Campylobacter-triggered reactive arthritis: a population-based study

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.     

Deletion of the Shiga toxin gene in a chlorate-resistant derivative of Shigella dysenteriae type 1 that retains virulence

We used a probe specific for detecting the structural-gene sequences of Shiga toxin to analyze the genetic nature of toxin synthesis in mutant derivatives of Shigella dysenteriae type 1. A chlorate-resistant (chl) mutant (725-78) of S. dysenteriae type 1 strain 3818T, which had retained virulence but had lost production of high levels of cytotoxic activity associated with Shiga toxin synthesis, contained a complete deletion of the Shiga toxin structural-gene sequences. These structural-gene sequences were also absent in a derivative of S. dysenteriae type 1 that contained a substitution of Escherichia coli DNA in the trp region of the chromosome. Isolates of Shigella flexneri and Shigella sonnei also did not react with the probe. The low-level cytotoxic activities associated with the mutant S. dysenteriae type 1 strains or with the virulent S. flexneri and S. sonnei strains are neutralizable with antiserum to Shiga toxin; however, these cytotoxic activities are not determined by the genes encoding classic Shiga toxin.     

The pathogenesis of Shigella diarrhea. VI. Toxin and antitoxin in Shigella flexneri and Shigella sonnei infections in humans.

Two strains of Shigella flexneri and one of Shigella sonnei were studied for toxin production in vitro. All of the three strains produced a cell-free cytotoxin that showed marked similarity to that produced by Shigella dysenteriae 1. Each toxin eluted in two distinct peaks on chromatography with Sephadex G-150, was destroyed by heating at 90 C for 30 min, and was neutralized by S. dysenteriae 1 antitoxin. Patients with infections due to S. flexneri and S. sonnei developed antibody that neutralized S. dysenteriae 1 toxin in vitro. In three of seven positive sera studied by sucrose density-gradient ultracentrifugation, antibody activity was associated only with the IgM fraction. The time course of the antibody response resembled that found in infections due to S. dysenteriae 1, in which an IgM antitoxin antibody has also been described. Since three species of Shigella have now been shown to be toxigenic, it is possible that bacterial toxin may play a role, along with bacterial invasion, in the pathogenesis of infections due to S. flexneri and S. sonnei, as well as those due to S. dysenteriae 1.     

Antimicrobial resistance in Shigella species isolated in Dakar, Senegal (2004-2006)

From May 2004 to October 2006, a prospective study was carried out in Dakar, Senegal, to update information about the antimicrobial susceptibility of Shigella spp. isolated from stool specimens. Among the 165 non-duplicate strains collected, 81 (49%) were identified as Shigella flexneri, 75 (45%) as Shigella sonnei, 5 (3%) as Shigella boydii, and 4 (2%) as Shigella dysenteriae. Disk diffusion testing revealed that the majority of isolates were resistant to sulphonamides, trimethoprim-sulfamethoxazole, streptomycin, and tetracycline (respective overall resistance rates: 90, 90, 96, and 94%). More than half of the S. flexneri isolates were resistant to amoxicillin, amoxicillin-clavulanic acid, and chloramphenicol (respective resistance rates: 59, 58, and 52%), and almost all of the S. sonnei isolates were susceptible to these antimicrobials (respective resistance rates: 4, 1, and 4%). Only one isolate (belonging to the species S. sonnei) was resistant to nalidixic acid and displayed reduced susceptibility to ciprofloxacin.     

The epidemiology of shigellosis in Israel

Analysis of Shigella isolates referred for serotyping to the Central Shigella Reference Laboratory has revealed a slight predominance of S. sonnei (47%) over S. flexneri (44%) in Israel. In female patients, the predominance of S. sonnei isolates was more accentuated (54 v. 37.5% for S. flexneri). On the other hand, an increased incidence of S. flexneri was observed in military personnel (59 v. 32% for S. sonnei), and even more so in the Arab population (69 v. 19%). Incidence peaked in summer (July, August) for all subgroups.     

Shigella infections in the United States, 1974-1980

During the seven-year period 1974-1980, 93,516 Shigella isolates from humans were reported to the Centers for Disease Control, Atlanta, through a nationwide surveillance system. Over the past 30 years, the reported incidence of shigellosis has been declining in contrast to that reported for salmonellosis. Shigella sonnei (group D) now accounts for approximately 70% of the Shigella isolates reported, since most of the decline has been due to the increasingly less frequent infections caused by Shigella flexneri (group B); Shigella dysenteriae infections are now uncommon. The highest reported rates of shigellosis are from the western states and among children from one to five years of age. Among the total population of the United States, the ratio of S. flexneri to S. sonnei isolates was 0.28 among persons from one to 19 years of age and 0.45 among persons greater than or equal to 20 years of age; among American Indians the proportion of S. flexneri was much greater, the corresponding ratios being 2.1 and 2.9, respectively; in both groups the ratios for children younger than one year of age resembled those obtaining for adults. Age-related acquisition of immunity to S. sonnei may explain these observations.     

Reactive arthritis after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection

OBJECTIVE: To determine the occurrence and clinical characteristics of reactive arthritis (ReA) after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection. METHODS: From 15 October to 6 November 1998, a widespread outbreak of Y pseudotuberculosis serotype O:3 occurred in Finland. A questionnaire on musculoskeletal symptoms was mailed to 38 patients with infection confirmed by culture. All patients who reported joint symptoms were interviewed by phone and their medical records of outpatient visits or hospital admission because of recent joint symptoms were reviewed. RESULTS: Thirty three of 38 (87%) patients returned the questionnaire. Reactive musculoskeletal symptoms were reported by 5/33 (15%): four patients (12%) fulfilled the criteria for ReA and one additional patient had reactive enthesopathy. The patients with ReA were adults (age range 40-47 years), whereas the patient with reactive enthesopathy was a 14 year old boy. In all patients with ReA, the arthritis was polyarticular. In addition to peripheral arthritis, other musculoskeletal symptoms included sacroiliitis (one patient), pain in Achilles tendon (one patient), and heel pain (two patients). HLA-B27 was positive in all the three patients tested. In three of four patients with ReA, the duration of acute arthritis was over six months. CONCLUSION: Y pseudotuberculosis serotype O:3 infection is frequently associated with ReA and the clinical picture is severe.     

Campylobacter reactive arthritis: a systematic review

OBJECTIVE: To review the literature on the epidemiology of Campylobacter-associated reactive arthritis (ReA). METHODS: A Medline (PubMed) search identified studies from 1966 to 2006 that investigated the epidemiology of Campylobacter-associated ReA. Search terms included: "reactive arthritis," "spondyloarthropathy," "Reiter's syndrome," "gastroenteritis," "diarrhea," "epidemiology," "incidence," "prevalence," and "Campylobacter." RESULTS: The literature available to date suggests that the incidence of Campylobacter ReA may occur in 1 to 5% of those infected. The annual incidence of ReA after Campylobacter or Shigella may be 4.3 and 1.3, respectively, per 100,000. The duration of acute ReA varies considerably among reports, and the incidence and impact of chronic ReA from Campylobacter infection is virtually unknown. CONCLUSIONS: Campylobacter-associated ReA incidence and prevalence varies widely among reviews due to case ascertainment differences, exposure differences, lack of diagnostic criteria for ReA, and perhaps genetics and ages of exposed individuals. At the population level it may not be associated with HLA-B27, and inflammatory back involvement is uncommon. Follow-up for long-term sequelae is largely unknown. Five percent of Campylobacter ReA may be chronic or relapsing (with respect to musculoskeletal symptoms).     

Effect of prior infection with virulent Shigella flexneri 2a on the resistance of monkeys to subsequent infection with Shigella sonnei

All virulent shigellae have large plasmids. Plasmid-associated genes encode the expression of membrane-associated proteins (MAP), some of which correlate with the ability to invade susceptible epithelial cells. These MAP are serologically related in all of the shigella serotypes and evoke an antibody response after infection. To determine whether the MAP have a significant role in protection, 24 monkeys were infected with virulent Shigella flexneri 2a. After recovery, one group (with controls) was rechallenged with S. flexneri 2a; another group (with controls) was fed Shigella sonnei. The animals that were rechallenged with S. flexneri 2a were protected, while those that were fed S. sonnei experienced the same incidence of disease as controls. No differences in serum immune response to MAP after primary infection with S. flexneri were detected in immunoblots using lysates of S. flexneri or S. sonnei or in ELISA using water extracts of these strains.     

Production of Shiga toxin and other cytotoxins by serogroups of Shigella

We measured the cytotoxic activity of 119 strains of Shigella by using a quantitative [3H]thymidine-labeled HeLa cell assay. We assayed 13 strains of Shigella dysenteriae 1; 18 strains of S. dysenteriae types 2 and 3; and 88 strains of Shigella sonnei, Shigella flexneri, and Shigella boydii. Strains of S. dysenteriae 1 demonstrated high levels of cytotoxicity (geometric mean, 10(5.04) CD50/mg of protein; range, 10(3.95)-10(6.10). Cytotoxic activities of the non-type 1 strains of S. dysenteriae and of the other Shigella serogroups were approximately 1/1,000 that of the S. dysenteriae 1 strains (range, 10(1.09)-10(3.11) CD50/mg of protein). Neutralization of cytotoxicity by using rabbit antiserum to purified Shiga toxin revealed that in all strains of S. dysenteriae 1, greater than or equal to 99.5% of cytotoxic activity was attributable to Shiga toxin. In contrast, 88 of the other Shigella strains produced only nonneutralizable cytotoxic activity. Six of 18 strains of non-type 1 S. dysenteriae and 12 of 88 strains from other Shigella serogroups produced both Shiga toxin and nonneutralizable toxin.     

Reactive arthritis following an outbreak of Salmonella typhimurium phage type 193 infection

OBJECTIVES: To determine the occurrence and the clinical picture of reactive arthritis (ReA) following an outbreak of Salmonella typhimurium. METHODS: An outbreak of S typhimurium phage type DT 193 occurred in several municipalities in Finland in 1999. A questionnaire which had a specific emphasis on musculoskeletal symptoms was mailed to all 78 subjects with a positive stool culture. Based on the answers, all subjects with recent joint complaints were clinically examined or interviewed by telephone. RESULTS: Sixty three of 78 subjects (81%) returned the questionnaire. Of these 63 subjects, five (8%) fulfilled the criteria for ReA. All the five subjects with ReA were adults with oligo- or polyarthritis. The antigen HLA-B27 was positive in two of the four subjects tested. In two of five subjects with ReA, the duration of acute arthritis was over six months. Subjects who had received antimicrobial drugs developed acute musculoskeletal symptoms significantly (p=0.013) less often than those without such treatment. None of the subjects with ReA had received antimicrobial drugs before the onset of joint symptoms. CONCLUSIONS: The occurrence of ReA following an outbreak of S typhimurium was at the same level as in outbreaks due to other salmonella serotypes reported previously by us, indicating that the frequency of ReA after various outbreaks is approximately 10%. Early use of antimicrobial drugs may prevent the development of musculoskeletal symptoms.     

Changing patterns of antimicrobial susceptibility of Shigella serotypes isolated from children with acute diarrhea in Manipal, South India, a 5 year study

This study was carried out to determine the current pattern of Shigella serogroups and their antimicrobial resistance in children with acute gastroenteritis in Manipal, South India. A total of 1,200 stool samples were collected from April 2001 to May 2006 in children suffering from acute gastroenteritis attending the out-patient department of pediatrics at Kasturba Hospital, Manipal, South India. These samples were cultured for enteric pathogens. The isolates were confirmed to be Shigella by biochemical reactions and slide agglutination tests using specific antisera. Antimicrobial susceptibility was performed using an agar diffusion technique method following the National Committee for Clinical Laboratory Standard guidelines. Of 1,200 stool samples, 68 (5.6%) were positive for Shigella spp, 31 (45%) were Shigella flexneri followed by S. sonnei in 20 (31%), S. boydii in 10 (15%), and S. dysenteriae in 6 (8%). Of the 68 isolates, 58 (85.7%) showed resistance to various drugs and 47 (70%) were resistant to two or more drugs. Resistance to trimethoprim-sulfmethoxazole, tetracycline, nalidixic acid and ampicillin was observed in this study. All the strains were resistant to nalidixic acid (100%) but sensitive to cefotaxime and ceftriaxone.     

北京地区1994-2005年腹泻病原菌的分布及其耐药趋势

目的 监测我院1994-2005年与腹泻有关的肠道致病菌的分布及耐药趋势,为本地区流行病学研究、疫苗制备及临床合理用药提供依据.方法 通过常规大便培养,筛出致病菌后经生化及血清学进一步鉴定到种、群或血清型,并以纸片扩散法测定抗菌药物的敏感性.结果 12年分离到肠道病原菌8426株,患者以男性为主,儿童和青年发病为多,每年7～9月为腹泻发病高峰.病原以志贺菌属居首位(占75.11%),其次是弧菌(占12.70%),再依次为沙门菌属、气单胞菌、致病及侵袭大肠埃希菌分别占6.28%、4.43%及1.25%.6329株志贺菌中,福氏志贺菌占75.62%,其次是宋内菌群(23.98%),痢疾志贺菌及鲍氏志贺菌分别占0.22%及0.01%.12年的变化趋势是,每年肠道病原菌总数在逐渐减少,特别是志贺菌、沙门菌减少明显,而弧菌及气单胞菌相对逐渐增多.各菌属及不同的血清型对抗菌药物的敏感率有差异,福氏志贺菌和气单胞菌属多重耐药较多,而宋内志贺菌和弧菌属对多数抗菌药物敏感.结论 北京地区感染性腹泻的病原种类多,随时间的变迁病原变化明显,耐药性不同,应重视监测.     

Distribution of Shigella enterotoxin genes and secreted autotransporter toxin gene among diverse species and serotypes of shigella isolated from Andaman Islands, India

We studied the prevalence and distribution of the newly described genes for Shigella enterotoxins (ShET1 and ShET2, encoded by set and sen genes) and secreted auto-transporter toxin (encoded by sat gene) in clinical isolates from the Andaman Islands, India. A total of 153 Shigella isolates obtained from hospitalized patients during 1994-2004 were analysed. These isolates included all the four species of Shigella (S. dyseteriae-29, S. flexneri-75, S. sonnei-38, S. boydii-5) that belonged to diverse serotypes (including serologically untypable-6) and each serotype included a wide variety of genotypes. Each isolate underwent polymerase chain reaction (PCR) for detection of set, sen and sat genes employing specific primers. We found the set gene in all S. flexneri 2a and 2b isolates (41 of 41, 100%) but not outside S. flexneri serotype 2. The sen gene was well distributed among all species and serotypes but its presence was apparently low at 49.1% (75 of 153), probably because of the loss of the large plasmid that harbours the gene in 76 of the 78 (97.4%) sen negative isolates. Also, all S. flexneri 2 isolates (including 2a and 2b serotypes) had the sat gene. It was present in 96% (72 of 75) of S. flexneri, in 6.9% (2 of 29) of S. dysenteriae, in 20% (1 of 5) of S. boydii, and in 33.3% (2 of 6) of untypable Shigella, but not in (0 of 38) S. sonnei. This study provides initial data on the prevalence and distribution of of the set, sen and sat genes in a wide variety of Shigella isolated over a 10-year period. Our results suggest a greater prevalence of the set and sat genes in S. flexneri 2 isolates than previously thought and might help in future pathochip designs.     

细菌性痢疾流行特点及志贺菌耐药性研究

目的研究近年来肠道门诊细菌性痢疾流行概况及志贺菌耐药特点,为细菌性痢疾临床治疗和预防控制提供依据。方法采用志贺菌及沙门菌琼脂培养基培养,可疑菌株经VITEK-32细菌鉴定仪及血清凝集鉴定到群,K-B法检测抗菌药物的耐药性,纸片确认试验检测产超广谱β-内酰胺酶（ESBLs）,三维试验检测AmpCβ-内酰胺酶（AmpC酶）。结果 279例细菌性痢疾感染患者主要以宋内志贺菌（201株,占72.4%）和福氏志贺菌（76株,占27.2%）感染为主,且患者主要集中在0～11岁年龄段,占总感染率的71.3%（199/279）,高发季节为7-11月。药敏结果显示,志贺菌对氨苄西林、哌拉西林和复方新诺明的耐药率较高,均〉60%;对环丙沙星和左旋氧氟沙星的耐药率较低,均〈40%,未发现耐哌拉西林/他唑巴坦和亚胺培南的志贺菌。151株志贺菌纸片确认试验为产ESBLs阳性菌株,占54.1%（151/279）;未发现AmpC酶阳性者。结论我院肠道门诊细菌性痢疾以感染宋内志贺菌和福氏志贺菌的婴幼儿为主,且宋内志贺菌有增高趋势,2种志贺菌对部分种类的抗菌药物药敏性差别较大,临床医师应根据菌群鉴定及药物敏感试验结果合理选择抗菌药物。     

Antimicrobial resistance of bacterial pathogens associated with diarrheal patients in Indonesia

The antimicrobial susceptibility patterns for 2,812 bacterial pathogens isolated from diarrheal patients admitted to hospitals in several provinces in the cities of Jakarta, Padang, Medan, Denpasar, Pontianak, Makassar, and Batam, Indonesia were analyzed from 1995 to 2001 to determine their changing trends in response to eight antibiotics: ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, cephalothin, ceftriaxone, norfloxacin, and ciprofloxacin. Vibrio cholerae O1 (37.1%) was the pathogen most frequently detected, followed by Shigella spp. (27.3%), Salmonella spp. (17.7%), V. parahaemolyticus (7.3%), Salmonella typhi (3.9%), Campylobacter jejuni (3.6%), V. cholerae non-O1 (2.4%), and Salmonella paratyphi A (0.7%). Of the 767 Shigella spp. isolated, 82.8% were S. flexneri, 15.0% were S. sonnei, and 2.2% were S. dysenteriae (2.2%). The re-emergence of Shigella dysenteriae was noted in 1998, after an absence of 15 years. Shigella spp. were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Salmonella typhi and Salmonella paratyphi A were susceptible to all antibiotics tested, while Salmonella spp. showed various resistance patterns according to species grouping. A small number of V. cholerae O1 were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline; however, they were still sensitive to ceftriaxon, norfloxacin, and ciprofloxacin. Similar results were shown for V. cholerae non-O1. Campylobacter jejuni showed an increased frequency of resistance to ceftriaxone, norfloxacin, and ciprofloxacin, but was susceptible to erythromycin. This study shows that except for C. jejuni and V. parahaemolyticus, which appeared to be resistant to ciprofloxacin, the majority of the enteric pathogens tested were still susceptible to fluoroquinolones.     

Reactive arthritis associated with Shigella sonnei infection

Several studies have failed to show an association between Shigella sonnei dysentery and reactive arthritis. We describe 3 patients who had reactive arthritis and a recent or concurrent S sonnei infection. To our knowledge, this is only the second study to suggest this association. We propose that S sonnei should be considered as a triggering agent for reactive arthritis.     

The relation between production of cytotoxin and clinical features in shigellosis

The relation between in vitro production of HeLa cell cytotoxin by strains of Shigella and clinical symptomatology was determined for 35 travelers from the United States who developed shigellosis in Guadalajara, Mexico. There were 25 patients with Shigella sonnei, eight with Shigella flexneri, one with Shigella boydii, and one with Shigella dysenteriae. These strains were evaluated for in vitro production of cytotoxin. The amount of cytotoxin did not correlate with the number of stools passed, the severity of abdominal pain, or the presence of nausea or vomiting. However, patients with strains of Shigella that produced more cytotoxic activity were more likely to have fever (P less than .02) and occult blood in their stools (P less than .004). The cytotoxicity produced by 30 (86%) strains could not be neutralized with rabbit antiserum to purified, formaldehyde-treated Shiga toxin from S. dysenteriae type 1 strain 60 R; the cytotoxicity of five (14%) of the strains was partially neutralized. When only nonneutralizable cytotoxin was considered, the presence of fecal leukocytes (P less than .04), as well as of occult blood (P less than .002) and fever (P less than .02), correlated with the amount of cytotoxin. The amount of nonneutralizable cytotoxin produced by shigella strains was related to the clinical findings. This cytotoxic activity was infrequently attributable to "Shiga toxin".     

Epidemiology of sporadic bloody diarrhea in rural Western Kenya

We conducted laboratory-based surveillance and a case-control study to characterize the epidemiology of bloody diarrhea in rural Western Kenya. From May 1997 through April 2001, we collected stool from 451 persons with bloody diarrhea presenting to four rural clinics. Cultures of 231 (51%) specimens yielded 247 bacterial pathogens: 198 Shigella (97 S. flexneri, 41 S. dysenteriae type 1, 39 S. dysenteriae type non-1, 13 S. boydii, 8 S. sonnei), 33 Campylobacter, 15 non-typhoidal Salmonella, and 1 Vibrio cholerae O1. More than 90% of the isolates (excluding Campylobacter) were resistant to trimethoprim-sulfamethoxazole and tetracycline, and more than 80% were resistant to ampicillin. Most (74%) ill persons received medication to which their isolate was resistant. Drinking Lake Victoria water and sharing latrines between multiple households increased risk of bloody diarrhea. Washing hands after defecating was protective. Providing safe drinking water and more latrines, and promoting hand washing could reduce the burden of illness from bloody diarrhea while limiting injudicious antimicrobial use.     

志贺菌喹诺酮类耐药株gyrA和parC基因突变研究

目的检测志贺菌对喹诺酮类药的耐药情况,指导临床合理用药;探讨志贺菌喹诺酮类耐药株gyrA和parC基因的突变,分析GyrA和ParC氨基酸改变与喹诺酮类耐药的关系。方法 2010~2012年从宿州市3家综合性医院收集志贺菌76株,进行分离培养和血清型鉴定;采用K-B纸片法进行药物敏感试验;采用PCR方法检测志贺菌喹诺酮耐药决定区（QRDR）相关gyrA和parC基因,并挑选部分PCR产物进行DNA测序分析。结果收集的76株志贺菌中福氏志贺菌74株（占97.4%）,宋内志贺菌2株（占2.6%）;药敏结果显示志贺菌耐药情况严重,其中对阿莫西林耐药率最高,达100%;对头孢噻肟耐药率最低,为6.5%。对gyrA基因的序列分析发现3个导致氨基酸改变的基因点突变：Ser83→Leu,Asp87→Gly及His211→Tyr;对parC基因序列分析发现2个导致氨基酸改变的基因点突变：parC Ser80→Ile和Asp197→Asn。结论宿州市志贺菌感染仍以福氏志贺菌为优势菌群,且耐药严重,临床治疗志贺菌感染可优先选择头孢噻肟。志贺菌属对喹诺酮类药物产生耐药性与gyrA和parC基因突变有关,GyrA His211→Tyr和ParC Asp197→Asn氨基酸变异与喹诺酮类耐药的关系需进一步研究。