Use of Whole-Genome Sequencing of Adenovirus in Immunocompromised Pediatric Patients to Identify Nosocomial Transmission and Mixed-Genotype Infection

Houldcroft, Charlotte J.; Roy, Sunando; Morfopoulou, Sofia; Margetts, Ben; Depledge, Daniel P.; Cudini, Juliana; Shah, Divya; Brown, Julianne R.; Romero, Erika Yara; Williams, Rachel; Cloutman-Green, Elaine; Rao, Kanchan; Standing, Joseph F.; Hartley, John C.; Breuer, Judith

doi:10.1093/infdis/jiy323

Cited by 43 publications

(64 citation statements)

References 46 publications

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“…HAdV types reported in the general population are types C1, C2, C5, B3, B7, B14, B21, E4, and F41 44,45 . The types of HAdV reported in HSCT patients are similar to those found in the general population, with C1, C2, C5, B3 and B7 dominating, apart from HAdV A31 having been found more frequently in HSCT patients 41,[46][47][48][49] .…”

Section: Human Adenovirus (Hadv)mentioning

confidence: 72%

Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients

Swartling

Nordén

Samuelsson

et al. 2020

Bone Marrow Transplant

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Gastrointestinal symptoms, and elevated liver enzymes, are common after HSCT, often due to drug toxicity, graft-versus-host disease (GVHD) or infections. It is essential to distinguish between GVHD and infection, since both conditions may progress to lethal disease, but require opposite strategies for the immunosuppressive treatment. Several of the viral gastrointestinal infections are easily transmitted and can cause outbreaks in health care facilities. Annika Allard för lärorikt samarbete i adenovirus-studien, och Annika Tiveljung, Mats Remberger och Mikael Sundin för samarbetet med första norovirus studien Rickard Nordén, Ebba Samuelsson, Helene Norder och Johan Westin för vårt samarbete, och allt ni lärt mig i samband med hepatit E studien Lennart Svensson och Johan Norgren, för ett roligt och bra samarbete med det senare norovirus-projektet Olle, Mona-Lisa, Mikael och Elda för vår fina gemenskap med kursen i pediatriska infektioner, och alla roliga kurs-utvärderingar hos Olle, till fantastiska måltider! Mina kollegor i "Opportunisterna" för våra väldigt trevliga möten (= terminens höjdpunkt) sedan minst 10 år tillbaka. Jag har lärt mig massor av er alla! Mina vänner, det går ofta lång tid mellan varven, men så glad att ni finns. Mina kära bröder Torbjörn, Gunnar och Janne, och mina svägerskor Christina, Sara och Johanna. För att ni är en så bra familj. Min kära mamma, för all kärlek och värme, och för din stora nyfikenhet och intresse för andra människor. Det är alltid roligt att vara med dig. Pappa, för din positiva livssyn, kärlek, och det kloka stöd du alltid gav. Jag saknar dig. Sist, men allra mest, min älskade familj, Patrik, Maj, David, Felix och Albin. För allt roligt, och för att ni är precis dom ni är.

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Section: Human Adenovirus (Hadv)mentioning

confidence: 72%

Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients

Swartling

Nordén

Samuelsson

et al. 2020

Bone Marrow Transplant

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“…The different types were initially defined by serum neutralisation methods as serotype, but are now identified based on molecular methods and named as genotypes. New genotypes are still identified [8,[11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Human adenovirus in nasopharyngeal and blood samples from children with and without respiratory tract infections

Nilsen

Nordbø

Krokstad

et al. 2019

Journal of Clinical Virology

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A B S T R A C TBackground: Human adenovirus (HAdV) is a double-stranded DNA virus associated with respiratory tract infections (RTI) in children. Using polymerase chain reaction (PCR) tests, HAdV often is detected together with other virus species, even in healthy controls. Objectives: The aim of this study was to compare molecular detection of HAdV with culture, and to examine the associations of various methods to RTI. Study design: Nasopharyngeal aspirates (NPA) were collected from 4319 children admitted with RTI and from 361 controls. The NPAs were examined for 23 viral and bacterial pathogens, using inhouse real-time PCR-assays based on TaqMan probes, in addition to bacterial and viral culture. HAdV concentration was evaluated semiquantitatively from the Ct-value and quantitatively by use of ADENOVIRUS R-gene®. Results: HAdV-DNA was detected in 6.1% patient samples and in 10.5% controls (p < 0.001). Compared to controls, patients had an OR of 3.8 (95% CI 1.4-10.3) for mono-detection of HAdV DNA, and an OR of 5.1 (95% CI 2.0-13.4) for HAdV-positive samples grew adenovirus by culture. HAdV DNA loads from children with RTI consisted of two clusters: one cluster with high viral loads (Ct < 30 and > 106 copies/ml) and one cluster with low viral loads, whereas among the controls, nearly all had low viral loads (OR 7.8, 95% CI 2.2-27.1). In 61 available plasma samples, 16.4% were positive for HAdV DNA, all were from patients. Conclusion: The detection of HAdV DNA per se by qualitative PCR is not useful as a diagnostic test. Detection of HAdV by use of viral culture and a high viral HAdV DNA load are the two methods most strongly associated with RTI in children.

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“…In our relatively small study, we were able to find new adenovirus genotypes and local variants of known genotypes, which highlights that the region is an un-tapped reservoir of novel adenoviruses that may be playing a significant and mutualistic role in local diarrhoeal outbreaks. The genotypes identified in this study are typical of adenoviruses identified elsewhere in patients with acute gastroenteritis, but quite different to those seen in adenoviraemic immune-compromised children in the UK [ 28 ]. Genotypes A61 and F40 were first described in patients with gastroenteritis [ 30, 43, 44 ].…”

Section: Discussionmentioning

confidence: 71%

“…Previous work [ 28 ] suggests that mixed infection with two or more adenovirus genotypes may mimic a recombinant when consensus genome sequences are compared phylogenetically. These ‘consensus chimeras’ can be detected using minority variant analysis [ 28 ]. We detected 12 minority variants in sequence data from patient SC_10 at frequencies of 5 to 50 %, with 7 present at frequencies ≤20 %.…”

Section: Resultsmentioning

confidence: 99%

“…S4 shows the distribution of pairwise differences between species A consensus sequences from the same patient (data from [ 28 ]) and differences between pairs of sequences from the same genotype. The identical sequences found in SC_4 and SC_5 may indicate infection from a common source [ 28 ]. Coverage plots for each sample are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

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Identification of novel adenovirus genotype 90 in children from Bangladesh

et al. 2018

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Novel adenovirus genotypes are associated with outbreaks of disease, such as acute gastroenteritis, renal disease, upper respiratory tract infection and keratoconjunctivitis. Here, we identify novel and variant adenovirus genotypes in children coinfected with enterotoxigenic Escherichia coli, in Bangladesh. Metagenomic sequencing of stool was performed and whole adenovirus genomes were extracted. A novel species D virus, designated genotype 90 (P33H27F67) was identified, and the partial genome of a putative recombinant species B virus was recovered. Furthermore, the enteric types HAdV-A61 and HAdV-A40 were found in stool specimens. Knowledge of the diversity of adenovirus genomes circulating worldwide, especially in low-income countries where the burden of disease is high, will be required to ensure that future vaccination strategies cover the diversity of adenovirus strains associated with disease.

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Use of Whole-Genome Sequencing of Adenovirus in Immunocompromised Pediatric Patients to Identify Nosocomial Transmission and Mixed-Genotype Infection

Cited by 43 publications

References 46 publications

Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients

Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients

Human adenovirus in nasopharyngeal and blood samples from children with and without respiratory tract infections

Identification of novel adenovirus genotype 90 in children from Bangladesh

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