Adjusting mobile phone data to account for children's travel and the impact on measles dynamics in Zambia.

Models of measles transmission can be used to identify areas of high risk to tailor immunization strategies. Estimates of spatial connectivity can be derived from data such as mobile phone records, however it is not clear how this maps to the movement of children who are more likely to be infected. Using travel surveys across two districts in Zambia and national mobile phone data, we compared estimates of out-of-district travel for the population captured in the mobile phone data and child-specific travel from travel surveys. We then evaluated the impact of unadjusted and adjusted connectivity measures on simulated measles virus introduction events across Zambia. The number of trips made by children from the travel survey was three to five times lower than the general population estimates from mobile phone data. This decreased the percentage of districts with measles virus introduction events from 78% when using unadjusted data to 51% - 64% following adjustment. Failure to account for age-specific heterogeneities in travel estimated from mobile phone data resulted in overestimating subnational areas at high risk of introduction events, which could divert mitigation efforts to districts that are at lower risk.

Times to key events in Zika virus infection and implications for blood donation: a systematic review.

OBJECTIVE: To estimate the timing of key events in the natural history of Zika virus infection. METHODS: In February 2016, we searched PubMed, Scopus and the Web of Science for publications containing the term Zika. By pooling data, we estimated the incubation period, the time to seroconversion and the duration of viral shedding. We estimated the risk of Zika virus contaminated blood donations. FINDINGS: We identified 20 articles on 25 patients with Zika virus infection. The median incubation period for the infection was estimated to be 5.9 days (95% credible interval, CrI: 4.4-7.6), with 95% of people who developed symptoms doing so within 11.2 days (95% CrI: 7.6-18.0) after infection. On average, seroconversion occurred 9.1 days (95% CrI: 7.0-11.6) after infection. The virus was detectable in blood for 9.9 days (95% CrI: 6.9-21.4) on average. Without screening, the estimated risk that a blood donation would come from an infected individual increased by approximately 1 in 10 000 for every 1 per 100 000 person-days increase in the incidence of Zika virus infection. Symptom-based screening may reduce this rate by 7% (relative risk, RR: 0.93; 95% CrI: 0.89-0.99) and antibody screening, by 29% (RR: 0.71; 95% CrI: 0.28-0.88). CONCLUSION: Neither symptom- nor antibody-based screening for Zika virus infection substantially reduced the risk that blood donations would be contaminated by the virus. Polymerase chain reaction testing should be considered for identifying blood safe for use in pregnant women in high-incidence areas.

Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Feasibility and acceptability of collecting dried blood spots (DBS) from children after vaccination during supplementary immunization activities to estimate measles and rubella seroprevalence.

Nested serosurveys within routine service delivery platforms such as planned supplemental immunization activities (SIAs) provide an opportunity to collect information that can be used to answer valuable questions on the effectiveness and efficiency of the delivery model to inform future activities. However, integrating research data collection in SIAs is rarely done due to concerns it will negatively impact the program. We conducted a serosurvey nested within the November 2020 measles-rubella SIA integrated with the Child Health Week activities in Zambia to evaluate this approach. In-depth interviews with the study teams and vaccination campaign staff at the vaccination sites were conducted. Recorded interviews were transcribed, transcripts were coded and then grouped into themes based on a process evaluation framework. A multi-methods analytical approach was used to assess the feasibility and acceptability of collecting dried blood spots from children during the SIA. This included a quantitative assessment of participant enrollment. The serosurvey successfully enrolled 90% of children from Child Health Week due to close coordination and teamwork between the vaccination teams and serosurvey team, in addition to substantial social mobilization efforts. Continually adjusting the sampling interval that was used to select eligible children allowed us to enroll throughout the SIA and capture a representative sample of children in attendance although it was challenging for the staff involved. As vaccination programs aim to tailor their approaches to reach the hardest-to-reach children, embedding research questions in SIAs will allow evaluation of the successes and challenges and compare alternative approaches. Lessons learned from this experience collecting data during an SIA can be applicable to future research activities embedded in SIAs or other delivery platforms.

Who is missed in a community-based survey: Assessment and implications of biases due to incomplete sampling frame in a community-based serosurvey, Choma and Ndola Districts, Zambia, 2022.

Community-based serological studies are increasingly relied upon to measure disease burden, identify population immunity gaps, and guide control and elimination strategies; however, there is little understanding of the potential for and impact of sampling biases on outcomes of interest. As part of efforts to quantify measles immunity gaps in Zambia, a community-based serological survey using stratified multi-stage cluster sampling approach was conducted in Ndola and Choma districts in May-June 2022, enrolling 1245 individuals. We carried out a follow-up study among individuals missed from the sampling frame of the serosurvey in July-August 2022, enrolling 672 individuals. We assessed the potential for and impact of biases in the community-based serosurvey by i) estimating differences in characteristics of households and individuals included and excluded (77% vs 23% of households) from the sampling frame of the serosurvey and ii) evaluating the magnitude these differences make on healthcare-seeking behavior, vaccination coverage, and measles seroprevalence. We found that missed households were 20% smaller and 25% less likely to have children. Missed individuals resided in less wealthy households, had different distributions of sex and occupation, and were more likely to seek care at health facilities. Despite these differences, simulating a survey in which missed households were included in the sampling frame resulted in less than a 5% estimated bias in these outcomes. Although community-based studies are upheld as the gold standard study design in assessing immunity gaps and underlying community health characteristics, these findings underscore the fact that sampling biases can impact the results of even well-conducted community-based surveys. Results from these studies should be interpreted in the context of the study methodology and challenges faced during implementation, which include shortcomings in establishing accurate and up-to-date sampling frames. Failure to account for these shortcomings may result in biased estimates and detrimental effects on decision-making.

Challenges and Approaches to Establishing Multi-Pathogen Serosurveillance: Findings from the 2023 Serosurveillance Summit.

Multiplex-based serological surveillance is a valuable but underutilized tool to understand gaps in population-level exposure, susceptibility, and immunity to infectious diseases. Assays for which blood samples can be tested for antibodies against several pathogens simultaneously, such as multiplex bead immunoassays, can more efficiently integrate public health surveillance in low- and middle-income countries. On March 7-8, 2023 a group of experts representing research institutions, multilateral organizations, private industry, and country partners met to discuss experiences, identify challenges and solutions, and create a community of practice for integrated, multi-pathogen serosurveillance using multiplex bead assay technologies. Participants were divided into six working groups: 1) supply chain; 2) laboratory assays; 3) seroepidemiology; 4) data analytics; 5) sustainable implementation; and 6) use case scenarios. These working groups discussed experiences, challenges, solutions, and research needs to facilitate integrated, multi-pathogen serosurveillance for public health. Several solutions were proposed to address challenges that cut across working groups.

Acceptability of serosurveys in southern Zambia: data collector and caregiver perspectives.

Background: Factors associated with whether individuals choose to participate in serosurveys are not well understood. Understanding perceptions from multiple perspectives, including the perspectives of both data collectors and participants, through a holistic model such as the socio-ecological model contextualizes individual, interpersonal, and structural level influences on survey research participation. We used a multiple methods approach to characterize reasons for serosurvey participation in communities in Southern Province, Zambia where a serosurvey was conducted in 2016. Methods: The first phase conducted focus group discussions and in-depth interviews with 24 data collectors who participated in a measles-rubella serosurvey in 2016. The second phase surveyed 34 caregivers at health facilities to identify barriers and facilitators to serosurvey participation. Emergent themes were then classified into a socio-ecological model using individual, interpersonal, and structural level constructs. Results: Common themes emerged from data collectors as well as caregivers surveyed. At the individual level, providing incentives was a facilitator, and some religious beliefs were described as a barrier to serosurvey participation. At the interpersonal level, family dynamics and community peer influences could help or hinder serosurvey participation. Community health workers were consistently named as facilitators of participation. At the structural level, concerns about specimen collection, who was selected for serosurveys, and not receiving test results arose as potential barriers. The most frequently reported facilitator was provision of information about the purpose of the serosurvey (85% of respondents). The most frequently reported barrier was lack of clarity regarding use of their blood specimen (53% of respondents). For specimen collection type, caregivers consistently preferred finger prick blood collection over both venous blood draw and oral swabs. Conclusion: Serosurvey participation was deemed acceptable to most study participants. The socio-ecological model revealed barriers and facilitators for participation to guide strategies to improve participation which can be applied to ongoing serosurveys for SARS-CoV-2. Serosurveys should continue to develop engagement plans to provide information about blood collection ahead of the serosurvey and communicate the objectives of such studies through trusted sources such as community health workers and traditional leaders.

An evaluation of the early impact of the COVID-19 pandemic on Zambia's routine immunization program.

Implications of the COVID-19 pandemic for both populations and healthcare systems are vast. In addition to morbidity and mortality from COVID-19, the pandemic also disrupted local health systems, including reductions or delays in routine vaccination services and catch-up vaccination campaigns. These disruptions could lead to outbreaks of other infectious diseases that result in an additional burden of disease and strain on the healthcare system. We evaluated the impact of the COVID-19 pandemic on Zambia's routine childhood immunization program in 2020 using multiple sources of data. We relied on administrative vaccination data and Zambia's 2018 Demographic and Health Survey to project national disruptions to district-specific routine childhood vaccination coverage within the pandemic year 2020. Next, we leveraged a 2016 population-based serological survey to predict age-specific measles seroprevalence and assessed the impact of changes in vaccination coverage on measles outbreak risk in each district. We found minor disruptions to routine administration of measles-rubella and pentavalent vaccines in 2020. This was in part due to Zambia's Child Health Week held in June of 2020 which helped to reach children missed during the first six months of the year. We estimated that the two-month delay in a measles-rubella vaccination campaign, originally planned for September of 2020 but conducted in November of 2020 as a result of the pandemic, had little impact on modeled district-specific measles outbreak risks. This study estimated minimal increases in the number of children missed by vaccination services in Zambia during 2020. However, the ongoing SARS-CoV-2 transmission since our analysis concluded means efforts to maintain routine immunization services and minimize the risk of measles outbreaks will continue to be critical. The methodological framework developed in this analysis relied on routinely collected data to estimate disruptions of the COVID-19 pandemic to national routine vaccination program performance and its impact on children missed at the subnational level can be deployed in other countries or for other vaccines.

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.

Leveraging a national biorepository in Zambia to assess measles and rubella immunity gaps across age and space.

High-quality, representative serological surveys allow direct estimates of immunity profiles to inform vaccination strategies but can be costly and logistically challenging. Leveraging residual serum samples is one way to increase their feasibility. We subsampled 9854 residual sera from a 2016 national HIV survey in Zambia and tested these specimens for anti-measles and anti-rubella virus IgG antibodies using indirect enzyme immunoassays. We demonstrate innovative methods for sampling residual sera and analyzing seroprevalence data, as well as the value of seroprevalence estimates to understand and control measles and rubella. National measles and rubella seroprevalence for individuals younger than 50 years was 82.8% (95% CI 81.6, 83.9%) and 74.9% (95% CI 73.7, 76.0%), respectively. Despite a successful childhood vaccination program, measles immunity gaps persisted across age groups and districts, indicating the need for additional activities to complement routine immunization. Prior to vaccine introduction, we estimated a rubella burden of 96 congenital rubella syndrome cases per 100,000 live births. Residual samples from large-scale surveys can reduce the cost and challenges of conducting serosurveys, and multiple pathogens can be tested. Procedures to access quality specimens, ensure ethical approvals, and link sociodemographic data can improve the timeliness and value of results.

COVID-19 vaccine hesitancy in Zambia: a glimpse at the possible challenges ahead for COVID-19 vaccination rollout in sub-Saharan Africa.

With unprecedented speed, multiple vaccines against SARS-CoV-2 are available 1 year after the COVID-19 pandemic was first identified. As we push to achieve global control through these new vaccines, old challenges present themselves, including cold-chain storage, the logistics of mass vaccination, and vaccine hesitancy. Understanding how much hesitancy toward COVID-19 vaccines might occur and what factors may be driving these concerns can improve the ability of public health workers and communicators to maximize vaccine uptake. We nested a survey within a measles-rubella mass vaccination campaign in Zambia in November 2020 and asked about sentiments and beliefs toward COVID-19 and COVID-19 vaccines. Among parents bringing their children to receive a measles-rubella vaccine, we found high acceptability of COVID-19 vaccination of their children, but substantial uncertainty and hesitancy about receiving the vaccine themselves. COVID-19 vaccination hesitancy was correlated with beliefs around COVID-19 severity and risk, as well as vaccine safety and effectiveness.

Perceptions and attitudes towards vaccination during pregnancy in a peri urban area of Lima, Peru.

BACKGROUND: Maternal immunization has the potential to reduce both maternal and infant morbidity and mortality by protecting women from complications during pregnancy as well as conferring protection for babies who are too young to be vaccinated. Limited evidence is available about the drivers of maternal immunization in middle-income countries such as Peru. Vaccines against tetanus, diphtheria and influenza are recommended beginning in the second trimester in Peru; however, vaccination coverage has remained low in Peru compared to other countries in the region. As additional vaccines are recommended for administration in pregnancy, a better understanding of the perceptions and attitudes of pregnant women that influence vaccination are needed to design communication materials. METHODS: We conducted an exploratory qualitative study to understand the individual level factors influencing pregnant women's vaccine uptake. We interviewed pregnant women about their knowledge, perceptions and experiences with vaccination during pregnancy. Community health workers recruited women in a peri urban area of Peru in April 2018. RESULTS: Twelve women were interviewed, the majority of which had received vaccination during the current pregnancy. The most common reasons for vaccination were to protect the baby and because vaccines are effective. Concerns included vaccine safety during pregnancy and adverse effects on the unborn baby. Some women mentioned that because vaccines are given later in pregnancy, the unborn baby is stronger, so vaccines will not harm them. Women highlighted that the main reason for not being vaccinated was lack of information. They also noted that they were the decision-maker in whether or not they were vaccinated. Most women said that they trusted healthcare providers and that trust was linked to providing information through open communication. CONCLUSIONS: Overall, participants were supportive of maternal vaccination. They believed that vaccines were effective in protecting both their unborn baby and themselves. The main reason given for non-vaccination was lack of knowledge about vaccination in pregnancy. The strong desire expressed by study participants to get more information presents an opportunity for immunization programs to develop interventions that facilitate better information dissemination to pregnant women to increase vaccination uptake.

Impact of a Measles and Rubella Vaccination Campaign on Seroprevalence in Southern Province, Zambia.

Zambia conducted a measles and rubella (MR) vaccination campaign targeting children 9 months to younger than 15 years of age in 2016. This campaign was the first introduction of a rubella-containing vaccine in Zambia. To evaluate the impact of the campaign, we compared the MR seroprevalence estimates from serosurveys conducted before and after the campaign in Southern Province, Zambia. The measles seroprevalence increased from 77.8% (95% confidence interval [CI], 73.2-81.9) to 96.4% (95% CI, 91.7-98.5) among children younger than 15 years. The rubella seroprevalence increased from 51.3% (95% CI, 45.6-57.0) to 98.3% (95% CI, 95.5-99.4). After the campaign, slightly lower seroprevalence remained for young adults 15 to 19 years old, who were not included in the campaign because of their age. These serosurveys highlighted the significant impact of the vaccination campaign and identified immunity gaps for those beyond the targeted vaccination age. Continued monitoring of population immunity can signal the need for future targeted vaccination strategies.

How much does it cost to measure immunity? A costing analysis of a measles and rubella serosurvey in southern Zambia.

BACKGROUND: Serosurveys are a valuable surveillance tool because they provide a more direct measure of population immunity to infectious diseases, such as measles and rubella, than vaccination coverage estimates. However, there is concern that serological surveys are costly. We adapted a framework to capture the costs associated with conducting a serosurvey in Zambia. METHODS: We costed a nested serosurvey in Southern Province, Zambia that collected dried blood spots from household residents in a post-campaign vaccine coverage survey. The financial costs were estimated using an ingredients-based costing approach. Inputs included personnel, transportation, field consumable items, social mobilization, laboratory supplies, and capital items, and were classified by serosurvey function (survey preparation, data collection, biospecimen collection, laboratory testing, and coordination). Inputs were stratified by whether they were applicable to surveys in general or attributable specifically to serosurveys. Finally, we calculated the average cost per cluster and participant. RESULTS: We estimated the total nested serosurvey cost was US $68,558 to collect dried blood spots from 658 participants in one province in Zambia. A breakdown of the cost by serosurvey phase showed data collection accounted for almost one third of the total serosurvey cost (32%), followed by survey preparation (25%) and biospecimen collection (20%). Analysis by input categories indicated personnel costs were the largest contributing input to overall serosurvey costs (51%), transportation was second (23%), and field consumables were third (9%). By combining the serosurvey with a vaccination coverage survey, there was a savings of $43,957. We estimated it cost $4,285 per average cluster and $104 per average participant sampled. CONCLUSIONS: Adding serological specimen collection to a planned vaccination coverage survey provided a more direct measurement of population immunity among a wide age group but increased the cost by approximately one-third. Future serosurveys could consider ways to leverage existing surveys conducted for other purposes to minimize costs.

Behavioral and Socioemotional Development in Preterm Children.

Prematurity is a significant risk factor for impaired neurodevelopmental outcomes. These include motor, cognitive, language, behavioral, and socioemotional competence. Long-term overall function depends on healthy socioemotional functioning. The vulnerability of the preterm brain during critical periods of development contributes to behavioral and socioemotional problems in preterm children. Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) clinical features are more frequent in preterm children compared with their full-term counterparts; however, true rates of ASD and ADHD vary across studies. Early detection of behavioral and socioemotional problems in preterm children would enable timely early intervention to improve long-term functional outcomes.

Assessing the global threat from Zika virus.

First discovered in 1947, Zika virus (ZIKV) infection remained a little-known tropical disease until 2015, when its apparent association with a considerable increase in the incidence of microcephaly in Brazil raised alarms worldwide. There is limited information on the key factors that determine the extent of the global threat from ZIKV infection and resulting complications. Here, we review what is known about the epidemiology, natural history, and public health effects of ZIKV infection, the empirical basis for this knowledge, and the critical knowledge gaps that need to be filled.