In silico design of a vaccine candidate based on autotransporters and HSP against the causal agent of shigellosis, Shigella flexneri.

Shigellosis is a diarrheal disease that causes high mortality every year, especially in children, elderly and immunocompromised patients. Recently, resistance strains to antibiotic therapy are in the rise and the World Health Organization prioritizes the development of a safe vaccine against the most common causal agent of shigellosis, Shigella flexneri. This pathogen uses autotransporter proteins such as SigA, Pic and Sap to increase virulence and some of them have been described as highly immunogenic proteins. In this study, we used immune-informatics analysis to identify the most antigenic epitope as a vaccine candidate on three passenger domains of auto-transporter proteins encoded on the pathogenic island SHI-1, to induce immunity against S. flexneri. Epitope identification was done using various servers such as Bepipred, Bcepred, nHLAPRED, NetMHCII, Rankpep and IEDB and the final selection was done based on its antigenicity using the VaxiJen server. Moreover, to enhance immunity, the GroEL adjuvant was added to the final construct as a Toll-like receptor 2 (TLR2) agonist. On the other hand, to predict the tertiary structure, the I-TASSER server was used, and the best model was structurally validated using the ProSA-web software and the Ramachandran plot. Subsequently, the model was refined and used for docking and molecular dynamics analyses with TLR2, which demonstrated an appropriate and stable interaction. In summary, a potential subunit vaccine candidate, that contains B and T cell epitopes with proper physicochemical properties was designed. This multiepitope vaccine is expected to elicit robust humoral and cellular immune responses and vest protective immunity against S. flexneri.

Management of acute infectious diarrhea for children living in resource-limited settings.

Acute infectious gastroenteritis continues to be a leading cause of morbidity and mortality in children below 5 years of age, with the majority of deaths concentrated in 35 'low income' countries. In these countries the under five years of age mortality rates reach 100 per 1000 live births, of which a significant proportion are associated with acute diarrhea. Rotavirus, cryptosporidium, Shigella spp and enterotoxigenic Escherichia coli are the main pathogens causing disease in these settings, although other bacteria and parasites can cause moderate to severe disease in different regions and situations. Treatment of children in these setting should be focused on appropriate rehydration, early hospitalization of severely malnourished children, zinc supplementation, and in specific situations, antimicrobials should be considered. The rationale for antimicrobial use should be based on the potential benefits based on published literature and the opportunity for use. This review provides a pathogen-specific update on the potential benefits of antimicrobials and suggests an empirical management approach for children suffering an acute watery or bloody diarrhea in a resource-limited region.

Epidemiological study of shigellosis in an urban area of Argentina.

INTRODUCTION: Shigellosis represents one of the main causes of bloody diarrhoea in South America. This study aimed to establish the incidence of shigellosis in an urban zone of Buenos Aires, Argentina, by examining the type of Shigella and living conditions associated with this infection. METHODOLOGY: Between January 2009 and December 2010 we analyzed shigellosis in children admitted to the public health service with bloody diarrhoea from La Plata, the capital of Buenos Aires, Argentina. A total of 372 children under 15 years old with Shigella present in their stool samples were admitted to the study. Variables studied were patient age, type of Shigella, family economic status, and access to sewage services and safe drinking water. RESULTS: Shigella flexneri was found to be present in 66.8% of the cases. Incidence was 187 cases/year/100,000 children under 15 years old. Cases were mainly observed during the summer (38.5%) in the population of under 5 years old (69.1% of all cases). The risk of shigellosis increased 12 times in those children who lacked safe drinking water and this risk increased 1.5 times in the population without sewage services. Fewer cases of shigellosis were noted in downtown areas, while hot spots were identified in the suburbs. Treating one case of shigellosis has a local cost of US $976 while assuring safe drinking water and sewage services for one family costs US $634.  CONCLUSION: Incidence of shigellosis in urban areas is associated with quality of water and sewage services. Policies aimed at providing education and improving public utilities networks can help to reduce the incidence of shigellosis.

Shigelosis en niños, susceptibilidad in vitro / Shigelosis in children, susceptibility in vitro

Para identificar la susceptibilidad in vitro de la Shigella al ácido nalidixico, amikacina, chloranfenicol, cotrimoxazol, furazolidona, defixima, cefotaxima y ceftriaxona, y evaluar la respuesta clínica al tratamiento antimicrobiano, se realizó un estudio entre enero y noviembre del año 2005 en el Hospital Belén de Trujillo, en niños menos de 14 años con cuadro clínico de diarrea disentérica y en quienes se asló Shigella sp.. El 100% de las cepas aisladas mostró buena sensibilidad in vitro a amikacina, cefotaxima, cefixima y ceftriaxona, el 96% fue sensible a ciprofloxacina; cotrimoxasol mostró una resistencia alta (64%) y ácido nalidixico muestra resistencia en 20% de las cepas. La evolución clínica fue buena en el 100% de pacientes entre las 24 y 72 horas después de iniciado el tratamiento, a pesar que una cepa mostró resistencia in vitro a ciprofloxacina. Conclusión: Shiguella es sensible in vitro y clínicamente a ciprofloxacina, amikacina y cefalosporinas de tercera y cuarta generación, sin embargo muestra alta resistencia a cotrimoxasol y resistencia moderada a furazolidona y cloranfenicol.

To identify the susceptibility in vitro of Shigella to the nalidixic acid, amikacin, chloranfenicol, cotrimoxazol, furazolidon, cefixim, cefotaxim, and ceftriaxon, and test the clinical reaction to the anti-microbe treatment, a study has been conducted in Belen Hospital of Trujillo between the months of Junuary and November 2005. The sample has been taken to children under 14 years old with a clinical scheme that involved dysenteric diarrhea , and on whom Shigella sp had been found. The 100% of the isolated samples presented high sensitivity in vitro to amikacin, cefotaxim, cefixim, ceftriaxon and 96% to ciprofloxacin; while cotrimoxasol was highly resistant (64%), and the nalidixic acid showed a resistance on 20% of the samples. In 100% of the patients the clinical evolution was satisfactory between 24 and 72 hours after the treatment was started, even though one of the samples presented resistance in vitro to ciprofloxacin. % of the isolated samples. Conclusion: Shiguella is sensible in vitro and clinically to ciprofloxacin, amikacin and cefalosporins of third generation, nevertheless it presents high resistance to cotrimoxasol y furazolidon.

Shigella and Shiga toxin-producing Escherichia coli causing bloody diarrhea in Latin America.

In Latin America, Shigella and shiga toxin-producing Escherichia coli are the two leading agents in the cause of bloody diarrhea. The already high and increasing antimicrobial resistance of Shigella also is a significant problem. Shiga toxin-producing E. coli is an emerging disease with life-threatening complications: hemolytic uremic syndrome. Although E. coli O157:H7 remains the most commonly recognized serotype, recently emerging, non-O157 bacteria may be the cause of a similar spectrum of disease in humans.

Shiguelose: diagnóstico e tratamento / Shiguellosis: diagnosis and therapy

É uma doença diarréica aguda infecciosa mundialmente distribuída, causada por um bacilo gram-negativo da família das enterobactérias, transmitido por contato inter-humano, por água e alimentos contaminados, causando diarréia mucopiossanguinolenta, associada à febre, cólicas abdominais, urgência e tenesmo retal. O diagnóstico é baseado na história clínica e exame físico, sendo confirmado principalmente pela coprocultura e, mais raramente, pela hemocultura. Outros exames inespecíficos podem ser usados, como o hemograma e a análise do mucofecal. A sorologia e o PCR podem ser úteis, porém nem sempre facilmente disponíveis. O tratamento visa a correçÝo dos distúrbios hidroeletrolíticos já que a shiguelose costuma ser autolimitada, sendo porém, eventualmente necessário o uso de antimicrobianos. Quando a shiguela isolada se mostra sensível à ampicilina, esta droga tem sido utilizada como primeira escolha; entretanto, nÝo se isolando o agente causal, o sulfametoxazoltrimethopim pode ser indicado. atualmente, os melhores resultados (e com baixos ídices de resistência) têm sido obtidos com o uso das quinolonas, devendo, porém, ser usadas com critério devido ao aparecimento de cepas multirresistentes.

Diarreia causada por Shigella: aspectos clinicos e terapeuticos / Diarrhea caused by Shigella: clinical and therapeutical aspects

Os autores estudaram diarreias graves causadas por Shigella sp que foram atendidas no Servico de Emergencias do Hospital Universtario da USP durante tres anos. Esse agente foi isolado de 65 casos de diarreia aguda que corresponderam a 3,1 por cento dos casos graves e 22,3 por cento dos quadros clinicos de disenteria. A S.flexneri foi a mais isolada, seguida pela S.sonnei, na proporcao de 3:1...

Vacunación contra la shigelosis / Vaccination against shigelosis

Se define como shigelosis a la enfermedad intestinal producida por las diferentes especies del género Shigella, de las cuales el humano es el principal hospedero. Shigella es un bacilo corto, Gram-negativo, de la familia Enterobacteriaceae. La shigelosis se manifiesta en tres formas: 1) disentería clásica (sangre, moco, pus), 2) diarrea acuosa no complicada y 3) una combinación de disentería y diarrea acuosa. La mayoría de los casos de diarrea acuosa no son distinguibles de las que son ocacionadas por otras etiologías. Concluye el documento enfatizando que, no existe hasta el momento actual ninguna vacuna contra Shigella que pueda ser recomendable para la aplicación en población general. Todos los esfuerzos hasta ahora realizados han quedado en pequeños estudios en voluntarios, en los cuales se han obtenido fracasos y en otros ensayos se han vislumbrado posibles vacunas para emplear en el futuro. Dentro de los modelos experimentales de vacunas que hasta el momento hay, se está intentando corregir los posibles errores y por otra parte conjuntar los mecanismos de acción propuestos para cada tipo de vacuna. Finalmente si la shigelosis es un problema de salud pública, principalmente en los países en vías de desarrollo, son importantes los esfuerzos para lograr obtener una vacuna que en lo futuro pueda reducir uno de los principales problemas de morbilidad infantil

Megacolon tóxico por Shigella: aporte de un nuevo caso / Toxic megacolon due to Shigella: a report of a new case

A new case of Shigella-caused megacolon is described in detailed form. Some considerations are made about frequency, pathology, clinic and prognostic features

Megacolon tóxico por Shigella: aporte de un nuevo caso / Toxic megacolon due to Shigella: a report of a new case

A new case of Shigella-caused megacolon is described in detailed form. Some considerations are made about frequency, pathology, clinic and prognostic features (Au)

[Toxic megacolon due to Shigella: a report of a new case]. / Megacolon tóxico por Shigella: aporte de un nuevo caso.

A new case of Shigella-caused megacolon is described in detailed form. Some considerations are made about frequency, pathology, clinic and prognostic features.

Shigella dysenteriae type 1 infections in US travellers to Mexico, 1988.

In 1988, the number of Shigella dysenteriae type 1 (Sd1) infections reported in the USA increased five-fold over the annual mean from the previous decade. 44 (94%) of 47 interviewed patients reported recent travel to Mexico; 33 (75%) of these had been tourists to the Yucatan peninsula. 27 patients who had travelled to Mexico were admitted to hospital, of whom 2 had a haemolytic uraemic syndrome; none died. The antimicrobial resistance pattern and plasmid profile of the Yucatan strain were similar to those of the 1969-72 pandemic strain. Antimicrobial resistances and plasmid profiles were different in sporadic Western hemisphere strains. This is the first outbreak of Sd1 among US tourists and it is the largest known outbreak in the Western hemisphere since the early 1970s. The dominant Sd1 strain is similar to that which caused the catastrophic 1969-72 pandemic. Surveillance and control measures have been instituted in the Yucatan peninsula.

Anticytotoxin-neutralizing antibodies in immune globulin preparations: potential use in hemolytic-uremic syndrome.

The pathogenesis of primary (classic) hemolytic-uremic syndrome (HUS) is thought to be related to cytotoxin-producing enteric pathogens such as Shigella dysenteriae serotype 1 and Escherichia coli serotypes O157:H7 and 026:H11. The relevant cytotoxins include Shiga toxin and the closely related Shiga-like toxins (SLTs) produced by some E. coli strains. Intravenously administered immune globulin (IVIG) therapy has been reported to be beneficial in a few children with HUS. We therefore examined commercially available immune globulin preparations for the presence of anticytotoxin-neutralizing antibodies. Cytotoxicity and neutralization of the HUS-associated cytotoxins were quantitatively determined by means of a (3H)thymidine-labeled HeLa cell assay. The immune globulin preparations tested almost completely neutralized Shiga toxin (produced by S. dysenteriae 1) and SLT-I (produced by E. coli serotype 026:H11). Twofold dilutions of the preparations showed significant (p less than 0.01) neutralizing titers of 1:64 to 1:128. No significant neutralization (greater than 20%) of SLT-II (produced by E. coli strain C600 (933W] was noted. The IVIG preparation lost its inhibitory activity when passed through a protein A-Sepharose column, which bound immune globulin, indicating that its neutralizing effect is related to the antibody content. We also examined sera from 30 children without diarrhea or HUS; only one child had neutralizing titers against Shiga toxin (1:64) and SLT-I (1:128). Immune globulin preparations contain anticytotoxin-neutralizing antibodies, a finding that warrants further investigation of the therapeutic role of these preparations in early treatment of children with HUS related to Shiga toxin and SLT-I.