Co-infections of Adenovirus Species in Previously Vaccinated Patients

Adenovirus infection is an important cause of morbidity and mortality in stem cell transplant recipients. We report species and type-specific analysis from a prospective study of high-risk adenovirus infections following hematopoietic progenitor cell transplantation prior to, during, and after treatment with cidofovir, as well as species analysis of contemporaneously collected samples from control patients. Nine different adenovirus types representing all six recognized species were identified, and mixed infections were commonly found in this group of patients. Adenovirus (ADV) infections are common in childhood.The 51 different currently recognized ADV serotypes are divided into six species (A through F) which have similar genetic and biological properties (3). ADVs commonly cause respiratory, gastrointestinal, and urinary tract disease. In the immunocompromised host, ADV infections can cause severe disease and death. In a recent review, Chakrabarti et al. (3) noted that ADV species B and C account for the majority of clinical isolates in hematopoietic progenitor cell transplantation (HPCT) recipients.In this study, we determined the types of ADVs infecting seven pediatric stem cell transplant recipients prior to, during, and after treatment with cidofovir, as previously described (1), and compared them with 25 consecutive ADV isolates from nontransplant pediatric patients collected contemporaneously to determine the type-specific epidemiology of ADV infections in HPCT recipients and controls. A companion paper (1) examined the epidemiology of ADV infections in HPCT recipients and the effectiveness (if any) of cidofovir against these infections. This study was approved by the IRB of the Children's Memorial Research Center, Children's Memorial Hospital, Chicago, IL.HPCT recipients and specimens. Patients underwent HPCT between 8 September 2003 and 1 December 2005 at our institution. Urine, stool, and throat samples were screened for ADV by viral culture (see below). Plasma was referred to ViraCor (Lee's Summit, MO) for quantitative ADV detection by PCR. Specimens were obtained weekly through the first 100 days (14 weeks) and then monthly until 1 year from the HPCT. A patient was defined as having a high-risk ADV infection (HRAI) if they had (i) a positive blood ADV PCR with or without symptoms, (ii) two or more positive ADV cultures from separate peripheral sites with or without symptoms, or (iii) one positive peripheral culture for ADV plus compatible clinical evidence of ADV (1). As previously described, 7 of the 38 children developed HRAI and received cidofovir treatment (1). Two additional asymptomatic patients had ADV identified transiently from a single body site only without clinical symptoms and were not further studied.Specimens from other patients. Twenty-five consecutive pediatric specimens from nontransplanted patients submitted to our virology laboratory during routine clinical care that grew ADV also had ADV species identification performed. These specimens included those from the respiratory trac...

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“…Thus, as was seen in the results of other studies, infections with multiple ADV types are not unusual (2,5,6,7,9,11,13,14).…”

Section: Adenovirus (Adv) Infections Are Common In Childhoodsupporting

confidence: 83%

Identification of Adenoviruses in Specimens from High-Risk Pediatric Stem Cell Transplant Recipients and Controls

Zheng

Erdman

et al. 2008

J Clin Microbiol

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“…As shown by others (33,34,35), species-and type-specific PCR assays are capable of revealing coinfections with different HAdVs that otherwise might go undetected. In this study, we identified several specimens by our qPCR assays that contained two HAdV types, one predominant type and one subordinate type.…”

Section: Discussionmentioning

confidence: 88%

Quantitative Real-Time PCR Assay Panel for Detection and Type-Specific Identification of Epidemic Respiratory Human Adenoviruses

Trujillo-Lopez²,

Lott³

et al. 2013

J Clin Microbiol

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bOutbreaks of human adenovirus (HAdV) acute respiratory illness (ARI) have been well documented among civilians and unvaccinated military recruits. Among the 7 recognized HAdV species (A to G), species B (particularly serotypes 3, 7, 11, 14, and 21) and E (serotype 4) have more often been associated with epidemic ARI. Rapid detection and type-specific identification of these viruses would enhance outbreak response and help guide prevention and control measures. To this end, we developed type-specific real-time quantitative PCR (qPCR) assays for HAdV types 3, 4, 7, 11, 14, 16, and 21 targeting the HAdV hexon gene. All typespecific qPCR assays reproducibly detected as few as 10 copies/reaction of quantified hexon recombinant plasmids with a linear dynamic range of 8 log units (10 1 to 10 8 copies); in contrast, a generic qPCR assay that detects all HAdV types run concurrently detected between 10 and 100 copies/reaction, depending on the virus type. No nonspecific amplifications were observed with concentrated nucleic acid from 51 HAdV prototype strains or other common respiratory pathogens. All members of a panel of 137 previously typed HAdV field isolates and positive clinical specimens were correctly characterized by the type-specific qPCR assays; two different HAdV types were detected in three of the clinical specimens and confirmed by amplicon sequencing. The qPCR assays permit sensitive, specific, and quantitative detection and identification of seven clinically important respiratory HAdVs and should provide a convenient adjunct to classical typing methods for a rapid response to HAdV outbreaks.

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“…It is important to note that such a preliminary study should be confirmed eventually with a whole-genome determination for a thorough description, since possible recombination events would not be surveyed. Genome recombination requires coinfection, which is observed in HAdV infections (8,26,39). Putative recombinants, based on the neutralization epsilon and hemagglutination gamma determinants, are recognized as different prototypes by the community, with additional field strains described based on these two markers (SN and hemagglutination inhibition assays) as case studies in the literature (9,11,12).…”

Section: Discussionmentioning

confidence: 99%

Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus

et al. 2011

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Human adenovirus C (HAdV-C) species are a common cause of respiratory infections and can occasionally produce severe clinical manifestations. A deeper understanding of the variation and evolution in species HAdV-C is especially important since these viruses, including HAdV-C6, are used as gene delivery vectors for human gene therapy and in other biotechnological applications. Here, the full-genome analysis of the prototype HAdV-C6 and a recently identified virus provisionally termed HAdV-C57 are reported. Although the genomes of all species HAdV-C members are very similar to each other, the E3 region, hexon and fiber (ten proteins total) present a wide range of identity values at the amino acid level. Studies of these viruses in comparison to the other three HAdV-C prototypes (1, 2, and 5) comprise a comprehensive analysis of the diversity and conservation within HAdV-C species. HAdV-C6 contains a recombination event within the constant region of the hexon gene. HAdV-C57 is a recombinant virus with a fiber gene nearly identical to HAdV-C6 and a unique hexon distinguished by its loop 2 motif.

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Co-infections of Adenovirus Species in Previously Vaccinated Patients

Abstract: Adenoviral infections associated with respiratory illness in military trainees involve multiple co-infecting species and serotypes.

Cited by 38 publications

References 40 publications

Identification of Adenoviruses in Specimens from High-Risk Pediatric Stem Cell Transplant Recipients and Controls

Identification of Adenoviruses in Specimens from High-Risk Pediatric Stem Cell Transplant Recipients and Controls

Quantitative Real-Time PCR Assay Panel for Detection and Type-Specific Identification of Epidemic Respiratory Human Adenoviruses

Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus

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