T-independent B-cell effect of agents associated with swine grower-finisher diarrhea.

Swine dysentery, spirochetal colitis, and salmonellosis are production-limiting enteric diseases of global importance to the swine industry. Despite decades of efforts, mitigation of these diseases still relies on antibiotic therapy. A common knowledge gap among the 3 agents is the early B-cell response to infection in pigs. Thus, this study aimed to characterize the porcine B-cell response to Brachyspira hyodysenteriae, Brachyspira hampsonii (virulent and avirulent strains), Brachyspira pilosicoli, and Salmonella Typhimurium, the agents of the syndromes mentioned above. Immortalized porcine B-cell line derived from a crossbred pig with lymphoma were co-incubated for 8 h with each pathogen, as well as E. coli lipopolysaccharide (LPS) and a sham-inoculum (n = 3/treatment). B-cell viability following treatments was evaluated using trypan blue, and the expression levels of B-cell activation-related genes was profiled using reverse transcription quantitative PCR. Only S. Typhimurium and LPS led to increased B-cell mortality. B. pilosicoli downregulated B-lymphocyte antigen (CD19), spleen associated tyrosine Kinase (syk), tyrosine-protein kinase (lyn), and Tumour Necrosis Factor alpha (TNF-α), and elicited no change in immunoglobulin-associated beta (CD79b) and swine leukocyte antigen class II (SLA-DRA) expression levels, when compared to the sham-inoculated group. In contrast, all other treatments significantly upregulated CD79b and stimulated responses in other B-cell downstream genes. These findings suggest that B. pilosicoli does not elicit an immediate T-independent B-cell response, nor does it trigger antigen-presenting mechanisms. All other agents activated at least one trigger within the T-independent pathways, as well as peptide antigen presenting mechanisms. Future research is warranted to verify these findings in vivo.

Hospitalizaciones por diarrea con sangre en un centro pediátrico de referencia en Uruguay / Hospitalizations due to bloody diarrhea in a pediatric reference center in Uruguay / Internações por diarreia sanguinolenta em um centro de referência pediátrica no Uruguai

Introducción: La diarrea con sangre es un motivo frecuente de admisión hospitalaria en niños, con gastroenteritis aguda; en la mayoría de los casos se tratan de infecciones leves y autolimitadas, pero pueden producirse complicaciones graves. Objetivos: Describir la etiología y características clínico- evolutivas de los niños menores de 15 años hospitalizados por diarrea con sangre en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre los años 2012- 2023. Materiales y métodos: Estudio retrospectivo mediante revisión de historias y registros de laboratorio. Variables: demográficas, estado nutricional, hidratación, motivos de hospitalización, ingreso unidades de cuidados intensivos (UCI), enteropatógenos, tratamientos, evolución. Resultados: Se incluyeron 229 niños, mediana de edad de 8 meses; sexo masculino 61%; eutróficos 88%, bien hidratados 55%, con comorbilidades 11%, prematurez 6,5%. El motivo de hospitalización fue diarrea con sangre/disentería sin otro síntoma 45%. Se solicitó coprovirológico/coprocultivo en 98% y detección por técnicas de ácidos nucleicos en materia fecal 5,2%. Se identificó al menos un agente patógeno en 34,3%: Shigella sp. 38%; Salmonella sp. 19,5%; coinfecciones en 12%. Se indicaron antibióticos a 86%; ceftriaxona 62%, azitromicina 35%. Ingresaron a UCI 6,5% (15), presentaron complicaciones 10/14, fallo renal agudo 5 y alteraciones del medio interno 3. La mayoría presentó buena evolución. Conclusiones: La diarrea con sangre/disentería continúa siendo una causa importante de hospitalización afectando en su mayoría a niños sanos menores de 5 años. Los patógenos detectados con mayor frecuencia fueron bacterias principalmente Shigella sp., Salmonella sp. y E coli diarreogénicas. Se reportó alta prescripción de antibióticos, cumpliendo en la mayoría de los casos con las recomendaciones.

Introduction: Bloody diarrhea is a common reason for hospital admission in children with acute gastroenteritis; In most cases these are mild and self-limiting infections, but serious complications can occur. Goals: To describe the etiology and clinical-evolutionary characteristics of children under 15 years of age hospitalized for bloody diarrhea at the Pediatric Hospital, Centro Hospitalario Pereira Rossell between the years 2012-2023. Materials and methods: Retrospective study through review of histories and laboratory records. Variables: demographics, nutritional status, hydration, reason for hospitalization, intensive care unit (ICU) admission, enteropathogens, treatments, evolution. Results: 229 children were included, median age 8 months; male sex 61%; eutrophic 88%, well hydrated 55%, with comorbidities 11%, prematurity 6.5%. The reason for hospitalization was bloody diarrhea/dysentery without other symptoms 45%. Coprovirological/coproculture was requested in 98% and detection by nucleic acid techniques in fecal matter was requested in 5,2%. At least one pathogenic agent was identified in 34,3%: Shigella sp. 38%; Salmonella sp 19,5%; coinfections in 12%. Antibiotics were indicated for 86%; ceftriaxone 62%, azithromycin 35%. Were admitted to the ICU 6,5% (15), 10/14 had complications, 5 had acute kidney failure and 3 had alterations in the internal environment. The majority had a good evolution. Conclusions: Bloody diarrhea/dysentery continues to be an important cause of hospitalization, affecting mostly healthy children under 5 years of age. The most frequently detected pathogens were bacteria, mainly Shigella sp., Salmonella sp. and diarrheagenic E coli. High prescription of antibiotics was reported, complying in most cases with the recommendations.

Introdução: A diarreia com sangue é um motivo comum de internação hospitalar em crianças com gastroenterite aguda; Na maioria dos casos, estas são infecções leves e autolimitadas, mas podem ocorrer complicações graves. Metas: Descrever a etiologia e as características clínico-evolutivas de crianças menores de 15 anos internadas por diarreia sanguinolenta no Hospital Pediátrico Centro Hospitalario Pereira Rossell entre os anos de 2012-2023. Materiais e métodos: Estudo retrospectivo por meio de revisão de histórias e registros laboratoriais. Variáveis: dados demográficos, estado nutricional, hidratação, motivo da internação, internação em unidade de terapia intensiva (UTI), enteropatógenos, tratamentos, evolução. Resultados: foram incluídas 229 crianças, mediana de idade 8 meses; sexo masculino 61%; eutrófico 88%, bem hidratado 55%, com comorbidades 11%, prematuridade 6,5%. O motivo da internação foi diarreia sanguinolenta/disenteria sem outros sintomas 45%. O estudo coprovirologico/coprocultivo foi solicitado em 98% e a detecção por técnicas de ácidos nucleicos em matéria fecal foi solicitada em 5,2%. Pelo menos um agente patogênico foi identificado em 34,3%: Shigella sp. 38%; Salmonella sp. 19,5%; coinfecções em 12%. Os antibióticos foram indicados para 86%; ceftriaxona 62%, azitromicina 35%. Foram internados em UTI 6,5% (15), 10/14 apresentaram complicações, 5 tiveram insuficiência renal aguda e 3 apresentaram alterações no meio interno, a maioria teve boa evolução. Conclusões: A diarreia/disenteria com sangue continua a ser uma causa importante de hospitalização, afetando sobretudo crianças saudáveis ​​com menos de 5 anos de idade. Os patógenos mais frequentemente detectados foram bactérias, principalmente Shigella sp., Salmonella sp. e E. coli diarreiogênica. Foi relatada elevada prescrição de antibióticos, cumprindo na maioria dos casos as recomendações.

Synergic Effect of Brachyspira hyodysenteriae and Lawsonia intracellularis Coinfection: Anatomopathological and Microbiome Evaluation.

Brachyspira hyodysenteriae and Lawsonia intracellularis coinfection has been observed in the diagnostic routine; however, no studies have evaluated their interaction. This study aimed to characterize lesions and possible synergisms in experimentally infected pigs. Four groups of piglets, coinfection (CO), B. hyodysenteriae (BRA), L. intracellularis (LAW), and negative control (NEG), were used. Clinical signals were evaluated, and fecal samples were collected for qPCR. At 21 days post infection (dpi), all animals were euthanized. Gross lesions, bacterial isolation, histopathology, immunohistochemistry, and fecal microbiome analyses were performed. Diarrhea started at 12 dpi, affecting 11/12 pigs in the CO group and 5/11 pigs in the BRA group. Histopathological lesions were significantly more severe in the CO than the other groups. B. hyodysenteriae was isolated from 11/12 pigs in CO and 5/11 BRA groups. Pigs started shedding L. intracellularis at 3 dpi, and all inoculated pigs tested positive on day 21. A total of 10/12 CO and 7/11 BRA animals tested positive for B. hyodysenteriae by qPCR. A relatively low abundance of microbiota was observed in the CO group. Clinical signs and macroscopic and microscopic lesions were significantly more severe in the CO group compared to the other groups. The presence of L. intracellularis in the CO group increased the severity of swine dysentery.

Temporal-Spatial Distribution of Vibrio cholerae in Cuba: July 1997-December 2019.

INTRODUCTION: Vibrio cholerae is a microorganism that causes acute diarrheal diseases and cholera, one of the leading causes of global morbidity and mortality, especially in children under five years old. It is present in many regions and has been isolated from diverse sources such as water, soil and food. Surveillance of this microorganism in Cuba from 1985 through June 1997 showed circulation of non-epidemic non-O1/non-O139 serogroups, but surveillance continued to identify distribution of V. cholerae serotypes and serogroups in the different geographic regions of the country during the following years, due to the risk of introducing cholera-causing serogroups that provoked cholera epidemics in other countries of the region. OBJECTIVE: Describe the temporal‒spatial distribution of serogroups and serotypes of V. cholerae in Cuba. METHODS: A cross-sectional study was conducted that included isolates from passive surveillance of V. cholerae in 16 hygiene and epidemiology centers throughout Cuba from July 1997 through December 2019, submitted to the National Reference Laboratory for Acute Diarrheal Diseases of the Pedro Kourí Tropical Medicine Institute in Havana, Cuba. The timeline was subdivided into three five-year periods and one eight-year period. The centers submitting isolates were grouped into three geographical regions: western, central and eastern Cuba. A total of 1060 V. cholerae isolates were studied, from the 1438 samples sent from 15 Provincial Hygiene, Epidemiology and Microbiology Centers and the Municipal Hygiene, Epidemiology and Microbiology Center of the Isle of Youth Special Municipality. Genus, species and serotype of all specimens were studied and reviewed in the context of the outbreaks of acute diarrheal diseases reported in the country. RESULTS: All 1060 isolates were confirmed as V. cholerae. In the distribution by time period and region, the highest percentage occurred in the 2012‒2019 period, and the eastern region contributed the most isolates in all periods. Approximately 63.9% (677/1060) were from outbreaks, and in the 2012‒2019 period, the most epidemic-causing isolates came from the western region. Approximately 52.8% (560/1060) were identified as non-O1/non-O139 V. cholerae, and 47.2% (500/1060) as O1 V. cholerae; of these, 96.4% (482/500) corresponded to Ogawa serotype and 3.6% (18/500) to Inaba. Circulation of non-O1/non-O139 V. cholerae occurred throughout the entire period. The O1 serogroup began to circulate in 2012 and continued through 2016; however, since 2017, it has not been identified again. In the western region, there were smaller percentages of isolates of non-O1/non-O139 V. cholerae in all periods, except 2012‒2019. In that period, V. cholerae O1 was identified to a lesser degree in the central region. CONCLUSIONS: Vibrio cholerae circulated in all three Cuban regions during the years studied, with a higher percentage of isolates of the non-O1/non-O139 serogroup, which caused outbreaks or sporadic cases of diarrhea in the eastern region, with the exception of the 2012‒2019 period, when epidemic outbreaks of the O1 serogroup (which causes cholera) occurred in all three regions, with higher percentages in the western region.

Experimental Infection of Pigs with a ST 245 Brachyspira hyodysenteriae Isolated from an Asymptomatic Pig in a Herd with No History of Swine Dysentery.

Swine dysentery (SD) is characterized by a severe mucohemorrhagic colitis caused by infection with Brachyspira species. In infected herds the disease causes considerable financial loss due to mortality, slow growth rates, poor feed conversion, and costs of treatment. B. hyodysenteriae is the most common etiological agent of SD and infection is usually associated with disease. However, isolated reports have described low pathogenic strains of B. hyodysenteriae. The aim of this study was to describe an experimental infection trial using a subclinical B. hyodysenteriae isolated from an animal without clinical signs and from a disease-free herd, to evaluate the pathogenicity and clinical pathological characteristics compared to a highly clinical isolate. Forty-eight 5-week-old pigs were divided into three groups: control, clinical and the subclinical isolates. The first detection/isolation of B. hyodysenteriae in samples of the animals challenged with a known clinical B. hyodysenteriae strain (clinical group) occurred 5th day post inoculation. Considering the whole period of the study, 11/16 animals from this group were qPCR positive in fecal samples, and diarrhea was observed in 10/16 pigs. In the subclinical isolate group, one animal had diarrhea. There were SD large intestine lesions in 3 animals at necropsy and positive B. hyodysenteriae isolation in 7/15 samples of the subclinical group. In the control group, no diarrhea, gross/microscopic lesions, or qPCR positivity were observed. Clinical signs, bacterial isolation, macroscopic and histologic lesions were significantly difference among groups, demonstrating low pathogenicity of the subclinical isolate in susceptible pigs.

Diversity and potential genetic relationships amongst Brazilian Brachyspira hyodysenteriae isolates from cases of swine dysentery.

The aim of this study was to evaluate genetic diversity, distribution, evolution and population structure of Brazilian Brachyspira hyodysenteriae strains isolated from swine. Multilocus Sequence Typing (MLST) analysis using seven housekeeping genes was applied to 46 isolates obtained from outbreaks of swine dysentery that occurred between 2011 and 2015 in the states of Minas Gerais, São Paulo, Mato Grosso, Rio Grande do Sul and Santa Catarina. Historical isolates from Rio Grande do Sul obtained in 1998 were also included in the study. An independent international profile of the global sequences deposited in the B. hyodysenteriae database was used for comparisons with the Brazilian strains. All isolates from 2011 to 2015 were classified into nine sequence type (STs) and divided into four clonal complexes. These findings indicated genetic relationships among the B. hyodysenteriae from different Brazilian states, among historical strains isolated in 1998 and from recent outbreaks, and relatedness with global isolates. Seven STs were unique and, to date, only reported in Brazil.

Laboratory-based surveillance of Shigella spp. from human clinical cases in Colombia, 1997-2018 / Vigilancia por el laboratorio de Shigella spp. aislada de casos clínicos humanos en Colombia, 1997-2018

INTRODUCTION: Shigellosis is endemic in low-and middle-income countries, causing approximately 125 million episodes of diarrhea and leading to approximately 160 .000 deaths annually one-third of which is associated with children. OBJECTIVE: To describe the characteristics and antimicrobial resistance profiles of Shigella species recovered in Colombia from 1997 to 2018. MATERIALS AND METHODS: We received isolates from laboratories in 29 Colombian departments. We serotyped with specific antiserum and determined antimicrobial resistance and minimal inhibitory concentrations for ten antibiotics with Kirby-Bauer tests following the Clinical and Laboratory Standards Institute recommendations. RESULTS: We analyzed 5,251 isolates of Shigella spp., most of them obtained from stools (96.4%); 2,511 (47.8%) were from children under five years of age. The two most common species were S. sonnei (55.1%) and S. flexneri (41.7%). The highest resistance rate was that of tetracycline (88.1%) followed by trimethoprim-sulfamethoxazole (79.3%) and ampicillin (65.5%); 50.8% of isolates were resistant to chloramphenicol, 43.6% to amoxicillin/clavulanic acid, and less than 1% to cefotaxime, ceftazidime, gentamicin, and ciprofloxacin. In S. sonnei, the most common resistance profile corresponded to trimethoprim-sulfamethoxazole (92%) whereas in S. flexneri the most common antibiotic profiles were multidrug resistance. CONCLUSIONS: In Colombia, children under five years are affected by all Shigella species. These findings should guide funders and public health officials to make evidence based decisions for protection and prevention measures. The antimicrobial resistance characteristics found in this study underline the importance of combating the dissemination of the most frequently isolated species, S. sonnei and S. flexneri.

Introducción. La shigelosis es endémica en los países de ingresos bajos y medios y ocasiona aproximadamente 125 millones de episodios de diarrea y 160.000 muertes al año, un tercio de los cuales se presenta en niños. Objetivo. Describir las características y los perfiles de resistencia antimicrobiana en aislamientos de Shigella spp. recuperados en Colombia entre 1997 y 2018. Materiales y métodos. Los aislamientos provenían de laboratorios en 29 departamentos de Colombia. La serotipificación se hizo con antisueros específicos de Shigella spp. y, la determinación de los perfiles de resistencia y la concentración inhibitoria mínima de diez antibióticos, por Kirby-Bauer. Resultados. Se estudiaron 5.251 aislamientos de Shigella spp. obtenidos de materia fecal (96,4 %); el 47,8 % de ellos correspondía a niños menores de cinco años. Las especies más frecuentes fueron S. sonnei (55,1 %) y S. flexneri (41,7 %). Se presentó resistencia a tetraciclina (88,1 %), trimetoprim-sulfametoxasol (79,3 %), ampicilina (65,5 %), cloranfenicol (50,8 %) y amoxicilina-acido clavulánico (43,6 %). La resistencia no superó el 1 % contra cefotaxime, ceftazidima, gentamicina y ciprofloxacina. Para S. sonnei, el perfil de resistencia más frecuente correspondió a trimetoprim-sulfametoxasol, en contraste con S. flexneri, cuyos perfiles fueron todos multirresistentes. Conclusiones. Los niños menores de cinco años se vieron afectados por todas las especies de Shigella spp., aspecto que los legisladores en salud pública deben considerar a la hora de tomar decisiones en torno a las medidas de prevención y protección frente a esta enfermedad. Las características de resistencia antimicrobiana de los aislamientos de Shigella spp. en Colombia ponen de manifiesto la importancia de combatir la diseminación de las dos especies más frecuentes en casos clínicos, S. sonnei y S. flexneri.

Laboratory-based surveillance of Shigella spp. from human clinical cases in Colombia, 1997-2018 / Vigilancia por el laboratorio de Shigella spp. aislada de casos clínicos humanos en Colombia, 1997-2018

Abstract | Introduction: Shigellosis is endemic in low-and middle-income countries, causing approximately 125 million episodes of diarrhea and leading to approximately 160.000 deaths annually one-third of which is associated with children. Objective: To describe the characteristics and antimicrobial resistance profiles of Shigella species recovered in Colombia from 1997 to 2018. Materials and methods: We received isolates from laboratories in 29 Colombian departments. We serotyped with specific antiserum and determined antimicrobial resistance and minimal inhibitory concentrations for ten antibiotics with Kirby-Bauer tests following the Clinical and Laboratory Standards Institute recommendations. Results: We analyzed 5,251 isolates of Shigella spp., most of them obtained from stools (96.4%); 2,511 (47.8%) were from children under five years of age. The two most common species were S. sonnei (55.1%) and S. fbxneri (41.7%). The highest resistance rate was that of tetracycline (88.1%) followed by trimethoprim-sulfamethoxazole (79.3%) and ampicillin (65.5%); 50.8% of isolates were resistant to chloramphenicol, 43.6% to amoxicillin/clavulanic acid, and less than 1% to cefotaxime, ceftazidime, gentamicin, and ciprofloxacin. In S. sonnei, the most common resistance profile corresponded to trimethoprim-sulfamethoxazole (92%) whereas in S. fbxneri the most common antibiotic profiles were multidrug resistance. Conclusions. In Colombia, children under five years are affected by all Shigella species. These findings should guide funders and public health officials to make evidence-based decisions for protection and prevention measures. The antimicrobial resistance characteristics found in this study underline the importance of combating the dissemination of the most frequently isolated species, S. sonnei and S. ftexneri.

Resumen | Introducción. La shigelosis es endémica en los países de ingresos bajos y medios y ocasiona aproximadamente 125 millones de episodios de diarrea y 160.000 muertes al año, un tercio de los cuales se presenta en niños. Objetivo. Describir las características y los perfiles de resistencia antimicrobiana en aislamientos de Shigella spp. recuperados en Colombia entre 1997 y 2018. Materiales y métodos. Los aislamientos provenían de laboratorios en 29 departamentos de Colombia. La serotipificación se hizo con antisueros específicos de Shigella spp. y, la determinación de los perfiles de resistencia y la concentración inhibitoria mínima de diez antibióticos, por Kirby-Bauer. Resultados. Se estudiaron 5.251 aislamientos de Shigella spp. obtenidos de materia fecal (96,4 %); el 47,8 % de ellos correspondía a niños menores de cinco años. Las especies más frecuentes fueron S. sonnei (55,1 %) y S. ftexneri (41,7 %). Se presentó resistencia a tetraciclina (88,1 %), trimetoprim-sulfametoxasol (79,3 %), ampicilina (65,5 %), cloranfenicol (50,8 %) y amoxicilina-acido clavulánico (43,6 %). La resistencia no superó el 1 % contra cefotaxime, ceftazidima, gentamicina y ciprofloxacina. Para S. sonnei, el perfil de resistencia más frecuente correspondió a trimetoprim-sulfametoxasol, en contraste con S. ftexneri, cuyos perfiles fueron todos multirresistentes. Conclusiones. Los niños menores de cinco años se vieron afectados por todas las especies de Shigella spp., aspecto que los legisladores en salud pública deben considerar a la hora de tomar decisiones en torno a las medidas de prevención y protección frente a esta enfermedad. Las características de resistencia antimicrobiana de los aislamientos de Shigella spp. en Colombia ponen de manifiesto la importancia de combatir la diseminación de las dos especies más frecuentes en casos clínicos, S. sonnei y S. ftexneri.

Colitis amebiana necrosante, presentación de un caso / Necrotizing amebian colitis, case report

Resumen Introducción: La Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS) han definido la amebiasis como la infección por Entamoeba histolytica, independientemente de los síntomas. La colitis amebiana necrosante es una forma rara de amebiasis que se asocia con una alta morbilidad y mortalidad. Caso clínico: Presentamos a un paciente femenino de 68 años, con antecedentes de diabetes mellitus tipo 2, con colitis amebiana necrosante con múltiples perforaciones, que fue sometida a una hemicolectomía derecha con íleo-transverso anastomosis. Conclusiones: Se necesitan intervenciones efectivas para prevenir la colitis amebiana y terapias adicionales para tratar la colitis amebiana fulminante y mejorar los resultados.

Abstract Background: Amebiasis has been defined by World Health Organization (WHO) and Pan American Health Organization (PAHO) as the infection with Entamoeba histolytica regardless of symptoms. Necrotizing amoebic colitis is a rare clinical form of amebosis that is associated with high morbidity and mortality. Case Report: We present a 68-years-old-female patient with necrotizing amoebic colitis with multiple perforations who survived after right hemicolectomy with ileus-transverse anastomosis. Conclusions: Effective interventions to prevent amebic colitis, and additional therapies to treat fulminant amebic colitis are needed to improve outcomes.

Intranasal Immunization of Mice with Multiepitope Chimeric Vaccine Candidate Based on Conserved Autotransporters SigA, Pic and Sap, Confers Protection against Shigella flexneri.

Shigellosis is a diarrheal disease and the World Health Organization prompts the development of a vaccine against Shigella flexneri. The autotransporters SigA, Pic and Sap are conserved among Shigella spp. We previously designed an in silico vaccine with immunodominat epitopes from those autotransporters, and the GroEL protein of S. typhi as an adjuvant. Here, we evaluated the immunogenicity and protective efficacy of the chimeric multiepitope protein, named rMESF, in mice against lethal infection with S. flexneri. rMESF was administered to mice alone through the intranasal (i.n.) route or accompanied with Complete Freund's adjuvant (CFA) intradermically (i.d.), subcutaneously (s.c.), and intramuscular (i.m.), as well as with Imject alum (i.m.). All immunized mice increased IgG, IgG1, IgG2a, IgA and fecal IgA titers compared to PBS+CFA and PBS+alum control groups. Furthermore, i.n. immunization of mice with rMESF alone presented the highest titers of serum and fecal IgA. Cytokine levels (IFN-γ, TNF-α, IL-4, and IL-17) and lymphocyte proliferation increased in all experimental groups, with the highest lymphoproliferative response in i.n. mice immunized with rMESF alone, which presented 100% protection against S. flexneri. In summary, this vaccine vests protective immunity and highlights the importance of mucosal immunity activation for the elimination of S. flexneri.

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.

Acute diarrhea with blood: diagnosis and drug treatment / Diarreia aguda com sangue: diagnóstico e tratamento medicamentoso

Abstract Objective To restate the epidemiological importance of Shigella in acute diarrhea with blood, providing an overview of the treatment and stressing the need for the correct indication of antibiotic therapy. Sources of Data A search was carried out in the Medline and Scopus databases, in addition to the World Health Organization scientific documents and guidelines, identifying review articles and original articles considered relevant to substantiate the narrative review. Synthesis of Data Different pathogens have been associated with acute diarrhea with blood; Shigella was the most frequently identified. The manifestations of shigellosis in healthy individuals are usually of moderate intensity and disappear within a few days. There may be progression to overt dysentery with blood and mucus, lower abdominal pain, and tenesmus. Conventional bacterial stool culture is the gold standard for the etiological diagnosis; however, new molecular tests have been developed to allow the physician to initiate targeted antibacterial treatment, addressing a major current concern caused by the increasing resistance of Shigella. Prevention strategies include breastfeeding, hygiene measures, health education, water treatment, and the potential use of vaccines. Conclusions Acute diarrhea is an important cause of mortality in children under 5 years and shigellosis is the leading cause of acute diarrhea with blood worldwide. The current concern is the increase in microbial resistance to the recommended antibiotics, which brings an additional difficulty to therapeutic management. Although no vaccine is yet available against Shigella, several candidates are undergoing clinical trials, and this may be the most cost-effective preventative measure in future.

Resumo Objetivo Reiterar a importância epidemiológica da Shigella na diarreia aguda com sangue, fornecer uma visão geral do tratamento e ressaltar a necessidade da correta indicação da antibioticoterapia. Fontes dos dados Realizada pesquisa nos bancos de dados Medline e Scopus, além de documentos científicos e diretrizes da Organização Mundial da Saúde, com a identificação de artigos de revisão e artigos originais considerados relevantes para fundamentar a revisão do tipo narrativa. Síntese dos dados Diferentes patógenos têm sido associados à diarreia aguda com sangue, a Shigella é o mais frequente. As manifestações da shigelose em indivíduos saudáveis são geralmente de intensidade moderada e desaparecem em poucos dias. Pode haver progressão para disenteria franca com sangue e muco, dor em abdome inferior e tenesmo. A coprocultura bacteriana convencional é o padrão-ouro para o diagnóstico etiológico, porém novos testes moleculares foram desenvolvidos, os quais permitem ao médico iniciar tratamento antibacteriano direcionado, sanar uma grande preocupação atual, devido à crescente resistência da Shigella. Estratégias de prevenção incluem aleitamento, medidas de higiene, educação em saúde, tratamento da água e o potencial uso de vacinas. Conclusões A diarreia aguda é uma importante causa de mortalidade em crianças com menos de cinco anos e a shigelose é a principal causa de diarreia aguda com sangue em todo o mundo. A preocupação atual é o aumento da resistência microbiana aos antibióticos preconizados, o que traz uma dificuldade adicional ao manejo terapêutico. Embora ainda não exista vacina disponível para Shigella, várias candidatas estão em fase de testes clínicos, podem futuramente ser a medida preventiva mais custo-efetiva.

Uso de probióticos en el tratamiento y la prevención de diarrea aguda en niños / Probiotics to prevent and treat acute diarrhea in children / Probióticos para o tratamento e prevenção da diarréia aguda em criancas

Resumen: El principio del uso de probióticos proviene de la utilización de productos fermentados, desde tiempos muy antiguos. Se definen como microorganismos vivos, que administrados en cantidades adecuadas, confieren beneficios para la salud. Entre las utilidades atribuidas a los probióticos, las más extensamente estudiadas han sido los efectos en niños con diarrea aguda. Existe abundante bibliografía sobre la utilización de estos productos en el tratamiento y la prevención de diarrea aguda infecciosa, y prevención de diarrea nosocomial y de diarrea asociada al uso de antibióticos. Los estudios son heterogéneos en su metodología y muestran resultados dispares, incluso contradictorios. En la interpretación de éstos es imprescindible tener en cuenta las cepas de probióticos utilizadas, las dosis administradas y las características de los pacientes en quienes fueron probadas. Existe evidencia del beneficio de algunas cepas de probióticos en el tratamiento y la prevención de diarrea aguda en niños. Varias guías de práctica clínica los recomiendan. En Uruguay existe poca oferta de estos productos, y la información disponible es escasa, lo cual dificulta su prescripción segura. Se revisa en este documento la evidencia científica publicada sobre el uso de probióticos en niños con diarrea aguda.

Summary: Probiotics from fermented products have been used since ancient times. They are living microorganisms, which, at appropriate levels, can provide health benefits. Among the benefits of probiotics, the most broadly studied has been the effect on children with acute diarrhea. There is extensive literature regarding the use of probiotics for the treatment and prevention of acute infectious diarrhea, for the prevention of nosocomial diarrhea and for antibiotic-caused diarrhea. The studies show heterogeneous methodologies and mixed results, even contradictory. For their interpretation, it is essential to take into account the probiotic strains used, the doses administered and the characteristics of the patients tested. There is evidence of the benefit of some probiotics strains in the treatment and prevention of acute diarrhea in children. Several Clinical Practice Guidelines recommend them. In Uruguay, there is little supply of these products, and the information available is scarce, which makes them difficult to prescribe. In the present document, we review the existing published scientific evidence regarding the use of probiotics in children with acute diarrhea.

Resumo: Os probióticos de produtos fermentados têm sido utilizados desde os tempos antigos. São microrganismos vivos que, em níveis adequados, podem proporcionar benefícios à saúde. Entre os benefícios dos probióticos, o mais amplamente estudado tem sido o efeito em crianças com diarréia aguda. Existe extensa literatura sobre o uso de probióticos para o tratamento e prevenção de diarreia infecciosa aguda, para prevenção de diarreia intra-hospitalar e diarreia causada por antibióticos. Os estudos mostram metodologias heterogêneas e resultados mistos, até contraditórios. Para sua interpretação, é essencial levar em consideração as cepas probióticas utilizadas, as doses administradas e as características dos pacientes testados. Há evidências do benefício de algumas cepas de probióticos no tratamento e prevenção de diarreia aguda em crianças. Várias diretrizes de prática clínica as recomendam. No Uruguai, há pouca oferta desses produtos e a informação disponível é escassa, o que dificulta sua prescrição. No presente documento, revisamos as evidências científicas publicadas sobre o uso de probióticos em crianças com diarreia aguda.

Acute diarrhea with blood: diagnosis and drug treatment.

OBJECTIVE: To restate the epidemiological importance of Shigella in acute diarrhea with blood, providing an overview of the treatment and stressing the need for the correct indication of antibiotic therapy. SOURCES OF DATA: A search was carried out in the Medline and Scopus databases, in addition to the World Health Organization scientific documents and guidelines, identifying review articles and original articles considered relevant to substantiate the narrative review. SYNTHESIS OF DATA: Different pathogens have been associated with acute diarrhea with blood; Shigella was the most frequently identified. The manifestations of shigellosis in healthy individuals are usually of moderate intensity and disappear within a few days. There may be progression to overt dysentery with blood and mucus, lower abdominal pain, and tenesmus. Conventional bacterial stool culture is the gold standard for the etiological diagnosis; however, new molecular tests have been developed to allow the physician to initiate targeted antibacterial treatment, addressing a major current concern caused by the increasing resistance of Shigella. Prevention strategies include breastfeeding, hygiene measures, health education, water treatment, and the potential use of vaccines. CONCLUSIONS: Acute diarrhea is an important cause of mortality in children under 5 years and shigellosis is the leading cause of acute diarrhea with blood worldwide. The current concern is the increase in microbial resistance to the recommended antibiotics, which brings an additional difficulty to therapeutic management. Although no vaccine is yet available against Shigella, several candidates are undergoing clinical trials, and this may be the most cost-effective preventative measure in future.

Epidemiological characteristics and strategies for the prevention of diarrheal disease in indigenous children: A scoping review.

AIM: The aim of the present scoping review was to map the scientific evidence about diarrheal disease in indigenous children and the strategies that can be used to prevent it. METHODS: The subject headings were indigenous population; child; diarrhea; dysentery; epidemiology; and prevention, primary; also the following keywords characteristic, epidemiologic study; and children. The databases consulted were Latin American and Caribbean Health Sciences Literature, MEDLINE via the US National Library of Medicine/National Institutes of Health, and Web of Science. Initially, 268 studies were identified, and after being screened using the eligibility criteria, six were selected. Finally, via reference tracking, five more were identified. The final sample was made up of eleven articles. RESULTS: The results confirmed higher mortality rates due to diarrheal disease among indigenous children who are socially disadvantaged and living in poor hygienic and basic sanitation conditions. Among the primary prevention strategies are basic sanitation, health education better hygiene habits, animal control, breastfeeding, supplementing the diet with zinc, vitamins, and the rotavirus vaccine. The preventive strategies included the use of oral rehydration solutions, adequate nutrition, prescribed antimicrobials, and intravenous fluid replacement with glycaemic and electrolyte correction in severe cases. CONCLUSION: In conclusion, public policies regarding the indigenous population and cross-cultural care should be strengthened. The present study confirmed that, at a global level, there is a lack of publications studying this issue.

Intestinal amoebiasis: 160 years of its first detection and still remains as a health problem in developing countries.

Amoebiasis is a parasitic disease caused by Entamoeba histolytica (E. histolytica), an extracellular enteric protozoan. This infection mainly affects people from developing countries with limited hygiene conditions, where it is endemic. Infective cysts are transmitted by the fecal-oral route, excysting in the terminal ileum and producing invasive trophozoites (amoebae). E. histolytica mainly lives in the large intestine without causing symptoms; however, possibly as a result of so far unknown signals, the amoebae invade the mucosa and epithelium causing intestinal amoebiasis. E. histolytica possesses different mechanisms of pathogenicity for the adherence to the intestinal epithelium and for degrading extracellular matrix proteins, producing tissue lesions that progress to abscesses and a host acute inflammatory response. Much information has been obtained regarding the virulence factors, metabolism, mechanisms of pathogenicity, and the host immune response against this parasite; in addition, alternative treatments to metronidazole are continually emerging. An accesible and low-cost diagnostic method that can distinguish E. histolytica from the most nonpathogenic amoebae and an effective vaccine are necessary for protecting against amoebiasis. However, research about the disease and its prevention has been a challenge due to the relationship between E. histolytica and the host during the distinct stages of the disease is multifaceted. In this review, we analyze the interaction between the parasite, the human host, and the colon microbiota or pathogenic microorganisms, which together give rise to intestinal amoebiasis.

Balantidiasis colónica: reporte de un caso fatal y revisión de la literatura

La balantidiasis es una zoonosis producida por el Balantidium coli, que habita el intestino grueso del cerdo y del hombre. La infección es infrecuente en humanos y afecta principalmente al colon. Se produce con mayor frecuencia en países en desarrollo, regiones tropicales y subtropicales. La balantidiasis colónica puede presentarse en la mayoría de los casos de forma asintomática y llegar en los casos más graves como diarrea disentérica que puede complicarse con hemorragia digestiva baja e incluso perforación. Presentamos el caso de un varón de 72 años, proveniente de la sierra peruana de ocupación agricultor y criador de ganado porcino y ovino, quién acude por 3 meses de enfermedad caracterizado inicialmente por deposiciones líquidas con moco sin sangre, dolor abdominal cólico, náuseas, vómitos y en el último mes de enfermedad presenta diarrea disentérica. Se ingresa a colonoscopía por sospecha de colitis infecciosa, encontrándose en la muestra en fresco y biopsia de tejido colónico trofozoitos de Balantidium coli. Paciente recibe tratamiento con amebicida y antibacteriano sin mejoría clínica, presentando como complicación múltiples perforaciones en colon sigmoides, tratado con resección y colostomía terminal. Finalmente, paciente fallece a pesar de recibir manejo médico y quirúrgico.

Balantidiasis is a zoonosis produced by Balantidium coli, which inhabits the large intestine of the pig and man. Infection is uncommon in humans and mainly affects the colon. It occurs more frequently in developing countries, tropical and subtropical regions. Colonic balantidiasis can occur in most cases asymptomatically and reach in the most severe cases such as dysenteric diarrhea that can be complicated by low digestive bleeding and even perforation. We present the case of a 72-year-old man, from the Peruvian highlands, who was a farmer and breeder of swine and sheep, who came for 3 months of illness, initially characterized by liquid stools with bloodless mucus, abdominal pain, nausea, vomiting and in the last month of illness he presents dysenteric diarrhea. Colonoscopy was performed due to suspicion of infectious colitis, Balantidium coli trophozoites were found in the fresh sample and colonic tissue biopsy. Patient receives treatment with amebicide and antibacterial without clinical improvement, presenting as a complication multiple perforation in the sigmoid colon, treated with resection and terminal colostomy. Finally, the patient died despite receiving medical and surgical treatment.

Dysentery by CTX-M Type ESBL Producing Shigella flexneri / Disentería por Shigella flexneri productora de BLEE tipo CTX-M

According to the World Health Organization, diarrheal infections cause 525 000 deaths of children under five years of age every year, and shigellosis. Shigellosis is a relevant cause of dysentery, which increases the morbidity and mortality in pediatric patients. Therefore, emergingthe emergence of antimicrobial resistant strains of Shigella is a concerningworrisome problem worldwide. We report the case of a 7-year-old patient with acute dysentery caused by CTX-M Type ESBL Producing Shigella flexneri, being. This was the first case treated in the Specialties Hospital of Specialties of the Armed Forces N°1, in Quito, Ecuador. The antibiogram demonstrated sensibilityshowed sensitivity to ampicillin-sulbactam. As a result, after five days of microbiologically directed treatment, the patient improved his condition without relapse. Proper clinical diagnoses and accurate laboratory studies like stool culture and antibiogram are crucial to givingindicate an appropriate therapy in infections caused by Shigella and other enteric bacilli(AU)

Según la Organización Mundial de la Salud, las infecciones diarreicas provocan 525 000 muertes de niños menores de cinco años de edad cada año. La shigelosis es una causa importante de disentería que aumenta la morbilidad y mortalidad de los pacientes pediátricos. Es por eso que el surgimiento de cepas de Shigella resistentes a los antibióticos es un preocupante problema a nivel mundial. Presentamos el caso de un paciente de 7 años de edad con disentería aguda provocada por Shigella flexneri productora de BLEE tipo CTX-M. Se trata del primer caso tratado en el Hospital de Especialidades de las Fuerzas Armadas Nº 1, en Quito, Ecuador. El antibiograma mostró sensibilidad a la combinación ampicilina/sulbactam. Al cabo de cinco días de tratamiento microbiológico, el paciente mejoró su estado y no se produjeron recaídas. Un diagnóstico clínico correcto, así como estudios precisos de laboratorio como los cultivos de heces y los antibiogramas, son vitales para indicar una terapia apropiada en las infecciones causadas por Shigella y otros bacilos entéricos(AU)

Entamoeba histolytica como causa de diarreia crônica / Entamoeba histolytica as a cause of chronic diarrhea / Entamoeba histolytica como causa de diarrea crónica

A diarreia crônica, caracterizada pela presença de mais de três dejeções de consistência pastosa durante pelo menos quatro semanas, é frequentemente encontrada na prática clínica. Na diarreia crônica, a probabilidade de uma etiologia infecciosa é baixa, sendo as causas funcionais, inflamatórias, osmóticas ou secretórias mais comuns. A amebíase intestinal é uma causa de diarreia crônica, causada pelo protozoário Entamoeba histolytica, sendo comum e prevalente em países em desenvolvimento. Pode ter várias formas de apresentação, sendo na maioria dos casos assintomática. Apresenta-se o caso clínico de um paciente de 27 anos, sexo masculino, raça caucasiana, homem que pratica sexo com homens (HSH), com diarreia crônica com início há cerca de seis anos. O exame objetivo não revelava alterações. Realizou exame parasitológico de fezes, com isolamento de quistos de Entamoeba histolytica. Foi medicado com metronidazol e paromomicina com resolução clínica do quadro. É importante para o Médico de Família equacionar esta etiologia na investigação de pacientes com diarreia, para um correto e atempado diagnóstico e tratamento, de modo a evitar exames desnecessários, possíveis complicações, a transmissão do agente e um grave problema de saúde pública.

Chronic diarrhea, characterized by the presence of more than three loose stools for at least four weeks, is often found in clinical practice. In chronic diarrhea, the probability of an infectious etiology is low, having usually a functional, inflammatory, osmotic or secretory origin. Intestinal amebiasis is a cause of chronic diarrhea, caused by the protozoan Entamoeba histolytica, common and prevalent in developing countries. It can have different presentations but most patients are asymptomatic. We present a 27-year-old Caucasian male, man who have sex with men (MSM), with chronic diarrhea starting six years ago. The physical exam was normal. A parasitological stool examination was performed with isolation of cysts of Entamoeba histolytica. He was treated with metronidazole and paromomycin with clinical resolution. It is important for General Practice to address this etiology in the investigation of patients with diarrhea for a correct and timely diagnosis and treatment, to avoid unnecessary testing, possible complications, transmission of the agent and a serious public health problem.

La diarrea crónica, caracterizada por la presencia de más de tres heces de consistencia blanda durante al menos cuatro semanas, es frecuentemente encontrada en la práctica clínica. En la diarrea crónica, la probabilidad de una etiología infecciosa es baja, siendo las causas funcionales, inflamatorias, osmóticas o secretoras más comunes. La amebiasis intestinal es una causa de diarrea crónica, causada por el protozoario Entamoeba histolytica, siendo común y prevalente en los países en desarrollo. Puede tener varias formas de presentación, siendo en la mayoría de los casos asintomática. Presentamos un paciente de 27 años, sexo masculino, caucásico, hombre que tiene sexo con hombres (HSH), con diarrea crónica con inicio hace cerca de seis años. El examen objetivo no reveló alteraciones. Realizó un examen parasitológico de heces, con aislamiento de quistes de Entamoeba histolytica. Fue medicado con metronidazol y paromomicina con resolución clínica del cuadro. Es importante para el médico de familia considerar esta etiología en la investigación de pacientes con diarrea, para un correcto y oportuno diagnóstico y tratamiento, de modo a evitar, exámenes innecesarios, posibles complicaciones, la transmisión del agente y un grave problema de salud pública.