Protection from killed oral cholera vaccine continues for 4 years
Authors: David A Sack, Mohammad Ali
Journal: The Lancet Global Health (2018)

The paper by Molly Franke and colleagues1Franke MF Ternier R Jerome JG Matias WR Harris JB Ivers LC Long-term effectiveness of one and two doses of a killed, bivalent, whole-cell oral cholera vaccine in Haiti: an extended case-control study.Lancet Glob Health. 2018; 6: e1028-e1035Summary Full Text Full Text PDF PubMed Scopus (24) Google Scholar in The Lancet Global Health describes results from a case-control study that reported protection from two doses of killed oral cholera vaccine persisted for at least 4 years and did not appear to wane during this time. This conclusion is based on follow-up of cholera cases after two vaccine campaigns in Haiti, including one in 2012 in Artibonite Department and a second in 2014 in the Central Department. The initial results from the Artibonite campaign were reported earlier2Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar but this new study provides data over a longer period and includes results from these two campaigns, using similar methods. This study found no evidence that two-dose effectiveness decreased during follow-up among the 178 people in the case group and 706 people in the control group—the adjusted average cumulative effectiveness was 76% (95% CI 59–86). For a single dose, effectiveness decreased over time to zero before the second year, with a vaccine effectiveness of 79% (95% CI 43–93) at 12 months. These estimates for two-dose protection are consistent with the review paper by Bi and colleagues3Bi Q Ferreras E Pezzoli L et al.Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis.Lancet Infect Dis. 2017; 17: 1080-1088Summary Full Text Full Text PDF PubMed Scopus (96) Google Scholar which concluded that protection lasted for at least 3 years, and also with results from the randomised, placebo controlled trial in Kolkata, India, which documented efficacy for 5 years.4Bhattacharya SK Sur D Ali M et al.5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial.Lancet Infect Dis. 2013; 13: 1050-1056Summary Full Text Full Text PDF PubMed Scopus (174) Google Scholar Franke and colleagues’ study from Haiti, however, cautions that protection after a single dose was shorter and was not apparent after 16 months. One should note, however, that this single-dose conclusion is based on the patient's recall of taking one or two doses during the campaign. Notably, very few control patients (≤2%) recalled taking only one dose after the second year. This result was in contrast to earlier years when more than 10% reported taking a single dose. Imprecise recall after such a long time could have lowered estimates of single-dose effectiveness during the last 2 years. The single-dose conclusions from the Haiti study should also be viewed in light of the double-blind, randomised, placebo controlled trial in Bangladesh, which reported sustained efficacy from a single dose, without waning, over a 2 year period.5Qadri F Ali M Lynch J et al.Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; 18: 666-674Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar In view of these somewhat conflicting results on single-dose protection from the two studies, additional evaluation to establish the duration of single-dose protection will be welcome. With these assessments of single-dose effectiveness, when should a single-dose strategy be considered? The vaccine is licensed to be given as two doses with the second dose 2 weeks after the first. However, a single dose appears to provide very high protection over a short period—eg, 3–6 months6Ferreras E Chizema-Kawesha E Blake A et al.Single-dose cholera vaccine in response to an outbreak in Zambia.N Engl J Med. 2018; 378: 577-579Crossref PubMed Scopus (36) Google Scholar, 7Azman AS Parker LA Rumunu J et al.Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.Lancet Glob Health. 2016; 4: e856-e863Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar with sizeable protection lasting longer.5Qadri F Ali M Lynch J et al.Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; 18: 666-674Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar Thus, when responding to an outbreak, at a time when risk of cholera is very high, and when vaccine supply is restricted, giving a single dose provides vaccine to twice as many people with a fixed number of doses and prevents more cases during the outbreak.8Azman AS Luquero FJ Ciglenecki I Grais RF Sack DA Lessler J The impact of a one-dose versus two-dose oral cholera vaccine regimen in outbreak settings: a modeling study.PLoS Med. 2015; 12: e1001867Crossref PubMed Scopus (68) Google Scholar By vaccinating twice as many people, herd protection will further increase the benefits of the single-dose strategy. Thus, there are clear public health advantages from a single-dose strategy when responding to an outbreak. However, pending further data for duration of protection from a single dose, and whenever possible, two doses should be provided to achieve longer term protection. In the Haiti campaigns, the second round was scheduled about 2 weeks after the first, but in other campaigns, the second round was sometimes delayed by many months owing to vaccine availability. The potential benefits of a delayed second dose, compared with a 2 week interval, still needs further investigation. Franke and colleagues1Franke MF Ternier R Jerome JG Matias WR Harris JB Ivers LC Long-term effectiveness of one and two doses of a killed, bivalent, whole-cell oral cholera vaccine in Haiti: an extended case-control study.Lancet Glob Health. 2018; 6: e1028-e1035Summary Full Text Full Text PDF PubMed Scopus (24) Google Scholar also stress the concept that Haiti is so-called newly endemic, in contrast to Bangladesh which is so-called historically endemic. Endemic exposure could theoretically affect vaccine-induced protection. For example, if patients were primed through natural exposure, the vaccine could act as a booster and thereby increase protection. Alternatively, a vaccinated patient could be boosted by a subsequent exposure, and this could likewise increase protection. Thus, this oral vaccine, unlike most injectable vaccines, might be viewed as working in concert with natural exposure, at least in areas with endemic cholera. Since Haiti became endemic during the course of this study, it is not clear whether the endemicity would yield different results from those observed in Bangladesh.5Qadri F Ali M Lynch J et al.Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; 18: 666-674Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar With regard to children younger than 5 years of age, both the Bangladesh and the Haiti study reported low or no direct protection after a single dose. Even two doses had lower protection compared with older children and adults.3Bi Q Ferreras E Pezzoli L et al.Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis.Lancet Infect Dis. 2017; 17: 1080-1088Summary Full Text Full Text PDF PubMed Scopus (96) Google Scholar However, with high vaccine coverage, herd protection can protect young children if others in the household have been vaccinated.9Ali M Debes AK Luquero FJ et al.Potential for controlling cholera using a ring vaccination strategy: re-analysis of data from a cluster-randomized clinical Trial.PLoS Med. 2016; 13: e1002120Crossref PubMed Scopus (30) Google Scholar Thus, until new improved vaccines are developed, or vaccine dosing strategies evolve to increase efficacy for young children, it is important to immunise other, older family members, especially in households with young children, thereby minimising transmission. It should be noted that when conducting a two-dose campaign, some people will inevitably receive the vaccine only during the first round or only in the second round. Most will ideally receive the vaccine during both rounds. During each round, everyone should be offered the vaccine regardless of whether they received an earlier dose. In summary, everyone who receives even one dose will contribute to the vaccine's population effectiveness. DAS and MA report grants through their university from the Bill & Melinda Gates Foundation to promote the effective use of oral cholera vaccine. Long-term effectiveness of one and two doses of a killed, bivalent, whole-cell oral cholera vaccine in Haiti: an extended case-control studyIn a setting of epidemic and newly endemic cholera in Haiti, single-dose vaccination with killed, bivalent, whole-cell oral cholera vaccination provided short-term protection; however, vaccination with two doses was required for long-term protection, which lasted up to 4 years after vaccination. These results add to the evidence in support of the use of killed, bivalent, whole-cell oral cholera vaccination as part of comprehensive cholera control plans. Full-Text PDF Open Access