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.

Accelerating measles elimination and strengthening routine immunization services in Guizhou Province, China, 2003-2009.

BACKGROUND: To develop a successful model for accelerating measles elimination in poor areas of China, we initiated a seven-year project in Guizhou, one of the poorest provinces, with reported highest measles incidence of 360 per million population in 2002. METHODS: Project strategies consisted of strengthening routine immunization services, enforcement of school entry immunization requirements at kindergarten and school, conducting supplemental measles immunization activities (SIAs), and enhancing measles surveillance. We measured coverage of measles containing vaccines (MCV) by administrative reporting and population-based sample surveys, systematic random sampling surveys, and convenience sampling surveys for routine immunization services, school entry immunization, and SIAs respectively. We measured impact using surveillance based measles incidence. RESULTS: Routine immunization coverage of the 1st dose of MCV (MCV1) increased from 82% to 93%, while 2nd dose of MCV (MCV2) coverage increased from 78% to 91%. Enforcement of school entry immunization requirements led to an increase in MCV2 coverage from 36% on primary school entry in 2004 to 93% in 2009. Province-wide SIAs achieved coverage greater than 90%. The reported annual incidence of measles dropped from 200 to 300 per million in 2003 to 6 per million in 2009, and sustained at 0.9-2.2 per million in 2010-2013. CONCLUSIONS: This project found that a package of strategies including periodic SIAs, strengthened routine immunization, and enforcing school entry immunization requirements, was an effective approach toward achieving and sustaining measles elimination in less-developed area of China.

Evaluation of the Integrated Management of Childhood Illness guidelines for treatment of intestinal helminth infections among sick children aged 2-4 years in western Kenya.

Anthelmintic treatment of sick preschool-age children at health facilities is a potentially effective strategy for intestinal helminth control in this age-group. We conducted a study from July 1998 to February 1999 in western Kenya to determine whether the Integrated Management of Childhood Illness (IMCI) guidelines' clinical assessment can be used to identify helminth-infected children, and to evaluate the nutritional benefit of treating sick children without pallor with an anthelmintic (mebendazole is already part of IMCI treatment for sick children aged 2-4 years with palmar pallor in areas where hookworm and Trichuris trichiura infections are endemic). Sick children aged 2-4 years seen at 3 rural health facilities were clinically evaluated and tested for haemoglobin concentration, malaria parasites, and intestinal helminths. Children without pallor were randomly assigned to receive a single dose of 500 mg of mebendazole or a placebo and re-examined 6 months later. Among the 574 children enrolled, 11% had one or more intestinal helminths. Most infections were of light intensity. Selected clinical signs and symptoms available from the IMCI assessment, including palmar pallor and low weight-for-age, were not associated with helminth infection. Six months after enrollment, no differences in growth of children without pallor were observed between the mebendazole (n = 166) and placebo (n = 181) groups. However, there was a significantly greater mean increase in weight, height, and weight-for-age Z score among the helminth-infected children in the mebendazole group (n = 22) as compared with helminth-infected children in the placebo group (n = 20). We conclude that even lightly infected preschool-age children without palmar pallor benefit from anthelmintic treatment; however, in this study setting of low helminth prevalence and intensity, helminth-infected children could not be identified using the IMCI guidelines. Cost-effectiveness studies are needed to help define helminth prevalence thresholds for routine anthelmintic treatment of sick preschool-age children seen at first-level health facilities.

The estimated mortality impact of vaccinations forecast to be administered during 2011-2020 in 73 countries supported by the GAVI Alliance.

INTRODUCTION: From August to December 2011, a multidisciplinary group with expertise in mathematical modeling was constituted by the GAVI Alliance and the Bill & Melinda Gates Foundation to estimate the impact of vaccination in 73 countries supported by the GAVI Alliance. METHODS: The number of deaths averted in persons projected to be vaccinated during 2011-2020 was estimated for ten antigens: hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, rotavirus, Neisseria meningitidis serogroup A, Japanese encephalitis, human papillomavirus, measles, and rubella. Impact was calculated as the difference in the number of deaths expected over the lifetime of vaccinated cohorts compared to the number of deaths expected in those cohorts with no vaccination. Numbers of persons vaccinated were based on 2011 GAVI Strategic Demand Forecasts with projected dates of vaccine introductions, vaccination coverage, and target population size in each country. RESULTS: By 2020, nearly all GAVI-supported countries with endemic disease are projected to have introduced hepatitis B, Hib, pneumococcal, rotavirus, rubella, yellow fever, N. meningitidis serogroup A, and Japanese encephalitis-containing vaccines; 55 (75 percent) countries are projected to have introduced human papillomavirus vaccine. Projected use of these vaccines during 2011-2020 is expected to avert an estimated 9.9 million deaths. Routine and supplementary immunization activities with measles vaccine are expected to avert an additional 13.4 million deaths. Estimated numbers of deaths averted per 1000 persons vaccinated were highest for first-dose measles (16.5), human papillomavirus (15.1), and hepatitis B (8.3) vaccination. Approximately 52 percent of the expected deaths averted will be in Africa, 27 percent in Southeast Asia, and 13 percent in the Eastern Mediterranean. CONCLUSION: Vaccination of persons during 2011-2020 in 73 GAVI-eligible countries is expected to have substantial public health impact, particularly in Africa and Southeast Asia, two regions with high mortality. The actual impact of vaccination in these countries may be higher than our estimates because several widely used antigens were not included in the analysis. The quality of our estimates is limited by lack of data on underlying disease burden and vaccine effectiveness against fatal disease outcomes in developing countries. We plan to update the estimates annually to reflect updated demand forecasts, to refine model assumptions based on results of new information, and to extend the analysis to include morbidity and economic benefits.

An outbreak of poliomyelitis caused by type 1 vaccine-derived poliovirus in China.

BACKGROUND: In May-July 2004, type 1 vaccine-derived poliovirus (VDPV) was isolated from 2 case patients with polio and a contact of a third case patient in Guizhou Province. METHODS: We conducted a field investigation of the outbreak, characterized outbreak isolates, and retrospectively reviewed national polio surveillance data for other VDPVs. RESULTS: Case patients were unimmunized children, 0.9-3.2 years old, living in 2 villages 40 km apart. Immunization coverage in the affected villages was very low. Isolates differed from the Sabin 1 type by 9-11 VP1 nucleotides (1.0%-1.2%); which indicated, on the basis of known rates of mutation of Sabin strains, that they had been circulating for <1 year. A province-wide immunization response targeting all children <5 years old was initiated in August, and the strain has not been isolated since. During 1997-2004, 10 VDPV strains (5 of type 2, 3 of type 1, and 2 of type 3) were isolated from >50,000 children with acute flaccid paralysis and their contacts; 8 (80%) were found in southern provinces, and 9 (90%) spontaneously disappeared. CONCLUSION: This is the first polio outbreak in China in over a decade and the first due to VDPV. The short duration of circulation demonstrates the rapidity with which attenuated Sabin strains can revert to a wild phenotype. One to two VDPVs have been identified each year, primarily in densely populated subtropical regions of southern China. This outbreak highlights the need to consider risks of paralysis from vaccine-derived strains in development of national poliomyelitis immunization policy.

Progress in accelerated measles control in the People's Republic of China, 1991-2000.

Measles incidence decreased dramatically following widespread use of measles vaccine in China in 1965. To evaluate continued progress in accelerated measles control, data on measles cases reported to the National Notifiable Disease Reporting System during 1991 to 2000 were analyzed. From 1991-1995 to 1996-2000, average annual measles incidence decreased from 9.0 to 5.7 cases per 100,000 population, mortality rates fell from <0.3 to 0.1 deaths per million population, and the percentage of China's total population residing in provinces with a measles incidence of <2 cases per 100,000 population and having a measles elimination goal increased from 21% to 29%. Incidence rates were highest in western provinces and in infants and young children. Additional attention must be focused on western provinces and toward ensuring that all infants are immunized. Achieving high routine two-dose coverage with measles vaccine and enforcing school entry requirements may be highly effective strategies to support further gains in measles control.

Active case-based surveillance for measles in China: lessons learned from Shandong and Henan provinces.

To identify issues relevant to nationwide implementation, a project was conducted during 1999-2001 to support and evaluate the development of a case-based measles surveillance system (MSS) in Shandong and Henan provinces, China. The performance of MSS surveillance and the descriptive characteristics of reported measles cases and outbreaks were analyzed. Of the 5782 suspected cases in 2001, 85% were investigated and 66% had serologic results. In all, 39% of cases were confirmed, 36% were compatible, and 25% were discarded; 81% of outbreaks identified involved <15 cases. In all, 15% of cases were temporary (floating) residents. The MSS was useful in monitoring the impact of measles control activities. Standardized laboratory quality-assurance activities and indicators should be developed while the system is still in the early stages of implementation.