Vaccine-preventable disease control in the People's Republic of China: 1949-2016.

BACKGROUND: China's immunization program is one of the oldest and largest in the world. Rates of vaccine-preventable diseases (VPD) are comparable to those in high-income countries. The program's evolution has been characterized by ambitious target setting and innovative strategies that have not been widely described. METHODS: We reviewed national and provincial health department archives; analyzed disease surveillance, vaccination coverage, and serosurvey data from 1950 through 2016; and, conducted in-depth interviews with senior Chinese experts involved early VPD control efforts. RESULTS: Widespread immunization began in the 1950s with smallpox, diphtheria, and Bacillus-Calmette Guerin vaccines, and in the 1960s with pertussis, tetanus, polio, measles, and Japanese encephalitis (JE) vaccines. The largest drops in absolute VPD burden occurred in the 1970s with establishment of the Rural Cooperative Medical System and a cadre of trained peasant health workers whose responsibilities included vaccinations. From 1970 to 1979, incidence per 100,000 population dropped 48% from 3.3 to 1.75 for diphtheria, 50% from 152.2 to 49.4 for pertussis, 77% from 2.5 to 0.6 for polio, 60% from 450.5 to 178.3 for measles, and 72% from 18.0 to 5.1 for JE, averting an average of 4 million VPD cases each year. Until the early 1980s, vaccines were delivered through annual winter campaigns using a coordinated 'rush-relay' system to expedite transport while leveraging vaccine thermostability. Establishment of the cold chain system during in the 1980s allowed bi-monthly vaccination rounds and more timely vaccination resulting in rates of diphtheria, pertussis, measles and meningitis falling over 90% from 1980 to 1989, while polio and JE rates fell 40-50%. In the 1990s, progress stalled as financing for public health was weakened by broad market reforms. Large investments in public health and immunizations by the central government since 2004 has led to further declines in VPD burden and increased equity. During 2011-2016, the incidence per 100,000 population was <2.0 for measles and <0.2 for pertussis, JE, meningococcal meningitis, and hepatitis A. From 1992 to 2014, the prevalence of chronic hepatitis B infection in children <5 years fell from 9.7% to 0.3%, a 97% decline. China was certified polio-free in 2000 and diphtheria was last reported in 2006. CONCLUSIONS: Long-term political commitment to immunizations as a basic right, ambitious targets, use of disease incidence as the primary metric to assess program performance, and nationwide scale-up of successful locally developed strategies that optimized use of available limited resources have been critical to China's success in controlling vaccine-preventable diseases.

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.

Loss of confidence in vaccines following media reports of infant deaths after hepatitis B vaccination in China.

BACKGROUND: China reduced hepatitis B virus (HBV) infection by 90% among children under 5 years old with safe and effective hepatitis B vaccines (HepB). In December 2013, this success was threatened by widespread media reports of infant deaths following HepB administration. Seventeen deaths and one case of anaphylactic shock following HBV vaccination had been reported. METHODS: We conducted a telephone survey to measure parental confidence in HepB in eleven provinces at four points in time; reviewed maternal HBV status and use of HepB for newborns in birth hospitals in eight provinces before and after the event; and monitored coverage with hepatitis B vaccine and other programme vaccines in ten provinces. RESULTS: HepB from the implicated company was suspended during the investigation, which showed that the deaths were not caused by HepB vaccination. Before the event, 85% respondents regarded domestic vaccines as safe, decreasing to 26.7% during the event. During the height of the crisis, 30% of parents reported being hesitant to vaccinate and 18.4% reported they would refuse HepB. Use of HepB in the monitored provinces decreased by 18.6%, from 53 653 doses the week before the event to 43 688 doses during the week that Biokangtai HepB was suspended. Use of HepB within the first day of life decreased by 10% among infants born to HBsAg-negative mothers, and by 6% among infants born to HBsAg-positive mothers. Vaccine refusal and HepB birth dose rates returned to baseline within 2 months; confidence increased, but remained below baseline. CONCLUSIONS: The HBV vaccine event resulted in the suspension of a safe vaccine, which was associated with a decline of parental confidence, and refusal of vaccination. Suspension of a vaccine can lead to loss of confidence that is difficult to recover. Timely and credible investigation, accompanied by proactive outreach to stakeholders and the media, may help mitigate negative impact of future coincidental adverse events following immunization.

Neurological sequelae of hospitalized Japanese encephalitis cases in Gansu province, China.

We conducted a follow-up survey for 55 Japanese encephalitis (JE) cases 1-2 years after hospital discharge in Gansu province, China. Community-, education-, and gender-matched healthy individuals without history of neurologic disease were selected as the comparison group. All subjects received neurological examination, intelligence quotient (IQ) measurement, adaptive behavior measurement, and Wechsler memory scale (WMS) assessment. We found 43.6% JE cases had at least one nervous system sequelae compared with 3.6% healthy individuals. Among JE cases, 22.4% had subnormal IQ, 18.4% subnormal verbal IQ (VIQ), 20.4% subnormal performance IQ (PIQ), and 78.4% had subnormal memory quotient (MQ). Among healthy individuals, 2.0% had subnormal IQ, VIQ, or PIQ and 8.1% had subnormal MQ. Among adult JE cases, 47.8% and 39.1% had adaptive behavior impairments and intellectual disability, respectively, compared with 18.8% and 9.7% among young cases, respectively. The results showed both adult and young surviving JE cases had significant neurological sequelae and mental disability 1-2 years after discharged.

An outbreak following importation of wild poliovirus in Xinjiang Uyghur Autonomous Region, China, 2011.

BACKGROUND: After more than 10 years without a case of wild poliovirus (WPV) in China, an outbreak occurred in 2011 in Xinjiang Uyghur Autonomous Region. METHODS: Acute flaccid paralysis (AFP) case surveillance was strengthened with epidemiological investigations and specimen collection and serological surveys were conducted among hospitalized patients. RESULTS: There were 21 WPV cases and 23 clinical compatible polio cases reported. WPV was isolated from 14 contacts of AFP cases and 13 in the healthy population. Incidence of WPV and clinical compatible polio cases were both highest among children <1 years, however, 24/44 (54.5%) polio cases were reported among adults aged 15-39 years. CONCLUSIONS: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Expansion of AFP case surveillance and use of serologic surveys to estimate population immunity should be conducted rapidly to guide preparedness and response planning for future WPV outbreaks.

Prevalence of meningococcal meningitis in China from 2005 to 2010.

BACKGROUND: We aimed to estimate the prevalence and epidemiologic characteristics of meningococcal meningitis (MM) in mainland China (excluding Taiwan, Hong Kong, and Macau) and to provide reference data for controlling the outbreak and prevalence of MM. METHODS: Data from the National Notifiable Diseases Registry System and the MM case information reporting system from 2005 to 2010 as well as data from the MM Surveillance System were used. RESULTS: The morbidity of MM for the whole country was, on average, 0.09 cases per 100,000 (range 0.02 [2010]-0.18 [2005] cases per 100,000) from 2005 to 2010, the incidence rate was highest in the Xinjiang autonomous region (average 0.56 cases per 100,000), and the majority of cases came from Anhui province (average 0.32 cases per 100,000). Morbidity was highest in children under 1 year old (average 0.60 cases per 100,000). The proportion of laboratory-confirmed cases of serogroups A, B, and C were 37.2, 11.5 and 42.7, respectively, from 2005 to 2010. CONCLUSIONS: The incidence level declined year-to-year in mainland China. Children and students are the most at risk groups. The proportion of serogroup C cases has increased year-to-year, and new cases of serogroup W135 have been found. Controlling the epidemic of serogroup C and preventing outbreaks of serogroup B and W135 represent major future challenges.

Sero-survey of polio antibodies during wild poliovirus outbreak in southern Xinjiang Uygur Autonomous Region, China.

BACKGROUND: After being polio free for more than 10 years, an outbreak following importation of wild poliovirus (WPV) was confirmed in Xinjiang Uygur Autonomous Region, China, in 2011. METHODS: A cross-sectional study was conducted prior to supplementary immunization activities (SIAs), immediately after the confirmation of the WPV outbreak. In selected prefectures, participants aged ≤ 60 years old who visited hospitals at county-level or above to have their blood drawn for reasons not related to the study, were invited to participate in our study. Antibody titers ≥ 8 were considered positive. RESULTS: Among the 2,611 participants enrolled, 2,253 (86.3%), 2,283 (87.4%), and 1,989 (76.2%) were seropositive to P1, P2 and P3 respectively, and 1744 (66.8%) participants were seropositive to all the three serotypes. Lower antibody seropositivities and geometric mean titers were observed in children <1 year of age and in adults aged 15-39 years. CONCLUSION: Serosurveys to estimate population immunity in districts at high risk of polio importation might be useful to gauge underlying population immunity gaps to polio and possibly to guide preparedness and response planning. Consideration should be given to older children and adults during polio risk assessment planning and outbreak response.

Identification and control of a poliomyelitis outbreak in Xinjiang, China.

BACKGROUND: The last case of infection with wild-type poliovirus indigenous to China was reported in 1994, and China was certified as a poliomyelitis-free region in 2000. In 2011, an outbreak of infection with imported wild-type poliovirus occurred in the province of Xinjiang. METHODS: We conducted an investigation to guide the response to the outbreak, performed sequence analysis of the poliovirus type 1 capsid protein VP1 to determine the source, and carried out serologic and coverage surveys to assess the risk of viral propagation. Surveillance for acute flaccid paralysis was intensified to enhance case ascertainment. RESULTS: Between July 3 and October 9, 2011, investigators identified 21 cases of infection with wild-type poliovirus and 23 clinically compatible cases in southern Xinjiang. Wild-type poliovirus type 1 was isolated from 14 of 673 contacts of patients with acute flaccid paralysis (2.1%) and from 13 of 491 healthy persons who were not in contact with affected persons (2.6%). Sequence analysis implicated an imported wild-type poliovirus that originated in Pakistan as the cause of the outbreak. A public health emergency was declared in Xinjiang after the outbreak was confirmed. Surveillance for acute flaccid paralysis was enhanced, with daily reporting from all public and private hospitals. Five rounds of vaccination with live, attenuated oral poliovirus vaccine (OPV) were conducted among children and adults, and 43 million doses of OPV were administered. Trivalent OPV was used in three rounds, and monovalent OPV type 1 was used in two rounds. The outbreak was stopped 1.5 months after laboratory confirmation of the index case. CONCLUSIONS: The 2011 outbreak in China showed that poliomyelitis-free countries remain at risk for outbreaks while the poliovirus circulates anywhere in the world. Global eradication of poliomyelitis will benefit all countries, even those that are currently free of poliomyelitis.

An economic evaluation of the use of Japanese encephalitis vaccine in the expanded program of immunization of Guizhou province, China.

BACKGROUND: Historically, China's Japanese encephalitis vaccination program was a mix of household purchase of vaccine and government provision of vaccine in some endemic provinces. In 2006, Guizhou, a highly endemic province in South West China, integrated JE vaccine into the provincial Expanded Program on Immunization (EPI); later, in 2007 China fully integrated 28 provinces into the national EPI, including Guizhou, allowing for vaccine and syringe costs to be paid at the national level. We conducted a retrospective economic analysis of JE integration into EPI in Guizhou province. METHODS: We modeled two theoretical cohorts of 100,000 persons for 65 years; one using JE live-attenuated vaccine in EPI (first dose: 95% coverage and 94.5% efficacy; second dose: 85% coverage and 98% efficacy) and one not. We assumed 60% sensitivity of surveillance for reported JE rates, 25% case fatality, 30% chronic disability and 3% discounting. We reviewed acute care medical records and interviewed a sample of survivors to estimate direct and indirect costs of illness. We reviewed the EPI offices expenditures in 2009 to estimate the average Guizhou program cost per vaccine dose. RESULTS: Use of JE vaccine in EPI for 100,000 persons would cost 434,898 US$ each year (46% of total cost due to vaccine) and prevent 406 JE cases, 102 deaths, and 122 chronic disabilities (4554 DALYs). If we ignore future cost savings and only use EPI program cost, the program would cost 95.5 US$/DALY, less than China Gross Domestic Product per capita in 2009 (3741 US$). From a cost-benefit perspective taking into account future savings, use of JE vaccine in EPI for a 100,000-person cohort would lead to savings of 1,591,975 US$ for the health system and 11,570,989 US$ from the societal perspective. CONCLUSIONS: In Guizhou, China, use of JE vaccine in EPI is a cost effective investment. Furthermore, it would lead to savings for the health system and society.

[Analysis of prevalence season and trend of meningococcal disease by circular distribution in China].

OBJECTIVE: To analyze the prevalence season and trend of meningococcal disease in China by epidemic years from 2004 to 2008 in order to provide scientific basis for making strategies ofmeningococcal disease prevention and control. METHODS: The incidence numbers of meningococcal disease were calculated by weeks, epidemic years and areas. The seasonality and prevalence trends of meningococcal disease were analyzed by circular distribution. RESULTS: The incidence trend of meningococcal disease had obvious seasonality in China (P < 0.01). The peak of meningococcal disease were different by epidemic years and areas (P < 0.01). There were no association between annual incidence rates and seasonality. CONCLUSIONS: We should strength meningococcal disease surveillance before epidemic peak period,and put immunoprophylaxis first and carry out comprehensive measures of prevention and control.

[Estimation on the level of birth and death rates of population in the three gorges area by means of capture-mark-recapture method].

OBJECTIVE: To evaluate quality of surveillance and emendate rates of birth and death of population of the Three Gorges area. METHODS: Data on the two samples collected were designed based on principle of capture-recapture method. An investigation of missing report of birth and death was conducted in 7061 families selected through stratified random sampling method. We collected and registered the data of birth and death in every family investigated and checked with correlative records reported in disease surveillance system of the Three Gorges area. The missing report rates and the 95% confidence intervals of birth rate and death rate were calculated. RESULTS: The underreporting rates of birth and death were 13.91% and 15.60% and death of infant was 33.33%. The emended birth rate was 8.92 per thousandth and the 95% confidence interval of birth rate was 8.38 per thousandth-9.45 per thousandth. The emended report rate of death was 6.88 per thousandth and the collectivity 95% confidence interval was 6.37%-7.38 per thousandth. CONCLUSION: Results showed that the quality of birth and death in the disease surveillance reporting system of Three Gorges area was competent to the quality level of the standard set for national disease surveillance system. The birth and death rates of population in the Three Gorges area were under 10.00 per thousandth.