| 1. |
|
|
| 2. |
|
|
| 3. |
- Aurelius, E, et al.
(författare)
-
Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial.
- 2012
-
Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 54:9, s. 1304-13
-
Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications.One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years.The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups.Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.
|
|
| 4. |
|
|
| 5. |
- Franzen-Rohl, E., et al.
(författare)
-
Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences
- 2017
-
Ingår i: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 93:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. Methods In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. Results HSV-specific interleukin(Il)-4 and II-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. Conclusions The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.
|
|
| 6. |
|
|
| 7. |
- Riise, Rebecca E, 1987, et al.
(författare)
-
TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses
- 2015
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 195:3, s. 1121-1128
-
Tidskriftsartikel (refereegranskat)abstract
- Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-gamma production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Abdelmagid, N., et al.
(författare)
-
Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
- 2016
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
-
Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
|
|
