Adenovirus Picture Clarified by New Technique

IOWA CITY, Iowa, Oct. 12 -- A new picture of adenoviruses and the disease associated with them in the U.S. is emerging from a novel molecular technique, according to researchers here.

The advantage of the new technique -- which involves sequencing of highly variable sections of the adenovirus hexon gene to identify the adenovirus strain -- is that it can be done within two days, according to Gregory Gray, M.D., of the University of Iowa, and colleagues.

In contrast, conventional serotyping can take weeks, which limits its use as a diagnostic and public health tool, Dr. Gray and colleagues said in the November issue of Clinical Infectious Diseases.

The genotyping method has "the potential to provide rapid results to clinicians and public health officials" to help treat individual patients and also to manage larger outbreaks, Dr. Gray and colleagues said.

The new molecular method was used to study specimens from 22 medical facilities -- 14 civilian and eight military -- over a 25-month period from July 2004 through September 2006.

All told, the method was used to characterize 2,237 clinical adenovirus-positive specimens, and to compare their sequences with the 51 currently recognized human adenovirus strains.

"In a blinded comparison, this method performed well and was much faster than the classic serologic typing method," the researchers reported.

Among the observations made using the new technique is a significant increase in the prevalence of type 21 adenovirus, which has been associated with more severe disease, the researchers found.

Also, multivariable risk factor analysis showed that adenovirus-infected patients:

• Younger than seven had a three-fold increase in the risk of severe disease, compared to others with an adenovirus infection. The odds ratio was 3.2 with a 95% confidence interval from 1.4 to 7.4.
• With a chronic disease had almost a four-fold increase in risk of severe disease. The odds ratio was 3.6, with a 95% confidence interval from 2.6 to 5.1.
• Who had recently had a transplant were nearly three times as likely to have severe adenovirus disease. The odds ratio was 2.7, with a 95% confidence interval from 1.3 to 5.2.

Unexpectedly, patients infected with adenovirus type five or 21 also had a significantly higher risk of severe disease than those with other strains. The odds ratios were 2.7 and 7.6, respectively.

Among civilians, the most prevalent adenovirus types were types three, two, one, and five, with rates of 34.6%, 24.3%, 17.7%, and 5.3%, respectively.

Among military personnel, the most prevalent types were four, three, and 21, with rates of 92.8%, 2.6%, and 2.4%, respectively.

Early investigations of adenovirus suggested that among civilians, infection was common among children, but about half of all infections were asymptomatic, and symptomatic infections were typically mild, Dr. Gray and colleagues noted.

On the other hand, military populations experienced severe epidemics of acute respiratory disease, including pneumonia and encephalitis, especially involving adenovirus types four, seven, and 21, they said.

Currently, 51 strains are known and investigators have linked them to a range of diseases, including chronic airway obstruction, pulmonary dysplasia, myocarditis and dilated cardiomyopathy, mononucleosis-like syndromes, intussusception, sudden infant perinatal death, and obesity, the researchers noted.

Among adenovirus isolates recovered from civilians in this study, 50% were associated with hospitalization, 19.6% with a chronic disease, 11% with a bone marrow or solid organ transplant, 7.4% with intensive care, and 4.2% with a cancer diagnosis, the researchers found.

Such findings "add to our new appreciation of the morbidity associated with adenovirus infection," the researchers concluded.

The authors pointed a limitation of the study. "Although a large number of adenovirus-positive specimens were tested in this study, the specimens were collected for diagnostic purposes and, thus, were likely to have been obtained from the most severely affected patients."