Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI ？27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect surveillance data and uncertainty about the transmission dynamics of cholera in each setting. Conclusions Reactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign.
References
[1]
Ali M, Lopez AL, You YA, Kim YE, Sah B, Maskery . et al. The global burden of cholera. Bull World Health Org. 2012;90:209–218A. doi: 10.2471/BLT.11.093427. pmid:22461716
[2]
Mengel MA, Delrieu I, Heyerdahl L, Gessner BD. Cholera outbreaks in Africa. In: Nair GB, Takeda Y, editors. Cholera outbreaks. Heidelberg: Springer; 2014. pp. 117–144.
[3]
Bhattacharya S, Black R, Bourgeois L, Clemens J, Deen JL, Dougan G, et al. The cholera crisis in Africa. Science. 2009;324:885. doi: 10.1126/science.1173890. pmid:19443768
[4]
Barzilay EJ, Schaad N, Magloire R, Mung KS, Boncy J, Dahourou , et al. Cholera surveillance during the Haiti epidemic—the first 2 years. N Engl J Med. 2013;368:599–609. doi: 10.1056/NEJMoa1204927. pmid:23301694
[5]
Luquero FJ, Grout L, Ciglenecki I, Sakoba K, Traore B, Heile , et al. Use of Vibrio cholerae vaccine in an outbreak in Guinea. N Engl J Med. 2014;370:2111–2120. doi: 10.1056/NEJMoa1312680. pmid:24869721
[6]
World Health Organization. Cholera vaccines: WHO position paper—recommendations. Vaccine. 2010;28:4687–4688. doi: 10.1016/j.vaccine.2010.05.008. pmid:20483196
[7]
World Health Organization. Cholera, 2013. Wkly Epidemiol Rec. 2014;89:345–356.
[8]
Mohammed AJ, Al Awaidy S, Bawikar S, Kurup PJ, Elamir E, Shaban MMA, et al. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med. 2010;362:2351–2359. doi: 10.1056/NEJMoa0909383. pmid:20573923
[9]
Guerin PJ, Naess LM, Fogg C, Rosenqvist E, Pinoges L, Bajunirwe F, et al. Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda. PLoS Negl Trop Dis. 2008;2:e342. doi: 10.1371/journal.pntd.0000342. pmid:19048025
[10]
Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.
[11]
Newcombe RG. MOVER-R confidence intervals for ratios and products of two independently estimated quantities. Stat Methods Med Res. 2013 Oct 9. doi: 10.1177/0962280213502144.
[12]
Anderson RM, May RM. Infectious diseases of humans: dynamics and control. Oxford: Oxford University Press; 1991.
[13]
Black RE, Levine MM, Clements ML, Young CR, Svennerholm A, Holmgren J. Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin. Infect Immun. 1987;55:1116–1120. pmid:3552989
[14]
Halloran ME, Longini IM Jr, Struchiner CJ. Design and analysis of vaccine studies. New York: Springer; 2009.
[15]
Morris JG. Cholera—modern pandemic disease of ancient lineage. Emerg Infect Dis. 2011;17:2099–2104. doi: 10.3201/eid1711.111109. pmid:22099113
[16]
Azman AS, Rudolph KE, Cummings DAT, Lessler J. The incubation period of cholera: a systematic review. J Infect. 2013;66:432–438. doi: 10.1016/j.jinf.2012.11.013. pmid:23201968
[17]
Weil AA, Khan AI, Chowdhury F, LaRocque RC, Faruque ASG, Ryan ET, et al. Clinical outcomes in household contacts of patients with cholera in Bangladesh. Clin Infect Dis. 2009;49:1473–1479. doi: 10.1086/644779. pmid:19842974
[18]
Ciglenecki I, Sakoba K, Luquero FJ, Heile M, Itama C, Mengel M, et al. Feasibility of mass vaccination campaign with oral cholera vaccines in response to an outbreak in Guinea. PLoS Med. 2013;10:e1001512. doi: 10.1371/journal.pmed.1001512. pmid:24058301
[19]
Luquero FJ, Banga CN, Remartínez D, Palma PP, Baron E, Grais RF. Cholera epidemic in Guinea-Bissau (2008): the importance of “place.” PLoS ONE. 2011;6:e19005. doi: 10.1371/journal.pone.0019005. pmid:21572530
[20]
Reyburn R, Clemens JD, Deen JL, Grais RF, Bhattacharya SK, Sur D, et al. The case for reactive mass oral cholera vaccinations. PLoS Negl Trop Dis. 2011;5:e952. doi: 10.1371/journal.pntd.0000952. pmid:21283614
[21]
Ministere de la Sante Publique et de la Population. Rapport de cas—30 Septembre 2011.
[22]
Ionides EL, Nguyen D, Atchadé Y, Stoev S, King AA. Inference for dynamic and latent variable models via iterated, perturbed Bayes maps. Proc Natl Acad Sci U S A. 2015;112:719–724. doi: 10.1073/pnas.1410597112. pmid:25568084
[23]
R Development Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2011.
[24]
Khatib AM, Ali M, Seidlein von L, Kim DR, Hashim R, Reyburn R, et al. Effectiveness of an oral cholera vaccine in Zanzibar: findings from a mass vaccination campaign and observational cohort study. Lancet Infect Dis. 2012;12:837–844. doi: 10.1016/S1473-3099(12)70196-2. pmid:22954655
[25]
Sur D, Lopez AL, Kanungo S, Paisley A, Manna B, Ali M, et al. Efficacy and safety of a modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:1694–1702. doi: 10.1016/S0140-6736(09)61297-6. pmid:19819004
[26]
Sanchez JL, Vasquez B, Begue RE, Meza R, Castellares G, Cabezas C, et al. Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits. Lancet. 1994;344:1273–1276. pmid:7967990 doi: 10.1016/s0140-6736(94)90755-2
[27]
Clemens JD, Harris JR, Khan MR, Kay BA, Yunus M, Svennerholm A, et al. Field trial of oral cholera vaccines in Bangladesh. Lancet. 1986;328:124–127. doi: 10.1016/s0140-6736(86)91944-6
[28]
Lucas MES, Deen JL, von Seidlein L, Wang XY, Ampuero J, Puri M, et al. Effectiveness of mass oral cholera vaccination in Beira, Mozambique. N Engl J Med. 2005;352:757–67. pmid:15728808 doi: 10.1056/nejmoa043323
[29]
Date KA, Vicari A, Hyde TB, Mintz E, Danovaro-Holliday MC, Henry A, et al. Considerations for oral cholera vaccine use during outbreak after earthquake in Haiti, 2010–2011. Emerg Infect Dis. 2011;17:2105–2112. doi: 10.3201/eid1711.110822. pmid:22099114
[30]
Chao DL, Halloran ME, Longini IM. Vaccination strategies for epidemic cholera in Haiti with implications for the developing world. Proc Natl Acad Sci U S A. 2011;108:7081–7085. doi: 10.1073/pnas.1102149108. pmid:21482756
[31]
Andrews JR, Basu S. Transmission dynamics and control of cholera in Haiti: an epidemic model. Lancet. 2011;377:1248–1255. doi: 10.1016/S0140-6736(11)60273-0. pmid:21414658
[32]
Azman AS, Luquero FJ, Rodrigues A, Palma PP, Grais RF, Banga CA, et al. Urban cholera transmission hotspots and their implications for reactive vaccination: evidence from Bissau city, Guinea Bissau. PLoS Negl Trop Dis. 2012;6:e1901. doi: 10.1371/journal.pntd.0001901. pmid:23145204
[33]
Constantin de Magny G, Guégan J-F, Petit M, Cazelles B. Regional-scale climate-variability synchrony of cholera epidemics in West Africa. BMC Infect Dis. 2007;7:20. pmid:17371602 doi: 10.1186/1471-2334-7-20
[34]
Kanungo S, Paisley A, Lopez AL, Bhattacharya M. Immune responses following one and two doses of the reformulated, bivalent, killed, whole-cell, oral cholera vaccine among adults and children in Kolkata, India: a randomized, placebo-controlled trial. Vaccine 2009;27:6887–6893. doi: 10.1016/j.vaccine.2009.09.008. pmid:19761838
[35]
Clemens JD, Sack DA, Harris JR, Van Loon F, Chakraborty J, Ahmed F, et al. Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet. 1990;335:270–273. pmid:1967730 doi: 10.1016/0140-6736(90)90080-o
[36]
Albert MJ, Qadri F, Wahed MA, Ahmed T, Rahman ASMH, Ahmed F, et al. Supplementation with zinc, but not vitamin A, improves seroconversion to vibriocidal antibody in children given an oral cholera vaccine. J Infect Dis. 2003;187:909–913. pmid:12660937 doi: 10.1086/368132
[37]
Sack DA, Clemens JD, Huda S, Harris JR, Khan MR, Chakraborty J, et al. Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh. J Infect Dis. 1991;164:407–411. pmid:1856488 doi: 10.1093/infdis/164.2.407
[38]
Clemens JD, Stanton BF, Chakraborty J, Sack DA, Khan MR, Huda S, et al. B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity. J Infect Dis. 1987;155:79–85. pmid:3540139 doi: 10.1093/infdis/155.1.79
[39]
Hashim R, Khatib AM, Enwere G, Park JK, Reyburn R, Ali M, et al. Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in pregnancy. PLoS Negl Trop Dis. 2012;6:e1743. doi: 10.1371/journal.pntd.0001743. pmid:22848772
[40]
Moodley K, Hardie K, Selgelid MJ, Waldman RJ, Strebel P, Rees H, et al. Ethical considerations for vaccination programmes in acute humanitarian emergencies. Bull World Health Organ. 2013;91:290–297. doi: 10.2471/BLT.12.113480. pmid:23599553
[41]
Mukandavire Z, Liao S, Wang J, Gaff H, Smith DL, Morris JG. Estimating the reproductive numbers for the 2008–2009 cholera outbreaks in Zimbabwe. Proc Natl Acad Sci U S A. 2011;108:8767–8772. doi: 10.1073/pnas.1019712108. pmid:21518855
[42]
Mukandavire Z, Smith DL, Morris JG Jr. Cholera in Haiti: reproductive numbers and vaccination coverage estimates. Sci Rep. 2013;3:997. doi: 10.1038/srep00997. pmid:23308338
