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.

COVID-19 Mortality and Vaccine Coverage - Hong Kong Special Administrative Region, China, January 6, 2022-March 21, 2022.

On January 6, 2022, a cluster of COVID-19 cases* caused by the Omicron variant of SARS-CoV-2, the virus that causes COVID-19, was detected in Hong Kong Special Administrative Region, China (Hong Kong), resulting in the territory's fifth wave of COVID-19 cases (1). This wave peaked on March 4, 2022, with 8,764 COVID-19 cases per million population (2), resulting in a total of 1,049,959 cases and 5,906 COVID-19-associated deaths reported to the Hong Kong Department of Health during January 6-March 21, 2022.† Throughout this period, the COVID-19 mortality rate in Hong Kong (37.7 per million population) was among the highest reported worldwide since the COVID-19 pandemic began (3). Publicly available data on age-specific vaccination coverage in Hong Kong with a 2-dose primary vaccination series (with either Sinovac-CoronaVac [Sinovac], an inactivated COVID-19 viral vaccine, recommended for persons aged ≥3 years or BNT162b2 [Pfizer-BioNTech], an mRNA vaccine, for persons aged ≥5 years), as of December 23, 2021,§,¶ and COVID-19 mortality during January 6-March 21, 2022, were analyzed. By December 23, 2021, 67% of vaccine-eligible persons in Hong Kong had received ≥1 dose of a COVID-19 vaccine, 64% had received ≥2 doses, and 5% had received a booster dose. Among persons aged ≥60 years, these proportions were 52%, 49%, and 7%, respectively. Among those aged ≥60 years, vaccination coverage declined with age: 48% of persons aged 70-79 years had received ≥1 dose, 45% received ≥2 doses, and 7% had received a booster, and among those aged ≥80 years, 20%, 18%, and 2% had received ≥1 dose, ≥2 doses, and a booster dose, respectively. Among 5,906 COVID-19 deaths reported, 5,655 (96%) occurred in persons aged ≥60 years**; among these decedents, 3,970 (70%) were unvaccinated, 18% (1,023) had received 1 vaccine dose, and 12% (662) had received ≥2 doses. The overall rates of COVID-19-associated mortality among persons aged ≥60 years who were unvaccinated, who had received 1 COVID-19 vaccine dose, and who had received ≥2 vaccine doses were 10,076, 1,099, and 473 per million population, respectively; the risk for COVID-19-associated death among unvaccinated persons was 21.3 times that among recipients of 2-3 doses in this age group. The high overall mortality rate during the ongoing 2022 Hong Kong Omicron COVID-19 outbreak is being driven by deaths among unvaccinated persons aged ≥60 years. Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially among persons aged ≥60 years.

National, Regional and Global Certification Bodies for Polio Eradication: A Framework for Verifying Measles Elimination.

The Global Certification Commission (GCC), Regional Certification Commissions (RCCs), and National Certification Committees (NCCs) provide a framework of independent bodies to assist the Global Polio Eradication Initiative (GPEI) in certifying and maintaining polio eradication in a standardized, ongoing, and credible manner. Their members meet regularly to comprehensively review population immunity, surveillance, laboratory, and other data to assess polio status in the country (NCC), World Health Organization (WHO) region (RCC), or globally (GCC). These highly visible bodies provide a framework to be replicated to independently verify measles and rubella elimination in the regions and globally.

Experience With Inactivated Polio Vaccine Introduction and the "Switch" From Trivalent to Bivalent Oral Polio Vaccine in the World Health Organization's Western Pacific Region.

The World Health Organization (WHO) Western Pacific Region (WPR) has maintained its polio-free status since 2000. The emergence of vaccine-derived polioviruses (VDPVs), however, remains a risk, as oral polio vaccine (OPV) is still used in many of the region's countries, and pockets of unimmunized or underimmunized children exist in some countries. From 2014 to 2016, the region participated in the globally coordinated efforts to introduce inactivated polio vaccine (IPV) into all countries that did not yet include it in their national immunization schedules, and to "switch" from trivalent OPV (tOPV) to bivalent OPV (bOPV) in all countries still using OPV in 2016.As of September 2016, 15 of 17 countries and areas that did not use IPV by the end of 2014 had introduced IPV. Introduction in the remaining 2 countries has been delayed because of the global shortage of IPV, making it unavailable to select lower-risk countries until the fourth quarter of 2017. All 16 countries using OPV as of 2016 successfully withdrew tOPV during the globally synchronized switch from April to May 2016, and 15 of 16 countries introduced bOPV at the same time, with the remaining country introducing it within 30 days. While countries were primarily responsible for self-funding these activities, additional support was provided.The main challenges encountered in the Western Pacific Region with both IPV introduction and the tOPV-bOPV switch were related to overcoming regulatory policies and challenges with vaccine procurement. As a result, substantial lead time was needed to resolve procurement and regulatory issues before the introductions of IPV and bOPV. As the global community prepares for the full removal of all OPV from immunization programs, this need for lead time and consideration of the impact on national policies should be considered.

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.

Using the World Health Organization Measles Programmatic Risk Assessment Tool for Monitoring of Supplemental Immunization Activities in the Philippines.

In 2012, the World Health Organization Regional Committee for the Western Pacific Region (WPR) reaffirmed its commitment to eliminate measles and urged WPR member states to interrupt endemic measles virus transmission as rapidly as possible. In 2013, a large measles outbreak occurred in the Philippines despite implementation of measles elimination strategies including a nationwide supplemental immunization activity (SIA) in 2011 using measles- and rubella-containing vaccine and targeting children aged nine months to seven years. To prevent future measles outbreaks a new tool was developed to assess district-level risk for measles outbreaks, based on the WPR polio risk assessment tool previously applied in the Philippines. Risk was assessed as a function of combined indicator scores from four data input categories: population immunity, surveillance quality, program performance, and threat assessment. On the basis of the overall score, the tool assigned each district a risk category of low, medium, high, or very high. Of the 122 districts and highly urbanized cities in the Philippines, 58 (48%) were classified as high risk or very high risk, including the district of the Metro Manila area and Region 4A where the outbreak began in 2013. Risk assessment results were used to guide the monitoring and supervision during the nationwide SIA conducted in 2014. The initial tool drafted in the Philippines served as a template for development of the global risk assessment tool. Regular annual measles programmatic risk assessments can be used to help plan risk mitigation activities and measure progress toward measles elimination.

Development of a District-Level Programmatic Assessment Tool for Risk of Measles Virus Transmission.

All six World Health Organization (WHO) regions have now set goals for measles elimination by or before 2020. To prioritize measles elimination efforts and use available resources efficiently, there is a need to identify at-risk areas that are offtrack from meeting performance targets and require strengthening of programmatic efforts. This article describes the development of a WHO measles programmatic risk assessment tool to be used for monitoring, guiding, and sustaining measles elimination efforts at the subnational level. We outline the tool development process; the tool specifications and requirements for data inputs; the framework of risk categories, indicators, and scoring; and the risk category assignment. Overall risk was assessed as a function of indicator scores that fall into four main categories: population immunity, surveillance quality, program performance, and threat assessment. On the basis of the overall score, the tool assigns each district a risk of either low, medium, high, or very high. The cut-off criteria for the risk assignment categories were based on the distribution of scores from all possible combinations of individual indicator cutoffs. The results may be used for advocacy to communicate risk to policymakers, mobilize resources for corrective actions, manage population immunity, and prioritize programmatic activities. Ongoing evaluation of indicators will be needed to evaluate programmatic performance and plan risk mitigation activities effectively. The availability of a comprehensive tool that can identify at-risk districts will enhance efforts to prioritize resources and implement strategies for achieving the Global Vaccine Action Plan goals for measles elimination.

Progress toward measles elimination­Philippines, 1998-2014.

In 2005, the Regional Committee for the World Health Organization (WHO) Western Pacific Region (WPR) established a goal to eliminate measles by 2012.The recommended elimination strategies in WPR include 1) ≥95% 2-dose coverage with measles-containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs); 2) high-quality case-based measles surveillance; 3) laboratory surveillance with timely and accurate testing of specimens to confirm or discard suspected cases and detect measles virus genotypes; and 4) measles outbreak preparedness, rapid response, and appropriate case management. In the WPR, the Philippines set a national goal in 1998 to eliminate measles by 2008. This report describes progress toward measles elimination in the Philippines during 1998-2014 and challenges remaining to achieve the goal. WHO-United Nations Children's Fund (UNICEF)-estimated coverage with the routine first dose of MCV (MCV1) increased from 80% in 1998 to 90% in 2013, and coverage with the routine second dose of MCV (MCV2) increased from 10% after nationwide introduction in 2010 to 53% in 2013. After nationwide SIAs in 1998 and 2004, historic lows in the numbers and incidence of reported measles cases occurred in 2006. Despite nationwide SIAs in 2007 and 2011, the number of reported cases and incidence generally increased during 2007-2012, and large measles outbreaks occurred during 2013-2014 that affected infants, young children, older children, and young adults and that were prolonged by delayed and geographically limited outbreak response immunization activities during 2013-2014. For the goal of measles elimination in WPR to be achieved, sustained investments are required in the Philippines to strengthen health systems, implement the recommended elimination strategies, and develop additional strategies to identify and reduce measles susceptibility in specific geographic areas and older age groups.

COVID-19 Mortality and Vaccine Coverage - Hong Kong Special Administrative Region, China, January 6, 2022-March 21, 2022.

What is already known about this topic?: COVID-19 vaccines are important tools to protect populations from severe disease and death. What is added by this report?: Among persons aged ≥60 years in Hong Kong, 49%, had received ≥2 doses of a COVID-19 vaccine, and vaccination coverage declined with age. During January-March 2022, reported COVID-19-associated deaths rose rapidly in Hong Kong. Among these deaths, 96% occurred in persons aged ≥60 years; within this age group, the risk for death was 20 times lower among those who were fully vaccinated compared with those who were unvaccinated. What are the implications for public health practice?: Efforts to identify and address gaps in age-specific vaccination coverage can help prevent high mortality from COVID-19, especially in older adults.

Age at first dose of measles vaccination in Ethiopia.

BACKGROUND: Although measles vaccination is recommended to be given at nine months of age in Ethiopia and in most of sub-Saharan Africa, no information is available about the age at which children actually receive their first dose of measles vaccine. This has important implications in terms of preventing infection and averting epidemics of measles. OBJECTIVE: To determine the age at which Ethiopian children actually receive their first dose of measles vaccine. DESIGN: Cross sectional study. SETTING: All major vaccination facilities including private and non-governmental health facilities that were registered with the Addis Ababa city Administration Health Bureau. SUBJECTS: A total of 17,674 records of children who received measles vaccination in health facilities were reviewed and in rural areas 615 children were surveyed over one year period September 2004 to August 2005. RESULTS: In both the urban and the rural settings the median age of children at first dose of measles vaccination was nine months. In the rural areas only 19.8% of children had vaccination cards. Measles coverage by card and history in rural areas was 84.4%. Many children from the rural site received measles vaccination during supplemental immunisation activities (SIAs) rather than from routine vaccination programmes. Measles coverage significantly varies among sub-cities in Addis Ababa. CONCLUSION: Vaccination practices and measles coverage levels do not support delaying the first measles vaccine dose. Strengthening the routine vaccination programmes must receive priority before changing recommended age for the first dose of measles vaccine.

Low population Japanese encephalitis virus (JEV) seroprevalence in Udayapur district, Nepal, three years after a JE vaccination programme: A case for further catch up campaigns?

The live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 has been used in Nepal for catch-up campaigns and is now included in the routine immunisation schedule. Previous studies have shown good vaccine efficacy after one dose in districts with a high incidence of JE. The first well-documented dengue outbreak occurred in Nepal in 2006 with ongoing cases now thought to be secondary to migration from India. Previous infection with dengue virus (DENV) partially protects against JE and might also influence serum neutralising antibody titres against JEV. This study aimed to determine whether serum anti-JEV neutralisation titres are: 1. maintained over time since vaccination, 2. vary with historic local JE incidence, and 3. are associated with DENV neutralising antibody levels. We conducted a cross-sectional study in three districts of Nepal: Banke, Rupandehi and Udayapur. Udayapur district had been vaccinated against JE most recently (2009), but had been the focus of only one campaign, compared with two in Banke and three in Rupandehi. Participants answered a short questionnaire and serum was assayed for anti-JEV and anti-DENV IgM and IgG (by ELISA) and 50% plaque reduction neutralisation titres (PRNT50) against JEV and DENV serotypes 1-4. A titre of ≥1:10 was considered seropositive to the respective virus. JEV neutralising antibody seroprevalence (PRNT50 ≥ 1:10) was 81% in Banke and Rupandehi, but only 41% in Udayapur, despite this district being vaccinated more recently. Sensitivity of ELISA for both anti-JEV and anti-DENV antibodies was low compared with PRNT50. DENV neutralising antibody correlated with the JEV PRNT50 ≥1:10, though the effect was modest. IgM (indicating recent infection) against both viruses was detected in a small number of participants. We also show that DENV IgM is present in Nepali subjects who have not travelled to India, suggesting that DENV may have become established in Nepal. We therefore propose that further JE vaccine campaigns should be considered in Udayapur district, and similar areas that have had fewer vaccination campaigns.

Polio outbreak response in Ethiopia.

BACKGROUND: Ethiopia had been polio-free for almost four years until December 2004. However, between December 2004 and February 2006, 24 children were paralysed as a result of infection with wild poliovirus imported from the neighbouring country of Sudan. In response, the country has attempted to document the impact of various response measures on the containment of wild poliovirus transmission. OBJECTIVES: This study aims at systematic and epidemiological assessment of the extent of the outbreak, its determinants, and the lessons learned as well as the implications for future control strategies to interrupt wild poliovirus transmission. DESIGN: A cross-sectional study design with qualitative and quantitative data collection approaches was used to conduct the epidemiologic assessment. SUBJECTS: All confirmed wild poliovirus cases, and reported acute flaccid paralysis cases in close proximity to the confirmed polio cases were the study subjects. Child caretakers and health service providers were interviewed as part of the investigation. RESULTS: Between December 2004 and February 2006, eight children from Tigray Regional State, nine children from Amhara Regional State and seven children from Oromia Regional State were paralysed as a result of infection with wild poliovirus type 1. Genetic sequencing demonstrated two separate importations to Ethiopia. Risk factors that may have facilitated spread of the outbreak within the country included gaps in vaccination coverage and interruption of the cold chain system, gaps in acute flaccid paralysis surveillance performance, high population mobility, poor environmental sanitation, crowded living conditions and unsafe drinking water. In response to the outbreak, Ethiopia conducted detailed outbreak investigations within two days of confirmation of the index cases. Large-scale, house-to-house vaccination campaigns were also implemented. As a result, the three regions interrupted the wild poliovirus transmission within the regions within one year of confirmation of the index case. CONCLUSION: Outbreak response activities were successful in interrupting the imported wild poliovirus transmission in Tigray, Amhara and Oromia Regional States of Ethiopia within a one-year period of time. In Ethiopia, programme strategies should be intensified to contain further spread and prevent future importation of wild poliovirus. Large-scale immunisation campaigns should reach every child, including those isolated by geography, poverty and security.

Seroprevalence of hepatitis B virus and hepatitis C virus co-infection among people living with HIV/AIDS visiting antiretroviral therapy centres in Nepal: a first nationally representative study.

OBJECTIVES: To assess the prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) co-infections among people living with HIV (PLHIV) in Nepal. METHODS: A sample of 677 PLHIV representing key affected populations (KAP) in Nepal, who were undergoing antiretroviral (ART) therapy in ART clinics around the country, were voluntarily enrolled in the study. Rapid kit-based testing followed by ELISA for validation was performed, focusing on HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV). A multivariate logistic regression model was used to identify factors associated with HBV and HCV co-infection. RESULTS: HCV and HBV co-infection among the 677 PLHIV was found to be 19% (95% confidence interval (CI) 16.6-22.7%) and 4.4% (95% CI 3.1-6.6%), respectively. The Eastern Region had the highest percentage of HCV infection (48%). The age group with the highest rates of co-infection was 30-39 years (58% and 70%, respectively, for HCV and HBV co-infection). After adjusting for confounding, males were more likely to have HBV co-infection than females (adjusted odds ratio (AOR) 4.61, 95% CI 1.42-14.98). Similarly, PLHIV who were male (AOR 5.7, 95% CI 2.06-15.98), had a secondary level of education (AOR 3.04, 95% CI 1.06-8.70), or who were drug users (AOR 28.7, 95% CI 14.9-55.22) were significantly more likely to have HCV co-infection. CONCLUSION: This first ever national assessment of HIV, HBV, and HCV co-infection performed among PLHIV in Nepal demonstrates that HCV and HBV infections are a health threat to this population and that interventions are required to mitigate the effects of co-infection and to prevent further morbidity and mortality.

The effect of diarrheal disease on bivalent oral polio vaccine (bOPV) immune response in infants in Nepal.

BACKGROUND: A globally-coordinated phase out of all type 2 containing oral polio vaccine (OPV) is planned for April 2016 during which bivalent 1+3 OPV (bOPV) will replace trivalent OPV (tOPV) in routine immunization schedules and campaigns. Diarrhea impairs the immune response to tOPV, but the effect of diarrhea on bOPV is unknown. METHODS: Infants aged 6 weeks to 11 months, who had received <3 doses of OPV and had mild-moderate diarrhea or no diarrhea, were recruited at five health facilities in Nepal. Neutralizing antibody titers to poliovirus types 1 and 3 were measured before and 28 days after bOPV administration. The effect of diarrhea and other factors on seroconversion or boosting in antibody titers to poliovirus was assessed by multivariable analysis. RESULTS: Infants with diarrhea, versus those without diarrhea, had reduced response for poliovirus types 1 (56% [87/156] vs 66% [109/164]) and 3 (34% [70/209] vs 52% [122/236]). After adjusting for other factors, infants with diarrhea had significantly reduced response for type 3 (odds ratio [OR]=0.44, 95% CI 0.29-0.68), as did infants with >5 loose stools per day (OR=0.36, 95% CI 0.21-0.62). CONCLUSIONS: Diarrhea reduced the immune response to bOPV. Provision of additional doses of polio vaccine is necessary to maintain high population immunity in areas with high prevalence of diarrheal disease. CLINICAL TRIAL REGISTRY: This study is registered at clinicaltrials.gov as NCT01559636.

The sensitivity of Medicare billing claims data for monitoring mammography use by elderly women.

Mammography use is monitored through Medicare billing claims; however, the sensitivity of this data source has not been previously described. This study included 10,852 Colorado women ages 65 and older with a mammogram in 1998 as registered by the Colorado Mammography Project who were Medicare fee-for-service (FFS) enrollees. These records were matched to Medicare billing data to assess the proportion of those mammograms submitted for payment to Medicare. The overall sensitivity of the FFS Medicare billing data for screening mammography was 85 percent. Medicare billing claims were less sensitive for younger women, African Americans, women with some college education, and women with supplementary private insurance. In Colorado, the Medicare FFS billing claims understates mammography usage by 15 percent. Care must be taken when comparing mammography use derived from Medicare billing claims, as the sensitivity of billing data can vary substantially by age, race, and socioeconomic status.

Postpartum HELLP syndrome.

Presented is a case of postpartum pre-eclampsia-eclampsia associated with hemolysis, elevated liver enzymes and low platelet count.

Influencing care in acute myocardial infarction: a randomized trial comparing 2 types of intervention.

The purpose of this study was to evaluate performance feedback delivered by on-site presentations compared to mailed feedback on improving acute myocardial infarction (AMI) care. We used a randomized trial including 18 hospitals nested within the Cooperative Cardiovascular Project. Patients comprised AMI Medicare patients admitted before (n = 929, 1994 and 1995) and after intervention (n = 438, 1996). Control hospitals received written feedback by mail. The experimental intervention group received a presentation led by a cardiologist and a quality improvement specialist. We assessed the proportion of patients receiving appropriate AMI care before and after the intervention. Both univariate and multivariate analyses demonstrated no effect of the intervention in increasing the proportion of patients who received reperfusion, aspirin, beta-blockers, or angiotensin-converting enzyme inhibitors. On-site feedback presentations were not associated with a larger improvement in AMI care compared to the mailed feedback. Other interventions, such as opinion leaders and patient-directed interventions, may be necessary in order to improve the care of AMI patients.

Increasing influenza and pneumococcal vaccination and tuberculosis screening among residents of Colorado long-term care facilities.

Persons residing in long-term care facilities are especially vulnerable to potentially preventable morbidity and mortality caused by influenza, S. pneumoniae, and tuberculosis. This project's objective was to increase the rates of pneumococcal vaccination, tuberculosis screening, and annual influenza vaccination. Intervention consisted of staff training videos, sample policies, and educational materials for residents and their families. At baseline during the 1995-1996 flu season, 84% of Colorado long-term care residents were vaccinated for influenza; 16% of residents had ever received pneumococcal vaccination; and 59% had been screened for tuberculosis. At remeasurement during 1997 to 1998, influenza vaccination rates were up to 89%, p = 0.006. The percentage of residents who had ever received pneumococcal vaccination increased to 48% at remeasurement, p < 0.001. Tuberculosis screening rates increased to 83%, p < 0.001. Following an educational intervention targeting both residents and staff, residents were significantly more likely to receive all three preventive services.