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Human Adenovirus-14p1 Infections | CDC EID - Volume 17, Number 8–August 2011

full-text ►Human Adenovirus-14p1 Infections | CDC EID: "EID Journal Home > Volume 17, Number 8–August 2011
Volume 17, Number 8–August 2011
Deaths Associated with Human Adenovirus-14p1 Infections, Europe, 2009–2010
Michael J. Carr, Comments to Author Adriana E. Kajon, Xiaoyan Lu, Linda Dunford, Paul O'Reilly, Paul Holder, Cillian F. De Gascun, Suzie Coughlan, Jeff Connell, Dean D. Erdman, and William W. Hall

Author affiliations: National Virus Reference Laboratory–University College Dublin, Dublin, Ireland (M.J. Carr, L. Dunford, P. O'Reilly, P. Holder, C.F. De Gascun, S. Coughlan, J. Connell, W.W. Hall); Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA (A.E. Kajon); and Centers for Disease Control and Prevention, Atlanta, Georgia, USA (X. Lu, D.D. Erdman)

Suggested citation for this article

Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV-14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease with high rates of illness and death. We retrospectively analyzed specimens confirmed positive for HAdV by immunofluorescence, virus culture, or real-time PCR during July 1, 2009–July 31, 2010, and describe 9 cases of HAdV-14p1 infection with characteristic mutations in the fiber and E1A genes that are phylogenetically indistinguishable from the viruses previously detected in the United States. Three patients died; 2 were immunocompromised, and 1 was an immunocompetent adult. We propose that surveillance should be increased for HAdV-14p1 and recommend that this virus be considered in the differential diagnosis of sudden-onset acute respiratory disease, particularly fatal infections, for which an etiology is not clear.

Human adenoviruses (HAdVs) were identified independently by 2 groups during the early 1950s (1,2). HAdVs are nonenveloped, linear double-stranded DNA viruses encapsidated within a protein shell and have been categorized into 6 species (A–F) that contain 51 immunologically distinct serotypes (3). HAdVs most commonly cause acute respiratory disease; however, depending on the infecting HAdV serotype and tropism resulting from differential host receptor use, the wide variety of symptoms can include pneumonia, febrile upper respiratory illness, conjunctivitis, cystitis, and gastroenteritis (4). The severity of disease appears dependent on the immunocompetence and cardiopulmonary health of the host, and the spectrum of disease can range from subclinical to severe respiratory distress and death (4). Immunocompromised patients (especially bone marrow transplant [BMT] recipients) are particularly susceptible to HAdV infection, resulting in severe illness and deaths, whereas illness in immunocompetent patients generally resolves without major complication.

HAdV species B comprises 2 subspecies: B1 (including HAdV-3, -7, -16, -21, and -50) and B2 (HAdV-11, -14, -34, and -35). The subspecies B2 HAdV-14 (agent de Wit) was originally identified as an etiologic agent of acute respiratory disease in military recruits in the Netherlands during 1955 (5). Despite reports of subsequent outbreaks in Europe and Asia during the 1950s and early 1960s (6), global surveillance in the subsequent decades had not identified circulation of this serotype until spring 2006, when HAdV-14 emerged as a cause of a major proportion of acute febrile respiratory illness in military bases across the United States (7–9). In 2007, community-associated outbreaks were identified in California and New York (10), and during March–June 2008, ≈140 cases of HAdV-14 were identified in Oregon, Washington, and Texas. Overall, 38% of patients were hospitalized, 17% were admitted to intensive care units, and 5% died. During September 2008, an outbreak was reported with 32 cases of pneumonia on Prince of Wales Island off the coast of Alaska (11). In the United States, the earliest documented case of HAdV-14 infection, by retrospective testing, occurred in California during December 2003, and the most recent evidence of HAdV-14 had been in Pennsylvania during June 2009 (7). The virus has circulated uninterrupted in some military recruit camps (A.E. Kajon, unpub. data).

Sequence analysis of the fiber gene of HAdV-14 associated with the recent outbreaks has shown a 6-bp deletion resulting in a 2-aa deletion (lys-glu) at positions 251 and 252 in the knob region compared with the de Wit HAdV-14p prototype strain (10). The 252glu site is conserved in all other species B HAdVs and is located in the F–G loop of the fiber protein knob near a putative host receptor binding site. Further sequencing of the hexon gene hypervariable regions 1–7 and the E1A genes demonstrated that this emerging HAdV-14 was clearly separable from the reference strain de Wit (genome restriction type HAdV-14p) (9,11). This new genomic variant has been designated HAdV-14p1 on the basis of novel restriction profiles. Viral receptor binding and internalization studies that used recombinant HAdV-14p1 fiber regions containing the 2-aa deletion did not demonstrate substantial phenotypic differences between the new agent and the prototype virus (12). This finding suggests that HAdV-14p1 could be an immune escape mutant that has lost a potential neutralizing epitope, has modified postinternalization steps, or has enhanced binding to host cells through a yet-unidentified viral receptor.

However, no evidence suggests that HAdV-14p1 has reemerged because of altered virulence. Despite the mutations in the fiber and EIA genes, no other genetic differences with the prototype HAdV-14 clearly explain differing disease severity in US outbreaks (13). This observation suggests that reemergence of this agent might be more likely to have resulted from spread of an infectious agent in immunologically naive populations and changes in the rate of specific immunity in host populations over time. The recent whole-genome analysis of HAdV-14p1 in mild and severe infections supports this idea (13). In addition, reports of recent HAdV-14 and HAdV-14–11 outbreaks in Asia and the United States have detailed similar dynamics (14,15). The observed characteristics (including periods of little activity punctuated by distinct outbreaks with occasional severe disease and death) may simply be the natural pattern of adenovirus species B2 respiratory pathogens.

Whether HAdV-14p1 had circulated elsewhere before, or at the same time as, the outbreaks in the United States and whether it is currently circulating in Europe is unclear. In this report, we show that recent infection and deaths associated with HAdV-14p1 infection have occurred in Ireland and that this virus is genetically indistinguishable from HAdV-14p1 described in the United States.

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Suggested Citation for this Article

Carr MJ, Kajon AE, Lu X, Dunford L, O'Reilly P, Holder P, et al. Deaths associated with human adenovirus-14p1 infections, Europe, 2009–2010. Emerg Infect Dis [serial on the Internet]. 2011 Aug [date cited].

DOI: 10.3201/1708.101760

Comments to the Authors

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Michael J. Carr, National Virus Reference Laboratory, University College Dublin, Dublin 4, Ireland; email:

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