Risk factors for measles virus infection and susceptibility in persons aged 15 years and older in China: A multi-site case-control study, 2012-2013.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. METHODS: Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. RESULTS: 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1-3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6-38.8%). CONCLUSIONS: Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.

Measles and Rubella Global Strategic Plan 2012-2020 midterm review report: Background and summary.

Measles, a vaccine-preventable illness, is one of the most infectious diseases known to man. In 2015, an estimated 134,200 measles deaths occurred globally. Rubella, also vaccine-preventable, is a concern because infection during pregnancy can result in congenital defects in the baby. More than 100,000 babies with congenital rubella syndrome were estimated to have been born globally in 2010. Eradication of both measles and rubella is considered to be feasible, beneficial, and more cost-effective than high-level control. All six World Health Organization (WHO) regions have measles elimination goals by 2020 and two have rubella elimination goals by that year. However, the World Health Assembly has not endorsed a global eradication goal for either disease. In 2012, the Measles and Rubella Initiative published a Global Measles and Rubella Strategic Plan, 2012-2020, referred to hereafter as the Plan, which aimed to achieve measles and rubella elimination in at least five WHO regions by end-2020 through the implementation of five core strategies, with progress evaluated against 2015 milestones. When, by end-2015, none of these milestones had been met, WHO's Strategic Advisory Group of Experts on Immunization (SAGE) recommended a mid-term review of the Plan to evaluate progress toward goals, assess the quality of strategy implementation, and formulate lessons learned. A five-member team reviewed documents and conducted interviews with stakeholders as the basis for the review's conclusions and recommendations. This team concluded that, although significant progress in measles elimination had been made, progress had slowed. It recommended that countries continue to work toward elimination goals with a focus on strengthening ongoing immunization systems. In addition, it concluded that the strategies articulated in the Plan were sound, however full implementation had been impeded by inadequate country ownership and global political will, reflected in inadequate resources. Detailed recommendations for each of the Plan's five strategies as well as the areas of polio transition, governance and resource mobilization are outlined.

Demographic transition and the dynamics of measles in six provinces in China: A modeling study.

BACKGROUND: Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. METHODS AND FINDINGS: We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%-97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%-73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%-87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting. CONCLUSIONS: The age distribution of measles cases changes in response to both demographic and vaccination processes. Combining both processes in a novel catalytic model, we illustrate that age-specific incidence patterns reveal regional differences in the progress to measles elimination and the impact of vaccination controls in China. The shift in the age distribution of measles susceptibility in response to demographic and vaccination processes emphasizes the importance of progressive control strategies and measures to evaluate program success that anticipate and react to this transition in observed incidence.

Risk factors for measles infection in 0-7 month old children in China after the 2010 nationwide measles campaign: A multi-site case-control study, 2012-2013.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case-control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0-7 months. METHODS: Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. RESULTS: Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5-7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. CONCLUSIONS: Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.

Risk factors for measles in children aged 8 months-14 years in China after nationwide measles campaign: A multi-site case-control study, 2012-2013.

INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. In 2011, almost half of the 9943 measles cases in China occurred in children eligible for measles vaccination. We conducted a case-control study during 2012-2013 to identify risk factors for measles infection in children aged 8 months-14 years. METHODS: Children with laboratory-confirmed measles were age- and neighborhood-matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. We calculated adjusted matched odds ratios and 95% confidence intervals of risk factors. We calculated attributable fractions for risk factors that could be interpreted as causal and vaccine efficacy (VE) for the measles containing vaccine (MCV) used in the Chinese immunization program. RESULTS: In all, 969 case-patients and 2845 controls were enrolled. In multivariable analysis, lack of measles vaccination both overall (mOR 22.7 [16.6, 31.1] and when stratified by region (east region, mOR 74.2 [27.3, 202]; central/western regions mOR 17.4 [12.5, 24.3]), hospital exposure (mOR 63.0, 95% CI [32.8, 121]), and migration among counties (overall mOR 3.0 [2.3, 3.9]) were significant risk factors. The calculated VE was 91.9-96.1% for a single dose of MCV and 96.6-99.5% for 2 doses. CONCLUSIONS: Lack of vaccination was the leading risk factor for measles infection, especially in children born since the 2010 supplementary immunization activity. Reducing missed vaccination opportunities, improving immunization access for migrant children, and strengthening school/kindergarten vaccine checks are needed to strengthen the routine immunization program and maintain progress toward measles elimination in China.

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.

Improving hepatitis B vaccine timely birth dose coverage: lessons from five demonstration projects in China, 2005-2009.

BACKGROUND: Delivery of a timely (within 24h) hepatitis B vaccine birth dose (TBD) is essential to prevent the long-term complications of hepatitis B virus (HBV) infection. China made substantial progress in hepatitis B immunization coverage, however, in 2004, TBD coverage was lower in Western, poorer provinces. METHODS: We reviewed five demonstration projects for the promotion of TBD in rural counties in Qinghai, Gansu and Ningxia. Interventions consisted of (1) work to increase TBD coverage in hospitals, including training of health-care workers, (2) information, education and communication [IEC] with the population and (3) micro-plans to deliver TBD for home births. We evaluated outcome through measuring TBD coverage for home and hospital births. RESULTS: These projects were implemented in the context of national efforts to promote institutional deliveries that lead to increases ranging from 10% to 17% to reach 43-97% proportion of institutional births at the end of the projects. Among institutional births, TBD coverage increased by 2% to 13% to reach post implementation coverage ranging from 98% to 100%. Among home births, TBD coverage increased by 7% to 56% to reach post implementation coverage ranging from 29% to 88%. Overall, TBD coverage increased by 4% to 36% to reach post implementation coverage ranging from 82% to 88%. CONCLUSIONS: Demonstration projects based on combined interventions increased TBD coverage. Increases in institutional births amplified the results obtained. Use of standardized indicators for such projects would facilitate evaluation and identify intervention components that are most effective.

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.

Etiology of a suspected measles outbreak: preceding measles reduction activities in Pakistan.

OBJECTIVE: To characterize patients with suspected measles, determine the magnitude of the outbreak in selected areas, and perform laboratory testing on patients with suspected measles to confirm the etiology of the outbreak. STUDY DESIGN: Cross-sectional survey. PLACE AND DURATION OF STUDY: Islamabad and Rawalpindi in June 2006. METHODOLOGY: Survey and specimen collection from households was carried out in areas affected by rash and fever during the outbreak. Teams asked if household members had rash and fever and administered a detailed questionnaire of clinical signs and symptoms for measles for each person who reported a rash and fever episode. A sample of cases with fever, rash, and either cough, conjunctivitis, or coryza was laboratory tested for measles and rubella. RESULTS: Of 2,225 households visited, 284 individuals met the rash and fever case definition. Laboratory testing of eleven blood specimens revealed that the rash and fever outbreak was caused by rubella in 6 and measles in 2 with three equivocal results. CONCLUSION: Laboratory confirmation of suspected measles cases is essential during measles elimination activities in Pakistan and other countries with endemic rubella.

Comparison of two survey methodologies to assess vaccination coverage.

BACKGROUND: Measuring vaccination coverage permits evaluation and appropriate targeting of vaccination services. The cluster survey methodology developed by the World Health Organization, known as the 'Expanded Program on Immunization (EPI) methodology', has been used worldwide to assess vaccination coverage; however, the manner in which households are selected has been criticized by survey statisticians as lacking methodological rigor and introducing bias. METHODS: Thirty clusters were selected from an urban (Ambo) and a rural (Yaya-Gulelena D/Libanos) district of Ethiopia; vaccination coverage surveys were conducted using both EPI sampling and systematic random sampling (SystRS) of households. Chi-square tests were used to compare results from the two methodologies; relative feasibility of the sampling methodologies was assessed. RESULTS: Vaccination coverage from a recent measles campaign among children aged 6 months through 14 years was high: 95% in Ambo (both methodologies), 91 and 94% (SystRS and EPI sampling, respectively, P-value = 0.05) in Yaya-Gulelena D/Libanos. Coverage with routine vaccinations among children aged 12-23 months was <20% in both districts; in Ambo, EPI sampling produced consistently higher estimates of routine coverage than SystRS. Differences between the two methods were found in demographic characteristics and recent health histories. Average time required to complete a cluster was 16h for EPI sampling and 17 h for SystRS; total cost was equivalent. Interviewers reported slightly more difficulty conducting SystRS. CONCLUSIONS: Because of the methodological advantages and demonstrated feasibility, SystRS would be preferred to EPI sampling in most situations. Validating results in additional settings is recommended.

Measles supplemental immunization activities improve measles vaccine coverage and equity: Evidence from Kenya, 2002.

OBJECTIVES: To compare the measles vaccine coverage achieved through the routine vaccination program with that achieved during the 2002 supplemental immunization activity (SIA) at the national and provincial level, the percentage of previously unvaccinated children (zero-dose children) reached during the SIA, and the equity of measles vaccine coverage among children aged 9-23 months in Kenya. METHODS: Using data from a post-SIA coverage survey conducted in Kenya, we compute routine and SIA measles vaccine coverage and the percent of zero-dose children vaccinated during the SIA at the national and provincial level. Nationwide and for each province, we use the concentration index (CI) to measure equity of measles vaccine coverage. RESULTS: The SIA improved both coverage and equity, achieving significantly higher coverage in all provinces with routine measles vaccination coverage less than 80%, reached a large percentage of zero-dose children in these provinces, and reached more children belonging to the poorest households. CONCLUSION: Overall, by improving both measles vaccine coverage and equity in Kenya, the 2002 SIA reduced the gap in immunity between rich and poor households. Measles SIAs provide an ideal platform for delivering other life-saving child health interventions.

Nationwide outbreak of red eye syndrome associated with transfusion of leukocyte-reduced red blood cell units.

OBJECTIVE: To characterize red eye reactions occurring within 24 hours after receipt of units of leukocyte-reduced red blood cells, determine their etiology, and investigate their potential link to transfusion. METHODS: We conducted a survey of transfusion facilities nationwide to determine the scope and magnitude of the reactions; performed case-control and cohort studies among transfused patients at the facility where most reactions occurred; and performed animal experiments, using cellulose acetate derivatives extracted from leukocyte-reduction filters and filter precursors, to reproduce reactions. RESULTS: From January 1, 1997, through January 15, 1998, we identified 159 reactions in 117 patients from 17 states. Reactions were characterized by conjunctival erythema or hemorrhage (in 100% of patients), eye pain (in 62%), photophobia (in 46%), and decreased visual acuity (in 32%). Symptom onset occurred 1-24 hours after initiation of transfusion and resolved within a median of 5 days. Reactions were associated with transfusion sessions that included units of red blood cells filtered with a specific brand of filter, the LeukoNet filter (HemaSure) (odds ratio, 100.4; P<.001). There was a dose-response relationship between the number of LeukoNet-filtered units transfused and the attack rate for reactions, ranging from 0.8% among sessions in which 1 unit was transfused to 27.3% among sessions in which 3 or more units were transfused (P<.001). A similar ocular syndrome was elicited in rabbits injected with cellulose acetate derivatives extracted from unused LeukoNet filters or filter precursors. No reactions were reported after LeukoNet filters were withdrawn from the market. CONCLUSIONS: This transfusion-associated red eye syndrome was linked to a specific brand of leukocyte-reduction filter and likely resulted from cellulose acetate derivatives leached from the filter membrane.

Retrospective measles outbreak investigation: Sudan, 2004.

Recent population-based studies of measles incidence and deaths in Sudan are not available. To determine the epidemiology and case-fatality rate (CFR) of measles, we conducted a retrospective outbreak investigation in two states in northern Sudan. Of 1144 case-patients identified, 92% were <15 years; 48.6% were vaccinated; and 62% received vitamin A before illness. Ten measles-associated deaths were identified (CFR 0.9%; 95% confidence interval 0.16-1.91). CFR determined by this investigation is lower than expected for the region but remains 10 times higher than that in developed countries. Measles control should be strengthened by improving vaccine coverage, measles surveillance and case-management.

Economic evaluation of measles catch-up and follow-up campaigns in Afghanistan in 2002 and 2003.

This paper assesses the cost-effectiveness of, and the return on the investment in, the 2002 catch-up and the 2003 follow-up measles campaigns in Afghanistan from the perspective of the donor. The catch-up campaign targeted nearly 12 million children aged between six months and 12 years, while the follow-up campaign targeted over five million children aged between 9 and 59 months. Both campaigns successfully vaccinated approximately 96 per cent of the respective target populations, and are expected to avert an estimated 301,000 measles deaths over the next 10 years. The average cost per dose of measles vaccine delivered was USD 0.40. The cost per death prevented is USD 23.6, assuming a case fatality rate of 10 per cent and a discount rate of three per cent. With more than 42,000 measles deaths avoided for every one million US dollars spent, the campaigns are an excellent public health investment for precluding childhood mortality in a country affected by a complex emergency.

Case-fatality rate during a measles outbreak in eastern Niger in 2003.

BACKGROUND: The World Health Organization (WHO) estimates that the case-fatality rate (CFR) for measles in West Africa is 4%-6%. In Niger, 50,138 measles cases and 201 deaths (CFR, 0.4%) were reported in 2003. We conducted an investigation to determine the epidemiology and the true CFR of measles in the Mirriah district in Niger. METHODS: Twenty-two villages from the Mirriah district that reported measles cases in 2003 were included in the investigation. A comprehensive household search for measles cases and deaths was conducted, and serum samples from 12 villages were collected for laboratory confirmation. A measles case was defined as illness characterized by fever, rash, and either cough, coryza, or conjunctivitis, with rash onset during the period from 1 January 2003 to 15 April 2003. Deaths occurring within 30 days after rash onset were attributed to measles unless they were obviously due to other causes. RESULTS: Measles was confirmed serologically in all villages from which samples were collected. Of 945 case patients identified, 900 (95.2%) were aged <15 years, 114 (12.3%) were vaccinated, and 789 (83.5%) sought treatment at a health care facility. A total of 92 deaths were attributed to measles (CFR, 9.7%; 95% confidence interval, 7.9%-11.5%). The CFR was highest in infants aged <1 year (15.6%). Households with >or=2 case patients had a higher CFR (10.8%) than that of households with only 1 case patient (6.0%). Households consisting of >or=8 members had a CFR of 12.8%, whereas the CFR of smaller households was 7.1%. CONCLUSIONS: This investigation suggests that the measles CFR in the Mirriah district may be 2-fold higher than the WHO regional estimate and 20-fold higher than the estimate derived from routine surveillance. Reducing measles mortality in Niger will require wide-age-range vaccination campaigns, improvement in routine immunization services, and periodic "follow-up" campaigns.

Cost-effectiveness of three different vaccination strategies against measles in Zambian children.

The vaccination program in Zambia includes one dose of measles vaccine at 9 months of age. The objective of this study was to compare the cost-effectiveness of the current one-dose measles vaccination program with an immunization schedule in which a second dose is provided either through routine health services or through supplemental immunization activities (SIAs). We simulated the expected cost and impact of the vaccination strategies for an annual cohort of 400,000 children, assuming 80% vaccination coverage in both routine and SIAs and an analytic horizon of 15 years. A vaccination program which includes SIAs reaching children not previously vaccinated would prevent on additional 29,242 measles cases and 1462 deaths for each vaccinated birth cohort when compared with a one-dose program. Given the parameters established for this analysis, such a program would be cost-saving and the most cost-effective vaccination strategy for Zambia.