Assessment of a school-based mass treatment for soil-transmitted helminth infections in Capiz, the Philippines.

We evaluated the War on Worms in the Western Visayas (WOW-V) school-based mass treatment strategy in Capiz, the Philippines by assessing potential determinants of program acceptance among parents, teachers, and local health and education officials involved. Written surveys were distributed to parents and teachers assessing knowledge, attitudes and practices regarding soil-transmitted helminth (STH) infections. Associations between data were examined using the Fisher's exact test (alpha = 0.05). Descriptive statistics and t-tests were employed to analyze teacher survey results. Local health and education officials participated in key-informant interviews (KIs) to evaluate their attitudes and practices regarding WOW-V; data was qualitatively analyzed and grouped. A strong association was observed between parental consent during the first two rounds of treatment and willingness to do so again. Most parents gave consent for their child to receive treatment at least once and demonstrated a high level of knowledge regarding STH infections. The majority of teachers had positive attitudes toward their role in the program. Many identified lack of training and a fear of side effects as barriers to higher coverage. Lack of funding, program monitoring difficulties and insufficient parental education were identified by local officials as barriers. Proper planning and design is important to achieve high initial consent for program acceptance. The results correlate with studies showing relationships between health education and treatment acceptance. The implementation of health education and monitoring measures has the potential to greatly improve both treatment coverage and program infrastructure.

Cost-effectiveness of adjuvanted versus nonadjuvanted influenza vaccine in adult hemodialysis patients.

BACKGROUND: Currently more than 340,000 individuals are receiving long-term hemodialysis (HD) therapy for end-stage renal disease and therefore are particularly vulnerable to influenza, prone to more severe influenza outcomes, and less likely to achieve seroprotection from standard influenza vaccines. Influenza vaccine adjuvants, chemical or biologic compounds added to a vaccine to boost the elicited immunologic response, may help overcome this problem. STUDY DESIGN: Economic stochastic decision analytic simulation model. SETTING & PARTICIPANTS: US adult HD population. MODEL, PERSPECTIVE, & TIMEFRAME: The model simulated the decision to use either an adjuvanted or nonadjuvanted vaccine, assumed the societal perspective, and represented a single influenza season, or 1 year. INTERVENTION: Adjuvanted influenza vaccine at different adjuvant costs and efficacies. Sensitivity analyses explored the impact of varying influenza clinical attack rate, influenza hospitalization rate, and influenza-related mortality. OUTCOMES: Incremental cost-effectiveness ratio of adjuvanted influenza vaccine (vs nonadjuvanted) with effectiveness measured in quality-adjusted life-years. RESULTS: Adjuvanted influenza vaccine would be cost-effective (incremental cost-effectiveness ratio <$50,000/quality-adjusted life-year) at a $1 adjuvant cost (on top of the standard vaccine cost) when adjuvant efficacy (in overcoming the difference between influenza vaccine response in HD patients and healthy adults) ≥60% and economically dominant (provides both cost savings and health benefits) when the $1 adjuvant's efficacy is 100%. A $2 adjuvant would be cost-effective if adjuvant efficacy was 100%. LIMITATIONS: All models are simplifications of real life and cannot capture all possible factors and outcomes. CONCLUSIONS: Adjuvanted influenza vaccine with adjuvant cost ≤$2 could be a cost-effective strategy in a standard influenza season depending on the potency of the adjuvant.

The impact of human immunodeficiency virus (HIV) co-infection on the economic burden of cutaneous leishmaniasis (CL) in Brazil and potential value of new CL drug treatments.

Convergence of geographic regions endemic for human immunodeficiency virus (HIV) and cutaneous leishmaniasis (CL) raise concerns that HIV co-infection may worsen CL burden, complicating already lengthy and costly CL treatments and highlighting a need for newer therapies. We constructed two Markov decision models to quantify impact of HIV on CL and help establish a target product profile for new CL treatments, accounting for co-infection. The HIV co-infection increased lifetime cost per CL case 11-371 times ($1,349-45,683) that of HIV-negative individuals ($123) and Brazil's CL burden from $1.6-16.0 million to $1.6-65.5 million. A new treatment could be a cost saving at ≤ $254 across several ranges (treatments seeking probabilities, side effect risks, cure rates) and continues to save costs up to $508 across treatment-seeking probabilities with a drug cure rate of ≥ 50%. The HIV co-infection can increase CL burden, suggesting more joint HIV and CL surveillance and control efforts are needed.

Global economic burden of Chagas disease: a computational simulation model.

BACKGROUND: As Chagas disease continues to expand beyond tropical and subtropical zones, a growing need exists to better understand its resulting economic burden to help guide stakeholders such as policy makers, funders, and product developers. We developed a Markov simulation model to estimate the global and regional health and economic burden of Chagas disease from the societal perspective. METHODS: Our Markov model structure had a 1 year cycle length and consisted of five states: acute disease, indeterminate disease, cardiomyopathy with or without congestive heart failure, megaviscera, and death. Major model parameter inputs, including the annual probabilities of transitioning from one state to another, and present case estimates for Chagas disease came from various sources, including WHO and other epidemiological and disease-surveillance-based reports. We calculated annual and lifetime health-care costs and disability-adjusted life-years (DALYs) for individuals, countries, and regions. We used a discount rate of 3% to adjust all costs and DALYs to present-day values. FINDINGS: On average, an infected individual incurs US$474 in health-care costs and 0·51 DALYs annually. Over his or her lifetime, an infected individual accrues an average net present value of $3456 and 3·57 DALYs. Globally, the annual burden is $627·46 million in health-care costs and 806,170 DALYs. The global net present value of currently infected individuals is $24·73 billion in health-care costs and 29,385,250 DALYs. Conversion of this burden into costs results in annual per-person costs of $4660 and lifetime per-person costs of $27,684. Global costs are $7·19 billion per year and $188·80 billion per lifetime. More than 10% of these costs emanate from the USA and Canada, where Chagas disease has not been traditionally endemic. A substantial proportion of the burden emerges from lost productivity from cardiovascular disease-induced early mortality. INTERPRETATION: The economic burden of Chagas disease is similar to or exceeds those of other prominent diseases globally (eg, rotavirus $2·0 billion, cervical cancer $4·7 billion) even in the USA (Lyme disease $2·5 billion), where Chagas disease has not been traditionally endemic, suggesting an economic argument for more attention and efforts towards control of Chagas disease. FUNDING: Bill & Melinda Gates Foundation, the National Institute of General Medical Sciences Models of Infectious Disease Agent Study.

The potential economic value of a cutaneous leishmaniasis vaccine in seven endemic countries in the Americas.

Cutaneous leishmaniasis (CL) and its associated complications, including mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL) have emerged as important neglected tropical diseases in Latin America, especially in areas associated with human migration, conflict, and recent deforestation. Because of the limitations of current chemotherapeutic approaches to CL, MCL, and DCL, several prototype vaccines are in different states of product and clinical development. We constructed and utilized a Markov decision analytic computer model to evaluate the potential economic value of a preventative CL vaccine in seven countries in Latin America: Bolivia, Brazil, Colombia, Ecuador, Mexico, Peru, and Venezuela. The results indicated that even a vaccine with a relatively short duration of protection and modest efficacy could be recommended for use in targeted locations, as it could prevent a substantial number of cases at low-cost and potentially even result in cost savings. If the population in the seven countries were vaccinated using a vaccine that provides at least 10 years of protection, an estimated 41,000-144,784 CL cases could be averted, each at a cost less than the cost of current recommended treatments. Further, even a vaccine providing as little as five years duration of protection with as little as 50% efficacy remains cost-effective compared with chemotherapy; additional scenarios resembling epidemic settings such as the one that occurred in Chaparral, Colombia in 2004 demonstrate important economic benefits.

The Human Hookworm Vaccine.

Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy. The recombinant proteins are formulated on Alhydrogel(®) and are being tested in combination with a synthetic Toll-like receptor 4 agonist. The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut. Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil. The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic. Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases.

The economic value of a visceral leishmaniasis vaccine in Bihar state, India.

Visceral leishmaniasis (VL) is responsible for substantial morbidity and mortality and current available treatments have many limitations. The ability of VL infection to generate life-long immunity offers promise for the development of a VL vaccine. A VL vaccine candidate has recently completed phase I clinical trials. We constructed a computer simulation model to determine the potential economic value of a VL vaccine in the endemic region of Bihar state, India. Results found a potential vaccine to be cost-effective (and in many cases economically dominant, i.e., saving costs and providing health benefits) throughout a wide range of vaccination costs and vaccine efficacies, and VL risks. Overall, our study strongly supports the continued development of a VL vaccine.

Modeling the economic value of a Chagas' disease therapeutic vaccine.

The health burden of Chagas' disease (resulting from Trypanosoma cruzi infection) in Latin America (estimated to outweigh that of malaria by 5-fold and affect 2-6 million people in Mexico alone) has motivated development of therapeutic vaccines to prevent infection progression to severe disease. Our economic model for a Chagas' therapeutic vaccine in Mexico suggests that a vaccine would be highly cost-effective and in many cases economically dominant (providing both cost savings and health benefits) throughout a range of protection durations, severe adverse event risk, and dosing regimens and would be most likely to provide a positive return on investment if the vaccine prevented (rather than delayed) the onset of cardiomyopathy.

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.

From the patient perspective: the economic value of seasonal and H1N1 influenza vaccination.

Although studies have suggested that a patient's perceived cost-benefit of a medical intervention could affect his or her utilization of the intervention, the economic value of influenza vaccine from the patient's perspective remains unclear. Therefore, we developed a stochastic decision analytic computer model representing an adult's decision of whether to get vaccinated. Different scenarios explored the impact of the patient being insured versus uninsured, influenza attack rate, vaccine administration costs and vaccination time costs. Results indicated that the cost of avoiding influenza was fairly low (with one driver being required vaccination time). To encourage vaccination, decision makers may want to focus on ways to reduce this time, such as vaccinating at work, churches, or other normally frequented locations.

The potential economic value of a hookworm vaccine.

Hookworm infection is a significant problem worldwide. As development of hookworm vaccine proceeds, it is essential for vaccine developers and manufacturers, policy makers, and other public health officials to understand the potential costs and benefits of such a vaccine. We developed a decision analytic model to evaluate the cost-effectiveness of introducing a hookworm vaccine into two populations in Brazil: school-age children and non-pregnant women of reproductive age. Results suggest that a vaccine would provide not only cost savings, but potential health benefits to both populations. In fact, the most cost-effective intervention strategy may be to combine vaccine with current drug treatment strategies.

Economic value of dispensing home-based preoperative chlorhexidine bathing cloths to prevent surgical site infection.

OBJECTIVE: To estimate the economic value of dispensing preoperative home-based chlorhexidine bathing cloth kits to orthopedic patients to prevent surgical site infection (SSI). METHODS: A stochastic decision-analytic computer simulation model was developed from the hospital's perspective depicting the decision of whether to dispense the kits preoperatively to orthopedic patients. We varied patient age, cloth cost, SSI-attributable excess length of stay, cost per bed-day, patient compliance with the regimen, and cloth antimicrobial efficacy to determine which variables were the most significant drivers of the model's outcomes. RESULTS: When all other variables remained at baseline and cloth efficacy was at least 50%, patient compliance only had to be half of baseline (baseline mean, 15.3%; range, 8.23%-20.0%) for chlorhexidine cloths to remain the dominant strategy (ie, less costly and providing better health outcomes). When cloth efficacy fell to 10%, 1.5 times the baseline bathing compliance also afforded dominance of the preoperative bath. CONCLUSIONS: The results of our study favor the routine distribution of bathing kits. Even with low patient compliance and cloth efficacy values, distribution of bathing kits is an economically beneficial strategy for the prevention of SSI.

The optimal number of routine vaccines to order at health clinics in low or middle income countries.

In a low or middle income country, determining the correct number of routine vaccines to order at a health clinic can be difficult, especially given the variability in the number of patients arriving, minimal vaccination days and resource (e.g., information technology and refrigerator space) constraints. We developed a spreadsheet model to determine the potential impact of different ordering policies, basing orders on the arrival rates seen in the previous 1, 3, 6, or 12 sessions, or on long-term historical averages (where these might be available) along with various buffer stock levels (range: 5-50%). Experiments varied patient arrival rates (mean range: 1-30 per session), arrival rate distributions (Poisson, Normal, and Uniform) and vaccine vial sizes (range: 1-dose to 10-dose vials). It was found that when the number of doses per vial is small and the expected number of patients is low, the ordering policy has a more significant impact on the ability to meet demand. Using data from more prior sessions to determine arrival rates generally equates to a better ability to meet demand, although the marginal benefit is relatively small after more than 6 sessions are averaged. As expected, the addition of more buffer is helpful in obtaining better performance; however, this advantage also has notable diminishing returns. In general, the long-term demand rate, the vial sizes of the vaccines used and the method of determining the patient arrival rate all have an effect on the ability of a clinic to maximize the demand that is met.

Economic value of dengue vaccine in Thailand.

With several candidate dengue vaccines under development, this is an important time to help stakeholders (e.g., policy makers, scientists, clinicians, and manufacturers) better understand the potential economic value (cost-effectiveness) of a dengue vaccine, especially while vaccine characteristics and strategies might be readily altered. We developed a decision analytic Markov simulation model to evaluate the potential health and economic value of administering a dengue vaccine to an individual (≤ 1 year of age) in Thailand from the societal perspective. Sensitivity analyses evaluated the effects of ranging various vaccine (e.g., cost, efficacy, side effect), epidemiological (dengue risk), and disease (treatment-seeking behavior) characteristics. A ≥ 50% efficacious vaccine was highly cost-effective [< 1× per capita gross domestic product (GDP) ($4,289)] up to a total vaccination cost of $60 and cost-effective [< 3× per capita GDP ($12,868)] up to a total vaccination cost of $200. When the total vaccine series was $1.50, many scenarios were cost saving.

The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), is the leading etiology of non-ischemic heart disease worldwide, with Latin America bearing the majority of the burden. This substantial burden and the limitations of current interventions have motivated efforts to develop a vaccine against T. cruzi. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a decision analytic Markov computer simulation model to assess the potential economic value of a T. cruzi vaccine in Latin America from the societal perspective. Each simulation run calculated the incremental cost-effectiveness ratio (ICER), or the cost per disability-adjusted life year (DALY) avoided, of vaccination. Sensitivity analyses evaluated the impact of varying key model parameters such as vaccine cost (range: $0.50-$200), vaccine efficacy (range: 25%-75%), the cost of acute-phase drug treatment (range: $10-$150 to account for variations in acute-phase treatment regimens), and risk of infection (range: 1%-20%). Additional analyses determined the incremental cost of vaccinating an individual and the cost per averted congestive heart failure case. Vaccination was considered highly cost-effective when the ICER was ≤1 times the GDP/capita, still cost-effective when the ICER was between 1 and 3 times the GDP/capita, and not cost-effective when the ICER was >3 times the GDP/capita. Our results showed vaccination to be very cost-effective and often economically dominant (i.e., saving costs as well providing health benefits) for a wide range of scenarios, e.g., even when risk of infection was as low as 1% and vaccine efficacy was as low as 25%. Vaccinating an individual could likely provide net cost savings that rise substantially as risk of infection or vaccine efficacy increase. CONCLUSIONS/SIGNIFICANCE: Results indicate that a T. cruzi vaccine could provide substantial economic benefit, depending on the cost of the vaccine, and support continued efforts to develop a human vaccine.

Forecasting the economic value of an Enterovirus 71 (EV71) vaccine.

Enterovirus 71 (EV71) is a growing public health concern, especially in Asia. A surge of EV71 cases in 2008 prompted authorities in China to go on national alert. While there is currently no treatment for EV71 infections, vaccines are under development. We developed a computer simulation model to determine the potential economic value of an EV71 vaccine for children (<5 years old) in China. Our results suggest that routine vaccination in China (EV71 infection incidence ≈0.04%) may be cost-effective when vaccine cost is $25 and efficacy ≥70% or cost is $10 and efficacy ≥50%. For populations with higher infection risk (≥0.4%), a $50 or $75 vaccine would be highly cost-effective even when vaccine efficacy is as low as 50%.

Vaccination deep into a pandemic wave potential mechanisms for a "third wave" and the impact of vaccination.

BACKGROUND: In December 2009, when the H1N1 influenza pandemic appeared to be subsiding, public health officials and unvaccinated individuals faced the question of whether continued H1N1 immunization was still worthwhile. PURPOSE: To delineate what combinations of possible mechanisms could generate a third pandemic wave and then explore whether vaccinating the population at different rates and times would mitigate the wave. METHODS: As part of ongoing work with the Office of the Assistant Secretary for Preparedness and Response at the USDHHS during the H1N1 influenza pandemic, the University of Pittsburgh Models of Infectious Disease Agent Study team employed an agent-based computer simulation model of the Washington DC metropolitan region to delineate what mechanisms could generate a "third pandemic wave" and explored whether vaccinating the population at different rates and times would mitigate the wave. This model included explicit representations of the region's individuals, school systems, workplaces/commutes, households, and communities. RESULTS: Three mechanisms were identified that could cause a third pandemic wave; substantially increased viral transmissibility from seasonal forcing (changing influenza transmission with changing environmental conditions, i.e., seasons) and progressive viral adaptation; an immune escape variant; and changes in social mixing from holiday school closures. Implementing vaccination for these mechanisms, even during the down-slope of the fall epidemic wave, significantly mitigated the third wave. Scenarios showed the gains from initiating vaccination earlier, increasing the speed of vaccination, and prioritizing population subgroups based on Advisory Committee on Immunization Practices recommendations. CONCLUSIONS: Additional waves in an epidemic can be mitigated by vaccination even when an epidemic appears to be waning.