1
|
Shi Y, Chen J, Cai L, Zhang X, Chen Z, Yang J, Jiang Y, Lu Y. Uncovering the Hidden World of Aqueous Humor Proteins for Discovery of Biomarkers for Marfan Syndrome. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2303161. [PMID: 38088571 PMCID: PMC10853735 DOI: 10.1002/advs.202303161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 10/23/2023] [Indexed: 12/19/2023]
Abstract
Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based data-independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation-related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.
Collapse
Affiliation(s)
- Yumeng Shi
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Jiahui Chen
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Lei Cai
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Xueling Zhang
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Zexu Chen
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Jin Yang
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Yongxiang Jiang
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| | - Yi Lu
- Eye Institute and Department of Ophthalmology, Eye and ENT HospitalFudan UniversityShanghai200031China
- NHC Key Laboratory of MyopiaFudan UniversityShanghai200031China
- Key Laboratory of MyopiaChinese Academy of Medical SciencesShanghai200031China
- Shanghai Key Laboratory of Visual Impairment and RestorationShanghai200031China
| |
Collapse
|
2
|
Leon LL, Lima RGD, Boffi LC, Bindilatti RN, Garlipp CR, Costa SCB, Bonon SHA. Arbovirus, herpesvirus, and enterovirus associated with neurological syndromes in adult patients of a university hospital, 2017-2018. Rev Soc Bras Med Trop 2021; 54:e0127. [PMID: 34787257 PMCID: PMC8582960 DOI: 10.1590/0037-8682-0127-2021] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/31/2021] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION: Herpesviruses, enteroviruses, and arboviruses are important because of their clinical relevance and ability to cause meningitis, encephalitis, meningoencephalitis, and other diseases. The clinical virology associated with diagnostic technologies can reduce the morbidity and mortality of such neurological manifestations. Here we aimed to identify the genomes of agents that cause neurological syndromes in cerebrospinal fluid (CSF) samples from patients with suspected nervous system infections admitted to the University Hospital of the University of Campinas, São Paulo, Brazil, in 2017-2018. METHODS: CSF samples collected from adult patients with neurological syndrome symptoms and negative CSF culture results were analyzed using polymerase chain reaction (PCR), reverse transcriptase-PCR, and real-time PCR, and their results were compared with their clinical symptoms. One CSF sample was obtained from each patient. RESULTS: Viral genomes were detected in 148/420 (35.2%) CSF samples: one of 148 (0.2%) was positive for herpes simplex virus-1; two (0.5%) for herpes simplex virus-2; eight (1.9%) for varicella-zoster virus; four (1%) for Epstein-Barr virus; one (0.2%) for cytomegalovirus; 32 (7.6%) for human herpesvirus-6; 30 (7.1%) for non-polio enterovirus; 67 (16.0%) for dengue virus, three (0.7%) for yellow fever virus, and 21 (5%) for Zika virus. CONCLUSIONS: The viral genomes were found in 35.2% of all analyzed samples, showing the high prevalence of viruses in the nervous system and the importance of using a nucleic acid amplification test to detect viral agents in CSF samples.
Collapse
Affiliation(s)
- Lucas Lopes Leon
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Rodrigo Gonçalves de Lima
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Lídia Cristian Boffi
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Raissa Nery Bindilatti
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Célia Regina Garlipp
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Patologia Clínica, Campinas, SP, Brasil
| | - Sandra Cecília Botelho Costa
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| | - Sandra Helena Alves Bonon
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Laboratório de Virologia, Campinas, SP, Brasil
| |
Collapse
|
3
|
Vishwakarma P, Mitra S, Beuria T, Barik MR, Sahu SK. Comparative profile of ocular surface microbiome in vernal keratoconjunctivitis patients and healthy subjects. Graefes Arch Clin Exp Ophthalmol 2021; 259:1925-1933. [PMID: 33651203 DOI: 10.1007/s00417-021-05109-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 01/26/2021] [Accepted: 01/30/2021] [Indexed: 01/07/2023] Open
Abstract
PURPOSE To compare ocular surface microbiome and its antibiotic sensitivity in vernal keratoconjunctivitis (VKC) with normal ocular surface. METHODS In this case-control study, thirty patients each with clinical diagnosis of VKC and age-matched controls with normal ocular surface were enrolled. Tear film samples were collected from each group and subjected to microbial evaluation with microscopy, conventional culture methods, and polymerase chain reaction (PCR). Microbial diversity and antibiotic sensitivity patterns were analyzed. RESULTS Most patients (67%) belonged to severe grades (3 and 4) of VKC, and allergic history could be elicited in 20%. On culture, bacteria were isolated in 50% of VKC patients and 47% of control group. Staphylococcus species were identified in 70% VKC group and 57% control group. S. aureus growth was seen in 52% and 21% of VKC patients and controls, respectively. S. pneumoniae was isolated only in controls (29%) (p<0.05). Confluent colonies (≥10 colonies/μl) were seen in 70% of VKC patients and 14% of controls (p<0.05). Fluoroquinolone resistance was more among higher grades of VKC (50%) (p<0.01) and was observed in 46% of VKC patients and 23% of control group (p<0.01). Both groups were negative for HSV-1 DNA and fungal growth. CONCLUSION Staphylococcus, the most common ocular surface flora, was predominant in VKC patients. Microbial analysis revealed similar microbial diversity in both groups. However, bacterial load was higher in VKC. Increased fluoroquinolone resistance was observed in VKC patients with more resistance among higher grades. Fungi and HSV-1 were not seen in VKC or normal ocular surface.
Collapse
Affiliation(s)
- Pratima Vishwakarma
- Cornea & Anterior Segment Service, LV Prasad Eye Institute, Bhubaneswar, Odisha, India
| | - Sanchita Mitra
- Ocular Microbiology Service, LV Prasad Eye Institute, Bhubaneswar, Odisha, India
| | - Tushar Beuria
- Institute of Life Sciences, Bhubaneswar, Odisha, India
| | - Manas Ranjan Barik
- Ocular Microbiology Service, LV Prasad Eye Institute, Bhubaneswar, Odisha, India
| | - Srikant K Sahu
- Cornea & Anterior Segment Service, LV Prasad Eye Institute, Bhubaneswar, Odisha, India.
| |
Collapse
|
4
|
Dupont D, Fricker-Hidalgo H, Brenier-Pinchart MP, Garnaud C, Wallon M, Pelloux H. Serology for Toxoplasma in Immunocompromised Patients: Still Useful? Trends Parasitol 2020; 37:205-213. [PMID: 33046380 DOI: 10.1016/j.pt.2020.09.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Revised: 09/11/2020] [Accepted: 09/15/2020] [Indexed: 12/22/2022]
Abstract
Toxoplasmosis represents one of the most common comorbidity factors in solid organ or hematopoietic stem cell transplant recipients as well as in other immunocompromised patients. In the past decades, availability and performance of molecular tools for the diagnosis or the exclusion of toxoplasmosis in these patients have greatly improved. However, if accurately used, serology remains a complementary and essential diagnostic tool for physicians and medical parasitologists for the prevention and management of toxoplasmosis in immunocompromised patients as well. It is required for determination of the immunological status of patients against Toxoplasma. It also helps diagnose and monitor complex cases of opportunistic Toxoplasma infection in immunocompromised patients. New perspectives are available to further enhance their yield and ease of use.
Collapse
Affiliation(s)
- Damien Dupont
- Institut des Agents Infectieux, Service de Parasitologie Mycologie Médicale, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, 69004, France; Physiologie intégrée du système d'éveil, Centre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR 5292, Faculté de Médecine, Université Claude Bernard Lyon 1, Bron, 69500, France.
| | - Hélène Fricker-Hidalgo
- Laboratoire de Parasitologie-Mycologie, CHU Grenoble Alpes, Grenoble, 38000, France; Institut pour l'Avancée des Biosciences (IAB), INSERM U1209-CNRS UMR 5309, Université Grenoble Alpes, Grenoble, 38000, France
| | - Marie-Pierre Brenier-Pinchart
- Laboratoire de Parasitologie-Mycologie, CHU Grenoble Alpes, Grenoble, 38000, France; Institut pour l'Avancée des Biosciences (IAB), INSERM U1209-CNRS UMR 5309, Université Grenoble Alpes, Grenoble, 38000, France
| | - Cécile Garnaud
- Laboratoire de Parasitologie-Mycologie, CHU Grenoble Alpes, Grenoble, 38000, France; Université Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, Grenoble, 38000, France
| | - Martine Wallon
- Institut des Agents Infectieux, Service de Parasitologie Mycologie Médicale, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, 69004, France; Physiologie intégrée du système d'éveil, Centre de Recherche en Neurosciences de Lyon, INSERM U1028-CNRS UMR 5292, Faculté de Médecine, Université Claude Bernard Lyon 1, Bron, 69500, France
| | - Hervé Pelloux
- Laboratoire de Parasitologie-Mycologie, CHU Grenoble Alpes, Grenoble, 38000, France; Institut pour l'Avancée des Biosciences (IAB), INSERM U1209-CNRS UMR 5309, Université Grenoble Alpes, Grenoble, 38000, France
| |
Collapse
|
5
|
Reis AD, Mudinutti C, de Freitas Peigo M, Leon LL, Costallat LTL, Rossi CL, Costa SCB, Bonon SHA. Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score. Adv Rheumatol 2020; 60:42. [PMID: 32831149 DOI: 10.1186/s42358-020-00144-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 08/11/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. METHODS Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. RESULTS Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. CONCLUSION Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.
Collapse
Affiliation(s)
- Alex Domingos Reis
- Laboratory of Virology, School of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Campinas, SP, 13.083-887, Brazil
| | - Cristiane Mudinutti
- Laboratory of Virology, School of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Campinas, SP, 13.083-887, Brazil
| | - Murilo de Freitas Peigo
- Laboratory of Virology, School of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Campinas, SP, 13.083-887, Brazil
| | - Lucas Lopes Leon
- Laboratory of Virology, School of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Campinas, SP, 13.083-887, Brazil
| | - Lilian Tereza Lavras Costallat
- Department of Internal Medicine, Discipline of Rheumatology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil
| | - Claudio Lucio Rossi
- Department of Clinical Pathology, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil
| | - Sandra Cecília Botelho Costa
- Laboratory of Virology, School of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Campinas, SP, 13.083-887, Brazil
| | - Sandra Helena Alves Bonon
- Laboratory of Virology, School of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Campinas, SP, 13.083-887, Brazil.
| |
Collapse
|
6
|
Development and evaluation of multiplex real-time PCR for diagnosis of HSV-1, VZV, CMV, and Toxoplasma gondii in patients with infectious uveitis. Diagn Microbiol Infect Dis 2017; 89:191-196. [PMID: 28911798 DOI: 10.1016/j.diagmicrobio.2017.08.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 07/26/2017] [Accepted: 08/04/2017] [Indexed: 02/07/2023]
Abstract
Infectious uveitis is a vision threatening inflammatory ocular disease wherein early diagnosis may prevent the loss of vision. The purpose of this study was to develop a multiplex real-time PCR for the diagnosis of Herpes simplex virus-1, Varicella zoster virus, cytomegalovirus and Toxoplasma gondii in patients with suspected infectious uveitis. A total of 126 intraocular samples (aqueous and vitreous humor) were collected and subjected to multiplex real-time PCR. Overall 26.2% (33/126) patients were found to be positive for one or more of the pathogens tested. The overall positivity for VZV, HSV, CMV and T. gondii was found to be 16 (12.7%), 7 (5.6%), 5 (3.9%), and 9 (7.1%); with mean pathogen load of 5.07×105, 9.5×104, 1.08×104 and 394 (copies/μl) respectively. The development of highly sensitive and specific assay for early differentiation of pathogens is important for the early initiation of treatment thereby preventing irreversible damage to the ocular structures.
Collapse
|
7
|
Bhat V, Joshi A, Sarode R, Chavan P. Cytomegalovirus infection in the bone marrow transplant patient. World J Transplant 2015; 5:287-291. [PMID: 26722656 PMCID: PMC4689939 DOI: 10.5500/wjt.v5.i4.287] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 09/09/2015] [Accepted: 11/17/2015] [Indexed: 02/05/2023] Open
Abstract
Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.
Collapse
|
8
|
Rimério CAT, De Oliveira RS, de Almeida Bonatelli MQ, Nucci A, Costa SCB, Bonon SHA. Human herpesvirus infections of the central nervous system: laboratory diagnosis based on DNA detection by nested PCR in plasma and cerebrospinal fluid samples. J Med Virol 2015; 87:648-55. [PMID: 25611195 DOI: 10.1002/jmv.24134] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2014] [Indexed: 11/10/2022]
Abstract
Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the "gold standard," and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture.
Collapse
|
9
|
Moon SM, Kim T, Lee EM, Kang JK, Lee SA, Choi SH. Comparison of clinical manifestations, outcomes and cerebrospinal fluid findings between herpes simplex type 1 and type 2 central nervous system infections in adults. J Med Virol 2014; 86:1766-71. [PMID: 25042344 DOI: 10.1002/jmv.23999] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2014] [Indexed: 12/28/2022]
Abstract
In previous reports on the viral causes of central nervous system (CNS) infections, it has been generally recognized that HSV-1 is a major cause of encephalitis, while HSV-2 is the predominant cause of aseptic meningitis in adults. To examine this matter, the clinical characteristics in the two types of HSV CNS infections were investigated. In a retrospective cohort study which included all adult patients (≥16 years) between January 1999 and December 2013 in a 2,700-bed tertiary care hospital, all the patients in whom PCR of the CSF for HSV was positive were identified. Ninety-five patients with positive CSF PCR results for HSV were included, 21 with HSV-1 and 74 with HSV-2. Many patients with HSV-1 had encephalitis (13/21, 61.9%), whereas most patients with HSV-2 had meningitis (62/74, 83.8%). However, HSV-1 and HSV-2 accounted for similar proportion of patients with HSV encephalitis (13/25, 52.0% vs. 12/25, 48.0%). Neurological sequelae were more frequent among patients with HSV-1 (9/21, 42.9% vs. 6/74, 8.1%; P = 0.001). The present study suggests that HSV-2 is not only a major cause of aseptic meningitis, but also it may cause serious manifestation as HSV-1 encephalitis in adults.
Collapse
Affiliation(s)
- Song Mi Moon
- Department of Infectious Diseases, Gachon University Gil Hospital, Incheon, Republic of Korea
| | | | | | | | | | | |
Collapse
|
10
|
Hong HL, Lee EM, Sung H, Kang JK, Lee SA, Choi SH. Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections. J Med Virol 2014; 86:2049-54. [PMID: 24532558 DOI: 10.1002/jmv.23902] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2014] [Indexed: 11/11/2022]
Abstract
Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis.
Collapse
Affiliation(s)
- Hyo-Lim Hong
- Department of Infectious Diseases, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | | | | | | | | | | |
Collapse
|
11
|
Abstract
Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances.
Collapse
Affiliation(s)
- Justus G Garweg
- Swiss Eye Institute and University of Bern, Bern, Switzerland.
| | | | | |
Collapse
|
12
|
Osunkalu VO, Akanmu SA, Ofomah NJ, Onyiaorah IV, Adediran AA, Akinde RO, Onwuezobe IA. Seroprevalence of Toxoplasma gondii IgG antibody in HIV-infected patients at the Lagos University Teaching Hospital. HIV AIDS (Auckl) 2011; 3:101-5. [PMID: 22096412 PMCID: PMC3218715 DOI: 10.2147/hiv.s15532] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Toxoplasmosis is caused by infection with a ubiquitous intracellular protozoan parasite, Toxoplasma gondii. With the advent of the HIV pandemic in Nigeria, toxoplasmic encephalitis has become one of the more frequent opportunistic infections and the most commonly implicated cause of focal brain lesions complicating the course of AIDS. OBJECTIVES This study was conducted to compare the pattern of seroprevalence of T. gondii (Toxo-IgG) antibodies among HIV-infected persons presenting with neurological complications and those without. MATERIALS AND METHODS Plasma specimens collected from 380 subjects were tested for Toxo- IgG antibodies by enzyme immunoassay technique and CD4 estimation by flow cytometry. Close-ended questionnaires were applied to all respondents to collect relevant data, with ethical approval from the hospital ethical committee. Plasma was obtained from two study groups comprising 300 HIV-positive respondents without neurological presentations, and 80 HIV-positive respondents with neurological complications. RESULTS Seroprevalence of Toxo-IgG antibodies was 58% in the HIV-positive study group without neurological complications (of these, 79.2% were males and 38.5% were females) and 40% in the study group with neurological complications (46.2% of these were males and 28.6% were females). The overall seroprevalence of Toxo-IgG antibodies among the HIV-positive respondents (with and without neurological complications) was 54.2% (206 of 380). Seroprevalence of Toxo-IgG antibodies was lowest among the educated subjects (19% of the respondents with tertiary education) and among females in both study groups. A higher proportion of the subjects with neurological complications had CD4 cell count <100 cells/μL compared with respondents without neurological defects (39% vs 22.7%; P = 0.000), but the seroprevalence of Toxo-IgG antibodies was higher in subjects without neurological complications (45% vs 31.3%; P = 0.000). CONCLUSION Toxoplasmosis, though an important opportunistic infection in our environment, may not account for the majority of neurological complications observed in patients with HIV infection in our center.
Collapse
Affiliation(s)
- Vincent O Osunkalu
- Department of Haematology and Blood Transfusion, College of Medicine Idi-Araba, Lagos, Nigeria
| | - Sulaimon A Akanmu
- Department of Haematology and Blood Transfusion, College of Medicine Idi-Araba, Lagos, Nigeria
| | - Nkolika J Ofomah
- Department of Haematology and Blood Transfusion, College of Medicine Idi-Araba, Lagos, Nigeria
| | - Igwebuike V Onyiaorah
- Department of Histopathology, Nnamdi Azikiwe University, Nnewi Campus, Lagos, Nigeria
| | - Adewumi A Adediran
- Department of Haematology and Blood Transfusion, College of Medicine Idi-Araba, Lagos, Nigeria
| | - Ralph O Akinde
- Department of Morbid Anatomy, College of Medicine Idi-Araba, Lagos, Nigeria
| | | |
Collapse
|
13
|
|
14
|
Abstract
Ocular toxoplasmosis is a local manifestation of systemic infection in which Toxoplasma spreads into the eye, affecting mainly the posterior segment of the eye. Reactivation of the initial retinal condition presumably results from the rupture of quiescent parasitic cysts lying adjacent to pre-existing scars and may secondarily involve the choroid (leading to retinochoroiditis). Although the molecular mechanisms underlying host-parasite interaction are largely unknown, toxoplasmic retinochoroiditis usually remains a local event, and does not necessarily evoke a detectable systemic immune response. Local immunotolerance mechanisms may likewise confound attempts to confirm the clinical diagnosis by serology. Aqueous humour may be analysed for the presence of parasite DNA or of specific antibodies, but the DNA burden therein is low, and a more definite confirmation would require risky puncturing of the vitreous. Laboratory confirmation of the diagnosis is also frustrated by marked individual differences in the time elapsing between the onset of clinical symptoms and the activation of specific antibody production, resulting in a high proportion of false negative results. Whether a delay in the onset of local specific antibody production reflects immunotolerance in cases of congenital - but not obviously in those of acquired - infection remains an open question, but it could account for a relatively low confirmation rate in laboratory tests for local antibody production. Against this background, current diagnostic strategies need to be re-evaluated with a view to future improvements.
Collapse
Affiliation(s)
- J G Garweg
- Department of Ophthalmology, University of Bern, Inselspital, 3010 Bern, Switzerland.
| |
Collapse
|
15
|
Tran THC, Bodaghi B, Rozenberg F, Cassoux N, Fardeau C, LeHoang P. Prise en charge diagnostique et thérapeutique des rétinites nécrosantes herpétiques. J Fr Ophtalmol 2004; 27:223-36. [PMID: 15039624 DOI: 10.1016/s0181-5512(04)96124-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
PURPOSE To study the viral cause and present the management of necrotizing herpetic retinopathies. METHODS Charts of patients presenting with acute retinal necrosis (ARN) or progressive outer retinal necrosis (PORN) diagnosed between March 1997 and June 2001 were retrospectively reviewed. Intraocular specimens were obtained in 33 cases to determine the viral cause using polymerase chain reaction-based assays and/or detection of intraocular antibody production. RESULTS The mean age was 43.4 Years. Herpesvirus genome was identified in 29 patients (80.5%). In the ARN group (32 patients, 38 eyes), herpes simplex virus (HSV) DNA was found in 11 patients (34.4%), varicella-zoster virus (VZV) in nine patients (28.1%), and cytomegalovirus (CMV) in four patients (12.5%). One patient (3.1%) presented an Epstein-Barr virus (EBV) infection. ARN was bilateral at initial examination in six patients and secondary bilateralization was observed in four patients. In the PORN group (four patients, eight eyes), the retinitis was bilateral and VZV DNA was detected in all cases. Two patients were treated with intravenous acyclovir, six with foscarnet alone, ten with intravenous foscarnet + acyclovir, 18 with intravenous foscarnet and intravitreous ganciclovir injections. Complications of necrotizing herpetic retinitis were cataract (26%), optic nerve atrophy (23.9%), and retinal detachment (17.4%). Final visual acuity was less or equal to 20/200 in 47.8% of cases. CONCLUSIONS It is important to determine the specific viral etiology since progression and prognosis may be different in herpetic necrotizing retinitis caused by HSV, VZV, or CMV. Visual prognosis is improved by intensive antiviral therapy, but remains poor if complications occur.
Collapse
Affiliation(s)
- T H C Tran
- Service d'Ophtalmologie, Hôpital Pitié Salpêtière, 47-83, boulevard de l'Hôpital, 75013 Paris
| | | | | | | | | | | |
Collapse
|
16
|
Robert-Gangneux F, Binisti P, Antonetti D, Brezin A, Yera H, Dupouy-Camet J. Usefulness of immunoblotting and Goldmann-Witmer coefficient for biological diagnosis of toxoplasmic retinochoroiditis. Eur J Clin Microbiol Infect Dis 2003; 23:34-8. [PMID: 14669070 DOI: 10.1007/s10096-003-1048-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Toxoplasmosis is a frequent cause of retinochoroiditis. Although the diagnosis relies mainly on ophthalmological examination, biological approaches are particularly useful in patients with atypical lesions. In a prospective study to determine the value of immunoblotting and immune load calculation in the diagnosis of active toxoplasmic retinochoroiditis, aqueous humor samples from 21 patients with retinochoroiditis and 5 control patients with cataracts were tested. Immune load was calculated on the basis of intraocular antibody production. The immune load ratio between aqueous humor and serum (Goldmann-Witmer coefficient) was significant (i.e. >2) in 9 of the 17 (53%) patients with retrospectively documented toxoplasmic retinochoroiditis. Immunoblotting suggested local antibody production in 10 of 17 (59%) patients. The combination of the two techniques gave a sensitivity of 71% (12/17). Both techniques were negative in the four patients in whom the final diagnosis of toxoplasmic retinochoroiditis was negative and in the five patients with cataracts. These results confirm the value of combining these two techniques. Moreover, immunoblotting has the advantages of being easy to perform and of requiring a very small sample.
Collapse
Affiliation(s)
- F Robert-Gangneux
- Laboratory of Parasitology and Mycology, University of Medicine Paris 5, Hospital Cochin-Port Royal, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France.
| | | | | | | | | | | |
Collapse
|
17
|
Fardeau C, Romand S, Rao NA, Cassoux N, Bettembourg O, Thulliez P, Lehoang P. Diagnosis of toxoplasmic retinochoroiditis with atypical clinical features. Am J Ophthalmol 2002; 134:196-203. [PMID: 12140026 DOI: 10.1016/s0002-9394(02)01500-3] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
PURPOSE To determine the value of aqueous humor analysis for confirming the diagnosis of ocular toxoplasmosis in patients who present with atypical clinical features and to relate the results of local antibody production and polymerase chain reaction (PCR) with the extent of active retinitis and the immune status of the patient. DESIGN Retrospective case series. METHODS Sixty-seven consecutive patients with retinitis or retinochoroiditis that was clinically consistent with atypical ocular toxoplasmosis underwent diagnostic anterior chamber paracentesis and serological studies. The aqueous humor was analyzed both by PCR to detect Toxoplasma gondii B1 gene and by the Goldman-Witmer coefficient to determine levels of local anti-T. gondii antibody production. RESULTS In nine of the 67 cases, PCR was positive for T. gondii; seven of these were negative for local antibody production. All nine patients had illnesses associated with immunosuppression or advanced old age and all had active retinitis with a mean area of 11.5 disk areas (DA). Twenty-five of the remaining 58 cases were positive for local antibody production. These 25 had a mean area of active retinitis measuring 2.6 DA, and 24 of these patients were immunocompetent. All 34 cases with laboratory evidence of ocular toxoplasmosis diagnosed by either method responded to anti-T. gondii agents. The remaining 33 were negative for T. gondii infection by these two methods; some had laboratory evidence of other infections. CONCLUSIONS Although in the present study, the sensitivity and specificity of the aqueous humor PCR and Goldman-Witmer coefficient could not be ascertained in the laboratory diagnosis of toxoplasmic retinochoroiditis, the PCR method appears to confirm the diagnosis in immunocompromised individuals with large atypical foci of retinitis. Conversely, determination of local antibody production may be appropriate for proper diagnosis in immunocompetent individuals presenting with small foci of retinitis.
Collapse
|
18
|
Gaudio PA, Gopinathan U, Sangwan V, Hughes TE. Polymerase chain reaction based detection of fungi in infected corneas. Br J Ophthalmol 2002; 86:755-60. [PMID: 12084744 PMCID: PMC1771212 DOI: 10.1136/bjo.86.7.755] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
AIMS To evaluate a polymerase chain reaction (PCR) based assay to detect fungi in scrapings from infected corneas. METHODS A PCR assay was developed to amplify a portion of the fungal 18S ribosome gene. Corneal scrapings from 30 patients with presumed infectious keratitis were evaluated using this assay, as well as by standard microbiological techniques, and the results were compared. Conjunctival swabs from each patient's healthy, fellow eye were also evaluated by PCR. RESULTS PCR and fungal culture results matched (were both positive or both negative for fungi) in 22 (74%) of 30 scrapings from infected corneas. Three (10%) of 30 samples were PCR positive but fungal culture negative; two of these appeared clinically to represent fungal infections, and the third was clinically indeterminate. Four (13%) scrapings were positive by PCR but also by bacterial and not fungal culture. One specimen (3%) was PCR negative but fungal culture positive. Of the conjunctival swabs from each patient's healthy fellow eye, five (17%) of 30 were positive by PCR, and the opposite, infected eye of all five of these harboured a fungal infection. CONCLUSIONS PCR is promising as a means to diagnose fungal keratitis and offers some advantages over culture methods, including rapid analysis and the ability to analyse specimens far from where they are collected.
Collapse
Affiliation(s)
- P A Gaudio
- Yale Eye Center, New Haven, CT 06520, USA
| | | | | | | |
Collapse
|
19
|
Sánchez R, Portilla J, Reus S, Merino E, Boix V, Manso MI. [Diagnosis of retinitis of uncertain origin by means of nucleic acid amplification in the vitreous humor]. Enferm Infecc Microbiol Clin 2001; 19:242-3. [PMID: 11446921 DOI: 10.1016/s0213-005x(01)72627-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
|
20
|
Nogueira ML, Siqueira RC, Freitas N, Amorim JB, Bonjardim CA, Ferreira PC, Oréfice F, Kroon EG. Detection of herpesvirus DNA by the polymerase chain reaction (PCR) in vitreous samples from patients with necrotising retinitis. J Clin Pathol 2001; 54:103-6. [PMID: 11215276 PMCID: PMC1731349 DOI: 10.1136/jcp.54.2.103] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
AIMS Viral uveitis and retinitis, usually caused by herpesviruses, are common in immunosuppressed patients. The diagnosis of viral anterior uveitis and retinitis is usually clinical. The polymerase chain reaction (PCR) has been used for the diagnosis of some viral infections, especially those caused by herpesviruses. This paper reports the use of PCR in the diagnosis of viral retinitis in vitreous samples from Brazilian patients. METHODS PCR was used for the diagnosis of necrotising retinitis in vitreous samples from patients from the Hospital São Geraldo, Universidade Federal de Minas Gerais, Brazil. The vitreous samples were collected by paracentesis and stored until analysis. Samples were analysed by PCR using specific primers designed to amplify herpes simplex virus 1 (HSV-1), varicella zoster virus (VZV), or human cytomegalovirus (HCMV). In a case of anterior uveitis, PCR was performed with a sample from the anterior chamber. RESULTS Herpesvirus DNA was amplified in 11 of 17 samples. HCVM DNA was detected in nine samples but DNA from HSV-1 and VZV were detected only once each. CONCLUSION These results strongly suggest that PCR could be used for a rapid complementary diagnosis of viral uveitis and retinitis. A prospective study to evaluate the PCR results, clinical evolution, and treatment is imperative to corroborate the real value of PCR in diagnosis and how it could help the clinicians' approach.
Collapse
Affiliation(s)
- M L Nogueira
- Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brazil
| | | | | | | | | | | | | | | |
Collapse
|
21
|
Crippa F, Corey L, Chuang EL, Sale G, Boeckh M. Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. Clin Infect Dis 2001; 32:214-9. [PMID: 11170910 DOI: 10.1086/318447] [Citation(s) in RCA: 95] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/1999] [Revised: 06/05/2000] [Indexed: 01/27/2023] Open
Abstract
We identified 10 patients who developed cytomegalovirus (CMV) retinitis after HSCT during a 14-year period. The median day of diagnosis of CMV retinitis after transplantation was day 251 (range, days 106--365). CMV retinitis was associated with CMV serostatus of donor or recipient (P=0.01), CMV reactivation before day 100 (P=0.007), delayed lymphocyte engraftment (P<0.05), and chronic graft versus host disease (GVHD; P<0.001). In allogeneic recipients of HSCT who were alive at day 100 after transplantation and had chronic clinical extensive GVHD, the incidence of GVHD was 1.4% (8 of 577). Five of 10 patients had other manifestation of CMV disease before retinitis occurred (4 with gastrointestinal disease and 1 with interstitial pneumonia; median time, 70 days before onset of CMV retinitis; range, 58--279 days), and 4 others had CMV excretion. CMV retinitis was bilateral in 4 patients; 9 of 10 patients had ocular symptoms (i.e., decreased vision and floaters). Six of 7 patients responded well to ganciclovir or foscarnet systemic treatment, 1 improved only after switching to cidofovir, and 1 patient who received a transplant in 1983 did not respond to acyclovir treatment. In conclusion, CMV retinitis is an uncommon late complication after HSCT that occurs mainly in seropositive allograft recipients with previous CMV reactivation and chronic GVHD, and with delayed engraftment of lymphocytes.
Collapse
Affiliation(s)
- F Crippa
- Scientific Institute and University San Raffaele, Milan, Italy
| | | | | | | | | |
Collapse
|
22
|
Grigg ME, Boothroyd JC. Rapid identification of virulent type I strains of the protozoan pathogen Toxoplasma gondii by PCR-restriction fragment length polymorphism analysis at the B1 gene. J Clin Microbiol 2001; 39:398-400. [PMID: 11136812 PMCID: PMC87743 DOI: 10.1128/jcm.39.1.398-400.2001] [Citation(s) in RCA: 115] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Sequence analysis at the 35-fold-repetitive B1 locus identified three restriction sites capable of discriminating type I (mouse-virulent) from type II or III (mouse-avirulent) strains of Toxoplasma gondii. B1 PCR-restriction fragment length polymorphism analysis of 8 type I, 17 type II, and 8 type III strains confirms the specificity of the assay. It should now be possible to ask whether strain genotype affects the severity and type of clinical disease in humans.
Collapse
Affiliation(s)
- M E Grigg
- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5124, USA
| | | |
Collapse
|
23
|
Garweg JG, Jacquier P, Boehnke M. Early aqueous humor analysis in patients with human ocular toxoplasmosis. J Clin Microbiol 2000; 38:996-1001. [PMID: 10698986 PMCID: PMC86322 DOI: 10.1128/jcm.38.3.996-1001.2000] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
To evaluate the diagnostic sensitivity of a panel of laboratory tests for ocular toxoplasmosis performed at the time of presentation, paired samples of aqueous humor and serum were collected from 49 consecutive episodes of ocular toxoplasmosis with a clinical course of less than 3 weeks. Total immunoglobulin G (IgG) and Toxoplasma gondii-specific IgG, IgM, and IgA were quantified by enzyme-linked immunosorbent assay. The avidity of T. gondii-specific IgG was determined, and DNA extracted from aqueous humor was amplified for detection of a glycoprotein B gene sequence of T. gondii. The diagnosis was confirmed for 73% (36 of 49) of the patients; this rate rose to 79.5% if data from a later analysis of aqueous humor derived from five of the negative patients were included. The analysis of serum (detection of T. gondii-specific IgM and analysis of consecutive serum samples) alone did not contribute to the diagnosis. Calculation of local antibody production lacked diagnostic sensitivity when it was determined less than 3 weeks after the manifestation of clinical symptoms (28 of 49 patients [57%]), but this rose to 70% after an analysis of a second aqueous humor sample. The antibody avidity index attained diagnostic significance in only 8 of 43 instances (19%), and T. gondii DNA was amplified from no more than 6 of 39 (16%) aqueous humor samples. However, T. gondii-specific IgA was found within the aqueous humors of 11 of 43 patients (26%); measurement of the T. gondii-specific IgA level thus contributed substantially to the diagnostic sensitivity of the laboratory tests.
Collapse
Affiliation(s)
- J G Garweg
- Department of Ophthalmology, University of Bern, Inselspital, CH-3010 Bern, Switzerland.
| | | | | |
Collapse
|
24
|
Chiou SH, Liu JH, Wong WW, Chan YJ, Chang YC, Wang JJ, Liu CY, Liu WT, Chen SC, Hsu WM. Detection of human cytomegalovirus retinitis and monitoring of ganciclovir treatment using conjunctival swab with polymerase chain reaction in AIDS patients. Int J STD AIDS 2000; 11:85-91. [PMID: 10678475 DOI: 10.1177/095646240001100204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
This report studies the accuracy of conjunctival swab polymerase chain reaction (CS-PCR) for the diagnosis of human cytomegalovirus retinitis (HCMV) in AIDS patients. PCR and virus culture were used for the detection of HCMV in conjunctival swab, serum, and urine specimens from 38 AIDS patients between April 1996 and April 1998. The clinical utility of the identification of HCMV retinitis by these 6 different methods was demonstrated by their prediction power to estimate AIDS patients at risk of contracting HCMV retinitis. The sensitivity, specificity, positive predictive value, and negative predictive value of CS-PCR for the detection of HCMV retinitis were 91.5%, 80.9%, 60.8%, and 92.7%, respectively; for serum PCR were 74.3%, 81.7%, 57.2%, and 90.3%; for urine PCR were 100%, 17.3%, 20.4%, and 100%; for conjunctival swab culture were 22.7%, 100%, 100%, and 86%; for serum culture were 27.3%, 98.1%, 75%, and 86.4%; and for urine culture were 90.9%, 44.2%, 25.6%, and 95.8%.
Collapse
Affiliation(s)
- S H Chiou
- Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, Republic of China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
25
|
Tang YW, Mitchell PS, Espy MJ, Smith TF, Persing DH. Molecular diagnosis of herpes simplex virus infections in the central nervous system. J Clin Microbiol 1999; 37:2127-36. [PMID: 10364574 PMCID: PMC85100 DOI: 10.1128/jcm.37.7.2127-2136.1999] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Y W Tang
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
| | | | | | | | | |
Collapse
|
26
|
|
27
|
Affiliation(s)
- D J Skiest
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9113, USA.
| |
Collapse
|
28
|
Verbraak FD, Bruinenberg M, van den Horn GJ, Meenken C, van der Lelij A, Hoyng CB, Kijlstra A, Peek R. Cytomegalovirus (CMV) strain differences between the eye and blood in AIDS patients with CMV retinitis. AIDS 1998; 12:713-8. [PMID: 9619802 DOI: 10.1097/00002030-199807000-00007] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate possible differences in cytomegalovirus (CMV) strain distribution between the eye and blood in AIDS patients with CMV retinitis. METHODS CMV DNA sequences from aqueous humour and peripheral blood leukocytes (PBL), obtained from 13 AIDS patients with CMV retinitis, were compared. DNA was isolated and the CMV IE-1 sequence (part of the immediate early-1 gene) and the a-sequence (located in the a-region) were amplified by polymerase chain reaction (PCR). The PCR products of the a-sequence were analysed by Southern blotting for amplified fragment-length polymorphisms. The level of divergence between the a-sequences of aqueous humour- and PBL-derived CMV was studied in two patients by cloning these sequences followed by sequence analysis. RESULTS CMV DNA could be detected in all aqueous humour samples and in 10 out of 13 paired blood samples. In the 10 patients, with CMV DNA detectable in both aqueous humour and PBL, seven cases showed differences between the amplified products of both compartments. Sequence analysis in two patients revealed that the aqueous humour and PBL of the same patient can harbour both identical, similar and highly divergent CMV a-sequences. CONCLUSION These results indicate that despite the haematogenous spread of CMV, the eye, being a relatively shielded organ, may contain CMV strains different from those found in the blood.
Collapse
Affiliation(s)
- F D Verbraak
- Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, The Netherlands
| | | | | | | | | | | | | | | |
Collapse
|