Cholera outbreak in Forcibly Displaced Myanmar National (FDMN) from a small population segment in Cox’s Bazar, Bangladesh, 2019

Background Bangladesh experienced a sudden, large influx of forcibly displaced persons from Myanmar in August 2017. A cholera outbreak occurred in the displaced population during September-December 2019. This study aims to describe the epidemiologic characteristics of cholera patients who were hospitalized in diarrhea treatment centers (DTCs) and sought care from settlements of Forcibly Displaced Myanmar Nationals (FDMN) as well as host country nationals during the cholera outbreak. Methods Diarrhea Treatment Center (DTC) based surveillance was carried out among the FDMN and host population in Teknaf and Leda DTCs hospitalized for cholera during September-December 2019. Results During the study period, 147 individuals with cholera were hospitalized. The majority, 72% of patients reported to Leda DTC. Nearly 65% sought care from FDMN settlements. About 47% of the cholera individuals were children less than 5 years old and 42% were aged 15 years and more. Half of the cholera patients were females. FDMN often reported from Camp # 26 (45%), followed by Camp # 24 (36%), and Camp # 27 (12%). Eighty-two percent of the cholera patients reported watery diarrhea. Some or severe dehydration was observed in 65% of cholera individuals. Eighty-one percent of people with cholera received pre-packaged ORS at home. About 88% of FDMN cholera patients reported consumption of public tap water. Pit latrine without water seal was often used by FDMN cholera individuals (78%). Conclusion Vigilance for cholera patients by routine surveillance, preparedness, and response readiness for surges and oral cholera vaccination campaigns can alleviate the threats of cholera.

Modern History of Cholera Vaccines and the Pivotal Role of icddr,b

The rapid spread of the 7 th cholera pandemic over Asia in the 1960s led to several large field studies that revealed that the traditional injectable cholera vaccines had poor efficacy, usually less than 50% for only 3-6 months, which led WHO in the 1970s to stop recommending cholera vaccination. At the same time, it stimulated research that has led to the development of the effective orally administered cholera vaccines (OCVs) that today are a cornerstone in WHO´s strategy for “Ending Cholera – A Global Roadmap to 2030”. The first effective OCV, Dukoral™, containing a mixture of inactivated Vibrio cholerae bacteria and cholera toxin B subunit, was licenced in 1993 and is together with two similar inactivated whole-cell OCVs, Shanchol™ and Euvichol™/Euvichol-Plus™, the OCVs currently prequalified and recommended by WHO. This brief review is a personalized account of the “modern history” of the development of these now universally recognized effective tools for the control and ultimate elimination of cholera, and of the pivotal role of icddr,b and Bangladesh for this development.

Vaccination against cholera per os. Zabolotny, Savchenko, and Zlatogorov (Vrach. Delo, No. 24-26, 1922)

Considering the question of the validity of cholera vaccination per os sufficiently clarified, thanks to the works of prof. Zabolotny and Savchenko, Zlatogorov, in connection with the studies of Bezredek on local immunity, set out to find out the significance of vaccination per os for the formation of specific antivirals in humans and came to the following conclusions.

Oral Cholera Vaccination as a Model to Assess Dietary Modulation of Gut Inflammation and Immunity

Objectives The aim was to develop a human challenge model in which modulation of immune and inflammatory response by food ingredients can be evaluated. We hypothesized that oral cholera vaccination, in addition to inducing a specific antibody response, induces a significant increase in gut inflammatory response. Methods Twenty healthy men (age 30.6 ± 1.8 y; BMI 24.9 ± 0.6) were enrolled in the study. Fecal and blood samples were collected at baseline. After a 2-week run-in period (D0-D14), subjects were vaccinated with oral cholera vaccine Dukoral (D15). After a period of 2 weeks, a second vaccination was administered (D29). Fecal samples were collected the day before (D14; D28) and the days (D16/D17; D30/D31) after each vaccination, as well as on D42. Blood samples were collected before vaccination (D15; D29), and on D16 and D17/D31, on D43. Primary outcome was fecal calprotectin concentration, secondary outcomes were serum levels of cholera toxin (CTB)-specific IgA and IgG. Other markers of local and systemic inflammatory response included beta-defensins, IP-10, IL-1 ra and hsCRP. Changes over time were tested by means of a linear mixed model. Outliers were identified with the 1.5xIQR rule and excluded from analysis. Results Fecal calprotectin did not increase after the first vaccination. After the second vaccination, a significant increase was observed: from 12.8 ± 2.5 μg/g feces (mean ± SEM) on day 29 to 18.0 ± 2.9 μg/g on day 31 (P = 0.017). Plasma CTB-specific IgA and IgG were strongly increased after the first vaccination, with a further increase after the second vaccination. Plasma CRP slightly decreased on D17, compared to D15 (P = 0.016). IL-1ra significantly decreased 2 days after the first vaccination (P = 0.011), whereas no change was observed after the second vaccination. Beta-defensin was significantly increased at D31 compared to D29 (from 42.7 ± 7.0 to 80.7 ± 16.1 (P = 0.014)). IP-10 did not show any response to vaccination. Conclusions In addition to the expected antibody response, oral cholera vaccination induces an increase in fecal calprotectin and beta defensin, pointing to vaccine induced intestinal inflammation. These readouts may be added to intervention studies with dietary compounds to evaluate the potential for modulating immune responsiveness. Funding Sources Bio&Medical Technol Developm Program of the Natl Res Foundation, Min Science & ICT of Rep Korea.

Parenteral Vaccination with a Cholera Conjugate Vaccine Boosts Vibriocidal and Anti-OSP Responses in Mice Previously Immunized with an Oral Cholera Vaccine

Oral cholera vaccination protects against cholera; however, responses in young children are low and of short duration. The best current correlates of protection against cholera target Vibrio cholerae O-specific polysaccharide (anti-OSP), including vibriocidal responses. A cholera conjugate vaccine has been developed that induces anti-OSP immune responses, including memory B-cell responses. To address whether cholera conjugate vaccine would boost immune responses following oral cholera vaccination, we immunized mice with oral cholera vaccine Inaba CVD 103-HgR or buffer only (placebo) on day 0, followed by parenteral boosting immunizations on days 14, 42, and 70 with cholera conjugate vaccine Inaba OSP: recombinant tetanus toxoid heavy chain fragment or PBS/placebo. Compared with responses in mice immunized with oral vaccine alone or intramuscular cholera conjugate vaccine alone, mice receiving combination vaccination developed significantly higher vibriocidal, IgM OSP-specific serum responses and OSP-specific IgM memory B-cell responses. A combined vaccination approach, which includes oral cholera vaccination followed by parenteral cholera conjugate vaccine boosting, results in increased immune responses that have been associated with protection against cholera. These results suggest that such an approach should be evaluated in humans.

Refugee Settlements and Cholera Risks in Uganda, 2016–2019

ABSTRACTDuring 2016 to 2019, cholera outbreaks were reported commonly to the Ministry of Health from refugee settlements. To further understand the risks cholera posed to refugees, a review of surveillance data on cholera in Uganda for the period 2016–2019 was carried out. During this 4-year period, there were seven such outbreaks with 1,495 cases and 30 deaths in five refugee settlements and one refugee reception center. Most deaths occurred early in the outbreak, often in the settlements or before arrival at a treatment center rather than after arrival at a treatment center. During the different years, these outbreaks occurred during different times of the year but simultaneously in settlements that were geographically separated and affected all ages and genders. Some outbreaks spread to the local populations within Uganda. Cholera control prevention measures are currently being implemented; however, additional measures are needed to reduce the risk of cholera among refugees including oral cholera vaccination and a water, sanitation and hygiene package during the refugee registration process. A standardized protocol is needed to quickly conduct case–control studies to generate information to guide future cholera outbreak prevention in refugees and the host population.

Licensed and Recommended Inactivated Oral CholeraVaccines: From Development to Innovative Deployment

Cholera is a disease of poverty and occurs where there is a lack of access to clean water and adequate sanitation. Since improved water supply and sanitation infrastructure cannot be implemented immediately in many high-risk areas, vaccination against cholera is an important additional tool for prevention and control. We describe the development of licensed and recommended inactivated oral cholera vaccines (OCVs), including the results of safety, efficacy and effectiveness studies and the creation of the global OCV stockpile. Over the years, the public health strategy for oral cholera vaccination has broadened—from purely pre-emptive use to reactive deployment to help control outbreaks. Limited supplies of OCV doses continues to be an important problem. We discuss various innovative dosing and delivery approaches that have been assessed and implemented and evidence of herd protection conferred by OCVs. We expect that the demand for OCVs will continue to increase in the coming years across many countries.

Cholera in travellers: improving vaccination guidance in Europe

Background Cholera is endemic in ~50 countries worldwide and remains a disease associated with poverty, causing illness and death in the poorest and most vulnerable people. In travellers, cholera is considered a low-incidence disease, but the true impact on travellers is difficult to assess. Cholera vaccination may improve safety for certain European travellers at risk. Effective vaccines are available; however, vaccination recommendations in Europe vary considerably between countries. Methods In this review, a comparison of cholera vaccination recommendations from 29 advice reference bodies across key European countries (United Kingdom, Germany, Spain, Italy, Portugal, Switzerland, Sweden, Finland, Norway, France and Denmark) is presented. The differences in perceived cholera risk are highlighted, and a comparison with the United States Centers for Disease Control and Prevention (CDC) recommendations is included. Results In general terms, the recommendations from European organizations are ambiguous and differ widely. This contrasts with the situation in the United States, where the CDC publishes a consistent set of guidelines. Conclusion With the ease of intra-European travel, it would seem sensible to harmonize the recommendations for cholera vaccination and risk perception across Europe, providing pre-travel health advisers with a trusted source of information that allows them to provide consistent recommendations.