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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., Author summary Cholera, which can be a severe watery diarrheal illness caused by the non-invasive bacterium Vibrio cholerae, remains a global public health concern for many developing countries. Immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae are involved in mediating protection against cholera. Evidence suggests that inactivated whole-cell oral cholera vaccine (OCV) that includes killed V. cholerae O1 and O139 organisms provides protection against cholera caused by V. cholerae O1, but the immune correlates of this protection are not fully defined. In this study, we specifically assessed induction of immune responses targeting V. cholerae O1 OSP following vaccination with the OCV in adults in a cholera endemic area, Bangladesh. Our results show that OCV induces serum, mucosal and memory anti-OSP responses, and that these responses are maximal following the first dose of vaccination, without evident boosting with the second dose. This result calls into question the day 0 and day 14 two dose regimen currently used among adults in a cholera-endemic zone.

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., Author summary Vibrio cholerae is a non-invasive pathogen which causes watery diarrheal diseases both in adults and children. Natural infection with Vibrio cholerae provides protection against subsequent diseases and protection against cholera is serogroup specific. Serogroup specificity is defined by O-specific polysaccharide (OSP) of V. cholerae. In this study, we have found that uninfected household contacts had higher baseline OSP-specific plasma IgA, IgG and IgM antibody responses than infected contacts. These observations demonstrate those plasma antibodies responses against OSP are associated with a decrease of the risk of infection of household contacts of cholera patients. We also found that OSP-specific IgG memory B cells are associated with a decrease in the risk of infection in contacts of cholera patients. This result further supports the hypothesis that immune responses targeting V. cholerae OSP is a prime mediator of protection against cholera, and suggests that future work should focus on more detailed analysis of mucosal immune responses targeting OSP, as well as evaluation of potential mechanisms of how antibodies targeting V. cholerae OSP might mediate protection against cholera.

Background Dengue virus (DENV) activity has been reported in Dhaka, Bangladesh since the early 1960s with the greatest burden of dengue fever and dengue hemorrhagic fever cases observed in 2000. Since this time, the intensity of dengue activity has varied from year to year, and its determining factors remained relatively unknown. In light of such gaps in knowledge, the main objectives of this study were to determine the magnitude of seroprevalence and seroconversion among the surveyed population, and establish the individual/household level risk factors for the presence of DENV antibodies among all age groups of target populations in the city of Dhaka. Methodology/Principal findings Considering the lack of fine scale investigations on the factors driving dengue activity in Bangladesh, a prospective cohort study involving serological surveys was undertaken with participant interviews and blood donation across the city of Dhaka in 2012. Study participants were recruited from 12 of 90 wards and blood samples were collected during both the pre-monsoon (n = 1125) and post-monsoon (n = 600) seasons of 2012. The findings revealed that the seroprevalence in all pre-monsoon samples was 80.0% (900/1125) while the seropositivity in the pre-monsoon samples that had paired post-monsoon samples was 83.3% (503/600). Of the 97 paired samples that were negative at the pre-monsoon time point, 56 were positive at the post-monsoon time point. This resulted in a seroprevalence of 93.2% (559/600) among individuals tested during the post-monsoon period. Seroprevalence trended higher with age with children exhibiting a lower seropositivity as compared to adults. Results from this study also indicated that DENV strains were the only flaviviruses circulating in Dhaka in 2012. A multivariate analysis revealed that age, possession of indoor potted plants, and types of mosquito control measures were significant factors associated with DENV seroprevalence; while attendance in public/mass gatherings, and use of mosquito control measures were significantly associated with DENV seroconversion after adjusting for all other variables. Conclusions/Significance Our study suggests that there is a high level of endemic dengue virus circulation in the city of Dhaka which has resulted in significant DENV seroprevalence among its residents. Seropositivity increased with age, however, a substantial proportion of children are at risk for DENV infections. Our serological analysis also documents considerable DENV seroconversion among study participants which indicates that a large proportion of the population in the city of Dhaka were newly exposed to DENV during the study period (pre-and post-monsoon 2012). High levels of seroconversion suggest that there was an intense circulation of DENV in 2012 and this may have resulted in a significant risk for viral associated illness. Findings of our study further indicated that home-based interventions, such as removing indoor potted plants and increased bed net use, in addition to vector control measures in public parks, would reduce exposure to DENV and further decrease risk of viral associated disease., Author summary Similar to many other tropical regions of the world, dengue is a major public health problem in Bangladesh where Aedes aegypti mosquitoes are the main vector. Through this serological survey, we present data on the magnitude (measured in proportions) of seroprevalence and seroconversion within 12 selected wards in the city of Dhaka, Bangladesh. In 2012 the observed dengue seroprevalence was 93% among individuals tested during post-monsoon with a seroconversion rate between pre- and post-monsoon periods of 57.7%. This finding suggests that dengue virus (DENV) circulated in the city during the observation period. Past exposure to dengue virus was highly associated with age, possession of indoor potted plants, types of mosquito control measures used, and human movement and attendance in mass gatherings, while the extent of dengue seroprevalence were not associated with the socioeconomic status of the study participants. Our findings suggest that household utilities and water management or storage practices and recognition and elimination of mosquito development sites and participation in mass gatherings are important factors that affect exposure to dengue. Intervention strategies should therefore target these factors for effective prevention and control of dengue infection.

Background There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot. Methodology For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer ≥1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis. Principle findings Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot. Conclusion These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives., Author Summary We compared the performance of the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and commercially available kits, Tubex and Typhidot in diagnosing the patients with typhoid fever. There is no acceptable gold standard; therefore, we estimated the sensitivity and specificity of these diagnostic methods with Bayesian latent class modeling. We found that the sensitivity and specificity of the TPTest is higher than other commonly used methods for diagnosis of typhoid fever.