Acute Shigellosis Research Articles

Pentraxin 3 and Shigella LPS and IpaB Antibodies Interplay to Defeat Shigellosis.

Shigella causes moderate to severe diarrhea or dysentery after invading the colon mucosa. Long Pentraxin 3 (PTX3) is recognized as the humoral component of the innate immune response to bacterial pathogens. We examined the interplay between levels of PTX3 and levels of anti-Shigella lipopolysaccharide (LPS) and anti-Shigella type 3 secretion system protein-IpaB antibodies in children during acute shigellosis and after recovery. PTX3 concentrations in serum and stool extracts were determined by sandwich ELISA using commercial anti-PTX3 antibodies. Serum IgG, IgM, and IgA anti-S. sonnei LPS or anti-S. sonnei IpaB were measured using in house ELISA. Children with acute shigellosis (n = 60) had elevated PTX3 levels in serum and stools as compared with recovered subjects (9.6 ng/mL versus 4.7 ng/mL, p < 0.009 in serum and 16.3 ng/g versus 1.1 ng/g in stool, p = 0.011). Very low levels of PTX3 were detected in stools of healthy children (0.3 ng/g). Increased serum levels of PTX3 correlated with high fever accompanied by bloody or numerous diarrheal stools characteristic of more severe shigellosis while short pentraxin; C-Reactive Protein (CRP) did not show such a correlation. PTX3 decreased in convalescence while anti-Shigella antibodies increased, switching the response from innate to adaptive toward the eradication of the invasive organism. These data can inform the development of Shigella vaccines and treatment options.

1194. Assessing Healthcare Professionals’ Knowledge of Shigella Transmission, Risk Factors, and Prevention – DocStyles Survey, 2020

Abstract Background Shigella infection typically manifests as a self-limited gastrointestinal illness (shigellosis) and affects some populations disproportionately, including children, travelers, people experiencing homelessness, and men who have sex with men (MSM). Healthcare professionals (HCPs) are positioned to play an active role in the prevention and control of shigellosis but may not be aware of the multiple routes of Shigella transmission, risk factors, and prevention strategies. Methods Porter Novelli Public Services’ Fall DocStyles 2020 web-based survey was administered to HCPs in the United States to assess their clinical practice and knowledge about many health-related issues. Questions about acute diarrhea and shigellosis were completed by pediatricians, primary care physicians, nurse practitioners, and physician assistants. We analyzed responses to four questions related to Shigella transmission, risk factors, prevention, and barriers to patient education. Results Of the 2196 panelists contacted, 1503 were included (68% response rate). Most identified contaminated food and water as potential routes of Shigella transmission (84.9% and 78.8%, respectively), but substantially fewer recognized person-to-person contact (39.5%), fomite transmission (32.5%), or sexual activity (17.6%) as ways adults can become infected. Similarly, MSM were infrequently identified as being at risk for shigellosis (34.5%). Many HCPs reported counseling patients to wash hands and avoid food preparation when ill with Shigella (85.9% and 77.2%), but only 29.4% reported recommending avoiding sex. Only 7.1% of respondents correctly identified all routes of transmission, 21% identified all risk factors, and 22% identified all prevention strategies. Delay in diagnosis was the most frequently reported barrier to educating patients about shigellosis. Conclusion HCP knowledge of shigellosis is incomplete. Identified gaps in knowledge were related to MSM as an at-risk population and transmission of Shigella through fomites and person-to-person contact (including sexual contact). Informing HCPs about transmission, risk factors, and opportunities for prevention could improve recognition and stop the spread of shigellosis in vulnerable communities. Disclosures All Authors: No reported disclosures

Shigellosis outbreak among MSM living with HIV: a case–control study in Taiwan, 2015–2016

ObjectivesOutbreaks of shigellosis among men who have sex with men (MSM) have been reported since the late 1990s. HIV infection is an important risk factor. Since 2014, the global shigellosis...

Lemon Juice Synergistically Preserved with Lactobacilli Ameliorates Inflammation in Shigellosis Mice

The use of probiotic Lactobacilli has moved from concept to implement in different applications. The study was carried out to establish the synergistic role of co-cultures of Lactobacillus casei, L. delbrueckii, L. plantarum and L. helveticus in lemon juice (LJ) preservation as well as investigate the inflammatory- and toxicity profiles of biopreserved LJ ingested shigellosis mice. Lactobacilli were cultured individually and cocultured with different combinations. Four strain Lactobacilli had significant preservative activity than any other combinations in both free and microencapsulated Lactobacilli. The four microencapsulated bacteria extended shelf-life of the LJ in about two weeks at 4°C. The free or microencapsulated bacteria were increased acidic pH into LJ. It was evidently proved that microencapsulated cocultures of different strains remained viable over a long period of time and the probiotically fermented juice were potentially inhibiting the pathogenic growth. For inflammatory acute shigellosis, therapies were divided into six groups: LJ only; LJ containing pathogenic bacteria (PB); LJ containing curd, the source of Lactobacilli; LJ containing curd and PB; LJ containing four Lactobacilli LAB1,3,4,6 and LJ containing chemical preservatives (PR, prophyl paraben and methyl paraben 9:1). Lactobacilli preserved LJ were found to be favorably lower inflammatory haematological profiles such as ESR, WBC count and C-reactive protein (CRP) agglutination in acute shigellosis mice. In addition, biopreserved LJ was safe owing to normal ranges of SGPT, SGOT, SALP and AA levels in shigellosis mice. Prospective studies on mechanisms of the probiotic activities might be enable their new medical applications for food preservation and treatment of inflammatory dysentery patients.

Differential expression of enteric neuroimmune‐network in invasive and acute watery diarrhoea

We aimed to evaluate the changes of nerve morphology and distribution of neurotransmitters and neuropeptides in the rectum of Shigella flexneri-infected patients and in the duodenum of Vibrio cholerae O1-infected patients. Nerve morphology was observed by transmission electron microscopy. Immunoreactivity of nerve growth factor (NGF), neurotransmitters and neuropeptides in tissues were studied by immunohistochemistry. Ultrastructural analysis of intestinal biopsy revealed persisting axons degeneration throughout the study period in all patients. Regeneration was already evident at the acute stage with marked increase at late convalescence. Both acute shigellosis and cholera were accompanied by increased expression of NGF and histamine and decreased expression of serotonin that was restored at convalescence. Immunoreactivity of vasoactive intestinal peptide (VIP) was increased during acute cholera, whereas in shigellosis VIP- and substance P-immunoreactive nerves appeared at early convalescence. Both shigellosis and cholera induced long-lasting degeneration of enteric neuronal axons, despite the presence of ongoing proliferation and regeneration processes. Neurotransmitters and neuropeptides may play differential roles in invasive and watery diarrhoea.

Trends in antimicrobial resistance in Shigella species in Karachi, Pakistan

Shigellosis is a common cause of morbidity, especially in the very young and old, in developing countries. The disease is treated with antibiotics. Surveillance of antimicrobial resistance trends is essential owing to the global emergence of antimicrobial resistance. The study involved 1,573 isolates of Shigella species (1996-2007) that were analyzed for trends in antimicrobial resistance. The majority of the specimens (1046; 66.5%) were from the pediatric population, and of these 887 (84.8%) were under 5 years of age (p = 0.001). S. flexineri was the most frequent species (54.5%) isolated. Isolation of S. sonnei increased from 15.4 % (1996) to 39% (2007) (p = 0.001). Although none of the isolates was found sensitive to all the antibiotics tested, 58% (n =9 07) were resistant to ampicillin and 85% (n = 1,338) were resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Out of a total of 198 (12.6%) nalidixic acid resistant isolates, 6 (3.0%) were also resistant to ofloxacin. Overall 1.7 % of isolates were resistant to ofloxacin, 2.4% to ceftriaxone and 2.3% were resistant to combination of ampicillin, nalidixic acid and TMP-SMX. Ofloxacin is still an effective drug for treatment of acute shigellosis in Pakistan. Emergence of resistance to ceftriaxone in Shigella may have grave implications in treatment of severe shigellosis in very young patients.

Zinc supplementation in the management of shigellosis in malnourished children in Bangladesh

To assess the impact of zinc supplementation on clinical recovery, weight gain and subsequent growth and morbidity in moderately malnourished children with shigellosis. A randomized, double-blind, controlled trial. Dhaka hospital of ICDDR,B: Centre for Health and Population Research, Dhaka, Bangladesh. Fifty-six moderately malnourished children, aged 12-59 months with culture-proven shigellosis. Subjects were randomly allocated to receive zinc (20 mg/day elemental) in multivitamin syrup (intervention) or multivitamin syrup without zinc (control) in two equally divided doses daily for 2 weeks. All children received pivmecillinam in a dose of 15 mg/kg every 6 h for 5 days. After supplementation, children were followed in their respective homes every 2 weeks for 6 months. Children receiving zinc recovered from acute illness significantly faster than the control children (P<0.05). The medians time (days) to recovery and disappearances of blood and mucous were significantly 50% shorter in the zinc-supplemented group compared to the control group. The mean body weight of zinc supplemented children increased significantly from 8.8 kg on admission to 9.2 kg (P<0.01) at recovery, which was not observed in the control children (from 9.3 to 9.6 kg; P=0.12). During the 6-month follow-up period, zinc-supplemented children had significantly fewer mean episodes of diarrhoea compared to the control children (2.2 vs 3.3; P=0.03). Zinc supplementation significantly shortens the duration of acute shigellosis, promotes better weight gain during recovery and reduces diarrhoeal morbidity during the subsequent 6 months.

Effects of zinc supplementation as adjunct therapy on the systemic immune responses in shigellosis

Zinc is lost during diarrheal diseases, and zinc deficiency induces intestinal morphology-altering inflammatory responses that zinc supplementation can correct. We assessed the in vivo effect of zinc supplementation on systemic and mucosal responses in mildly to moderately malnourished (defined as <-1 but >-2 and <-2 but >-3 weight-for-height z scores, respectively, based on the National Center for Health Statistics growth reference) children with shigellosis. A double-blind placebo-controlled trial was conducted in Shigella flexneri-infected children aged 12-59 mo. Daily for 14 d, elemental zinc (20 mg) and multivitamins (vitamins A and D, thiamine, riboflavin, and nicotinamide) plus calcium were given at twice the US recommended dietary allowance to the zinc group (n=28), and multivitamins plus calcium were given to the control group (n=28). All subjects received standard antibiotic therapy. There was no significant interaction between zinc supplementation and time, but zinc supplementation showed a significant effect on serum zinc concentrations. With a >or=4-fold increase in serum shigellacidal antibody titers from baseline used as the cutoff, the proportion of children with shigellacidal antibody response was greater in the zinc group than in the control group (P<0.03). There was a significant (P=0.02) treatment x time interaction for the proportions of circulating CD20+ and CD20+CD38+ cells, which were higher on day 7 in the zinc group than in the control group (P<0.007). No effect was seen on histopathologic features or the expression of innate and inflammatory mediators in the rectum. Adjunct therapy with zinc during acute shigellosis significantly improved seroconversion to shigellacidal antibody response and increased the proportions of circulating B lymphocytes and plasma cells.

Effect of zinc supplementation on immune and inflammatory responses in pediatric patients with shigellosis

Several studies showed benefits of long-term zinc supplementation on the incidence, severity, and duration of diarrhea and on the incidence of respiratory infections. Prolonged zinc supplementation also improves cell-mediated immunity in severely malnourished children. We studied the effect of short-term zinc supplementation on intrinsic and specific immune and inflammatory responses in moderately malnourished children with acute shigellosis. A randomized, double-blind, placebo-controlled trial was conducted in Shigella-infected children aged 12-59 mo. Elemental zinc (20 mg) and a multivitamin containing vitamins A and D, thiamine, riboflavin, nicotinamide, and calcium at twice the recommended dietary allowance were given daily for 2 wk to the zinc group (n = 28), whereas the multivitamin alone was given to the control group (n = 28). Standard antibiotic therapy was given to all patients. Serum zinc concentrations increased in both groups during convalescence; however, zinc supplementation showed a significant effect. The lymphocyte proliferation response in the zinc group increased relative to that in the control group (P = 0.002), but no significant effects were seen on concentrations of cytokines (interleukin 2 and interferon gamma) released from mitogen-stimulated mononuclear cells or on concentrations of cytokines (interleukin 2, interferon gamma, and interleukin 1beta) in feces. Among the antigen [lipopolysaccharide and invasion plasmid-encoded antigen (Ipa)]-specific antibodies, plasma Ipa-specific immunoglobulin G responses at day 30 were significantly higher in the zinc group than in the control group. However, the 2 groups did not differ significantly in the other antigen-specific responses in plasma and stool. A 14-d course of zinc supplementation during acute shigellosis increases the lymphocyte proliferation response and the Ipa-specific immunoglobulin G response.

Green banana reduces clinical severity and colonic inflammation in acute childhood shigellosis: A double-blind, randomized, controlled trial

Green banana reduces clinical severity and colonic inflammation in acute childhood shigellosis: A double-blind, randomized, controlled trial

Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2.

Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from patients infected with Shigella dysenteriae type 1 was studied by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and annexin V staining. Expression of proteins and cytokines participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL-18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute and convalescent stages of dysentery was quantified at the single-cell level by in situ immunostaining. Apoptotic cell death in the lamina propria was markedly up-regulated at the acute stage (P < 0.05), where an increased number of necrotic cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL-18, but not IL-2, at the acute stage than at the convalescent stage was observed. Increased expression of caspase-3 and IL-18 in tissues with severe inflammation compared to expression in those with mild inflammation was evident, implying a possible role in the perpetuation of inflammation. Significantly reduced cell death during convalescence was associated with a significant up-regulation of Bcl-2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of infection. Thus, induction of apoptosis at the local site in the early phase of S. dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival.

A Review of the Evidence for the Benefits and Safety of Adding Vitamin A to the Treatment of Six Common Health Problems in Children

It has been more than 70 years since vitamin A was first reported to play a role in the treatment of measles. the addition of vitamin A to the treatment of other common childhood illnesses remains controversial, with differing guidelines. This review analyzes the strength of the evidence for the role of vitamin A in six common childhood illnesses. We found no published papers on the use of vitamin A in chickenpox or malaria. There is strong published evidence for the use of adjuvant vitamin A in children requiring hospital admission for measles and some evidence for its use in acute shigellosis. the available evidence does not support a role for adjuvant vitamin A in acute lower respiratory tract infections or acute watery diarrhea. There is insufficient evidence on the role of vitamin A in the treatment of persistent diarrhea, acute measles not requiring admission, and protein-energy malnutrition to guide policy

Effect of an energy-dense diet on the clinical course of acute shigellosis in undernourished children

To date there have been few reports on the impact of dietary intervention on the clinical course of acute shigellosis. Current management of acute shigellosis is primarily focused on antibiotic therapy with less emphasis on nutritional management. In a randomised clinical trial, we examined the role of an energy-dense diet on the clinical outcome in malnourished children with acute dysentery due to shigellosis. Seventy-five children aged 12--48 months with acute dysentery randomly received either a milk--cereal formula with an energy density of 4960 kJ/l (test group) or a milk-cereal formula with energy of 2480 kJ/l (control group) for 10 d in hospital. In both milk-cereal formulas, protein provided 11 % energy. In addition, the standard hospital diet was offered to all children and all children received an appropriate antibiotic for 5 d. The mean food intakes (g/kg per d) in the test and control groups were: 112 (SE 2.28) and 116 (SE 3.48) on day 1; 118 (SE 2.72) and 107 (SE 3.13) on day 5; 120 (SE 2.25) and 100 (SE 3.83) on day 10. The mean energy intakes (kJ/kg per d) in the test and control groups respectively were: 622 (SE 13.2) and 315 (SE 11.3) on day 1; 655 (SE 15.1) and 311 (SE 7.98) on day 5; 672 (SE 14.7) and 294 (SE 11.1) on day 10. The food and energy intakes were mostly from the milk-cereal diet. There was no difference between two groups in resolution of fever, dysenteric (bloody and or mucoid) stools, stool frequency and tenesmus. However, vomiting was more frequently observed among the test-group children during the first 5 d of intervention (67 % v. 41 %, There was an increase in the mean weight-for-age (%) in the test group compared with the control group after the 10 d of dietary intervention (6.2 (SE 0.6) v. 2.7 (SE 0.4), In addition, resolution of rectal prolapse was better (26 % v. 8 %, in the test group v. control group after 5 d, and 13 % v. 6 %, after 10 d of dietary intervention. Supplementation with a high-energy diet does not have any adverse effect on clinical course of acute shigellosis and reduces the incidence of rectal prolapse in malnourished children.

Disease-dependent changes in T-cell populations in patients with shigellosis.

In shigellosis, bacterial infection is associated with an extensive inflammation of the rectal mucosa, resulting in bloody dysentery. The role of T-cell-mediated pro-inflammatory mechanisms has been implicated in this process, but the specific role of T-cell subsets is still not well understood. In this study we attempted to identify the changes in T-cell populations in patients with shigellosis during the disease course. The T-cell subset distribution was analyzed by immunohistochemistry in the rectal mucosa and by immuno-flow cytometry in the peripheral blood. Blood and rectal biopsies were studied from patients with Shigella dysenteriae 1 (n= 11) and S. flexneri (n= 11) infection and 20 healthy age-matched controls. We found an expansion of gammadelta+T cells in the rectal mucosa, but a decrease in the percentage of gammadelta+T cells in the blood in acute shigellosis. There was also a preferential increase in CD8+ T cells in the surface epithelium of rectal tissue in patients infected with S. dysenteriae 1, but not in patients infected with S. flexneri. Our findings suggest that the rectal mucosal inflammation in shigellosis is associated with an expansion of T cells, in particular CD8+ and gammadelta+T-cell subsets in the gut mucosa, which may be of importance for the pathogenesis of shigellosis.

Host responses to secreted Shigella virulence factors

Shigella and related enteropathogens deliver effector molecules into the cytoplasm of epithelial cells and macrophages via a type III secretion system. Epithelial cells respond to contact with Shigella by rearranging the cytoskeleton, which leads to uptake of the bacterium. Apart from several cytoskeletal proteins, this process involves the recruitment and activation of kinases, and the small GTPase rho. Macrophages infected with Shigella undergo apoptosis and release mature IL-1beta, a pro-inflammatory cytokine. This apoptotic pathway requires caspase-1 (IL-1beta-converting enzyme). Pro-inflammatory macrophage apoptosis triggers acute shigellosis and might be relevant in other infectious diseases.

Vitamin A administration reduces enteric protein loss in children during acute shigellosis

Vitamin A administration reduces enteric protein loss in children during acute shigellosis

Single dose vitamin A treatment in acute shigellosis in Bangladeshi children: randomised double blind controlled trial

Objective: To evaluate the efficacy of a single large oral dose of vitamin A in treating acute shigellosis in children in Bangladesh.Design: Randomised double blind controlled clinical trial.Setting: Dhaka Hospital,...

Vitamin A reduces severity of dysentery in acute shigellosis

Vitamin A reduces severity of dysentery in acute shigellosis

Quantitative and ultrastructural analysis of rectal mucosal mast cells in acute infectious diarrhea.

The role of mast cells, potential mediators of mucosal immunity and inflammation, was studied morphologically in the rectal mucosa in two acute diarrheal diseases, cholera and shigellosis. Quantitation of mucosal mast cells showed that they were significantly higher in the deeper lamina propria where blood vessels and nerves were more abundant. There was no difference in mast cell counts or degranulation in the mucosa in both groups of patients and controls. Intraepithelial mast cells were decreased in the patients. The prevalence of lipid bodies was significantly higher in mast cells from patients with cholera and shigellosis (P < 0.01). These findings suggest that mast cell populations are more dense around blood vessels and nerves and that inflammatory mediators derived from arachidonic acid metabolites, as indicated by the lipid bodies, are the response of mast cells to the alterations in diarrhea, despite differences in the etiology of diarrhea.

A systemic downregulation of gamma interferon production is associated with acute shigellosis.

Production of cytokines by peripheral blood mononuclear cells from Shigella-infected patients was assessed. The frequencies of tumor necrosis factor alpha (TNF-alpha), TNF-beta, and transforming growth factor beta mRNA-expressing cells were persistently upregulated during the course of shigellosis in comparison to those of healthy controls. In contrast, the frequency of gamma interferon (IFN-gamma) mRNA-expressing cells was significantly reduced during the acute stage compared to that during the convalescent stage and to that of healthy Bangladeshi controls (P < 0.01). Constitutive IFN-gamma production in Bangladeshi controls was significantly upregulated compared to that in Swedish controls.