**Preface to "Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options"**

In 2017, the Global Task Force on Cholera Control launched an initiative to reduce cholera deaths by 90% in at least 20 countries by 2030 [1]. This Special Issue focuses on the search for strategies to control cholera and non-cholera dehydrating diarrheas, including vaccinology and therapeutics, and provides the opportunity to release these ten original papers in book form as an overview of the current control options for cholera and related diseases. The papers include 7 original reports, 2 reviews and 1 perspective article.

Moiz Usmani and colleagues[1] discuss climate variables' influence on epidemics and the role of trigger and transmission components in relation to pathogens' environmental distribution. The extra-human bioecologic cycle of V. cholerae (and related organisms) shifts the focus from eradication, which is not possible, to control. Instead, effective control is likely to require improved environmental risk modeling and the identification of trigger components and their role in transmission and transition from endemic to epidemic form.

In this context, the study of Amanda Debes and colleagues on cholera "hot-spots" and contextual factors in Burundi [2] can provide a useful approach to the improved control developing from oral vaccination and comprehensive community-based WASH and treatment modules to eliminate ongoing high case-fatality rates in affected African Nations.

Thomas Bollyky [3] discusses the challenges posed by shifting demographics and urbanization regarding the impact of planning and control programs on both vaccine-based and treatment-based components. Effective control measures will require careful attention to gaps in the urban health agenda.

Jan Holmgren [4] discusses the expanded research on cholera immunity leading to oral cholera vaccines (OCV), which have improved prospects for a reduction in clinical disease burden and deaths, as well as cross-protection against severe ETEC disease in both endemic and epidemic situations. Although contaminated water (imbibed or contaminating food) is key to cholera transmission, a surprising added benefit of OCV, noted in several trials in endemic areas, is the protection of unvaccinated family or community members when vaccine coverage exceeds 50%.

Novel deployment strategies for inactivated oral cholera vaccines are discussed by Jacqueline Dean and John Clemens[5] in a review of follow-up data from single-dose, targeted deployment ring vaccination trials and other new delivery strategies, as well as indirect effects such as herd immunity.

The limitations of current vaccines require solutions based on continued research on human local and humoral responses to *V. cholera* antigens. The provision of adequately protective vaccines for immune-na¨ıve individuals (young children and natives of non-endemic regions) remains a future goal. Achieving long-term protection with (preferably) single-dose vaccines and the role of memory immune responses and questions regarding correlates of protection are discussed in detail in the article by Edward Ryan and co-workers [6].

Focusing on the treatment arm of control measures, the history of progress (and regress) in transitional medicine regarding intravenous and oral therapy for cholera and related diseases is comprehensively reviewed in the article by David Nalin [7] on the "Bench to Bedside" vs. "Bedside to Bench" perspectives.

The essentials when delivering oral rehydration therapy (ORT) at the community level are

reviewed by Richard Cash [8] based on his experience in the programs conducted by BRAC in Bangladesh villages.

Current controversies in ORT are discussed in David Nalin's review [9] of ongoing modifications to oral solution composition in relation to electrolyte balance, efficacy during rehydration and maintenance phases, and potential safety issues, with a special focus on safety concerns and the differences between cholera and non-cholera dehydrating diarrheas.

Farzana Afroze and co-workers [10] report on the confirmation of a role for Vasoactive Intestinal Polypeptide (VIP) in human cholera pathogenesis, potentially pointing the way to new therapies aiming to quickly stop cholera diarrhea.

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