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Rubhana Raqib - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of sodium butyrate adjunct therapy in Shigellosis: a randomized, double-blind, placebo-controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Background Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration ClinicalTrials.gov, NCT00800930.
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efficacy of sodium butyrate adjunct therapy in Shigellosis a randomized double blind placebo controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. ClinicalTrials.gov, NCT00800930.
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cytokine secretion in acute Shigellosis is correlated to disease activity and directed more to stool than to plasma
The Journal of Infectious Diseases, 1995Co-Authors: Rubhana Raqib, Bengt Wretlind, Jan Andersson, Alf A LindbergAbstract:Stool and plasma cytokine levels in 60 adults with acute Shigellosis were studied by EIA at various intervals (0-45 days) after onset of diarrhea. Cytokine levels correlated with severity of disease. Significantly higher levels of proinflammatory cytokines peaked at onset of disease in stool of patients with severe disease (P < .05). In contrast, interferon-gamma (IFN-gamma) levels, depressed at disease onset, progressively increased during the convalescent stage. Concomitantly obtained plasma cytokine levels were 100 times lower than levels in stool. Controls in Shigella-endemic areas (n = 42) had persistently significantly higher levels of IFN-gamma and interleukin-1 receptor antagonist in both stool and plasma. The lack of host defense activity against Shigellosis may be linked to delayed recovery of IFN-gamma. This cytokine may play an important role in elimination of the infection and development of immunity against Shigellosis.
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Pathology of Shigellosis and its complications
Histopathology, 1994Co-Authors: M.m. Islam, Pradip Kumar Bardhan, A.k. Azad, Rubhana Raqib, D. IslamAbstract:One hundred and thirty-three colonic biopsies of proven cases of Shigella colitis were examined and post-mortem examinations were carried out on 29 fatal cases at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) hospital between 1988 and 1992. The distribution of pathological lesions and the spectrum of histopathological changes in the intestinal tract of these patients, and the features of intestinal and extra-intestinal complications of Shigellosis are presented. Septicaemia, hyponatraemia, hypokalaemia and hypoglycaemia were present in a high percentage of these cases. All but two patients were malnourished at the time of autopsy. Shigellosis patients rapidly became hypoproteinaemic and were susceptible to other infections including opportunistic infections. Mortality amongst Shigellosis patients admitted to our hospital continues to be high in spite of adequate antibiotic and supportive therapy.
Birgitta Agerberth - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of sodium butyrate adjunct therapy in Shigellosis: a randomized, double-blind, placebo-controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Background Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration ClinicalTrials.gov, NCT00800930.
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efficacy of sodium butyrate adjunct therapy in Shigellosis a randomized double blind placebo controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. ClinicalTrials.gov, NCT00800930.
Dani Cohen - One of the best experts on this subject based on the ideXlab platform.
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Burden and risk factors of Shigella sonnei Shigellosis among children aged 0–59 months in hyperendemic communities in Israel
Elsevier, 2019Co-Authors: Dani Cohen, Hadar Korin, Ravit Bassal, Michal Perry Markovich, Yoram Sivan, Sophy Goren, Khitam MuhsenAbstract:Objectives: Ultraorthodox Jewish populations living in towns with good sanitary infrastructure but with conditions of crowding have been the epicenter of Shigella sonnei Shigellosis outbreaks. In this study, the incidence and risk factors of S. sonnei Shigellosis in children living in an ultraorthodox community were determined. Methods: Data for the years 2000–2013 for all reported culture-proven S. sonnei Shigellosis cases in children aged 0–59 months in the city of Elad were compared with data for the rest of the sub-district. Environmental factors obtained through parental interviews were evaluated for 78 incident cases of S. sonnei Shigellosis and 141 community controls, matched by age, sex, and neighborhood. Conditional logistic regression models were performed. Results: Cyclic epidemics of S. sonnei Shigellosis occurred every 2 years. The mean annual incidence was 10.0 per 1000 children in Elad (95% confidence interval 7.9–12.6) vs. 3.8 per 1000 children (95% confidence interval 3.3–4.4) in the sub-district (p
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whole genome analysis to detect potential vaccine induced changes on shigella sonnei genome
Vaccine, 2015Co-Authors: Adi Behar, Sophy Goren, Maria Fookes, Nicholas R Thomson, Dani CohenAbstract:Abstract Shigellosis or bacillary dysentery is endemic worldwide and is a significant cause of death in children less than five years of age in developing countries. There are no licensed Shigella vaccines and glycoconjugates are among the leading candidate vaccines against Shigellosis today. We used whole genome sequence analysis (WGA) to find out whether immunization, with an investigational Shigella sonnei glycoconjugate, could induce selective pressure leading to changes in the genome of S. sonnei . An outbreak of culture-proven S. sonnei Shigellosis which occurred immediately after vaccination in one of the cohorts of volunteers participating in a phase III trial of the vaccine in Israel created a unique condition in which the epidemic agent “co-existed” with the developing immune responses induced by the vaccine and natural infection among vaccinees who developed S. sonnei Shigellosis. By comparing the whole genomes of S. sonnei isolated from vaccinees and from volunteers in the control group, we show at a very high sensitivity that a potent S. sonnei glycoconjugate that conferred 74% protective efficacy against the homologous disease did not induce changes in the genome of S. sonnei and in particular on the O-antigen gene cluster.
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recent trends in the epidemiology of Shigellosis in israel
Epidemiology and Infection, 2014Co-Authors: Dani Cohen, Ravit Bassal, Sophy Goren, T. Rouach, D. Taran, B. Schemberg, N. Peled, Y. Keness, S Kendror, V. VasilevAbstract:SUMMARY We provide an update on the epidemiology of Shigellosis in Israel using data generated by a sentinel laboratory-based surveillance network for the period 1998–2012. The average annual incidence of culture-proven Shigellosis was 97/100000. We estimated that each case of Shigellosis accounted for 25 cases in the community indicating the high burden of disease. Orthodox Jewish communities, living in highly crowded conditions and with a high number of children aged <5 years were the epicentre of country-wide biennial propagated epidemics of S. sonnei Shigellosis. S. flexneri was the leading Shigella serogroup in Israeli Arabs. S. flexneri 2a and S. flexneri 6 alternated as the most common serotypes. Both S. sonnei and S. flexneri isolates showed high rates of resistance to ampicillin and trimethoprim/sulfamethoxazole and very low rates of resistance to quinolones and third-generation cephalosporins. Shigellosis due to S. sonnei conferred 81% (95% confidence interval 69–89) protection against the homologous Shigella serotype when epidemic exposure re-occurred 2 years later. These data are of value in the process of Shigella vaccine development.
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Recent trends in the epidemiology of Shigellosis in Israel.
Epidemiology and infection, 2014Co-Authors: Dani Cohen, Ravit Bassal, Sophy Goren, T. Rouach, D. Taran, B. Schemberg, N. Peled, Y. Keness, S. Ken-dror, V. VasilevAbstract:SUMMARY We provide an update on the epidemiology of Shigellosis in Israel using data generated by a sentinel laboratory-based surveillance network for the period 1998–2012. The average annual incidence of culture-proven Shigellosis was 97/100000. We estimated that each case of Shigellosis accounted for 25 cases in the community indicating the high burden of disease. Orthodox Jewish communities, living in highly crowded conditions and with a high number of children aged
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Prospective cohort studies of Shigellosis during military field training.
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2001Co-Authors: Dani Cohen, Tamar Sela, Raphael Slepon, M. Yavzori, Ruhama Ambar, Nadav Orr, Guy Robin, O. Shpielberg, A. Eldad, Manfred S. GreenAbstract:Epidemiological and clinical features of Shigellosis occurring among cohorts of Israeli recruits followed-up for 3–6 months during the summer field training of years 1993–1997 were studied. The incidence rate of culture-proven Shigellosis was the highest (78 cases per 1,000 recruits) in 1996 and the lowest (13 cases per 1,000 recruits) in 1995. Shigella sonnei (152 isolates) and Shigella flexneri (151 isolates) were the most common species. Fifty percent of the patients with Shigellosis had fever (>37.5 °C), compared to only 18% of the subjects with other diarrheal diseases (P
Jan Andersson - One of the best experts on this subject based on the ideXlab platform.
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efficacy of sodium butyrate adjunct therapy in Shigellosis a randomized double blind placebo controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. ClinicalTrials.gov, NCT00800930.
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Efficacy of sodium butyrate adjunct therapy in Shigellosis: a randomized, double-blind, placebo-controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Background Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration ClinicalTrials.gov, NCT00800930.
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cytokine secretion in acute Shigellosis is correlated to disease activity and directed more to stool than to plasma
The Journal of Infectious Diseases, 1995Co-Authors: Rubhana Raqib, Bengt Wretlind, Jan Andersson, Alf A LindbergAbstract:Stool and plasma cytokine levels in 60 adults with acute Shigellosis were studied by EIA at various intervals (0-45 days) after onset of diarrhea. Cytokine levels correlated with severity of disease. Significantly higher levels of proinflammatory cytokines peaked at onset of disease in stool of patients with severe disease (P < .05). In contrast, interferon-gamma (IFN-gamma) levels, depressed at disease onset, progressively increased during the convalescent stage. Concomitantly obtained plasma cytokine levels were 100 times lower than levels in stool. Controls in Shigella-endemic areas (n = 42) had persistently significantly higher levels of IFN-gamma and interleukin-1 receptor antagonist in both stool and plasma. The lack of host defense activity against Shigellosis may be linked to delayed recovery of IFN-gamma. This cytokine may play an important role in elimination of the infection and development of immunity against Shigellosis.
Protim Sarker - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of sodium butyrate adjunct therapy in Shigellosis: a randomized, double-blind, placebo-controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Background Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. Methods A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Results Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Conclusion Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. Trial Registration ClinicalTrials.gov, NCT00800930.
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efficacy of sodium butyrate adjunct therapy in Shigellosis a randomized double blind placebo controlled clinical trial
BMC Infectious Diseases, 2012Co-Authors: Rubhana Raqib, Jan Andersson, Protim Sarker, Akhirunnesa Mily, Nur Haque Alam, Abu Saleh Mohammed Arifuzzaman, Rokeya Sultana Rekha, Gudmundur H Gudmundsson, Alejandro Cravioto, Birgitta AgerberthAbstract:Treatment of Shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of Shigellosis in patients. A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with Shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of Shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients. Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7. Adjunct therapy with butyrate during Shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool. ClinicalTrials.gov, NCT00800930.
