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Yap DYH, Chan GCK, Ho S, Wong RSM, Chan SL, Lee VHF, Lam W, Li PH. Prevention of herpes zoster in acquired immunocompromised conditions: Review of updates and perspectives from Hong Kong. Hum Vaccin Immunother 2025; 21:2463185. [PMID: 40063340 PMCID: PMC11901394 DOI: 10.1080/21645515.2025.2463185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 01/23/2025] [Accepted: 02/01/2025] [Indexed: 03/14/2025] Open
Abstract
Patients with acquired immunocompromising conditions face considerable risk of developing herpes zoster (HZ). Based on the underlying medical conditions and degree of immune dysfunction, these patients require tailored strategies for HZ prevention. In Hong Kong, there is currently a lack of guidelines addressing the unique needs of this vulnerable population, including the use of prophylactic measures such as antivirals and vaccines. An expert panel comprising clinical immunologists, nephrologists, infectious diseases specialists, rheumatologists, hematologists and oncologists in Hong Kong met to review current literature and international guidelines to propose a locally adapted decision-making framework for HZ prophylaxis, in patients with acquired immunocompromised conditions. This article summarizes the consensus and presents a guiding criteria for clinicians to navigate the complexities associated with HZ prevention, in the context of acquired immunodeficiency.
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Affiliation(s)
- Desmond Y. H. Yap
- Department of Medicine, Division of Nephrology, The University of Hong Kong, Hong Kong
| | - Gordon C. K. Chan
- Department of Medicine and Therapeutics, Division of Nephrology, The Chinese University of Hong Kong, Hong Kong
| | - So Ho
- Department of Medicine and Therapeutics, Division of Rheumatology, The Chinese University of Hong Kong, Hong Kong
| | - Raymond S. M. Wong
- Sir YK Pao Centre for Cancer & Department of Medicine and Therapeutics, Division of Haematology, The Chinese University of Hong Kong, Hong Kong
| | - Stephen L. Chan
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Hong Kong Cancer Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong
| | - Victor H. F. Lee
- LKS Faculty of Medicine, School of Clinical Medicine, Department of Clinical Oncology institution, The University of Hong Kong, Hong Kong
| | | | - Philip H. Li
- Department of Medicine, Division of Rheumatology & Clinical Immunology, The University of Hong Kong, Hong Kong
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George S, Carrico J, Hicks KA, Loukov D, Ng C, Curran D. Cost-effectiveness and public health impact of recombinant zoster vaccine versus no herpes zoster vaccination in selected populations of immunocompromised adults in Canada. BMC Health Serv Res 2025; 25:604. [PMID: 40281614 PMCID: PMC12023514 DOI: 10.1186/s12913-025-12550-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 03/10/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND The risk of herpes zoster (HZ) increases with age and in immunocompromised (IC) patients. Recombinant zoster vaccine (RZV) is currently recommended in Canada for people aged ≥ 50 years. The objectives of the current study were to evaluate the cost-effectiveness and public health impact of RZV versus no HZ vaccination in select Canadian IC adult populations. METHODS The ZOster ecoNomic Analysis ImmunoCompromised (ZONA IC) model followed a base-case cohort of 1600 patients with hematopoietic stem-cell transplant (HSCT) from a starting age of 55 years, who maintained IC status for 5 years, from a societal perspective. Scenario analyses were conducted for patients with breast cancer, renal transplant, human immunodeficiency virus (HIV), and Hodgkin lymphoma. These probabilistic analyses used a life-long time horizon and discount rates of 1.5% for costs and quality-adjusted life-years (QALYs). First-dose coverage was assumed to be 60% and second-dose completion 100%. Deterministic one-way sensitivity analysis for the base case was performed. Costs are reported in 2022 Canadian dollars, with an assumed cost-effectiveness threshold of $50,000 per QALY gained. RESULTS In the base-case analysis (HSCT), it was estimated that RZV would prevent medians of 116 HZ and 27 postherpetic neuralgia (PHN) cases, respectively versus no HZ vaccination. Estimated median numbers needed to vaccinate were 8 and 35 to avoid one HZ and one PHN case, respectively. The median incremental cost-effectiveness ratio (ICER) was $22,648 per QALY gained and was most sensitive to assumptions of HZ incidence, direct medical costs for unvaccinated HZ without PHN, and RZV efficacy against PHN. In other IC populations, estimated median ICERs were $24,328 (breast cancer), $27,237 (renal transplant), $67,207 (HIV), and $81,470 (Hodgkin lymphoma). CONCLUSIONS RZV in Canada improves public health outcomes and is likely cost-effective for several IC conditions.
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Zhou Q, Jing M, Ren H, Li G, Wang Z. Efficacy of electroacupuncture on clinical signs and immunological factors in herpes zoster: The first systematic review, meta-analysis, and trial sequential analysis of randomized clinical trials. Medicine (Baltimore) 2025; 104:e41458. [PMID: 40128056 PMCID: PMC11936656 DOI: 10.1097/md.0000000000041458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 01/17/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Electroacupuncture (EA) is utilized to address various health conditions. Herein, we designed a systematic review and meta-analysis to evaluate the efficacy of EA on clinical and immunological factors in herpes zoster (HZ) based on randomized clinical trials. METHODS Four international databases and 3 Chinese databases were searched until January 2024. We used RevMan 5.3 for meta-analysis and presented the data as standardized mean difference (SMD) or odds ratio (OR) and 95% confidence interval. RESULTS A total of 1361 records were identified in the databases and at last, 19 articles were entered into the meta-analysis. The result shows a negative pooled SMD of -2.55 (P < .00001) for the VAS score. The pooled SMD for cessation of pustules time in the case group compared to the control group was -0.69 (P = .0008), for pain relief time was -1.36 (P = .002), for the time to scab was -0.47 (P = .009), and for time to remove scab was -1.01 (P = .0003). The pooled OR for the incidence of postherpetic neuralgia was 0.11 (P < .00001), and the total effective rate was 4.25 (P < .00001). The pooled SMD for the cluster of differentiation (CD)3 count was 2.59 (P = .07), for the CD4 count was 2.81 (P = .04), for the CD8 count was -0.75 (P = .50), and for theCD4/CD8 ratio was 1.12 (P = .15). CONCLUSIONS The results indicate that the EA treatment had several significant benefits compared to Western medicine (WM) in HZ patients in terms of clinical and immunological factors. But, the combination of treatments of EA with WM had better effects compared to EA treatment alone.
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Affiliation(s)
- Qiaoli Zhou
- Department of Nursing, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Mao Jing
- Department of Acupuncture and moxibustion and Trauma College of Hubei University of Traditional Chinese Medicine, Wuhan City, Hubei Province, China
| | - Haitao Ren
- School of Life and Health of Huzhou College, Huzhou City, Zhejiang Province, China
| | - Gaokai Li
- School of Life and Health of Huzhou College, Huzhou City, Zhejiang Province, China
| | - Zongjiao Wang
- Fitness Teaching and Research Office, Professional Tennis Academy, Wuhan Urban Vocational College, Wuhan City, Hubei Province, China
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Sohal A, Kohli I, Chaudhry H, Singh I, Arora K, Kalra S, Dukovic D, Roytman M. Vaccine-Preventable Illness Leads to Adverse Outcomes in Liver Transplant Recipients. Dig Dis Sci 2024; 69:588-595. [PMID: 38030833 DOI: 10.1007/s10620-023-08202-x] [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: 07/24/2023] [Accepted: 11/19/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Liver transplant recipients (LTR) and patients with chronic liver disease (CLD) are at an increased risk of infections. AIMS The objective of our study was to assess the incidence, and impact of vaccine preventable illness (VPI) on outcomes in LTR. METHODS National Inpatient Sample (NIS) 2016-2020 was used to identify adults (age > 18) hospitalized LTR using ICD-10 codes. Data were collected on patient demographics, hospital characteristics, etiology of liver disease, hepatic decompensations and outcomes. Patients were stratified into two groups based on the presence or absence of VPI. Multivariate logistic regression analysis was performed to identify the association between VPI and outcomes. RESULTS Out of 170,650 hospitalized LTR, 13.5% of the patients had VPI. The most common VPI was noted to be influenza (10.7%), followed by pneumococcal infection (2.7%). Incidence of mortality (6.9% vs. 1.6%, p < 0.001), ICU admissions (14.3% vs. 3.4%, p < 0.001), and acute kidney injury (AKI) (43.7% vs 37.35%, p < 0.001) was higher in the VPI group. CONCLUSION More than 13% of the LT hospitalizations had concomitant VPI. VPI in LTR was associated with worse outcomes. Our data suggests the need to identify factors associated with reduced vaccination rates and identify strategies to improve vaccination rates and responses in these patients.
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Affiliation(s)
- Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, 3216 NE 45Th Pl, Suite 212, Seattle, WA, 98105, USA.
| | - Isha Kohli
- Graduate Program in Public Health, Icahn School of Medicine, Mount Sinai, New York, NY, USA
| | - Hunza Chaudhry
- Department of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
| | | | - Kirti Arora
- Dayanand Medical College and Hospital, Ludhiana, India
| | - Shivam Kalra
- Dayanand Medical College and Hospital, Ludhiana, India
| | - Dino Dukovic
- Ross University of Medical Sciences, Miramar, FL, USA
| | - Marina Roytman
- Department of Gastroenterology and Hepatology, University of California, San Francisco, Fresno, CA, USA
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Patrucco F, Curtoni A, Sidoti F, Zanotto E, Bondi A, Albera C, Boffini M, Cavallo R, Costa C, Solidoro P. Herpes Virus Infection in Lung Transplantation: Diagnosis, Treatment and Prevention Strategies. Viruses 2023; 15:2326. [PMID: 38140567 PMCID: PMC10747259 DOI: 10.3390/v15122326] [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: 09/23/2023] [Revised: 11/12/2023] [Accepted: 11/14/2023] [Indexed: 12/24/2023] Open
Abstract
Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.
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Affiliation(s)
- Filippo Patrucco
- Respiratory Diseases Unit, Medical Department, AOU Maggiore della Carità di Novara, Corso Mazzini 18, 28100 Novara, Italy
| | - Antonio Curtoni
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Francesca Sidoti
- Division of Virology, Department of Public Health and Pediatrics, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Elisa Zanotto
- Division of Virology, Department of Public Health and Pediatrics, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Alessandro Bondi
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Carlo Albera
- Division of Respiratory Medicine, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Medical Sciences Department, University of Turin, 10126 Turin, Italy
| | - Massimo Boffini
- Cardiac Surgery Division, Surgical Sciences Department, AOU Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Rossana Cavallo
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Cristina Costa
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Paolo Solidoro
- Division of Respiratory Medicine, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Medical Sciences Department, University of Turin, 10126 Turin, Italy
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Salem A, La EM, Curran D, Patterson BJ, Carrico J, Lorenc S, Hicks KA, Poston S, Carpenter CF. Cost-Effectiveness of Recombinant Zoster Vaccine for the Prevention of Herpes Zoster in Hematopoietic Stem Cell Transplant Recipients and Other Immunocompromised Adults in the United States. PHARMACOECONOMICS - OPEN 2023; 7:975-985. [PMID: 37917310 PMCID: PMC10721768 DOI: 10.1007/s41669-023-00438-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/24/2023] [Indexed: 11/04/2023]
Abstract
INTRODUCTION Immunocompromised (IC) adults are at increased risk of developing herpes zoster (HZ) and HZ-related complications due to therapy or underlying disease. This study evaluated the cost effectiveness of recombinant zoster vaccine (RZV) versus no vaccine for the prevention of HZ in hematopoietic stem cell transplant (HSCT) recipients and other IC adults aged ≥ 18 years in the United States (US). METHODS A static Markov model simulated cohorts of IC individuals using a 1-year cycle length and 30-year time horizon to estimate the cost effectiveness of RZV. Inputs were sourced from clinical trial results and publicly available sources/literature. Modeled populations included US adult HSCT recipients (base case), patients with human immunodeficiency virus (HIV), patients with breast cancer, patients with Hodgkin's lymphoma, and renal transplant recipients. The model reported societal costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity and threshold analyses were conducted. RESULTS In the base case of 19,671 US adult HSCT recipients, RZV resulted in total societal cost savings of US$0.1 million and 109 incremental QALYs versus no vaccine. RZV was a 'dominant strategy' versus no vaccine because vaccination resulted in cost savings with QALY gains. RZV was also cost saving in renal transplant recipients, and cost effective at a willingness-to-pay threshold of US$100,000 per QALY gained in patients with HIV, breast cancer, and Hodgkin's lymphoma, with ICERs of US$33,268, US$67,682, and US$95,972 per QALY gained, respectively, versus no vaccine. CONCLUSIONS Model results show RZV is potentially cost saving for the prevention of HZ in US adult HSCT recipients and US adults with selected immunocompromising conditions, and cost effective for others, supporting the use of RZV to prevent HZ and HZ-related complications in IC adults.
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Affiliation(s)
- Ahmed Salem
- GSK, Avenue Pascal 2/4-6, 1300, Wavre, Belgium.
| | | | | | | | | | | | | | | | - Christopher F Carpenter
- Beaumont Hospital, Royal Oak, MI, USA
- Oakland University William Beaumont School of Medicine, Rochester, MI, USA
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Bahakel H, Feldman AG, Danziger-Isakov L. Immunization of Solid Organ Transplant Candidates and Recipients: A 2022 Update. Infect Dis Clin North Am 2023:S0891-5520(23)00025-9. [PMID: 37142511 DOI: 10.1016/j.idc.2023.03.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
Immunizations are a relatively safe and cost-effective intervention to prevent morbidity and mortality associated with vaccine preventable infection (VPIs). As such, immunizations are a critical part of the care of pre and posttransplant patients and should be prioritized. New tools are needed to continue to disseminate and implement the most up-to-date vaccine recommendations for the SOT population. These tools will help both primary care providers and multi-disciplinary transplant team members taking care of transplant patients to stay abreast of evidence-based best practices regarding the immunization of the SOT patient.
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Affiliation(s)
- Hannah Bahakel
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA
| | - Amy G Feldman
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, University of Colorado School of Medicine and Children's Hospital Colorado, 13123 East 16th Avenue, Aurora, CO 80045, USA
| | - Lara Danziger-Isakov
- Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3026, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Kim SH, Huh K, Lee KW, Park JB, Huh WS, Ko JH, Cho SY, Kang CI, Chung DR, Peck KR. Clinical effectiveness of zoster vaccine live in kidney transplant recipients immunized prior to transplantation: a retrospective single-centre cohort study. Clin Microbiol Infect 2023:S1198-743X(23)00084-8. [PMID: 36868356 DOI: 10.1016/j.cmi.2023.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/16/2023] [Accepted: 02/22/2023] [Indexed: 03/04/2023]
Abstract
OBJECTIVES Kidney transplant (KT) recipients have an increased risk of herpes zoster (HZ) and its complications. Although recombinant zoster vaccine is favoured over zoster vaccine live (ZVL), ZVL is also recommended to prevent HZ for KT candidates. We aimed to evaluate the clinical effectiveness of ZVL in KT recipients immunized before transplantation. METHODS Adult patients who received kidney transplantation from January 2014 to December 2018 were enrolled. Patients were observed until HZ occurrence, death, loss of allograft, loss to follow-up, or 5 years after transplantation. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare the incidence of HZ after transplantation between vaccinated and unvaccinated patients. RESULTS A total of 84 vaccinated and 340 unvaccinated patients were included. The median age was higher in the vaccinated group (57 vs. 54 years, p 0.003). Grafts from deceased donors were more frequently transplanted in the unvaccinated group (16.7% vs. 51.8%, p < 0.001). Five-year cumulative HZ incidence was 11.9%, which translated to 26.27 (95% CI, 19.33-34.95) per 1000 person-years. The incidence in the vaccinated and unvaccinated groups was 3.9% and 13.7%, respectively. After adjustment, vaccination showed significant protective effectiveness against HZ (adjusted hazard ratio, 0.18, 95% CI, 0.05-0.60). In addition, all four cases of disseminated zoster occurred in the unvaccinated group. DISCUSSION Our study, the first on the clinical effectiveness of zoster vaccines for KT recipients, suggests that ZVL before transplantation effectively prevents HZ.
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Affiliation(s)
- Si-Ho Kim
- Division of Infectious Diseases, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
| | - Kyungmin Huh
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Kyo Won Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Berm Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Seong Huh
- Division of Nephrology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae-Hoon Ko
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun Young Cho
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Cheol-In Kang
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Doo Ryeon Chung
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyong Ran Peck
- Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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Hurley LP, O'Leary ST, Dooling K, Anderson TC, Crane LA, Cataldi JR, Brtnikova M, Beaty BL, Gorman C, Guo A, Lindley MC, Kempe A. Survey of Physician Practices, Attitudes, and Knowledge Regarding Recombinant Zoster Vaccine. J Gen Intern Med 2023; 38:986-993. [PMID: 35794307 PMCID: PMC9261227 DOI: 10.1007/s11606-022-07721-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 06/17/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Herpes zoster vaccination rates remain low despite longstanding national recommendations to vaccinate immunocompetent adults aged ≥ 50 years. The Advisory Committee on Immunization Practice (ACIP) updated its recommendations for recombinant zoster vaccine (RZV) in October 2021 to include immunocompromised adults aged ≥19 years. OBJECTIVE To assess practices, attitudes, and knowledge about RZV, barriers to recommending RZV, and likelihood of recommending RZV to patients with various immunocompromising conditions. DESIGN Mail and internet-based survey conducted from May through July 2020. PARTICIPANTS General internists and family physicians throughout the USA. MAIN MEASURES Survey responses. KEY RESULTS The response rate was 66% (632/955). Many physicians were already recommending RZV to immunocompromised populations, including adults ≥50 years with HIV (67% of respondents) and on recombinant human immune modulator therapy (56%). Forty-seven percent of respondents both stocked/administered RZV and referred patients elsewhere, frequently a pharmacy, for vaccination; 42% did not stock RZV and only referred patients. The majority agreed pharmacies do not inform them when RZV has been given (64%). Physicians were generally knowledgeable about RZV; however, 25% incorrectly thought experiencing side effects from the first dose of RZV that interfere with normal activities was a reason to not receive the second dose. The top reported barrier to recommending RZV was experience with patients declining RZV due to cost concerns (67%). Most physicians reported they would be likely to recommend RZV to immunocompromised patients. CONCLUSION Most primary care physicians welcome updated ACIP RZV recommendations for immunocompromised adults. Knowledge gaps, communication issues, and financial barriers need to be addressed to optimize vaccination delivery.
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Affiliation(s)
- Laura P Hurley
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA.
- Division of General Internal Medicine, Denver Health, Denver, CO, USA.
| | - Sean T O'Leary
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
- Department of Pediatrics University of Colorado Anschutz Medical Center, Aurora, CO, USA
| | - Kathleen Dooling
- National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Tara C Anderson
- National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Lori A Crane
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
- Department of Community and Behavioral Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Jessica R Cataldi
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
- Department of Pediatrics University of Colorado Anschutz Medical Center, Aurora, CO, USA
| | - Michaela Brtnikova
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
- Department of Pediatrics University of Colorado Anschutz Medical Center, Aurora, CO, USA
| | - Brenda L Beaty
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
| | - Carol Gorman
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
| | - Angela Guo
- National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
- Strategic Innovative Solutions, LLC, Atlanta, GA, USA
| | - Megan C Lindley
- National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Allison Kempe
- Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, USA
- Department of Pediatrics University of Colorado Anschutz Medical Center, Aurora, CO, USA
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Kidney Transplant Patients Generate Varicella Zoster-Reactive T-cell and Humoral Immunity Following Protein-based Varicella Zoster Vaccination. Transplantation 2023; 107:e58-e59. [PMID: 36696521 DOI: 10.1097/tp.0000000000004406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Sullivan KM, Farraye FA, Winthrop KL, Willer DO, Vink P, Tavares-Da-Silva F. Safety and efficacy of recombinant and live herpes zoster vaccines for prevention in at-risk adults with chronic diseases and immunocompromising conditions. Vaccine 2023; 41:36-48. [PMID: 36460534 DOI: 10.1016/j.vaccine.2022.10.063] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 10/21/2022] [Accepted: 10/23/2022] [Indexed: 11/30/2022]
Abstract
Compared with the general population, older adults with immune senescence and individuals who are immunocompromised (IC) due to disease or immunosuppressive therapy are at increased risk for herpes zoster (HZ) and its associated complications, which can be debilitating and life-threatening. Vaccination can be an effective strategy against HZ and studies have shown that HZ vaccination in IC individuals can elicit immune responses and provide protection from infection. Recently, the first approvals have been granted in the United States and the European Union for the recombinant HZ vaccine (RZV) in adults ≥ 18 years of age at risk of HZ due to immunodeficiency or immunosuppression. Existing systematic reviews have highlighted the risks for HZ in limited immunocompromising conditions and have only examined clinical data for RZV. This review details the risks and burden of HZ in a broad range of clinically relevant IC populations and summarizes key efficacy and safety data for RZV and live HZ vaccine in these individuals. Research has shown IC individuals can benefit from HZ vaccination; however, these insights have yet to be fully incorporated into vaccination guidelines and clinical care. Clinicians should consider HZ vaccination in eligible at-risk populations to protect against HZ and its associated complications and thereby, reduce the burden that HZ poses on the healthcare system. Electronic health records and linked personal health records could be used to identify and contact patients eligible for HZ vaccination and provide clinical decision support-generated alerts for missing or delayed vaccinations. This review will help clinicians identify eligible IC individuals who may benefit from HZ vaccination. A video abstract linked to this article is available on Figshare https://doi.org/10.6084/m9.figshare.21517605.
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Affiliation(s)
- Keith M Sullivan
- Duke University Medical Center, 200 Trent Dr, Durham, NC 27710, USA.
| | - Francis A Farraye
- Inflammatory Bowel Disease Center, Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
| | - Kevin L Winthrop
- Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
| | - David O Willer
- GSK Vaccines, 100 Milverton Drive Suite 800, Mississauga, ON, Canada.
| | - Peter Vink
- GSK Vaccines, 14200 Shady Grove Rd, Rockville, MD 20850, USA.
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12
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Bhatia SS, Canepa C, Notarianni A. Bickerstaff’s brainstem encephalitis mimicking herpetic encephalomyelitis in a liver transplant patient with anti-GQ1b antibodies. BMJ Case Rep 2022; 15:15/12/e251784. [DOI: 10.1136/bcr-2022-251784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
A woman in her late 70s with a history of liver transplant presented with ophthalmoplegia, ataxia, areflexia, positive Babinski’s sign and reduced consciousness. This followed an antecedent illness in the form of a herpes zoster infection. MRI of the brain/spinal cord, cerebrospinal fluid analysis with viral PCR and routine blood tests were normal, and tacrolimus neurotoxicity was ruled out. Serum anti-GQ1b antibodies were positive. A diagnosis of Bickerstaff’s brainstem encephalitis was made, forming part of the continuum that involves Miller-Fisher syndrome, entitled the ‘anti-GQ1b syndrome’. Complete recovery ensued without intravenous immunoglobulins or plasma exchange. The role of monitoring anti-ganglioside pattern change to predict or confirm disease recurrence and disease severity is further discussed.
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13
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Fronek L, Giansiracusa D, Nourmohammadi N, Johnson C, Yelich A, Hogan D. A Review of Cutaneous Diseases Observed in Solid Organ Transplant Recipients. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2022; 15:21-31. [PMID: 36312823 PMCID: PMC9586525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Solid organ transplant recipients are at increased risk for numerous cutaneous conditions that fall within four categories: pre-neoplastic, neoplastic, infectious, or idiopathic. Many of these diseases can be attributed to immunosuppressive medications, including mycophenolate mofetil, cyclosporine, azathioprine, tacrolimus, or glucocorticoids. Iatrogenic lessening of the immune system places the patient at risk of malignancies, opportunistic infections, immune-mediated dermatoses, and adverse effects of medications. As the life expectancy of patients with solid organ transplants continues to increase, dermatologists and transplant physicians must stay abreast of this spectrum of dermatologic conditions, their respective prognoses, prevention, mitigation, and treatment.
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Affiliation(s)
- Lisa Fronek
- Dr. Fronek is with Bighorn Mohs Surgery and Dermatology Center, Scripps Clinic, La Jolla, California
| | - Derrek Giansiracusa
- Mr. Giansiracusa and Ms. Nourmohammadi are with Lake Erie College of Osteopathic Medicine in Bradenton, Florida
| | - Niki Nourmohammadi
- Mr. Giansiracusa and Ms. Nourmohammadi are with Lake Erie College of Osteopathic Medicine in Bradenton, Florida
| | - Cassandra Johnson
- Drs. Johnson, Yelich, and Hogan are with HCA Healthcare and USF Morsani College of Medicine at Largo Medical Center in Largo, Florida
| | - Allyson Yelich
- Drs. Johnson, Yelich, and Hogan are with HCA Healthcare and USF Morsani College of Medicine at Largo Medical Center in Largo, Florida
| | - Daniel Hogan
- Drs. Johnson, Yelich, and Hogan are with HCA Healthcare and USF Morsani College of Medicine at Largo Medical Center in Largo, Florida
- Dr. Hogan is additionally with the Department of Dermatology at Bay Pines Veterans Affairs Healthcare System in Bay Pines, Florida
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14
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Adjuvanted recombinant zoster vaccine in solid organ transplant and hematopoietic stem-cell transplant recipients. Curr Opin Infect Dis 2022; 35:312-320. [PMID: 35849521 DOI: 10.1097/qco.0000000000000845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW Hematopoietic stem-cell (HSCT) and solid organ transplant (SOT) recipients are particularly at risk to develop herpes zoster and its complications. A recently approved nonlive, adjuvanted recombinant zoster vaccine (aRZV) is a potential candidate to provide durable prevention of herpes zoster. This review summarizes current scientific evidence and expert recommendations for its use in these populations and offers practical clinical guidance. RECENT FINDINGS Recent clinical trials have shown aRZV to be well tolerated and efficacious in the prevention of herpes zoster, even in the elderly. Data are emerging that this vaccine might also be effective in immunocompromised individuals, such as SOT and HSCT recipients. Evidence is sparse regarding optimal timing of vaccination and durability of responses. However, several specialized societies have already established expert-based aRZV immunization recommendations for these vulnerable populations. SUMMARY Practical considerations, safety concerns, and timing of vaccine administration vary from one immunocompromised subpopulation to another. Initial studies show that aRZV has a favorable safety and immunogenicity profile in SOT and HSCT recipients. However, data are sparse, particularly in allogeneic HSCT, and practical recommendations are mostly based on expert opinion. Additional research is needed to offer better insight on aRZV administration in immunocompromised patients.
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15
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Herpes Zoster in Children with Underlying Comorbidities: Evaluation of the 10-Year Retrospective Single Center Experience. JOURNAL OF CONTEMPORARY MEDICINE 2022. [DOI: 10.16899/jcm.1076070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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16
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Fiore J, Co-van der Mee MM, Maldonado A, Glasser L, Watson P. Safety and reactogenicity of the adjuvanted recombinant zoster vaccine: experience from clinical trials and post-marketing surveillance. Ther Adv Vaccines Immunother 2022; 9:25151355211057479. [PMID: 35005428 PMCID: PMC8734271 DOI: 10.1177/25151355211057479] [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: 05/12/2021] [Accepted: 10/15/2021] [Indexed: 12/02/2022] Open
Abstract
An adjuvanted recombinant zoster vaccine (RZV) is licensed for the prevention of
herpes zoster. This paper reviews its safety and reactogenicity. A pooled
analysis of two pivotal randomized Phase-3 trials (NCT01165177, NCT01165229) in
adults ⩾50 years found that more solicited adverse events (AEs) were reported
with RZV than placebo. Injection site pain was the most common solicited AE
(RZV: 78.0% participants; placebo: 10.9%). Grade-3 pain occurred in 6.4% of RZV
and 0.3% of placebo recipients. Myalgia, fatigue, and headache were the most
commonly reported general solicited AEs (RZV: 44.7%, 44.5%, and 37.7%,
respectively; placebo: 11.7%, 16.5%, and 15.5%, respectively). Most symptoms
were mild to moderate in intensity with a median duration of 2–3 days. The
intensity of reactogenicity symptoms did not differ substantially after the
first and second vaccine doses. The pooled analysis of the pivotal Phase-3
trials did not identify any clinically relevant differences in the overall
incidence of serious adverse events (SAEs), fatal AEs or potential
immune-mediated diseases (pIMDs) between RZV and placebo. Reactogenicity in five
studies of immunocompromised patients ⩾18 years (autologous stem cell
transplant, human immunodeficiency virus, solid tumors, hematological
malignancies, and renal transplant; NCT01610414, NCT01165203, NCT01798056,
NCT01767467, and NCT02058589) was consistent with that observed in the pivotal
Phase-3 trials. There were no clinically relevant differences between RZV and
placebo in the immunocompromised populations with regard to overall incidence of
SAEs, fatal AEs, pIMDs, or AEs related to patients’ underlying condition.
Post-marketing surveillance found that the most commonly reported AEs were
consistent with the reactogenicity profile of the vaccine in clinical trials.
Overall, the clinical safety data for RZV are reassuring.
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17
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Dang A, Khaled Soufi M, Nguyen C, Orndorff J, Baliss M, Berbarie RF, Khalife WI. The Burden of Hospitalizations for Vaccine-Preventable Infections in Heart Transplant Recipients. Am J Cardiol 2021; 157:148-150. [PMID: 34373079 DOI: 10.1016/j.amjcard.2021.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 07/13/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Alexander Dang
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Mohamad Khaled Soufi
- Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Christopher Nguyen
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Joseph Orndorff
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas
| | - Michelle Baliss
- Division of Gastroenterology and Hepatology, St. Louis University, St. Louis, Missouri
| | - Rafic F Berbarie
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Wissam I Khalife
- Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, Texas
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18
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Successful Use of Kidneys from a Deceased Donor with Active Herpes Zoster Infection. Case Rep Transplant 2021; 2021:7719041. [PMID: 34434591 PMCID: PMC8382547 DOI: 10.1155/2021/7719041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 08/04/2021] [Indexed: 11/21/2022] Open
Abstract
Background The limited donor pool and increasing recipient wait list require a reevaluation of kidney organ suitability for transplantation. Use of higher infectious risk organs that were previously discarded may help improve access to transplantation and reduce patient mortality without placing patients at a higher risk of poor posttransplant outcomes. There is very little data available regarding the safe use of kidney organs from deceased donors with varicella zoster virus infection at the time of organ retrieval. Case Presentation. Here, we report a case of successful transplantation of both kidneys from a deceased donor with active herpes zoster infection at the time of organ retrieval. Recipients were treated preemptively with acyclovir. At 4 months posttransplant, both kidney recipients experienced no infectious complications and were off dialysis with functioning transplant grafts. Conclusions The use of kidney organs from donors with active herpes zoster infection appears to be a safe option to expand the kidney donor pool.
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19
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Association between Neutrophil-Lymphocyte Ratio and Herpes Zoster Infection in 1688 Living Donor Liver Transplantation Recipients at a Large Single Center. Biomedicines 2021; 9:biomedicines9080963. [PMID: 34440167 PMCID: PMC8391531 DOI: 10.3390/biomedicines9080963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 08/04/2021] [Indexed: 12/05/2022] Open
Abstract
Liver transplantation (LT) is closely associated with decreased immune function, a contributor to herpes zoster (HZ). However, risk factors for HZ in living donor LT (LDLT) remain unknown. Neutrophil-lymphocyte ratio (NLR) and immune system function are reportedly correlated. This study investigated the association between NLR and HZ in 1688 patients who underwent LDLT between January 2010 and July 2020 and evaluated risk factors for HZ and postherpetic neuralgia (PHN). The predictive power of NLR was assessed through the concordance index and an integrated discrimination improvement (IDI) analysis. Of the total cohort, 138 (8.2%) had HZ. The incidence of HZ after LT was 11.2 per 1000 person-years and 0.1%, 1.3%, 2.9%, and 13.5% at 1, 3, 5, and 10 years, respectively. In the Cox regression analysis, preoperative NLR was significantly associated with HZ (adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02–1.09; p = 0.005) and PHN (HR, 1.08; 95% CI, 1.03–1.13; p = 0.001). Age, sex, mycophenolate mofetil use, and hepatitis B virus infection were risk factors for HZ versus age and sex for PHN. In the IDI analysis, NLR was discriminative for HZ and PHN (p = 0.020 and p = 0.047, respectively). Preoperative NLR might predict HZ and PHN in LDLT recipients.
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20
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Dagnew AF, Vink P, Drame M, Willer DO, Salaun B, Schuind AE. Immune responses to the adjuvanted recombinant zoster vaccine in immunocompromised adults: a comprehensive overview. Hum Vaccin Immunother 2021; 17:4132-4143. [PMID: 34190658 PMCID: PMC8827627 DOI: 10.1080/21645515.2021.1930846] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Immunocompromised (IC) persons are at increased risk for herpes zoster (HZ) and its complications, mainly due to impairment of cell-mediated immunity (CMI). The adjuvanted recombinant zoster vaccine (RZV) demonstrated efficacy against HZ in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and hematologic malignancy (HM) patients. We review immune responses to RZV in 5 adult IC populations, 4 of which were receiving multiple, concomitant immunosuppressive medications: auto-HSCT and renal transplant recipients, HM and solid tumor patients, and human immunodeficiency virus-infected adults. Although administered in most cases when immunosuppression was near its maximum, including concomitantly with chemotherapy cycles, RZV induced robust and persistent humoral and, more importantly, CMI responses in all 5 IC populations. Based on the overall clinical data generated in older adults and IC individuals, RZV is expected to provide benefit in a broad adult population at risk for HZ.
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21
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Kwon DE, Lee HS, Lee KH, La Y, Han SH, Song YG. Incidence of herpes zoster in adult solid organ transplant recipients: A meta-analysis and comprehensive review. Transpl Infect Dis 2021; 23:e13674. [PMID: 34153168 DOI: 10.1111/tid.13674] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 06/01/2021] [Accepted: 06/04/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic immunosuppressive therapy in solid organ transplant (SOT) recipients can trigger latent varicella zoster virus reactivation even in those with stable graft function. The inactivated herpes zoster (HZ) vaccine can be effective in preventing post-transplant HZ, which can cause severe neuralgia or disseminated disease. This meta-analysis aims to assess the incidences of HZ across transplant organs in SOT recipients. METHODS We included 12 observational studies (6560 recipients) from a PubMed and EMBASE search of articles through October 2019 and collected data from single-center dating from January 2001 to December 2017 (3498 recipients). The pooled HZ incidence and its differences between subgroups were obtained from random-effect models and meta-analysis of variance tests using R package. RESULTS The overall pooled crude incidence was 9.1% (95% confidence interval [CI], 7.6%-10.8%). The pooled incidence was similar between sexes but significantly different between transplanted organs (P < .001). Heart transplants (HT) (n = 644) have the highest pooled incidence with 15.2% (95% CI, 12.7%-18.2%), followed by lung transplants (LTX) (n = 780) with 11.0% (8.3%-14.4%). Kidney transplants (n = 5435) have the lowest incidence of 6.7 (5.1%-8.8%). The meta-regression analysis revealed that HZ development had a relationship with past graft rejection (P = .024). CONCLUSION These data support the need for subunit HZ vaccination in SOT recipients with a high risk for HZ, especially HT and LTX recipients, without respect to the late post-transplant period.
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Affiliation(s)
- Da Eun Kwon
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Sun Lee
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyoung Hwa Lee
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yeonju La
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Han
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong Goo Song
- Division of Infectious Disease, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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22
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López-Fauqued M, Co-van der Mee M, Bastidas A, Beukelaers P, Dagnew AF, Fernandez Garcia JJ, Schuind A, Tavares-da-Silva F. Safety Profile of the Adjuvanted Recombinant Zoster Vaccine in Immunocompromised Populations: An Overview of Six Trials. Drug Saf 2021; 44:811-823. [PMID: 34115324 PMCID: PMC8217041 DOI: 10.1007/s40264-021-01076-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/23/2021] [Indexed: 12/29/2022]
Abstract
Introduction The adjuvanted recombinant zoster vaccine (RZV) has demonstrated high efficacy against herpes zoster in older adults and immunocompromised populations. We present comprehensive safety data from six clinical trials in immunocompromised populations (autologous hematopoietic stem cell transplant and renal transplant recipients, patients with hematologic malignancies, patients with solid tumors, and human immunodeficiency virus-infected adults) who are at an increased risk of herpes zoster. Methods In all trials, immunocompromised adults ≥ 18 years of age were administered RZV or placebo. Safety was evaluated in the total vaccinated cohort. Solicited adverse events (AEs) were collected for 7 days and unsolicited AEs for 30 days after each dose. Serious AEs, fatal serious AEs, and potential immune-mediated diseases were collected from dose 1 until 12 months post-last dose or study end. Data were pooled for solicited AEs; unsolicited AEs, (fatal) serious AEs, and potential immune-mediated diseases were analyzed for each individual trial. All AEs were analyzed for sub-strata of adults 18–49 years of age and ≥ 50 years of age. Results In total, 1587 (RZV) and 1529 (placebo) adults were included in the pooled total vaccinated cohort. Solicited AEs were more common after RZV than placebo, were generally more common in the younger age stratum, and were mostly mild to moderate and resolved within 3 days (median duration). Unsolicited AEs and serious AEs were in line with underlying diseases and therapies. Across studies, the percentage of adults reporting one or more unsolicited AE was comparable between RZV and placebo, irrespective of age stratum. The percentage of adults reporting one or more serious AE, fatal serious AE, or potential immune-mediated diseases was generally similar for RZV and placebo, irrespective of age stratum. Overall, no safety concerns were identified. Conclusions Recombinant zoster vaccine has a clinically acceptable safety profile. With the previously published vaccine efficacy and immunogenicity results, these data support a favorable benefit-risk profile of RZV vaccination in immunocompromised populations who are at an increased risk of herpes zoster. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01076-w. Varicella zoster virus leads to chickenpox after primary infection and herpes zoster upon reactivation of the latent virus. Older adults and immunocompromised people, whose immune system is impaired because of the age-related decline in immunity and their underlying disease and/or treatment, respectively, are at an increased risk of herpes zoster and its complications. Recombinant zoster vaccine has been approved to prevent herpes zoster and its complications in adults aged ≥ 50 years in over 30 countries. In Europe, the vaccine has recently received approval to expand its use in adults aged 18 years or older who are at an increased risk of herpes zoster. We present an overview of the safety data from six clinical trials in immunocompromised patients vaccinated with recombinant zoster vaccine. We found that solicited adverse events were more common after the vaccine than placebo but that these were mild to moderate in intensity. Furthermore, the frequency of unsolicited adverse events was similar between the vaccine and placebo, and most of the reported adverse events and severe adverse events (e.g., infections or tumors) could be attributed to the pre-existent diseases and/or therapies. As such, no safety concern was identified following the review of the available clinical data. This overview, together with the published efficacy data in the prevention of herpes zoster and the vaccine immunogenicity, provides useful medical information and supports the use of the recombinant zoster vaccine in an immunocompromised population at an increased risk of herpes zoster.
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Affiliation(s)
| | | | - Adriana Bastidas
- GSK, Avenue Fleming 20, 1300 Wavre, Belgium
- Present Address: Current affiliation: Mithra Pharmaceuticals, Flemalle, Belgium
| | | | - Alemnew F. Dagnew
- GSK, Rockville, MD USA
- Present Address: Bill & Melinda Gates Medical Research Institute, Cambridge, MA USA
| | | | - Anne Schuind
- GSK, Rockville, MD USA
- Present Address: PATH, Washington DC, WA USA
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23
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Hirzel C, L'Huillier AG, Ferreira VH, Marinelli T, Ku T, Ierullo M, Miao C, Schmid DS, Juvet S, Humar A, Kumar D. Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients. Am J Transplant 2021; 21:2246-2253. [PMID: 33565711 PMCID: PMC9169546 DOI: 10.1111/ajt.16534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/26/2021] [Accepted: 01/28/2021] [Indexed: 01/25/2023]
Abstract
Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 106 CD4+ T cells; IQR: 46-180) to the first (median 128 per 106 CD4+ T cells; IQR: 82-353; p = .023) and after the second dose (median 361 per 106 CD4+ T cells; IQR: 146-848; p < .0001). Tenderness (83.0%; 95%CI: 69.2-92.4%) and redness (31.9%; 95%CI: 19.1-47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.
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Affiliation(s)
- Cedric Hirzel
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada,Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Arnaud G. L'Huillier
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada,Pediatric Infectious Diseases Unit, Department of Child and Adolescent Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland
| | - Victor H. Ferreira
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Tina Marinelli
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Terrance Ku
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Matthew Ierullo
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Congrong Miao
- Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - D. Scott Schmid
- Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Stephen Juvet
- Toronto Lung Transplant Program, University Health Network, Toronto, ON, Canada
| | - Atul Humar
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
| | - Deepali Kumar
- Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada
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24
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McKay SL, Guo A, Pergam SA, Dooling K. Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review. Clin Infect Dis 2021; 71:e125-e134. [PMID: 31677266 DOI: 10.1093/cid/ciz1090] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 10/31/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The primary reported risk factors for herpes zoster (HZ) include increasing age and immunodeficiency, yet estimates of HZ risk by immunocompromising condition have not been well characterized. We undertook a systematic literature review to estimate the HZ risk in immunocompromised patients. METHODS We systematically reviewed studies that examined the risk of HZ and associated complications in adult patients with hematopoietic cell transplants (HCT), cancer, human immunodeficiency virus (HIV), and solid organ transplant (SOT). We identified studies in PubMed, Embase, Medline, Cochrane, Scopus, and clinicaltrials.gov that presented original data from the United States and were published after 1992. We assessed the risk of bias with Cochrane or Grading of Recommendations Assessment, Development, and Evaluation methods. RESULTS We identified and screened 3765 records and synthesized 34 studies with low or moderate risks of bias. Most studies that were included (32/34) reported at least 1 estimate of the HZ cumulative incidence (range, 0-41%). There were 12 studies that reported HZ incidences that varied widely within and between immunocompromised populations. Incidence estimates ranged from 9 to 92 HZ cases/1000 patient-years and were highest in HCT, followed by hematologic malignancies, SOT, and solid tumor malignancies, and were lowest in people living with HIV. Among 17 HCT studies, the absence of or use of antiviral prophylaxis at <1 year post-transplant was associated with a higher HZ incidence. CONCLUSIONS HZ was common among all immunocompromised populations studied, exceeding the expected HZ incidence among immunocompetent adults aged ≥60 years. Better evidence of the incidence of HZ complications and their severity in immunocompromised populations is needed to inform economic and HZ vaccine policies.
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Affiliation(s)
- Susannah L McKay
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.,Division of Viral Diseases, National Center Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Angela Guo
- Division of Viral Diseases, National Center Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Steven A Pergam
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.,Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.,Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.,Infection Prevention, Seattle Cancer Care Alliance, Seattle, Washington, USA
| | - Kathleen Dooling
- Division of Viral Diseases, National Center Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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25
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Kho MML, Roest S, Bovée DM, Metselaar HJ, Hoek RAS, van der Eijk AA, Manintveld OC, Roodnat JI, van Besouw NM. Herpes Zoster in Solid Organ Transplantation: Incidence and Risk Factors. Front Immunol 2021; 12:645718. [PMID: 33815403 PMCID: PMC8012754 DOI: 10.3389/fimmu.2021.645718] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 03/01/2021] [Indexed: 12/20/2022] Open
Abstract
Background Studies on herpes zoster (HZ) incidence in solid organ transplant (SOT) recipients report widely varying numbers. We investigated HZ incidence, severity, and risk factors in recipients of four different SOTs, with a follow-up time of 6-14 years. Methods Records of 1,033 transplant recipients after first heart (HTx: n = 211), lung (LuTx: n = 121), liver (LiTx: n = 258) and kidney (KTx: n = 443) transplantation between 2000 and 2014 were analyzed for VZV-PCR, clinical signs of HZ, and complications. Results HZ was diagnosed in 108 of 1,033 patients (10.5%): 36 HTx, 17 LuTx, 15 LiTx, and 40 KTx recipients. Overall HZ incidence rate after HTx (30.7 cases/1,000 person-years (PY)), LuTx (38.8 cases/1,000 PY), LiTx (22.7 cases/1,000 PY) and KTx (14.5 cases/1,000 PY) was significantly higher than in the general 50-70 year population. Multivariable analysis demonstrated age ≥50 years at transplantation (p = 0.038, RR 1.536), type of organ transplant (overall p = 0.002; LuTx p = 0.393; RR 1.314; LiTx p = 0.011, RR 0.444; KTx p = 0.034, RR 0.575), CMV prophylaxis (p = 0.043, RR 0.631) and type of anti-rejection therapy (overall p = 0.020; methylprednisolone p = 0.008, RR 0.475; r-ATG p = 0.64, RR1.194) as significant risk factors. Complications occurred in 33 of 108 (31%) patients (39% of HTx, 47% of LuTx, 20% of LiTx, 20% of KTx): post-herpetic neuralgia, disseminated disease, and cranial nerve involvement. Conclusion HZ incidence and severity in SOT recipients are most pronounced after heart and lung transplantation, in older patients, and when CMV prophylaxis is lacking.
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Affiliation(s)
- Marcia M L Kho
- Department of Internal Medicine-Nephrology and Transplantation, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.,Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Stefan Roest
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.,Department of Cardiology, Thorax Center, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Dominique M Bovée
- Department of Internal Medicine-Nephrology and Transplantation, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.,Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Herold J Metselaar
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.,Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Rogier A S Hoek
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.,Department of Respiratory Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Annemiek A van der Eijk
- Department of Viroscience, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Olivier C Manintveld
- Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.,Department of Cardiology, Thorax Center, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Joke I Roodnat
- Department of Internal Medicine-Nephrology and Transplantation, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.,Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Nicole M van Besouw
- Department of Internal Medicine-Nephrology and Transplantation, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.,Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
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26
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Vink P, Ramon Torrell JM, Sanchez Fructuoso A, Kim SJ, Kim SI, Zaltzman J, Ortiz F, Campistol Plana JM, Fernandez Rodriguez AM, Rebollo Rodrigo H, Campins Marti M, Perez R, González Roncero FM, Kumar D, Chiang YJ, Doucette K, Pipeleers L, Agüera Morales ML, Rodriguez-Ferrero ML, Secchi A, McNeil SA, Campora L, Di Paolo E, El Idrissi M, López-Fauqued M, Salaun B, Heineman TC, Oostvogels L. Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clin Infect Dis 2021; 70:181-190. [PMID: 30843046 PMCID: PMC6938982 DOI: 10.1093/cid/ciz177] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 02/28/2019] [Indexed: 12/23/2022] Open
Abstract
Background The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1–2 months (M) apart 4–18M posttransplant. Anti–glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post–dose 1, and 1M and 12M post–dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post–dose 2. Results Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post–dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. Conclusions RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. Clinical Trials Registration NCT02058589.
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Affiliation(s)
- Peter Vink
- GlaxoSmithKline (GSK), Rockville, Maryland
| | | | | | | | - Sang-Il Kim
- Seoul St Mary's Hospital, College of Medicine, Catholic University of Korea, Republic of Korea
| | - Jeff Zaltzman
- St Michael's Hospital, University of Toronto, Ontario, Canada
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Shelly A McNeil
- Canadian Center for Vaccinology, Izaak Walton Killam Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, Canada
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27
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La Hoz RM, Wallace A, Barros N, Xie D, Hynan LS, Liu T, Yek C, Schexnayder S, Grodin JL, Garg S, Drazner MH, Peltz M, Haley RW, Greenberg DE. Epidemiology and risk factors for varicella zoster virus reactivation in heart transplant recipients. Transpl Infect Dis 2020; 23:e13519. [PMID: 33220133 DOI: 10.1111/tid.13519] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 11/11/2020] [Indexed: 12/15/2022]
Abstract
Heart transplant (HT) recipients are at higher risk of varicella zoster virus (VZV) reactivation. Risk factors for VZV reactivation are currently not well defined, impeding the ability to design and implement strategies to minimize the burden of this illness in this population. Automated data extraction tools were used to retrieve data from the electronic health record (EHR) of all adult HT recipients at our center between 2010 and 2016. Information from the Organ Procurement and Transplantation Network Standard Analysis and Research Files was merged with the extracted data. Potential cases were manually reviewed and adjudicated using consensus definitions. Cumulative incidence and risk factors for VZV reactivation in HT recipients were assessed by the Kaplan-Meier method and Cox modeling, respectively. In 203 HT recipients, the cumulative incidence of VZV reactivation at 8-years post-transplantation was 26.4% (95% CI: 17.8-38.0). The median time to VZV reactivation was 2.1 years (IQR, 1.5-4.1). Half (14/28) of the cases experienced post-herpetic neuralgia (PHN). Post-transplant CMV infection (HR 9.05 [95% CI: 3.76-21.77) and post-transplant pulse-dose steroids (HR 3.19 [95% CI: 1.05-9.68]) were independently associated with a higher risk of VZV reactivation in multivariable modeling. Identification of risk factors will aid in the development of targeted preventive strategies.
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Affiliation(s)
- Ricardo M La Hoz
- Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ashley Wallace
- University of Texas Southwestern Medical School, Dallas, TX, USA
| | - Nicolas Barros
- Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Donglu Xie
- Academic Information Systems-Information Resources, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Linda S Hynan
- Departments of Populations and Data Sciences (Biostatistics) and Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Terrence Liu
- University of Texas Southwestern Medical School, Dallas, TX, USA
| | - Christina Yek
- Department of Critical Care Medicine, National Institutes of Health, Bethesda, MD, USA
| | | | - Justin L Grodin
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Sonia Garg
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Mark H Drazner
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Matthias Peltz
- Department of Cardiothoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Robert W Haley
- Division of Epidemiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - David E Greenberg
- Division of Infectious Diseases and Geographic Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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28
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Barghash MH, Taimur S, Rana M, Behar J, Mancini DM. Recombinant herpes zoster vaccine after heart transplantation: A single-center experience. J Heart Lung Transplant 2020; 39:1501-1503. [DOI: 10.1016/j.healun.2020.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/07/2020] [Accepted: 09/01/2020] [Indexed: 10/23/2022] Open
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29
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Occupational exposure to varicella zoster in a tertiary-care healthcare setting. Infect Control Hosp Epidemiol 2020; 42:793-795. [PMID: 32972465 DOI: 10.1017/ice.2020.351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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30
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Waller KMJ, De La Mata NL, Hedley JA, Rosales BM, O'Leary MJ, Cavazzoni E, Ramachandran V, Rawlinson WD, Kelly PJ, Wyburn KR, Webster AC. New blood-borne virus infections among organ transplant recipients: An Australian data-linked cohort study examining donor transmissions and other HIV, hepatitis C and hepatitis B notifications, 2000-2015. Transpl Infect Dis 2020; 22:e13437. [PMID: 32767859 DOI: 10.1111/tid.13437] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/29/2020] [Accepted: 07/30/2020] [Indexed: 01/11/2023]
Abstract
BACKGROUND Blood-borne viral infections can complicate organ transplantation. Systematic monitoring to distinguish donor-transmitted infections from other new infections post transplant is challenging. Administrative health data can be informative. We aimed to quantify post-transplant viral infections, specifically those transmitted by donors and those reactivating or arising new in recipients. METHODS We linked transplant registries with administrative health data for all solid organ donor-recipient pairs in New South Wales, Australia, 2000-2015. All new recipient notifications of hepatitis B (HBV), C (HCV), or human immunodeficiency virus (HIV) after transplant were identified. Proven/probable donor transmissions within 12 months of transplant were classified using an international algorithm. RESULTS Of 2120 organ donors, there were 72 with a viral infection (9/72 active, 63/72 past). These 72 donors donated to 173 recipients, of whom 24/173 already had the same infection as their donor, and 149/173 did not, so were at risk of donor transmission. Among those at risk, 3/149 recipients had proven/probable viral transmissions (1 HCV, 2 HBV); none were unrecognized by donation services. There were no deaths from transmissions. There were no donor transmissions from donors without known blood-borne viruses. An additional 68 recipients had new virus notifications, of whom 2/68 died, due to HBV infection. CONCLUSION This work confirms the safety of organ donation in an Australian cohort, with no unrecognized viral transmissions and most donors with viral infections not transmitting the virus. This may support targeted increases in donation from donors with viral infections. However, other new virus notifications post transplant were substantial and are preventable. Data linkage can enhance current biovigilance systems.
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Affiliation(s)
- Karen M J Waller
- Faculty of Health and Medicine, Sydney School of Public Health, Centre for Organ Donation Evidence, University of Sydney, Sydney, NSW, Australia
| | - Nicole L De La Mata
- Faculty of Health and Medicine, Sydney School of Public Health, Centre for Organ Donation Evidence, University of Sydney, Sydney, NSW, Australia
| | - James A Hedley
- Faculty of Health and Medicine, Sydney School of Public Health, Centre for Organ Donation Evidence, University of Sydney, Sydney, NSW, Australia
| | - Brenda M Rosales
- Faculty of Health and Medicine, Sydney School of Public Health, Centre for Organ Donation Evidence, University of Sydney, Sydney, NSW, Australia.,Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Michael J O'Leary
- New South Wales Organ and Tissue Donation Service, Sydney, NSW, Australia.,Department of Intensive Care Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Elena Cavazzoni
- New South Wales Organ and Tissue Donation Service, Sydney, NSW, Australia
| | - Vidiya Ramachandran
- Serology and Virology Division, NSW Health Pathology Randwick Prince of Wales Hospital, Randwick, NSW, Australia
| | - William D Rawlinson
- Serology and Virology Division, NSW Health Pathology Randwick Prince of Wales Hospital, Randwick, NSW, Australia.,Schools of SOMS, BABS and Women's and Children's, University of NSW, Kensington, NSW, Australia
| | - Patrick J Kelly
- Faculty of Health and Medicine, Sydney School of Public Health, Centre for Organ Donation Evidence, University of Sydney, Sydney, NSW, Australia
| | - Kate R Wyburn
- Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.,Faculty of Health and Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Angela C Webster
- Faculty of Health and Medicine, Sydney School of Public Health, Centre for Organ Donation Evidence, University of Sydney, Sydney, NSW, Australia.,Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia
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31
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Clinical and Laboratory Characteristics of Herpes Zoster in Patients With HIV/AIDS and Those With Juvenile Systemic Lupus Erythematosus. Pediatr Infect Dis J 2020; 39:624-627. [PMID: 32221168 DOI: 10.1097/inf.0000000000002617] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND HIV infection and juvenile systemic lupus erythematosus (jSLE) are risk factors for the development of herpes zoster (HZ) and its complications. Both diseases share similar immunologic aspects, such as immunodeficiency and immune activation. Therefore, our objective was to evaluate and compare the frequency and characteristics of HZ episodes in pediatric patients with HIV infection and jSLE. METHODS A retrospective cohort study was carried out with the evaluation of 2 pediatric cohorts: HIV patients who were followed from January 1987 to December 2014 and patients with jSLE followed up from January 1990 to December 2014 in outpatient clinics. RESULTS Of the 190 HIV patients, 48 had HZ (25.3%), with 67 episodes; of the 92 patients with jSLE, 27 had HZ (29.3%), totaling 28 episodes. The median age at the first episode of HZ was higher in the jSLE than in the HIV group (8.9 vs. 12.5 years, respectively) (P = 0.020). HIV patients were more likely to have recurrent HZ (P = 0.025). In addition, there was a tendency for HIV patients to present with disseminated HZ more frequently (P = 0.060). Although the hospitalization rate was similar between groups, patients with jSLE received intravenous acyclovir more frequently (P = 0.014). When HIV non-immune reconstitution syndrome patients were compared with jSLE group, recurrence of HZ in HIV was the only significant difference between groups (P = 0.017). CONCLUSIONS Patients with HIV had more recurrent HZ than patients with jSLE.
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32
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Laws HJ, Baumann U, Bogdan C, Burchard G, Christopeit M, Hecht J, Heininger U, Hilgendorf I, Kern W, Kling K, Kobbe G, Külper W, Lehrnbecher T, Meisel R, Simon A, Ullmann A, de Wit M, Zepp F. Impfen bei Immundefizienz. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020; 63:588-644. [PMID: 32350583 PMCID: PMC7223132 DOI: 10.1007/s00103-020-03123-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Hans-Jürgen Laws
- Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Ulrich Baumann
- Klinik für Pädiatrische Pneumologie, Allergologie und Neonatologie, Medizinische Hochschule Hannover, Hannover, Deutschland
| | - Christian Bogdan
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität FAU Erlangen-Nürnberg, Erlangen, Deutschland
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
| | - Gerd Burchard
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Deutschland
| | - Maximilian Christopeit
- Interdisziplinäre Klinik für Stammzelltransplantation, Universitätsklinikum Eppendorf, Hamburg, Deutschland
| | - Jane Hecht
- Abteilung für Infektionsepidemiologie, Fachgebiet Nosokomiale Infektionen, Surveillance von Antibiotikaresistenz und -verbrauch, Robert Koch-Institut, Berlin, Deutschland
| | - Ulrich Heininger
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Universitäts-Kinderspital beider Basel, Basel, Schweiz
| | - Inken Hilgendorf
- Klinik für Innere Medizin II, Abteilung für Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Jena, Deutschland
| | - Winfried Kern
- Klinik für Innere Medizin II, Abteilung Infektiologie, Universitätsklinikum Freiburg, Freiburg, Deutschland
| | - Kerstin Kling
- Abteilung für Infektionsepidemiologie, Fachgebiet Impfprävention, Robert Koch-Institut, Berlin, Deutschland.
| | - Guido Kobbe
- Klinik für Hämatologie, Onkologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Wiebe Külper
- Abteilung für Infektionsepidemiologie, Fachgebiet Impfprävention, Robert Koch-Institut, Berlin, Deutschland
| | - Thomas Lehrnbecher
- Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Frankfurt, Frankfurt am Main, Deutschland
| | - Roland Meisel
- Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland
| | - Arne Simon
- Klinik für Pädiatrische Onkologie und Hämatologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland
| | - Andrew Ullmann
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Maike de Wit
- Klinik für Innere Medizin - Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Deutschland
- Klinik für Innere Medizin - Onkologie, Vivantes Auguste-Viktoria-Klinikum, Berlin, Deutschland
| | - Fred Zepp
- Ständige Impfkommission (STIKO), Robert Koch-Institut, Berlin, Deutschland
- Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz, Mainz, Deutschland
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33
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Silva JT, Fernández-Ruiz M, Aguado JM. Prevention and therapy of viral infections in patients with solid organ transplantation. Enferm Infecc Microbiol Clin 2020; 39:87-97. [PMID: 32143894 DOI: 10.1016/j.eimc.2020.01.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/13/2020] [Accepted: 01/16/2020] [Indexed: 12/28/2022]
Abstract
Solid organ transplantation (SOT) is the best treatment option for end-stage organ disease. The number of SOT procedures has been steadily increasing worldwide during the past decades. This trend has been accompanied by the continuous incorporation of new antimicrobial drugs and by the refinement of strategies aimed at minimizing the risk of opportunistic infection. Nonetheless, viral infections, which can occur at any stage of the post-transplant period, remain a clinical challenge that negatively impacts both patient and graft outcomes. This review offers an overview of the most relevant viral infections in the SOT population, with a focus on herpesviruses (cytomegalovirus, Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus 1 and 2) and polyomaviruses (human BK polyomavirus). In addition, the currently recommended prophylactic and treatment approaches are summarized, as well as the new antiviral agents in different phases of clinical development.
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Affiliation(s)
- Jose Tiago Silva
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain.
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34
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Feldman AG, Atkinson K, Wilson K, Kumar D. Underimmunization of the solid organ transplant population: An urgent problem with potential digital health solutions. Am J Transplant 2020; 20:34-39. [PMID: 31553135 PMCID: PMC6940518 DOI: 10.1111/ajt.15605] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 08/11/2019] [Accepted: 09/07/2019] [Indexed: 01/25/2023]
Abstract
Solid organ transplant recipients are at risk for potentially life-threatening infections due to lifelong immunosuppression. Vaccine-preventable infections result in graft injury, morbidity, mortality, and significantly increased medical costs. Unfortunately, the majority of transplant recipients continue to be underimmunized at the time of transplant and thereafter. Given the rising rates of vaccine hesitancy and refusal in the general population, transplant recipients can no longer rely on herd immunity to protect them from vaccine-preventable infections. Novel tools are desperately needed to overcome transplant-specific immunization barriers to improve immunization rates in this high-risk population. Digital health technologies may offer a solution by addressing transplant-specific barriers: specifically, providing accurate information about vaccine safety, efficacy, and timing in the pre- and posttransplant periods; making a complete immunization record universally available and easily accessible; enabling communication between patients and multiple providers; and providing automated vaccine reminders to both patients and providers when vaccines are due using transplant-specific immunization guidelines. Digital health has transformed health care by empowering patients with their own health information and connecting patients, their providers, and public health officials. In doing so, it offers a potential platform to address and overcome the problem of underimmunization in the transplant population.
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Affiliation(s)
- Amy G. Feldman
- Section of Gastroenterology, Hepatology and Nutrition and the Digestive Health Institute, Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS), Children’s Hospital Colorado and the University of Colorado School of Medicine, Aurora, CO
| | - Katherine Atkinson
- Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden 17177
| | - Kumanan Wilson
- Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, The Ottawa Hospital, Civic Campus, Ottawa, ON
| | - Deepali Kumar
- Transplant Infectious Diseases and Multi Organ Transplant Program, University Health Network, Toronto ON
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35
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Hwang JH, Kim KH, Han SB, Kim HH, Kim JH, Lee SY, Choi UY, Kang JH. A clinico-epidemiological multicenter study of herpes zoster in immunocompetent and immunocompromised hospitalized children. Clin Exp Vaccine Res 2019; 8:116-123. [PMID: 31406693 PMCID: PMC6689498 DOI: 10.7774/cevr.2019.8.2.116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 07/11/2019] [Indexed: 11/15/2022] Open
Abstract
Purpose There are limited population-based data regarding herpes zoster in children. Thus we conducted a multi-institutional epidemiological analysis of herpes zoster in children and comparative analysis according to their immune status. Materials and Methods The study included 126 children under the age of 18 years who were hospitalized for herpes zoster at 8 hospitals in South Korea, between July 2009 and June 2015. The subjects were divided into 2 groups according to their immune status, and medical records were reviewed. Results There were 61 cases (48.4%) in the immunocompetent group and 65 cases (51.6%) in the immunocompromised group. Median age was older in immunocompromised group (11.4 vs. 8.6) (p<0.001). The mean duration of hospitalization was longer in immunocompromised group (11.0 vs. 6.6) (p<0.001). Patients were treated with oral or intravenous antiviral agents. A total of 12 in immunocompetent group were cured only by oral acyclovir. No treatment failure was found in both groups. Six immunocompromised patients had postherpetic neuralgia and 1 case was in immunocompetent group. In immunocompetent children, herpes zoster was likely caused by early varicella infection. There was no increase in progression of severity in both groups due to appropriate treatment. Conclusion Early initiation of therapy is necessary for those in immunocompromised conditions. And inactivated herpes zoster vaccination may be considered in immunocompromised adolescents in the future.
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Affiliation(s)
- Ji Hyen Hwang
- Department of Pediatrics, Seoul St. Mary's Hospital, Seoul, Korea
| | - Ki Hwan Kim
- Department of Pediatrics, Incheon St. Mary's Hospital, Incheon, Korea
| | - Seung Beom Han
- Department of Pediatrics, Daejeon St. Mary's Hospital, Daejeon, Korea
| | - Hyun Hee Kim
- Department of Pediatrics, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
| | - Jong-Hyun Kim
- Department of Pediatrics, St. Vincent's Hospital, Suwon, Korea
| | - Soo Young Lee
- Department of Pediatrics, Bucheon St. Mary's Hospital, Bucheon, Korea
| | - Ui Yoon Choi
- Department of Pediatrics, St. Paul's Hospital, Seoul, Korea
| | - Jin Han Kang
- Department of Pediatrics, Seoul St. Mary's Hospital, Seoul, Korea.,The Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea
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36
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Pergam SA, Limaye AP. Varicella zoster virus in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13622. [PMID: 31162727 DOI: 10.1111/ctr.13622] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 06/19/2019] [Accepted: 05/29/2019] [Indexed: 12/21/2022]
Abstract
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice review the diagnosis, prevention, and management of varicella zoster virus (VZV) in the pre- and post-transplant period. Primary varicella is an uncommon complication post-solid-organ transplant (SOT), except among pediatric transplant patients and those seronegative for VZV. As the majority of SOT recipients are seropositive for VZV, herpes zoster (HZ) occurs frequently following SOT, particularly among recipients who are older (≥65 years of age) and those receiving more intensive immunosuppression. Transplant providers should aware of the increased risk for HZ-related complications such as dissemination, organ-specific involvement, and post-herpetic neuralgia. Treatment for localized zoster is primarily given as oral regimens, but those with more complicated presentations or those at risk for dissemination should be treated initially with IV therapy. Available antiviral prophylaxis regimens and vaccination strategies for varicella and HZ among these immunosuppressed patients remain a mainstay for prevention in the pre-and post-transplant periods. Finally, we discuss important approaches to addressing post-exposure prophylaxis and infection control practices for those SOT patients with documented VZV infections.
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Affiliation(s)
- Steven A Pergam
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington.,Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Ajit P Limaye
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington
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Abeysekera N, Graver A, Cooley L, Kirkland G, Jose MD. Infectious complications in the Southern Tasmanian kidney transplant population. Nephrology (Carlton) 2019; 24:849-854. [PMID: 30152077 DOI: 10.1111/nep.13482] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2018] [Indexed: 11/28/2022]
Abstract
AIM Examine the incidence of suspected and proven infections, the range of infections, antimicrobial use and hospital admissions in kidney transplant recipients (KTx) in southern Tasmania. METHODS An audit of the medical records of KTx managed by the Royal Hobart Hospital for the period 1 January 2015 to 31 December 2016. Data were collected on positive microbiological investigations, antimicrobial use and hospital admissions. RESULTS Of the 151 evaluable KTx, there were 339 episodes of suspected infection in 95 (63%) patients with a preponderance of urinary tract infections. Overall, these 95 KTx received a total of 249 courses of antimicrobials, with predominantly monotherapy (n = 101, 65%). There were 11 vaccine preventable infections, including herpes zoster (n = 7), Influenza A (n = 3) and invasive pneumococcal disease (n = 1). Hospitalization was required for 50 infectious episodes, for a total of 227 admitted bed days (median 4; interquartile range 2-7; range 1-18 days). CONCLUSION In conclusion, episodes of infection, hospitalization, antimicrobial use and development of multi-resistant organisms are common following kidney transplantation in this southern Tasmanian cohort. This study has identified several areas of focus for improved patient care including antimicrobial management of urinary tract infections, implementation of programmes to vaccinate KTx prior to transplantation, and development of transplantation specific antimicrobial stewardship programmes.
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Affiliation(s)
| | - Alison Graver
- Renal Unit, Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Louise Cooley
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.,Infectious Disease Unit, Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Geoff Kirkland
- Renal Unit, Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Matthew D Jose
- School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.,Renal Unit, Royal Hobart Hospital, Hobart, Tasmania, Australia
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38
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Loftus MJ, Yong MK, Wilson S, Peleg AY. Fatal disseminated visceral varicella zoster virus infection in a renal transplant recipient. Transpl Infect Dis 2019; 21:e13062. [PMID: 30756453 DOI: 10.1111/tid.13062] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 01/23/2019] [Accepted: 02/07/2019] [Indexed: 12/12/2022]
Abstract
We report a case of fatal disseminated varicella zoster virus (VZV) with delayed-onset rash in a 66-year-old female more than 2 years following uncomplicated deceased donor renal transplantation. Whilst on a stable regimen of maintenance immunosuppression, the patient presented with chest and abdominal pain with concomitant hepatitis and pancreatitis. After pursuing multiple other potential causes of her symptoms, the correct diagnosis of VZV was only suspected after the development of a widespread vesicular rash-11 days after her initial symptoms. Despite antiviral therapy and inotropic support in the intensive care unit, the patient died. Simultaneous VZV hepatitis and pancreatitis in solid organ transplant recipients is uncommon. The new inactivated VZV vaccines have the potential to prevent post-transplant infections, with promising early clinical data on safety and efficacy in renal transplant recipients. VZV is an important preventable infection that should be considered in immunocompromised patients, even in the absence of rash.
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Affiliation(s)
- Michael J Loftus
- Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia
| | - Michelle K Yong
- Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.,National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Scott Wilson
- Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Renal Medicine, Alfred Health, Melbourne, Victoria, Australia
| | - Anton Y Peleg
- Department of Infectious Diseases, Alfred Health, Melbourne, Victoria, Australia.,Department of Microbiology, Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
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39
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Lui SL, Yap D, Cheng V, Chan TM, Yuen KY. Clinical practice guidelines for the provision of renal service in Hong Kong: Infection Control in Renal Service. Nephrology (Carlton) 2019; 24 Suppl 1:98-129. [PMID: 30900339 PMCID: PMC7167703 DOI: 10.1111/nep.13497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Affiliation(s)
| | - Desmond Yap
- Department of MedicineThe University of Hong KongHong Kong
| | - Vincent Cheng
- Department of MicrobiologyQueen Mary HospitalHong Kong
| | - Tak Mao Chan
- Department of MedicineThe University of Hong KongHong Kong
| | - Kwok Yung Yuen
- Department of MicrobiologyThe University of Hong KongHong Kong
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40
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Arora S, Kipp G, Bhanot N, Sureshkumar KK. Vaccinations in kidney transplant recipients: Clearing the muddy waters. World J Transplant 2019; 9:1-13. [PMID: 30697516 PMCID: PMC6347668 DOI: 10.5500/wjt.v9.i1.1] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 11/13/2018] [Accepted: 01/01/2019] [Indexed: 02/05/2023] Open
Abstract
Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant. Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.
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Affiliation(s)
- Swati Arora
- Divisions of Nephrology and Hypertension, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
| | - Gretchen Kipp
- Department of Pharmacy, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
| | - Nitin Bhanot
- Infectious Diseases, Department of Medicine, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
| | - Kalathil K Sureshkumar
- Divisions of Nephrology and Hypertension, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United States
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41
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Kang M, Aslam S. Varicella zoster virus encephalitis in solid organ transplant recipients: Case series and review of literature. Transpl Infect Dis 2018; 21:e13038. [PMID: 30548548 DOI: 10.1111/tid.13038] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 10/12/2018] [Accepted: 11/21/2018] [Indexed: 12/20/2022]
Abstract
Herpes zoster encephalitis (HZE) is a rare complication of varicella zoster virus (VZV) infection. We report two cases of HZE in solid organ transplant (SOT) recipients and review 10 other cases in the literature. In this review, rash was present in 67% of cases. Despite the absence of a rash, high clinical suspicion for HZE is necessary and empiric antiviral therapy should be considered. While with variable outcome, it was associated with high mortality rate of 42%. Prompt initiation of antiviral therapy remains crucial in decreasing morbidity and mortality from this fatal disease.
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Affiliation(s)
- Minji Kang
- Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, California
| | - Saima Aslam
- Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, California
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42
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Amon E, Huzly D, Kalbhenn J, Hettich I, Kotter E, Bansbach J. Abdominal pain, unconsciousness, and skin rash after lung transplantation. Transpl Infect Dis 2018; 20:e12993. [PMID: 30187615 DOI: 10.1111/tid.12993] [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: 04/23/2018] [Revised: 08/06/2018] [Accepted: 08/21/2018] [Indexed: 11/28/2022]
Abstract
Long-term success of lung transplantation is limited by allograft dysfunction and frequent infections. Varicella zoster virus infection (VZV) is one of the most common opportunistic infections among solid organ transplantation recipients. However the occurrence of visceral involvement or disseminated disease, as seen after bone marrow transplantation, is rare. We report a case of a 59-year-old woman who underwent double-lung transplantation with a fatal visceral and disseminated varicella zoster virus infection.
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Affiliation(s)
- Elisa Amon
- Faculty of Medicine, Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Freiburg, Germany
| | - Daniela Huzly
- Faculty of Medicine, Institute of Virology, Medical Center - University of Freiburg, Freiburg, Germany
| | - Johannes Kalbhenn
- Faculty of Medicine, Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Freiburg, Germany
| | - Ina Hettich
- Faculty of Medicine, Department of Pneumology, Medical Center - University of Freiburg, Freiburg, Germany
| | - Elmar Kotter
- Faculty of Medicine, Department of Radiology, Medical Center - University of Freiburg, Freiburg, Germany
| | - Joachim Bansbach
- Faculty of Medicine, Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Freiburg, Germany
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43
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Wang L, Verschuuren EAM, van Leer-Buter CC, Bakker SJL, de Joode AAE, Westra J, Bos NA. Herpes Zoster and Immunogenicity and Safety of Zoster Vaccines in Transplant Patients: A Narrative Review of the Literature. Front Immunol 2018; 9:1632. [PMID: 30079064 PMCID: PMC6062765 DOI: 10.3389/fimmu.2018.01632] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 07/02/2018] [Indexed: 12/14/2022] Open
Abstract
This narrative review focuses on the herpes zoster (HZ) and its prevention in transplant patients. Varicella zoster virus (VZV) is highly contagious and distributed worldwide in humans. Primary VZV infection usually causes varicella and then establishes a lifelong latency in dorsal root ganglia. Reactivation of VZV leads to HZ and related complications such as postherpetic neuralgia. Age and decreased immunity against VZV are important risk factors for developing HZ. Transplant patients are at increased risk for developing HZ and related complications due to their immunocompromised status and the need for lifetime immunosuppression. Diagnosis of HZ in transplant patients is often clinically difficult, and VZV-specific antibodies should be determined by serologic testing to document prior exposure to VZV during their pre-transplant evaluation process. Although antiviral agents are available, vaccination should be recommended for preventing HZ in transplant patients considering their complicated condition and weak organ function. Currently, there are two licensed HZ vaccines, of which one is a live-attenuated vaccine and the other is a HZ subunit vaccine. Both vaccines have shown promising safety and efficacy in transplants patients and especially the subunit vaccine could be administered post-transplant since this vaccine does not contain any live virus. Larger studies are needed about safety and immunogenicity of HZ vaccines in transplant populations, and extra efforts are needed to increase vaccine usage according to guidelines.
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Affiliation(s)
- Lei Wang
- Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Erik A M Verschuuren
- Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Coretta C van Leer-Buter
- Department of Medical Microbiology, Division of Clinical Virology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Stephan J L Bakker
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Anoek A E de Joode
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Johanna Westra
- Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Nicolaas A Bos
- Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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44
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Buonomo AR, Zappulo E, Viceconte G, Scotto R, Borgia G, Gentile I. Risk of opportunistic infections in patients treated with alemtuzumab for multiple sclerosis. Expert Opin Drug Saf 2018; 17:709-717. [PMID: 29848085 DOI: 10.1080/14740338.2018.1483330] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
INTRODUCTION Alemtuzumab is a monoclonal anti CD-52 antibody recently approved for use in relapsing-remitting multiple sclerosis(MS). Given that the targeted antigen is primarily expressed on B and T lymphocytes, the administration of this biological drug is associated with rapid but protracted peripheral lymphopenia. AREAS COVERED The impact on infective risk of this immune impairment is still to be fully understood. In this review, we attempt to summarize all the available literature concerning opportunistic infections occurring in patients with MS receiving alemtuzumab. Infective adverse events were observed in more than 70% of patients in phase 2/3 RCTs, mainly of mild-to-moderate severity. Nevertheless, several post-marketing reports documented cases of serious, rare, and unexpected infections. EXPERT OPINION Predictive risk factors and prognostic features of opportunistic infections in this setting still need to be exactly assessed. At present, the only recommended preventive measures consist in anti-herpetic prophylaxis, Listeria-free diet, Tuberculosis prophylaxis and annual Papillomavirus screening. Given the non-negligible risk of unpredicted infective events, we advise physicians to take into account patients' history of infectious diseases and vaccine status and to consider supplementary prophylactic strategies, including screening for Toxoplasma gondii and viral hepatitis serostatus as well as pre-emptive approaches to avert CMV reactivation and Pneumocystosis.
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Affiliation(s)
- Antonio Riccardo Buonomo
- a Department of Clinical Medicine and Surgery - Section of Infectious Diseases , University of Naples "Federico II" , Naples , Italy
| | - Emanuela Zappulo
- a Department of Clinical Medicine and Surgery - Section of Infectious Diseases , University of Naples "Federico II" , Naples , Italy
| | - Giulio Viceconte
- a Department of Clinical Medicine and Surgery - Section of Infectious Diseases , University of Naples "Federico II" , Naples , Italy
| | - Riccardo Scotto
- a Department of Clinical Medicine and Surgery - Section of Infectious Diseases , University of Naples "Federico II" , Naples , Italy
| | - Guglielmo Borgia
- a Department of Clinical Medicine and Surgery - Section of Infectious Diseases , University of Naples "Federico II" , Naples , Italy
| | - Ivan Gentile
- a Department of Clinical Medicine and Surgery - Section of Infectious Diseases , University of Naples "Federico II" , Naples , Italy
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45
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Kim W, Kim S, Oh J, Jeong YJ, Rhu J, Kim KS, Lee J, Choi GS, Kim JM, Joh JW. Incidence and risk factors for herpes zoster after adult liver transplantation. Ann Surg Treat Res 2018; 96:95-99. [PMID: 30746357 PMCID: PMC6358591 DOI: 10.4174/astr.2019.96.2.95] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/18/2018] [Accepted: 10/05/2018] [Indexed: 12/16/2022] Open
Abstract
Purpose Herpes zoster (HZ) is caused by reactivation of the varicella zoster virus, which occurs frequently in liver transplant recipients with impaired cellular immunity. The purpose of this study was to evaluate the incidence and risk factors for HZ after adult liver transplantation (LT). Methods In our institution, 993 patients underwent adult LT from January 1997 to December 2013. We retrospectively analyzed the incidence rate of HZ and risk factors for HZ after LT. Results Of 993 LT recipients, 101 (10.2%) were diagnosed with HZ. The incidence of HZ at 1, 3, 5, and 10 years was 6.6%, 9.1%, 10.0%, and 11.9%, respectively. Therefore, we observed that the incidence of HZ after LT was 16.3 per 1,000 person-years. Older age (≥50 years) at LT and mycophenolate mofetil (MMF) exposure were independent risk factors of HZ infection after adult LT. Conclusion Patients older than 50 years or with MMF exposure are considered to be at high risk for HZ. Therefore, adult liver recipients with such factors should not be given strong immunosuppression treatments.
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Affiliation(s)
- Wontae Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sangjin Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jongwook Oh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Jae Jeong
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyung Sik Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jisoo Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gyu-Sung Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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46
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Fernández-Ruiz M, Origüen J, Lora D, López-Medrano F, González E, Polanco N, San Juan R, Ruiz-Merlo T, Parra P, Andrés A, Aguado JM. Herpes zoster in kidney transplant recipients: protective effect of anti-cytomegalovirus prophylaxis and natural killer cell count. A single-center cohort study. Transpl Int 2017; 31:187-197. [PMID: 28940695 DOI: 10.1111/tri.13076] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 06/20/2017] [Accepted: 09/18/2017] [Indexed: 12/11/2022]
Abstract
Despite its impact on quality of life and potential for complications, specific risk and protective factors for herpes zoster (HZ) after kidney transplantation (KT) remain to be clarified. We included 444 patients undergoing KT between November 2008 and March 2013. Peripheral blood lymphocyte subpopulations were measured at baseline and months 1 and 6. The risk factors for early (first post-transplant year) and late HZ (years 1-5) were separately assessed. We observed 35 episodes of post-transplant HZ after a median follow-up of 48.3 months (incidence rate: 0.057 per 1000 transplant-days). Median interval from transplantation was 18.3 months. Six patients (17.1%) developed disseminated infection. Postherpetic neuralgia occurred in 10 cases (28.6%). The receipt of anti-cytomegalovirus (CMV) prophylaxis with (val)ganciclovir decreased the risk of early HZ [adjusted hazard ratio (aHR): 0.08; 95% CI: 0.01-1.13; P-value = 0.062], whereas the natural killer (NK) cell at month 6 was protective for the occurrence of late HZ [aHR (per 10-cells/μl increase): 0.94; 95% CI: 0.88-1.00; P-value = 0.054]. In conclusion, two easily ascertainable factors (whether the patient is receiving anti-CMV prophylaxis and the NK cell count at month 6) might be potentially useful to tailor preventive strategies according to individual susceptibility to post-transplant HZ.
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Affiliation(s)
- Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Julia Origüen
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - David Lora
- Unit of Clinical Research, Instituto de Investigación Hospital "12 de Octubre" (i+12), Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Esther González
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Madrid, Spain
| | - Natalia Polanco
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Patricia Parra
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
| | - Amado Andrés
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain
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47
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Martin-Gandul C, Stampf S, Héquet D, Mueller NJ, Cusini A, van Delden C, Khanna N, Boggian K, Hirzel C, Soccal P, Hirsch HH, Pascual M, Meylan P, Manuel O. Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study. Am J Transplant 2017; 17:1813-1822. [PMID: 28039960 DOI: 10.1111/ajt.14192] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 12/15/2016] [Accepted: 12/29/2016] [Indexed: 01/25/2023]
Abstract
We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.
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Affiliation(s)
- C Martin-Gandul
- Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.,Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - S Stampf
- Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland
| | - D Héquet
- Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.,Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - N J Mueller
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zürich, Switzerland
| | - A Cusini
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - C van Delden
- Transplant Infectious Diseases Unit, University Hospital Geneva, Geneva, Switzerland
| | - N Khanna
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland
| | - K Boggian
- Division of Infectious Diseases and Hospital Hygiene, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - C Hirzel
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
| | - P Soccal
- Division of Pneumology, Department of Medicine, University Hospital Geneva, Geneva, Switzerland
| | - H H Hirsch
- Transplantation & Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, Basel, Switzerland
| | - M Pascual
- Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - P Meylan
- Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.,Institute of Microbiology, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - O Manuel
- Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.,Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
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48
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Helfrich M, Dorschner P, Thomas K, Stosor V, Ison MG. A retrospective study to describe the epidemiology and outcomes of opportunistic infections after abdominal organ transplantation. Transpl Infect Dis 2017; 19. [PMID: 28273393 DOI: 10.1111/tid.12691] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Revised: 10/26/2016] [Accepted: 12/11/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND Most epidemiologic studies of opportunistic infections (OI) following abdominal organ transplantation are derived prior to the era of contemporary immunosuppression and prophylaxis. These studies suggest that most OI occur within the first 6 months post transplant. METHOD In this single-center, retrospective cohort study, we describe the epidemiology of OI in 359 consecutive abdominal organ transplant recipients, in the era of contemporary prophylaxis practices and alemtuzumab induction in kidney and simultaneous pancreas-kidney transplant recipients. RESULTS Ninety patients (25.1%) developed OI, with 53.3% of these occurring beyond 6 months. The most common OI were BK polyomavirus nephropathy (5.0%), cytomegalovirus (10.2%), varicella zoster virus (4.4%), and herpes simplex virus (1.1%), which typically occurred after discontinuation of antiviral prophylaxis, and Clostridium difficile infections (7.8%). CONCLUSION OI had no impact on patient or graft survival at 12 months post transplant. In the era of contemporary immunosuppression and prophylaxis, a significant proportion of OI occur beyond 6 months. Additional strategies may be important to reduce the incidence of such late-onset infections.
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Affiliation(s)
- Mia Helfrich
- Northwestern University Transplant Outcomes Research Collaborative, Chicago, IL, USA
| | - Peter Dorschner
- Northwestern University Transplant Outcomes Research Collaborative, Chicago, IL, USA
| | - Kathryn Thomas
- Northwestern University Transplant Outcomes Research Collaborative, Chicago, IL, USA.,Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Valentina Stosor
- Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.,Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Michael G Ison
- Northwestern University Transplant Outcomes Research Collaborative, Chicago, IL, USA.,Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.,Division of Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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49
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Robust gene expression changes in the ganglia following subclinical reactivation in rhesus macaques infected with simian varicella virus. J Neurovirol 2017; 23:520-538. [PMID: 28321697 DOI: 10.1007/s13365-017-0522-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 02/03/2017] [Accepted: 02/17/2017] [Indexed: 12/20/2022]
Abstract
Varicella zoster virus (VZV) causes varicella during acute infection and establishes latency in the sensory ganglia. Reactivation of VZV results in herpes zoster, a debilitating and painful disease. It is believed that VZV reactivates due to a decline in cell-mediated immunity; however, the roles that CD4 versus CD8 T cells play in the prevention of herpes zoster remain poorly understood. To address this question, we used a well-characterized model of VZV infection where rhesus macaques are intrabronchially infected with the homologous simian varicella virus (SVV). Latently infected rhesus macaques were thymectomized and depleted of either CD4 or CD8 T cells to induce selective senescence of each T cell subset. After T cell depletion, the animals were transferred to a new housing room to induce stress. SVV reactivation (viremia in the absence of rash) was detected in three out of six CD8-depleted and two out of six CD4-depleted animals suggesting that both CD4 and CD8 T cells play a critical role in preventing SVV reactivation. Viral loads in multiple ganglia were higher in reactivated animals compared to non-reactivated animals. In addition, reactivation results in sustained transcriptional changes in the ganglia that enriched to gene ontology and diseases terms associated with neuronal function and inflammation indicative of potential damage as a result of viral reactivation. These studies support the critical role of cellular immunity in preventing varicella virus reactivation and indicate that reactivation results in long-lasting remodeling of the ganglia transcriptome.
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50
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Clinical Presentation of Herpes Zoster in Immunocompetent and Immunocompromised Hospitalized Children Treated With Acyclovir. J Pediatr Hematol Oncol 2016; 38:394-7. [PMID: 27347778 DOI: 10.1097/mph.0000000000000567] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Herpes zoster, defined as the reactivation of a latent varicella-zoster virus (VZV) infection, used to be a serious disease in immunocompromised children until recently. The aim of this study was to describe the clinical presentation of herpes zoster in hospitalized immunocompromised children compared with hospitalized immunocompetent counterparts. We reviewed the hospital charts of 72 children aged 6 months to 18 years diagnosed with herpes zoster and treated with acyclovir in our department covering a 19-year period. Forty-six of the children were immunocompromised which was mainly due to hematologic diseases. There were no differences in the age at which herpes zoster occurred, length of hospitalization, and the location or extent of the skin eruption. General symptoms were observed more frequently in the hospitalized immunocompetent patients compared with the hospitalized immunocompromised children (80% vs. 56%). The average age at which primary VZV infection occurred was higher among the immunocompromised children than the immunocompetent children with the latter group suffering from significantly more primary VZV infections during infancy. The presentation of herpes zoster in immunocompromised children is similar to that of herpes zoster in hospitalized immunocompetent children.
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