scholarly journals Deciphering an Adenovirus F41 Outbreak in Pediatric Hematopoietic Stem Cell Transplant Recipients by Whole-Genome Sequencing

2021 ◽  
Vol 59 (5) ◽  
Author(s):  
Caroline Lefeuvre ◽  
Maud Salmona ◽  
Linda Feghoul ◽  
Noémie Ranger ◽  
Séverine Mercier-Delarue ◽  
...  

ABSTRACT Human adenovirus (HAdV) represents a major cause of mortality and morbidity in pediatric recipients of allogeneic hematopoietic stem cell transplants (HSCT). HAdV species F type 41 (HAdV-F41) infections in HSCT patients are scarce, whereas HAdV-F41 circulates commonly in healthy individuals. Between March and July 2018, HAdV-F41 infections were identified in four children (A, B, C, and E) who received allogeneic HSCT and one child before HSCT (D) at Robert Debré Hospital, Paris, France. We report here the clinical course of HAdV-F41 infection and the phylogenetic investigation to identify interpatient transmission. HAdV DNA was quantified in stool and plasma samples by real-time PCR. HAdV type was determined by sequencing of the fiber and hexon genes. Phylogenetic investigation was done with whole-genome sequences obtained by next-generation sequencing. HAdV loads in stool samples ranged from 6.60 to 10.10 log10 copies/ml. HAdV-F41 detection in plasma was observed in four patients, but no disseminated disease was reported. Two patients died, but neither death was attributed to HAdV. While sequencing limited to the fiber gene suggested a cluster with four patients, phylogenetic analysis with whole-genome sequencing (WGS) and HVR7 revealed a cluster that included three patients (C, D, and E), suggesting an interpatient transmission in that cluster and two other independent infections. HAdV-F41 levels in stool specimens of pediatric HSCT patients are high and represent a risk of interpatient transmission. WGS helped to identify related cases. Prompt detection of HAdV in stool and control measures are warranted to limit any risk of nosocomial transmission.

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1523
Author(s):  
Alessia G. Servidio ◽  
Roberto Simeone ◽  
Davide Zanon ◽  
Egidio Barbi ◽  
Natalia Maximova

Infectious complications are the most common and significant cause of mortality and morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Antibacterial prophylaxis in pediatric cancer patients is a controversial issue. Our study compared the outcomes of levofloxacin versus ciprofloxacin prophylaxis in allogeneic HSCT pediatric recipients treated for hematological malignancies. A total of 120 patients received levofloxacin prophylaxis, and 60 patients received ciprofloxacin prophylaxis. Baseline characteristics such as age, gender, primary diagnosis, type of conditioning, donor type, stem cell source, and supportive care of the patients were similar, and duration of antibiotics prophylaxis was similar. Both prophylaxis regimens demonstrated the same efficacy on the risk of febrile neutropenia and severe complications such as sepsis, the same rate of overall mortality, hospital readmission, and length of hospital stay. Levofloxacin prophylaxis was associated with significantly lower cumulative antibiotic exposure. The median of Gram-positive infection-related antibiotic days was 10 days in the levofloxacin group versus 25 days in the ciprofloxacin group (p < 0.0001). The median of Gram-negative infection-related antibiotics was 10 days in the levofloxacin group compared with 20 days in the ciprofloxacin group (p < 0.0001). The number of days with body temperature ≥38 °C was significantly less in the levofloxacin group (p < 0.001).


2020 ◽  
Author(s):  
Bilal Olcay Peker ◽  
Gülen Tüysüz Kintrup ◽  
İmran Sağlık ◽  
Rabia Can Sarınoğlu ◽  
Elif Güler ◽  
...  

2017 ◽  
Vol 55 (10) ◽  
pp. 2956-2963 ◽  
Author(s):  
Yijun Zhu ◽  
Teresa R. Zembower ◽  
Kristen E. Metzger ◽  
Zhengdeng Lei ◽  
Stefan J. Green ◽  
...  

ABSTRACTA viral whole-genome sequencing (WGS) strategy, based on PCR amplification followed by next-generation sequencing, was used to investigate a nosocomial respiratory syncytial virus-B (RSV-B) outbreak in a hematology-oncology and stem cell transplant unit. RSV-B genomes from 16 patients and health care workers (HCWs) suspected to be involved in the outbreak were compared to RSV-B genomes that were acquired from outpatients during the same time period but epidemiologically unrelated to the outbreak. Phylogenetic analysis of the whole genome identified a cluster of 11 patients and HCWs who had an identical RSV-B strain which was clearly distinct from strains recovered from individuals unrelated to the outbreak. Sequence variation of the glycoprotein (G) gene alone was insufficient to distinguish the outbreak strains from the outbreak-unrelated strains, thereby demonstrating that WGS is valuable for local outbreak investigation.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18611-e18611
Author(s):  
Sibgha Gull Chaudhary ◽  
Muhammad Usman Zafar ◽  
Maha Awaiz Hassan ◽  
Moazzam Shahzad ◽  
Ali Hussain ◽  
...  

e18611 Background: Coronavirus Disease 2019 (COVID-19) was declared a pandemic on March 11, 2020. COVID-19 has caused over 100 million infections and over 2 million deaths globally. Patients who have received a hematogenic stem cell transplant or cellular therapy (HCT) have a high risk of mortality and morbidity with COVID-19 due to severe immune dysregulation. We conducted a systematic review and meta-analysis aimed to evaluate the outcomes of COVID-19 in HCT patients. Methods: A literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA) guidelines was performed on 3 databases (PubMed, Cochrane, and Clinical trials.gov) from the date of inception to Jan 2021. MeSH terms included ‘hematological malignancies’, ‘hematopoietic stem cell transplantation’, ‘SARS-CoV-2’, and ‘COVID 19’. We screened 99 articles and 6 studies (4 retrospective studies, 2 prospective) were included after excluding review, duplicate, and non-relevant articles. Quality evaluation was done using the NIH quality assessment tool. The Inter-study heterogeneity among the studies was assessed using the Q statistic proposed by Cochrane and the I2 index introduced by Higgins and Thompson. Pooled analysis was done using the ‘metaXL’, and the random effects model was used to estimate the pooled prevalence with 95% CI. Results: Of 1619 patients in 6studies, 646 HCT patients were analyzed (Table ). The median age of patients was 63 years and 59% were males. Median days since HCT for autologous (auto) HCT and allogeneic (allo) HCT patients were 690 and 450 days respectively. The average follow-up duration after COVID-19 was 24 days. COVID-19 mortality in HCT patients was 20% (95%CI 0.17 to 0.23, I2=0). Roedl et al (n=6) reported a mortality of 83% and was excluded from the pooled analysis. The mortality rate was 19% (95% CI 0.15 to 0.24, I2=0%) in auto HCT patients and 21% (95% CI 0.17 to 0.25, I2=0%) in allo HCT patients. Conclusions: The HCT patients are at significant risk of increased mortality and morbidity due to COVID-19. There is a need to prioritize HCT patients for COVID-19 vaccination, close surveillance, and aggressive management.[Table: see text]


2020 ◽  
Author(s):  
Chloe E. Myers ◽  
Charlotte J. Houldcroft ◽  
Sunando Roy ◽  
Ben K. Margetts ◽  
Timothy Best ◽  
...  

AbstractBackgroundHuman mastadenoviruses (HAdV) are associated with significant morbidity and mortality amongst the immunocompromised population. A recent surge in HAdV cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate.MethodsTo gain a complete transmission picture, we compared outbreak and non-outbreak sequences (54 sequences from 37 patients) with GenBank sequences and our own database of previously sequenced HAdVs (132 sequences from 37 patients). An improved bait set for WGS was used. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships paired with epidemiological data from routine Infection, Prevention and Control (IPC) activity.ResultsNine monophyletic clusters were identified, seven of which were corroborated by epidemiological evidence and by comparison of single nucleotide polymorphisms. Two incomplete patient clusters were identified by IPC over the same time period. Of the five patients who died, one had a mixed HAdV infection and two were the source of transmission events.ConclusionsThe clinical consequences of unmitigated HAdV transmission events are high. Focusing on two high risk wards using WGS we identified six transmission events, over prolonged periods, that would have gone unnoticed using traditional polymerase chain reaction and epidemiology. Mixed infection is frequent (10% of patients), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harbouring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into a clinical algorithm to prevent transmission and influence IPC policy in real-time.SummaryWhole genome sequencing of adenovirus, direct from clinical samples, can be used to identify cryptic health care associated transmission events, and to resolve transmission suspected by traditional epidemiology. It can also identify mixed genotype infections in immunocompromised patient populations.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 340
Author(s):  
Baptiste Demey ◽  
Clément Brault ◽  
Julien Maizel ◽  
Catherine Francois

Human adenovirus infection is rare in adult population, except for in immunocompromised individuals. Recipients of allogenic haploidentical hematopoietic stem cell transplantation are reported at high risk for human adenovirus, which is often lethal when it evolves into the disseminated form. Despite existent guidelines, prevention, early diagnosis, and therapeutics remain challenging. Here, we report the case of a fatal evolution of human adenovirus respiratory infection and discuss the actual recommendations to prevent recurrence of this major issue.


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