Project description:BACKGROUND AND AIMS:Hepatitis C virus (HCV) and its sequelae present a significant source of economic and societal burden. Introduction of highly effective curative therapies has made HCV elimination attainable. The study used a predictive model to assess the clinical and economic impact of implementing national screening and treatment policies toward HCV elimination in Korea. METHODS:A previously validated Markov disease progression model of HCV infection was employed to analyze the clinical and economic impact of various strategies for HCV diagnosis and treatment in Korea. In this analysis, the model compared the clinical and economic outcomes of current HCV-related interventions in Korea (7,000 patients treated and 4,200 patients newly diagnosed annually, starting in 2017) to four elimination scenarios: 1) initiating sufficient diagnosis and treatment interventions to meet the World Health Organization's GHSS elimination targets by 2030, 2) delaying initiation of interventions by one year, 3) delaying initiation of interventions by two years and 4) accelerating initiation of interventions to meet elimination targets by 2025. Modelled historical incidence of HCV was calibrated to match a viremic HCV prevalence of 0.44% in 2009. Elimination scenarios required 24,000 treatments and 34,000 newly diagnosed patients annually, starting in 2018, to reach the 2030 targets. RESULTS:Compared to current "status quo" interventions, elimination (or accelerated elimination by 2025) would avert 23,700 (27,000) incident cases of HCV, 1,300 (1,400) liver-related deaths (LRDs) and 2,900 (3,100) cases of end-stage liver disease (ESLD) over the 2017-2030 time period. Postponing interventions by one (or two) years would avert 21,100 (18,600) new HCV infections, 920 (660) LRDs and 2,000 (1,400) cases of ESLD by 2030. Following elimination or accelerated elimination strategies would save 860 million USD or 1.1 billion USD by 2030, respectively, compared to the status quo, requiring an up-front investment in prevention that decreases spending on liver-related complications and death. CONCLUSIONS:By projecting the impact of interventions and tracking progress toward GHSS elimination targets using modelling, we demonstrate that Korea can prevent significant morbidity, mortality and spending on HCV. Results should serve as the backbone for policy and decision-making, demonstrating how aggressive prevention measures are designed to reduce future costs and increase the health of the public.
Project description:BackgroundThe introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment.MethodsThe model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018-2030.ResultsThe optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15-113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6-8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7-10.8) billion cost reduction across 78 countries (47%).ConclusionsThese findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.
Project description:Background & aimsGlobally, one-third of individuals infected with HBV live in China. Eliminating HBV in China would therefore be paramount in achieving the World Health Organization's (WHO's) targets of viral hepatitis elimination as a worldwide public health threat.MethodsWe constructed a dynamic HBV transmission model in China, structured by age and sex. We calibrated the model by HBsAg prevalence, acute HBV incidence, and nationally reported HBV-related cancer mortality. We investigated seven intervention scenarios (A-G) based on assumptions in diagnostic, linkage-to-care, and treatment coverages in achieving the WHO's HBV elimination goals.ResultsWith the status quo, HBsAg prevalence among children 1-4 years would reduce to 0.09% (95% CI 0.09-0.10%) by 2025; acute HBV incidence would drop to <2/100,000 person-years by 2024, achieving the elimination target of 90% incidence reduction. Nonetheless, China would not achieve a 65% reduction target in HBV-related mortality until 2059 with 9.98 (95% CI 9.27-10.70) million HBV-related deaths occurred by 2100. If China achieves 90% diagnostic and 80% treatment coverages (scenario E), HBV elimination would be achieved 8 years earlier, potentially saving 1.98 (95% CI 1.83-2.12) million lives. With more effective therapies for HBV control in preventing cirrhosis and hepatocellular carcinoma, elimination targets could be achieved in 2048 (scenario F) and 2038 (scenario G), additionally saving 3.59 (95% CI 3.37-3.82) and 5.19 (95% CI 4.83-5.55) million lives, respectively.ConclusionsEliminating HBV will require interventional strategies to improve diagnostic, linkage-to-care, and treatment coverages. Developing novel therapies will be crucial in further reducing HBV-related mortality and removing HBV as a public health threat.Impact and implicationsThis study explores the key developments and optimal intervention strategies needed to achieve WHO hepatitis B elimination targets by 2030 in China. It highlights that China can realise the HBV elimination targets in the incidence by 2025, and by upscaling diagnostic, linkage-to-care, and treatment coverages, up to 2 million lives could potentially be saved from HBV-related deaths.
Project description:BackgroundMalaria was once one of the most serious public health problems in China. However, the disease burden has sharply declined and epidemic areas have shrunk after the implementation of an integrated malaria control and elimination strategy, especially since 2000. In this review, the lessons were distilled from the Chinese national malaria elimination programme and further efforts to mitigate the challenges of malaria resurgence are being discussed.MethodsA retrospective evaluation was performed to assess the changes in malaria epidemic patterns from 1950 to 2017 at national level. The malaria data before 2004 were collected from paper-based annual reports. After 2004, each of the different cases from the Infectious Diseases Information Reporting Management System (IDIRMS) was closely examined and scrutinized. An additional documenting system, the National Information Management System for Malaria, established in 2012 to document the interventions of three parasitic diseases, was also examined to complete the missing data from IDIRMS.ResultsFrom 1950 to 2017, the occurrence of indigenous malaria has been steeply reduced, and malaria-epidemic regions have substantially shrunk, especially after the launch of the national malaria elimination programme. There were approximately 30 million malaria cases annually before 1949 with a mortality rate of 1%. A total of 5999 indigenous cases were documented from 2010 to 2016, with a drastic reduction of 99% over the 6 years (2010, n?=?4262; 2016, n?=?3). There were indigenous cases reported in 303 counties from 18 provinces in 2010, but only 3 indigenous cases were reported in 2 provinces nationwide in 2016. While in 2017, for the first time, zero indigenous case was reported in China, and only 7 of imported cases were in individuals who died of Plasmodium falciparum infection.ConclusionMalaria elimination in China is a country-led and country-owned endeavour. The country-own efforts were a clear national elimination strategy, supported by two systems, namely a case-based surveillance and response system and reference laboratory system. The country-led efforts were regional and inter-sectoral collaboration as well as sustained monitoring and evaluation. However, there are still some challenges, such as the maintenance of non-transmission status, the implementation of a qualified verification and assessment system, and the management of imported cases in border areas, through regional cooperation. The findings from this review can probably help improving malaria surveillance systems in China, but also in other elimination countries.
Project description:BackgroundEffective case identification strategies are fundamental to capturing the remaining visceral leishmaniasis (VL) cases in India. To inform government strategies to reach and sustain elimination benchmarks, this study presents costs of active- and passive- case detection (ACD and PCD) strategies used in India's most VL-endemic state, Bihar, with a focus on programme outcomes stratified by district-level incidence.MethodsExpenditure analysis was complemented by onsite micro-costing to compare the cost of PCD in hospitals alongside index case-based ACD and a combination of blanket (house-to-house) and camp ACD from January to December 2018. From the provider's perspective, a cost analysis evaluated the overall programme cost of each activity, the cost per case detected, and the cost of scaling up ACD.ResultsDuring 2018, index case-based ACD, blanket and camp ACD, and PCD reported 1,497, 131, and 1,983 VL-positive cases at a unit cost of $522.81, $4,186.81, and $246.79, respectively. In high endemic districts, more VL cases were identified through PCD while in meso- and low-endemic districts more cases were identified through ACD. The cost of scaling up ACD to identify 3,000 additional cases ranged from $1.6-4 million, depending on the extent to which blanket and camp ACD was relied upon.ConclusionCost per VL test conducted (rather than VL-positive case identified) may be a better metric estimating unit costs to scale up ACD in Bihar. As more VL cases were identified in meso-and low-endemic districts through ACD than PCD, health authorities in India should consider bolstering ACD in these areas. Blanket and camp ACD identified fewer cases at a higher unit cost than index case-based ACD. However, the value of detecting additional VL cases early outweighs long-term costs for reaching and sustaining VL elimination benchmarks in India.
Project description:Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints.
Project description:The 'Ending the HIV Epidemic (EHE)' national plan aims to reduce annual HIV incidence in the United States from 38,000 in 2015 to 9300 by 2025 and 3300 by 2030. Diagnosis and treatment are two most effective interventions, and thus, identifying corresponding optimal combinations of testing and retention-in-care rates would help inform implementation of relevant programs. Considering the dynamic and stochastic complexity of the disease and the time dynamics of decision-making, solving for optimal combinations using commonly used methods of parametric optimization or exhaustive evaluation of pre-selected options are infeasible. Reinforcement learning (RL), an artificial intelligence method, is ideal; however, training RL algorithms and ensuring convergence to optimality are computationally challenging for large-scale stochastic problems. We evaluate its feasibility in the context of the EHE goal. We trained an RL algorithm to identify a 'sequence' of combinations of HIV-testing and retention-in-care rates at 5-year intervals over 2015-2070 that optimally leads towards HIV elimination. We defined optimality as a sequence that maximizes quality-adjusted-life-years lived and minimizes HIV-testing and care-and-treatment costs. We show that solving for testing and retention-in-care rates through appropriate reformulation using proxy decision-metrics overcomes the computational challenges of RL. We used a stochastic agent-based simulation to train the RL algorithm. As there is variability in support-programs needed to address barriers to care-access, we evaluated the sensitivity of optimal decisions to three cost-functions. The model suggests to scale-up retention-in-care programs to achieve and maintain high annual retention-rates while initiating with a high testing-frequency but relaxing it over a 10-year period as incidence decreases. Results were mainly robust to the uncertainty in costs. However, testing and retention-in-care alone did not achieve the 2030 EHE targets, suggesting the need for additional interventions. The results from the model demonstrated convergence. RL is suitable for evaluating phased public health decisions for infectious disease control.
Project description:BackgroundChina has one of the highest hepatitis B virus (HBV) disease burdens worldwide and tracking progress toward the 2030 HBV elimination targets is essential. This study aimed to assess the impact of biomedical interventions (i.e., adult vaccination, screening and treatment) on the adult HBV epidemic, estimate the time for HBV elimination, and evaluate the cost-effectiveness of the interventions in China.MethodsA deterministic compartmental model was developed to project the HBV epidemic from 2022 to 2050 and estimate the time to meet elimination targets under four intervention scenarios. Cost-effectiveness was calculated using incremental cost per quality-adjusted life year (QALY) gained, i.e., average cost-effectiveness ratio (CER).ResultsUnder the status quo, there will be 42.09-45.42 million adults living with HBV in 2050 and 11.04-14.36 million HBV-related deaths cumulatively from 2022 to 2050. Universal vaccination would cumulatively avert 3.44-3.95 million new cases at a cost of US$1027-1261/QALY gained. The comprehensive strategy would cumulatively avert 4.67-5.24 million new chronic cases and 1.39-1.85 million deaths, expediting the realization of the elimination targets forward to 2049. This strategy was also cost-effective with an average CER of US$20,796-26,685/QALY and a saved healthcare cost of US$16.10-26.84 per person.ConclusionChina is not on track to meet the elimination targets but comprehensive biomedical interventions can accelerate the realization of the targets. A comprehensive strategy is cost-effective and cost-saving, which should be promoted in primary care infrastructures. Universal adult vaccination may be appropriate in the near future considering practical feasibility.
Project description:Currently, there are two safe and effective therapeutic strategies for chronic hepatitis B treatment, namely, nucleoside analogs and interferon alpha (pegylated or non-pegylated). These treatments can control viral replication and improve survival; however, they do not eliminate the virus and therefore require long-term continued therapy. In addition, there are significant concerns about virus rebound on discontinuation of therapy and the development of fibrosis and hepatocellular carcinoma despite therapy. Therefore, the search for new, more effective, and safer antiviral agents that can cure hepatitis B virus (HBV) continues. Anti-HBV drug discovery and development is fundamentally impacted by our current understanding of HBV replication, disease physiopathology, and persistence of HBV covalently closed circular DNA (cccDNA). Several HBV replication targets are the basis for novel anti-HBV drug development strategies. Many of them are already in clinical trial phase 1 or 2, while others with promising results are still in preclinical stages. As research intensifies, potential HBV curative therapies and modalities in the pipeline are now on the horizon.