Implementation of a Prospective Index-Cluster Sampling Strategy for the Detection of Presymptomatic Viral Respiratory Infection in Undergraduate Students

Abstract

Background. Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implementation in a college population. Methods. We enrolled an annual cohort of first-year undergraduates who completed daily electronic symptom diaries to identify index cases (ICs) with respiratory illness. Investigators then selected 5-10 potentially exposed, asymptomatic close contacts (CCs) who were geographically co-located to follow for infections. Symptoms and nasopharyngeal samples were collected for 5 days. Logistic regression model-based predictions for proportions of self-reported illness were compared graphically for the whole cohort sampling group and the CC group. Results. We enrolled 1379 participants between 2009 and 2015, including 288 ICs and 882 CCs. The median number of CCs per IC was 6 (interquartile range, 3-8). Among the 882 CCs, 111 (13%) developed acute respiratory illnesses. Viral etiology testing in 246 ICs (85%) and 719 CCs (82%) identified a pathogen in 57% of ICs and 15% of CCs. Among those with detectable virus, rhinovirus was the most common (IC: 18%; CC: 6%) followed by coxsackievirus/echovirus (IC: 11%; CC: 4%). Among 106 CCs with a detected virus, only 18% had the same virus as their associated IC. Graphically, CCs did not have a higher frequency of self-reported illness relative to the whole cohort sampling group. Conclusions. Establishing clusters by geographic proximity did not enrich for cases of viral transmission, suggesting that ICSS may be a less effective strategy to detect spread of respiratory infection.