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Fashina OA, Chuang TM, Galardy PJ, Huskins WC, Levy ER, Streck NT, Chakraborty R. Disseminated vaccine-strain varicella-zoster virus reactivation in an adolescent with secondary immunodeficiency: a case report and literature review. BMC Infect Dis 2024; 24:1296. [PMID: 39543470 PMCID: PMC11566423 DOI: 10.1186/s12879-024-09776-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 08/20/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND Routine childhood immunization against varicella-zoster virus has led to a dramatic reduction in the incidence of primary varicella. However, there are rare, yet significant cases reported of reactivated Oka-strain varicella, primarily in immunocompromised hosts. CASE PRESENTATION A 16-year-old female with Hodgkin's lymphoma developed a vesicular rash shortly after completing all chemotherapy treatment. Swabs obtained from the vesicles were positive for varicella-zoster virus. By the time of hospitalization, the patient developed a disseminated rash involving multiple dermatomes. Subsequent polymerase chain reaction confirmed Oka vaccine-strain varicella-zoster virus. The patient had previously received a primary series of immunizations against varicella in 2008 and 2012, with her 2nd dose given 11 years prior to her development of vaccine-strain herpes zoster and 10 years prior to her diagnosis of Hodgkin's lymphoma, respectively. The patient was treated with parenteral acyclovir upon hospitalization and monitored clinically for cutaneous disease progression as well as sequelae. After 8 days of inpatient treatment, her rash had stopped spreading with no new lesions. All earlier lesions had crusted over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery. CONCLUSIONS There are individual and community-wide benefits to childhood immunization against varicella. This case highlights an unusual presentation of disseminated vaccine-strain herpes zoster in an adolescent with secondary immunodeficiency 11 years after completing primary immunization. In addition, this case informs pediatricians of complications that can arise in immunized subjects if they become immunosuppressed years later. The only way to distinguish between wild-type and vaccine-strain herpes zoster was by viral genotyping. Providers should be cognizant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases.
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Affiliation(s)
| | - Tony M Chuang
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
| | - Paul J Galardy
- Division of Pediatric Hematology and Oncology, Mayo Clinic, Rochester, MN, USA
| | - W Charles Huskins
- Division of Pediatric Infectious Diseases, Mayo Clinic, 200 1st St SW, Rochester, MN, 55901, USA
| | - Emily R Levy
- Division of Pediatric Infectious Diseases, Mayo Clinic, 200 1st St SW, Rochester, MN, 55901, USA
| | | | - Rana Chakraborty
- Division of Pediatric Infectious Diseases, Mayo Clinic, 200 1st St SW, Rochester, MN, 55901, USA.
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2
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Rajashekar V, Stern L, Almeida CF, Slobedman B, Abendroth A. The surveillance of viral infections by the unconventional Type I NKT cell. Front Immunol 2024; 15:1472854. [PMID: 39355244 PMCID: PMC11442276 DOI: 10.3389/fimmu.2024.1472854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 08/26/2024] [Indexed: 10/03/2024] Open
Abstract
Type I NKT cells, also known as Invariant Natural Killer T (iNKT) cells, are a subpopulation of unconventional, innate-like T (ILT) cells which can proficiently influence downstream immune effector functions. Type I NKT cells express a semi-invariant αβ T cell receptor (TCR) that recognises lipid-based ligands specifically presented by the non-classical cluster of differentiation (CD1) protein d (CD1d) molecule. Due to their potent immunomodulatory functional capacity, type I NKT cells are being increasingly considered in prophylactic and therapeutic approaches towards various diseases, including as vaccine-adjuvants. As viruses do not encode lipid synthesis, it is surprising that many studies have shown that some viruses can directly impede type I NKT activation through downregulating CD1d expression. Therefore, in order to harness type I NKT cells for potential anti-viral therapeutic uses, it is critical that we fully appreciate how the CD1d-iNKT cell axis interacts with viral immunity. In this review, we examine clinical findings that underpin the importance of type I NKT cell function in viral infections. This review also explores how certain viruses employ immunoevasive mechanisms and directly encode functions to target CD1d expression and type I NKT cell function. Overall, we suggest that the CD1d-iNKT cell axis may hold greater gravity within viral infections than what was previously appreciated.
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Affiliation(s)
- Varshini Rajashekar
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Sydney Institute for Infectious Diseases , University of Sydney, Sydney, NSW, Australia
| | - Lauren Stern
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Sydney Institute for Infectious Diseases , University of Sydney, Sydney, NSW, Australia
| | - Catarina F. Almeida
- Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
| | - Barry Slobedman
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Sydney Institute for Infectious Diseases , University of Sydney, Sydney, NSW, Australia
| | - Allison Abendroth
- Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Sydney Institute for Infectious Diseases , University of Sydney, Sydney, NSW, Australia
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3
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Sharma D, Ben Yakov G, Kapuria D, Viana Rodriguez G, Gewirtz M, Haddad J, Kleiner DE, Koh C, Bergerson JRE, Freeman AF, Heller T. Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity. Hepatology 2022; 76:1845-1861. [PMID: 35466407 DOI: 10.1002/hep.32539] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 03/30/2022] [Accepted: 04/17/2022] [Indexed: 12/08/2022]
Abstract
Inborn errors of immunity (IEIs) consist of numerous rare, inherited defects of the immune system that affect about 500,000 people in the United States. As advancements in diagnosis through genetic testing and treatment with targeted immunotherapy and bone marrow transplant emerge, increasing numbers of patients survive into adulthood posing fresh clinical challenges. A large spectrum of hepatobiliary diseases now present in those with immunodeficiency diseases, leading to morbidity and mortality in this population. Awareness of these hepatobiliary diseases has lagged the improved management of the underlying disorders, leading to missed opportunities to improve clinical outcomes. This review article provides a detailed description of specific liver diseases occurring in various inborn errors of immunity. A generalized approach to diagnosis and management of hepatic complications is provided, and collaboration with hepatologists, immunologists, and pathologists is emphasized as a requirement for optimizing management and outcomes.
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Affiliation(s)
- Disha Sharma
- Department of Internal MedicineMedStar Washington Hospital Center & Georgetown UniversityWashingtonDCUSA.,Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA
| | - Gil Ben Yakov
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA.,26744Center for Liver DiseaseSheba Medical CenterTel HaShomerIsrael
| | - Devika Kapuria
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA.,Department of GastroenterologyUniversity of New MexicoAlbuquerqueNew MexicoUSA
| | - Gracia Viana Rodriguez
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA
| | - Meital Gewirtz
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA
| | - James Haddad
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA
| | - David E Kleiner
- 3421Laboratory of PathologyNational Cancer InstituteBethesdaMarylandUSA
| | - Christopher Koh
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA
| | - Jenna R E Bergerson
- Laboratory of Clinical Immunology and MicrobiologyNIAID, NIHBethesdaMarylandUSA
| | - Alexandra F Freeman
- Laboratory of Clinical Immunology and MicrobiologyNIAID, NIHBethesdaMarylandUSA
| | - Theo Heller
- Liver Diseases Branch, Translational Hepatology SectionNational Institute of Diabetes and Digestive and Kidney Diseases, NIHBethesdaMarylandUSA
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Suresh S, Zafack J, Pham-Huy A, Derfalvi B, Sadarangani M, McConnell A, Tapiéro B, Halperin SA, De Serres G, M Pernica J, Top KA. Physician vaccination practices in mild to moderate inborn errors of immunity and retrospective review of vaccine completeness in IEI: results from the Canadian Immunization Research Network. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2022; 18:32. [PMID: 35397595 PMCID: PMC8994318 DOI: 10.1186/s13223-022-00667-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 03/08/2022] [Indexed: 11/26/2022]
Abstract
Background and objectives Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs. Methods Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required. Results Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively. Conclusion Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines. Supplementary Information The online version contains supplementary material available at 10.1186/s13223-022-00667-1.
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Affiliation(s)
- Sneha Suresh
- Division of Immunology, Department of Pediatrics, Edmonton Clinic Health Academy, 3-529, 11405 87 Ave, Edmonton, AB, T6G 1C9, Canada. .,Division of Infectious Disease and IHOPE, Department of Paediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, Canada.
| | | | - Anne Pham-Huy
- Division of Infectious Diseases, Immunology and Allergy, Department of Paediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada
| | - Beata Derfalvi
- Division of Immunology, Departments of Paediatrics and Microbiology and Immunology, IWK Health Centre, Dalhousie University, Halifax, Canada
| | - Manish Sadarangani
- Vaccine Evaluation Center, BC Children's Hospital Research Institute, Department of Pediatrics, University of British Columbia, Vancouver, Canada
| | - Athena McConnell
- Division of Infectious Diseases, Department of Pediatrics, Jim Pattison Children's Hospital, University of Saskatchewan, Saskatoon, Canada
| | - Bruce Tapiéro
- Division of Infectious Diseases, Department of Pediatrics, CHU Sainte Justine, Université de Montreal, Montreal, Canada
| | - Scott A Halperin
- Departments of Paediatrics and Microbiology and Immunology, Canadian Center for Vaccinology IWK Health Centre, Dalhousie University, Halifax, Canada
| | - Gaston De Serres
- Department of Social and Preventive Medicine, Institut Nationale de Santé Publique du Québec, Université Laval, Québec, Canada
| | - Jeffrey M Pernica
- Division of Infectious Diseases, Department of Pediatrics, McMaster University, Hamilton, Canada
| | - Karina A Top
- Departments of Pediatrics and Community Health and Epidemiology, Canadian Center for Vaccinology, IWK Health Centre, Dalhousie University, Halifax, Canada.
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5
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Le Voyer T, Sakata S, Tsumura M, Khan T, Esteve-Sole A, Al-Saud BK, Gungor HE, Taur P, Jeanne-Julien V, Christiansen M, Köhler LM, ElGhazali GE, Rosain J, Nishimura S, Sakura F, Bouaziz M, Oleaga-Quintas C, Nieto-Patlán A, Deyà-Martinez À, Altuner Torun Y, Neehus AL, Roynard M, Bozdemir SE, Al Kaabi N, Al Hassani M, Mersiyanova I, Rozenberg F, Speckmann C, Hainmann I, Hauck F, Alzahrani MH, Alhajjar SH, Al-Muhsen S, Cole T, Fuleihan R, Arkwright PD, Badolato R, Alsina L, Abel L, Desai M, Al-Mousa H, Shcherbina A, Marr N, Boisson-Dupuis S, Casanova JL, Okada S, Bustamante J. Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency. THE JOURNAL OF IMMUNOLOGY 2021; 207:133-152. [PMID: 34183371 DOI: 10.4049/jimmunol.2001451] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 04/28/2021] [Indexed: 11/19/2022]
Abstract
Autosomal recessive (AR) STAT1 deficiency is a severe inborn error of immunity disrupting cellular responses to type I, II, and III IFNs, and IL-27, and conferring a predisposition to both viral and mycobacterial infections. We report the genetic, immunological, and clinical features of an international cohort of 32 patients from 20 kindreds: 24 patients with complete deficiency, and 8 patients with partial deficiency. Twenty-four patients suffered from mycobacterial disease (bacillus Calmette-Guérin = 13, environmental mycobacteria = 10, or both in 1 patient). Fifty-four severe viral episodes occurred in sixteen patients, mainly caused by Herpesviridae viruses. Attenuated live measles, mumps, and rubella and/or varicella zoster virus vaccines triggered severe reactions in the five patients with complete deficiency who were vaccinated. Seven patients developed features of hemophagocytic syndrome. Twenty-one patients died, and death was almost twice as likely in patients with complete STAT1 deficiency than in those with partial STAT1 deficiency. All but one of the eight survivors with AR complete deficiency underwent hematopoietic stem cell transplantation. Overall survival after hematopoietic stem cell transplantation was 64%. A diagnosis of AR STAT1 deficiency should be considered in children with mycobacterial and/or viral infectious diseases. It is important to distinguish between complete and partial forms of AR STAT1 deficiency, as their clinical outcome and management differ significantly.
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Affiliation(s)
- Tom Le Voyer
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France; .,University of Paris, Imagine Institute, Paris, France
| | - Sonoko Sakata
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Miyuki Tsumura
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Taushif Khan
- Division of Translational Medicine, Sidra Medicine, Doha, Qatar
| | - Ana Esteve-Sole
- Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, and Functional Unit of Immunology, Sant Joan de Déu Hospital, Institut de Recerca Sant Joan de Déu, University of Barcelona, Barcelona, Spain
| | - Bandar K Al-Saud
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hatice Eke Gungor
- Department of Pediatrics, Pediatric Allergy and Immunology Unit, Kayseri Education and Research Hospital, Erkilet, Kayseri, Turkey
| | - Prasad Taur
- Department of Pediatric Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, India
| | - Valentine Jeanne-Julien
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Mette Christiansen
- Department of Clinical Immunology, Aarhus University Hospital, Aarhus N, Denmark
| | - Lisa-Maria Köhler
- Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Gehad Eltayeb ElGhazali
- Sheikh Khalifa Medical City-Union71, Abu Dhabi and Department of Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
| | - Jérémie Rosain
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Shiho Nishimura
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Fumiaki Sakura
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Matthieu Bouaziz
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Carmen Oleaga-Quintas
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Alejandro Nieto-Patlán
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,Research and Development in Bioprocess Unit, National School of Biological Sciences, National Polytechnic Institute, Mexico City, Mexico
| | - Àngela Deyà-Martinez
- Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, and Functional Unit of Immunology, Sant Joan de Déu Hospital, Institut de Recerca Sant Joan de Déu, University of Barcelona, Barcelona, Spain
| | - Yasemin Altuner Torun
- Pediatric Hematology and Oncology Unit, Istinye University, School of Medicine, İstanbul, Turkey
| | - Anna-Lena Neehus
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Manon Roynard
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France
| | - Sefika Elmas Bozdemir
- Pediatric İnfectious Disease Unit, Department of Pediatrics, Kayseri Education and Research Hospital, Erkilet, Kayseri, Turkey
| | - Nawal Al Kaabi
- Sheikh Khalifa Medical City-Union71, Abu Dhabi and Department of Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
| | - Moza Al Hassani
- Sheikh Khalifa Medical City-Union71, Abu Dhabi and Department of Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
| | - Irina Mersiyanova
- Molecular Biology Laboratory, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Flore Rozenberg
- Department of Virology, Cochin Hospital, University of Paris, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Carsten Speckmann
- Center for Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Center for Chronic Immunodeficiency, Institute for Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Ina Hainmann
- Department of Pediatric Hematology and Oncology, University Hospital Bonn, Bonn, Germany
| | - Fabian Hauck
- Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
| | | | - Sami Hussain Alhajjar
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Saleh Al-Muhsen
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.,Immunology Research Laboratory, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Theresa Cole
- Department of Immunology, The Royal Children's Hospital, Melbourne, Australia
| | - Ramsay Fuleihan
- Division of Allergy & Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Peter D Arkwright
- Department of Paediatric Allergy and Immunology, Lydia Becker Institute of Immunology and Inflammation, Royal Manchester Children's Hospital, University of Manchester, Manchester, United Kingdom
| | - Raffaele Badolato
- Institute of Molecular Medicine Angelo Nocivelli, University of Brescia, Civil Hospital of Brescia, Brescia, Italy
| | - Laia Alsina
- Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, and Functional Unit of Immunology, Sant Joan de Déu Hospital, Institut de Recerca Sant Joan de Déu, University of Barcelona, Barcelona, Spain
| | - Laurent Abel
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY
| | - Mukesh Desai
- Department of Pediatric Immunology, Bai Jerbai Wadia Hospital for Children, Mumbai, India
| | - Hamoud Al-Mousa
- Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Anna Shcherbina
- Department of Clinical Immunology and Allergy, Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia
| | - Nico Marr
- Division of Translational Medicine, Sidra Medicine, Doha, Qatar
| | - Stéphanie Boisson-Dupuis
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY
| | - Jean-Laurent Casanova
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France.,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.,Howard Hughes Medical Institute, New York, NY; and
| | - Satoshi Okada
- Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Jacinta Bustamante
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France; .,University of Paris, Imagine Institute, Paris, France.,St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.,Study Center for Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris, Paris, France
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Monogenic susceptibility to live viral vaccines. Curr Opin Immunol 2021; 72:167-175. [PMID: 34107321 PMCID: PMC9586878 DOI: 10.1016/j.coi.2021.05.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 11/25/2022]
Abstract
Live attenuated viral vaccines (LAV) have saved millions of lives globally through their capacity to elicit strong, cross-reactive and enduring adaptive immune responses. However, LAV can also act as a Trojan horse to reveal inborn errors of immunity, thereby highlighting important protective elements of the healthy antiviral immune response. In the following article, we draw out these lessons by reviewing the spectrum of LAV-associated disease reported in a variety of inborn errors of immunity. We note the contrast between adaptive disorders, which predispose to both LAV and their wild type counterparts, and defects of innate immunity in which parenterally delivered LAV behave in a particularly threatening manner. Recognition of the underlying pathomechanisms can inform our approach to disease management and vaccination in a wider group of individuals, including those receiving immunomodulators that impact the relevant pathways.
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7
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Corticosteroids Contribute to Serious Adverse Events Following Live Attenuated Varicella Vaccination and Live Attenuated Zoster Vaccination. Vaccines (Basel) 2021; 9:vaccines9010023. [PMID: 33418856 PMCID: PMC7825138 DOI: 10.3390/vaccines9010023] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 12/28/2020] [Accepted: 01/01/2021] [Indexed: 12/28/2022] Open
Abstract
Corticosteroids, when given in high dosages, have long been recognized as a risk factor for severe infection with wild-type varicella-zoster virus in both children and adults. The goal of this review is to assess the degree to which both low-dosage and high-dosage corticosteroids contribute to serious adverse events (SAEs) following live varicella vaccination and live zoster vaccination. To this end, we examined multiple published reports of SAEs following varicella vaccination (VarivaxTM) and zoster vaccination (ZostavaxTM). We observed that five of eight viral SAEs following varicella vaccination, including two deaths, occurred in children receiving corticosteroids, while one of three fatal viral SAEs following live zoster vaccination occurred in an adult being treated with low-dosage prednisone. The latter death after live zoster vaccination occurred in a 70 year-old man with rheumatoid arthritis, being treated with prednisone 10 mg daily. Thus, corticosteroids contributed to more severe infectious complications in subjects immunized with each of the two live virus vaccines. Further, when we surveyed the rheumatology literature as well as individual case reports, we documented examples where daily dosages of 7.5–20 mg prednisone were associated with increased rates of severe wild-type varicella-zoster virus infections in children and adults.
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8
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Varicella-zoster-virus vaccination of immunosuppressed children with inflammatory bowel disease or autoimmune hepatitis: A prospective observational study. Vaccine 2020; 38:8024-8031. [PMID: 33160754 DOI: 10.1016/j.vaccine.2020.10.028] [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: 06/01/2020] [Revised: 10/01/2020] [Accepted: 10/08/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND AIMS Children with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS). METHODS This prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response. RESULTS A total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3-16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination. All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn's disease the day after vaccination. The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078). CONCLUSIONS VZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).
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Schreiner P, Mueller NJ, Fehr J, Maillard MH, Brand S, Michetti P, Schoepfer A, Restellini S, Vulliemoz M, Vavricka SR, Juillerat P, Rogler G, Biedermann L. Varicella zoster virus in inflammatory bowel disease patients: what every gastroenterologist should know. J Crohns Colitis 2020; 15:jjaa132. [PMID: 32592587 DOI: 10.1093/ecco-jcc/jjaa132] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Indexed: 12/17/2022]
Abstract
Primary Varicella Zoster virus (VZV) infection results in varicella (chickenpox) while its reactivation results in herpes zoster (HZ; shingles). Patients with Inflammatory Bowel Disease (IBD) are susceptible to complications of primary VZV infection and have an increased risk of HZ. Concerns of VZV and HZ infection in the IBD population has been highlighted by the emergence of JAK-inhibitors and their safety profile in this patient population such as tofacitinib for the treatment of ulcerative colitis (UC). The current pipeline of emerging therapies include novel molecules targeting multiple pathways including JAK/signal transducer and cytokine signalling pathways such as JAK/STAT. Hence VZV and HZ will be increasingly relevant for gastroenterologists treating IBD patients in light of these emerging therapies.
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Affiliation(s)
- Philipp Schreiner
- Department of Gastroenterology & Hepatology, University Hospital Zurich
| | - Nicolas J Mueller
- Department of Infectious Diseases & Hospital Epidemiology, University Hospital Zurich, Switzerland
| | - Jan Fehr
- Department of Infectious Diseases & Hospital Epidemiology, University Hospital Zurich, Switzerland
- Department of Public & Global Health, University of Zurich, Zurich, Switzerland
| | - Michel H Maillard
- Crohn and Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
| | - Stephan Brand
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kantonsspital Sankt Gallen, St. Gallen, Switzerland
| | - Pierre Michetti
- Crohn and Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
| | - Alain Schoepfer
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
| | - Sophie Restellini
- Department of Gastroenterology and Hepatology, Geneva University Hospitals and University of Geneva, Switzerland
| | - Marianne Vulliemoz
- Crohn and Colitis Center, Gastroentérologie Beaulieu SA, Lausanne, Switzerland
| | - Stephan R Vavricka
- Department of Gastroenterology & Hepatology, University Hospital Zurich
- Center of Gastroenterology and Hepatology, CH, Zurich, Switzerland
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology & Hepatology, University Hospital Zurich
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Speth F, Hinze CH, Andel S, Mertens T, Haas JP. Varicella-zoster-virus vaccination in immunosuppressed children with rheumatic diseases using a pre-vaccination check list. Pediatr Rheumatol Online J 2018; 16:15. [PMID: 29499726 PMCID: PMC5833060 DOI: 10.1186/s12969-018-0231-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 02/20/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The goal of this study was to apply the varicella zoster virus (VZV) vaccine to patients with pediatric rheumatic diseases (PRD) at risk for severe chickenpox, without interrupting their current immunosuppression, including biological agents, using an immunological-based pre-vaccination checklist to assure safety. A pre-vaccination checklist was implemented to ensure adequate immune competence prior to immunization. METHODS This prospective study included seronegative patients (VZV-IgG ≤200 mIU/ml) and patients who had previously received only a single dose of VZV vaccine. All vaccinees demonstrated clinically inactive PRD. Patients were categorized according to their actual treatment in low-intensity IS (LIIS) and high-intensity IS (HIIS) including biological therapy. The pre-vaccination checklist defined thresholds for the following basic laboratory tests: white blood cell count ≥3000/mm3, lymphocytes ≥1200/mm3, serum IgG ≥500 mg/dl, IgM ≥20 mg/dl, tetanus toxoid antibody ≥0.1 IU/ml. In case of HIIS additional specifications included a CD4+ lymphocyte count ≥200/mm3 and a positive T-cell function (via analyzable positive control of a standard tuberculosis interferon-gamma-release-assay (TB-IGRA) indicating mitogen-induced T cell proliferation). Patients who met the criteria of the pre-vaccination checklist received the first and/or second VZV vaccination. Immunologic response and side effects were monitored. RESULTS Twenty-three patients were recruited of whom nine had already received one VZV immunization before initiating IS. All patients met the pre-vaccination checklist criteria despite ongoing IS. There was no overall difference in VZV-IgG levels when comparing the LIIS (n=9) and HIIS (n=14) groups. In total, 21 patients (91%) showed a positive vaccination response, after the first immunization the median VZV-IgG across all patients was 224 (59-1219) mIU/ml (median (range)), after booster immunization it increased to 882 (30-4685) mIU/ml. Two patients in the HIIS group failed to raise positive VZV-IgG, despite booster immunization. All nine patients receiving only the second immunization on IS reached high titers of VZV-IgG >500 mIU/ml (1117 (513-4685) mIU/ml). There were no cases of rash or other vaccine-induced varicella disease symptoms and no evidence of PRD flare. CONCLUSIONS VZV vaccination is safe and largely immunogenic in children with ongoing IS fulfilling an immunological based pre-vaccination checklist. This new approach is based on immunologic function rather than on type of medications. TRIAL REGISTRATION NUMBER ISRCRTN trial registration number 21654693 , date of registration February 12, 2018, retrospectively registered.
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Affiliation(s)
- Fabian Speth
- German Center for Pediatric and Adolescent Rheumatology, Gehfeldstr. 24, 82467, Garmisch-Partenkirchen, Germany
| | - Claas H Hinze
- Department of Pediatric Rheumatology and Immunology, University Hospital Münster, Albert-Schweitzer-Campus I, Building W30, 48149, Münster, Germany.
| | - Susanne Andel
- German Center for Pediatric and Adolescent Rheumatology, Gehfeldstr. 24, 82467, Garmisch-Partenkirchen, Germany
| | - Thomas Mertens
- Institute of Virology, Ulm University Medical Center, Albert-Einstein-Allee 11, 89081, Ulm, Germany
| | - Johannes-Peter Haas
- German Center for Pediatric and Adolescent Rheumatology, Gehfeldstr. 24, 82467, Garmisch-Partenkirchen, Germany
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11
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Poowuttikul P, McGrath E, Kamat D. Deficit of Anterior Pituitary Function and Variable Immune Deficiency Syndrome: A Novel Mutation. Glob Pediatr Health 2017; 4:2333794X16686870. [PMID: 28229099 PMCID: PMC5308421 DOI: 10.1177/2333794x16686870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 12/04/2016] [Indexed: 11/19/2022] Open
Affiliation(s)
- Pavadee Poowuttikul
- Children's Hospital of Michigan, Detroit, MI, USA; Wayne State University, Detroit, MI, USA
| | - Eric McGrath
- Children's Hospital of Michigan, Detroit, MI, USA; Wayne State University, Detroit, MI, USA
| | - Deepak Kamat
- Children's Hospital of Michigan, Detroit, MI, USA; Wayne State University, Detroit, MI, USA
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12
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Nanishi E, Hoshina T, Takada H, Ishimura M, Nishio H, Uehara T, Mizuno Y, Hasegawa S, Ohga S, Nagao M, Igarashi M, Yajima S, Kusumoto Y, Onishi N, Sasahara Y, Yasumi T, Heike T, Hara T. A nationwide survey of common viral infections in childhood among patients with primary immunodeficiency diseases. J Infect 2016; 73:358-68. [PMID: 27498293 DOI: 10.1016/j.jinf.2016.07.018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 07/25/2016] [Accepted: 07/26/2016] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Patients with primary immunodeficiency diseases (PID) are highly susceptible to various microorganisms. However, no population-based studies have been performed among common viral pathogens, such as respiratory syncytial virus (RSV), rotavirus (RV), varicella-zoster virus (VZV) and influenza virus (IV). The objective of this study was to reveal the clinical burden of these four infections among PID patients in Japan. METHODS We conducted a nationwide survey by sending questionnaires to 898 hospitals with pediatric departments throughout Japan. RESULTS Nine hundred ten PID patients from 621 hospitals were registered (response rate: 69.2%). Fifty-four of the patients were hospitalized due to these viral infections. The durations of hospitalization due to RSV and RV infections differed significantly in the PID patients with and without cellular immunodeficiency (12.0 vs 6.5 days, p = 0.041; and 14.0 vs 6.0 days, p = 0.031, respectively). There was no significant difference in the duration of hospitalization in PID patients with and without cellular immunodeficiency who were hospitalized with IV infections (7.3 vs 6.1 days, p = 0.53). CONCLUSIONS Special attention should be paid to PID patients with compromised cellular immunity who present with RSV and RV infection due to their high risk for severe disease.
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Affiliation(s)
- Etsuro Nanishi
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Takayuki Hoshina
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
| | - Hidetoshi Takada
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Perinatal and Pediatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masataka Ishimura
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hisanori Nishio
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Center for the Study of Global Infection, Kyushu University Hospital, Fukuoka, Japan
| | - Takahiro Uehara
- Department of Pediatrics, Kameda Medical Center, Kamogawa, Japan
| | - Yumi Mizuno
- Department of Pediatric Infectious Disease, Fukuoka Children's Hospital, Fukuoka, Japan
| | - Shunji Hasegawa
- Department of Pediatrics, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Shouichi Ohga
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatrics, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Masayoshi Nagao
- Department of Pediatrics and Clinical Research, NHO Hokkaido Medical Center, Sapporo, Japan
| | - Maiko Igarashi
- Department of Pediatrics, Saiseikai Kawaguchi General Hospital, Kawaguchi, Japan
| | - Shuhei Yajima
- Department of Pediatrics, Hamamatsu Medical Center, Hamamatsu, Japan
| | - Yoshio Kusumoto
- Department of Pediatrics, Osaka General Medical Center, Osaka, Japan
| | - Noriko Onishi
- Department of Pediatrics, Fujita General Hospital, Fukushima, Japan
| | - Yoji Sasahara
- Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takahiro Yasumi
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshio Heike
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshiro Hara
- Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Fukuoka Children's Hospital, Fukuoka, Japan
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13
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Smith C, Dutmer C, Schmid DS, Dishop MK, Bellini WJ, Gelfand EW, Asturias EJ. A Toddler With Rash, Encephalopathy, and Hemolytic Anemia. J Pediatric Infect Dis Soc 2015; 4:376-80. [PMID: 26407265 PMCID: PMC4681381 DOI: 10.1093/jpids/piv032] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 04/25/2015] [Indexed: 11/12/2022]
Affiliation(s)
| | - Cullen Dutmer
- Department of Pediatric Allergy and Clinical Immunology, National Jewish Health, Denver, Colorado
| | - D. Scott Schmid
- Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Megan K. Dishop
- Department of Pathology, University of Colorado School of Medicine, Aurora
| | - William J. Bellini
- Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Erwin W. Gelfand
- Department of Pediatric Allergy and Clinical Immunology, National Jewish Health, Denver, Colorado
| | - Edwin J. Asturias
- Department of Pediatric Infectious Diseases,Center for Global Health, Colorado School of Public Health, Aurora
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14
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Hernandez-Trujillo VP, Scalchunes C, Hernandez-Trujillo HS, Boyle J, Williams P, Boyle M, Orange JS. Primary Immunodeficiency Diseases: An Opportunity in Pediatrics for Improving Patient Outcomes. Clin Pediatr (Phila) 2015; 54:1265-75. [PMID: 25780256 DOI: 10.1177/0009922815574079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Primary immunodeficiency diseases (PIDDs) are caused by inherent deficits in immune defenses that result in abnormal susceptibility to infection. In most cases, early and appropriate diagnosis can improve patient outcomes. The objective of this study was to evaluate understanding, recognition, and diagnosis of PIDD among pediatricians. METHODS A mail survey sent to a sample of pediatricians obtained from the American Medical Association and American Osteopathic Association. Results were compared with a similar survey of specialists who are members of the American Academy of Asthma, Allergy and Immunology. RESULTS More than a third (35%) of pediatricians were uncomfortable with the recognition and diagnosis of PIDD despite 95% having ordered screening tests or referring patients to specialists to be evaluated for PIDD, and 77% having followed at leastone patient with PIDD. In all, 84% of pediatricians were unaware that professional guidelines for PIDD exist. CONCLUSIONS Patients with PIDD would benefit from improved recognition of the diseases by pediatricians in order to facilitate earlier diagnosis and optimize ongoing therapy.
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Affiliation(s)
| | | | - Hillary S Hernandez-Trujillo
- Connecticut Asthma and Allergy Center, West Hartford, CT, USA University of Connecticut School of Medicine, Farmington, CT, USA Children's Hospital of Philadelphia, Philadelphia, PA, USA University of Pennsylvania School of Medicine, Philadelphia, PA, USA
| | - John Boyle
- Immune Deficiency Foundation, Towson, MD, USA Abt SRBI Inc, Government Services Division, Silver Spring, MD, USA
| | - Paul Williams
- University of Washington School of Medicine, Seattle, WA, USA
| | | | - Jordan S Orange
- Texas Children's Hospital, Houston, TX, USA Baylor College of Medicine, Houston, TX, USA
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15
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Bhalla P, Forrest GN, Gershon M, Zhou Y, Chen J, LaRussa P, Steinberg S, Gershon AA. Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation. Clin Infect Dis 2014; 60:1068-74. [PMID: 25452596 DOI: 10.1093/cid/ciu970] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Live attenuated varicella vaccine is recommended for healthy individuals who are susceptible to varicella. Although the vaccine is safe, effective, and used worldwide, serious adverse events have been reported, mainly in immunocompromised patients who subsequently recovered. Here, we describe the fatality of an immunocompromised patient who received the varicella vaccine. His medical history provides a cautionary lens through which to view the decision of when vaccination is appropriate. A middle-aged man with non-Hodgkin lymphoma received chemotherapy and a stem cell transplant. He was vaccinated 4 years post-transplantation, despite diagnosis of a new low-grade lymphoma confined to the lymph nodes. Within 3 months of vaccination, he developed recurrent rashes with fever, malaise, weakness, hepatitis, weight loss, and renal failure. The syndrome was eventually determined to be associated with persistent disseminated zoster caused by the vaccine virus. This case illustrates a circumstance when a live viral vaccine should not be used.
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Affiliation(s)
- Preeti Bhalla
- Department of Medicine, Oregon Health Science University, Portland
| | - Graeme N Forrest
- Department of Medicine, Oregon Health Science University, Portland Portland Veterans Affairs Medical Center, Oregon
| | | | - Yan Zhou
- Department of Pathology and Cell Biology
| | - Jason Chen
- Department of Pathology and Cell Biology
| | - Philip LaRussa
- Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York
| | - Sharon Steinberg
- Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York
| | - Anne A Gershon
- Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York
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16
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Bayer DK, Martinez CA, Sorte HS, Forbes LR, Demmler-Harrison GJ, Hanson IC, Pearson NM, Noroski LM, Zaki SR, Bellini WJ, Leduc MS, Yang Y, Eng CM, Patel A, Rodningen OK, Muzny DM, Gibbs RA, Campbell IM, Shaw CA, Baker MW, Zhang V, Lupski JR, Orange JS, Seeborg FO, Stray-Pedersen A. Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray. Clin Exp Immunol 2014; 178:459-69. [PMID: 25046553 PMCID: PMC4238873 DOI: 10.1111/cei.12421] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/16/2014] [Indexed: 12/22/2022] Open
Abstract
In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.
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Affiliation(s)
- D K Bayer
- Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
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17
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Non dermatomal rash and pancytopenia in a 5 year old child. J Clin Virol 2014; 60:81-3. [PMID: 24793965 DOI: 10.1016/j.jcv.2014.03.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Revised: 03/26/2014] [Accepted: 03/31/2014] [Indexed: 11/20/2022]
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18
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Gershon AA, Gershon MD. Pathogenesis and current approaches to control of varicella-zoster virus infections. Clin Microbiol Rev 2013; 26:728-43. [PMID: 24092852 PMCID: PMC3811230 DOI: 10.1128/cmr.00052-13] [Citation(s) in RCA: 127] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Varicella-zoster virus (VZV) was once thought to be a fairly innocuous pathogen. That view is no longer tenable. The morbidity and mortality due to the primary and secondary diseases that VZV causes, varicella and herpes zoster (HZ), are significant. Fortunately, modern advances, including an available vaccine to prevent varicella, a therapeutic vaccine to diminish the incidence and ameliorate sequelae of HZ, effective antiviral drugs, a better understanding of VZV pathogenesis, and advances in diagnostic virology have made it possible to control VZV in the United States. Occult forms of VZV-induced disease have been recognized, including zoster sine herpete and enteric zoster, which have expanded the field. Future progress should include development of more effective vaccines to prevent HZ and a more complete understanding of the consequences of VZV latency in the enteric nervous system.
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19
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Leung J, Siegel S, Jones JF, Schulte C, Blog D, Schmid DS, Bialek SR, Marin M. Fatal varicella due to the vaccine-strain varicella-zoster virus. Hum Vaccin Immunother 2013; 10:146-9. [PMID: 23982221 DOI: 10.4161/hv.26200] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
We describe a death in a 15-mo-old girl who developed a varicella-like rash 20 d after varicella vaccination that lasted for 2 mo despite acyclovir treatment. The rash was confirmed to be due to vaccine-strain varicella-zoster virus (VZV). This is the first case of fatal varicella due to vaccine-strain VZV reported from the United States. The patient developed severe respiratory complications that worsened with each new crop of varicella lesions; vaccine-strain VZV was detected in the bronchial lavage specimen. Sepsis and multi-organ failure led to death. The patient did not have a previously diagnosed primary immune deficiency, but her failure to thrive and repeated hospitalizations early in life (starting at 5 mo) for presumed infections and respiratory compromise treated with corticosteroids were suggestive of a primary or acquired immune deficiency. Providers should monitor for adverse reactions after varicella vaccination. If severe adverse events develop, acyclovir should be administered as soon as possible. The possibility of acyclovir resistance and use of foscarnet should be considered if lesions do not improve after 10 d of treatment (or if they become atypical [e.g., verrucous]). Experience with use of varicella vaccine indicates that the vaccine has an excellent safety profile and that serious adverse events are very rare and mostly described in immunocompromised patients. The benefit of vaccination in preventing severe disease and mortality outweigh the low risk of severe events occurring after vaccination.
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Affiliation(s)
- Jessica Leung
- National Center for Immunization and Respiratory Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA
| | - Subhadra Siegel
- Department of Pediatrics; New York Medical College; New York, NY USA
| | - James F Jones
- National Center for Emerging and Zoonotic Infectious Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA
| | - Cynthia Schulte
- Bureau of Immunization; New York State Health Department; Albany, NY USA
| | - Debra Blog
- Bureau of Immunization; New York State Health Department; Albany, NY USA
| | - D Scott Schmid
- National Center for Immunization and Respiratory Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA
| | - Stephanie R Bialek
- National Center for Immunization and Respiratory Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA
| | - Mona Marin
- National Center for Immunization and Respiratory Diseases; Centers for Disease Control and Prevention; Atlanta, GA USA
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21
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Orange JS, Ballow M, Stiehm ER, Ballas ZK, Chinen J, De La Morena M, Kumararatne D, Harville TO, Hesterberg P, Koleilat M, McGhee S, Perez EE, Raasch J, Scherzer R, Schroeder H, Seroogy C, Huissoon A, Sorensen RU, Katial R. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 2012; 130:S1-24. [PMID: 22935624 DOI: 10.1016/j.jaci.2012.07.002] [Citation(s) in RCA: 329] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Revised: 07/02/2012] [Accepted: 07/03/2012] [Indexed: 12/24/2022]
Abstract
A major diagnostic intervention in the consideration of many patients suspected to have primary immunodeficiency diseases (PIDDs) is the application and interpretation of vaccination. Specifically, the antibody response to antigenic challenge with vaccines can provide substantive insight into the status of human immune function. There are numerous vaccines that are commonly used in healthy individuals, as well as others that are available for specialized applications. Both can potentially be used to facilitate consideration of PIDD. However, the application of vaccines and interpretation of antibody responses in this context are complex. These rely on consideration of numerous existing specific studies, interpolation of data from healthy populations, current diagnostic guidelines, and expert subspecialist practice. This document represents an attempt of a working group of the American Academy of Allergy, Asthma & Immunology to provide further guidance and synthesis in this use of vaccination for diagnostic purposes in consideration of PIDD, as well as to identify key areas for further research.
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Affiliation(s)
- Jordan S Orange
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
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Gershman MD, Staples JE, Bentsi-Enchill AD, Breugelmans JG, Brito GS, Camacho LAB, Cottin P, Domingo C, Durbin A, Gascon J, Guenaneche F, Hayes EB, Jelenik Z, Khromava A, Martins RDM, Wilson MM, Massy N, Nasidi A, Niedrig M, Sherwat A, Tsai T, Vilella A, Wilson ME, Kohl KS. Viscerotropic disease: case definition and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 2012; 30:5038-58. [PMID: 22561144 DOI: 10.1016/j.vaccine.2012.04.067] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2012] [Accepted: 04/19/2012] [Indexed: 12/12/2022]
Affiliation(s)
- Mark D Gershman
- Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, N.E., MS-E03, Atlanta, GA 30333, USA.
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Williams SE, Klein NP, Halsey N, Dekker CL, Baxter RP, Marchant CD, LaRussa PS, Sparks RC, Tokars JI, Pahud BA, Aukes L, Jakob K, Coronel S, Choi H, Slade BA, Edwards KM. Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004-2009. Vaccine 2011; 29:6920-7. [PMID: 21801776 DOI: 10.1016/j.vaccine.2011.07.044] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2011] [Revised: 06/30/2011] [Accepted: 07/13/2011] [Indexed: 11/15/2022]
Abstract
BACKGROUND In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical Immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). METHODS Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. RESULTS CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of the cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. CONCLUSIONS The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations.
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Chouliaras G, Spoulou V, Quinlivan M, Breuer J, Theodoridou M. Vaccine-associated herpes zoster ophthalmicus [correction of opthalmicus] and encephalitis in an immunocompetent child. Pediatrics 2010; 125:e969-72. [PMID: 20194287 DOI: 10.1542/peds.2009-2633] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Varicella-zoster virus vaccine has diminished the consequences of chicken pox in terms of health and economical burden. The increasing number of doses administered worldwide has revealed rare but important adverse effects that had not occurred during clinical trials. We report here the case of an immunocompetent 3(1/2)-year-old girl who developed encephalitis and herpes zoster opthalmicus 20 months after her immunization with varicella-zoster virus vaccine. Molecular analysis confirmed the vaccine strain as the causative agent. After an intravenous course with acyclovir, the child made a full recovery with no neurologic sequelae.
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Affiliation(s)
- Giorgos Chouliaras
- First Department of Pediatrics, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
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25
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Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology. Clin Immunol 2009; 135:255-63. [PMID: 19914873 DOI: 10.1016/j.clim.2009.10.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2009] [Revised: 10/07/2009] [Accepted: 10/14/2009] [Indexed: 11/22/2022]
Abstract
There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.
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26
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Chaves SS, Haber P, Walton K, Wise RP, Izurieta HS, Schmid DS, Seward JF. Safety of varicella vaccine after licensure in the United States: experience from reports to the vaccine adverse event reporting system, 1995-2005. J Infect Dis 2008; 197 Suppl 2:S170-7. [PMID: 18419393 DOI: 10.1086/522161] [Citation(s) in RCA: 93] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Widespread use of varicella vaccine in the United States could enable detection of rare adverse events not identified previously. We reviewed data from 1995 to 2005 from the Vaccine Adverse Event Reporting System, including data from laboratory analyses, to distinguish adverse events associated with wild-type varicella-zoster virus (VZV) versus those associated with vaccine strain. Almost 48 million doses of varicella vaccine were distributed between 1995 and 2005. There were 25,306 adverse events reported (52.7/100,000 doses distributed); 5.0% were classified as serious (2.6/100,000 doses distributed). Adverse events associated with evidence of vaccine-strain VZV included meningitis in patients with concurrent herpes zoster. Patients with genetic predispositions may rarely have disease triggered by receipt of varicella vaccine. Overall, serious adverse events reported after varicella vaccination continue to be rare and must be considered relative to the substantial benefits of varicella vaccination. Ongoing safety surveillance and further studies may shed light on some of the hypothesized associations.
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Affiliation(s)
- Sandra S Chaves
- Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
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27
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Malavige GN, Jones L, Black AP, Ogg GS. Varicella zoster virus glycoprotein E-specific CD4+ T cells show evidence of recent activation and effector differentiation, consistent with frequent exposure to replicative cycle antigens in healthy immune donors. Clin Exp Immunol 2008; 152:522-31. [PMID: 18363743 DOI: 10.1111/j.1365-2249.2008.03633.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Varicella zoster viru (VZV)-specific T cell responses are believed to be vital in recovery from primary VZV infection and also in the prevention of viral reactivation. While glycoprotein E (gE) is the most abundant and one of the most immunogenic proteins of the virus, there are no data addressing potential T cell epitopes within gE, nor the phenotype of specific T cells. Using interferon gamma enzyme-linked immunospot assays and intracellular cytokine assays, we identified gE-specific immune responses in 20 adult healthy immune donors which were found to be dominated by the CD4+ subset of T cells. We characterized three immune dominant epitopes within gE restricted through DRB1*1501, DRB1*07 and DRB4*01, and used DRB1*1501 class II tetrameric complexes to determine the ex vivo frequency and phenotype of specific T cells. In healthy immune donors, the cells were largely positive for CCR7, CD28 and CD27, but expressed variable CD62L and low levels of cutaneous lymphocyte associated antigen with evidence of recent activation. In summary, we show that circulating gE-specific CD4+ T cells are detected at a relatively high frequency in healthy immune donors and show evidence of recent activation and mixed central and effector memory phenotype. These data would be compatible with frequent exposure to replicative cycle antigens in healthy donors and are consistent with a role for gE-specific CD4+ T cells in the control of viral replication.
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Affiliation(s)
- G N Malavige
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
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29
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Jean-Philippe P, Freedman A, Chang MW, Steinberg SP, Gershon AA, LaRussa PS, Borkowsky W. Severe varicella caused by varicella-vaccine strain in a child with significant T-cell dysfunction. Pediatrics 2007; 120:e1345-9. [PMID: 17974726 DOI: 10.1542/peds.2004-1681] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
In March 1995, the US Food and Drug Administration approved a live attenuated varicella vaccine for use in healthy children 12 months to 12 years old. We report here an 18-month-old girl with cell-mediated immunodeficiency who developed a severe vaccine-associated rash and clinical evidence of vaccine-associated pneumonia 1 month after inadvertent receipt of varicella vaccine.
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Affiliation(s)
- Patrick Jean-Philippe
- Department of Pediatrics, New York University School of Medicine, New York, New York, USA.
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30
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Zhang JK, Zhao LF, Cheng J, Guo J, Wang DQ, Hong Y, Mao Y. Screening and cloning for proteins transactivated by the PS1TP5 protein of hepatitis B virus: A suppression subtractive hybridization study. World J Gastroenterol 2007; 13:1602-7. [PMID: 17461456 PMCID: PMC4146906 DOI: 10.3748/wjg.v13.i10.1602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To clone and identify human genes transactivated by PS1TP5 by constructing a cDNA subtractive library with suppression subtractive hybridization (SSH) technique.
METHODS: SSH and bioinformatics techniques were used for screening and cloning of the target genes transactivated by PS1TP5 protein. The mRNA was isolated from HepG2 cells transfected with pcDNA3.1(-)-myc-his(A)-PS1TP5 and pcDNA3.1(-)-myc-his(A) empty vector, respectively, and SSH technique was employed to analyze the differentially expressed DNA sequence between the two groups. After digestion with restriction enzyme RsaI, small size cDNAs were obtained. Then tester cDNA was divided into two groups and ligated to the specific adaptor 1 and adaptor 2, respectively. The tester cDNA was hybridized with driver cDNA twice and subjected to nested PCR for two times, and then subcloned into T/A plasmid vectors to set up the subtractive library. Amplification of the library was carried out with E. coli strain DH5α. The cDNA was sequenced and analyzed in GenBank with Vector NTI 9.1 and NCBI BLAST software after PCR amplification.
RESULTS: The subtractive library of genes transactivated by PS1TP5 was constructed successfully. The amplified library contained 90 positive clones. Colony PCR showed that 70 clones contained 200-1000-bp inserts. Sequence analysis was performed in 30 clones randomly, and the full-length sequences were obtained by bioinformatics technique. Altogether 24 coding sequences were obtained, which consisted of 23 known and 1 unknown. One novel gene with unknown functions was found and named as PS1TP5TP1 after being electronically spliced, and deposited in GenBank (accession number: DQ487761).
CONCLUSION: PS1TP5 is closely correlated with immunoregulation, carbohydrate metabolism, signal transduction, formation mechanism of hepatic fibrosis, and occurrence and development of tumor. Understanding PS1TP5 transactive proteins may help to bring some new clues for further studying the biological functions of pre-S1 protein.
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Affiliation(s)
- Jian-Kang Zhang
- Department of Gastroenterology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.
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31
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Cisneros-Herreros JM, Herrero-Romero M. Hepatitis por virus del grupo herpes. Enferm Infecc Microbiol Clin 2006; 24:392-7; quiz 398. [PMID: 16792943 DOI: 10.1157/13089695] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
In immunocompetent patients, primary infection by herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6, and Epstein-Barr virus (EBV) generally produces mild, self-limited hepatitis. Primary infection by HSV in neonates and pregnant women, and infection by VZV in hematological and bone marrow recipients can cause fulminant hepatitis without characteristic skin lesions. In liver transplant recipients, hepatitis is the most common expression of CMV infection and the related symptoms are indistinguishable from those of acute rejection. Persistent hepatitis is a manifestation of the syndrome of active chronic infection by the EBV. Fulminating hepatitis due to herpes virus can be treated effectively if therapy is started early; hence, a high degree of clinical suspicion and inclusion of herpes virus in the differential diagnosis of this syndrome is necessary.
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MESH Headings
- Adult
- Antiviral Agents/therapeutic use
- Chickenpox/complications
- Cytomegalovirus/isolation & purification
- Cytomegalovirus/pathogenicity
- Cytomegalovirus Infections/complications
- Epstein-Barr Virus Infections/complications
- Female
- Hepatitis, Viral, Human/diagnosis
- Hepatitis, Viral, Human/drug therapy
- Hepatitis, Viral, Human/etiology
- Hepatitis, Viral, Human/virology
- Herpes Simplex/complications
- Herpesviridae/isolation & purification
- Herpesviridae/pathogenicity
- Herpesvirus 3, Human/isolation & purification
- Herpesvirus 3, Human/pathogenicity
- Herpesvirus 4, Human/isolation & purification
- Herpesvirus 4, Human/pathogenicity
- Herpesvirus 6, Human/isolation & purification
- Herpesvirus 6, Human/pathogenicity
- Humans
- Immunocompromised Host
- Infant, Newborn
- Male
- Pregnancy
- Pregnancy Complications, Infectious/virology
- Simplexvirus/isolation & purification
- Simplexvirus/pathogenicity
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Abstract
The addition of varicella vaccine to the universal childhood immunization schedule in the United States in 1995 can be seen as a bold step. Shown to be safe and efficacious against varicella in extensive prelicensure studies, it is nonetheless the first vaccine against a herpesvirus and, furthermore, it is a live, attenuated vaccine. Both wild-type and vaccine strain varicella zoster virus (VZV) are noteworthy for their ability to establish latent infection within the host, with the subsequent possibility of reactivation. Therefore, at the population level, a successful vaccination program could result in the eventual displacement of wild-type VZV by the attenuated vaccine virus. The immediate objective of universal vaccination, however, was to reduce the significant morbidity and mortality associated with primary VZV infection. Data now accumulating suggest that the varicella vaccine as used in the United States has so far been highly effective. The challenge for the future is to predict how the resulting substantial reduction in circulation of VZV will affect immunity among both vaccinees and the unvaccinated. Vaccination strategies likely will need to be adjusted as the epidemiology of VZV in the United States continues to evolve.
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Affiliation(s)
- Sophie Hambleton
- Department of Pediatrics, Columbia University, New York, NY 10032, USA
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34
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Abstract
Varicella-zoster virus (VZV), the cause of chickenpox and shingles, is a pathogen in retreat following the introduction of mass vaccination in the United States in 1995. The live attenuated Oka vaccine, which is safe and immunogenic, gives good protection against both varicella and zoster in the short to medium term. It has undoubtedly been highly effective to date in reducing all forms of varicella, especially severe disease. However, the huge pool of latent wild-type virus in the population represents a continuing threat. Both the biology and the epidemiology of VZV disease suggest that new vaccination strategies will be required over time.
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Affiliation(s)
- Sophie Hambleton
- Columbia University College of Physicians and Surgeons, 650 W. 168th Street, New York, NY 10032, USA
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35
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White FV, Dehner LP. Viral diseases of the liver in children: diagnostic and differential diagnostic considerations. Pediatr Dev Pathol 2004; 7:552-67. [PMID: 15630523 DOI: 10.1007/s10024-004-8101-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2004] [Accepted: 09/01/2004] [Indexed: 01/04/2023]
Abstract
This review summarizes the general histologic features of acute and chronic hepatitides and highlights those morphologic findings that may suggest or be diagnostic of a specific agent or etiology. The main epidemiologic, clinical, and pathologic features of the hepatotropic viruses are discussed, with an emphasis on pediatric studies and the differential diagnosis of hepatitis in childhood.
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Affiliation(s)
- Frances V White
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology,St. Louis Children's Hospital at the Washington University Medical Center, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
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36
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Sartori AMC. A review of the varicella vaccine in immunocompromised individuals. Int J Infect Dis 2004; 8:259-70. [PMID: 15325594 DOI: 10.1016/j.ijid.2003.09.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2003] [Accepted: 09/18/2003] [Indexed: 10/26/2022] Open
Abstract
BACKGROUND Individuals with underlying cell-mediated immunodeficiency disorders are at high risk of developing severe, life-threatening illness associated with varicella-zoster virus infection. A live-attenuated varicella vaccine is recommended for routine childhood immunisation in some countries. In healthy children, the vaccine is efficacious and safe but because immunocompromised individuals may be unable to limit replication of live-attenuated vaccine viruses, the varicella vaccine is not recommended for them and there are few exceptions. OBJECTIVES The purpose of this paper is to review the published studies addressing the use of the varicella vaccine in people with cell-mediated immunodeficiency disorders. METHODS A computerised search on the PubMed database was used to collect the relevant papers published up to March 2003. RESULTS The varicella vaccine has been extensively studied in susceptible children with acute lymphoblastic leukaemia in remission, but studies involving individuals with other immunodeficiency disorders are scarce. Some of the current recommendations are based on very few and small studies with short follow-up. Immunocompromised individuals should be given the varicella vaccine only with complete knowledge of their clinical and immunological conditions and after considering the risks of natural infection and vaccination.
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Affiliation(s)
- Ana Marli Christovam Sartori
- Clinic of Infectious and Parasitic Diseases, Hospital das Clínicas, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
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Abstract
There are a surprisingly large number of human natural killer (NK) cell deficiency states that provide insight into the role of NK cells in defense against human infectious disease. Many disorders associated with NK cell defects are caused by single gene mutations and, thus, give additional understanding concerning the function of specific molecules in NK cell development and activities. A resounding theme of NK cell deficiencies is susceptibility to herpesviruses, suggesting that unexplained severe herpesviral infection should raise the possibility of an NK cell deficit.
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Affiliation(s)
- Jordan S Orange
- Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, 300 Longwood Avenue, MA, Boston, USA.
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Offit PA, Quarles J, Gerber MA, Hackett CJ, Marcuse EK, Kollman TR, Gellin BG, Landry S. Addressing parents' concerns: do multiple vaccines overwhelm or weaken the infant's immune system? Pediatrics 2002; 109:124-9. [PMID: 11773551 DOI: 10.1542/peds.109.1.124] [Citation(s) in RCA: 169] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant's immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant's immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant's ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago.
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Affiliation(s)
- Paul A Offit
- Section of Infectious Diseases, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, and Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania, USA.
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