The impact of assumptions regarding vaccine-induced immunity on the public health and cost-effectiveness of hepatitis A vaccination: Is one dose sufficient?

Hepatitis A vaccination stimulates memory cells to produce an anamnestic response. In this study, we used a mathematical model to examine how long-term immune memory might convey additional protection against clinical/icteric infections. Dynamic and decision models were used to estimate the expected number of cases, and the costs and quality-adjusted life-years (QALYs), respectively. Several scenarios were explored by assuming: (1) varying duration of vaccine-induced immune memory, (2) and/or varying levels of vaccine-induced immune memory protection (IMP), (3) and/or varying levels of infectiousness in vaccinated individuals with IMP. The base case analysis assumed a time horizon of 25 y (2012 - 2036), with additional analyses over 50 and 75 y. The analyses were conducted in the Mexican public health system perspective. In the base case that assumed no vaccine-induced IMP, the 2-dose hepatitis A vaccination strategy was cost-effective compared with the 1-dose strategy over the 3 time horizons. However, it was not cost-effective if we assumed additional IMP durations of at least 10 y in the 25-y horizon. In the 50- and 75-y horizons, the 2-dose strategy was always cost-effective, except when 100% reduction in the probability of icteric Infections, 75% reduction in infectiousness, and mean durations of IMP of at least 50 y were assumed. This analysis indicates that routine vaccination of toddlers against hepatitis A virus would be cost-effective in Mexico using a single-dose vaccination strategy. However, the cost-effectiveness of a second dose depends on the assumptions of additional protection by IMP and the time horizon over which the analysis is performed.

Health economic assessment of universal immunization of toddlers against Hepatitis A Virus (HAV) in Mexico.

Hepatitis A virus (HAV) has shifted from high to intermediate endemicity in Mexico, which may increase the risk of clinically significant HAV infections in older children, adolescents and adults. The objective of this study was to evaluate the cost-utility of single-dose or 2-dose universal infant HAV vaccination strategy in Mexico, compared with no vaccination. A previously published dynamic model estimated the expected number of HAV cases with each strategy, and a decision model was used to estimate the costs and quality-adjusted life-years (QALYs) expected with each strategy. The time horizon was 25 years (2012-2036) and the base case analysis was conducted from the perspective of the Mexican public health system. Costs and QALYs after the first year were discounted at 5% annually. Input data were taken from national databases and published sources where available. The single-dose HAV vaccination strategy had an incremental cost-utility ratio (ICUR) of Mexican peso (MXN) 2,270 per QALY gained, compared with no vaccination. The two-dose strategy had an ICUR of MXN 14,961/QALY compared with no vaccination, and an ICUR of MXN 78,280/QALY compared with the single-dose strategy. The estimated ICURs were below the threshold of 1 x Mexican gross domestic product per capita. When indirect costs were included (societal perspective), the single-dose HAV vaccination strategy would be expected to improve health outcomes and to be cost-saving. This analysis indicates that routine vaccination of toddlers against HAV would be cost-effective in Mexico using either a single-dose or a 2-dose vaccination strategy. GSK study identifier: HO-12-12877.

Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

BACKGROUND: Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. METHODS: A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. RESULTS: Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. CONCLUSION: After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the standard two-dose scheme, can be a good alternative for future vaccination policies in other countries where HA is endemic.

Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: regional analyses according to the endemic context.

OBJECTIVE: To conduct a cost-effectiveness analysis of a universal childhood hepatitis A vaccination program in Brazil. METHODS: An age and time-dependent dynamic model was developed to estimate the incidence of hepatitis A for 24 years. The analysis was run separately according to the pattern of regional endemicity, one for South+Southeast (low endemicity) and one for the North+Northeast+Midwest (intermediate endemicity). The decision analysis model compared universal childhood vaccination with current program of vaccinating high risk individuals. Epidemiologic and cost estimates were based on data from a nationwide seroprevalence survey of viral hepatitis, primary data collection, National Health Information Systems and literature. The analysis was conducted from both the health system and societal perspectives. Costs are expressed in 2008 Brazilian currency (Real). RESULTS: A universal immunization program would have a significant impact on disease epidemiology in all regions, resulting in 64% reduction in the number of cases of icteric hepatitis, 59% reduction in deaths for the disease and a 62% decrease of life years lost, in a national perspective. With a vaccine price of R$16.89 (US$7.23) per dose, vaccination against hepatitis A was a cost-saving strategy in the low and intermediate endemicity regions and in Brazil as a whole from both health system and society perspective. Results were most sensitive to the frequency of icteric hepatitis, ambulatory care and vaccine costs. CONCLUSIONS: Universal childhood vaccination program against hepatitis A could be a cost-saving strategy in all regions of Brazil. These results are useful for the Brazilian government for vaccine related decisions and for monitoring population impact if the vaccine is included in the National Immunization Program.

Hepatitis A: the costs and benefits of the disease prevention by vaccine, Paraná, Brazil

This study evaluated the epidemiological behavior of the hepatitis A in Paraná state and compared the costs of the disease and the vaccination. This is an epidemiological descriptive study including a pharmacoeconomy analysis. We collected information in the national database reported cases (SINAN), in the mortality information system (SIM) and in the hospital information system (AIH) among 2000/2003 (Paraná State Public Health Department). We estimated the probability of one cohort of children to acquire hepatitis A during their lifetime and the costs with their treatment. We compared those costs with the cost of vaccinating the children. 14,682 hepatitis A cases were registered during the period studied, and 12,102 (82.4 percent) occurred in the 0-15 years-old age group. The annual incidence in the general population was 37.5/100,000. We observed 20 deaths caused by this disease; 7 of those occurred by liver failure. The estimated costs with the disease included the hospital costs, liver transplantation, liver failure treatment, and laboratory tests were high. The price of the vaccine is 10 USD/dose. Two doses are necessary to get the protection. The results showed a positive cost - benefit relation when we vaccinate children. We save 2.26 USD in treatment for each dollar invested in the vaccine. Paraná record high number of hepatitis A cases each year. We confirmed the positive cost - benefit relation when we vaccinate children against hepatitis A, reducing suffering, hospitalization, death and social costs. Vaccination against hepatitis A should be recommended in the routine of immunization program in Paraná state.

Should Brazilian patients with chronic hepatitis C virus infection be vaccinated against hepatitis A virus?

BACKGROUND AND AIM: Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with hepatitis C virus (HCV) infection. The aim of this study was to investigate the presence of serological and molecular HAV markers in a population of HCV-infected patients in order to determine a cost-effective strategy to vaccinate against HAV. METHODS: The presence of total and immunoglobulin (Ig)M anti-HAV antibodies was investigated in 399 patients (median age, 50 years; range, 4-81) referred to the Public Health Central Laboratory of Pernambuco State who tested positive for anti-HCV antibodies and HCV RNA. HAV RNA was investigated by reverse transcription-nested polymerase chain reaction in these patients. RESULTS: Three hundred and eighty-four (96%) patients were positive for anti-HAV total and negative for IgM anti-HAV antibodies (immune patients). Three patients had IgM (and total) anti-HAV antibodies, showing an acute infection, and two of them had HAV RNA detected in serum samples. HAV RNA was also found in another patient in the absence of detectable anti-HAV antibodies. By nucleotide sequencing, it was demonstrated that the HAV isolates infecting these patients belonged to subgenotype 1B. CONCLUSION: This study provides valuable new data on anti-HAV prevalence among HCV carriers in Brazil. In the present study, we found a high proportion of patients with anti-HAV positivity, indicating that anti-HAV testing of HCV-infected patients is a cost-effective strategy and should be carried out before vaccination against HAV in these patients, particularly in regions such as our geographical area with high total anti-HAV prevalence.

Hepatitis A: the costs and benefits of the disease prevention by vaccine, Paraná, Brazil.

This study evaluated the epidemiological behavior of the hepatitis A in Paraná state and compared the costs of the disease and the vaccination. This is an epidemiological descriptive study including a pharmacoeconomy analysis. We collected information in the national database reported cases (SINAN), in the mortality information system (SIM) and in the hospital information system (AIH) among 2000/2003 (Paraná State Public Health Department). We estimated the probability of one cohort of children to acquire hepatitis A during their lifetime and the costs with their treatment. We compared those costs with the cost of vaccinating the children. 14,682 hepatitis A cases were registered during the period studied, and 12,102 (82.4%) occurred in the 0-15 years-old age group. The annual incidence in the general population was 37.5/100,000. We observed 20 deaths caused by this disease; 7 of those occurred by liver failure. The estimated costs with the disease included the hospital costs, liver transplantation, liver failure treatment, and laboratory tests were high. The price of the vaccine is 10 USD/dose. Two doses are necessary to get the protection. The results showed a positive cost - benefit relation when we vaccinate children. We save 2.26 USD in treatment for each dollar invested in the vaccine. Paraná record high number of hepatitis A cases each year. We confirmed the positive cost - benefit relation when we vaccinate children against hepatitis A, reducing suffering, hospitalization, death and social costs. Vaccination against hepatitis A should be recommended in the routine of immunization program in Paraná state.

The need for an evidence-based decision-making process with regard to control of hepatitis A.

Universal hepatitis A (HA) vaccination was implemented by the Argentinean Ministry of Health in June 2005 with a single dose at age 12 months. The decision was made taking into account the following factors. (1) Disease burden: The incidence rate for the disease increased from 2003 to 2004; the northern and western regions of the country were the most affected. Sero-prevalence data for children 1-15 years old was 54% for the whole country, with differences per region and age. From May 1982 to September 2002, 210 patients were recruited with acute hepatic failure; HA was the aetiology in 61% of them. (2) Cost-effectiveness: Compared with no vaccination, the one-dose schedule would save US$15.3 millions, with regional variations. (3) Vaccine features: Immunization with one-dose schedule HA vaccine confers good immunogenicity and effectiveness. (4) Programmatic feasibility: The National Immunizations Program has appropriate distribution system for vaccines, with adequate cold chain. (5) Social acceptance and political compromise: The population largely accepts HA vaccination and the national authorities should be committed to providing it regularly. The main global issue is that hepatitis A virus infection remains the most commonly reported vaccine-preventable disease in many parts of the world despite the availability of vaccines.

Universal vaccination of children against hepatitis A in Chile: a cost-effectiveness study.

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% vaccination coverage, 100-year time horizon, 1% annual decrease in force of infection), the average number of infections fell by 76.6% annually, and associated deaths fell by 59.7%. Even at 50% 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.

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.

Cost-effectiveness of childhood hepatitis A vaccination in Argentina: a second dose is warranted.

OBJECTIVES: To investigate the cost-effectiveness of childhood vaccination against hepatitis A in the five geographic regions of Argentina, and to determine whether adding a second dose to the current one-dose schedule would provide health gains justifying its added cost. METHODS: A Markov model was used to consider four immunization options for the 2005 birth cohort: (1) no vaccination; (2) vaccination at 12 months of age, (3) vaccinations at 12 and 72 months of age; or (4) vaccinations at 12 and 18 months of age. Hepatitis A costs and consequences were predicted over 50 years. The cost-effectiveness of first and second vaccine doses was assessed through a range of vaccine prices and assumptions regarding the duration of vaccine protection. Costs and health gains (measured in quality-adjusted life years) were adjusted to present values using a 3% annual discount rate. RESULTS: The one-dose vaccination policy is predicted to reduce each birth cohort member's 50-year probability of overt hepatitis A from 7.2% to 4.1%. A second dose would reduce the probability to between 2.0% and 2.2%. Vaccination at 12 months of age, at 12 and 72 months, or at 12 and 18 months would reduce cases among personal contacts by 82%, 87%, and 92%, respectively. The first vaccine dose would meet accepted standards of cost-effectiveness in each region, and reduce costs in the Northeast, Central, and South regions. Adding a second dose at age 18 months would be cost-effective in each region, and further reduce costs in the Cuyo region. If the duration of protection with one dose is less than anticipated, the second dose would be more cost-effective. CONCLUSIONS: Greater health gains are derived from the first than second hepatitis A vaccine dose. However, this analysis supports the cost-effectiveness of providing both first and second doses to Argentina's children.

Cost-effectiveness of childhood hepatitis A vaccination in Argentina: a second dose is warranted / Efectividad en función del costo de la vacunación infantil contra la hepatitis A en Argentina: se justifica una segunda dosis

OBJECTIVES: To investigate the cost-effectiveness of childhood vaccination against hepatitis A in the five geographic regions of Argentina, and to determine whether adding a second dose to the current one-dose schedule would provide health gains justifying its added cost. METHODS: A Markov model was used to consider four immunization options for the 2005 birth cohort: (1) no vaccination; (2) vaccination at 12 months of age, (3) vaccinations at 12 and 72 months of age; or (4) vaccinations at 12 and 18 months of age. Hepatitis A costs and consequences were predicted over 50 years. The cost-effectiveness of first and second vaccine doses was assessed through a range of vaccine prices and assumptions regarding the duration of vaccine protection. Costs and health gains (measured in quality-adjusted life years) were adjusted to present values using a 3 percent annual discount rate. RESULTS: The one-dose vaccination policy is predicted to reduce each birth cohort member's 50-year probability of overt hepatitis A from 7.2 percent to 4.1 percent. A second dose would reduce the probability to between 2.0 percent and 2.2 percent. Vaccination at 12 months of age, at 12 and 72 months, or at 12 and 18 months would reduce cases among personal contacts by 82 percent, 87 percent, and 92 percent, respectively. The first vaccine dose would meet accepted standards of cost-effectiveness in each region, and reduce costs in the Northeast, Central, and South regions. Adding a second dose at age 18 months would be cost-effective in each region, and further reduce costs in the Cuyo region. If the duration of protection with one dose is less than anticipated, the second dose would be more cost-effective. CONCLUSIONS: Greater health gains are derived from the first than second hepatitis A vaccine dose. However, this analysis supports the cost-effectiveness of providing both first and second doses to Argentina's children.

OBJETIVOS: Investigar la efectividad en función del costo de la vacunación infantil contra la hepatitis A en las cinco regiones de Argentina y determinar si la adición de una segunda dosis al esquema actual de una dosis aumentaría los beneficios a la salud y si estos justificarían el costo adicional. MÉTODOS: Se empleó el modelo de Markov para valorar cuatro opciones de vacunación para la cohorte nacida en el año 2005: 1) no vacunar; 2) vacunar a los 12 meses de edad; 3) vacunar a los 12 y a los 72 meses; y 4) vacunar a los 12 y a los 18 meses de edad. Se estimaron el costo y las consecuencias de la enfermedad a 50 años. La efectividad en función del costo de la primera y la segunda dosis de la vacuna se calculó a partir de varios precios de la vacuna e hipótesis acerca de la duración de la protección. Los costos y los beneficios para la salud (medidos en años de vida ajustados por la calidad de vida) se ajustaron por los valores actuales utilizando una tasa de descuento anual de 3 por ciento. RESULTADOS: Se estima que la política de vacunación con una dosis reduciría la probabilidad de cada miembro de la cohorte de padecer hepatitis A sintomática en 50 años de 7,2 por ciento a 4,1 por ciento. Una segunda dosis reduciría esa probabilidad a 2,0 por ciento-2,2 por ciento. La vacunación a los 12 meses de edad, a los 12 y a los 72 meses, o a los 12 y a los 18 meses reduciría el número de casos entre los contactos personales en 82 por ciento, 87 por ciento y 92 por ciento, respectivamente. La primera dosis de la vacuna satisfaría los estándares aceptados de efectividad en función del costo en todas las regiones del país y reduciría los costos en las regiones Nordeste, Central y Sur. La aplicación de una segunda dosis a los 18 meses resultaría efectiva en función del costo en todas las regiones y reduciría adicionalmente los costos en la región de Cuyo. Si la duración de la protección con una dosis fuera menor de la esperada, la segunda dosis tendría una mayor efectividad en función del costo. Conclusiones. La primera dosis de la vacuna contra la hepatitis A genera mayores beneficios a la salud que la segunda. Sin embargo, este análisis sustenta la efectividad en función del costo de aplicar ambas dosis a los niños en Argentina.

Cost-effectiveness of universal childhood hepatitis A vaccination in Chile.

Hepatitis A is an important public health problem in Chile. Childhood vaccination has reduced hepatitis A rates in several countries, prompting this evaluation of its cost-effectiveness in Chile. Using a Markov model, we project mass vaccination would reduce hepatitis A cases among birth cohort members and their personal contacts >80%. Vaccination costs of US dollars 5.3-6.4 million would be offset by US dollars 9.2-9.4 million reductions in disease costs. Further, approximately 70 fatal infections would be averted and >4600 quality-adjusted life years would be saved. This analysis supports the cost-effectiveness of universal childhood hepatitis A vaccination in Chile.