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COMMENTARY
Year : 2021  |  Volume : 65  |  Issue : 3  |  Page : 311-314  

Cholera pulse vaccination: A possible elimination strategy for cholera in endemic countries


1 Professor and In-charge Enteric Laboratory, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Senior Resident, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission09-Jan-2021
Date of Decision01-Jun-2021
Date of Acceptance27-Jul-2021
Date of Web Publication22-Sep-2021

Correspondence Address:
Neelam Taneja
Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijph.IJPH_21_21

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   Abstract 


Cholera is a diarrheal disease causing major health issue in developing countries where it is endemic and causes outbreaks. India ranks first with an estimated 675,188 number of cases and 20,256 number of deaths annually with one-third of its population at risk. The two broad approaches for cholera control are improving sanitation and vaccination. Now both live and killed oral vaccines are available. Live vaccines are advantageous in respect of intestinal colonization and rapid immune response and also lead to in vivo exposure of bacterial products leading to good immunological response against wild Vibrio cholerae infection. The three major delivery strategies which can be considered for the implementation of oral cholera vaccine are preemptive vaccination, reactive vaccinations, and National Immunization Program. We propose the use of cholera live oral vaccines for achieving control of this disease by repeated vaccination of the susceptible population in a series of pulses to control it from the entire population.

Keywords: Cholera, vaccination, vaccines, Vibrio cholerae


How to cite this article:
Taneja N, Gupta S, Tiewsoh JB, Srivastava S. Cholera pulse vaccination: A possible elimination strategy for cholera in endemic countries. Indian J Public Health 2021;65:311-4

How to cite this URL:
Taneja N, Gupta S, Tiewsoh JB, Srivastava S. Cholera pulse vaccination: A possible elimination strategy for cholera in endemic countries. Indian J Public Health [serial online] 2021 [cited 2021 Dec 2];65:311-4. Available from: https://www.ijph.in/text.asp?2021/65/3/311/326390




   Introduction Top


Cholera is an acute severe watery diarrheal disease of antiquity. In spite of decades of research, many aspects of the disease still remain enigmatic. Cholera is a key indicator of lack of social development.[1] Overcrowding, poor hygiene, inadequate sanitation, and lack of safe drinking water are some of the factors which favor its spread. Therefore, the disease still remains a major health issue in developing countries where it exists as endemic infection and also causes outbreaks.[2] Ali et al. conducted a study on the global burden of cholera in endemic countries using spatial regression model where they predicted that 675,188 cholera cases occur annually in India and the estimated annual number of deaths was 20,256 which makes India rank first among the 47 countries affected by cholera. They also highlighted the fact that poor disease surveillance solely based on clinical scenario leads to lower disease incidence estimation.[3] In another recent study conducted by Ali et al., where 24 of 36 states of India reported cholera during 2010–2015, they found that the mean value of households at district level who were using tap water from treated source was 28.24%; those using piped sewer system was 8.88% and those using closed drainage was 13.48% with nearly one-third (30.69%) of the population at risk.[4]

Way back in 1959, Pollitzer segregated India on the basis of prevalence of disease into two regions (a) Regions prone for cholera epidemic with inter epidemic period free of infection such as Punjab, Delhi, United Provinces (Uttar Pradesh), Central Provinces (Madhya Pradesh), Hyderabad, Mysore, and Bombay, (b) Regions at a high level endemicity such as Bengal, coastal Orissa, and some districts of Assam and Bihar. However, the present disease burden is much higher than that considered in the past.[5] Actual hotspots of cholera still are not well explored due to poor surveillance. Moreover, the disease can occur in some naïve area due to migrating population from endemic regions or post natural disasters. The two broad approaches for cholera control constitute improving sanitation and vaccination. Both the interventions are essential strategies in the fight against cholera, however universal access to Water, Sanitation and Hygiene (WASH) strategy being a long-term initiative, a more targeted approach in the form of vaccination effort is needed. In 2016, the National Technical Advisory Group on Immunization of the government of India considered to complement the WASH measures with immunization.[6]


   Available Vaccines Top


Vaccines for cholera have been around for a number of years. The popularity of these vaccines in the initial years was limited due to availability of only parenteral formulations. However, now both live and killed oral formulation of vaccines are available. Live vaccine has an advantage over the killed in respect of intestinal colonization and rapid immune response thus obviating the need of repeat doses. Live cholera vaccine leads to in vivo exposure of bacterial products thus leading to good immunological response against wild Vibrio cholerae infection.[7] Whereas killed oral cholera vaccines (OCV) are more popular due to lower cost of development and no risk of vaccine derived infection. At present, there are three WHO prequalified killed oral vaccines, of these Dukoral®(SBL Vaccines) is a monovalent killed whole cell vaccine, containing a nontoxic B-subunit of cholera toxin and providing protection against V. cholerae O1, and other two vaccines are bivalent against both V. cholerae O1 and O139 namedShanchol (Shantha Biotechlimited India) and Euvichol® (developed in South Korea).[8] Whereas for live oral vaccine formulation, CVD 103-HgR has been approved by the United States Food and Drug Administration in 2016 while others such as Peru-15and V. cholerae 638 are at different stages of development. The vaccine CVD 103-HgR had been around for the past few years but was unfortunately shelved due to economic and patent reasons.[9]

Shanchol is indigenous to India developed by Sanofi Company at Hyderabad and reformulated at International Vaccine Institute, Korea. It has been considered superior to Dukoral® which was used previously in terms of efficacy (5 years vs. 3 years), cost (Rs. 120 vs. Rs. 320 per dose) and coverage (bivalent vs. monovalent). This vaccine was first introduced at Haiti postcholera outbreak.[8] A randomized, placebo-controlled trial in India showed that Shanchol™ is safe and confers 67% protective efficacy against cholera within 2 years of vaccination, 66% at 3 years and 65% at 5 years of follow-up. Shanchol™ was licensed in India in 2009.[2] Following its licensure in India, feasibility and costs of a local mass vaccination campaign using government health staff, resources, and logistics for Shanchol has been demonstrated in Odisha.[10] Herd immunity provided by the vaccine depends on the coverage as inferred in a study done at Kolkata by Ali et al., two dose OCV indirectly cover >28% of the population.[11] The data also showed that vaccinating 50% of the population can result in a 93% reduction in cholera incidence in the population through the synergistic effect of both direct and indirect protection and another analysis suggests that 60% or higher vaccine coverage in the population may stop cholera transmission.[12]


   Vaccine Delivery Strategies Top


Implementing the newer vaccine in a country is challenging in its operational/delivery strategies. There are three major delivery strategies which can be considered for implementation of OCV in any country. They are as follows (1) Preemptive vaccination which is deploying vaccine prior to seasonal outbreak, (2) Reactive vaccinations which is done when outbreak has started and the targeted population is covered, and (3) National Immunization Program which is a part of Expanded Program of Immunization (EPI) or as pulse vaccination.

Preemptive vaccination concept

Preemptive vaccination is carried out in targeted populations in areas at risk for outbreaks including those during humanitarian crisis or before any potential upsurge in cholera transmission. Such vaccination campaigns help to prevent a potential outbreak from occurring and also can reduce spread of the disease.[13] This concept of vaccination is more logical if vaccine supply is adequate. Although the major challenges in its implementation is identification of the hotspots and vaccine coverage. As cholera surveillance system is not very effective and efficient which creates a lacuna to identify the target areas and population. Vaccine coverage still remains a major challenge even if the target population is identified, as it has been experienced from other mass campaigns that population acceptance for newer vaccine remains low. Preemptive campaigns have been conducted in (a) endemic settings in Mozambique (2003/04) and Zanzibar (2009); (b) use in refugee camps and postcrisis situations in Uganda (1997), Darfur, Sudan (2004), Aceh, Indonesia (2005), Haiti (2012), South Sudan (2013), and Thailand (2013).[14] These campaigns have yielded valuable lessons by reinforcing the need of a global cholera vaccine stockpile.

Reactive vaccinations strategy

In 1998, Vietnamese used bottom-up approach in assessing OCV use and stand out as first and only country using killed OCVs in their immunization program. They first deployed the OCVs prior to expected cholera season, later, they conducted reactive vaccination campaigns in many of their states despite OCV were readily available at that time from the National EPI. They had delivered more than 10 million doses of vaccine and spent approximately US$1.07 per person and hardly any adverse events reported. Cholera vaccination became a part of their public health program. Its more than 15 years of deployment of two doses of OCV which indicates that vaccine can be used in public health settings.[15] In 2008, for the first time, they conducted a study to see the effect of reactive vaccination using killed cholera OCV during outbreak. The study was conducted at the two districts of Hanoi.[16] Hence, learning lesson from the Vietnamese development and deployment of the mORC-Vax™ (Vabiotech, Viet Nam) is that it can be considered as a major delivery strategy in India.

National immunization program

Cholera vaccine campaigns similar to polio vaccination may help in our public health efforts in controlling cholera. We propose the use of cholera live oral vaccines in mass vaccination programs for achieving control of this disease. The concept of pulse vaccination has been successfully implemented in the eradication of diseases like poliomyelitis. It is intriguing to note that many epidemiological and demographical features are shared between cholera and polio including the organism ecology, where both have water bodies as important reservoirs of the pathogen. There are two important aspects of pulsed polio program, first, a live oral vaccine with vaccine strain shedding and second the timed/pulsed mass vaccination to the susceptible population with a target to block wild pathogen transmission and eventually replace the wild strain with the attenuated vaccine strain in the environment. With the availability of live OCV both these aspects can be successfully applied for cholera control and eradication by the development of herd immunity in the community. This strategy could be of immense importance in resource-poor nations and areas with a huge population where community mobilization for vaccination is difficult.

The scientific basis of polio eradication using OPV was to create an epidemic of subclinical infection so that the number of susceptible individuals would suddenly decline, upsetting the normal epidemiology of wild pathogen transmission.[17] In the case of oral polio vaccine, the vaccine strain shedding was high enough to predict complete replacement of the wild virus in the environment. However, in the setting of oral live cholera vaccine, the vaccine strain shedding is minimal (19%).[18],[19] The theoretical possibility of protection of household contacts of the vaccinees cannot be negated. Furthermore, the target population for mass cholera immunization would comprise of a significantly higher number of individuals compared to mass polio immunization (targeting kids <5 years), which would lead to a significantly higher degree of organism shedding in the environment theoretically leading to better protection. Various mathematical modeling strategies predict that by repeated vaccination of the susceptible population in a series of pulses, it is possible to eradicate the infection from the entire model population in a random environment. In a modeling study by Longini et al., in the Matlab region of Bangladesh which is an endemic area, it indicated that cholera transmission can be controlled when 50% of the population had received an OCV. Also, with the same coverage the model predicted that there will be a 89%reduction of cholera cases in unvaccinated individuals and a 93% overall reduction in the entire population.[20] However, when we consider live oral cholera vaccination, the model dynamics could change, further bringing down the target population to be vaccinated with the protective effect from live vaccine strain shedding and single dose regimes against the two-dose regimen of the killed vaccine. Instead of targeting the whole country, the five top states which contribute to cholera including West Bengal, Karnataka, Punjab, Gujarat, and Maharashtra could be targeted for vaccination on a pilot basis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
World Health Organization (WHO). Cholera Factsheet. Available from: https://www.who.int/news-room/fact-sheets/detail/cholera. [Last accessed on 2021 Jun 02].  Back to cited text no. 1
    
2.
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3.
Ali M, Nelson AR, Lopez AL, Sack DA. Updated global burden of cholera in endemic countries. PLoS Negl Trop Dis 2015;9:e0003832.  Back to cited text no. 3
    
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Ali M, Sen Gupta S, Arora N, Khasnobis P, Venkatesh S, Sur D, et al. Identification of burden hotspots and risk factors for cholera in India: An observational study. PLoS One 2017;12:e0183100.  Back to cited text no. 4
    
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Time Trends of Cholera in India: An Overview. Available from: https://www.semanticscholar.org/paper/Time-Trends-of-Cholera-in-India-%3A-An-Overview/e6168b3eb6b29310e956c3a64af8d56891590d7f#related-papers. [Last accessed on 2020 Nov 25].  Back to cited text no. 5
    
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Ray A, Sarkar K, Haldar P, Ghosh R. Oral cholera vaccine delivery strategy in India: Routine or campaign? - A scoping review. Vaccine 2020;38 Suppl 1:A184-93.  Back to cited text no. 6
    
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8.
Gupta SS, Bharati K, Sur D, Khera A, Ganguly NK, Nair GB. Why is the oral cholera vaccine not considered an option for prevention of cholera in India? Analysis of possible reasons. Indian J Med Res 2016;143:545-51.  Back to cited text no. 8
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9.
Mayo-Smith LM, Simon JK, Chen WH, Haney D, Lock M, Lyon CE, et al. The Live Attenuated Cholera Vaccine CVD 103-HgR primes responses to the toxin-coregulated pilus antigen tcpa in subjects challenged with wild-type Vibrio cholerae. Clin Vaccine Immunol 2017;24:e00470-16.  Back to cited text no. 9
    
10.
Kar SK, Sah B, Patnaik B, Kim YH, Kerketta AS, Shin S, et al. Mass vaccination with a new, less expensive oral cholera vaccine using public health infrastructure in India: The Odisha model. PLoS Negl Trop Dis 2014;8:e2629.  Back to cited text no. 10
    
11.
Ali M, Sur D, You YA, Kanungo S, Sah B, Manna B, et al. Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India. Clin Infect Dis 2013;56:1123-31.  Back to cited text no. 11
    
12.
Saha A, Rosewell A, Hayen A, MacIntyre CR, Qadri F. Improving immunization approaches to cholera. Expert Rev Vaccines 2017;16:235-48.  Back to cited text no. 12
    
13.
STOP CHOLERA. Guidance Note on the Use of Oral Cholera Vaccines for UNICEF. Available from: https://www.stopcholera.org/photo-gallery/guidance-note-use-oral-cholera-vaccines-unicef. [Last accessed on 2021 Jun 15].  Back to cited text no. 13
    
14.
World Health Organization (WHO). Use of Oral Cholera Vaccine in Humanitarian Emergencies. Available from: https://www.who.int/publications/i/item/use-of-oral-cholera-vaccine-in-humanitarian-emergencies. [Last accessed on 2021 Jun 15].  Back to cited text no. 14
    
15.
Anh DD, Lopez AL, Tran HT, Cuong NV, Thiem VD, Ali M, et al. Oral cholera vaccine development and use in Vietnam. PLoS Med 2014;11:e1001712.  Back to cited text no. 15
    
16.
Anh DD, Lopez AL, Thiem VD, Grahek SL, Duong TN, Park JK, et al. Use of oral cholera vaccines in an outbreak in Vietnam: A case control study. PLoS Negl Trop Dis 2011;5:e1006.  Back to cited text no. 16
    
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John TJ. Understanding the scientific basis of preventing polio by immunization.pioneering contributions from India. Proc.Indian Natn Sci Acad 2003;69:393-422.  Back to cited text no. 17
    
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Tacket CO, Cohen MB, Wasserman SS, Losonsky G, Livio S, Kotloff K, et al. Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination. Infect Immun 1999;67:6341-5.  Back to cited text no. 18
    
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Migasena S, Pitisuttitham P, Prayurahong B, Suntharasamai P, Supanaranond W, Desakorn V, et al. Preliminary assessment of the safety and immunogenicity of live oral cholera vaccine strain CVD 103-HgR in healthy Thai adults. Infect Immun 1989;57:3261-4.  Back to cited text no. 19
    
20.
Longini IM Jr., Nizam A, Ali M, Yunus M, Shenvi N, Clemens JD. Controlling endemic cholera with oral vaccines. PLoS Med 2007;4:e336.  Back to cited text no. 20
    




 

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