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Narsana N, Ha D, Ho DY. Treating Adenovirus Infection in Transplant Populations: Therapeutic Options Beyond Cidofovir? Viruses 2025; 17:599. [PMID: 40431613 DOI: 10.3390/v17050599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2025] [Revised: 04/21/2025] [Accepted: 04/22/2025] [Indexed: 05/29/2025] Open
Abstract
Adenovirus (AdV) infections can lead to significant morbidity and increased mortality in immunocompromised populations such as hematopoietic stem cell and solid organ transplant recipients. This review evaluates currently available and emerging therapies for AdV infections. Cidofovir, while most commonly used, is limited by its variable efficacy and nephrotoxicity. This led to the development of brincidofovir, which has a better safety profile and great in vitro potency against AdV. The use of ribavirin and ganciclovir has been reported in the literature, but their use is limited due to inconsistent efficacy. Immune-based approaches, such as adoptive T-cell therapy, have shown promise in achieving viral clearance and improving survival but remain constrained by challenges related to manufacturing complexity and risks of graft-versus-host disease. This review underscores the need for standardized treatment protocols as well as comparative studies to identify optimal dosing and timing to initiate treatment. Future research should focus on individualized treatment approaches and the development of novel therapeutic agents to address the unmet clinical needs of AdV management.
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Affiliation(s)
- Niyati Narsana
- Division of Infectious Diseases, UC Davis Medical Center, Sacramento, CA 95817, USA
| | - David Ha
- Stanford Antimicrobial Safety and Sustainability Program, Stanford Health Care, Stanford, CA 94305, USA
- Division of Infectious Diseases & Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Dora Y Ho
- Division of Infectious Diseases & Geographic Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
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Yu C, Xu Y. Development and validation of a nomogram for predicting severe adenovirus pneumonia in children. Front Pediatr 2025; 13:1428090. [PMID: 40309168 PMCID: PMC12040940 DOI: 10.3389/fped.2025.1428090] [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: 05/05/2024] [Accepted: 04/01/2025] [Indexed: 05/02/2025] Open
Abstract
Background Adenovirus is a common respiratory pathogen in children. Severe adenovirus pneumonia(SAP) can cause serious complications in children. In this study, The nomogram we developed quantifies the severity of adenoviral pneumonia into percentage risk in a scientific, simple, intuitive, and effective manner, showing unique advantages compared to current empirical assessments and chart evaluations. Methods 228 children with adenoviral pneumonia admitted to the Respiratory Department of Tianjin Children's Hospital from January 2020 to January 2024 were collected. According to the clinical manifestations, the patients were divided into SAP (SAP) group and general adenoviral pneumonia (GAP) group. The clinical manifestations, laboratory indexes and some imaging data of the two groups were observed. Univariate and multivariate logical regression were used to select the variables of SAP. Select the prediction factor, construct the prediction model, and express the prediction factor with nomogram. Calibration curve, ROC curve and clinical decision curve were used to evaluate the performance and clinical practicability of the prediction model. Results The time of fever and complications in SAP group were longer than those in GAP group. The data of diagnosis and prediction of adenoviral pneumonia and clinical significance were included in logical regression. Univariate logical regression was performed first, followed by multivariate logical regression, atelectasis (OR = 2.757; 95%CI, 1.454-5.34), FER (OR = 2.232; 95%CI, 1.442-3.536), IL-6 (OR = 2.001; 95%CI, 1.368-3.009), LDH (OR = 2.860; 95%CI, 1.839-4.680) were independent significant predictors of SAP. The probability of prediction is consistent with that of observation in the training queue (0.819) and the verification queue (0.317). The area under the ROC curve of the model group and verification group was 0.873 (95%CI: 0.82-0.926) and 0.738 (95%CI: 0.620-0.856), respectively. The clinical decision curve indicated that the prediction model had high clinical practicability. Conclusion Atelectasis, LDH and IL-6 are predictive factors of SAP. The construction of clinical predictive model nomogram plays a key role in simple and efficient judgment of the occurrence and development of SAP, and has value in guiding clinical treatment.
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Affiliation(s)
| | - Yongsheng Xu
- Department of Pediatric Respiratory Medicine, Tianjin Children's Hospital (Children's Hospital, Tianjin University), Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin, China
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Li X, Ma J, Li Y, Hu Z. One-year epidemiological patterns of respiratory pathogens across age, gender, and seasons in Chengdu during the post-COVID era. Sci Rep 2025; 15:357. [PMID: 39747544 PMCID: PMC11697200 DOI: 10.1038/s41598-024-84586-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Accepted: 12/24/2024] [Indexed: 01/04/2025] Open
Abstract
Respiratory tract infections caused by various pathogens remain a significant public health concern due to their high prevalence and potential for severe complications. This study systematically analyzed the epidemiological characteristics of six common respiratory pathogens-Chlamydia pneumoniae (CP), Mycoplasma pneumoniae (MP), Adenovirus (AdV), Influenza A virus (FluA), Influenza B virus (FluB), and Respiratory Syncytial Virus (RSV)-in patients from Sichuan Jinxin Xinan Women and Children's Hospital between April 2023 and March 2024. Throat swab samples were collected from a total of 22,717 individuals. Each sample was processed using the AUTOMOLEC 3000 analyzer and the PCR-fluorescent probe method. The results showed that 10,171 (44.8%) individuals tested positive for at least one pathogen. MP had the highest overall positive rate (21.83%), followed by FluA (17.50%) and FluB (14.84%). MP showed the highest mean monthly (average) positive rate (16.84% ± 8.41). Significant differences were found between MP and AdV, CP and RSV in average positive rate (p < 0.05). Co-infection analysis revealed frequent associations between MP and AdV, MP and CP, and FluB with MP. Seasonal analysis indicated distinct peaks: FluA and FluB in winter, RSV in spring, and MP in summer, autumn and winter. Age-stratified analysis showed higher positivity rates of RSV in children aged 0-6 years, MP and CP in the 7-17 years group. Gender-based differences were only observed in RSV positive samples. These findings provide crucial insights into the prevalence and seasonal distribution of respiratory pathogens in Chengdu, offering valuable data to inform public health strategies in the post-COVID era.
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Affiliation(s)
- Xiang Li
- Sichuan Jinxin Xinan Women and Children Hospital, Chengdu, China
| | - Jian Ma
- Sichuan Jinxin Xinan Women and Children Hospital, Chengdu, China
| | - Yi Li
- Aba Teachers College, Wenchuan, Scichuan, China
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Wang J, Feng Q, Duan Y, Ai J, Zhu Y, Wang R, Chen X, Lu G, Sun Y, Li C, Jin R, Shang Y, Xu B, Xie Z. Human adenovirus type 4 (HAdV-4) associated acute respiratory tract infection in children & genetic characteristics of HAdV-4 in China: a prospective multicenter study. BMC Infect Dis 2024; 24:936. [PMID: 39251906 PMCID: PMC11385803 DOI: 10.1186/s12879-024-09835-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 08/28/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Human adenovirus (HAdV) is an important pathogen causing acute respiratory infection (ARI) in children. Many countries, including China, have experienced sporadic or outbreaks related to HAdV-4, and death cases were reported. However, there is little research on HAdV-4 and the epidemic situation of HAdV-4 in China is little known. This study was designed to comprehend the prevalence and genetic characteristics of HAdV-4 in ARI children in China. METHODS Respiratory tract samples from ARI children hospitalized in six hospitals of Northern and Southern China from 2017 to 2020 were collected for HAdV detection and typing. Clinical information was collected from HAdV-4 positive patients for clinical characteristics and epidemiological analysis. The main capsid proteins and the whole genome sequences were amplified and sequenced for bioinformatics analysis. RESULTS There were 2847 ARI children enrolled, and 156 (5.48%) HAdV positive samples were detected. Eleven HAdV-4 positive samples were identified, accounting for 0.39% of the total samples and 7.05% of the HAdV positive samples. The main manifestations were fever and cough. Two children had conjunctivitis. Two children were diagnosed with severe pneumonia and developed respiratory failure. One of them developed hemophagocytic syndrome and checked in pediatric intensive care unit (PICU). This child had ventricular septal defect. All the children recovered. The isolated strains of HAdV-4 obtained in this study and the reference strains from China located in the same phylogenetic branch (HAdV-4a), while the prototype strain and vaccine strains formed another branch (HAdV-4p). Upon comparison with the prototype strain, there were a few amino acid mutations existing in three major capsid proteins. According to recombination analysis, no new recombination was found. CONCLUSIONS The detection rate of HAdV-4 in children hospitalized with ARI was 0.39% in the total samples and 7.05% of all HAdV positive samples. HAdV-4 isolates obtained in this study and other reference strains from China belonged to the HAdV-4a subtype. Our data provided reference for the monitoring, prevention and control of HAdV-4, as well as the research and development of vaccines and drugs.
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Affiliation(s)
- Jinjin Wang
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Qianyu Feng
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Yali Duan
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Junhong Ai
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Yun Zhu
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Ran Wang
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Xiangpeng Chen
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Gen Lu
- Department of Respiratory, GuangZhou Women and Children's Medical Center, GuangZhou, 510623, China
| | - Yun Sun
- Department of General Pediatrics, Yinchuan Women and Children Healthcare Hospital, Yinchuan, 750002, China
| | - Changchong Li
- Department of Respiratory, the 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325027, China
| | - Rong Jin
- Department of Respiratory, Guiyang Maternal and Child Health Hospital, Guiyang, 550003, China
| | - Yunxiao Shang
- Department of Pediatric Respiratory, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Baoping Xu
- National Clinical Research Center for Respiratory Diseases, Department of Respiratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Zhengde Xie
- Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
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Piñana JL, Cesaro S, Mikulska M, Verweij PE, Bergeron A, Neofytos D, Styczynski J, Sánchez-Ortega I, Greco R, Onida F, Yakoub-Agha I, Averbuch D, Cámara RDL, Ljungman P. Pitfalls in definitions on respiratory viruses and particularities of Adenovirus infection in hematopoietic cell transplantation patients: Recommendations from the EBMT practice harmonization and guidelines committee. Curr Res Transl Med 2024; 72:103461. [PMID: 39032263 DOI: 10.1016/j.retram.2024.103461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 07/10/2024] [Indexed: 07/23/2024]
Abstract
In 2023, the EBMT Practice harmonization and Guidelines Committee partnered with the EBMT Infection Diseases Working Party (IDWP) to undertake the task of delivering best practice recommendations, aiming to harmonize by expert consensus, the already existing definitions and future epidemiological and clinical studies among centers of the EBMT network. To attain this objective, a group of experts in the field was convened. The workgroup identified and discussed some critical aspects in definitions of community-acquired respiratory viruses (CARV) and adenovirus (ADV) infections in recipient of hematopoietic cell transplant (HCT). The methodology involved literature review and expert consensus. For CARV, expert consensus focused on defining infection severity, infection duration, and establishing criteria for lower respiratory tract disease (LRTD). For ADV, the expert consensus focused on surveillance methods and the definitions of ADV infection, certainty levels of disease, response to treatment, and attributable mortality. This consensus workshop provided indications to EBMT community aimed at facilitating data collection and consistency in the EBMT registry for respiratory viral infectious complications.
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Affiliation(s)
- José Luis Piñana
- Department of Hematology. Hospital Clínico Universitario of Valencia, INCLIVA, Biomedical Research Institute, Valencia, Spain
| | - Simone Cesaro
- Pediatric Hematology Oncology, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Malgorzata Mikulska
- Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Paul E Verweij
- Department of Medical Microbiology and Radboudumc-CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Anne Bergeron
- Division of Pulmonology, University Hospitals of Geneva, Geneva, Switzerland
| | - Dionysios Neofytos
- Transplant Infectious Diseases Unit, Division of Infectious Diseases, University Hospitals Geneva, Geneva, Switzerland
| | - Jan Styczynski
- Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun UMK, University Hospital, Bydgoszcz, Poland
| | | | - Raffaella Greco
- Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesco Onida
- Hematology and BMT Unit ASST Fatebenefratelli, Sacco University of Milan, Italy
| | | | - Dina Averbuch
- Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Jerusalem, Israel
| | | | - Per Ljungman
- Dept. of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska Comprehensive Cancer Center, Karolinska University Hospital Huddinge, Stockholm, Sweden; Dept. of Medicine Huddinge, Karolinska Institutet (KI), Stockholm, Sweden.
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Büttner-Herold M, Amann K, Velden J. [Nephropathology of infectious disease]. PATHOLOGIE (HEIDELBERG, GERMANY) 2024; 45:254-260. [PMID: 38598098 DOI: 10.1007/s00292-024-01322-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 03/05/2024] [Indexed: 04/11/2024]
Abstract
Infections can affect the kidney via different pathways. Urinary tract infections can directly involve the renal tissue by spreading along pre-existing canalicular structures. Such an ascending infection can manifest as a highly active and purulent or even abscessing interstitial nephritis or as a chronic-fibrosing process in recurrent pyelonephritis. Viral infections can also use the canalicular route as in polyomavirus nephropathy or spread via the blood stream in a hematogenous manner as in the case of cytomegalovirus or hantavirus infections. Likewise, bacterial infections can reach the kidney via the blood in the case of systemic infection. Another large group of nephropathies taking place as a sequel of infections includes infection-related glomerulonephritides (IRGN), which are mediated by a series of immunological mechanisms. These IRGN can be subdivided according to their temporal association with the infectious process, occurring either after the infection has healed (postinfectious) or accompanying the ongoing infectious process (parainfectious). The latter, in particular, is of increasing importance in the daily practice of nephropathologists, especially in older patients. A number of other glomerulonephritis forms, i.e., membranous or membranoproliferative forms, can occur as a consequence of infection. In addition, infections can trigger nephropathies, such as thrombotic microangiopathy. The present article gives an overview of morphologic changes in renal parenchyma that take place as a consequence of infectious processes, with particular focus on IRGN.
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Affiliation(s)
- Maike Büttner-Herold
- Abt. Nephropathologie, Patholog. Institut, Friedrich-Alexander-Universität Erlangen-Nürnberg/Universitätsklinikum Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Deutschland.
| | - Kerstin Amann
- Abt. Nephropathologie, Patholog. Institut, Friedrich-Alexander-Universität Erlangen-Nürnberg/Universitätsklinikum Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Deutschland
| | - Joachim Velden
- Abt. Nephropathologie, Patholog. Institut, Friedrich-Alexander-Universität Erlangen-Nürnberg/Universitätsklinikum Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Deutschland
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Hissong E, Arora K, Andy C, Jessurun J, Yantiss RK. Histologic Manifestations of Gastrointestinal Adenovirus Infection After Stem Cell Transplant. Am J Surg Pathol 2024; 48:521-527. [PMID: 38329327 DOI: 10.1097/pas.0000000000002197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
Adenovirus can cause severe disease in hematopoietic stem cell transplant (HSCT) patients. Histopathologic features of this infection in gastrointestinal biopsies and their distinction from graft-versus-host disease (GVHD) have been incompletely studied. We retrospectively identified patients with gastrointestinal adenovirus infection. H&E-stained sections were reviewed and the histologic features were recorded. The extent of immunostaining was determined using a semiquantitative scale and a maximum number of positive cells per high-power field. Information regarding the clinical course and endoscopic findings were obtained from the electronic medical records. The study group included 32 HSCT patients. Most (81%) presented with diarrhea and detectable virus in the serum. Twenty patients had multiorgan involvement in the gastrointestinal tract, mostly in the duodenum (62%) and colon (56%). Characteristic features included apoptotic epithelial cells with nuclear disarray (84%) and tufted aggregates of degenerating epithelial cells (69%), the latter of which was more commonly seen in the study population more than a control group of HSCT patients with GI involvement by GVHD. Viral inclusions were limited to the superficial epithelium in 59% of samples, and the density of viral inclusions within biopsies was variable (grade 1: 40%, grade 2: 38%, and grade 3: 22%). Following therapy, 10 patients (30%) improved and 14 (42%) had progressive disease. Patients with disease progression were often older (64 vs. 36 years, P =0.01) with higher serologic viral loads, prior history of GVHD, multifocal involvement, and increased number and density of immunoreactive nuclei. Adenovirus infection elicits a spectrum of histologic changes that can simulate or occur in combination with gastrointestinal GVHD. Patients with progressive disease are more likely to have high viral loads and more extensive infection of the gastrointestinal tract.
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Affiliation(s)
| | | | - Caroline Andy
- Population Health Sciences, Weill Cornell Medicine, New York, NY
| | | | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Miller School of Medicine, University of Miami, Miami, FL
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Dawson LM, Alshawabkeh M, Schröer K, Arakrak F, Ehrhardt A, Zhang W. Role of homologous recombination/recombineering on human adenovirus genome engineering: Not the only but the most competent solution. ENGINEERING MICROBIOLOGY 2024; 4:100140. [PMID: 39628785 PMCID: PMC11611009 DOI: 10.1016/j.engmic.2024.100140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 02/06/2024] [Accepted: 02/06/2024] [Indexed: 12/06/2024]
Abstract
Adenoviruses typically cause mild illnesses, but severe diseases may occur primarily in immunodeficient individuals, particularly children. Recently, adenoviruses have garnered significant interest as a versatile tool in gene therapy, tumor treatment, and vaccine vector development. Over the past two decades, the advent of recombineering, a method based on homologous recombination, has notably enhanced the utility of adenoviral vectors in therapeutic applications. This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors. Additionally, it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.
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Affiliation(s)
| | | | | | - Fatima Arakrak
- Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke University, Stockumer Str. 10 58453 Witten, Germany
| | - Anja Ehrhardt
- Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke University, Stockumer Str. 10 58453 Witten, Germany
| | - Wenli Zhang
- Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), School of Medicine, Faculty of Health, Witten/Herdecke University, Stockumer Str. 10 58453 Witten, Germany
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Lin F, Zhou Q, Li W, Xiao W, Li S, Liu B, Li H, Cui Y, Lu R, Li Y, Zhang Y, Pan P. A prediction model for acute respiratory distress syndrome in immunocompetent adults with adenovirus-associated Pneumonia: a multicenter retrospective analysis. BMC Pulm Med 2023; 23:431. [PMID: 37932725 PMCID: PMC10629070 DOI: 10.1186/s12890-023-02742-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 10/30/2023] [Indexed: 11/08/2023] Open
Abstract
BACKGROUND In recent years, the number of human adenovirus (HAdV)-related pneumonia cases has increased in immunocompetent adults. Acute respiratory distress syndrome (ARDS) in these patients is the predominant cause of HADV-associated fatality rates. This study aimed to identify early risk factors to predict early HAdV-related ARDS. METHODS Data from immunocompetent adults with HAdV pneumonia between June 2018 and May 2022 in ten tertiary general hospitals in central China was analyzed retrospectively. Patients were categorized into the ARDS group based on the Berlin definition. The prediction model of HAdV-related ARDS was developed using multivariate stepwise logistic regression and visualized using a nomogram. RESULTS Of 102 patients with adenovirus pneumonia, 41 (40.2%) developed ARDS. Overall, most patients were male (94.1%), the median age was 38.0 years. Multivariate logistic regression showed that dyspnea, SOFA (Sequential Organ Failure Assessment) score, lactate dehydrogenase (LDH) and mechanical ventilation status were independent risk factors for this development, which has a high mortality rate (41.5%). Incorporating these factors, we established a nomogram with good concordance statistics of 0.904 (95% CI 0.844-0.963) which may help to predict early HAdV-related ARDS. CONCLUSION A nomogram with good accuracy in the early prediction of ARDS in patients with HAdV-associated pneumonia may could contribute to the early management and effective treatment of severe HAdV infection.
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Affiliation(s)
- Fengyu Lin
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China
| | - Qianhui Zhou
- Department of Respiratory Medicine, Zhuzhou Central Hospital, Zhuzhou, China
| | - Wen Li
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China
| | - Wenchao Xiao
- Department of Cardiology, Yiyang Central Hospital, Yiyang, China
| | - Sha Li
- Department of Radiology, Xiangya Hospital, Central South University, Changsha, China
| | - Ben Liu
- Department of Emergency Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Haitao Li
- First Department of Thoracic Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, China
| | - Yanhui Cui
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China
| | - Rongli Lu
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China.
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China.
- Furong Laboratory, Changsha, China.
| | - Yi Li
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China.
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China.
- Furong Laboratory, Changsha, China.
| | - Yan Zhang
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China.
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China.
- Furong Laboratory, Changsha, China.
| | - Pinhua Pan
- Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, National Key Clinical Specialty, Central South University, Changsha, China.
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, China.
- Furong Laboratory, Changsha, China.
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10
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Page NA, Netshikweta R, Tate JE, Madhi SA, Parashar UD, Groome MJ. Microorganisms Detected in Intussusception Cases and Controls in Children <3 Years in South Africa From 2013 to 2017. Open Forum Infect Dis 2023; 10:ofad458. [PMID: 37720699 PMCID: PMC10500044 DOI: 10.1093/ofid/ofad458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 08/31/2023] [Indexed: 09/19/2023] Open
Abstract
A matched case-control evaluated infectious etiologies in children <3 years in post-rotavirus vaccine intussusception surveillance. Adenovirus and adenovirus types C, A, and B were detected more frequently in cases versus controls at statistically significant values. Wild-type rotavirus, rotavirus vaccine strains, and human herpesvirus were not associated with intussusception.
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Affiliation(s)
- Nicola Anne Page
- National Institute for Communicable Diseases, A Division of the National Health Laboratory Services, Johannesburg, South Africa
- Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Rembuluwani Netshikweta
- National Institute for Communicable Diseases, A Division of the National Health Laboratory Services, Johannesburg, South Africa
| | - Jacqueline E Tate
- Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Shabir A Madhi
- South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Umesh D Parashar
- Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Michelle J Groome
- South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit (VIDA), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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11
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Geisler A, Dieringer B, Elsner L, Klingel K, Klopfleisch R, Vornlocher HP, Kurreck J, Fechner H. Lipid nanoparticle-encapsulated, chemically modified anti-adenoviral siRNAs inhibit hepatic adenovirus infection in immunosuppressed Syrian hamsters. MOLECULAR THERAPY. NUCLEIC ACIDS 2023; 32:923-936. [PMID: 37346978 PMCID: PMC10280093 DOI: 10.1016/j.omtn.2023.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 05/10/2023] [Indexed: 06/23/2023]
Abstract
RNA interference has demonstrated its potential as an antiviral therapy for treatment of human adenovirus (hAd) infections. The only existing viral vector-based system for delivery of anti-adenoviral artificial microRNAs available for in vivo use, however, has proven to be inefficient in therapeutic applications. In this study, we investigated the potential of stabilized small interfering RNA (siRNA) encapsulated in lipid nanoparticles (LNPs) for treatment of hepatic hAd serotype 5 (hAd5) infection in an hAd infection model using immunosuppressed Syrian hamsters. The siRNA sipTPmod directed against the adenoviral pre-terminal protein (pTP) and containing 2'-O-methyl modifications as well as phosphorothioate linkages effectively inhibited hAd5 infection in vitro. In light of this success, sipTPmod was encapsulated in LNPs containing the cationic lipid XL-10, which enables hepatocyte-specific siRNA transfer, and injected intravenously into hAd5-infected immunosuppressed Syrian hamsters. This resulted in a significant reduction of liver hAd5 titers, a trend toward reduced liver injury and inflammation, and reduction of viral titers in the blood and spleen compared with hAd5-infected animals that received a non-silencing siRNA. These effects were demonstrated in animals infected with low and moderate doses of hAd5. These data demonstrate that hepatic hAd5 infection can be successfully treated with anti-adenoviral sipTPmod encapsulated in LNPs.
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Affiliation(s)
- Anja Geisler
- Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - Babette Dieringer
- Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - Leslie Elsner
- Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - Karin Klingel
- Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany
| | - Robert Klopfleisch
- Institute of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163 Berlin, Germany
| | | | - Jens Kurreck
- Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
| | - Henry Fechner
- Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
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12
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Muto T, Imaizumi S, Kamoi K. Viral Conjunctivitis. Viruses 2023; 15:v15030676. [PMID: 36992385 PMCID: PMC10057170 DOI: 10.3390/v15030676] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 02/25/2023] [Accepted: 02/28/2023] [Indexed: 03/08/2023] Open
Abstract
Viruses account for 80% of all cases of acute conjunctivitis and adenovirus; enterovirus and herpes virus are the common causative agents. In general, viral conjunctivitis spreads easily. Therefore, to control the spread, it is crucial to quickly diagnose illnesses, strictly implement hand washing laws, and sanitize surfaces. Swelling of the lid margin and ciliary injection are subjective symptoms, and eye discharge is frequently serofibrinous. Preauricular lymph node swelling can occasionally occur. Approximately 80% of cases of viral conjunctivitis are caused by adenoviruses. Adenoviral conjunctivitis may become a big global concern and may cause a pandemic. Diagnosis of herpes simplex viral conjunctivitis is crucial for using corticosteroid eye solution as a treatment for adenovirus conjunctivitis. Although specific treatments are not always accessible, early diagnosis of viral conjunctivitis may help to alleviate short-term symptoms and avoid long-term consequences.
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Affiliation(s)
- Tetsuaya Muto
- Department of Ophthalmology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Japan
- Imaizumi Eye Hospital, Koriyama 963-8877, Japan
- Correspondence:
| | | | - Koju Kamoi
- Department of Ophthalmology and Visual Science, Tokyo Medical Dental University, Tokyo 113-8519, Japan
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13
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Saint-Pierre Contreras G, Conei Valencia D, Lizama L, Vargas Zuñiga D, Avendaño Carvajal LF, Ampuero Llanos S. An Old Acquaintance: Could Adenoviruses Be Our Next Pandemic Threat? Viruses 2023; 15:330. [PMID: 36851544 PMCID: PMC9966032 DOI: 10.3390/v15020330] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 01/26/2023] Open
Abstract
Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases in pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for the first time in oropharyngeal lymphatic tissue. To date, more than 110 types of HAdV have been described, with different cellular tropisms. They can cause respiratory and gastrointestinal symptoms, even urinary tract inflammation, although most infections are asymptomatic. However, there is a population at risk that can develop serious and even lethal conditions. These viruses have a double-stranded DNA genome, 25-48 kbp, 90 nm in diameter, without a mantle, are stable in the environment, and resistant to fat-soluble detergents. Currently the diagnosis is made with lateral flow immunochromatography or molecular biology through a polymerase chain reaction. This review aimed to highlight the HAdV variability and the pandemic potential that a HAdV3 and 7 recombinant could have considering the aggressive outbreaks produced in health facilities. Herein, we described the characteristics of HAdV, from the infection to treatment, vaccine development, and the evaluation of the social determinants of health associated with HAdV, suggesting the necessary measures for future sanitary control to prevent disasters such as the SARS-CoV-2 pandemic, with an emphasis on the use of recombinant AdV vaccines to control other potential pandemics.
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Affiliation(s)
- Gustavo Saint-Pierre Contreras
- Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile
- Unidad Microbiología, Hospital Barros Luco Trudeau, Servicio de Salud Metropolitano Sur, Santiago 8900000, Chile
| | - Daniel Conei Valencia
- Departamento de Ciencias de la Salud, Universidad de Aysén, Coyhaique 5951537, Chile
| | - Luis Lizama
- Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile
| | - Daniela Vargas Zuñiga
- Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile
| | - Luis Fidel Avendaño Carvajal
- Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile
| | - Sandra Ampuero Llanos
- Programa de Virología, ICBM, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago 8380453, Chile
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14
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MacNeil KM, Dodge MJ, Evans AM, Tessier TM, Weinberg JB, Mymryk JS. Adenoviruses in medicine: innocuous pathogen, predator, or partner. Trends Mol Med 2023; 29:4-19. [PMID: 36336610 PMCID: PMC9742145 DOI: 10.1016/j.molmed.2022.10.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/09/2022] [Accepted: 10/03/2022] [Indexed: 11/06/2022]
Abstract
The consequences of human adenovirus (HAdV) infections are generally mild. However, despite the perception that HAdVs are harmless, infections can cause severe disease in certain individuals, including newborns, the immunocompromised, and those with pre-existing conditions, including respiratory or cardiac disease. In addition, HAdV outbreaks remain relatively common events and the recent emergence of more pathogenic genomic variants of various genotypes has been well documented. Coupled with evidence of zoonotic transmission, interspecies recombination, and the lack of approved AdV antivirals or widely available vaccines, HAdVs remain a threat to public health. At the same time, the detailed understanding of AdV biology garnered over nearly 7 decades of study has made this group of viruses a molecular workhorse for vaccine and gene therapy applications.
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Affiliation(s)
- Katelyn M MacNeil
- Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
| | - Mackenzie J Dodge
- Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
| | - Andris M Evans
- Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
| | - Tanner M Tessier
- Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada
| | - 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.
| | - Joe S Mymryk
- Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada; Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON, Canada; Department of Oncology, The University of Western Ontario, London, ON, Canada; London Regional Cancer Program, Lawson Health Research Institute, London, ON, Canada.
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15
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Gong K, Xu X, Yao J, Ye S, Yu X, Tu H, Lan Y, Fan YC, Shi Y. Acute hepatitis of unknown origin in children: A combination of factors. Front Pharmacol 2022; 13:1056385. [PMID: 36438816 PMCID: PMC9698116 DOI: 10.3389/fphar.2022.1056385] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 10/31/2022] [Indexed: 08/16/2023] Open
Abstract
On 5 April 2022, the World Health Organization was notified of 10 cases of severe acute hepatitis of unknown etiology in children under 10 years of age in the United Kingdom. Although the exact cause of a proportion of pediatric acute hepatitis and acute liver failure cases was unclear, the above event has caused widespread concern worldwide. As of 14 September 2022, approximately 1,296 probable cases of acute hepatitis of unknown etiology have been reported from 37 countries/regions, of which approximately 55 required or received liver transplantation and 29 died. Although the etiology of acute hepatitis of unknown origin in children remains unclear, many hypotheses have been proposed about the disease. Instead of individual factors such as "adenovirus infection," "SARS-CoV-2 related," and "Adeno-associated virus 2 with helper virus coinfection," it is more likely due to a combination of factors. Accordingly, there is an urgent need for more data and research to clarify the disease etiology. This review aims to provide a historical perspective of acute hepatitis of unknown etiology in children in the past decades and summarize the current hypothesis and evidence on this emerging disease.
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Affiliation(s)
- Kai Gong
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xianbin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Junjie Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shaoheng Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xia Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Huilan Tu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yan Lan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yu-chen Fan
- Department of Hepatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
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16
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Christian VJ, Sarwar R, Resch JC, Lim S, Somani A, Larson-Nath C, McAllister S, Thielen BK, Adeyi O, Chinnakotla S, Bhatt H. Use of Cidofovir for Safe Transplantation in a Toddler with Acute Liver Failure and Adenovirus Viremia. Case Rep Transplant 2022; 2022:9426175. [PMID: 36405892 PMCID: PMC9668457 DOI: 10.1155/2022/9426175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 10/21/2022] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Since October 2021, there have been more than 500 cases of severe hepatitis of unknown origin in children reported worldwide, including 180 cases in the U.S. The most frequently detected potential pathogen to date has been adenovirus, typically serotype 41. Adenovirus is known to cause a self-limited infection in the immunocompetent host. However, in immunosuppressed individuals, severe or disseminated infections may occur. METHOD We present the case of a two-year-old female who presented with cholestatic hepatitis and acute liver failure (ALF). Work up for etiologies of ALF was significant for adenovirus viremia, but liver biopsy was consistently negative for the virus. The risk for severe adenoviral infection in the setting of anticipated immunosuppression prompted us to initiate cidofovir to decrease viral load prior to undergoing liver transplantation. RESULT Our patient received a successful liver transplant, cleared the viremia after 5 doses of cidofovir, and continues to maintain allograft function without signs of infection at the time of this report, 5 months posttransplant. CONCLUSION Recent reports of pediatric hepatitis cases may be associated with adenoviral infection although the exact relationship is unclear. There is the possibility of the ongoing SARS-CoV-2 environment, or other immunologic modifying factors. All patients presenting with hepatitis or acute liver failure should be screened for adenovirus and reported to state health departments. Cidofovir may be used to decrease viral load prior to liver transplantation, to decrease risk of severe adenoviral infection.
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Affiliation(s)
- Vikram J. Christian
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Raiya Sarwar
- Department of Medicine, Division of Transplant Hepatology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Joseph C. Resch
- Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Sarah Lim
- Minnesota Department of Health, St. Paul, Minnesota, USA
| | - Arif Somani
- Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Catherine Larson-Nath
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Shane McAllister
- Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Beth K. Thielen
- Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
| | - Oyedele Adeyi
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Srinath Chinnakotla
- Department of Surgery, Division of Transplant Surgery, University of Minnesota, Minneapolis, Minnesota, USA
| | - Heli Bhatt
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Minnesota Masonic Children's Hospital, Minneapolis, Minnesota, USA
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17
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Wu YJ, Chen F, Zhao Y, Zhang YM, Cao JJ, Lin GQ, Wang TJ, Xia J, Tang XW, Xue SL, Jin ZM, Wu DP. [A clinical analysis of adenovirus infection diagnosed by metagenomic next-generation sequencing or the diagnosis of adenovirus infection after haploidentical hematopoietic stem cell transplantation clinical analysis of six cases]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:869-872. [PMID: 36709204 PMCID: PMC9669634 DOI: 10.3760/cma.j.issn.0253-2727.2022.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Indexed: 11/28/2022]
Affiliation(s)
- Y J Wu
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - F Chen
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - Y Zhao
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - Y M Zhang
- Department of Hematology, Huai'an Second People's Hospital, Huai'an 223002, China
| | - J J Cao
- Department of Hematology, Yinzhou People's Hospital, Ningbo 315040, China
| | - G Q Lin
- Department of Hematology, Huai'an Second People's Hospital, Huai'an 223002, China
| | - T J Wang
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - J Xia
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - X W Tang
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - S L Xue
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - Z M Jin
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
| | - D P Wu
- First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215006, China
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18
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Qashqari FSI. Human Mastadenovirus Infections in Children: A Review of the Current Status in the Arab World in the Middle East and North Africa. CHILDREN (BASEL, SWITZERLAND) 2022; 9:1356. [PMID: 36138665 PMCID: PMC9497993 DOI: 10.3390/children9091356] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 08/08/2022] [Accepted: 09/03/2022] [Indexed: 11/17/2022]
Abstract
Human mastadenovirus (HAdV) is a non-enveloped icosahedral virus with double-stranded DNA genomes. The mortality rate of HAdV infections can reach 35.5%, while gastroenteritis HAdV infections, HAdV pneumonia, and disseminated disease tend to show a worse outcome, with rates ranging from 44.2% to 50%. In addition, HAdV can cause infections at any age but most commonly in the pediatric population, especially in young children and infants. Therefore, this review aims to assess the current status of HAdV infections among children in the Arab World, particularly in the Middle East and North Africa. Web of Science, Scopus, PubMed, EMBASE, and Google Scholar databases for publications in English were searched up to July 2022 for relevant articles. The literature search yielded a total of 21 studies, which were included in this review. Studies reporting HAdV infections in children were conducted in 17 out of the 22 countries. The average prevalence rate of HAdV infections in children was 12.7%, with average prevalence rates of 12.82% and 12.58% in the Middle East and North African countries, respectively. The highest prevalence rate (28.3%) was reported in Egypt, whereas the lowest prevalence (1.5%) was reported in Sudan. The included studies presented children with signs and symptoms of gastroenteritis, acute respiratory infection, acute diarrhea, and acute hemorrhagic conjunctivitis. In conclusion, the average prevalence rate of HAdV infections in children was 12.7%, with average prevalence rates of 12.82% and 12.58% in the Middle East and North African countries, respectively. Finding the precise prevalence rate of this virus is crucial because it will guide future planning for effective disease control and the selection of particular treatment options during epidemics and special seasons.
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Affiliation(s)
- Fadi S I Qashqari
- Department of Microbiology, College of Medicine, Umm Al-Qura University, Makkah 24381, Saudi Arabia
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19
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Adenovirus Infection in Pediatric Hematopoietic Cell Transplantation: A Challenge Still Open for Survival. J Clin Med 2022; 11:jcm11164827. [PMID: 36013066 PMCID: PMC9410345 DOI: 10.3390/jcm11164827] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 08/13/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Human Adenovirus (HAdV) infection occurs in 14−16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk of developing HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical, or HLA mismatched parent), and severe lymphopenia (<0.2 × 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold in the blood (≥102−3 copies/mL) and/or in the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3−5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention, applicable both in prevention and therapeutic settings.
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20
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Zhu M, Chen L. Hepatitis of unknown etiology in children: What we know and what we can do? Front Microbiol 2022; 13:956887. [PMID: 36003929 PMCID: PMC9393628 DOI: 10.3389/fmicb.2022.956887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/14/2022] [Indexed: 11/22/2022] Open
Abstract
Recently, acute hepatitis of unknown etiology in children has gained great concern since March 2022. The disease was first reported by Public Health Scotland. Cases increased rapidly and are now reported in 33 countries worldwide. All cases are predominantly aged under 5 years old. Most patients presented with jaundice, and remarkably, some cases progress to acute liver failure. Until now, the etiology is not fully elucidated, and the investigations are ongoing. Adenovirus infection seems to be an important factor. Several hypotheses on the etiology have been proposed. This review aims to summarize current research progress and put forward some suggestions.
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Affiliation(s)
| | - Li Chen
- Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
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21
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Mücke MM, Zeuzem S. The recent outbreak of acute severe hepatitis in children of unknown origin - what is known so far. J Hepatol 2022; 77:237-242. [PMID: 35533802 DOI: 10.1016/j.jhep.2022.05.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 05/03/2022] [Indexed: 02/01/2023]
Abstract
At the beginning of April 2022, 10 cases of severe acute hepatitis of unknown origin in children <10 years of age were reported across central Scotland. Since then, case numbers have increased rapidly, with 191 probable cases identified across Europe, the United States of America, Israel and Japan. Until now, 17 children required liver transplantation and 1 died. Accordingly, the Centers for Disease Control and Prevention and the European Centre for Diseases Prevention and Control have both issued a warning on a hepatitis of unknown origin in children. This review focuses on the available information concerning this recent outbreak and introduces some of the potential explanations for its development.
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Affiliation(s)
- Marcus Maximilian Mücke
- Department of Internal Medicine I, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
| | - Stefan Zeuzem
- Department of Internal Medicine I, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
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Rabaan AA, Bakhrebah MA, Nassar MS, Natto ZS, Al Mutair A, Alhumaid S, Aljeldah M, Garout M, Alfouzan WA, Alshahrani FS, Sulaiman T, AlFonaisan MK, Alfaresi M, Alshamrani SA, Nainu F, Yong SJ, Choudhary OP, Ahmed N. Suspected Adenovirus Causing an Emerging HEPATITIS among Children below 10 Years: A Review. Pathogens 2022; 11:712. [PMID: 35889958 PMCID: PMC9317240 DOI: 10.3390/pathogens11070712] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/16/2022] [Accepted: 06/20/2022] [Indexed: 02/01/2023] Open
Abstract
In October 2021, a case of acute hepatic failure without any known cause was identified in the United States of America. Upon further investigation, other children aged 1-6 years were reported to have the same liver failure, and some of them were positive for adenovirus 41 type F. On 21 April 2022, the Centers for Disease Control and Prevention (CDC) released an alert after 74 cases were identified in United Kingdom (UK) between 5 and 8 April in children below 10 years of age, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients' liver enzymes were remarkably increased. A total of 650 cases had been reported from 33 countries as of 27 May 2022, among which 222 cases were reported in the UK alone. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.
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Affiliation(s)
- Ali A. Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan
| | - Muhammed A. Bakhrebah
- Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia; (M.A.B.); (M.S.N.)
| | - Majed S. Nassar
- Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11442, Saudi Arabia; (M.A.B.); (M.S.N.)
| | - Zuhair S. Natto
- Department of Dental Public Health, Faculty of Dentistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia;
| | - Abbas Al Mutair
- Research Center, Almoosa Specialist Hospital, Al-Ahsa 36342, Saudi Arabia;
- College of Nursing, Princess Norah Bint Abdulrahman University, Riyadh 11564, Saudi Arabia
- School of Nursing, Wollongong University, Wollongong, NSW 2522, Australia
- Nursing Department, Prince Sultan Military College of Health Sciences, Dhahran 33048, Saudi Arabia
| | - Saad Alhumaid
- Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 31982, Saudi Arabia;
| | - Mohammed Aljeldah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Hafr Al Batin, Hafr Al Batin 39831, Saudi Arabia;
| | - Mohammed Garout
- Department of Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia;
| | - Wadha A. Alfouzan
- Department of Microbiology, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait;
- Microbiology Unit, Department of Laboratories, Farwania Hospital, Farwania 85000, Kuwait
| | - Fatimah S. Alshahrani
- Department of Internal Medicine, College of Medicine, King Saud University, Riyadh 11362, Saudi Arabia;
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, King Saud University Medical City, King Saud University, Riyadh 11451, Saudi Arabia
| | - Tarek Sulaiman
- Infectious Diseases Section, Medical Specialties Department, King Fahad Medical City, Riyadh 12231, Saudi Arabia;
| | | | - Mubarak Alfaresi
- Department of Pathology and Laboratory Medicine, Sheikh Khalifa General Hospital, Umm Al Quwain P.O. Box 499, United Arab Emirates;
- Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates
| | - Saleh A. Alshamrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia;
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia;
| | - Shin Jie Yong
- Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya 47500, Selangor, Malaysia;
| | - Om Prakash Choudhary
- Department of Veterinary Anatomy and Histology, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University (I), Selesih, Aizawl 796 015, Mizoram, India;
| | - Naveed Ahmed
- Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia
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Abstract
Adenoviruses result in a wide array of clinical presentations, including primarily respiratory, gastrointestinal, genitourinary, or systemic infections. Although adenovirus causes mild disease limited to a single organ system in immunocompetent individuals, severe and life-threatening infections do rarely occur. Disseminated disease and severe localized disease resulting in significant morbidity and mortality have been well described in the immunocompromised populations. Although asymptomatic viremia, respiratory tract, and gastrointestinal infections are the most common disease in most transplant patients, renal transplant patients more commonly experience urinary tract infections, including hemorrhagic cystitis or nephritis. Diagnosis requires astute clinical awareness of the patient's clinical presentation that would be compatible with adenovirus combined with cultures, molecular testing, polymerase chain reaction, and tissue sampling. There is no Food and Drug Administration-approved treatment for adenovirus; however, several studies have evaluated therapeutic options including cidofovir, brincidofovir, and immunotherapy. This article will summarize our current understanding of adenovirus in the transplant population.
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Affiliation(s)
- Omar M. Al-Heeti
- Divisions of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Helen P. Cathro
- Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA
| | - Michael G. Ison
- Divisions of Infectious Diseases and Organ Transplantation, Transplant and Immunocompromised Host Infectious Diseases Service, Northwestern University Feinberg School of Medicine, Chicago, IL
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Gao SH, Gong MC, Song HM. Acute severe hepatitis of unknown origin in children: considerations from the perspective of immunology. World J Pediatr 2022; 18:529-532. [PMID: 35768757 PMCID: PMC9244185 DOI: 10.1007/s12519-022-00580-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 06/06/2022] [Indexed: 12/19/2022]
Affiliation(s)
- Si-Hao Gao
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Meng-Chun Gong
- Institute of Health Management, Southern Medical University, Guangzhou, China
| | - Hong-Mei Song
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
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Angurana S, Suthar R, Dhaliwal M. Severe adenoviral pneumonia in children: Much more to learn. JOURNAL OF PEDIATRIC CRITICAL CARE 2022. [DOI: 10.4103/jpcc.jpcc_49_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Dashti-Khavidaki S, Saidi R, Lu H. Current status of glucocorticoid usage in solid organ transplantation. World J Transplant 2021; 11:443-465. [PMID: 34868896 PMCID: PMC8603633 DOI: 10.5500/wjt.v11.i11.443] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 09/16/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering “transplantation” and “glucocorticoids”. GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.
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Affiliation(s)
- Simin Dashti-Khavidaki
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14155, Iran
| | - Reza Saidi
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY 13210, United States
| | - Hong Lu
- Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States
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Shieh WJ. Human adenovirus infections in pediatric population - an update on clinico-pathologic correlation. Biomed J 2021; 45:38-49. [PMID: 34506970 PMCID: PMC9133246 DOI: 10.1016/j.bj.2021.08.009] [Citation(s) in RCA: 97] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/30/2021] [Accepted: 08/30/2021] [Indexed: 01/23/2023] Open
Abstract
Human adenoviruses can cause infections at any age but most commonly in pediatric population, especially in young children and infants. By the time of 10 years old, most children have had at least one episode of adenovirus infection. Adenoviruses can cause many symptoms similar to common cold, including rhinorrhea, fever, cough, and sore throat. Lower respiratory infections such as bronchitis, bronchiolitis, and pneumonia can be severe and even fatal. Other diseases such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, and meningoencephalitis can also be associated with adenovirus infections. A variety of recent advancement of structural and molecular biology methods have revamped the taxonomy of adenoviruses and furthered our understanding of the diversity of related clinical diseases. Because of the wide spectrum and complexity of diseases associated with human adenovirus infections, the scope of this review is limited to basic virology and epidemiology of adenoviruses with a main focus on the clinico–pathologic correlation. Clinical manifestations and pathology of any infectious disease are always related; therefore, it is logical to review clinico–pathologic correlation within the specific disease entity caused by adenoviruses to better understand this common viral infection in pediatric population.
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Affiliation(s)
- Wun-Ju Shieh
- Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
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Chen X, Qin L, Hu W, Adah D. The mechanisms of action of Plasmodium infection against cancer. Cell Commun Signal 2021; 19:74. [PMID: 34243757 PMCID: PMC8268363 DOI: 10.1186/s12964-021-00748-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/14/2021] [Indexed: 01/12/2023] Open
Abstract
Our murine cancer model studies have demonstrated that Plasmodium infection activates the immune system that has been inhibited by cancer cells, counteracts tumor immunosuppressive microenvironment, inhibits tumor angiogenesis, inhibits tumor growth and metastasis, and prolongs the survival time of tumor-bearing mice. Based on these studies, three clinical trials of Plasmodium immunotherapy for advanced cancers have been approved and are ongoing in China. After comparing the mechanisms of action of Plasmodium immunotherapy with those of immune checkpoint blockade therapy, we propose the notion that cancer is an ecological disease and that Plasmodium immunotherapy is a systemic ecological counterattack therapy for this ecological disease, with limited side effects and without danger to public health based on the use of artesunate and other measures. Recent reports of tolerance to treatment and limitations in majority of patients associated with the use of checkpoint blockers further support this notion. We advocate further studies on the mechanisms of action of Plasmodium infection against cancer and investigations on Plasmodium-based combination therapy in the coming future.
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