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.     

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.     

Emergence of highly trimethoprim-sulfamethoxazole-resistant Shigella in a native American population: an epidemiologic study

Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) emerged among Shigella isolates from the Navajo Reservation in the southwestern United States in 1985, years after this antimicrobial agent came into common use. In the study area, TMP-SMX resistance increased dramatically from 3 per cent in 1983 to 21 per cent in 1985. Resistance was polyclonal and occurred in both S. sonnei and S. flexneri. No single plasmid was common to all resistant strains. However, all 28 TMP-SMX resistant isolates examined were resistant to ampicillin and streptomycin and had minimum inhibitory concentrations to sulfamethoxazole of greater than or equal to 4,096 micrograms/ml and to trimethoprim of greater than or equal to 1,024 micrograms/ml. The authors found that 28 of 101 Navajo children with gastrointestinal symptoms who were not taking antimicrobials had TMP-SMX-resistant aerobic fecal flora. To determine risk factors for acquiring resistant strains, they compared 40 case-patients with TMP-SMX-resistant Shigella to 66 controls with TMP-SMX-sensitive Shigella. Case-patients were more likely than controls to have used antimicrobials recently (p = 0.004) and to be hospitalized for shigellosis (p = 0.05). These findings suggest that polyclonal highly TMP-SMX-resistant Shigella emerged by transfer of trimethoprim resistance genes from aerobic bowel flora to endemic Shigella strains, that use of antimicrobials can lead to symptomatic shigellosis and thus the persistence of trimethoprim-resistant Shigella, and that appropriate therapy of shigellosis on the reservation is now a major challenge.     

Evaluating health risk models

Interest in targeted disease prevention has stimulated development of models that assign risks to individuals, using their personal covariates. We need to evaluate these models and quantify the gains achieved by expanding a model to include additional covariates. This paper reviews several performance measures and shows how they are related. Examples are used to show that appropriate performance criteria for a risk model depend upon how the model is used. Application of the performance measures to risk models for hypothetical populations and for US women at risk of breast cancer illustrate two additional points. First, model performance is constrained by the distribution of risk‐determining covariates in the population. This complicates the comparison of two models when applied to populations with different covariate distributions. Second, all summary performance measures obscure model features of relevance to its utility for the application at hand, such as performance in specific subgroups of the population. In particular, the precision gained by adding covariates to a model can be small overall, but large in certain subgroups. We propose new ways to identify these subgroups and to quantify how much they gain by measuring the additional covariates. Those with largest gains could be targeted for cost‐efficient covariate assessment. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

Development of vaccines against shigellosis: Memorandum from a WHO Meeting

Endemic shigellosis is a worldwide problem, with a high morbidity rate in most developing countries; substantial mortality may also occur, especially with disease caused by Shigella dysenteriae serotype 1. The limited efficacy of current measures to control this infection makes the development of vaccines for the prevention of shigellosis particularly important. This Memorandum describes the clinical features of and immunity to shigellosis, summarizes the present status of efforts to develop suitable vaccines, and lists the topics that should be given priority in research.     

Epidemiologic patterns of acute diarrhea and endemic Shigella infections in children in a poor periurban setting in Santiago, Chile

To prepare a field site for evaluating preventive interventions against endemic shigellosis, the authors followed prospectively a cohort of 360 children (90 each of children aged 0-11, 12-23, 24-35, and 36-47 months) in Santa Julia, a low socioeconomic area in Santiago, Chile, from November 1986 through April 1989 with twice weekly household visits for diarrheal disease; infants replaced children who reached 60 months of age. Coprocultures on 2 consecutive days from children with diarrhea and from age-matched controls within the cohort were cultured for Shigella. Bacteriologic surveillance was also maintained in the health center and children's hospital serving Santa Julia. In this community, where all households had access to potable water (68% inside) and all but 3% had access to a toilet, but where there was marked crowding, the overall incidence of diarrheal disease in the cohort was low (2.26 episodes/12 child months of observation in children aged 0-11 months and 2.09 in those aged 12-23 months), yet Shigella infections were common. Shigella accounted for 10% of diarrheal episodes in the cohort (vs. 3.2% isolation rate in controls, p less than 0.0001). The incidence of shigellosis in children aged 12-47 months was 0.16 cases per 12 child months of observation; in the first 5 years of life, a child had a 67% chance of experiencing shigellosis. Shigella sonnei, Shigella flexneri 2a, and S. flexneri 6 caused greater than 79% of the infections. Shigella occurred more often in hospitalized cases of diarrhea than in age-matched cases detected in the health center or by household surveillance (p less than 0.0001). An initial episode of Shigella diarrhea did not diminish overall the risk of subsequent shigellosis but did confer 72% protection (p = 0.05) against illness due to the homologous serotype. The high rate of both S. sonnei and S. flexneri shigellosis in a population with a low background rate of diarrhea makes Santa Julia an appropriate site for assessing the efficacy and effectiveness of measures to reduce Shigella infections.     

北京市2004年-2010年志贺菌菌型分布及毒力基因分析

目的:了解近年来北京市志贺菌菌型变化及毒力基因分布特征。方法:对2004年-2010年监测到的1413株志贺菌进行血清分型;应用荧光PCR方法进行ipaHs、et1和sen基因的检测。结果:宋内志贺菌741株(52.4%),福氏志贺菌664株(47.0%),痢疾和鲍氏志贺菌各4株(1.2%)。福氏志贺菌共分为19种血清型,以F4c、F2a、F1a为主。宋内志贺菌自2007年首次超过福氏成为优势菌型后,所占比例逐渐加大,2010年已达到79.3%。福氏志贺菌也逐步由F4c转向以F2a为主,并伴有其它血清型交替出现。ipaH s,et1和sen三种基因的携带率分别为95.4%,82.3%和57.5%。set1和sen在福氏志贺菌的携带率明显高于宋内志贺菌。结论:近8年北京市志贺菌菌型发生了显著变化,宋内志贺菌正逐步成为主导菌型。毒力相关基因在不同菌型的分布存在差异。     

Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella flexneri 2a

Development of a subunit vaccine for shigellosis requires identification of protective antigens and delivering these antigens in a manner that stimulates immunity comparable to that induced by natural infection. The Shigella invasin complex (Invaplex) vaccine is an ion-exchange-purified extract from virulent Shigella that consists of LPS and several other proteins, including the invasins IpaB and IpaC. Intranasal delivery of Invaplex stimulates protective immunity in small animal models for shigellosis. To identify the active component(s) of Invaplex responsible for its immunogenicity and efficacy, size-exclusion chromatography (SEC) was used to separate Invaplex into several different fractions. A high-molecular mass complex with a molecular mass between 669 MDa and 2 MDa consisted primarily of LPS, IpaB and IpaC and was considered to be a highly purified (HP) form of Invaplex. Using the mouse lung model to evaluate the immunogenicity and efficacy of the SEC fractions it was clearly demonstrated that the high-molecular mass complex of the invasins and LPS was responsible for the protective capacity of parent native Invaplex. Other smaller mass SEC fractions were mostly non-immunogenic and did not stimulate solid protection. In guinea pigs, the HP Invaplex stimulated an enhanced immune response as compared to the parent Invaplex and was fully protective. Isolation and characterization of the immunogenic and protective moiety within Invaplex will allow better standardization of the Invaplex product and may allow future development of an Invaplex assembled from purified components.     

Shifting dominance of Shigella species in men who have sex with men

SUMMARY Historically, Shigella sonnei has dominated other Shigella species infection in men who have sex with men (MSM) in Montréal. In early 2010, Toronto reported increased proportions of the more pathogenic S. flexneri, HIV co-infection and MSM in shigellosis cases since 2009. Analytical methods were used to assess whether S. flexneri had dominated Montréal's MSM cases since 2009 and whether changes had occurred in notifications in MSM and HIV-co-infected MSM. S. flexneri increased by 6·7% per month since 2007 and predominated in MSM since 2009 without changes in HIV co-infection or similar shifts in the general population. The results suggest that the surveillance of Shigella species in order to detect species shifts is beneficial for surveillance, given the potential for increased transmission and severity of S. flexneri in HIV-positive MSM.     

Treatment of severe bacillary dysentery with trimethoprim alone

Trimethoprim (300 mg twice daily for five days) and co-trimoxazole (two tablets twice daily for five days) were compared as treatment for adult patients with severe shigellosis in Rwanda. Excellent bacteriological and clinical results were obtained with both regimens, with the exception of patients infected with a trimethoprim-resistant strain of Shigella dysenteriae type 1. Since only 20 patients were investigated, the conclusions of our study do not reach statistical significance. Before recommending trimethoprim as standard therapy for shigellosis, the validity of our results should be tested in a larger trial and the long-term ecological consequences of monotherapy carefully monitored.     

Decrease in shigellosis-related deaths without Shigella spp.-specific interventions, Asia

In 1999, a review of the literature for 1966-1997 suggested that ≈1.1 million persons die annually of shigellosis, including ≈880,000 in Asia. Our recent review of the literature for 1990-2009 indicates that ≈125 million shigellosis cases occur annually in Asia, of which ≈14,000 are fatal. This estimate for illnesses is similar to the earlier estimate, but the number of deaths is 98% lower; that is, the lower estimate of deaths is associated with markedly reduced case-fatality rates rather than fewer cases. Shigella spp.-related deaths decreased substantially during a period without Shigella spp.-specific interventions. We speculate that nonspecific interventions, e.g., measles vaccination, vitamin A supplementation, and improved nutrition, may have led to the reduced number of shigellosis-related deaths.     

A shigellosis outbreak traced to commercially distributed shredded lettuce

In the period August 30-October 7, 1986, 347 persons in adjacent west Texas counties (Ector and Midland) contracted culture-confirmed Shigella sonnei gastroenteritis. A case-control study showed an increased risk of acquiring shigellosis in Ector County with eating at outlets of fast-food Restaurant A, and in Midland County with eating at Restaurant B or C. A second case-control study, of persons who had eaten at Ector County outlets of Restaurant A, showed an increased risk of acquiring shigellosis with eating foods containing shredded lettuce and tomatoes, which were served together (odds ratio = 68.8; 95% confidence interval 8.5-293.1). All implicated restaurants received shredded lettuce produced at one lettuce-shredding plant; two implicated restaurants did not receive tomatoes from the lot delivered to other implicated restaurants. The lettuce-shredding plant distributed shredded lettuce and intact lettuce; restaurants that received only intact lettuce were not involved in the outbreak. Investigation at the lettuce-shredding plant suggested that a food handler might have been the source of contamination and that the method of processing might have allowed cross-contamination to occur. In the laboratory, the outbreak strain of S. sonnei multiplied rapidly on shredded lettuce at 22 C and survived on refrigerated shredded lettuce for at least seven days. This outbreak, one of the largest outbreaks of Shigella infections in the United States in the last decade, indicates that a large, geographically widespread shigellosis outbreak can result from contaminated shredded lettuce that is distributed commercially.     

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.     

Prevalence of Shigella species and their antimicrobial resistance patterns in Eastern Nepal

The study was conducted to determine the prevalence of Shigella species and their antimicrobial resistance patterns in eastern Nepal. Stool samples submitted to the diagnostic laboratory of B.P. Koirala Institute of Health Sciences, Nepal, during August 2000-July 2004, were cultured for Shigella species and were confirmed by biochemical and serological tests. Of 53 Shigella species isolated, Shigella dysenteriae type 1 was the most predominant isolate (73.7%), followed by S. flexneri (23%) and S. boydii (4%). The majority (79%) of Shigella species were isolated from children aged less than five years. An overall high resistance was observed for trimethoprim-sulphamethoxazole, ampicillin, nalidixic acid, mecillinam, and ciprofloxacin. There was a statistically significant (p < 0.001) increasing trend in the prevalence of ciprofloxacin resistance in S. dysenteriae type 1. The results suggest reconsideration of the empiric use of these antimicrobial agents for shigellosis. A further study is required to evaluate additional antimicrobial agents.     

Fourteen years of shigellosis in Dhaka: an epidemiological analysis

We examined whether the proportion of Shigellae patients among diarrhoeal cases, the distribution, species, case-fatality rates and hospital visits changed over time in Dhaka. We isolated 19639 Shigella strains from 822812 diarrhoea cases treated at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), between 1969 and 1982. The number of cases increased from 209 (2.5%) in 1969 to 4833 (7.7%) in 1976. Extrapolating from a 4% vigorous systematic sample of ICDDR,B hospital visits shigellosis cases and their proportion among diarrhoea cases increased to more than 9500 (12.0%) in 1981. The prevalence of various shigellae species altered over time. For example: in 1969 Shigella flexneri predominated in 74% of all Shigella cases; in 1973 Shigella dysenteriae accounted for 56%, and in 1981 Shigella flexneri again predominated (75%). More than 20% of all Shigella isolations were from infants: 60% in males and 40% in females. Over 7% of severe cases of Shigella infection referred from the outpatient department and admitted for treatment died. Nearly 40% of all the Shigella deaths were in infants of less than a year old while 49% were in 1-4 year old children. Increasing prevalence of shigellosis appears to be an important cause of diarrhoea in Dhaka especially among children. Areas with poor sanitation and water supply had higher prevalence. However, hospitalized cases represented a fraction of the actual problem. Resistance to antibiotics appears to be increasing and the development of new drugs and preventive methods within economic reach of less developed countries are crucial for reduction of the disease and related deaths.     

Shigellocidal properties of three Nigerian medicinal plants: Ocimum gratissimum, Terminalia avicennoides, and Momordica balsamina

The prevalence of multidrug-resistant shigellae is an important concern in the treatment of shigellosis in many developing countries, and other therapies, including herbal agents, may provide an important alternative to antimicrobial agents. In this study, three Nigerian medicinal plants: Ocimum gratissimum, Terminalia avicennoides, and Momordica balsamina were investigated for their activities against multidrug-resistant Shigella species isolated from patients with bacilliary dysentery in Lagos. Decoctions of O. gratissimum and concoctions of O. gratissimum and T. avicennoides at crude concentration of 3,000 micrograms/mL markedly inhibited the growth of all isolates tested. Zones of inhibition indicating susceptibilities of the organisms varied from 18.3 to 21.5 mm for Shigella dysenteriae, 15.3 to 16.3 mm for S. flexneri, 18.8 to 19.3 mm for S. sonnei, and 16.5 mm for S. boydii. Except S. flexneri, minimum inhibitory concentration and minimum bactericidal concentration revealed a higher shigellocidal property of O. gratissimum/T. avicennoides concoction than other extracts in S. dysenteriae (300-515.6 vs 337.5-1,312.5 micrograms/mL), S. sonnei (309.4-543.8 vs 403.1-1,312.5 micrograms/mL), and S. boydii (243.8-337.5 vs 253-1,312.5 micrograms/mL). O. gratissimum showed a greater shigellocidal effect against the S. flexneri isolates, while extracts of M. balsamina possessed low shigellocidal potential. The results suggest that aqueous extracts of O. gratissimum and T. avicennoides as decoctions and concoctions could be useful in the treatment of shigellosis and should be clinically evaluated specially in Nigerian region.     

Remote sensing,land cover changes,and vector-borne diseases: Use of high spatial resolution satellite imagery to map the risk of occurrence of cutaneous leishmaniasis in Ghardaïa,Algeria

Ghardaïa, central Algeria, experienced a major outbreak of cutaneous leishmaniasis (CL) in 2005. Two Leishmania species occur in this region: Leishmania major (MON-25) and Leishmania killicki (MON-301). The two species are transmitted respectively by the sandflies Phlebotomus papatasi and Phlebotomus sergenti and probably involve rodent reservoirs with different ecologies, suggesting distinct epidemiological patterns and distribution areas.The aims of this study were to establish risk maps for each Leishmania species in Ghardaïa, taking into account the specificities of their vectors and reservoirs biotopes, using land cover and topographical characteristics derived from remote sensing imagery. Using expert and bibliographic knowledge, habitats of vectors and reservoirs were mapped. Hazard maps, defined as areas of presence of both vectors and reservoirs, were then combined with vulnerability maps, defined as areas with human presence, to map the risk of CL occurrence due to each species. The vector habitat maps and risk maps were validated using available entomological data and epidemiological data.The results showed that remote sensing analysis can be used to map and differentiate risk areas for the two species causing CL and identify palm groves and areas bordering the river crossing the city as areas at risk of CL due to L. major, whereas more limited rocky hills on the outskirts of the city are identified as areas at risk of CL due to L. killicki.In the current context of urban development in Ghardaïa, this study provides useful information for the local authorities on the respective risk areas for CL caused by both parasites, in order to take prevention and control measures to prevent future CL outbreaks.     

Shigellosis from swimming in a park pond in Michigan

In July 1989 an outbreak of shigellosis occurred among visitors to a recreational park in Oakland County, MI. An epidemiologic investigation discovered an association between illness and swimming in a pond at the park, especially for those who had put their head underwater. No other factors were epidemiologically incriminated. A total of 65 cases were identified; nine were culture confirmed, all Shigella sonnei. Several water samples evaluated for fecal coliform counts shortly after the outbreak were found satisfactory. Cultures of water samples were negative for Shigella species. Inspection of the park's sewage disposal and toilet facilities found all equipment in proper working condition and no evidence of a sewage contamination event from these potential sources. No other commercial or residential sources of potential sewage contamination existed near the pond. Investigators concluded that Shigella contamination of the pond by a swimmer or swimmers on one or more occasions was a strong possibility. Factors supporting this conclusion included elevated incidence of S. sonnei in the community during the 2 months prior to the outbreak, greater use of the pond, warm water and air temperatures, and inadequate water exchange in the pond. This report adds one of the few documented outbreaks of shigellosis implicating bather contamination to the literature on the growing number of incidents that have been associated with recreational use of water.     

An outbreak of diarrhoeal disease attributed to Shigella sonnei.

An outbreak of gastroenteritis occurred in a village on the Island of Crete, with 1479 inhabitants. One hundred and thirty-eight symptomatic patients from 57 different families were examined. Thirty percent of children under 12 years were affected compared with 4% of adolescents and adults (P < 0.0001). Thirty-five out of 105 stool cultures (33%) grew Shigella sonnei. Thirty-four isolates had the same susceptibility pattern and were sensitive to ampicillin, while one was resistant to this antibiotic. Thirty-three isolates had the same plasmid profile. Based on epidemiologic and environmental findings, it was concluded that the transmission of shigellosis was waterborne. Shigella were not isolated from water, but one of the three village springs was found to be contaminated with faecal coliforms. This spring was probably contaminated by sewage material, due to its proximity to a source of untreated sewage effluent. Implementation of environmental and control measures brought the epidemic to an end.