrapartum antibiotic prophylaxis coincided with a significant 50% risk reduction of neonatal early-onset GBS infection in infants of parturients presenting with one or more risk factors. A stricter adherence to guidelines could probably have reduced the infant morbidity further.

An expert opinion on PANDAS/PANS: highlights and controversies.

OBJECTIVES: 'Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections' (PANDAS) identified a unique subgroup of patients with abrupt onset of obsessive compulsive disorder (OCD) symptoms clinically related to Streptococcus infection and accompanied by neuropsychological and motor symptoms. After almost 20 years, PANDAS has not been accepted as distinct disorder and new criteria for paediatric acute-onset neuropsychiatric syndrome (PANS) have been replaced it, highlighting the fact that several agents rather than only Streptococcus might be involved. METHODS: Extensive review of the PANDAS/PANS literature was performed on PubMed. RESULTS: Although antibiotics have been reported to be effective for acute and prophylactic phases in several uncontrolled studies and non-steroidal anti-inflammatory drugs (NSAID) are used during exacerbations, clinical multicenter trials are still missing. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) are still the first line of recommendation for acute onset OCD spectrum. Immunological therapies should be restricted to a few cases. CONCLUSIONS: While PANDAS has found no confirmation as a distinct syndrome, and it is not presented in DSM-5, patients with acute onset OCD spectrum, neurocognitive and motor symptoms should be evaluated for inflammatory, infective, immunological and metabolic abnormalities with a comprehensive diagnostic algorithm.

Clinical and Microbiological Characteristics of Invasive Group A Streptococcal Infections Before and After Implementation of a Universal Varicella Vaccine Program.

Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly.

Integration of Genomic and Other Epidemiologic Data to Investigate and Control a Cross-Institutional Outbreak of Streptococcus pyogenes.

Single-strain outbreaks of Streptococcus pyogenes infections are common and often go undetected. In 2013, two clusters of invasive group A Streptococcus (iGAS) infection were identified in independent but closely located care homes in Oxfordshire, United Kingdom. Investigation included visits to each home, chart review, staff survey, microbiologic sampling, and genome sequencing. S. pyogenes emm type 1.0, the most common circulating type nationally, was identified from all cases yielding GAS isolates. A tailored whole-genome reference population comprising epidemiologically relevant contemporaneous isolates and published isolates was assembled. Data were analyzed independently using whole-genome multilocus sequencing and single-nucleotide polymorphism analyses. Six isolates from staff and residents of the homes formed a single cluster that was separated from the reference population by both analytical approaches. No further cases occurred after mass chemoprophylaxis and enhanced infection control. Our findings demonstrate the ability of 2 independent analytical approaches to enable robust conclusions from nonstandardized whole-genome analysis to support public health practice.

Antibody-mediated rejection after ABO-incompatible pediatric living donor liver transplantation for propionic acidemia: A case report.

We herein present the case of a four-yr-old boy with PA who developed AMR after ABO-incompatible LDLT despite undergoing B cell desensitization using rituximab. Although the CD19+ lymphocyte count decreased to 0.1% nine days after the administration of rituximab, he developed a high fever which was accompanied by arthralgia due to a streptococcal infection 13 days after rituximab prophylaxis. After the clearance of the infection, he underwent ABO-incompatible LDLT 36 days after the administration of rituximab. The CD19+ lymphocyte count just prior to LDLT was 1.2%. He developed AMR five days after LDLT, and the antidonor-type IgM and IgG antibody titers increased to 1:1024 and 1:1024, respectively. He was treated by plasma exchange, IVIG, steroid pulse therapy, and rituximab re-administration; however, his liver dysfunction continued. Despite intensive treatment, he died due to complicated abdominal hernia, acute renal failure, and ARDS. This case suggests that a streptococcal infection may induce the activation of innate immune responses; thus, additional desensitization therapy should be considered prior to ABO-incompatible LDLT if B cell reactivation is suspected.