Macroeconomic impact of Ebola outbreaks in Sub-Saharan Africa and potential mitigation of GDP loss with prophylactic Ebola vaccination programs.

INTRODUCTION: Decisions about prevention of and response to Ebola outbreaks require an understanding of the macroeconomic implications of these interventions. Prophylactic vaccines hold promise to mitigate the negative economic impacts of infectious disease outbreaks. The objective of this study was to evaluate the relationship between outbreak size and economic impact among countries with recorded Ebola outbreaks and to quantify the hypothetical benefits of prophylactic Ebola vaccination interventions in these outbreaks. METHODS: The synthetic control method was used to estimate the causal impacts of Ebola outbreaks on per capita gross domestic product (GDP) of five countries in sub-Saharan Africa that have previously experienced Ebola outbreaks between 2000 and 2016, where no vaccines were deployed. Using illustrative assumptions about vaccine coverage, efficacy, and protective immunity, the potential economic benefits of prophylactic Ebola vaccination were estimated using the number of cases in an outbreak as a key indicator. RESULTS: The impact of Ebola outbreaks on the macroeconomy of the selected countries led to a decline in GDP of up to 36%, which was greatest in the third year after the onset of each outbreak and increased exponentially with the size of outbreak (i.e., number of reported cases). Over three years, the aggregate loss estimated for Sierra Leone from its 2014-2016 outbreak is estimated at 16.1 billion International$. Prophylactic vaccination could have prevented up to 89% of an outbreak's negative impact on GDP, reducing the outbreak's impact to as little as 1.6% of GDP lost. CONCLUSION: This study supports the case that macroeconomic returns are associated with prophylactic Ebola vaccination. Our findings support recommendations for prophylactic Ebola vaccination as a core component of prevention and response measures for global health security.

Targeted preventive vaccination campaigns to reduce Ebola outbreaks: An individual-based modeling study.

INTRODUCTION: Nonpharmaceutical interventions (NPI) and ring vaccination (i.e., vaccination that primarily targets contacts and contacts of contacts of Ebola cases) are currently used to reduce the spread of Ebola during outbreaks. Because these measures are typically initiated after an outbreak is declared, they are limited by real-time implementation challenges. Preventive vaccination may provide a complementary option to help protect communities against unpredictable outbreaks. This study aimed to assess the impact of preventive vaccination strategies when implemented in conjunction with NPI and ring vaccination. METHODS: A spatial-explicit, individual-based model (IBM) that accounts for heterogeneity of human contact, human movement, and timing of interventions was built to represent Ebola transmission in the Democratic Republic of the Congo. Simulated preventive vaccination strategies targeted healthcare workers (HCW), frontline workers (FW), and the general population (GP) with varying levels of coverage (lower coverage: 30% of HCW/FW, 5% of GP; higher coverage: 60% of HCW/FW, 10% of GP) and efficacy (lower efficacy: 60%; higher efficacy: 90%). RESULTS: The IBM estimated that the addition of preventive vaccination for HCW reduced cases, hospitalizations, and deaths by âˆ¼11 % to âˆ¼25 % compared with NPI + ring vaccination alone. Including HCW and FW in the preventive vaccination campaign yielded âˆ¼14 % to âˆ¼38 % improvements in epidemic outcomes. Further including the GP yielded the greatest improvements, with âˆ¼21 % to âˆ¼52 % reductions in epidemic outcomes compared with NPI + ring vaccination alone. In a scenario without ring vaccination, preventive vaccination reduced cases, hospitalizations, and deaths by âˆ¼28 % to âˆ¼59 % compared with NPI alone. In all scenarios, preventive vaccination reduced Ebola transmission particularly during the initial phases of the epidemic, resulting in flatter epidemic curves. CONCLUSIONS: The IBM showed that preventive vaccination may reduce Ebola cases, hospitalizations, and deaths, thus safeguarding the healthcare system and providing more time to implement additional interventions during an outbreak.

Model-based evaluation of the impact of prophylactic vaccination applied to Ebola epidemics in Sierra Leone and Democratic Republic of Congo.

BACKGROUND: Protection by preventive Ebola vaccines has been demonstrated in clinical trials, but a complete picture of real-world effectiveness is lacking. Our previous study modeling the impact of preventively vaccinating healthcare workers (HCW) alone or with a proportion of the general population (GP) estimated significant reductions in incidence and mortality. The model assumed 100% vaccine efficacy, which is unlikely in the real world. We enhanced this model to account for lower vaccine efficacy and to factor in reduced infectiousness and lower case fatality rate in vaccinated individuals with breakthrough infections. METHODS: The previous model was enhanced to still permit a risk, although lower, for vaccinated individuals to become infected. The enhanced model, calibrated with data from epidemics in Sierra Leone (SL) and North Kivu, Democratic Republic of the Congo, helped evaluate the impact of preventive Ebola vaccination in different scenarios based on different vaccine efficacy rates (90% and 30% reductions in infection risk in the base and conservative scenarios, respectively; additionally, both scenarios with 50% reductions in infectiousness and mortality) and vaccination coverage among HCWs (30%, 90%) and GP (0%, 5%, and 10%). RESULTS: The base scenario estimated that, depending upon the proportions of vaccinated HCWs and GP, 33-85% of cases and 34-87% of deaths during the 2014 SL epidemic and 42-89% of cases and 41-89% of deaths during the 2018 North Kivu epidemic would be averted versus no vaccination. Corresponding estimates for the conservative scenario were: 23-74% of cases and 23-77% of deaths averted during the SL epidemic and 31-80% of both cases and deaths averted during the North Kivu epidemic. CONCLUSIONS: Preventive vaccination targeting HCW alone or with GP may significantly reduce the size and mortality of an EVD outbreak, even with modest efficacy and coverage. Vaccines may also confer additional benefits through reduced infectiousness and mortality in breakthrough cases.

The cost-effectiveness of a bedaquiline-containing short-course regimen for the treatment of multidrug-resistant tuberculosis in South Africa.

Background: Bedaquiline-containing regimens have demonstrated improved outcomes over injectable-containing regimens in the long-term treatment of multidrug-resistant tuberculosis (MDR-TB). Recently, the World Health Organization (WHO) recommended replacing injectables in the standard short-course regimen (SCR) with a bedaquiline-containing regimen. The South African national TB program similarly recommends a bedaquiline-containing regimen. Here, we investigated the cost-effectiveness of a bedaquiline-containing SCR versus an injectable-containing SCR for the treatment of MDR-TB in South Africa.Methods: A Markov model was adapted to simulate the incidence of active patients with MDR-TB. Patients could transition through eight health states: active MDR-TB, culture conversion, cure, follow-up loss, secondary MDR-TB, extensively DR-TB, end-of-life care, and death. A 5% discount was assumed on costs and outcomes. Health outcomes were expressed as disability-adjusted life years (DALYs).Results: Over a 10-year time horizon, a bedaquiline-containing SCR dominated an injectable-containing SCR, with an incremental saving of US $982 per DALY averted. A bedaquiline-containing SCR was associated with lower total costs versus an injectable-containing SCR (US $597 versus $657 million), of which US $3.2 versus $21.9 million was attributed to adverse event management.Conclusions: Replacing an injectable-containing SCR with a bedaquiline-containing SCR is cost-effective, offering a cost-saving alternative with improved patient outcomes for MDR-TB.

Long-term impact of the adoption of bedaquiline-containing regimens on the burden of drug-resistant tuberculosis in China.

BACKGROUND: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China. METHODS: A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment. RESULTS: In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption. CONCLUSIONS: Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.

Bedaquiline- versus injectable-containing drug-resistant tuberculosis regimens: a cost-effectiveness analysis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) continues to be a major public health challenge with suboptimal treatment outcomes including well-documented treatment-related toxicities. We compared the cost-effectiveness of bedaquiline (BDQ) containing regimens with injectable containing regimens (short-course regimen [SCR] and long-course regiman [LCR]) in India, Russia, and South Africa. METHODS: The analysis evaluated the direct costs of DR-TB treatment which included drugs, hospitalization, injectable-related adverse event costs, and other costs. Scenarios altered regimen costs, SCR/LCR ratio, and substitution rate between regimens (whether BDQ or injectable containing). RESULTS: BDQ containing regimens are more cost effective based on cost per treatment success compared with injectable containing regimens, reducing these in SCR by 18-20% and in LCR by 49-54%. Average cost effectiveness ratios (ACERs) of BDQ containing regimens are lower. The incremental cost effectiveness ratio (ICER) is negative. Exclusive use of BDQ containing regimens results in approximately 61,000 more patients treated successfully over 5 years. CONCLUSIONS: Across all countries, BDQ containing regimens are dominant compared to injectable containing regimens, entailing lower treatment costs to achieve better clinical outcomes. This analysis can provide insight and support to local and global decision-makers and public health organizations to allocate efficiently resources improving patient and public health outcomes.

Cost-effectiveness of treatments for dysfunctional uterine bleeding.

OBJECTIVE: To compare the cost-effectiveness of treatments for dysfunctional uterine bleeding (DUB). STUDY DESIGN: The decision analytic model used a third-party payer perspective and 18-month horizon to compare treatment of DUB patients > or = 40 years old with no desire for fertility. Treatments were oral contraceptives (OCs) vs. surgery (first-/second-generation ablation or hysterectomy) after 3-9 months of OCs. Costs were based on publications and expert opinion. Efficacy measures were based on months with pictorial blood loss assessment chart (PBAC) score < 100 and number of months of amenorrhea. RESULTS: Treatment costs were estimated at 513 dollars per patient per year (OCs), 3,500 dollars (first-generation ablation), 3,000 dollars (second-generation ablation) and 7,500 dollars (hysterectomy). Adverse event costs ranged from 12 dollars per year or episode (OCs, second-generation ablation) to 164 dollars per episode (hysterectomy). To achieve PBAC < 100, second-generation ablation after 3 months of OCs was the most cost-effective (7.6 additional DUB-free months vs. OCs, 215 dollars per additional month). Second-generation ablation was less costly and more effective than first-generation ablation. Early treatment with hysterectomy was more effective than ablation, but at substantial cost. When using the end point of amenorrhea, hysterectomy was most cost-effective. Results were not sensitive to variations in costs, effectiveness or length of OC use. CONCLUSION: A short OC trial followed by second-generation ablation is the most cost-effective strategy for women with DUB, although hysterectomy is more cost-effective to achieve amenorrhea. Hysterectomy cost-effectiveness might improve if evaluated over more time. Cost-effectiveness and patient preference must all play a role in treatment decisions.