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Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis.

ABSTRACT: Ebola epidemics constitute serious public health emergencies. Multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. Assessing the potential impact of these vaccines on morbidity and mortality of Ebola is essential for devising prevention strategies. A mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 Sierra Leone epidemic. We assessed the impacts of prophylactic vaccination of healthcare workers (HCW) both alone and in combination with the vaccination of the general population (entire susceptible population other than HCW). The model simulated 8,706 (95% confidence intervals [CI]: 478-21,942) cases and 3,575 (95%CI: 179-9,031) deaths in Sierra Leone, in line with WHO-reported statistics for the 2014 epidemic (8,704 cases and 3,587 deaths). Relative to this base case, the model then estimated that prophylactic vaccination of only 10% of HCW will avert 12% (95% CI: 6%-14%) of overall cases and deaths, while vaccination of 30% of HCW will avert 34% of overall cases (95% CI: 30%-64%) and deaths (95% CI: 30%-65%). Prophylactic vaccination of 1% and 5% of the general population in addition to vaccinating 30% of HCW was estimated to result in reduction in cases by 44% (95% CI: 39%-61%) and 72% (95% CI: 68%-84%) respectively, and deaths by 45% (95% CI: 40%-61%) and 74% (95% CI: 70%-85%) respectively. Prophylactic vaccination of even small proportions of HCW is estimated to significantly reduce incidence of Ebola and associated mortality. The effect is greatly enhanced by the additional vaccination even of small percentages of the general population. These findings could be used to inform the planning of prevention strategies.

SUBMITTER: Potluri R

PROVIDER: S-EPMC7185698 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis.

Potluri Ravi R Kumar Amit A Maheshwari Vikalp V Smith Charlie C Oriol Mathieu Valerie V Luhn Kerstin K Callendret Benoit B Bhandari Hitesh H

PloS one 20200427 4

Ebola epidemics constitute serious public health emergencies. Multiple vaccines are under development to prevent these epidemics and avoid the associated morbidity and mortality. Assessing the potential impact of these vaccines on morbidity and mortality of Ebola is essential for devising prevention strategies. A mean-field compartmental stochastic model was developed for this purpose and validated by simulating the 2014 Sierra Leone epidemic. We assessed the impacts of prophylactic vaccination ...[more]

PMID: 32339195

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Project description:Ebola virus (EBOV) has been responsible for sporadic outbreaks in Central Africa since 1976 and has the potential of causing social disruption and public panic as illustrated by the 2013-2016 epidemic in West Africa. Transmission of EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk. Parameters influencing transmission of EBOV are, however, largely undefined in part due to the lack of an established animal model to study mechanisms of pathogen spread. Here, we investigated EBOV transmissibility in male and female ferrets. After intranasal challenge, an infected animal was placed in direct contact with a naive ferret and in contact with another naive ferret (separated from the infected animal by a metal mesh) that served as the indirect-contact animal. All challenged animals, male direct contacts, and one male indirect contact developed disease and died. The remaining animals were not viremic and remained asymptomatic but developed EBOV-glycoprotein IgM and/or IgG specific antibodies-indicative of virus transmission. EBOV transmission via indirect contact was frequently observed in this model but resulted in less-severe disease compared to direct contact. Interestingly, these observations are consistent with the detection of specific antibodies in humans living in areas of EBOV endemicity.IMPORTANCE Our knowledge regarding transmission of EBOV between individuals is vague and is mostly limited to spreading via direct contact with infectious bodily fluids. Studying transmission parameters such as dose and route of infection is nearly impossible in naturally acquired cases-hence the requirement for a laboratory animal model. Here, we show as a proof of concept that ferrets can be used to study EBOV transmission. We also show that transmission in the absence of direct contact is frequent, as all animals with indirect contact with the infected ferrets had detectable antibodies to the virus, and one succumbed to infection. Our report provides a new small-animal model for studying EBOV transmission that does not require adaptation of the virus, providing insight into virus transmission among humans during epidemics.

Project description:BackgroundRotavirus incidence remains relatively high in low-income countries (LICs) compared to high-income countries (HICs) after vaccine introduction. Ghana introduced monovalent rotavirus vaccine in April 2012 and despite the high coverage, vaccine performance has been modest compared to developed countries. The predictors of low vaccine effectiveness in LICs are poorly understood, and the drivers of subnational heterogeneity in rotavirus vaccine impact are unknown.MethodsWe used mathematical models to investigate variations in rotavirus incidence in children <5 years old in Ghana. We fit models to surveillance and case-control data from three different hospitals: Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and War Memorial Hospital in Navrongo. The models were fitted to both pre- and post-vaccine data to estimate parameters describing the transmission rate, waning of maternal immunity, and vaccine response rate.ResultsThe seasonal pattern and age distribution of rotavirus cases varied among the three study sites in Ghana. Our model was able to capture the spatio-temporal variations in rotavirus incidence across the three sites and showed good agreement with the age distribution of observed cases. The rotavirus transmission rate was highest in Accra and lowest in Navrongo, while the estimated duration of maternal immunity was longer (~5 months) in Accra and Kumasi and shorter (~3 months) in Navrongo. The proportion of infants who responded to the vaccine was estimated to be high in Accra and Kumasi and low in Navrongo.ConclusionsRotavirus vaccine impact varies within Ghana. A low vaccine response rate was estimated for Navrongo, where rotavirus is highly seasonal and incidence limited to a few months of the year. Our findings highlight the need to further explore the relationship between rotavirus seasonality, maternal immunity, and vaccine response rate to determine how they influence vaccine effectiveness and to develop strategies to improve vaccine impact.

Project description:The quarantine of people suspected of being exposed to an infectious agent is one of the most basic public health measure that has historically been used to combat the spread of communicable diseases in human communities. This study presents a new deterministic model for assessing the population-level impact of the quarantine of individuals suspected of being exposed to disease on the spread of the 2014-2015 outbreaks of Ebola viral disease. It is assumed that quarantine is imperfect (i.e., individuals can acquire infection during quarantine). In the absence of quarantine, the model is shown to exhibit global dynamics with respect to the disease-free and its unique endemic equilibrium when a certain epidemiological threshold (denoted by R0 ) is either less than or greater than unity. Thus, unlike the full model with imperfect quarantine (which is known to exhibit the phenomenon of backward bifurcation), the version of the model with no quarantine does not undergo a backward bifurcation. Using data relevant to the 2014-2015 Ebola transmission dynamics in the three West African countries (Guinea, Liberia and Sierra Leone), uncertainty analysis of the model show that, although the current level and effectiveness of quarantine can lead to significant reduction in disease burden, they fail to bring the associated quarantine reproduction number ( R0Q ) to a value less than unity (which is needed to make effective disease control or elimination feasible). This reduction of R0Q is, however, very possible with a modest increase in quarantine rate and effectiveness. It is further shown, via sensitivity analysis, that the parameters related to the effectiveness of quarantine (namely the parameter associated with the reduction in infectiousness of infected quarantined individuals and the contact rate during quarantine) are the main drivers of the disease transmission dynamics. Overall, this study shows that the singular implementation of a quarantine intervention strategy can lead to the effective control or elimination of Ebola viral disease in a community if its coverage and effectiveness levels are high enough.

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Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis.

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Impact of prophylactic vaccination strategies on Ebola virus transmission: A modeling analysis.

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