| 1. |
- Franzen-Röhl, Elisabeth, et al.
(författare)
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Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.
- 2011
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Ingår i: Clinical and vaccine immunology : CVI. - 1556-679X. ; 18:4, s. 655-60
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Tidskriftsartikel (refereegranskat)abstract
- The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.
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| 2. |
- Studahl, Marie, 1957, et al.
(författare)
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Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management.
- 2013
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 73:2, s. 131-58
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Forskningsöversikt (refereegranskat)abstract
- Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.
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| 3. |
- Franzén-Röhl, Elisabeth
(författare)
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Diagnosis in aseptic meningitis and immune response in herpes simplex virus infections
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Herpes simplex virus type 1 and 2 are ubiquitous and appear often asymptomatic but some individuals suffer from recurrent infections and the causes are largely unknown. In this thesis I present results from evaluations of diagnostic and etiologic studies of methods used for the detection of acute aseptic meningitis (AAM) and in HSV-2 meningitis in particular. The second part we investigated the innate and/or adaptive immune response in patients affected by HSV-1 and 2 in primary genital infection as well as recurrent HSV-2 meningitis compared to recurrent genital infection or seropositive blood donors. The first paper addresses the need for efficient and sensitive diagnostic methods in the management of virus infections in the central nervous system. The objective was to evaluate a real-time PCR for the detection of HSV-2 and VZV DNA from cerebrospinal fluid samples in clinically well characterized patients with HSV-2 meningitis and AAM of unknown origin. The sensitivity of real-time PCR was found to be 87% (33/38) in primary and 70% (19/27) in recurrent HSV-2 meningitis. VZV was detected in 2 of 45 samples (4.4%). The quantitative real-time PCR was also compared with the nested qualitative PCR and found to identify more cases in the recurrent meningitis group. The second paper addresses the etiology of AAM and the diagnostic efficiency in an adult population in Stockholm, using a limited first-line combination of microbiological assays. PCR assays for HSV- DNA and enterovirus (EV) RNA in the CSF as well as ELISA for IgM to tick-borne encephalitis virus (TBEV) in serum were performed. A viral diagnosis was obtained in 255 of the 419 cases (62%) with these routinely performed assays. Thus, consistent use of CSF-PCR for EV and HSV and TBEV serology established a diagnosis in the majority of AAM patients. The third paper addresses the immune response in patients experiencing a first episode genital HSV infection. In a prospective clinical study the cell-mediated immune response (CMI) was measured and the cytokine profile identified and followed during one year. In patients with primary HSV infection CMI responses declined over time, whereas patients with non-primary HSV infection displayed stable CMI during the follow up year. For patients with primary HSV-2 infection, levels of HSV-specific IL-10 and IL-4 responses at first visit were significantly inversely correlated with number of recurrences during the subsequent year. The fourth paper addresses HSV-specific immune response in patients affected by recurrent meningitis caused by HSV-2. During asymptomatic periods, these patients expressed elevated T-cell blasting and cytokine responses against HSV-antigens an also an increased expression of TLR 3 and 9 on dendritic cells as well as increased TLR induced interferon responses in comparison with patients with recurrent genital HSV-2 infection and asymptomatic seropositive HSV-2 individuals. Thus, we did not find that recurrent HSV-2 meningitis was due to deficiencies in adaptive or innate immune functions.
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