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While seasonal influenza vaccines (SIV) remain the best method to prevent influenza-associated illnesses, implementing SIV programs may benefit countries beyond disease reduction, strengthening health systems and national immunization programs, or conversely, introduce new challenges. Few studies have examined perceived impacts of SIV introduction beyond disease reduction on health systems; understanding such impacts will be particularly salient in the context of COVID-19 vaccine introduction. We collected qualitative data from key informants-Partnership for Influenza Vaccine Introduction (PIVI) contacts in six middle-income PIVI vaccine recipient countries-to understand perceptions of ancillary benefits and challenges from SIV implementation. Respondents reported benefits associated with SIV introduction, including improved attitudes to SIV among risk groups (characterized by increased demand) and perceptions that SIV introduction improved relationships with other ministries and collaboration with mass media. Challenges included sustaining investment in SIV programs, as vaccine supply did not always meet coverage goals, and managing SIV campaigns.

Background Respiratory diphtheria is a toxin-mediated disease caused by Corynebacterium diphtheriae. Diphtheria-like illness, clinically indistinguishable from diphtheria, is caused by Corynebacterium ulcerans, a zoonotic bacterium that can also produce diphtheria toxin. In the United States, respiratory diphtheria is nationally notifiable: specimens from suspected cases are submitted to the Centers for Disease Control and Prevention (CDC) for species and toxin confirmation, and diphtheria antitoxin (DAT) is obtained from CDC for treatment. We summarize the epidemiology of respiratory diphtheria and diphtheria-like illness and describe DAT use during 1996–2018 in the United States. Methods We described respiratory diphtheria cases reported to the National Notifiable Diseases Surveillance System (NNDSS) and C. ulcerans-related diphtheria-like illness identified through specimen submissions to CDC during 1996–2018. We reviewed DAT requests from 1997 to 2018. Results From 1996 to 2018, 14 respiratory diphtheria cases were reported to NNDSS. Among these 14 cases, 1 was toxigenic and 3 were nontoxigenic C. diphtheriae by culture and Elek, 6 were culture-negative but polymerase chain reaction (PCR)-positive for diphtheria toxin gene, 1 was culture-positive without further testing, and the remaining 3 were either not tested or tested negative. Five cases of respiratory diphtheria-like illness caused by toxigenic C. ulcerans were identified. DAT was requested by healthcare providers for 151 suspected diphtheria cases between 1997 and 2018, with an average of 11 requests per year from 1997 to 2007, and 3 per year from 2008 to 2018. Conclusions Respiratory diphtheria remains rare in the United States, and requests for DAT have declined. Incidental identification of C. ulcerans-related diphtheria-like illness suggests surveillance of this condition might be warranted.

In 2017, a total of 8,819 cases of diphtheria were reported worldwide, the most since 2004. However, recent diphtheria epidemiology has not been well described. We analyzed incidence data and data from the literature to describe diphtheria epidemiology. World Health Organization surveillance data were 81% complete; completeness varied by region, indicating underreporting. As national diphtheria–tetanus–pertussis (DTP) 3 coverage increased, the proportion of case-patients 15 years of age, consistent with waning vaccine immunity. Global DTP3 coverage is suboptimal. Attaining high DTP3 coverage and implementing recommended booster doses are necessary to decrease diphtheria incidence. Collection and use of data on subnational and booster dose coverage, enhanced laboratory capacity, and case-based surveillance would improve data quality.

The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE), a phase 2/3 trial of investigational rVSV∆G-ZEBOV-GP vaccine, was conducted during an unprecedented Ebola epidemic. More than 8600 eligible healthcare and frontline response workers were individually randomized to immediate (within 7 days) or deferred (within 18–24 weeks) vaccination and followed for 6 months after vaccination for serious adverse events and Ebola virus infection. Key challenges included limited infrastructure to support trial activities, unreliable electricity, and staff with limited clinical trial experience. Study staff made substantial infrastructure investments, including renovation of enrollment sites, laboratories, and government cold chain facilities, and imported equipment to store and transport vaccine at ≤−60oC. STRIVE built capacity by providing didactic and practical research training to >350 staff, which was reinforced with daily review and feedback meetings. The operational challenges of safety follow-up were addressed by issuing mobile telephones to participants, making home visits, and establishing a nurse triage hotline. Before the Ebola outbreak, Sierra Leone had limited infrastructure and staff to conduct clinical trials. Without interfering with the outbreak response, STRIVE responded to an urgent need and helped build this capacity. Clinical Trials Registration. ClinicalTrials.gov [{"type":"clinical-trial","attrs":{"text":"NCT02378753","term_id":"NCT02378753"}}NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220].

Background. The Basic Package of Health Services (BPHS) program has increased access to immunization services for children living in rural Afghanistan. However, multiple surveys have indicated persistent immunization coverage gaps. Hence, to identify gaps in implementation, an assessment of the BPHS program was undertaken, with specific focus on the routine immunization (RI) component. Methods. A cross-sectional survey was conducted in 2014 on a representative sample drawn from a sampling frame of 1858 BPHS health facilities. Basic descriptive analysis was performed, capturing general characteristics of survey respondents and assessing specific RI components, and χ2 tests were used to evaluate possible differences in service delivery by type of health facility. Results. Of 447 survey respondents, 27% were health subcenters (HSCs), 30% were basic health centers, 32% were comprehensive health centers, and 12% were district hospitals. Eighty-seven percent of all respondents offered RI services, though only 61% of HSCs did so. Compared with other facility types, HSCs were less likely to have adequate stock of vaccines, essential cold-chain equipment, or proper documentation of vaccination activities. Conclusions. There is an urgent need to address manpower and infrastructural deficits in RI service delivery through the BPHS program, especially at the HSC level.

Greater use of appropriate specimen collection and confirmatory laboratory testing is needed., During September 2006–December 2009, we conducted active population and sentinel laboratory–based surveillance for bacterial meningitis pathogens, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b, in 4 China prefectures. We identified 7,876 acute meningitis and encephalitis syndrome cases, including 6,388 among prefecture residents. A total of 833 resident cases from sentinel hospitals met the World Health Organization case definition for probable bacterial meningitis; 339 of these cases were among children

Background Mother to Child Transmission (MTCT) has remained a leading cause of HBV infection in China, accounting for 40% of total infections. Providing hepatitis B vaccine (HepB) to all infants within 24 h of birth (Timely Birth Dose, TBD), and subsequent completion of at least 3 vaccine doses is key to preventing perinatal HBV infection. In 2002, with the financial support of the Global Alliance on Vaccine and Immunization (GAVI) targeted to Western region and 223 poverty-affected counties in Central region, hepatitis B vaccine was provided for free. In 2010, we evaluated the China GAVI project in terms of its activities to prevent perinatal infections. Objective The objectives of the evaluation were to (1) measure achievements in the China GAVI project in terms of TBD coverage, and (2) describe practices for HBsAg screening of pregnant women and HBIG use outside the GAVI China project. Methods We used the methods recommended by WHO to select a cluster sample of health care facilities for the purpose of an injection safety assessment. We stratified China into three regions based on economic criteria, and selected eight counties with a probability proportional to population size in each region. In each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. In each hospital, we abstracted 2002 through 2009 records to collect information regarding birth cohorts, hospitals deliveries, vaccine management, hepatitis B vaccination delivery, HBsAg screening practices and results, and HBIG administration. In addition, in all hospitals, we abstracted records regarding the delivery of TBD. Results We visited 244 facilities in the three regions, including 24 county hospitals and 220 township hospitals. We reviewed 837,409 birth summary records, 699,249 for infants born at county or township hospitals. Hospital delivery rates increased from 58% in 2002 to 93% in 2009. Surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 (+31%). Surveyed TBD coverage among children born in hospitals increased from 73% in 2002 to 98% in 2009. Between 2002 and 2009, the proportion of pregnant women screened for HBsAg increased from 64% in 2002 to 85% in 2009. In 2009, the proportion of infants born to women screened and found to be HBsAg positive who did not receive any immunization within 24 h after birth ranged from 0% to 0.7% across regions. Conclusions Increased availability of hepatitis B vaccine, along with efforts to improve hospital deliveries, increased TBD coverage in China. This decreased perinatal HBV transmission and will reduce disease burden in the future. Screening for HBsAg to guide HBIG administration has begun, but with heterogeneous immuno-prophylaxis practices and a poor system for follow up.

The China GAVI Project (CGP) was initiated in 2002 to provide hepatitis B (HB) vaccine to infants born in the less developed areas of China including the Western provinces and poverty counties of Middle provinces, to prevent the consequences of hepatitis B virus infection. By 2009, the project areas had raised coverage of 3 doses of HB vaccine and timely birth doses to almost 90% among infants, comparable to those in wealthier Eastern provinces, and reduced HBV prevalence to

To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants.National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA.The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age15 years compared to that found in the 1992 national serosurvey, and among children age5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other).China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.

During the China GAVI project, implemented between 2002 and 2010, more than 25 million children received hepatitis B vaccine with the support of project, and the vaccine proved to be safe and effective. With careful consideration for project savings, China and GAVI continually adjusted the budget, additionally allowing the project to spend operational funds to support demonstration projects to improve timely birth dose (TBD), conduct training of EPI staff, and to monitor the project impact. Results from the final evaluation indicated the achievement of key outcomes. As a result of government co-investment, human resources at county level engaged in hepatitis B vaccination increased from 29 per county on average in 2002 to 66 in 2009. All project counties funded by the GAVI project use auto-disable syringes for hepatitis B vaccination and other vaccines. Surveyed hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009 among infants. The HBsAg prevalence declined from 9.67% in 1992 to 0.96% in 2006 among children under 5 years of age. However, several important issues remain: (1) China still accounts for the largest annual number of perinatal HBV infections (estimated 84,121) in the WHO WPR region; (2) China still lacks a clear national policy for safe injection of vaccines; (3) vaccination of high risk adults and protection of health care workers are still not implemented; (4) hepatitis B surveillance needs to be refined to more accurately monitor acute hepatitis B; and (5) a program for treatment of persons with chronic HBV infection is needed. Recommendations for future hepatitis B control include: using the lessons learned from the China GAVI project for future introductions of new vaccines; addressing unmet needs with a second generation hepatitis B program to reach every infant, including screening mothers, and providing HBIG for infants born to HBsAg positive mothers; expanding vaccination to high risk adults; addressing remaining unsafe injection issues; and improving monitoring of acute hepatitis B. This paper describes findings and discusses perspectives from a final project evaluation, a national stratified validated cross-sectional survey done in October 2010.

Objective In order to measure hepatitis B coverage and progress in equality with respect to protection against hepatitis B in poverty-affected areas funded by the Global Alliance on Vaccine and Immunization project funded in poverty-affected counties. Methods We reviewed routinely reported coverage data and conducted a national stratified, validation, cross-sectional survey in October 2010, according to WHO recommended sampling method. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county. Results We visited 244 townships as part of the final evaluation (71 in the East, 86 in the Center and 87 in the West). Overall, in these 244 townships, surveyed TBD coverage increased from 60% in 2002 to 91% in 2009 and surveyed three dose of hepatitis B vaccine coverage increased from 71% in 2002 to 93% in 2009. Overall, in the GAVI supported areas, the HepB3/DTP3 ratio increased from 57% in 2002 to 94% in 2009. Conclusion Pro-poor GAVI approach was an effective way to reduce inequity among children through provision of free vaccination. When vaccine and AD syringes were provided for free, they closed the gap between Eastern and Western regions and between the rich and the poor.

The incidence rate of Japanese encephalitis (JE) in the People's Republic of China has decreased substantially with the wide use of JE vaccine, but the accuracy of JE reporting is uncertain. We established active surveillance for acute meningitis and encephalitis syndrome (AMES) in four prefectures in China during 2006–2008 and performed JE laboratory testing on AMES cases identified from six sentinel hospitals in each prefecture. We estimated JE incidence for each prefecture by applying age-adjusted and season-adjusted JE positivity rates from sentinel hospitals to the total AMES resident cases. We identified 4,513 AMES cases, including 3,561 (79%) among residents of four prefectures. Among 2,294 AMES cases from sentinel hospitals, we identified 213 (9.2%) laboratory-confirmed JE cases. Adjusted estimates of JE incidence per 100,000 persons ranged from 0.08 in Shijiazhuang to 1.58 in Guigang. Active surveillance and laboratory confirmation provides a better estimate of the actual JE disease burden and should be used to further refine JE prevention strategies.

Background In China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination. Methods We conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24 h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth. Results Three-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992–1997 to 93.2% for children born in 2002–2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992–2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose ( p = 0.04), birth after 1998 ( p p = 0.008) and hospital birth ( p = 0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87). Conclusions Hospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.

To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants.National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA.The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age15 years compared to that found in the 1992 national serosurvey, and among children age5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other).China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.

Surveillance for acute flaccid paralysis with laboratory confirmation has been a key strategy in the global polio eradication initiative, and the laboratory platform established for polio testing has been expanded in many countries to include surveillance for cases of febrile rash illness to identify measles and rubella cases. Vaccine-preventable disease surveillance is essential to detect outbreaks, define disease burden, guide vaccination strategies and assess immunization impact. Vaccines now exist to prevent Japanese encephalitis (JE) and some etiologies of bacterial meningitis.We evaluated the feasibility of expanding polio-measles surveillance and laboratory networks to detect bacterial meningitis and JE, using surveillance for acute meningitis-encephalitis syndrome in Bangladesh and China and acute encephalitis syndrome in India. We developed nine syndromic surveillance performance indicators based on international surveillance guidelines and calculated scores using supervisory visit reports, annual reports, and case-based surveillance data.Scores, variable by country and targeted disease, were highest for the presence of national guidelines, sustainability, training, availability of JE laboratory resources, and effectiveness of using polio-measles networks for JE surveillance. Scores for effectiveness of building on polio-measles networks for bacterial meningitis surveillance and specimen referral were the lowest, because of differences in specimens and techniques.Polio-measles surveillance and laboratory networks provided useful infrastructure for establishing syndromic surveillance and building capacity for JE diagnosis, but were less applicable for bacterial meningitis. Laboratory-supported surveillance for vaccine-preventable bacterial diseases will require substantial technical and financial support to enhance local diagnostic capacity.

BACKGROUND This article reviews the epidemiology of polio, acute flaccid paralysis (AFP) surveillance, and the implementation of supplemental immunization activities (SIAs) in Afghanistan from 1997 thru 2013. METHODS Published reports and unpublished national data on polio cases, AFP surveillance, and SIAs were analyzed. Recommendations from independent advisory groups and Afghan government informed the conclusions. RESULTS From 1997 thru 2013, the annual number of confirmed polio cases fluctuated from a low of 4 in 2004 to a high of 80 in 2011. Wild poliovirus types 2 and 3 were last reported in 1997 and 2010, respectively. Circulating vaccine-derived poliovirus type 2 emerged in 2009. AFP surveillance quality in children aged 8 per 100,000 population. Since 2001, at least 6 SIAs have been conducted annually. CONCLUSIONS Afghanistan has made progress moving closer to eliminating polio. The program struggles to reach all children because of management and accountability problems in the field, inaccessible populations, and inadequate social mobilization. Consequently, too many children are missed during SIAs. Afghanistan adopted a national emergency action plan in 2012 to address these issues, but national elimination will require consistent and complete implementation of proven strategies.

Data obtained in the third National Health and Nutrition Examination Survey (NHANES III), conducted during 1988-1994, were analyzed to determine the epidemiology of rubella seropositivity in the United States, including risk factors for low rubella seropositivity. Serological samples obtained from NHANES III study participants > or =6 years of age were tested for rubella IgG antibodies. "Rubella seropositivity" was defined as serum rubella IgG antibody level > or =10 IU by enzyme immunoassay. Overall, rubella seropositivity rates in the United States were 92% in persons aged 6-11 years, 83% in persons aged 12-19 years, 85% in persons aged 20-29 years, 89% in persons aged 30-39 years, and >or =93% in persons aged > or =40 years. The lowest rate (78%) of any United States birth cohort of the 20th century occurred among persons born from 1970-1974. Eliminating rubella and chronic rubella syndrome in the United States will require international efforts, including vaccination of preschool- and school-age children and all susceptible young adults.

Despite substantial efforts to eradicate poliomyelitis by administering oral poliovirus vaccine through routine immunization and annual national immunization days (NIDs), Pakistan reported 22% (1147) of the worldwide cases in 1997. Reasons for continued high poliomyelitis incidence include failure to vaccinate, vaccine failure, or inadequate immunization strategies. A case-control study was conducted to measure vaccination status and reasons for undervaccination among 66 poliomyelitis cases and 130 age- and neighborhood-matched controls. Cases were undervaccinated through routine immunization (matched odds ratio [MOR], 0.3; 95% confidence interval [CI], 0.1-0.5); however, NID immunization was similar for cases and controls (MOR, 0.6; 95% CI, 0.3-1.2). Reasons for undervaccination included not being informed, considering vaccination unimportant, and long distances to vaccination sites. Failure to vaccinate through routine immunization was a major risk factor for poliomyelitis in Pakistan. Successful NIDs alone will not interrupt poliovirus circulation in Pakistan, and children remain at risk unless routine immunization is strengthened or additional supplementary immunization is provided.

Measles incidence is at a nadir in many parts of the world due to vaccination efforts. Although the technical feasibility of eradication has been acknowledged, financial and political commitment need to be concomitantly identified on the national and global level. We demonstrate the potential value of measles eradication by identifying the potential cost-savings to one country resulting from measles eradication. For the US, measles eradication would save $45 million annually. If achieved by the year 2010, the US would save $500 million to $4.1 billion depending on the year of elimination, post-eradication schedule and discount rate. Intensification of measles control efforts in the US beyond current levels would have minimal marginal benefits on disease burden reduction. Allocation of resources to achieve global measles eradication is the next level of efficiency which would provide substantial savings. Countries may adapt this model to estimate their savings for consideration of the required political and financial contribution towards a global measles eradication program.

As the WHO verified that China reached the target of 1% prevalence of chronic hepatitis B infection among children targeted by universal hepatitis B immunization of newborns, the country considered new options for hepatitis B prevention and control. We reviewed hepatitis B surveillance in the broader context of viral hepatitis surveillance to propose recommendations to improve the system.We described surveillance for viral hepatitis in China with a specific focus on hepatitis B. We assessed critical attributes of the system, including data quality, predictive positive value and usefulness.While remarkable progress in hepatitis B immunization of infants and children has likely almost eliminated transmission in younger age groups, reported rates of hepatitis B increased steadily in China between 1990 and 2008, probably because of a failure to distinguish acute from chronic infections. Elements that prevented a clearer separation between acute and chronic cases included (1) missed opportunity to report cases accurately among clinicians, (2) low availability and use of tests to detect IgM against the hepatitis B core antigen (IgM anti-HBc) and (3) lack of systems to sort, manage and analyze surveillance data.To improve hepatitis B surveillance, China may consider (1) training clinicians to diagnose acute cases and to use IgM anti-HBc to confirm them, (2) improving access and use of validated IgM anti-HBc tests and (3) developing data management and analysis techniques that sort out acute from chronic cases.

Rotavirus infection produces a serious health burden in the United States, causing an estimated >100,000 hospitalizations and >100 deaths annually. This health burden is comparable to that for measles, pertussis, mumps, and varicella before vaccines for these diseases were routinely given to children. Rotavirus vaccines have the potential to significantly reduce a serious public health problem in the United States. However, while development and licensure of vaccines is a major breakthrough, it represents only the first step in disease prevention. Vaccines must be recommended by major immunization advisory committees, financed in both the public and private sectors, and successfully integrated into the existing vaccination schedule. Vaccines must reach all targeted children, and monitoring systems must be established or adapted to better determine vaccine safety and disease impact. Reevaluation of disease prevention strategies must be ongoing and fueled by new information on safety and disease reduction.

China received GAVI support for hepatitis B vaccination in 2001 because of high disease burden and strong government will to protect infants at risk. The China/GAVI project, implemented since 2002, was funded 50% by GAVI and 50% by the Government of China. The purpose of the project was to increase coverage of hepatitis B vaccine through a pro-poor approach targeting all counties of the 12 Western provinces and poverty counties of the 10 Central provinces, to accelerate integration of hepatitis B vaccine into routine immunization, and assure immunization injection safety. The mechanism of internal coordination among multiple government entities and international cooperation was established and comprehensive strategies were used to improve vaccine coverage and injection safety. After 8 years of implementation, 193,000 health care workers in 118,316 health care facilities participated in the project, mostly at the township hospitals level (55,051) and in community centres (104,547). Through the China GAVI project, the 85% HepB3 coverage goal was reached in 98% of GAVI China project counties, the 75% timely birth dose (TBD) coverage goal was reached in 80% of GAVI project counties, and AD syringes were introduced into 100% of GAVI-supported areas. Additionally, the GAVI project was instrumental in convincing the Chinese Government to sustainably introduce and fully fund HepB vaccine for all newborns in China. The impact of hepB vaccination on HBsAg prevalence was observed throughout China, as HBsAg prevalence (previously ∼10%) is now less than 1% among children under 5 years of age.

Objective The study objectives were to evaluate injection practices in China in the post GAVI project era and provide guidance for policy makers to update national standards for injection practices and further improve vaccination services. Methods We conducted a national stratified, cross-sectional survey in October 2010, according to WHO recommended sampling methods. First, we stratified China into three regions (Eastern, Central and Western) based on economic criteria. Second, in each region, we selected eight counties with a probability proportional to population size. Third, in each selected county, we selected (a) 10 townships at random among the list of townships of the county and (b) the one county level hospital. Results With respect to the risk to the patient, we never observed open injection equipment lying around or needles left in the septum of multi-dose vials. We never observed sterilizable injection devices syringes in any of the facilities. The proportion of facilities using sharps containers was highest in the East (85%), intermediate in the West (79%) and lowest in the Central region (56%). In 2009, auto-disable syringes and safety boxes were used in 78% and 79% facilities in GAVI supported areas of the Western region, respectively. Only one facility presented evidence of attempts to re-sterilize disposable injection equipment in the Eastern region. Conclusions Use of AD syringe and sharps containers increased in vaccination services in China, especially in GAVI supported areas, leading to sustainable progress in terms of elimination of reuse of injection devices. However, risk to patients still existed, including persisting use of standard disposable syringes and attempts to re-use disposable devices.

Childhood acellular pertussis vaccines were licensed and implemented in the US in the 1990s following an effort to improve on the safety profile of whole-cell vaccines. However, waning of immunity from acellular vaccines may be driving the recent resurgence of pertussis, raising the need to consider new prevention strategies.

Risk factors for and serologic evidence of hepatitis B virus (HBV) infection were analyzed among 557 women. Study subjects were attending a clinic for sexually transmitted diseases and enrolled in a clinical trial of nonoxynol-9 prevention of gonococcal and chlamydial infections. Seventy-eight (14%) showed serologic evidence of past HBV infection. Only age at time of serum collection was significantly associated with HBV marker prevalence (P = 0.04). None of the four measures of sexual activity taken (number of sex partners per month, frequency of sexual intercourse, number of documented episodes of sexually transmitted diseases, and lifetime number of sexual partners) were significantly related to the presence of HBV markers. For each measure, however, differences observed between HBV positive and negative subjects were consistent with what would be expected if these factors did contribute to HBV infection risk. These results support the role of heterosexual transmission of HBV infection in women and are consistent with recommendations for hepatitis B immunization of heterosexually active persons with multiple sexual partners.

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%.

Background. Endemic hepatitis B virus (HBV) infection is a serious health problem in China. Hepatitis B vaccination of infants was introduced in 1992 and was progressively expanded during the subsequent 15 years. Methods. We conducted a national serosurvey, with participants selected by multiple-stage random sampling. Demographic characteristics and hepatitis B vaccination history were collected by a questionnaire and a review of vaccination records, and serum specimens were tested for hepatitis B surface antigen, antibody to hepatitis B core antigen, and hepatitis B surface antibody by enzyme-linked immunosorbent assay. Results. Hepatitis B vaccine coverage (3 doses) increased from 30.0% for children born in 1992 to 93.4% for children born in 2005. Receipt of a timely birth dose increased from 22.2% to 82.6% for children born during this interval. Multivariate analysis showed that older age, western and rural residence, birth at home, and certain ethnicities were risk factors for undervaccination with both full vaccine series and timely birth dose. The prevalence of hepatitis B surface antigen was reduced to 2.1% among all children and 1.0% among children born after 1999. The efficacy of hepatitis B vaccination with a timely birth dose was 88.3%. Conclusions. Hepatitis B vaccine has been successfully integrated into routine infant immunization in China, now reaching most infants within 24 h after birth, and the prevalence of hepatitis B surface antigen has been greatly reduced among children born after 1992.

The intradermal route of hepatitis B vaccine administration has been tested in several clinical trials and has produced various degrees of immunogenicity, but usually among small groups of participants. To assess more adequately the immunogenicity of hepatitis B vaccine using the intradermal route, the Centers for Disease Control conducted a clinical trial among 425 well health-care workers in a hospital setting. Participants were randomly assigned to one of two treatment groups: those receiving a 20 micrograms intramuscular injection, and those receiving a 2 micrograms intradermal injection. Participants received the plasma-derived hepatitis B vaccine by the standard schedule at 0, 1 and 6 months, and serum samples were collected at 3, 8, 12 and 24 months after the first dose. Antibody response rates (anti-HBs titre greater than or equal to 10 sample ratio units by radioimmunoassay) for the intradermal vaccination group were consistently lower than those for the intramuscular vaccination group at each testing interval. The differences were greatest for the 3-month test and decreased over time. Geometric mean titres for anti-HBs for the intradermal group were significantly lower than those for the intramuscular group at the 8-month test point. In addition to inoculation route, factors of gender, smoking and age were found to have significant effects on immune response. The results suggest that intradermal vaccination with hepatitis B vaccine may be appropriate under certain conditions and for certain population subgroups.

To investigate the effect of human immunodeficiency virus type 1 (HIV-1) infection on subsequent hepatitis B virus (HBV) infection, HIV antibody was sought in homosexual men who developed HBV infection during a hepatitis B vaccine trial. Among 134 unvaccinated HIV-1-negative men, 7% became HBV carriers, 64% had viremia, and 42% had clinical illness. Among vaccinated HIV-1-negative men, HBV infection severity decreased with number of vaccine doses administered. When adjusted for prior hepatitis B vaccination status, persons with HIV-1 infection preceding HBV infection had a significantly higher risk of developing HBV carriage, viremia, prolonged ALT elevation, and clinical illness. Among HIV-1-infected men, the risk of HBV carriage was increased in unvaccinated persons (21%) and those who failed to respond to vaccination (31%) and further increased in those who received vaccine doses at the time they developed new HBV infection (56%-80%), suggesting inactivated hepatitis B vaccine may temporarily impair the immune response to HBV infection in HIV-1-infected persons. HIV-1 infection was also associated with reduced alanine aminotransferase elevations during the first 36 months of follow-up of men who became HBV carriers.

A population-based serosurvey of human immunodeficiency virus in Belle Glade, FL, enabled evaluation of risk factors for hepatitis B virus (HBV) infection in this racially mixed community. Serum samples from 725 adults and 130 children were tested for markers of HBV infection, and histories of exposure to HBV were obtained by interview. The overall prevalence of past or present HBV infection was 26%; prevalence was 9% among whites, 5% among Hispanics, 30% among blacks, and 57% among Haitians. Prevalence of HBV infection was 3% in children aged 2-10 years and increased to 31% in adults greater than 17 years. Of adults seropositive for HBV, only 5% had homosexual partners or used parenteral drugs, but 47% had a positive serologic test for syphilis. Factors associated with HBV infection in adults were positive serologic test for syphilis (odd ratio [OR] = 3.1; 95% confidence limits [CL] = 2.0, 4.8), and having had two or more lifetime heterosexual partners (OR = 3.2; 95% CL = 1.6, 6.4). In this community, HBV infection was transmitted predominantly by heterosexual contact.

Vaccines to prevent hepatitis B infection became available in 1982, and were recommended primarily for adults considered at high risk because of exposure in the workplace or lifestyles that lead to sexual or parenteral exposure to the virus. Plasma-derived and recombinant vaccines produced in yeast are highly immunogenic, safe, and effective for all age groups. Decreased response and protection by vaccine occur in older persons and in persons with immunosuppressive illnesses. The main issues concerning current vaccination programs include the possible use of lower doses to reduce the cost of the vaccine, the duration of protection and need for vaccine booster doses, and the need for postvaccination testing in hospitals. The failure of current vaccination programs to decrease disease incidence, a matter of great concern nationally, can be ascribed to failure to deliver vaccine to the groups at highest risk. More effective strategies for control, including the universal vaccination of infants or adolescents, must now be examined. Newer vaccines that incorporate other viral antigens and that may offer increased efficacy are being developed. Vaccines to prevent hepatitis A--both killed and live attenuated vaccines--are undergoing clinical trials and may become available in the next 5 years.

At the time of varicella vaccine introduction in the United States, an estimated 4 million episodes of varicella occurred annually. This survey of varicella seroprevalence is the first to describe immunity to a vaccine-preventable disease prior to vaccine introduction in the United States population. The objective of this analysis is to describe patterns of naturally-acquired varicella and understand characteristics associated with infection in the varicella vaccine–naive United States population. A nationally representative cross-sectional health examination survey that included venipuncture was conducted among 21,288 U.S. participants aged 6 years and older from 1988 through 1994. Serologic evidence of varicella-zoster virus infection was measured by enzyme immunoassay of varicella-zoster virus-specific IgG antibody. The seroprevalence of IgG antibody to varicella-zoster virus increased from 86.0% in children aged 6 through 11 years to 99.6% in adults aged 40 through 49 years. Immunity to varicella remained at 99% or higher in Americans aged 50 years and older. Among persons aged 6 through 19 years, non-Hispanic black children were 40% less likely to be seropositive compared with white children (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4–0.8). Among young adults aged 20 through 39 years, women with a history of live birth (OR, 4.3; 95% CI, 2.1–8.7) and married men (OR, 2.7; 95% CI, 1.2–5.7) were more likely to have naturally-acquired immunity to varicella. This study found that, prior to use of varicella vaccine in the United States, age, race, and marital characteristics were independently associated with naturally acquired varicella. Future varicella serosurveys in Americans will provide essential information to interpret the population impact of varicella vaccine. J. Med. Virol. 70:S111–S118, 2003. © 2003 Wiley-Liss, Inc.

The United States has a goal to eliminate all indigenous cases of measles by the year 2000. Initial interruption of indigenous measles transmission would be expected during a period of very low measles incidence as occurred during late 1993.Indigenous measles cases (i.e. cases acquired in the United States and not traceable to any imported case) from 1993 were investigated to determine their source of infection. The probability of sustained undetected measles transmission between isolated indigenous cases was estimated.Of the 312 measles cases reported for 1993, only 25 (8%) occurred after September 19. Of these only 4 cases (16%) could be classified as indigenous. The estimated probability that any of these 4 cases resulted from indigenous measles transmission in theirs or any adjoining counties was 0.05 or less.Interruption of indigenous measles transmission appears to have occurred for the first time throughout the United States in 1993. This event provides strong support for the current national strategy for measles elimination. However, complete elimination of indigenous measles will require maintaining high population immunity to prevent spread from imported cases and attaining global measles control to prevent the importation of measles.

The screening method was used to evaluate the effectiveness of the pertussis vaccination program in the United States during 1992-1994. The formula VE = 1 - [PCV/(1 - PCV)][(1 - PPV)/PPV] was used (VE = vaccine effectiveness; PCV = proportion of cases vaccinated; PPV = proportion of population vaccinated). Data from the national Supplementary Pertussis Surveillance System and the National Health Interview Survey were used to determine PCV and PPV, respectively. Among children aged 7-18 months, VE for 3 doses of pertussis vaccine was 79% (95% confidence interval, 74%-83%) for preventing culture-confirmed pertussis. Between the ages of 19 and 47 months, VE for > or = 4 doses was 90% (95% confidence interval, 88%-92%). VE estimates appeared lower in epidemic (1993) than non-epidemic years (1992, 1994). VE estimates determined using the screening method were consistent with the previous estimates from the United States. This method will continue to be useful for assessing the effectiveness of the pertussis vaccination program in the United States, where acellular pertussis vaccines are recommended for infants.

During 1989 and 1990 reported measles cases in the United States increased 6- to 9-fold over the annual mean of 3000 between 1985 and 1988. To evaluate recent epidemiology we summarized measles outbreaks.Confirmed measles cases reported to the National Notifiable Disease Surveillance System during 1987 through 1990 were analyzed. An outbreak was defined asor = 5 epidemiologically linked cases.There were 815 outbreaks, accounting for 94% of the 52,846 cases reported. Similar to 1985 and 1986, 3 patterns of measles transmission during outbreaks were identified: (1) predominantly among unvaccinated pre-school age children5 years of age (38% of outbreaks); (2) predominantly among vaccinated school age children 5 to 17 years of age (40%); and (3) predominantly among unvaccinated and vaccinated post-school age personsor = 18 years of age (22%). Most outbreaks were small (median, 12 cases), but very large outbreaks occurred (maximum size, 10,670). Although school age outbreaks (58%) predominated during 1987 and 1988, preschool age (40%) and post-school age (23%) outbreaks were more important during 1989 and 1990.Recent epidemiology suggests that to achieve elimination of measles, ACIP recommendations must be fully implemented, including (1) routine administration of the first dose of measles vaccine from 12 to 15 months of age and (2) use of a routine two-dose schedule to prevent school age and post-school age outbreaks.

An outbreak of hepatitis A virus (HAV) infection in a neonatal intensive care unit (NICU) provided the opportunity to examine the duration of HAV excretion in infants and the mechanisms by which HAV epidemics are propagated in NICUs. The outbreak affected 13 NICU infants (20%), 22 NICU nurses (24%), 8 other staff caring for NICU infants, and 4 household contacts; 2 seropositive infants (primary cases) received blood transfusions from a donor with HAV infection. Risk factors for infection among nurses were care for a primary infant-case (relative risk [RR], 3.2), drinking beverages in the unit (odds ratio [OR], infinity), and not wearing gloves when taping an intravenous line (OR, 13.7). Among infants, risk factors were care by a nurse who cared for a primary infant-case during the same shift (RR, 6.1). Serial stool samples from infant-cases were tested for HAV antigen (HAV-Ag) by enzyme immunoassay and HAV RNA by nucleic acid amplification using the polymerase chain reaction. Infant-cases excreted HAV-Ag (n = 2) and HAV RNA (n = 3) 4-5 months after they were identified as being infected. Breaks in infection control procedures and possibly prolonged HAV shedding in infants propagated the epidemic in a critical care setting.

During July 1988, 68 persons in Chattanooga, Tennessee, developed serologically confirmed hepatitis A. Between 15 June and 3 July, 93% of case-patients ate at a specific restaurant compared with only 3% of the local community. An intravenous drug user who worked as a cook was identified as the source. A case-control study was done to identify the vehicle of transmission. Case-patients were more likely than controls to have eaten hamburger buns and pickles, the only foods routinely handled after cooking. Of the restaurant patrons included in the study, 12 microwaved their food before consumption; none developed clinical illness despite eating large amounts of food handled after cooking. Sandwiches that were not microwaved were significantly associated with illness (odds ratio = 9.6; P less than .02). This epidemiologic evidence suggests that microwaves inactivate hepatitis A virus in food.

An outbreak of hepatitis A virus (HAV) infection occurred among cancer patients treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells between July and September 1986 at six different clinical centers. Among 85 patients tested serologically for recent HAV infection, 22 (39%) of 56 susceptible patients developed acute HAV infection. Only exposure to LAK cells cultured in medium containing human serum from two specific manufactured pools was associated with HAV infection. Attack rates were 85% among patients exposed to pool X, 62% in patients exposed to pool Y, and 50% in those exposed to both pools, compared with none among the 24 susceptible persons exposed to other serum pools (P less than .001). The serum used in production of LAK cell medium was obtained from multiple paid donors. Twenty persons donated plasma to both serum pools X and Y. Although none of 12 donors tested had evidence of recent HAV infection, it is likely that an asymptomatic plasma donor viremic for HAV contaminated both serum pools and the LAK cell medium made from it.

Hospital personnel may be exposed to or transmit certain vaccine-preventable diseases. Using immunizing agents optimally in hospitals will protect personnel as well as patients. Preventing illness in hospitals through comprehensive immunization policies can be more cost-effective than case management and outbreak control. Hospital-based immunization programs for patients provide an important strategy for immunizing high-risk patients. Immunizing patients protects them against preventable illnesses that may be acquired in the hospital or the community following discharge.

Hepatitis B is a disease that affects people throughout the world, and over 200 million are persistent carriers of the hepatitis B virus (HBV). The chronic sequelae of this infection include chronic active hepatitis, cirrhosis, and primary hepatocellular carcinoma. The development of safe and highly effective hepatitis B vaccines now provides the means by which HBV infection, including the HBV chronic carrier state, can be prevented and the related mortality significantly reduced. The cost of these vaccines has significantly decreased and will soon approach levels at which the cost-effectiveness (cost per death prevented) of hepatitis B vaccine will be similar to that of other childhood vaccines. Integration of hepatitis B vaccine into the Expanded Programme on Immunization for mass vaccination of infants in areas where HBV infection is endemic and morbidity is high would be the most effective means of providing the coverage necessary for effective control and prevention.

In a large hepatitis B prevention programme, hepatitis B vaccine was given in standard doses to greater than 1000 susceptible Yucpa Indians between 1983 and 1985. Thirteen months after the programme began, 373 vaccine recipients were tested using commercial radioimmunoassay to titre antibody response to the vaccine. Because of logistic difficulties, only 32% had received vaccine by the recommended schedule (second and third doses at one and six months after the first, respectively). The second and third doses were received early by 4 and 31%, respectively, and 27 and 16% received these doses later than intended. Overall response to vaccine was excellent: 98% of vaccinees developed anti-HBs greater than 10 mIU (geometric mean titre 688 mIU). Multivariate analysis showed that the response to vaccination was inversely related to the age of the vaccinee and directly related to the timing of the third vaccine dose. In particular, those receiving the third vaccine dose late (greater than 7 months after the first dose) developed antibody titres two-fold higher than those receiving the third dose on schedule (p less than 0.01). The response to vaccination was not significantly related to the timing of the second dose. A satisfactory response was obtained with various schedules of dose timing, including early second and third doses, late second and third doses and late second but normal third doses. These findings suggest that the response to hepatitis B vaccine is not highly dependent on timing of vaccine doses and that modest alterations in timing of doses, such as those necessary to integrate hepatitis B vaccine with other childhood vaccines, do not affect the excellent response to this vaccine.

Of 3,816 homosexual men examined in five sexually transmitted disease clinics in the United States, 6.1% had hepatitis B surface antigen, 52.4% had antibody to hepatitis B surface antigen, and 3.0% of the men who had no other indicator of infection with hepatitis B virus (HBV) had antibody to hepatitis B core antigen. The rate of seropositivity for HBV indicated by the presence of one or more of these serologic markers was 61.5%; seropositivity was significantly related to the duration of regular homosexual activity and to the number of nonsteady male sexual contacts in the four months before the patients were interviewed. Anal-genital intercourse, oral-anal intercourse, and rectal douching were significantly related to evidence of HBV infection, but oral-oral contact and oral-genital contact were not. Trauma to the rectal mucosa is a feature common to the practices that were significantly related to seropositivity for HBV.

Of 479 homosexual men immunized with three 20-microgram doses of the hepatitis B vaccine, approximately 15% failed to develop protective titers of antibody to the surface antigen of hepatitis B virus (greater than 10 sample ratio units [SRU]). We revaccinated 34 nonresponders with an additional three doses of vaccine and compared their immunologic status with that of 14 control men who had responded to initial vaccination. Most men (15 of 19) who had measurable antibody to hepatitis B surface antigen (SRU, 2.1-9.9) after initial vaccination responded to revaccination, whereas ten of the remaining 15 nonresponders (SRU, less than 2.1) did not. No single immunologic measure distinguished ultimate responders from nonresponders; however, the initial responders differed from delayed responders and nonresponders by having higher numbers of total lymphocytes, B, T, and T helper and suppressor cells.

We investigated two situations involving hepatitis B virus exposure among children in day care. In the first a 4-year-old boy who attended a day care center developed acute hepatitis B; another child at the center, who had a history of aggressive behavior (biting/scratching), was subsequently found to be a hepatitis B carrier. No other source of infection among family and other contacts was identified and no other persons at the center became infected. In the second situation a 4-year-old boy with frequently bleeding eczematous lesions was discovered to be a hepatitis B carrier after having attended a day care center for 17 months. Testing of contacts at the center revealed no transmission to other children or staff (representing 887 person months of exposure). Nationwide surveillance data showed that for the period 1983 to 1987, 161 children 1 to 4 years of age were reported with acute hepatitis B. After children with known hepatitis B risk factors were excluded, 25% (7 of 28) of children with known day care status were reported as day care attendees, a percentage comparable to national estimates of day care attendance by this age group. This is the first reported case of hepatitis B virus transmission between children in day care in the United States. Although it appears that day care transmission of hepatitis B is infrequent, further studies are needed to define the risk more accurately.