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.     

Prospective study on streptococcal pharyngitis among a town population

A one-year-round study on pharyngitis incidence among the general population of a town (24,300 inhabitants) was carried out. All patients, with pharyngitis who visited health centres were examined clinically and mcirobiologically. The overall pharyngitis incidence rate and the streptococcal pharyngitis incidence rate were, respectively, 8.3 and 3.9 cases per 100 population. Age-related incidence was highest in the group of 5-10 years, seasonal incidence was highest in autumn. Clinical diagnoses made preliminary to bacteriological examination were correct in only a half of the streptococcal pharyngitis cases. The accuracy of clinical diagnosis of streptococcal pharyngitis could, at best, be raised to 80% if fever of less than or equal to 38.0 degrees C and presence of exudate on tonsils should be considered significant criteria. A great majority of the streptococcal pharyngitis cases were caused by group A streptococci; the prevailing M types were 12, 1 and 3. Emphasis is laid on the necessity of performing microbiological examination of all pharyngitis cases in order to ensure etiological diagnosis and causal therapy. 15)     

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.     

Distribution of beta haemolytic streptococci in pharyngitis specimens obtained from children

One hundred and nine isolates of beta haemolytic streptococci were recovered from 840 (13%) pharyngeal cultures obtained from children with acute pharyngitis. Seventy-four percent of these were group A, 4% were group B, 9% were group C, 1% were group D, 4.5% were group F, and 5.5% were group G. The significance of non-group A isolates in pharyngitis could not be evaluated in the absence of viral and serological studies. However, these findings demonstrate the predominance of group A beta haemolytic streptococci in acute pharyngitis in children, as compared to findings in adults.     

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.     

Prevalence of haemolytic streptococcal infection in rhesus monkeys.

Seventy-six monkeys arriving in 10 batches were investigated within a day or two of their arrival for beta-haemolytic streptococcal infections. 10.53 per cent of monkeys yielded group A beta haemolytic streptococcus. Majority of the isolates were T pattern I. With ASO test, 44.7 per cent monkeys had low titres while with A-DNase 'B' 'test, 64.5 per cent of the monkeys had low titres.     

Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection

Group A streptococcal (GAS) pharyngitis and the subsequent bacterial colonization of the human throat elicit an immune response that may precipitate acute rheumatic fever in a susceptible host. To study the bacterial determinants that influence throat colonization and induction of humoral immunity, we characterized the behavior of GAS strains in a baboon model. An M-type 3 clinical isolate of GAS typical of strains that cause pharyngitis and invasive infection was recovered from the pharynx of six out of six baboons for at least 6 weeks after oral inoculation. By contrast, an isogenic mutant deficient in M protein failed to colonize most animals or was rapidly cleared. An isogenic mutant deficient in hyaluronic acid capsule colonized five out of six animals, but only persisted in the pharynx for 14–21 days. Colonized animals developed serum anti- streptolysin O (SLO) and anti-M protein immunoglobulin (Ig)G. The kinetics of the antibody responses were similar to those seen after human infection. Peak titres increased with the duration of throat carriage. Colonization with GAS prevented recurrent colonization after challenge with the homologous wild-type strain, but not after challenge with a strain of different M protein type. Early clearance of the M protein-deficient strain was associated with increased susceptibility of this strain to phagocytic killing in non-immune serum, whereas clearance of the acapsular strain was associated with increased susceptibility to phagocytic killing in the presence of specific antibody. These studies support critical and distinct effects of the GAS M protein and capsule on throat colonization and induction of humoral immunity in a model that reproduces important features of pharyngeal colonization and immune response following human infection.     

Selective testing strategies for diagnosing group A streptococcal infection in children with pharyngitis: a systematic review and prospective multicentre external validation study

Background:Several clinical prediction rules for diagnosing group A streptococcal infection in children with pharyngitis are available. We aimed to compare the diagnostic accuracy of rules-based selective testing strategies in a prospective cohort of children with pharyngitis.Methods:We identified clinical prediction rules through a systematic search of MEDLINE and Embase (1975–2014), which we then validated in a prospective cohort involving French children who presented with pharyngitis during a 1-year period (2010–2011). We diagnosed infection with group A streptococcus using two throat swabs: one obtained for a rapid antigen detection test (StreptAtest, Dectrapharm) and one obtained for culture (reference standard). We validated rules-based selective testing strategies as follows: low risk of group A streptococcal infection, no further testing or antibiotic therapy needed; intermediate risk of infection, rapid antigen detection for all patients and antibiotic therapy for those with a positive test result; and high risk of infection, empiric antibiotic treatment.Results:We identified 8 clinical prediction rules, 6 of which could be prospectively validated. Sensitivity and specificity of rules-based selective testing strategies ranged from 66% (95% confidence interval [CI] 61–72) to 94% (95% CI 92–97) and from 40% (95% CI 35–45) to 88% (95% CI 85–91), respectively. Use of rapid antigen detection testing following the clinical prediction rule ranged from 24% (95% CI 21–27) to 86% (95% CI 84–89). None of the rules-based selective testing strategies achieved our diagnostic accuracy target (sensitivity and specificity > 85%).Interpretation:Rules-based selective testing strategies did not show sufficient diagnostic accuracy in this study population. The relevance of clinical prediction rules for determining which children with pharyngitis should undergo a rapid antigen detection test remains questionable.Pharyngitis accounts for about 6% of visits by children to primary care physicians each year in high-income nations.¹ Group A streptococcus is found in 30%–40% of cases of childhood pharyngitis; the remaining cases are considered viral.² Antibiotic treatment is indicated for group A streptococcal infection to prevent suppurative (e.g., retropharyngeal abscess and quinsy) and nonsuppurative complications (e.g., acute rheumatic fever and rheumatic heart disease) and to reduce the duration of symptoms and the spread of the condition.³ In settings where poststreptococcal diseases have become uncommon, such as Western Europe and North America,⁴ the public health goal is shifting from preventing complications to minimizing the inappropriate use of antibiotic agents to contain antimicrobial resistance.⁵ However, 60%–70% of the visits by children with pharyngitis to American primary care physicians result in antibiotic agents being prescribed.^6–8Because signs and symptoms of streptococcal and viral pharyngitis overlap, most experts recommend that the diagnosis of group A streptococcal infection be confirmed by a throat culture or rapid antigen detection test.^9–13 Whereas European guidelines suggest all children with pharyngitis undergo such testing,¹⁴ North American guidelines recommend that clinicians select patients on the basis of clinical and epidemiologic grounds.^11–13 Currently, there is no guidance from the Canadian Medical Association or Canadian Paediatric Society for the management of pharyngitis.Various clinical prediction rules that combine signs and symptoms have been proposed to help clinicians define groups of patients according to the clinical likelihood of group A streptococcal infection.^15–18 These rules aim to identify patients at low risk in whom the disease can be managed without further testing and without antibiotic treatment, and patients at high risk who could receive empiric antibiotic treatment without testing.¹⁶ Clinical prediction rules for pharyngitis have not been sufficiently validated for clinical practice and have never been compared head-to-head in a single pediatric population from a high-income country.¹⁸The purpose of our study was to externally validate and directly compare the diagnostic accuracy of relevant rules-based selective testing strategies with original data from a French prospective multicentre cohort of children with pharyngitis. To optimize this validation study, we first conducted a systematic review of existing clinical prediction rules.     

Robotic versus Open Radical Cystectomy: An Updated Systematic Review and Meta-Analysis

Objective

To critically review the currently available evidence of studies comparing robot-assisted radical cystectomy (RARC) with open radical cystectomy (ORC).

Methods

A comprehensive review of the literature from Pubmed, Web of Science and Scopus was performed in April 2014. All relevant studies comparing RARC with ORC were included for further screening. A pooled meta-analysis of all comparative studies was performed and publication bias was assessed by a funnel plot.

Results

Nineteen studies were included for the analysis, including a total of 1779 patients (787 patients in the RARC group and 992 patients in the ORC group). Although RARC was associated with longer operative time (p <0.0001), patients in this group might benefit from significantly lower overall perioperative complication rates within 30 days and 90 days (p = 0.005 and 0.0002, respectively), more lymph node yields (p = 0.009), less estimated blood loss (p <0.00001), lower need for perioperative and intraoperative transfusions (p <0.0001 and <0.0001, respectively), and shorter postoperative length of stay (p = 0.0002). There was no difference between two groups regarding positive surgical margin rates (p = 0.19).

Conclusions

RARC appears to be an efficient alternative to ORC with advantages of less perioperative complications, more lymph node yields, less estimated blood loss, lower need for transfusions, and shorter postoperative length of stay. Further studies should be performed to compare the long-term oncologic outcomes between RARC and ORC.     

Do clinical guidelines improve general practice management and referral of infertile couples?

OBJECTIVE--To evaluate guidelines for general practice management and referral of infertile couples. Guidelines were implemented with a disease specific reminder at the time of consultation (the guidelines were embedded within a structured infertility management sheet for each couple). DESIGN--Pragmatic randomised controlled trial. Participating practices were randomised to a group that received the guidelines and a control group. SETTING--82 general practices in Grampian region. SUBJECTS--100 couples referred by general practitioners receiving the guideline and 100 couples referred by control general practitioners. MAIN OUTCOME MEASURES--Whether the general practitioner had taken a full sexual history and examined and investigated both partners appropriately. RESULTS--Characteristics of patients referred by study and control general practitioners did not differ significantly at baseline. Compliance with the guidelines increased for all targeted activities. General practitioners in the study group were more likely to take a sexual history (for example, couples'' use of fertile period, 85% v 69%, p < 0.01); examine both partners (female partner, 68% v 52%, p < 0.05; male partner 39% v 13%, p < 0.01); and investigate both partners (day 21 progesterone, 72% v 41%, p < 0.001; semen analysis, 51% v 41%, p > 0.05). Improvements were greater when general practitioners used the disease specific reminder. CONCLUSION--Receiving guidelines led to improvements in the process of care of infertile couples within general practice. This effect was enhanced when the guidelines were embedded in a structured infertility management sheet for each couple.     

High Mortality from Blood Stream Infection in Addis Ababa,Ethiopia, Is Due to Antimicrobial Resistance

Background

Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa.

Methods

Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time.

Results

Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38–25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3–164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3^rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3–4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32–7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole.

Conclusion

Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3^rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality.     

Effect of cimetidine suspension on appetite and weight in overweight subjects.

OBJECTIVE--To investigate the weight reducing effect of cimetidine, comparing it with placebo. DESIGN--Block randomised parallel group double blind study using suspensions with identical appearance and taste. SETTING--Primary care practice. SUBJECTS--55 women and 5 men aged 18-59, body mass index 25-37 kg/m2, completed the study according to the protocol. INTERVENTIONS--Cimetidine suspension 200 mg or placebo 30 minutes was given before the three main meals for eight weeks. Subjects followed a diet restricted to 5 MJ/day supplemented with 9 g fibre per day. MAIN OUTCOME MEASURES--Weight reduction; abdominal and hip circumferences and systolic and diastolic blood pressures were also recorded. RESULTS--Subjects given cimetidine lost a mean of 7.3 (95% confidence interval 6.5 to 8.3) kg more than subjects given placebo (p < 0.001); body mass index decreased 3.33 (SD 0.76) and 0.77 (0.43), respectively (p < 0.001). Abdominal and hip circumference was decreased more in the cimetidine group (8.6 (3.9) cm and 7.8 (3.1) cm) than in the placebo group (2.2 (1.5) cm and 2.1 (1.5) cm). Mean reductions in systolic and diastolic blood pressure were greater in the cimetidine group than the placebo group (mean 5.8 v 0.4 and 6.5 v 0.4, p < 0.001). CONCLUSION--Intake of cimetidine suspension 30 minutes before meals in overweight subjects may lead to reduced hunger, less food intake, and subsequent weight loss. This effect may be due to the suppression of gastric acid secretion. Cimetidine suspension may be a valuable adjunct in treating obesity.     

Effects of intranasal challenge with group A beta haemolytic streptococcus M type 49 in Swiss albino mice

Mice are susceptible to natural infections with streptococci and therefore can serve as suitable animal models to study experimental streptococcal infections. In an earlier study, we had shown the development of pharyngeal colonization, antibody response and histopathological changes in the heart following intranasal (IN) challenge with a rheumatogenic serotype of group A beta haemolytic streptococcus, the M type 18. To determine if nonpharyngitis associated serotypes can also elicit similar responses, 30 Swiss albino mice were challenged intranasally with 2 x 10(7) colony forming units of a skin associated serotype of group A beta haemolytic streptococcus, the M type 49. Pharyngeal colonization varied from 64% (n = 30) in the first week to 69% (n = 16) during the fourth week after IN challenge. Eleven (36.7%) of the 30 animals studied showed antibody response to DNase B (ADNB) with peak titers varying from 150 to 1200 units. Wide variations were seen in ADNB titers in individual mice. Histopathological evidence for cardiac lesions were seen in three animals. The changes were mild and varied from mild to chronic endocardial inflammation to calcification. The study shows that Swiss albino mice are also susceptible to IN challenge with skin associated strains of GABHS and therefore can serve as useful models to study the effects of experimental infection with diverse serotypes of GABHS.     

No association of PTPN22 R620 W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus

Rheumatic heart disease (RHD) or acute rheumatic fever (ARF) develops as a consequence of an exaggerated immune response to Group A beta haemolytic streptococci causing pharyngitis. The molecular mimicry appears between human cardiac myosin and M protein of group A streptococcal membranes. The polymorphism of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene, which encodes an important negative regulator of T cell activation, has been reported to be associated with susceptibility to several autoimmune diseases such as SLE and RA. The objective of this study was to investigate whether PTPN22 R620W polymorphism confers susceptibility to RHD in Turkish population. PTPN 22 R620W (rs2476601, A/G) polymorphism was genotyped by PCR-RFLP in 121 patients with RHD who fulfilling the revised classification criteria of Jones, and 160 healthy control (HC), and also 137 SLE as a diseased–control. The frequency of GG and AG genotypes were found to be 94% (114), 6% (7) in RHD, respectively and 96% (153) and 4% (7) in HC, respectively. The homozygous AA genotype was not present in RHD and HC. There was no statistically significant difference between RHD and HC according to the frequency of AG heterozygote genotype (P = 0.831; OR = 1.13; 95% CI 0.37–3.46). The frequency of the rare allele A was also very similar in RHD patients and HC (3, 2% respectively). A similar result was also found between SLE and HC. Our results demonstrated that the PTPN22 R620W polymorphism is not associated with RHD nor with SLE in Turkish population.     

Preliminary Evidence that American Bullfrogs (Rana catesbeiana) Are Suitable Hosts for Escherichia coli O157:H7

We orally inoculated Rana catesbeiana tadpoles (n = 23) and metamorphs (n = 24) to test their suitability as hosts for Escherichia coli O157:H7. Tadpoles were housed in flowthrough aquaria and did not become infected. Metamorphs were housed in stagnant aquaria, and 54% tested positive through 14 days postinoculation, suggesting that they are suitable hosts for E. coli O157:H7.     

Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial

ObjectiveTo study the effect of recolonisation with α streptococci with the ability to inhibit the growth of otopathogens (“interfering” activity) on the recurrence of acute otitis media in susceptible children and the effect on the frequency of secretory otitis media.DesignDouble blind, randomised, placebo controlled study.SettingEar, nose, and throat clinic with three doctors.Participants130 children prone to otitis media aged between 6 months and 6 years, 108 of whom were eligible and followed for 3 months.InterventionsChildren with no recurrences during the last month received phenoxymethylpenicillin (n=22), and those with a recurrence within 1 month received amoxicillin clavulanic acid (n=86), both twice daily for 10 days. These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days. At day 60 the same spray was started for another 10 days.ResultsAt 3 months 22 children (42%) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 (22%) of those given placebo. This difference was shown separately for recurrences of both acute otitis media and secretory otitis media.ConclusionsSelected bacteria with the ability to inhibit the growth of common otopathogens can be used to protect against recurrent acute otitis media and secretory otitis media in children.     

The effect of antibiotic treatment on the in vivo selection of resistant haemolytic Escherichia coli clones in mice

Abstract The appearance of resistant haemolytic Escherichia coli clones was studied in mice treated with a synergistic combination of antibiotics. The R plasmid donor and the haemolytic recipient were given orally. Ten animals were treated i.p. with 2.5 mg carbenicillin and 2.5 mg kanamycin pro die for 7 days. Ten control mice were injected with saline. Out of 80 faecal samples of animals receiving antibiotic treatment resistant haemolytic transconjugants were isolated from 13 samples by direct plating, and from 27 samples after selective enrichment. Out of 80 parallel samples of control animals a single one yielded a positive culture — after enrichment.     

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.