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1.
《Vaccine》2021,39(16):2201-2213
BackgroundMeningococcal serogroup B (MenB) has emerged as the leading cause of invasive meningococcal disease (IMD) in several countries following the release of effective vaccines against serogroups A, C, W, and Y. In 2013, however, the first multicomponent MenB vaccine (Bexsero®) was licensed in Europe.AimTo review the evidence on the cost-effectiveness of vaccination against MenB.MethodsSearches were performed in MEDLINE, EMBASE, Web of Science, NHS EED, Econlit, Tufts CEA registry, and HTA. Three reviewers independently screened and selected studies. Using a narrative synthesis, studies were categorized by vaccination strategies. The quality of included studies was assessed using the Comparative Health Economics Evaluation Reporting Standards (CHEERS) checklist.Results13 studies were included. Ten studies were conducted in the European region and three in the Americas. None of the vaccination strategies were considered cost-effective. Including herd effects improved value for money for MenB vaccines. Routine infant vaccination was the most effective short-term strategy, however, adolescent strategies offered the best value for money. Without herd immunity, routine infant vaccination had the lowest incremental cost-effectiveness ratio estimates.ConclusionRoutine MenB vaccination does not offer substantial value for money, mainly due to high vaccine costs and low disease incidence.  相似文献   

2.
OBJECTIVE: To estimate the cost-effectiveness of introducing hepatitis B vaccine into routine infant immunization services in Mozambique, which took place in the year 2001. METHODS: A decision analytic model was used to estimate the impact of hepatitis B vaccination. This model was developed for the WHO to estimate the global burden of disease from hepatitis B. Cost data of vaccine delivery and medical treatment related to hepatitis B infection were collected for the analysis. FINDINGS: The introduction of hepatitis B vaccine has increased the annual budget for immunization services by approximately 56%. It is predicted that more than 4000 future deaths are averted annually by the intervention. In the base case scenario, the incremental costs per undiscounted deaths averted amount to US$436, and the costs per undiscounted DALY averted amount to US$36. Since the major impact of hepatitis B vaccination will not start to be evident for at least another 40 years (deaths from hepatitis B mainly occur between 40-60 years of age), the cost per DALY averted rises to US$47, when using a discount rate of 3% on health effects. We found that the monovalent hepatitis B vaccine was considerably more cost-effective than the hepatitis B vaccine in combination with DTP. INTERPRETATION: If policy makers value future health benefits equal to current benefits, the cost-effectiveness of infant hepatitis B vaccination is in the range of other primary health care interventions for which similar analysis has been undertaken.  相似文献   

3.
《Vaccine》2015,33(32):3850-3858
ObjectiveThe multicomponent, recombinant serogroup B vaccine, 4CMenB, is approved in Europe, Canada and Australia from two months of age. We investigated persistence to booster doses at 12 months of age following infant vaccination, and immune response to catch-up vaccination of toddlers and children up to two years of age.MethodsWe assessed persistence of immune responses after one year in participants vaccinated as infants, and responses to two doses at 12–15 or 24–26 months of age in vaccine-naïve children, as serum bactericidal activity with human complement (hSBA) against indicator strains for four vaccine antigens. Adverse events were recorded after each vaccination.ResultsHigh antibody titers were induced against all four 4CMenB components following booster vaccination in infant-primed toddlers and after two doses in previously unvaccinated toddlers or two-year-olds. Antibodies waned over 12 months, particularly those against NZ OMV. Systemic reactogenicity in toddlers was lower than in infants, and lower again in vaccine-naïve two-year-olds. Local reactogenicity was common in all groups.ConclusionsFour infant or two toddler 4CMenB vaccinations elicit immune responses believed to be protective for the first two years of life, which can be boosted. Reactogenicity is lower in toddlers than in infants.  相似文献   

4.
目的 报告A+C群脑膜炎球菌多糖疫苗(A+C群MPV)在C群流行性脑脊髓膜炎(流脑)暴发疫情中应急接种的安全性、免疫原性和保护效果.方法 在2002年广西来宾市发生C群流脑局部暴发接种A群MPV人群中约6周后应急接种A+C群MPV,观察接种对象局部和全身反应.选择疫点人群71人和非疫点人群43人于应急接种前和接种后1个月采血,用ELISA检测脑膜炎球菌C群和A群多糖抗体IgG.随访接种人群流脑发病情况至免疫后5年.结果 A+C群MPV应急接种率为97%,接种后未观察到严重不良反应.疫点人群、非疫点人群、应急接种前C群抗体阴性者和阳性者的C群流脑抗体阳性率为97.67%~100%,几何平均浓度(GMC)为30.81~37.44 μg/ml,各组人群抗体水平差异无统计学意义.流脑罹患率在及时接种学校(218.58/10万)比不及时接种学校(705.72/10万)减少69.02%.接种人群随访15 760人年未发现流脑临床确诊病例.结论 国产A+C群MPV应急接种可成功扑灭C群流脑暴发疫情,与A群MPV仅间隔6周接种仍然安全,对易感人群可诱导产生高水平的特异性抗体,对已有抗体者可显著提高抗体水平,保护效果至少持续5年.  相似文献   

5.
《Vaccine》2021,39(24):3296-3303
The study investigated the safety of 4-component meningococcal serogroup B vaccination (4CMenB) in routine care. 4CMenB exposure and seizures, febrile seizures and Kawasaki disease were identified from The Health Improvement Network (THIN) database of UK electronic primary healthcare records, 2015–2018. A self-controlled case series analysis was completed. Anaphylaxis, Guillain-Barré syndrome and acute disseminated encephalomyelitis were secondary outcomes.A total of 107,231 children aged 1–18 months received ≥1 doses of 4CMenB vaccination. Most 4CMenB exposure (93%) was on the same day as other vaccines within a complete national immunisation program stage. With day 0 as day of vaccination, 43 seizures occurred in days 0–6 after 239,505 doses, and 23 febrile seizures occurred in days 0–6, and 4 Kawasaki disease cases in days 1–28 after 194,929 4CMenB doses. Adjusted incidence rate ratios including all 4CMenB exposures were 1.43 (95%CI: 1.02–2.02) for seizures and 1.72 (95%CI: 1.08–2.75) for febrile seizures. There were insufficient cases to model Kawasaki disease, and no cases of the secondary outcomes in risk periods when they may be associated with the vaccination.This study shows few cases of the outcomes after vaccination including 4CMenB with an increased risk of seizures and febrile seizures. It is not possible to attribute the finding to one specific vaccination as the majority of 4CMenB was given with other vaccinations.Trial registration: NA.  相似文献   

6.
《Vaccine》2016,34(50):6158-6165
BackgroundTo evaluate the cost-effectiveness of adding 23-valent pneumococcal polysaccharide vaccine (PPSV23) to the immunization schedule for the elderly population (age > 60 years) in Shanghai, China.MethodsA decision-tree model, with data and assumptions adapted from the societal perspective of Shanghai City, was developed to project the health outcomes of PPSV23 vaccination (compared with no vaccination) over a lifetime course. Sensitivity analysis was used to test the model’s robustness. The clinical data, utility and treatment costs related to pneumococcal diseases were either cited from the literature or calculated from local sources.ResultsThe incremental cost-effectiveness ratio of PPSV23 vaccination compared with no vaccination was $16,699/quality-adjusted life years gained, which was lower than the per capita GDP of Shanghai ($16,840). Sensitivity analyses showed that the model’s outcome is robust.ConclusionsRoutine vaccination of the elderly population with PPSV23 is cost-effective in Shanghai, China.  相似文献   

7.
《Vaccine》2015,33(48):6529-6536
The Global Meningococcal Initiative (GMI) was established in 2009 and comprises an international team of scientists, clinicians, and public health officials with expertise in meningococcal disease (MD). Its primary goal is to promote global prevention of MD through education, research, international cooperation, and developing recommendations that include decreasing the burden of severe disease. The group held its first roundtable meeting with experts from Latin American countries in 2011, and subsequently proposed several recommendations to reduce the regional burden of MD. A second roundtable meeting was convened with Latin American representatives in June 2013 to reassess MD epidemiology, vaccination strategies, and unmet needs in the region, as well as to update the earlier recommendations. Special emphasis was placed on the emergence and spread of serogroup W disease in Argentina and Chile, and the control measures put in place in Chile were a particular focus of discussions. The impact of routine meningococcal vaccination programs, notably in Brazil, was also evaluated. There have been considerable improvements in MD surveillance systems and diagnostic techniques in some countries (e.g., Brazil and Chile), but the lack of adequate infrastructure, trained personnel, and equipment/reagents remains a major barrier to progress in resource-poor countries. The Pan American Health Organization's Revolving Fund is likely to play an important role in improving access to meningococcal vaccines in Latin America. Additional innovative approaches are needed to redress the imbalance in expertise and resources between countries, and thereby improve the control of MD. In Latin America, the GMI recommends establishment of a detailed and comprehensive national/regional surveillance system, standardization of laboratory procedures, adoption of a uniform MD case definition, maintaining laboratory-based surveillance, replacement of polysaccharide vaccines with conjugate formulations (wherever possible), monitoring and evaluating implemented vaccination strategies, conducting cost-effectiveness studies, and developing specific recommendations for vaccination of high-risk groups.  相似文献   

8.
Sexually transmitted diseases, a source of widespread morbidity and sometimes mortality, are caused by a diverse group of infections with a common route of transmission. Existing vaccines against hepatitis B virus (HBV) and human papilloma virus 16, 18, 6 and 11 are highly efficacious and cost effective. In reviewing the potential role for other vaccines against sexually transmitted infections (STIs) a series of questions needs to be addressed about the burden of disease, the potential characteristics of a new vaccine, and the impact of other interventions. These questions can be viewed in the light of the population dynamics of sexually transmitted infections as a group and how a vaccine can impact these dynamics. Mathematical models show the potential for substantial impact, especially if vaccines are widely used. To better make the case for sexually transmitted infection vaccines we need better data and analyses of the burden of disease, especially severe disease. However, cost effectiveness analyses using a wide range of assumptions show that STI vaccines would be cost effective and their development a worthwhile investment.  相似文献   

9.
Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar®) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data. Net-indirect effects result from herd protection minus serotype replacement effects. In this study we analyze the impact of net-indirect effects in non-vaccine protected groups of 5 years of age and older with updated assumptions regarding epidemiologic data and health care unit costs. Without net-indirect benefits for non-vaccine protected groups included the cost-effectiveness ratio is estimated at €72,360 per QALY. In order to obtain cost-effectiveness ratios below the threshold of €50,000 per QALY – which is in the middle of the range that is often referred to in the Netherlands – the net-indirect protective effect should at least be 16% of which has been observed in the USA after the introduction of PCV-7.  相似文献   

10.
《Vaccine》2018,36(19):2529-2544
BackgroundThe success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization.MethodsSearches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies.ResultsThirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9–18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9–14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates.ConclusionsThese findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys’ vaccination or extending the age of vaccination.  相似文献   

11.
A live-attenuated vaccine against herpes zoster (HZ) has been approved for use, on the basis of a large-scale clinical trial that suggests that the vaccine is safe and efficacious. This study uses a Markov cohort model to estimate whether routine vaccination of the elderly (60+) would be cost-effective, when compared with other uses of health care resources. Vaccine efficacy parameters are estimated by fitting a model to clinical trial data. Estimates of QALY losses due to acute HZ and post-herpetic neuralgia were derived by fitting models to data on the duration of pain by severity and the QoL detriment associated with different severity categories, as reported in a number of different studies. Other parameters (such as cost and incidence estimates) were based on the literature, or UK data sources. The results suggest that vaccination of 65 year olds is likely to be cost-effective (base-case ICER = £20,400 per QALY gained). If the vaccine does offer additional protection against either the severity of disease or the likelihood of developing PHN (as suggested by the clinical trial), then vaccination of all elderly age groups is highly likely to be deemed cost-effective. Vaccination at either 65 or 70 years (depending on assumptions of the vaccine action) is most cost-effective. Including a booster dose at a later age is unlikely to be cost-effective.  相似文献   

12.
《Vaccine》2016,34(25):2766-2778
Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3 + 1 schedule (with catch-up for children <2 years-old). This review represents the first analysis of the overall impact of a second-generation pneumococcal conjugate vaccine on nasopharyngeal carriage and all the major pneumococcal disease manifestations in a single, pneumococcal conjugate vaccine-naïve, developing country. A total of 15 published articles and 13 congress abstracts were included in the analysis. In children <5 years-old, studies showed a positive impact of PHiD-CV on the incidence of vaccine-type and any-type invasive pneumococcal disease (including decreases in pneumococcal meningitis morbidity and mortality), on pneumonia incidence and mortality, and on otitis media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population.  相似文献   

13.
For over 100 years, large epidemics of meningococcal meningitis have occurred every few years in areas of the African Sahel and sub-Sahel known as the African meningitis belt. Until recently, the main approach to the control of these epidemics has been reactive vaccination with a polysaccharide vaccine after an outbreak has reached a defined threshold and provision of easy access to effective treatment but this approach has not prevented the occurrence of new epidemics. Meningococcal conjugate vaccines, which can prevent meningococcal carriage and thus interrupt transmission, may be more effective than polysaccharide vaccines at preventing epidemics. Because the majority of African epidemics have been caused by serogroup A meningococci, a serogroup A polysaccharide/tetanus toxoid protein conjugate vaccine (PsA–TT) has recently been developed. Results from an initial evaluation of the impact of this vaccine on meningococcal disease and meningococcal carriage in Burkina Faso have been encouraging.  相似文献   

14.
《Vaccine》2018,36(51):7780-7789
Globally, rotavirus is a leading cause of childhood diarrhea and related mortality. Although rotavirus vaccination has been introduced in many countries worldwide, there are numerous low- to middle-income countries that have not yet introduced. Pakistan is one of the countries with the highest number of rotavirus deaths in children under five years. Although rotavirus infection is almost universal among children, mortality is often a result of poor nutrition and lack of access to health care and other aspects of poverty. We assess the impact and cost-effectiveness of introducing childhood rotavirus vaccination in Pakistan. We use household data from the 2012–2013 Demographic Health survey in Pakistan to estimate heterogeneity in rotavirus mortality risk, vaccination benefits, and cost-effectiveness across geographic and economic groups. We estimate two-dose rotavirus vaccination coverage that would be distributed through a routine vaccination program. In addition, we estimate rotavirus mortality (burden), and other measures of vaccine cost-effectiveness and impact by subpopulations of children aggregated by region and economic status. Results indicate that the highest estimated regional rotavirus burden is in Sindh (3.3 rotavirus deaths/1000 births) and Balochistan (3.1 rotavirus deaths/1000 births), which also have the lowest estimated vaccination coverage, particularly for children living in the poorest households. In Pakistan, introduction could prevent 3061 deaths per year with current routine immunization patterns at an estimated $279/DALY averted. Increases in coverage to match the region with highest coverage (Islamabad) could prevent an additional 1648 deaths per year. Vaccination of children in the highest risk regions could result in a fourfold mortality reduction as compared to low risk children, and children in the poorest households have a three to four times greater mortality reduction benefit than the richest. Based on the analysis presented here, the benefits and cost-effectiveness of rotavirus vaccination can be maximized by reaching economically and geographically vulnerable children.  相似文献   

15.
ObjectivesUsing dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions.MethodsWe tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014–2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System.ResultsBased on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs.ConclusionsThe same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.  相似文献   

16.
17.
STUDY OBJECTIVES: The objective of this study was to evaluate the effectiveness of a mass vaccination programme carried out in Catalonia (Spain) in the last quarter of 1997 in response to an upsurge of serogroup C meningococcal disease (SCMD). DESIGN: Vaccination coverage in the 18 month to 19 years age group was investigated by means of a specific vaccination register. Vaccination effectiveness was calculated using the prospective cohort method. Cases of SCMD were identified on the basis of compulsory reporting and microbiological notification by hospital laboratories. Vaccination histories were investigated in all cases. Unadjusted and age adjusted vaccination effectiveness referred to the time of vaccination and the corresponding 95% confidence intervals (CI) were estimated at 6, 12, 18 and 24 months of follow up. SETTING: All population aged 18 months to 19 years of Catalonia. MAIN RESULTS: A total of seven cases of SCMD were detected at six months of follow up (one in the vaccinated cohort), 12 cases at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort). The age adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98) at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24 months. In the target population, cases have been reduced by more than two thirds (68%) two years after the vaccination programme. In the total population the reduction was 43%. CONCLUSION: Vaccination effectiveness has been high in Catalonia, with a dramatic reduction in disease incidence in the vaccinated cohort accompanied by a relevant reduction in the overall population. Given that vaccination coverage was only 54.6%, it may be supposed that this vaccination effectiveness is attributable, in part, to the herd immunity conferred by the vaccine.  相似文献   

18.
《Vaccine》2020,38(31):4816-4819
A possible increased risk of nephrotic syndrome (NS) following a meningococal group B vaccination campaign was identified during active safety surveillance in a province in Quebec, Canada where 4 cases were reported from an exposed population of ~490,000, a higher rate than in provinces not using the vaccine. Meningococcal B vaccine has been given routinely at 2, 4 and 12 months of age in the United Kingdom since September 2015. To investigate the Canadian signal we used English hospital admissions data from 2005 to 2019 in 2–23 month old children to determine whether the rate of NS changed following the introduction of the vaccine. The analysis was stratified by age 2–5 months, 6–11 months, 12–17 months and 18–23 months. The results showed no evidence of an increased risk with incidence rate ratios between 0.81 (95% confidence interval 0.56–1.19) for age 6–11 months and 1.18 (0.84–1.66) for age 12–17 months.  相似文献   

19.
《Vaccine》2023,41(18):2914-2921
BackgroundAlthough use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2–5 years who have already received a full PCV13 series.MethodsWe estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer.ResultsOur base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2–5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained.ConclusionsA further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.  相似文献   

20.
《Vaccine》2020,38(6):1352-1362
IntroductionHuman papillomavirus (HPV) vaccination has not been introduced in many countries in South-Central Asia, including Afghanistan, despite the sub-region having the highest incidence rate of cervical cancer in Asia. This study estimates the potential health impact and cost-effectiveness of HPV vaccination in Afghanistan to inform national decision-making.MethodAn Excel-based static cohort model was used to estimate the lifetime costs and health outcomes of vaccinating a single cohort of 9-year-old girls in the year 2018 with the bivalent HPV vaccine, compared to no vaccination. We also explored a scenario with a catch-up campaign for girls aged 10–14 years. Input parameters were based on local sources, published literature, or assumptions when no data was available. The primary outcome measure was the discounted cost per disability-adjusted life-year (DALY) averted, evaluated from both government and societal perspectives.ResultsVaccinating a single cohort of 9-year-old girls against HPV in Afghanistan could avert 1718 cervical cancer cases, 125 hospitalizations, and 1612 deaths over the lifetime of the cohort. The incremental cost-effectiveness ratio was US$426 per DALY averted from the government perspective and US$400 per DALY averted from the societal perspective. The estimated annual cost of the HPV vaccination program (US$3,343,311) represents approximately 3.53% of the country′s total immunization budget for 2018 or 0.13% of total health expenditures.ConclusionIn Afghanistan, HPV vaccine introduction targeting a single cohort is potentially cost-effective (0.7 times the GDP per capita of $586) from both the government and societal perspective with additional health benefits generated by a catch-up campaign, depending on the government′s willingness to pay for the projected health outcomes.  相似文献   

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