ABSTRACT
COVID-19 vaccines have demonstrated significant efficacy in reducing severe symptoms and fatalities, although their effectiveness in preventing transmission varies depending on the population's age profile and the dominant variant. This study evaluates the impact of the COVID-19 vaccination campaign in the Basque Country region of Spain, which has the fourth highest proportion of elderly individuals worldwide. Using epidemiological data on hospitalizations, ICU admissions, fatalities, and vaccination coverage, we calibrated four versions of an ordinary differential equations model with varying assumptions on the age structure and transmission function. Counterfactual no-vaccine scenarios were simulated by setting the vaccination rate to zero while all other parameters were held constant. The initial vaccination rollout is estimated to have prevented 46,000 to 75,000 hospitalizations, 6,000 to 11,000 ICU admissions, and 15,000 to 24,000 deaths, reducing these outcomes by 73-86%. The most significant impact occurred during the third quarter of 2021, coinciding with the Delta variant's dominance and a vaccination rate exceeding 60%. Sensitivity analysis revealed that vaccination coverage had a more substantial effect on averted outcomes than vaccine efficacy. Overall, the vaccination campaign in the Basque Country significantly reduced severe COVID-19 outcomes, aligning with global estimates and demonstrating robustness across different modeling approaches.
ABSTRACT
The emergence of infectious diseases with pandemic potential is a major public health threat worldwide. The World Health Organization reports that about 60% of emerging infectious diseases are zoonoses, originating from spillover events. Although the mechanisms behind spillover events remain unclear, mathematical modeling offers a way to understand the intricate interactions among pathogens, wildlife, humans, and their shared environment. Aiming at gaining insights into the dynamics of spillover events and the outcome of an eventual disease outbreak in a population, we propose a continuous time stochastic modeling framework. This framework links the dynamics of animal reservoirs and human hosts to simulate cross-species disease transmission. We conduct a thorough analysis of the model followed by numerical experiments that explore various spillover scenarios. The results suggest that although most epidemic outbreaks caused by novel zoonotic pathogens do not persist in the human population, the rising number of spillover events can avoid long-lasting extinction and lead to unexpected large outbreaks. Hence, global efforts to reduce the impacts of emerging diseases should not only address post-emergence outbreak control but also need to prevent pandemics before they are established.
Subject(s)
Communicable Diseases, Emerging , Public Health , Zoonoses , Humans , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/transmission , Animals , Zoonoses/epidemiology , Zoonoses/transmission , Disease Outbreaks , Models, Theoretical , Disease Reservoirs , PandemicsABSTRACT
Caused by four serotypes, dengue fever is a major public health concern worldwide. Current modeling efforts have mostly focused on primary and heterologous secondary infections, assuming that lifelong immunity prevents reinfections by the same serotype. However, recent findings challenge this assumption, prompting a reevaluation of dengue immunity dynamics. In this study, we develop a within-host modeling framework to explore different scenarios of dengue infections. Unlike previous studies, we go beyond a deterministic framework, considering individual immunological variability. Both deterministic and stochastic models are calibrated using empirical data on viral load and antibody (IgM and IgG) concentrations for all dengue serotypes, incorporating confidence intervals derived from stochastic realizations. With good agreement between the mean of the stochastic realizations and the mean field solution for each model, our approach not only successfully captures primary and heterologous secondary infection dynamics facilitated by antibody-dependent enhancement (ADE) but also provides, for the first time, insights into homotypic reinfection dynamics. Our study discusses the relevance of homotypic reinfections in dengue transmission at the population level, highlighting potential implications for disease prevention and control strategies.
ABSTRACT
BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccines are extremely effective in preventing severe disease, but their real-world cost effectiveness is still an open question. We present an analysis of the cost-effectiveness and economic impact of the initial phase of the COVID-19 vaccination rollout in the Basque Country, Spain. METHODS: To calculate costs and quality-adjusted life years for the entire population of the Basque Country, dynamic modelling and a real-world data analysis were combined. Data on COVID-19 infection outcomes (cases, hospitalisations, intensive care unit admissions and deaths) and population characteristics (age, sex, socioeconomic status and comorbidity) during the initial phase of the vaccination rollout, from January to June of 2021, were retrieved from the Basque Health Service database. The outcomes in the alternative scenario (without vaccination) were estimated with the dynamic model used to guide public health authority policies, from February to December 2020. Individual comorbidity-adjusted life expectancy and costs were estimated. RESULTS: By averting severe disease-related outcomes, COVID-19 vaccination resulted in monetary savings of 26.44 million for the first semester of 2021. The incremental cost-effectiveness ratio was 707/quality-adjusted life year considering official vaccine prices and dominant real prices. While the analysis by comorbidity showed that vaccines were considerably more cost effective in individuals with pre-existing health conditions, this benefit was lower in the low socioeconomic status group. CONCLUSIONS: The incremental cost-effectiveness ratio of the vaccination programme justified the policy of prioritising high-comorbidity patients. The initial phase of COVID-19 vaccination was dominant from the perspective of the healthcare payer.
Subject(s)
COVID-19 , Vaccines , Humans , Cost-Effectiveness Analysis , COVID-19 Vaccines , Cost-Benefit Analysis , COVID-19/epidemiology , COVID-19/prevention & control , Vaccination , Comorbidity , Social ClassABSTRACT
The burden of sexually transmitted infections (STIs) poses a challenge due to its large negative impact on sexual and reproductive health worldwide. Besides simple prevention measures and available treatment efforts, prophylactic vaccination is a powerful tool for controlling some viral STIs and their associated diseases. Here, we investigate how prophylactic vaccines are best distributed to prevent and control STIs. We consider sex-specific differences in susceptibility to infection, as well as disease severity outcomes. Different vaccination strategies are compared assuming distinct budget constraints that mimic a scarce vaccine stockpile. Vaccination strategies are obtained as solutions to an optimal control problem subject to a two-sex Kermack-McKendrick-type model, where the control variables are the daily vaccination rates for females and males. One important aspect of our approach relies on conceptualizing a limited but specific vaccine stockpile via an isoperimetric constraint. We solve the optimal control problem via Pontryagin's Maximum Principle and obtain a numerical approximation for the solution using a modified version of the forward-backward sweep method that handles the isoperimetric budget constraint in our formulation. The results suggest that for a limited vaccine supply ([Formula: see text]-[Formula: see text] vaccination coverage), one-sex vaccination, prioritizing females, appears to be more beneficial than the inclusion of both sexes into the vaccination program. Whereas, if the vaccine supply is relatively large (enough to reach at least [Formula: see text] coverage), vaccinating both sexes, with a slightly higher rate for females, is optimal and provides an effective and faster approach to reducing the prevalence of the infection.
Subject(s)
Sexually Transmitted Diseases, Viral , Sexually Transmitted Diseases , Vaccines , Male , Female , Humans , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Vaccination , Vaccination CoverageABSTRACT
Vaccines have measurable efficacy obtained first from vaccine trials. However, vaccine efficacy (VE) is not a static measure and long-term population studies are needed to evaluate its performance and impact. COVID-19 vaccines have been developed in record time and the currently licensed vaccines are extremely effective against severe disease with higher VE after the full immunization schedule. To assess the impact of the initial phase of the COVID-19 vaccination rollout programmes, we used an extended Susceptible - Hospitalized - Asymptomatic/mild - Recovered (SHAR) model. Vaccination models were proposed to evaluate different vaccine types: vaccine type 1 which protects against severe disease only but fails to block disease transmission, and vaccine type 2 which protects against both severe disease and infection. VE was assumed as reported by the vaccine trials incorporating the difference in efficacy between one and two doses of vaccine administration. We described the performance of the vaccine in reducing hospitalizations during a momentary scenario in the Basque Country, Spain. With a population in a mixed vaccination setting, our results have shown that reductions in hospitalized COVID-19 cases were observed five months after the vaccination rollout started, from May to June 2021. Specifically in June, a good agreement between modelling simulation and empirical data was well pronounced.
ABSTRACT
BACKGROUND: The objective of this study was to assess changes in social and clinical determinants of COVID-19 outcomes associated with the first year of COVID-19 vaccination rollout in the Basque population. METHODS: A retrospective study was performed using the complete database of the Basque Health Service (n = 2,343,858). We analyzed data on age, sex, socioeconomic status, the Charlson comorbidity index (CCI), hospitalization and intensive care unit (ICU) admission, and COVID-19 infection by Cox regression models and Kaplan-Meier curves. RESULTS: Women had a higher hazard ratio (HR) of infection (1.1) and a much lower rate of hospitalization (0.7). With older age, the risk of infection fell, but the risks of hospitalization and ICU admission increased. The higher the CCI, the higher the risks of infection and hospitalization. The risk of infection was higher in high-income individuals in all periods (HR = 1.2-1.4) while their risk of hospitalization was lower in the post-vaccination period (HR = 0.451). CONCLUSION: Despite the lifting of many control measures during the second half of 2021, restoring human mobility patterns, the situation could not be defined as syndemic, clinical determinants seeming to have more influence than social ones on COVID-19 outcomes, both before and after vaccination program implementation.
Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Cohort Studies , Comorbidity , Female , Hospitalization , Humans , Retrospective Studies , VaccinationABSTRACT
Declared a pandemic by the World Health Organization (WHO), COVID-19 has spread rapidly around the globe. With eventually substantial global underestimation of infection, by the end of March 2022, more than 470 million cases were confirmed, counting more than 6.1 million deaths worldwide. COVID-19 symptoms range from mild (or no) symptoms to severe illness, with disease severity and death occurring according to a hierarchy of risks, with age and pre-existing health conditions enhancing risks of disease severity. In order to understand the dynamics of disease severity during the initial phase of the pandemic, we propose a modeling framework stratifying the studied population into two groups, older and younger, assuming different risks for severe disease manifestation. The deterministic and the stochastic models are parametrized using epidemiological data for the Basque Country population referring to confirmed cases, hospitalizations and deaths, from February to the end of March 2020. Using similar parameter values, both models were able to describe well the existing data. A detailed sensitivity analysis was performed to identify the key parameters influencing the transmission dynamics of COVID-19 in the population. We observed that the population younger than 60 years old of age would contribute more to the overall force of infection than the older population, as opposed to the already existing age-structured models, opening new ways to understand the effect of population age on disease severity during the COVID-19 pandemic. With mild/asymptomatic cases significantly influencing the disease spreading and control, our findings support the vaccination strategy prioritising the most vulnerable individuals to reduce hospitalization and deaths, as well as the non-pharmaceutical intervention measures to reduce disease transmission.
Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Middle Aged , Pandemics/prevention & control , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiologyABSTRACT
INTRODUCTION: Different COVID-19 vaccine efficacies are reported, with remarkable effectiveness against severe disease. The so called sterilizing immunity, occurring when vaccinated individuals cannot transmit the virus, is still being evaluated. It is also unclear to what extent people with no symptoms or mild infection transmit the disease, and estimating their contribution to outbreaks is challenging. OBJECTIVE: With an uneven roll out of vaccination, the purpose of this study is to investigate the role of mild and asymptomatic infections on COVID-19 vaccine performance as vaccine efficacy and vaccine coverage vary. METHODS: We use an epidemiological SHAR (Susceptible-Hospitalized-Asymptomatic-Recovered) model framework to evaluate the effects of vaccination in different epidemiological scenarios of coverage and efficacy. Two vaccination models, the vaccine V1 protecting against severe disease, and the vaccine V2, protecting against infection as well as severe disease, are compared to evaluate the reduction of overall infections and hospitalizations. RESULTS: Vaccine performance is driven by the ability of asymptomatic or mild disease cases transmitting the virus. Vaccines protecting against severe disease but failing to block transmission might not be able to reduce significantly the severe disease burden during the initial stage of a vaccination roll out programme, with an eventual increase on the number of overall infections in a population. CONCLUSION: The different COVID-19 vaccines currently in use have features placing them closer to one or the other of these two extreme cases, V1 and V2, and insights on the importance of asymptomatic infection in a vaccinated population are of a major importance for the future planning of vaccination programmes. Our results give insights on how to best combine the use of the available COVID-19 vaccines, optimizing the reduction of hospitalizations.
Subject(s)
COVID-19 , Vaccines , Asymptomatic Infections/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , VaccinationABSTRACT
Mathematical models have a long history in epidemiological research, and as the COVID-19 pandemic progressed, research on mathematical modeling became imperative and very influential to understand the epidemiological dynamics of disease spreading. Mathematical models describing dengue fever epidemiological dynamics are found back from 1970. Dengue fever is a viral mosquito-borne infection caused by four antigenically related but distinct serotypes (DENV-1 to DENV-4). With 2.5 billion people at risk of acquiring the infection, it is a major international public health concern. Although most of the cases are asymptomatic or mild, the disease immunological response is complex, with severe disease linked to the antibody-dependent enhancement (ADE) - a disease augmentation phenomenon where pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection. Here, we present a 10-year systematic review on mathematical models for dengue fever epidemiology. Specifically, we review multi-strain frameworks describing host-to-host and vector-host transmission models and within-host models describing viral replication and the respective immune response. Following a detailed literature search in standard scientific databases, different mathematical models in terms of their scope, analytical approach and structural form, including model validation and parameter estimation using empirical data, are described and analyzed. Aiming to identify a consensus on infectious diseases modeling aspects that can contribute to public health authorities for disease control, we revise the current understanding of epidemiological and immunological factors influencing the transmission dynamics of dengue. This review provide insights on general features to be considered to model aspects of real-world public health problems, such as the current epidemiological scenario we are living in.
Subject(s)
COVID-19 , Dengue Virus , Dengue , Animals , Antibodies, Viral , Dengue/epidemiology , Humans , Models, Theoretical , Mosquito Vectors , Pandemics , SARS-CoV-2ABSTRACT
Dengue fever is a viral mosquito-borne infection and a major international public health concern. With 2.5 billion people at risk of acquiring the infection around the world, disease severity is influenced by the immunological status of the individual, seronegative or seropositive, prior to natural infection. Caused by four antigenically related but distinct serotypes, DENV-1 to DENV-4, infection by one serotype confers life-long immunity to that serotype and a period of temporary cross-immunity (TCI) to other serotypes. The clinical response on exposure to a second serotype is complex with the so-called antibody-dependent enhancement (ADE) process, a disease augmentation phenomenon when pre-existing antibodies to previous dengue infection do not neutralize but rather enhance the new infection, used to explain the etiology of severe disease. In this paper, we present a minimalistic mathematical model framework developed to describe qualitatively the dengue immunological response mediated by antibodies. Three models are analyzed and compared: (i) primary dengue infection, (ii) secondary dengue infection with the same (homologous) dengue virus and (iii) secondary dengue infection with a different (heterologous) dengue virus. We explore the features of viral replication, antibody production and infection clearance over time. The model is developed based on body cells and free virus interactions resulting in infected cells activating antibody production. Our mathematical results are qualitatively similar to the ones described in the empiric immunology literature, providing insights into the immunopathogenesis of severe disease. Results presented here are of use for future research directions to evaluate the impact of dengue vaccines.
ABSTRACT
As the COVID-19 pandemic progressed, research on mathematical modeling became imperative and very influential to understand the epidemiological dynamics of disease spreading. The momentary reproduction ratio r(t) of an epidemic is used as a public health guiding tool to evaluate the course of the epidemic, with the evolution of r(t) being the reasoning behind tightening and relaxing control measures over time. Here we investigate critical fluctuations around the epidemiological threshold, resembling new waves, even when the community disease transmission rate [Formula: see text] is not significantly changing. Without loss of generality, we use simple models that can be treated analytically and results are applied to more complex models describing COVID-19 epidemics. Our analysis shows that, rather than the supercritical regime (infectivity larger than a critical value, [Formula: see text]) leading to new exponential growth of infection, the subcritical regime (infectivity smaller than a critical value, [Formula: see text]) with small import is able to explain the dynamic behaviour of COVID-19 spreading after a lockdown lifting, with [Formula: see text] hovering around its threshold value.
Subject(s)
COVID-19/epidemiology , Models, Biological , Models, Theoretical , SARS-CoV-2/pathogenicity , Basic Reproduction Number/statistics & numerical data , Communicable Disease Control/methods , Computer Simulation/statistics & numerical data , Epidemics , Humans , Public Health/statistics & numerical dataABSTRACT
There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV-Sanofi Pasteur) and DENVax (TAK 003-Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.
ABSTRACT
In March 2020, a multidisciplinary task force (so-called Basque Modelling Task Force, BMTF) was created to assist the Basque health managers and Government during the COVID-19 responses. BMTF is a modelling team, working on different approaches, including stochastic processes, statistical methods and artificial intelligence. Here we describe the efforts and challenges to develop a flexible modeling framework able to describe the dynamics observed for the tested positive cases, including the modelling development steps. The results obtained by a new stochastic SHARUCD model framework are presented. Our models differentiate mild and asymptomatic from severe infections prone to be hospitalized and were able to predict the course of the epidemic, providing important projections on the national health system's necessities during the increased population demand on hospital admissions. Short and longer-term predictions were tested with good results adjusted to the available epidemiological data. We have shown that the partial lockdown measures were effective and enough to slow down disease transmission in the Basque Country. The growth rate [Formula: see text] was calculated from the model and from the data and the implications for the reproduction ratio r are shown. The analysis of the growth rates from the data led to improved model versions describing after the exponential phase also the new information obtained during the phase of response to the control measures. This framework is now being used to monitor disease transmission while the country lockdown was gradually lifted, with insights to specific programs for a general policy of "social distancing" and home quarantining.
Subject(s)
Coronavirus Infections/prevention & control , Models, Theoretical , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Quarantine , SARS-CoV-2 , Spain/epidemiologyABSTRACT
The initial exponential growth rate of an epidemic is an important measure that follows directly from data at hand, commonly used to infer the basic reproduction number. As the growth rates λ(t) of tested positive COVID-19 cases have crossed the threshold in many countries, with negative numbers as surrogate for disease transmission deceleration, lockdowns lifting are linked to the behavior of the momentary reproduction numbers r(t), often called R0. Important to note that this concept alone can be easily misinterpreted as it is bound to many internal assumptions of the underlying model and significantly affected by the assumed recovery period. Here we present our experience, as part of the Basque Country Modeling Task Force (BMTF), in monitoring the development of the COVID-19 epidemic, by considering not only the behaviour of r(t) estimated for the new tested positive cases-significantly affected by the increased testing capacities, but also the momentary growth rates for hospitalizations, ICU admissions, deceased and recovered cases, in assisting the Basque Health Managers and the Basque Government during the lockdown lifting measures. Two different data sets, collected and then refined during the COVID-19 responses, are used as an exercise to estimate the momentary growth rates and reproduction numbers over time in the Basque Country, and the implications of using those concepts to make decisions about easing lockdown and relaxing social distancing measures are discussed. These results are potentially helpful for task forces around the globe which are now struggling to provide real scientific advice for health managers and governments while the lockdown measures are relaxed.
Subject(s)
Basic Reproduction Number , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Betacoronavirus , COVID-19 , Coronavirus Infections/transmission , Hospitalization/statistics & numerical data , Humans , Intensive Care Units , Models, Theoretical , Pandemics , Pneumonia, Viral/transmission , SARS-CoV-2 , SpainABSTRACT
The motivation for the research reported in this paper comes from modeling the spread of vector-borne virus diseases. To study the role of the host versus vector dynamics and their interaction we use the susceptible-infected-removed (SIR) host model and the susceptible-infected (SI) vector model. When the vector dynamical processes occur at a faster scale than those in the host-epidemics dynamics, we can use a time-scale argument to reduce the dimension of the model. This is often implemented as a quasi steady-state assumption (qssa) where the slow varying variable is set at equilibrium and an ode equation is replaced by an algebraic equation. Singular perturbation theory will appear to be a useful tool to perform this derivation. An asymptotic expansion in the small parameter that represents the ratio of the two time scales for the dynamics of the host and vector is obtained using an invariant manifold equation. In the case of a susceptible-infected-susceptible (SIS) host model this algebraic equation is a hyperbolic relationship modeling a saturated incidence rate. This is similar to the Holling type II functional response (Ecology) and the Michaelis-Menten kinetics (Biochemistry). We calculate the value for the force of infection leading to an endemic situation by performing a bifurcation analysis. The effect of seasonality is studied where the force of infection changes sinusoidally to model the annual fluctuations of the vector population. The resulting non-autonomous system is studied in the same way as the autonomous system using bifurcation analysis.