Changes in on-time vaccination following the introduction of an electronic immunization registry, Tanzania 2016-2018: interrupted time-series analysis.

BACKGROUND: Digital health interventions (DHI) have the potential to improve the management and utilization of health information to optimize health care worker performance and provision of care. Despite the proliferation of DHI projects in low-and middle-income countries, few have been evaluated in an effort to understand their impact on health systems and health-related outcomes. Although more evidence is needed on their impact and effectiveness, the use of DHIs among immunization programs has become more widespread and shows promise for improving vaccination uptake and adherence to immunization schedules. METHODS: Our aim was to assess the impact of an electronic immunization registry (EIR) using an interrupted time-series analysis to analyze the effect on proportion of on-time vaccinations following introduction of an EIR in Tanzania. We hypothesized that the introduction of the EIR would lead to statistically significant changes in vaccination timeliness at 3, 6, and > 6 months post-introduction. RESULTS: For our primary analysis, we observed a decrease in the proportion of on-time vaccinations following EIR introduction. In contrast, our sensitivity analysis estimated improvements in timeliness among those children with complete vaccination records. However, we must emphasize caution interpreting these findings as they are likely affected by implementation challenges. CONCLUSIONS: This study highlights the complexities of using digitized individual-level routine health information system data for evaluation and research purposes. EIRs have the potential to improve vaccination timeliness, but analyses using EIR data can be complicated by data quality issues and inconsistent data entry leading to difficulties interpreting findings.

Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa.

BACKGROUND: Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings. METHODS: Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data. CONCLUSIONS: Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact.

Partnership and Participation-A Social Network Analysis of the 2017 Global Fund Application Process in the Democratic Republic of the Congo and Uganda.

Background: The Global Fund to Fight AIDS, Tuberculosis and Malaria was founded in 2002 as a public-private partnership between governments, the private sector, civil society, and populations affected by the three diseases. A key principle of the Global Fund is country ownership in accessing funding through "engagement of in-country stakeholders, including key and vulnerable populations, communities, and civil society." Research documenting whether diverse stakeholders are actually engaged and on how stakeholder engagement affects processes and outcomes of grant applications is limited. Objective: To examine representation during the 2017 Global Fund application process in the Democratic Republic of the Congo (DRC) and Uganda and the benefits and drawbacks of partnership to the process. Methods: We developed a mixed-methods social network survey to measure network structure and assess perceptions of how working together in partnership with other individuals/organizations affected perceived effectiveness, efficiency, and country ownership of the application process. Surveys were administered from December 2017-May 2018, initially to a set of central actors, followed by any individuals named during the surveys (up to 10) as collaborators. Network analyses were conducted using R. Findings: Collaborators spanning many organizations and expertise areas contributed to the 2017 applications (DRC: 152 nodes, 237 ties; Uganda: 118 nodes, 241 ties). Participation from NGOs and civil society representatives was relatively strong, with most of their ties being to different organization types, Uganda (63%), and DRC (67%), highlighting their collaborative efforts across the network. Overall, the perceived benefits of partnership were high, including very strong ratings for effectiveness in both countries. Perceived drawbacks of partnership were minimal; however, less than half of respondents thought partnership helped reduce transaction costs or financial costs, suggesting an inclusive and participatory process may come with short-term efficiency tradeoffs. Conclusions: Social network analysis can be useful for identifying who is included and excluded from the process, which can support efforts to ensure stronger, more meaningful engagement in future Global Fund application processes.

Determinants of Facility-Level Use of Electronic Immunization Registries in Tanzania and Zambia: An Observational Analysis.

BACKGROUND: As more countries transition from paper-based to electronic immunization registries (EIRs) to collect and track individual immunization data, guidance is needed for successful adoption and use of these systems. Little research is available on the determinants of EIR use soon after introduction. This observational study assesses the determinants of facility health care workers' use of new EIRs in Tanzania and Zambia, implemented during 2016 to 2018. METHODS: We used EIR data entered between 2016 and 2018 from 3 regions in Tanzania and 1 province in Zambia to measure weekly EIR system use for a total of 50,639 facility-weeks. We joined secondary data on facility characteristics and applied the Performance of Routine Information System Management framework to categorize characteristics as organizational, technical, or behavioral. We used a generalized estimating equations logistic regression model to assess facility characteristics as potential determinants of system use. RESULTS: In both countries, the estimated odds of weekly EIR use declined weekly after EIR introduction. In Tanzania, health centers and hospitals had increased odds of system use compared to dispensaries. For each additional health care worker trained in a facility during the EIR introduction, the estimated odds of weekly EIR use increased. Tanzanian facilities that had transitioned entirely to paperless reporting had higher odds of sustained use compared to those maintaining parallel electronic and paper-based reporting systems. In Zambia, distance from the district health office was significantly associated with decreasing odds of system use. There were significant differences in EIR use by district in both countries. DISCUSSION: The results highlight the importance of organizational and behavioral factors in explaining sustained EIR use. As EIRs are introduced in new settings, we recommend indicators of engagement and use be built directly into the system so they can be routinely monitored, and course corrections can be implemented as needed.

Perceptions of factors influencing the introduction and adoption of electronic immunization registries in Tanzania and Zambia: a mixed methods study.

BACKGROUND: As technology has become cheaper and more accessible, health programs are adopting digital health interventions (DHI) to improve the provision of and demand for health services. These interventions are complex and require strong coordination and support across different health system levels and government departments, and they need significant capacities in technology and information to be properly implemented. Electronic immunization registries (EIRs) are types of DHI used to capture, store, access, and share individual-level, longitudinal health information in digitized records. The BID Initiative worked in partnership with the governments of Tanzania and Zambia to introduce an EIR at the sub-national level in both countries within 5 years as part of a multi-component complex intervention package focusing on data use capacity-building. METHODS: We aimed to gather and describe learnings from the BID experience by conducting a framework-based mixed methods study to describe perceptions of factors that influenced scale-up of the EIR. Data were collected through key informant interviews, a desk review, EIRs, and health management information systems. We described how implementation of the EIRs fulfilled domains described in our conceptual framework and used cases to illustrate the relationships and relative influence of domains for scale-up and adoption of the EIR. RESULTS: We found that there was no single factor that seemed to influence the introduction or sustained adoption of the EIR as many of the factors were interrelated. For EIR introduction, strong strategic engagement among partners was important, while EIR adoption was influenced by adequate staffing at facilities, training, use of data for supervision, internet and electricity connectivity, and community sensitization. CONCLUSIONS: Organizations deploying DHIs in the future should consider how best to adapt their intervention to the existing ecosystem, including human resources and organizational capacity, as well as the changing technological landscape during planning and implementation.

The impact of an integrated electronic immunization registry and logistics management information system (EIR-eLMIS) on vaccine availability in three regions in Tanzania: A pre-post and time-series analysis.

BACKGROUND: Since 2016, the Government of Tanzania has been implementing TImR, an integrated Electronic Immunization registry-logistics management information system (EIR-LMIS) that includes stock notifications. The objective of this study is to estimate the impact of this intervention on vaccine availability. METHODS: Monthly stock-out data were collected from paper registers at facilities, an Excel-based system at districts, and the new system (TImR) across all 924 health facilities in Arusha, Tanga and Kilimanjaro Regions. Six months of stockout rates pre- and post-introduction, by antigen, were compared via a two-way analysis of variance (ANOVA). A mixed-effects logistic regression model with the TImR data identified predictors of vaccine availability across antigens. FINDINGS: Post-introduction, ANOVA models estimated that overall stock-out rates declined from a monthly average of 7.1% to 2.1% (p < 0.01). Three specific vaccines had fewer stock-outs; OPV's monthly average dropped from 12.5% to 2.1% (p < 0.01), MR from 9.4% to 1.0% (p < 0.01) and DTP-HepB-HiB from 8.1% to 1.7% (p < 0.01). In the mixed-effects logistic regression model, controlling for antigen, odds of stock-out were 4.1% (95% CI: 3.3 - 4.9) lower for each week of tenure. Compared to DTP-HepB-HiB vaccine, odds of BCG vaccine being stocked out were 4.31 as high (95% CI: 3.1 - 5.0). The odds of being stocked-out were 29.7% lower for PCV (95% CI: 8.8 - 45.8) and 26.6% (95% CI: 3.4 - 44.1) lower for rotavirus vaccines compared to DTP-HepB-HiB. The odds of stock out were 37.7% lower for MR vaccine than DTP-HepB-HiB (95% CI: 18.1 - 52.6). CONCLUSIONS: Tanzania's integrated EIR-eLMIS may increase vaccine availability compared to its paper and Excel based system. Post-introduction of an eLMIS, the odds of a vaccine stock-out reduced over time. Further research could determine the impact of this intervention on vaccine wastage and replenishment response times.

Redefining vaccination coverage and timeliness measures using electronic immunization registry data in low- and middle-income countries.

Vaccine coverage is routinely used as a performance indicator for immunization programs both at local and global levels. For many national immunization programs, there are challenges with accurately estimating vaccination coverage based on available data sources, however an increasing number of low- and middle-income countries (LMICs) have begun implementing electronic immunization registries to replace health facilities' paper-based tools and aggregate reporting systems. These systems allow for more efficient capture and use of routinely reported individual-level data that can be used to calculate dose-specific and cohort vaccination coverage, replacing the commonly used aggregate routine health information system data. With these individual-level data immunization programs have the opportunity to redefine performance measures to enhance programmatic decision-making at all levels of the health system. In this commentary, we discuss how measures for assessing vaccination status and program performance can be redefined and recalculated using these data when generated at the health facility level and the implications of the use and availability of electronic individual-level data.

Statistical Modeling for Quality Assurance of Human Papillomavirus DNA Batch Testing.

OBJECTIVES: Our objective was to simulate the distribution of human papillomavirus (HPV) DNA test results from a 96-well microplate assay to identify results that may be consistent with well-to-well contamination, enabling programs to apply specific quality assurance parameters. MATERIALS AND METHODS: For this modeling study, we designed an algorithm that generated the analysis population of 900,000 to simulate the results of 10,000 microplate assays, assuming discrete HPV prevalences of 12%, 13%, 14%, 15%, and 16%. Using binomial draws, the algorithm created a vector of results for each prevalence and reassembled them into 96-well matrices for results distribution analysis of the number of positive cells and number and size of cell clusters (≥2 positive cells horizontally or vertically adjacent) per matrix. RESULTS: For simulation conditions of 12% and 16% HPV prevalence, 95% of the matrices displayed the following characteristics: 5 to 17 and 8 to 22 total positive cells, 0 to 4 and 0 to 5 positive cell clusters, and largest cluster sizes of up to 5 and up to 6 positive cells, respectively. CONCLUSIONS: Our results suggest that screening programs in regions with an oncogenic HPV prevalence of 12% to 16% can expect 5 to 22 positive results per microplate in approximately 95% of assays and 0 to 5 positive results clusters with no cluster larger than 6 positive results. Results consistently outside of these ranges deviate from what is statistically expected and could be the result of well-to-well contamination. Our results provide guidance that laboratories can use to identify microplates suspicious for well-to-well contamination, enabling improved quality assurance.

Impact of the Centers for Disease Control's HIV Preexposure Prophylaxis Guidelines for Men Who Have Sex With Men in the United States.

BACKGROUND: Preexposure prophylaxis (PrEP) is effective for preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) within trial settings. Population impact will depend on clinical indications for PrEP initiation, coverage levels, and drug adherence. No modeling studies have estimated the impact of clinical practice guidelines for PrEP issued by the Centers for Disease Control and Prevention (CDC). METHODS: Mathematical models of HIV transmission among MSM were used to estimate the percentage of infections averted (PIA) and the number needed to treat (NNT) under behavioral indications of the CDC's PrEP guidelines. We modeled the contribution of these indications while varying treatment coverage and adherence. RESULTS: At 40% coverage of indicated MSM over the next decade, application of CDC guidelines would avert 1162 infections per 100 000 person-years, 33.0% of expected infections. The predicted NNT for the guidelines would be 25. Increasing coverage and adherence jointly raise the PIA, but reductions to the NNT were associated with better adherence only. CONCLUSIONS: Implementation of CDC PrEP guidelines would result in strong and sustained reductions in HIV incidence among MSM in the United States. The guidelines strike a good balance between epidemiological impact (PIA) and efficiency (NNT) at plausible scale-up levels. Adherence counseling could maximize public health investment in PrEP by decreasing the NNT.

Automated Cell Detection and Morphometry on Growth Plate Images of Mouse Bone.

Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image's plane of focus, and lack of cell-specific features, interfered with identification of cell. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes' number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CKO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth.