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Background Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. Methods Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. Results Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91–1210) per life-year saved. Clinical Trials Registration ISRCTN45035509. Conclusions Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments. [ABSTRACT FROM AUTHOR]

Background: Novel tuberculosis (TB) drugs and the need to treat drug-resistant tuberculosis (DR-TB) are likely to bring about substantial transformations in TB treatment in coming years. An evidence base for cost and cost-effectiveness analyses of these developments is needed. Objective: Our objective was to perform a review of papers assessing provider-incurred as well as patient-incurred costs of treating both drug-susceptible (DS) and multidrug-resistant (MDR)-TB. Methods: Five databases (EMBASE, Medline, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and Latin American and Caribbean Health Services Literature) were searched for cost and economic evaluation full-text papers containing primary DS-TB and MDR-TB treatment cost data published in peer-reviewed journals between January 1990 and February 2015. No language restrictions were set. The search terms were a combination of 'tuberculosis', 'multidrug-resistant tuberculosis', 'cost', and 'treatment'. In the selected papers, study methods and characteristics, quality indicators and costs were extracted into summary tables according to pre-defined criteria. Results were analysed according to country income groups and for provider costs, patient costs and productivity losses. All values were converted to $US, year 2014 values, so that studies could be compared. Results: We selected 71 treatment cost papers on DS-TB only, ten papers on MDR-TB only and nine papers that included both DS-TB and MDR-TB. These papers provided evidence on the costs of treating DS-TB and MDR-TB in 50 and 16 countries, respectively. In 31 % of the papers, only provider costs were included; 26 % included only patient-incurred costs, and the remaining 43 % estimated costs incurred by both. From the provider perspective, mean DS-TB treatment costs per patient were US$14,659 in high-income countries (HICs), US$840 in upper middle-income countries (UMICs), US$273 in lower middle-income (LMICs), and US$258 in low-income countries (LICs), showing a strong positive correlation. The respective costs for treating MDR-TB were US$83,365, US$5284, US$6313 and US$1218. Costs incurred by patients when seeking treatment for DS-TB accounted for an additional 3 % of the provider costs in HICs. A greater burden was seen in the other income groups, increasing the costs of DS-TB treatment by 72 % in UMICs, 60 % in LICs and 31 % in LMICs. When provider costs, patient costs and productivity losses were combined, productivity losses accounted for 16 % in HICs, 29 % in UMICs, 40 % in LMICs and 38 % in LICs. Conclusion: Cost data for MDR-TB treatment are limited, and the variation in delivery mechanisms, as well as the rapidly evolving diagnosis and treatment regimens, means that it is essential to increase the number of studies assessing the cost from both provider and patient perspectives. There is substantial evidence available on the costs of DS-TB treatment from all regions of the world. The patient-incurred costs illustrate that the financial burden of illness is relatively greater for patients in poorer countries without universal healthcare coverage. [ABSTRACT FROM AUTHOR]

Background With GAVI support, Vietnam introduced Haemophilus influenzae type b (Hib) vaccine in 2010 without evidence on cost-effectiveness. We aimed to analyze the cost-effectiveness of Hib vaccine from societal and governmental perspectives. Method We constructed a decision-tree cohort model to estimate the costs and effectiveness of Hib vaccine versus no Hib vaccine for the 2011 birth cohort. The disease burden was estimated from local epidemiologic data and literature. Vaccine delivery costs were calculated from governmental reports and 2013 vaccine prices. A prospective cost-of-illness study was conducted to estimate treatment costs. The human capital approach was employed to estimate productivity loss. The incremental costs of Hib vaccine were divided by cases, deaths, and disability-adjusted life years (DALY) averted. We used the WHO recommended cost-effectiveness thresholds of an intervention being highly cost-effective if incremental costs per DALY were below GDP per capita. Result From the societal perspective, incremental costs per discounted case, death and DALY averted were US$ 6252, US$ 26,476 and US$ 1231, respectively; the break-even vaccine price was US$ 0.69/dose. From the governmental perspective, the results were US$ 6954, US$ 29,449, and US$ 1373, respectively; the break-even vaccine price was US$ 0.48/dose. Vietnam's GDP per capita was US$ 1911 in 2013. In deterministic sensitivity analysis, morbidity and mortality parameters were among the most influential factors. In probabilistic sensitivity analysis, Hib vaccine had an 84% and 78% probability to be highly cost-effective from the societal and governmental perspectives, respectively. Conclusion Hib vaccine was highly cost-effective from both societal and governmental perspectives. However, with GAVI support ending in 2016, the government will face a six-fold increase in its vaccine budget at the 2013 vaccine price. The variability of vaccine market prices adds an element of uncertainty. Increased government commitment and improved resource allocation decision making will be necessary to retain Hib vaccine. [ABSTRACT FROM AUTHOR]

To help reach the target of tuberculosis (TB) disease elimination by 2050, vaccine development needs to occur now. We estimated the impact and cost-effectiveness of potential TB vaccines in low- and middle-income countries using an age-structured transmission model. New vaccines were assumed to be available in 2024, to prevent active TB in all individuals, to have a 5-y to lifetime duration of protection, to have 40–80% efficacy, and to be targeted at "infants" or "adolescents/adults." Vaccine prices were tiered by income group (US $1.50–$10 per dose), and cost-effectiveness was assessed using incremental cost per disability adjusted life year (DALY) averted compared against gross national income per capita. Our results suggest that over 2024–2050, a vaccine targeted to adolescents/adults could have a greater impact than one targeted at infants. In low-income countries, a vaccine with a 10-y duration and 60% efficacy targeted at adolescents/adults could prevent 17 (95% range: 11–24) million TB cases by 2050 and could be considered cost-effective at $149 (cost saving to $387) per DALY averted. If targeted at infants, 0.89 (0.42–1.58) million TB cases could be prevented at $1,692 ($634–$4,603) per DALY averted. This profile targeted at adolescents/adults could be cost-effective at $4, $9, and $20 per dose in low-, lower-middle–, and upper-middle–income countries, respectively. Increased investments in adult-targeted TB vaccines may be warranted, even if only short duration and low efficacy vaccines are likely to be feasible, and trials among adults should be powered to detect low efficacies. [ABSTRACT FROM AUTHOR]

Objective To estimate the cost-effectiveness of cataract surgery and refractive error/presbyopia correction in Zambia. Methods Primary data on costs and health related quality of life were collected in a prospective cohort study of 170 cataract and 113 refractive error/presbyopia patients recruited from three health facilities. Six months later, follow-up data were available from 77 and 41 patients who had received cataract surgery and spectacles, respectively. Costs were determined from patient interviews and micro-costing at the three health facilities. Utility values were gathered by administering the EQ-5D quality of life instrument immediately before and six months after cataract surgery or acquiring spectacles. A probabilistic state-transition model was used to generate cost-effectiveness estimates with uncertainty ranges. Results Utility values significantly improved across the patient sample after cataract surgery and acquiring spectacles. Incremental costs per Quality Adjusted Life Years gained were US$ 259 for cataract surgery and US$ 375 for refractive error correction. The probabilities of the incremental cost-effectiveness ratios being below the Zambian gross national income per capita were 95% for both cataract surgery and refractive error correction. Conclusion In spite of proven cost-effectiveness, severe health system constraints are likely to hamper scaling up of the interventions. [ABSTRACT FROM AUTHOR]

We employ a single-country dynamically-recursive Computable General Equilibrium model to make health-focussed macroeconomic assessments of three contingent UK Greenhouse Gas (GHG) mitigation strategies, designed to achieve 2030 emission targets as suggested by the UK Committee on Climate Change. In contrast to previous assessment studies, our main focus is on health co-benefits additional to those from reduced local air pollution. We employ a conservative cost-effectiveness methodology with a zero net cost threshold. Our urban transport strategy (with cleaner vehicles and increased active travel) brings important health co-benefits and is likely to be strongly cost-effective; our food and agriculture strategy (based on abatement technologies and reduction in livestock production) brings worthwhile health co-benefits, but is unlikely to eliminate net costs unless new technological measures are included; our household energy efficiency strategy is likely to breakeven only over the long term after the investment programme has ceased (beyond our 20 year time horizon). We conclude that UK policy makers will, most likely, have to adopt elements which involve initial net societal costs in order to achieve future emission targets and longer-term benefits from GHG reduction. Cost-effectiveness of GHG strategies is likely to require technological mitigation interventions and/or demand-constraining interventions with important health co-benefits and other efficiency-enhancing policies that promote internalization of externalities. Health co-benefits can play a crucial role in bringing down net costs, but our results also suggest the need for adopting holistic assessment methodologies which give proper consideration to welfare-improving health co-benefits with potentially negative economic repercussions (such as increased longevity). [ABSTRACT FROM AUTHOR]

Background: The GAVI Alliance supported10-valent pneumococcal conjugate vaccine (PCV10) introduction in Kenya. We estimated the cost-effectiveness of introducing either PCV10 or the13-valent vaccine (PCV13) from a societal perspective and explored the incremental impact of including indirect vaccine effects. Methods: The costs and effects of pneumococcal vaccination among infants born in Kenya in 2010 were assessed using a decision analytic model comparing PCV10 or PCV13, in turn, with no vaccination. Direct vaccine effects were estimated as a reduction in the incidence of pneumococcal meningitis, sepsis, bacteraemic pneumonia and non-bacteraemic pneumonia. Pneumococcal disease incidence was extrapolated from a population-based hospital surveillance system in Kilifi and adjustments were made for variable access to care across Kenya. We used vaccine efficacy estimates from a trial in The Gambia and accounted for serotype distribution in Kilifi. We estimated indirect vaccine protection and serotype replacement by extrapolating from the USA. Multivariable sensitivity analysis was conducted using Monte Carlo simulation. We assumed a vaccine price of US$ 3.50 per dose. Findings: The annual cost of delivering PCV10 was approximately US$14 million. We projected a 42.7% reduction in pneumococcal disease episodes leading to a US$1.97 million reduction in treatment costs and a 6.1% reduction in childhood mortality annually. In the base case analysis, costs per discounted DALY and per death averted by PCV10, amounted to US$ 59 (95% CI 26–103) and US$ 1,958 (95% CI 866–3,425), respectively. PCV13 introduction improved the cost-effectiveness ratios by approximately 20% and inclusion of indirect effects improved cost-effectiveness ratios by 43–56%. The break-even prices for introduction of PCV10 and PCV13 are US$ 0.41 and 0.51, respectively. Conclusions: Introducing either PCV10 or PCV13 in Kenya is highly cost-effective from a societal perspective. Indirect effects, if they occur, would significantly improve the cost-effectiveness. [ABSTRACT FROM AUTHOR]

Abstract: Objective: With support from the GAVI Alliance a fully liquid combined DTwP–HepB–Hib (pentavalent) vaccine in a single dose vial was introduced into Ethiopia''s routine immunization services in March 2007. This vaccine was substituted with DTwP in a 10-dose vial. We aimed to estimate the incremental system costs of pentavalent vaccine delivery. Methods: Data on cold storage expansion and increased vaccine transport frequency were collected in four regions of Ethiopia over a 2-week period, as part of a Post-Introduction Evaluation of the new vaccine. Interviews were conducted with individuals at all levels of the health system. Information on the costs of training and communication to facilitate the introduction was collected from the Ministry of Health, UNICEF and WHO in Addis Ababa. Results: The switch from a 10-dose DTwP to a single dose pentavalent vaccine increased refrigeration storage volume per fully vaccinated child by 106% at national and regional levels and by 71% at the three lower levels of vaccine distribution. Cold storage equipments were purchased at all levels and the frequency of vaccine collection more than doubled in many places. Incremental capital costs of cold storage equipment, training and communication amounted to US$ 4.8 million, or US$ 1.53 per child in the 2007 birth cohort. After annualizing capital costs and adding recurrent costs, system costs came to US$ 0.80 per child in the 2007 birth cohort. With a vaccination coverage rate of 78% this is equivalent to US$ 1.13 per fully vaccinated child. The most important system cost item is cold storage, amounting to US$ 0.62 per child in the birth cohort and US$ 0.03 per additional cm3 of cold storage. Conclusion: In Ethiopia introduction of pentavalent vaccine necessitated considerable investments in additional cold storage equipment as well as an increase in vaccine transport frequency. A GAVI Alliance introduction grant of US$ 0.30 per child in the birth cohort would cover approximately 20% of the capital investments undertaken to facilitate introduction. [Copyright &y& Elsevier]

Abstract: Aims: To assess the cost-effectiveness of switching from oral polio vaccine (OPV) to inactivated poliovirus vaccine (IPV), or to cease polio vaccination in routine immunization services in South Africa at the time of OPV cessation globally following polio eradication. Methods: The cost-effectiveness of nine different polio immunization alternatives were evaluated. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated, and IPV schedules with 2, 3 and 4 doses were compared with the current 6-dose OPV schedule. Assumptions about IPV prices were based on indications from vaccine manufacturers. The health impact of OPV cessation was measured in terms of vaccine associated paralytic paralysis (VAPP) cases and disability adjusted life years (DALYs) averted. Conclusions: The use of OPV in routine immunization services is predicted to result in 2.96 VAPP cases in the 2005 cohort. The cost-effectiveness of the different IPV alternatives varies between US$ 740,000 and US$ 7.2 million per VAPP case averted. The costs per discounted DALY averted amount to between US$ 61,000 and US$ 594,000. Among the IPV strategies evaluated, the 2-dose schedule in a 10-dose vial is the most cost-effective option. At the assumed vaccine prices, all IPV options do not appear to be cost-effective in the South African situation. OPV cessation without IPV replacement would result in cost savings of US$ 1.6 million per year compared to the current situation. This is approximately a 9% decrease in the budget for vaccine delivery in South Africa. However, with this option there is a risk (albeit small) of vaccine-derived poliovirus circulating in a progressively susceptible population. For IPV in a single dose vial, the break-even price, at which the costs of IPV delivery equal the current OPV delivery costs, is US$ 0.39. [Copyright &y& Elsevier]

Background: Measles vaccination is associated with major reductions in child mortality and morbidity. In Guinea-Bissau, to limit vaccine wastage, children are only measles-vaccinated if at least six children aged 9–11 months are present at a vaccination session. Objective: To estimate the incremental cost-effectiveness of providing measles vaccine (MV) to all children regardless of age and number of children present. Methods: We estimated MV coverage among children living in villages cluster-randomized to MV for all children and among children cluster-randomized to the current restrictive MV policy (status quo). Prices of MV and injection equipment were obtained from the United Nations Children’s Fund (UNICEF). Cost savings of hospital admissions averted were collected from a sample of health facilities. The non-specific mortality effects of MV were estimated and presented as deaths averted and life years gained (LYG) from providing MV-for-all. Results: MV coverage at 36 months was 97% in MV-for-all clusters and 84% in restrictive MV policy clusters. Conservatively assuming 90% wastage of MV under the MV-for-all policy and 40% under the restrictive MV policy, cost per child vaccinated was USD 3.08 and USD 1.19, respectively. The incremental costs per LYG and death averted of the MV-for-all policy were USD 5.61 and USD 148, respectively. The MV-for-all policy became cost-saving at 88% wastage. Conclusions: Taking the low cost of MV and the beneficial non-specific effects of MV into consideration, a 10-dose MV vial should be reclassified as a ‘1+ dose vial’. The vial should be opened for a single child, irrespective of age, but can vaccinate up to 10 children. [ABSTRACT FROM PUBLISHER]

Highlights: [•] We describe the TRIVAC model for evaluating the cost-effectiveness of 3 childhood vaccines. [•] We examine the key drivers of the TRIVAC decision support model. [•] Cost-effectiveness ratios were most sensitive to changes in relative coverage and the herd effect multiplier. [•] Identifying the key drivers helps to prioritise influential parameters for data collection. [ABSTRACT FROM AUTHOR]

Objective Haemophilus influenzae type b (Hib) vaccine was introduced into routine immunization services in Kenya in 2001. We aimed to estimate the cost-effectiveness of Hib vaccine delivery. Methods A model was developed to follow the Kenyan 2004 birth cohort until death, with and without Hib vaccine. Incidence of invasive Hib disease was estimated at Kilifi District Hospital and in the surrounding demographic surveillance system in coastal Kenya. National Hib disease incidence was estimated by adjusting incidence observed by passive hospital surveillance using assumptions about access to care. Case fatality rates were also assumed dependent on access to care. A price of US$ 3.65 per dose of pentavalent diphtheria-tetanus-pertussis-hep B-Hib vaccine was used. Multivariate Monte Carlo simulations were performed in order to assess the impact on the cost-effectiveness ratios of uncertainty in parameter values. Findings The introduction of Hib vaccine reduced the estimated incidence of Hib meningitis per 100 000 children aged < 5 years from 71 to 8; of Hib non-meningitic invasive disease from 61 to 7; and of non-bacteraemic Hib pneumonia from 296 to 34. The costs per discounted disability adjusted life year (DALY) and per discounted death averted were US$ 38 (95% confidence interval, CI: 26-63) and US$ 1197 (95% CI: 814-2021) respectively. Most of the uncertainty in the results was due to uncertain access to care parameters. The break-even pentavalent vaccine price - where incremental Hib vaccination costs equal treatment costs averted from Hib disease - was US$ 1.82 per dose. Conclusion Hib vaccine is a highly cost-effective intervention in Kenya. It would be cost-saving if the vaccine price was below half of its present level. [ABSTRACT FROM AUTHOR]