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Yao MM, Gao TJ, Zhao M, Fu YH, Liu J, Wang TJ, Yang Y. Risk factors for bronchiolitis obliterans complicating adenovirus pneumonia in children: a meta-analysis. Front Pediatr 2024; 12:1361850. [PMID: 39149537 PMCID: PMC11324480 DOI: 10.3389/fped.2024.1361850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/29/2024] [Indexed: 08/17/2024] Open
Abstract
Objective To preliminarily explore the risk factors for post-infectious bronchiolitis obliterans (PIBO) complicating adenovirus pneumonia (ADVP) in children through a meta-analysis. Methods A systematic search was conducted on three English-language databases (PubMed, Web of Science and The National Library of Medicine) and two Chinese-language databases (China National Knowledge Infrastructure and the Wanfang Database) between database inception and 1 January 2023. Data analysis was conducted using Stata 15.1 software. Results A total of 10 articles, reporting 14 risk factors, were included in the analysis, with 8 risk factors taken into consideration. Through the meta-analysis, 5 risk factors were identified for PIBO complicating ADVP in paediatric patients: hypoxaemia [odds ratio (OR) = 9.37, 95% CI: 4.22, 20.77, p < 0.001], persistent wheezing (OR = 4.65, 95% CI: 2.20, 9.82, p < 0.001), mechanical ventilation (OR = 3.87, 95% CI: 2.37, 6.33, p < 0.001), length of hospital stay (LoHS) (OR = 1.25, 95% CI: 1.09, 1.43, p < 0.001) and fever duration (OR = 1.08, 95% CI: 1.02, 1.14, p = 0.009). Conclusion Existing evidence suggests that hypoxaemia, persistent wheezing, mechanical ventilation, LoHS and fever duration are risk factors for PIBO complicating ADVP in children. These findings underscore the need for enhanced assessment and management in clinical practice. This study may provide such a clinical prediction model from the identified 5 risk factors for PIBO and offer valuable insights for preventing bronchiolitis obliterans in children with ADVP.
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Affiliation(s)
- Mei-Mei Yao
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
| | - Tian-Ji Gao
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
| | - Min Zhao
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
| | - Yan-Hua Fu
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
| | - Jing Liu
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
| | - Tian-Jiao Wang
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
| | - Ying Yang
- Department of Rheumatology and Immunology, Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University, Baoding, China
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Liu X, Ding Y, Hu R, Tang H. Evaluation of Risk Factors for Children with Severe Adenovirus Respiratory Infection: Retrospective Study. IRANIAN JOURNAL OF PEDIATRICS 2024; 34. [DOI: 10.5812/ijp-134296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2022] [Revised: 12/12/2023] [Accepted: 01/17/2024] [Indexed: 01/04/2025]
Abstract
Background: Human adenovirus (HAdV) commonly affects children hospitalized with any form of respiratory infection (RI). Severe HAdV infection leads to one of the most serious types of infantile RI, with rapidly progressive illness and a poor prognosis. Objectives: This study investigated the relationship between aspartate aminotransferase (AST) levels and the severity of HAdV RI in children. Methods: We collected clinical data from 665 cases of HAdV RI in children hospitalized at the pediatric ward of Changde First People's Hospital between January and December 2019. We analyzed the relationship between AST levels and disease severity. Results: Of the 665 HAdV-positive cases, 89.8% were < 6 years of age. Among them, upper RI was diagnosed in 18.8% of cases, bronchiolitis in 4.8%, and mild pneumonia in 48.1%. Severe pneumonia was observed in 28.2% of cases. The 665 patients in the cohort were divided into a mild group (n = 477 cases, 71.73%) and a severe group (n = 188 cases, 28.27%). Univariate analysis showed that children with severe HAdV RI had a lower age of onset and lower hemoglobin and serum albumin levels while having higher platelet counts, lactic acid dehydrogenase, creatine kinase, creatine kinase isoenzyme, alanine aminotransferase, and AST levels compared to those with mild infections (P < 0.05). Multivariate analysis revealed that these factors were related to disease severity (P < 0.05). The ROC curve analysis indicated that the area under the AST curve was 0.782. When the intercept value was 52.5 U/L, the sensitivity was 60.6%, and the specificity was 83.4%. Conclusions: Serum AST levels can serve as a predictor of adenoviral RI severity in children.
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Liu A, Tian Z, Yin C, Zou J, Wu S, Luo Y, Chen X, Dai Y, Yang S, Li Y, Li T, Guo P, Hu X. The Analysis of Oral and Fecal Virome Detects Multiple Novel Emerging Viruses in Snakes. Transbound Emerg Dis 2023; 2023:4214812. [PMID: 40303824 PMCID: PMC12016970 DOI: 10.1155/2023/4214812] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 04/29/2023] [Accepted: 05/05/2023] [Indexed: 05/02/2025]
Abstract
Wild animals are considered reservoirs for emerging and reemerging viruses, such as the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies have reported that bats and ticks harbored variable important pathogenic viruses, some of which could cause potential diseases in humans and livestock, while viruses carried by reptiles were rarely reported. Our study first conducted snakes' virome analysis to establish effective surveillance of potential transboundary emerging diseases. Consequently, Adenoviridae, Circoviridae, Retroviridae, and Parvoviridae were identified in oral samples from Protobothrops mucrosquamatus, Elaphe dione, and Gloydius angusticeps based on sequence similarity to existing viruses. Picornaviridae and Adenoviridae were also identified in fecal samples of Protobothrops mucrosquamatus. Notably, the iflavirus and foamy virus were first reported in Protobothrops mucrosquamatus, enriching the transboundary viral diversity in snakes. Furthermore, phylogenetic analysis revealed that both the novel-identified viruses showed low genetic similarity with previously reported viruses. This study provided a basis for our understanding of microbiome diversity and the surveillance and prevention of emerging and unknown viruses in snakes.
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Affiliation(s)
- Aijing Liu
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
- Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China
| | - Zhige Tian
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Chuanming Yin
- Clinical Medicine Department, Harbin Medical University, Orthopaedics Department, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jie Zou
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Shan Wu
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Yi Luo
- Liuzhou Integrated Chinese and Western Medicine Snake Injury Treatment Center, Liuzhou Traditional Chinese Medicine Hospital, Liuzhou, China
| | - Xin Chen
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Yi Dai
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Siyi Yang
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Yanxi Li
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Tongyu Li
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Peng Guo
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
| | - Xiaoliang Hu
- Faculty of Agriculture, Forestry, and Food Engineering, Yibin University, Yibin Animal and Plant Inspection and Quarantine Engineering Technology Research Center, Yibin Key Laboratory of Zoological Diversity and Ecological Conservation, Yibin, China
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Inamoto Y, Takeda W, Hirakawa T, Sakaguchi H, Nakano N, Uchida N, Doki N, Ikegame K, Katayama Y, Sawa M, Kuriyama T, Hiramoto N, Ota S, Ozawa Y, Kataoka K, Kanda Y, Hino M, Kimura T, Atsuta Y, Fukuda T, Nagafuji K. Adenovirus disease after hematopoietic cell transplantation: A Japanese transplant registry analysis. Am J Hematol 2022; 97:1568-1579. [PMID: 36087061 DOI: 10.1002/ajh.26723] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/23/2022] [Accepted: 09/02/2022] [Indexed: 01/31/2023]
Abstract
We analyzed a Japanese registry database to elucidate the incidence, risk factors, and outcomes of adenovirus (AdV) disease after autologous and allogeneic hematopoietic cell transplantation (HCT) in contemporary real-world patients. We evaluated the cumulative incidence of AdV disease, as well as risk factors, survival, and treatment details, among 25 233 patients who underwent autologous HCT and 48 380 patients who underwent allogeneic HCT between 2005 and 2019. The 1-year cumulative incidences of AdV disease after autologous and allogeneic HCT were 0.18% and 1.52%, respectively, in children, and 0.49% and 2.99%, respectively, in adults. Among patients with AdV disease, renourinary infection was the most common manifestation, and viremia or disseminated disease occurred in 6% of those after autologous HCT and 19% of those after allogeneic HCT. In multivariate analysis, age ≥50 years and lymphoma were associated with AdV disease after autologous HCT, while patients age ≥50 years, male patients, lymphoma, HCT-specific comorbidity index ≥3, human leukocyte antigen-mismatched or haploidentical donors, cord blood, in vivo T-cell depletion, HCT from 2005 to 2009, acute graft-versus-host disease (GVHD), and chronic GVHD were associated with AdV disease after allogeneic HCT. The 1-year probabilities of survival after disease diagnosis were 65% in autologous HCT and 44% in allogeneic HCT. Regardless of the AdV disease burden, there was an increased risk of mortality after both autologous and allogeneic HCT. The most commonly used antiviral agents were cidofovir and vidarabine. The probabilities of improvement and survival with currently available agents were suboptimal. AdV disease after HCT remains a challenge. Better antiviral modalities are necessary.
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Affiliation(s)
- Yoshihiro Inamoto
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Wataru Takeda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | | | - Hirotoshi Sakaguchi
- Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Nobuaki Nakano
- Department of Hematology, Imamura General Hospital, Kagoshima, Japan
| | - Naoyuki Uchida
- Department of Hematology, Toranomon Hospital, Tokyo, Japan
| | - Noriko Doki
- Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Kazuhiro Ikegame
- Department of Hematology, Hyogo Medical University Hospital, Nishinomiya, Japan
| | - Yuta Katayama
- Department of Hematology, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Takuro Kuriyama
- Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
| | - Nobuhiro Hiramoto
- Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Shuichi Ota
- Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan
| | - Yukiyasu Ozawa
- Department of Hematology, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital, Nagoya, Japan
| | - Keisuke Kataoka
- Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.,Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Yoshinobu Kanda
- Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
| | - Moeko Hino
- Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takafumi Kimura
- Preparation Department, Japanese Red Cross Kinki Block Blood Center, Osaka, Japan
| | - Yoshiko Atsuta
- Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan.,Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Takahiro Fukuda
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
| | - Koji Nagafuji
- Department of Hematology and Oncology, Kurume University School of Medicine, Kurume, Japan
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Götting J, Baier C, Panagiota V, Maecker-Kolhoff B, Dhingra A, Heim A. High genetic stability of co-circulating human adenovirus type 31 lineages over 59 years. Virus Evol 2022; 8:veac067. [PMID: 36533152 PMCID: PMC9748976 DOI: 10.1093/ve/veac067] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/29/2022] [Accepted: 08/03/2022] [Indexed: 06/22/2024] Open
Abstract
Type 31 of human adenovirus species A (HAdV-A31) is a significant pathogen primarily associated with diarrhoea in children but also with life-threatening disseminated disease in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Nosocomial outbreaks of HAdV-A31 have been frequently described. However, the evolution of HAdV-A31 has not been studied in detail. The evolution of other HAdV types is driven either by intertypic recombination, where different types exchange genome regions, or by immune escape selection of neutralisation determinants. Complete genomic HAdV-A31 sequences from sixty diagnostic specimens of the past 18 years (2003-21) were generated, including fourteen specimens of a presumed outbreak on two HSCT wards. Additionally, twenty-three complete genomes from GenBank were added to our phylogenetic analysis as well as in silico generated and previously published restriction fragment polymorphism (RFLP) data. Phylogenetic analysis of eighty-three genomes indicated that HAdV-A31 evolved slowly with six lineages co-circulating. The two major lineages were lineage 1, which included the prototype from 1962 and nine recent isolates, and lineage 2, which split into four sublineages and included most isolates from 2003 to 2021. The average nucleotide identity within lineages was high (99.8 per cent) and identity between lineages was 98.7 and 99.2 per cent. RFLP data allowed the construction of a lower-resolution phylogeny with two additional putative lineages. Surprisingly, regions of higher diversity separating lineages were found in gene regions coding for non-structural and minor capsid proteins. Intertypic recombinations were not observed, but the phylogeny of lineage 3 was compatible with an interlineage recombination event in the fibre gene. Applying the phylogenetic analysis to the presumed nosocomial outbreak excluded two suspected transmission events and separated it into two different, simultaneous outbreaks caused by different sublineages of lineage 2. However, due to the high nucleotide identity within HAdV-A31 lineages, the proof of infection chains remains debatable. This in-depth study on the molecular phylogeny of HAdV-A31 highlights the high genetic stability of co-circulating HAdV-A31 lineages over almost six decades. It also supports the epidemiological hypothesis that HAdV-A31 circulates as an etiological agent of a childhood disease infecting immunologically naive patients without strong positive selection of immune escape variants and recombinants.
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Affiliation(s)
- Jasper Götting
- Institute of Virology, Hannover Medical
School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
| | - Claas Baier
- Institute for Medical Microbiology and Hospital
Epidemiology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover
30625, Germany
| | - Victoria Panagiota
- Department of Hematology, Hemostaseology,
Oncology and Stem Cell Transplantation, Hannover Medical School,
Carl-Neuberg-Str. 1, Hannover 30625, Germany
| | - Britta Maecker-Kolhoff
- Department of Paediatric Haematology and
Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625,
Germany
| | - Akshay Dhingra
- Institute of Virology, Hannover Medical
School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
| | - Albert Heim
- Institute of Virology, Hannover Medical
School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
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Zhang J, Cao J, Ye Q. Nonpharmaceutical interventions against the COVID-19 pandemic significantly decreased the spread of enterovirus in children. J Med Virol 2022; 94:3581-3588. [PMID: 35474224 PMCID: PMC9088497 DOI: 10.1002/jmv.27806] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/17/2022] [Accepted: 04/25/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Precise prevention and control measures have been adopted to impede the transmission of COVID-19 in China. This study was performed to investigate the effect of protective measures on gastrointestinal infection in children during the COVID-19 pandemic. METHODS The data on the rotavirus and adenovirus antigen tests were collected in outpatient children due to gastroenteritis from January 1, 2019, to December 31, 2020, at the Children's Hospital of Zhejiang University School of Medicine. According to age and month distribution, the positive number and rate of rotavirus and adenovirus in 2020 were compared with 2019. RESULTS A 3.8-fold and 4-fold reduction in the number of rotavirus- and adenovirus-positive patients in 2020 were found, respectively. The overall positive rate of rotavirus and adenovirus infection was drastically decreased in 2020 (rotavirus 2020: 18.18% vs 2019: 9.75%, P < 0.001; adenovirus 2020: 3.13% vs 2019: 1.58%, P < 0.001). The proportions of rotavirus and adenovirus in all age groups in 2020 decreased compared with those in 2019. The highest frequency of rotavirus infection occurred among children aged 1-3 years both in 2019 and 2020 (2019: 27.95% vs 2020: 17.19%, P < 0.001), while adenovirus infection was detected in children aged 3-5 years, which had the highest percent positivity (2019: 8.19% vs 2020: 4.46%; P < 0.001). An obvious peak prevalence of rotavirus incidence was found during December-April, and the percent positivity of rotavirus significantly decreased in 2020 (December 2019: 24.26% vs 2020: 8.44%, P < 0.001; January 2019: 40.67% vs 2020: 38.18%, P < 0.05; February 2019: 40.73% vs 2020: 15.04%, P < 0.001; March 2019: 31.47% vs 2020: 7.88%, P < 0.001; April 2019: 15.52% vs 2020: 4.78%, P < 0.001). The positive rate of adenovirus distributed throughout 2019 was 1.91%-4.86%, while the percent positivity during 2020 in the same period was much lower (0.00%-3.58%). CONCLUSIONS Our results confirmed that the preventive and control measures adopted during the COVID-19 pandemic and the collateral benefit of these interventions have significantly decreased the transmission of rotavirus or adenovirus. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Junfeng Zhang
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - JiaJia Cao
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Qing Ye
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
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Acute Neurological Involvement after Donor Lymphocyte Infusion for Post-Transplant Viral Infection: The Same Pattern of Novel Cancer Immunotherapy-Related CNS Toxicity? Int J Mol Sci 2022; 23:ijms23073553. [PMID: 35408912 PMCID: PMC8998460 DOI: 10.3390/ijms23073553] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 02/01/2023] Open
Abstract
Early post-transplant is the critical phase for the success of hematopoietic stem cell transplantation (HSCT). New viral infections and the reactivations associated with complete ablation of the recipient's T-cell immunity and inefficient reconstitution of the donor-derived system represent the main risks of HSCT. To date, the pharmacological treatments for post-HSCT viral infection-related complications have many limitations. Adoptive cell therapy (ACT) represents a new pharmacological strategy, allowing us to reconstitute the immune response to infectious agents in the post-HSC period. To demonstrate the potential advantage of this novel immunotherapy strategy, we report three cases of pediatric patients and the respective central nervous system complications after donor lymphocyte infusion.
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Mangare C, Tischer-Zimmermann S, Bonifacius A, Riese SB, Dragon AC, Blasczyk R, Maecker-Kolhoff B, Eiz-Vesper B. Variances in Antiviral Memory T-Cell Repertoire of CD45RA- and CD62L-Depleted Lymphocyte Products Reflect the Need of Individual T-Cell Selection Strategies to Reduce the Risk of GvHD while Preserving Antiviral Immunity in Adoptive T-Cell Therapy. Transfus Med Hemother 2022; 49:30-43. [PMID: 35221866 PMCID: PMC8832244 DOI: 10.1159/000516284] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 04/01/2021] [Indexed: 04/03/2025] Open
Abstract
INTRODUCTION Viral infections and reactivations still remain a cause of morbidity and mortality after hematopoietic stem cell transplantation due to immunodeficiency and immunosuppression. Transfer of unmanipulated donor-derived lymphocytes (DLI) represents a promising strategy for improving cellular immunity but carries the risk of graft versus host disease (GvHD). Depleting alloreactive naïve T cells (TN) from DLIs was implemented to reduce the risk of GvHD induction while preserving antiviral memory T-cell activity. Here, we compared two TN depletion strategies via CD45RA and CD62L expression and investigated the presence of antiviral memory T cells against human adenovirus (AdV) and Epstein-Barr virus (EBV) in the depleted fractions in relation to their functional and immunophenotypic characteristics. METHODS T-cell responses against ppEBV_EBNA1, ppEBV_Consensus and ppAdV_Hexon within TN-depleted (CD45RA-/CD62L-) and TN-enriched (CD45RA+/CD62L+) fractions were quantified by interferon-gamma (IFN-γ) ELISpot assay after short- and long-term in vitro stimulation. T-cell frequencies and immunophenotypic composition were assessed in all fractions by flow cytometry. Moreover, alloimmune T-cell responses were evaluated by mixed lymphocyte reaction. RESULTS According to differences in the phenotype composition, antigen-specific T-cell responses in CD45RA- fraction were up to 2 times higher than those in the CD62L- fraction, with the highest increase (up to 4-fold) observed after 7 days for ppEBV_EBNA1-specific T cells. The CD4+ effector memory T cells (TEM) were mainly responsible for EBV_EBNA1- and AdV_Hexon-specific T-cell responses, whereas the main functionally active T cells against ppEBV_Consensus were CD8+ central memory T cells (TCM) and TEM. Moreover, comparison of both depletion strategies indicated that alloreactivity in CD45RA- was lower than that in CD62L- fraction. CONCLUSION Taken together, our results indicate that CD45RA depletion is a more suitable strategy for generating TN-depleted products consisting of memory T cells against ppEBV_EBNA1 and ppAdV_Hexon than CD62L in terms of depletion effectiveness, T-cell functionality and alloreactivity. To maximally exploit the beneficial effects mediated by antiviral memory T cells in TN-depleted products, depletion methods should be selected individually according to phenotype composition and CD4/CD8 antigen restriction. TN-depleted DLIs may improve the clinical outcome in terms of infections, GvHD, and disease relapse if selection of pathogen-specific donor T cells is not available.
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Affiliation(s)
- Caroline Mangare
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Sabine Tischer-Zimmermann
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Agnes Bonifacius
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Sebastian B. Riese
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Anna Christina Dragon
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Rainer Blasczyk
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Britta Maecker-Kolhoff
- Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
| | - Britta Eiz-Vesper
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
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9
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Atay D, Akcay A, Akinci B, Yenigurbuz FD, Ovali E, Ozturk G. Co-transplantation of mesenchymal stromal cell and haploidentical hematopoietic stem cell with TCR αβ depletion in children with primary immunodeficiency syndromes. Pediatr Transplant 2021; 25:e14120. [PMID: 34409718 DOI: 10.1111/petr.14120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 08/08/2021] [Accepted: 08/09/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Haploidentical HSCT is a good option for children with PIDs lacking an HLA-matched donor. Co-transplantation of MSCs during haploidentical HSCT in patients with PIDs may enhance engraftment, decrease the risk of GVHD, and ensure stable donor chimerism. METHODS Twenty-seven pediatric patients (median age, 1.4 years; range, .3-10.9) with PIDs undergoing thirty haploidentical HSCT with TCR αβ depletion and co-transplantation of MSCs were enrolled to study. Most patients (73.3%) received myeloablative conditioning consisting of treosulfan or busulfan, fludarabine, and thiotepa. The median duration of follow-up was 14.3 months (range, 1-69 months). RESULTS Acute GVHD occurred in 7 patients (grade I-II n = 5, grade III-IV n = 2). Chronic GVHD was observed in only one patient. Twenty-one patients (70.2%) had 100% donor chimerism in all cell lines including T-cell and B-cell lineages. Primary graft failure was observed in 7 patients (25.9%). The cumulative incidences of TRM were 20% at day 100, and 26.7% at one year and five years. Probabilities of OS were 80% at day 100, and 71.9% at 1 year and 5 years. Infants transplanted younger than 6 months of age had the highest 5-year survival rate (85.7%). CONCLUSION We conclude that use of TCR αβ depleted haploidentical transplantation with MSCs may ensure a rapid engraftment rate, low incidence of significant acute and chronic GVHD, and acceptable post-transplantation morbidity, especially in patients diagnosed with SCID and may be considered in children with PIDs. In younger patients (≤6 months), survival is comparable between HLA-matched graft and CD3+ TCRαβ depleted HLA-mismatched graft recipients.
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Affiliation(s)
- Didem Atay
- Department of Pediatric Hematology/Oncology & Bone Marrow Transplantation Unit, Acıbadem University, Istanbul, Turkey
| | - Arzu Akcay
- Department of Pediatric Hematology/Oncology & Bone Marrow Transplantation Unit, Acıbadem University, Istanbul, Turkey
| | - Burcu Akinci
- Department of Pediatric Hematology/Oncology & Bone Marrow Transplantation Unit, Acıbadem University, Istanbul, Turkey
| | - Fatma Demir Yenigurbuz
- Department of Pediatric Hematology/Oncology & Bone Marrow Transplantation Unit, Acıbadem University, Istanbul, Turkey
| | - Ercument Ovali
- Acibadem Labcell Cellular Therapy Laboratory, Istanbul, Turkey
| | - Gulyuz Ozturk
- Department of Pediatric Hematology/Oncology & Bone Marrow Transplantation Unit, Acıbadem University, Istanbul, Turkey
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10
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Characterization of Tonsil Microbiota and Their Effect on Adenovirus Reactivation in Tonsillectomy Samples. Microbiol Spectr 2021; 9:e0124621. [PMID: 34668748 PMCID: PMC8528100 DOI: 10.1128/spectrum.01246-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The adenoviral DNA is prevalent in adenotonsillectomy specimens from pediatric patients, though the virus seems to be in latent state. The tonsils are at the forefront of airway entry point and are the first line of defense against airway viral and bacterial infections. We hypothesized that tonsil microbiota plays a role in human adenovirus (HAdV) latency and reactivation. In this study, we surveyed the presence of HAdV in tonsillectomy samples from 81 patients and found that HAdV DNA was in 85.2% of the tonsil samples. We then determined the microbiota of the samples. Taxonomic profiling showed that Proteobacteria, Firmicutes, Fusobacteriota, and Bacteroidota accounted for approximately 70% of the total phyla in tonsil samples. A correlation analysis showed that the HAdV-positive samples had significantly higher abundance of Neisseria and Bifidobacterium and lower abundance of Streptococcus, Ochrobactrum, and Lactobacillus than that of the HAdV-negative samples. Culture-based isolation followed by 16S rRNA sequencing identified Staphylococcus aureus, Streptococcus pneumoniae, Veillonella, Prevotella,Capnocytophaga sputigena, Pseudomonas aeruginosa, Neisseria, and Moraxella catarrhalis from the samples. Gas chromatography-mass spectrometry (GC-MS) profiling of short-chain fatty acids in bacterial cultures of minced tonsillectomy tissues or representative isolates showed the cultures contained various amounts of short-chain fatty acids (SCFAs). Treatment of isolated tonsil lymphocytes with bacterial lipopolysaccharide (LPS) or with SCFAs promoted HAdV reactivation. The compounds also promoted HAdV reactivation in a xenograft model with implanted tonsil fragments. This study shows a potential interplay between tonsil microbiota and HAdV reactivation that may lead to recurrent virus infection of respiratory tract disease. IMPORTANCE Human adenovirus infection is common among pediatric patients and can be life-threatening among organ transplant recipients. Adenovirus is transmitted by close contact, but it is believed that a majority of invasive events appear to arise from viral reactivation. The human tonsil is a reservoir for virus latency and has a high prevalence of latently infected adenovirus. Also, tonsils are located at the gateway of the respiratory tracts and are commonly exposed to bacterial pathogens. Here, we uncovered adenoviral DNA-positive and -negative samples that appeared to harbor distinct distribution patterns of microorganisms. SCFAs, primary metabolites of microbiota on tonsils, could induce the adenovirus reactivation in tonsil lymphocytes, resulting in adenovirus replication and production of infectious virions. The study suggests that viral-bacterial interaction plays a role in virus reactivation from latency and could be a contributing factor for recurrent viral infection in pediatric patients.
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11
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Liu L, Qian Y, Jia L, Dong H, Deng L, Huang H, Zhao L, Zhu R. Genetic diversity and molecular evolution of human adenovirus serotype 41 strains circulating in Beijing, China, during 2010-2019. INFECTION GENETICS AND EVOLUTION 2021; 95:105056. [PMID: 34481061 DOI: 10.1016/j.meegid.2021.105056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/01/2021] [Accepted: 08/29/2021] [Indexed: 11/20/2022]
Abstract
Human adenovirus serotype 41 (HAdV-F41) is an important pathogen that causes diarrhea in children. However, the data on its molecular genetic characteristics and evolutionary history are still neither comprehensive nor sufficient. Four capsid protein genes from 58 HAdV-F41-positive specimens taken from diarrheal children in Beijing during 2010-2019 were amplified and analyzed. Variant amino acids in the hexon gene (18 sites) and short fiber gene (4 sites) clustered these strains into two clades and four subclades. The deletion of 15 amino acids found in the gene seemed to have little effect on the genomic strain cluster same as to penton gene. The HAdV-F41 strains had high diversity, as assessed from the intraspecific recombination of hexon, short fiber and long fiber. The molecular evolutionary rate of HAdV-F41's concatenated genes was 4.07 × 10-5 substitutions/site/year, and it diverged from the most recent common ancestor in 1720. Apart from in the penton gene, positive selection codons were predicted in the other three genes, which may play a synergistic role in the evolution of HAdV-F41. These results provide new insights for understanding the characteristics of infectivity and developing vectors and vaccine vehicles for HAdV-F41.
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Affiliation(s)
- Liying Liu
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Yuan Qian
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Liping Jia
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Huijin Dong
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Li Deng
- Infectious Department, Children's Hospital of Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Hui Huang
- Infectious Department, Children's Hospital of Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Linqing Zhao
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China
| | - Runan Zhu
- Laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, 2 Yabao Road, Beijing 100020, China.
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12
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Avula K, Singh B, Kumar PV, Syed GH. Role of Lipid Transfer Proteins (LTPs) in the Viral Life Cycle. Front Microbiol 2021; 12:673509. [PMID: 34248884 PMCID: PMC8260984 DOI: 10.3389/fmicb.2021.673509] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 05/17/2021] [Indexed: 12/14/2022] Open
Abstract
Viruses are obligate parasites that depend on the host cell machinery for their replication and dissemination. Cellular lipids play a central role in multiple stages of the viral life cycle such as entry, replication, morphogenesis, and egress. Most viruses reorganize the host cell membranes for the establishment of viral replication complex. These specialized structures allow the segregation of replicating viral RNA from ribosomes and protect it from host nucleases. They also facilitate localized enrichment of cellular components required for viral replication and assembly. The specific composition of the lipid membrane governs its ability to form negative or positive curvature and possess a rigid or flexible form, which is crucial for membrane rearrangement and establishment of viral replication complexes. In this review, we highlight how different viruses manipulate host lipid transfer proteins and harness their functions to enrich different membrane compartments with specific lipids in order to facilitate multiple aspects of the viral life cycle.
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Affiliation(s)
- Kiran Avula
- Virus-Host Interaction Lab, Institute of Life Sciences, Bhubaneshwar, India.,Regional Centre for Biotechnology, Faridabad, India
| | - Bharati Singh
- Virus-Host Interaction Lab, Institute of Life Sciences, Bhubaneshwar, India.,School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneshwar, India
| | - Preethy V Kumar
- Virus-Host Interaction Lab, Institute of Life Sciences, Bhubaneshwar, India.,School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneshwar, India
| | - Gulam H Syed
- Virus-Host Interaction Lab, Institute of Life Sciences, Bhubaneshwar, India
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13
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Chandra P, Lo M, Mitra S, Banerjee A, Saha P, Okamoto K, Deb AK, Ghosh SK, Manna A, Dutta S, Chawla-Sarkar M. Genetic characterization and phylogenetic variations of human adenovirus-F strains circulating in eastern India during 2017-2020. J Med Virol 2021; 93:6180-6190. [PMID: 34138479 DOI: 10.1002/jmv.27136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 05/10/2021] [Accepted: 06/05/2021] [Indexed: 01/27/2023]
Abstract
Human adenovirus-F (HAdV-F) (genotype 40/41) is the second-most leading cause of pediatric gastroenteritis after rotavirus, worldwide, accounting for 2.8%-11.8% of infantile diarrheal cases. Earlier studies across eastern India revealed a shift in the predominance of genotypes from HAdV41 in 2007-09 to HAdV40 in 2013-14. Thus, the surveillance for HAdV-F genotypes in this geographical setting was undertaken over 2017-2020 to analyze the viral evolutionary dynamics. A total of 3882 stool samples collected from children (≤5 years) were screened for HAdV-F positivity by conventional PCR. The hypervariable regions of the hexon and the partial shaft region of long fiber genes were amplified, sequenced, and phylogenetically analyzed with respect to the prototype strains. A marginal decrease in enteric HAdV prevalence was observed (9.04%, n = 351/3882) compared to the previous report (11.8%) in this endemic setting. Children <2 years were found most vulnerable to enteric HAdV infection. Reduction in adenovirus-rotavirus co-infection was evident compared to the sole adenovirus infection. HAdV-F genotypes 40 and 41 were found to co-circulate, but HAdV41 was predominant. HAdV40 strains were genetically conserved, whereas HAdV41 strains accumulated new mutations. On the basis of a different set of mutations in their genome, HAdV41 strains segregated into 2 genome type clusters (GTCs). Circulating HAdV41 strains clustered with GTC1 of the fiber gene, for the first time during this study period. This study will provide much-needed baseline data on the emergence and circulation of HAdV40/41 strains for future vaccine development.
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Affiliation(s)
- Pritam Chandra
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Mahadeb Lo
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Suvrotoa Mitra
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Anindita Banerjee
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Priyanka Saha
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Keinosuke Okamoto
- Collaborative Research Centre of Okayama University for Infectious Disease at Indian ICMR-National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Alok Kumar Deb
- Division of Epidemiology, ICMR-National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Sanat Kumar Ghosh
- Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, Kolkata, West Bengal, India
| | - Asis Manna
- Infectious diseases and Beliaghata General (ID & BG) Hospital, Beliaghata, Kolkata, West Bengal, India
| | - Shanta Dutta
- Regional Virus Research and Diagnostic Laboratory, ICMR-National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
| | - Mamta Chawla-Sarkar
- Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
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14
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Wang X, Patel SA, Haddadin M, Cerny J. Post-allogeneic hematopoietic stem cell transplantation viral reactivations and viremias: a focused review on human herpesvirus-6, BK virus and adenovirus. Ther Adv Infect Dis 2021; 8:20499361211018027. [PMID: 34104434 PMCID: PMC8155777 DOI: 10.1177/20499361211018027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 04/27/2021] [Indexed: 12/30/2022] Open
Abstract
Human cytomegalovirus and Epstein-Barr virus have been recognized as potential drivers of morbidity and mortality of patients undergoing allogeneic stem cell transplantation for years. Specific protocols for monitoring, prophylaxis and pre-emptive therapy are in place in many transplant settings. In this review, we focus on the next three most frequent viruses, human herpesvirus-6, BK virus and adenovirus, causing reactivation and/or viremia after allogeneic transplant, which are increasingly detected in patients in the post-transplant period owing to emerging techniques of molecular biology, recipients' characteristics, treatment modalities used for conditioning and factors related donors or stem cell source. Given the less frequent detection of an illness related to these viruses, there are often no specific protocols in place for the management of affected patients. While some patients develop significant morbidity (generally older), others may not need therapy at all (generally younger or children). Furthermore, some of the antiviral therapies used are potentially toxic. With the addition of increased risk of secondary infections, risk of graft failure or increased risk of graft-versus-host disease as well as the relationship with other post-transplant complications, the outcomes of patients with these viremias remain unsatisfactory and even long-term survivors experience increased morbidity.
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Affiliation(s)
- Xin Wang
- Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
| | - Shyam A Patel
- Division of Hematology-Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
| | - Michael Haddadin
- Division of Hematology-Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
| | - Jan Cerny
- Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, 55 Lake Avenue North, Worcester, MA, 01655, USA
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15
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Gómez de Oña C, Alvarez-Argüelles ME, Rojo-Alba S, Casares H, Arroyo M, Rodríguez J, de Oña M, Melón S. Alterations in biochemical markers in adenovirus infection. Transl Pediatr 2021; 10:1248-1258. [PMID: 34189083 PMCID: PMC8193001 DOI: 10.21037/tp-20-333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Analyze possible relationships between HAdV and markers for inflammation, specifically the C-reactive protein (CRP) and procalcitonin (PCT) tests, along with other haematological markers. METHODS Retrospective study of 487 children presenting with fever and/or acute respiratory symptoms in the Paediatric Emergency Department. Analyses included viral presence/absence (both HAdV and other respiratory viruses) in respiratory exudates, CRP and PCT alterations in plasma, and haematological markers in whole blood. RESULTS Viral load was >500 copies/103 cells of HAdV in 127 cases (26.1%), of which 66 (52%, P<0.0001) had alterations in PCT, and 112 (88.1%, P<0.0001) in CRP. Haematological markers were similar either HAdV was present or not, although many HAdV positive patients demonstrated leukocytosis (66%). Bacterial cultures from 141 samples showed altered PCT in 27 (60%) with HAdV infection, in 3 (18.7%) with bacterial infection, and 13 (26.5%) without either viral or bacterial infection (P<0.05). CRP was altered in 88.9% of HAdV infected children and in 87% infected with bacteria, although the percentage was greater than in cases where other respiratory viruses were present (61.3% P<0.05). CONCLUSIONS Results demonstrate a clear relationship between HAdV infection and alterations in PCT and CRP which should be taken into account in paediatric patient management.
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Affiliation(s)
| | | | - Susana Rojo-Alba
- Microbiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Helena Casares
- Pediatric Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Mireia Arroyo
- Pediatric Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Julián Rodríguez
- Pediatric Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - María de Oña
- Microbiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Santiago Melón
- Microbiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
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16
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Majee P, Shankar U, Pasadi S, Muniyappa K, Nayak D, Kumar A. Genome-wide analysis reveals a regulatory role for G-quadruplexes during Adenovirus multiplication. Virus Res 2020; 283:197960. [DOI: 10.1016/j.virusres.2020.197960] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 03/31/2020] [Accepted: 03/31/2020] [Indexed: 12/17/2022]
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17
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Zaraket R, Salami A, Bahmad M, El Roz A, Khalaf B, Ghssein G, Bahmad HF. Prevalence, risk factors, and clinical characteristics of rotavirus and adenovirus among Lebanese hospitalized children with acute gastroenteritis. Heliyon 2020; 6:e04248. [PMID: 32613122 PMCID: PMC7322251 DOI: 10.1016/j.heliyon.2020.e04248] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 05/16/2020] [Accepted: 06/15/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Acute gastroenteritis is a very common infectious disease facing all age groups worldwide, especially the pediatric population. Viruses, bacteria, and parasites are all possible causes of infectious gastroenteritis; however, viruses have become more frequently identified with the advances in the ability to diagnose viral infections, particularly rotavirus and adenovirus. We aimed in our study to compare between the prevalence, risk factors, and clinical characteristics of rotavirus and adenovirus among children with viral gastroenteritis in Lebanon. MATERIALS AND METHODS A 12-months retrospective study was performed between January 1st and December 31st, 2018 including 308 children aged 1 month to 12 years, who were admitted to three tertiary healthcare centers in South Lebanon. Medical data were retrieved from patients' files, including clinical and laboratory information. RESULTS Rotavirus was found in stool of 204 patients (66.23 %), followed by adenovirus in 78 cases (25.32 %), and mixed group (rotavirus and adenovirus) in 26 cases (8.44%). The highest prevalence of rotavirus in our present study was seen among children between 12 and 23 months old, whereas patients infected with adenovirus were mainly aged between 24-35 months or 4-11 months. Majority of patients in the adenovirus and mixed groups had high-grade fever compared to the rotavirus group. Laboratory findings presented significantly higher average of white blood cells (WBCs), absolute neutrophil count (ANC), and C-reactive protein (CRP) in the mixed group compared to the two other groups. Monthly distribution of rotavirus and adenovirus infection revealed a biennial pattern of rotavirus incidence during January and July-August while frequency of adenovirus infection was highest during July-August. CONCLUSION Due to the high prevalence of viral diarrhea among the pediatric age group in our region, particularly rotavirus and adenovirus, along with the associated non-specific signs and symptoms, we highly recommend that medical laboratories be equipped for virus detection. Also, vaccination against rotavirus should be considered as a prevention strategy.
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Affiliation(s)
- Rasha Zaraket
- Faculty of Medicine, Beirut Arab University, Beirut, Lebanon
| | - Ali Salami
- Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research Group, Lebanese University, Faculty of Sciences (V), Nabatieh, Lebanon
| | - Marwan Bahmad
- Faculty of Medicine, Beirut Arab University, Beirut, Lebanon
| | - Ali El Roz
- Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research Group, Lebanese University, Faculty of Sciences (V), Nabatieh, Lebanon
| | - Batoul Khalaf
- Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research Group, Lebanese University, Faculty of Sciences (V), Nabatieh, Lebanon
| | - Ghassan Ghssein
- Rammal Hassan Rammal Research Laboratory, Physio-toxicity (PhyTox) Research Group, Lebanese University, Faculty of Sciences (V), Nabatieh, Lebanon
- Department of Laboratory Sciences, Faculty of Nursing and Health Sciences, Islamic University of Lebanon, Khalde, Lebanon
| | - Hisham F. Bahmad
- Faculty of Medicine, Beirut Arab University, Beirut, Lebanon
- Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
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18
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Histone Deacetylase Inhibitors Promote Latent Adenovirus Reactivation from Tonsillectomy Specimens. J Virol 2020; 94:JVI.00100-20. [PMID: 32269118 DOI: 10.1128/jvi.00100-20] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 03/24/2020] [Indexed: 12/20/2022] Open
Abstract
Adenovirus (HAdV) infection is a common cause of illness among young children, immunocompromised patients, and transplant recipients. The majority of HAdV infections are self-limited, but recurring infection is frequently encountered in young children and may require hospitalization. In this study, we surveyed the presence of HAdV in tonsillectomy samples and investigated epigenetic conditions that contributed to HAdV reactivation. HAdV DNA was detected from 86.7% donors. The lymphocytes isolated from the samples failed to produce infectious HAdV after incubation, suggesting the viruses remained in a latent status. To determine whether epigenetic factors played a role in HAdV reactivation, isolated lymphocytes were treated with a small compound library. Viral DNA replication and infectious HAdV production were assayed by PCR and by a secondary infection assay. We identified several compounds, mainly pan- and selective histone deacetylase (HDAC) inhibitors, which showed activity to reactivate HAdV from latency. The viruses were isolated and were determined as species C HAdV. Using a model of HAdV lytic infection, we showed that the compounds promoted histone-3 acetylation and association with viral early gene promoters. In addition to demonstrate the palatine tonsils as a reservoir of latent HAdV, this study uncovers a critical role of histone acetylation in HAdV reactivation, linking HAdV latency to recurrent HAdV infection.IMPORTANCE Respiratory tract infection by adenoviruses is among the most common diseases in children, attributing to approximately 20% of hospitalizations of children with acute respiratory infection (ARI). Adenovirus transmits by direct contact, but recurrent infection is common. Ever since its isolation, adenovirus has been known to have the ability to establish persistent or latent infection. We found 87.7% tonsillectomy specimens contained detectable amounts of adenoviral DNA. Isolated lymphocytes did not produce infectious adenoviruses without stimulation. By screening an epigenetic informer compound library, we identified several histone deacetylase inhibitors that promoted adenovirus reactivation that was evidenced by increased viral DNA replication and production of infectious viruses. The human tonsils are covered with bacterial pathogens that may utilize pathogen-associated pattern molecules or metabolites to cause epigenetic activation and proinflammatory gene transcription, which may lead to viral reactivation from latency. The study shows that recurrent adenovirus infection could arise from reactivation of residing virus from previous infections.
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19
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Pant K, Chandrasekaran A, Chang CJ, Vageesh A, Popkov AJ, Weinberg JB. Effects of tumor necrosis factor on viral replication and pulmonary inflammation during acute mouse adenovirus type 1 respiratory infection. Virology 2020; 547:12-19. [PMID: 32560900 DOI: 10.1016/j.virol.2020.05.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/18/2020] [Accepted: 05/19/2020] [Indexed: 01/22/2023]
Abstract
CD8 T cells contribute to effective clearance of mouse adenovirus type 1 (MAV-1) and to virus-induced pulmonary inflammation. We characterized effects of a CD8 T cell effector, TNF, on MAV-1 pathogenesis. TNF inhibited MAV-1 replication in vitro. TNF deficiency or immunoneutralization had no effect on lung viral loads or viral gene expression in mice infected intranasally with MAV-1. Absence of TNF delayed virus-induced weight loss and reduced histological evidence of pulmonary inflammation, although concentrations of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) were not significantly affected. BALF concentrations of IL-10 were greater in TNF-deficient mice compared to controls. Our data indicate that TNF is not essential for control of viral replication in vivo, but virus-induced TNF contributes to some aspects of immunopathology and disease. Redundant CD8 T cell effectors and other aspects of immune function are sufficient for antiviral and pro-inflammatory responses to acute MAV-1 respiratory infection.
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Affiliation(s)
- Krittika Pant
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | | | - Christine J Chang
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | - Aditya Vageesh
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
| | | | - Jason B Weinberg
- Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.
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20
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Preclinical Development and Clinical-Scale Manufacturing of HIV Gag-Specific, LentivirusModified CD4 T Cells for HIV Functional Cure. MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT 2020; 17:1048-1060. [PMID: 32462053 PMCID: PMC7240062 DOI: 10.1016/j.omtm.2020.04.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 04/27/2020] [Indexed: 02/07/2023]
Abstract
Activation, infection, and eventual depletion of human immunodeficiency virus (HIV)-specific cluster of differentiation 4 (CD4) T cells are the crucial pathogenetic events in acquired immunodeficiency syndrome (AIDS). We developed a cell and gene therapy to reconstitute HIV-specific CD4 T cells and prevent their destruction by HIV. Antigen-specific CD4 T cells will provide helper functions to support antiviral cytotoxic T lymphocyte (CTL) function and the production of virus-specific antibodies. However, ex vivo expansion of HIV-specific CD4 T cells is poor and previous gene therapies focused on bulk CD4 T cells without enriching for an antigen-specific subset. We developed a method for manufacturing autologous CD4+ T cell products highly enriched with Gag-specific T cells. Rare Gag-specific CD4 T cells in peripheral blood mononuclear cells (PBMCs) were increased nearly 1,000-fold by stimulating PBMC with Gag peptides, followed by depleting nontarget cells and transducing with lentivirus vector AGT103 to protect against HIV-mediated depletion and inhibit HIV release from latently infected cells. The average percentage of HIV-specific CD4 cells in the final products was 15.13%, and the average yield was 7 × 108 cells. The protocol for clinical-scale manufacturing of HIV-specific and HIV-resistant CD4 T cells is an important step toward effective immunotherapy for HIV disease.
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21
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Successful Treatment of Adenovirus Infection with Brincidofovir in an Immunocompromised Patient after Hematological Stem Cell Transplantation. Case Rep Infect Dis 2020; 2020:5981289. [PMID: 31970003 PMCID: PMC6973187 DOI: 10.1155/2020/5981289] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 12/12/2019] [Indexed: 01/27/2023] Open
Abstract
Immunocompromised patients, including hematopoietic stem cell transplantation (HSCT), HIV, and malnourished patients, are at increased risk for viral infections with high incidences of morbidity and mortality. In HSCT patients, the infection risk is increased until immune reconstitution is re-established. Therapy with standard of care antiviral drugs, for example Cidofovir, is expensive, requires prolonged administration, and has unfavorable toxicity profiles. Our case describes the successful use of Brincidofovir (CMX001), a lipid-conjugate of the nucleotide analog Cidofovir, in a 9-year-old post-HSCT girl with disseminated adenovirus infection. The increased efficacy of Brincidofovir (BCV) against multiple viral infections, limited toxicity, and oral-administered schedule opens options in different resource settings.
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Marinelli T, Wee LYA, Rowe E, Chhetri R, Friel O, Higgins G, Bardy P, Singhal D, Pradhan A, Crawford L, Hiwase DK. Respiratory Viruses Cause Late Morbidity in Recipients of Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2019; 26:782-788. [PMID: 31866345 DOI: 10.1016/j.bbmt.2019.12.724] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 12/04/2019] [Accepted: 12/16/2019] [Indexed: 02/07/2023]
Abstract
Common respiratory viral infections (CRVIs) frequently complicate hematopoietic stem cell transplantation (HSCT). We conducted a retrospective, single-center, observational cohort study to determine the incidence of CRVI in patients who received an allogeneic (allo) or autologous (auto) HSCT at the Royal Adelaide Hospital between 2009 and 2017. The median follow-up was 8.9 and 4.5 years for auto- and allo-HSCT recipients, respectively. There were 149 CRVI episodes in 74 patients, with rhinovirus being the most commonly isolated virus (n = 81, 47%). The majority of CRVIs (113/149, 75.8%) occurred more than 100 days post-HSCT and 67% were diagnosed in the outpatient setting. There was evidence of lower respiratory tract infection (LRTI) in 45.6% (68/149) of CRVIs. On multivariate logistic regression analysis, coviral infections and cytomegalovirus viremia were independent risk factors for progression of CRVI to LRTI. Ten (6.7%) CRVI episodes resulted in admission to intensive care for ventilatory support and 8 (5.4%) patients died within 30 days of CRVI diagnosis. In our study, 10.4% of HSCT recipients experienced a CRVI post-transplant, primarily causing late morbidity and potentially mortality. Prevention with strict infection control practices, vaccination, and patient education is essential.
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Affiliation(s)
- Tina Marinelli
- Department of Infectious Diseases, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia
| | - Li Yan A Wee
- Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Emily Rowe
- Department of Infectious Diseases, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Rakchha Chhetri
- Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Oisin Friel
- Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia
| | - Geoffrey Higgins
- Department of Infectious Diseases, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; SA Pathology, Central Adelaide Local Health Network, Adelaide, Australia
| | - Peter Bardy
- Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Deepak Singhal
- Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, Australia
| | - Alyssa Pradhan
- Department of Infectious Diseases, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia
| | - Lucy Crawford
- Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, Australia; SA Pathology, Central Adelaide Local Health Network, Adelaide, Australia
| | - Devendra K Hiwase
- Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, Australia; Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, Australia; Discipline of Medicine, Adelaide Medical School, The University of Adelaide, Adelaide, Australia.
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23
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Fisher BT, Boge CLK, Petersen H, Seif AE, Bryan M, Hodinka RL, Cardenas AM, Purdy DR, Loudon B, Kajon AE. Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients. J Pediatric Infect Dis Soc 2019; 8:317-324. [PMID: 29893957 DOI: 10.1093/jpids/piy049] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 06/01/2018] [Indexed: 11/13/2022]
Abstract
BACKGROUND Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. METHODS A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection. RESULTS Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]). CONCLUSIONS HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.
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Affiliation(s)
- Brian T Fisher
- Division of Infectious Diseases, Pennsylvania.,Center for Pediatric Clinical Effectiveness, Pennsylvania.,Division of Oncology, Pennsylvania.,Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico
| | - Craig L K Boge
- Division of Infectious Diseases, Pennsylvania.,Center for Pediatric Clinical Effectiveness, Pennsylvania
| | - Hans Petersen
- Infectious Disease Diagnostics Laboratory, Children's Hospital of Philadelphia, Pennsylvania
| | - Alix E Seif
- Department of Pediatrics, Philadelphia.,Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico
| | - Matthew Bryan
- Center for Pediatric Clinical Effectiveness, Pennsylvania.,Division of Oncology, Pennsylvania.,Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico
| | - Richard L Hodinka
- Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
| | - Ana Maria Cardenas
- Center for Clinical Epidemiology and Biostatistics, Philadelphia.,Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville Health System
| | - Dale R Purdy
- Center for Pediatric Clinical Effectiveness, Pennsylvania
| | | | - Adriana E Kajon
- Infectious Disease Diagnostics Laboratory, Children's Hospital of Philadelphia, Pennsylvania
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24
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Lun JH, Crosbie ND, White PA. Genetic diversity and quantification of human mastadenoviruses in wastewater from Sydney and Melbourne, Australia. THE SCIENCE OF THE TOTAL ENVIRONMENT 2019; 675:305-312. [PMID: 31030137 DOI: 10.1016/j.scitotenv.2019.04.162] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 04/10/2019] [Accepted: 04/11/2019] [Indexed: 05/27/2023]
Abstract
Human mastadenoviruses (HAdVs) are DNA viruses that can cause a wide range of clinical diseases, including gastroenteritis, respiratory illnesses, conjunctivitis, and in more severe cases hepatitis, pancreatitis and disseminated diseases. HAdV infections are generally asymptomatic or self-limiting, but can cause adverse outcomes within vulnerable populations. Since most HAdV serotypes replicate within the human gastrointestinal tract, high levels of HAdV DNA are excreted into wastewater systems. In this study, we identified the genetic diversity of HAdV at a population level using wastewater samples collected from Sydney and Melbourne from 2016 to 2017, with the use of next generation sequencing (NGS) technologies. In addition, HAdV DNA levels were quantified using quantitative polymerase chain reaction (qPCR) based methods to better understand the health risks involved if wastewater contamination occurs. An average of 1.8 × 107 genome copies of HAdV DNA was detected in one litre of wastewater collected in Sydney and Melbourne, over the two-year study period. A total of six major groups of HAdV were identified in wastewater samples using MiSeq, which included 19 different serotypes. Of those, the most prevalent was F41 (83.5%), followed by F40 (11.0%) and A31 (3.7%). In contrast, five groups of HAdV were identified in clinical samples with F41 as the most dominant serotype, (52.5% of gastroenteritis cases), followed by C1 and C2 (each responsible for 15.0%), and B3 was the fourth most common serotype (7.5%). This study demonstrated the practicability of using amplicon based NGS to identify HAdV diversity and quantify HAdV genome levels in environmental water samples, as well as broadening our current understanding of circulating HAdV in the Australian population.
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Affiliation(s)
- Jennifer H Lun
- School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW, Australia.
| | - Nicholas D Crosbie
- Melbourne Water Corporation, Docklands, VIC, Australia; School of Civil and Environmental Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW, Australia.
| | - Peter A White
- School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW, Australia.
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25
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Noroozi-aghideh A, Kheirandish M. Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety: A mini review. World J Stem Cells 2019; 11:73-83. [PMID: 30842806 PMCID: PMC6397803 DOI: 10.4252/wjsc.v11.i2.73] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Revised: 01/14/2019] [Accepted: 01/26/2019] [Indexed: 02/06/2023] Open
Abstract
Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen (HLA)-matched donors. The main practical advantages of UCB over other HSC sources are the immediate availability, lower incidence of graft-versus-host disease, minimal risk to the donor, and lower requirement for HLA compatibility. However, the use of UCB is limited by delayed engraftment and poor immune reconstitution, leading to a high rate of infection-related mortality. Therefore, severe infectious complications, especially due to viral pathogens remain the leading cause of morbidity and mortality during the post-UCB transplantation (UCBT) period. In this context, careful screening and excluding the viral-contaminated UCB units might be an effective policy to reduce the rate of UCBT-related infection and mortality. Taken together, complete prevention of the transmission of donor-derived viral pathogens in stem cell transplantation is not possible. However, having the knowledge of the transmission route and prevalence of viruses will improve the safety of transplantation. To the best of our knowledge, there are few studies that focused on the risk of virus transmission through the UCB transplant compared to other HSC sources. This review summarizes the general aspects concerning the prevalence, characteristics, and risk factors of viral infections with a focus on the impact of viral pathogens on cord blood transplantation safety.
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Affiliation(s)
- Ali Noroozi-aghideh
- Department of Hematology, Faculty of Paramedicine, Aja University of Medical Sciences, Tehran 14665-1157, Iran
| | - Maryam Kheirandish
- Immunology Department, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine (IBTO), Tehran 14665-1157, Iran
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26
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Haddad-Boubaker S, Joffret ML, Pérot P, Bessaud M, Meddeb Z, Touzi H, Delpeyroux F, Triki H, Eloit M. Metagenomic analysis identifies human adenovirus 31 in children with acute flaccid paralysis in Tunisia. Arch Virol 2019; 164:747-755. [DOI: 10.1007/s00705-018-04141-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 12/29/2018] [Indexed: 01/24/2023]
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27
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Monette A, Mouland AJ. T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2019; 342:175-263. [PMID: 30635091 PMCID: PMC7104940 DOI: 10.1016/bs.ircmb.2018.07.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Continuous epidemiological surveillance of existing and emerging viruses and their associated disorders is gaining importance in light of their abilities to cause unpredictable outbreaks as a result of increased travel and vaccination choices by steadily growing and aging populations. Close surveillance of outbreaks and herd immunity are also at the forefront, even in industrialized countries, where previously eradicated viruses are now at risk of re-emergence due to instances of strain recombination, contractions in viral vector geographies, and from their potential use as agents of bioterrorism. There is a great need for the rational design of current and future vaccines targeting viruses, with a strong focus on vaccine targeting of adaptive immune effector memory T cells as the gold standard of immunity conferring long-lived protection against a wide variety of pathogens and malignancies. Here, we review viruses that have historically caused large outbreaks and severe lethal disorders, including respiratory, gastric, skin, hepatic, neurologic, and hemorrhagic fevers. To observe trends in vaccinology against these viral disorders, we describe viral genetic, replication, transmission, and tropism, host-immune evasion strategies, and the epidemiology and health risks of their associated syndromes. We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates.
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28
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A survey on incidence and management of adenovirus infection after allogeneic HSCT. Bone Marrow Transplant 2018; 54:1275-1280. [PMID: 30546071 DOI: 10.1038/s41409-018-0421-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Revised: 11/03/2018] [Accepted: 11/24/2018] [Indexed: 12/25/2022]
Abstract
To determine the current practices on the management of Adenovirus (ADV) infection after allogenic stem cell transplantation, a survey was undertook among EBMT centres. The response rate was 20% (91/446): 46% were adult, 44% were paediatric and 10% were mixed centres, respectively. The overall incidence of ADV infection was 7.1%: 4.1% in adult, 15.4% in paediatric, and 3.6% in mixed population. The determination of ADV-DNA in biological samples was used in 96% of centres; 58% of them monitored asymptomatic patients with a frequency of twice a week in 9%, once a week in 45%, every two weeks in 4% of centres. The treatment of ADV infection was mainly based on the administration of cidofovir (87%), being the schedule of 5 mg/kg/week with probenecid the most used, and the reduction of immunosuppression (84%). The threshold of ADV-DNAemia to start cidofovir in high-risk patients was most frequently >1000 copies/ml. Innovative treatments, such as brincidofovir and adoptive ADV-cytotoxic-T-lymphocytes, were used in 27% and 20% of centres, respectively. Almost all responding centres consider ADV infection serious enough to deserve testing asymptomatic or symptomatic patients. Cidofovir and reduction of immunosuppression represent the main therapeutic options but one fourth of responding centres experimented novel therapies.
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29
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Human adenovirus load in respiratory tract secretions are predictors for disease severity in children with human adenovirus pneumonia. Virol J 2018; 15:123. [PMID: 30086789 PMCID: PMC6081882 DOI: 10.1186/s12985-018-1037-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 08/02/2018] [Indexed: 12/02/2022] Open
Abstract
Background Pneumonia is a serious public health issue and is concerned around the world. This study is to investigate the association between viral load in children with human adenovirus (HAdV) pneumonia and disease severity. Methods A total of 1313 cases of children hospitalized in Hunan Provincial People’s Hospital due to community acquired pneumonia (CAP) from April 2011 to May 2014 were enrolled in this study. Samples of nasopharyngeal aspirate were collected for the cohort. WHO criteria for CAP grading was emerged for pneumonia severity classification. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect 12 kinds of respiratory viruses. HAdV types were identified by nested PCR. The relationship between HAdV load and severity of disease was there by analyzed. Results Finally, 174 cases (174/1313, 13.3%) were positive for HAdV, and HAdV type 7 (HAdV-7) was the main serotype (76/174, 43.7%). Among the 174 cases, 70 cases were with HAdV infection alone and 104 cases were accompanied by other viruses. The patients were divided into mild pneumonia group (n = 108 cases) and severe pneumonia group (n = 66 cases). HAdV load of children in severe pneumonia group was higher than that in mild pneumonia group. Similar result was obtained in the 70 cases with HAdV infection alone after subgrouping. Relevant factors analysis results showed that severe pneumonia children presented lower onset age, more prone to fever, longer fever time, and longer hospital stay compared with that of mild pneumonia children. Children with HAdV-7 infection developed more frequently severe pneumonia. Multivariate regression analysis showed that HAdV load, age, and fever time were risk factors for pneumonia severity. Conclusion The severity of HAdV infection is significantly correlated with viral load and serotype.
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30
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Fas activity mediates airway inflammation during mouse adenovirus type 1 respiratory infection. Virology 2018; 521:129-137. [PMID: 29908447 DOI: 10.1016/j.virol.2018.06.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 06/04/2018] [Accepted: 06/06/2018] [Indexed: 12/14/2022]
Abstract
CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice. Virus-induced apoptosis in lungs was not affected by Fas deficiency. Our results suggest that the proinflammatory effects of CD8 T cells during MAV-1 infection are mediated in part by Fas activation and are distinct from CD8 T cell antiviral functions.
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31
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Bello AB, Park H, Lee SH. Current approaches in biomaterial-based hematopoietic stem cell niches. Acta Biomater 2018; 72:1-15. [PMID: 29578087 DOI: 10.1016/j.actbio.2018.03.028] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 02/07/2018] [Accepted: 03/14/2018] [Indexed: 12/20/2022]
Abstract
Hematopoietic stem cells (HSCs) are multipotent progenitor cells that can differentiate and replenish blood and immune cells. While there is a growing demand for autologous and allogeneic HSC transplantation owing to the increasing incidence of hereditary and hematologic diseases, the low population of HSCs in cord-blood and bone marrow (the main source of HSCs) hinders their medical applicability. Several cytokine and growth factor-based methods have been developed to expand the HSCs in vitro; however, the expansion rate is low, or the expanded cells fail to survive upon engraftment. This is at least in part because the overly simplistic polystyrene culture substrates fail to fully replicate the microenvironments or niches where these stem cells live. Bone marrow niches are multi-dimensional, complex systems that involve both biochemical (cells, growth factors, and cytokines) and physiochemical (stiffness, O2 concentration, and extracellular matrix presentation) factors that regulate the quiescence, proliferation, activation, and differentiation of the HSCs. Although several studies have been conducted on in vitro HSC expansion via 2D and 3D biomaterial-based platforms, additional work is required to engineer an effective biomaterial platform that mimics bone marrow niches. In this study, the factors that regulate the HSC in vivo were explained and their applications in the engineering of a bone marrow biomaterial-based platform were discussed. In addition, current approaches, challenges, and the future direction of a biomaterial-based culture and expansion of the HSC were examined. STATEMENT OF SIGNIFICANCE Hematopoietic stem cells (HSC) are multipotent cells that can differentiate and replace the blood and immune cells of the body. However, in vivo, there is a low population of these cells, and thus their use in biotherapeutic and medical applications is limited (i.e., bone marrow transplantation). In this review, the biochemical factors (growth factors, cytokines, co-existing cells, ECM, gas concentrations, and differential gene expression) that may regulate the over-all fate of HSC, in vivo, were summarized and discussed. Moreover, different conventional and recent biomaterial platforms were reviewed, and their potential in generating a biomaterial-based, BM niche-mimicking platform for the efficient growth and expansion of clinically relevant HSCs in-vitro, was discussed.
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Affiliation(s)
- Alvin Bacero Bello
- School of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea; Department of Biomedical Science, CHA University, Seongnam-Si 13488, Republic of Korea
| | - Hansoo Park
- School of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea.
| | - Soo-Hong Lee
- Department of Biomedical Science, CHA University, Seongnam-Si 13488, Republic of Korea.
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32
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Hiwarkar P, Kosulin K, Cesaro S, Mikulska M, Styczynski J, Wynn R, Lion T. Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State-of-the-art and real-life current approach: A position statement on behalf of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation. Rev Med Virol 2018; 28:e1980. [PMID: 29663594 DOI: 10.1002/rmv.1980] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 03/05/2018] [Accepted: 03/06/2018] [Indexed: 12/12/2022]
Abstract
The important insights gained over the past years in diagnosis and treatment of invasive adenoviral infections provide new paradigms for the monitoring and clinical management of these life-threatening complications. A meeting was held to discuss and subsequently disseminate the current advances in our understanding of the aetiology/pathogenesis and future treatment options facilitating effective control or prevention of adenovirus-related diseases in the allogeneic haematopoietic stem cell transplant setting. Invited experts in the field discussed recent progress with leading members of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation at the "State-of-the-art" Meeting in Poznan, Poland, in October 2017. In this review article, the panel of experts presents a concise summary of the current evidence based on published data from the last 15 years and on recent achievements resulting from real-life practice. The present position statement reflects an expert opinion on current approaches to clinical management of adenovirus infections in patients undergoing allogeneic haematopoietic stem cell transplant and provides graded recommendations of the panel for diagnostic approaches and preemptive therapy reflecting the present state of knowledge.
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Affiliation(s)
- Prashant Hiwarkar
- Department of Haematology and Bone Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, UK
| | - Karin Kosulin
- Division of Molecular Microbiology, Children's Cancer Research Institute, Vienna, Austria
| | - Simone Cesaro
- Paediatric Hematology-Oncology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
| | - Malgorzata Mikulska
- Division of Infectious Diseases, University of Genoa (DISSAL) and Ospedale Policlinico San Martino, Genoa, Italy
| | - Jan Styczynski
- Department of Paediatric Haematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland
| | - Robert Wynn
- Department of Haematology and Bone Marrow Transplantation, Royal Manchester Children's Hospital, Manchester, UK
| | - Thomas Lion
- Division of Molecular Microbiology, Children's Cancer Research Institute, Vienna, Austria.,Department of Pediatrics, Medical University of Vienna, Vienna, Austria
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33
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Li J, Lu X, Jiang B, Du Y, Yang Y, Qian H, Liu B, Lin C, Jia L, Chen L, Wang Q. Adenovirus-associated acute conjunctivitis in Beijing, China, 2011-2013. BMC Infect Dis 2018; 18:135. [PMID: 29558885 PMCID: PMC5859447 DOI: 10.1186/s12879-018-3014-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Accepted: 02/28/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Human adenovirus (HAdV)-associated acute conjunctivitis is a common infectious disease and causes significant morbidity among residents in Beijing, China. However, little is known about the epidemiology and type distribution of acute adenoviral conjunctivitis in Beijing. METHODS Acute conjunctivitis surveillance was conducted in 18 hospitals in Beijing from July through October during 2011-2013. HAdVs were detected by PCR from eye swab and types were determined by partial hexon and fiber gene sequencing. Risk factors associated with adenoviral conjunctivitis were analyzed. RESULTS Of 876 conjunctivitis cases, 349 (39.8%) were HAdV positive. HAdV detection was most common in conjunctivitis patients aged 18-40 years; patients with contact history with a conjunctivitis case; patients with specimen collected on days 4-6 post symptom onset and patients who worked in food service as catering attendants. Fifteen types were identified among adenoviral conjunctivitis cases. Five HAdV types (HAdV-4, - 37, - 53, - 64 and - 8) accounted for 81.1% of all adenoviral conjunctivitis cases. HAdV-37, - 4 and - 53 were the most common types associated with adenoviral conjunctivitis in 2011, 2012 and 2013, respectively. CONCLUSION Multiple HAdV types were associated with acute conjunctivitis in Beijing. Predominant types associated with adenoviral conjunctivitis circulating in Beijing varied from year to year.
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Affiliation(s)
- Jie Li
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Xiaoyan Lu
- Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA, 30329, USA
| | - Baoming Jiang
- Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA, 30329, USA
| | - Yiwei Du
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Yang Yang
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Haikun Qian
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Baiwei Liu
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Changying Lin
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Lei Jia
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China
| | - Lijuan Chen
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China. .,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.
| | - Quanyi Wang
- Beijing Center for Disease Prevention and Control, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China. .,Research Centre for Preventive Medicine of Beijing, No.16, Hepingli Middle Road, Beijing, 100013, People's Republic of China.
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Rayne F, Wittkop L, Bader C, Kassab S, Tumiotto C, Berciaud S, Wodrich H, Lafon ME. Rapid Adenovirus typing method for species identification. J Virol Methods 2017; 249:156-160. [PMID: 28918074 DOI: 10.1016/j.jviromet.2017.09.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 07/28/2017] [Accepted: 09/12/2017] [Indexed: 10/18/2022]
Abstract
Adenoviruses are characterized by a large variability, reflected by their classification in species A to G. Certain species, eg A and C, could be associated with increased clinical severity, both in immunocompetent and immunocompromised hosts suggesting that in some instances species identification provides clinically relevant information. Here we designed a novel "pVI rapid typing method" to obtain quick, simple and cost effective species assignment for Adenoviruses, thanks to combined fusion temperature (Tm) and amplicon size analysis. Rapid typing results were compared to Sanger sequencing in the hexon gene for 140 Adenovirus-positive clinical samples included in the Typadeno study. Species A and C could be identified with a 100% positive predictive value, thus confirming the value of this simple typing method.
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Affiliation(s)
- Fabienne Rayne
- Univ Bordeaux, CNRS, UMR 5234 Fundamental Microbiology and Pathogenicity, F-33000, Bordeaux, France
| | - Linda Wittkop
- Univ Bordeaux, ISPED Inserm, Bordeaux Population Health Research Center, team MORPH3EUS, UMR 1219, CIC-EC 1401, F-33000 Bordeaux, France; CHU de Bordeaux, Pôle de santé publique, Service d'information médicale, F-33000 Bordeaux, France
| | - Clément Bader
- CHU de Bordeaux, Pôle de santé publique, Service d'information médicale, F-33000 Bordeaux, France
| | - Somar Kassab
- Univ Bordeaux, CNRS, UMR 5234 Fundamental Microbiology and Pathogenicity, F-33000, Bordeaux, France
| | - Camille Tumiotto
- Univ Bordeaux, CNRS, UMR 5234 Fundamental Microbiology and Pathogenicity, F-33000, Bordeaux, France; CHU de Bordeaux, Pôle de Biologie et Pathologie, Laboratoire de Virologie, F-33000 Bordeaux, France
| | - Sylvie Berciaud
- CHU de Bordeaux, Pôle de Pédiatrie, F-33000 Bordeaux, France
| | - Harald Wodrich
- Univ Bordeaux, CNRS, UMR 5234 Fundamental Microbiology and Pathogenicity, F-33000, Bordeaux, France
| | - Marie-Edith Lafon
- Univ Bordeaux, CNRS, UMR 5234 Fundamental Microbiology and Pathogenicity, F-33000, Bordeaux, France; CHU de Bordeaux, Pôle de Biologie et Pathologie, Laboratoire de Virologie, F-33000 Bordeaux, France.
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Molecularly imprinted polymer for human viral pathogen detection. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017; 77:1341-1348. [DOI: 10.1016/j.msec.2017.03.209] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 03/22/2017] [Accepted: 03/23/2017] [Indexed: 11/18/2022]
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Locatelli F, Bernardo ME, Bertaina A, Rognoni C, Comoli P, Rovelli A, Pession A, Fagioli F, Favre C, Lanino E, Giorgiani G, Merli P, Pagliara D, Prete A, Zecca M. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2017; 18:1126-1136. [PMID: 28705454 DOI: 10.1016/s1470-2045(17)30417-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Revised: 04/27/2017] [Accepted: 05/02/2017] [Indexed: 01/26/2023]
Abstract
BACKGROUND Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). METHODS We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci. All patients received a myeloablative regimen and cyclosporine-A plus short-term methotrexate as post-transplantation GVHD prophylaxis. Patients were randomly assigned (1:1) to either of the two groups and were stratified by the degree of HLA-compatibility with their donor, the source of haemopoietic stem cells used (bone marrow vs peripheral blood stem cells), and the disease risk category. The randomisation was open label; all investigators were aware of the treatment allocation. The primary endpoint of the study was 100-day cumulative incidence of grade II-IV acute GVHD. Statistical analyses were done according to the per-protocol principle. Other outcomes included cumulative incidence of chronic GVHD, non-relapse mortality, disease recurrence, and probability of overall survival and event-free survival. This study was registered with ClinicalTrials.gov, number NCT00934557. FINDINGS Between Jan 15, 2008, and Sept 25, 2012, 89 patients were randomly assigned to the 30 mg/kg ATLG group and 91 to the 15 mg/kg ATLG group; 84 patients in the 30 mg/kg ATLG group and 88 in the 15 mg/kg ATLG group were included in the analysis. The median follow-up for the whole study population was 3·4 years (IQR 1·7-5·1). The 100-day cumulative incidence of grade II-IV acute GVHD was 36% (95% CI 28-48) in the 15 mg/kg ATLG group and 29% (20-40) in the 30 mg/kg ATLG group (hazard ratio [HR] 0·74, 95% CI 0·44-1·25; p=0·26). The cumulative incidence of non-relapse mortality was 9% (5-18) in the 15 mg/kg ATLG group and 19% (12-30) in the 30 mg/kg ATLG group (HR 2·08, 0·89-4·96; p=0·092). Cumulative incidence of disease recurrence was 15% (12-24): 14% (8-23) in the 15 mg/kg ATLG group versus 20% (13-31) in the 30 mg/kg ATLG group (HR 1·54, 0·74-3·21; p=0·25). The 5-year overall survival probability was 70% (62-77) for the whole study population: 78% (69-87) in the 15 mg/kg ATLG group versus 62% (50-73) in the 30 mg/kg ATLG group (HR 1·80, 1·01-3·20; p=0·045). The 5-year event-free survival was 77% for children in the 15 mg/kg ATLG group versus 61% in the 30 mg/kg ATLG group (HR 1·87, 1·07-3·28; p=0·028). INTERPRETATION Children with haematological malignancies transplanted from unrelated donors selected through high-resolution HLA-typing benefit from the use of a 15 mg/kg ATLG dose in comparison with a 30 mg/kg ATLG dose. ATLG at 15 mg/kg should thus be regarded as the standard serotherapy regimen for unrelated donor allogeneic HSCT in this patient population. Future randomised studies will continue to aim to optimise patient outcome and strategies to prevent acute GVHD occurrence. FUNDING Fresenius/Neovii Biotech.
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Affiliation(s)
- Franco Locatelli
- Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale "Bambino Gesù", Rome, Italy; Università degli Studi di Pavia, Pavia, Italy.
| | - Maria Ester Bernardo
- Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale "Bambino Gesù", Rome, Italy
| | - Alice Bertaina
- Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale "Bambino Gesù", Rome, Italy
| | - Carla Rognoni
- Centre for Research on Health and Social Care Management (CERGAS), Università Bocconi, Milan, Italy
| | - Patrizia Comoli
- Oncoematologia Pediatrica, Fondazione IRCCS Policlinico "San Matteo", Pavia, Italy
| | - Attilio Rovelli
- Clinica Pediatrica, Fondazione MBBM/AO "San Gerardo", Monza, Italy
| | - Andrea Pession
- Oncologia ed Ematologia "Lalla Seràgnoli", Clinica Pediatrica, Policlinico Sant'Orsola Malpighi, Bologna, Italy
| | - Franca Fagioli
- Oncoematologia Pediatrica e Centro Trapianti, AOU Città della Salute e della Scienza, Torino, Italy
| | - Claudio Favre
- Dipartimento di Oncoematologia, Tumori pediatrici e Trapianto di cellule staminali, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy
| | - Edoardo Lanino
- Dipartimento di Ematologia e Oncologia Pediatrica, Istituto "G Gaslini", Genoa, Italy
| | - Giovanna Giorgiani
- Oncoematologia Pediatrica, Fondazione IRCCS Policlinico "San Matteo", Pavia, Italy
| | - Pietro Merli
- Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale "Bambino Gesù", Rome, Italy
| | - Daria Pagliara
- Dipartimento di Oncoematologia Pediatrica, IRCCS Ospedale "Bambino Gesù", Rome, Italy
| | - Arcangelo Prete
- Oncologia ed Ematologia "Lalla Seràgnoli", Clinica Pediatrica, Policlinico Sant'Orsola Malpighi, Bologna, Italy
| | - Marco Zecca
- Oncoematologia Pediatrica, Fondazione IRCCS Policlinico "San Matteo", Pavia, Italy
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Qian C, Campidelli A, Wang Y, Cai H, Venard V, Jeulin H, Dalle JH, Pochon C, D'aveni M, Bruno B, Paillard C, Vigouroux S, Jubert C, Ceballos P, Marie-Cardine A, Galambrun C, Cholle C, Clerc Urmes I, Petitpain N, De Carvalho Bittencourt M, Decot V, Reppel L, Salmon A, Clement L, Bensoussan D. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial. J Hematol Oncol 2017; 10:102. [PMID: 28482908 PMCID: PMC5421327 DOI: 10.1186/s13045-017-0469-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Accepted: 04/20/2017] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). METHODS Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. RESULTS One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. CONCLUSIONS Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).
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Affiliation(s)
- Chongsheng Qian
- Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France.,UMR 7365 and FR 3209 CNRS-UL-CHU, Université de Lorraine, Vandoeuvre-Lès-Nancy, F54511, France
| | - Arnaud Campidelli
- Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France
| | - Yingying Wang
- Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France.,UMR 7365 and FR 3209 CNRS-UL-CHU, Université de Lorraine, Vandoeuvre-Lès-Nancy, F54511, France
| | - Huili Cai
- Laboratoire d'Immunologie and Plateforme Nancytomique, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France
| | - Véronique Venard
- Laboratoire de Virologie, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France
| | - Hélène Jeulin
- Laboratoire de Virologie, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France
| | - Jean Hugues Dalle
- Immuno-Hématologie pédiatrique, Hôpital Robert Debré, Paris, F75935, France
| | - Cécile Pochon
- Unité de Transplantation Médullaire Allogénique, CHRU de Nancy, Vandoeuvre-lès-Nancy, F54511, France
| | - Maud D'aveni
- Unité de Transplantation Médullaire Allogénique, CHRU de Nancy, Vandoeuvre-lès-Nancy, F54511, France
| | - Benedicte Bruno
- Hématologie pédiatrique, Hôpital Jeanne de Flandres CHU de Lille, Lille cedex, F59037, France
| | | | - Stéphane Vigouroux
- Groupe hospitalier Sud Hôpital Haut-Lévêque, Hématologie clinique et thérapie cellulaire, Pessac Cedex, F33604, France
| | - Charlotte Jubert
- Hématologie Oncologie Pédiatrique, Hôpital des Enfants Pellegrin, Bordeaux, F33000, France
| | - Patrice Ceballos
- Hématologie Clinique, Hôpital St Eloi, Montpellier, Cedex 5, F34295, France
| | - Aude Marie-Cardine
- Hématologie et Oncologie Pédiatrique, Hôpital Charles Nicolle-CHU de Rouen, Rouen, F76031, France
| | - Claire Galambrun
- Immuno-hématologie Pédiatrique, CHU de la Timone, Marseille, F13385, France
| | - Clément Cholle
- Faculté de Pharmacie, Département de Microbiologie-Immunologie, Université de Lorraine, Nancy, F54001, France
| | - Isabelle Clerc Urmes
- Plateform of Clinical Research Facility PARC, Unit of Methodology, Data Management and Statistics, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France
| | - Nadine Petitpain
- Centre Régional de Pharmacovigilance de Lorraine, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France
| | | | - Véronique Decot
- Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France.,UMR 7365 and FR 3209 CNRS-UL-CHU, Université de Lorraine, Vandoeuvre-Lès-Nancy, F54511, France
| | - Loïc Reppel
- Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France.,UMR 7365 and FR 3209 CNRS-UL-CHU, Université de Lorraine, Vandoeuvre-Lès-Nancy, F54511, France
| | - Alexandra Salmon
- Unité de Transplantation Médullaire Allogénique, CHRU de Nancy, Vandoeuvre-lès-Nancy, F54511, France
| | - Laurence Clement
- Unité de Transplantation Médullaire Allogénique, CHRU de Nancy, Vandoeuvre-lès-Nancy, F54511, France
| | - Danièle Bensoussan
- Unité de Thérapie cellulaire et Tissus and FR 3209, CHRU de Nancy, Vandoeuvre-Lès-Nancy, F54511, France. .,UMR 7365 and FR 3209 CNRS-UL-CHU, Université de Lorraine, Vandoeuvre-Lès-Nancy, F54511, France. .,Faculté de Pharmacie, Département de Microbiologie-Immunologie, Université de Lorraine, Nancy, F54001, France.
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Molloy CT, Andonian JS, Seltzer HM, Procario MC, Watson ME, Weinberg JB. Contributions of CD8 T cells to the pathogenesis of mouse adenovirus type 1 respiratory infection. Virology 2017; 507:64-74. [PMID: 28410483 DOI: 10.1016/j.virol.2017.04.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 03/22/2017] [Accepted: 04/05/2017] [Indexed: 01/08/2023]
Abstract
CD8 T cells are key components of the immune response to viruses, but their roles in the pathogenesis of adenovirus respiratory infection have not been characterized. We used mouse adenovirus type 1 (MAV-1) to define CD8 T cell contributions to the pathogenesis of adenovirus respiratory infection. CD8 T cell deficiency in β2m-/- mice had no effect on peak viral replication in lungs, but clearance of virus was delayed in β2m-/- mice. Virus-induced weight loss and increases in bronchoalveolar lavage fluid total protein, IFN-γ, TNF-α, IL-10, CCL2, and CCL5 concentrations were less in β2m-/- mice than in controls. CD8 T cell depletion had similar effects on virus clearance, weight loss, and inflammation. Deficiency of IFN-γ or perforin had no effect on viral replication or inflammation, but perforin-deficient mice were partially protected from weight loss. CD8 T cells promote MAV-1-induced pulmonary inflammation via a mechanism that is independent of direct antiviral effects.
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Affiliation(s)
- Caitlyn T Molloy
- Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Harrison M Seltzer
- Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA
| | - Megan C Procario
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA
| | - Michael E Watson
- Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA
| | - Jason B Weinberg
- Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
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Ahmadi P, Haruyama T, Kobayashi N, de Voogd NJ, Tanaka J. Spongian Diterpenes from the Sponge Hyattella aff. intestinalis. Chem Pharm Bull (Tokyo) 2017; 65:874-877. [DOI: 10.1248/cpb.c17-00297] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Peni Ahmadi
- Department of Chemistry, Biology and Marine Science, University of the Ryukyus
| | | | | | | | - Junichi Tanaka
- Department of Chemistry, Biology and Marine Science, University of the Ryukyus
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40
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41
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Hai LT, Thach HN, Tuan TA, Nam DH, Dien TM, Sato Y, Kumasaka T, Suzuki T, Hanaoka N, Fujimoto T, Katano H, Hasegawa H, Kawachi S, Nakajima N. Adenovirus Type 7 Pneumonia in Children Who Died from Measles-Associated Pneumonia, Hanoi, Vietnam, 2014. Emerg Infect Dis 2016; 22:687-90. [PMID: 26926035 PMCID: PMC4806935 DOI: 10.3201/eid2204.151595] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
During a 2014 measles outbreak in Vietnam, postmortem pathologic examination of hospitalized children who died showed that adenovirus type 7 pneumonia was a contributory cause of death in children with measles-associated immune suppression. Adenovirus type 7 pneumonia should be recognized as a major cause of secondary infection after measles.
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Reis M, Ogonek J, Qesari M, Borges NM, Nicholson L, Preußner L, Dickinson AM, Wang XN, Weissinger EM, Richter A. Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications. Front Immunol 2016; 7:500. [PMID: 27895644 PMCID: PMC5107577 DOI: 10.3389/fimmu.2016.00500] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 10/26/2016] [Indexed: 12/13/2022] Open
Abstract
Allogeneic hematopoietic stem cell transplantation is associated with serious complications, and improvement of the overall clinical outcome of patients with hematological malignancies is necessary. During the last decades, posttransplant donor-derived adoptive cellular immunotherapeutic strategies have been progressively developed for the treatment of graft-versus-host disease (GvHD), infectious complications, and tumor relapses. To date, the common challenge of all these cell-based approaches is their implementation for clinical application. Establishing an appropriate manufacturing process, to guarantee safe and effective therapeutics with simultaneous consideration of economic requirements is one of the most critical hurdles. In this review, we will discuss the recent scientific findings, clinical experiences, and technological advances for cell processing toward the application of mesenchymal stromal cells as a therapy for treatment of severe GvHD, virus-specific T cells for targeting life-threating infections, and of chimeric antigen receptors-engineered T cells to treat relapsed leukemia.
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Affiliation(s)
- Monica Reis
- Haematological Sciences, Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK
| | - Justyna Ogonek
- Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover , Germany
| | | | - Nuno M Borges
- Haematological Sciences, Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK
| | - Lindsay Nicholson
- Haematological Sciences, Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK
| | | | - Anne Mary Dickinson
- Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Alcyomics Ltd., Newcastle upon Tyne, UK
| | - Xiao-Nong Wang
- Haematological Sciences, Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK
| | - Eva M Weissinger
- Transplantation Biology, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School , Hannover , Germany
| | - Anne Richter
- Miltenyi Biotec GmbH , Bergisch Gladbach , Germany
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Serological and molecular epidemiology of canine adenovirus type 1 in red foxes (Vulpes vulpes) in the United Kingdom. Sci Rep 2016; 6:36051. [PMID: 27796367 PMCID: PMC5086850 DOI: 10.1038/srep36051] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 10/11/2016] [Indexed: 11/09/2022] Open
Abstract
Canine adenovirus type 1 (CAV-1) causes infectious canine hepatitis (ICH), a frequently fatal disease which primarily affects canids. In this study, serology (ELISA) and molecular techniques (PCR/qPCR) were utilised to investigate the exposure of free-ranging red foxes (Vulpes vulpes) to CAV-1 in the United Kingdom (UK) and to examine their role as a wildlife reservoir of infection for susceptible species. The role of canine adenovirus type 2 (CAV-2), primarily a respiratory pathogen, was also explored. In foxes with no evidence of ICH on post-mortem examination, 29 of 154 (18.8%) red foxes had inapparent infections with CAV-1, as detected by a nested PCR, in a range of samples, including liver, kidney, spleen, brain, and lung. CAV-1 was detected in the urine of three red foxes with inapparent infections. It was estimated that 302 of 469 (64.4%) red foxes were seropositive for canine adenovirus (CAV) by ELISA. CAV-2 was not detected by PCR in any red foxes examined. Additional sequence data were obtained from CAV-1 positive samples, revealing regional variations in CAV-1 sequences. It is concluded that CAV-1 is endemic in free-ranging red foxes in the UK and that many foxes have inapparent infections in a range of tissues.
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Abstract
Keratoconjunctivitis caused by adenoviruses (epidemic keratoconjunctivitis, EKC, ICD-10 B30.0+) is common, can be severe and may cause significant morbidity. In the early stages of adenoviral infections it is often difficult to differentiate the clinical presentation from other causes of a red eye. Because of its highly contagious nature that can rapidly lead to epidemic outbreaks, prompt viral identification and prevention of further spread are major challenges. Even today the diagnosis is still mainly clinical, with laboratory tests only rarely contributing. New diagnostic tests, such as the Rapid Pathogen Detector (RPS, Sarasota FL) AdenoPlus detection kit, that are practical, rapid and inexpensive to use in the general practice may obviate these problems. Because of its highly resistant properties to desiccation and highly developed escape mechanisms which protect the virus from the host's immune response, long-term problems often remain. Remnants of viral proteins often persist on the corneal surface of Bowman's layer for a long time and may lead to the formation of subepithelial infiltrates. No treatment other than symptomatic eye drops is available. The major sequelae are subepithelial infiltrates, which are difficult to treat. Cyclosporin A eye drops are a good option with a low risk profile. The use of topical steroids can possibly be disadvantageous but can be discussed at all stages of the disease. As nosocomial spread of adenoviruses is relatively common, preventive measures remain a major responsibility for ophthalmologists.
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45
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Rodríguez E, Ip WH, Kolbe V, Hartmann K, Pilnitz-Stolze G, Tekin N, Gómez-Medina S, Muñoz-Fontela C, Krasemann S, Dobner T. Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection. J Infect Dis 2016; 215:70-79. [PMID: 28077585 DOI: 10.1093/infdis/jiw499] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Accepted: 10/13/2016] [Indexed: 11/12/2022] Open
Abstract
Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
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Affiliation(s)
- Estefanía Rodríguez
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - Wing Hang Ip
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - Viktoria Kolbe
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - Kristin Hartmann
- Institute for Neuropathology, University Medical Center Hamburg-Eppendorf
| | - Gundula Pilnitz-Stolze
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - Nilgün Tekin
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - Sergio Gómez-Medina
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - César Muñoz-Fontela
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
| | - Susanne Krasemann
- Institute for Neuropathology, University Medical Center Hamburg-Eppendorf
| | - Thomas Dobner
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.,German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany
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César Pereira Santos H, Nunes Vieira Almeida T, Souza Fiaccadori F, das Dôres de Paula Cardoso D, de Moraes Arantes A, Delleon da Silva H, Resende Alo Nagib P, Souza M. Adenovirus infection among allogeneic stem cell transplant recipients. J Med Virol 2016; 89:298-303. [PMID: 27197569 DOI: 10.1002/jmv.24579] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2016] [Indexed: 11/06/2022]
Abstract
The human adenovirus (HAdV) infection can cause severe disease in immunocompromised patients, such as those undergoing allogeneic hematopoietic stem cell transplant (ASCT). The main objective of this study was to prospectively monitor ASCT recipients for HAdV occurrence in a reference center in Brazil, and also to correlate viral positivity, viral load, molecular variant, clinical symptoms, and patients' prognosis. From October/2012 to October/2014, blood and feces of 21 ASCT recipients were screened for HAdV by Nested-PCR. Viral loads were determined by real-time PCR. In total, 57% of the patients had at least one positive sample (serum or feces) for HAdV. Patients presented significantly higher viral load in feces when compared to serum. Positive samples were characterized as HAdVs of species HAdV-C, -D, and -F. The main clinical symptom presented by infected patients was diarrhea, and Graft-versus-host disease (GVHD) was the main intercurrence. An association was observed between HAdV-positivity and diarrhea and also between HAdV-positivity and GVHD. Results from this study may contribute to a better understanding of the HAdV infection pattern in patients submitted to ASCT. Data therein highlight the importance of including HAdV testing during all routine laboratory exams performed on ASCT patients. J. Med. Virol. 89:298-303, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | | | | | | | | | - Hugo Delleon da Silva
- Laboratory of Molecular Genetics and Cytogenetics, Federal University of Goiás, Goiânia, Goiás, Brazil
| | | | - Menira Souza
- Laboratory of Virology, Federal University of Goiás, Goiânia, Goiás, Brazil
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Liu L, Qian Y, Zhang Y, Zhao L, Jia L, Dong H. Epidemiological aspects of rotavirus and adenovirus in hospitalized children with diarrhea: a 5-year survey in Beijing. BMC Infect Dis 2016; 16:508. [PMID: 27663354 PMCID: PMC5035450 DOI: 10.1186/s12879-016-1829-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2016] [Accepted: 09/10/2016] [Indexed: 12/03/2022] Open
Abstract
Background Diarrhea caused by viruses is a global problem among young children. We investigated two of the most important agents, rotavirus and adenovirus, to provide epidemiological evidence for a better understanding of their role among children with acute diarrhea. Methods A total of 3147 hospitalized children were enrolled in the study during 2010 ~ 2014. Antigen testing for rotavirus and DNA testing for adenovirus were performed on stool specimens collected from participants. Results There were 1985 cases of community-acquired diarrhea (CAD) and 1162 cases of hospital-acquired diarrhea (HAD). A total of 692 cases (22.0 %) were positive for rotavirus. Rotavirus was detected in more children with HAD than in those with CAD (24.6 %; 286/1162 vs. 20.5 %; 406/1985). A total of 324 cases (10.3 %) were adenovirus positive. There was a significant difference between the CAD group and HAD group (9.5 %; 188/1985 vs. 11.7 %; 136/1162: χ2 = 3.957, p = 0.047). Co-infection was found in only 35 children (1.11 %), and the co-infection rate was similar between the CAD and HAD groups (χ2 = 1.174, p = 0.279). There was no association between sex and the detection rate of these viruses. The positive rate was significantly different for rotavirus among CAD cases (χ2 = 27.979, p < 0.001) and for adenovirus (χ2 = 34.362, p < 0.001) in the five age groups. Compared with the other four age groups (15.8–19.8 %), the prevalence of rotaviruses was highest among children aged 12–24 months (28.6 %). Adenovirus was detected in 3.6 % of neonates compared with 5.8 % of infants from 1 to 6 months old; this increased to 12.0–13.8 % in children over 6 months of age. In HAD cases, age differences were not found for rotavirus and adenovirus. Seasonal variation of rotavirus was observed, with peaks in November and December and with through in July and August; however, no clear seasonal pattern was found for adenovirus. Conclusion Detection rates for rotavirus and adenovirus were significantly higher in children with HAD than those with CAD, but co-infection was very low. A high prevalence of rotavirus was identified in neonates with diarrhea. Vaccination for rotavirus gastroenteritis should be considered in neonates. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1829-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Liying Liu
- laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Yuan Qian
- laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China.
| | - You Zhang
- laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Linqing Zhao
- laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Liping Jia
- laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China
| | - Huijing Dong
- laboratory of Virology, Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, 100020, China
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Koçluk Y, Alyamaç Sukgen E. Different Clinical Presentations of the Same Epidemic Keratoconjunctivitis Outbreak in Premature Babies and Their Parents. Ocul Immunol Inflamm 2016; 26:406-411. [PMID: 27598721 DOI: 10.1080/09273948.2016.1219751] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
PURPOSE This study aims to report the differences in the findings of epidemic keratoconjunctivitis (EKC) between premature babies and their families at an outbreak of viral conjunctivitis. METHODS In this prospective observational study, premature babies (25 patients) who were diagnosed with EKC and the family members (30 patients, mother, father, or grandmother/father) who had EKC after contacting them were monitored closely. Patients were divided into two groups as preterm babies (group 1) and adults (group 2). RESULTS The present study investigated particularly subepithelial corneal infiltrates (SEI) occurrence after EKC, which was searched for at each visit in the 2nd week, 1st month, and 3rd month after EKC. Distribution of SEI in two groups was statistically significant at each visit (<0.0001). There was more SEI in group 2. CONCLUSIONS None of the preterm cases were found to have SEI after EKC.
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Affiliation(s)
- Yusuf Koçluk
- a Department of Ophthalmology, Adana Numune Training and Research Hospital, Eye Department , Adana , Turkey
| | - Emine Alyamaç Sukgen
- a Department of Ophthalmology, Adana Numune Training and Research Hospital, Eye Department , Adana , Turkey
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Lu X, Erdman DD. Quantitative real-time PCR assays for detection and type-specific identification of the endemic species C human adenoviruses. J Virol Methods 2016; 237:174-178. [PMID: 27363737 PMCID: PMC7173114 DOI: 10.1016/j.jviromet.2016.05.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 05/02/2016] [Accepted: 05/02/2016] [Indexed: 11/25/2022]
Abstract
Human adenoviruses (HAdVs) are medically important respiratory pathogens. Among the 7 recognized species (A-G), species C HAdVs (serotypes 1, 2, 5 and 6) are globally endemic and infect most people early in life. Species C HAdV infections are most often subclinical or mild and can lead to persistent shedding from the gastrointestinal and upper respiratory tracts. They can also cause severe disseminated disease in newborn and immunocompromised persons, where rapid and quantitative detection and identification of the virus would help guide therapeutic intervention. To this end, we developed quantitative type-specific real-time PCR (qPCR) assays for HAdV-1, -2, -5 and -6 targeting the HAdV hexon gene. All type-specific qPCR assays reproducibly detected as few as 5 copies/reaction of quantified hexon recombinant plasmids with a linear dynamic range of 8 log units (5-5×107 copies). No non-specific amplifications were observed with concentrated nucleic acid from other HAdV types or other common respiratory pathogens. Of 199 previously typed HAdV field isolates and positive clinical specimens, all were detected and correctly identified to type by the qPCR assays; 10 samples had 2 HAdV types and 1 sample had 3 types identified which were confirmed by amplicon sequencing. The species C HAdV qPCR assays permit rapid, sensitive, specific and quantitative detection and identification of four recognized endemic HAdVs. Together with our previously developed qPCR assays for the epidemic respiratory HAdVs, these assays provide a convenient alternative to classical typing methods.
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Affiliation(s)
- Xiaoyan Lu
- Gastroenteritis and Respiratory Viruses Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Dean D Erdman
- Gastroenteritis and Respiratory Viruses Laboratory Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
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Abstract
ABSTRACT
Gastrointestinal infections in the immunocompromised host are caused by the common bacterial, viral, fungal, and parasitic agents that also cause infections in the immunocompetent host. Of special consideration is that immunocompromised patients may be at increased risk for infection or disease severity and by pathogens not seen in the competent host. This chapter reviews the various agents, risk factors, and diagnostic approaches to detect gastrointestinal infections in this patient population.
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