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.

BACKGROUND: 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.
CONCLUSIONS: Our findings suggest that IgY may offer therapeutic potential in treating Shigella infections and combating antibiotic resistance.

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.

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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.