Increasing opportunities for prevention of infectious diseases by new, effective vaccines and the expansion of global immunization programs across the life course highlight the importance and value of evidence-informed decision-making (EIDM) by National Immunization Technical Advisory Groups (NITAGs). The U.S. Centers for Disease Control and Prevention (CDC) and Task Force for Global Health (TFGH) have developed and made available new tools to support NITAGs in EIDM. These include a toolkit for conducting facilitated training of NITAGs, Secretariats, or work groups on the use of the Evidence to Recommendations (EtR) approach to advise Ministries of Health (MoH) on specific vaccine policies, and an eLearning module on the EtR approach for NITAG members, Secretariat and others. The CDC and TFGH have also supported final development and implementation of the NITAG Maturity Assessment Tool (NMAT) for assessing maturity of NITAG capabilities in seven functional domains. The EtR toolkit and eLearning have been widely promoted in collaboration with the World Health Organization (WHO) Headquarters and Regional Offices through workshops engaging over 30 countries to date, and the NMAT assessment tool used in most countries in 3 WHO regions (Americas, Eastern Mediterranean, African). Important lessons have been learned regarding planning and conducting trainings for multiple countries and additional ways to support countries in applying the EtR approach to complete vaccine recommendations. Priorities for future work include the need to evaluate the impact of EtR training and NMAT assessments, working with partners to expand and adapt these tools for wider use, synergizing with other approaches for NITAG strengthening, and developing the best approaches to empower NITAGs to use the EtR approach.

To inform Advisory Committee for Immunization Practices (ACIP) COVID-19 vaccine policy decisions, we developed a benefit-risk assessment framework that directly compared the estimated benefits of COVID-19 vaccination to individuals (e.g., prevention of COVID-19-associated hospitalization) with risks associated with COVID-19 vaccines. This assessment framework originated following the identification of thrombosis with thrombocytopenia syndrome (TTS) after Janssen COVID-19 vaccination in April 2021. We adapted the benefit-risk assessment framework for use in subsequent policy decisions, including the adverse events of myocarditis and Guillain-Barre syndrome (GBS) following mRNA and Janssen COVID-19 vaccination respectively, expansion of COVID-19 vaccine approvals or authorizations to new age groups, and use of booster doses. Over the first year of COVID-19 vaccine administration in the United States (December 2020-December 2021), we used the benefit-risk assessment framework to inform seven different ACIP policy decisions. This framework allowed for rapid and direct comparison of the benefits and potential harms of vaccination, which may be helpful in informing other vaccine policy decisions. The assessments were a useful tool for decision-making but required reliable and granular data to stratify analyses and appropriately focus on populations most at risk for a specific adverse event. Additionally, careful decision-making was needed on parameters for data inputs. Sensitivity analyses were used where data were limited or uncertain; adjustments in the methodology were made over time to ensure the assessments remained relevant and applicable to the policy questions under consideration.

The mRNA-1273 (Moderna) COVID-19 vaccine is a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. During December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA), and the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use among persons aged 18 years (1), which was adopted by CDC. During December 19, 2020-January 30, 2022, approximately 204 million doses of Moderna COVID-19 vaccine were administered in the United States (2) as a primary series of 2 intramuscular doses (100 g [0.5 mL] each) 4 weeks apart. On January 31, 2022, FDA approved a Biologics License Application (BLA) for use of the Moderna COVID-19 vaccine (Spikevax, ModernaTX, Inc.) in persons aged 18 years (3). On February 4, 2022, the ACIP COVID-19 Vaccines Work Group conclusions regarding recommendations for the use of the Moderna COVID-19 vaccine were presented to ACIP at a public meeting. The Work Group's deliberations were based on the Evidence to Recommendation (EtR) Framework,* which incorporates the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach() to rank evidence quality. In addition to initial clinical trial data, ACIP considered new information gathered in the 12 months since issuance of the interim recommendations, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. ACIP also considered comparisons of mRNA vaccine effectiveness and safety in real-world settings when first doses were administered 8 weeks apart instead of the original intervals used in clinical trials (3 weeks for BNT162b2 [Pfizer-BioNTech] COVID-19 vaccine and 4 weeks for Moderna COVID-19 vaccine). Based on this evidence, CDC has provided guidance that an 8-week interval might be optimal for some adolescents and adults. The additional information gathered since the issuance of the interim recommendations increased certainty that the benefits of preventing symptomatic and asymptomatic SARS-CoV-2 infection, hospitalization, and death outweigh vaccine-associated risks of the Moderna COVID-19 vaccine. On February 4, 2022, ACIP modified its interim recommendation to a standard recommendation() for use of the fully licensed Moderna COVID-19 vaccine in persons aged 18 years.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines.

Three COVID-19 vaccines are currently approved under a Biologics License Application (BLA) or authorized under an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) and recommended for primary vaccination by the Advisory Committee on Immunization Practices (ACIP) in the United States: the 2-dose mRNA-based Pfizer-BioNTech/Comirnaty and Moderna COVID-19 vaccines and the single-dose adenovirus vector-based Janssen (Johnson & Johnson) COVID-19 vaccine (1,2) (Box 1). In August 2021, FDA amended the EUAs for the two mRNA COVID-19 vaccines to allow for an additional primary dose in certain immunocompromised recipients of an initial mRNA COVID-19 vaccination series (1). During September-October 2021, FDA amended the EUAs to allow for a COVID-19 vaccine booster dose following a primary mRNA COVID-19 vaccination series in certain recipients aged ≥18 years who are at increased risk for serious complications of COVID-19 or exposure to SARS-CoV-2 (the virus that causes COVID-19), as well as in recipients aged ≥18 years of Janssen COVID-19 vaccine (1) (Table). For the purposes of these recommendations, an additional primary (hereafter additional) dose refers to a dose of vaccine administered to persons who likely did not mount a protective immune response after initial vaccination. A booster dose refers to a dose of vaccine administered to enhance or restore protection by the primary vaccination, which might have waned over time. Health care professionals play a critical role in COVID-19 vaccination efforts, including for primary, additional, and booster vaccination, particularly to protect patients who are at increased risk for severe illness and death.

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. On August 23, 2021, the Food and Drug Administration (FDA) approved a Biologics License Application (BLA) for use of the Pfizer-BioNTech COVID-19 vaccine, marketed as Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (1). The Pfizer-BioNTech COVID-19 vaccine is also recommended for adolescents aged 12-15 years under an Emergency Use Authorization (EUA) (1). All persons aged ≥12 years are recommended to receive 2 doses (30 μg, 0.3 mL each), administered 3 weeks apart (2,3). As of November 2, 2021, approximately 248 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥12 years in the United States.* On October 29, 2021, FDA issued an EUA amendment for a new formulation of Pfizer-BioNTech COVID-19 vaccine for use in children aged 5-11 years, administered as 2 doses (10 μg, 0.2 mL each), 3 weeks apart (Table) (1). On November 2, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years for the prevention of COVID-19. To guide its deliberations regarding recommendations for the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework(§) and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5-11 years under an EUA is interim and will be updated as additional information becomes available. The Pfizer-BioNTech COVID-19 vaccine has high efficacy (>90%) against COVID-19 in children aged 5-11 years, and ACIP determined benefits outweigh risks for vaccination. Vaccination is important to protect children against COVID-19 and reduce community transmission of SARS-CoV-2.

The Pfizer-BioNTech COVID-19 vaccine (BNT162b2) is a lipid nanoparticle-formulated, nucleoside mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. In December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) as well as an interim recommendation for use among persons aged ≥16 years by the Advisory Committee on Immunization Practices (ACIP) (1). In May 2021, the EUA and interim ACIP recommendations for Pfizer-BioNTech COVID-19 vaccine were extended to adolescents aged 12-15 years (2). During December 14, 2020-September 1, 2021, approximately 211 million doses of Pfizer-BioNTech COVID-19 vaccine were administered in the United States.* On August 23, 2021, FDA approved a Biologics License Application for use of the Pfizer-BioNTech COVID-19 vaccine, Comirnaty (Pfizer, Inc.), in persons aged ≥16 years (3). The ACIP COVID-19 Vaccines Work Group's conclusions regarding the evidence for the Pfizer-BioNTech COVID-19 vaccine were presented to ACIP at a public meeting on August 30, 2021. To guide its deliberations regarding the Pfizer-BioNTech COVID-19 vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(†) and incorporated a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(§) In addition to initial clinical trial data, ACIP considered new information gathered in the 8 months since issuance of the interim recommendation for Pfizer-BioNTech COVID-19 vaccine, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. The additional information increased certainty that benefits from prevention of asymptomatic infection, COVID-19, and associated hospitalization and death outweighs vaccine-associated risks. On August 30, 2021, ACIP issued a recommendation(¶) for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barré syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine and the Moderna COVID-19 (mRNA-1273) vaccine,(†) and the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for their use in persons aged ≥16 years and ≥18 years, respectively.(§) In May 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; ACIP recommends that all persons aged ≥12 years receive a COVID-19 vaccine. Both Pfizer-BioNTech and Moderna vaccines are mRNA vaccines encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Both mRNA vaccines were authorized and recommended as a 2-dose schedule, with second doses administered 21 days (Pfizer-BioNTech) or 28 days (Moderna) after the first dose. After reports of myocarditis and pericarditis in mRNA vaccine recipients,(¶) which predominantly occurred in young males after the second dose, an ACIP meeting was rapidly convened to review reported cases of myocarditis and pericarditis and discuss the benefits and risks of mRNA COVID-19 vaccination in the United States. Myocarditis is an inflammation of the heart muscle; if it is accompanied by pericarditis, an inflammation of the thin tissue surrounding the heart (the pericardium), it is referred to as myopericarditis. Hereafter, myocarditis is used to refer to myocarditis, pericarditis, or myopericarditis. On June 23, 2021, after reviewing available evidence including that for risks of myocarditis, ACIP determined that the benefits of using mRNA COVID-19 vaccines under the FDA's EUA clearly outweigh the risks in all populations, including adolescents and young adults. The EUA has been modified to include information on myocarditis after receipt of mRNA COVID-19 vaccines. The EUA fact sheets should be provided before vaccination; in addition, CDC has developed patient and provider education materials about the possibility of myocarditis and symptoms of concern, to ensure prompt recognition and management of myocarditis.

The Pfizer-BioNTech COVID-19 (BNT162b2) vaccine is a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 intramuscular doses (30 μg, 0.3 mL each) administered 3 weeks apart. On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for use of the Pfizer-BioNTech COVID-19 vaccine (Pfizer, Inc; Philadelphia, Pennsylvania) in persons aged ≥16 years (1); on December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the vaccine in the same age group (2). As of May 12, 2021, approximately 141.6 million doses of the Pfizer-BioNTech COVID-19 vaccine had been administered to persons aged ≥16 years.* On May 10, 2021, FDA expanded the EUA for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years (1). On May 12, 2021, ACIP issued an interim recommendation(†) for use of the Pfizer-BioNTech COVID-19 vaccine in adolescents aged 12-15 years for the prevention of COVID-19. To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendation (EtR) Framework,(§) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.(¶) The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥12 years under an EUA is interim and will be updated as additional information becomes available.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged <50 years, as well as the availability of alternative COVID-19 vaccines, is required to guide vaccine decision-making and ensure early recognition and clinical management of TTS.

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.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc, a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey). The Janssen COVID-19 vaccine is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector vaccine, encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19 (1). Vaccination with the Janssen COVID-19 vaccine consists of a single dose (5 × 1010 virus particles per 0.5-mL dose) administered intramuscularly. On February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Janssen COVID-19 vaccine in persons aged ≥18 years for the prevention of COVID-19. This vaccine is the third COVID-19 vaccine authorized under an EUA for the prevention of COVID-19 in the United States (2). To guide its deliberations regarding the vaccine, ACIP used the Evidence to Recommendations (EtR) framework,† following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.§ The ACIP recommendation for the use of the Janssen COVID-19 vaccine under an EUA is interim and will be updated as additional information becomes available.

Respiratory illness caused by Corynebacterium diphtheriae and C. ulcerans, and use of diphtheria anti-toxin in the United States, 1996-2018. BACKGROUND: Respiratory diphtheria is a toxin-mediated disease caused by Corynebacterium diphtheriae. Diphtheria-like illness, clinically indistinguishable from diphtheria, is caused by C. 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 (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 1997-2018. RESULTS: From 1996-2018, 14 respiratory diphtheria cases were reported to NNDSS. Among these 14 cases, 1 was toxigenic and 3 were non-toxigenic C. diphtheriae by culture and Elek, 6 were culture-negative but 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 1997-2018, with an average of 11 requests per year from 1997-2007, and 3 per year from 2008-2018. 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.

Epidemic meningitis has posed a recurrent threat for more than a century for the approximately 430 million people living in the 26 countries in the sub-Saharan region of Africa known as the “meningitis belt.” This population experiences high rates of endemic meningitis, annual seasonal outbreaks, and explosive epidemics occurring every 5–12 years. Hope to eliminate this devastating public health threat came in the form of a novel meningococcal serogroup A conjugate vaccine (MACV [MenAfriVac]) developed by the Meningitis Vaccine Project (MVP; available at: http://www.meningvax.org) specifically for use in the meningitis belt and priced at less than $1.00 per dose [1]. Licensed in 2009, MACV was subsequently prequalified by the World Health Organization (WHO) on the basis of its safety and immunogenicity data but without phase 3 efficacy studies. Starting in 2010, MACV was rolled out across the meningitis belt via mass campaigns to vaccinate all persons 1–29 years of age. By the end of 2018, >300 million people in 22 African countries had been immunized with MACV [2]. The vaccine has been a remarkable public health success, effectively eliminating serogroup A meningitis epidemics in sub-Saharan Africa [3].

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.

OBJECTIVES: Acute meningitis and encephalitis (AME) are common diseases with the main pathogens being viruses and bacteria. As specific treatments are different, it is important to develop clinical prediction rules to distinguish aseptic from bacterial or fungal infection. In this study we evaluated the incidence rates, seasonal variety and the main etiologic agents of AME, and identified factors that could be used to predict the etiologic agents. METHODS: A population-based AME syndrome surveillance system was set up in Guigang City, Guangxi, involving 12 hospitals serving the study communities. All patients meeting the case definition were investigated. Blood and/or cerebrospinal fluid were tested for bacterial pathogens using culture or RT-PCR and serological tests for viruses using enzyme-linked immunosorbent assays. Laboratory testing variables were grouped using factor analysis. Multinomial logistic regression was used to predict the etiology of AME. RESULTS: From May 2007 to June 2012, the annual incidence rate of AME syndrome, and disease specifically caused by Japanese encephalitis (JE), other viruses, bacteria and fungi were 12.55, 0.58, 4.57, 0.45 and 0.14 per 100,000 population, respectively. The top three identified viral etiologic agents were enterovirus, mumps virus, and JE virus, and for bacteria/fungi were Streptococcus sp., Cryptococcus neoformans and Staphylococcus sp. The incidence of JE and other viruses affected younger populations and peaked from April to August. Alteration of consciousness and leukocytosis were more likely to be caused by JE, bacteria and fungi whereas CSF inflammation was associated with bacterial/fungal infection. CONCLUSIONS: With limited predictive validity of symptoms and signs and routine laboratory tests, specific tests for JE virus, mumps virus and enteroviruses are required to evaluate the immunization impact and plan for further intervention. CSF bacterial culture cannot be omitted in guiding clinical decisions regarding patient treatment.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 <15 years improved over time, achieving rates >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.

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.

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.

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 24h 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 24h 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 <1% among children in these areas. We estimated the impact in disease prevented by HB vaccine in China between 1992, when the vaccine was routinely recommended, and 2009, and in CGP areas for the years 2003-2009, when the CGP was active. A published model was used to estimate the burden of chronic and acute HBV infection and death prevented due to HB vaccination in China and the CGP areas using data from national serosurveys in China in 1992 and 2006, and HB vaccine coverage from surveys in 2004, 2006 and 2010. We used sigmoid modeling to estimate vaccine coverage nationally, regionally, and CGP areas. We also estimated the incremental impact of the CGP on HB vaccine coverage in those underserved areas. Our findings suggest that between 1992 and 2009, HB vaccination in China has prevented 24million chronic HBV infections and 4.3million future deaths due to cirrhosis, hepatocellular carcinoma and acute hepatitis. During the CGP between 2003 and 2009, an estimated 3.8million chronic HBV infections and 680,000 deaths were prevented in CGP areas. We found that the CGP funding increased HB vaccine coverage in project areas by 4-15% for HB3 and 4-27% for timely birth dose beyond the coverage expected without the CGP. The CGP represents a highly successful public health collaboration between the national government and international partners.

The China GAVI Hepatitis B Immunization Project was initiated in 2002 with the signing of a Memorandum of Understanding between GAVI and the Government of China. The Project was one of the three (China, India, and Indonesia) GAVI-initiated special projects done to support countries too large to receive full GAVI support for hepatitis B vaccine and safe injections. The Project in China was designed by the Chinese Government and partners to deliver free hepatitis B vaccine and safe injections to all newborns in the 12 Western Provinces and Poverty Counties in 10 Provinces of Central China (1301 Counties with approximately 5.6 million births per year), eliminating the gap in immunization coverage between wealthier and poorer regions of China. The project budget (USD 76 million) was equally shared by GAVI and the Chinese Government. Initially planned for 5 years, two no cost extensions extended the project to 2011. Although China produced hepatitis B vaccine, before the project the vaccine was sold to parents who were also charged a "user fee" for the syringe and vaccine administration. Basic Expanded Program on Immunization (EPI) vaccines such as BCG, DTP, Polio, and measles vaccines were provided free to parents, although they were charged a user fee. Vaccines were sold by China CDC Offices at provincial, prefecture, county level and township hospitals, and village doctors received a substantial portion of their income from the sale of hepatitis B and other vaccines. The result of charging for hepatitis B vaccine was that coverage was relatively high in Eastern and wealthier counties in Central China ( approximately 80-90%), but was much lower ( approximately 40%) in Western China and Poverty Counties where parents could not afford the vaccine. The Project was administered by the China MOH and China CDC EPI program, and two Project Co-managers, one from the Chinese Government and the other an international assignee, were chosen. The project had an oversight Operational Advisory Group composed of the Chinese Government, WHO, UNICEF, and GAVI. The initial targets of the project as delineated in the initial MOU for the Project areas (HepB3 coverage will reach 85% at the county level, >75% of newborns at the county level will receive the first dose of hepatitis B within 24h of birth, and all immunization injections will be with auto disable [AD] syringes) were substantially exceeded. The differential in vaccine coverage between wealthier and poorer parts of China was eliminated contributing to a great improvement in equity. With additional contributions of the Chinese Government the Project was accomplished substantially under budget allowing for additional catch up immunization of children under 15 years of age. More than 5 million health workers were trained in how to deliver hepatitis B vaccine, timely birth dose (TBD), and safe injections, and public awareness of hepatitis B and its prevention rose significantly. TBD coverage was expedited by concurrent efforts to have women deliver in township clinics and district hospitals instead of at home. The effective management of the Project, with a Project office sitting within the China EPI and an Operational Advisory Group for oversight, could serve as a model for other GAVI projects worldwide. Most importantly, the carrier rate in Chinese children less than 5 years of age has fallen to 1%, from a level of 10% before the inception of the Project. Liver cancer, one of the major cancer killers in China (250,000-300,000 annual estimated deaths), will dramatically decline as immunized cohorts of Chinese children age. While hepatitis C and non-alcoholic liver disease also exist in China and can lead to liver cancer and cirrhosis, the majority of liver disease in China is hepatitis B related and therefore preventable. The authors believe that China's success in preventing hepatitis B is one of the greatest public health achievements of the 21st century. Work remains to be done in several key areas. There are still pockets of home births in rural provinces where a TBD is difficult to deliver, and China is strengthening its policy of screening pregnant women for HBsAg and delivering HBIG plus vaccine to newborns of HBV carrier mothers. Approximately 10% of the adult population of China remain chronic carriers of hepatitis B virus and cannot be helped by the vaccine, so prevention of liver cancer and cirrhosis in those groups remains a future challenge for China.

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.

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.

Infectious respiratory pathogens were the suspected cause of 480 outbreaks investigated by the Centers for Disease Control and Prevention's Epidemic Intelligence Service officers during 1946-2005. All epidemic-assistance investigation reports and associated articles from scientific journals were reviewed. Investigations identified 25 different infectious respiratory pathogens including, most frequently, tuberculosis, influenza, and legionellosis. Other bacterial-, viral-, and fungal-related pathogens also were identified. Epidemic-assistance investigations were notable for first identifying Legionnaires disease and Pontiac fever, hantavirus pulmonary syndrome, and new strains of human and avian influenza, as well as emerging challenges (e.g., multidrug-resistant tuberculosis and pneumococcus). The investigations provided clinical insights into such diseases as pulmonary anthrax and identified high risks of serious respiratory illnesses for persons infected with human immunodeficiency virus, other immunocompromised persons, and persons with diabetes. They identified settings placing persons at high risk of acquiring disease, including nursing homes, prisons, homeless shelters, and hospitals. Travel also placed persons at risk. Key environmental factors related to spread of diseases and occupational risks for brucellosis and psittacosis were identified. The outbreak investigations constitute a wealth of prevention experience and provide the basis for recommendations to mitigate outbreaks and reduce future risks.

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 24h 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<0.001), living in an urban setting (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.

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%.