The Experts below are selected from a list of 52188 Experts worldwide ranked by ideXlab platform
Balakrish G Nair - One of the best experts on this subject based on the ideXlab platform.
-
whole genome sequence comparisons reveal the evolution of vibrio Cholerae o1
Trends in Microbiology, 2015Co-Authors: Eun Jin Kim, Balakrish G Nair, Chan Hee Lee, Dongwook KimAbstract:The analysis of the whole-genome sequences of Vibrio Cholerae strains from previous and current Cholera pandemics has demonstrated that genomic changes and alterations in phage CTX (particularly in the gene encoding the B subunit of Cholera toxin) were major features in the evolution of V. Cholerae. Recent studies have revealed the genetic mechanisms in these bacteria by which new variants of V. Cholerae are generated from type-specific strains; these mechanisms suggest that certain strains are selected by environmental or human factors over time. By understanding the mechanisms and driving forces of historical and current changes in the V. Cholerae population, it would be possible to predict the direction of such changes and the evolution of new variants; this has implications for the battle against Cholera.
-
isolation of viable but nonculturable vibrio Cholerae o1 from environmental water samples in kolkata india in a culturable state
MicrobiologyOpen, 2014Co-Authors: Mitsutoshi Senoh, Balakrish G Nair, Jayeeta Ghoshbanerjee, Tamaki Mizuno, Sumio Shinoda, Shinichi Miyoshi, Takashi Hamabata, Yoshifumi TakedaAbstract:Previously, we reported that viable but nonculturable (VBNC) Vibrio Cholerae was converted into a culturable state by coculture with several eukaryotic cell lines including HT-29 cells. In this study, we found that a factor converting VBNC V. Cholerae into a culturable state (FCVC) existed in cell extracts of eukaryotic cells. FCVC was nondialyzable, proteinase K-sensitive, and stable to heating at <60°C for 5 min. We prepared thiosulfate citrate bile salts sucrose (TCBS) plates with FCVC (F-TCBS plates). After confirming that VBNC V. Cholerae O1 and O139 formed typical yellow colonies on F-TCBS plates, we tried to isolate Cholera toxin gene-positive VBNC V. Cholerae from environmental water samples collected in urban slum areas of Kolkata, India and succeeded in isolating V. Cholerae O1 El Tor variant strains harboring a gene for the Cholera toxin. The possible importance of VBNC V. Cholerae O1 as a source of Cholera outbreaks is discussed.
-
Cholera outbreaks in the el tor biotype era and the impact of the new el tor variants
Current Topics in Microbiology and Immunology, 2014Co-Authors: Asish K Mukhopadhyay, Yoshifumi Takeda, Balakrish G NairAbstract:Vibrio Cholerae O1, the causative agent of the disease Cholera, has two biotypes namely the classical and El Tor. Biotype is a subspecific taxonomic classification of V. Cholerae O1. Differentiation of V. Cholerae strains into biotype does not alter the clinical management of Cholera but is of immense public health and epidemiological importance in identifying the source and spread of infection, particularly when V. Cholerae is first isolated in a country or geographic area. From recorded history, till date, the world has experienced seven pandemics of Cholera. Among these, the first six pandemics are believed to have been caused by the classical biotype whereas the ongoing seventh pandemic is caused by the El Tor biotype. In recent years, new pathogenic variants of V. Cholerae have emerged and spread throughout many Asian and African countries with corresponding cryptic changes in the epidemiology of Cholera. In this chapter, we describe the outbreaks during the seventh pandemic El Tor biotype era spanning more than five decades along with the recent advances in our understanding of the development, evolution, spread, and impact of the new variants of El Tor strains.
-
environmental signatures associated with Cholera epidemics
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Guillaume Constantin De Magny, Balakrish G Nair, Mohammad Yunus, Azhar Nizam, Raghu Murtugudde, Mathew R P Sapiano, Chris W Brown, Antonio J Busalacchi, Ana I GilAbstract:The causative agent of Cholera, Vibrio Cholerae, has been shown to be autochthonous to riverine, estuarine, and coastal waters along with its host, the copepod, a significant member of the zooplankton community. Temperature, salinity, rainfall and plankton have proven to be important factors in the ecology of V. Cholerae, influencing the transmission of the disease in those regions of the world where the human population relies on untreated water as a source of drinking water. In this study, the pattern of Cholera outbreaks during 1998-2006 in Kolkata, India, and Matlab, Bangladesh, and the earth observation data were analyzed with the objective of developing a prediction model for Cholera. Satellite sensors were used to measure chlorophyll a concentration (CHL) and sea surface temperature (SST). In addition, rainfall data were obtained from both satellite and in situ gauge measurements. From the analyses, a statistically significant relationship between the time series for Cholera in Kolkata, India, and CHL and rainfall anomalies was determined. A statistically significant one month lag was observed between CHL anomaly and number of Cholera cases in Matlab, Bangladesh. From the results of the study, it is concluded that ocean and climate patterns are useful predictors of Cholera epidemics, with the dynamics of endemic Cholera being related to climate and/or changes in the aquatic ecosystem. When the ecology of V. Cholerae is considered in predictive models, a robust early warning system for Cholera in endemic regions of the world can be developed for public health planning and decision making.
-
seasonal Cholera caused by vibrio Cholerae serogroups o1 and o139 in the coastal aquatic environment of bangladesh
Applied and Environmental Microbiology, 2006Co-Authors: Munirul Alam, Balakrish G Nair, N A Bhuiyan, A K Siddique, Bradley R Sack, Nur A Hasan, Abdus Sadique, Kabir Uddin Ahmed, Suraia Nusrin, David A. SackAbstract:Since Vibrio Cholerae O139 first appeared in 1992, both O1 El Tor and O139 have been recognized as the epidemic serogroups, although their geographic distribution, endemicity, and reservoir are not fully understood. To address this lack of information, a study of the epidemiology and ecology of V. Cholerae O1 and O139 was carried out in two coastal areas, Bakerganj and Mathbaria, Bangladesh, where Cholera occurs seasonally. The results of a biweekly clinical study (January 2004 to May 2005), employing culture methods, and of an ecological study (monthly in Bakerganj and biweekly in Mathbaria from March 2004 to May 2005), employing direct and enrichment culture, colony blot hybridization, and direct fluorescent-antibody methods, showed that Cholera is endemic in both Bakerganj and Mathbaria and that V. Cholerae O1, O139, and non-O1/non-O139 are autochthonous to the aquatic environment. Although V. Cholerae O1 and O139 were isolated from both areas, most noteworthy was the isolation of V. Cholerae O139 in March, July, and September 2004 in Mathbaria, where seasonal Cholera was clinically linked only to V. Cholerae O1. In Mathbaria, V. Cholerae O139 emerged as the sole cause of a significant outbreak of Cholera in March 2005. V. Cholerae O1 reemerged clinically in April 2005 and established dominance over V. Cholerae O139, continuing to cause Cholera in Mathbaria. In conclusion, the epidemic potential and coastal aquatic reservoir for V. Cholerae O139 have been demonstrated. Based on the results of this study, the coastal ecosystem of the Bay of Bengal is concluded to be a significant reservoir for the epidemic serogroups of V. Cholerae.
David A. Sack - One of the best experts on this subject based on the ideXlab platform.
-
diagnostic techniques for rapid detection of vibrio Cholerae o1 o139
Vaccine, 2020Co-Authors: Thandavarayan Ramamurthy, Bhabatosh Das, Subhra Chakraborty, Asish K Mukhopadhyay, David A. SackAbstract:Abstract Cholera caused by the toxigenic Vibrio Cholerae is still a major public health problem in many countries. This disease is mainly due to poor sanitation, hygiene and consumption of unsafe water. Several recent epidemics of Cholera showed its increasing intensity, duration and severity of the illness. This indicates an urgent need for effective management and preventive measures in controlling the outbreaks and epidemics. In preventing and spread of epidemic Cholera, rapid diagnostic tests (RDTs) are useful in screening suspected stool specimens, water/food samples. Several RDTs developed recently are considered as investigative tools in confirming Cholera cases, as the culture techniques are difficult to establish and/or maintain. The usefulness of RDTs will be more at the point-of-care facilities as it helps to make appropriate decisions in the management of outbreaks or epidemiological surveillance by the public health authorities. Apart from RDTs, several other tests are available for the direct detection of either V. Cholerae or its Cholera toxin. Viable but non-culturable (VBNC) state of V. Cholerae poses a great challenge in developing RDTs. The aim of this article is to provide an overview of current knowledge about RDT and other techniques with reference to their status and future potentials in detecting Cholera/V. Cholerae.
-
randomized controlled trial of hospital based hygiene and water treatment intervention chobi7 to reduce Cholera
Emerging Infectious Diseases, 2016Co-Authors: Christine Marie George, David A. Sack, Shirajum Monira, Mahamudur Rashid, K M Saifurrahman, Toslim Mahmud, Zillur Rahman, Munshi Mustafiz, Sazzadul Islam Bhuyian, Peter J WinchAbstract:The risk for Cholera infection is >100 times higher for household contacts of Cholera patients during the week after the index patient seeks hospital care than it is for the general population. To initiate a standard of care for this high-risk population, we developed Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7), which promotes hand washing with soap and treatment of water. To test CHoBI7, we conducted a randomized controlled trial among 219 intervention household contacts of 82 Cholera patients and 220 control contacts of 83 Cholera patients in Dhaka, Bangladesh, during 2013-2014. Intervention contacts had significantly fewer symptomatic Vibrio Cholerae infections than did control contacts and 47% fewer overall V. Cholerae infections. Intervention households had no stored drinking water with V. Cholerae and 14 times higher odds of hand washing with soap at key events during structured observation on surveillance days 5, 6, or 7. CHoBI7 presents a promising approach for controlling Cholera among highly susceptible household contacts of Cholera patients.
-
robust gut associated vaccine specific antibody secreting cell responses are detected at the mucosal surface of bangladeshi subjects after immunization with an oral killed bivalent v Cholerae o1 o139 whole cell Cholera vaccine comparison with other m
Vaccine, 2009Co-Authors: Sohel Shamsuzzaman, Ann-mari Svennerholm, David A. Sack, Tanvir Ahmed, Kaiissar Mannoor, Yasmin Ara Begum, Pradip Kumar Bardhan, Bradley R Sack, Jan HolmgrenAbstract:Abstract The emergence of V. Cholerae O139 serogroup of V. Cholerae capable of causing severe dehydrating Cholera has over the decade led to efforts in formulation of vaccines to protect against this pathogen. Although the prevalence of diarrhea due to V. Cholerae O139 has recorded a decrease, efforts on vaccine development continues to formulate an oral vaccine capable of stimulating the gut mucosal system. We have studied the mucosal immunogenicity in Bangladeshi adults to a killed whole cell (WC) bivalent Cholera vaccine composed of V. Cholerae O139 as well as V. Cholerae O1 strains together with the recombinant Cholera toxin B subunit (CTB) (WC-O1/O139/CTB) and compared the immune responses to that obtained with the licensed monovalent Cholera vaccine, Dukoral (WC-O1/CTB). Direct estimation of the WC-O1/O139/CTB vaccine-specific mucosal responses were carried out using lymphocytes isolated from duodenal biopsies, intestinal lavage fluid and feces. The vaccine induced robust antibody-secreting cell responses in the duodenum specific to CTB as well as the O1 and O139 lipopolysaccharide (LPS). Magnitude of response was higher in the gut than in the circulation in all three antibody isotypes. The CTB and LPS-specific mucosal antibody responses were also seen in intestinal lavage fluid and fecal extracts. Vibriocidal antibody responses in plasma were observed to both the V. Cholerae O1 and O139 serogroups (76% and 57% response rates, respectively). Plasma IgA and IgG responses to CTB and IgA responses to both O1 and O139 LPS were elevated. The immune responses were comparable to that seen to the monovalent WC-O1/CTB recipients in all components studied. Overall, the bivalent Cholera vaccine induces strong mucosal responses and the addition of the O139 component does not interfere with the responses to the licensed vaccine Dukoral. This sets the ground for testing such vaccines in large field trials in Bangladesh and also demonstrates that addition of other vibrio components to the existing Cholera vaccine does not alter the responses to the O1 vaccine components.
-
seasonal Cholera caused by vibrio Cholerae serogroups o1 and o139 in the coastal aquatic environment of bangladesh
Applied and Environmental Microbiology, 2006Co-Authors: Munirul Alam, Balakrish G Nair, N A Bhuiyan, A K Siddique, Bradley R Sack, Nur A Hasan, Abdus Sadique, Kabir Uddin Ahmed, Suraia Nusrin, David A. SackAbstract:Since Vibrio Cholerae O139 first appeared in 1992, both O1 El Tor and O139 have been recognized as the epidemic serogroups, although their geographic distribution, endemicity, and reservoir are not fully understood. To address this lack of information, a study of the epidemiology and ecology of V. Cholerae O1 and O139 was carried out in two coastal areas, Bakerganj and Mathbaria, Bangladesh, where Cholera occurs seasonally. The results of a biweekly clinical study (January 2004 to May 2005), employing culture methods, and of an ecological study (monthly in Bakerganj and biweekly in Mathbaria from March 2004 to May 2005), employing direct and enrichment culture, colony blot hybridization, and direct fluorescent-antibody methods, showed that Cholera is endemic in both Bakerganj and Mathbaria and that V. Cholerae O1, O139, and non-O1/non-O139 are autochthonous to the aquatic environment. Although V. Cholerae O1 and O139 were isolated from both areas, most noteworthy was the isolation of V. Cholerae O139 in March, July, and September 2004 in Mathbaria, where seasonal Cholera was clinically linked only to V. Cholerae O1. In Mathbaria, V. Cholerae O139 emerged as the sole cause of a significant outbreak of Cholera in March 2005. V. Cholerae O1 reemerged clinically in April 2005 and established dominance over V. Cholerae O139, continuing to cause Cholera in Mathbaria. In conclusion, the epidemic potential and coastal aquatic reservoir for V. Cholerae O139 have been demonstrated. Based on the results of this study, the coastal ecosystem of the Bay of Bengal is concluded to be a significant reservoir for the epidemic serogroups of V. Cholerae.
-
Transmissibility of Cholera: In vivo-formed biofilms and their relationship to infectivity and persistence in the environment
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Shah M. Faruque, Q. S. Ahmad, David A. Sack, G. Balakrish Nair, K. R. Biswas, S. M. Nashir Udden, John J. MekalanosAbstract:The factors that enhance the waterborne spread of bacterial epidemics and sustain the epidemic strain in nature are unclear. Although the epidemic diarrheal disease Cholera is known to be transmitted by water contaminated with pathogenic Vibrio Cholerae, routine isolation of pathogenic strains from aquatic environments is challenging. Here, we show that conditionally viable environmental cells (CVEC) of pathogenic V. Cholerae that resist cultivation by conventional techniques exist in surface water as aggregates (biofilms) of partially dormant cells. Such CVEC can be recovered as fully virulent bacteria by inoculating the water into rabbit intestines. Furthermore, when V. Cholerae shed in stools of Cholera patients are inoculated in environmental water samples in the laboratory, the cells exhibit characteristics similar to CVEC, suggesting that CVEC are the infectious form of V. Cholerae in water and that CVEC in nature may have been derived from human Cholera stools. We also observed that stools from Cholera patients contain a heterogenous mixture of biofilm-like aggregates and free-swimming planktonic cells of V. Cholerae. Estimation of the relative infectivity of these different forms of V. Cholerae cells suggested that the enhanced infectivity of V. Cholerae shed in human stools is largely due to the presence of clumps of cells that disperse in vivo, providing a high dose of the pathogen. The results of this study support a model of Cholera transmission in which in vivo-formed biofilms contribute to enhanced infectivity and environmental persistence of pathogenic V. Cholerae.
Fahima Chowdhury - One of the best experts on this subject based on the ideXlab platform.
-
cognate t and b cell interaction and association of follicular helper t cells with b cell responses in vibrio Cholerae o1 infected bangladeshi adults
Microbes and Infection, 2019Co-Authors: Rasheduzzaman Rashu, Fahima Chowdhury, Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Jason B Harris, Anik Paul, Mohammad Rubel Hoq, Lazina Hossain, Stephen B CalderwoodAbstract:Abstract Vibrio Cholerae O1 can cause life threatening diarrheal disease if left untreated. T cells can play critical roles in inducing B cell mediated immunity. As the mechanism of T cell dependent B cell maturation is not well established, we hypothesized that a specific population of T (follicular helper T, Tfh) cells, are involved in B cell maturation following Cholera. We found flowcytometrically that V. Cholerae infection induces significant increases in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize Cholera toxin most prominently, with lessened responses to V. Cholerae membrane preparation (MP) and V. Cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after Cholera can stimulate class switching of co-cultured, isolated B cells from patients with Cholera, leading to production of the more durable IgG antibody isotype colorimetrically. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during Cholera directly in gut mucosa of biopsied samples, at the single cell level if feasible.
-
human gut microbiota predicts susceptibility to vibrio Cholerae infection
The Journal of Infectious Diseases, 2018Co-Authors: Firas S Midani, Yasmin Ara Begum, Ana A Weil, Fahima Chowdhury, Ashraful Islam Khan, Meti D Debela, Heather K Durand, Aspen T Reese, Sai N Nimmagadda, Justin D SilvermanAbstract:Background Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood. Methods We prospectively studied household contacts of patients with Cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio Cholerae infection and tested these taxa for interactions with V. Cholerae in vitro. Results We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. Cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to Cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with Cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. Cholerae. Gut microbiota structure, clinical outcome, and age were also linked. Conclusion These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. Cholerae susceptibility.
-
defining endemic Cholera at three levels of spatiotemporal resolution within bangladesh
Nature Genetics, 2018Co-Authors: Daryl Domman, Yasmin Ara Begum, Ankur Mutreja, Fahima Chowdhury, Ashraful Islam Khan, Matthew J. Dorman, Muhammad Ikhtear Uddin, Anik Paul, Richelle C CharlesAbstract:Although much focus is placed on Cholera epidemics, the greatest burden occurs in settings in which Cholera is endemic, including areas of South Asia, Africa and now Haiti1,2. Dhaka, Bangladesh is a megacity that is hyper-endemic for Cholera, and experiences two regular seasonal outbreaks of Cholera each year3. Despite this, a detailed understanding of the diversity of Vibrio Cholerae strains circulating in this setting, and their relationships to annual outbreaks, has not yet been obtained. Here we performed whole-genome sequencing of V. Cholerae across several levels of focus and scale, at the maximum possible resolution. We analyzed bacterial isolates to define Cholera dynamics at multiple levels, ranging from infection within individuals, to disease dynamics at the household level, to regional and intercontinental Cholera transmission. Our analyses provide a genomic framework for understanding Cholera diversity and transmission in an endemic setting.
-
plasma and memory b cell responses targeting o specific polysaccharide osp are associated with protection against vibrio Cholerae o1 infection among household contacts of Cholera patients in bangladesh
PLOS Neglected Tropical Diseases, 2018Co-Authors: Amena Aktar, Taher Uddin, Arifur M Rahman, Sadia Afrin, Aklima Akter, Tahirah Yasmin, Md Israk Nur Sami, Pinki Dash, Sultana Rownok Jahan, Fahima ChowdhuryAbstract:Background The mediators of protection against Cholera, a severe dehydrating illness of humans caused by Vibrio Cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells targeting lipopolysaccharide (LPS) of Vibrio Cholerae O1 correlate with protection against V. Cholerae O1 infection among household contacts of Cholera patients. Protection against Cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of Cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. Cholerae infection. Methodology In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio Cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2). Principle findings The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with Cholera toxin B subunit (CtxB)-specific memory B cell responses. Conclusion These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. Cholerae O1.
-
cognate t and b cell interaction and association of follicular helper t cells with b cell responses in vibrio Cholerae o1 infected bangladeshi adults
bioRxiv, 2018Co-Authors: Rasheduzzaman Rashu, Fahima Chowdhury, Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Jason B Harris, Anik Paul, Mohammad Rubel Hoq, Lazina Hossain, Stephen B CalderwoodAbstract:Abstract Vibrio Cholerae O1 can cause life threatening diarrheal disease if left untreated. A long lasting immune response, producing 3-5 years of protection from subsequent, symptomatic disease following natural infection, is mediated by B cell mediated humoral immunity. T cells can play critical roles in inducing such immunity. However, the mechanism of T cell dependent B cell maturation and whether a key sub-population of T cells are involved is not well established in Cholera. We hypothesized that a specific population of T cells, follicular helper T (Tfh) cells, are involved in B cell maturation following Cholera; we used flow cytometry, culture and colorimetric assays to address this question. We found that V. Cholerae infection induces significant increase in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize Cholera toxin most prominently, with lessened responses to two antigens tested, V. Cholerae membrane preparation (MP) and Vibrio Cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after Cholera can stimulate class switching of cocultured, isolated B cells from patients with Cholera, leading to production of the more durable IgG antibody isotype. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during Cholera directly in the gut mucosa of biopsied samples, at the single cell level if feasible.
Ashraful Islam Khan - One of the best experts on this subject based on the ideXlab platform.
-
cognate t and b cell interaction and association of follicular helper t cells with b cell responses in vibrio Cholerae o1 infected bangladeshi adults
Microbes and Infection, 2019Co-Authors: Rasheduzzaman Rashu, Fahima Chowdhury, Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Jason B Harris, Anik Paul, Mohammad Rubel Hoq, Lazina Hossain, Stephen B CalderwoodAbstract:Abstract Vibrio Cholerae O1 can cause life threatening diarrheal disease if left untreated. T cells can play critical roles in inducing B cell mediated immunity. As the mechanism of T cell dependent B cell maturation is not well established, we hypothesized that a specific population of T (follicular helper T, Tfh) cells, are involved in B cell maturation following Cholera. We found flowcytometrically that V. Cholerae infection induces significant increases in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize Cholera toxin most prominently, with lessened responses to V. Cholerae membrane preparation (MP) and V. Cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after Cholera can stimulate class switching of co-cultured, isolated B cells from patients with Cholera, leading to production of the more durable IgG antibody isotype colorimetrically. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during Cholera directly in gut mucosa of biopsied samples, at the single cell level if feasible.
-
human gut microbiota predicts susceptibility to vibrio Cholerae infection
The Journal of Infectious Diseases, 2018Co-Authors: Firas S Midani, Yasmin Ara Begum, Ana A Weil, Fahima Chowdhury, Ashraful Islam Khan, Meti D Debela, Heather K Durand, Aspen T Reese, Sai N Nimmagadda, Justin D SilvermanAbstract:Background Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood. Methods We prospectively studied household contacts of patients with Cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio Cholerae infection and tested these taxa for interactions with V. Cholerae in vitro. Results We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. Cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to Cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with Cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. Cholerae. Gut microbiota structure, clinical outcome, and age were also linked. Conclusion These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. Cholerae susceptibility.
-
defining endemic Cholera at three levels of spatiotemporal resolution within bangladesh
Nature Genetics, 2018Co-Authors: Daryl Domman, Yasmin Ara Begum, Ankur Mutreja, Fahima Chowdhury, Ashraful Islam Khan, Matthew J. Dorman, Muhammad Ikhtear Uddin, Anik Paul, Richelle C CharlesAbstract:Although much focus is placed on Cholera epidemics, the greatest burden occurs in settings in which Cholera is endemic, including areas of South Asia, Africa and now Haiti1,2. Dhaka, Bangladesh is a megacity that is hyper-endemic for Cholera, and experiences two regular seasonal outbreaks of Cholera each year3. Despite this, a detailed understanding of the diversity of Vibrio Cholerae strains circulating in this setting, and their relationships to annual outbreaks, has not yet been obtained. Here we performed whole-genome sequencing of V. Cholerae across several levels of focus and scale, at the maximum possible resolution. We analyzed bacterial isolates to define Cholera dynamics at multiple levels, ranging from infection within individuals, to disease dynamics at the household level, to regional and intercontinental Cholera transmission. Our analyses provide a genomic framework for understanding Cholera diversity and transmission in an endemic setting.
-
cognate t and b cell interaction and association of follicular helper t cells with b cell responses in vibrio Cholerae o1 infected bangladeshi adults
bioRxiv, 2018Co-Authors: Rasheduzzaman Rashu, Fahima Chowdhury, Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Jason B Harris, Anik Paul, Mohammad Rubel Hoq, Lazina Hossain, Stephen B CalderwoodAbstract:Abstract Vibrio Cholerae O1 can cause life threatening diarrheal disease if left untreated. A long lasting immune response, producing 3-5 years of protection from subsequent, symptomatic disease following natural infection, is mediated by B cell mediated humoral immunity. T cells can play critical roles in inducing such immunity. However, the mechanism of T cell dependent B cell maturation and whether a key sub-population of T cells are involved is not well established in Cholera. We hypothesized that a specific population of T cells, follicular helper T (Tfh) cells, are involved in B cell maturation following Cholera; we used flow cytometry, culture and colorimetric assays to address this question. We found that V. Cholerae infection induces significant increase in circulating Tfh cells expressing B cell maturation associated protein CD40L early in disease. The increased Tfh cells expressing CD40L recognize Cholera toxin most prominently, with lessened responses to two antigens tested, V. Cholerae membrane preparation (MP) and Vibrio Cholerae cytolysin (VCC). We further showed that early induction of Tfh cells and CD40L was associated with later memory B cell responses to same antigens. Lastly, we demonstrated in vitro that Tfh cells isolated after Cholera can stimulate class switching of cocultured, isolated B cells from patients with Cholera, leading to production of the more durable IgG antibody isotype. These studies were conducted on circulating Tfh cells; future studies will be directed at examining role of Tfh cells during Cholera directly in the gut mucosa of biopsied samples, at the single cell level if feasible.
-
antibody secreting cell responses after vibrio Cholerae o1 infection and oral Cholera vaccination in adults in bangladesh
Clinical and Vaccine Immunology, 2013Co-Authors: Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Atiqur Rahman, Rasheduzzaman Rashu, Kamrul Islam, Regina C Larocque, Jens WrammertAbstract:Infection with Vibrio Cholerae and oral Cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. Cholerae-specific duodenal antibodies up to 6 months after V. Cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. Cholerae infection using a flow cytometrically defined population and compared V. Cholerae-specific responses in adult patients with V. Cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either Cholera toxin B subunit (CtxB) or V. Cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. Cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. Cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. Cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where Cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. Cholerae infection is endemic and those where it is not.
Regina C Larocque - One of the best experts on this subject based on the ideXlab platform.
-
anti o specific polysaccharide osp immune responses following vaccination with oral Cholera vaccine cvd 103 hgr correlate with protection against Cholera after infection with wild type vibrio Cholerae o1 el tor inaba in north american volunteers
PLOS Neglected Tropical Diseases, 2018Co-Authors: Richelle C Charles, Meagan Kelly, Pavol Kovac, Taufiqur Rahman Bhuiyan, Kamrul Islam, Motaher Hossain, Leslie Mayo M Smith, Regina C LarocqueAbstract:Background Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio Cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. Cholerae are involved in mediating protection against Cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral Cholera vaccine CVD 103-HgR, and whether such responses correlate with protection against Cholera. Methodology We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral Cholera vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. Cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination. Principal findings Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = −0.44, P = 0.002; r = −0.36, P = 0.01; respectively), and none of 27 vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe Cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01). Conclusion Oral vaccination with live attenuated Cholera vaccine CVD 103-HgR induces antibodies that target V. Cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. Cholerae O1. Trial registration ClinicalTrials.gov NCT01895855
-
vibrio Cholerae serogroup o139 isolation from Cholera patients and asymptomatic household family members in bangladesh between 2013 and 2014
PLOS Neglected Tropical Diseases, 2015Co-Authors: Fahima Chowdhury, Yasmin Ara Begum, Regina C Larocque, Muhammad Ikhtear Uddin, Rajib Biswas, Alison E Mather, Muhammad Asaduzzaman, Nabilah Ibnat Baby, Salma Sharmin, Jason B HarrisAbstract:Background Cholera is endemic in Bangladesh, with outbreaks reported annually. Currently, the majority of epidemic Cholera reported globally is El Tor biotype Vibrio Cholerae isolates of the serogroup O1. However, in Bangladesh, outbreaks attributed to V. Cholerae serogroup O139 isolates, which fall within the same phylogenetic lineage as the O1 serogroup isolates, were seen between 1992 and 1993 and in 2002 to 2005. Since then, V. Cholerae serogroup O139 has only been sporadically isolated in Bangladesh and is now rarely isolated elsewhere.
-
antibody secreting cell responses after vibrio Cholerae o1 infection and oral Cholera vaccination in adults in bangladesh
Clinical and Vaccine Immunology, 2013Co-Authors: Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Atiqur Rahman, Rasheduzzaman Rashu, Kamrul Islam, Regina C Larocque, Jens WrammertAbstract:Infection with Vibrio Cholerae and oral Cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. Cholerae-specific duodenal antibodies up to 6 months after V. Cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. Cholerae infection using a flow cytometrically defined population and compared V. Cholerae-specific responses in adult patients with V. Cholerae O1 infection and vaccinees who received the OCV Dukoral (Crucell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the cells recognized either Cholera toxin B subunit (CtxB) or V. Cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. Cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. Cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. Cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where Cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. Cholerae infection is endemic and those where it is not.
-
transcutaneous immunization with a vibrio Cholerae o1 ogawa synthetic hexasaccharide conjugate following oral whole cell Cholera vaccination boosts vibriocidal responses and induces protective immunity in mice
Clinical and Vaccine Immunology, 2012Co-Authors: Richelle C Charles, Daniel T Leung, Anuj Kalsy, Jason B Harris, Abdullah A Tarique, Mohammad Arifuzzaman, Sean M Rollins, Regina C LarocqueAbstract:ABSTRACT A shortcoming of currently available oral Cholera vaccines is their induction of relatively short-term protection against Cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio Cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell Cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative Cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. Cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. Cholerae LPS IgG, IgM, and IgA ( P P P P
-
familial aggregation of vibrio Cholerae associated infection in matlab bangladesh
Journal of Health Population and Nutrition, 2010Co-Authors: Kazi Mizanur Rahman, Firdausi Qadri, Stephen B Calderwood, Edward T Ryan, Priya Duggal, Jason B Harris, Sajal K Saha, Peter Kim Streatfield, Mohammad Yunus, Regina C LarocqueAbstract:Vibrio Cholerae is a major cause of diarrhoeal illness in endemic regions, such as Bangladesh. Understanding the factors that determine an individual's susceptibility to infection due to V. Cholerae may lead to improved prevention and control strategies. Increasing evidence suggests that human genetic factors affect the severity of V. Cholerae-associated infection. This study, therefore, sought to characterize the heritable component of susceptibility to infection due to V. Cholerae using the Matlab Health and Demographic Surveillance System database of the International Centre for Diarrhoeal Disease Research, Bangladesh. In total, 144 pedigrees that included a Cholera patient and 341 pedigrees without a Cholera patient were evaluated during 1 January–31 December 1992. The odds of the sibling of a patient being admitted with Cholera were 7.67 times the odds of the sibling of an unaffected individual being admitted with Cholera [95% confidence interval (CI) 2.40–24.5, p<0.001], after adjustment for gender, age, socioeconomic status, and hygiene practices. Although exposure to environmental reservoirs is essential in the epidemiology of Cholera, household-specific factors, such as familial relatedness to an index case, may also be important determinants of risk of Cholera. Further analysis of human genetic factors that contribute to susceptibility to Cholera may be productive.