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The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

Azman AS, Luquero FJ, Ciglenecki I, Grais RF, Sack DA, Lessler J - PLoS Med. (2015)

Bottom Line: Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE.This threshold decreases as vaccination is delayed.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Comparison of individual- and population-level benefits of one- and two-dose campaigns by vaccination start time and relative single-dose efficacy.Colors in each panel represent the cumulative incidence ratio, comparing cumulative incidence among those ever receiving vaccine in one-dose campaigns (numerator) with the cumulative incidence among those ever receiving vaccine in two-dose campaigns (denominator). Solid lines in each panel outline the region where single-dose campaigns are better for vaccinees (a result of indirect effects). Dashed lines represent the population-level threshold above which overall cumulative incidence is lower in a one-dose campaign compared to a two-dose campaign. Panels illustrate settings where enough susceptibility-reducing vaccine is available to cover (A) 20%, (B) 40%, and (C) 100% of the population with a single dose. In each plot, region 1 corresponds to the area where two doses are better for both the vaccinees and population, region 2 is where one dose is better for the population but not the vaccinees, and region 3 is where one dose is better for vaccinees and the population. Similar plots for different forms of vaccine protection are shown in S4 Text. VE, vaccine efficacy.
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pmed.1001867.g006: Comparison of individual- and population-level benefits of one- and two-dose campaigns by vaccination start time and relative single-dose efficacy.Colors in each panel represent the cumulative incidence ratio, comparing cumulative incidence among those ever receiving vaccine in one-dose campaigns (numerator) with the cumulative incidence among those ever receiving vaccine in two-dose campaigns (denominator). Solid lines in each panel outline the region where single-dose campaigns are better for vaccinees (a result of indirect effects). Dashed lines represent the population-level threshold above which overall cumulative incidence is lower in a one-dose campaign compared to a two-dose campaign. Panels illustrate settings where enough susceptibility-reducing vaccine is available to cover (A) 20%, (B) 40%, and (C) 100% of the population with a single dose. In each plot, region 1 corresponds to the area where two doses are better for both the vaccinees and population, region 2 is where one dose is better for the population but not the vaccinees, and region 3 is where one dose is better for vaccinees and the population. Similar plots for different forms of vaccine protection are shown in S4 Text. VE, vaccine efficacy.

Mentions: Early in an epidemic, those vaccinated are sometimes better off in a two-dose campaign, even if a single-dose campaign will prevent more cases overall (green-shaded areas in Fig 6). For instance, in simulations with 200,000 doses distributed early in a population of 500,000, the MRSE was 51%; however, those receiving the vaccine were better off (i.e., had a lower risk of infection) in a single-dose campaign only if a single dose was at least 62% as efficacious as the two-dose protocol (Fig 6B). In general, both vaccination timing and coverage play a large role in determining the gap in the RSE thresholds for individual- and population-level benefits (i.e., the gap between the dashed and solid lines in Fig 6). When vaccine coverage is low, vaccinees will often experience higher risk in a one-dose scenario than they would in a two-dose scenario unless the one-dose efficacy is much higher than the MRSE (Fig 6A). As vaccination is delayed towards the end of the epidemic, the impact of both vaccination strategies diminishes, and while one-dose campaigns may avert more cases, the risk of disease within vaccinees, though low, is relatively higher than it would be if they received two doses.


The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

Azman AS, Luquero FJ, Ciglenecki I, Grais RF, Sack DA, Lessler J - PLoS Med. (2015)

Comparison of individual- and population-level benefits of one- and two-dose campaigns by vaccination start time and relative single-dose efficacy.Colors in each panel represent the cumulative incidence ratio, comparing cumulative incidence among those ever receiving vaccine in one-dose campaigns (numerator) with the cumulative incidence among those ever receiving vaccine in two-dose campaigns (denominator). Solid lines in each panel outline the region where single-dose campaigns are better for vaccinees (a result of indirect effects). Dashed lines represent the population-level threshold above which overall cumulative incidence is lower in a one-dose campaign compared to a two-dose campaign. Panels illustrate settings where enough susceptibility-reducing vaccine is available to cover (A) 20%, (B) 40%, and (C) 100% of the population with a single dose. In each plot, region 1 corresponds to the area where two doses are better for both the vaccinees and population, region 2 is where one dose is better for the population but not the vaccinees, and region 3 is where one dose is better for vaccinees and the population. Similar plots for different forms of vaccine protection are shown in S4 Text. VE, vaccine efficacy.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549326&req=5

pmed.1001867.g006: Comparison of individual- and population-level benefits of one- and two-dose campaigns by vaccination start time and relative single-dose efficacy.Colors in each panel represent the cumulative incidence ratio, comparing cumulative incidence among those ever receiving vaccine in one-dose campaigns (numerator) with the cumulative incidence among those ever receiving vaccine in two-dose campaigns (denominator). Solid lines in each panel outline the region where single-dose campaigns are better for vaccinees (a result of indirect effects). Dashed lines represent the population-level threshold above which overall cumulative incidence is lower in a one-dose campaign compared to a two-dose campaign. Panels illustrate settings where enough susceptibility-reducing vaccine is available to cover (A) 20%, (B) 40%, and (C) 100% of the population with a single dose. In each plot, region 1 corresponds to the area where two doses are better for both the vaccinees and population, region 2 is where one dose is better for the population but not the vaccinees, and region 3 is where one dose is better for vaccinees and the population. Similar plots for different forms of vaccine protection are shown in S4 Text. VE, vaccine efficacy.
Mentions: Early in an epidemic, those vaccinated are sometimes better off in a two-dose campaign, even if a single-dose campaign will prevent more cases overall (green-shaded areas in Fig 6). For instance, in simulations with 200,000 doses distributed early in a population of 500,000, the MRSE was 51%; however, those receiving the vaccine were better off (i.e., had a lower risk of infection) in a single-dose campaign only if a single dose was at least 62% as efficacious as the two-dose protocol (Fig 6B). In general, both vaccination timing and coverage play a large role in determining the gap in the RSE thresholds for individual- and population-level benefits (i.e., the gap between the dashed and solid lines in Fig 6). When vaccine coverage is low, vaccinees will often experience higher risk in a one-dose scenario than they would in a two-dose scenario unless the one-dose efficacy is much higher than the MRSE (Fig 6A). As vaccination is delayed towards the end of the epidemic, the impact of both vaccination strategies diminishes, and while one-dose campaigns may avert more cases, the risk of disease within vaccinees, though low, is relatively higher than it would be if they received two doses.

Bottom Line: Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE.This threshold decreases as vaccination is delayed.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus