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Wang S, Ye Q, Sheng Y. From treatment to threat: the fatal impact of cumulative glucocorticoid dosage on outcomes in immunocompromised patients with community-acquired pneumonia. Ther Adv Respir Dis 2025; 19:17534666251332085. [PMID: 40257372 PMCID: PMC12033499 DOI: 10.1177/17534666251332085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 03/16/2025] [Indexed: 04/22/2025] Open
Abstract
BACKGROUND Chronic glucocorticoid therapy is known to heighten the risk of secondary pulmonary infections. However, the impact of cumulative glucocorticoid dosage (CGD) on mortality risk in patients who develop community-acquired pneumonia (CAP) while undergoing glucocorticoid therapy remains inadequately explored. OBJECTIVES This study aims to clarify the relationship between CGD and mortality outcomes in immunocompromised patients with CAP. DESIGN This study is a retrospective cohort analysis utilizing data from the DRYAD database. METHODS We examined data from 561 patients diagnosed with CAP who had received either oral or intravenous glucocorticoids prior to their CAP diagnosis. To evaluate the effect of CGD on mortality risk, we employed piecewise linear regression and Cox regression analyses, adjusting for relevant confounders. RESULTS Among the study population, the median CGD was 4 g of methylprednisolone (interquartile range 2.16-8.80 g). The 30-, 60-, and 90-day mortality rates were 22.28%, 25.13%, and 25.49%, respectively. Piecewise linear regression analysis revealed a nonlinear relationship between methylprednisolone dose and mortality risk, indicating a threshold effect at a methylprednisolone level of 20 g. In addition, Cox regression analysis showed a significantly higher mortality risk in patients with CGD exceeding 40 g of methylprednisolone compared to those with CGD between 20 and 40 g, after adjusting for potential confounding factors (adjusted HR 5.16, 95% CI: 1.16-22.99, p < 0.05). CONCLUSION CAP occurring in close proximity to recent high doses of steroids is associated with pathogens typically seen in immunocompromised hosts and is linked to higher mortality compared to usual CAP.
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Affiliation(s)
- Saibin Wang
- Department of Pulmonary and Critical Care Medicine, Jinhua Municipal Central Hospital, Jinhua, Zhejiang Province, China
- School of Medicine, Shaoxing University, Shaoxing, Zhejiang Province, China
| | - Qian Ye
- Department of Medical Records Quality Management, Jinhua Municipal Central Hospital, Jinhua, Zhejiang Province, China
| | - Yijun Sheng
- Department of Pulmonary and Critical Care Medicine, Jinhua Municipal Central Hospital, No. 365, East Renmin Road, Jinhua 321000, Zhejiang Province, China
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Wang X, Lu Y, Chen F, Ruan L, Gu L, Wang T, Dong H, Wang Y, Hao C, Huang L, Yan Y, Sun H, Chen Z. Clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia and cytomegalovirus DNA detected in bronchoalveolar lavage fluid. Front Pediatr 2024; 12:1407174. [PMID: 39114856 PMCID: PMC11303221 DOI: 10.3389/fped.2024.1407174] [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: 03/26/2024] [Accepted: 07/16/2024] [Indexed: 08/10/2024] Open
Abstract
Background This study aimed to investigate the clinical characteristics of pediatric patients hospitalized with community-acquired pneumonia (CAP) and concomitant cytomegalovirus (CMV) infection. Methods This cross-sectional study enrolled consecutive pediatric patients admitted with CAP who tested positive for CMV DNA in bronchoalveolar lavage fluid (BALF). Flexible fiberoptic bronchoscopy was performed when routine treatment for CAP proved ineffective. The study participants were further stratified into two groups based on CMV serological test results: recent CMV infection group and CMV replication group. Clinical characteristics were compared between these two groups. Results Among 124 patients aged 1-11 months included in this study, 80 (64.5%) patients were categorized as having recent CMV infection, and 44 (35.5%) tested positive for CMV replication. Co-infection with other pathogens was detected more frequently in the CMV replication group (n = 29, 65.9%) than in the recent CMV infection group (n = 35, 43.7%; P = 0.018). Patients with recent CMV infection were younger and exhibited higher levels of alanine transaminase (ALT) and aspartate aminotransferase compared to those with CMV replication (all P < 0.05). Multivariable regression analysis showed age was independently associated with recent CMV infection (odds ratio [OR], 0.707; 95% confidence interval [CI], 0.586-0.853; P < 0.001). Notably, receiver operating characteristic curve analysis showed that a CMV PCR level of 3,840 copies/ml in blood samples had a sensitivity of 34.7% and specificity of 90.0% for diagnosis of recent CMV infection with an area under the curve (AUC) of 0.625 (95% CI: 0.513-0.736, P = 0.048). A CMV PCR level of 6,375 copies/ml in urine samples had a sensitivity of 77.1% and specificity of 61.5% for diagnosis of recent CMV infection with an AUC of 0.695 (95% CI: 0.531-0.858, P = 0.04). Furthermore, multivariate linear regression analysis revealed that the blood CMV DNA copy number was associated with ALT (B = 0.001; P < 0.001). Conclusions The CMV DNA copy numbers in blood and urine could serve as discriminatory markers between recent CMV infection and CMV replication. Measuring CMV DNA levels in blood may be an effective method for monitoring liver function impairment in pediatric patients presenting with CAP and concurrent CMV infection.
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Affiliation(s)
- Xinyu Wang
- Clinical Pediatrics School, Soochow University, Suzhou, Jiangsu, China
| | - Yanhong Lu
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Feng Chen
- Department of Respiratory Medicine, Luodian Hospital, Shanghai, China
| | - Linan Ruan
- Clinical Pediatrics School, Soochow University, Suzhou, Jiangsu, China
| | - Lingtong Gu
- Clinical Pediatrics School, Soochow University, Suzhou, Jiangsu, China
| | - Ting Wang
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Heting Dong
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yuqing Wang
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Chuangli Hao
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Li Huang
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yongdong Yan
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Huiming Sun
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zhengrong Chen
- Department of Respiratory Medicine, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
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Şener YZ, Gultekin AE, Guler AC, Canpolat U, Alp S. A Challenging Case of Viral Pneumonia in the COVID-19 Pandemic Era. Cureus 2024; 16:e59360. [PMID: 38817494 PMCID: PMC11137628 DOI: 10.7759/cureus.59360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2024] [Indexed: 06/01/2024] Open
Abstract
Cytomegalovirus (CMV) is a DNA virus that can cause widespread, severe infection in immunocompromised patients. While CMV usually leads to a subclinical infection in immunocompetent individuals, it can rarely cause severe disease in this population. The SARS-CoV-2 virus is an RNA virus and part of the Coronaviridae family. SARS-CoV-2 led to the COVID-19 (coronavirus disease 2019) pandemic. Even though COVID-19 usually presents with signs and symptoms of upper respiratory tract infection in younger adults, viral pneumonia, cytopenia, and neurological symptoms become more apparent with increasing age. Herein, we describe an immunocompetent 73-year-old female patient in whom oxygen demand and pancytopenia developed during hospitalization for post-ablation inguinal access site infection. The thorax CT revealed viral pneumonia, but two subsequent SARS-CoV-2 polymerase chain reaction (PCR) tests and a viral respiratory multiplex PCR panel were negative. The CMV viral load was high in the blood sample, and the patient responded to valganciclovir treatment. Although SARS-CoV-2 should be evaluated in patients with viral pneumonia and cytopenia, other viral etiologies mimicking SARS-CoV-2 infection, such as CMV, should not be overlooked in the era of the COVID-19 pandemic.
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Affiliation(s)
- Yusuf Ziya Şener
- Cardiology Department, Hacettepe University Faculty of Medicine, Ankara, TUR
| | - Ahmet Emre Gultekin
- Cardiology Department, Hacettepe University Faculty of Medicine, Ankara, TUR
| | - Akif Can Guler
- Internal Medicine Department, Hacettepe University Faculty of Medicine, Ankara, TUR
| | - Ugur Canpolat
- Cardiology Department, Hacettepe University Faculty of Medicine, Ankara, TUR
| | - Sehnaz Alp
- Infectious Diseases Department, Hacettepe University Faculty of Medicine, Ankara, TUR
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4
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Gocho K, Yamashita A, Iizuka N, Sato K, Imasaka K, Hamanaka N, Kimura T. Primary Cytomegalovirus Pneumonia Successfully Treated with Corticosteroid Therapy and Valganciclovir. Intern Med 2024; 63:271-276. [PMID: 37225488 PMCID: PMC10864076 DOI: 10.2169/internalmedicine.1638-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/23/2023] [Indexed: 05/26/2023] Open
Abstract
Cytomegalovirus infection is typically asymptomatic in immunocompetent individuals. A 26-year-old woman was admitted to our hospital with a fever and breathlessness. Chest computed tomography (CT) revealed bilateral diffuse reticulation and nodules. Laboratory investigations showed atypical lymphocytosis and increased transaminases. She was treated with corticosteroid pulse therapy because of acute lung injury, and her clinical condition improved. Based on the presence of cytomegalovirus antibodies, antigen, and polymerase chain reaction findings, she was diagnosed with primary cytomegalovirus pneumonia and treated with valganciclovir. Primary cytomegalovirus pneumonia is very rare in immunocompetent individuals. The efficacy of corticosteroid and valganciclovir against cytomegalovirus pneumonia in this patient is noteworthy.
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Affiliation(s)
- Kyoko Gocho
- Department of Respiratory Medicine, Saiseikai Yokohamashi Tobu Hospital, Japan
| | - Aya Yamashita
- Department of Respiratory Medicine, Saiseikai Yokohamashi Tobu Hospital, Japan
| | - Noboru Iizuka
- Department of Respiratory Medicine, Saiseikai Yokohamashi Tobu Hospital, Japan
| | - Kenya Sato
- Department of Respiratory Medicine, Saiseikai Yokohamashi Tobu Hospital, Japan
| | - Keisuke Imasaka
- Department of Respiratory Medicine, Saiseikai Yokohamashi Tobu Hospital, Japan
| | - Nobuyuki Hamanaka
- Department of Respiratory Medicine, Saiseikai Yokohamashi Tobu Hospital, Japan
| | - Tokuhiro Kimura
- Department of Diagnostic Pathology, Saiseikai Yokohamashi Tobu Hospital, Japan
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5
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Ren K, Yong C, Wang Y, Wei H, Zhao K, He B, Cui M, Chen Y, Wang J. Cytomegalovirus Pneumonia in Inflammatory Bowel Disease: Literature Review and Clinical Recommendations. Infect Drug Resist 2023; 16:6195-6208. [PMID: 37724090 PMCID: PMC10505384 DOI: 10.2147/idr.s420244] [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: 05/07/2023] [Accepted: 08/22/2023] [Indexed: 09/20/2023] Open
Abstract
Aim The objective was to elucidate the correlation between CMVP and immunosuppressive therapy in IBD patients, we hope this review could expand on the significance of CMV as an opportunistic pathogen and the potential impact on morbidity and mortality in IBD patients. Methods Records and clinical trajectories linked to CMVP in IBD patients were extracted from the PubMed database, irrespective of language barriers. The reference lists incorporated in these studies were manually inspected. Conclusions were generated using straightforward descriptive analysis. Results In total, 18 IBD patients, including Crohn's disease (CD, 67%) and Ulcerative Colitis (UC, 33%), affected by CMVP were identified from 17 published articles. A minority of these patients (17%) exhibited active disease, whereas the majority (83%) presented with quiescent disease. Fever (100%) and dyspnea (44%) emerged as the most prevalent clinical symptoms. All the patients had undergone immunosuppressive therapy. A significant proportion, up to 89%, had received thiopurine treatment prior to the CMVP diagnosis. Interestingly, none of the patients were subjected to biological therapy. Half of the patients manifested with Hemophagocytic Lymphohistiocytosis (HLH). Almost all patients (94%) were administered antiviral treatment and a substantial 83% experienced full recovery. Immunosuppressive agents were either tapered or discontinued altogether. A subset of patients, 17%, suffered fatal outcomes. Conclusion Our findings underscore the need for heightened suspicion of CMVP in IBD patients who exhibit symptoms such as fever and dyspnea. During the COVID-19 pandemic, CMVP should be considered a potential differential diagnosis. It was observed that CMVP primarily transpires during CD remission. Azathioprine emerged as the predominant immunosuppressant linked to CMV reactivation. The prompt application of effective antiviral therapy can substantially enhance patient outcomes. CMV vaccine might serve as a viable prevention strategy.
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Affiliation(s)
- Keyu Ren
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Chunming Yong
- Department of Emergency, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Yanting Wang
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Hongyun Wei
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Kun Zhao
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Baoguo He
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Mingjuan Cui
- Department of Gastroenterology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Yunqing Chen
- Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
| | - Jin Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China
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Kanika A, Soldera J. Pulmonary cytomegalovirus infection: A case report and systematic review. World J Meta-Anal 2023; 11:151-166. [DOI: 10.13105/wjma.v11.i5.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 04/08/2023] [Accepted: 06/09/2023] [Indexed: 06/16/2023] Open
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Shi Y, Peng JM, Qin HY, Du B. Metagenomic next-generation sequencing: A promising tool for diagnosis and treatment of suspected pneumonia in rheumatic patients with acute respiratory failure: Retrospective cohort study. Front Cell Infect Microbiol 2022; 12:941930. [PMID: 35992169 PMCID: PMC9381725 DOI: 10.3389/fcimb.2022.941930] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/12/2022] [Indexed: 11/17/2022] Open
Abstract
Background The effectiveness of metagenomic next-generation sequencing (mNGS) in respiratory pathogen detection and clinical decision-making in critically rheumatic patients remains largely unexplored. Methods A single-center retrospective study of 58 rheumatic patients who were admitted to ICU due to suspected pneumonia with acute respiratory failure if they underwent both bronchoalveolar lavage fluid specimen mNGS and combined microbiological tests (CMTs) was conducted to compare their diagnostic performance, using clinical composite diagnosis as the gold standard. Treatment modifications based on mNGS results were also reviewed. Results Forty-three patients were diagnosed with microbiologically confirmed pneumonia and 15 were considered as a non-infectious disease. mNGS outperformed CMTs in the accurate diagnosis of infectious and non-infectious lung infiltration (98.1% [57/58] vs. 87.9% [51/58], P = 0.031). A total of 94 causative pathogens were defined by the gold standard and 27 patients had polymicrobial pneumonia. The sensitivity of pathogen detection and complete concordance with the gold standard by mNGS exceeded those by CMTs (92.6% [87/94] vs. 76.6% [72/94], P < 0.001 and 72.1% [31/43] vs. 51.2% [22/43], P = 0.004, respectively). Moreover, 22 pathogens were detected only by mNGS and confirmed by orthogonal test. Accordingly, the etiological diagnosis changed in 19 cases, and the empirical treatment improved in 14 cases, including 8 cases of rescue treatment and 11 of antibiotics de-escalation. At the pathogen-type level, both methods were comparable for bacteria, but mNGS was advantageous to identify viruses (accuracy: 100% vs. 81%, P = 0.004). For Pneumocystis jirovecii detection, mNGS improved the sensitivity compared with Gomori’s methenamine silver stain (91.7% vs. 4.2%, P < 0.001) and was higher than polymerase chain reaction (79.2%), but the difference was not significant (P = 0.289). In terms of Aspergillus, the better sensitivity with a combination of culture and galactomannan test than that with mNGS was found (100% vs. 66.7%, P = 0.033). Conclusions mNGS has an excellent accuracy in etiological diagnosis and pathogen detection of suspected pneumonia in critically rheumatic patients, which has potential significance for clinical decision-making. Its superiority to different types of pathogens depends on the comprehensiveness of CMTs.
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8
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Comparative real-time PCR quantification of cytomegalovirus in severe early childhood caries and caries-free children. Eur Arch Paediatr Dent 2022; 23:797-801. [PMID: 35751745 DOI: 10.1007/s40368-022-00711-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 04/12/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE The present study was undertaken to evaluate cytomegalovirus (CMV) load in carious lesions in children with severe early childhood caries (S-ECC) and compare it with caries-free (CF), healthy children, by quantitative real-time polymerase chain reaction (PCR). MATERIALS AND METHODS Dental plaque samples were collected from 57 subjects including S-ECC (n = 33) and CF (n = 24) patients. The two groups were matched in terms of age, gender, and socioeconomic status. After deoxyribonucleic acid (DNA) extraction, SYBR Green real-time PCR was used to quantify CMV DNA. RESULTS The CMV DNA was detected in seven patients in the S-ECC group. The mean of decayed, missing, and filled tooth surfaces (dmfs) was 11.90 ± 5.95 in the S-ECC group. There was no significant difference in gender between the two groups. There was a significant relationship between CMV positivity in children and the S-ECC group (p = 0.043). CONCLUSION Results of this study suggest a relationship between the presence of CMV in the oral cavity and S-ECC. We can design clinical trials to confirm these results and improve children's dental care.
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9
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Padmanabhan A, Balakrishnan R, Ameer KA, Arjun R, Muralidharan P. Cytomegalovirus pneumonitis in an immunocompromised host. Lung India 2022; 39:202-204. [PMID: 35259808 PMCID: PMC9053925 DOI: 10.4103/lungindia.lungindia_662_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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10
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Waqas QA, Abdullah HMA, Khan UI, Oliver T. Human cytomegalovirus pneumonia in an immunocompetent patient: a very uncommon but treatable condition. BMJ Case Rep 2019; 12:12/8/e230229. [PMID: 31451465 DOI: 10.1136/bcr-2019-230229] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Human cytomegalovirus (CMV) is a double-stranded DNA virus that can cause widespread severe infection in immunocompromised individuals but is more typically a subclinical infection in immunocompetent individuals. Rarely, it can cause a serious infection in immunocompetent individuals. Here, we describe a 36-year-old otherwise healthy male who presented with fever, cough and malaise who was diagnosed with CMV pneumonia. He made a rapid recovery after initiation of ganciclovir and has been doing well on follow-up visits. We performed a comprehensive review of CMV pneumonia in immunocompetent individuals and have summarised the prior 16 reported cases of CMV pneumonia in immunocompetent patients. This article highlights the importance of considering CMV as a cause of pneumonia even in immunocompetent individuals, especially when the more common causes have been excluded. Early diagnosis allows prompt treatment and potentially complete recovery.
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Affiliation(s)
- Qazi Ahmed Waqas
- Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA
| | | | | | - Tony Oliver
- Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, USA
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11
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Wahl A, De C, Abad Fernandez M, Lenarcic EM, Xu Y, Cockrell AS, Cleary RA, Johnson CE, Schramm NJ, Rank LM, Newsome IG, Vincent HA, Sanders W, Aguilera-Sandoval CR, Boone A, Hildebrand WH, Dayton PA, Baric RS, Pickles RJ, Braunstein M, Moorman NJ, Goonetilleke N, Victor Garcia J. Precision mouse models with expanded tropism for human pathogens. Nat Biotechnol 2019; 37:1163-1173. [PMID: 31451733 PMCID: PMC6776695 DOI: 10.1038/s41587-019-0225-9] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 07/12/2019] [Indexed: 12/12/2022]
Abstract
A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics. Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.
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Affiliation(s)
- Angela Wahl
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA.
| | - Chandrav De
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA
| | - Maria Abad Fernandez
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA
| | - Erik M Lenarcic
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Yinyan Xu
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA
| | - Adam S Cockrell
- Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
| | - Rachel A Cleary
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA
| | - Claire E Johnson
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA
| | - Nathaniel J Schramm
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA
| | - Laura M Rank
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA
| | - Isabel G Newsome
- Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC, USA
| | - Heather A Vincent
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Wes Sanders
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Christian R Aguilera-Sandoval
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA.,BD Life Sciences, San Jose, CA, USA
| | - Allison Boone
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA
| | - William H Hildebrand
- Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Paul A Dayton
- Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC, USA
| | - Ralph S Baric
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA
| | - Raymond J Pickles
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA
| | - Miriam Braunstein
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA
| | - Nathaniel J Moorman
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA
| | - Nilu Goonetilleke
- Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA.,UNC HIV Cure Center, University of North Carolina, Chapel Hill, NC, USA
| | - J Victor Garcia
- Division of Infectious Diseases, International Center for the Advancement of Translational Science, Center for AIDS Research, University of North Carolina, School of Medicine, Chapel Hill, NC, USA.
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12
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Manandhar T, Hò GGT, Pump WC, Blasczyk R, Bade-Doeding C. Battle between Host Immune Cellular Responses and HCMV Immune Evasion. Int J Mol Sci 2019; 20:E3626. [PMID: 31344940 PMCID: PMC6695940 DOI: 10.3390/ijms20153626] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 07/18/2019] [Accepted: 07/19/2019] [Indexed: 12/16/2022] Open
Abstract
Human cytomegalovirus (HCMV) is ubiquitously prevalent. HCMV infection is typically asymptomatic and controlled by the immune system in healthy individuals, yet HCMV can be severely pathogenic for the fetus during pregnancy and in immunocompromised persons, such as transplant recipients or HIV infected patients. HCMV has co-evolved with the hosts, developed strategies to hide from immune effector cells and to successfully survive in the human organism. One strategy for evading or delaying the immune response is maintenance of the viral genome to establish the phase of latency. Furthermore, HCMV immune evasion involves the downregulation of human leukocyte antigens (HLA)-Ia molecules to hide infected cells from T-cell recognition. HCMV expresses several proteins that are described for downregulation of the HLA class I pathway via various mechanisms. Here, we review the wide range of immune evasion mechanisms of HCMV. Understanding the mechanisms of HCMV immune evasion will contribute to the development of new customized therapeutic strategies against the virus.
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Affiliation(s)
- Trishna Manandhar
- Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
| | - Gia-Gia T Hò
- Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
| | - Wiebke C Pump
- Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
| | - Rainer Blasczyk
- Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
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Challenges and Clinical Implications of the Diagnosis of Cytomegalovirus Lung Infection in Children. Curr Infect Dis Rep 2019; 21:24. [PMID: 31147863 DOI: 10.1007/s11908-019-0681-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW Pulmonary cytomegalovirus (CMV) infection is a potential lethal disease in children, but it remains a diagnostic challenge. The differentiation between latent CMV infections with viral shedding and active infections is difficult and may lead to false positives in bronchoalvolar lavage (BAL) PCR detection. This review summarizes current diagnostic approaches for CMV lung infection in children including progress in the identification of underlying immune defects linked to this condition. RECENT FINDINGS There is increasing literature supporting that the combined assessment of host risk factors and lung disease pattern is essential for the diagnosis of pulmonary CMV infection in children. The most important host risk factor is an immunecompromised state that has expanded from primary or acquired immunodeficiency (e.g., HIV) to include a myriad of immune-dysregulation syndromes (e.g., CTLA4, PIK3 defects). Newborns, paricularly those born premature, are also a high-risk group. At the pulmonary level, active CMV infection is typically characterized by alveolar compromise leading to hypoxemia, ground-glass opacities, and intra-alveolar infiltrates with CMV inclusions in lung biopsy. The identification of active CMV lung infection should trigger additional evaluation of immune defects (primary or secondary) impairing T and NK cell function or innate antiviral responses as well as other immune dysregulation disorders. Lung CMV infections in children are more prevalent in immunocompromised hosts and premature newborns. Lung CMV infections should prompt further investigation into conditions altering immune mechanisms usually in place to contain CMV infections. Common clinical and radiological patterns such as hypoxemia and ground-glass pulmonary opacities may allow early identification and treatment of CMV lung infection and underlying causes in the pediatric population.
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Wu XN, Lightman S, Tomkins‐Netzer O. Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review. Clin Exp Ophthalmol 2019; 47:381-395. [DOI: 10.1111/ceo.13500] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 02/08/2019] [Accepted: 02/18/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Xia Ni Wu
- Ophthalmology, Moorfields Eye Hospital London UK
- Faculty of Brain Sciences, Institute of Ophthalmology London UK
| | - Sue Lightman
- Ophthalmology, Moorfields Eye Hospital London UK
- Faculty of Brain Sciences, Institute of Ophthalmology London UK
| | - Oren Tomkins‐Netzer
- Ophthalmology, Moorfields Eye Hospital London UK
- Faculty of Brain Sciences, Institute of Ophthalmology London UK
- Department of OphthalmologyBnai Zion Medical Centre Haifa Israel
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Carpani G, Foresti S, Dell’Oro R, Grassi G, Bombelli M. Severe systemic cytomegalovirus infection in an immunocompetent patient outside the intensive care unit: a case report. BMC Infect Dis 2019; 19:34. [PMID: 30626344 PMCID: PMC6327531 DOI: 10.1186/s12879-018-3621-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 12/14/2018] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Cytomegalovirus is responsible for an opportunistic infection that can be life threatening in immunocompromised patients, while it is usually mild or completely asymptomatic in immunocompetent subjects. In the recent years, however, some cases of severe cytomegalovirus infection in immunocompetent patients have been reported, showing this to be a less rare occurrence than previously reported. CASE PRESENTATION We report the case of an 83-year-old man, admitted to our hospital for gastroenteritis, complicated by dehydration and severe prothrombin time prolongation due to oral anticoagulant therapy accumulation, who developed hospital-acquired pneumonia; neither of these illnesses responded to several lines of antibiotic therapy. All microbiologic tests were negative, except cytomegalovirus DNA test in blood, which showed high viral load. Antiviral therapy with ganciclovir was then started and a quick favourable response followed. A state of immunodeficiency was excluded, based on normal CD4 count and patient's clinical history. CONCLUSION Different risk factors for severe cytomegalovirus disease in immunocompetent patients may exist, besides the ones already known, which could be responsible for severe cytomegalovirus disease in immunocompetent patients; thus, these patients should be tested for cytomegalovirus infection, if the clinical picture is compatible, to avoid delay in diagnosis and allow prompt start of specific therapy.
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Affiliation(s)
- Giovanni Carpani
- Department of Medicine and Surgery, Clinica Medica, University of Milano-Bicocca, San Gerardo Hospital, Via G.B. Pergolesi 33, 20900 Monza, Italy
| | - Sergio Foresti
- Division of Infectious Diseases, San Gerardo Hospital, Via G.B. Pergolesi 33, 20900 Monza, Italy
| | - Raffaella Dell’Oro
- Department of Medicine and Surgery, Clinica Medica, University of Milano-Bicocca, San Gerardo Hospital, Via G.B. Pergolesi 33, 20900 Monza, Italy
| | - Guido Grassi
- Department of Medicine and Surgery, Clinica Medica, University of Milano-Bicocca, San Gerardo Hospital, Via G.B. Pergolesi 33, 20900 Monza, Italy
| | - Michele Bombelli
- Department of Medicine and Surgery, Clinica Medica, University of Milano-Bicocca, San Gerardo Hospital, Via G.B. Pergolesi 33, 20900 Monza, Italy
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Gonçalves C, Cipriano A, Videira Santos F, Abreu M, Méndez J, Sarmento E Castro R. Cytomegalovirus acute infection with pulmonary involvement in an immunocompetent patient. IDCases 2018; 14:e00445. [PMID: 30191130 PMCID: PMC6125764 DOI: 10.1016/j.idcr.2018.e00445] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 08/19/2018] [Accepted: 08/19/2018] [Indexed: 11/24/2022] Open
Abstract
Introduction Cytomegalovirus (CMV) infection in healthy adults is usually asymptomatic or causes a mild mononucleosis syndrome, while severe infections are rare in immunocompetent patients and poorly documented. When described, gastrointestinal tract and the central nervous systems are the most frequent sites of severe CMV infection. Lung disease can occur, but it’s rare. Clinical case A 29 years old man presenting with a 2-weeks history of fever, headache, malaise, dry non-productive cough and thoracic pleuritic pain, without improvement after one-week therapy with levofloxacin. Blood exams showed lymphocytosis of almost 50%, nine percent of atypical lymphocytes and elevated transaminases. Thoracic CT-scan showed bilateral infiltrate with internal air bronchogram. Blood serology showed positivity for CMV IgG and IgM, with low CMV IgG avidity. Serum and bronchoalveolar detection of CMV by polymerase chain reaction (PCR) technique was also positive. Cultures were all negative. The patient became increasingly hypoxemic and the liver transaminases worsening, the reason for which ganciclovir was started. He made a full recovery and was discharged seven days later with oral valganciclovir, completing a 3 weeks antiviral course at home. Discussion CMV pneumonia is a rare condition, however it’s one of the three most common cause of severe viral community acquired pneumonia (CAP), along with influenza and adenovirus. CMV pneumonia should be considered in patients with atypical lymphocytes and mildly elevated serum transaminases. Conclusion In immunocompetent hosts, even with severe CMV-CAP, the prognosis is good. However, antiviral treatment should be considered in the rare occasion of severe CMV infection. Nevertheless, more studies are needed to clarify the clinical benefit of antiviral treatment.
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Affiliation(s)
- Celina Gonçalves
- Infectious Disease Department, Centro Hospitalar do Porto, Portugal
| | - Ana Cipriano
- Infectious Disease Department, Centro Hospitalar do Porto, Portugal
| | | | - Miguel Abreu
- Infectious Disease Department, Centro Hospitalar do Porto, Portugal
| | - Josefina Méndez
- Infectious Disease Department, Centro Hospitalar do Porto, Portugal
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Fever of unknown origin (FUO): CMV infectious mononucleosis or lymphoma? Eur J Clin Microbiol Infect Dis 2018; 37:1373-1376. [PMID: 29679253 DOI: 10.1007/s10096-018-3262-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 04/11/2018] [Indexed: 10/17/2022]
Abstract
Fever of unknown origin (FUO) refers to fevers of > 101 °F that persist for > 3 weeks and remain undiagnosed after a focused inpatient or outpatient workup. FUO may be due to infectious, malignant/neoplastic, rheumatic/inflammatory, or miscellaneous disorders. The FUO category determines the focus of the diagnostic workup. In the case presented of an FUO in a young woman, there were clinical findings of both CMV infectious mononucleosis or a lymphoma, e.g., highly elevated ESR, elevated ferritin levels, and elevated ACE level, β-2 microglobulins. The indium scan showed intense splenic uptake. Lymph node biopsy, PET scan, and flow cytometry were negative for lymphoma. CMV infectious mononucleosis was the diagnosis, and she made a slow recovery.
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Abstract
Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.
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Affiliation(s)
- Biswajit G Roy
- Department of Chemistry, Sikkim University, Gangtok, India
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Cunha BA, Sivarajah T, Jimada I. Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma? Heart Lung 2017; 46:394-396. [PMID: 28705467 DOI: 10.1016/j.hrtlng.2017.05.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 05/04/2017] [Accepted: 05/22/2017] [Indexed: 10/19/2022]
Abstract
We present a case of an adult female with a past history of pulmonary sarcoidosis who presented with fever, night sweats, profound fatigue, and LUQ abdominal pain. Sarcoidosis is an afebrile disorder (excluding Lofgren's syndrome, Heerfordt's syndrome or neurosarcoidosis). Therefore, the presence of fever with sarcoidosis should suggest infection, usually viral, or lymphoma. Sarcoidosis-lymphoma syndrome describes the evolution of a lymphoma in long standing sarcoidosis. Fever aside, possible lymphoma is suggested by otherwise unexplained fever, pleural unilateral effusion, highly elevated ESR or ferritin levels. In this case, a viral etiology was suggested because of atypical lymphocytosis and mildly elevated transaminases. In this patient, CMV IgM titers and elevated CMV PCR viral load confirmed the diagnosis of CMV infectious mononucleosis with lung and liver involvement. In this case CMV infectious mononucleosis was accompanied by procoagulant activity which resulted a DVT, pulmonary emboli and splenic infarct. We believe this to be the first reported case of CMV infectious mononucleosis splenic infarct in a patient with a history of sarcoidosis.
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Affiliation(s)
- Burke A Cunha
- Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA; State University of New York, School of Medicine, Stony Brook, NY, USA.
| | - Thulashie Sivarajah
- Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA; State University of New York, School of Medicine, Stony Brook, NY, USA
| | - Ismail Jimada
- Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA; State University of New York, School of Medicine, Stony Brook, NY, USA
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Beswick L, Ye B, van Langenberg DR. Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis. Inflamm Bowel Dis 2016; 22:2966-2976. [PMID: 27763950 DOI: 10.1097/mib.0000000000000958] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented. RESULTS This review discusses the concept of CMV reactivation which frequently occurs in inflammatory bowel disease-related colitis, most commonly in those presenting with steroid-refractory colitis. In this context, although signifying a poorer prognosis, in most cases, the virus is nonpathogenic and thus antiviral treatment is unhelpful. However, when reactivation gives rise to true CMV disease (colitis) as best discriminated by histology with immunohistochemistry (and the density of such) in colonic biopsy tissue, the patient does benefit from antivirals. CONCLUSION Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.
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Affiliation(s)
- Lauren Beswick
- *Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia; and †Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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Pathogen profiles and molecular epidemiology of respiratory viruses in Japanese inpatients with community-acquired pneumonia. Respir Investig 2016; 54:255-63. [PMID: 27424825 PMCID: PMC7185461 DOI: 10.1016/j.resinv.2016.01.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 12/27/2015] [Accepted: 01/04/2016] [Indexed: 11/23/2022]
Abstract
Background The etiological profile of viruses among adult patients with community-acquired pneumonia (CAP) has not been characterized yet. The aim of this study was twofold: first, investigate the pathogen profiles and the molecular epidemiology of respiratory viruses among Japanese CAP patients; and second, explore the clinical significance of viral infections. Methods A cross-sectional observational study was conducted at Kyorin University Hospital. To identify respiratory pathogens, hospitalized CAP patients were enrolled, and reverse transcriptase–polymerase chain reaction technology was applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed. CAP patients were divided into four etiological groups (virus alone, bacteria alone, co-detection of virus and bacteria, and not detected) and the clinical findings were compared. Results Seventy-six patients were enrolled. Bacteria alone were detected in 39.5% (n=30) of CAP patients. Virus alone or co-detection were found in 10.5% (n=8) and 11.8% (n=9) of cases, respectively. Streptococcus pneumoniae and human metapneumovirus were the most frequently detected bacterium and virus, respectively. Phylogenetic analyses of human metapneumovirus, human rhinovirus, and human respiratory syncytial virus showed that different subgroups and genotypes might be associated with CAP. Respiratory failure was more common when a virus was detected (both virus alone and co-detection groups; n=17, 100%, p<0.05) than when a bacteria alone was detected (n=17, 56.7%). Conclusion Prevalence of respiratory virus infection in CAP inpatients was 22.3%. The detected viruses display high genetic divergence and correlate with increased respiratory failure.
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Josephson CD, Caliendo AM, Easley KA, Knezevic A, Shenvi N, Hinkes MT, Patel RM, Hillyer CD, Roback JD. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr 2014; 168:1054-62. [PMID: 25243446 PMCID: PMC4392178 DOI: 10.1001/jamapediatrics.2014.1360] [Citation(s) in RCA: 112] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
IMPORTANCE Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low-birth-weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, as well as the efficacy of approaches to prevent CMV transmission, are poorly characterized. OBJECTIVE To estimate the risk of postnatal CMV transmission from 2 sources: (1) transfusion of CMV-seronegative and leukoreduced blood and (2) maternal breast milk. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter birth-cohort study was conducted from January 2010 to June 2013 at 3 neonatal intensive care units (2 academically affiliated and 1 private) in Atlanta, Georgia. Cytomegalovirus serologic testing of enrolled mothers was performed to determine their status. Cytomegalovirus nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. A total of 539 VLBW infants (birth weight, ≤ 1500 g) who had not received a blood transfusion were enrolled, with their mothers (n = 462), within 5 days of birth. The infants underwent serum and urine CMV NAT at birth to evaluate congenital infection and surveillance CMV NAT at 5 additional intervals between birth and 90 days, discharge, or death. EXPOSURES Blood transfusion and breast milk feeding. MAIN OUTCOMES AND MEASURES Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT. RESULTS The seroprevalence of CMV among the 462 enrolled mothers was 76.2% (n = 352). Among the 539 VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI, 4.2%-9.2%); 5 of 29 infants (17.2%) with postnatal CMV infection developed symptomatic disease or died. A total of 2061 transfusions were administered among 57.5% (n = 310) of the infants; none of the CMV infections was linked to transfusion, resulting in a CMV infection incidence of 0.0% (95% CI, 0.0%-0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence, 15.3%; 95% CI, 9.3%-20.2%). CONCLUSIONS AND RELEVANCE Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants whose care is managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00907686.
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Affiliation(s)
- Cassandra D. Josephson
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA,Department of Pathology, Children’s Healthcare of Altanta, and Emory University School of Medicine, Atlanta GA,Aflac Cancer Center and Blood Disorders Center, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Emory University School of Medicine, Atlanta GA
| | - Angela M. Caliendo
- Department of Medicine, Alpert Medical School of Brown University, Providence, RI
| | - Kirk A. Easley
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta GA
| | - Andrea Knezevic
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta GA
| | - Neeta Shenvi
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta GA
| | | | - Ravi M. Patel
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta GA
| | | | - John D. Roback
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta GA
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Characterization of cytomegalovirus lung infection in non-HIV infected children. Viruses 2014; 6:2038-51. [PMID: 24811320 PMCID: PMC4036547 DOI: 10.3390/v6052038] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 03/29/2014] [Accepted: 04/03/2014] [Indexed: 11/16/2022] Open
Abstract
UNLABELLED Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2-4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. CONCLUSION CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.
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Pneumonitis due to cytomegalovirus during chronic methotrexate treatment. ACTA ACUST UNITED AC 2014; 10:328-30. [PMID: 24646908 DOI: 10.1016/j.reuma.2013.07.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2013] [Revised: 07/19/2013] [Accepted: 07/24/2013] [Indexed: 11/20/2022]
Abstract
Although hypersensitivity pneumonitis is the most common pulmonary complication described during treatment with methotrexate, other complications like lymphoproliferative and infectious disease may be considered in the study of respiratory disease associated to methotrexate. The existence of an increased risk to developing infectious diseases may be similar to that observed during treatment with antagonists of tumor necrosis factor and corticosteroids, where Cytomegalovirus pneumonia is a serious complication; early diagnosis and treatment will prevent a potentially fatal outcome.
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Cytomegalovirus pneumonia in immunocompetent host: case report and literature review. J Clin Virol 2012; 55:356-9. [PMID: 22975082 DOI: 10.1016/j.jcv.2012.08.010] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2012] [Revised: 08/10/2012] [Accepted: 08/12/2012] [Indexed: 11/21/2022]
Abstract
CMV infection is highly prevalent in general population and its clinical picture generally ranges from asymptomatic disease to mononucleosis-like syndrome. While severe life-threatening CMV disease is well documented in certain immunocompromised risk groups, severe infection with symptomatic pneumonia in immunocompetent hosts has been rarely documented. In this paper we describe a case of primary CMV infection, complicated by severe CMV pneumonia in an immunocompetent host, successfully treated with oral valganciclovir. Moreover, we reviewed CMV pneumonia cases in immunocompetent adults reported in the literature.
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D'Journo XB, Bittar F, Trousse D, Gaillat F, Doddoli C, Dutau H, Papazian L, Raoult D, Rolain JM, Thomas PA. Molecular detection of microorganisms in distal airways of patients undergoing lung cancer surgery. Ann Thorac Surg 2011; 93:413-22. [PMID: 22206956 DOI: 10.1016/j.athoracsur.2011.09.049] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2011] [Revised: 09/19/2011] [Accepted: 09/20/2011] [Indexed: 11/17/2022]
Abstract
BACKGROUND Whereas proximal airways of patients undergoing lung cancer surgery are known to present specific microbiota incriminated in the occurrence of postoperative respiratory complications, little attention has been paid to distal airways and lung parenchyma considered to be free from bacteria. We have hypothesized that molecular culture-independent techniques applied to distal airways should allow identification of uncultured bacteria, virus, or emerging pathogens and predict the occurrence of postoperative respiratory complications. METHODS Microbiological assessments were obtained from the distal airways of resected lung specimens from a prospective cohort of patients undergoing major lung resections for cancer. Microorganisms were detected using real-time polymerase chain reaction (PCR) assays targeting the bacterial 16s ribosomal RNA gene and Herpesviridae, cytomegalovirus (CMV), and herpesvirus simplex. All postoperative microbiological assessments were compared with the PCR results. RESULTS In all, 240 samples from 87 patients were investigated. Colonizing agents were exclusively Herpesviridae (CMV, n=13, and herpesvirus simplex, n=1). All 16s ribosomal RNA PCR remained negative. Thirteen patients (15%) had a positive CMV PCR (positive-PCR group), whereas the remaining 74 patients constituted the negative-PCR group. Postoperative pneumonia occurred in 24% of the negative-PCR group and in 69% of the positive-PCR group (p=0.003). Upon stepwise logistic regression, performance status, percent of predicted diffusion lung capacity for carbon monoxide, and positive PCR were the risk factors of postoperative respiratory complications. The CMV PCR had a positive predictive value of 0.70 in prediction of respiratory complications. CONCLUSIONS When tested by molecular techniques, lung parenchyma and distal airways are free of bacteria, but CMV was found in a high proportion of the samples. Molecular CMV detection in distal airways should be seen as a reliable marker to identify patients at risk for postoperative respiratory complications.
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Affiliation(s)
- Xavier Benoit D'Journo
- Department of Thoracic Surgery and Diseases of the Esophagus, Aix-Marseille University and Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France.
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Respiratory syncytial virus (RSV) community-acquired pneumonia (CAP) in a hospitalized adult with human immunodeficiency virus (HIV) mimicking influenza A and Pneumocystis (carinii) jiroveci pneumonia (PCP). Heart Lung 2011; 41:76-82. [PMID: 22005289 DOI: 10.1016/j.hrtlng.2011.05.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2011] [Revised: 05/09/2011] [Accepted: 05/09/2011] [Indexed: 11/21/2022]
Abstract
BACKGROUND Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infections in young children, the elderly, and immunocompromised hosts, but RSV is a rare cause of community-acquired pneumonia (CAP) in hospitalized adults with human immunodeficiency virus (HIV). In patients with HIV, CAP is most frequently attributable to the usual bacterial respiratory pathogens that cause CAP in immunocompetent hosts, eg, Streptococcuspneumoniae or Hemophilus influenzae. Adults with HIV are also predisposed to intracellular CAP pathogens, ie, Mycoplasmatuberculosis, Salmonella spp., Pneumocystis (carinii) jiroveci (PCP), cytomegalovirus, and Legionella spp. This year, co-circulating in the community during influenza season were strains of human seasonal influenza A (H3N2) and swine influenza A (H1N1). During the influenza season, in adults hospitalized with HIV, the diagnostic possibilities should include influenza-like illnesses, eg, human parainfluenza virus types 3 and 4, human metapneumovirus, and pertussis. CASE REPORT We present an adult with HIV, hospitalized for an influenza-like illness during influenza season. The differential diagnosis of CAP in this patient included influenza A and PCP. CONCLUSION We report on an adult patient with HIV with CAP that mimicked influenza and PCP, and was attributable to RSV.
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Cunha BA, Hage JE, Nouri Y. Fever of unknown origin (FUO) in an immunocompetent adult due to cytomegalovirus (CMV) with polyclonal gammopathy. Infection 2011; 40:327-30. [PMID: 21918866 DOI: 10.1007/s15010-011-0191-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Accepted: 08/15/2011] [Indexed: 10/17/2022]
Abstract
Fever of unknown origin (FUO) may be due to infection, malignancy, collagen vascular/inflammatory disorders, or other causes. Cytomegalovirus (CMV) infection is a rare cause of FUO in immunocompetent adults. We present a case of FUO due to CMV in an immunocompetent adult with polyclonal gammopathy on serum protein electrophoresis (SPEP).
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Affiliation(s)
- B A Cunha
- Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA.
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30
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Abstract
Human cytomegalovirus (CMV), one of the eight herpesviruses that commonly infect humans, is best known for its propensity to cause disease in immunocompromised patients, especially transplant recipients, patients with advanced AIDS, and congenitally infected newborns. Advances in molecular virology coupled with improvements in diagnostic methods and treatment options have vastly improved our understanding of and ability to manage CMV, but many uncertainties remain, including the mechanisms of persistence and pathogenesis and its hypothesized roles in a variety of human illnesses. Here we review recent advances that are reshaping our view and approach to this fascinating virus.
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Affiliation(s)
- Michael Boeckh
- Division of Vaccine and Infectious Disease and
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Medicine, University of Washington, Seattle, Washington, USA.
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Microbiology, University of Washington, Seattle, Washington, USA
| | - Adam P. Geballe
- Division of Vaccine and Infectious Disease and
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Medicine, University of Washington, Seattle, Washington, USA.
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Department of Microbiology, University of Washington, Seattle, Washington, USA
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31
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Snape SE, Venkatesan P. Valganciclovir treatment of primary cytomegalovirus pneumonitis in an immunocompetent adult. BMJ Case Rep 2011; 2011:2011/mar01_1/bcr1120103489. [PMID: 22707605 DOI: 10.1136/bcr.11.2010.3489] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Interstitial pneumonitis is a rare complication of cytomegalovirus (CMV) infection in the immunocompetent. There is a paucity of literature regarding treatment in these patients. A previously healthy, immunocompetent female patient presented with fever, shortness of breath, a dry non-productive cough and myalgia and was subsequently diagnosed with CMV interstitial pneumonitis. She was treated with valganciclovir and swiftly improved but experienced neutropenia, which resolved on treatment cessation.
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Affiliation(s)
- Susan E Snape
- Department of Infectious Diseases, Nottingham University Hospitals City Campus, Nottingham, UK
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