Impact of Influenza and Pneumococcal Polysaccharide Vaccination on Economic Burden from Acute Exacerbations of Chronic Obstructive Pulmonary Disease - Hebei Province, China, November 2018 to November 2020.

What is already known on this topic?: Chronic obstructive pulmonary disease (COPD) exacerbations increase household economic burden, but there is limited evidence from prospective cohort studies in China about the impact of vaccination on economic burden. What is added by this report?: This study demonstrated the economic burden of COPD exacerbations, pneumonia, and hospitalization in COPD patients in China is substantial. Influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately or together, were significantly associated with decreased economic burden. What are the implications for public health practice?: Our study supports evidence on recommendations that COPD patients in China are offered both influenza vaccine and PPSV23.

The Cost-Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine in Seven Chinese Cities.

Objective: This study estimates the cost-effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) among infants in Beijing, Shanghai, Shenzhen, Chengdu, Karamay, Qingdao, and Suzhou. Methods: A previously published cost-effectiveness model comparing vaccination with PCV13 to no vaccination was localized to the included Chinese cities. A systematic literature review was undertaken to identify age-specific incidence rates for pneumococcal bacteremia, pneumococcal meningitis, pneumonia, and otitis media (AOM). Age-specific direct medical costs of treating the included pneumococcal diseases were taken from the Chinese Health Insurance Association database. The base case analysis evaluated vaccine efficacy using direct effect and indirect effects (DE+ IDE). A subsequent scenario analysis evaluated the model outcomes if only DE was considered. A vaccination rate of 70% was used. The model reported outcomes over a one-year period after it was assumed the vaccine effects had reached a steady state (5-7 years after vaccine introduction) to include the direct and indirect effects of vaccination. Health outcomes were discounted at 5% during the steady-state period. Results: Vaccination with PCV13 was cost-effective in the base case analysis for all included cities with the incremental cost-effectiveness ratio (ICER) ranging from 1145 CNY(Shenzhen) to 15,422 CNY (Qingdao) per quality-adjusted life-year (QALY) gained. PCV13 was the dominant strategy in Shanghai with lower incremental costs and higher incremental QALYs. PCV13 remained cost-effective in the DE-only analysis with all ICERs falling below a cost-effectiveness threshold of three times GDP per capita in each city. Conclusions: Vaccination with PCV13 was a cost-effective strategy in the analyzed cities for both the DE-only and DE + IDE analyses. PCV13 became very cost-effective when a vaccination rate was reached where IDE is observed.

Assessment of clogging of managed aquifer recharge in a semi-arid region.

To overcome water scarcity issues in arid and semi-arid regions, Managed Aquifer Recharge (MAR) remains a viable and suitable solution to manage and restore aquifers. However, clogging represents a major issue that can affect the durability and efficiency of MAR structures. The aim of this study was to evaluate the extent of clogging in MAR sites (Berrechid, Morocco). To achieve this objective, two field-based studies were undertaken: the first one consists of implantation of sand-filled columns in the recharge sites to evaluate the surface and subsurface clogging. The second one consists of the implantation of pickets over a 750 m2 area in each recharge site to measure the extent of deposit thickness on the surface of the wadi bed. Results show that, despite the low rainfall (<1.4 mm/day) and the short period (91 days) of the study, the deposits thickness exceeds 3 cm in a large part of the MAR. The suspended solids concentrations measured in recharge sites ranged from 1.1 to 1.4 g/L. Due to the particles retention, the estimation of the saturated hydraulic conductivity (k) of the sand declines over 90% in the immediate entrance of the columns. The k values measured in situ during the drying period ranged from 10-5 to 10-6 m/s. The k values of the cake formed, without cracks, was about 10-8 m/s. The presence of cracks drives the entire infiltration. However, due to the high plasticity index of the MAR soil, a slight reduction of cracks opening during wetting cycles is observed. In addition, particles deposited in these cracks, would contribute actively to the reduction of infiltration. The results of this study clearly showed the MAR sites vulnerability in semi-arid regions due to physical clogging.

Effects of greenspace morphology on mortality at the neighbourhood level: a cross-sectional ecological study.

BACKGROUND: The association between urban greenspace and mortality risk is well known, but less is known about how the spatial arrangement of greenspace affects population health. We aimed to investigate the relation between urban greenspace distribution and mortality risk. METHODS: We did a cross-sectional study in Philadelphia, PA, USA, using high-resolution landcover data for 2008 from the Pennsylvania Spatial Data Access database. We calculated landscape metrics to measure the greenness, fragmentation, connectedness, aggregation, and shape of greenspace, including and omitting green areas 83·6 m2 or smaller, using Geographical Information System and spatial pattern analysis programs. We analysed all-cause and cause-specific mortality (related to heart disease, chronic lower respiratory diseases, and neoplasms) recorded in 2006 for 369 census tracts (small geographical areas with a population of 2500-8000 people). We did negative binomial regression and principal component analyses to assess associations between landscape spatial metrics and mortality, controlling for geographical, demographic, and socioeconomic factors. FINDINGS: A 1% increase in the percentage of greenspace was predicted to reduce all-cause mortality by 0·419% (95% CI 0·050-0·777), with no effect on cause-specific mortality. All-cause mortality was negatively associated with the area of greenspace. A 1 m2 increase in the mean area of greenspace led to a 0·011% (95% CI 0·004-0·018) fall in all-cause mortality and a 0·019% (0·007-0·032) decrease in cardiac mortality; considering only green areas larger than 83·6 m2 would contribute to a 0·002% (95% CI 0·001-0·003) decrease in all-cause mortality and a 0·003% (0·001-0·006) reduction in cardiac deaths. Census tracts with more connected, aggregated, coherent, and complex shape greenspaces had a lower risk of all-cause and cause-specific mortality. The negative association between articulated landscape parcels and all-cause mortality varied with age and education, such that the relation was stronger for census tracts with a higher percentage of older and less well-educated adults. INTERPRETATION: A significant modest association exists between the spatial distribution of greenspace in cities and mortality risk. The overall amount of greenspace alone is probably failing to capture significant variance in local health outcomes and, thus, environment-based health planning should consider the shape, form, and function of greenspace. FUNDING: None.

Evaluating vaccination policies to accelerate measles elimination in China: a meta-population modelling study.

BACKGROUND: Measles is among the most highly infectious human diseases. By virtue of increasingly effective childhood vaccination, together with targeted supplemental immunization activities (SIAs), health authorities in the People's Republic of China have reduced measles' reproduction number from about 18 to 2.3. Despite substantial residual susceptibility among young adults, more in some locales than others, sustained routine childhood immunization likely would eliminate measles eventually. To support global eradication efforts, as well as expedite morbidity and mortality reductions in China, we evaluated alternative SIAs via mechanistic mathematical modelling. METHODS: Our model Chinese population is stratified by immune status (susceptible to measles infection; infected, but not yet infectious; infectious; and recovered or immunized), age (0, 1-4, 5-9, …, 65+ years) and location (31 provinces). Contacts between sub-populations are either empirical or a mixture of preferential and proportionate with respect to age and decline exponentially with distance between locations at age-dependent rates. We estimated initial conditions and most parameters from recent cross-sectional serological surveys, disease surveillance and demographic observations. Then we calculated the reproduction numbers and gradient of the effective number with respect to age- and location-specific immunization rates. We corroborated these analytical results by simulating adolescent and young adult SIAs using a version of our model in which the age-specific contact rates vary seasonally. RESULTS: Whereas the gradient indicates that vaccinating young adults generally is the optimal strategy, simulations indicate that a catch-up campaign among susceptible adolescent schoolchildren would accelerate elimination, with timing dependent on uptake. CONCLUSIONS: These results are largely due to indirect effects (i.e. fewer infections than immunized people might otherwise cause), which meta-population models with realistic mixing are uniquely capable of reproducing accurately.

Routine immunization services costs and financing in China, 2015.

OBJECTIVE: To estimate the costs of routine immunization (RI) services in China in 2015, to provide objective data relevant to investment in the Expanded Program on Immunization, and to contribute to global data on costing and financing of RI. METHODS: The study was conducted between January and March 2016. We selected 276 villages, 138 townships, 46 counties, and 40 prefectures from 15 provinces as investigation sites at random, stratified by eastern, middle, and western regions. Direct cost items included vaccines, personnel, cold chain, surveillance, communication, training, and supervision at the national, provincial, prefecture, county, township, and village levels. We obtained financial data from governmental and external sources. Indirect costs of RI included parents' transportation costs and productivity lost due to taking their children for vaccination. RESULTS: Total direct costs were $92.42 for each child fully immunized ($4.20/dose), which equates to $1529.55 million per birth cohort. RI costs were higher in the eastern region than in the western region, and higher than that of the central region. Vaccination coverage was positively associated with direct routine immunization costs. The cost of the recommended vaccines was $19.08/child and vaccine only accounted for 20.64% of total costs. Operational cost, including surveillance, communication, training and supervision, was $217.31/child, accounting for 14.21% of total cost. The indirect cost per child was $72.86; the total indirect cost was $1205.83 million for the birth cohort. Government investment in RI accounted for about 70% of total costs. Revenue from sales of private-sector vaccine supported the remaining 30% of RI costs. CONCLUSIONS: While government financing has increased, some operating costs continue to be provided from revenue generated by sales of Category 2 (private-sector) vaccines to families. China could benefit from bringing new and underutilized vaccines into the EPI system based on evidence that includes routine immunization vaccine and operations costs.

Assessment of mumps-containing vaccine effectiveness during an outbreak: Importance to introduce the 2-dose schedule for China.

INTRODUCTION: China has used 3 different mumps-containing vaccines (MuCV) since 1990: monovalent mumps vaccine, measles-mumps (MM) vaccine, and measles-mumps-rubella (MMR) vaccine, and one dose MuCV (using MMR at 18 months) has been included in the EPI since 2007. MuCV effectiveness has been of concern following large-scale mumps outbreaks. In 2015, an outbreak of mumps occurred in a primary school, which allow us assess vaccine effectiveness of different MuCVs. METHOD: All children in the school were studied as a retrospective cohort. Vaccination histories and case information were obtained from vaccination records and clinic/hospital logs. Parental questionnaires were used to confirm students' illnesses and calculate attack rate (AR). VE was assessed using the formula, VE = (AR in unvaccinated students- AR in the vaccinated students) / (AR in unvaccinated students). VEs of different type of MuCV were compared. RESULTS: In total, 283 students were identified as clinical mumps among the 2370 students, and 1908 students were included for MuCV VE assessment. 213 (including 21 [8.9%] patients) were 2-dose MuCV recipients (AR: 9.9%), 1165 (including 123 [51.9%] patients) were 1-dose recipients (AR: 10.6%), and 530 (including 93 [39.2%] patients) were unvaccinated (AR: 17.5%). VE was 44% for 2 doses and 40% for one dose. For one-MuCV-dose students, estimated mumps VE was 63% for vaccinated within 3 years (between vaccination and this outbreak); 50% for vaccinated within 3 to 5 years; and 34% for vaccinated more than 5 years. Comparing VE by vaccine type and 5-year interval since vaccination, VE for MMR was 60%, which was consistently higher than VE for monovalent mumps vaccine (22%) and MM (2%). CONCLUSION: This outbreak was associated with low and declining 1-dose MuCV effectiveness. China's immunization program should evaluate the potential of a 2-dose MMR schedule to adequately control mumps.

Cost-effectiveness of the Haemophilus influenzae type b vaccine for infants in mainland China.

OBJECTIVE: The aims of this study were to estimate the cost-effectiveness of the Haemophilus influenzae type b (Hib) vaccine for the prevention of childhood pneumonia, meningitis and other vaccine-preventable diseases in mainland China from a societal perspective and to provide information about the addition of the Hib vaccine to Chinese immunization programs. METHODS: A decision tree and the Markov model were used to estimate the costs and effectiveness of the Hib vaccine versus no Hib vaccine for a birth cohort of 100,000 children in 2016. The disease burden was estimated from the literature, statistical yearbooks and field surveys. Vaccine costs were calculated from government reports and the United Nations International Children's Emergency Fund (UNICEF) website. The WHO cost-effectiveness thresholds were used to evaluate the Hib vaccine intervention. A one-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the parameter uncertainties. RESULTS: Within the hypothetical cohort, under a vaccination coverage of 90%, the Hib vaccine could reduce 91.4% of Hib pneumonia and 88.3% of Hib meningitis; the Hib vaccine could also prevent 25 deaths, 24 meningitis sequelae cases and 9 hearing loss cases caused by Hib infection. From a societal perspective, the incremental cost-effectiveness ratio (ICER) of the Hib vaccine compared with no vaccination was US$ 13,640.1 at the market price, which was less than 3 times the GDP per capita of China in 2016. The ICER of the Hib vaccine was US$ -59,122.9 at the UNICEF price, indicating a cost savings. The largest portion of the uncertainty in the result was caused by the annual incidence of all-cause pneumonia, proportion of pneumonia caused by Hi, vaccine costs per dose, annual incidence of Hib meningitis and costs per episode of meningitis. The models were robust considering parameter uncertainties. CONCLUSION: The Hib vaccine is a cost-effective intervention among children in mainland China. The cost of Hib vaccine should be reduced, and it should be introduced into Chinese immunization programs.

The etiology of community-acquired pneumonia among children under 5 years of age in mainland China, 2001-2015: A systematic review.

BACKGROUND: The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 y and provide evidence for further cost-effectiveness analyses for vaccine development, diagnostic strategies and empirical treatments. METHODS: The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained by searching PubMed, Embase, Web-of Science, and the Chinese databases Wanfang Data and China National Knowledge Infrastructure. All CAP etiological studies on children under 5 y of age from China published in Chinese and English between the years of 2001 and 2015 were included. A total of 48 studies were included in the final review, comprising 100 151 hospitalized children with CAP episodes. Heterogeneity and the percentage of variation between studies was analyzed based on Q statistic and I2 indices, respectively. Random effect models were used to calculate the weighted average rate in all analyses. RESULTS: The most frequently detected bacterial agents were Klebsiella pneumoniae (5.4%), Streptococcus pneumoniae (5.2%), Escherichia coli (5.2%), Staphylococcus aureus (3.9%), Haemophilus influenza (3.6%) and Haemophilus parainfluenzae (3.3%). The most frequently detected viruses were human rhinovirus (20.3%, in just 2 studies), respiratory syncytial virus (RSV, 17.3%), human bocavirus (9.9%), parainfluenza virus (5.8%), human metapneumovirus (3.9%) and influenza (3.5%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were identified in 9.5% and 2.9%, respectively, of children under 5 y of age with CAP. CONCLUSION: This article provides the most comprehensive analysis to date of the factors contributing to CAP in children under 5 y of age. S. pneumoniae, H. influenzae and influenza were the most common vaccine-preventable diseases in children. Corresponding, vaccines should be introduced into Chinese immunization programs, and further economic evaluations should be conducted. RSV is common in Chinese children and preventative measures could have a substantial impact on public health. These data also have major implications for diagnostic strategies and empirical treatments.

Disease burden of community acquired pneumonia among children under 5 y old in China: A population based survey.

BACKGROUND: To obtain the baseline data on the incidence and cost of community acquired pneumonia among under-5 children for future studies, and provide evidence for shaping China's strategies regarding pneumococcal conjugate vaccine (PCV). METHODS: Three townships from Heilongjiang, Hebei and Gansu Province and one community in Shanghai were selected as study areas. A questionnaire survey was conducted to collect data on incidence and cost of pneumonia among children under 5 y old in 2012. RESULTS: The overall incidence of clinically diagnosed pneumonia in children under 5 y old was 2.55%. The incidence in urban area was 7.97%, higher than that in rural areas (1.68%). However, no difference was found in the incidences of chest X-ray confirmed pneumonia between urban and rural areas (1.67% vs 1.23%). X-ray confirmed cases in rural and urban areas respectively accounted for 73.45% and 20.93% of all clinically diagnosed pneumonia. The hospitalization rate of all cases was 1.40%. Incidence and hospitalization rate of pneumonia decreased with age, with the highest rates found among children younger than one year and the lowest among children aged 4 (incidence: 4.25% vs 0.83%; hospitalization: 2.75% vs 0.36%). The incidence was slightly higher among boys (2.92% vs 2.08%). The total cost due to pneumonia for the participants was 1138 733 CNY. The average cost and median cost was 5722 CNY and 3540 CNY separately. Multivariate analysis showed that the only factor related to higher cost was hospitalization. CONCLUSIONS: The disease burden was high for children under 5 y old, especially the infant. PCV has not been widely used among children, and thus further health economics evaluation on introducing PCV into National Immunization Program should be conducted.

Quick assessment of the influence of the Hepatitis B vaccine event on children's vaccination.

OBJECTIVE: From December 2013 to January 2014, a large number of medias in China reported negative information about Hepatitis B vaccine (HepB) safety issues using eye-catching titles, such as "3 infants in Hunan inoculated with HepB occurred adverse event, and 2 died," and that caused crisis of confidence in vaccination, which we called "HepB event." The progress of "HepB event" could be divided into 3 stages which were initiation, peak and ending stages. In order to evaluate the influence of "HepB event" on the attitudes of participants toward Hepatitis B vaccine safety and their intention of vaccinating their children in different stages, and provide evidence for authority departments as soon as possible to take measures to prevent decrease of HepB coverage rate, a quick field investigation was carried out. METHODS: Using convenience sampling methods during the initiation, peak and ending stages of the "HepB event." RESULTS: In the 3 stages of the "HepB event," the awareness rate of the event among participants was rapidly rising, showing that the participants paid great attention to the event, and the information was spread very quickly. The proportion of participants who knew the event but thought that the Hepatitis B vaccine was unsafe were 31%, 37% and 26% respectively in 3 stages. In addition, the acceptance of vaccination by the participants was influenced, the proportion of participants who would like to delay or reject vaccinating their children was up to 43% in the peak stage of the event. CONCLUSIONS: The "HepB event" had impacted on the participants' confidence in the safety of Hepatitis B vaccine. For such event, relevant authority departments need effectively communicate with the media and the public, and promptly issue positive information and the investigation result, thereby reducing the negative impact of the event, and improve the vaccine confidence among the public.

Importance and challenges of accurately counting rotavirus deaths in China, 2002.

Rotavirus mortality is an important component of the total burden of rotavirus disease for children under 5 years old, but accurate estimation is difficult for many developing countries. Here we applied a more direct method to improve estimates of rotavirus mortality in China using 2002 Chinese-specific data. Results indicate that in 2002, approximately 13,400 children under 5 years old in China died from rotavirus and 70% of these deaths occur in rural areas. Thus, a national rotavirus immunization program targeting rural areas with high mortality from diarrhoea could dramatically reduce these deaths and urban areas could reduce childhood hospitalizations attributed to rotavirus by 43%.