| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Kang, S, et al.
(författare)
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Are better existing WASH practices in urban slums associated with a lower long-term risk of severe cholera? A prospective cohort study with 4 years of follow-up in Mirpur, Bangladesh
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e060858-
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the association between existing household water quality, sanitation and hygiene (WASH) practices and severe cholera risk in a dense urban slum where cholera is highly endemic.Design, setting and participantsWe assembled a large prospective cohort within a cluster randomised trial evaluating the effectiveness of oral cholera vaccine. Our dynamic cohort population (n=193 576) comprised individuals living in the ‘non-intervention’ clusters of the trial, and were followed over 4 years. This study was conducted in a dense urban slum community of Dhaka, Bangladesh and cholera surveillance was undertaken in 12 hospitals serving the study area.Primary outcome measureFirst severe cholera episode detected during follow-up period.MethodsWe applied a machine learning algorithm on a training subpopulation (n=96 943) to develop a binary (‘better’, ‘not better’) composite WASH variable predictive of severe cholera. The WASH rule was evaluated for performance in a separate validation subpopulation (n=96 633). Afterwards, we used Cox regression models to evaluate the association between ‘better’ WASH households and severe cholera risk over 4 years in the entire study population.ResultsThe ‘better’ WASH rule found that water quality and access were the most significant factors associated with severe cholera risk. Members of ‘better’ WASH households, constituting one-third of the population, had a 47% reduced risk of severe cholera (95% CI: 29 to 69; p<0.001), after adjusting for covariates. The protective association between living in a ‘better’ WASH household and severe cholera persisted in all age groups.ConclusionsSalutary existing household WASH practices were associated with a significantly reduced long-term risk of severe cholera in an urban slum of Dhaka. These findings suggest that WASH adaptations already practised in the community may be important for developing and implementing effective and sustainable cholera control programmes in similar settings.Trial registration numberThis article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.govNCT01339845
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| 9. |
- Akhtar, M., et al.
(författare)
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Evaluation of the safety and immunogenicity of the oral inactivated multivalent enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi adults in a double-blind, randomized, placebo-controlled Phase I trial using electrochemiluminescence and ELISA assays for immunogenicity analyses
- 2019
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 37:37, s. 5645-5656
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Tidskriftsartikel (refereegranskat)abstract
- The safety and immunogenicity of the second generation oral enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX, consisting of inactivated recombinant E. coli strains over-expressing the colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the heat labile toxoid LCTBA, were evaluated in Bangladeshi volunteers. To enable analysis of antibody responses against multiple vaccine antigens for subsequent use in small sample volumes from children, a sensitive electrochemiluminescence (ECL) assay for analysis of intestine-derived antibody-secreting cell responses using the antibodies in lymphocyte secretions (ALS) assay was established using Meso Scale Discovery technology. Three groups of Bangladeshi adults (n = 15 per group) received two oral doses of ETVAX with or without double mutant LT (dmLT) adjuvant or placebo in the initial part of a randomized, double-blind, placebo-controlled, age-descending, dose-escalation trial. CF- and LTB-specific ALS and plasma IgA responses were analyzed by ECL and/or ELISA. ETVAX was safe and well tolerated in the adults. Magnitudes of IgA ALS responses determined by ECL and ELISA correlated well (r = 0.85 to 0.98 for the five primary antigens, P < 0.001) and ECL was selected as the ALS readout method. ALS IgA responses against each of the primary antigens were detected in 87-100% of vaccinees after the first and in 100% after the second vaccine dose. Plasma IgA responses against different CFs and LTB were observed in 62-93% and 100% of vaccinees, respectively. No statistically significant adjuvant effect of dmLT on antibody responses to any antigen was detected, but the overall anti-genic breadth of the plasma IgA response tended to favor the adjuvanted vaccine when responses to 4 or more or 5 vaccine antigens were considered. Responses in placebo recipients were infrequent and mainly detected against single antigens. The promising results in adults supported testing ETVAX in descending age groups of children.
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| 10. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Evaluation of immune responses to an oral typhoid vaccine, Ty21a, in children from 2 to 5 years of age in Bangladesh
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 32:9, s. 1055-1060
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Tidskriftsartikel (refereegranskat)abstract
- Young children are very susceptible to typhoid fever, emphasizing the need for vaccination in under five age groups. The parenteral Vi polysaccharide vaccine is not immunogenic in children under 2 years and the oral Ty21a vaccine (Vivotif) available in capsular formulation is only recommended for those over 5 years. We studied immune responses to a liquid formulation of Ty21a in children 2-5 years of age. Since children in developing countries are in general hypo responsive to oral vaccines, the study was designed to determine if anti-helminthic treatment prior to vaccination, improves responses. In a pilot study in 20 children aged 4-5 years, the immune responses in plasma and in antibody in lymphocyte secretions (ALS) to the enteric coated capsule formulation of Ty21a was found to be comparable to a liquid formulation (P > 0.05). Based on this, children (n = 252) aged ≥2-<3 years and ≥3-<5 years were randomized to receive a liquid formulation of Ty21a with and without previous anti-helminthic treatment. The vaccine was well tolerated with only a few mild adverse events recorded in <1% of the children. De-worming did not improve immune responses and both age groups developed 32-71% IgA, IgG, and IgM responses in plasma and 63-86% IgA responses in ALS and stool specimens to a membrane preparation (MP) of Ty21a. An early MP specific proliferative T cell response was also seen. We recommend that safety and efficacy studies with a liquid formulation of the vaccine are carried out in children under five, including those less than two years of age to determine if Ty21a is protective in these age groups and applicable as a public health tool for controlling typhoid fever in high prevalence areas of typhoid fever including Bangladesh. © 2014 Elsevier Ltd. All rights reserved.
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| 11. |
- Chowdhury, F., et al.
(författare)
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A phase I/II study to evaluate safety, tolerability and immunogenicity of Hillchol®, an inactivated single Hikojima strain based oral cholera vaccine, in a sequentially age descending population in Bangladesh
- 2021
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 39:32, s. 4450-4457
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Tidskriftsartikel (refereegranskat)abstract
- Background: The World Health Organization (WHO) recommends the use of oral cholera vaccines (OCVs) as part of an integrated control program, both in highly endemic settings and during cholera epidemics. The available and internationally recommended WHO-prequalified OCVs (Dukoral, Shanchol, Euvichol) contain multiple heat and formalin-killed V. cholerae strains of Inaba and Ogawa serotypes. MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd. in technical collaboration with University of Gothenburg, Sweden has developed a new single strain OCV, Hillchol. This vaccine consists of formaldehyde-inactivated whole cell El Tor V. cholerae O1 bacteria engineered into the Hikojima serotype for stable expression of both the Ogawa (AB) and Inaba (AC) LPS antigens on the bacterial surface. We evaluated the safety and immunogenicity of this novel and potentially much less expensive OCV in comparison with Shanchol. Methods: We conducted a randomized, non-inferiority, age-descending clinical trial of OCV (Hillchol vs. Shanchol) in the Mirpur area of Dhaka city from July 2016 to May 2017. This study was carried out in three different age cohorts (1–<5, 5–17 and ≥18 years old). Two doses of vaccine were given at 14 days intervals to 560 healthy participants. Findings: No serious adverse events were reported. There were no significant differences in the rates of adverse events between the test vaccine (Hillchol) and the comparator (Shanchol) group. Serum vibriocidal antibody responses in all age groups combined were comparable for all the O1 Ogawa (59% vs. 67%; 90% CI of difference: −14.55, −0.84) and Inaba (70% vs. 71%; 90% CI of difference: −7.24, 5.77) serotypes, showing that the Hillchol vaccine was non-inferior to Shanchol. This new vaccine was also non-inferior to Shanchol in the different age strata. Conclusion: The safety and immunogenicity profile of the new OCV Hillchol is comparable to Shanchol in persons residing in a cholera-endemic setting. ClinicalTrials.gov number: NCT02823899. © 2021
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| 12. |
- Haselbeck, AH, et al.
(författare)
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Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics
- 2021
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Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).
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| 13. |
- Alam, M., et al.
(författare)
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Antigen-Specific Memory B-cell Responses to Enterotoxigenic Escherichia coli Infection in Bangladeshi Adults
- 2014
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple infections with diverse enterotoxigenic E. coli (ETEC) strains lead to broad spectrum protection against ETEC diarrhea. However, the precise mechanism of protection against ETEC infection is still unknown. Therefore, memory B cell responses and affinity maturation of antibodies to the specific ETEC antigens might be important to understand the mechanism of protection. Methodology: In this study, we investigated the heat labile toxin B subunit (LTB) and colonization factor antigens (CFA/I and CS6) specific IgA and IgG memory B cell responses in Bangladeshi adults (n = 52) who were infected with ETEC. We also investigated the avidity of IgA and IgG antibodies that developed after infection to these antigens. Principal Findings: Patients infected with ETEC expressing LT or LT+heat stable toxin (ST) and CFA/I group or CS6 colonization factors developed LTB, CFA/I or CS6 specific memory B cell responses at day 30 after infection. Similarly, these patients developed high avidity IgA and IgG antibodies to LTB, CFA/I or CS6 at day 7 that remained significantly elevated at day 30 when compared to the avidity of these specific antibodies at the acute stage of infection (day 2). The memory B cell responses, antibody avidity and other immune responses to CFA/I not only developed in patients infected with ETEC expressing CFA/I but also in those infected with ETEC expressing CFA/I cross-reacting epitopes. We also detected a significant positive correlation of LTB, CFA/I and CS6 specific memory B cell responses with the corresponding increase in antibody avidity. Conclusion: This study demonstrates that natural infection with ETEC induces memory B cells and high avidity antibodies to LTB and colonization factor CFA/I and CS6 antigens that could mediate anamnestic responses on re-exposure to ETEC and may help in understanding the requirements to design an effective vaccination strategies.
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| 14. |
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| 15. |
- Girardi, P., et al.
(författare)
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Anti-Toxin Responses to Natural Enterotoxigenic Escherichia coli (ETEC) Infection in Adults and Children in Bangladesh
- 2023
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Ingår i: Microorganisms. - 2076-2607. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- A sero-epidemiology study was conducted in Dhaka, Bangladesh between January 2020 and February 2021 to assess the immune responses to ETEC infection in adults and children. (1) Background: Enterotoxigenic Escherichia coli infection is a main cause of diarrheal disease in endemic countries. The characterization of the immune responses evoked by natural infection can guide vaccine development efforts. (2) Methods: A total of 617 adult and 480 pediatric diarrheal patients were screened, and 43 adults and 46 children (below 5 years of age) with an acute ETEC infection completed the study. The plasma samples were analyzed for antibody responses against the ETEC toxins. (3) Results: Heat-stable toxin (ST)-positive ETEC is the main cause of ETEC infection in adults, unlike in children in an endemic setting. We detected very low levels of anti-ST antibodies, and no ST-neutralizing activity. However, infection with ETEC strains expressing the heat-labile toxin (LT) induced systemic antibody responses in less than 25% of subjects. The antibody levels against LTA and LTB, as well as cholera toxin (CT), correlated well. The anti-LT antibodies were shown to have LT- and CT- neutralizing activity. The antibody reactivity against linear LT epitopes did not correlate with toxin-neutralizing activity. (4) Conclusions: Unlike LT, ST is a poor antigen and even adults have low anti-ST antibody levels that do not allow for the detection of toxin-neutralizing activity.
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| 16. |
- Mani, S., et al.
(författare)
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Role of antigen specific T and B cells in systemic and mucosal immune responses in ETEC and Shigella infections, and their potential to serve as correlates of protection in vaccine development
- 2019
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 37:34, s. 4787-4793
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Tidskriftsartikel (refereegranskat)abstract
- The generation of robust systemic and mucosal antibody and cell-mediated immune (CMI) responses that are protective, long-lasting, and can quickly be recalled upon subsequent re-exposure to the cognate antigen is the key to the development of effective vaccine candidates. These responses, whether they represent mechanistic or non-mechanistic immunological correlates of protection, usually entail the activation of T cell memory and effector subsets (T-CMI) and induction of long-lasting memory B cells. However, for ETEC and Shigella, the precise role of these key immune cells in primary and secondary (anamnestic) immune responses remains ill-defined. A workshop to address immune correlates for ETEC and Shigella, in general, and to elucidate the mechanistic role of T-cell subsets and B-cells, both systemically and in the mucosal microenvironment, in the development of durable protective immunity against ETEC and Shigella was held at the recent 2nd Vaccines against Shigella and ETEC (VASE) conference in June 2018. This report is a summary of the presentations and the discussion that ensued at the workshop. © 2019
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| 17. |
- Qadri, F., et al.
(författare)
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Enterotoxigenic Escherichia coli and Vibrio cholerae diarrhea, Bangladesh, 2004
- 2005
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Ingår i: Emerg Infect Dis. ; 11:7, s. 1104-7
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Tidskriftsartikel (refereegranskat)abstract
- Flooding in Dhaka in July 2004 caused epidemics of diarrhea. Enterotoxigenic Escherichia coli (ETEC) was almost as prevalent as Vibrio cholerae O1 in diarrheal stools. ETEC that produced heat-stable enterotoxin alone was most prevalent, and 78% of strains had colonization factors. Like V. cholerae O1, ETEC can cause epidemic diarrhea.
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| 18. |
- Qadri, F., et al.
(författare)
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Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: a double-blind, randomised, placebo-controlled phase 1/2 trial
- 2020
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Ingår i: Lancet Infectious Diseases. - : Elsevier BV. - 1473-3099. ; 20:2, s. 208-219
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Tidskriftsartikel (refereegranskat)abstract
- Background Enterotoxigenic Escherichia coil causes diarrhoea, leading to substantial mortality and morbidity in children, but no specific vaccine exists. This trial tested an oral, inactivated, enterotoxigenic E coli vaccine (ETVAX), which has been previously shown to be safe and highly immuongenic in Swedish and Bangladeshi adults. We tested the safety and immunogenicity of ETVAX, consisting of four E coli strains overexpressing the most prevalent colonisation factors (CFA/I, CS3, CSS, and CS6) and a toxoid (LCTBA) administered with or without a double-mutant heat-labile enterotoxin (dmLT) as an adjuvant, in Bangladeshi children. Methods We did a randomised, double-blind, placebo-controlled, dose-escalation, age-descending, phase 1/2 trial in Dhaka, Bangladesh. Healthy children in one of three age groups (24-59 months, 12-23 months, and 6-11 months) were eligible. Children were randomly assigned with block randomisation to receive either ETVAX, with or without dmLT, or placebo. ETVAX (half [5.5 x 10(10) cells], quarter [2.5 x 10(10) cells], or eighth [1.25 x 10(10) cells] adult dose), with or without dmLT adjuvant (2.5 mu g, 5.0 mu g, or 10.0 mu g), or placebo were administered orally in two doses 2 weeks apart. Investigators and participants were masked to treatment allocation. The primary endpoint was safety and tolerability, assessed in all children who received at least one dose of vaccine. Antibody responses to vaccine antigens, defined as at least a two-times increase in antibody levels between baseline and post-immunisation, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov , NCT02531802. Findings Between Dec 7, 2015, and Jan 10, 2017, we screened 1500 children across the three age groups, of whom 430 were enrolled and randomly assigned to the different treatment groups (130 aged 24-59 months, 100 aged 12-23 months, and 200 aged 6-11 months). All participants received at least one dose of vaccine. No solicited adverse events occurred that were greater than moderate in severity, and most were mild. The most common solicited event was vomiting (ten [8%] of 130 patients aged 24-59 months, 13 [13%] of 100 aged 12-23 months, and 29 115%1 of 200 aged 6-11 months; mostly of mild severity), which appeared related to dose and age. The addition of dmLT did not modify the safety profile. Three serious adverse events occurred but they were not considered related to the study drug. Mucosal IgA antibody responses in lymphocyte secretions were detected against all primary vaccine antigens (CFA/I, CS3, CSS, CS6, and the LCTBA toxoid) in most participants in the two older age groups, whereas such responses to four of the five antigens were less frequent and of lower magnitude in infants aged 6-11 months than in older children. Faecal secretory IgA immune responses were recorded against all vaccine antigens in infants aged 6-11 months. 78 (56%) of 139 infants aged 6-11 months who were vaccinated developed mucosal responses against at least three of the vaccine antigens versus 14 (29%) of 49 of the infants given placebo. Addition of the adjuvant dmLT enhanced the magnitude, breadth, and kinetics (based on number of responders after the first dose of vaccine) of immune responses in infants. Interpretation The encouraging safety and immunogenicity of ETVAX and benefit of dmLT adjuvant in young children support its further assessment for protective efficacy in children in enterotoxigenic E coli-endemic areas. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Ahmed, D., et al.
(författare)
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Presence of enterotoxigenic Escherichia coli in biofilms formed in water containers in poor households coincides with epidemic seasons in Dhaka
- 2013
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Ingår i: Journal of Applied Microbiology. - : Oxford University Press (OUP). - 1364-5072. ; 114:4, s. 1223-1229
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Tidskriftsartikel (refereegranskat)abstract
- Aims The objective of this study was to investigate if biofilms may be potential reservoirs for the waterborne pathogen enterotoxigenic Escherichia coli (ETEC) in household water in Dhaka, Bangladesh. Methods and Results Biofilms formed on submerged glass slides. Mature biofilms were found significantly more often on glass slides collected in the monsoon period between the two annual ETEC peaks in Bangladesh, that is, between May and August than the rest of the year (P < 0·03). Sixty-four per cent (49/77) of all biofilms analysed by quantitative real-time PCR were positive for ETEC. Significantly more ETEC-PCR positive biofilms were found during the epidemic peaks and during flooding periods than the rest of the year (P < 0·008). Planktonic ETEC was present in the household water during all seasons, but there was no correlation between presence or numbers of ETEC in water and the epidemic peaks. Conclusions We conclude that ETEC is continuously present in water and biofilms in household water reservoirs in Dhaka, which has a high prevalence of ETEC diarrhoea. The frequency of biofilms with ETEC was significantly associated (P < 0·008) with seasonal epidemic peaks of ETEC diarrhoea. Significance and impact of the study We show for the first time that enterotoxigenic Escherichia coli (ETEC), the causative agent of acute watery diarrhoea and travellers' diarrhoea is present in biofilms in household water tanks in Dhaka, Bangladesh.
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| 23. |
- Akhtar, M., et al.
(författare)
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dmLT Adjuvant Enhances Cytokine Responses to T Cell Stimuli, Whole Cell Vaccine Antigens and Lipopolysaccharide in Both Adults and Infants
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Enhancement of mucosal immune responses in children and infants using novel adjuvants such as double mutant heat labile toxin (dmLT) is an important goal in the enteric vaccine field. dmLT has been shown to enhance mucosal IgA responses to the oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX. dmLT can enhance IL-17A production from adult T cells, which may increase the production and secretion of mucosal IgA antibodies. However, the adjuvant mechanism remains to be fully elucidated and might differ between infants and adults due to age-related differences in the development of the immune system. The main objective of this study was to determine how dmLT influences antigen presenting cells and T cells from infants compared to adults, and the role of IL-1 beta for mediating the adjuvant activity. Peripheral blood mononuclear cells (PBMCs) from Bangladeshi infants (6-11 months) and adults (18-40 years) were stimulated with the mitogen phytohaemagglutinin (PHA), the superantigen Staphylococcal enterotoxin B (SEB), ETVAX whole cell component (WCC) or E. coli lipopolysaccharide (LPS) +/- dmLT, and cytokine production was measured using ELISA and electrochemiluminescence assays. The adjuvant dmLT significantly enhanced SEB- and PHA-induced IL-17A, but not IFN-gamma responses, in PBMCs from both infants and adults. Blocking experiments using an IL-1 receptor antagonist demonstrated the importance of IL-1 signaling for the adjuvant effect. dmLT, ETVAX WCC and LPS induced dose-dependent IL-1 beta responses of comparable magnitudes in infant and adult cells. Depletion experiments suggested that IL-1 beta was mainly produced by monocytes. dmLT enhanced IL-1 beta responses to low doses of WCC and LPS, and the adjuvant effect appeared over a wider dose-range of WCC in infants. dmLT and WCC also induced IL-6, IL-23 and IL-12p70 production in both age groups and dmLT tended to particularly enhance IL-23 responses to WCC. Our results show that dmLT can induce IL-1 beta as well as other cytokines, which in turn may enhance IL-17A and potentially modulate other immunological responses in both infants and adults. Thus, dmLT may have an important function in promoting immune responses to the ETVAX vaccine, as well as other whole cell- or LPS-based vaccines in infants in low- and middle-income countries.
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| 24. |
- Akhtar, M., et al.
(författare)
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Kinetics of antibody-secreting cell and fecal IgA responses after oral cholera vaccination in different age groups in a cholera endemic country
- 2017
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 35:2, s. 321-328
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Tidskriftsartikel (refereegranskat)abstract
- Immune responses to oral enteric vaccines in children and infants may be influenced by factors such as age, previous priming with related microorganisms and breast feeding. In this study, we aimed to determine optimal time points to assess immune responses to oral enteric vaccines in different clinical specimens. This was done by investigating antibody secreting cell (ASC) and fecal antibody responses on different days after vaccination using the licensed oral cholera vaccine Dukoral, containing cholera toxin B-subunit (rCTB) and inactivated Vibrio cholerae bacteria, as a model vaccine. Two vaccine doses were given 2 weeks apart to infants (6-11 months), young children (12-18 months), toddlers (19 months-5 years) and adults in a cholera endemic country (Bangladesh). IgA ASC responses, as determined by the antibodies in lymphocyte supernatant (ALS) assay, plasma IgA and IgG responses and secretory IgA (SIgA) responses in extracts of fecal samples were evaluated 4/5 and 7 days after each vaccination. After the first vaccine dose, anti-CTB ALS IgA responses in adults and toddlers were high and comparable on day 5 and 7, while responses were low and infrequent in young children. After the second dose, highest ALS responses were detected on day 5 among the time points studied in all age groups and the responses declined until day 7. In contrast, plasma IgA and IgG anti-CTB responses were high both on day 5 and 7 after the second dose. Fecal SIgA responses in young children and infants were highest on day 7 after the second dose. Our results suggest that ASC/ALS responses to two doses of the oral cholera vaccine Dukoral and related oral vaccines should be analyzed earlier than previously recommended (day 7) at all ages. Fecal antibody responses should preferably be analyzed later than ASC/ALS responses to detect the highest antibody responses. (C) 2016 Elsevier Ltd. All rights reserved.
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| 25. |
- Akter, S., et al.
(författare)
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The frequency of circulating integrin alpha 4 beta 7(+) cells correlates with protection against Helicobacter pylori infection in immunized mice
- 2019
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic Helicobacter pylori infection is the cause of peptic ulcers in a subpopulation of individuals and a risk factor for the development of gastric cancer. A vaccine against H pylori infection can prevent the acquisition of the infection and protect against reinfections. Clinical trials to date evaluating the efficacy of H pylori vaccines in human challenge models have shown moderate to poor protection with difficulties in predicting efficacy. Thus, while further studies are needed to design an effective vaccine, we also need to find relevant correlates for vaccine efficacy. Objective To find immune correlates to vaccine efficacy, the frequencies of neutrophils, eosinophils and inflammatory monocytes and CD4(+) T-cell memory and mucosa homing integrin alpha 4 beta 7(+) cells were assessed by flow cytometry in the blood of mice after vaccination. Materials and Methods H pylori antigens and cholera toxin or the multiple mutant CT (mmCT) were administered via the sublingual (SL) and intragastric route (IG). The vaccinated mice were infected with H pylori strain SS1 bacteria, and colonization in the stomach and immune responses were evaluated. Results The H pylori vaccine was effective in reducing bacterial load in the stomach of mice and enhancing immune responses compared to unvaccinated infection controls. In the blood of mice after SL or IG route of vaccination, we observed changes in frequencies of innate and adaptive immune cell subsets compared to infection controls. Remarkably, the frequency of circulating mucosal homing alpha 4 beta 7(+)CD4(+) T cells after vaccination correlated with low bacterial load in the stomach of individual mice irrespective of the immunization route. Conclusions Our study shows that the innate and adaptive immune cell subsets can be measured in the blood after vaccination and that increased frequency of alpha 4 beta 7(+)CD4(+) in the blood after immunization could be used as a predictive marker for the efficacy of vaccine against H pylori infection.
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| 26. |
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| 27. |
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| 28. |
- Albert, MJ, et al.
(författare)
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Rapid detection of Vibrio cholerae O139 Bengal from stool specimens by PCR
- 1997
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Ingår i: Journal of clinical microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 35:6, s. 1633-1635
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study using pure bacterial cultures in a PCR assay, a primer pair corresponding to a unique chromosomal region of Vibrio cholerae O139 Bengal generated an amplicon from only V. cholerae O139 Bengal. PCR with the same primer pair was used to screen 180 diarrheal stool specimens. All the 67 V. cholerae O139 culture-positive stool specimens were positive by PCR, and the remaining specimens, which contained either other recognized enteric pathogens or no pathogens, were all negative by PCR.
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| 29. |
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| 30. |
- Begum, Y. A., et al.
(författare)
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In situ Analyses Directly in Diarrheal Stool Reveal Large Variations in Bacterial Load and Active Toxin Expression o Enterotoxigenic Escherichia coli and Vibrio cholerae
- 2018
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Ingår i: Msphere. - 2379-5042. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The bacterial pathogens enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae are major causes of diarrhea. ETEC causes diarrhea by production of the heat-labile toxin (LT) and heat-stable toxins (STh and STp), while V. cholerae produces cholera toxin (CT). In this study, we determined the occurrence and bacterial doses of the two pathogens and their respective toxin expression levels directly in liquid diarrheal stools of patients in Dhaka, Bangladesh. By quantitative culture and real-time quantitative PCR (qPCR) detection of the toxin genes, the two pathogens were found to coexist in several of the patients, at concentrations between 10(2) and 10(8) bacterial gene copies per ml. Even in culture-negative samples, gene copy numbers of 10(2) to 10(4) of either ETEC or V. cholerae toxin genes were detected by qPCR. RNA was extracted directly from stool, and gene expression levels, quantified by reverse transcriptase qPCR (RT-qPCR), of the genes encoding CT, LT, STh, and STp showed expression of toxin genes. Toxin enzyme-linked immunosorbent assay (ELISA) confirmed active toxin secretion directly in the liquid diarrhea. Analysis of ETEC isolates by multiplex PCR, dot blot analysis, and genome sequencing suggested that there are genetic ETEC profiles that are more commonly found as dominating single pathogens and others that are coinfectants with lower bacterial loads. The ETEC genomes, including assembled genomes of dominating ETEC isolates expressing LT/STh/CS5/CS6 and LT/CS7, are provided. In addition, this study highlights an emerging important ETEC strain expressing LT/STp and the novel colonization factor CS27b. These findings have implications for investigations of pathogenesis as well as for vaccine development.& para;& para;IMPORTANCE The cause of diarrhea! disease is usually determined by screening for several microorganisms by various methods, and sole detection is used to assign the agent as the cause of disease. However, it has become increasingly clear that many infections are caused by coinfections with several pathogens and that the dose of the infecting pathogen is important. We quantified the absolute numbers of enterotoxigenic E. coil (ETEC) and Vibrio cholerae directly in diarrheal fluid. We noted several events where both pathogens were found but also a large dose dependency. In three samples, we found ETEC as the only pathogen sought for. These isolates belonged to globally distributed ETEC clones and were the dominating species in stool with active toxin expression. This suggests that certain superior virulent ETEC lineages are able to outcompete the gut microbiota and be the sole cause of disease and hence need to be specifically monitored.
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| 31. |
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| 32. |
- Begum, Y. A., et al.
(författare)
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Resistance Pattern and Molecular Characterization of Enterotoxigenic Escherichia coli (ETEC) Strains Isolated in Bangladesh
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Enterotoxigenic Escherichia coli (ETEC) is a common cause of bacterial infection leading to acute watery diarrhea in infants and young children as well as in travellers to ETEC endemic countries. Ciprofloxacin is a broad-spectrum antimicrobial agent nowadays used for the treatment of diarrhea. This study aimed to characterize ciprofloxacin resistant ETEC strains isolated from diarrheal patients in Bangladesh. A total of 8580 stool specimens from diarrheal patients attending the icddr, b Dhaka hospital was screened for ETEC between 2005 and 2009. PCR and Ganglioside GM1-Enzyme Linked Immuno sorbent Assay (ELISA) was used for detection of Heat labile (LT) and Heat stable (ST) toxins of ETEC. Antimicrobial susceptibilities for commonly used antibiotics and the minimum inhibitory concentration (MIC) of nalidixic acid, ciprofloxacin and azithromycin were examined. DNA sequencing of representative ciprofloxacin resistant strains was performed to analyze mutations of the quinolone resistance-determining region of gyrA, gyrB, parC and parE. PCR was used for the detection of qnr, a plasmid mediated ciprofloxacin resistance gene. Clonal variations among ciprofloxacin resistant (Cip(R)) and ciprofloxacin susceptible (Cip(S)) strains were determined by Pulsed-field gel electrophoresis (PFGE). Among 1067 (12%) ETEC isolates identified, 42% produced LT/ST, 28% ST and 30% LT alone. Forty nine percent (n = 523) of the ETEC strains expressed one or more of the 13 tested colonization factors (CFs) as determined by dot blot immunoassay. Antibiotic resistance of the ETEC strains was observed as follows: ampicillin 66%, azithromycin 27%, ciprofloxacin 27%, ceftriazone 13%, cotrimaxazole 46%, doxycycline 44%, erythromycin 96%, nalidixic acid 83%, norfloxacin 27%, streptomycin 48% and tetracycline 42%. Resistance to ciprofloxacin increased from 13% in 2005 to 34% in 2009. None of the strains was resistant to mecillinam. The MIC of the nalidixic acid and ciprofloxacin of representative Cip(R) strains were 256 mu g/ml and 32 mu g/ml respectively. A single mutation (Ser(83)-Leu) in gyrA was observed in the nalidixic acid resistant ETEC strains. In contrast, double mutation in gyrA (Ser(83)-Leu, Asp(87)-Asn) and a single mutation in parC (Glu(84)-Ly) were found in ciprofloxacin resistant strains. Mutation of gyrB was not found in either the nalidixic acid or ciprofloxacin resistant strains. None of the ciprofloxacin resistant strains was found to be positive for the qnr gene. Diverse clones were identified from all ciprofloxacin resistant strains by PFGE analysis in both CF positive and CF negative ETEC strains. Emergence of ciprofloxacin resistant ETEC strains results in a major challenge in current treatment strategies of ETEC diarrhea.
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| 33. |
- Begum, Y. A., et al.
(författare)
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Shift in Phenotypic Characteristics of Enterotoxigenic Escherichia coli (ETEC) Isolated from Diarrheal Patients in Bangladesh
- 2014
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Ingår i: Plos Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2735. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of bacterial diarrhea. Over the last decade, from 1996 to 2012, changes in the virulence antigen properties of ETEC such as heat labile (LT) and heat stable (ST) toxins, colonization factors (CFs), and 'O'-serogroups have been observed. The aim of this prospective study was to compare changes in antigenic profiles of ETEC strains isolated from a 2% surveillance system at the icddr,b hospital in Dhaka, Bangladesh between 2007-2012 and an earlier time period of 1996-1998 conducted at the same surveillance site. Methodology: In the surveillance system every 50th patient attending the hospital was screened for major enteric pathogens including ETEC, Vibrio cholerae, Shigella spp. and Salmonella spp. from January 2007 to December 2012. Principal Findings: Of the 15,152 diarrheal specimens tested between 2007-2012, the overall rate of ETEC isolation was 11%; of these, 43% were LT/ST, 27% LT and 30% ST positive. Isolation rate of ST-ETEC (p<0.009) and LT/ST ETEC (p<0.011) during 2007-2012 period differed significantly compared to those seen between 1996-1998. In comparison to the 19961998 period, difference in CF profile of ETEC isolates during 2007-2012 was observed particularly for strains expressing CS7 (12.4%), CS14 (9.5%) and CS17 (10.0%). The predominant CF types were CS5+CS6, CFA/I, CS7, CS17, CS1+CS3, CS6 and CS14. The most common serogroups among the CF positive ETEC isolates were O115, O114, O6, O25 and O8. A strong association was found between CFs and 'O' serogroups i.e. between CS5+CS6 and (O115 and O126); CS7 and (O114), CFA/I and (O78 and O126), CS17 and (O8 and O167) and CS1/CS2+CS3 and (O6). Conclusion: The analyses show a shift in prevalence of antigenic types of ETEC over the study period; the information is important in designing effective ETEC vaccines with broad protective coverage.
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| 34. |
- Bhuiyan, T. R., et al.
(författare)
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Assessing antigen specific HLA-DR plus antibody secreting cell (DR plus ASC) responses in whole blood in enteric infections using an ELISPOT technique
- 2018
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 20:2, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Antibody secreting cells (ASCs) generate antibodies in an antigen-specific manner as part of the adaptive immune response to infections, and these cells increase their surface expression of HLA-DR. We have studied this parameter (HLA-DR+ASC) in patients with recent diarrheal infection using immuno-magnetic cell sorting and an enzyme linked immunospot (ELISPOT) technique that requires only one milliliter of blood. We validated this approach in adult patients with cholera (n = 15) or ETEC diarrhea (n = 30) on days 2, 7 and 30 after showing clinical symptom at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) hospital in Dhaka, and we compared responses to age-matched healthy controls (n = 7). We found that HLA-DRthorn ASC (DR+ASC) responses specific both for T cell-dependent (cholera toxin B subunit), and T cell-independent (lipopolysaccharide) antigens were elevated at day 7 after showing clinical cholera symptom. Similarly, DR+ASCs were elevated against both heat-labile toxin and colonization factors following ETEC infection. We observed significant correlations between antigen-specific DR+ASC responses and antigen-specific, gut homing ASC and plasma antibody responses. This study demonstrates that a simple ELISPOT procedure allows determination of antigen-specific ASC responses using a small volume of whole blood following diarrhea. This technique may be particularly useful in studying DR+ASC responses in young children and infants, either following infection or vaccination. (c) 2017 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
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| 35. |
- Bhuiyan, T. R., et al.
(författare)
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Enumeration of Gut-Homing beta 7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique
- 2016
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Ingår i: Clinical and Vaccine Immunology. - : American Society for Microbiology. - 1556-6811 .- 1556-679X. ; 23:1, s. 27-36
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Tidskriftsartikel (refereegranskat)abstract
- Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates beta 7-positive cells from a small volume of blood would allow measurement of the antigen-specific immune responses in patients with cholera and ETEC infection. beta 7 is a cell surface marker associated with mucosal homing. We isolated beta 7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6- and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination.
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| 36. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Th1 and Th17 responses to Helicobacter pylori in Bangladeshi infants, children and adults
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Both Th1 and Th17 cells are important components of the immune response to Helicobacter pylori (Hp) in adults, but less is known about T cell responses to Hp during early childhood, when the infection is often acquired. We investigated Th1 and Th17 type responses to Hp in adults, children and infants in Bangladesh, where Hp is highly endemic. IL-17 and IFN-γ mRNA levels in gastric biopsies from Hp-infected Bangladeshi adults were analyzed and compared to levels in infected and uninfected Swedish controls. Since biopsies could not be collected from infants and children, cytokine responses in Bangladeshi infants (6-12 months), children (3-5 years) and adults (>19 years) were instead compared by stimulating peripheral blood mononuclear cells (PBMCs) with a Hp membrane preparation (MP) and analyzing culture supernatants by ELISA and cytometric bead array. We found significantly higher expression of IL-17 and IFN-γ mRNA in gastric mucosa of Hpinfected Bangladeshi and Swedish adults compared to uninfected Swedish controls. PBMCs from all age groups produced IL-17 and IFN-γ after MP stimulation, but little Th2 cytokines. IL-17 and IFN-γ were primarily produced by CD4+ T cells, since CD4 + T cell depleted PBMCs produced reduced amounts of these cytokines. Infant cells produced significantly more IL-17, but similar levels of IFN-γ, compared to adult cells after MP stimulation. In contrast, polyclonal stimulation induced lower levels IL-17 and IFN-γ in infant compared to adult PBMCs and CD4+ T cells. The strong IL-17 production in infants after MP stimulation was paralleled by significantly higher production of the IL-17 promoting cytokine IL-1β from infant compared to adult PBMCs and monocytes. In conclusion, these results show that T cells can produce high levels of IL-17 and IFN-β in response to Hp from an early age and indicate a potential role for IL-1β in promoting Th17 responses to Hp during infancy. © 2014 Bhuiyan et al.
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| 37. |
- Chakraborty, S., et al.
(författare)
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Phenotypic and genomic analyses of bacteriophages targeting environmental and clinical CS3-expressing enterotoxigenic Escherichia coli (ETEC) strains
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Diarrhea due to infection of enterotoxigenic Escherichia coli (ETEC) is of great concern in several low and middle-income countries. ETEC infection is considered to be the most common cause of diarrhea in Bangladesh and is mainly spread through contaminated water and food. ETEC pathogenesis is mediated by the expression of enterotoxins and colonization factors (CFs) that target the intestinal mucosa. ETEC can survive for extended time periods in water, where they are likely to be attacked by bacteriophages. Antibiotic resistance is common amongst enteric pathogens and therefore is the use of bacteriophages (phage) as a therapeutic tool an interesting approach. This study was designed to identify novel phages that specifically target ETEC virulence factors. In total, 48 phages and 195 ETEC isolates were collected from water sources and stool samples. Amongst the identified ETEC specific phages, an enterobacteria phage T7, designated as IMM-002, showed a significant specificity towards colonization factor CS3-expressing ETEC isolates. Antibody-blocking and phage-neutralization assays revealed that CS3 is used as a host receptor for the IMM-002 phage. The bacterial CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated) defence mechanism can invoke immunity against phages. Genomic analyses coupled with plaque assay experiments indicate that the ETEC CRISPR-Cas system is involved in the resistance against the CS3-specific phage (IMM-002) and the previously identified CS7-specific phage (IMM-001). As environmental water serves as a reservoir for ETEC, it is important to search for new antimicrobial agents such as phages in environmental water as well as the human gut. A better understanding of how the interplay between ETEC-specific phages and ETEC isolates affects the ETEC diversity, both in environmental ecosystems and within the host, is important for the development of new treatments for ETEC infections.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Lothigius, Åsa, 1980, et al.
(författare)
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Enterotoxigenic Escherichia coli is detectable in water samples from an endemic area by real-time PCR.
- 2008
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Ingår i: Journal of applied microbiology. - : Oxford University Press (OUP). - 1365-2672 .- 1364-5072. ; 104:4, s. 1128-36
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We aimed to develop an assay for sensitive detection and quantification of enterotoxigenic Escherichia coli (ETEC) in different types of water samples. METHODS AND RESULTS: Real-time polymerase chain reaction (PCR) assays with primers against ETEC enterotoxin genes estA (STh) estB (STp) and eltB (LT) were designed and the detection levels were determined to be three bacteria per PCR reaction. Gene copy numbers were estimated to be four (LT), two (STh) and one (STp) per bacteria. Twenty-six household and 13 environmental water samples from Bangladesh were filtered through 0.22-microm filters; DNA was extracted from the filters and analysed by real-time PCR. The results were compared with toxin GM1-enzyme-linked immunosorbent assay (ELISA), in which colonies were tested for toxin production after cultivation of the filters. Out of the 39 samples tested, 18 household and 8 environmental samples were positive for ETEC in real-time PCR, but only 6 positive samples were found with GM1-ELISA. CONCLUSIONS: The method allows for highly sensitive detection and quantification of ETEC based on detection of toxin DNA in water samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The method facilitates detection and identification of ETEC in water and allows comparison between water contamination and incidence of ETEC diarrhoea in endemic areas.
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| 46. |
- Mottram, Lynda, et al.
(författare)
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FUT2 non-secretor status is associated with altered susceptibility to symptomatic enterotoxigenic Escherichia coli infection in Bangladeshiw
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms of the FUT2 gene alters glycan ABO(H) blood group and Lewis antigen expression (commonly known as non-secretor status) in the small intestinal mucosa. Whilst non-secretor status affects 20% of the population worldwide, it has been reported to be present in up to 40% of all Bangladeshis. Furthermore, Bangladeshi children are reportedly more susceptible to symptomatic enterotoxigenic Escherichia coli (ETEC) infection if they are non-secretors. Therefore, in an attempt to identify a non-secretor status genotypic biomarker of altered susceptibility to ETEC infection, we used the 1000 Genomes Project to identify three population related non-synonymous FUT2 single nucleotide polymorphisms (SNPs). We then assessed the genotypic frequency of these SNPs in Bangladeshi children who had been clinically monitored for ETEC infection. One novel missense FUT2 SNP, rs200157007-TT and the earlier established rs601338-AA SNP were shown to be causing non-secretor status, with these SNPs being associated with symptomatic but not asymptomatic ETEC infection. Moreover, rs200157007-TT and rs601338-AA were associated with symptomatic but not asymptomatic ETEC infection irrespective of the child's Lewis secretor status, suggesting FUT2, the regulator of Lewis and ABO(H) antigens in the intestinal mucosa, could be a host genotypic feature affecting susceptibility to ETEC infection.
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| 47. |
- Qadri, F, et al.
(författare)
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Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut
- 2004
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Ingår i: Gut. ; 53:1, s. 62-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The general concept is that as Vibrio cholerae is not invasive, it mediates a non-inflammatory type of infection. This is being re-evaluated based on available data that natural cholera infection or cholera toxin induces a Th2-type of immune profile and stimulates the humoral immune response, innate cells, and mediators in the host. METHODS: To perform a comprehensive analyses of the inflammatory components, we studied mucosal biopsies from patients, both adults and children with acute watery diarrhoea caused by V cholerae O1 and O139. Patients with cholera, adults (n = 30) and children (n = 18), as well as healthy controls (n = 24) were studied. Histochemical, immunohistochemical, and ultrastructural studies were carried out to elucidate the contribution of the different factors using paraffin and frozen duodenal and/or rectal sections as appropriate. Samples were collected during the acute stage and during early and/or late convalescence. RESULTS: Following natural cholera infection, patients responded with increases in neutrophil polymorphs during the acute stage (p<0.001) compared with healthy controls whereas mucosal mast cells (MMC) (p = 0.008) and eosinophils (p = 0.034) increased in the gut during convalescence. Electron microscopic analyses of duodenal biopsies from adult patients showed increased piecemeal degranulation in both MMC and eosinophils and accumulation of lipid bodies in MMC. Duodenal biopsies from V cholerae O1 infected patients showed upregulation of myeloperoxidase, lactoferrin, PGHS-1, SCF, tryptase, tumour necrosis factor alpha, alpha-defensin, and eotaxin during the acute stage and chymase, interleukin 3 and major basic protein during convalescence. CONCLUSION: We have shown that innate cells and their mediators are upregulated in acute watery diarrhoea. These cells and factors of the innate arm may be important in the host's defence against cholera. Such effects may need to be simulated in a vaccine to achieve long lasting protection from cholera.
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| 48. |
- Qadri, F., et al.
(författare)
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Cholera immunity and development and use of oral cholera vaccines for disease control
- 2020
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Ingår i: Mucosal Vaccines. Innovation for Preventing Infectious Diseases. Hiroshi Kiyono and David W. Pascual (red.). - : Elsevier. - 9780128119242 ; , s. 537-561
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The development of oral cholera vaccines (OCVs) is a good example of how basic research can generate new knowledge that can be translated into a life-saving medical product. The key mechanisms of disease and immunity in cholera, which allowed outlining the principles for the first effective OCV, the inactivated whole cell/B subunit (WC-BS) OCV, later to be licensed as Dukoral, were defined already in the 1970s. Cholera was identified as an archetype for noninvasive, enterotoxin-mediated infectious diarrheal diseases in which immune protection is mediated largely by locally produced secretory immunoglobulin A (SIgA) antibodies interfering with bacterial attachment and colonization and/or preventing toxin binding and action in the intestine. These antibodies are directed primarily against the cell wall lipopolysaccharide (LPS) and cholera toxin B subunit (CTB), respectively. Since the intestinal SIgA responses in cholera lasts for only approximately 6-9 months, the continued protection for over 2-3 more years seen after infection or vaccination depends on mucosal immunological memory with a duration of more than 10 years, allowing a rapid SIgA antibacterial and antitoxic anamnestic response upon renewed pathogen exposure. Serum vibriocidal antibodies, although often correlating with adaptive immune protection, are only a proxy for the intestinal SIgA immune status. After Dukoral, which was internationally licensed in 1993, both inactivated and live, genetically attenuated OCVs have been developed. Inactivated OCVs have had the greatest success in achieving licensure and international acceptance. Three WHO-prequalified OCVs-Dukoral, Shanchol, and Euvichol-are currently available and differ mainly in that, in addition to several killed whole cell components shared with the other OCVs, the Dukoral OCV contains CTB. More than 15 large field trials have consistently shown that the described inactivated OCVs are quite safe and provide 60%-70% specific immune protection for at least 3 years. In addition, they confer significant “herd protection,” which further increases their total impact for reducing (or even eliminating) cholera in vaccinated communities. OCVs are now a cornerstone of a global initiative, “Ending Cholera-A Global Roadmap to 2030,” which was launched in October 2017 by the World Health Organization’s Global Task Force for Cholera Control together with more than 50 other signatories, with the stated goal of reducing cholera deaths by at least 90% by 2030. © 2020 Elsevier Inc. All rights reserved.
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| 49. |
- Qadri, Firdausi, et al.
(författare)
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Reduced doses of oral killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine is safe and immunogenic in Bangladeshi infants 6-17 months of age: dosing studies in different age groups
- 2006
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 24:10, s. 1726-33
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Forskningsöversikt (refereegranskat)abstract
- The oral-formalin inactivated whole cell enterotoxigenic Escherichia coli (ETEC) vaccine needs to be further tested in developing countries in order to determine the dose at which it will be safe and immunogenic for infants who are the target population for the vaccine. To determine the immunogenicity of reduced doses, studies were first carried out in children, 2-12 years of age (n = 60). The full, half or a quarter doses of the vaccine were comparable in immunogenicity with similar frequency of responses seen to the different antigens (P = NS). Following this result, a pilot study carried out in infants, 6-17 months of age (n = 50), showed that the frequency of episodes of vomiting was lowest when a quarter of the full dose was used. The infants however showed comparable immune responses to the half and quarter dose of vaccine that was tested (P = NS). Based on these results in the infants, a randomized double blind placebo-controlled Phase II study was carried out in 158 children, 6-17 months of age, where a quarter dose of the ETEC vaccine was tested. Adverse events of mild vomiting were seen in only 4% of vaccinees and in 2.5% of placebo recipients. The IgA-antibody secreting cell (ASC) responses to CFA/I (GM: 28.1 ASC/10(7) PBMC) and BS (GM: 55.7 ASC/10(7) PBMC) were elevated compared to placebo recipients (CFA/I-2.0; BS-4.8 ASC/10(7) PBMC) (P = 0.01 to < 0.001). The plasma-IgA antibody titers in vaccinees were also significantly elevated to CFA/I (GM-93.00), CS1 (GM-62.0), CS2 (GM-55.0), CS4 (GM-66.0) and BS (1057.0) compared to preimmune levels or responses or levels in placebo recipients (P < or = 0.05-0.001). This study thus demonstrates that reduced doses of the ETEC vaccine is immunogenic in children and infants as well as safe in infants down to 6 months of age.
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