Routine Vaccination Coverage - Worldwide, 2022.

In 2020, the World Health Assembly endorsed the Immunization Agenda 2030 (IA2030), the 2021-2030 global strategy that envisions a world where everyone, everywhere, at every age, fully benefits from vaccines. This report reviews trends in World Health Organization and UNICEF immunization coverage estimates at global, regional, and national levels through 2022 and documents progress toward improving coverage with respect to the IA2030 strategy, which aims to reduce the number of children who have not received the first dose of a diphtheria-tetanus-pertussis-containing vaccine (DTPcv1) worldwide by 50% and to increase coverage with 3 diphtheria-tetanus-pertussis-containing vaccine doses (DTPcv3) to 90%. Worldwide, coverage ≥1 dose of DTPcv1 increased from 86% in 2021 to 89% in 2022 but remained below the 90% coverage achieved in 2019. Estimated DTPcv3 coverage increased from 81% in 2021 to 84% in 2022 but also remained below the 2019 coverage of 86%. Worldwide in 2022, 14.3 million children were not vaccinated with DTPcv1, a 21% decrease from 18.1 million in 2021, but an 11% increase from 12.9 million in 2019. Most children (84%) who did not receive DTPcv1 in 2022 lived in low- and lower-middle-income countries. COVID-19 pandemic-associated immunization recovery occurred in 2022 at the global level, but progress was unevenly distributed, especially among low-income countries. Urgent action is needed to provide incompletely vaccinated children with catch-up vaccinations that were missed during the pandemic, restore national vaccination coverage to prepandemic levels, strengthen immunization programs to build resiliency to withstand future unforeseen public health events, and further improve coverage to protect children from vaccine-preventable diseases.

Ganglioneuroblastoma Presenting as Obstructive Sleep Apnea in a 5-Year-Old Boy.

The authors present an interesting case of ganglioneuroblastoma, a tumor of the sympathetic chain, presenting as severe obstructive sleep apnea in a healthy 5-year-old boy. The patient's initial polysomnogram demonstrated an apnea-hypopnea index (AHI) of 86 events/hour. He underwent an adenotonsillectomy at an outside hospital and his repeat AHI was still 62. The patient was nonobese and nonsyndromic appearing, which made his incredibly high AHI perplexing. He underwent sleep endoscopy and direct laryngoscopy for further evaluation, which demonstrated a large mass in the left posterior pharynx. He then underwent surgical excision with a resolution of his obstructive sleep apnea.

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

Routine Vaccination Coverage - Worldwide, 2021.

In 2020, the World Health Assembly endorsed the Immunization Agenda 2030, an ambitious global immunization strategy to reduce morbidity and mortality from vaccine-preventable diseases (1). This report updates a 2020 report (2) with global, regional,* and national vaccination coverage estimates and trends through 2021. Global estimates of coverage with 3 doses of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) decreased from an average of 86% during 2015-2019 to 83% in 2020 and 81% in 2021. Worldwide in 2021, 25.0 million infants (19% of the target population) were not vaccinated with DTPcv3, 2.1 million more than in 2020 and 5.9 million more than in 2019. In 2021, the number of infants who did not receive any DTPcv dose by age 12 months (18.2 million) was 37% higher than in 2019 (13.3 million). Coverage with the first dose of measles-containing vaccine (MCV1) decreased from an average of 85% during 2015-2019 to 84% in 2020 and 81% in 2021. These are the lowest coverage levels for DTPcv3 and MCV1 since 2008. ​Global coverage estimates were also lower in 2021 than in 2020 and 2019 for bacillus Calmette-Guérin vaccine (BCG) as well as for the completed series of Haemophilus influenzae type b vaccine (Hib), hepatitis B vaccine (HepB), polio vaccine (Pol), and rubella-containing vaccine (RCV). The COVID-19 pandemic has resulted in disruptions to routine immunization services worldwide. Full recovery to immunization programs will require context-specific strategies to address immunization gaps by catching up missed children, prioritizing essential health services, and strengthening immunization programs to prevent outbreaks (3).

Routine Vaccination Coverage - Worldwide, 2020.

Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).

Human Anti-HIV-1 gp120 Monoclonal Antibodies with Neutralizing Activity Cloned from Humanized Mice Infected with HIV-1.

Broadly neutralizing, anti-HIV-1 gp120 mAbs have been isolated from infected individuals, and there is considerable interest in developing these reagents for Ab-based immunoprophylaxis and treatment. As a means to identify potentially new anti-HIV Abs, we exploited humanized NOD-scid IL2rγnull mice systemically infected with HIV-1 to generate a wide variety of Ag-specific human mAbs. The Abs were encoded by a diverse range of variable gene families and Ig classes, including IgA, and several showed significant levels of somatic mutation. Moreover, the isolated Abs not only bound target Ags with similar affinity as broadly neutralizing Abs, they also demonstrated neutralizing ability against multiple HIV-1 clades. The use of humanized mice will allow us to use our knowledge of HIV-1 gp120 structure and function, and the immune response targeting this protein, to generate native human prophylactic Abs to reduce the infection and spread of HIV-1.

Routine Vaccination Coverage - Worldwide, 2019.

Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates previous reports (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2019 and describes the number of surviving infants who did not receive the first dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP1) during the first year of life (i.e., zero-dose children), which serves as a proxy for children with poor access to immunization and other health services. Global estimates of coverage with the third dose of DTP (DTP3), the first dose of measles-containing vaccine (MCV1), and the third dose of polio vaccine (Pol3) ranged from 84% to 86% during 2010-2019. Worldwide, 19.7 million children (15%) were not vaccinated with DTP3 in 2019, 13.8 million (70%) of whom were zero-dose children. During 2010-2019, the number of zero-dose children increased in the African, Americas, and Western Pacific regions. Global coverage with the second MCV dose (MCV2) increased from 42% in 2010 to 71% in 2019. During 2010-2019, global coverage with underused vaccines increased for the completed series of rotavirus vaccine (rota), pneumococcal conjugate vaccine (PCV), rubella-containing vaccine (RCV), Haemophilus influenzae type b vaccine (Hib), hepatitis B vaccine (HepB), and human papillomavirus vaccine (HPV). Achieving universal coverage with all recommended vaccines will require tailored, context-specific strategies to reach communities with substantial proportions of zero-dose and incompletely vaccinated children, particularly those in remote rural, urban poor, and conflict-affected communities (3).

Pituitary Adenoma Deposit in the Nasolabial Region Following Sublabial Transsphenoidal Surgery in the Setting of Nelson Syndrome.

Pituitary adenomas are a group of tumors arising from the anterior pituitary gland, and with the exception of prolactin-secreting adenomas, transsphenoidal resection is the cornerstone of treatment. Although most adenomas are located within the pituitary fossa, ectopic adenomas have been reported, primarily occurring along the route of embryologic development. In this article, we present the case of an ectopic pituitary adenoma in the nasolabial fold that likely resulted from seeding during transsphenoidal resection via sublabial approach.

Assessment of Economic Burden of Concurrent Measles and Rubella Outbreaks, Romania, 2011-2012.

We estimated the economic impact of concurrent measles and rubella outbreaks in Romania during 2011-2012. We collected costs from surveys of 428 case-patients and caretakers, government records, and health staff interviews. We then estimated financial and opportunity costs. During the study period, 12,427 measles cases and 24,627 rubella cases were recorded; 27 infants had congenital rubella syndrome (CRS). The cost of the outbreaks was US $9.9 million. Cost per case was US $439 for measles, US $132 for rubella, and US $44,051 for CRS. Up to 36% of households needed to borrow money to pay for illness treatment. Approximately 17% of patients continued to work while ill to pay their treatment expenses. Our key study findings were that households incurred a high economic burden compared with their incomes, the health sector bore most costs, and CRS costs were substantial and relevant to include in rubella outbreak cost studies.

HIV-1 R5 Macrophage-Tropic Envelope Glycoprotein Trimers Bind CD4 with High Affinity, while the CD4 Binding Site on Non-macrophage-tropic, T-Tropic R5 Envelopes Is Occluded.

HIV-1 R5 variants exploit CCR5 as a coreceptor to infect both T cells and macrophages. R5 viruses that are transmitted or derived from immune tissue and peripheral blood are mainly inefficient at mediating infection of macrophages. In contrast, highly macrophage-tropic (mac-tropic) R5 viruses predominate in brain tissue and can be detected in cerebrospinal fluid but are infrequent in immune tissue or blood even in late disease. These mac-tropic R5 variants carry envelope glycoproteins (Envs) adapted to exploit low levels of CD4 on macrophages to induce infection. However, it is unclear whether this adaptation is conferred by an increased affinity of the Env trimer for CD4 or is mediated by postbinding structural rearrangements in the trimer that enhance the exposure of the coreceptor binding site and facilitate events leading to fusion and virus entry. In this study, we investigated CD4 binding to mac-tropic and non-mac-tropic Env trimers and showed that CD4-IgG binds efficiently to mac-tropic R5 Env trimers, while binding to non-mac-tropic trimers was undetectable. Our data indicated that the CD4 binding site (CD4bs) is highly occluded on Env trimers of non-mac-tropic R5 viruses. Such viruses may therefore infect T cells via viral synapses where Env and CD4 become highly concentrated. This environment will enable high-avidity interactions that overcome extremely low Env-CD4 affinities.IMPORTANCE HIV R5 variants bind to CD4 and CCR5 receptors on T cells and macrophages to initiate infection. Transmitted HIV variants infect T cells but not macrophages, and these viral strains persist in immune tissue even in late disease. Here we show that the binding site for CD4 present on HIV's envelope protein is occluded on viruses replicating in immune tissue. This occlusion likely prevents antibody binding to this site and neutralization of the virus, but it makes it difficult for virus-CD4 interactions to occur. Such viruses probably pass from T cell to T cell via cell contacts where CD4 is highly concentrated and allows infection via inefficient envelope-CD4 binding. Our data are highly relevant for vaccines that aim to induce antibodies targeting the CD4 binding site on the envelope protein.

Lessons learned from a single-surgeon series of paediatric robot-assisted laparoscopic urological procedures: predictors of high-grade postoperative complications.

OBJECTIVES: To describe postoperative complications after robot-assisted laparoscopic urological surgery in children, and identify potential predictors of these complications by analysing the outcomes of a large-volume single-surgeon experience. PATIENTS AND METHODS: We reviewed our institutional database to identify all robot-assisted laparoscopy (RAL) cases performed between December 2007 and December 2017. Patients were grouped into three cohorts based on the anatomical location of the procedure: upper urinary tract (kidney and renal pelvis); lower urinary tract (ureter); and lower urinary tract reconstruction with bowel (bladder reconstruction). A descriptive analysis of baseline characteristics, intra-operative variables and postoperative outcomes was carried out. All complications were graded using the Clavien-Dindo scale, and grouped based on type and time of occurrence (<30, 30-90, >90 days). Multivariable logistic regression analysis was performed to identify predictors of high-grade complications (Clavien-Dindo grade ≥ III). We also measured complication rates based on year of surgery and surgical caseload. RESULTS: Our database included a total of 326 patients, of whom 57% (n = 186) underwent upper urinary tract procedures, 30% (n = 97) ureteric procedures, and 13% bladder reconstruction. The median follow-up for each procedure was 13, 11 and 57 months, respectively. Of the total, 10 cases were converted to an open approach and excluded from further analysis. The most common types of complication in all groups were infections (urinary tract infections) and urinary complications (urine leaks and urolithiasis). Bladder reconstructive procedures, which require the use of bowel, presented the highest rate of high-grade complications (32%). Length of hospital stay (LOS; odds ratio [OR] 1.33, confidence interval [CI] 1.16-1.53), estimated blood loss (EBL) in surgery (OR 1.01, CI 1.002-1.019) and operating time (OR 1.004, CI 1.002-1.006) were all associated with increased odds of high-grade complications on multivariate analysis (P < 0.05). CONCLUSIONS: In this single-surgeon series, we have described the most commonly encountered complications after RAL in paediatric urology, finding rates similar to the complication rates reported in the current literature on other surgical approaches. In addition, LOS, operating time and EBL, which are probable surrogates of case complexity, were associated with increased odds of high-grade complications.

Global Routine Vaccination Coverage, 2018.

Endorsed by the World Health Assembly in 2012, the Global Vaccine Action Plan 2011-2020 (GVAP) (1) calls on all countries to reach ≥90% national coverage with all vaccines in the country's national immunization schedule by 2020. Building on previous analyses (2) and using the World Health Organization (WHO) and United Nations Children's Fund (UNICEF) global vaccination coverage estimates as of 2018, this report presents global, regional, and national vaccination coverage estimates and trends, including vaccination dropout rates. According to these estimates, global coverage with the first dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP1) remained relatively unchanged from 2010 (89%) to 2018 (90%). Global coverage with the third DTP dose (DTP3) followed a similar global trend to that of DTP1, remaining relatively consistent from 2010 (84%) to 2018 (86%) (3). Globally, 19.4 million children (14%) were not fully vaccinated in 2018, and among them, 13.5 million (70%) did not receive any DTP doses. Overall, dropout rates from DTP1 to DTP3 decreased globally from 6% in 2010 to 4% in 2018. Global coverage with the first dose of measles-containing vaccine (MCV1) remained between 84% and 86% during 2010-2018. Among countries that offer a second MCV dose (MCV2) during the second year of life, coverage increased from 19% in 2007 to 54% in 2018; among countries offering MCV2 to older age groups (children aged 3-14 years), coverage also increased, from 36% in 2007 to 69% in 2018 (3). Globally, the estimated difference in coverage with MCV1 and MCV2 in 2018 was 17%. However, among new and underused vaccines, global coverage increased from 2007 to 2018 for completed series of rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b vaccine (Hib), and hepatitis B vaccine (HepB). To reach global vaccination coverage goals for vaccines recommended during childhood, adolescence, and adulthood, tailored strategies that address local determinants for incomplete vaccination are needed, including targeting hard-to-reach and hard-to-vaccinate populations.

Pulmonary Surfactant Promotes Virulence Gene Expression and Biofilm Formation in Klebsiella pneumoniae.

The interactions between Klebsiella pneumoniae and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional response of K. pneumoniae MGH 78578 to purified pulmonary surfactant. This work revealed changes within the K. pneumoniae transcriptome that likely contribute to host colonization, adaptation, and virulence in vivo Notable transcripts expressed under these conditions include genes involved in capsule synthesis, lipopolysaccharide modification, antibiotic resistance, biofilm formation, and metabolism. In addition, we tested the contributions of other surfactant-induced transcripts to K. pneumoniae survival using engineered isogenic KPPR1 deletion strains in a murine model of acute pneumonia. In these infection studies, we identified the MdtJI polyamine efflux pump and the ProU glycine betaine ABC transporter to be significant mediators of K. pneumoniae survival within the lung and confirmed previous evidence for the importance of de novo leucine synthesis to bacterial survival during infection. Finally, we determined that pulmonary surfactant promoted type 3 fimbria-mediated biofilm formation in K. pneumoniae and identified two surfactant constituents, phosphatidylcholine and cholesterol, that drive this response. This study provides novel insight into the interactions occurring between K. pneumoniae and the host at an important infection site and demonstrates the utility of purified lung surfactant preparations for dissecting host-lung pathogen interactions in vitro.

Global Routine Vaccination Coverage - 2017.

Endorsed by the World Health Assembly in 2012, the Global Vaccine Action Plan 2011-2020 (GVAP) (1) calls on all countries to reach ≥90% national coverage with all vaccines in the country's national immunization schedule by 2020. This report updates previous reports (2,3) and presents global, regional, and national vaccination coverage estimates and trends as of 2017. It also describes the number of infants surviving to age 1 year (surviving infants) who did not receive the third dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP3), a key indicator of immunization program performance (4,5), with a focus on the countries with the highest number of children who did not receive DTP3 in 2017. Based on the World Health Organization (WHO) and United Nations Children's Fund (UNICEF) estimates, global DTP3 coverage increased from 79% in 2007 to 84% in 2010, and has remained stable from 2010 to 2017 (84% to 85%). In 2017, among the 19.9 million children who did not receive DTP3 in the first year of life, 62% (12.4 million) lived in 10 countries. From 2007 to 2017, the number of children who had not received DTP3 decreased in five of these 10 countries and remained stable or increased in the other five. Similar to DTP3 coverage, global coverage with the first measles-containing vaccine dose (MCV1) increased from 80% in 2007 to 84% in 2010, and has remained stable from 2010 to 2017 (84% to 85%). Coverage with the third dose of polio vaccine (Pol3) has remained stable at 84%-85% since 2010. From 2007 to 2017, estimated global coverage with the second MCV dose (MCV2) increased from 33% to 67%, as did coverage with the completed series of rotavirus (2% to 28%), pneumococcal conjugate (PCV) (4% to 44%), rubella (26% to 52%), Haemophilus influenzae type b (Hib) (25% to 72%) and hepatitis B (HepB) (birth dose: 24% to 43%; 3-dose series: 63% to 84%) vaccines. Targeted, context-specific strategies are needed to reach and sustain high vaccination coverage, particularly in countries with the highest number of unvaccinated children.

Acceptance of the Administration of Multiple Injectable Vaccines in a Single Immunization Visit in Albania.

Background: Albania introduced inactivated polio vaccine (IPV) into its immunization system in May 2014, increasing the maximum recommended number of injectable vaccines given in a single visit from 2 to 3. Methods: Health-care providers and caregivers were interviewed at 42 health facilities in Albania to assess knowledge, attitudes, and practices regarding injectable vaccine administration. Immunization register data were abstracted from December 2014 to July 2015 at the same facilities to explore the number of injectable vaccines children received during their 2- and 4-month visits. Results: The majority of children (87%) identified in the record review at either their 2- or 4-month immunization visit received all 3 injectable vaccines in a single visit. Almost all children who did not receive the vaccines in a single visit were subsequently fully immunized, most within a 2-week period. Over half of caregivers whose children got 3 or more injectable vaccines in a single visit reported being only comfortable with 1 or 2 injectable vaccines in a single visit. Conclusions: Despite most caregivers expressing hesitation regarding children receiving multiple injectable vaccines in a single visit, most children received vaccines according to the recommended schedule. Almost all children eventually received all recommended vaccines.

Monitoring Results in Routine Immunization: Development of Routine Immunization Dashboard in Selected African Countries in the Context of the Polio Eradication Endgame Strategic Plan.

Background: To monitor immunization-system strengthening in the Polio Eradication Endgame Strategic Plan 2013-2018 (PEESP), the Global Polio Eradication Initiative identified 1 indicator: 10% annual improvement in third dose of diphtheria- tetanus-pertussis-containing vaccine (DTP3) coverage in polio high-risk districts of 10 polio focus countries. Methods: A multiagency team, including staff from the African Region, developed a comprehensive list of outcome and process indicators measuring various aspects of the performance of an immunization system. Results: The development and implementation of the dashboard to assess immunization system performance allowed national program managers to monitor the key immunization indicators and stratify by high-risk and non-high-risk districts. Discussion: Although only a single outcome indicator goal (at least 10% annual increase in DTP3 coverage achieved in 80% of high-risk districts) initially existed in the endgame strategy, we successfully added additional outcome indicators (eg, decreasing the number of DTP3-unvaccinated children) as well as program process indicators focusing on cold chain, stock availability, and vaccination sessions to better describe progress on the pathway to raising immunization coverage. Conclusion: When measuring progress toward improving immunization systems, it is helpful to use a comprehensive approach that allows for measuring multiple dimensions of the system.

Administering Multiple Injectable Vaccines During a Single Visit-Summary of Findings From the Accelerated Introduction of Inactivated Polio Vaccine Globally.

Background: In 2013, the World Health Organization's (WHO's) Strategic Advisory Group of Experts (SAGE) recommended that all 126 countries using only oral polio vaccine (OPV) introduce at least 1 dose of inactivated polio vaccine (IPV) into their routine immunization schedules by the end of 2015. In many countries, the addition of IPV would necessitate delivery of multiple injectable vaccines (hereafter, "multiple injections") during a single visit, with infants receiving IPV alongside pentavalent vaccine (which covers diphtheria, tetanus, and whole-cell pertussis; hepatitis B; and Haemophilus influenzae type b) and pneumococcal vaccine. Unanticipated concerns emerged from countries over acceptability of multiple injections, sites of administration, and safety. We contextualized the issues surrounding multiple injections by documenting concerns associated with administration of ≥3 injections, existing evidence in the published literature, and findings of a systematic review on administration practices and techniques. Methods: Concerns associated with multiple-injection visits were documented from meetings and personal communications with immunization program managers. Published literature on the acceptability of multiple injections by providers and caregivers was summarized, and a systematic review of the literature on administration practices was completed on the following topics: spacing between injection sites (ie, vaccine spacing), site of injection, route of injection, and procedural preparedness. WHO and United Nations Children's Fund data from 2013-2015 were used to assess multiple-injection visits included in national immunization schedules. Results: Healthcare provider and caregiver attitudes and practices indicated concerns about infant pain, potential adverse effects, and uncertainty about vaccine effectiveness with multiple-injection visits. Published literature reinforced the record of safety and acceptance of the recommended schedule of IPV by the SAGE, but the evidence was largely from developed countries. Parental acceptance of multiple injections was associated with a positive provider recommendation to the caregiver. Findings of the systematic review identified that the intramuscular route is preferred over the subcutaneous route for vaccine administration and that the vastus lateralis muscle is preferred over the deltoid muscle for intramuscular injections. Recommendations on vaccine spacing and procedural preparedness were based on practical necessities, but comparative evidence was not identified. During 2013-2015, 85 countries added IPV to their immunization schedules, 46 (55%) of which adopted a schedule resulting in 3 injectable vaccines being administered in a single visit. Conclusion: The multiple-injection experience identified gaps in guidance for future vaccine introductions. Global partner organizations quickly mobilized to assess, document, and communicate the existing global experience on multiple-injection visits. This evidence-based approach provided reassurance to opinion leaders, health workers, and professional societies, thus encouraging uptake of IPV as a second or third injection in an accelerated manner globally.

Impact of an Intervention to Use a Measles, Rubella, and Polio Mass Vaccination Campaign to Strengthen Routine Immunization Services in Nepal.

Background: The potential to strengthen routine immunization (RI) services through supplementary immunization activities (SIAs) is an important benefit of global measles and rubella elimination and polio eradication strategies. However, little evidence exists on how best to use SIAs to strengthen RI. As part the 2012 Nepal measles-rubella and polio SIA, we developed an intervention package designed to improve RI processes and evaluated its effect on specific RI process measures. Methods: The intervention package was incorporated into existing SIA activities and materials to improve healthcare providers' RI knowledge and practices throughout Nepal. In 1 region (Central Region) we surveyed the same 100 randomly selected health facilities before and after the SIA and evaluated the following RI process measures: vaccine safety, RI planning, RI service delivery, vaccine supply chain, and RI data recording practices. Data collection included observations of vaccination sessions, interviews with the primary healthcare provider who administered vaccines at each facility, and administrative record reviews. Pair-matched analytical methods were used to determine whether statistically significant changes in the selected RI process measures occurred over time. Results: After the SIA, significant positive changes were measured in healthcare provider knowledge of adverse events following immunization (11% increase), availability of RI microplans (+17%) and maps (+12%), and awareness of how long a reconstituted measles vial can be used before it must be discarded (+14%). For the SIA, 42% of providers created an SIA high-risk villages list, and >50% incorporated this information into RI outreach session site planning. Significant negative changes occurred in correct knowledge of measles vaccination contraindications (-11%), correct definition for a measles outbreak (-21%), and how to treat a child with a severe adverse event following immunization (-10%). Twenty percent of providers reported cancelling ≥1 RI sessions during the SIA. Many RI process measures were at high proportions (>90%) before the SIA and remained high afterward, including proper vaccine administration techniques, proper vaccine waste management, and availability of vaccine carriers and vaccine registers. Conclusions: Focusing on activities that are easily linked between SIAs and RI services, such as using SIA high-risk village list to strengthen RI microplanning and examining ways to minimize the impact of an SIA on RI session scheduling, should be prioritized when implementing SIAs.

Structural Analysis of the Glycosylated Intact HIV-1 gp120-b12 Antibody Complex Using Hydroxyl Radical Protein Footprinting.

Glycoprotein gp120 is a surface antigen and virulence factor of human immunodeficiency virus 1. Broadly neutralizing antibodies (bNAbs) that react to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system because of its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions. Here, the interaction of full-length, glycosylated gp120 with bNAb b12 is probed using high-resolution hydroxyl radical protein footprinting (HR-HRPF) by fast photochemical oxidation of proteins. HR-HRPF allows for the measurement of changes in the average solvent accessible surface area of multiple amino acids without the need for measures that might alter the protein conformation, such as mutagenesis. HR-HRPF of the gp120-b12 complex coupled with computational modeling shows a novel extensive interaction of the V1/V2 domain, probably with the light chain of b12. Our data also reveal HR-HRPF protection in the C3 domain caused by interaction of the N330 glycan with the b12 light chain. In addition to providing information about the interactions of full-length, glycosylated gp120 with b12, this work serves as a template for the structural interrogation of full-length glycosylated gp120 with other bNAbs to better characterize the interactions that drive the broad specificity of the bNAb.

Global Routine Vaccination Coverage, 2016.

The Global Vaccine Action Plan 2011-2020 (GVAP) (1), endorsed by the World Health Assembly in 2012, calls on all countries to reach ≥90% national coverage for all vaccines in the country's routine immunization schedule by 2020. CDC and the World Health Organization (WHO) evaluated the WHO and United Nations Children's Fund (UNICEF) global vaccination coverage estimates to describe changes in global and regional coverage as of 2016. Global coverage estimates for the third dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP3), the third dose of polio vaccine, and the first dose of measles-containing vaccine (MCV1) have ranged from 84% to 86% since 2010. The dropout rate (the proportion of children who started but did not complete a vaccination series), an indicator of immunization program performance, was estimated to be 5% in 2016 for the 3-dose DTP series, with dropout highest in the African Region (11%) and lowest in the Western Pacific Region (0.4%). During 2010-2016, estimated global coverage with the second MCV dose (MCV2) increased from 21% to 46% by the end of the second year of life and from 39% to 64% when older age groups (3-14 years) were included (2). Improvements in national immunization program performance are necessary to reach and sustain high vaccination coverage to increase protection from vaccine-preventable diseases for all persons.