Group A Beta-hemolytic Streptococcus Infections Research Articles

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Myth or Reality? The State of the Art on a Controversial Disease.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is one of the most controversial diseases in pediatric rheumatology. Despite first being described more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine release in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

Severe acute otitis media and mastoiditis caused by group A beta-hemolytic streptococcus.

ObjectiveTo describe the characteristics, diagnostics, treatment, and outcome of severe acute otitis media (AOM) and acute mastoiditis (AM) caused by group A beta‐hemolytic streptococcus (GAS).Study designA retrospective cohort study.MethodsThe yearly incidence of inpatient care‐needing GAS AOM/AM patients in our hospital catchment area between 2002 and 2018 was investigated. A detailed analysis was performed for cases treated during the last GAS epidemic in 2017‐2018. Anamnesis, signs and symptoms, pure‐tone audiometry results, treatment, complications, and outcome were collected from medical charts. Patients responded to an otology‐specific health‐related quality of life survey (EOS‐16) 1.5 to 3 years after their treatment.ResultsThe number of GAS infections peaks at approximately 7‐year intervals. During 2017 and 2018, altogether 37 patients (29 adults and 8 children) were hospitalized due to GAS AOM/AM. AM was diagnosed in 14 (38%) patients. The disease progression was typically very rapid. At presentation, all patients had severe ear pain, 68% tympanic membrane perforation and discharge, 43% fever, and 43% vertigo. In pure‐tone audiometry, there was usually a marked mixed hearing loss at presentation. There was a significant recovery in both air and bone conduction thresholds; the pure tone average improvement from presentation was 32.3 ± 14.8 dB. Rapid strep tests (RST) proved to be more sensitive than bacterial culture in identifying GAS as a cause of AOM/AM.ConclusionGAS AOM/AM has a rapid onset. Hearing loss usually includes a sensorineural component, which is usually reversible with adequate treatment. RST seems to be useful in detecting GAS from middle ear discharge.Level of Evidence4.

Streptococcal Infection as a Major Historical Cause of Stuttering: Data, Mechanisms, and Current Importance.

Stuttering is one of the most well-known speech disorders, but the underlying neurological mechanisms are debated. In addition to genetic factors, there are also major non-genetic contributions. It is here proposed that infection with group A beta-hemolytic streptococcus (GAS) was a major underlying cause of stuttering until the mid-1900s when penicillin was introduced in 1943. The main mechanism proposed is an autoimmune reaction from tonsillitis, targeting specific molecules, for example within the basal ganglia. It is here also proposed that GAS infections may have continued to cause stuttering to some extent, to the present date, though more rarely. If so, early diagnosis of such cases would be of importance. Childhood cases with sudden onset of stuttering after throat infection may be particularly important to assess for possible GAS infection. The support for this hypothesis primarily comes from three lines of argument. First, medical record data from the 1930s strongly indicates that there was one type of medical event in particular that preceded the onset of childhood stuttering with unexpected frequency: diseases related to GAS throat infections. In particular, this included tonsillitis and scarlet fever, but also rheumatic fever. Rheumatic fever is a childhood autoimmune sequela of GAS infection, which was a relatively widespread medical problem until the early 1960s. Second, available reports of changes of the childhood prevalence of stuttering indicate striking parallels between stuttering and the incidence of rheumatic fever, with: (1) decline from the early 1900s; (2) marked decline from the introduction of penicillin in the mid 1940s; and (3) reaching a more stable level in the 1960s. The correlations between the data for stuttering and rheumatic fever after the introduction of penicillin are very high, at about 0.95. Third, there are established biological mechanisms linking GAS tonsillitis to immunological effects on the brain. Also, a small number of more recent case reports have provided further support for the hypothesis linking stuttering to GAS infection. Overall, it is proposed that the available data provides strong evidence for the hypothesis that GAS infection was a major cause of stuttering until the mid-1900s, interacting with genetic predisposition.

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.

Preventing rheumatic fever: M-protein based vaccine

Group A beta hemolytic streptococcus (GAS), the organism which initiates rheumatic fever (RF) continues to be sensitive to penicillin. However, penicillin cannot prevent RF if the preceding sore throat is asymptomatic in more than 70 percent children. Prevention of rheumatic fever (RF) may be possible only with the use of a vaccine. Efforts to design a vaccine based on emm gene identification of GAS, M-protein going on for more than 40 years, is unlikely to succeed. M-protein is strain specific. Infection with one strain does not provide immunity from infection with another strain. Based on the emm gene identification, of 250 or more identified strains of GAS, the distribution is heterogenous and keeps changing. The M-protein gene sequence of the organism tends to mutate. A vaccine prepared from available strains may not be effective against a strain following mutation.Lethal toxic shock syndrome due to GAS infection has been described with organisms without identifiable or functional M-protein. M-protein has been excluded as the antigen responsible for acute glomerulonephritis (GN). Therefore M-protein plays no role in one suppurative (toxic shock syndrome) and one non-suppurative (acute GN) manifestation due to GAS infection. Lastly there is no direct evidence to indicate that M-protein is involved in inducing RF. The role of M-protein and the GAS component resulting in the suppurative manifestations of GAS infections like pyoderma, septic arthritis or necrotizing fasciitis etc is unknown. For a vaccine to be effective, an epitope of the streptococcus which is stable and uniformly present in all strains, needs to be identified and tested for its safety and efficacy. The vaccine if and when available is expected to prevent GAS infection. Preventing GAS infection will prevent all the suppurative as well as non-suppurative manifestations including RF.

Streptococcal Upper Respiratory Tract Infections and Psychosocial Stress Predict Future Tic and Obsessive-Compulsive Symptom Severity in Children and Adolescents with Tourette Syndrome and Obsessive-Compulsive Disorder

One goal of this prospective longitudinal study was to identify new group A beta-hemolytic streptococcal infections (GABHS) in children and adolescents with Tourette syndrome (TS) and/or obsessive-compulsive disorder (OCD) compared with healthy control subjects. We then examined the power of GABHS infections and measures of psychosocial stress to predict future tic, obsessive-compulsive (OC), and depressive symptom severity. Consecutive ratings of tic, OC, and depressive symptom severity were obtained for 45 cases and 41 matched control subjects over a 2-year period. Clinical raters were blinded to the results of laboratory tests. Laboratory personnel were blinded to case or control status and clinical ratings. Structural equation modeling for unbalanced repeated measures was used to assess the sequence of new GABHS infections and psychosocial stress and their impact on future symptom severity. Increases in tic and OC symptom severity did not occur after every new GABHS infection. However, the structural equation model found that these newly diagnosed infections were predictive of modest increases in future tic and OC symptom severity but did not predict future depressive symptom severity. In addition, the inclusion of new infections in the model greatly enhanced, by a factor of three, the power of psychosocial stress in predicting future tic and OC symptom severity. Our data suggest that a minority of children with TS and early-onset OCD were sensitive to antecedent GABHS infections. These infections also enhanced the predictive power of current psychosocial stress on future tic and OC symptom severity.

Group A streptococcal puerperal sepsis: initial characterization of virulence factors in association with clinical parameters

Group A beta-hemolytic streptococcus (GAS) is an uncommon but potentially fatal source of postpartum infection. Pathogenesis in invasive GAS infections has been linked to bacterial virulence factors. In this study, we sought to provide an initial description of potential virulence factors in association with puerperal morbidity by virtue of specific M-protein type antigens. Women with confirmed GAS puerperal infection in the Salt Lake City region were prospectively identified over a 6-year interval (1991-1997). From this cohort, GAS isolates were analyzed with respect to M-serotype and presence of genes encoding the Streptococcal Pyogenic Exotoxins A and B (SPE-A and SPE-B). Bacterial isolates from 18 subjects with GAS puerperal infection underwent M-serotyping and PCR-based genotyping for the speA and speB genes. Among these, 8/18 subjects manifest criteria of severe disease. All 18 isolate strains expressed speB; 6/18 isolates expressed speA. Of the M-serotypes, 8/8 severe disease isolates expressed M-types 1 (N=3) or 28 (N=5). Pulse-field gel electrophoresis did not indicate an outbreak strain among similar isolates. We conclude that in this initial characterization, morbidity among women with GAS puerperal infection is associated with M-types 1 and 28, but not speB genotype.

Management of necrotizing myositis in a field hospital: a case report

Necrotizing myositis is a rare and fatal disease of skeletal muscles caused by group A beta hemolytic streptococci (GABHS). Its early detection by advanced imaging forms the basis of current management strategy. Paucity of advanced imaging in field/rural hospitals necessitates adoption of management strategy excluding imaging as its basis. Such a protocol, based on our experience and literature, constitutes:i. Prompt recognition of the clinical triad: disproportionate pain; precipitous course; and early loss of power- in a swollen limb with/without preceding trauma.ii. Support of clinical suspicion by 2 ubiquitous laboratory tests: gram staining- of exudates from bullae/muscles to indicate GABHS infection; and CPK estimation- to indicate myonecrosis.iii. Replacement of empirical antibiotics with high intravenous doses of sodium penicillin and clindamyciniv. Exploratory fasciotomy: to confirm myonecrosis without suppuration- its hallmarkv. Emergent radical debridementvi. Primary closure with viable flaps – unconventional, if need be.

Clinical utility of a new rapid test for the detection of group A Streptococcus and discriminate use of antibiotics for bacterial pharyngitis in an outpatient setting

To evaluate the clinical usefulness of the Diaquick Strep. A Test (SAT) as a rapid streptococcal antigen test, and its effect on antibiotic use in children. This was a prospective study of children with acute catarrh, fever, and acutely inflamed throat/tonsils. Paired throat swabs for SAT and culture were collected. None of the children received antibiotics prior to testing. Five hundred and five children were included in the study: 278 were boys (55%) and 409 (81%) were aged under 5 years. The SAT was negative in 434 cases (86%) and positive in 71 (14%); culture was negative in 425 cases (84%) and positive in 80 (16%), including nine cultures that grew bacteria other than group A beta-hemolytic streptococci (GAS). Both the SAT and culture were negative in 422 cases (84%) and positive in 68 (13%), but were inconsistent in 15 cases (3%). For GAS infection, the SAT positive predictive value was 95.8% (68/71). The negative predictive value for the whole group as well as for children under five years of age was over 99% (422/425 and 355/358, respectively). SAT sensitivity was almost 96%. Finally, only 74 children (15%) were given antibiotics, while a staggering 431 (85%) were not. The Diaquick Strep. A Test (SAT) is a quick, reliable, and clinically useful test, which could help to dramatically reduce the usage of antibiotics in children with fever, catarrh, and acute pharyngotonsillitis.

Group A beta hemolytic streptococcal infections and obsessive‐compulsive symptoms in a Turkish pediatric population

The purpose of the present study was to evaluate obsessive-compulsive disease (OCD) in Turkish Children who had group A beta hemolytic streptococcal (GABHS) infections and those who had not. Thirty-one children and adolescents (the study group) were compared with 28 children and adolescents. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores were rated between study group and control group. The mean score, obsession and compulsion scores of CY-BOCS in the study group were significantly higher than they were in the control group (P < 0.05). The GABHS infections should be assessed in the etiology of OCD in children. Considering GABHS infections may help the treatment of OCD.

The PANDAS Subgroup: Recognition and Treatment

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) has been identified who share a common clinical course characterized by dramatic symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS) infections. The term PANDAS has been applied to the subgroup, to indicate the postulated etiology of their symptoms: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations (sawtooth course), association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations), and temporal association between symptom exacerbations and GABHS infections. Post-streptococcal symptom exacerbations are typically quite dramatic, with patients reporting that their symptoms "...came on overnight" or "...appeared all of a sudden a few days after I had a sore throat." The post-streptococcal inflammatory nature of the neuropsychiatric symptoms provides novel opportunities for treatment and prevention, including immunomodulatory therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed placebo-controlled trial revealed that both IVIG and TPE were effective in reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively) for a group of severely ill children with OCD and/or tic disorders. Further research is required to determine why the treatments are helpful, as well as to ascertain whether or not antibiotic prophylaxis can help prevent post-streptococcal symptom exacerbations.

Antibiotic Prophylaxis for Group A Streptococcal Burn Wound Infection Is Not Necessary

Historically, group A beta-hemolytic streptococci (GAS) burn wound infection has been a major source of morbidity and mortality in burn patients and has prompted the prophylactic administration of antibiotics to children with burns. Wound monitoring, surveillance cultures, and early excision of deep wounds may have changed this. Our objective in this project was to determine the efficacy of routine antibiotic prophylaxis in the era of early excision and closure of deep burn wounds. Two cohorts of burned children were compared: all children admitted during calendar years 1992 through 1994 (group 1) and during calendar years 1995 through 1997 (group 2). All group 1 children received routine GAS antibiotic prophylaxis. Only those group 2 children with documented positive admission or surveillance cultures for GAS were treated. There were 511 children in group 1 and 406 children in group 2. They were well matched for age (4.7 +/- 0.21 years vs. 5.3 +/- 0.26 years, p = 0.06) and burn size (11.0% +/- 0.7% vs. 12.4% +/- 0.8%, p = 0.18). GAS species were recovered at admission or during hospitalization from 11 (2.6%) of group 1 children and 18 (4.4%) of group 2 children (p = 0.05), indicating a marginally higher rate of carriage in group 2. Nevertheless, in group 1 there were three (0.6%) who developed GAS wound infection and in group 2 there were four (0.98%, p = 0.71). The incidence of GAS infection in those patients with positive admission cultures was three (27%) of group 1 and four (22%) of group 2. No child developed fulminant GAS infection. Routine antibiotic prophylaxis of burn wounds in children in not effective in further reducing a low baseline incidence of GAS wound infection if admission screening by culture is used to identify those children who carry the organism and early excision of deep burns is practiced.

Rapid strep tests in the pediatric clinical setting

I T IS FRIDAY afternoon in a busy elementary school-based clinic, 7-year-old Crystal is referred due to a temperature of 102~ is complaining of a sore throat, pain with swallowing, headache, and stomach ache. Her physical exam reveals tonsillopharyngeal erythema, and tender, enlarged cervical lymph nodes. Tonsils are 2+ with slight patchy exudate. Crystal's family does not have a phone and there is no identified emergency contact. It will take considerable school resources to locate her mother. A routine throat culture result would be available Monday, but there is difficulty contacting Crystal's mother to either start an antibiotic if the culture is positive, or stop the antibiotic, if the culture is negative. Pharyngitis is a common symptom seen in pediatric populations. The most frequent cause of bacterial pharyngitis is group A beta-hemolytic streptococci (GABHS). Although the cause of pharyngitis is often viral, it is important to make an accurate diagnosis because GABHS can have acute morbidity and can lead to serious complications such as peritonsillar abscess, cervical lymphadenitis, rheumatic fever, and glomerulonephritis (Committee on Infectious Diseases of the AAP, 1997). Antimicrobial therapy should start as soon as possible in order to improve the clinical course of the GABHS illness and reduce the risk of transmission of the organism to others (Gerber, 1989; Randolph, Gerber, DeMeo, et al., 1985). The gold standard for diagnosis of GABHS pharyngitis is a throat swab specimen on a sheep blood agar plate. It is a highly accurate and sensitive test (Gerber, 1989). However, the disadvantage is the delay in obtaining results, often 24 to 48 hours later. This makes it particularly difficult with situations like the case scenario presented. The rapid antigen detection tests offer quick results in identifying GABHS pharyngitis. In 1988 Congress passed the Clinical Laboratory Improvement Amendments (CLIA) which set standards to improve the quality of clinical laboratory testing (National Committee for Clinical Laboratory Standards, 1992). This has allowed clinics to provide sophisticated scientific tests, such as the rapid strep test, to screen and confirm diagnoses or observations made by health care providers. All clinics that perform laboratory testing on-site hold a certificate from their state health department which authorizes testing, such as a nonculture Group A rapid strep screen. The rapid strep test takes a few minutes to perform and is easily read. The screens are only for use in the qualitative detection of GABHS; the rapid strep test does not differentiate between asymptomatic carriers and those patients with GABHS infection. Most of the current rapid strep screens have an excellent specificity of 95% or greater as compared with blood agar plate cultures (Gerber, 1989). Therefore, it is very unusual to get a false-positive result. If the rapid strep screen indicates a positive result, then antibiotic treatment should be instituted, (Gerber, 1997). The accuracy of the rapid antigen detection tests rely on staff who are well-trained in the steps involved in the screening test and good quality control procedures. The first step in the procedure is to take the throat specimen using only the swabs provided in the test kit box. Using a tongue blade to hold the tongue down, the specimen should be taken directly from the back of the throat, being careful not to touch the teeth, cheeks, gums, or tongue when inserting or removing the swab. The throat should be swabbed, not gently touched, and the specimen should be obtained from both tonsils (or fossae) and the posterior pharyngeal wall. If exudate is present, those areas should be collected

Food-borne outbreak of streptococcal pharyngitis in an Israeli Airforce Base.

A food-borne outbreak of group A beta hemolytic streptococcus (GAS) pharyngitis occurred in an Israeli airforce base between 15 and 18 April, 1992. An epidemiologic investigation was conducted in a random sample of the base personnel. The effectiveness of prophylactic administration of penicillin to healthy individuals during the outbreak in preventing secondary spread of the disease was evaluated. 197 patients with pharyngitis were seen at the base clinic during the outbreak. The epidemiologic investigation indicated that the outbreak was food-borne. Consumption of processed white cheese that had been prepared without using a proper hand washing technique, 24 h before lunch on 15 April 1992, and subsequently kept at room temperature for 5 h, was significantly associated with GAS infection of the epidemic strain (p < 0.05). The food handler who processed the cheese had anterior cervical lymphadenopathy and GAS T type 8/25/Imp19 (the epidemic type) was found in his throat culture. The secondary respiratory attack rate among the healthy base personnel (n > 1,000) was 1.6%. 40 base personnel were treated by penicillin prophylaxis and had a secondary attack rate of 0%. The medical personnel who were on duty during the outbreak had a secondary attack rate of 75% (p < 0.001). The use of penicillin prophylaxis did not have an advantage in preventing secondary respiratory spread of streptococcal pharyngitis. Penicillin prophylaxis might reduce the high secondary attack rate of the disease in risk groups such as the medical personnel.

Community-Acquired Invasive Group A ß-Hemolytic Streptococcal Infections in Zuni Indians

Outbreaks of invasive group A beta-hemolytic streptococcal (GABS) infections have recently been reported. We observed a high incidence of invasive GABS disease among Native Americans at a small rural community hospital between 1982 and 1991. A retrospective chart review was performed, and all cases of invasive GABS disease were studied for their clinical features. Sixteen cases of invasive GABS infection were identified during the 10-year study period. The rate of invasive GABS infection was 13.3 cases per 100,000 population per year. Mortality was 25%. Nearly half of the patients presented with systemic signs of sepsis without any obvious source of infection. Our experience documents a high rate of invasive GABS infections in a defined Native American population. To determine whether this population has a unique susceptibility to GABS disease requires further study.

Rationality and cost-effectiveness of diagnosis and treatment of group a streptococci in primary care patients with pharyngitis

Rationality and cost-effectiveness of several strategies for diagnosing and treating sore throat patients were evaluated in primary care. In an empirical material of 2016 patients, 3 different bacteriological methods (traditional culture, slide culture, and latex agglutination test) for the detection of group A beta-hemolytic streptococci (GAS) were compared. Sensitivity analyses were done for several variables, including GAS test performance, testing frequencies, medication rates, and accuracy of clinical evaluation. The amounts of unnecessary medication varied from 19 to 33%, and there were 2.2-8.9% of untreated GAS infections. Strategies based on bacteriology achieved more rational and economic results than treating no one, treating all patients, or using clinical evaluation without bacteriology. The cost-effectiveness of the latex agglutination test depended on the sensitivity of the test. The results were further sensitive to sick leave lengths, cost of antibacterials, and clinical accuracy, but not to GAS test cost. Rapid tests for GAS detection can be recommended, if the sensitivity of the test in the actual working conditions is acceptable.