Expansion of wastewater-based disease surveillance to improve health equity in California's Central Valley: sequential shifts in case-to-wastewater and hospitalization-to-wastewater ratios.

Introduction: Over a third of the communities (39%) in the Central Valley of California, a richly diverse and important agricultural region, are classified as disadvantaged-with inadequate access to healthcare, lower socio-economic status, and higher exposure to air and water pollution. The majority of racial and ethnic minorities are also at higher risk of COVID-19 infection, hospitalization, and death according to the Centers for Disease Control and Prevention. Healthy Central Valley Together established a wastewater-based disease surveillance (WDS) program that aims to achieve greater health equity in the region through partnership with Central Valley communities and the Sewer Coronavirus Alert Network. WDS offers a cost-effective strategy to monitor trends in SARS-CoV-2 community infection rates. Methods: In this study, we evaluated correlations between public health and wastewater data (represented as SARS-CoV-2 target gene copies normalized by pepper mild mottle virus target gene copies) collected for three Central Valley communities over two periods of COVID-19 infection waves between October 2021 and September 2022. Public health data included clinical case counts at county and sewershed scales as well as COVID-19 hospitalization and intensive care unit admissions. Lag-adjusted hospitalization:wastewater ratios were also evaluated as a retrospective metric of disease severity and corollary to hospitalization:case ratios. Results: Consistent with other studies, strong correlations were found between wastewater and public health data. However, a significant reduction in case:wastewater ratios was observed for all three communities from the first to the second wave of infections, decreasing from an average of 4.7 ± 1.4 over the first infection wave to 0.8 ± 0.4 over the second. Discussion: The decline in case:wastewater ratios was likely due to reduced clinical testing availability and test seeking behavior, highlighting how WDS can fill data gaps associated with under-reporting of cases. Overall, the hospitalization:wastewater ratios remained more stable through the two waves of infections, averaging 0.5 ± 0.3 and 0.3 ± 0.4 over the first and second waves, respectively.

Formative research to address vaccine hesitancy in Tajikistan.

INTRODUCTION: Incomplete childhood vaccination is associated with caregiver vaccine hesitancy, conceptualized by "3 Cs": high complacency, low confidence, and low convenience. To expand on existing evidence drawn primarily from the Americas and Europe, and develop culturally appropriate interventions, this research explored drivers of vaccine hesitancy in the Central Asian country of Tajikistan. METHODS: In twelve diverse districts, clinic-based immunization record abstraction identified purposive samples of children who were up-to-date (N = 300) or not (N = 300) on all first year vaccines. Using a modified case-control design, the structured face-to-face in-home survey of 600 caregivers compared knowledge, attitudes and practices regarding childhood vaccination by up-to-date status. Socio-demographic and psychological factors associated with hesitancy were identified, using a 22-item vaccine hesitancy scale, with subscales measuring complacency, confidence, and convenience. Overall contribution of vaccine hesitancy to up-to-date status was modeled, adjusting for other significant covariates. RESULTS: Caregivers of not up-to-date children were more likely to report their child's health as poor, and report many logistical barriers to vaccination. Knowledge of vaccine-preventable illnesses was low, and complacency regarding vaccination was high among not up-to-date caregivers. In final multivariable models of predisposing, enabling and reinforcing influences on vaccination status, urban children, those with transportation and employed mothers were more likely to be up-to-date, while not up-to-date children included those born at home, seen as having fair or poor health, or reportedly told by clinicians to avoid immunization. Reinforcing factors included having a "vaccine passport", receiving useful information from medical providers, and believing that vaccine-preventable illnesses are serious and that most in their community are vaccinated. Additionally, vaccine hesitancy was negatively associated with up-to-date status (odds ratio 0.15, 95% C.I. 0.08, 0.26). CONCLUSIONS: Results confirm that in this traditional culture, there is a strong need for tailored communication campaigns to address vaccine hesitancy, while continuing to address systems-level barriers.

A mouse model of seizures in anti-N-methyl-d-aspartate receptor encephalitis.

OBJECTIVE: Seizures develop in 80% of patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, and these represent a major cause of morbidity and mortality. Anti-NMDAR antibodies have been linked to memory loss in encephalitis; however, their role in seizures has not been established. We determined whether anti-NMDAR antibodies from autoimmune encephalitis patients are pathogenic for seizures. METHODS: We performed continuous intracerebroventricular infusion of cerebrospinal fluid (CSF) or purified immunoglobulin (IgG) from the CSF of patients with anti-NMDAR encephalitis or polyclonal rabbit anti-NMDAR IgG, in male C57BL/6 mice. Seizure status during a 2-week treatment was assessed with video-electroencephalography. We assessed memory, anxiety-related behavior, and motor function at the end of treatment and assessed the extent of neuronal damage and gliosis in the CA1 region of hippocampus. We also performed whole-cell patch recordings from the CA1 pyramidal neurons in hippocampal slices of mice with seizures. RESULTS: Prolonged exposure to rabbit anti-NMDAR IgG, patient CSF, or human IgG purified from the CSF of patients with encephalitis induced seizures in 33 of 36 mice. The median number of seizures recorded in 2 weeks was 13, 39, and 35 per mouse in these groups, respectively. We observed only 18 brief nonconvulsive seizures in 11 of 29 control mice (median seizure count of 0) infused with vehicle (n = 4), normal CSF obtained from patients with noninflammatory central nervous system (CNS) conditions (n = 12), polyclonal rabbit IgG (n = 7), albumin (n = 3), and normal human IgG (n = 3). We did not observe memory deficits, anxiety-related behavior, or motor impairment measured at 2 weeks in animals treated with CSF from affected patients or rabbit IgG. Furthermore, there was no evidence of hippocampal cell loss or astrocyte proliferation in the same mice. SIGNIFICANCE: Our findings indicate that autoantibodies can induce seizures in anti-NMDAR encephalitis and offer a model for testing novel therapies for refractory autoimmune seizures.