Diagnosing streptococcal pharyngitis.
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Biomedical subjects
Publications and source records attributed to E L Kaplan.
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During the 1980s there was a resurgence of serious Streptococcus pyogenes infections with complications, including rheumatic fever, sepsis, severe soft-tissue invasion, and toxic-shock-like syndrome (TSLS). We have investigated the suggested association between expression of a scarlet fever toxin, SPE A, and systemic toxicity, and the possibility that a new highly virulent clone of S pyogenes has emerged and spread world wide. We studied serotype M1 strains, the serotype most commonly associated with serious complications. 19 isolates from patients with sepsis, with or without TSLS, and 48 from patients with uncomplicated pharyngitis or superficial skin infection were subjected to restriction-enzyme digestion and electrophoresis; 56 isolates (19 serious, 37 uncomplicated disease) were then examined by hybridisation to an speA gene probe. 17 (90%) of the 19 serious-disease isolates had a characteristic ("invasive", I) restriction-fragment profile and were positive for the speA gene. Significantly lower proportions of the isolates from patients with uncomplicated disease had the I profile (21/48 [44%]; p = 0.0035) and speA (20/37 [54%]; p less than 0.001). These findings suggest that the strains from patients with serious disease are a unique clone, which became the predominant cause of severe streptococcal infections in the United States and elsewhere in the late 1980s.
During the past several decades the operation for primary hyperparathyroidism at The University of Chicago, Ill, has changed from subtotal parathyroidectomy for all patients to removal of an adenoma with performance of biopsies of all other glands to bilateral neck exploration, resection of the adenoma, and performance of fewer biopsies of normal glands. During the 1980s, 308 operations were performed; 288 patients underwent first operations. Two hundred forty-five (85.1%) of these patients had an adenoma and forty-three (14.9%) had hyperplasia (multiglandular disease); none had a carcinoma. Resolution of hypercalcemia was achieved in 281 patients (97.5%); seven patients experienced failed explorations. The early cure was the same whether or not preoperative localization studies were performed. Nineteen patients underwent 20 reoperative parathyroidectomies during this period. Preoperative localization studies, done in 16 (80%) of 20 cases, were very helpful. Ninety percent of patients with abnormal parathyroid glands in their neck or mediastinum were cured with their initial reoperation.
The pyrogenic exotoxin profiles were determined of group A streptococci isolated from patients in Zagreb, Croatia in the period 1989-1990. A total of 12 strains were studied, five from patients with serious infections and seven from patients with uncomplicated infections. Serotypes M1 and M3 were found in seven (58%) patients. Seven strains produced exotoxin A and ten strains exotoxin B. The proportion of exotoxin A and B producing strains in patients with severe infections (3 patients respectively) was similar to that found in patients with uncomplicated infections (4 and 7 patients respectively).
A 43-year-old male who sustained a superficial hand injury developed streptococcal toxic shock-like syndrome and died within 48 hours. The clinical course of the illness in this previously well patient was rapid and fulminant. The organism responsible was a group A beta-hemolytic streptococcus which was identified as opacity factor negative, M serotype 1, T type 1. The organism produced streptococcal pyrogenic exotoxins B and C, but no detectable exotoxin A although it carried speA, the gene for exotoxin A. This is the first case reported in Italy, and further emphasizes the virulence of these organisms and the rapidity with which the illness can progress.
Historically, military recruits have required benzathine penicillin G to prevent epidemics of Streptococcus pyogenes. In this randomized clinical trial, low-dose oral erythromycin was evaluated as an alternative for prophylaxis against group A beta-hemolytic streptococci in penicillin-allergic recruits. US Marine Corps recruits (186) reporting penicillin allergy were randomly given either oral erythromycin (250 mg twice a day) or a vitamin (one tablet daily) for 60 days. Evidence of infection was defined as a two-dilution rise in anti-streptolysin O titer. The erythromycin group had a significantly lower risk of S. pyogenes infection than did the vitamin group (relative risk 0.44; 95% confidence interval, 0.22-0.89). There was no significant difference among the treatment groups in isolation of group A beta-hemolytic streptococci from throat cultures. Low-dose oral erythromycin appears as effective as benzanthine penicillin G in preventing S. pyogenes infection.
More than 1100 group A streptococcal isolates collected in the United States (1988-1990) were examined to document an association of individual serotypes with specific clinical infections during the recent resurgence of group A infections and their sequelae. The most commonly isolated strains from patients with only uncomplicated streptococcal pharyngitis ("control" strains) were M serotypes 1, 2, 4, and 12. M1, M3, and M18 were statistically significantly more frequently isolated from patients with serious invasive infections and M3 and M18 from patients with rheumatic fever compared with the distribution of serotypes from the 866 control strains. An unexpected and important finding indicated that isolation rates of M1 streptococci varied geographically within the United States by year. The propensity for M1 streptococci to be statistically associated with severe systemic infections appeared unrelated to the M1 isolation rates from patients with only uncomplicated pharyngitis, thus offering additional support for the concept of strain-associated virulence rather than virulence broadly related to a given serotype.
US military recruits receive benzathine penicillin prophylaxis because of endemicity of group A beta-hemolytic streptococcal (GABHS) infections. GABHS prevalence in Navy recruits receiving single-dose benzathine penicillin prophylaxis was assessed during spring and fall 1989 by culturing throat specimens from randomly selected groups of approximately 230 men before and 2, 4, and 7 weeks after prophylaxis and from men with pharyngitis diagnosed at sick call. Of 60 GABHS isolates, 75% were serotype M-3. The pharyngitis rate increased from 0.18% in the spring to 1.55% in the fall with a concurrent increase in serotype M-3 prevalence from 35% to 91%. The GABHS prevalence rate was three- to fourfold lower after prophylaxis. There were no cases of acute rheumatic fever (ARF) despite predominance of M-3, a rheumatogenic serotype. It was concluded that penicillin prophylaxis continues to be effective for control of GABHS infections and prevention of ARF in Navy recruits.
Many advances have occurred in recent years in the diagnosis, localization, and treatment of primary hyperparathyroidism. Several different operative choices for primary hyperparathyroidism also have been proposed--a unilateral approach versus the standard bilateral parathyroid exploration. The unilateral approach is based on the concept that if an enlarged parathyroid gland and a normal gland are found on the first side of the neck that is explored, then this is an adenoma and the second side should not be explored. Only if both glands on the initial side are recognized to be abnormal is the second side explored. The theoretical advantages of this unilateral approach are a decrease in operative morbidity rates--hypoparathyroidism and nerve injuries--and a decrease in operative time. Furthermore, proponents argue that if persistent hyperparathyroidism occurs, the second side can be easily explored because it was previously untouched. In the hands of several expert parathyroid surgeons, excellent results have been achieved. However, the unilateral approach has a number of disadvantages. It places considerable pressure on the surgeon and pathologist, for they have only one parathyroid gland other than the large one to examine. There is a significant potential risk of missing double adenomas or asymmetric hyperplasia because the second, ipsilateral parathyroid gland may appear normal or near normal in these conditions. This could lead to an increased incidence of persistent or recurrent hyperparathyroidism. Furthermore, a significant reduction of operative time may be questioned, especially when the time for performing special fat stains, which often are performed with unilateral explorations, is added. Finally, even if the intent is to perform a unilateral exploration, a bilateral exploration will be necessary about half of the time. The authors strongly recommend a bilateral parathyroid exploration for all patients undergoing an initial parathyroid operation. In cases of adenoma, bilateral visualization of normal parathyroid glands and careful biopsy of only one of them will minimize hypoparathyroidism. This operative approach will lead to better results, especially for the less experienced parathyroid surgeon.
A new approach for the typing of Streptococcus pyogenes is described. Oligonucleotide probes of 30 nucleotides in length were derived from currently known sequences of the N-terminal regions of M protein genes (emm genes). The oligonucleotides were labeled with digoxigenin-dUTP and hybridized to dot-blotted genomic DNA from 116 group A streptococcal strains of serotypes M-1, M-2, M-3, M-5, M-6, M-12, M-18, M-19, M-24, and M-49. Hybridization reactions were visualized with a chemiluminescent substrate. In comparison with conventional serological typing of expressed M proteins, the binding of the probes to the corresponding emm genes exhibited 100% sensitivity and specificity. The results emphasize the high degree of type-specific conservation of the N-terminal regions of emm genes from reference strains and epidemiologically unrelated U.S. and European clinical isolates. The existence of two distinct genetic subgroups among eight investigated M-49 strains was unequivocally shown by hybridization assays and further confirmed by nucleotide sequence data obtained from four selected M-49 strains. Because oligonucleotide probes are relatively easy to prepare, easy to handle, and known to give consistent interlaboratory results, the "oligotyping" technique appears to offer potential advantages over conventional serological typing methods.
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Characterization of group A beta-haemolytic streptococci in upper respiratory tract isolates from the USA and Thailand revealed that whereas 80% of the U.S. isolates could be M or opacity factor (OF) typed, less than 20% of the Thai isolates could be characterized with the available typing sera (P less than 0.001). There was also a statistically significant difference observed in the percentage of strains that could be characterized by the T-agglutination pattern (93% in the USA vs 61% in Thailand, P less than 0.001). Even among the identifiable strains, marked differences in the distribution of the recovered serotypes were noted between the two countries. These results show that there are a significant number of as yet unidentified group A streptococcal strains in parts of the world where streptococcal infections and their sequelae are important public health problems. They further imply that such findings must be taken into consideration in the future when designing possible streptococcal vaccines for worldwide use.
Although the relationship between group A streptococcal upper respiratory tract infection and the development of acute rheumatic fever has been known for many years, the pathogenetic mechanism(s) have never been defined. Thus, the mechanism of damage to the valves and to the myocardium in patients with rheumatic fever remains unexplained. Traditionally, emphasis has been placed on the valvular damage in rheumatic heart disease, but there is considerable evidence for myocardial involvement. An abnormal immune response to some as yet unrecognized somatic or extracellular antigen of the group A streptococcus is probably related to the cardiomyopathy. This abnormal immune response is supported by considerable clinical and experimental evidence. Recent studies have suggested other mechanism to explain the myocardial damage including the influx of lymphocytes into the area as well as the possibility of damage relating to generation of oxygen-free radicals. As more sophisticated molecular biological studies of the group A streptococcus become available, perhaps the mystery of this very unique and common cardiomyopathy can be resolved.
Group A beta-hemolytic streptococci (GABHS) have once again become an important cause of serious suppurative disease in children. A 100% increase in the rate of GABHS bacteremia and an increased frequency in GABHS bacteremia in previously healthy children were observed in 1989 through 1990 compared with 1984 to 1988. Streptococcal isolates were characterized and patient demographic data were tabulated from children hospitalized with GABHS suppurative infections in 1989 through 1990. The differences in clinical manifestations and strains of GABHS were examined in patients with bacteremia, with or without focal site of infection, and in those with focal infections without bacteremia. Bacteremic children were significantly younger and had higher white blood cell counts at admission. No patient had a toxic shock-like syndrome. Although no specific strain was associated with suppurative infections, serum opacity reaction-negative organisms were more frequently associated with focal infections without bacteremia. The data suggest that GABHS may have become more virulent. Physicians should consider GABHS as an important cause of serious suppurative infection in children.
Beginning in the mid-1980s and continuing to the present, there has been an apparent increase in the number of severe group A streptococcal infections and their suppurative and nonsuppurative sequelae. The reasons for this epidemiologic change remain incompletely explained. At present, the data seem to suggest that this change is related to the reappearance in the population of not only "new" serotypes, but most likely virulent strains of these serotypes. This has been suggested by available epidemiologic surveys. The pathogenetic mechanism by which these virulent strains cause an increased severity of disease is also incompletely understood. It has been suggested that certain of the streptococcal pyrogenic exotoxins (pyrogenic exotoxin A or B) are associated with strains isolated from severe cases of systemic group A streptococcal infections, but the data conflict in many instances. Clinically, this is an extraordinarily virulent syndrome often leading to the death of the patient within a matter of hours or days. This is despite what would seem to be adequate and appropriate antimicrobial therapy with agents which are effective in vitro against the offending group A streptococcus. Therapy therefore is still based on appropriate antibiotic therapy and support of other systemic manifestations with appropriate medical therapy. At present, prevention of these suppurative and nonsuppurative sequelae is impractical simply because the initial streptococcal infection or colonization is rarely recognized. These events of the last half decade strongly support the need for additional understanding of the epidemiology, pathogenesis, treatment, and prevention of serious group A beta-hemolytic streptococcal infections.
BACKGROUND: In closely confined populations, in which epidemics of Streptococcus pyogenes infection are common, penicillin G benzathine has long been used prophylactically to reduce morbidity from this pathogen. We report on our investigations of the effectiveness of penicillin G benzathine prophylaxis at a military recruit camp. METHODS: We prospectively studied the rates of pharyngeal colonization and infection by S. pyogenes among 736 male U.S. Marine Corps recruits from January through March 1989. Throat swabs for culture, clinical data, and questionnaire data were obtained during six examinations at intervals of two weeks. Serum samples obtained before training, after training, and from acutely ill recruits were analyzed with use of an antistreptolysin O microtitration technique. RESULTS: Although 93 percent of the recruits received prophylaxis with two intramuscular injections of 1.2 million units of penicillin G benzathine each (administered 30 to 39 days apart), 33 percent of the recruits were colonized by S. pyogenes, and 42 percent had infection (as defined by a two-dilution increase in the antistreptolysin O titer). Thirty-seven percent of 265 recruits who reported a sore throat and were infected with S. pyogenes did not seek medical attention. The recruits who were allergic to penicillin (7 percent of the total), who received no prophylaxis, were more likely to be colonized; an increased risk of colonization and infection among the nonallergic recruits was associated with the presence of a higher percentage of allergic recruits in the platoon. After the study was completed, all recruits who were allergic to penicillin were prescribed 250 mg of oral erythromycin twice daily (a total daily dose of 500 mg) for 60 days. Subsequently, the average weekly rate of clinically evident S. pyogenes pharyngitis fell by more than 75 percent. CONCLUSIONS: If the prevention of S. pyogenes infection is to be effective in closely confined populations such as military recruits, prophylactic antibiotics must be administered to all members of the population. Exempting those who are allergic to penicillin may create a bacterial reservoir from which infection can be transmitted to nonallergic members of the population.
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Several cases of a toxic shocklike syndrome have been reported in the United States during the past five years in association with Streptococcus pyogenes infection. We report a case of a firefighter exposed during attempted CPR to the secretions of an S pyogenes-infected child. The firefighter developed an infection of the hand and subsequent febrile illness with hypotension, erythematous rash, renal failure, and hypocalcemia. Bacterial isolates of blood and cerebrospinal fluid from the deceased child were identical in type and exotoxin production with isolates grown from the hand wound of the firefighter. This is the first reported case of documented transmission of S pyogenes, causing a toxic shocklike syndrome in an emergency medical technician.