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Background: Oral cholera vaccine (OCV) containing killed Vibrio cholerae O1 and O139 organisms (Bivalent-OCV; Biv-OCV) are playing a central role in global cholera control strategies. OCV is currently administered in a 2-dose regimen (day 0 and 14). There is a growing body of evidence that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae mediate protection against cholera. There are limited data on anti-OSP responses in recipients of Biv-OCV. We assessed serum antibody responses against O1 OSP, as well as antibody secreting cell (ASC) responses (a surrogate marker for mucosal immunity) and memory B cell responses in blood of adult recipients of Biv-OCV in Dhaka, Bangladesh. Methodology/Principal findings: We enrolled 30 healthy adults in this study and administered two doses of OCV (Shanchol) at days 0 and 14. Blood samples were collected before vaccination (day 0) and 7 days after each vaccination (day 7 and day 21), as well as on day 44. Serum responses were largely IgA with minimal IgG and IgM responses in this population. There was no appreciable boosting following day 14 vaccination. There were significant anti-OSP IgA ASC responses on day 7 following the first vaccination, but none after the second immunization. Anti-OSP IgA memory B cell responses were detectable 30 days after completion of the vaccination series, with no evident induction of IgG memory responses. In this population, anti-Ogawa OSP responses were more prominent than anti-Inaba responses, perhaps reflecting impact of previous exposure. Serum anti-OSP responses returned to baseline within 30 days of completing the vaccine series. Conclusion: Our results call into question the utility of the 2-dose regimen separated by 14 days in adults in cholera endemic areas, and also suggest that Biv-OCV-induced immune responses targeting OSP are largely IgA in this highly endemic cholera area. Studies in children in cholera-endemic areas need to be performed. Protective efficacy that extends for more than a month after vaccination presumably is mediated by direct mucosal immune response which is not assessed in this study. Our results suggest a single dose of OCV in adults in a cholera endemic zone may be sufficient to mediate at least short-term protection. [ABSTRACT FROM AUTHOR]

Background: Cholera remains a substantial health burden in Asia and Africa particularly in resource poor settings. The standard procedures to identify the etiological organism V. cholerae are isolation from microbiological culture from stool as well as Polymerase Chain Reaction (PCR). Both the processes are highly lab oriented, labor extensive, time consuming, and expensive. In an effort to control for outbreaks and epidemics; an effective, convenient, quick and relatively less expensive detection method is imperative, without compromising the sensitivity and specificity that exists at present. The objective of this component of the study was to evaluate the effectiveness of a locally produced rapid diagnostic test (RDT) for cholera diagnosis. Methods: In Bangladesh, nationwide cholera surveillance is ongoing in 22 hospitals covering all 8 divisions of the country since June, 2016. In the surveillance, stool samples have been collected from patients presenting to hospitals with acute watery diarrhea. Crystal VCTM (Span diagnostics, India) and Cholkit (locally produced RDT) have been used to detect V. cholerae from stool samples. Samples have also been sent to the main laboratory at icddr,b where the culture based isolation is routinely performed. All the tests were carried out for both direct and enriched stool samples. RDT sensitivity and specificity were calculated using stool culture as the gold standard. Results: A total of 7720 samples were tested. Among these, 5865 samples were solely tested with Crystal VC and 1355 samples with Cholkit whereas 381 samples were tested with both the RDTs. In comparison with culture, direct testing with Crystal VC showed a sensitivity of 72% (95% CI: 50.6% to 87.9%) and specificity of 86.8% (95% CI: 82.8% to 90.1%). After enrichment the sensitivity and specificity was 68% (95% CI: 46.5% to 85.1%) and 97.5% (95% CI: 95.3% to 98.8%) respectively. The direct Cholkit test showed sensitivity of 76% (95% CI: 54.9% to 90.6%) and specificity of 90.2% (95% CI: 86.6% to 93.1%). Conclusion: This evaluation has demonstrated that the sensitivity and specificity of Cholkit is similar to the commercially available test, Crystal VC when used in field settings for detecting V. cholerae from stool specimens. The findings from this study suggest that the Cholkit could be a possible alternative for cholera endemic regions where V. cholerae O1 is the major causative organism causing cholera. [ABSTRACT FROM AUTHOR]

Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3–14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO) and alpha anti-trypsin (AAT), and plasma endotoxin core antibody (EndoCab), intestinal fatty acid binding protein (i-FABP), and soluble CD14 (sCD14). We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional) status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03) and IgA responses to LPS (P = 0.02); plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07); plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01) and with memory T cell responses specific to cholera toxin (P = 0.01); stool AAT to be negatively associated with IL-10 (regulatory) T cell responses specific to cholera toxin (P = 0.02), and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02). In summary, in a cohort of children 3–14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV. [ABSTRACT FROM AUTHOR]