Adenovirus Type 4 Respiratory Infections Among Civilian Adults

Northeastern United States, 2011-2015

Adriana E. Kajon; Daryl M. Lamson; Camden R. Bair; Xiaoyan Lu; Marie L. Landry; Marilyn Menegus; Dean D. Erdman; Kirsten St. George


Emerging Infectious Diseases. 2018;24(2):201-209. 

In This Article

Abstract and Introduction


Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011–2015. Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases. Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician's office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults.


Human adenovirus type 4 (HAdV-4), the only human adenovirus classified within species E, was first identified in the early 1950s in association with military outbreaks of febrile respiratory illness and is well-recognized worldwide as a prevalent causative agent of acute respiratory disease (ARD) and ocular disease.[1–6] Surveillance studies conducted in the United States and other countries have demonstrated a leading role for this particular adenovirus type in the etiology of outbreaks of febrile respiratory illness in military recruit training facilities,[7–11] where crowding and environmental contamination appear to facilitate transmission among nonvaccinated trainees.[12,13] By using restriction enzyme analyses of viral DNA, several studies have reported extensive intratypic genetic variability for HAdV-4.[14–16] Two major clusters of genetic homology have been identified among circulating genomic variants: prototype (p)–like viruses, which are closely related to prototype strain RI-67, and a-like viruses, which exhibit, among other characteristics, distinct BamHI restriction profiles,[15] a distinct inverted terminal repeat,[17,18] and a different genetic make-up in the E3 region (A.E. Kajon, unpub. data).

HAdV-4 respiratory infections are preventable by vaccination with the live oral formulation of the nonattenuated p-like strain exclusively licensed for military use.[19,20] After 15 years of discontinuation of HAdV-4 vaccination protocols with the consequent resurgence of continuous outbreaks of HAdV-4–associated illness in US recruit training facilities nationwide, US Department of Defense reinstated the vaccine in November 2011, dramatically reducing the number of cases of HAdV infection in basic training camps.[21,22]

The absence of a sentinel system for HAdV surveillance outside of the military has made assessing the burden of disease attributable to HAdV-4 infection among civilians difficult. The limited epidemiologic data available in the published literature suggest that respiratory disease associated with HAdV-4 infection is detected at a significantly lower frequency than disease associated with species C or B HAdV types among children and that HAdV-4 infection occurs rarely among civilian adults.[23–27]

Consequently, the apparent increased frequency of detection of cases and case clusters of HAdV-4 respiratory infection in the northeastern United States, documented by the New York State Department of Health (NYSDOH) or the Centers for Disease Control and Prevention (CDC) (data not shown), caught our attention. In this article, we report the molecular characterization of 36 select HAdV-4 isolates from a selection of retrospectively evaluated cases among civilians.