Measles immunity gaps among children and adolescents with HIV in Zambia despite high measles vaccination and antiretroviral therapy coverage.

OBJECTIVE: The study objective was to identify measles and rubella immunity gaps among people with HIV (PWH) in Zambia despite high measles vaccine coverage and widespread access to antiretroviral therapy. DESIGN: Nationally representative cross-sectional serosurvey using biorepository specimens. METHODS: Blood specimens collected in the Zambia Population HIV Impact Assessment survey (ZAMPHIA) of 2016 were tested for measles and rubella immunoglobulin G (IgG) antibodies by enzyme immunoassay. Hierarchical generalized additive models were fit to characterize age-specific measles and rubella seroprevalence profiles by HIV infection status. Log-binomial regression was performed to identify factors associated with seronegativity. RESULTS: Of the 25 383 specimens, a subsample of 11 500 were selected and 9852 (85%) were successfully tested. Measles seroprevalence was lower among PWH compared with HIV-uninfected individuals until approximately 30 years of age. Among children younger than the age of 10 years, measles seroprevalence was 47.2% [95% confidence interval (CI): 32.7, 61.7] in PWH and 76.4% (95% CI: 74.9, 78.0) in HIV-uninfected children in same age category. In contrast, rubella seroprevalence was higher among PWH than HIV-uninfected individuals, particularly for children younger than 10 years (68.6% vs. 44.3%, P  < 0.001). Having a detectable viral load was associated with being measles seronegative (adjusted prevalence ratio 0.15, 95% CI: 0.06, 0.38). CONCLUSIONS: These results from a nationally representative serosurvey demonstrate persistence of measles immunity gaps among PWH younger than 30 years of age. There is need to implement the World Health Organization's recommendation to revaccinate children living with HIV against measles following immune reconstitution with antiretroviral therapy to protect these children and prevent measles outbreaks.

Challenges Addressing Inequalities in Measles Vaccine Coverage in Zambia through a Measles-Rubella Supplementary Immunization Activity during the COVID-19 Pandemic.

BACKGROUND: Measles-rubella supplementary immunization activities (MR-SIAs) are conducted to address inequalities in coverage and fill population immunity gaps when routine immunization services fail to reach all children with two doses of a measles-containing vaccine (MCV). We used data from a post-campaign coverage survey in Zambia to measure the proportion of measles zero-dose and under-immunized children who were reached by the 2020 MR-SIA and identified reasons associated with persistent inequalities following the MR-SIA. METHODS: Children between 9 and 59 months were enrolled in a nationally representative, cross-sectional, multistage stratified cluster survey in October 2021 to estimate vaccination coverage during the November 2020 MR-SIA. Vaccination status was determined by immunization card or through caregivers' recall. MR-SIA coverage and the proportion of measles zero-dose and under-immunized children reached by MR-SIA were estimated. Log-binomial models were used to assess risk factors for missing the MR-SIA dose. RESULTS: Overall, 4640 children were enrolled in the nationwide coverage survey. Only 68.6% (95% CI: 66.7%, 70.6%) received MCV during the MR-SIA. The MR-SIA provided MCV1 to 4.2% (95% CI: 0.9%, 4.6%) and MCV2 to 6.3% (95% CI: 5.6%, 7.1%) of enrolled children, but 58.1% (95% CI: 59.8%, 62.8%) of children receiving the MR-SIA dose had received at least two prior MCV doses. Furthermore, 27.8% of measles zero-dose children were vaccinated through the MR-SIA. The MR-SIA reduced the proportion of measles zero-dose children from 15.1% (95% CI: 13.6%, 16.7%) to 10.9% (95% CI: 9.7%, 12.3%). Zero-dose and under-immunized children were more likely to miss MR-SIA doses (prevalence ratio (PR): 2.81; 95% CI: 1.80, 4.41 and 2.22; 95% CI: 1.21 and 4.07) compared to fully vaccinated children. CONCLUSIONS: The MR-SIA reached more under-immunized children with MCV2 than measles zero-dose children with MCV1. However, improvement is needed to reach the remaining measles zero-dose children after SIA. One possible solution to address the inequalities in vaccination is to transition from nationwide non-selective SIAs to more targeted and selective strategies.

Using geospatial models to map zero-dose children: factors associated with zero-dose vaccination status before and after a mass measles and rubella vaccination campaign in Southern province, Zambia.

INTRODUCTION: Despite gains in global coverage of childhood vaccines, many children remain undervaccinated. Although mass vaccination campaigns are commonly conducted to reach these children their effectiveness is unclear. We evaluated the effectiveness of a mass vaccination campaign in reaching zero-dose children. METHODS: We conducted a prospective study in 10 health centre catchment areas in Southern province, Zambia in November 2020. About 2 months before a national mass measles and rubella vaccination campaign conducted by the Ministry of Health, we used aerial satellite maps to identify built structures. These structures were visited and diphtheria-tetanus-pertussis (DTP) and measles zero-dose children were identified (children who had not received any DTP or measles-containing vaccines, respectively). After the campaign, households where measles zero-dose children were previously identified were targeted for mop-up vaccination and to assess if these children were vaccinated during the campaign. A Bayesian geospatial model was used to identify factors associated with zero-dose status and measles zero-dose children being reached during the campaign. We also produced fine-scale zero-dose prevalence maps and identified optimal locations for additional vaccination sites. RESULTS: Before the vaccination campaign, 17.3% of children under 9 months were DTP zero-dose and 4.3% of children 9-60 months were measles zero-dose. Of the 461 measles zero-dose children identified before the vaccination campaign, 338 (73.3%) were vaccinated during the campaign and 118 (25.6%) were reached by a targeted mop-up activity. The presence of other children in the household, younger age, greater travel time to health facilities and living between health facility catchment areas were associated with zero-dose status. Mapping zero-dose prevalence revealed substantial heterogeneity within and between catchment areas. Several potential locations were identified for additional vaccination sites. CONCLUSION: Fine-scale variation in zero-dose prevalence and the impact of accessibility to healthcare facilities on vaccination coverage were identified. Geospatial modelling can aid targeted vaccination activities.

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.