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 (319) 384-5008 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 (n=127 cases): >49% with fever • >400C 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. • Conclusions • US populations would benefit from better Ad surveillance, the identification of • populations at high risk of severe Ad disease, and selected use of Ad7 vaccine. • National Surveillance for Emerging Adenovirus Infections (NIH R01 funded 2004) • Leading adenoviral researchers in the United States • 15 viral labs linked across the United States submitting all adenoviral isolates 3 high risk populations x 3 years: • children <7 years of age; • allogeneic stem cell or solid organ transplant patients • military trainees and other patients with adenoviral disease • Serotyping and selective genotyping • Case-control molecular study predictors for virulence in the E1, E3, and E4 regions • References • 1. J Gen Virol 2003; 84:687-695 • 2. Annals of Asthma, Allergy, and Immunology 1997;78:449-56 • 3. Blood 2002; 100:1619-27 • 4. Emerg Infect Dis 2002 Mar;8(3):269-77 • 5. J Med Virology 1996;48:151-6 • 6. Jpn J Med Sci Biol 1998; 51:43-51 • 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 Iowa’s 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 (N=77) • 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.