Indictment by Association: Once Is Not Enough

Early life infections with human bocavirus 1 (HBoV-1) are common, and the virus is readily detected in the upper respiratory tract, often during acute upper respiratory tract illness. Its etiological role in respiratory tract infections has been uncertain because of its presence in asymptomatic children and frequent concurrent detection of other respiratory viruses. Longitudinal cohort studies, in which sampling is done at intervals that include periods of illness and health, have begun to bring clarity to the story. In this issue of the Journal, Martin et al [1] performed noninvasive weekly sampling and collected health data during the first 2 years of life and provide substantial evidence that HBoV-1 is indeed a respiratory pathogen in young children. This story is an excellent example of the power of longitudinal cohort study designs in identifying etiologic roles for viruses that embody combinations of being highly prevalent, being able to reinfect previously exposed individuals and to persist for long periods in the infected host in the absence of symptoms, and, often, causing mild disease.