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IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS. III. PRESENCE IN HUMAN SERA OF STREPTOCOCCAL ANTIBODY CROSS-REACTIVE WITH HEART TISSUE. ASSOCIATION WITH STREPTOCOCCAL INFECTION, RHEUMATIC FEVER, AND GLOMERULONEPHRITIS.

Sera from patients with recent streptococcal infection or non-suppurative sequelae exhibit with variable frequency a precipitin reaction in agar gel with a partially purified streptococcal antigen which has been shown previously to be immunologically related to human heart tissue. This precipitin could be absorbed from sera with normal human heart tissue homogenates but not with homogenates of other organs. Demonstration of this cross-reaction by heart absorption was found dependent both upon the serologic properties of individual sera and the nature or state of purification of the streptococcal product employed as test antigen. Evidence was obtained of a close association of heart-related and non-heart-related antigenic determinants in partially purified preparations of the streptococcal antigen by both gel diffusion and immunoelectrophoresis. On immunoelectrophoretic analysis, cross-reactive antigen exhibited a more rapid mobility toward the anode than M protein. It was destroyed by digestion with trypsin, pepsin, and chymotrypsin. Based on specific absorption tests with a Type 5 and Type 19 strain, the antigen was localized to cell walls and to a lesser extent to cell membranes of these strains. Precipitating activity related to cross-reactive antibody was localized to the immunoglobulin zone in immunoelectrophoresis. Reactive sera showed diminution or loss of serological activity following heat inactivation at 56 degrees C or after prolonged storage at 4 degrees C. Sera containing cross-reactive precipitating antibody exhibited an immunofluorescent reaction with sarcolemma of cardiac myofibers, which was inhibited by streptococcal cross-reactive antigen. By this inhibition test, the immunofluorescent reaction related to cross-reactive antibody could be distinguished from that due to other heart-reactive factors. Antibody to streptococcal cross-reactive antigen defined by precipitation-absorption tests was observed in 24 per cent of patients with recent history of uncomplicated streptococcal infection and in the majority of patients with acute rheumatic fever, rheumatic heart disease, or acute glomerulonephritis. It was observed rarely in patients with non-streptococcal related disease. These data provide evidence that induction of cross-reactive autoantibody to heart in certain individuals is associated with streptococcal infection.

Aged↗

A nursery outbreak of group A streptococcal infection.

We report an outbreak of 23 neonatal group A streptococcal infections including two cases of septicaemia in a nursery for the newborn. At the same time, 19 mothers had puerperal endometritis. The outbreak lasted for about 2 months and could not be eradicated by ordinary hygienic measures. In a colonisation study, 19 of 90 umbilical stumps studied on the day of discharge from hospital harboured group A streptococci, all of the same epidemic strain T28 provisional M-type 2841/opacity factor positive (T28/MPT2841/OF+). Chlorhexidine gluconate was therefore applied daily to the umbilical stumps. The outbreak came to an end with the introduction of this procedure. The time interval between delivery and recognition of infection was shorter in infants than in mothers. There were also only two infected mother-infant pairs. Taken together, this suggests that infected umbilical stumps on symptomless infants were a likely source of the maternal infections. Throughout 1 year from the introduction of the chlorhexidine treatment, we have not seen a case of group A streptococcal infection in neonates. Surveillance cultures from umbilical cords after the outbreak have also been negative. We conclude that bacteriological surveillance of umbilical stumps is valuable in recognising an outbreak and should be seriously considered when a group A streptococcal infection has been recorded in a nursery.

Disease Outbreaks↗

Morbidity related to maternal group B streptococcal infections.

Group B streptococcus is known to be a leading cause of neonatal infection, but less appreciated is the fact that it causes maternal infection also. Maternal group B streptococcal infections during pregnancy and delivery threaten not only the mother, but the child as well. Postpartum infection, such as mastitis, bacteremia, sepsis, meningitis, endometritis, and wound infections are hazards to the mother. We describe the various maternal group B streptococcal infections, their characteristics, associated neonatal morbidity, and prevention and treatment strategies during pregnancy, delivery, and in the postpartum period.

Female↗

A survey of physician's attitudes regarding management of severe group A streptococcal infections.

Intravenous immunoglobulins (IVIG) use in the management of streptococcal toxic shock syndrome remains highly controversial. To evaluate the current management of severe group A streptococcal infections and the feasibility of a randomized controlled trial comparing immunoglobulins versus placebo for streptococcal toxic shock syndrome and/or necrotizing fasciitis, a 32-question mail and web-based survey of Canadian infectious disease specialists was conducted between December 2003 and February 2004. Overall, 172 respondents (90.5%) recommended immunoglobulins as adjunctive treatment of streptococcal toxic shock compared to 67 (35.3%) for fasciitis without toxic shock and 93 (48.9%) for invasive group A streptococcal infections with hypotension. A considerable proportion of respondents agreed that a randomized clinical trial in streptococcal toxic shock (70.1%, 131/187) and necrotizing fasciitis without toxic shock (88.2%, 162/186) would be ethical. From these, a great majority would be willing to enroll patients in a trial comparing IVIG to placebo for streptococcal toxic shock (125/131, 95.4%) and necrotizing fasciitis without shock (152/162, 93.8%). These initial results clearly demonstrate ambivalence in the utilization of intravenous immunoglobulins (IVIG) in invasive group A streptococcal infections in Canada and emphasize the need for further clinical data on immunoglobulin use in streptococcal toxic shock syndrome. They also demonstrate that, although the majority of physicians recommend immunoglobulins, there is important variability between physician recommendations with regard to the indications of use, dose, and time of administration.

Canada↗

Perianal group A streptococcal infection.

Four cases of perianal group A streptococcal infection presented with typical features of this condition; but because of lack of recognition appropriate therapy was delayed. Once group A streptococcal infection was diagnosed there was a high frequency of relapses. The need for prolonged treatment is illustrated.

Anus Diseases↗

Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production.

Previous studies have suggested a central role for superantigen-induced immune responses in the pathogenesis of streptococcal toxic shock syndrome. The production of streptococcal superantigens by clinical group A streptococcal (GAS) isolates was studied, and the ability of plasma collected from patients with severe invasive GAS infections to neutralize the proliferative- and cytokine-inducing activities of these superantigens was investigated. Overnight culture supernatants from all GAS isolates obtained from patients with invasive disease were found to contain superantigenic activity, as evident from their ability to drive potent T cell proliferation, induce high production of cytokines, and stimulate T cells in a V beta-specific manner. Twelve patients with severe invasive GAS infections, including 11 streptococcal toxic shock syndrome cases and one necrotizing fasciitis without shock, were treated with i.v. infusions of normal polyspecific Ig (IVIG). Plasma samples collected from each patient before and after IVIG administration were analyzed for their ability to neutralize the activity of streptococcal superantigens produced by the GAS isolate that caused their disease. In all IVIG-treated patients, the capacity to neutralize the superantigenic activity, produced by their respective GAS isolate or by purified streptococcal pyrogenic exotoxins, increased in plasma following IVIG administration. Of particular clinical relevance, post-IVIG plasma from each patient completely blocked cytokine production elicited by their respective GAS culture supernatants or by purified streptococcal pyrogenic exotoxins. This study shows that IVIG treatment confers in vivo inhibitory activity against a large array of streptococcal superantigens and suggests that IVIG may be useful in the treatment of severe invasive streptococcal infections.

Cytokines↗

Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder.

OBJECTIVE: Reports have suggested that streptococcal infection may be etiologically related to pediatric autoimmune neuropsychiatric disorders (PANDAS), but there are few good epidemiologic studies to support this theory. Using population-based data from a large West-Coast health maintenance organization, we assessed whether streptococcal infection was associated with increased risk for obsessive-compulsive disorder (OCD), Tourette's syndrome (TS), or tic disorder. METHODS: This is a case-control study of children 4 to 13 years old receiving their first diagnosis of OCD, TS, or tic disorder between January 1992 and December 1999 at Group Health Cooperative outpatient facilities. Cases were matched to controls by birth date, gender, primary physician, and propensity to seek health care. RESULTS: Patients with OCD, TS, or tic disorder were more likely than controls to have had prior streptococcal infection (OR: 2.22; 95% CI: 1.05, 4.69) in the 3 months before onset date. The risk was higher among children with multiple streptococcal infections within 12 months (OR: 3.10; 95% CI: 1.77, 8.96). Having multiple infections with group A beta-hemolytic streptococcus within a 12-month period was associated with an increased risk for TS (OR: 13.6; 95% CI: 1.93, 51.0). These associations did not change appreciably when limited to cases with a clear date of onset of symptoms or with tighter matching on health care behavior. CONCLUSION: These findings lend epidemiologic evidence that PANDAS may arise as a result of a postinfectious autoimmune phenomenon induced by childhood streptococcal infection.

Adolescent↗

Hospital-acquired invasive group a streptococcal infections in Ontario, Canada, 1992-2000.

BACKGROUND: A significant proportion of invasive group A streptococcal infections are hospital acquired. No large, prospective studies have characterized this subgroup of cases and evaluated the risk of transmission in hospitals. METHODS: We conducted prospective, population-based surveillance of invasive group A streptococcal infections in Ontario, Canada, from 1992 to 2000. Epidemiologic and microbiologic investigations were conducted to identify cross-transmission. RESULTS: We identified 291 hospital-acquired cases (12.4%) among 2351 cases of invasive group A streptococcal disease. Hospital-acquired invasive group A streptococcal infections are heterogeneous, including surgical site (96 cases), postpartum (86 cases), and nonsurgical, nonobstetrical infections (109 cases). Surgical site infections affected 1 of 100,000 surgical procedures and involved all organ systems. Postpartum infections occurred at a rate of 0.7 cases per 10,000 live births and exhibited an excellent prognosis. Nonsurgical, nonobstetrical infections encompassed a broad range of infectious syndromes (case-fatality rate, 37%). Nine percent of cases were associated with in-hospital transmission. Transmission occurred from 3 of 142 patients with community-acquired cases of necrotizing fasciitis requiring intensive care unit (ICU) admission, compared with 1 of 367 patients with community-acquired cases without necrotizing fasciitis admitted to the ICU and 1 of 1551 patients with other cases (P<.001). Fifteen outbreaks were identified; 9 (60%) involved only 2 cases. Hospital staff were infected in 1 of 15 outbreaks, but colonized staff were identified in 6 (60%) of 10 investigations in which staff were screened. CONCLUSIONS: Presentation of hospital-associated invasive group A streptococcal infections is diverse. Cross-transmission is common; illness occurs in patients but rarely in staff. Isolation of new cases of necrotizing fasciitis and intervention after a single nosocomial case may also prevent transmission.

Adult↗

Facial abscess due to group L streptococcal infection.

A Lancefield group L streptococcal infection was found in a previously healthy male adult during a survey of beta-hemolytic streptococci. The infection was apparently acquired subsequent to a mild injury to the face and contact with soil. Treatment with cephalothin and cephalexin was successful after surgical drainage of the wound abscess.

Abscess↗

Group L beta-haemolytic streptococcal infection in meat handlers: another streptococcal zoonosis?

Group L, beta-haemolytic streptococci can cause infection in dogs, pigs, cattle and sheep but there have been very few reports in man. In studies of skin infection in meat handlers we cultured group L streptococci from clinically infected wounds, impetigo and paronychia of 15 patients involved in the slaughter and processing of chickens and pigs. Staphylococcus aureus was also present in eight (53%) of the lesions. At least five other infections with group L streptococci in meat and animal handlers are known to have occurred in other parts of England in recent years, and brief details are given.

Abattoirs↗

[The development of the maxillodental system in the fetus and the newborn animal in intrauterine streptococcal infection].

Effects of an intrauterine streptococcal infection induced at different stages of pregnancy on the developing fetus and newborn were studied in non-inbred white rats. The course of denture development was found changed in both fetuses and newborns. A number of functional shifts in the central nervous system and physical status, presenting in the postnatal period, were detected in the experimental animals.

Animals↗

Invasive streptococcal infection of the periorbita and forehead.

Recent epidemiological reports suggest an increased frequency of invasive streptococcal infections linked to the appearance of a dominant group A Streptococcus serotype. Necrotizing streptococcal infections involving the skin and soft tissues of the face are uncommon. This case demonstrates the aggressive and invasive nature of these infections. The patient presented with symptoms of angioedema and was treated with corticosteroids. Her condition worsened and plastic surgery was consulted. There was extensive necrosis of the periorbital and forehead soft tissue, requiring extensive debridement to control the invasive process. Multiple reconstructive procedures were performed to close the defects and to preserve function of the facial muscles and eyelids. The literature indicates less than 50 reported cases of necrotizing streptococcal infections limited to the periorbita. This case reflects the importance of rapid diagnosis, and emphasizes the need for prompt and appropriate surgical treatment.

Debridement↗