Christopher Rizzo

The target populations and financing mechanisms for a new health technology may affect health inequalities in access and impact. We projected the distributional consequences of introducing nirsevimab for prevention of respiratory syncytial virus in a US birth cohort of infants through alternative reimbursement pathway scenarios. Using the RSV immunization impact model, we estimated that a vaccine-like reimbursement pathway would cover 32% more infants than a pharmaceutical pathway. The vaccine pathway would avert 30% more hospitalizations and 39% more emergency room visits overall, and 44% and 44%, respectively, in publicly insured infants. The vaccine pathway would benefit infants from poorer households.

Background: Respiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States. Methods: We analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants’ first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis. Results: According to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants’ first RSV season occurred among term infants without known comorbidities. Conclusions: Term infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants’ first RSV season. Future prevention efforts should consider all infants.

Respiratory syncytial virus (RSV) accounts for the majority of lower respiratory tract illnesses in hospitalized infants. In the U.S., RSV hospitalizations are well characterized; yet, emergency department (ED) and outpatient (OP) visits are underrecognized. We evaluated the burden of RSV across three distinct healthcare settings during one respiratory season. From 12/16/19-4/30/20, we conducted a prospective RSV surveillance study among Davidson County, TN infants under one year who presented to an inpatient (IP), ED, or one of four OP clinics with either fever or any upper respiratory (i.e., cough, earache, nasal congestion, rhinorrhea, sore throat) and/or lower respiratory [i.e., wheezing, crackles, rales, diminished breath sounds, shortness of breath (SOB)] symptoms. Demographic and illness history were collected during parental/guardian interviews, followed by medical chart abstraction. Nasal swabs were collected and tested for RSV using Luminex® NxTAG RPP. Due to the COVID-19 pandemic, on 3/16/20 enrollment at three of the four OP clinics ceased. A total of 627 infants were screened, of whom 473 (75%) were confirmed eligible, 364 (77%) enrolled, 361 (99%) were tested for RSV of which 101 (28%) were RSV+ (IP=37, ED=18, OP=46) (Figure 1). Compared to RSV-negative subjects, RSV+ subjects were younger (6.6 vs. 4.9 months, p< 0.001), 56% were male and 48% white. By setting, infants in the OP setting were older than those seen in the IP and ED [(p=0.002), Figure 2]. Compared to infants in the OP setting, hospitalized infants were more likely to present with SOB and rhonchi/rales, but less likely to have only upper respiratory symptoms (Figure 3) and be African American (p=0.046). Infants in the IP setting had a higher proportion of clinical RSV diagnostic testing (73%) compared to the ED (39%) and OP (28%) settings (p< 0.001). Figure 1. Davidson County Infants with RSV by MMWR Week and Healthcare Setting (n=101) Figure 2. Cumulative Enrollment of Davidson County Infants with RSV by Age in Months and Healthcare Setting (n=101) Figure 3. Proportion of Davidson County Infants with RSV Showing each Clinical Symptom, by Healthcare Setting Two-thirds of RSV+ infants sought care from either an OP or ED setting, with nearly all hospitalized infants presenting with both upper and lower respiratory symptoms. The underutilization of diagnostic testing in the OP settings may underestimate the true burden of RSV. Future studies are essential to document the true prevalence of RSV in order to assess the need and impact of new interventions (e.g., immunizations, antivirals). Danielle A. Rankin, MPH, CIC, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) Jon Fryzek, PhD, MPH, EpidStrategies (Employee) Mina Suh, MPH, International Health, EpidStrategies (Employee) Donald S. Shepard, PhD, Sanofi Pasteur (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

Hepatic cytochrome P450 enzyme induction is associated with certain antiepileptic drugs (AEDs) and may result in hypocalcaemia secondary to vitamin D deficiency. We report a case of a 44-year-old man with a history of epilepsy, who presented with breakthrough seizures after having previously been seizure-free for 11 years. Investigations revealed severe hypocalcaemia with a corrected calcium of 1.7 mmol/L. His phenytoin dose was increased, and he was started on calcium supplementation. He was discharged with a corrected calcium level of 2.05 mmol/L but was readmitted 1 week later with further seizures and a corrected calcium of 1.89 mmol/L. 25-hydroxyvitamin D was low. AED-induced hypocalcaemia was suspected, which had been made paradoxically worse by the increase in phenytoin dose. Alfacalcidol was prescribed and he was switched from phenytoin to levetiracetam with resolution of hypocalcaemia and no further seizures. The authors recommend screening for calcium and vitamin D deficiency in patients on enzyme-inducing AEDs.