Safety and immunogenicity of a 4-component GMMA-based Shigella vaccine in healthy European adults: Stage 1 of a randomized, controlled phase I/II clinical trial.

BACKGROUND: We report data from Stage 1 of an ongoing two-staged, phase I/II randomized clinical trial (NCT05073003) with a 4-component Generalized Modules for Membrane Antigens-based vaccine against Shigella sonnei and S. flexneri 1b, 2a and 3a (altSonflex1-2-3, GSK). METHODS: 18-50-year-old Europeans (N=102) were randomized (2:1) to receive two injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at pre-specified timepoints. RESULTS: The most common solicited administration-site event (until 7 days post-each injection) and unsolicited adverse event (until 28 days post-each injection) were pain (altSonflex1-2-3: 97.1%; Placebo: 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14-28 days post-injection 1 and remained substantially higher than pre-vaccination at 3 or 6 months post-vaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (ELISA: post-injection 1: 91.0%; post-injection 2 [Day {D}113; D197]: 100%; 97.0%; serum bactericidal activity (SBA): post-injection 1: 94.4%; post-injection 2: 85.7%; 88.9%) followed by S. sonnei (ELISA: post-injection 1: 77.6%; post-injection 2: 84.6%; 78.8%; SBA: post-injection 1: 83.3%; post-injection 2: 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a. CONCLUSIONS: No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population.

What is the context? Shigella bacteria cause severe and often bloody diarrhea, called shigellosis, that affects mostly young children and can be life-threatening. Shigellosis is particularly common in low- and middle-income countries due to inadequate sanitation and limited access to healthcare. Since the immune response to Shigella is serotype-specific, an ideal vaccine should include multiple Shigella serotypes to ensure broad protection. What is new? We developed a novel vaccine against Shigella that includes Shigella sonnei and three prevalent Shigella flexneri serotypes. In Stage 1 (phase I) of the study, healthy European adults received two vaccine injections given 3 or 6 months apart. We found that: The vaccine was well tolerated, and no safety signals or concerns were identified.Regardless of the interval between injections, specific antibodies were elicited against all four Shigella serotypes, with highest levels against Shigella flexneri 2a and Shigella sonnei.Functional antibody levels peaked after the first injection, remaining higher than the baseline up to 6 months. A second injection did not boost responses but restored functional antibody levels to those after the first injection. What is the impact? The vaccine can now be tested in Stage 2 (phase II) of the study in Africa, a region highly affected by shigellosis.

Modulating the antibacterial effect of the existing antibiotics along with repurposing drug metformin.

Owing to the extensive prevalence of resistant bacteria to numerous antibiotic classes, antimicrobial resistance (AMR) poses a well-known hazard to world health. As an alternate approach in the field of antimicrobial drug discovery, repurposing the available medications which are also called antibiotic resistance breakers has been pursued for the treatment of infections with antimicrobial resistance pathogens. In this study, we used Haloperidol, Metformin and Hydroxychloroquine as repurposing drugs in in vitro (Antibacterial Antibiotic Sensitivity Test and Minimum Inhibitory Concentration-MIC) and in vivo (Shigellosis in Swiss albino mice) tests in combination with traditional antibiotics (Oxytetracycline, Erythromycin, Doxycycline, Gentamicin, Ampicillin, Chloramphenicol, and Penicillin) against a group of AMR resistance bacteria (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Shigella boydii). After observing the results of the conducted in vitro experiments we studied the effects of the above non antibiotic drugs in combination with the said antibiotics. As an repurposing adjuvant antibiotic drug, Metformin exhibited noteworthy activity in almost all in vitro, in vivo and in silico tests (Zone of inhibition for 30 to 43 mm for E.coli in combination with Doxycycline; MIC value decreased 50 µM to 0.781 µM with Doxycycline on S. boydii).In rodents Doxycycline and Metformin showed prominent against Shigellosis in White blood cell count (6.47 ± 0.152 thousand/mm3) and Erythrocyte sedimentation rate (10.5 ± 1.73 mm/hr). Our findings indicated that Metformin and Doxycycline combination has a crucial impact on Shigellosis. The molecular docking study was performed targeting the Acriflavine resistance protein B (AcrB) (PDB ID: 4CDI) and MexA protein (PDB ID: 6IOK) protein with Metformin (met8) drug which showed the highest binding energy with - 6.4 kcal/mol and - 5.5 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period. This study suggest Metformin and other experimented drugs can be used as adjuvants boost up antibiosis but further study is needed to find out the safety and efficacy of this non-antibiotic drug as potent antibiotic adjuvant.

Unlocking the potential of Extensin Signal peptide and Elastin-like polypeptide tag fused to Shigella dysenteriae's IpaDSTxB to improve protein expression and purification in Nicotiana tabacum and Medicagosativa.

Plants are often seen as a potent tool in the recombinant protein production industry. However, unlike bacterial expression, it is not a popular method due to the low yield and difficulty of protein extraction and purification. Therefore, developing a new high efficient and easy to purify platform is crucial. One of the best approaches to make extraction easier is to utilize the Extensin Signal peptide (EXT) to translocate the recombinant protein to the outside of the cell, along with incorporating an Elastin-like polypeptide tag (ELP) to enhance purification and accumulation rates. In this research, we transiently expressed Shigella dysenteriae's IpaDSTxB fused to both NtEXT and ELP in both Nicotiana tabacum and Medicago sativa. Our results demonstrated that N. tabacum, with an average yield of 6.39 ng/µg TSP, outperforms M. sativa, which had an average yield of 3.58 ng/µg TSP. On the other hand, analyzing NtEXT signal peptide indicated that merging EXT to the constructs facilitates translocation of IpaDSTxB to the apoplast by 78.4% and 65.9% in N. tabacum and M. sativa, respectively. Conversely, the mean level for constructs without EXT was below 25% for both plants. Furthermore, investigation into the orientation of ELP showed that merging it to the C-terminal of IpaDSTxB leads to a higher accumulation rate in both N. tabacum and M. sativa by 1.39 and 1.28 times, respectively. It also facilitates purification rate by over 70% in comparison to 20% of the 6His tag. The results show a highly efficient and easy to purify platform for the expression of heterologous proteins in plant.

First report of Shigella sonnei carrying a blaCTX-M-15 sexually transmitted among men who have sex with men.

Epidemiology of shigellosis has drastically changed in recent years due to globalization and sexual risk behaviors. Here, through whole-genome sequencing, we characterized two ESBL-producing Shigella sonnei strains (ShSoBUH1 and ShSoBUH2) carrying a blaCTX-M-15 among men who have sex with men (MSM), who had not recently traveled and presented sexual risk behaviors. Both strains harbored IncB/O/K/Z and IncFII plasmids, which carry aadA1, aadA5, sul1, sul2, dfrA1, dfrA17, mph(A), erm(B), tet(B), qacE and blaCTX-M-15 genes conferring resistance to 2nd and 3rd generation cephalosporins, cotrimoxazole, erythromycin, azithromycin and quinolones. IncFII plasmids containing blaCTX-M-15 from ShSoBUH1 and ShSoBUH2 presented 99,8-99,9% similarity with plasmids from another five CTX-M-15 S. sonnei strains detected in Belgium and Switzerland. A single-nucleotide polymorphism (SNP) analysis determined that the study strains differed by 361 SNPs, belonging to different clusters. To the best of our knowledge, this is the first report describing two extensively drug-resistant (XDR) CTX-M-15 S. sonnei strains in MSM.

Collecting a Sexual History During Shigellosis Case Investigations: Nationwide Practices and an Assessment of Data Quality.

Shigellosis is spread through the fecal-oral route, including sexual activity. The Centers for Disease Control and Prevention recommends collecting a sexual history from people diagnosed with shigellosis to enhance the understanding of its epidemiology and outbreak detection and the design of disease prevention messaging, although individual jurisdictions decide if and how this is done. Moreover, enteric disease interviewers typically receive in-depth general interviewing training, but often not sexual history question training. The goal of this project was to inform national practices around sexual history questions asked during shigellosis interviews by collecting information from U.S. state health agencies and evaluating sexual history data from people diagnosed with shigellosis in Colorado. From November 2021 to January 2022, information on sexual history questions asked of persons with reported shigellosis and accompanying training resources were collected from U.S. state health departments. Data completeness and quality of shigellosis sexual history questions from Colorado's notifiable disease database from 2018 to 2022 were also evaluated. Of 48 states, 54% reported routinely asking all adults about their sexual history during shigellosis interviews. Of 44 states, 18% indicated having accompanying training materials for interviewers. In Colorado, the proportion of unknown/missing responses to questions about recent sexual contact with male and female partners was lower for males (3.3% unknown and 3.3% missing) than females (5.4% and 6.2%) and highest among those 66 years and older (6.7% and 10%). Among those reporting new sexual partners, 93.5% indicated how they met. The evaluation of Colorado data demonstrates that routine collection of complete, high-quality, actionable sexual history data from all adults with reported shigellosis is feasible. Nearly half of the responding states indicated not doing so, and few had training resources. We recommend training enteric disease interviewers to routinely ask all adults with reported shigellosis about their sexual history, including new partner meeting location.

Shigella Vaccines: The Continuing Unmet Challenge.

Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality in low-income regions; however, it is not confined to these regions and occurs in high-income nations when conditions allow. The ill effects of shigellosis are at their highest in children ages 2 to 5, with survivors often exhibiting impaired growth due to infection-induced malnutrition. The escalating threat of antibiotic resistance further amplifies shigellosis as a serious public health concern. This review explores Shigella pathology, with a primary focus on the status of Shigella vaccine candidates. These candidates include killed whole-cells, live attenuated organisms, LPS-based, and subunit vaccines. The strengths and weaknesses of each vaccination strategy are considered. The discussion includes potential Shigella immunogens, such as LPS, conserved T3SS proteins, outer membrane proteins, diverse animal models used in Shigella vaccine research, and innovative vaccine development approaches. Additionally, this review addresses ongoing challenges that necessitate action toward advancing effective Shigella prevention and control measures.

Risk Factors of Seizure in Childhood Shigellosis.

Objectives: Shigellosis is one of the common causes of bacterial diarrhea in children. Seizures are common in shigellosis. It is essential to identify the risk factors of seizure in this disease. Materials & Methods: This study was conducted on 224 children with shigellosis. The patients were divided into: With (case groups = 63 cases) and without seizures (control group = 161 cases). Groups were compared regarding different variables such as age, gender, clinical symptoms, and laboratory findings. Data analysis was done using statistical tests and SPSS software. Logistic regression analysis was used to determine the risk factors of seizures. Results: Out of 224 cases of children with shigellosis, 107 (47.8%) were male and 117 (52.2%) female. Significant differences were observed between the two groups in terms of age, history of febrile convulsions, frequency of bloody diarrhea, frequency of fever, duration of diarrhea before hospitalization, abdominal pain, increase in BUN, hyponatremia, hypocalcemia, and red blood cell count in stool (P<0.05). Logistic regression analysis showed that a history of febrile seizure, fever, and hyponatremia are the risk factors for seizures in shigellosis. Conclusion: This study concluded that a history of febrile seizure, fever, and hyponatremia are risk factors for seizure in childhood shigellosis, thus rapid diagnosis and treatment of childhood shigellosis with risk factors is very important.

IgG Serum Antibodies to Shigella sonnei Lipopolysaccharide Are Inversely Associated with the Incidence of Culture-Proven S. sonnei Shigellosis in Israeli Children and Adolescents.

BACKGROUND: Shigella is a leading cause of moderate-to-severe diarrhea globally, with young children most affected. The burden of shigellosis drops increasingly with age, inferring the acquisition of natural immunity. We tested the hypothesis that IgG antibodies elicited against Shigella O-specific polysaccharide (O-SP) are correlates of age-acquired immunity. OBJECTIVES: We examined levels and determinants of serum IgG to S. sonnei LPS and the association with the incidence of S. sonnei shigellosis in Israeli children and adolescents. METHODS: We analyzed 1096 serum samples from 0- to 19-year-olds collected in 2008-2015 for IgG anti-S. sonnei LPS levels by ELISA. Corresponding age-specific incidences of culture-proven S. sonnei shigellosis from 2008 to 2015 were obtained. We compared ecologically IgG levels, prevalence above a proposed protective threshold, and S. sonnei shigellosis incidence. RESULTS: In a multivariable analysis model, children aged 1-4, 5-14, and 15-19 years were 6.71, 27.68, and 48.62 times more likely to have IgG anti-S. sonnei LPS above the threshold than those aged < 1 year, respectively (p < 0.001). Infants 0-3 months old had relatively high IgG anti-S. sonnei LPS levels of maternal origin that dropped thereafter. Children of low socioeconomic status had a 2.73 times higher likelihood of having IgG anti-S. sonnei LPS above the threshold (p < 0.001). A significant inverse correlation between age-specific IgG anti-S. sonnei LPS levels and S. sonnei shigellosis incidence was observed (Spearman rho= -0.76, p = 0.028). CONCLUSIONS: The study results support anti-S. sonnei LPS antibodies as correlates of protection that can inform Shigella vaccine development.

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Peru.

Background: The Enterics for Global Health (EFGH) Peru site will enroll subjects in a periurban area of the low Amazon rainforest. The political department of Loreto lags behind most of Peru in access to improved sources of water and sanitation, per capita income, children born <2.5 kg, and infant and child mortality. Chronic undernutrition as manifested by linear growth shortfalls is common, but wasting and acute malnutrition are not. Methods: The recruitment of children seeking care for acute diarrheal disease takes place at a geographic cluster of government-based primary care centers in an area where most residents are beneficiaries of free primary healthcare. Results: Rates of diarrheal disease, dysentery, and Shigella are known to be high in the region, with some of the highest rates of disease documented in the literature and little evidence in improvement over the last 2 decades. This study will update estimates of shigellosis by measuring the prevalence of Shigella by polymerase chain reaction and culture in children seeking care and deriving population-based estimates by measuring healthcare seeking at the community level. Conclusions: Immunization has been offered universally against rotavirus in the region since 2009, and in a context where adequate water and sanitation are unlikely to obtain high standards in the near future, control of principal enteropathogens through immunization may be the most feasible way to decrease the high burden of disease in the area in the near future.

Rapid diagnostic tests and loop-mediated isothermal amplification method for the detection of Shigella species: A systematic review and meta-analysis.

We meta-analyzed the diagnostic accuracy of rapid diagnostic tests (dipsticks) and loop-mediated isothermal amplification (LAMP) method to detect Shigella species. We searched MEDLINE, Embase, Web of Science and Google Scholar from inception to 2023 for studies reporting on the performance of Shigella dipstick and LAMP tests compared with culture or polymerase chain reaction (PCR). Our search identified 2618 studies, of which fourteen met the inclusion criteria for the systematic review. Ten studies covering 4056 tests (from twelve countries) were included in the meta-analysis. The overall pooled sensitivity and specificity were 98% (95% CI: 94-100) and 97% (95% CI: 92-99), respectively. Pooled sensitivity and specificity of dipsticks were 95% and 98%, respectively. In contrast, LAMP showed higher pooled sensitivity (100%) and diagnostic odds ratio (431752), but similar specificity (97%). LAMP and dipstick tests exhibited promising performance, suggesting that they could be useful for assisting in the diagnosis of shigellosis.

Evaluation of the prophylactic effect of egg yolk antibody (IgY) produced against the recombinant protein containing IpaD, IpaB, StxB, and VirG proteins from Shigella.

INTRODUCTION: Shigellosis is a gastrointestinal disease causes high morbidity and mortality worldwide, however, there is no anti-Shigella vaccine. The use of antibiotics in shigellosis treatment exacerbates antibiotic resistance. Antibodies, particularly egg yolk antibody (IgY), offer a promising approach to address this challenge. This study aimed to investigate the prophylactic effect of IgY produced against a recombinant chimeric protein containing the immunogens IpaD, IpaB, StxB, and VirG from Shigella. METHODS: The chimeric protein, comprising IpaD, IpaB, StxB, and VirG, was expressed in E. coli BL21 and purified using the Ni-NTA column. Following immunization of chickens, IgY was extracted from egg yolk using the PEG-6000 method and analyzed through SDS-PAGE and ELISA techniques. Subsequently, the prophylactic efficacy of IgY was assessed by challenging of mice with 10 LD50 of S. dysenteriae and administering different concentrations of IgY (1.25, 2.5, 5, and 10 mg/kg) under various time conditions. RESULTS: The recombinant protein, weighing 82 kDa, was purified and confirmed by western blotting. The IgY concentration was determined as 9.5 mg/ml of egg yolk and the purity of the extracted IgY was over 90 %. The results of the ELISA showed that at least 19 ng of pure antibody identified recombinant protein and reacts with it. The challenge test employing IgY and Shigella demonstrated a direct correlation between the survival rate and antibody concentration, with increased concentrations leading to decreased mortality rates. Treatment of mice with 10 mg/kg IgY leads to 80 % survival of the mice against 10 LD50 S. dysenteriae. CONCLUSION: Our findings suggest that IgY may offer therapeutic potential in treating Shigella infections and combating antibiotic resistance.

Investigation of the vaccine potential of an in silico designed FepA peptide vaccine against Shigella flexneri in mice model.

Background: Shigellosis is one of the significant causes of diarrhea in Bangladesh. It is a global health problem; approximately 1.3 million people die yearly from Shigellosis. The current treatment method, using different antibiotics against Shigellosis is ineffective. Moreover, it becomes a worrying situation due to the emergence of antibiotic-resistant pathogenic microbes responsible for these diarrheal diseases. Methodology: Previous immunoinformatics study predicted a potential peptide from the Ferric enterobactin protein (FepA) of Shigella spp. In this study, we have chemically synthesized the FepA peptide. As a highly immunogenic, FepA peptide conjugated with KLH has been tested in mice model with complete and incomplete adjuvants as a vaccine candidate. Results: Immunological analysis showed that all vaccinated mice were immunologically boosted, which was statistically significant (P-value 0.0325) compared to control mice. Immunological analysis for bacterial neutralization test result was also statistically significant (P-value 0.0468), where each ELISA plate was coated with 1 × 107S. flexneri cells. The Challenge test with 1 × 1012S. flexneri cells to each vaccinated and controlled mice showed that 37.5 % of control (non-vaccinated) mice died within seven days after the challenge was given while 100 % of vaccinated mice remained strong and stout. The analyses of the post-challenge weight loss of the mice were also significant (P-value 0.0367) as the weight loss percentage in control mice was much higher than in the vaccinated mice. The pathological and phenotypic appearances of vaccinated mice were also clearly differentiable compared with control mice. Thus all these immunological analysis and pathological appearances directly supported our FepA peptide as a potential immune booster. Conclusion: This study provides evidence that the FepA peptide is a highly immunogenic vaccine candidate against S. flexneri. Therefore, these findings inspire future trials for the evaluation of the suitability of this vaccine candidate against Shigellosis.

Designing a multi-epitope vaccine against Shigella dysenteriae using immuno-informatics approach.

Shigella dysenteriae has been recognized as the second most prevalent pathogen associated with diarrhea that contains blood, contributing to 12.9% of reported cases, and it is additionally responsible for approximately 200,000 deaths each year. Currently, there is no S. dysenteriae licensed vaccine. Multidrug resistance in all Shigella spp. is a growing concern. Current vaccines, such as O-polysaccharide (OPS) conjugates, are in clinical trials but are ineffective in children but protective in adults. Thus, innovative treatments and vaccines are needed to combat antibiotic resistance. In this study, we used immuno-informatics to design a new multiepitope vaccine and identified S. dysenteriae strain SD197's membrane protein targets using in-silico methods. The target protein was prioritized using membrane protein topology analysis to find membrane proteins. B and T-cell epitopes were predicted for vaccine formulation. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, a total of 8 B-cell epitopes, 12 MHC Class I epitopes, and 7 MHC Class II epitopes were identified for the Lipopolysaccharide export system permease protein LptF. Additionally, 17 MHC Class I epitopes and 14 MHC Class II epitopes were predicted for the Lipoprotein-releasing ABC transporter permease subunit LolE. These epitopes were selected and linked via KK, AAY, and GGGS linkers, respectively. To enhance the immunogenic response, RGD (arginine-glycine-aspartate) adjuvant was incorporated into the final vaccine construct. The refined vaccine structure exhibits a Ramachandran score of 91.5% and demonstrates stable interaction with TLR4. Normal Mode Analysis (NMA) reveals low eigenvalues (3.925996e-07), indicating steady and flexible molecular mobility of docked complexes. Codon optimization was carried out in an effective microbial expression system of the Escherichia coli K12 strain using the recombinant plasmid pET-28a (+). Finally, the entire in-silico analysis suggests that the suggested vaccine may induce a significant immune response against S. dysenteriae, making it a promising option for additional experimental trials.

Multidrug-Resistant Shigellosis as a Sexually Transmitted Infection in Advanced HIV: A Case Report.

Shigellosis, a significant public health concern, has increasingly been recognized as a sexually transmitted infection (STI) among men who have sex with men (MSM), particularly in those with HIV. This case report describes a 25-year-old MSM with advanced HIV who presented with recurrent multidrug-resistant (MDR) Shigella flexneri infection despite multiple hospitalizations and antibiotic courses. The patient's high-risk sexual behaviors and suboptimal HIV management likely contributed to recurrent exposure to Shigella and the selection of resistant strains. This case highlights the complex interplay of individual behaviors, immune suppression, antimicrobial resistance, and the healthcare system in the context of this emerging STI. It underscores the importance of optimized HIV care, comprehensive patient education, robust healthcare coordination, and strengthened surveillance to effectively combat MDR shigellosis in vulnerable populations.

Patrones de susceptibilidad antimicrobiana de cepas de Shigella sonnei aisladas durante tres períodos diferentes en la Región Metropolitana, Chile / Antibiotic susceptibility patterns among Shigella sonnei, isolated during three different periods in Región Metropolitana, Chile

Background: Shigella sonnei gastroenteritis improves clinically and microbiologically with antibacterial treatment; however choosing a useful drug is a universal challenge because of in vitro susceptibility of S. sonnei frequently evolves to be resistant. Objective: To evaluate in vitro susceptibility of S. sonnei strains isolated from patients attending at the Chilean Región Metropolitana and to know the evolution that resistant patterns of S. sonnei have experienced. Material: In this study, the antimicrobial susceptibility profile of 277 isolates of Shigella sonnei was compared. The analyzed periods of time were: period I (1995-1997) 85 strains; period II (2004-2006) 92 strains and period III (2008-2009) 100 strains, in Santiago, Chile. The method performed to analyze susceptibility patterns was the disc diffusion (Kirby-Bauer). Results: The strains showed rates of resistance to ampicillin: period I, 85.8%; period II, 53.3%; period III, 100%, trimethoprim/sulfamethoxazole: period I, 50.5%; period, II 46.7%; period III, 100%, chloramphenicol: period I, 36.4%; period II, 12%; period III, 100% and tetracycline: period I, 38.8%; period II, 30.4%; period III, 100%. 98.9% of the strains showed susceptibility to quinolones. Significant differences were observed in patterns of antimicrobial resistance for both individuals and for multidrug resistance (≥ 3 antimicrobials) in the three periods (p < 0.001, χ2 test). Of all resistant strains, 17% were resistant to 1 or 2 antibiotics, while 65.7% showed a pattern of multidrug resistance; 100% of the period III strains presented multidrug resistance. Conclusion: These results showed the temporal resistance dynamics of S. sonnei circulating strains in the Chilean Región Metropolitana. Due to the endemic behavior of shigellosis in Chile, it is urgent to maintain permanent surveillance of antimicrobial resistance profiles to improve both prevention and treatment of shigellosis.

Introducción: La infección entérica producida por Shigella sonnei mejora clínicamente y microbiológicamente con antibioterapia; sin embargo, la elección del antimicrobiano es un problema universal pues la susceptibilidad in vitro de S. sonnei evoluciona frecuentemente hacia la resistencia. Objetivo: Evaluar la susceptibilidad in vitro a antimicrobianos de S. sonnei y conocer la evolución que han experimentado los patrones de resistencia de cepas aisladas de cuadros clínicos en pacientes de la Región Metropolitana, Chile. Material y Métodos: Se comparó el perfil de susceptibilidad a antimicrobianos, de 277 cepas clínicas de S. sonnei aisladas durante tres períodos: período I (1995-1997) 85 cepas; período II (2004-2006) 92 cepas y período III (2008-2009) 100 cepas, en Santiago, Chile. El perfil de susceptibilidad a antimicrobianos se determinó mediante test de difusión en agar. Resultados: Las tasas de resistencia de las cepas en los periodos I, II y III respectivamente fueron: ampicilina: 85,8%; 53,3%; 100%, cotrimoxazol: 50,5%; 46,7%; 100%, cloranfenicol: 36,4%; 12%; 100% y tetraciclina: 38,8%; 30,4%; 100%. El 98,9% de las cepas fue susceptible a quinolonas. Se observó diferencias significativas en los porcentajes de resistencia para antimicrobianos individuales y multi-resistencia (≥ 3 antimicrobianos) en los tres períodos (p < 0,001; Test de χ2). De las cepas resistentes, 17% presentó resistencia a uno ó dos antimicrobianos, 65,7% mostró multi-resistencia antimicrobiana. El 100% de las cepas del período III presentó multi-resistencia. Discusión: Estos resultados evidencian la dinámica temporal de la resistencia en cepas de S. sonnei circulantes en la Región Metropolitana. Dado que en Chile la shigelosis tiene un carácter endémico, es prioritario mantener una vigilancia constante de los perfiles de resistencia a antimicrobianos, para mejorar la prevención y el tratamiento de la shigelosis.

Conocimientos sobre shigellosis y su manejo epidemiológico en personal médico / Knowledges on shigellosis and its epidemiological management in medical staff

Introducción: la Shigella como agente causal de episodios diarreicos con sangre ha sido el germen aislado con mayor frecuencia en los laboratorios clínicos, no obstante, el número de casos reportados por el Sistema de Enfermedades de Declaración Obligatoria es inferior, lo que demuestra un subregistro en su notificación. Objetivos: elevar el nivel de conocimientos de médicos y alumnos internos sobre la shigellosis. Métodos: se realizó un estudio cuasi experimental antes-después, de una intervención educativa sobre la shigellosis y su manejo epidemiológico. La investigación se hizo en los policlínicos comunitarios docentes Marcio Manduley y Nguyen Van Troi en el período de enero a junio de 2008. La muestra quedó conformada por 64 médicos, de ellos 21 eran alumnos internos. Todos expresaron su consentimiento para participar en la investigación. Se aplicó la prueba no paramétrica ji cuadrada con un nivel de significación de p < 0,05. Los datos se expresaron en valores absolutos y relativos. Resultados: antes de la intervención se observó que los conocimientos taxonómicos eran buenos en solo 9 encuestados para el 14,06 por ciento, después de la intervención, el número de personas con buen nivel de conocimientos ascendió hasta el 90,63 por ciento. Se constató que el personal médico tenía escaso nivel de conocimientos sobre los principales síntomas de inicio de la shigellosis. Los encuestados con buenos conocimientos sobre las principales medidas profilácticas para prevenir la enfermedad, aumentaron significativamente después de la intervención e igual comportamiento se observó en relación con el tratamiento idóneo en pacientes con Shigella. Conclusiones: la intervención educativa elevó el nivel de conocimientos en el personal médico sobre Shigella. Es necesario continuar promoviendo e investigando esta temática en el nivel primario de atención y extender un plan de acción no sólo a los hospitales, policlínicos y consultorios sino que...

Introduction: Shigella as causal agent of diarrheic episodes with presence of blood has been the more frequent isolated agent in clinical laboratories; however, the number of cases reported by System of Diseases of Mandatory Statement is lower demonstrating a sub-registry of its notification. Objectives: to confirm the knowledge level of medical staff on the Shigellosis. Methods: a quasi-experimental study was conducted before and after a educational intervention on the Shigellosis and its epidemiological management. Research was made in the "Marcio Manduley" and "Nguyen Van Troi" Teaching and Community polyclinics from January to June, 2008. Sample included 43 physicians and 21 internal students in which the intervention was applied. Information was obtained by application of anonymous questionnaire. Results: before intervention it was possible to verify that taxonomic knowledges were satisfactory in only 9 polled persons for a 14,06 percent, after it, the figure of persons with a good level of knowledges raised to 90,63 percent. Authors confirmed that the medical staff had limited knowledges on the main symptoms of Shigellosis onset. The persons polled with high knowledges on main prophylactic measures to prevent this disease, increase significantly after intervention and a similar behavior was noted in relation to subject on suitable treatment in Shigella patients. Conclusions: educational intervention raised the knowledge level on Shigella in the medical staff. It is necessary to continue promoting and researching this subject matter at primary care level and to extend an action plan not only to hospitals, polyclinics and consulting rooms but also to involve family...

Antimicrobial resistance and PCR-ribotyping of Shigella responsible for foodborne outbreaks occurred in southern Brazil

Little information about Shigella responsible for foodborne shigellosis is available in Brazil. The present study aimed to investigate the antimicrobial resistance and PCR-ribotyping patterns of Shigella isolates responsible for foodborne outbreaks occurred in Rio Grande do Sul State (RS), Southern Brazil in the period between 2003 and 2007. Shigella strains (n=152) were isolated from foods and fecal samples of victims of shigellosis outbreaks investigated by the Surveillance Service. Identification of the strains at specie level indicated that 71.1 percent of them were S. flexneri, 21.5 percent S. sonnei, and 0.7 percent S. dysenteriae. Ten strains (6.7 percent) were identified only as Shigella spp. An increasing occurrence of S. sonnei was observed after 2004. Most of the strains were resistant to streptomycin (88.6 percent), followed by ampicillin (84.6 percent), and sulfamethoxazole/trimethoprim (80.5 percent). Resistant strains belonged to 73 patterns, and pattern A (resistance to ampicillin, sulfamethoxazole/trimethoprim, tetracycline, streptomycin, chloramphenicol, and intermediate resistance to kanamycin) grouped the largest number of isolates (n=36). PCR-ribotyping identified three banding patterns (SH1, SH2, and SH3). SH1 grouped all S. flexneri and SH2 grouped all S. sonnei. The S. dysenteriae strain belonged to group SH3. According to the results, several Shigella isolates shared the same PCR-rybotyping banding pattern and the same resistance profile, suggesting that closely related strains were responsible for the outbreaks. However, other molecular typing methods need to be applied to confirm the clonal relationship of these isolates.

Serotipos y resistencia antimicrobiana de cepas de Shigella flexneri aisladas de niños con diarrea aguda: Relación entre el serotipo y la severidad del episodio / Serotype and antimicrobial resistance of Shigella flexneri strains isolated from children with acute diarrhea: Relationship between serotype and severity of the episode

Se determinó el serotipo, susceptibilidad a los antimicrobianos y la relación de severidad de la infección con el serotipo, a un grupo de 50 cepas de S. flexneri aisladas de niños menores de 5 años con diarrea: 25 niños deshidratados y 25 no deshidratados. Para la tipificación se utilizaron antisueros comerciales y la susceptibilidad a los antimicrobianos se realizó por el método de difusión en disco. Características epidemiológicas y clínicas de los episodios: media de edad 13,32 meses ± 12, clase obrera y marginal 94% (P< 0,05), eutróficos 80% (P<0,05), sangre macroscópica en heces 82% (P< 0,05), vómitos 60% (P> 0,05). El serotipo con mayor frecuencia fue el 2a (40%), seguido por el 3a (24%), 2b (18%), 1a (6%), 6 (4%), 3b (2%), 4a (2%), variante “X” (2%) y variante “Y” (2%). El mayor porcentaje de resistencia se observó a tetraciclina (96%), seguido por ampicilina (94%), cloranfenicol (90%), amoxicilina ácido clavulánico (84%) y trimetoprin-sulfametoxazol (72%). La desnutrición (36%, P< 0,05) y el serotipo 2a (56%, P< 0,05) se observaron con mayor frecuencia en los niños deshidratados, mientras que el serotipo 2b predominó en los no deshidratados (32%, P< 0,05). La prevalencia del serotipo 2a, su asociación con la severidad del episodio y la elevada resistencia a los antibióticos alertan sobre la problemática de la infección por Shigella en el país y refuerza la necesidad de estudios para ajustar pautas en el tratamiento.

Serotype, antimicrobial susceptibility, and severity of the infection according to serotype, were determined in a group of 50 Shigella flexneri strains isolated from children less than 5 years old with diarrhea: 25 children dehydrated and 25 non dehydrated. Commercial antisera were used for serotyping and antimicrobial susceptibility was determined by the disc diffusion method. Clinical and epidemiological characteristics of the episodes: mean age 13.22 ± 12 months; 94% belonged to laborer and marginal classes (P<0.05); 80% eutrophic (P<0.05); 82% macroscopic blood in feces (P<0.05); 60% vomits (P>0.05). The most frequent serotype was 2a (40%), followed by 3a (24%), 2b (18%), 1a (6%), 6 (4%), 3b (2%), 4a (2%), variant “X” (2%) and variant “Y” (2%). The highest resistance percent was found for tetracycline (96%), followed by ampicylline (94%), chloramphenicol (90%), amoxicylline clavulonic acid (84%) and trimetoprim-sulfametoxazol (72%). Malnourishment (32%, P<0.05) and serotype 2a (56%, P<0.05) were seen more frequently in dehydrated children, while serotype 2b predominated in non dehydrated children (32%, P<0.05). Prevalence of serotype 2a and its association with the severity of the episode and high antibiotic resistance alert regarding the problem of Shigella infections in our country and reinforce the need of further studies to adjust treatment norms.