Projecting vaccine demand and impact for emerging zoonotic pathogens

Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response. We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies. Annual vaccine regimen requirements for a population-wide strategy ranged from >670,000 (95% prediction interval: 0-3,630,000) for Lassa virus to 1,190,000 (95% PrI: 0-8,480,000) for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R0 values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination. Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios.

Reactive vaccination of workplaces and schools against COVID-19

As vaccination against COVID-19 stalls in some countries, increased accessibility and more adaptive approaches may be useful to keep the epidemic under control. Here we study the impact of reactive vaccination targeting schools and workplaces where cases have been detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, individuals' demography and behaviour and social distancing. We study epidemic scenarios ranging from sustained spread to flare-up of cases, and we consider reactive vaccination alone and in combination with mass vaccination. With the same number of doses, reactive vaccination reduces cases more than non-reactive approaches, but may require concentrating a high number of doses over a short time in case of sustained spread. In case of flare-ups, quick implementation of reactive vaccination supported by enhanced test-trace-isolate practices would limit further spread. These results provide key information to promote an adaptive vaccination plan in the months to come.

Comparing alternative cholera vaccination strategies in Maela refugee camp: using a transmission model in public health practice

Background Cholera is a major public health concern in displaced-person camps, which often contend with overcrowding and scarcity of resources. Maela, the largest and longest-standing refugee camp in Thailand, located along the Thai-Burmese border, experienced four cholera outbreaks between 2005 and 2010. In 2013, a cholera vaccine campaign was implemented in the camp. To assist in the evaluation of the campaign and planning for subsequent campaigns, we developed a mathematical model of cholera in Maela. Methods We formulated a Susceptible-Infectious-Water-Recovered-based transmission model and estimated parameters using incidence data from 2010. We next evaluated the reduction in cases conferred by several immunization strategies, varying timing, effectiveness, and resources (i.e., vaccine availability). After the vaccine campaign, we generated case forecasts for the next year, to inform on-the-ground decision-making regarding whether a booster campaign was needed. Results We found that preexposure vaccination can substantially reduce the risk of cholera even when <50% of the population is given the full two-dose series. Additionally, the preferred number of doses per person should be considered in the context of one vs. two dose effectiveness and vaccine availability. For reactive vaccination, a trade-off between timing and effectiveness was revealed, indicating that it may be beneficial to give one dose to more people rather than two doses to fewer people, given that a two-dose schedule would incur a delay in administration of the second dose. Forecasting using realistic coverage levels predicted that there was no need for a booster campaign in 2014 (consistent with our predictions, there was not a cholera epidemic in 2014). Conclusions Our analyses suggest that vaccination in conjunction with ongoing water sanitation and hygiene efforts provides an effective strategy for controlling cholera outbreaks in refugee camps. Effective preexposure vaccination depends on timing and effectiveness. If a camp is facing an outbreak, delayed distribution of vaccines can substantially alter the effectiveness of reactive vaccination, suggesting that quick distribution of vaccines may be more important than ensuring every individual receives both vaccine doses. Overall, this analysis illustrates how mathematical models can be applied in public health practice, to assist in evaluating alternative intervention strategies and inform decision-making.

Meningococcal Meningitis Outbreaks in the African Meningitis Belt After Meningococcal Serogroup A Conjugate Vaccine Introduction, 2011–2017

Background In 2010–2017, meningococcal serogroup A conjugate vaccine (MACV) was introduced in 21 African meningitis belt countries. Neisseria meningitidis A epidemics have been eliminated here; however, non-A serogroup epidemics continue. Methods We reviewed epidemiological and laboratory World Health Organization data after MACV introduction in 20 countries. Information from the International Coordinating Group documented reactive vaccination. Results In 2011–2017, 17 outbreaks were reported (31 786 suspected cases from 8 countries, 1–6 outbreaks/year). Outbreaks were of 18–14 542 cases in 113 districts (median 3 districts/outbreak). The most affected countries were Nigeria (17 375 cases) and Niger (9343 cases). Cumulative average attack rates per outbreak were 37–203 cases/100 000 population (median 112). Serogroup C accounted for 11 outbreaks and W for 6. The median proportion of laboratory confirmed cases was 20%. Reactive vaccination was conducted during 14 outbreaks (5.7 million people vaccinated, median response time 36 days). Conclusion Outbreaks due to non-A serogroup meningococci continue to be a significant burden in this region. Until an affordable multivalent conjugate vaccine becomes available, the need for timely reactive vaccination and an emergency vaccine stockpile remains high. Countries must continue to strengthen detection, confirmation, and timeliness of outbreak control measures.

Modeling control of foot and mouth disease with two time delays

We develop a delay ordinary differential equation model that captures the effects of prophylactic vaccination, reactive vaccination, prophylactic treatment and reactive culling on the spread of foot and mouth disease (FMD) with time delays. Simulation results from the study suggest that increasing time delay while increasing the control strategies decreases the burden of FMD. Further, the results reveal, that decreasing time delay while decreasing the control strategies increases the burden of FMD. The intermediate scenarios of either (i) increasing time delay while decreasing control or (ii) decreasing time delay while increasing control have intermediate effects on burden reduction. Thus, the implementation of effective control strategies combination can play an important role in mitigating against the FMD burden.

Comparing alternative cholera vaccination strategies in Maela refugee camp using a transmission model

BackgroundCholera remains a major public health concern, particularly in refugee camps, which may contend with overcrowding and scarcity of resources. Maela, the largest long-standing refugee camp in Thailand, experienced four cholera outbreaks between 2005 and 2010. In 2013, a cholera vaccine campaign was implemented in the camp. To assist in the evaluation of the campaign and planning for subsequent campaigns, we developed a mathematical model of cholera in Maela.MethodsWe formulated a Susceptible-Infectious-Water-Recovered-based cholera transmission model and estimated parameters using incidence data from 2010. We next evaluated the reduction in cases conferred by several immunization strategies, varying timing, effectiveness, and resources (i.e., vaccine availability). Finally, we generated post-campaign case forecasts, to determine whether a booster campaign was needed.ResultsWe found that preexposure vaccination can substantially reduce the risk of cholera even when the < 50% of the population is given the full two-dose series. Additionally, the preferred number of doses per person should be considered in the context of one vs. two dose effectiveness and vaccine availability. For reactive vaccination, a trade-off between timing and effectiveness was revealed, indicating that it may be beneficial to give one dose to more people rather than two doses to fewer people, given that a two-dose schedule would incur a delay in administration of the second dose. Forecasting using realistic coverage levels predicted that there was no need for a booster campaign in 2014 (consistent with our predictions, there was not a cholera epidemic in the 2014 season).ConclusionsOur analyses suggest that vaccination in conjunction with ongoing water sanitation and hygiene efforts provides an effective strategy for cholera outbreaks in refugee camps. Effective preexposure vaccination depends on timing and effectiveness. If a camp is facing an outbreak, delayed distribution of vaccines can substantially alter the effectiveness of reactive vaccination, suggesting that quick distribution of vaccines may be more important than ensuring every individual receives both vaccine doses.