Abstract: With one-third of nations at risk of cholera, we can expect to experience massive, rapidly disseminated, and prolonged cholera outbreaks such as those recently experienced in Yemen and Haiti. The p...

Abstract: Exposure to cholera is a risk for individuals and groups travelling to endemic areas, and the bacteria can be imported to cholera-free countries by returning travellers. This systematic review of the literature describes the circumstances in which cholera infection can occur in travellers and considers the possible value of the cholera vaccine for prevention in travellers. PubMed and EMBASE were searched for case reports of cholera or diarrhoea among travellers, with date limits of 1 January 1990-30 April 2018. Search results were screened to exclude the following articles: diarrhoea not caused by cholera, cholera in animals, intentional cholera infection in humans, non-English articles and publications on epidemics that did not report clinical details of individual cases and publications of cases pre-dating 1990. Articles were reviewed through descriptive analytic methods and information summarized. We identified 156 cases of cholera imported as a consequence of travel, and these were reviewed for type of traveller, source country, serogroup of cholera, treatment and outcomes. The case reports retrieved in the search did not report consistent levels of detail, making it difficult to synthesize data across reports and draw firm conclusions from the data. This clinical review sheds light on the paucity of actionable published data regarding the risk of cholera in travellers and identifies a number of gaps that should drive additional effort. Further information is needed to better inform evidence-based disease prevention strategies, including vaccination for travellers visiting areas of cholera risk. Modifications to current vaccination recommendations to include or exclude current or additional traveller populations may be considered as additional risk data become available. The protocol for this systematic review is registered with PROSPERO (registration number: 122797).

Abstract: Cholera is a secretory diarrhoeal disease caused by infection with Vibrio cholerae, primarily the V. cholerae O1 El Tor biotype. There are approximately 2.9 million cases in 69 endemic countries annually, resulting in 95 000 deaths. Cholera is associated with poor infrastructure and lack of access to sanitation and clean drinking water. The current cholera epidemic in Yemen, linked to spread of V. cholerae O1 (Ogawa serotype), is associated with the ongoing war. This has devastated infrastructure and health services. The World Health Organization had estimated that 172 286 suspected cases arose between 27th April and 19th June 2017, including 1170 deaths. While there are three oral cholera vaccines prequalified by the World Health Organization, there are issues surrounding vaccination campaigns in conflict situations, exacerbated by external factors such as a global vaccine shortage. Major movements of people complicates surveillance and administration of double doses of vaccines. Cholera therapy mainly depends on rehydration, with use of antibiotics in more severe infections. Concerns have arisen about the rise of antibiotic resistance in cholera, due to mobile genetic elements. In this review, we give an overview of cholera epidemiology, virulence, antibiotic resistance, therapy and vaccines, in the light of the ongoing epidemic in Yemen.

Abstract: Cholera toxin B subunit (CTB), a non-toxic homopentameric component of Vibrio cholerae holotoxin, is an oral cholera vaccine antigen that induces an anti-toxin antibody response. Recently, we demonstrated that a recombinant CTB variant with a Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention motif (CTB-KDEL) exhibits colon mucosal healing effects that have therapeutic implications for inflammatory bowel disease (IBD). Herein, we investigated the feasibility of CTB-KDEL for the treatment of chronic colitis. We found that weekly oral administration of CTB-KDEL, dosed before or after the onset of chronic colitis, induced by repeated dextran sodium sulfate (DSS) exposure, could significantly reduce disease activity index scores, intestinal permeability, inflammation, and histological signs of chronicity. To address the consequences of immunogenicity, mice (C57BL/6 or C3H/HeJ strains) were pre-exposed to CTB-KDEL then subjected to DSS colitis and CTB-KDEL treatment. While the pre-dosing of CTB-KDEL elicited high-titer anti-drug antibodies (ADAs) of the immunoglobin A (IgA) isotype in the intestine of C57BL/6 mice, the therapeutic effects of CTB-KDEL were similar to those observed in C3H/HeJ mice, which showed minimal ADAs under the same experimental conditions. Thus, the immunogenicity of CTB-KDEL does not seem to impede the protein's mucosal healing efficacy. These results support the development of CTB-KDEL for IBD therapy.

Abstract: Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset of adaptive immunity. Here, we orally immunized adult germ-free female mice to test the immunogenicity of HaitiV. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera.

Abstract: Catastrophic damage and floods followed the deadliest cyclone on record for the Southern Hemisphere. In the aftermath of Cyclone Idai, a cholera outbreak was detected. The global stockpile of oral cholera vaccine was rapidly deployed to counter this fast-growing epidemic. We urge the international community to continue to highlight the importance of water, sanitation, and hygiene as the long-term goal for controlling cholera and meeting the 2030 Sustainable Development Goals.

Abstract: Introduction Individual and household-level evidence suggests a relationship between food insecurity and cholera risk. The relationship between national food security and the size of cholera outbreaks is unknown. Methods We analysed the relationship between national food security and annual cholera incidence rate from 2012 to 2015 across 30 countries. We used components of the Global Food Security Index (GFSI) as measures of food security. We included countries with available GFSI reporting cases of cholera during the study period, excluding high-income countries. We developed multivariable zero-inflated negative binomial models with annual cholera incidence rate as the outcome, GFSI components as the exposure of interest, fixed effects for country and year, and time-varying effects related to water, sanitation, and hygiene, oral cholera vaccine deployment, healthcare expenditure, conflict and extreme weather. Results The 30 countries reported 550 106 total cases of cholera from 2012 to 2015, with a median annual incidence rate of 3.1 cases per 100 000 people (IQR 0.3–9.9). We found independent inverse relationships between cholera and Overall GFSI (incidence rate ratio (IRR) 0.57, 95% CI 0.43 to 0.78), GFSI-Availability (IRR 0.81, 95% CI 0.70 to 0.95) and GFSI-Affordability (IRR 0.76, 95% CI 0.62 to 0.92). Conclusions We identified a strong inverse relationship between national food security and annual incidence rate of cholera. In the context of prior evidence at the individual and household levels, this suggests that there is a linkage between food insecurity and cholera at the national level that should be further considered in assessing cholera risk in vulnerable regions and in designing cholera control interventions.

Abstract: Background and Objectives: Cholera disease remains an important global health problem affecting 3-5 million subjects worldwide. Outer membrane vesicles (OMVs) have been found in a variety of Gram-negative bacteria and act as protective transport vesicles. The aim of this study was to evaluate Immune responses against Vibrio cholerae O1 El Tor clinical strain OMV and compare it with killed whole cell (KWC), complex of (KWC-OMV) as well as the internationally licensed oral cholera vaccine, Dukoral, in serum and intestinal secretions of mice. Materials and Methods: OMVs were prepared by using modified detergent-centrifugation procedure from V. cholerae O1 El Tor clinical strain from 2005 outbreak. The ultrastructure and content of OMVs were investigated via the Scanning Elec- tron Microscopy (SEM) and SDS-PAGE analysis. Three doses of oral immunization were adjusted and total IgG and IgA in serum and intestinal secretion were measured by enzyme-linked immunosorbent assay (ELISA). Results: Extracted OMVs from the V. cholerae were spherical vesicles with a size ranging from 10 to 300 nm. OMV-im- munized mice showed an increased level of total IgG and IgA both in serum and intestinal secretion when compared to the negative controls. Also, there existed a higher level of secretory IgA than the total IgG, suggesting the most of protection against V. cholerae colonization provided by sIgA. Conclusion: Our findings revealed that oral immunization with V. cholerae OMVs might induce a long-term immunity, es- pecially when administered in combination with KWC. This study tested the adjuvant activity of OMVs and may be useful in future nano vaccine research.

Abstract: Diarrheal diseases remain a leading cause of mortality globally.1 Recent estimates of the Global Burden Disease study showed that nearly 1.65 million diarrheal diseases deaths occurred in 2016 in a...

Abstract: Background Antibodies targeting O-specific polysaccharide (OSP) of Vibrio cholerae may protect against cholera; however, little is known about this immune response in infected immunologically naive humans. Methodology We measured serum anti-OSP antibodies in adult North American volunteers experimentally infected with V. cholerae O1 Inaba El Tor N16961. We also measured vibriocidal and anti-cholera toxin B subunit (CtxB) antibodies and compared responses to those in matched cholera patients in Dhaka, Bangladesh, an area endemic for cholera. Principal findings We found prominent anti-OSP antibody responses following initial cholera infection: these responses were largely IgM and IgA, and highest to infecting serotype with significant cross-serotype reactivity. The anti-OSP responses peaked 10 days after infection and remained elevated over baseline for ≥ 6 months, correlated with vibriocidal responses, and may have been blunted in blood group O individuals (IgA anti-OSP). We found significant differences in immune responses between naive and endemic zone cohorts, presumably reflecting previous exposure in the latter. Conclusions Our results define immune responses to O-specific polysaccharide in immunologically naive humans with cholera, find that they are largely IgM and IgA, may be blunted in blood group O individuals, and differ in a number of significant ways from responses in previously humans. These differences may explain in part varying degrees of protective efficacy afforded by cholera vaccination between these two populations. Trial registration number ClinicalTrials.gov NCT01895855.

Abstract: Background: The new influx of Forcibly Displaced Myanmar Nationals (FDMNs) into Bangladesh started in August 2017 through different entry points of Bangladesh. Considering the imminent threat of infectious diseases outbreaks, the Government of Bangladesh (GoB) decided to vaccinate children against three deadly diseases (measles, rubella and poliomyelitis) and oral cholera vaccine (OCV) for all except <1 year children. After completion of the campaigns, post-vaccination campaign evaluation was carried out to assess the coverage of OCV, OPV and MR vaccines during campaigns.Methods: Post-vaccination campaign evaluation was conducted after completion of the 2nd dose of oral cholera vaccine (OCV2) and oral polio vaccine (OPV2) through a cross-sectional survey. The evaluation was conducted in the Balukhali camps under Ukhiya upazilla. Precision-based sample size was calculated to estimate the vaccine coverage. Ninety-two trained interviewers were involved to collect data from the target of approximately 40000 FDMNs between 18 and 25 November 2017.Results: Data were collected from 39,438 FDMNs during the survey period. The highest coverage was observed for OCVs (94% for OCV1 and 92% for OCV2). On the other hand, lower coverage was observed for the other vaccines; the coverage for OPV1, OPV2 and MR were 75%, 88% and 38%, respectively. Unawareness (30.7% did not know about the campaign) was the most notable cause of lowering down MR vaccine coverage.Conclusion: The experience in Bangladesh demonstrates that vaccine campaigns can be successfully implemented as part of a comprehensive response toward disease outbreak among high-risk populations in humanitarian crisis.

Abstract: 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: Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to other OCVs to stimulate adaptive immunity against V. cholerae. Here, we orally immunized adult germ-free female mice to test HaitiV’s immunogenicity. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera.

Abstract: The population level effectiveness of a vaccine may arise as the result of direct protection of vaccinees and vaccine herd protection, which may protect non-vaccinees, vaccinees, or both. Indirect, total, enhanced, and overall vaccine protection are measures of vaccine herd protection. The level of population level effectiveness induced by a vaccine is driven by several factors, including known vaccine-induced protective efficacy, the magnitude, and distribution of vaccine coverage at a point in time and the extent to which different groups mix with one another in the community. Data on vaccine herd protection are valuable in understanding the importance and cost-effectiveness in deploying the e vaccine in public health program. Killed whole-cell (WC) oral cholera vaccines (OCVs) have been evaluated for herd protection in various study settings, leveraging geographic information system (GIS) tools for the analyses. This article provides a brief description of the herd protective effects of killed WC OCVs measured using various study deigns that include (a) individually randomized, controlled clinical trials, (b) cluster randomized clinical trials, (c) observational cohort studies, and (d) observational case-control studies. In all of the study designs, significant herd protection was observed in unvaccinated persons as well as in the community as a whole. The findings of these studies suggest that using killed WC OCV as a public health tool for controlling cholera is impactful and cost-effective.

Abstract: Background: Cholera is a considerable health burden in developing country settings including Bangladesh. The oral cholera vaccine (OCV) is a preventative tool to control the disease. The objective ...

Abstract: Background Blood collection, transportation and storage remain a problem in countries where infrastructure, laboratory facilities and skilled manpower are scarce. This limits evaluation of immune responses in natural infections and vaccination in field studies. We developed methods to measure antigen specific antibody responses using dried blood spot (DBS) in cholera, ETEC and typhoid fever patients as well as recipients of oral cholera vaccine (OCV). Methodology/Principle findings We processed heparinized blood for preparing DBS and plasma specimens from patients with, cholera, ETEC and typhoid as well as OCV recipients. We optimized the conventional vibriocidal method to measure vibriocidal antibody response in DBS eluates. We measured responses in DBS samples and plasma (range of titer of 5 to 10240). Vibriocidal titer showed strong agreement between DBS eluates and plasma in cholera patients (ICC = 0.9) and in OCV recipients (ICC = 0.8) using the Bland-Altman analysis and a positive correlation was seen (r = 0.7, p = 0.02 and r = 0.6, p = 0.006, respectively). We observed a strong agreement of lipopolysaccharide (LPS) and cholera toxin B (CTB)-specific antibody responses between DBS eluates and plasma in cholera patients and OCV recipients. We also found agreement of heat labile toxin B (LTB) and membrane protein (MP)-specific antibody responses in DBS eluates and plasma specimen of ETEC and typhoid patients respectively. Conclusion Our results demonstrate that dried blood specimens can be used as an alternate method for preservation of samples to measure antibody responses in enteric diseases and vaccine trials and can be applied to assessment of responses in humanitarian crisis and other adverse field settings.

Abstract: Analyses of stool from patients with acute watery diarrhea (AWD) using sensitive molecular diagnostics have challenged whether fecal microbiological cultures have acceptably high sensitivity for cholera diagnosis. If true, these findings imply that current estimates of the global burden of cholera, which rely largely on culture-confirmation, may be underestimates. We conducted a vaccine probe study to evaluate this possibility, assessing whether an effective killed oral cholera vaccine (OCV) tested in a field trial in a cholera-endemic population conferred protection against cholera culture-negative AWD, with the assumption that if cultures are indeed insensitive, OCV protection in such cases should be detectable. We re-analysed the data of a Phase III individually-randomized placebo-controlled efficacy trial of killed OCVs conducted in Matlab, Bangladesh in 1985. We calculated the protective efficacy (PE) of a killed whole cell-only (WC-only) OCV against first-episodes of cholera culture-negative AWD during two years of post-dosing follow-up. In secondary analyses, we evaluated PE against cholera culture-negative AWD by age at vaccination, season of onset, and disease severity. In this trial 50,770 people received at least 2 complete doses of either WC-only OCV or placebo, and 791 first episodes of AWD were reported during the follow-up period, of which 365 were culture-positive for Vibrio cholerae O1. Of the 426 culture-negative AWD episodes, 215 occurred in the WC group and 211 occurred in the placebo group (adjusted PE = -1.7%; 95%CI -23.0 to 13.9%, p = 0.859). No measurable PE of OCV was observed against all or severe cholera culture-negative AWD when measured overall or by age and season subgroups. In this OCV probe study we detected no vaccine protection against AWD episodes for which fecal cultures were negative for Vibrio cholera O1. Results from this setting suggest that fecal cultures from patients with AWD were highly sensitive for cholera episodes that were etiologically attributable to this pathogen. Similar analyses of other OCV randomized controlled trials are recommended to corroborate these findings.

Abstract: Background Cholera was introduced into Haiti in 2010. Since, there have been over 820,000 reported cases and nearly 10,000 deaths. The year 2019 has seen the lowest reported number of cases since the epidemic began. Oral cholera vaccine (OCV) is safe and effective, but has generally not been seen as a primary tool for cholera elimination due to a limited period of protection and constrained supplies. Regionally, epidemic cholera is contained to the island of Hispaniola. Hence, Haiti may represent a unique opportunity to eliminate cholera by use of OCV. Methods We assess the probability of elimination and the potential health impact of OCV use in Haiti by leveraging simulations from four independent modeling teams. For a 10-year projection period, we compared the impact of five vaccination campaign scenarios, differing in geographic scope, vaccination coverage, and rollout duration to a status quo scenario without vaccination. Teams used common calibration data and assumptions for vaccine efficacy and vaccination scenarios, but all other model features and assumptions were determined independently. Findings A two-department OCV campaign proposed in Haiti9s national plan for elimination had less than 50% probability of elimination across models, and only ambitious, nationwide campaigns had a high probability of reaching this goal. Despite their low probability of elimination, two-department campaigns averted a median of 13-58% of infections across models over the five years after the start of vaccination campaigns; a nationwide campaign implemented at the same coverage and rollout duration averted a median of 58-95% of infections across models. Interpretation Despite recent declines in cholera cases in Haiti, bold action is needed to promote elimination of cholera from the region. Large-scale cholera vaccination campaigns in Haiti offer the opportunity to synchronize nationwide immunity, providing near-term protection to the population while improvements to water and sanitation infrastructure create an environment favorable to long-term cholera elimination.

Abstract: Background In May 2018, the World Health Assembly committed to reducing worldwide cholera deaths by 90% by 2030. Oral cholera vaccine (OCV) plays a key role in reducing the near-term risk of cholera, although global supplies are limited. Characterizing the potential impact and cost-effectiveness of mass OCV deployment strategies is critical for setting expectations and developing cholera control plans that maximize chances of success. Methods We compared the projected impacts of vaccination campaigns across sub-Saharan Africa from 2018 through 2030 when targeting geographically according to historical cholera burden and risk factors. We assessed the number of averted cases, deaths, disability-adjusted life-years, and cost-effectiveness with models that account for direct and indirect vaccine effects and population projections over time. Findings Under current vaccine supply projections, an approach that balances logistical feasibility with targeting historical burden is projected to avert 620,000 cases cumulatively (9-26% of cases annually). Targeting by access to improved water and sanitation prevents one-half to one-seventh as many cases as targeting by burden. We find that effective geographic targeting of OCV campaigns can have a greater impact on cost-effectiveness than improvements to vaccine efficacy and moderate increases in coverage. Conclusions Oral cholera vaccines must be targeted strategically in order for campaigns to be cost-effective and impactful. While OCV campaigns will improve cholera control in the near-term, we need a greater supply of vaccines and rapid progress in developing safely managed water and sanitation services in order to achieve the 2030 goals.

Abstract: Background: Cholera remains a major public health concern, particularly in refugee camps, which may contend with overcrowding and scarcity of resources. Maela, the largest long-standing refugee camp in Thailand, experienced four cholera outbreaks between 2005 and 2010. In 2013, a cholera vaccine campaign was implemented in the camp. To assist in the evaluation of the campaign and planning for subsequent campaigns, we developed a mathematical model of cholera in Maela. Methods: We formulated a Susceptible-Infectious-Water-Recovered-based cholera transmission model and estimated parameters using incidence data from 2010. We next evaluated the reduction in cases conferred by several immunization strategies, varying timing, effectiveness, and resources (i.e., vaccine availability). Finally, we generated post-campaign case forecasts, to determine whether a booster campaign was needed. Results: We found that preexposure vaccination can substantially reduce the risk of cholera even when the 50% of the population is given the full two-dose series. Additionally, the preferred number of doses per person should be considered in the context of one vs. two dose effectiveness and vaccine availability. For reactive vaccination, a trade-off between timing and effectiveness was revealed, indicating that it may be beneficial to give one dose to more people rather than two doses to fewer people, given that a two-dose schedule would incur a delay in administration of the second dose. Forecasting using realistic coverage levels predicted that there was no need for a booster campaign in 2014 (consistent with our predictions, there was not a cholera epidemic in the 2014 season). Conclusions: Our analyses suggest that vaccination in conjunction with ongoing water sanitation and hygiene efforts provides an effective strategy for cholera outbreaks in refugee camps. Effective preexposure vaccination depends on timing and effectiveness. If a camp is facing an outbreak, delayed distribution of vaccines can substantially alter the effectiveness of reactive vaccination, suggesting that quick distribution of vaccines may be more important than ensuring every individual receives both vaccine doses.

Abstract: Background Cholera remains a major public health concern, particularly in refugee camps, which may contend with overcrowding and scarcity of resources. Maela, the largest long-standing refugee camp in Thailand, experienced four cholera outbreaks between 2005 and 2010. In 2013, a cholera vaccine campaign was implemented in the camp. To assist in the evaluation of the campaign, we developed a mathematical model of cholera in Maela. Methodology/Principal Findings We formulated a Susceptible-Infectious-Water-Recovered-based cholera transmission model and estimated parameters using incidence data from 2010. We next evaluated the reduction in cases conferred by several immunization strategies, varying timing, effectiveness, and resources (i.e., vaccine availability). Finally, we generated post-campaign case forecasts, to determine whether a booster campaign was needed. Using parameters from our calibrated model, our analyses suggest that preexposure vaccination can substantially reduce the risk of cholera even when the Conclusions/Significance Our analyses suggest that vaccination in conjunction with water sanitation and hygiene improvements provides an effective strategy for cholera outbreaks in refugee camps. Effective preexposure vaccination depends on timing and effectiveness. If a camp is facing an ongoing outbreak, delayed distribution of vaccines can substantially alter the effectiveness of reactive vaccination, suggesting that quick distribution of vaccines may be more important than ensuring every individual receives both vaccine doses. Author summary We developed an age-structured Susceptible-Infectious-Water-Recovered (SIWR)-based transmission model to consider different cholera vaccination strategies in Maela, the largest long-standing refugee camp in Thailand. Our model was fit to cholera incidence data from 2010 and was in part parameterized by demographic data collected from the camp. We considered multiple scenarios, including both a theoretical exploration of the effects of variation in timing, effectiveness and supply, as well as the real-world coverage of vaccine in Maela. The preferred number of doses per person and timing of vaccination campaigns should be considered in the context of one vs. two dose effectiveness and logistical constraints. Importantly, our analysis coincided with an actual cholera vaccination campaign in the camp and was used to evaluate the campaign and to help determine that there was no need for a follow-up booster campaign. The setting of our analysis is particularly relevant given the recent worldwide increase in total numbers of refugees. Results from our model highlight the utility of vaccination to prevent cholera. Vaccination campaigns can be combined with more permanent water, sanitation, and hygiene infrastructure improvements to reduce the risk of cholera and other enteric disease epidemics. Overall, this study demonstrates that mathematical modeling can generate useful insights into real-world policy decisions.

Abstract: Infectious diseases are a risk when traveling internationally, and it is important to know the potential disease burden of a region and take appropriate preventative actions before traveling. For individuals with HIV, there are special considerations and contradictions for various vaccines and medications as well as interactions with likely antiviral drugs. The purpose of this review is to summarize the vaccine and medication recommendations for travelers with HIV infection. We also review recent studies to update these recommendations. The recommendation for yellow fever vaccine has changed in June of 2016, and it is now a once in a lifetime vaccine instead of being given every 10 years. A new cholera vaccine, Vaxchora™ was approved in 2016. Since it is a live vaccine, its impact on immunocompromised individuals is still not fully known. A recent study found that immunocompromised patients responded well to the hepatitis A vaccine, although acquiring immunity may take longer than in non-immunocompromised people. There are some new anti-viral medicines that need to be considered with interactions for other travel medicines, in particular, the anti-malaria drugs. This review provides current knowledge on how HIV-infected and immunocompromised persons respond to medications and vaccines for prevention of infectious diseases in travelers. These recommendations will be useful to recommend safer travel for the HIV-infected patient. Some newer vaccines and medications will need further evaluation and assessment to determine safety and impact on HIV-positive travelers.

Abstract: introduction Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. The disease is associated with poverty, lack of clean drinking water, inadequate sanitation and poor hygiene. V. cholerae has a short incubation period, ranging between a few hours to five days. It is characterised by explosive watery diarrhoea accompanied by vomiting, followed by rapid dehydration, and in the absence of prompt treatment, death can ensue within a matter of 3-4 hours. Treatments include administration of antibiotics and Oral Rehydration Solution (ORS). Although prompt administration of ORS is highly effective and strongly recommended by experts, its use is rather low. Globally, the usage rate of ORS is 75%, while in India this value is only 2342%. The disease can exhibit endemic or epidemic patterns. The incidence of cholera has been steadily rising worldwide since 2005 and it is estimated that the annual burden of cholera is 1.3-4.0 million cases and 21,000-143,000 deaths worldwide [1].

Abstract: FIELD: medicine.SUBSTANCE: invention refers to experimental medicine, namely to a method for increasing the effectiveness of cholera vaccination in a model of experimental animals. For this purpose, animals are initially immunized according to the following scheme: a single tablet dose of the vaccine, namely 1/3 of the human dose, is ground in a mortar and is suspended in 6.5 ml of distilled water to obtain a suspension, which is orally administered into 0.5 ml rabbits. Further, the vaccine is also administered orally with the lycopid immunomodulator in the following dose: tablet weighing 10 mg is dissolved in 1 ml of distilled water, 0.27 ml is taken and 4.73 ml of distilled water is added thereto, then one rabbit is introduced with 0.5 ml of the prepared solution containing 285 mcg of lycopid. After that, immunized and control animals are infected with cholera in a month; an increase in cholera vaccine effectiveness is evaluated by the presence of manifestations of cholerogenic and enteropathogenic effects in the rabbit small intestine.EFFECT: invention makes it possible to intensify anti-cholera immunity in experimental animals due to combined application of chemical tabletted cholera bivalent vaccine and lycopid immunomodulator.3 cl, 1 tbl, 4 ex

Abstract: Background In April 2016, an emergency vaccination campaign using one dose of Oral Cholera Vaccine (OCV) was organized in response to a cholera outbreak that started in Lusaka in February 2016. In December 2016, a second round of vaccination was conducted, with the objective of increasing the duration of protection, before the high-risk period for cholera transmission. We assessed vaccination coverage for the first and second rounds of the OCV campaign. Methods Vaccination coverage was estimated after each round from a sample selected from targeted-areas for vaccination using a cross-sectional survey in to establish the vaccination status of the individuals recruited. The study population included all individuals older than 12 months residing in the areas targeted for vaccination. We interviewed 505 randomly selected individuals after the first round and 442 after the second round. Vaccination status was ascertained either by vaccination card or verbal reporting. Households were selected using spatial random sampling. Results The vaccination coverage with two doses was 58.1% (25/43; 95%CI: 42.1–72.9) in children 1–5 years old, 59.5% (69/116; 95%CI: 49.9–68.5) in children 5–15 years old and 19.9% (56/281; 95%CI: 15.4–25.1) in adults above 15 years old. The overall dropout rate was 10.9% (95%CI: 8.1–14.1). Overall, 69.9% (n = 309/442; 95%CI: 65.4–74.1) reported to have received at least one OCV dose. Conclusions The areas at highest risk of suffering cholera outbreaks were targeted for vaccination obtaining relatively high vaccine coverage after each round. However, the long delay between doses in areas subject to considerable population movement resulted in many individuals receiving only one OCV dose. Additional vaccination campaigns may be required to sustain protection over time in case of persistence of risk. Further evidence is needed to establish a maximum optimal interval time of a delayed second dose and variations in different settings.

Abstract: This open-label study assessed the safety and immunogenicity of two doses (14 days apart) of an indigenously manufactured, killed, bivalent (Vibrio cholerae O1 and O139), whole-cell oral cholera vaccine (SHANCHOL; Shantha Biotechnics) in healthy adults (n = 100) and children (n = 100) in a cholera endemic area (Vellore, South India) to fulfill post-licensure regulatory requirements and post-World Health Organization (WHO) prequalification commitments. Safety and reactogenicity were assessed, and seroconversion rates (i.e. proportion of participants with a ≥ 4-fold rise from baseline in serum vibriocidal antibody titers against V. cholerae O1 Inaba, O1 Ogawa and O139, respectively) were determined 14 days after each vaccine dose. No serious adverse events were reported during the study. Commonly reported solicited adverse events were headache and general ill feeling. Seroconversion rates after the first and second dose in adults were 67.7% and 55.2%, respectively, against O1 Inaba; 47.9% and 45.8% against O1 Ogawa; and 19.8% and 20.8% against O139. In children, seroconversion rates after the first and second dose were 80.2% and 68.8%, respectively, against O1 Inaba; 72.9% and 67.7% against O1 Ogawa; and 26.0% and 18.8% against O139. The geometric mean titers against O1 Inaba, O1 Ogawa, and O139 in both adults and children were significantly higher after each vaccine dose compared to baseline titers (P < 0.001; for both age groups after each dose versus baseline). The seroconversion rates for O1 Inaba, O1 Ogawa, and O139 in both age groups were similar to those in previous studies with the vaccine. In conclusion, the killed, bivalent, whole-cell oral cholera vaccine has a good safety and reactogenicity profile, and is immunogenic in healthy adults and children. Trial Registration: ClinicalTrials.gov NCT00760825; CTRI/2012/01/002354.