Large-scale frequent testing and tracing to supplement control of Covid-19 and vaccination rollout constrained by supply.

Non-pharmaceutical interventions (NPI) were implemented all around the world in the fight against COVID-19: Social distancing, shelter-in-place, mask wearing, etc. to mitigate transmission, together with testing and contact-tracing to identify, isolate and treat the infected. The majority of countries have relied on the former measures, followed by a ramping up of their testing and tracing capabilities. We present here the cases of South Korea, Italy, Canada and the United States, as a look back to lessons that can be drawn for controlling the pandemic, specifically through the means of testing and tracing. By fitting a disease transmission model to daily case report data in each of the four countries, we first show that their combination of social-distancing and testing/tracing have had a significant impact on the evolution of their first wave of pandemic curves. We then consider the hypothetical scenario where the only NPI measures implemented past the first pandemic wave consisted of isolating individuals due to repeated, country-scale testing and contact tracing, as a mean of lifting social distancing measures without a resurgence of COVID-19. We give estimates on the average isolation rates needed to occur in each country. We find that testing and tracing each individual of a country, on average, every 4.5 days (South Korea), 5.7 days (Canada), 6 days (Italy) and 3.5 days (US), would have been sufficient to mitigate their second pandemic waves. We also considered the situation in Canada to see how a frequent large-scale asymptomatic testing and contact tracing could have been used in combination with vaccination rollout to reduce the infection in the population. This could offer an alternative approach towards preventing and controlling an outbreak when vaccine supply is limited, while testing capacity has been increasingly enhanced.

The potential impact of dengue vaccination with, and without, pre-vaccination screening.

BACKGROUND: The World Health Organization defined a 'screen and vaccinate' strategy as its recommended policy for the licensed dengue vaccine (Dengvaxia, Sanofi Pasteur), so that only individuals with previous dengue infection are vaccinated. The objectives of the present study were to build upon a recently published analysis of the benefits and risks associated with dengue vaccination to evaluate the public health impact and cost-effectiveness of a screen and vaccinate strategy. METHODS: The current analysis was based on a previously reported transmission model and added, for the screening part, three rapid diagnostic tests with identical specificity (99%) but alternative sensitivities (50-70-90%) in the detection of prior dengue infection. The impact of a screen-and-vaccinate strategy considered nine settings representing different levels of transmission intensity. Outcomes (dengue-related hospitalizations, severe dengue, and symptomatic dengue) were assessed according to the level of transmission setting. The cost-effectiveness of vaccination in 10 endemic countries was also assessed. RESULTS: Although associated, in most cases, with a lower population impact than a 'no-screening' approach, a screen and vaccinate strategy is more effective in reducing the number of hospitalized and severe cases prevented per vaccination performed and generates positive health benefits for individuals screened and subsequently vaccinated. As a result, this intervention is cost-effective in all countries considered except for very low transmission settings. The overall population impact of a screen and vaccinate approach is also likely to be improved by the use of several rounds of screening (up to 48% reduction in dengue hospitalization over 10 years with 5 rounds). CONCLUSIONS: WHO recommended option of a screen and vaccinate policy is likely to have a positive impact both at the individual and population level across a wide range of transmission settings and has the potential to be as, if not more, cost-effective than a no screening strategy.

Real-world evidence of dengue burden on hospitals in mexico: insights from the automated subsystem of hospital discharges (saeh) database

Abstract Background The incidence of dengue in Mexico has increased in recent decades. It has been suggested that dengue outbreaks may compromise treatment quality in hospitals. Objective The objective of the study was to quantify the burden imposed by dengue on hospital services in Mexico. Methods We analyzed 19.2 million records contained in the database of hospital services of the Mexican Ministry of Health between 2008 and 2014. The number of admissions due to dengue was compared to other potentially preventable hospitalizations. Hospital departments were categorized to reflect dengue-related activity as high dengue activity (HDA), low dengue activity (LDA), or zero dengue activity departments, and the impact of dengue activity on general in-hospital mortality in HDA departments was assessed. Results Dengue was the cause of more hospital admissions than most of the potentially preventable prevalent acute and chronic conditions and other infectious diseases. In HDA departments, dengue patient load was found to be a significant risk factor for overall in-hospital mortality. There was an approximately two-fold higher dengue case-fatality rate in LDA versus HDA departments, irrespective of dengue severity. Conclusions This study confirms that dengue is an important cause of hospitalization in Mexico and highlights the impact of dengue activity not only on dengue case-fatality rate but also on the overall in-hospital mortality.

Comorbidities increase in-hospital mortality in dengue patients in Brazil

Dengue remains an unmet public health burden. We determined risk factors for dengue in-hospital mortality in Brazil. Of 326,380 hospitalised dengue cases in 9-45-year-old individuals, there were 971 deaths. Risk of dying was 11-times higher in the presence of underlying common comorbidities (renal, infectious, pulmonary disease and diabetes), similar to the risk of dying from severe dengue and much higher with the combination. Ensuring access to integrated dengue preventative measures in individuals aged ≥ 9 years including those with comorbidities may help achieve the WHO objective of 50% reduction in mortality and 25% reduction in morbidity due to dengue by 2020.

Designing a vaccination strategy against dengue / Modelos para implementar a vacinação contra dengue

In this work we propose a mathematical approach to estimate the dengue force of infection, the average age of dengue first infection, the optimum age to vaccinate children against dengue in a routine fashion and the optimum age interval to introduce the dengue vaccine in a mass vaccination campaign. The model is based on previously published models for vaccination against other childhood infections, which resulted in actual vaccination programmes in Brazil. The model was applied for three areas of distinct levels of endemicity of the city of Recife in Northeastern State of Pernambuco, Brazil. Our results point to an optimal age to introduce the dengue vaccine in the routine immunization programme at two years of age and an age interval to introduce a mass vaccination between three and 14 years of age.

Neste trabalho propomos um modelo matemático para a estimativa da força de infecção, da idade média de primo-infecção, da idade ótima para vacinação de rotina e do intervalo ótimo de cobertura vacina em uma campanha para a introdução da vacina contra a dengue. O modelo baseia-se em publicações anteriores de desenhos de estratégias de vacinação contra outras infecções e que resultaram em estratégias de vacinação no Brasil. O modelo foi aplicado em três áreas com níveis endêmicos de dengue distintos na cidade de Recife, Pernambuco. Nossos resultados apontam para uma idade ótima de vacinação na rotina de dois anos de idade e para um intervalo de vacinação em campanha entre três e 14 anos.

Economic impact of dengue illness in the Americas.

The growing burden of dengue in endemic countries and outbreaks in previously unaffected countries stress the need to assess the economic impact of this disease. This paper synthesizes existing studies to calculate the economic burden of dengue illness in the Americas from a societal perspective. Major data sources include national case reporting data from 2000 to 2007, prospective cost of illness studies, and analyses quantifying underreporting in national routine surveillance systems. Dengue illness in the Americas was estimated to cost $2.1 billion per year on average (in 2010 US dollars), with a range of $1-4 billion in sensitivity analyses and substantial year to year variation. The results highlight the substantial economic burden from dengue in the Americas. The burden for dengue exceeds that from other viral illnesses, such as human papillomavirus (HPV) or rotavirus. Because this study does not include some components (e.g., vector control), it may still underestimate total economic consequences of dengue.

Universal vaccination of children against hepatitis a in Chile: a cost-effectiveness study / La vacunación infantil universal contra la hepatitis a en Chile: análisis de la relación costo-efectividad

OBJECTIVE: To evaluate the healthcare and economic impact of routine hepatitis A vaccination of toddlers in Chile. METHODS: We used a dynamic model of hepatitis A infection to evaluate the impact of a two-dose vaccination program, administered at ages 12 and 18 months. The model incorporated the changing epidemiology of hepatitis A in Chile and the development of vaccine-induced herd immunity. Our analysis was conducted from the public payer perspective, and an estimation of the societal perspective was performed. Costs are expressed in 2005 U.S. dollars. RESULTS: Vaccination of toddlers rapidly reduced the healthcare burden of hepatitis A. In the base case (95 percent vaccination coverage, 100-year time horizon, 1 percent annual decrease in force of infection), the average number of infections fell by 76.6 percent annually, and associated deaths fell by 59.7 percent. Even at 50 percent coverage, the program reduced infection rates substantially. Routine vaccination of toddlers had economic as well as health benefits, saving $4 984 per life-year gained (base case scenario). The program became cost saving after 6 years, and its overall cost-effectiveness per life-year gained was largely unaffected by changes in disease-related costs, herd immunity, coverage rate, and annual decrease in force of infection. CONCLUSIONS: Routine vaccination of toddlers will reduce the rates of symptomatic hepatitis A and associated mortality. The two-dose schedule evaluated here will be less expensive than disease-related costs in the absence of vaccination from the sixth year of its implementation. These findings support the establishment of a routine vaccination program for toddlers in Chile.

OBJETIVO: Evaluar el impacto sanitario y económico de la vacunación sistemática de infantes contra la hepatitis A en Chile. MÉTODOS: Se empleó un modelo dinámico de hepatitis A para evaluar el impacto de un programa de vacunación de dos dosis administradas a los 12 y 18 meses. El modelo incorporó la epidemiología cambiante de la hepatitis A en Chile y la aparición de la inmunidad de grupo inducida por la vacuna. El análisis se realizó desde la perspectiva del financiador público y se hizo un estimado desde la perspectiva de la sociedad. Los costos se expresaron en dólares estadounidenses del año 2005. RESULTADOS: La vacunación de los infantes redujo rápidamente la carga de la hepatitis A para los servicios de salud. En la variante de base (cobertura de la vacunación: 95 por ciento; horizonte temporal: 100 años; reducción anual de la virulencia de la infección: 1 por ciento), el número promedio de casos se redujo anualmente en 76 por ciento y el número de muertes asociadas disminuyó en 59,7 por ciento. Incluso con una cobertura de vacunación de 50 por ciento, el programa redujo notablemente la tasa de infección. La vacunación sistemática de los infantes presentó beneficios económicos y sanitarios y ahorró US$ 4 984,00 por año de vida ganado (en el escenario base). El programa generó ahorros a partir del sexto año y la efectividad general en función del costo por año de vida ganado no se afectó por cambios en los costos relacionados con la enfermedad, la inmunidad de grupo, la cobertura de vacunación o la reducción anual de la virulencia de la infección. CONCLUSIONES: La vacunación sistemática de los infantes reduciría la tasa de hepatitis A sintomática y la mortalidad asociada. A partir del sexto año del programa, los costos de aplicar el esquema evaluado de dos dosis serían menores que los relacionados con la enfermedad si no se aplicara la vacuna. Estos resultados apoyan la implantación de programas de vacunación sistemática de infantes contra la hepatitis A en Chile.

The economic value of childhood varicella vaccination in France and Germany.

OBJECTIVE: To determine the economic impact of childhood varicella vaccination in France and Germany. METHODS: A common methodology based on the use of a varicella transmission model was used for the two countries. Cost data (2002 per thousand) were derived from two previous studies. The analysis focused on a routine vaccination program for which three different coverage rates (CRs) were considered (90%, 70%, and 45%). Catch-up strategies were also analyzed. A societal perspective including both direct and indirect costs and a third-party payer perspective were considered (Social Security in France and Sickness Funds in Germany). RESULTS: A routine vaccination program has a clear positive impact on varicella-related morbidity in both countries. With a 90% CR, the number of varicella-related deaths was reduced by 87% in Germany and by 84% in France. In addition, with a CR of 90%, routine varicella vaccination induces savings in both countries from both societal (Germany 61%, France 60%) and third-party payer perspectives (Germany 51%, France 6.7%). For lower CRs, routine vaccination remains cost saving from a third-party payer perspective in Germany but not in France, where it is nevertheless cost-effective (cost per life-year gained of 6521 per thousand in the base case with a 45% CR). CONCLUSION: Considering the impact of vaccination on varicella morbidity and costs, a routine varicella vaccination program appears to be cost saving in Germany and France from both a societal and a third-party payer perspective. For France, routine varicella vaccination remains cost-effective in worst cases when a third-party payer perspective is adopted. Catch-up programs provide additional savings.

Varicella vaccination in Italy : an economic evaluation of different scenarios.

AIM: To determine the economic impact (cost-benefit analysis) of childhood varicella vaccination, with the Oka/Merck varicella zoster virus vaccine live (Varivax) in Italy. METHODS: This analysis is based on an epidemiological model of varicella zoster virus (VZV) dynamics adapted to the Italian situation. Cost data (Euro, 2002 values) were collected through a literature review. Several vaccination scenarios were analysed: (i) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) without any catch-up programme; (ii) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) completed by a catch-up programme for 6-year-old children over the first 5 years of vaccine marketing; and (iii) routine vaccination programme for children aged 1-2 years with different levels of vaccination coverage (90%, 70% and 45%) completed by a catch-up programme during the first year of vaccine marketing for children aged 2-11 years. PERSPECTIVES: A societal perspective, including both direct and indirect costs, and a health-system perspective, limited to costs supported by Italian Health Authorities, were considered. RESULTS: A routine vaccination programme has a clearly positive impact on chickenpox morbidity. Respectively, 68% and 57% of chickenpox-related hospitalisations and deaths could be prevented with a 90% coverage rate. With vaccination costs being more than offset by a reduction in chickenpox treatment costs in the base case, such a programme could also induce savings from both a societal and a health-system perspective (40% and 12% savings, respectively for a 90% coverage rate). A lower coverage rate reduces cost savings, but there is still a 9% decrease in overall societal costs for a 45% coverage rate. Although the reduction in total societal costs was robust to the sensitivity analyses performed, a slight uncertainty remains regarding cost reduction from a health-system perspective. However, in this latter perspective, even in the worst-case scenario of the sensitivity analysis, routine vaccination programmes may be cost effective, the worst-case scenario for cost parameters leading to cost per life-year gained of Euro2853. Catch-up programmes combined with routine vaccination should lead to further cost reductions from a societal perspective: 15% for a massive catch-up during the first year of vaccine marketing compared with toddlers' vaccination alone, and 11% for a catch-up focused on 6-year-old children for a period of 5 years. However, the impact of catch-up programmes on the costs from an Italian health-system perspective remains close to zero (+/-1%). CONCLUSION: This model suggests, with its underlying assumptions and data, that routine ZVZ vaccination may be cost saving from both a societal and a health system perspective in the base case. In the worst-case scenario of the sensitivity analysis, vaccination remains cost effective.