Mutation and SARS-CoV-2 strain competition under vaccination in a modified SIR model.

The crisis caused by the COVID-19 outbreak around the globe raised an increasing concern about the ongoing emergence of variants of the virus that may evade the immune response provided by vaccines. New variants appear due to mutation, and as the cases accumulate, the probability of the emergence of a variant of concern increases. In this article, we propose a modified susceptible, infected, and recovered (SIR) model with waning immunity that captures the competition of two strain classes of an infectious disease under the effect of vaccination with a highly contagious and deadlier strain class emerging from a prior strain due to mutation. When these strains compete for a limited supply of susceptible individuals, changes in the efficiency of vaccines may affect the behaviour of the disease in a non-trivial way, resulting in complex outcomes. We characterise the parameter space including intrinsic parameters of the disease, and using the vaccine efficiencies as control variables. We find different types of transcritical bifurcations between endemic fixed points and a disease-free equilibrium and identify a region of strain competition where the two strain classes coexist during a transient period. We show that a strain can be extinguished either due to strain competition or vaccination, and we obtain the critical values of the efficiency of vaccines to eradicate the disease. Numerical studies using parameters estimated from publicly reported data agree with our theoretical results. Our mathematical model could be a tool to assess quantitatively the vaccination policies of competing and emerging strains using the dynamics in epidemics of infectious diseases.

COVID-19 reinfections in Mexico City: implications for public health.

Background: Since its appearance, COVID-19 has immensely impacted our society. Public health measures, from the initial lockdowns to vaccination campaigns, have mitigated the crisis. However, SARS-CoV-2's persistence and evolving variants continue to pose global threats, increasing the risk of reinfections. Despite vaccination progress, understanding reinfections remains crucial for informed public health responses. Methods: We collected available data on clinical and genomic information for SARS-CoV-2 samples from patients treated in Mexico City from 2020 epidemiological week 10 to 2023 epidemiological week 06 encompassing the whole public health emergency's period. To identify clinical data we utilized the SISVER (Respiratory Disease Epidemiological Surveillance System) database for SARS-CoV-2 patients who received medical attention in Mexico City. For genomic surveillance we analyzed genomic data previously uploaded to GISAID generated by Mexican institutions. We used these data sources to generate descriptors of case number, hospitalization, death and reinfection rates, and viral variant prevalence throughout the pandemic period. Findings: The fraction of reinfected individuals in the COVID-19 infected population steadily increased as the pandemic progressed in Mexico City. Most reinfections occurred during the fifth wave (40%). This wave was characterized by the coexistence of multiple variants exceeding 80% prevalence; whereas all other waves showed a unique characteristic dominant variant (prevalence >95%). Shifts in symptom patient care type and severity were observed, 2.53% transitioned from hospitalized to ambulatory care type during reinfection and 0.597% showed the opposite behavior; also 7.23% showed a reduction in severity of symptoms and 6.05% displayed an increase in severity. Unvaccinated individuals accounted for the highest percentage of reinfections (41.6%), followed by vaccinated individuals (31.9%). Most reinfections occurred after the fourth wave, dominated by the Omicron variant; and after the vaccination campaign was already underway. Interpretation: Our analysis suggests reduced infection severity in reinfections, evident through shifts in symptom severity and care patterns. Unvaccinated individuals accounted for most reinfections. While our study centers on Mexico City, its findings may hold implications for broader regions, contributing insights into reinfection dynamics.

COVID-19 underreporting and its impact on vaccination strategies.

BACKGROUND: Underreporting cases of infectious diseases poses a major challenge in the analysis of their epidemiological characteristics and dynamical aspects. Without accurate numerical estimates it is difficult to precisely quantify the proportions of severe and critical cases, as well as the mortality rate. Such estimates can be provided for instance by testing the presence of the virus. However, during an ongoing epidemic, such tests' implementation is a daunting task. This work addresses this issue by presenting a methodology to estimate underreported infections based on approximations of the stable rates of hospitalization and death. METHODS: We present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease 2019 (COVID-19) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease-transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model. RESULTS: For the considered locations, during the period of study, the estimations suggest that the number of infected individuals could reach 30% of the population of these places, representing, in some cases, more than six times the observed numbers. These results are in close agreement with estimates from independent seroprevalence studies, thus providing a strong validation of the proposed methodology. Moreover, the presence of large numbers of underreported infections can reduce the perceived impact of vaccination strategies in reducing rates of mortality and hospitalization. CONCLUSIONS: pBy using the proposed methodology and employing a judiciously chosen data analysis implementation, we estimate COVID-19 underreporting from publicly available data. This leads to a powerful way of quantifying underreporting impact on the efficacy of vaccination strategies. As a byproduct, we evaluate the impact of underreporting in the designing of vaccination strategies.

Pig vaccination strategies based on enterotoxigenic Escherichia coli toxins.

Enterotoxigenic Escherichia coli (ETEC) are responsible for diarrhea in humans as well as in farm animals. ETEC infections in newborn, suckling, and especially in post-weaning piglets are associated with reduced growth rate, morbidity, and mortality. ETEC express virulence factors as adhesin and enterotoxins that play a central role in the pathogenic process. Adhesins associated with pigs are of diverse type being either fimbrial or non-fimbrial. Enterotoxins belong to two groups: heat-labile (LT) and heat-stable (ST). Heterogeneity of ETEC strains encompass expression of various fimbriae (F4, F5, F6, F18, and F41) and enterotoxins (LT, STa, STb, and EAST1). In the late years, attempts to immunize animals against neonatal and post-weaning diarrhea were focused on the development of anti-adhesin strategies as this is the initial step of ETEC pathogenesis. Although those vaccines demonstrated some protection against ETEC infections, as enterotoxins are pivotal to the virulence of ETEC, a new generation of vaccinal molecules, which include adhesin and one or more enterotoxins, were recently tested. Some of these newly developed chimeric fusion proteins are intended to control as well human diarrhea as enterotoxins are more or less common with the ones found in pigs. As these could not be tested in the natural host (human), either a mouse or pig model was substituted to evaluate the protection efficacy. For the advancement of pig vaccine, mice were sometimes used for preliminary testing. This review summarizes advances in the anti-enterotoxin immunization strategies considered in the last 10 years.

Cost-effectiveness of Hepatitis A vaccination in a developed and developing country.

PURPOSE: Hepatitis A is a prevalent disease that is largely preventable by vaccine usage. The vaccine for this illness is highly underused in most regions. In an attempt to find the strategies that are most beneficial in regard to quality-adjusted life years (QALYs) and cost in current environments, the purpose of this paper is to conduct cost-effectiveness analyses to investigate vaccination strategies in a more economically developed country (MEDC), generally known as a "developed" area: the USA, and a less economically developed country (LEDC), generally known as a "developing" area: the state of Rio de Janeiro, Brazil. DESIGN/METHODOLOGY/APPROACH: This study used a dynamic transmission model for comparative effectiveness analyses. The model ran two different scenarios. The two regions studied have different policies and strategies for Hepatitis A vaccination currently, and also used different strategies in 2009. In the USA, a universal vaccination policy was modeled, along with a scenario in which it was removed. In Rio de Janeiro, a no vaccination policy was modeled, along with a scenario in which a universal vaccination policy was effected. FINDINGS: The comparison of resulting incremental cost-effectiveness ratio values to accepted threshold values showed universal vaccination to be cost-effective in both the USA and Rio de Janeiro as compared to no vaccination. When episode and vaccination costs and vaccination efficacy were varied, this still remained true. Universal vaccination was found to result in lower incidence of Hepatitis A in both the USA and Rio de Janeiro. Over the twenty-year time horizon, universal vaccination is projected to prevent 506,945 cases of symptomatic Hepatitis A in the USA and 42,318 cases of Hepatitis A in Rio de Janeiro. Other benefits include a projected increase in cumulative QALYs through the use of universal vaccination. ORIGINALITY/VALUE: This analysis showed universal vaccination to be cost-effective as compared to no vaccination, and portions of the study's approach had not previously been applied in tandem to investigate Hepatitis A interventions. The results may help foster higher compliance rates for Hepatitis A vaccination and even greater per-person economic benefits of universal vaccination, particularly in the USA. The purpose of this study is also to encourage elevated levels of surveillance on age of infection in developing regions and consistent reevaluation utilizing dynamic transmission models in both the USA and Brazil, as well as other rapidly developing regions, in order to prevent future epidemics and costs associated with the disease.

How to eliminate taeniasis/cysticercosis: porcine vaccination and human chemotherapy (Part 2).

BACKGROUND: The application of effective vaccines against pig cysticercosis and mass chemotherapy against pig cysticercosis and human taeniasis have shown the feasibility of interrupting the parasite's life cycle in endemic areas. METHODS: A mathematical model that divides the population into susceptible, infected, and vaccinated individuals is formulated. The model is based upon the life cycle of the parasite. Computer numerical simulation experiments to evaluate the impact of pig vaccination under different vaccination schedules, and combined intervention strategies including pig vaccination and anthelmintic treatment against human taeniasis are carried out. RESULTS: Vaccination against either pig cysticercosis or against human taeniasis will influence the transmission dynamics not only among vaccinees but also the dynamics of the other hosts as well. When the protective efficacy and/or the coverage rate is less than 100%, different mass interventions like vaccinating the pig population twice in combination with chemotherapeutic treatment against human taeniasis, the elimination of the infection in both pigs and humans can also be achieved. CONCLUSIONS: Our mathematical model has the potential for planning, and designing effective intervention strategies including both mass vaccination and/or chemotherapeutic treatment to eliminate pig cysticercosis, human taeniasis and human neurocysticercosis. The model can be adapted to any given community with mild, moderate endemicity, or even in hyperendemic regions.

Heterogeneities in dengue spatial-temporal transmission in Brazilian cities and its influence on the optimal age of vaccination.

BACKGROUND: The development of a safe and effective vaccine is considered crucial for dengue transmission control since vetor control has been failed; some potential candidates are currently in test, and in this context theoretical studies are necessary to evaluate vaccination strategies such as the age groups that should be vaccinated, the percentage of the population at risk, and the target geographic regions to make dengue control feasible and optimal. METHODS: A partial differential model is used to mimics dengue transmission in human population in order to estimate the optimal vaccination age, using data collected from dengue reported cases in ten cities of Brazil from 2001 to 2014. For this purpose, the basic reproduction number of the disease was minimized assuming a single-dose vaccination strategy, equal vaccine efficacy for all circulating serotypes, and no vaccine failure. Numerical methods were used to assess the optimal vaccination age and its confidence age range. RESULTS: The results reveal complex spatial-temporal patterns associated to the disease transmission, highlighting the heterogeneity in defining the target population for dengue vaccination. However, the values obtained for the optimal age of vaccination, as targeting individuals under 13 years old, are compatible with the ones reported in similar studies in Brazil. The results also show that the optimal age for vaccination in general does not match with the age of the highest number of cases. CONCLUSIONS: The variation of the optimal age for vaccination across the country reflects heterogeneities in dengue spatial-temporal transmission in Brazilian cities, and can be used to define the target population and cities to optimize vaccination strategies in a context of high cost and low quantity of available vaccine.

A multi-country study of dengue vaccination strategies with Dengvaxia and a future vaccine candidate in three dengue-endemic countries: Vietnam, Thailand, and Colombia.

BACKGROUND: The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia. METHODS: The vaccination impacts of CYD-TDV and NVC were derived by fitting the empirical seroprevalence rates of 9 year olds into an individual-based meta-population transmission model, previously used for the WHO-SAGE working group. The disability-adjusted life years were estimated by applying country-specific parametric values. The cost-effectiveness analyses of four intervention strategies in combination with routine and catch-up campaigns were compared for both vaccines to inform decision makers regarding the most suitable immunization program in each of the three countries. RESULTS AND CONCLUSION: Both CYD-TDV and NVC could be cost-effective at the DALY threshold cost of $2000 depending upon vaccination costs. With CYD-TDV, targeting 9 year olds in routine vaccination programs and 10-29 year olds as a one-off catch-up campaign was the most cost-effective strategy in all three countries. With NVC, while the most cost-effective strategy was to vaccinate 9-29 and 9-18 year olds in Vietnam and Thailand respectively, vaccinating younger age cohorts between 1 and 5 years old in Colombia was more cost-effective than other strategies. Given that three countries will soon face decisions regarding whether and how to incorporate CYD-TDV or future dengue vaccines into their budget-constrained national immunization programs, the current study outcomes can be used to help decision makers understand the expected impacts and cost-effectiveness of such vaccines.

Dengue vaccine supplies under endemic and epidemic conditions in three dengue-endemic countries: Colombia, Thailand, and Vietnam.

BACKGROUND: Dengue fever has been a major public health concern in Colombia, Thailand, and Vietnam. Unlike other infectious diseases, dengue vaccines had not been available for a long time, causing difficulties to control the disease. However, the first live attenuated, tetravalent dengue vaccine (CYD-TDV) became available in 2016 and has been already licensed in some dengue-endemic countries. Because several second-generation dengue vaccines are also in the pipeline, it is critical to understand the efficient allocation of dengue vaccines considering the geographical variation of the disease. METHODS: The Climate Risk Factor (CRF) index was created using the climate and non-climate factors in the three countries. A random-coefficient negative binomial model was chosen to validate the relationship between the CRF index and dengue incidence proxy. Given the statistical significance of the CRF index, high risk areas for dengue fever were identified at the 5 km by 5 km resolution and used to estimate vaccination coverage rates and the number of doses required for various types of vaccination scenarios by country. RESULTS AND CONCLUSIONS: Based upon a three-dose scheme, the estimated number of vaccines required for routine vaccination targeting 9 years old ranged from 1 to 2.6 million doses across the countries during the first year of introduction. A one-off catch-up campaign targeting the age group of 10-17 year olds would require 8 to 18 million additional doses. Routine vaccination (with or without a catch-up campaign) covered 63%, 90%, and 91% of the targeted age group populations in Colombia, Thailand, and Vietnam respectively. Given that many dengue-endemic countries face limited resources and that the costs for mass vaccination campaigns may not be trivial, the findings of this study can guide the decision makers in the three countries regarding the efficient distribution of vaccines by identifying populations at high risk at 5 km by 5 km resolution.

Typhoid fever vaccination strategies.

Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control.

Meningococcal disease serogroup C.

Despite current advances in antibiotic therapy and vaccines, meningococcal disease serogroup C (MDC) remains a serious threat to global health, particularly in countries in North and Latin America, Europe, and Asia. MDC is a leading cause of morbidity, mortality, and neurological sequelae and it is a heavy economic burden. At the individual level, despite advances in antibiotics and supportive therapies, case fatality rate remains nearly 10% and severe neurological sequelae are frequent. At the population level, prevention and control of infection is more challenging. The main approaches include health education, providing information to the public, specific treatment, chemoprophylaxis, and the use of vaccines. Plain and conjugate meningococcal C polysaccharide vaccines are considered safe, are well tolerated, and have been used successfully for over 30 years. Most high-income countries use vaccination as a part of public health strategies, and different meningococcal C vaccination schedules have proven to be effective in reducing incidence. This is particularly so with conjugate vaccines, which have been found to induce immunogenicity in infants (the age group with the highest incidence rates of disease), stimulate immunologic memory, have longer effects, not lead to hyporesponsiveness with repeated dosing, and decrease acquisition of nasopharyngeal carriage, inducing herd immunity. Antibiotics are considered a cornerstone of MDC treatment and must be administered empirically as soon as possible. The choice of which antibiotic to use should be made based on local antibiotic resistance, availability, and circulating strains. Excellent options for a 7-day course are penicillin, ampicillin, chloramphenicol, and third-generation cephalosporins (ceftriaxone and cefotaxime) intravenously, although the latter are considerably more expensive than the others. The use of steroids as adjunctive therapy for MDC is still controversial and remains a topic of debate. A combination of all of the aforementioned approaches is useful in the prevention and control of MDC, and each country should tailor its public health policy to its own particular needs and knowledge of disease burden.

Modelos matemáticos sobre la transmisión de coqueluche y estrategias de vacunación en Argentina / Mathematical models about pertussis transmission and vaccination strategies in Argentina

INTRODUCCION: La tos convulsa o pertussis es una enfermedad respiratoria que es más severa en los lactantes. Antes de que la vacunación infantil se introdujera en la década de 1950, la tos convulsa era una de las principales causas de mortalidad infantil en el mundo. La enfermedad hoy es reconocida como una infección frecuente, no sólo para los niños sino también para los adultos. Las razones de esta situación epidemiológica y las estrategias de control para la enfermedad son objeto de debate en la comunidad científica. En este contexto, los modelos matemáticos se utilizan cada vez más como un herramienta no sólo para el análisis, sino también para predicciones con el fin de contribuir al conocimiento de este complejo problema.OBJETIVO: En este estudio se presenta un modelo compartamentalizado, que de manera simplificada permite describir la propagación de la tos convulsa en la Argentina y evaluar el impacto de los cambios en el calendario de vacunación en el control de la enfermedad.METODOS: El modelo epidemiológico aplicado considera que la exposición a la tos convulsa a través de la infección natural o vacunación induce una respuesta inmune que previene la enfermedad grave. Además, se considera que estos efectos protectores son temporales debido a la disminución de la inmunidad.RESULTADOS: El estudio señala que la dosis administrada a los 11 años (recientemente introducidos en el esquema de vacunación de Argentina) disminuye la incidencia de la enfermedad en el grupo etario de 11 a 13 años de edad en una proporción de alrededor del 40%. Sin embargo, este refuerzo podría tener un impacto mucho menor (menos del 5%) para los niños menores de 1 año de edad que son el grupo más vulnerable.CONCLUSIONES: Nuestro estudio sugiere que un esfuerzo dirigido a la mejora de la cobertura de las primeras dosis tendrá un impacto mucho mayor que el refuerzo de los 11 en lo que se refiere a la reducción de la incidencia de tos convulsa en los niños más pequeños.

INTRODUCTION: Whooping cough, or pertussis, is a respiratory disease that is mose severe in infants. Before childhood vaccination was introduced in the 1950s, pertussis was a major cause of infant mortality worldwide. The disease is now recognized as a frequent infection not only for infants but also for adults. The reasons for this epidemiological situation and strategies for disease control are matters of debate in the scientific community. In this context, the mathematical models are being used increasingly as a tool not only for analysis but also for predictions in order to contribute to the knowledge of this complex problem.OBJECTIVE: The study has a compartmental model that, in a simplistic way, allows to describe the propagation of pertussis in Argentina and to assess the impact of changes in the vaccination schedule on the disease control.METHODS: The model here presented considers that pertussis exposure through natural infection or vaccination induces an immune response that prevents severe disease and assumes that these protective effects are temporary due to waning of immunity.RESULTS: The study points out that the dose given at 11 years of age (recently introduced in Argentica vaccination schedule) would decrease around 40% the incidence of the disease in the age group from 11 to 13 years old. However, this reinforcement would have a much lower impact (less than 5%) in children under 1 year, who are the most vulnerable group.CONCLUSIONS: It would be important to make an effort towards vigilance, so as to improve the coverage of the primary close and then significantly reduce the incidence of pertussis in the youngest children.

Modelos matemáticos sobre la transmisión de coqueluche y estrategias de vacunación en Argentina / Mathematical models about pertussis transmission and vaccination strategies in Argentina

INTRODUCCION: La tos convulsa o pertussis es una enfermedad respiratoria que es más severa en los lactantes. Antes de que la vacunación infantil se introdujera en la década de 1950, la tos convulsa era una de las principales causas de mortalidad infantil en el mundo. La enfermedad hoy es reconocida como una infección frecuente, no sólo para los niños sino también para los adultos. Las razones de esta situación epidemiológica y las estrategias de control para la enfermedad son objeto de debate en la comunidad científica. En este contexto, los modelos matemáticos se utilizan cada vez más como un herramienta no sólo para el análisis, sino también para predicciones con el fin de contribuir al conocimiento de este complejo problema.OBJETIVO: En este estudio se presenta un modelo compartamentalizado, que de manera simplificada permite describir la propagación de la tos convulsa en la Argentina y evaluar el impacto de los cambios en el calendario de vacunación en el control de la enfermedad.METODOS: El modelo epidemiológico aplicado considera que la exposición a la tos convulsa a través de la infección natural o vacunación induce una respuesta inmune que previene la enfermedad grave. Además, se considera que estos efectos protectores son temporales debido a la disminución de la inmunidad.RESULTADOS: El estudio señala que la dosis administrada a los 11 años (recientemente introducidos en el esquema de vacunación de Argentina) disminuye la incidencia de la enfermedad en el grupo etario de 11 a 13 años de edad en una proporción de alrededor del 40%. Sin embargo, este refuerzo podría tener un impacto mucho menor (menos del 5%) para los niños menores de 1 año de edad que son el grupo más vulnerable.CONCLUSIONES: Nuestro estudio sugiere que un esfuerzo dirigido a la mejora de la cobertura de las primeras dosis tendrá un impacto mucho mayor que el refuerzo de los 11 en lo que se refiere a la reducción de la incidencia de tos convulsa en los niños más pequeños.

INTRODUCTION: Whooping cough, or pertussis, is a respiratory disease that is mose severe in infants. Before childhood vaccination was introduced in the 1950s, pertussis was a major cause of infant mortality worldwide. The disease is now recognized as a frequent infection not only for infants but also for adults. The reasons for this epidemiological situation and strategies for disease control are matters of debate in the scientific community. In this context, the mathematical models are being used increasingly as a tool not only for analysis but also for predictions in order to contribute to the knowledge of this complex problem.OBJECTIVE: The study has a compartmental model that, in a simplistic way, allows to describe the propagation of pertussis in Argentina and to assess the impact of changes in the vaccination schedule on the disease control.METHODS: The model here presented considers that pertussis exposure through natural infection or vaccination induces an immune response that prevents severe disease and assumes that these protective effects are temporary due to waning of immunity.RESULTS: The study points out that the dose given at 11 years of age (recently introduced in Argentica vaccination schedule) would decrease around 40% the incidence of the disease in the age group from 11 to 13 years old. However, this reinforcement would have a much lower impact (less than 5%) in children under 1 year, who are the most vulnerable group.CONCLUSIONS: It would be important to make an effort towards vigilance, so as to improve the coverage of the primary close and then significantly reduce the incidence of pertussis in the youngest children.