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Laing KJ, Ouwendijk WJD, Campbell VL, McClurkan CL, Mortazavi S, Elder Waters M, Krist MP, Tu R, Nguyen N, Basu K, Miao C, Schmid DS, Johnston C, Verjans GMGM, Koelle DM. Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster. Nat Commun 2022; 13:6957. [PMID: 36376285 PMCID: PMC9663441 DOI: 10.1038/s41467-022-34698-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 10/27/2022] [Indexed: 11/16/2022] Open
Abstract
Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin.
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Affiliation(s)
- Kerry J Laing
- Department of Medicine, University of Washington, Seattle, WA, USA.
| | - Werner J D Ouwendijk
- HerpeslabNL of the Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | | | | | - Shahin Mortazavi
- Department of Medicine, University of Washington, Seattle, WA, USA
| | | | - Maxwell P Krist
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Richard Tu
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Nhi Nguyen
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Krithi Basu
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Congrong Miao
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, USA
| | - D Scott Schmid
- Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, GA, USA
| | - Christine Johnston
- Department of Medicine, University of Washington, Seattle, WA, USA
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Georges M G M Verjans
- HerpeslabNL of the Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - David M Koelle
- Department of Medicine, University of Washington, Seattle, WA, USA
- Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
- Department of Global Health, University of Washington, Seattle, WA, USA
- Department of Translational Research, Benaroya Research Institute, Seattle, WA, USA
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Mazzara C, Milani GP, Lava SAG, Bianchetti MG, Gualco G, Simonetti GD, Camozzi P, Kottanattu L. Atypical primary varicella rash: Systematic literature review. Acta Paediatr 2022; 111:935-939. [PMID: 35178772 PMCID: PMC9306993 DOI: 10.1111/apa.16300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 02/01/2022] [Accepted: 02/15/2022] [Indexed: 11/30/2022]
Abstract
Aim In previously healthy subjects, primary varicella presents with a distinctive vesicular rash that is more intense on the trunk and head than on the extremities. However, an atypical presentation may occasionally develop. We aimed at systematically assessing the characteristics of cases affected by atypical primary varicella rash. Methods The United States National Library of Medicine, Excerpta Medica and Web of Science databases were reviewed, without date or language restrictions. Articles were eligible if reporting previously healthy and immunocompetent subjects with a primary varicella rash (i.e., a photo‐localised primary varicella or skin inflammation‐associated primary varicella). Results Thirty‐eight reports providing information on 59 cases of atypical primary varicella were identified. Twenty‐four cases (median 8.5 years of age, 19 females) were photo‐localised and 35 (median 4.8 years of age, 15 females) were associated with pre‐existing skin inflammation (including cast occlusion, diaper irritation, operative sites, burns, insect bites, vaccinations or pre‐existing skin disease). The skin rash was monomorphic and without a “starry sky” appearance. Conclusion Primary varicella may have a modified presentation in areas of irritation such as sun exposure or pre‐existing inflammation. There is a need for a wider awareness of these modulators of varicella rash.
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Affiliation(s)
- Calogero Mazzara
- Pediatric Institute of Southern Switzerland Ospedale San Giovanni Ente Ospedaliero Cantonale Bellinzona Switzerland
| | - Gregorio Paolo Milani
- Pediatric Unit Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milan Italy
- Department of Clinical Sciences and Community Health Università degli Studi di Milano Milan Italy
| | - Sebastiano A. G. Lava
- Pediatric Cardiology Unit Department of Pediatrics Centre Hospitalier Universitaire Vaudois and University of Lausanne Lausanne Switzerland
| | - Mario Giovanni Bianchetti
- Faculty of Biomedical Sciences Family Medicine Institute Università della Svizzera Italiana Lugano Switzerland
| | - Gianluca Gualco
- Pediatric Institute of Southern Switzerland Ospedale San Giovanni Ente Ospedaliero Cantonale Bellinzona Switzerland
| | - Giacomo D. Simonetti
- Pediatric Institute of Southern Switzerland Ospedale San Giovanni Ente Ospedaliero Cantonale Bellinzona Switzerland
- Faculty of Biomedical Sciences Università della Svizzera Italiana Lugano Switzerland
| | - Pietro Camozzi
- Faculty of Biomedical Sciences Family Medicine Institute Università della Svizzera Italiana Lugano Switzerland
| | - Lisa Kottanattu
- Pediatric Institute of Southern Switzerland Ospedale San Giovanni Ente Ospedaliero Cantonale Bellinzona Switzerland
- Faculty of Biomedical Sciences Università della Svizzera Italiana Lugano Switzerland
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Meng Q, Wang B, Zhang X, Li Z, Wang W, Yao K. Case Report: Various Clinical Manifestations Caused by Varicella-Zoster Virus in a Family. Front Pediatr 2022; 10:876250. [PMID: 35733808 PMCID: PMC9207272 DOI: 10.3389/fped.2022.876250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
A family cluster of varicella-zoster virus (VZV) infections was reported. Four family members (two children and their parents) continuously develop varicella after the grandmother's herpes zoster. The unvaccinated 16-month-old infant and his mother developed primary varicella with atypical clinical presentation; however, his 28-year-old father presented with a typical generalized vesicular rash. His vaccinated 4-year-old sister was clinically mild, which could be defined as a breakthrough varicella case. They infected the same virus strain but presented various clinical forms.
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Affiliation(s)
- Qinghong Meng
- Laboratory of Dermatology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Bingsong Wang
- Department of Pediatrics, Wuhu No. 1 People's Hospital, Wuhu, China
| | - Xianlai Zhang
- Department of Pediatrics, Wuhu No. 1 People's Hospital, Wuhu, China
| | - Zhen Li
- Department of Laboratory Medicine, Wuhu No. 1 People's Hospital, Wuhu, China
| | - Wenjie Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
| | - Kaihu Yao
- Laboratory of Dermatology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
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Hattori F, Kozawa K, Miura H, Kawamura Y, Higashimoto Y, Yoshikawa A, Ihira M, Yoshikawa T. Trend in varicella patients 4 years after implementation of universal two-dose varicella vaccination in Japan. Vaccine 2020; 38:7331-7336. [PMID: 33008671 DOI: 10.1016/j.vaccine.2020.09.038] [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: 05/06/2020] [Revised: 09/05/2020] [Accepted: 09/13/2020] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To elucidate the trend and clinical spectrum of virologically diagnosed varicella patients after implementation of universal vaccination as a national immunization program in Japan. PATIENTS AND METHODS Study subjects were patients suspected of varicella, less than 15 years of age, who visited 14 pediatric clinics in the Nagoya VZV Study Group from September 2015 to August 2019. Practitioners collected patient samples and information such as backgrounds, clinical symptoms, and previous immunization status. All patients were confirmed as having varicella based on molecular diagnostic assays. RESULTS Varicella zoster virus (VZV) DNA was detected in swab samples from 506 (83.1%) of the 609 suspected patients. The 455 varicella patients for whom vaccination status was available were divided into two groups: 180 universal vaccination targets and 275 non-targets. Numbers of monthly varicella patients decreased gradually during the observation period. In the 2016/17 season, the seasonal epidemic of varicella became undetectable in the universal vaccination target group, and starting in the 2017/18 season, it was obscured even in the non-target group. The median age of patients was significantly lower in the universal vaccination target group (3 years) than the non-target group (7 years) (P < 0.001). Vaccination status differed significantly between the two groups (P < 0.001). Most varicella patients were in the non-target group, especially those who had been vaccinated once (60.4%). Frequency of fever (P < 0.001) and number of skin rashes at the time of the first hospital visit (P = 0.001) were significantly higher in the non-target group. CONCLUSIONS Although the number of childhood varicella patients declined after implementation of national immunization with two doses of varicella vaccination, sporadic outbreaks still occurred, mainly in the non-universal vaccination target group. Insufficient vaccination of members of this group is likely to be a major reason for small local outbreaks.
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Affiliation(s)
- Fumihiko Hattori
- Department of Pediatrics, Kariya Toyota General Hospital, Kariya, Aichi 448-8505, Japan; Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
| | - Kei Kozawa
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Hiroki Miura
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Yoshiki Kawamura
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Yuki Higashimoto
- Faculty of Medical Technology, Fujita Health University School of Medical Sciences, Toyoake, Aichi, Japan
| | - Akiko Yoshikawa
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
| | - Masaru Ihira
- Faculty of Clinical Engineering, Fujita Health University School of Medical Sciences, Toyoake, Aichi, Japan
| | - Tetsushi Yoshikawa
- Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination. J Virol 2020; 94:JVI.02127-19. [PMID: 32321817 DOI: 10.1128/jvi.02127-19] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 03/26/2020] [Indexed: 01/30/2023] Open
Abstract
Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults (n = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow.IMPORTANCE Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.
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Reliability of direct varicella zoster virus loop-mediated isothermal amplification method for rapid diagnosis of breakthrough varicella. J Clin Virol 2019; 119:53-58. [PMID: 31491710 DOI: 10.1016/j.jcv.2019.07.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/23/2019] [Accepted: 07/25/2019] [Indexed: 12/29/2022]
Abstract
BACKGROUND Since patients with breakthrough varicella (BV) have mild symptoms, clinical diagnosis is difficult. In high vaccine coverage area, as BV occurs sporadically, point of care test is required for controlling varicella outbreak. In this study, the reliability of varicella zoster virus (VZV)-loop mediated isothermal amplification (LAMP) was evaluated for the rapid diagnosis of BV. STUDY DESIGN A total of 328 swab samples collected from patients with suspected varicella were analyzed. For the laboratory diagnosis of varicella, VZV real-time PCR was carried out using DNA extracted from swab samples. Swab samples without DNA extraction were used for VZV-LAMP(direct-LAMP). RESULTS VZV infection was diagnosed by real-time PCR in 285 cases, including 105 natural varicella cases and 180 BV cases. VZV DNA was detected in 250 (87.8%) of the 285 cases by direct-LAMP. The presence and duration of fever, number of skin eruptions, and VZV DNA load were significantly lower in BV than natural varicella. The sensitivity of direct-LAMP for the diagnosis of varicella and BV was 93.3% and 84.4%, respectively. CONCLUSIONS Direct LAMP was considered to be useful for rapid diagnosis of BV as it has several advantages such as low cost, ease and rapidity, as compared to real time PCR.
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Abstract
The most common specimens from immunocompromised patients that are analyzed for detection of herpes simplex virus (HSV) or varicella-zoster virus (VZV) are from skin lesions. Many types of assays are applicable to these samples, but some, such as virus isolation and direct fluorescent antibody testing, are useful only in the early phases of the lesions. In contrast, nucleic acid (NA) detection methods, which generally have superior sensitivity and specificity, can be applied to skin lesions at any stage of progression. NA methods are also the best choice, and sometimes the only choice, for detecting HSV or VZV in blood, cerebrospinal fluid, aqueous or vitreous humor, and from mucosal surfaces. NA methods provide the best performance when reliability and speed (within 24 hours) are considered together. They readily distinguish the type of HSV detected or the source of VZV detected (wild type or vaccine strain). Nucleic acid detection methods are constantly being improved with respect to speed and ease of performance. Broader applications are under study, such as the use of quantitative results of viral load for prognosis and to assess the efficacy of antiviral therapy.
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Watanabe M, Ochiai H, Ito M, Negoro M, Suga S, Ihara T. Laboratory Diagnosis of Breakthrough Varicella in Children. Pediatr Infect Dis J 2017; 36:560-563. [PMID: 27997521 DOI: 10.1097/inf.0000000000001475] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Breakthrough varicella (BV) develops in vaccinated persons as a result of infection by wild-type varicella-zoster virus more than 42 days after varicella vaccination. The clinical symptoms are atypical, and clinical diagnosis can be difficult. We investigated laboratory-based diagnostic methods that are relatively simple and highly precise to conduct accurate surveillance. SUBJECTS AND METHODS We enrolled 42 patients with suspected BV at 2 pediatric hospitals and performed a real-time polymerase chain reaction (PCR) on the skin lesions to confirm the BV diagnosis. We performed PCR on saliva and blood collected during the acute phase, as well as direct fluorescent antibody (DFA) imaging on lesions, and measured varicella-zoster virus immunoglobulin (Ig) G and IgM during the acute and convalescent phases. RESULTS We confirmed the BV diagnosis in 31 of 42 enrolled patients. The sensitivity of DFA imaging of the lesion, and PCR of saliva and blood were 93.5%, 87.1% and 61.3%, respectively. IgM was detected in 12.9% of patients during the acute phase and in 65.5% during the convalescent phase. IgG increased more than 4-fold in 86.2% of patients between the acute and convalescent phases. The sensitivity and specificity of the assay were 83.9% and 81.8%, respectively, when the diagnostic criteria for IgG were set to greater than 20 during the acute phase. CONCLUSIONS The gold standard of laboratory-based diagnosis of BV has been the PCR of samples taken from lesions. However, DFA of the lesion showed equivalent sensitivity when compared with PCR. PCR using saliva samples is an effective, noninvasive method of diagnosis. We found that high values of IgG during the acute phase can aid in the diagnosis of BV.
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Affiliation(s)
- Masahiro Watanabe
- From the *Suzuka Pediatrics, Suzuka, Mie, Japan; †Ochiai Children Clinic, Kameyama, Mie, Japan; ‡Biwako Gakuen Yasu Medical and Welfare motor and Intellectual Disabilities Yasu, Yasu, Shiga, Japan; and §Mie National Hospital, Tsu, Mie, Japan
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Abstract
Little is known about varicella-zoster virus (VZV) susceptibility in US-bound refugee populations, although published data suggest that VZV seroprevalence in these refugee populations may be lower than US populations. We describe VZV seroprevalence in five US-bound refugee groups: (1) Bhutanese in Nepal, (2) Burmese on the Thailand-Burma (Myanmar) border, (3) Burmese in Malaysia, (4) Iraqi in Jordan, and (5) Somali in Kenya. Sera were tested for presence of VZV IgG antibodies among adults aged 18-45 years. Overall VZV seroprevalence was 97% across all refugee groups. VZV seroprevalence was also high across all age groups, with seroprevalence ranging from 92-100% for 18-26 year-olds depending on refugee group and 93-100% for 27-45 year-olds. VZV seroprevalence was unexpectedly high in these five US-bound refugee groups, though may not reflect seroprevalence in other refugee groups. Additional studies are needed to better understand VZV seroprevalence in refugee populations over time and by region.
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De Paschale M, Clerici P. Microbiology laboratory and the management of mother-child varicella-zoster virus infection. World J Virol 2016; 5:97-124. [PMID: 27563537 PMCID: PMC4981827 DOI: 10.5501/wjv.v5.i3.97] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Revised: 07/08/2016] [Accepted: 07/22/2016] [Indexed: 02/05/2023] Open
Abstract
Varicella-zoster virus, which is responsible for varicella (chickenpox) and herpes zoster (shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella (particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times: (1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection; (2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear (atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation; (3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and (4) when the baby is born and it is necessary to confirm a diagnosis of varicella (and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn.
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Perella D, Wang C, Civen R, Viner K, Kuguru K, Daskalaki I, Schmid DS, Lopez AS, Tseng HF, Newbern EC, Mascola L, Bialek SR. Varicella Vaccine Effectiveness in Preventing Community Transmission in the 2-Dose Era. Pediatrics 2016; 137:e20152802. [PMID: 26977081 PMCID: PMC4887293 DOI: 10.1542/peds.2015-2802] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/21/2015] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES We examined overall and incremental effectiveness of 2-dose varicella vaccination in preventing community transmission of varicella among children aged 4 to 18 years in 2 active surveillance sites. One-dose varicella vaccine effectiveness (VE) was examined in those aged 1 to 18 years. METHODS From May 2009 through June 2011, varicella cases identified during active surveillance in Antelope Valley, CA and Philadelphia, PA were enrolled into a matched case-control study. Matched controls within 2 years of the patient's age were selected from immunization registries. A standardized questionnaire was administered to participants' parents, and varicella vaccination history was obtained from health care provider, immunization registry, or parent records. We used conditional logistic regression to estimate varicella VE against clinically diagnosed and laboratory-confirmed varicella. RESULTS A total of 125 clinically diagnosed varicella cases and 408 matched controls were enrolled. Twenty-nine cases were laboratory confirmed. One-dose VE (1-dose versus unvaccinated) was 75.6% (95% confidence interval [CI], 38.7%-90.3%) in preventing any clinically diagnosed varicella and 78.1% (95% CI, 12.7%-94.5%) against moderate or severe, clinically diagnosed disease (≥50 lesions). Among subjects aged ≥4 years, 2-dose VE (2-dose versus unvaccinated) was 93.6% (95% CI, 75.6%-98.3%) against any varicella and 97.9% (95% CI, 83.0%-99.7%) against moderate or severe varicella. Incremental effectiveness (2-dose versus 1-dose) was 87.5% against clinically diagnosed varicella and 97.3% against laboratory-confirmed varicella. CONCLUSIONS Two-dose varicella vaccination offered better protection against varicella from community transmission among school-aged children compared with 1-dose vaccination.
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Affiliation(s)
- Dana Perella
- Philadelphia Department of Public Health, Philadelphia, Pennsylvania;
| | - Chengbin Wang
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Rachel Civen
- Los Angeles County Department of Public Health, Los Angeles, California; and
| | - Kendra Viner
- Philadelphia Department of Public Health, Philadelphia, Pennsylvania
| | - Karen Kuguru
- Los Angeles County Department of Public Health, Los Angeles, California; and
| | - Irini Daskalaki
- Philadelphia Department of Public Health, Philadelphia, Pennsylvania
| | - D Scott Schmid
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Adriana S Lopez
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Hung Fu Tseng
- Southern California Permanente Medical Group, Kaiser Permanente, Pasadena, California
| | - E Claire Newbern
- Philadelphia Department of Public Health, Philadelphia, Pennsylvania
| | - Laurene Mascola
- Los Angeles County Department of Public Health, Los Angeles, California; and
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Fu J, Wang J, Jiang C, Shi R, Ma T. Outbreak of varicella in a highly vaccinated preschool population. Int J Infect Dis 2015; 37:14-8. [PMID: 26072038 DOI: 10.1016/j.ijid.2015.06.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2015] [Revised: 05/21/2015] [Accepted: 06/06/2015] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Varicella vaccine is available for private purchase in Beijing, with single dose recommended for children aged ≥12 months before 2013. Despite the success achieved in reducing varicella incidence, varicella outbreaks continued to occur, including in schools and kindergartens among highly vaccinated children. We investigated a varicella outbreak in a preschool with high varicella vaccination coverage in Haidian district, Beijing. METHODS Through questionnaires, data including children's medical and vaccination history were collected from their parents. A case of varicella was defined as an acute, generalized, maculopapulovesicular rash without other apparent cause in a child in the preschool from March 10 through March 29, 2010. Attack rates in vaccinated and unvaccinated children were calculated, and the analyses of vaccine effectiveness (VE) and of risk factors for breakthrough disease (varicella occurring >42 days after vaccination) were conducted. RESULTS A total of 12 cases occurred during the outbreak, and ten of them (83.3%) had breakthrough varicella. The index case with mild varicella occurred in a child who had been vaccinated four years previously. Questionnaires were returned for all of 150 children in the preschool. Of all the 150 children, 144 (96.0%) had no prior history of varicella disease. Among these children, 135(93.7%) had received single-dose varicella vaccine before the outbreak. VE was 84.5% [95% confidence interval (CI): 62.8%∼93.5%] in preventing varicella of any severity, and VE was 92.2% (95% CI: 81.4%∼96.8%) against moderate to severe varicella. Age at vaccination (<15 months vs. ≥15 months) and time since vaccination before the outbreak (<3 years vs. ≥3 years) were not associated with the increased risk of breakthrough varicella(P=0.124 and 1, respectively). All the varicella cases with vaccination history verified through immunization records had received varicella vaccine and measles-mumps-rubella vaccine >30 days apart. CONCLUSIONS Breakthrough infection with fever in vaccinated person may be as infectious as varicella in unvaccinated persons. High single-dose varicella vaccination coverage is effective in reducing varicella incidence, but not sufficient to prevent outbreak. To control varicella outbreak a second dose may deserve additional consideration.
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Affiliation(s)
- Jiye Fu
- Beijing Haidian Center for Disease Control and Prevention, NO.5 Xibeiwang 2nd Road, Haidian district, Beijing 100094, People's Republic of China.
| | - Juguang Wang
- Beijing Haidian Center for Disease Control and Prevention, NO.5 Xibeiwang 2nd Road, Haidian district, Beijing 100094, People's Republic of China
| | - Chu Jiang
- Beijing Haidian Center for Disease Control and Prevention, NO.5 Xibeiwang 2nd Road, Haidian district, Beijing 100094, People's Republic of China
| | - Rujing Shi
- Beijing Haidian Center for Disease Control and Prevention, NO.5 Xibeiwang 2nd Road, Haidian district, Beijing 100094, People's Republic of China
| | - Tianwei Ma
- Beijing Haidian Center for Disease Control and Prevention, NO.5 Xibeiwang 2nd Road, Haidian district, Beijing 100094, People's Republic of China
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Gupta SN, Gupta N, Gupta S. Concurrent multiple outbreaks of varicella, rubeola, german measles in unvaccinated children of co-educational mount carmel senior secondary school, thakurdwara palampur of northern himachal, India. J Family Med Prim Care 2015; 4:117-23. [PMID: 25811001 PMCID: PMC4366981 DOI: 10.4103/2249-4863.152267] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: In April, 2009, in a co-education school, we investigated suspected triple outbreak; varicella first and then with chance detection of rubeola and rubella. The aim was to confirm diagnosis and recommend remedial measures to prevent further outbreaks. Materials and Methods: We defined a case of varicella with maculopapulovesicular rash without other apparent cause in students or staff of the school and residents of neighboring villages of Khalet and Roady since 23rd March to 14th October, 2009. We line listed case patients and collected information on age, sex, residence, date of onset, symptoms, signs, traveling, treatment history, and vaccination status. The outbreak was described by time, place, and person characteristics. Diagnosis was confirmed epidemiologically and serologically; first to chickenpox, measles, and german measles viruses. Results: We identified 505 case patients from mixed outbreaks of varicella, measles, and german measles (30/505 clinically, 467/505 epidemiologically linked and 8/505 laboratory confirmed case patients from a study population of 3280. We investigated the suspected outbreak with case definition of varicella but measles 20/3280 (0.60%) and rubella 34/3280 (1.03%) cases were also observed. The overall attack rate (AR) was 15% while in school; it was 22% but highest (56%) in Nursery up to 4th standard with index case in first standard. Sex-specific AR was (23%) more in boys. Triple concurrent infection caused 05% complications but no death was reported. Severity of the symptoms was more in 5th standard onwards with 49–249 lesions and severer in poor villages Roady and Khalet (P < 0.05). Only 4% were immunized against varicella/german measles privately. Seventeen percent of the cases went for traditional treatment vs modern medicine (P < 0.001). 5/10 samples for IgM antibodies for chickenpox and 2/10 samples were positive for rubella. Conclusions: Triple infection of varicella, measles, and rubella was confirmed epidemiologically and serologically. We recommended local authorities for MMRV in the school and near villages with aggressive IEC activities in affected areas.
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Affiliation(s)
- Surender Nikhil Gupta
- Department of Health and Family Welfare, District AIDS Program Officer, Chief Medical Officer Office, Kangra at Dharamshala, Himachal Pradesh, India
| | - Naveen Gupta
- Freelance Researcher in Epidemiology and Ayurveda, Kangra, Himachal Pradesh, India
| | - Shivani Gupta
- Freelance Researcher in Infectious Diseases and Food Technology, Shoolini University, Solan, Himachal Pradesh, India
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Laing KJ, Russell RM, Dong L, Schmid DS, Stern M, Magaret A, Haas JG, Johnston C, Wald A, Koelle DM. Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus. J Infect Dis 2015; 212:1022-31. [PMID: 25784732 DOI: 10.1093/infdis/jiv164] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2015] [Accepted: 03/06/2015] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)-specific cellular immunity is a likely mechanism of action. We examined memory CD4(+) T-cell responses to each VZV protein at baseline and after zoster vaccination. METHODS Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4(+) T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets. RESULTS Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4(+) T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4 T-cell epitopes. CONCLUSIONS The breadth and magnitude of the VZV-specific CD4(+) T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines.
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Affiliation(s)
- Kerry J Laing
- Department of Medicine, University of Washington, Seattle
| | | | - Lichun Dong
- Department of Medicine, University of Washington, Seattle
| | - D Scott Schmid
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | - Amalia Magaret
- Department of Laboratory Medicine Department of Biostatistics, University of Washington Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jürgen G Haas
- Division of Infection and Pathway Medicine, University of Edinburgh, United Kingdom
| | - Christine Johnston
- Department of Medicine, University of Washington, Seattle Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Anna Wald
- Department of Medicine, University of Washington, Seattle Department of Laboratory Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington Department of Epidemiology
| | - David M Koelle
- Department of Medicine, University of Washington, Seattle Department of Laboratory Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington Department of Global Health, University of Washington Benaroya Research Institute, Seattle, Washington
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15
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Abdel-Aziz M, Azab NA, Khalifa B, Rashed M, Naguib N. The association of Varicella zoster virus reactivation with Bell's palsy in children. Int J Pediatr Otorhinolaryngol 2015; 79:328-331. [PMID: 25599860 DOI: 10.1016/j.ijporl.2014.12.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 12/03/2014] [Accepted: 12/09/2014] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Bell's palsy is considered the most common cause of facial nerve paralysis in children. Although different theories have been postulated for its diagnosis, reactivation of the Varicella zoster virus (VZV) has been implicated as one of the causes of Bell's palsy. The aim of the study was to evaluate the association of Varicella-zoster virus infection with Bell's palsy and its outcome in children. METHODS A total of 30 children with Bell's palsy were recruited and were assayed for evidence of VZV infection. The severity of facial nerve dysfunction and the recovery rate were evaluated according to House-Brackmann Facial Nerve Grading Scale (HB FGS). Paired whole blood samples from all patients were obtained at their initial visit and 3 weeks later, and serum samples were analyzed for VZV IgG and IgM antibodies using ELISA. RESULTS A significantly higher percentage of Bell's palsy patients were seropositive for VZV IgM antibodies than controls (36.6% of patients vs 10% of controls) while for VZV IgG antibodies the difference was statistically nonsignificant. HB FGS in Bell's palsy patients with serologic evidence of VZV recent infection or reactivation showed a statistiacally significant less cure rate than other patients. CONCLUSIONS VZV reactivation may be an important cause of acute peripheral facial paralysis in children. The appropriate diagnosis of VZV reactivation should be done to improve the outcome and the cure rate by the early use of antiviral treatment.
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Affiliation(s)
| | - Noha A Azab
- Department of Rheumatology and Rehabilitation, Cairo University, Cairo, Egypt
| | - Badwy Khalifa
- Department of Otolaryngology, Cairo University, Cairo, Egypt
| | - Mohammed Rashed
- Department of Otolaryngology, Beni Suef University, Beni Suef, Egypt
| | - Nader Naguib
- Department of Otolaryngology, Beni Suef University, Beni Suef, Egypt
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Silver B, Zhu H. Varicella zoster virus and the neuro-attenuated vaccine necessity. Future Virol 2014. [DOI: 10.2217/fvl.14.43] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- B Silver
- Rutgers, the State University of New Jersey, New Jersey Medical School, Department of Microbiology & Molecular Genetics, Newark, NJ, USA
| | - H Zhu
- Rutgers, the State University of New Jersey, New Jersey Medical School, Department of Microbiology & Molecular Genetics, Newark, NJ, USA
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Behrman A, Lopez AS, Chaves SS, Watson BM, Schmid DS. Varicella immunity in vaccinated healthcare workers. J Clin Virol 2013; 57:109-14. [DOI: 10.1016/j.jcv.2013.01.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2012] [Revised: 01/22/2013] [Accepted: 01/23/2013] [Indexed: 02/04/2023]
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Zuckerman RA, Limaye AP. Varicella zoster virus (VZV) and herpes simplex virus (HSV) in solid organ transplant patients. Am J Transplant 2013; 13 Suppl 3:55-66; quiz 66. [PMID: 23347214 DOI: 10.1111/ajt.12003] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Revised: 09/06/2012] [Accepted: 09/07/2012] [Indexed: 01/25/2023]
Abstract
Varicella zoster virus (VZV) and the two herpes simplex viruses (HSV) are human α-herpesviruses that establish life-long latency in neural ganglia after initial primary infection. In the solid organ transplant (SOT) population, manifestations of VZV or HSV may be seen in up to 70% of recipients if no prophylaxis is used, some of them life and organ threatening. While there are effective vaccines to prevent VZV primary infection and reactivation in immunocompetent adults, these vaccines are contraindicated after SOT because they are live-virus vaccines. For HSV, prevention has focused primarily on antiviral strategies because the immunologic correlates of protection and control are different from VZV, making vaccine development more challenging. Current antiviral therapy remains effective for the majority of clinical VZV and HSV infections.
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Affiliation(s)
- R A Zuckerman
- Department of Medicine, Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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20
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Abstract
Varicella vaccination of children has decreased varicella disease incidence, but introduced the occurrence of herpes zoster (HZ) from vaccine-type virus. We identified 14 vaccinated children with suspected HZ and confirmed varicella virus by polymerase chain reaction in 6 cases. Two cases were due to vaccine-type virus. Serum varicella IgM and IgG were not useful for diagnosis of HZ among vaccinated children.
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Literature Review on One-Dose and Two-Dose Varicella Vaccination: An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI) †. ACTA ACUST UNITED AC 2010; 36:1-24. [PMID: 31682662 DOI: 10.14745/ccdr.v36i00a10] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Tan B, Ismail S. Varicella Vaccination Two-Dose Recommendations: An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI) †. CANADA COMMUNICABLE DISEASE REPORT = RELEVE DES MALADIES TRANSMISSIBLES AU CANADA 2010; 36:1-26. [PMID: 31682648 PMCID: PMC6802434 DOI: 10.14745/ccdr.v36i00a08] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Schmid DS, Jumaan AO. Impact of varicella vaccine on varicella-zoster virus dynamics. Clin Microbiol Rev 2010; 23:202-17. [PMID: 20065330 PMCID: PMC2806663 DOI: 10.1128/cmr.00031-09] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The licensure and recommendation of varicella vaccine in the mid-1990s in the United States have led to dramatic declines in varicella incidence and varicella-related deaths and hospitalizations. Varicella outbreaks remain common and occur increasingly in highly vaccinated populations. Breakthrough varicella in vaccinated individuals is characteristically mild, typically with fewer lesions that frequently do not progress to a vesicular stage. As such, the laboratory diagnosis of varicella has grown increasingly important, particularly in outbreak settings. In this review the impact of varicella vaccine on varicella-zoster virus (VZV) disease, arising complications in the effective diagnosis and monitoring of VZV transmission, and the relative strengths and limitations of currently available laboratory diagnostic techniques are all addressed. Since disease symptoms often resolve in outbreak settings before suitable test specimens can be obtained, the need to develop new diagnostic approaches that rely on alternative patient samples is also discussed.
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Affiliation(s)
- D Scott Schmid
- Herpesvirus Team and National VZV Laboratory, Measles, Mumps, Rubella, and Herpesvirus Laboratory Branch, Centers for Disease Control and Prevention, National Center for Immunizations and Respiratory Diseases, Division of Viral Diseases, Atlanta, Georgia 30333, USA.
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An outbreak of varicella in elementary school children with two-dose varicella vaccine recipients--Arkansas, 2006. Pediatr Infect Dis J 2009; 28:678-81. [PMID: 19593254 DOI: 10.1097/inf.0b013e31819c1041] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND In June 2006, the Advisory Committee on Immunization Practices (ACIP) expanded its June 2005 recommendation for a second dose of varicella vaccine during outbreaks to a recommendation for routine school entry second dose varicella vaccination. In October 2006, the Arkansas Department of Health was notified of a varicella outbreak among students where some received a second dose during an outbreak-related vaccination campaign in February 2006. METHODS The outbreak was investigated using a school-wide parental survey with a follow-up survey of identified case patients. Vaccination status was verified using state and local immunization records. Limited laboratory testing confirmed circulation of wild-type varicella, including varicella in 2-dose vaccine recipients. RESULTS Vaccination information was available for 871 (99%) of the 880 children. Varicella vaccination coverage was 97% (2-dose, 39%; 1-dose, 58%). A review of the February vaccination clinic found no deficiencies; lot numbers did not differ between cases and noncases. Varicella was confirmed by PCR in 5 (42%) of 12 lesion specimens and by IgM in 1 (6%) of 16 serum specimens. Varicella was reported in 84 children, including 25 (30%) two-dose and 53 (63%) one-dose recipients. Attack rates among 2-dose recipients (10.4%) and 1-dose recipients (14.6%) were not significantly different (RR: 0.72, 95% CI: 0.44-1.15). All 2-dose recipients and 80% of 1-dose recipients reported having 50 or fewer skin lesions. CONCLUSION This outbreak is the first to document varicella in both 1- and 2-dose vaccine recipients; both groups had mild disease. The vaccine effectiveness of 1 and 2 doses were similar.
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