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Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines...
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Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 55863

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Prof. Dr. David Nalin

E-Mail Website
Guest Editor
Center for Immunology and Microbial Diseases, Albany Medical College, Albany, NY 12208, USA
Interests: vaccine development; vaccinology; immunology of infectious diseases; intestinal infectious and pathophysiology; cholera; hepatitis; malaria
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues:

Cholera continues to be a global threat in the 21st century, chiefly due to the continued lack of adequate resource provision and political will to ensure safe potable water supply and sanitary waste disposal for a burgeoning global population. The current Special Issue on cholera provides an overview of the available control measures from the perspectives of bioecology, immunology and vaccinology and treatment. These modalities have the potential to reduce cholera case fatality rates to less than 1% if properly implemented. In this Special Issue on cholera, the current state of the art of science-based control measures is reported on by several of the world’s leaders in the research on the control of cholera and allied acute watery diarrheal diseases.

Dr. Rita Colwell, Dr. Anwar Huq and colleagues at the University of Maryland and the University of Florida will review the latest information on environmental factors for the prediction and prevention of cholera. Dr. Jacqueline Dean and Dr. John Clemens will contribute an overview of recent insights into the performance of licensed and recommended cholera vaccines. Dr. Jan Holmgren will present an update on cholera immunity and the next generation of cholera vaccines. Dr. David Nalin will discuss cholera treatment options and optimums for the 21st century, and Dr. Richard A. Cash will focus on bringing diarrhea treatment, control, and prevention to the community.

You may choose our Joint Special Issue in Life.

Prof. Dr. David Nalin
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Tropical Medicine and Infectious Disease is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cholera
  • control
  • immunology
  • vaccines
  • treatment

Related Special Issue

Published Papers (12 papers)

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Editorial

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2 pages, 159 KiB  
Editorial
Eliminating Cholera Incidence and Mortality: Unfulfilled Tasks
by David Nalin
Trop. Med. Infect. Dis. 2022, 7(5), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed7050069 - 09 May 2022
Viewed by 1637
Abstract
Impressive advances have been made in new cholera vaccine development and vaccination control strategies [...] Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)

Research

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6 pages, 161 KiB  
Article
Using Oral Rehydration Therapy (ORT) in the Community
by Richard A. Cash
Trop. Med. Infect. Dis. 2021, 6(2), 92; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020092 - 29 May 2021
Cited by 2 | Viewed by 4996
Abstract
For ORT to have a maximum impact on public health it should be used in the community, in the home. A number of programs have been developed over the years to extend ORT to home use. One of the most successful approaches was [...] Read more.
For ORT to have a maximum impact on public health it should be used in the community, in the home. A number of programs have been developed over the years to extend ORT to home use. One of the most successful approaches was the Oral Therapy Education Program (OTEP) developed by BRAC, the world’s largest NGO. Mothers were taught in the home by an OTEP worker using seven simple messages and a demonstration. The program, which led to high levels of use and knowledge retention, is described. What the OTEP and other successful home-based programs have demonstrated is that home care of diarrhea using ORS can be effectively implemented and can have a positive impact on the reduction of diarrhea morbidity and mortality. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
12 pages, 7859 KiB  
Article
Cholera Hot-Spots and Contextual Factors in Burundi, Planning for Elimination
by Amanda K. Debes, Allison M. Shaffer, Thaddee Ndikumana, Iteka Liesse, Eric Ribaira, Clement Djumo, Mohammad Ali and David A. Sack
Trop. Med. Infect. Dis. 2021, 6(2), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020076 - 11 May 2021
Cited by 8 | Viewed by 5226
Abstract
The Republic of Burundi first reported cholera cases in 1978 and outbreaks have been occurring nearly every year since then. From 2008–2020, 6949 cases and 43 deaths were officially reported. To evaluate Burundi’s potential to eliminate cholera, we identified hotspots using cholera incidence [...] Read more.
The Republic of Burundi first reported cholera cases in 1978 and outbreaks have been occurring nearly every year since then. From 2008–2020, 6949 cases and 43 deaths were officially reported. To evaluate Burundi’s potential to eliminate cholera, we identified hotspots using cholera incidence and disease persistence as suggested by the Global Task Force for Cholera Control. The mean annual incidence for each district that reported cholera ranged from 0.29 to 563.14 cases per 100,000 population per year from 2014–2020. Ten of 12 Health Districts which recorded cholera cases reported a mean annual incidence ≥5 per 100,000 for this time period. Cholera cases occur during the second half of the year in the areas near Lake Tanganyika and along the Ruzizi River, with the highest risk district being Bujumbura Centre. Additional research is needed to understand the role of Lake Tanganyika; risks associated with fishing; migration patterns; and other factors that may explain cholera’s seasonality. Due to the consistent epidemiological pattern and the relatively small area affected by cholera, control and elimination are feasible with an integrated program of campaigns using oral cholera vaccine over the short term and community-based interventions including WASH activities for sustained control. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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20 pages, 2129 KiB  
Article
An Update on Cholera Immunity and Current and Future Cholera Vaccines
by Jan Holmgren
Trop. Med. Infect. Dis. 2021, 6(2), 64; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6020064 - 28 Apr 2021
Cited by 19 | Viewed by 6715
Abstract
Individual resistance to cholera infection and disease depends on both innate host factors and adaptive immunity acquired by a previous infection or vaccination. Locally produced, intestinal-mucosal secretory IgA (SIgA) antibodies against bacterial surface lipopolysaccharide (LPS) O antigens and/or secreted cholera toxins are responsible [...] Read more.
Individual resistance to cholera infection and disease depends on both innate host factors and adaptive immunity acquired by a previous infection or vaccination. Locally produced, intestinal-mucosal secretory IgA (SIgA) antibodies against bacterial surface lipopolysaccharide (LPS) O antigens and/or secreted cholera toxins are responsible for the protective adaptive immunity, in conjunction with an effective mucosal immunologic memory that can elicit a rapid anamnestic SIgA antibody response upon re-exposure to the antigen/pathogen even many years later. Oral cholera vaccines (OCVs), based on inactivated Vibrio cholerae whole-cell components, either together with the cholera toxin B subunit (Dukoral™) or administered alone (Shanchol™/Euvichol-Plus™) were shown to be consistently safe and effective in large field trials in all settings. These OCVs are recommended by the World Health Organisation (WHO) for the control of both endemic cholera and epidemic cholera outbreaks. OCVs are now a cornerstone in WHO’s global strategy found in “Ending Cholera: A Global Roadmap to 2030.” However, the forecasted global demands for OCV, estimated by the Global Alliance for Vaccines and Immunization (GAVI) to 1.5 billion doses for the period 2020–2029, markedly exceed the existing manufacturing capacity. This calls for an increased production capacity of existing OCVs, as well as the rapid introduction of additional and improved vaccines under development. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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11 pages, 501 KiB  
Article
Cholera and Pancreatic Cholera: Is VIP the Common Pathophysiologic Factor?
by Farzana Afroze, Steven Bloom, Paul Bech, Tahmeed Ahmed, Shafiqul Alam Sarker, John D. Clemens, Farhana Islam and David Nalin
Trop. Med. Infect. Dis. 2020, 5(3), 111; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed5030111 - 02 Jul 2020
Cited by 3 | Viewed by 2896
Abstract
Background: Cholera remains a major global health problem, causing high output diarrhea leading to severe dehydration and shock in developing countries. We aimed to determine whether vasoactive intestinal polypeptide (VIP), the mediator of pancreatic cholera syndrome, has a role in the pathophysiology of [...] Read more.
Background: Cholera remains a major global health problem, causing high output diarrhea leading to severe dehydration and shock in developing countries. We aimed to determine whether vasoactive intestinal polypeptide (VIP), the mediator of pancreatic cholera syndrome, has a role in the pathophysiology of human cholera. Methods: We conducted a prospective observational study of cholera cases hospitalized with severe dehydration. Plasma and stool water levels of VIP were measured just after admission, after complete rehydration (3–4 h), at 24 h post-rehydration and at discharge after diarrhea ceased. Results: In total, 23 cholera patients were examined between January and August 2018. The geometric mean of stool VIP (sVIP) and plasma VIP (pVIP) on admission were 207.67 and 8.34 pmol/L, respectively. pVIP values were all within the normal range (</= 30 pcmol/L); however, sVIP levels were very high at all timepoints, though less so just after rehydration. In multivariable GEE models, after adjustment for covariates, sVIP levels were significantly associated with duration of hospitalization (p = 0.026), total stool volume (p = 0.023) as well as stool output in the first 24 h (p = 0.013). Conclusions: The data suggest that VIP, which is released by intestinal nerves, may play an important role in human choleragenesis, and inhibitors of intestinal VIP merit testing for potential therapeutic benefits. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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Review

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28 pages, 812 KiB  
Review
The History of Intravenous and Oral Rehydration and Maintenance Therapy of Cholera and Non-Cholera Dehydrating Diarrheas: A Deconstruction of Translational Medicine: From Bench to Bedside?
by David R. Nalin
Trop. Med. Infect. Dis. 2022, 7(3), 50; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed7030050 - 12 Mar 2022
Cited by 2 | Viewed by 5901
Abstract
The “bench to bedside” (BTB) paradigm of translational medicine (TM) assumes that medical progress emanates from basic science discoveries transforming clinical therapeutic models. However, a recent report found that most published medical research is false due, among other factors, to small samples, inherent [...] Read more.
The “bench to bedside” (BTB) paradigm of translational medicine (TM) assumes that medical progress emanates from basic science discoveries transforming clinical therapeutic models. However, a recent report found that most published medical research is false due, among other factors, to small samples, inherent bias and inappropriate statistical applications. Translation-blocking factors include the validity (or lack thereof) of the underlying pathophysiological constructs and related therapeutic paradigms and adherence to faulty traditional beliefs. Empirical discoveries have also led to major therapeutic advances, but scientific dogma has retrospectively retranslated these into the BTB paradigm. A review of the history of intravenous (I.V.) and oral therapy for cholera and NDDs illustrates some fallacies of the BTB model and highlights pitfalls blocking translational and transformative progress, and retro-translational factors, including programmatic modifications of therapeutic advances contradicting therapeutic paradigms and medical economic factors promoting more expensive and profitable medical applications inaccessible to resource-limited environments. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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12 pages, 299 KiB  
Review
Systemic, Mucosal, and Memory Immune Responses following Cholera
by Edward T. Ryan, Daniel T. Leung, Owen Jensen, Ana A. Weil, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Fahima Chowdhury, Regina C. LaRocque, Jason B. Harris, Stephen B. Calderwood, Firdausi Qadri and Richelle C. Charles
Trop. Med. Infect. Dis. 2021, 6(4), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6040192 - 27 Oct 2021
Cited by 4 | Viewed by 4122
Abstract
Vibrio cholerae O1, the major causative agent of cholera, remains a significant public health threat. Although there are available vaccines for cholera, the protection provided by killed whole-cell cholera vaccines in young children is poor. An obstacle to the development of improved cholera [...] Read more.
Vibrio cholerae O1, the major causative agent of cholera, remains a significant public health threat. Although there are available vaccines for cholera, the protection provided by killed whole-cell cholera vaccines in young children is poor. An obstacle to the development of improved cholera vaccines is the need for a better understanding of the primary mechanisms of cholera immunity and identification of improved correlates of protection. Considerable progress has been made over the last decade in understanding the adaptive and innate immune responses to cholera disease as well as V. cholerae infection. This review will assess what is currently known about the systemic, mucosal, memory, and innate immune responses to clinical cholera, as well as recent advances in our understanding of the mechanisms and correlates of protection against V. cholerae O1 infection. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
13 pages, 589 KiB  
Review
A Review of the Environmental Trigger and Transmission Components for Prediction of Cholera
by Moiz Usmani, Kyle D. Brumfield, Yusuf Jamal, Anwar Huq, Rita R. Colwell and Antarpreet Jutla
Trop. Med. Infect. Dis. 2021, 6(3), 147; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6030147 - 05 Aug 2021
Cited by 14 | Viewed by 8177
Abstract
Climate variables influence the occurrence, growth, and distribution of Vibrio cholerae in the aquatic environment. Together with socio-economic factors, these variables affect the incidence and intensity of cholera outbreaks. The current pandemic of cholera began in the 1960s, and millions of cholera cases [...] Read more.
Climate variables influence the occurrence, growth, and distribution of Vibrio cholerae in the aquatic environment. Together with socio-economic factors, these variables affect the incidence and intensity of cholera outbreaks. The current pandemic of cholera began in the 1960s, and millions of cholera cases are reported each year globally. Hence, cholera remains a significant health challenge, notably where human vulnerability intersects with changes in hydrological and environmental processes. Cholera outbreaks may be epidemic or endemic, the mode of which is governed by trigger and transmission components that control the outbreak and spread of the disease, respectively. Traditional cholera risk assessment models, namely compartmental susceptible-exposed-infected-recovered (SEIR) type models, have been used to determine the predictive spread of cholera through the fecal–oral route in human populations. However, these models often fail to capture modes of infection via indirect routes, such as pathogen movement in the environment and heterogeneities relevant to disease transmission. Conversely, other models that rely solely on variability of selected environmental factors (i.e., examine only triggers) have accomplished real-time outbreak prediction but fail to capture the transmission of cholera within impacted populations. Since the mode of cholera outbreaks can transition from epidemic to endemic, a comprehensive transmission model is needed to achieve timely and reliable prediction with respect to quantitative environmental risk. Here, we discuss progression of the trigger module associated with both epidemic and endemic cholera, in the context of the autochthonous aquatic nature of the causative agent of cholera, V. cholerae, as well as disease prediction. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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16 pages, 3205 KiB  
Review
Issues and Controversies in the Evolution of Oral Rehydration Therapy (ORT)
by David Nalin
Trop. Med. Infect. Dis. 2021, 6(1), 34; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6010034 - 12 Mar 2021
Cited by 4 | Viewed by 4674 | Correction
Abstract
The original studies demonstrating the efficacy of oral glucose-electrolytes solutions in reducing or eliminating the need for intravenous therapy to correct dehydration caused by acute watery diarrheas (AWD) were focused chiefly on cholera patients. Later research adapted the oral therapy (ORT) methodology for [...] Read more.
The original studies demonstrating the efficacy of oral glucose-electrolytes solutions in reducing or eliminating the need for intravenous therapy to correct dehydration caused by acute watery diarrheas (AWD) were focused chiefly on cholera patients. Later research adapted the oral therapy (ORT) methodology for treatment of non-cholera AWDs including for pediatric patients. These adaptations included the 2:1 regimen using 2 parts of the original WHO oral rehydration solution (ORS) formulation followed by 1 part additional plain water, and a “low sodium” packet formulation with similar average electrolyte and glucose concentrations when dissolved in the recommended volume of water. The programmatic desire for a single ORS packet formulation has led to controversy over use of the “low sodium” formulations to treat cholera patients. This is the subject of the current review, with the conclusion that use of the low-sodium ORS to treat cholera patients leads to negative sodium balance, leading to hyponatremia and, in severe cases, particularly in pediatric cholera, to seizures and other complications of sodium depletion. Therefore it is recommended that two separate ORS packet formulations be used, one for cholera therapy and the other for non-cholera pediatric AWD. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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11 pages, 973 KiB  
Review
Licensed and Recommended Inactivated Oral CholeraVaccines: From Development to Innovative Deployment
by Jacqueline Deen and John D. Clemens
Trop. Med. Infect. Dis. 2021, 6(1), 32; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed6010032 - 09 Mar 2021
Cited by 4 | Viewed by 3237
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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Other

1 pages, 169 KiB  
Correction
Correction: Nalin, D. Issues and Controversies in the Evolution of Oral Rehydration Therapy (ORT). Trop. Med. Infect. Dis. 2021, 6, 34
by David Nalin
Trop. Med. Infect. Dis. 2022, 7(6), 103; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed7060103 - 14 Jun 2022
Cited by 1 | Viewed by 950
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
5 pages, 197 KiB  
Perspective
Oral Rehydration Salts, Cholera, and the Unfinished Urban Health Agenda
by Thomas J. Bollyky
Trop. Med. Infect. Dis. 2022, 7(5), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/tropicalmed7050067 - 29 Apr 2022
Cited by 3 | Viewed by 4164
Abstract
Cholera has played an outsized role in the history of how cities have transformed from the victims of disease into great disease conquerors. Yet the current burden of cholera and diarrheal diseases in the fast-urbanizing areas of low-income nations shows the many ways [...] Read more.
Cholera has played an outsized role in the history of how cities have transformed from the victims of disease into great disease conquerors. Yet the current burden of cholera and diarrheal diseases in the fast-urbanizing areas of low-income nations shows the many ways in which the urban health agenda remains unfinished and must continue to evolve. Full article
(This article belongs to the Special Issue Cholera Control in 2021: Bioecology, Immunology, Current and Future Vaccines and Treatment Options)
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