WHAT'S NEW THIS SUNDAY: A CASE FOR ORAL CHOLERA VACCINATION IN AFRICA

Saturday, 3rd of November 2012

Is it time for governments and partners to consider oral cholera vaccine as a new and under-used vaccine?

The Lancet Infectious Diseases, Volume 12, Issue 11, Pages 818 - 819, November 2012

Published Online: 04 September 2012

A case for control of cholera in Africa by vaccination

Original Text

Jan Holmgren a

In The Lancet Infectious Diseases, Ahmed Khatib and colleagues1 describe the direct and indirect (herd protection) effectiveness of an oral killed Vibrio cholerae whole-cell B-subunit cholera vaccine deployed in a mass vaccination campaign in almost 50 000 individuals in Zanzibar, east Africa, a region that has had regular outbreaks of cholera since 1978. Two vaccine doses were offered and given through the public health services to individuals in the study areas aged 2 years and older. Over the next 14 months the vaccine was shown to confer 79% direct protection against cholera and also significant indirect protection (50% in the non-vaccinated residents and as much as 75—90% in clusters with the highest vaccine coverage). This is the first prospective study showing herd protection from oral cholera vaccination and the first study in sub-Saharan Africa showing such an effect.

The seventh cholera pandemic, which started in the 1960s, now involves almost the entire developing world. WHO estimates that there are 3—5 million cases and more than 100 000 cholera-related deaths every year, predominantly in Asia and Africa. Cholera is endemic in more than 50 countries, and has in the past decade caused progressively more frequent and worse epidemics both in endemic and non-endemic settings, often as a result of natural or man-made disasters. The particular severity of recent epidemics in places such as Angola, Zimbabwe, Haiti, and Democratic Republic of the Congo might relate to molecular changes leading to increased virulence in the causative V cholerae organisms, which in more than 95% of all cholera cases belong to serogroup O1, biotype El Tor.2

WHO's recommended cholera control programmes focus on provision of clean water, adequate sanitation, and appropriate management of cholera patients. Even though safe and effective oral vaccines have been available for almost 20 years, they have been little used in control programmes against either endemic or epidemic cholera. Vaccine opponents have argued that, especially in epidemic situations, vaccination campaigns might divert attention from other more cost-effective interventions, and also that the available oral vaccines requiring two doses with at least a 1-week interval would be logistically too difficult to deploy.

However, in recent years interest in the use of oral vaccines for control of endemic as well as epidemic cholera has strongly increased. In October, 2009, WHO's Strategic Advisory Group of Experts on Immunization reinforced a previous WHO recommendation to use such vaccines in areas where cholera is endemic and consider their use in conjunction with other prevention and control strategies in areas at risk for outbreaks. They also made the pivotal additional recommendation that oral cholera vaccination should be considered as a reactive strategy in areas with ongoing outbreaks.3

This change in attitude is largely owing to recent data supporting the usefulness of oral vaccines against both endemic and epidemic cholera. The case for use of oral vaccines in areas where cholera has high endemicity has gained further support from recent large effectiveness studies, such as those from Zanzibar1and a previous study from Mozambique.4 Collectively, these studies show the feasibility of deploying a two-dose vaccine such as the whole-cell B-subunit vaccine through mass vaccination campaigns, the high acceptability and the consistent strong (79—84%) direct effectiveness against the present altered, more virulent cholera organisms, and in populations with a high HIV prevalence. These levels of protection are similar to those recorded in previous randomised efficacy studies in Asia and South America.5, 6 The additional important finding from Khatib and colleagues' study, that mass vaccination also confers significant herd protection, further supports WHO's recommendation.

Retrospective studies of recent epidemics7—10 also support the reactive use of vaccines in cholera outbreaks and emphasise the urgent need to establish a stockpile of at least 5 million doses to enable rapid use in outbreak situations. Chao and colleagues8 reported that strategic deployment of 5 million doses of oral vaccine alongside with other interventions in the 2010 epidemic in Haiti could have roughly halved the number of cholera cases and deaths. Similarly, Mukandavire and colleagues,9 analysing the severe cholera epidemic in Zimbabwe in 2008—09 noted that mass vaccination deployed strategically could prevent future epidemics and eventually eliminate cholera from the region. A study directly testing the effectiveness of reactive use of whole-cell oral cholera vaccine in an outbreak of cholera in Hanoi, Vietnam also showed that the vaccine intervention was effective, providing 76% reduction of cholera.11

These findings certainly reinforce the conclusion by Khatib and colleagues that “In view of the burden of disease caused by cholera, not to mention the economic damage, it is becoming increasingly unconscionable not to include oral cholera vaccine in the public health response to this disease”.

I declare that I have no conflicts of interest.

References

1 Khatib M, Ali M, von Seidlein L, et al. Effectiveness of an oral cholera vaccine in Zanzibar: findings from a large mass vaccination campaign and observational cohort study. Lancet Infect Dis 2012. published online Sept 4. http://dx.doi.org/10.1016/S1473-3099(12)70196-2.

2 Clemens J, Shin S, Sur D, Nair GB, Holmgren J. New-generation vaccines against cholera. Nat Rev Gastroenterol Hepatol 2011; 8: 701-710. PubMed

3 WHO. Cholera vaccines: WHO position paper—recommendations. Vaccine 2010; 28: 4687-4688. CrossRef |PubMed

4 Lucas MES, Deen JL, von Seidlein L, et al. Effectiveness of mass cholera vaccination in Beira, Mozambique.New Engl J Med 2005; 352: 757-767. PubMed

5 Clemens J, Sack DA, Harris JR, et al. Field trial of oral cholera vaccines in Bangladesh. Lancet 1986; 2: 124-127. CrossRef | PubMed

6 Sanchez JL, Vasquez B, Begue RE, et al. Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits. Lancet 1994; 344: 1273-1276. Summary | CrossRef | PubMed

7 Ali M, Emch M, von Seidlein L, et al. Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis. Lancet 2005; 366: 44-49. Summary | Full Text | PDF(350KB) | CrossRef | PubMed

8 Chao DL, Halloran ME, Longini IM. Vaccination strategies for epidemic cholera in Haiti with implications for the developing world. Proc Natl Acad Sci USA 2011; 108: 7081-7085. PubMed

9 Mukandavire Z, Liao S, Wang J, et al. Estimating the reproductive numbers for the 2008-2009 cholera outbreaks in Zimbabwe. Proc Natl Acad Sci USA 2011; 108: 8767-8772. PubMed

10 Reyburn R, Deen JL, Grais RF, et al. The case for reactive mass oral cholera vaccinations. PLoS Negl Trop Dis 2011; 5: e952. PubMed

11 Anh DD, Lopez AL, Thiem VD, et al. Use of oral cholera vaccines in an outbreak in Vietnam: a case control study. PLoS Negl Trop Dis 2011; 5: e1006. PubMed

a Gothenburg University Vaccine Research Institute, University of Gothenburg, Sweden