Measurement error and information bias in causal diagrams: mapping epidemiological concepts and graphical structures.

Measurement error and information bias are ubiquitous in epidemiology, yet directed acyclic graphs (DAGs) are infrequently used to represent them, in contrast with confounding and selection bias. This represents a missed opportunity to leverage the full utility of DAGs to depict associations between the variables we actually analyse in practice: empirically measured variables, which are necessarily measured with error. In this article, we focus on applying causal diagrams to depict the data-generating mechanisms that give rise to the data we analyse, including measurement error. We begin by considering empirical data considerations using a general example, and then build up to a specific worked example from the clinical epidemiology of hearing health. Throughout, our goal is to highlight both the challenges and the benefits of using DAGs to depict measurement error. In addition to the application of DAGs to conceptual causal questions (which pertain to unmeasured constructs free from measurement error), which is common, we highlight the advantages associated with applying DAGs to also include empirically measured variables and-potentially-information bias. We also highlight the implications implied by this use of DAGs, particularly regarding the unblocked backdoor path causal structure. Ultimately, we seek to help increase the clarity with which epidemiologists can map traditional epidemiological concepts (such as information bias and confounding) onto causal graphical structures.

Mass chemotherapy with niclosamide for the control of Taenia solium: population-based safety profile and treatment effectiveness.

Background: Mass drug administration (MDA) with niclosamide (NSM) can be used to control taeniasis, the cause of neurocysticercosis. NSM is 84.3% effective against taeniasis and is considered safe as it is not absorbed from the intestinal tract. However, information on its safety and effectiveness during MDA is limited. We evaluated the effectiveness of NSM and reported adverse events (AEs) during a cysticercosis elimination program in Tumbes, Peru. Methods: Three rounds of NSM at 4-month intervals were offered to 77,397 eligible residents. We revisited all participants in their homes 72 h after each round to collect information regarding AEs. We also collected post-treatment stool samples to diagnose taeniasis after the first round, followed by a second sample at 30 days from those infected to evaluate NSM's effectiveness. Findings: During implementation, 68,751 individuals were administered at least one dose of NSM (mean age 29 years, SD 20; 52% male), and 65,551 (95.3%) were visited post-treatment. 988 (1.5%) reported experiencing at least one AE. Almost all AEs (99.2%) were of mild intensity, with no severe AEs recorded. Of 211 participants diagnosed with taeniasis, 188 provided a follow-up stool sample 30-days after treatment and 141 were cured (treatment effectiveness 75.0%). Older age and higher coproantigen levels were significantly associated with treatment failure. Interpretation: MDA with NSM is safe in Taenia solium endemic settings. However, the effectiveness following one dose is lower than expected, which suggests additional treatment may be necessary to enhance the infection control efforts. Funding: The Bill and Melinda Gates Foundation.

Timeliness of Childhood Vaccinations Following Strengthening of the Second Year of Life (2YL) Immunization Platform and Introduction of Catch-Up Vaccination Policy in Ghana.

Strengthening routine immunization systems to successfully deliver childhood vaccines during the second year of life (2YL) is critical for vaccine-preventable disease control. In Ghana, the 18-month visit provides opportunities to deliver the second dose of the measles-rubella vaccine (MR2) and for healthcare workers to assess for and provide children with any missed vaccine doses. In 2016, the Ghana Health Service (GHS) revised its national immunization policies to include guidelines for catch-up vaccinations. This study assessed the change in the timely receipt of vaccinations per Ghana's Expanded Program on Immunizations (EPI) schedule, an important indicator of service quality, following the introduction of the catch-up policy and implementation of a multifaceted intervention package. Vaccination coverage was assessed from household surveys conducted in the Greater Accra, Northern, and Volta regions for 392 and 931 children aged 24-35 months with documented immunization history in 2016 and 2020, respectively. Age at receipt of childhood vaccines was compared to the recommended age, as per the EPI schedule. Cumulative days under-vaccinated during the first 24 months of life for each recommended dose were assessed. Multivariable Cox regression was used to assess the associations between child and caregiver characteristics and time to MR2 vaccination. From 2016 to 2020, the proportion of children receiving all recommended doses on schedule generally improved, the duration of under-vaccination was shortened for most doses, and higher coverage rates were achieved at earlier ages for the MR series. More timely infant doses and caregiver awareness of the 2YL visit were positively associated with MR2 vaccination. Fostering a well-supported cadre of vaccinators, building community demand for 2YL vaccination, sustaining service utilization through strengthened defaulter tracking and caregiver-reminder systems, and creating a favorable policy environment that promotes vaccination over the life course are critical to improving the timeliness of childhood vaccinations.

Clinical Characteristics of Neurocysticercosis in a Peruvian Population-Based Epilepsy Cohort: A Descriptive Cross-Sectional Study of Baseline Clinical Intake.

(1) Background: This study presents the baseline characteristics of a community-level population of people with epilepsy (n = 1975) living in an area endemic for Taenia solium, the pathogen responsible for neurocysticercosis (NCC). (2) Methods: Participants were sequentially enrolled in a clinical cohort from 2007 to 2020 in Tumbes, Peru. All participants provided demographic and clinical history and received clinical evaluations. Diagnostics, including neuroimaging, cysticercosis serologies, and EEG, were obtained where possible. The data presented are from the cross-sectional baseline assessment of cohort participants. (3) Results: Approximately 38% of participants met the criteria for NCC. Those with NCC were more likely to have adult-onset epilepsy, as well as a longer duration of epilepsy, as compared to their counterparts without NCC. Overall, the data indicate a large treatment gap, with only approximately a quarter of the baseline population with prescriptions for anti-seizure medications. (4) Conclusions: These data reveal a high proportion of NCC among people living with epilepsy in these communities, with limited health care resources. At baseline, 74% of the population were not receiving anti-seizure treatments. Further analyses of these data will clarify the natural history of the disease for this population.

Predictors for Uptake of Vaccines Offered during the Second Year of Life: Second Dose of Measles-Containing Vaccine and Meningococcal Serogroup A-Containing Vaccine, Ghana, 2020.

BACKGROUND: Understanding the drivers of coverage for vaccines offered in the second year of life (2YL) is a critical focus area for Ghana's life course approach to vaccination. This study characterizes the predictors of vaccine receipt for 2YL vaccines-meningococcal serogroup A conjugate vaccine (MACV) and the second dose of measles-containing vaccine (MCV2)-in Ghana. METHODS: 1522 children aged 18-35 months were randomly sampled through household surveys in the Greater Accra Region (GAR), Northern Region (NR), and Volta Region (VR). The association between predictors and vaccination status was modeled using logistic regression with backwards elimination procedures. Predictors included child, caregiver, and household characteristics. RESULTS: Coverage was high for infant vaccines (>85%) but lower for 2YL vaccines (ranging from 60.2% for MACV in GAR to 82.8% for MCV2 in VR). Predictors of vaccination status varied by region. Generally, older, first-born children, those living in rural settlements and those who received their recommended infant vaccines by their first birthday were the most likely to have received 2YL vaccines. Uptake was higher among those with older mothers and children whose caregivers were aware of the vaccination schedule. CONCLUSIONS: Improving infant immunization uptake through increased community awareness and targeted strategies, such as parental reminders about vaccination visits, may improve 2YL vaccination coverage.

Development and Laboratory Evaluation of a Simple, Field-Applicable Coproantigen Enzyme-Linked Immunosorbent Assay for Diagnosis of Taeniasis in Northern Peru.

Coproantigen detection by enzyme-linked immunosorbent assay (coAg ELISA) is a vital tool for detecting and treating cases of Taenia solium taeniasis. However, the assay's procedures require costly materials and sophisticated equipment, which are typically inaccessible in rural settings where the disease is endemic. To overcome these barriers, we developed and evaluated a field-applicable coAg ELISA. The field coAg ELISA was developed and evaluated across four phases using known positive and negative stool samples collected from northern Peru. Phase I focused on field assay development, phase II on a small-scale performance evaluation, phase III on a large-scale evaluation, and phase IV on the use and reliability of a colorimetric scale card. All samples were processed using the field and standard assay procedures and compared using signal-to-noise ratios, correlation tests, performance characteristics, and agreement statistics where appropriate. The field coAg ELISA using reagents stored at -20°C and commercially available water and milk powder, and relying on spontaneous separation of the supernatant, had performance comparable to the standard assay. The field coAg ELISA was strongly correlated with the standard in both the small- and large-scale laboratory evaluation (r = 0.99 and r = 0.98, respectively). Finally, the field assay had an almost perfect agreement between independent readers (kappa = 0.975) and between each reader and the spectrophotometer. The field coAg ELISA demonstrated performance comparable to the standard, providing a low-cost alternative to the standard assay for identifying cases of intestinal taeniasis in a low-resource setting.

Evaluation of Container Clinics as an Urban Immunization Strategy: Findings from the First Year of Implementation in Ghana, 2017-2018.

BACKGROUND: In 2017, the Expanded Programme on Immunization in Ghana opened two container clinics in Accra, which were cargo containers outfitted to deliver immunizations. At each clinic, we assessed performance and clinic acceptance during the first 12 months of implementation. METHODS: We employed a descriptive mixed-method design using monthly administrative immunization data, exit interviews with caregivers of children of <5 years (N = 107), focus group discussions (FGDs) with caregivers (n = 6 FGDs) and nurses (n = 2 FGDs), and in-depth interviews (IDIs) with community leaders (n = 3) and health authorities (n = 3). RESULTS: Monthly administrative data showed that administered vaccine doses increased from 94 during the opening month to 376 in the 12th month across both clinics. Each clinic exceeded its target doses for the 12-23 month population (second dose of measles). Almost all (98%) exit interview participants stated that the clinics made it easier to receive child health services compared to previous health service interactions. The accessibility and acceptability of the container clinics were also supported from health worker and community perspectives. CONCLUSIONS: Our initial data support container clinics as an acceptable strategy for delivering immunization services in urban populations, at least in the short term. They can be rapidly deployed and designed to serve working mothers in strategic areas.

Maternal influenza immunization and birth outcomes of stillbirth and spontaneous abortion: a systematic review and meta-analysis.

Despite strong evidence that maternal influenza vaccination during pregnancy is safe, uptake of influenza vaccination during pregnancy remains low. We identified studies that assessed outcomes of stillbirth or spontaneous abortion after administration of influenza vaccine during pregnancy. We conducted a literature search in November 2013 that yielded 447 total citations. After removal of duplicates and studies deemed not relevant based on the title and abstract, 36 records underwent a full text review and 7 studies were included in the final review. Where possible, adjusted results were included in the meta-analysis. Women in the influenza vaccine group had a lower likelihood of stillbirth (relative risk [RR], 0.73; 95% confidence interval [CI], .55-.96); this association was similar when restricted to the H1N1pdm09 vaccine (RR, 0.69; 95% CI, .53-.90). The pooled estimate for spontaneous abortion was not significant (RR, 0.91; 95% CI, .68-1.22). These analyses add to the evidence base for the safety of influenza vaccination in pregnancy.