A comparison of disease caused by Shigella and Campylobacter species: 24 months community based surveillance in 4 slums of Karachi, Pakistan

Despite the efforts of the international community diarrheal diseases still pose a major threat to children in children less than five years of age. Bacterial diarrhea has also emerged as a public health concern due to the proliferation of drug resistant species in many parts of the world. There is a paucity of population-based data about the incidence of shigellosis and Campylobacter infections in Pakistan. We report country specific results for Shigella diarrhea that were derived from a multicenter study conducted in six Asian countries. Disease surveillance was conducted over a 24 month period in urban slums of Karachi, Pakistan, a city with a population of 59,584. Cases were detected through passive detection in study treatment centers. Stool specimens or rectal swabs were collected from all consenting patients. Between January 2002 and December 2003 10,540 enteric infection cases were detected. The incidence rate of treated diarrhea in children under 5 was 488/1000/year. In children, 5 years and older, the diarrhea rate was 22/1000/year. 576 (7%) Campylobacter isolates were detected. The pre-dominant Campylobacter species was C. jenuni with an increase of 29/1000 year in children under 5 years. Shigella species were isolated from 394 of 8032 children under 5 years of age. Shigella flexneri was the dominant species (10/1000/year in children under 5 years) followed by Shigella sonnei (3.9/1000/year), Shigella boydii (2.0/1000/year) and Shigella dysenteriae (1.3/1000/year). Shigellosis and Campylobacter infection rates peaked during the second year of life. The incidence rate of shigellosis increased in old age but such a trend was not observed in Campylobacter infections. Of 394 shigellosis patients 123 (31%) presented with dysentery in contrast to only 54 (9%) of 576 patients with Campylobacter infections (p<0.001). Both Campylobacter infections and shigellosis are common in community settings of Pakistan but shigellosis presented more frequently with abdominal pain and dysentery than Campylobacter infections indicating that shigellosis may be a more severe illness than Campylobacter infections. Due to the increased and disease severity, drug resistant shigella have become a significant health problem; moreover it is a disease of poor and impoverished people who do not have the access to standard water and sanitary conditions, health care services or optimal treatment. In the face of these facts it is empirically important to develop a low cost effective vaccine that can protect these populations for a longer duration.     

Communitywide shigellosis: control of an outbreak and risk factors in child day-care centers.

OBJECTIVES. The study's objectives were to assess (1) control of a community outbreak of shigellosis through the promotion of handwashing, (2) risk factors in day-care centers, and (3) shigellosis attributable to attendance at a day-care center. METHODS. In 1991, an outbreak of Shigella sonnei infections occurred in Lexington-Fayette County, Ky; 14 licensed child day-care centers were involved. Communitywide promotion of hand washing was instituted along with diarrhea surveillance. A case-control study compared day-care centers that had confirmed cases of shigellosis with centers that had none. A family transmission study determined those cases attributable to attendance at day-care centers. RESULTS. The outbreak abated 3 weeks after the interventions' initiation. Day-care centers with outbreaks were more likely than those with no cases to have a food handler who changed diapers and to provide transportation for children from their homes to the center. These centers also had a higher toddler-to-toilet ratio than control centers (21 vs 12). In 58% of families with shigellosis, the first person with diarrhea during the outbreak was a child younger than 6 years; 92% of diarrheal illnesses among these children were attributable to day-care attendance. CONCLUSIONS. Community involvement in increasing hand washing most likely resulted in control of this shigellosis outbreak. Diarrhea prevention strategies in day-care centers could prevent substantial communitywide disease.     

Estimating the burden of shigellosis in Thailand: 36-month population-based surveillance study

OBJECTIVE: To estimate incidence of shigellosis in the Kaengkhoi district, Saraburi Province, Thailand. METHODS: Population-based surveillance of shigellosis based in treatment centres. The detected rates of treated shigellosis were corrected for the number of cases missed due to the low sensitivity of microbiological culture methods and participants' use of health-care providers not participating in the study. FINDINGS: The overall uncorrected incidence of shigellosis was 0.6/1000 population per year (95% confidence interval (CI) = 0.5-0.8). The unadjusted incidence of treated shigellosis was highest among children less than 5 years old (4/1000 children per year; 95% CI = 3-6) and significantly lower among people aged > 5 years (0.3/1000 population per year; 95% CI = 0.2-0.5; P < 0.001). Adjusting for cases likely to be missed as a result of culture and surveillance methods increased estimates approximately five times. The majority of Shigella isolates (122/146; 84%) were S. sonnei; the rest were S. flexneri. Of the 22 S. flexneri isolates, the three most frequently encountered serotypes were 2a (36%), 1b (23%) and 3b (28%). A total of 90-95% of S. sonnei and S. flexneri isolates were resistant to tetracycline and co-trimoxazole. In contrast to S. sonnei isolates, more than 90% of the S. flexneri isolates were also resistant to ampicillin and chloramphenicol (P < 0.0001). CONCLUSION: Estimates of incidence of Shigella infection in the community are 10-fold to 100-fold greater than those found from routine government surveillance. The high prevalence of Shigella strains resistant to multiple antibiotics adds urgency to the development of a vaccine to protect against shigellosis in this region of Thailand.     

An outbreak of shigellosis in a child care centre.

Outbreaks of shigellosis in child care are not commonly reported in Australia, however Shigella bacteria can easily spread in these settings. We report an outbreak of shigellosis in a child care centre and discuss the control measures implemented. This investigation identified 20 confirmed cases of Shigella sonnei biotype g and a further 47 probable cases in children and staff who attended a child care centre, and their household contacts. The investigation highlighted the importance of stringent control measures and protocols for dealing with outbreaks of Shigella and other enteric infections in the child care setting, and the importance of prompt notification by both doctors and child care centres, of suspected outbreaks.     

Control of day care shigellosis: a trial of convalescent day care in isolation.

Simultaneous outbreaks of S. sonnei infections occurred in September 1983 at two day care centers in Seattle, Washington. At both centers, there were high rates of diarrheal illness in the children (22/80 and 11/23, respectively), in staff members, and in family members of the ill children. The smaller center was temporarily closed, but the larger one remained open. Convalescent children and staff whose diarrhea had resolved and who were receiving appropriate antimicrobials were allowed to return to the larger center before negative cultures were obtained and were separated in an isolation room. No culture-proven cases of shigellosis occurred at either center in the following two months. Plasmid profile determinations suggested the Shigella were not transmitted from the center that remained open to the community. Estimated need for alternate child care requirements at the closed center were 100-fold greater than at the center with the isolation room. Caring for convalescent children in isolation at day care centers while they receive antimicrobial therapy may be a useful strategy for controlling day care shigellosis.     

Evaluation of an intervention program in the control of an urban outbreak of shigellosis.

Community-wide outbreaks of shigellosis are a persistent public health problem. We evaluated the effect of a household-based intervention program on the control of an urban outbreak of S. sonnei gastroenteritis. During the intervention we attempted to contact all households with culture-confirmed S. sonnei and provide education in methods to prevent spread of Shigella. Subsequently we conducted a survey of intervention (n = 43) and nonintervention (n = 33) households. We also conducted a serosurvey of children three to five years of age. The number of new cases of S. sonnei infection declined steadily over several months after the intervention began. Members of the intervention households were more knowledgeable about handwashing (rate ratio [RR] 4.7, 95% confidence interval [CI] = 2.1-10.8) and others methods of S. sonnei transmission and control than members of nonintervention households. However, intervention households had higher attack rates of Shigella-associated diarrhea in susceptible household members (RR 1.4, 95% CI = 1.0-2.0). During the intervention we were able to contact only 25% of households by the eighth day after onset of diarrhea in the index case, when 90% of intrahousehold transmission of Shigella had already occurred. Two months after the outbreak ended, 42% of children in the outbreak community had elevated antibody titers against S. sonnei; an additional 19% had borderline elevated titers. The intervention program improved knowledge but may have occurred too late to prevent intrahousehold transmission of Shigella. Exhaustion of susceptible hosts, rather than the education program, likely accounted for the decline in shigellosis cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

2008—2010年北京市西城区志贺菌血清型变迁及耐药性分析

目的 2008—2010年北京市西城区志贺菌血清型变迁及耐药性分析。方法按《全国细菌性痢疾监测方案》的要求进行。结果 2008年西城区福氏志贺菌7株,占63.6%;宋内志贺菌4株,占36.4%。2009年西城区福氏志贺菌12株,占37.5%;宋内志贺菌19株,占59.4%;鲍氏志贺菌1株,占3.1%。2010年福氏志贺菌6株,占14.3%;宋内志贺菌36株,占85.7%。药敏试验结果:志贺菌对头孢吡肟、头孢西丁、头孢他啶、氧氟沙星、左氧氟沙星、诺氟沙星、氨曲南药物敏感。对氨苄西林、磺胺、奈啶酸耐药。结论 2008—2010年北京市西城区志贺菌血清型主要为福氏志贺菌和宋内志贺菌,但是福氏志贺菌已呈逐年减少趋势,而宋内志贺菌呈逐年增多趋势。志贺菌对头孢类药物和氟喹诺酮类药物敏感,临床宜选用此类药品进行治疗。     

腹泻患儿151株志贺菌分布特征与耐药性分析

摘要:目的　探讨少儿腹泻患儿的志贺菌菌群分布特征与耐药特征,为临床防治提供依据。方法　选用志贺菌与沙门菌琼脂培养基进行培养,对于可疑的菌株经VITEK-32细菌鉴定仪与血清凝集鉴定到群,采用K-B的方法分析抗生素的耐药性。结果　151株志贺菌中主要为宋内志贺菌（85株,占56.3%）和福氏志贺菌（64株,占42.4%）,且感染患儿主要集中在0～10岁年龄段,占总感染率的72.2%（109/151）。药敏结果显示,福氏志贺菌和宋内志贺菌对氨苄西林、氨苄西林/舒巴坦、哌拉西林和复方磺胺甲噁唑的耐药率较高,均大于50%,对三代头孢及四代头孢的耐药率均在35%以下;福氏志贺菌对环丙沙星和左氧氟沙星的耐药率分别为29.6%和21.8%,未发现宋内志贺菌对环丙沙星和左氧氟沙星耐药,且两者对哌拉西林/三唑巴坦和亚胺培南全部敏感。31株多重耐药菌经纸片确认试验均为超光谱β-内酰酯酶（ESBLs）阳性菌株,但未发现头孢菌素酶（AmpC）酶阳性者。结论　腹泻患儿以感染宋内志贺菌与福氏志贺菌的婴幼儿为主,两种志贺菌对抗生素的药敏性差别比较大。     

Quantitative analysis of IgG class and subclass and IgA serum response to Shigella sonnei and Shigella flexneri 2a polysaccharides following vaccination with Shigella conjugate vaccines.

It has been recently reported that a conjugate vaccine composed of the O-specific polysaccharide of S. sonnei bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conferred 74% protection against S. sonnei shigellosis. In the present study affinity purified Shigella antibodies were used as standards to quantify and characterize the serum antibody response to vaccination with Shigella sonnei or Shigella flexneri 2a polysaccharide conjugated to rEPA. The geometric mean concentrations of antibodies at the pre-vaccination stage were 3.8 microg/ml for IgG anti-S. sonnei LPS and 11.26 microg/ml for IgG anti-S. flexneri 2a LPS. Vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA induced the production of specific IgG antibodies to levels of 115.8 microg/ml and 126.5 microg/ml, respectively. The levels of specific antibodies above the pre-vaccination values persisted for at least 2 years. The IgG response to S. flexneri 2a-rEPA conjugate was almost entirely represented by the IgG2 subclass. The concentration of IgG1 anti-S. sonnei LPS was significantly higher than that of IgG2 14 days after vaccination with the homologous conjugate, but decreased to similar levels to those of IgG2 6, 12 and 24 months after immunization. Since the only difference between the S. sonnei and S. flexneri 2a conjugates lies in the different polysaccharides of the two Shigella serogroups (the protein rEPA, is identical in both cases), it follows that the different pattern of IgG subclass response is a result of the different structures of the two O-polysaccharides of S. sonnei and S. flexneri 2a.     

Development of antimicrobial drug resistance among Shigellas isolated at an Israeli hospital from 1977 through 1990

BACKGROUND: Treatment of diarrhea due to Shigella sp. has become complicated in recent years by drug resistance. The emergence of resistance to antibiotics important in the treatment of shigellosis was studied among Shigella sp. isolated at the Sheba Medical Center between 1977 and 1990. METHOD: A retrospective study of resistance patterns of Shigella sp. using the Kirby-Bauer disc diffusion test. RESULTS: In the early 1980s S. sonnei replaced S. flexneri as the most frequent isolate. Ampicillin resistance rose steadily, peaking at 70% for S. sonnei in 1990 and 50% for S. flexneri in 1987 and 1990. Resistance to tetracycline roughly paralleled this. By 1990, 68% of S. sonnei and 75% of S. flexneri were insensitive. Cotrimoxazole resistance developed rapidly from 1981. By 1990, 88% of strains of S. sonnei had become resistant, compared to 63% of S. flexneri. S. boydii and S. dysenteriae were encountered less frequently, but showed important rates of resistance. Chloramphenicol remained active against almost all strains of S. sonnei, while resistance in S. flexneri reached about 30% in the late 1980s. Relatively few isolates were resistant to all four drugs. Only 20/841 (2.4%) of strains tested from 1984 to 1990 were resistant to nalidixic acid. CONCLUSION: The data presented document the emergence of antibiotic resistance as a serious public health problem among strains of Shigella isolated at a large medical center in Israel.     

福建省2005～2006年细菌性痢疾病原学监测结果分析

目的:了解福建省志贺菌属感染的病原学特征及药敏特点,为细菌性痢疾的防治和临床合理用药提供依据。方法:复核鉴定监测点送检的阳性菌株,按《全国细菌性痢疾监测方案》提供的方法进行系统检测。结果:两年共复核鉴定阳性菌株70株,检出志贺菌49株,其中宋内志贺菌34株,福氏志贺菌15株,分别占检出菌株数的69.4%和30.6%。药敏试验显示,49株志贺菌对头孢噻肟及环丙沙星高度敏感,全部耐药药物为四环素、利福平及复方新诺明。结论:2005～2006年福建省分离的菌株以宋内志贺菌所占比重较大,其次为福氏志贺菌,并对目前常用的抗菌药物表现一定的耐药性,应引起重视。     

Molecular epidemiology of Shigella infection in Central Australia

Shigellosis is endemic in Central Australia and the infections are predominantly due to Shigella flexneri 6, Shigella flexneri 2a and Shigella sonnei. Plasmid profiles of isolates collected from 1985-9, suggested that infections caused by Shigella flexneri 6 were predominantly due to a single clone, whereas those caused by Shigella flexneri 2a and Shigella sonnei were due to several genetically diverse strains, although strains with identical plasmid profiles were found in widely separated geographical areas and in different years.     

Risk areas and neighborhood-level risk factors for Shigella dysenteriae 1 and Shigella flexneri

Annually, there are 165 million cases of shigellosis resulting in 1.1 million deaths in the developing world. Two species of the causative agent, Shigella dysenteriae 1 and Shigella flexneri, are responsible for acute diarrheal illness. Vaccines are being developed against both but many questions remain about the disease burden, distribution of species in space and time, and community-level risk factors. This study answers two questions. What are the differences in neighborhood-level risk factors between S. dysenteriae 1 and S. flexneri? Does shigellosis caused by the two different species occur in the same neighborhoods and are those high-risk neighborhoods persistent in time? Cases from a hospital in rural Bangladesh were assigned to one of the two shigellosis types and age-matched individuals were randomly chosen from the community to be controls. Information was collected for neighborhood-level variables hypothesized to be related to shigellosis. During the 3-year study period, there were 161 cases of S. dysenteriae 1 and 225 cases of S. flexneri. Incidence of both types was highest in children under 2 followed by children from 2 to 5. The location of S. dysenteriae 1 risk varies in time but S. flexneri risk areas were persistent in time. Neighborhoods near bazaars with many non-septic latrines were at highest risk for S. dysenteriae 1. S. flexneri was most common in flood-controlled areas. S. dysenteriae 1 risk is more related to hygiene and sanitation and S. flexneri is more related to the environment.     

2013-2017年河南省婴幼儿志贺菌流行特征与耐药分析

  目的  了解河南省2013-2017年婴幼儿志贺菌的病原学特征。  方法  以河南省5岁以下腹泻患儿5 149份粪便分离的606株志贺菌为研究对象,采用血清分型、药物敏感试验及聚合酶链式反应(polymerase chain reaction,PCR)检测毒力基因方法,对其进行病原学检测。  结果  儿童志贺菌总检出率为11.77%(606/5 149),1~岁年龄组幼儿检出率最高,为24.08%;606株志贺菌共分为2群、11种血清型,其中福氏志贺菌占73.43%,宋内志贺菌占26.57℅。176株志贺菌对氨苄西林、萘啶酸的耐药严重(耐药率>90%),对氯霉素、环丙沙星,诺氟沙星、复方新诺明的耐药率>65%,对亚胺培南和头孢类抗生素敏感度较高,且福氏与宋内志贺菌耐药有差异。婴幼儿毒力基因组合模式以shET-1+、shET-2+、ipaH+、ial+为主,并检出5株无毒力株。  结论  河南省婴幼儿细菌性痢疾以福氏志贺菌为主,对常用的抗生素存在严重的耐药问题,不同血清型菌株携带优势基因模式不同。     

101株儿童腹泻病原菌分布及耐药性监测

目的:监测本地区2004～2006年与腹泻有关的肠道致病菌的组成及耐药性,为本地区流行病学研究及临床合理用药提供依据。方法:通过粪便培养,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:志贺菌属、沙门菌属、单胞菌属、弧菌属分别占65.3%(66/101)、28.7%(29/101)、4.0%(4/101)、2.0%(2/101)。志贺菌属中福氏志贺菌、宋内志贺菌分别占87.9%(58/66)、12.1%(8/66)。各菌属对抗菌药物的敏感率有差异,志贺菌属对复方新诺明及氨苄西林的耐药率较高,沙门菌属对多种抗菌药物敏感。结论:福氏志贺菌为本地区细菌性腹泻的主要致病菌,应重视耐药性监测,合理使用抗菌药物。     

Shigellosis and Escherichia coli diarrhea: relative importance of invasive and toxigenic mechanisms.

Shigellae and dysentery-like Escherichia coli must invade the epithelium of the colon to cause disease which can present as dysentery, diarrhea, or both. This paper addresses the possible role of a Shigella dysenteriae-like (Shiga-like) toxin in the pathogenesis of shigellosis and E. coli diarrheal diseases. The possibility for such a role is suggested by the following observations: 1) diarrhea, considered to be a result of secretion of water by the small bowel, is frequently observed in shigellosis, a large bowel disease. 2) Even though shigellae do not invade the jejunum of monkeys fed Shigella flexneri, jejunal secretion is seen in animals with diarrhea. 3) The Shiga toxin of S. dysenteriae has enterotoxic activity and other serotypes of shigellae produce Shiga-like toxins. 4) E. coli 015 RDEC-1 causes a diarrheal disease and frequently death in young rabbits. This organism neither produces E. coli enterotoxins nor is it invasive, but it may produce low levels of a Shiga-like toxin.     

Prospective study of the incidence of diarrhoea and prevalence of bacterial pathogens in a cohort of Vietnamese children along the Red River.

We prospectively studied diarrhoea incidence among 1655 children < 5 years of age in northern Vietnam for 1 year using primarily passive surveillance. Standard culture methods were used to detect bacterial pathogens. Overall 2160 cases occurred (13 cases/child per year). Peak rates of diarrhoea occurred in children < 12 months old. Rates ranged from 3.3 cases/child per year in children < 1 year old, to 0.7 cases/child per year in 4-year-olds. Campylobacter, shigella and enterotoxigenic Escherichia coli were most commonly isolated. Rates detected by active surveillance were about twice those detected passively. S. flexneri was the most common shigella serogroup (65 %). S. flexneri serotypes 6, 4, 1 and Y were most common, but 40% were untypable using commercial antisera. The data illustrate important regional differences in pathogen prevalence and shigella serotype distribution. Shigella vaccine development strategies, commonly targeting S. flexneri 2a, S. sonnei and S. dysenteriae 1, will have little impact on diarrhoea rates in Vietnam.     

Pathogenicity and convalescent excretion of Campylobacter in rural Egyptian children.

Campylobacter infection in developing countries has not received much public health attention because of the observation that infections are not associated with disease beyond the first 6 months of life. A cohort of 397 Egyptian children aged less than 3 years, who were observed twice weekly during 1995--1998, experienced an incidence of 0.6 episodes of Campylobacter diarrhea per child-year. A total of 13% of the Campylobacter diarrheal episodes were characterized by severe dehydration. Age-specific incidence rates (episodes per year) were 0.9 in infants aged less than 6 months, 1.5 in those 6--12 months, and 0.4 and 0.2 in the second and third years of life, respectively. Convalescent excretion of Campylobacter after a diarrheal episode might be enhancing transmission and contributing to this high incidence. Observed risk factors for Campylobacter diarrhea were poor hygienic conditions and the presence of animals in the house. Regardless of the child's age, a first infection by Campylobacter was associated with diarrhea (odds ratio = 2.45; 95% confidence interval: 1.61, 3.71); however, subsequent infections were associated with diarrhea only in children aged less than 6 months. This observation that natural infection did not confer protection during the first 6 months of life poses a challenge to vaccine development.     

Species diversity and antimicrobial resistance of Shigella spp. isolated between 2001 and 2004 from hospitalized children with diarrhoea in Kolkata (Calcutta), India

The incidence, phenotypic characteristics and antimicrobial resistance patterns of 193 Shigella strains isolated from 2489 hospitalized children with acute diarrhoea were studied during January 2001 to August 2004. S. flexneri (60%) was the most prevalent serogroup, followed by S. sonnei (23.8%), S. dysenteriae (9.8%) and S. boydii (5.7%). Since 2002, S. flexneri 2a was the most dominant serotype. Almost all S. flexneri strains exhibited resistance to ampicillin, co-trimoxazole, tetracycline, nalidixic acid and fluoroquinolones. After a lapse of almost 14 years, S. dysenteriae type 1 strains reemerged for the first time during 2002 and these strains were resistant to more than two antibiotics (multidrug resistance), including fluoroquinolones. An upsurge of similar resistance patterns was also noted among S. flexneri type 2a since December 2003. Resistance to fluoroquinolone increased year on year among S. dysenteriae type 1 and S. flexneri, but not in S. boydii or S. sonnei. Monitoring of antimicrobial susceptibility through a surveillance programme is recommended to select appropriate antibiotics for the effective treatment of shigellosis in this region.     

Development and evaluation of a Shigella flexneri 2a and S. sonnei bivalent invasin complex (Invaplex) vaccine

Over 160 million cases of shigellosis occur annually worldwide, with the two most prevalent species being Shigella flexneri and S. sonnei. Protective immunity against Shigella infection is primarily directed at the lipopolysaccharide (LPS) of the homologous serotype, so it may be necessary to combine monovalent vaccines for multiple Shigella serotypes to construct a multivalent vaccine against predominant serotypes. Recently, we described a subcellular vaccine isolated from virulent S. flexneri, consisting of proteins (including the invasins IpaB and IpaC) and LPS, that protected mice and guinea pigs from homologous challenge. In the present study, a bivalent Invaplex vaccine consisting of S. flexneri 2a and S. sonnei Invaplex was used to intranasally immunize mice and guinea pigs to determine the bivalent vaccine's immunogenicity and protective capacity against challenge with either strain. Mice and guinea pigs immunized with the bivalent S. flexneri 2a/S. sonnei Invaplex vaccine produced serum IgA and IgG antibodies to S. flexneri LPS, S. sonnei LPS, the homologous Invaplex and the water extract antigens (invasins) as determined by ELISA. The immune responses in animals immunized with the bivalent vaccine were similar to responses in animals immunized with the monovalent Invaplex vaccines. Mice and guinea pigs immunized with the bivalent vaccine were protected from a lethal lung challenge (mice, P<0.001) or severe keratoconjunctivitis (guinea pigs, P< or = 0.002) after challenge with either S. flexneri 2a or S. sonnei. Animals immunized with monovalent Invaplex vaccines were protected (P<0.001) against the homologous agent at levels comparable to the bivalent vaccine. After challenge, immunized animals demonstrated boosts in antibody titers to LPS, water extract antigens and Invaplex. These studies indicate that the subcellular Invaplex vaccine will be readily adaptable to a multivalent vaccine approach for shigellosis.