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[Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A report of two cases].

AIM: To critically review the past years of research on paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in children and adolescents. METHOD: Literature on PANDAS published from 1995 onward was systematically reviewed. The review focuses on definition and diagnostic consideration aetiological and therapeutical issues. To illustrate the clinical characteristic of PANDAS authors present two cases of children with a severe course of obsessive-compulsive disorder and Tourette's syndrome. RESULTS: Post-streptococcal autoimmunity has been postulated as an aetiologic factor in the development of childhood-onset obsessive-compulsive disorder, tic disorders including Tourette's disorder. This hypothesis arose from a series of clinical observations including the documentation of obsessive-compulsive symptoms of children affected by Sydenham's chorea, a variant of rheumatic fever characterised by neurological dysfunction and also by concomitant investigations of childhood-onset OCD and Tourette's syndrome. CONCLUSION: Results of these studies led to the identification of children whose clinical course is characterised by abrupt and dramatic symptom exacerbations which are temporally related to group A beta-hemolytic streptococcal infections. The identification of such a subgroup will allow for testing of the model of pathogenesis as well as development of novel treatment and prevention strategies. Future research are needed to explore the nature of PANDAS and their relationship with different psychiatric disorders in children and adolescents.

Adolescent↗

Antistreptokinase antibodies: implications for thrombolysis in a region with endemic streptococcal infection.

AIMS: To determine antistreptokinase antibody (anti-SK) titres in patients with the acute coronary syndrome from communities with endemic group A streptococcal infection because of the implications for streptokinase (SK) thrombolysis. METHODS: Anti-SK titres were determined using a standard method in 47 consecutive SK naive patients, presenting to the Mt Isa Hospital emergency department, Australia, with an acute coronary syndrome. Both indigenous and non-indigenous subjects were enrolled. Antistreptolysin O (ASOT) and anti-DNAse B (ADB) titres were also determined. RESULTS: Indigenous patients were more likely to have anti-SK antibodies (p < 0.001) than the non-indigenous cohort. Anti-SK antibody titres also correlated well with ASOT/ADB titres. CONCLUSIONS: Anti-SK antibodies are highly prevalent in SK naive indigenous patients presenting with the acute coronary syndrome. Streptokinase should not be used for thrombolysis in populations with endemic group A streptococcal infection.

Acute Disease↗

[Comparative study of the semisynthetic penicillins in the experimental therapy of pneumococcal and streptococcal infections in mice].

Penicillins were studied comparatively on mice with infections caused by pneumococci and streptococci. It was shown that klomethacillin was superior by its chemotherapeutic effect to other penicillins in treatment of pneumococcal septicemia when used subcutaneously or intragastrically. Ampicillin was superior in treatment of streptococcal infection.

Administration, Oral↗

A review of beta-haemolytic streptococcal infection in babies.

The incidence of beta-haemolytic group B streptococcal infection in babies at or shortly after birth appears to have risen during the last 20 years. About 30% of women could be colonized at any one time, and because of the transient nature of this organism research has failed to find a way of identifying women who will be colonized at the end of pregnancy. The baby is at risk of early-onset disease from mother-to-baby transmission during the birth process. If identified early enough, those mothers who present a risk can be treated in time to protect the baby during the birth. Late-onset disease can be the result of cross-infection from carers, and the education of midwives, nurses and mothers could reduce the risk. Education could also aid identification of the early signs of disease, and therefore increase the likelihood of a successful outcome of treatment.

Cross Infection↗

A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections.

BACKGROUND: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea. Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations. METHODS: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V. Tic, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained. RESULTS: There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases. CONCLUSIONS: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size.

Adolescent↗

[Clinical and laboratory diagnosis of streptococcal infection].

The problems related to the clinical and laboratory diagnosis of streptococcal infection at all levels of health service are analysed. The principles of microbiological streptococcal identification with the aid of express-systems and standard culture techniques are outlined. Particular emphasis is placed upon immunoassay of streptococci using a broad spectrum of extracellular products and antigens of the cell wall of group A streptococcus, and upon methodological approaches to solving certain clinical and diagnostic problems.

Antibodies, Bacterial↗

Clinical characteristics and antimicrobial susceptibility of invasive group B streptococcal infections in nonpregnant adults in Taiwan.

To understand group B streptococcal infections other than peripartum events in adults and to provide a regional antimicrobial therapy guide, we conducted a retrospective analysis of invasive diseases caused by group B streptococcus (GBS) in 33 nonpregnant adults treated in a medical center in southern Taiwan, from January 1993 to July 1994. Antimicrobial susceptibility tests were performed using the agar dilution method. The incidence of the disease was 1.6 per 1,000 nonpregnant adult admissions, and the mean age of patients was 58 years (range 17-86 years). Primary bacteremia (13) and soft-tissue infections (11) were the most common manifestations. Nearly all the patients had underlying disease(s) and/or condition(s); the three most common were diabetes mellitus (13), malignancy (5), and liver cirrhosis (5). There were eight nosocomial infections and six patients died. Of 32 GBS strains tested, 27 were susceptible to penicillin G and the rest were intermediately susceptible. All strains were uniformly susceptible to cephalothin, cefotaxime, ofloxacin, and vancomycin; two strains were susceptible to gentamicin and nearly half were intermediately susceptible. Our findings imply a requirement for higher doses of penicillin or combination with an aminoglycoside for treatment of GBS infection. First-generation cephalosporins may be an alternative for the treatment of GBS infections in Taiwan.

Adolescent↗

Myocardial infarction associated with pseudoephedrine use and acute streptococcal infection in a boy with normal coronary arteries.

A 16-year-old boy presented to the emergency department with chest pain. He had no history of other health problems and did not smoke. Acute myocardial infarction (AMI) in an adolescent boy with normal coronary arteries, associated with pseudoephedrine use and acute streptococcal infection, is reported. The diagnosis of AMI was based on typical electrocardiographic signs, enzyme changes and echocardiographic evaluation. Coronary vasospasm associated with pseudoephedrine use, endothelial dysfunction and prothrombotic state caused by acute streptococcal infection may be the mechanisms responsible for AMI in this case. The possibility of AMI should be considered even in very young adolescents that have acute streptococcal pharyngeal infection, and it is important to obtain a complete history of the drugs used.

Acute Disease↗

Group B streptococcal infections in adult males.

A 19-month study of group B streptococcal infection was performed to investigate the spectrum of such infections in adult males, the relation of serotypes to clinical illnesses, the effects of previous antibiotic therapy on infection and colonization, and the antibiotic susceptibility pattern of these organisms. Twenty-four patients had definite or possible infections while 41 patients were colonized with group B streptococci. The most frequent infections encountered were pneumonia (ten cases) and soft tissue infections (nine cases). Five infections (21%) were nosocomial in origin. The most frequent serotypes were Ia and II. No correlation of serotype and type of infection was observed. Patients receiving previous antibiotic therapy were significantly more likely to be colonized than infected with group B streptococci. Penicillin was the antibiotic to which these organisms were most susceptible; tetracycline and gentamicin showed the least activity.

Adult↗

Viridans-group streptococcal infections in immunocompromised hosts.

Viridans streptococci, a diverse group of streptococcal species, are important causes of sepsis and pneumonia in the neutropenic host and sepsis and meningitis in the neonate. The oral mucosa is the most common portal of entry. Among the factors that predispose to development of viridans streptococcal sepsis are: profound neutropenia; mucositis, especially oral mucositis; cytarabine (Ara-C) therapy, which seems to have an effect beyond its association with mucositis; young age; and trimethoprim-sulphamethoxazole or quinolone administration. Fever is usually more than 39 degrees C and prolonged for several days even though blood cultures are typically negative after 24 h of therapy. The majority of patients recover uneventfully if appropriate therapy is initiated early. However, fulminant septic shock may occasional occur at onset. Delayed shock 2 or 3 days after presentation may also occur despite administration of microbiologically effective antibiotics. In severe cases, adult respiratory distress syndrome may be manifested two or three days after the initial bacteremia. There is considerable variability among institutions, but the median death rate associated with viridans streptococcal sepsis is about 10%. Local susceptibility patterns should be used to guide initial therapy for suspected viridans streptococcal infections. Some isolates of viridans streptococci are resistant to penicillins and cephalosporins, in which case vancomycin is preferred. Recurrence during subsequent neutropenic episodes is not unusual.

Anti-Bacterial Agents↗

Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988-1989.

Serotypes of serious, sometimes fatal, streptococcal infections in Sweden during 1988-1989 were analyzed. The T1M1 type totally dominated, representing almost 70% of all group A streptococci from serious and uncomplicated infections at the peak of the outbreak. Immunoblots of isolates from various patient groups showed that all isolates produced high amounts of erythrogenic toxin (ET) B and high amounts of ET-C, whereas ET-A was released only in small amounts and from few isolates. ELISAs showed high antibody levels to these toxins and to the M1 antigen in patients with uncomplicated infections. Low antibody levels against M1 were seen in patients with bacteremia and in fatal cases; the latter also had low antibody levels against ET-B. It seems likely that a combination of production of large amounts of toxin and low antibody titers to it and to the M antigen of the infecting isolate are determining factors for the outcome of the infection. No signs of primary immune deficiency were noted.

Adolescent↗

Occurrence and specificity of antibodies against group-specific polysaccharides in beta-hemolytic streptococcal infections.

We studied the possibility of detecting beta-hemolytic streptococcal infections by determining antibodies against the group specific polysaccharides from streptococci of groups A, A-variant, C and G. The methods used were radio-immunoassay with these four polysaccharides and hemagglutination of group A polysaccharide sensitized erythrocytes. Significant increases in these antibodies were rare in tonsillitis patients, whereas high concentrations of antibodies could often be observed in association with severe systemic infections or rheumatic fever. Both strictly immunogen-restricted and crossreactive antibodies could be demonstrated by isoelectric focusing and inhibition of antigen-binding. Although previously considered nonexistent, group specific carbohydrate antibodies of IgM class could also be demonstrated.

Adolescent↗

MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection.

OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection.

Autoimmune Diseases↗

Orthopaedic manifestations of invasive group A streptococcal infections complicating primary varicella.

The incidence of invasive group A streptococcal (GAS) infections in primary varicella appears to be increasing. GAS infections complicating varicella range from cellulitis, abscess, and septic arthritis to life-threatening necrotizing fasciitis and pyomyositis in association with GAS toxic shock syndrome (TSS). Four patients admitted in 1 year to the Children's Hospital and Medical Center in Seattle, whose care included evaluation and treatment by the Orthopaedic service, are presented to illustrate this spectrum. Three had a delay in diagnosis, including discharge from previous emergency department visits. One patient with polyarticular septic arthritis was treated with diagnostic aspiration and intravenous antibiotics. The remainder required urgent surgical debridement for treatment of deep infection. Patients with necrotizing fasciitis or pyomyositis had life-threatening complications of TSS, including hypotension, adult respiratory distress syndrome (ARDS), coagulopathy, and acute renal failure. These patients required aggressive fluid resuscitation and prolonged intensive care unit support. Diagnostic imaging studies were obtained in one patient with necrotizing pyomyositis but may have served only to delay definitive treatment. Recognition of the potential for secondary GAS infections and a high index of suspicion for the presence of necrotizing soft-tissue infection are essential in the evaluation of any child with fever and localized extremity pain with varicella.

Arthritis, Infectious↗

Immunological response to antioxidant vitamin supplementation in rural Bangladeshi school children with group A streptococcal infection.

Group A beta haemolytic streptococcal (GABHS) infection induce an abnormal immune response in a susceptible host. Micronutrient deficiency may affect the immune response of an individual. The aim of this study was to determine whether antioxidant vitamins could improve the abnormal immune response in GABHS infected children in rural Bangladesh. A total of 516 GABHS infected school children aged 5 to 15 years were randomly assigned to two groups. Group 1 (N=258) was treated with phenoxymethyl penicillin V and group 2 (N=258) was treated with penicillin V plus antioxidant vitamins (beta carotene, alpha tocopherol and ascorbic acid). From each group two blood samples were drawn; the first sample at the beginning of the study and another one after eight weeks. Streptococcal antibodies and immunoglobulin levels were compared between the two samples. The mean age of the study population was 10.6 years. Equal number of boys and girls were included in both groups. After treatment, antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) titres were decreased in both groups. Serum alpha tocopherol and beta-carotene levels were increased significantly in group 2. In group 1 immunoglobulin M and A levels decreased significantly (P =0.0001) whereas immunoglobulin G showed no change. To the contrary, concentration of three immunoglobulins decreased significantly (P=0.0001) in group 2. Least-square means of between-group differences showed highly significant results for ASO, ADNase B, immunoglobulins M, A and G (P=0.0001). Our data indicate that treatment by antioxidant vitamins plus penicillin is more effective in decreasing immunological abnormalities in GABHS infected children then penicillin alone.

Adolescent↗

Group B streptococcal infections of the central nervous system in infants with myelomeningocele.

Three cases of group B streptococcal infection of the central nervous system (CNS) occurred among 147 neonates treated for myelomeningocele at The Children's Hospital in Boston from 1970 to 1985. This pathogen was responsible for one third of the nine CNS infections noted in these patients over the 15-year study period. All three children with group B streptococcal CNS infections subsequently required multiple CNS shunting procedures and prolonged hospitalizations. Two children suffered major neurological sequelae. In neonates with myelomeningocele, group B streptococci have direct access to the CNS, perhaps explaining the high incidence of serious meningitis and ventriculitis in this population. Antibiotic prophylaxis for early myelomeningocele repair should be adjusted accordingly.

Central Nervous System Diseases↗