Adenovirus type 4 respiratory infections with a concurrent outbreak of coxsackievirus A21 among United States Army Basic Trainees, a retrospective viral etiology study using next‐generation sequencing

Abstract

Human adenoviruses (HAdV), in particular types 4 and 7, frequently cause acute respiratory disease (ARD) during basic military training. HAdV4 and HAdV7 vaccines reduced the ARD risk in U.S. military. It is important to identify other respiratory pathogens and assess their potential impact on military readiness. In 2002, during a period when the HAdV vaccines were not available, throat swabs were taken from trainees (n = 184) with respiratory infections at Fort Jackson, South Carolina. Viral etiology was investigated initially with viral culture and neutralization assay and recently in this study by sequencing the viral isolates. Viral culture and neutralization assays identified 90 HAdV4 isolates and 27 additional cultures that showed viral cytopathic effects (CPE), including some with picornavirus-like CPE. Next-generation sequencing confirmed these results and determined viral genotypes, including 77 HAdV4, 4 HAdV3, 1 HAdV2, 17 coxsackievirus A21 (CAV21), and 1 enterovirus D68. Two samples were positive for both HAdV4 and CAV21. The identified genotypes are phylogenetically close to but distinct from those found during other years or in other military/non-military sites. HAdV4 is the predominant respiratory pathogen in unvaccinated military trainee. HAdV4 has temporal and demographic variability. CAV21 is a significant respiratory pathogen and needs to be evaluated for its current significance in military basic trainees.

Adenoviral Infections in Singapore: Should New Antiviral Therapies and Vaccines Be Adopted?

“…The NF-I human transcription factor and its binding have been extensively characterized molecularly and biochemically as required for optimal HAdV DNA replication [46,47]. This putative genome-based host adaptation may be the "tipping point" that has allowed HAdV-E4 entry into a global general population, which is presumably immunologically naive to its epsilon (hexon) antigen, because HAdV-E4 had been known to circulate sporadically outside the US military basic trainee populations [20,[48][49][50]. The recombination event is likely a recent one, with the earliest appearance in 1978 (KX384956 V0014/France/1978) as noted in a resurvey [23] of 2 sets of recently released genomes that include archived and currently circulating military and civilian HAdV-E4 isolates [20,49], and it may be important as an example of a molecular evolution pathway by which zoonosis may be a source of emergent human pathogens [44].…”

Adenovirus Type 4 Respiratory Infections among Civilian Adults, Northeastern United States, 2011–20151

“…In addition, while the failure to detect influenza virus does not guarantee the virus was never present, the detection of HAdV in these cases assists in alleviating concerns regarding influenza vaccine failure. Finally, the potential differences in pathogenicity, transmissibility, and fitness between p-like and a-like genomic variants of HAdV-4 that would explain the marked predominance of a-like variants in the examined collections of HAdV-4–positive respiratory specimens representing sampling of ARD in civilian and military populations in the United States over the past 5 decades ( 16 , 40 ) deserve further investigation.…”

Isolation of Coxsackievirus A21 from Patients with Acute Respiratory Infection in Yamagata, Japan in 2019

“…Coxsackievirus A21 (CV-A21) is a member of the species HEV-C and has been detected from patients with mild respiratory infections and poliomyelitis/acute flaccid paralysis (1)(2)(3)(4)(5). However, reports of CV-A21…”