The Health Burden of Invasive Meningococcal Disease: A Systematic Review.

OF KEY POINTS: Although relatively rare, invasive meningococcal disease continues to be a health concern, especially in young children. This systematic review clearly delineates both the near- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. BACKGROUND: Although rare, invasive meningococcal disease (IMD) continues to be a health concern in high-income countries because of its severe morbidity and relatively high case fatality rate, especially in young children. However, studies measuring sequelae of IMD across the spectrum of invasive syndromes have not been systematically reviewed. We conducted a systematic review of sequelae attributable to IMD and quality of life (QoL) in IMD survivors in high-income countries. METHODS: We searched Medline, Embase, and HealthSTAR for primary studies that assessed sequelae or QoL in individuals of any age with and without IMD. Two independent reviewers screened articles, abstracted data, and performed quality appraisal. The findings were summarized qualitatively. RESULTS: Of 1884 citations screened, 17 studies were included. The most commonly assessed sequelae were hearing impairment, cognitive impairment, and psychological problems. In general, children with IMD had a greater incidence of hearing loss and psychological disorders, including attention-deficit/hyperactivity disorder. However, its effects on intelligence in children remain unclear. No statistical differences in overall cognitive function in adults were reported. The odds of death were significantly increased with IMD at hospital discharge and up to 30 years after disease. Lower overall QoL was observed in those who had IMD versus controls. CONCLUSIONS: The results of this systematic review delineate both the short- and long-term morbidities that can occur after, and persist beyond, the period of acute illness. A better understanding of the full spectrum of IMD sequelae is critical for assessing the burden of IMD and supporting healthcare planning and decision making in light of new vaccines.

Economic evaluation of meningococcal serogroup B childhood vaccination in Ontario, Canada.

OBJECTIVE: Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective. METHODS: A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n=150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%. RESULTS: A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine-associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust. CONCLUSIONS: An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions.

Economic evaluations of hepatitis A vaccination in middle-income countries.

Economic evaluations of hepatitis A vaccination are important to assist national and international policy makers in different jurisdictions on making effective decisions. Up to now, a comprehensive review of the potential health and economic benefits on hepatitis A vaccination in middle-income countries (MICs) has not been performed yet. In this study, we reviewed the literature on the cost-effectiveness of hepatitis A vaccination in MICs. Most of the studies confirmed that hepatitis A vaccination was cost effective or even cost saving under certain conditions. We found that vaccine price, medical costs, incidence and discount rate were the most influential parameters on the sensitivity analyses. Vaccine price has been shown as a barrier for MICs in implementing universal vaccination of hepatitis A. Given their relatively limited financial resources, implementation of single-dose vaccination could be considered. Despite our findings, we argue that further economic evaluations in MICs are still required in the near future.

Cost-effectiveness of rotavirus immunization in Indonesia: taking breastfeeding patterns into account.

OBJECTIVE: This study aims to assess the cost-effectiveness of rotavirus immunization in Indonesia, taking breastfeeding patterns explicitly into account. METHOD: An age-structured cohort model was developed for the 2011 Indonesia birth cohort. Next, we compared two strategies, the current situation without rotavirus immunization versus the alternative of a national immunization program. The model applies a 5 year time horizon, with 1 monthly analytical cycles for children less than 1 year of age and annually thereafter. Three scenarios were compared to the base case reflecting the actual distribution over the different breastfeeding modes as present in Indonesia; i.e., the population under 2 years old with (i) 100% exclusive breastfeeding, (ii) 100% partial breastfeeding and (iii) 100% no breastfeeding. Monte Carlo simulations were used to examine the economic acceptability and affordability of the rotavirus vaccination. RESULTS: Rotavirus immunization would effectively reduce severe cases of rotavirus during the first 5 years of life of a child. Under the market vaccine price the total yearly vaccine cost would amount to US$ 65 million. The incremental cost per quality-adjusted-life-year (QALY) in the base case was US$ 174 from the societal perspective. Obviously, it was much lower than the 2011 Indonesian Gross Domestic Product (GDP) per capita of US$ 3495. Affordability results showed that at the Global Alliance for Vaccines and Immunization (GAVI)-subsidized vaccine price, rotavirus vaccination could be affordable for the Indonesian health system. Increased uptake of breastfeeding might slightly reduce cost-effectiveness results. CONCLUSION: Rotavirus immunization in Indonesia would be a highly cost-effective health intervention even under the market vaccine price. The results illustrate that rotavirus immunization would greatly reduce the burden of disease due to rotavirus infection. Even within increased uptake of breastfeeding, cost-effectiveness remains favorable.

An update of "Cost-effectiveness of rotavirus vaccination in the Netherlands: the results of a Consensus Rotavirus Vaccine model".

BACKGROUND: To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011. METHODS: The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated. RESULTS: When updated data was used, routine infant rotavirus vaccination in the Netherlands would potentially become an even more cost-effective strategy than previously estimated with the incremental cost per QALY at only €3,000-4,000. Break-even total vaccination costs were indicated at €92-122, depending on the applied threshold. CONCLUSIONS: We concluded that the results on potentially favourable cost-effectiveness in the previous study remained valid, however, the new data suggested that previous results might represent an underestimation of the economic attractiveness of rotavirus vaccination.

A review of the literature on the economics of vaccination against TB.

The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

Health economics of rotavirus immunization in Vietnam: potentials for favorable cost-effectiveness in developing countries.

INTRODUCTION: Rotavirus is the most common cause of severe diarrhoea worldwide. Vietnam is situated in the region of high rotavirus infection incidence and eligible for financial support to introduce rotavirus vaccines into the Expanded Program of Immunization (EPI) from the GAVI. This study was designed to assess the cost-effectiveness of rotavirus immunization in Vietnam, explicitly the use of Rotateq(®) and to assess the affordability of implementing universal rotavirus immunization based on GAVI-subsidized vaccine price in the context of Vietnamese healthcare system for the next 5 years. METHODOLOGY: An age-structured cohort model was developed for the 2009 birth cohort in Vietnam. Two strategies were compared: one being the current situation without vaccination, and the other being mass universal rotavirus vaccination. The time horizon of the model was 5 years with time cycles of 1 month for children less than 1 year of age and annual analysis thereafter. Outcomes included mild, moderate, severe cases and death. Multiple outcomes per rotavirus infection are possible in the model. Monte Carlo simulations were used to examine the acceptability and affordability of the rotavirus vaccination. All costs were expressed in 2009 US$. RESULTS: Rotavirus vaccination would not completely protect young children against rotavirus infection due to partial nature of vaccine immunity, however, would effectively reduce severe cases of rotavirus by roughly 55% during the first 5 years of life. Under GAVI-subsidized vaccine price (US$ 0.3/dose), the vaccine cost would amount to US$ 5.5 million per annum for 3-dose of the Rotateq(®) vaccine. In the base-case, the incremental cost per quality-adjusted-life-year (QALY) was US$ 665 from the health system perspective, much lower than per-capita GDP of ∼US$ 1150 in 2009. Affordability results showed that at the GAVI-subsidized vaccine price, rotavirus vaccination could be affordable for Vietnamese health system. CONCLUSION: Rotavirus vaccination in Vietnam would be a cost-effective health intervention. Vaccination only becomes affordable if the country receives GAVI's financial support due to the current high market vaccine price. Given the high mortality rate of under-five-year children, the results showed that rotavirus immunization is the "best hope" for prevention of rotavirus-related diarrhoeal disease in Vietnam. In the next five years, Vietnam is definitely in debt to financial support from international organizations in implementing rotavirus immunization. It is recommended that new rotavirus vaccine candidates be developed at cheaper price to speed up the introduction of rotavirus immunization in the developing world in general.

Cost of Illness of Chronic Hepatitis B Infection in Vietnam.

OBJECTIVES: To estimate the total financial burden of chronic hepatitis B virus (HBV) infection for Vietnam by quantifying the direct medical, the direct nonmedical, and indirect costs among patients with various stages of chronic HBV infection. METHODS: Direct medical cost data were retrieved retrospectively from medical histories of inpatients and outpatients in 2008 from a large referral hospital in Hanoi, Vietnam. Direct nonmedical and indirect costs data were obtained from face-to-face interviews of outpatients from the same hospital. The treatment cost per patient per chronic HBV infection stage was multiplied by the total estimated patients in Vietnam to get the total cost of illness for the nation. RESULTS: Nationally, the total cost attributable to chronic HBV infection and its complications in 2008 was estimated to be approximately US $4.4 billion, with the direct medical cost accounting for about 70% of that estimate. The cost of antivirals was the major cost driver in treating chronic HBV infection. The per-patient total annual direct medical cost increased with the severity of the disease, with the estimated costs for chronic HBV infection and hepatocellular carcinoma as US $450.35 and US $1883.05, respectively. When compared with the 2008 per-capita gross domestic product of ∼US $1024, the financial burden of treating chronic HBV infection is very high in Vietnam. CONCLUSIONS: This study confirmed that chronic HBV infection poses a significant financial burden for the average patient and that lacking treatment would become a social issue in Vietnam. Although HBV vaccination has been universally implemented, more health care investment and the greater availability of affordable medications are still needed to attain equity in proper treatment for patients with HBV infection.

Cost-Effectiveness Analysis of Hepatitis B Immunization in Vietnam: Application of Cost-Effectiveness Affordability Curves in Health Care Decision Making.

OBJECTIVES: To perform a cost-effectiveness analysis and to identify the cost-effectiveness affordability levels for a newborn universal vaccination program against hepatitis B virus (HBV) in Vietnam. METHODS: By using a Markov model, we simulated a Vietnamese birth cohort using 1,639,000 newborns in 2002 and estimated the incremental cost-effectiveness ratios for quality-adjusted life-year gained following universal newborn HBV vaccination. Two types of analyses were performed, including and excluding expenditures on the treatment of chronic hepatitis B and its complications. We used Monte Carlo simulations to examine cost-effectiveness acceptability and affordability from the payer's perspective and constructed a cost-effectiveness affordability curve to assess the costs and health effects of the program. RESULTS: In the base-case analysis, newborn universal HBV vaccination reduced the carrier rate by 58% at a cost of US $42 per carrier averted. From the payer's perspective, incremental cost-effectiveness ratio per quality-adjusted life-year gained was US $3.77, much lower than the 2002 per-capita gross domestic product of US $440. Vaccination could potentially be affordable starting at a US $2.1 million budget. At the cost-effectiveness threshold of US $3.77 per quality-adjusted life-year and an annual budget of US $5.9 million, the probability that vaccination will be both cost-effective and affordable was 21%. CONCLUSIONS: Universal newborn HBV vaccination is highly cost-effective in Vietnam. In low-income, high-endemic countries, where funds are limited and the economic results are uncertain, our findings on the cost-effectiveness affordability options may assist decision makers in proper health investments.

Economic evaluations of rotavirus immunization for developing countries: a review of the literature.

Diarrhea is a leading cause of mortality for children under 5 years of age, and rotavirus is identified as the main cause of severe diarrhea worldwide. Since 2006, two rotavirus vaccines, Rotarix and Rotateq, have been available in the market. These vaccines have proved to have high efficacy in developed countries. Clinical trials are being undertaken in Asia and Africa, and early clinical results found that the vaccine significantly reduces severe diarrhea episodes due to rotavirus (48.3% for Asia and 30.2% for Africa). The WHO recommended that rotavirus immunization be included in all national immunization programs. Based on WHO's recommendations, the Global Alliance for Vaccines and Immunization decided to provide financial support for rotavirus immunization in the developing world. In this article, we attempted to ascertain the cost-effectiveness of universal rotavirus immunization in developing countries. After an extensive literature search, we identified and evaluated 15 cost-effectiveness studies conducted in the developing world. The results from these studies showed that rotavirus immunization is a cost-effective strategy and one of the best interventions to prevent rotavirus-related diarrheal disease. However, rotavirus vaccines are expensive and the vaccine price appears to be the most challenging and crucial factor for decision-makers regarding whether to introduce this vaccine into developing countries' immunization schedules. All the studies concluded that rotavirus immunization is cost effective but may not be affordable for the developing world at present. Developing countries will definitely rely on financial support from international organizations to introduce rotavirus vaccination. It is recommended that more research on cost-effective rotavirus immunization with updated data be conducted and new rotavirus vaccine candidates be developed at a cheaper price to speed up the introduction of rotavirus immunization to the developing world.

Results of a retrospective database analysis of drug utilization and costs for treatment of chronic hepatitis B virus infection in the northern Netherlands between 2000 and 2006.

OBJECTIVES: The main aims of this work were to describe patterns of medication use in the treatment of chronic hepatitis B virus (HBV) infection in patients in the northern part of the Netherlands and to compare these practices with established guidelines. In addition, the duration of use and the costs of these treatments were investigated. METHODS: We selected subjects from the University of Groningen's IADB.nl database; by 2006, the database provided information about drug utilization from 55 community pharmacies in the northern Netherlands and included a population of 528,911 individuals, of which 49% were male. Eligible subjects had received >or=1 prescription for drugs used to treat chronic HBV infection (ie, lamivudine, pegylated interferon-alpha2a, pegylated interferon-alpha2b, adefovir, tenofovir, and entecavir) between the years 2000 and 2006. The annual prevalence and cumulative incidence of HBV treatment per 1000 people covered in the database were calculated and stratified by sex. Kaplan-Meier survival analysis was used to analyze the duration of use. Drug costs in the treatment were calculated for all patients or per patient, and by drugs used per subperiod (2000-2003 and 2004-2006). Treatments for hepatitis C virus and HIV were excluded from the analyses. RESULTS: From the database, we identified 59 patients (46 male, 13 female), aged 25 to 60 years, who received >or=1 prescription for a medication to treat chronic HBV infection between 2000 and 2006. The overall prevalence of people using chronic treatments for HBV was between 0.03 and 0.06 per 1000 during the years of the study. The cumulative incidence of treatment was approximately 0.01 per 1000 per year (ranging from a high of 0.021 in 2000 to a low of 0.009 in 2006). When stratified by sex, there were more male than female subjects who received medications for HBV. Lamivudine was the most commonly prescribed drug, followed by adefovir and pegylated interferon-alpha2b. In 2000 and 2001, lamivudine was the only medication prescribed for the treatment of chronic HBV. From 2002 to 2006, the prescription rate for lamivudine dropped from 90% to 61%. In contrast, the prescription rate for adefovir increased from 4% in 2003 to 36% in 2006. Pegylated interferon-alpha2b remained stable at 8% to 11% between 2002 and 2006. Twenty-five percent of patients had stopped HBV treatment by the end of 1 year. Fifty-five percent had stopped by 3 years. Seventy-seven percent of patients received their first HBV prescription from a medical specialist. Per patient, the cost of drug therapy was highest with adefovir. From 2004 to 2006, the cost of adefovir therapy accounted for 49% of total expenditures for the treatment of chronic HBV (equivalent to euro128,037; as of January 2010, euro1.00 = US $1.43). The second and third most expensive drugs were tenofovir and pegylated interferon-alpha2b (euro33,700 and euro33,250, respectively). Costs incurred per patient increased over the years of the study period. CONCLUSIONS: The overall prevalence and cumulative incidence of patients with treatments for chronic HBV were relatively low in the northern part of the Netherlands between 2000 and 2006. The prescribing and utilization patterns were in agreement with international and Dutch guidelines. Given the low numbers of prescriptions, the costs also remained relatively low.

Economic evaluations of hepatitis B vaccination for developing countries.

Economic evaluations, in particular cost-effectiveness, are important determinants for policy makers and stakeholders involved in decision-making for health interventions. Up until now, most evaluations of cost-effectiveness of hepatitis B vaccination have been performed in developed countries. Appropriate health-economic studies on this topic specifically targeted at the developing world are essential in order to justify adding another vaccine into the existing Expanded Program on Immunization in these countries. We present a systematic review of economic evaluations of vaccination against HBV for developing and less-developed countries. Vaccine price, the discount rate, incidence and prevalence of HBV infection were found to be major drivers of cost-effectiveness. Data accuracy and reliability were also major issues, with major potentials for improvement in studies of these countries. The choice between monovalent or combination vaccines (diphteria, tetanus and polio-hepatitis B) poses new challenges to cost-effectiveness analysis. It is concluded that for many developing countries implementation of universal immunization against HBV to reduce the level of endemicity of hepatitis B is an appropriate strategy, and probably cost effective in many settings. Given their limited financial resources, developing countries should properly plan how to achieve this. Further country-specific economic evaluations and related gathering of high-quality data must be conducted in developing countries in order to raise both public awareness of the effectiveness and economic attractiveness of universal immunization against HBV.