Invasive Group A Streptococcus Infection Research Articles

The multiplication of invasive Streptococcus pyogenes in endothelial cell accompanies autophagy formation (40.13)

Abstract Streptococcus pyogenes, also known as group A streptococcus (GAS), is one of most common human pathogens. Severe life-threatening disease, such as sepsis, results from the breakdown of blood vessel barrier. Although GAS has been identified as an extracellular bacterium, internalization of GAS by many eukaryotic cells may provide a mechanism of clinical severe damage due to evading from immune surveillance or antibiotic treatment. Previous report showed that GAS can be efficiently killed by autophagy (an intracellular innate immune system) in some nonphagocytes including epithelial cells. In this study, we showed that invasive GAS, but not noninvasive GAS strains, multiplied inside endothelial cells and bacterial growth reached plateau at 6 ~ 8 h. The intracellular sites of multiplication of GAS were first in vesicles and then in cytoplasm where most of the GAS was liberated from vesicle by streptolysin before endosomal degradation. GAS further induced autophagy formation but only a small portion of GAS was completely enveloped by GAS-containing autophagosome-like vacuoles at 6 h. Furthermore, endothelial cells underwent a caspase-indepandent cell death caused by persistent multiplication of GAS. The interrelationship between autophagy induction, cell death, and GAS multiplication remains further investigation. Our studies demonstrate that the insufficient autophagy induction during invasive GAS infection, particularly in endothelial cells, results in multiplication of GAS.

Invasive group A streptococcal infection in children: clinical manifestations and molecular characterization in a French pediatric tertiary care center

Invasive group A streptococcal (GAS) infections have a broad and evolving clinical spectrum, associated with various GAS genotypes and/or virulence factors that are only poorly described in children. We aimed to assess the clinical and molecular characteristics of invasive GAS infections in 28 children admitted from 2000 to 2007 at a large French pediatric tertiary care center. The GAS isolates were characterized molecularly by emm-typing and by the determination of the main virulence factors: speA, speB, speC, smeZ-1, ssa, sic, and silC. The median age of the children was 2.9 years. Osteoarticular infection (OAI) was the main clinical manifestation (n=15/28, 53%). emm-1 predominated (n=10/28), followed by emm-12, 3, and 4. No significant correlation was found between emm type and clinical manifestations, but emm-1 predominated in cases of OAI (n=7/15) and was associated with speA, speB, smeZ-1, and sic virulence factor genes. In this pediatric study, we describe a predominance of OAI associated with emm-1 GAS. Further larger international pediatric studies, including host immunity evaluation, are needed in order to better assess the pathogenesis of GAS infection in children.

Novel strategies for controlling Streptococcus pyogenes infection and associated diseases: from potential peptide vaccines to antibody immunotherapy

Infections caused by group A streptococcus (GAS) represent a public health problem in both developing and developed countries. The current available methods of prevention are either inadequate or ineffective, which is highlighted by the resurgence in invasive GAS infections over the past two decades. The management of GAS and associated diseases requires new and improved approaches. This review discusses various potential approaches in controlling GAS infections, ranging from prophylactic vaccines to antibody immunotherapy.

Méningite à streptocoque A : caractéristiques d’une méningite rare chez l'enfant

Group A streptococcal (GAS) invasive infections have been increasingly reported in recent years but meningitis due to GAS remains a rare affection. In children some scarce case reports have been described. The aim of this study was to describe and analyze the clinical and biological data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV). From 2001 through end 2006, 2539 children suffering from proven bacterial meningitis were recorded in the data base. Among them 10 children presented GAS infections. The mean age was 6 years (9 months to 14.1 years) and the sex ratio (male/female) 4/1. Seven out of the 10 patients had a history of community acquired infection before the onset of GAS meningitis : 3 had previous acute otitis media, 1 otitis media with mastoiditis, 2 sinusitis and 1 soft tissue infection. In the 3 remaining children no risk factors of invasive GAS infection could be identified. All but 1 patient survived. The patient who died had no risk factors for invasive infectious disease. He presented with fulminant septicaemia and died 6hours after hospital admission despite appropriate supportive care and prompt antibiotic treatment. The cerebrospinal fluid examination revealed high white blood cells counts (>500/mm(3)) in 8 patients and Gram stained smear showed gram-positive cocci in 6 patients. All the patients received antibiotic regimen including 3(rd) generation cephalosporins before definite bacterial identification and all the strains were susceptible to the first line antibiotic treatment chosen. GAS is an uncommon organism causing meningitis in children. In our study upper respiratory tract infection is the most common predisposing factor for GAS meningitis but even apparently healthy children can suffer from this severe form of bacterial meningitis.

Neumonía grave por Streptococcus pyogenes: Reporte de un caso

During the past two decades there has been a resurgence of invasive group A streptococcal (GAS) infection, specially pneumonia and bacteremia. We report a 35 year-old female previously subjected to a thyroidectomy for a thyroid cancer, that five days after operation, presented with a severe community-acquired pneumonia caused by Streptococcus pyogenes (Lancefield Group A Streptococcus) that was complicated by acute respiratory failure and septic shock. She was treated with a combination of 3 g/day of cefotaxime and 1.8 g/day of clindamycin with a good clinical response and discharged from the hospital in good conditions. Although this microorganism is an uncommon cause of community-acquired pneumonia, previously healthy individuals may be infected and the clinical course may be fulminant. Patients with invasive GAS infection admitted to ICU have a high mortality rate. Treatment of choice of Group A streptococcal infection is penicillin. However, clindamycin should be added in severe infections .

Incompetence of Neutrophils to Invasive Group A streptococcus Is Attributed to Induction of Plural Virulence Factors by Dysfunction of a Regulator

Group A streptococcus (GAS) causes variety of diseases ranging from common pharyngitis to life-threatening severe invasive diseases, including necrotizing fasciitis and streptococcal toxic shock-like syndrome. The characteristic of invasive GAS infections has been thought to attribute to genetic changes in bacteria, however, no clear evidence has shown due to lack of an intriguingly study using serotype-matched isolates from clinical severe invasive GAS infections. In addition, rare outbreaks of invasive infections and their distinctive pathology in which infectious foci without neutrophil infiltration hypothesized us invasive GAS could evade host defense, especially neutrophil functions. Herein we report that a panel of serotype-matched GAS, which were clinically isolated from severe invasive but not from non-invaive infections, could abrogate functions of human polymorphnuclear neutrophils (PMN) in at least two independent ways; due to inducing necrosis to PMN by enhanced production of a pore-forming toxin streptolysin O (SLO) and due to impairment of PMN migration via digesting interleukin-8, a PMN attracting chemokine, by increased production of a serine protease ScpC. Expression of genes was upregulated by a loss of repressive function with the mutation of csrS gene in the all emm49 severe invasive GAS isolates. The csrS mutants from clinical severe invasive GAS isolates exhibited high mortality and disseminated infection with paucity of neutrophils, a characteristic pathology seen in human invasive GAS infection, in a mouse model. However, GAS which lack either SLO or ScpC exhibit much less mortality than the csrS-mutated parent invasive GAS isolate to the infected mice. These results suggest that the abilities of GAS to abrogate PMN functions can determine the onset and severity of invasive GAS infection.

The IL-8 Protease SpyCEP/ScpC of Group A Streptococcus Promotes Resistance to Neutrophil Killing

Interleukin-8 (IL-8) promotes neutrophil-mediated host defense through its chemoattractant and immunostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called ScpC) cleaves IL-8, and SpyCEP expression is strongly upregulated in vivo in the M1T1 GAS strains associated with life-threatening systemic disease including necrotizing fasciitis. Coupling allelic replacement with heterologous gene expression, we show that SpyCEP is necessary and sufficient for IL-8 degradation. SpyCEP decreased IL-8-dependent neutrophil endothelial transmigration and bacterial killing, the latter by reducing neutrophil extracellular trap formation. The knockout mutant lacking SpyCEP was attenuated for virulence in murine infection models, and SpyCEP expression conferred protection to coinfecting bacteria. We also show that the zoonotic pathogen Streptococcus iniae possesses a functional homolog of SpyCEP (CepI) that cleaves IL-8, promotes neutrophil resistance, and contributes to virulence. By inactivating the multifunctional host defense peptide IL-8, the SpyCEP protease impairs neutrophil clearance mechanisms, contributing to the pathogenesis of invasive streptococcal infection.

Group A streptococcal infection caused by emm1 strains among children in southern Taiwan

The aim of this study was to characterize the molecular epidemiology of invasive and non-invasive group A streptococcus (GAS) infections in children from 1997 through 2004 in southern Taiwan. A collection of 32 invasive and 150 non-invasive isolates were recruited for analysis. emm1 (34.4%) and emm12 (40.0%) predominated in the invasive and non-invasive isolates, respectively. The peak incidence of invasive GAS infection (IGASI) occurred between 2002 and 2003. emm4 and emm12 were the major types among clinical isolates before 2001, and was replaced by emm1 during 2002-2003. All emm1 isolates were clonal relatedness. The declined prevalence of erythromycin resistance occurred in the major shift of the endemic isolates to emm1 strains during 2002-2003 in the community.

Outbreak of Invasive Group A Streptococcal Disease Among Children Attending a Day-Care Center

Most cases of invasive group A streptococcal (GAS) disease arise sporadically in the community, but outbreaks of severe invasive GAS infections have been reported in closed environments, such as military populations, family communities and hospitals. An outbreak of invasive GAS disease involving 3 cases of streptococcal toxic shock syndrome (TSS), one with a fatal course, occurred among children attending a day-care center located in Cantabria, Northern Spain. To determine the characteristics of GAS isolates obtained from the outbreak environment. GAS isolates obtained from children attending the same day-care facility, staff members, and family contacts were assayed for emm typing, pulse-field gel electrophoresis (PFGE), and toxin-gene content. One isolate obtained from the fatal case was also characterized by multilocus sequence typing. Antimicrobial susceptibility testing was done. Strains from patients unrelated to the outbreak were included for comparison. All GAS isolates from children attending the day-care center, including those from streptococcal TSS cases, shared the same emm type 4, genomic pattern by PFGE (A) and toxin-gene profile. Neither the emm type nor the PFGE pattern or toxin gene profile of the outbreak-associated strains were encountered among GAS isolated from household or staff contacts. A clone of GAS belonging to emm type 4 and characterized by a specific PFGE pattern and toxin-gene profile was responsible for a community outbreak of streptococcal TSS disease in a child day-care center in Spain. This is the first day-care outbreak reported in our country.

The severity of Streptococcus pyogenes infections in children is significantly associated with plasma levels of inflammatory cytokines

Cytokines are intimately involved with the innate and adaptive immune response to bacterial infections. This study was designed to determine the expression of inflammatory cytokines in children by the severity of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. The study population consisted of 16 invasive, 20 noninvasive, and 24 pharyngeal colonization, and 21 healthy controls. All children underwent the laboratory tests and cytokine measurement. GAS isolates were analyzed for emm gene typing. Patients with invasive GAS diseases had significantly higher interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-18 than those with noninvasive diseases, colonization, and healthy controls. There was no difference in tumor necrosis factor (TNF)-α, IL-12, and IL-2 levels among the groups. Elevated white blood cell counts and levels of C-reactive protein and C3 were detected only in patients with invasive diseases. emm1 and emm12 predominated in invasive disease and colonization. Children with invasive GAS infections exhibited significant up-regulation of plasma levels of IFN-γ, IL-1β, IL-6, IL-8, IL-10, and IL-18, and suppression of TNF-α and IL-12 during the acute phase of their illness. An exuberant cytokine response was associated with the severity of illness.

Postpartum Invasive Group A Streptococcal Disease in the Modern Era

To describe the clinical features of individuals hospitalized for postpartum invasive group A Streptococcus (GAS) infection, a retrospective, population-based study of hospitalized patients in the state of Florida was conducted. Cases of postpartum invasive GAS infection (occurring within 42 days of delivery) were compared to women with other manifestations of invasive GAS disease with respect to their age at the time of admission. Four cases of postpartum invasive GAS infection were detected in this population, yielding a prevalence of 1.6% (4/257) of postpartum disease in this invasive GAS infection database. Patients presented a median of 4 days (mean of 9 days) after delivery with signs and symptoms of infection. Three cases were complicated by bacteremia and one patient had streptococcal toxic shock syndrome. Each patient received multiple antibiotics and survived. No patients received intravenous immunoglobulin. For comparison, a secondary retrospective investigation of a large hospital discharge dataset obtained from the Florida Agency for Health Care Administration was assessed for patients with puerperal GAS infections. This method yielded an additional three cases, whose clinical and demographic characteristics were summarized. These data highlight that postpartum invasive GAS infection continues to complicate pregnancy, though the frequency has decreased markedly over the past century.

Invasive Group A Streptococcal Infection in Older Adults in Long-term Care Facilities and the Community, United States, 1998–20031

Limited information exists on the incidence and characteristics of invasive group A streptococcal (GAS) infections among residents of long-term care facilities (LTCFs). We reviewed cases of invasive GAS infections occurring among persons > or =65 years of age identified through active, population-based surveillance from 1998 through 2003. We identified 1,762 invasive GAS cases among persons > or =65 years, including 1,662 with known residence type (LTCF or community). Incidence of invasive GAS infection among LTCF residents compared to community-based elderly was 41.0 versus 6.9 cases per 100,000 population. LTCF case-patients were 1.5 times as likely to die from the infection as community-based case-patients (33% vs. 21%, p<0.01) but were less often hospitalized (90% vs. 95%, p<0.01). In multivariate logistic regression modeling, LTCF residence remained an independent predictor of death. Additional prevention strategies against GAS infection in this high-risk population are urgently needed.

Invasive Group A Streptococcal Infections

Group A streptococcus (GAS) causes the most diverse range of syndromes of any bacterium. Recently, there has been a resurgence of severe, invasive GAS infections despite the success of the varicella vaccine in decreasing the incidence of these infections in the pediatric population. Fortunately, advances in the management of life-threatening conditions such as necrotizing fasciitis and streptococcal toxic shock syndrome (STSS) have reduced mortality, but these remain devastating diseases. There continues to be significant morbidity, mortality and economic burden from invasive GAS infections and their sequelae. Advances in molecular biology have shed new light on the pathogenesis of GAS infections and have identified a number of potential vaccine targets. This review provides an overview of invasive GAS infections in children, their presentation and management, and advances in the development of a GAS vaccine.

Group A Streptococcus Epidemiology and Vaccine Implications

Group A Streptococcus (GAS ) species are responsible for a wide variety of human diseases that range from noninvasive, mild infections, such as pharyngitis and impetigo, to life-threatening, invasive conditions, such as bacteremia, pneumonia, necrotizing fasciitis (NF), and streptococcal toxic shock syndrome (STSS). In addition, GAS is responsible for nonsuppurative sequelae of infection-specifically, acute rheumatic fever and poststreptococcal glomerulonephritis. The global impact of disease has been estimated to be >500,000 deaths per year, primarily due to rheumatic fever, rheumatic heart disease, and invasive GAS infection. These figures place GAS among the world's major human pathogens, exceeded only by HIV, Mycobacterium tuberculosis, Plasmodium falciparum, and Streptococcus pneumoniae, with mortality rates comparable to those for rotavirus infection, measles, Haemophilus influenzae type b infection, and hepatitis [1]. A previous report by the Centers for Disease Control and Prevention Active

The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000-2004

Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. From January 2000 through December 2004, we collected data from Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950-11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050-1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.

High burden of invasive β-haemolytic streptococcal infections in Fiji

We undertook a 5-year retrospective study of group A streptococcal (GAS) bacteraemia in Fiji, supplemented by a 9-month detailed retrospective study of beta-haemolytic streptococcal (BHS) infections. The all-age incidence of GAS bacteraemia over 5 years was 11.6/100,000. Indigenous Fijians were 4.7 times more likely to present with invasive BHS disease than people of other ethnicities, and 6.4 times more likely than Indo-Fijians. The case-fatality rate for invasive BHS infections was 28%. emm-typing was performed on 23 isolates: 17 different emm-types were found, and the emm-type profile was different from that found in industrialized nations. These data support the contentions that elevated rates of invasive BHS and GAS infections are widespread in developing countries, and that the profile of invasive organisms in these settings reflects a wide diversity of emm-types and a paucity of types typically found in industrialized countries.

Clinical and epidemiologic features of invasive group A streptococcal infections in children

Invasive group A streptococcal infection (IGASI) is a disease of public health importance. The clinical epidemiology of IGASI in children has not been studied extensively in Florida, USA. The objective of this study was to describe the clinical and epidemiologic features of children hospitalized for IGASI in Florida, USA, during a 4-year period. Data from a previous retrospective cohort study of IGASI were analyzed. The study subjects were children and adults who had been hospitalized throughout Florida for IGASI between 1996 and 2000 and reported to the Florida Department of Health. A total of 25 patients who were 0 to 17 years of age were identified and included in the current pediatric case series. The median age at the time of admission was 4 years (range, 0.05-17 years). A total of 14 cases (56%) were boys. In total, 18 of the pediatric patients had group A streptococcal bacteremia and three children were diagnosed with group A streptococcal necrotizing fasciitis. Various antibiotic regimens were used. A total of 33% (7/21) of the patients received clindamycin during their hospital stay. Data on mortality were available for 23 pediatric IGASI cases and 205 adult IGASI cases. The mortality rate was 4.4% in children as compared to 19.5% in adults (Fisher's two-sided P = 0.087). The low case-fatality in children was consistent with other pediatric series of IGASI.

Emm Types, virulence factors, and antibiotic resistance of invasive Streptococcus pyogenes isolates from Italy: What has changed in 11 years?

To investigate the epidemiology and characteristics of invasive group A streptococcal (GAS) disease over 11 years in Italy, this study compared the emm types and the superantigen toxin genes speA and speC as well as the erythromycin, clindamycin, and tetracycline susceptibilities of 207 invasive GAS strains collected during two national enhanced surveillance periods (1994 to 1996 and 2003 to 2005) and the time between each set of surveillance periods. The present study demonstrated that emm1 strains were consistently responsible for about 20% of invasive GAS infections, while variations in the frequencies of the other types were noted, although the causes of most cases of invasive infections were restricted to emm1, emm3, emm4, emm6, emm12, and emm18. During the 1994 to 1996 surveillance period, an emm89 epidemic clone spread across the northern part of Italy. A restricted macrolide resistance phenotype-type distribution of the bacteriophage-encoded speA toxin as well as of macrolide resistance genes was noted over time. Indeed, the recent acquisition of macrolide resistance in previously susceptible emm types was observed.

Group a Streptococcal Carriage among Residents of an Urban Homeless Shelter

Group a Streptococcal Carriage among Residents of an Urban Homeless Shelter

Nursing Home Outbreak of Invasive Group A Streptococcal Infections Caused by 2 Distinct Strains

Objective.To identify factors contributing to a cluster of deaths from invasive group A streptococcus (GAS) infection in a nursing home facility and to prevent additional cases.Design.Outbreak investigation.Setting.A 146-bed nursing home facility in northern Nevada.Methods.We defined a case as the isolation of GAS from a normally sterile site in a resident of nursing home A. To identify case patients, we reviewed resident records from nursing home A, the local hospital, and the hospital laboratory. We obtained oropharyngeal and skin lesion swabs from staff and residents to assess GAS colonization and performed emm typing on available isolates. To identify potential risk factors for transmission, we performed a cohort study and investigated concurrent illness among residents and surveyed staff regarding infection control practices.Results.Six residents met the case patient definition; 3 (50%) of them died. Among invasive GAS isolates available for analysis, 2 distinct strains were identified: emm11 (3 isolates) and emm89 (2 isolates). The rate of GAS carriage was 6% among residents and 4% among staff; carriage isolates were emm89 (8 isolates), emm11 (2 isolates), and emm1 (1 isolate). Concurrently, 35 (24%) of the residents developed a respiratory illness of unknown etiology; 41% of these persons died. Twenty-one (30%) of the surveyed employees did not always wash their hands before patient contacts, and 27 (38%) did not always wash their hands between patient contacts.Conclusions.Concurrent respiratory illness likely contributed to an outbreak of invasive GAS infection from 2 strains in a highly susceptible population. This outbreak highlights the importance of appropriate infection control measures, including respiratory hygiene practices, in nursing home facilities.