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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

Illustration of model including fast and slow cholera transmission.Circles represent states, with the variable letters representing susceptible, exposed, infectious, and removed states and the subscripts indicating the number of doses of vaccine those in that state have received. In the infectious states, those with a star indicate states involved with the slow (environmentally mediated) transmission pathway. Arrows between states represent rates of transition between states. More details can be found in S1 Text.
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pmed.1001867.g002: Illustration of model including fast and slow cholera transmission.Circles represent states, with the variable letters representing susceptible, exposed, infectious, and removed states and the subscripts indicating the number of doses of vaccine those in that state have received. In the infectious states, those with a star indicate states involved with the slow (environmentally mediated) transmission pathway. Arrows between states represent rates of transition between states. More details can be found in S1 Text.

Mentions: We constructed deterministic compartmental transmission models where individuals are susceptible, exposed but not infectious, infectious, or removed from the system due to immunity or death (an SEIR model) [12]. Although some evidence suggests that cholera vaccine reduces susceptibility to disease and illness severity [13], there is much uncertainty about how the vaccine protects individuals. To capture this uncertainty in our results, we modeled vaccines providing protection by completely preventing infection in a percent of vaccinees (an “all-or-nothing” vaccine), reducing susceptibility among all vaccinees by a percent (a susceptibility-reducing vaccine; Fig 1), or preventing severe disease in a percent of vaccinees (a severity-reducing vaccine) [14]. In the last case, mild and asymptomatic cases are presumed to be less infectious. In addition, we considered a model that included both “fast” (i.e., person-to-person) and “slow” (i.e., environmentally mediated) transmission pathways to understand how mixtures of modes of transmission may impact our findings (Fig 2) [15]. Epidemic simulations were seeded with a single case unless otherwise noted. See Table 1 and S3 Text for model structure and parameter details.


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)

Illustration of model including fast and slow cholera transmission.Circles represent states, with the variable letters representing susceptible, exposed, infectious, and removed states and the subscripts indicating the number of doses of vaccine those in that state have received. In the infectious states, those with a star indicate states involved with the slow (environmentally mediated) transmission pathway. Arrows between states represent rates of transition between states. More details can be found in S1 Text.
© Copyright Policy
Related In: Results  -  Collection

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

pmed.1001867.g002: Illustration of model including fast and slow cholera transmission.Circles represent states, with the variable letters representing susceptible, exposed, infectious, and removed states and the subscripts indicating the number of doses of vaccine those in that state have received. In the infectious states, those with a star indicate states involved with the slow (environmentally mediated) transmission pathway. Arrows between states represent rates of transition between states. More details can be found in S1 Text.
Mentions: We constructed deterministic compartmental transmission models where individuals are susceptible, exposed but not infectious, infectious, or removed from the system due to immunity or death (an SEIR model) [12]. Although some evidence suggests that cholera vaccine reduces susceptibility to disease and illness severity [13], there is much uncertainty about how the vaccine protects individuals. To capture this uncertainty in our results, we modeled vaccines providing protection by completely preventing infection in a percent of vaccinees (an “all-or-nothing” vaccine), reducing susceptibility among all vaccinees by a percent (a susceptibility-reducing vaccine; Fig 1), or preventing severe disease in a percent of vaccinees (a severity-reducing vaccine) [14]. In the last case, mild and asymptomatic cases are presumed to be less infectious. In addition, we considered a model that included both “fast” (i.e., person-to-person) and “slow” (i.e., environmentally mediated) transmission pathways to understand how mixtures of modes of transmission may impact our findings (Fig 2) [15]. Epidemic simulations were seeded with a single case unless otherwise noted. See Table 1 and S3 Text for model structure and parameter details.

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