CDC Investigators Gain New Clues on 2016-17 Human Adenovirus Outbreak in New Jersey

Tests revealed similar genome type—the potentially lethal 7d variant—among cases despite various facilities of origin.

Human adenovirus has been described as a “viral pathogen with increasing importance," and outbreaks, though still relatively rare, typically occur in “congregate settings." Think college campuses and long-term care centers.

In fact, the authors of a review published in March 2018 in Biomedicines described military personnel, namely those permanently stationed and thus housed at bases worldwide, as a “vulnerable target” for the virus. According to surveillance reports submitted to the US Centers for Disease Control and Prevention’s (CDC) National Adenovirus Type Reporting System, nearly 2400 cases of human adenovirus were reported in the 50 states between 2006 and 2016, the most recent period for which data are available.

Now, researchers from the CDC have a better understanding of a recent outbreak—or series of case clusters—in New Jersey, as reported to the state’s Department of Health between December 2016 and February 2017. The findings, published on January 11, 2019, in Open Forum Infectious Diseases, will hopefully assist researchers in gaining a better understanding of disease morbidity and mortality, transmission, and the epidemiologic and clinical features of affected patients.

“Adenovirus is not a nationally notifiable disease in the United States, meaning clinicians are not required to test for or report cases to CDC,” Marie Killerby, VetMB, CDC epidemiologist and study lead author, told Contagion®. “However, increased awareness of human adenoviruses and availability of molecular testing methods has allowed for increased detection and identification of human adenoviruses. This has helped improve our understanding of respiratory illness associated with human adenoviruses in the United States.”

Notably, the 12 cases reported between December 2016 and February 2017 in New Jersey involved the human adenovirus genome type 7d. The 12 cases, 4 of which resulted in patient death, were identified in 3 neighboring counties in the Garden State. The affected counties were not identified in the report; however, health officials from Cumberland County, in the southern part of the state, are listed in the acknowledgements section of the published report. In all, 7 cases involved college students (at the same school), 3 cases were patients at a substance-abuse treatment center, and 2 were patients at a tertiary-care center.

The CDC investigators tested respiratory specimens using generic pan-human adenovirus rPCR (pan-rPCR) assay to confirm detection and then typed the specimens using PCR and sequencing of hexon capsid protein gene hypervariable regions 1-6. Virus isolation was attempted on all positive specimens (with sufficient volume) from all 3 settings, and whole genomic sequencing was also performed, with enzyme analysis of the genomes and genome types determined using established guidelines.

In all, 95 students at the affected college submitted samples for testing, with the majority returning positive for influenza or another respiratory virus (eg, rhinovirus). At the treatment facility, 79 cases (59 inpatients and 20 staff) reported acute respiratory infection symptoms, and multiple samples were collected for testing. Unfortunately, 3 of the 4 fatalities linked with this human adenovirus case cluster occurred in this population. The last 2 patients were identified following admission to a hospital in nearby Philadelphia. The patient who ultimately died at the hospital as a result of her infection had a history of non-Hodgkin’s lymphoma (and radiation and chemotherapy).

The authors emphasized that all 4 of the fatalities in this case cluster occurred in patients over 50 years of age with preexisting co-morbidities (eg, congestive heart failure, hepatic cirrhosis, alcohol use disorder, and type 2 diabetes), although human adenovirus-7d has been associated with severe illness and higher fatality rates compared to other types, particularly in children. Importantly, all of the 9 human adenovirus-7d whole genome sequences obtained were “nearly identical…and nearly identical to the strains circulating in Oregon from 2013 to 2014 and in China in 2009 and 2011.”

“Substantial morbidity and mortality occurred among case-patients in the substance abuse facility and 2 nearby community residents,” Killerby et al wrote in their concluding remarks. “While these cases were temporally and spatially connected, no known epidemiologic links were found between cases presenting at different locations.”