Amy K. Winter

Background: Combination antiretroviral therapy (cART) reduces morbidity among children living with HIV (CHIV) but does not restore vaccine-induced measles immunity. Many CHIV now initiate cART before measles vaccination but the impact on measles seroprevalence is not understood. This study compared measles seropositivty between CHIV initiating cART before and after 9 months in Zambia. Methods: This retrospective study was nested within a cohort study of CHIV and community-based studies in Macha, Zambia conducted from 2007-2020. Samples were tested for measles IgG antibodies by enzyme immunoassay from CHIV initiating cART at ages 0-8, 9-23, and 24-59 months and age-matched community-based controls. A cross-sectional analysis compared measles seroprevalence between CHIV groups after 6-12 months of cART and controls. A longitudinal analysis evaluated antibody concentrations from age 9 months through 48 months of cART and during the 2010-11 measles outbreak. Results: In the cross-sectional analysis, measles seropositivity did not statistically differ after 6-12 months of cART by age at initiation (0-8: 30.8% [n=12/39]; 9-23: 37.0% [n=51/138]; 24-59 months: 26.6% [n=33/124]). Within CHIV groups, seropositivity was significantly lower than age-matched controls (63.5%, 75.7%, and 80.3%). Among 242 CHIV followed longitudinally, 46-56% had an antibody response, with estimated seroreversion in only 1.8-3.2 years. Among CHIV in 2010-11, 50% seroconverted or boosted with estimated seroreversion in 2.1 years. Conclusions: Measles seroprevalence was low among CHIV, even when starting cART before 9 months of age, and the time to seroreversion was short. These findings support recommendations that CHIV, including infants, would benefit from periodic revaccination after immune reconstitution.

Many children in Zambia miss measles vaccination through routine immunization, while supplementary immunization activities (SIAs) targeting children under five may not reach older under-vaccinated children. School-based vaccination screening and catch-up (SVS) is a recommended strategy to identify and vaccinate these children, but evidence on its implementation and cost in sub-Saharan Africa is limited. We estimated the cost of an SVS pilot for measles vaccination in Zambia to inform implementation and potential scale-up.,We conducted an ingredients-based costing from the Government of Zambia perspective of an SVS pilot in 20 urban schools in Lusaka and rural schools in Masaiti. Costs were estimated under three scenarios: base case (full pilot costs); post-introduction (excluding start-up and technical support); and budgeting (assuming full program integration and excluding start-up, technical support, and Ministry of Health and Education staff costs). One-way and probabilistic sensitivity analyses were conducted. Costs are reported in 2024 USD and Zambian kwacha (ZMW).,Among 3,351 children screened, 215 were identified as measles-rubella (MR) zero-dose and 211 were vaccinated. Total implementation cost was USD 75,886 (ZMW 2,111,157) in the base case. By input, personnel accounted for 70.6% of costs. By SVS activity, coordination and training accounted for 46.8% and 34.0% of total costs, respectively. Costs decreased by 28.3% in the post-introduction and 42.3% in the budgeting scenario. Cost per child screened ranged from USD 13.05–22.65, and per MR zero-dose child vaccinated from USD 208.29–360.70. Coordination time was the most influential parameter.,While costs per child are relatively high, SVS is a targeted strategy that can be used to reach older children who remain unreached by routine immunization programs and SIAs. Efficiency could improve through streamlined documentation, integration with school health activities, and reduced coordination and personnel requirements. Further research should assess its comparative value and cost-effectiveness against other approaches.

School-based vaccination screening is a promising platform to identify and vaccinate older children missed by routine services. In 2024, Zambia’s Ministry of Health and Ministry of Education implemented a pilot school-based vaccination screening and catch-up (SVS) program in 20 schools across one urban and one rural district, supported by our research team. We conducted an explanatory sequential mixed-methods process evaluation to assess reach, fidelity, effectiveness, feasibility, acceptability and sustainability using the Consolidated Framework for Implementation Research and Proctor et al.’s implementation outcomes. Between June–November 2024 we undertook document review, implementation strength assessment surveys, direct observations and in-depth interviews with implementers and caregivers. Quantitative indicators were summarized descriptively, and qualitative data were thematically analyzed and triangulated across components.Of 4,092 enrolled learners, 81.9% were screened and 77.1% presented vaccination cards. Among those screened, 6.4% missed both measles-rubella (MR) doses and 13.7% missed only MR2. Catch-up uptake was high: 98.1% of MR zero-dose learners received MR1 and 95% of those missing MR2 received catch-up vaccination. Key implementation enablers included strong teacher-nurse coordination, high training participation, the perception of schools as convenient and efficient platforms for SVS activities and the flexibility to adapt community sensitization strategies to local contexts. However, operational constraints included transport limitations, short training duration and burdensome documentation.Zambia’s SVS pilot was feasible, acceptable, and implemented with high reach and uptake through school-based measles screening and catch-up. Future scale-up would require a national catch-up policy for children older than 5 years, clear operational guidance, and evidence on costs and sustainability. With these in place, SVS could be integrated into school health programs to reach children missing measles doses.

School vaccination screening (SVS) programs can facilitate catch-up vaccination among children who have missed routine immunization, but assessing vaccination status in school-aged children is challenging because vaccination records are often unavailable and caregiver recall may be unreliable. We conducted a school-based cross-sectional serosurvey nested within an SVS program in Ndola District, Zambia, from March to July 2025 to estimate measles seroprevalence and evaluate the relationship between serology and vaccination status ascertained through vaccination cards and caregiver recall. Caregiver-reported measles-containing vaccine (MCV) history was collected, and dried blood spots were tested for measles IgG antibodies by ELISA; children aged <9 years were additionally tested for rubella IgG antibodies.Of 964 eligible children, 924 (95.8%) participated. Nearly one-third lacked a readable vaccination card, primarily children aged ≥5 years. Based on vaccination cards or caregiver recall, 85.2% had received ≥1 routine MCV dose, while 14.8% had received no routine MCV doses; 72.6% reported at least one MCV dose received outside routine services. Overall measles seroprevalence was 85.6% and was higher among children with vaccination documented by card than caregiver recall. Among children aged <9 years classified by caregiver recall as having received no routine MCV doses, 83.6% were seropositive for both measles and rubella, suggesting misclassification of vaccination status. Screening based on vaccination cards alone would have referred 488 children and identified 69.2% (n=93) of measles-seronegative children requiring catch-up vaccination. Adding caregiver recall reduced referrals to 353 children but identified 53.3% (n=71), while including non-routine doses recall further reduced referrals to 194 children and identified 31.5% (n=42). Caregiver recall was more prone to misclassification than vaccination cards, highlighting the need to balance sensitivity and efficiency when designing SVS strategies. Strengthening vaccination documentation systems and clarifying the role of caregiver recall will be important for optimizing school-based vaccination screening programs.

Background: Vaccination coverage estimates and case-based surveillance have limitations in evaluating immunization programs. Serosurveillance offers a complementary approach by directly measuring population immunity. We assessed whether serologic analyses across multiple antigens (i.e., measles, diphtheria, tetanus) could provide additional insights into vaccination program performance. Methods: We conducted a matched case-control study among children aged 2- to 10-years-old (n=1286) in Zambia using specimens from the 2016 ZAMPHIA survey. Using previously generated data on measles serostatus, measles seronegative children (i.e., “cases”) were matched to measles seropositive children (i.e., “controls”) on sex, age, HIV infection status, and province. Samples were tested for tetanus and diphtheria antitoxin IgG antibodies using commercial enzyme immunoassays. We estimated the odds of tetanus and diphtheria seropositivity by measles serostatus using conditional logistic regression and examined age-specific antibody dynamics. Results: Measles seronegative children had 1.7-fold increased odds (95% credible interval [CrI]: 1.3-2.1) of being tetanus seronegative compared to measles seropositive children. Diphtheria serostatus had no significant association with measles serostatus (odds ratio: 1.3; 95% CrI: 0.9-1.7). Tetanus seroprevalence declined monotonically with age. However, diphtheria seroprevalence initially declined through 5 years of age, then increased again beginning at 6 years of age despite the lack of vaccine booster doses given after the primary series in infancy, potentially from asymptomatic or subclinical infections. Conclusions: Serologic analyses revealed measles serostatus was positively associated with tetanus serostatus (where seropositivity arises only via vaccination and not infection), suggesting children who are measles seronegative are more likely to have missed DTP vaccination. We additionally found that measles serostatus was not associated with diphtheria serostatus, suggesting that antibody responses to diphtheria continue to boost beyond infancy when DTP vaccination is given. Our findings support consideration of DTP booster doses in Zambia to address waning tetanus immunity and further investigation of potential diphtheria carriage and transmission.

Background: Norovirus is a major cause of acute gastroenteritis. Several vaccines are in development. Identifying a reliable immunological correlate of protection (CoP) would aid vaccine development and evaluation; however, no strong CoP has been established to date. Methods: We evaluated the relationships between prechallenge genogroup I, genotype 1 (GI.1) and GII.4 norovirus antibodies and clinical outcomes in two human vaccine-challenge studies. We analyzed genotype-specific histo-blood group antigen blocking titers, serum IgA and IgG, and total antibody ELISA. We used Bayesian regression models to assess relationships between antibody levels and protection against infection, illness, and disease severity. Results: Associations between antibody titers and protection were generally weak, and varied by genotype and vaccination status. GI.1 antibodies showed the strongest relationships, particularly among vaccinated participants, whereas naturally acquired GI.1 antibodies in unvaccinated individuals were weakly or not associated with protection. In contrast, GII.4 antibodies exhibited weak and inconsistent relationships among vaccinated participants, while unvaccinated participants showed only modest and more stable positive associations. Conclusions: Currently measured serum antibodies do not provide reliable and robust estimates of protection against norovirus clinical outcomes in all settings. Immune markers beyond serum antibody titers should be evaluated to identify more robust correlates of protection for norovirus.

Background: Combination antiretroviral therapy (cART) reduces morbidity among children living with HIV (CHIV) but does not restore measles immunity. Many CHIV now initiate cART before measles vaccination but the impact on measles-specific immunity is not understood. This study compared measles antibodies between CHIV initiating cART before and after 9 months of age in Zambia. Methods: This retrospective study was nested within an open cohort study of CHIV and community-based malaria studies in Macha, Zambia conducted from 2007-2020. Samples were tested for measles IgG antibodies from CHIV defined by age at cART initiation (aged 0-8, 9-23, and 24-59 months) and age-matched community-based controls. A cross-sectional analysis compared antibody concentrations between CHIV groups after 6-12 months of cART and aged >12 months and controls. A longitudinal analysis evaluated antibody trajectories from 9 months of age through 48 months of cART and during the 2010-11 measles outbreak. Results: In the cross-sectional analysis, 31.9% of 301 CHIV were seropositive after 6-12 of cART, with no significant difference by group (0-8: 30.8%; 9-23: 37.0%; 24-59 months: 26.6%). Within each CHIV group, the proportion seropositive was significantly lower than age-matched controls. Among 242 CHIV included in the longitudinal analysis, 46-56% had an antibody response, with an estimated time to seroreversion of 1.8-3.2 years. Among CHIV followed in 2010-11, 50% seroconverted or boosted; the estimated time to seroreversion was 2.1 years. Conclusions: Low levels of measles antibodies were found among CHIV, even when cART was started before 9 months of age, supporting a recommendation that CHIV, including infants, would benefit from revaccination.

Vaccination programs have averted millions of childhood deaths, yet vaccine-preventable diseases (VPDs) continue to resurge as coverage declines and pathogen evolution undermines previously successful vaccines. Anticipating resurgence is a public health priority. We review theoretical and empirical advances in the study of early warning signals (EWS) of epidemic transitions, with a focus on critical slowing down (CSD) - a phenomenon in which recovery from perturbations becomes slower near the epidemic threshold. We summarize the mechanisms that generate CSD, indicators that can be extracted from surveillance data, and the conditions under which signals may be detectable. We then examine case studies to illustrate the opportunities and challenges of applying EWS to VPD resurgence. Theory and computer simulations show that CSD can precede both elimination and resurgence, with increases in variance and autocorrelation calculated from disease surveillance reports emerging as consistent indicators. Empirical evidence supports this potential, though performance depends on noise structure, seasonality, spatial clustering, and outbreak responses. Case studies highlight both successful applications and contexts where signals were weak or absent. EWS offer a promising framework for anticipating VPD resurgence, but further research is required to refine methods, integrate mechanistic and social-behavioral drivers, and evaluate applicability across pathogens and settings.