CONTROL OF STREPTOCOCCAL THROAT INFECTIONS IN SCHOOLS—A Cooperative Program Followed in Orange County

Attempts to identify streptococcal throat infections on clinical evidence alone do not provide an adequate or reliable index of the prevalence of these infections in the community.Epidemiologic information on streptococcal throat infections based on bacteriological identification permits a more accurate assessment of the situation and more logical and more effective control measures.Recent refinements in laboratory procedures have provided a simple, reliable and relatively inexpensive method for the identification of Group A beta hemolytic streptococci by public health or clinical laboratories.In Orange County a program for the identification of streptococcal throat infections by cooperative action of the medical profession, the health department and the school authorities greatly aided in control of the disease. A voluntary health agency (heart association) made an important contribution toward the success of the control program.     

Simplified Extraction Procedure for Serological Grouping of Beta-Hemolytic Streptococci

An adaptation of the nitrous acid extraction of streptococci proved to be a reliable and practical method for the preparation of extracts for routine serological group identification. The extracts of all groups tested gave strong capillary precipitin reactions as well as reactions of double diffusion in gel. For routine grouping, extracts were prepared from the first one-half-plate subculture of the initial throat culture. The technique is simple and reliable, and it requires a minimum of technical skill, reagents, and equipment. Its use would facilitate epidemiological surveillance of group A streptococci and rapid diagnosis of streptococcal infections at a low cost.     

Use of tomicid in prophylaxis of respiratory streptococcal infection in the organized groups of children of pre-school age

The results of the approbation of the use of Tomicid for the prophylaxis of scarlet fever and other manifestations of streptococcal infection in an organized group of children of pre-school age are presented. The pronounced prophylactic effect of Tomicid, manifested by a reliable decrease of group A streptococcal carrier state, as well as in a decrease in morbidity in respiratory streptococcal infection among children in the test group in comparison with those in the control one. The simplicity of the use of the preparation (as throat gargle for 5 days) makes it possible to regard this preparation as a promising remedy for the urgent prophylaxis of scarlet fever.     

Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants

Exacerbation of chronic psoriasis can be associated with streptococcal throat infections, and T cells that respond to peptide sequences common to streptococcal M proteins and skin keratins have been detected in patients' blood. To our knowledge, we have conducted the first blinded, prospective study to assess the impact of tonsillectomy on psoriasis. Twenty-nine patients with chronic psoriasis and history of exacerbation after sore throat were randomly assigned to tonsillectomy (n = 15) or control (n = 14) groups and monitored for 2 y clinically and by enumeration of circulating skin homing T cells that respond to short homologous M protein or keratin peptides. Thirteen patients (86%) showed sustained improvement after tonsillectomy ranging from 30 to 90% reduction in disease severity. Furthermore, there was a close correlation between the degree of clinical improvement in individual patients and reduction in the frequency of peptide-reactive skin-homing T cells in their circulation. No corresponding clinical or immunologic changes were observed among the controls. These findings indicate that tonsillectomy may have a beneficial effect on chronic psoriasis because the palatine tonsils generate effector T cells that recognize keratin determinants in the skin.     

Protective immunity evoked by locally administered group A streptococcal vaccines in mice

The present studies were undertaken to determine the pathogenicity of group A streptococci introduced intranasally (i.n.) into mice in an attempt to mimic mucosal infections in humans and to determine the efficacy of streptococcal vaccines administered via the mucosal route. The LD50 of type 24 streptococci (M24 strep) administered i.n. was 3 x 10(4) CFU. Throat cultures were performed in M24 strep-inoculated mice. Of 11 mice that died, 9 had positive throat cultures 3 or 4 days after i.n. challenge, and of 9 mice that survived, only 1 had a positive throat culture, indicating an association between mucosal infection and death. Postmortem examination performed on 35 mice that died after i.n. challenge showed that all had evidence of disseminated infections, and group A streptococci were recovered from the cervical lymph nodes, blood, spleen, liver, and brain. To determine vaccine efficacy, heat-killed M24 strep or pep M24 were administered i.n. to groups of mice. Whole, heat-killed streptococci and pep M24 administered locally protected mice against death from i.n. challenge infections with homologous M24 strep. The whole cell vaccine also protected against i.n. challenge infections with heterologous type 6 streptococci. Our data suggest that streptococcal vaccines administered locally evoke protective immunity against streptococcal infections.     

Development of PCR assays for detection of Streptococcus canis

Streptococcus canis isolates, also including S. canis of artificially contaminated milk, could be identified by polymerase chain reaction (PCR) amplification using oligonucleotide primers designed according to species-specific parts of the 16S rRNA gene and, after sequencing, according to S. canis-specific parts of the 16S-23S rDNA intergenic spacer region and with oligonucleotide primers detecting an internal fragment of the group G streptococcal CAMP factor gene cfg. The 16S rRNA gene- and CAMP factor gene cfg-specific oligonucleotide primers could be used together in a multiplex PCR. No cross-reactivities could be observed with other group G streptococcal isolates or with any of the other control strains of various streptococcal species and serogroups. The PCR methods presented in this study allowed a rapid and reliable identification of S. canis and might help to improve the diagnosis of this bacterial species in animal and human infections.     

Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open,randomised controlled trial

Objective To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy.Design Open, randomised controlled trial.Setting 21 general hospitals and three academic centres in the Netherlands.Participants 300 children aged 2-8 years requiring adenotonsillectomy.Intervention Adenotonsillectomy compared with watchful waiting.Main outcome measures Episodes of fever, throat infections, upper respiratory tract infections, and health related quality of life.Results During the median follow up period of 22 months, children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group (difference -0.21, 95% confidence interval -0.54 to 0.12), 0.56 throat infections per person year compared with 0.77 (-0.21, -0.36 to -0.06), and 5.47 upper respiratory tract infections per person year compared with 6.00 (-0.53, -0.97 to -0.08). No clinically relevant differences were found for health related quality of life. Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two. 12 children had complications related to surgery.Conclusion Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy.     

Streptococcal Superantigen,Mitogenic Factor,and Pyrogenic Exotoxin B Expressed by Streptococcus pyogenes

Abstract

Streptococcus pyogenes is a Gram-positive human bacterial pathogen that causes pharyngitis, tonsillitis, skin infections (impetigo, erysipelis, and other forms of pyoderma), acute rheumatic fever (ARF), scarlet fever (SF), poststreptococcal glomerulonephritis (PSGN), a streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis. These infections are some of the most economically and medically important conditions that affect humans. For example, globally, ARF is the most common cause of pediatric heart disease. It is estimated that in India more than six million school-aged children suffer from rheumatic heart disease (1). In the United States, “sore throat” is the third most common reason for physician office visits and S. pyogenes is recovered from about 30% of children with this complaint (2). It has been estimated that there are 25–35 million cases of streptococcal pharyngitis per year in the United States, and these infections cause 1–2 billion dollars per year in direct health care costs (3,4). Although the continued great morbidity and mortality caused by S. pyogenes in developing nations, the significant health care financial burden attributable to group A streptococci in the United States, and increasing levels of antibiotic resistance (5), have highlighted the need for a fuller understanding of the molecular pathogenesis of streptococcal infection, it has been the relatively recent intercontinental increase in streptococcal disease frequency and severity (6,7) that has resulted in renewed interest in S. pyogenes virulence factors and host-parasite interactions.     

Is plasminogen deployed as a Streptococcus pyogenes virulence factor?

Streptococcus pyogenes (group A streptococcus) causes human skin and throat infections as well as highly invasive diseases including necrotizing fasciitis. Group A streptococcal infections and invasive disease have made a resurgence in developed countries during the past two decades. S. pyogenes use multiple pathways for the acquisition and activation of human plasminogen, securing potent proteolytic activity on the bacterial cell surface. Recent experimental evidence using a humanized transgenic mouse model suggests a crucial role for human plasminogen in the dissemination of S. pyogenes in vivo.     

I. Clinical evaluation

A study was undertaken to evaluate the therapy of streptococcal pharyngitis. The compliance of 118 patients with beta-hemolytic streptococcal pharyngitis to follow-up was 72%. Of 74 patients checked by means of urine tests 66 took their oral medication. No differences were detected in the clinical and bacteriological results (>98% streptococcal eradication) after the 7th or 10th day of therapy after taking either cephalexin or penicillin.It was concluded that: (a) for effective surveillance and follow-up special attention should be given to the uncooperative segment of the patient population; (b) a seven-day course of penicillin may be satisfactory in the eradication of BHS from the throat; and (c) cephalexin appears to be an effective alternative to penicillin for the treatment of streptococcal pharyngitis.     

Significance of Hemolytic Colonies in Throat Cultures

These studies indicate that a single strain of hemolytic streptococci almost exclusively predominates the bacterial flora in patients with streptococcal infections and in the carrier state. One can proceed with confidence that, in isolating streptococci from throat swabs cultured on blood-agar plates, only a single hemolytic colony need be picked for serological grouping and typing.     

Treatment of streptococcal pharyngitis with amoxycillin once a day.

OBJECTIVE--To evaluate treatment of group A beta haemolytic streptococcal pharyngitis with amoxycillin once daily compared with phenoxymethylpenicillin three or four times a day. DESIGN--Randomised controlled study of consecutive patients presenting with symptoms suggestive of group A beta haemolytic streptococcal pharyngitis in whom culture of a throat swab yielded positive results. SETTING--Five family medicine practices. SUBJECTS--157 patients aged over 3 years who required treatment with antibiotics. MAIN OUTCOME MEASURES--Clinical response, bacteriological response, days at work and school lost, and compliance. RESULTS--During the period of the study 393 patients presented with symptoms suggesting streptococcal pharyngitis; 157 of them had throat swabs that yielded positive results on culture. Eighty two were treated with phenoxymethylpenicillin and 75 with amoxycillin. No difference was observed in the clinical response, days at work and school lost (139 days for 64 patients taking phenoxymethylpenicillin v 100 days for 57 patients taking amoxycillin; p > 0.2), or residual positive cultures after two days (6 (7.3%) v 3 (4%); p > 0.5). A significant difference in the bacteriological response was found after 14 days (5 (6.1%) v 0; p < 0.04) with no positive cultures observed in the amoxycillin group. CONCLUSIONS--These findings support the hypothesis that amoxycillin once daily is as effective as phenoxymethylpenicillin in the treatment of group A beta haemolytic streptococcal pharyngitis.     

Identification of beta-hemolytic streptococci isolated from hospitalized children in Baghdad.

Two hundred and twenty four hospitalized children in Baghdad aged between 1 month and 10 years were examined for Streptococcal infections. Thirty-four percent of the throat and saliva specimens were positive for beta-hemolytic streptococci. Males were more susceptible to infection with group A streptococci than females. Streptococcus of group A was isolated from 39.5% of the positive cases while group G was 47.4%. The etiological significance of the latter group in tonsillitis and otitis media is to be further investigated. Ninety six percent of the isolated streptococci were T typable and 13.3% of the strains were M typable. A high frequency of type T-11 was found in streptococcal infections. T type 3875 was found to be a new provisional type. All isolates were M untypable, and antiopacity factor negative except for two isolates of T type 4 which were positive in both typings.     

Streptococcal L forms and phage. A clinical-epidemiologic study

This study showed that streptococcal L forms could not be isolated from children who were either carriers of group A streptococci or had disease due to this pathogen. It was possible to induce L colony formation in 15 strains of group A. Streptococcal bacteriophages were demonstrated in 20% of group A streptococci isolated from school children who were carriers, but did not have clinical evidence of streptococcal disease, and from 44.9% of children whose physicians considered they had acute streptococcal upper respiratory infections. Lysogeny (bacteriophage) was demonstrated more frequently during 1969-70 when carrier rates were high and from children who had manifest streptococcal disease, suggesting a possible positive relationship between lysogeny, high carrier rates, and infection in the children studied. Lysogeny and erythrogenic toxin production by group A streptococci occurred simultaneously in approximately half of the strains of group A streptococci tested, suggesting that lysogeny is not a sine qua non for erythrogenic toxin production.     

Genetic regulation of host responses to group A streptococcus in mice.

The group A streptococci (GAS, Streptococcus pyogenes) are important human pathogens which can cause a variety of diseases, ranging from mild infections to very severe invasive diseases. In recent years, evidence has been accumulated that host genetic factors have a major influence on the outcome of streptococcal infections. Variability in the degree of susceptibility of different inbred mouse strains to infection with GAS has demonstrated that the host genetic background largely determines the susceptibility of mice to this pathogen. This information is particularly useful for studying the immune mechanisms underlying disease susceptibility in mice, and provides an entry point for the identification of host defence loci. This paper reviews the recent advances in the characterisation of pathogenic mechanisms associated with the development of GAS-induced septic shock in the mouse model and outlines the current knowledge regarding the genetic control of immune responses to Group A streptococcus in mice.     

A program against bacterial bioterrorism: improved patient management and acquisition of new knowledge on infectious diseases

In 2002 it was decided to establish laboratory facilities in Denmark for diagnosing agents associated with bioterrorism in order to make an immediate appropriate response to the release of such agents possible. Molecular assays for detection of specific agents and molecular and proteomic techniques for identification of bacteria were introduced as part of the program. All assays and techniques were made accessible for use in diagnosing patients, even when an intentional release was not suspected. Medical expertise on different diseases was established at the department as an integrated part of the program. The analyses included PCR assays for specific bacteria, identification of isolated bacteria by DNA sequencing, detection and identification of bacteria in clinical sample material by universal bacterial PCR and DNA sequencing, and identification of bacteria by mass spectrometry. The established analyses formed a basis on which a series of further developments was built. In addition to reducing the time for obtaining diagnoses and improving the accuracy of diagnosis of individual infected patients, the analyses provided new knowledge on the frequency and distribution of some bacterial infections, including Q fever, tularemia, trench fever, brucellosis, and melioidosis. The implementation of an antibioterrorism program in a clinical diagnostic setting improved the diagnostic possibilities for patients in Denmark and provided new epidemiologic information. It also introduced a number of diagnostic assays for bacterial infections not associated with bioterrorism that are difficult to culture or identify.     

Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves.

Serotype M1 group A Streptococcus strains cause epidemic waves of human infections long thought to be mono- or pauciclonal. The gene encoding an extracellular group A Streptococcus protein (streptococcal inhibitor of complement) that inhibits human complement was sequenced in 1,132 M1 strains recovered from population-based surveillance of infections in Canada, Finland and the United States. Epidemic waves are composed of strains expressing a remarkably heterogeneous array of variants of streptococcal inhibitor of complement that arise very rapidly by natural selection on mucosal surfaces. Thus, our results enhance the understanding of pathogen population dynamics in epidemic waves and infectious disease reemergence.     

Aetiology of upper respiratory tract infections in children in Arak city: a community based study

Viruses are frequent causes of upper respiratory tract infections in children. We investigated the viral aetiology of community-acquired upper respiratory tract infections (URIs) in young children treated as outpatients in community settings. During November 2008, nasal swab specimens were taken from children with recent onset of upper respiratory tract infections. The patients attended day care or primary schools; the specimens were randomly obtained by pediatricians from schools and childcare institutions and sent for identification by PCR method. A total of 300 specimens were collected. From all samples, 40.67% were positive for at least 1 virus, viz. adenovirus 11.76%, rhinovirus 9.8%, respiratory syncytial virus 6.08%, influenza virus 5.56%, parainfluenza virus 4.9%, enterovirus 2.94% and a combination of 2 viruses 2%. Clinical manifestations of the respiratory infections were as follows: 70.7% of the patients had coryza, 69.3% cough, 26% sneezing, 19.7% sore throat, 2.7% headache, 7.7% fever, 2.3% conjunctivitis, 1.3% abdominal pain and 1% hoarseness. The results of this study demonstrate that adenoviruses and rhinoviruses are the two most common viral agents isolated from pediatric outpatients with acute URIs in autumn in Arak City. Coryza and cough were the most common symptoms in children. Sore throat and hoarseness were more prevalent in infections caused by influenza virus, conjunctivitis in parainfluenza, and coryza in rhinovirus infections.     

Development and Evaluation of Capture Enzyme-Linked Immunosorbent Assays for Detection of Immunoglobulin G and M Antibodies to Group A Streptococcal Antigens

Capture enzyme-linked immunosorbent assays (ELISAs) were developed to detect immunoglobulin G and M antibodies to group A streptococcal (GAS) antigens, streptolysin O, streptokinase, and group A carbohydrate. The sensitivities and the specificities of the IgM capture ELISAs to each GAS antigen were high enough to distinguish the patients with GAS infections (diagnosed as GAS pharyngitis or scarlet fever) from the control groups (healthy people and patients with pharyngitis from whom GAS could not be isolated). On the other hand, the specificities of the IgG capture ELISAs were not very effective in diagnosis of GAS infections. When the capture ELISA and an indirect ELISA detecting IgM antibodies to group A carbohydrate were compared, false-positive reactions due to rheumatoid factor occurred in the indirect ELISA, but did not occur in the capture ELISA. These results indicate that the capture ELISA works better than the indirect ELISA in detecting the IgM antibody, and that the IgM capture ELISA to GAS antigen provides a rapid and highly reliable serodiagnosis for GAS infections employing only a single serum.     

Epidemiology of group A streptococcal infections--their changing frequency and severity

The frequency and severity of streptococcal infections and their sequelae have declined dramatically in the past century, yet the prevalence of streptococcal infections is still high. The reasons for this decline must be intimately related to host resistance, virulence of the agent, and environmental factors, especially crowding. Close examination of these fundamental influences does not reveal any evidence that humans have become less resistant to streptococcal infections, but they react less violently. There is some evidence that the agent may have lost a degree of its virulence. The decline in morbidity and mortality due to streptococcal infections began long before antibiotics, especially penicillin, were available. However, penicillin has proved to be an important factor in prevention of streptococcal infections, especially in rheumatic fever prophylaxis. There are certain indications that repeated streptococcal infections due to similar M types, occurring in young children over the past several decades, have resulted in some degree of immunity as well as the possible evolution of less virulent, but not less infectious, strains of group A streptococci. Also, a decrease in crowding would be expected to result in fewer streptococcal infections. Although there are more people in the world than at any other time in the history of man, urban population density in the western world, at least, is less than in the late 1800s and early 1900s.