The Severity and Characteristics of Pediatric Group A Streptococcal Meningitis in the Netherlands (2015-June 2024): Results From a Nationwide Multicenter Cohort Study.

Group A Streptococcal meningitis in adults

STREPTOCOCCUS PYOGENES: A DEVASTATING CAUSE OF MENINGITIS IN A YOUNG ADULT

Burden of group A streptococcal meningitis in Salvador, Brazil: report of 11 years of population-based surveillance

As group A Streptococcus (GAS) meningitis is seldom reported in children, emm-type distribution data are scare. We report eight cases of GAS meningitis in Belgium (2008–2013) and compare molecular characteristics of our strains with a further 55 cases previously reported with their corresponding emm-types. emm1 type was the most frequent (24%) followed by emm6 (11%), emm12 (11%) and emm3 (6%). Together these four emm-types accounted for 52% of the cases, while the rest of the cases are due to 24 different emm-types. These 28 emm-types associated with GAS meningitis belonged to 16 different emm-clusters suggesting that there is no propensity for particular emm-types or emm-cluster to cause meningitis. Theoretical coverage of the 30-valent vaccine candidate would be 77.8% (49/63 isolates) among children with GAS meningitis.

Induction of cyclophilin A by influenza A virus infection facilitates group A Streptococcus coinfection.

To the Editors: During the second and third year of the COVID pandemic, an increased number of serious cases due to different microorganisms have been reported. In the second half of 2022, it has been reported that there has been an increase in invasive group A streptococcal (iGAS) infections in many countries including England, the Netherlands and others.1–3 iGAS is defined as a life-threatening invasive infection characterized by the isolation of Streptococcus pyogenes from normally sterile body fluids with culture or by pathogen-specific polymerase chain reaction (PCR). If GAS has grown from a probable carrier location, such as the throat, and the clinical course is compatible with GAS disease and no other causing organism has been found, these patients need to be handled as iGAS.4 Before the pandemic, GAS was the most common pathogen among children in Europe who had to be hospitalized for a community-acquired bacterial infection. Patients with GAS infection had a 12% impairment at discharge and a 2% fatality rate. Increases in toxic shock syndrome, necrotizing fasciitis and pleural empyema have all been linked to increased mortality.4 In UK, during the last couple of months, the rate per 100,000 population of iGAS is higher among children.1 Between December 2022 and January 2023, in our tertiary care facility, we followed up 7 consecutive cases of iGAS infection—3 boys and 4 girls, ages 37–96 months—without any relation to one another (Table 1). All children were previously healthy. Five children were admitted to the pediatric intensive care unit, including 1 with toxic shock syndrome and 4 with pleural effusion/empyema. In 6 out of 7 children, the diagnosis of iGAS infection was made based on a positive culture and/or PCR from a typically sterile place, with the pleural fluid being the most frequent site. iGAS infection was defined in a child with toxic shock syndrome based on positive throat culture. In Table 1, antibiotic therapy is displayed. Each patient received clindamycin and 1 patient received intravenous immunoglobulin (IVIG). Due to empyema, thoracic tubes had to be inserted in 5 patients. In 2 of the pleural empyema cases, tube thoracostomy was carried out; in the third video assisted thoracostomy and in the fourth, thoracotomy and decortication were carried out. One child with GAS bacteremia required surgery for mastoiditis, and throughout the course of the investigation, sinus venous thrombosis was detected. Five children required pediatric intensive care unit stay. The length of hospital stay ranged from 7 to 21 days. TABLE 1. - Clinical Characteristics of 7 Children with Invasive Group A Streptococcal Infection Patient Age (month) Gender Diagnosis Culture Multiplex PCR Treatment PICU Stay Length of hospital stay (day) 1 37 Girl Pleural Empyema - Pleural fluid Streptococcus pyogenes Meropenem + vancomycin + clindamycin IVIG Thoracotomy and decortication + 14 2 40 Girl Pleural Empyema Throat Streptococcus pyogenes Pleural fluid Streptococcus pyogenes Tube thoracostomy Ceftriaxone + clindamycin + 9 3 96 Girl Pleural Empyema - Pleural fluid Streptococcus pyogenes Meropenem + vancomycin + clindamycin Tube thoracostomy Video assisted thoracostomy + 15 4 62 Boy Bacteremia, Mastoiditis, Sinus vein thrombosis Blood Streptococcus pyogenes - Meropenem + vancomycin + clindamycin Mastoidectomy - 21 5 48 Boy Pleural Empyema - Pleural fluid Streptococcus pyogenes Ceftriaxone + vancomycin + clindamycin Tube thoracostomy + 10 6 59 Boy Toxic Shock Syndrome Throat Streptococcus pyogenes - Ceftriaxone + vancomycin + clindamycin + 7 7 42 Girl Bacteremia, Pleural Empyema Blood Streptococcus pyogenes - Ceftriaxone + clindamycin - 10 IVIG, intravenous immune globulin; PICU, pediatric intensive care unit. Both the frequency and morbidity of iGAS infections increased after the COVID-19 pandemic as before. While there was only one iGAS case during the previous 3 years, 7 patients in a row were hospitalized during a 2-month period in our setting. Clindamycin would be efficient to deactivate M-protein and these exotoxins because S. pyogenes has the cell wall M-protein that prevents complement activation and reduces phagocytosis. This would produce a positive outcome similar to our case series.4,5 Although culture is the gold standard method for diagnosis, molecular methods such as multiplex PCR are important in identifying the causative agent. Despite treatment, we have seen serious complications in our case series, such as pleural decortication, mastoiditis, sinus venous thrombosis and toxic shock syndrome. Early diagnosis of patients (using molecular techniques included) and the initiation of appropriate treatment including clindamycin, are crucial. To comprehend the postpandemic condition, it is essential to monitor the clinical findings and prognosis of iGAS cases from various countries.

BackgroundGroup A Streptococcus (GAS) is a known cause of invasive infections (iGAS), with the incidence of GAS pneumonia (GAS PNM) being traditionally low. During the COVID pandemic, the rate of iGAS decreased, followed by a rebound in the years after. Several clusters of GAS PNM were described during this time. Systematic data on GAS PNM epidemiology and outcomes is lacking. In this retrospective study we evaluate the rate of GAS PNM in relation to the pandemic, as well as patient population and outcomes in order to identify risk factors for severe infection.Patients’ recruitmentOf all hospitalized patients between April 1, 2018, and March 31, 2024, with positive Group A Streptococcus (GAS) culture, we identified the patients with invasive GAS infection (iGAS) that was defined as a positive culture from any site other than skin and throat. Among patients with iGAS infection, we identified patients with positive sputum cultures and positive blood cultures. Patients with positive blood culture who had an alternative source of bacteremia were excluded by chart review. Remaining patients with positive blood culture and patients with positive sputum culture were reviewed to confirm the presence of pneumonia on imaging, either CT or chest x-ray*, based on radiology reading. If pneumonia was confirmed on imaging, patients were included in the analysis: 11 patients had both positive blood and sputum culture, 37 only sputum culture and 6 only blood culture, making a total of 56 patients**. GAS= Group A Streptococcus infection; iGAS=invasive Group A Streptococcus infection; Bcx=blood cultures; Cx=culture; PNM=pneumoniaNumber of invasive Group A Streptococcus infection (iGAS) and Group A Streptococcus Pneumonia (GAS PNM) in hospitalized patients in relation to COVID pandemic. iGAS infection is defined as a positive culture isolated from any site other than the skin and throat. GAS PNM is defined as pneumonia on imaging (CT and/or chest x-ray) and either positive sputum culture and/or positive blood culture with no other explanation for GAS bacteremia. The evaluated timeframe was divided into pre-pandemic: April 1, 2018, until March 31, 2020); pandemic (April 1, 2020, until March 31, 2022), and post-pandemic (April 1, 2022, until March 31, 2024). The number of both iGAS and GAS PNM increased in post-pandemic compared with pandemic and pre-pandemic period, although the difference was not statistically significant (p=0.48 and p=0.26, respectively).MethodsAmong patients hospitalized between April 1st, 2018, and March 31st, 2024, in Corewell Health West in Michigan, with positive GAS blood and sputum culture, we identified those with GAS PNM (figure 1). A retrospective chart review was conducted to evaluate patients' characteristics and outcomes defined as hospital and ICU length of stay, 90-day all-cause mortality, and readmission rates. The outcomes were evaluated by the time frame (pre-COVID, COVID, and post-COVID) and mortality status using Chi-squared and Fisher exact tests for categorical and Wilcoxon Rank Sum test for numeric variables to assess statistical significance using an alpha of p< 0.05.Patient characteristics, presentation, clinical course and outcome of Group A Strep pneumonia (GAS PNA) by 90-day mortalityViral coinfection and mortality. Deceased patients were more likely to have viral coinfection on admission (p=0.022).ResultsThe absolute number of GAS PNM increased post-COVID compared with COVID and pre-COVID (Figure 2), but there was no difference in the patients’ characteristics or outcomes among the groups. Overall, 35.7% of patients had a viral coinfection and 66.10% needed ICU level of care with the median ICU stay of 3.21 days (9.1, 0.31-23.56) including 50% of patients requiring ventilator support and 50% of patients experiencing shock requiring vasopressors. 26.8% died within 90 days, with a median time between positive culture and death of 2 days (3.5, 0-59). Deceased patients were more likely to have viral coinfection (p=0.022) and lower WBC (0.0088), and to be febrile (p=0.043) (Figure 3).ConclusionOur data suggests GAS PNM is a severe, rapidly progressive disease, especially with viral coinfection with many patients requiring ICU care with complications including acute renal failure, shock, ventilator dependent respiratory failure, and even death. Recognizing disease early and identifying risk factors for severe disease is vital to improving outcomes.DisclosuresAll Authors: No reported disclosures

The Food and Drug Administration published a public health warning on the association of bacterial meningitis and cochlear implants in June 2002. This article reports the first case of group A streptococcal (GAS) meningitis in a cochlear-implanted patient, followed by a review on cochlear implantation and GAS meningitis.

Relevance. Despite many studies devoted to diverticular colon disease, the results of treatment of this pathology cannot be considered satisfactory. This is primarily due to the fact that the pathogenesis of this pathology has not been fully studied, there are conflicting data on the clinical significance of the level of intraluminal pressure in the intestine and the degree of violation of collagen synthesis in patients. To a certain extent, these criteria can be decisive in assessing the prognosis of the course of the disease in order to timely conduct proactive conservative therapy and adequate surgical aid. The purpose of the study. Improving the results of treatment of patients with complicated course of diverticular colon disease. Materials and methods. There were 194 patients with diverticular colon disease under observation. In 86% of cases, diverticula were localized in the left half of the colon, and isolated sigmoid colon diverticulosis was detected in 68.0% of patients, in the right half — in 4.7% of cases, total diverticulosis — in 9.3% of patients. In patients, the leukocyte intoxication index, the body resistance index, the neutrophil reactive response, the determination of connective tissue dysplasia, connective tissue metabolism indicators, and the measurement of intraluminal pressure in the sigmoid colon were calculated. Results. Conservative therapy was effective in 158 patients (81.4%). Surgical treatment was required for 36 patients (18.6%), with perforation of the diverticulum — in 13.4%, with stenosis — in 5.2% of cases. The nature of the operation was determined by the localization of diverticula and the variant of complication. Postoperative mortality was 2.8%. It was found that connective tissue dysplasia is observed in all patients with diverticular disease, mild — in 36.6% of patients, moderate — in 63.4%. When assessing the intraluminal pressure in 46 patients, its increase was found in all variants of the course of diverticular disease. The average intraluminal pressure was 13.5 ± 0.4 mm Hg. The maximum pressure level was detected in patients with uncomplicated course of the disease. With the development of complications, a decrease in intraluminal pressure was noted. A decrease in intraluminal pressure to 12 mm Hg or less was an unfavourable factor and a predisposition to the development of a complicated course of the disease. The following signs had a significant effect on the recurrence of the disease: age (61-68 years), complications, duration of the disease (more than 4 years), the size of the diverticulum mouth (less than 0.6 cm and more than 1.0 cm), leukocyte intoxication index (more than 2.4 conventional units), the maximum number of rows of the muscle plate of the mucosa and muscle membranes (more than 8.3 and 84 respectively). Conclusions. To predict the course of diverticular disease, a comprehensive analysis of the age of patients, the stage of the disease and its duration, the diameter of the diverticular mouth, the sum of alternative signs of trouble, leukocyte intoxication index, the reactive response of neutrophils, the number of rows of myocytes of the muscle plate of the mucosa and muscle membranes is necessary. Their evidentiary value exceeds 70%. The level of intraluminal pressure in the colon can act as a criterion for the complicated course of diverticular disease.

Group A streptococcus (GAS) is a rare cause of bacterial meningitis in children and is associated with a high cerebral complication rate. In this case report, we present a 9-year-old girl with GAS meningitis complicated with cerebritis. Clear guidelines about choice of treatment and indications of follow-up by imaging tests are lacking, making GAS meningitis unpredictable and difficult to treat. Eventually, we found 25 paediatric cases of GAS meningitis presented in the literature and reviewed their treatment choices, outcomes and follow-up by imaging tests. Penicillin and ceftriaxone are most preferred for the treatment of GAS meningitis and adding rifampicin to the antibiotic treatment could be of potential benefit. When considering the duration of antibiotic treatment and follow-up by imaging tests, no clear recommendations were found. We found that GAS meningitis is associated with higher mortality and cerebral complication rates compared to other, more common, bacterial causes of meningitis in children. This should alert the clinician to consider imaging tests routinely, even if the patient improves clinically. We advise clinicians to routinely evaluate for possible cerebral complications through magnetic resonance imaging (MRI) scans. When cerebral complications are found, antibiotic treatment should be prolonged and adding rifampicin to the antibiotic regime may be considered.

Group A streptococcus (GAS) is responsible for a wide range of noninvasive group A streptococcal (non-iGAS) and invasive group A streptococcal (iGAS) infections. Information about the emm type variants of the M protein causing GAS disease is important to assess potential vaccine coverage of a 30-valent vaccine under development, particularly with respect to how they compare and contrast with non-iGAS isolates, especially in regions with a high burden of GAS. We conducted a prospective passive surveillance study of samples from patients attending public health facilities in Cape Town, South Africa. We documented demographic data and clinical presentation. emm typing was conducted using CDC protocols. GAS was commonly isolated from pus swabs, blood, deep tissue, and aspirates. Clinical presentations included wound infections (20%), bacteremia (15%), abscesses (9%), and septic arthritis (8%). Forty-six different emm types were identified, including M76 (16%), M81 (10%), M80 (6%), M43 (6%), and M183 (6%), and the emm types were almost evenly distributed between non-iGAS and iGAS isolates. There was a statistically significant association with M80 in patients presenting with noninvasive abscesses. Compared to the 30-valent vaccine under development, the levels of potential vaccine coverage for non-iGAS and iGAS infection were 60% and 58%, respectively, notably lower than the coverage in developed countries; five of the most prevalent emm types, M76, M81, M80, M43, and M183, were not included. The emm types from GAS isolated from patients with invasive disease did not differ significantly from those from noninvasive disease cases. There is low coverage of the multivalent M protein vaccine in our setting, emphasizing the need to reformulate the vaccine to improve coverage in areas where the burden of disease is high.IMPORTANCE The development of a vaccine for group A streptococcus (GAS) is of paramount importance given that GAS infections cause more than 500,000 deaths annually across the world. This prospective passive surveillance laboratory study evaluated the potential coverage of the M protein-based vaccine currently under development. While a number of GAS strains isolated from this sub-Sahara African study were included in the current vaccine formulation, we nevertheless report that potential vaccine coverage for GAS infection in our setting was approximately 60%, with four of the most prevalent strains not included. This research emphasizes the need to reformulate the vaccine to improve coverage in areas where the burden of disease is high.

Invasive group A streptococcal (iGAS) infections are known to be potentially life-threatening. Few detailed pediatric cases of streptococcal toxic shock syndrome (STSS) caused byiGAS with the M1UK strain have been reported. This report describes the case of a child with STSS due to M1UK strain, with detailed documentation of the treatment progress. A 10-year-old female patient without predisposing factors associated with iGAS, initially presented with pneumonia and developed progressive multi-organ failure. A precise diagnosis by the primary hospital's attending physician and effective critical care in the pediatric intensive care unit (PICU) at a tertiary children's hospital led to lifesaving and favorable functional outcomes. The clinical course highlights the importance of recognizing the common presentation of iGAS and prompt medical coordination between general hospitals and PICU. Furthermore, public health measures against iGAS infection are just as important as early diagnosis and treatment to prevent deaths in the community after rapid deterioration.

: Background: Group A β-hemolytic Streptococcus (GAS) and Group B streptococcus (GBS) are two common pathogens that are associated with many diseases in children. Severe infections as a result of these two streptococci are albeit uncommon but associated with high mortality and morbidity, and often necessitate intensive care support. This paper aims to review the mortality and morbidity of severe infection associated with GAS and GBS isolations at a Pediatric Intensive Care Unit (PICU).Methods: All children admitted to PICU of a teaching hospital between October 2002 and May 2018 with laboratory-proven GAS and GBS isolations were included.Results: There were 19 patients (0.7% PICU admissions) with streptococcal isolations (GAS, n=11 and GBS, n=8). Comparing to GAS, GBS affected infants were younger (median age 0.13 versus 5.47 years, 95% CI, 1.7-8.5, p=0.0003), and cerebrospinal fluids more likely positive (p = 0.0181). All GAS and GBS were sensitive to penicillin (CLSI: MICs 0.06 – 2.0 μg/mL), with the majority of GAS sensitive to clindamycin and erythromycin, and half of the GBS resistant to clindamycin and erythromycin. Co-infections were prevalent, but viruses were only isolated with GAS (p=0.024). Isolation of GAS and GBS was associated with nearly 40% mortality and high rates of mechanical ventilation and inotropic supports. All non-survivors had high mortality (PIM2) and sepsis scores.Conclusions: Severe GAS and GBS are rare but associated with high mortality and rates of mechanical ventilation and inotropic supports in PICU. The streptococci are invariably sensitive to penicillin. The high PIM2 and Sepsis scores suggest that prompt recognition of sepsis and the timely judicious institution of antibiotics and intensive care support may be life-saving for these devastating infections.

Caractéristiques des méningites à streptocoque du groupe A de l’enfant

Background: Korean children are often treated in Intensive Care Units (ICUs) rather than in Pediatric Intensive Care Units (PICUs). However, pediatric critical care (PCC) in ICUs, other than in PICUs, may have effects on patient’s outcome. Objectives: To compare the PCC outcomes of pediatric patients in the PICU with the outcomes of pediatric patients in other ICUs. Methods: This is a retrospective study of pediatric patients treated in ICUs. The participants of this study were children aged < 18 years who were admitted to the ICUs from the Pediatric Department of Seoul St. Mary’s Hospital from April 2009 to June 2017. Patients with hemato-oncologic diseases or those needing postoperative care were excluded. Results: Among the 429 ICU cases, 306 were PICU and 123 were ICU patients. The age (18 months vs. 26 months; P = 0.104) and male sex ratio (57% vs. 54%; P = 0.587) were not significantly different between PICU and other ICU patients. PICU patients (73%) were commonly admitted from another hospital compared with ICU patients (63%, P = 0.043). The pediatric index of mortality -3 score was not significantly different between the PICU and ICU patients (-4.3 vs -4.1; P = 0.128); the ICU and hospital length of stay were 5 days vs 5 days (P = 0.357) and 11 days vs 11 days (P = 0.317); and the mortality rate was 4% vs 11% (P = 0.008), respectively. Respiratory and neurologic complications were 5% vs 11% (P = 0.021) and 4% vs 2% (P = 0.282), respectively. The risk of mortality was higher for ICUs patients (odds ratio = 2.56; 95% CI = 1.11 - 5.87), adjusted for source of ICU admission, and type of ICU. Conclusions: Pediatric patients treated in a PICU had a lower mortality compared to those treated in other ICUs.