An Emergent, Possibly More Virulent, Strain of Human Adenovirus

1
An Emergent, Possibly More Virulent, Strain of
Human Adenovirus Has Become Endemic in the
Midwestern United States Gregory C. Gray, MD,
MPH1 Sharon Setterquist MT(ASCP)1 Sandra J.
Jirsa2 Lucy E. Desjardin, PhD2 Dean D. Erdman,
DrPH3 1Center for Emerging Infectious Diseases,
Department of Epidemiology, University of Iowa
College of Public Health, Iowa City, IA
2University of Iowa Hygienic Laboratory, Iowa
City, IA 3Respiratory Virus Section, Centers for
Disease Control and Prevention, Atlanta, GA
Gregory C. Gray, MD, MPH Center for Emerging
Infectious Diseases Univ. of Iowa College of
Public Health 200 Hawkins Dr., C21K GH Iowa City,
IA 52245 Tel [phone] Fax (319)
384-5004 www.public-health.uiowa.edu/CEID

• Discussion
• Ad7h supplanted Ad7c in 1986 in Chile, Uruguay,
  and Argentina pediatric
• epidemics were reported with longer
  hospitalizations, higher temperature, more
• oxygen, Ad7h explained 94 of Ad mortality.5
  Estimated 55 secondary attack
• rates.
• Ad7d2 caused a 1995-97 epidemic in Japan (n127
  cases) gt49 with fever
• gt400C and 5 deaths6
• US surveillance for Ad is passive and incomplete.
  However, 4 (66) of the 6
• US Ad7 epidemics evaluated since 1996 have been
  due to Ad7d2 (19 deaths). All
• Civilian Ad7d2 epidemics have occurred among
  institutionalized children.
• Bone marrow and solid organ transplant patients
  may also be at high risk of severe
• disease from Ad7 infection
• The US military will produce Ad7 vaccine in 2009
  that may benefit civilian
• populations at high risk of Ad infection and
  severe disease.

Revised Abstract Background In 2002, two
possibly more virulent human adenovirus (Ad)
genotypes (Ad7d2 and Ad7h) were shown to have
recently entered US populations. Ad7d2
was associated with several US epidemics since
1996 and at least 19 deaths (4 deaths among
institutionalized pediatric patients in Iowa).
Methods We sought to evaluate the prevalence of
Ad7 genotypes from archived Ad isolates collected
by Iowas state public health laboratory. Using
restriction enzyme analyses, we evaluated the
genotypes of 77 Ad7 isolates collected statewide
from Iowa patients during the period of 1992 to
2002. Results Beginning in 1994, Ad7d2 had
become increasingly more prevalent across
Iowa and in 2002, evidence suggested it had
supplanted all other Ad7 genotypes (9 of 9
Ad7 isolates were A7d2). A7d2 was recovered from
patients of both genders ranging in age from 3
months to 49 years from numerous sites across the
state. Although available clinical data from
this passive surveillance system are limited, a
number of patients infected with Ad7d2 had
pneumonia and/or respiratory distress syndrome.
Conclusions These data suggest that Ad7d2 has
become endemic in Iowa and is responsible for
severe illness. Independent of this emergent
genotype, Ad is now recognized to cause severe
morbidity and often death among
immunocompromised patients, particularly bone
marrow and solid organ transplant recipients. As
high risk patients might one day be protected by
the live Ad7 vaccine, we argue that
more comprehensive Ad surveillance and risk
factor identification should be performed to
guide future Ad public health interventions.
Introduction Ads are classified by species (A
F) by their hemagglutination properties. Each
species May have numerous serotypes (51 serotypes
recognized) which are determined by serum
neutralization (hexon proteins targets). Among
serotypes, Ad are further classified by genotypes
via restriction enzyme analyses (REA) or via
hexon gene sequencing (Fig. 1). Different Ad
serotypes have different affinities for different
tissues.1 Pediatric patients with Ad3, Ad7 or
Ad21 infection often have severe disease. Among
those with Ad bronchiolitis or pneumonia, 1-4
will develop chronic pulmonary disease
bronchiolitis obliterans, asthma.2 Solid organ
and bone marrow transplant patients have been
shown to have up to 89 adenoviral attack rates
and up to 50 case-fatality.3 Two possibly more
virulent human adenovirus (Ad) genotypes (Ad7d2
and Ad7h) emerged in the 1990s and been
associated with more severe disease. Recently,
Ad7d2 and Ad7h been found among US populations.4
Fig. 1 Genotyping by restriction enzyme analysis
Fig. 2 Prevalence of Ad7 Genotypes from Iowa
State Hygienic Lab Isolates 1992-2002 (N77)
Methods Using the endonuclease Bam HI, we studied
77 archived Ad isolates collected from among
numerous influenza-like-illness surveillance
sites across Iowa during the period of 1992 to
2002. Results 44 (57) of the 77 isolates were
Ad7d2 and 6 (7.8) were Ad7h. The first Ad7d2
specimen was isolated in March 1994 from a child
living in Mystic, Iowa. The first Ad7h specimen
was isolate in November 1993 from a child living
in Waterloo, IA. These are some of the first
specimens of these genotypes detected in the
United States. The next oldest US Ad7h isolate
was isolated in 1998. Ad7d2 caused illness among
patients ranging in age from 3 months to 49
years. 75 of the patients were male. Although
the clinical details are sparse, numerous
patients were thought to have influenza or
diagnosed with respiratory distress syndrome.
Ad7d2 isolates were obtained from 12 different
sites in Iowa. Beginning in 1994, Ad7d2 had
become increasingly more prevalent across Iowa.
In 2002, data suggest that it has supplanted all
other Ad7 genotypes (9 of 9 Ad7 isolates were
A7d2) (Fig. 2). Ad7h was detected in 4 Iowa
counties. 66 of the Ad7h isolates came from
male patients.