BACKGROUND: In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0·1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non-pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response. METHODS: Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT(50)). Participants with a PRNT(50) titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years. FINDINGS: Among the 764 participants enrolled, 566 (74%) completed the 5-year visit. 5 years after vaccination, 539 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older. INTERPRETATION: A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity. FUNDING: Gavi, the Vaccine Alliance through the CDC Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

OBJECTIVE: To analyse progress in global vaccination against human papillomavirus (HPV) during the covid-19 pandemic, with a particular focus on equity. DESIGN: Descriptive study of World Health Organization-Unicef vaccination coverage estimates. SETTING: WHO-Unicef estimates of global, regional, and national HPV vaccination coverage, before (2010-19) and during (2020-21) the covid-19 pandemic. PARTICIPANTS: Girls aged 9-14 years who received a HPV vaccine globally before (12.3 million in 2019) and during (2020-21) the covid-19 pandemic (10.6 million in 2021). MAIN OUTCOME MEASURES: Mean programme and population adjusted coverage for first dose HPV vaccine (HPV1) by country, country income (World Bank income categories), sex, and WHO region, before (2010-19) and during (2020-21) the covid-19 pandemic, based on WHO-Unicef estimates of HPV vaccination coverage. Annual number of national HPV vaccine programme introduced since the first HPV vaccine licence was granted in 2006, based on data reported to WHO-Unicef. Number of girls vaccinated before (2019) versus during (2020-21) the covid-19 pandemic period. RESULTS: Mean coverage of HPV vaccination programmes among girls decreased from 65% in 2010-19 to 50% in 2020-21 in low and middle income countries compared with an increase in high income countries from 61% to 69% for the same periods. Population adjusted HPV1 coverage was higher among girls in high income countries before and during the covid-19 pandemic than in girls in low and middle income countries. During the covid-19 pandemic, population adjusted HPV1 coverage among boys in high income countries was higher and remained higher than coverage among girls in low and middle income countries. Globally, 23 countries recorded a severe reduction in their HPV programme (≥50% reduction in coverage), and another 3.8 million girls globally did not receive a HPV vaccine in countries with existing HPV vaccination programmes in 2020-21 compared with 2019. A reduction was seen in the annual rate of new introductions of national HPV vaccine programmes during 2020-21, affecting countries in all income categories, followed by an increase in introductions during 2022. During the second half of 2023, several low and middle income countries with large birth cohorts and a high relative burden of cervical cancer have yet to introduce HPV vaccination. CONCLUSIONS: Although HPV vaccines have been available for more than 15 years, global HPV vaccination coverage is low. During the covid-19 pandemic period (2020-21 globally), worsening coverage, delayed introductions of national vaccine programmes, and an increase in missed girls globally (ie, girls who did not receive a HPV vaccine compared with the previous year in countries with an existing HPV vaccination programme) that disproportionately affected girls in low and middle income countries were found. Urgent and innovative recovery efforts are needed to accelerate national introduction of HPV vaccination programmes and achieve high coverage of HPV vaccination worldwide.

BACKGROUND: In 2016, the World Health Organization recommended that a fractional dose of yellow fever (YF) vaccine could be used in persons 2 years of age or older in response to an emergency that resulted in a global shortage of available YF vaccine. However, this recommendation did not extend to the youngest age group licensed for YF vaccine because there were no published data on the use or safety of fractional dose YF vaccination in children aged 9-23 months. We conducted a single-blind randomized controlled trial, comparing the immunogenicity and safety of fractional one-fifth and one-half doses of Bio-Manguinhos 17DD YF vaccine with full dose in children aged 9-23 months old in Uganda. In this paper, we present the interim analysis on safety. METHODS: Children aged 9-23 months presenting for routine well-child services were recruited for inclusion at one of three study sites. We collected data during March 26, 2019-August 31, 2020, on all adverse events following immunization (AEFI) during active surveillance for 28 days post-vaccination using multiple collection tools including a diary card with an objective measurement of fever. An independent team from the Uganda national AEFI Committee investigated and classified serious AEFI (SAE) according to Brighton Collaboration Criteria. RESULTS: Among 1053 enrolled children, 672 (64%) were reported to have a non-serious AEFI (NSAE) and 17 (2%) were reported to have a SAE. The most common AEFI were diarrhoea, fever, and rash, each reported by 355 (34%), 338 (33%), and 188 (18%) participants, respectively. Among 17 participants with SAE, eight were reported to have had seizures and five were hospitalised for seizures or other causes (respiratory symptoms, gastrointestinal illness, malaria). Four SAEs (deaths) occurred >28 days after vaccination. There were no reported cases of pre-specified or vaccine-related SAEs. We observed no significant difference in frequency or severity of adverse events among the study groups. CONCLUSIONS: Using comprehensive active surveillance monitoring, we did not identify any unexpected safety concerns among children aged <2 years receiving YF vaccination, including with the fractional doses. Although we identified a high number of both serious and non-serious AEFI, none were determined to be causally related to YF vaccination. These results provide evidence for the safety of fractional dose YF vaccination among children aged 9-23 months.

This report describes the status of introductions globally for eight World Health Organization (WHO)-recommended new and underutilized vaccines, comprising 10 individual vaccine antigens. By 2021, among 194 countries worldwide, 33 (17%) provided all of these 10 WHO-recommended antigens as part of their routine immunization schedules; only one low-income country had introduced all of these recommended vaccines. Universal hepatitis B birth dose; human papillomavirus vaccine; rotavirus vaccine; and diphtheria, tetanus, and pertussis-containing vaccine first booster dose have been introduced by 57%, 59%, 60%, and 72% of all countries worldwide, respectively. Pneumococcal conjugate vaccine, rubella-containing vaccine, measles-containing vaccine second dose, and Haemophilus influenzae type b vaccine have been introduced by 78%, 89%, 94%, and 99% of all countries, respectively. The annual rate of new vaccine introductions declined precipitously when the COVID-19 pandemic started, from 48 in 2019 to 15 in 2020 before rising to 26 in 2021. Increased efforts to accelerate new and underutilized vaccine introductions are urgently needed to improve universal equitable access to all recommended vaccines to achieve the global Immunization Agenda 2021-2030 (IA2030) targets.

BACKGROUND: Despite providing tetanus-toxoid-containing vaccine (TTCV) to infants and reproductive-age women, Uganda reports one of the highest incidences of non-neonatal tetanus (non-NT). Prompted by unusual epidemiologic trends among reported non-NT cases, we conducted a retrospective record review to see whether these data reflected true disease burden. METHODS: We analysed nationally reported non-NT cases during 2012-2017. We visited 26 facilities (14 hospitals, 12 health centres) reporting high numbers of non-NT cases (n = 20) or zero cases (n = 6). We identified non-NT cases in facility registers during 1 January 2016-30 June 2017; the identified case records were abstracted. RESULTS: During 2012-2017, a total of 24 518 non-NT cases were reported and 74% were ≥5 years old. The average annual incidence was 3.43 per 100 000 population based on inpatient admissions. Among 482 non-NT inpatient cases reported during 1 January 2016-30 June 2017 from hospitals visited, 342 (71%) were identified in facility registers, despite missing register data (21%). Males comprised 283 (83%) of identified cases and 60% were ≥15 years old. Of 145 cases with detailed records, 134 (92%) were clinically confirmed tetanus; among these, the case-fatality ratio (CFR) was 54%. Fourteen cases were identified at two hospitals reporting zero cases. Among >4000 outpatient cases reported from health centres visited, only 3 cases were identified; the remainder were data errors. CONCLUSIONS: A substantial number of non-NT cases and deaths occur in Uganda. The high CFR and high non-NT burden among men and older children indicate the need for TTCV booster doses across the life course to all individuals as well as improved coverage with the TTCV primary series. The observed data errors indicate the need for data quality improvement activities.

In Senegal, cervical cancer is the most common cancer among women and the leading cause of morbidity and mortality from all cancers. In 2018, Senegal launched a national human papillomavirus (HPV) vaccination program with Gavi, the Vaccine Alliance (Gavi), support. HPV vaccination was incorporated into the national immunization program as a two-dose schedule, with a 6-12-month interval, to nine-year-old girls via routine immunization (RI) services at health facilities, schools and community outreach services throughout the year. During February to March 2020, we conducted interviews to assess the awareness, feasibility, and acceptability of the HPV vaccination program with a cross-sectional convenience sample of healthcare workers (HCWs), school personnel, community healthcare workers (cHCWs), parents, and community leaders from 77 rural and urban health facility catchment areas. Participants were asked questions on HPV vaccine knowledge, delivery, training, and community acceptability of the program. We conducted a descriptive analysis stratified by respondent type. Data were collected from 465 individuals: 77 HCW, 78 school personnel, 78 cHCWs, 152 parents, and community leaders. The majority of HCWs (83.1%) and cHCWs (74.4%) and school personnel (57.7%) attended a training on HPV vaccine before program launch. Of all respondents, most (52.5-87.2%) were able to correctly identify the target population. The majority of respondents (60.2-77.5%) felt that the vaccine was very accepted or accepted in the community. Senegal's HPV vaccine introduction program, among the first national programs in the African region, was accepted by community stakeholders. Training rates were high, and most respondents identified the target population correctly. However, continued technical support is needed for the integration of HPV vaccination as a RI activity for this non-traditional age group. The Senegal experience can be a useful resource for countries planning to introduce the HPV vaccine.

Following successful school-based demonstration programs in 2014-2016, the human papillomavirus (HPV) vaccine was introduced nationwide in Senegal for 9-year-old girls in 2018, using a routine service delivery strategy at health facilities, schools, and other outreach sites. We reviewed the HPV vaccine introduction in Senegal to understand the successes, challenges, and lessons learned. Focusing on three key domains (program decision-making, planning, and implementation), we conducted ten semi-structured interviews during 2019-2020 with purposively selected national-level stakeholders (government, expert advisory committee, key technical and implementation partners) and comprehensive desk reviews of country documents on HPV vaccine introduction. Due to the global HPV vaccine shortage, the introduction was limited to a single-age cohort; therefore, 9-year-old girls were chosen. This strategy enabled Senegal to potentially reach more girls in primary education because school enrolment rates decline thereafter. Vaccination through routine delivery platforms (i.e., health facility, school-based, and community outreach) was perceived to be more cost-effective than a campaign approach. High-level political commitment and collaborations between immunization and education partners were frequently cited by key informants as reasons for a successful vaccine introduction. All key informants reported that the health care worker (HCW) strike, rumors, and vaccine hesitancy negatively impacted the introduction. Other challenges noted included insufficient information on attitudes towards HPV vaccination among HCWs, teachers, and community members. Senegal successfully introduced HPV vaccine into the national immunization schedule, using a routine delivery strategy. Strong leadership and a multi-sectoral approach likely contributed to this success. To build sustainability of the HPV vaccination program in the future, it is important to improve the understanding and engagement among all stakeholders, including HCWs and community members, and to strengthen and innovate communication and crisis management strategies. To better understand the efficiency and effectiveness of Senegal's vaccination strategy, additional assessments of the operational costs and coverage achieved are needed.

BACKGROUND: In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. METHODS: We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and at 1 month and 1 year after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. RESULTS: Among 716 participants who completed the 1-month follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Among 684 participants who completed the 1-year follow-up, 666 (97%; 95% CI, 96 to 98) were seropositive for yellow fever antibody. The distribution of titers among the participants who were seronegative for yellow fever antibody at baseline varied significantly among age groups at 1 month and at 1 year (P<0.001 for both comparisons). CONCLUSIONS: A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in participants who were seronegative at baseline. Titers remained above the threshold for seropositivity at 1 year after vaccination in nearly all participants who were seropositive at 1 month after vaccination. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

Background In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. Methods We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and 28 to 35 days after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT50). Participants with a PRNT50 titer of 10 or higher at baseline were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. Results Among 716 participants who completed follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Conclusions A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in most of the participants who were seronegative at baseline. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers for Disease Control and Prevention.).

Introduction: In 2010, the Global Vaccine Action Plan called on all countries to reach and sustain 90% national coverage and 80% coverage in all districts for the third dose of diphtheria-tetanus-pertussis vaccine (DTP3) by 2015 and for all vaccines in national immunization schedules by 2020. The aims of this study are to analyze recent trends in national vaccination coverage in the World Health Organization African Region andto assess how these trends differ by country income category. Methods: We compared national vaccination coverage estimates for DTP3 and the first dose of measles-containing vaccine (MCV) obtained from the World Health Organization (WHO)/United Nations Children's Fund (UNICEF) joint estimates of national immunization coverage for all African Region countries. Using United Nations (UN) population estimates of surviving infants and country income category for the corresponding year, we calculated population-weighted average vaccination coverage by country income category (i.e., low, lower middle, and upper middle-income) for the years 2000, 2005, 2010 and 2015. Results: DTP3 coverage in the African Region increased from 52% in 2000 to 76% in 2015,and MCV1 coverage increased from 53% to 74% during the same period, but with considerable differences among countries. Thirty-six African Region countries were low income in 2000 with an average DTP3 coverage of 50% while 26 were low income in 2015 with an average coverage of 80%. Five countries were lower middle-income in 2000 with an average DTP3 coverage of 84% while 12 were lower middle-income in 2015 with an average coverage of 69%. Five countries were upper middle-income in 2000 with an average DTP3 coverage of 73% and eight were upper middle-income in 2015 with an average coverage of 76%. Conclusion: Disparities in vaccination coverage by country persist in the African Region, with countries that were lower middle-income having the lowest coverage on average in 2015. Monitoring and addressing these disparities is essential for meeting global immunization targets.

In 1974, the World Health Organization (WHO) established the Expanded Program on Immunization* to provide protection against six vaccine-preventable diseases through routine infant immunization (1). Based on 2015 WHO and United Nations Children's Fund (UNICEF) estimates, global coverage with the third dose of diphtheria-tetanus-pertussis vaccine (DTP3), the first dose of measles-containing vaccine (MCV1) and the third dose of polio vaccine (Pol3) has remained stable (84%-86%) since 2010. From 2014 to 2015, estimated global coverage with the second MCV dose (MCV2) increased from 39% to 43% by the end of the second year of life and from 58% to 61% when older age groups were included. Global coverage was higher in 2015 than 2010 for newer or underused vaccines, including rotavirus vaccine, pneumococcal conjugate vaccine (PCV), rubella vaccine, Haemophilus influenzae type b (Hib) vaccine, and 3 doses of hepatitis B (HepB3) vaccine. Coverage estimates varied widely by WHO Region, country, and district; in addition, for the vaccines evaluated (MCV, DTP3, Pol3, HepB3, Hib3), wide disparities were found in coverage by country income classification. Improvements in equity of access are necessary to reach and sustain higher coverage and increase protection from vaccine-preventable diseases for all persons.