Title : An immunopathogenetically based therapy program for atypical chronic active herpesvirus co-infections associated with postvirus chronic fatigue syndrome.

Abstract:

Introduction: Due to the annual steady increase in the number of immuno-dependent, chronic herpes-viral-induced diseases accompanied postviral chronic fatigue syndrome (CFS), associated with amnestic mild cognitive impairment(aMCI). At the same time, the role of disorders NG subpopulation and IFN system in patients with AChA-HVI and methods for their correcting have not been well studied.

The aim: to develop an immunopathogenetically based program of combine immunotherapy for patients, suffering from AChA-HVI, associated with CFS and aMCI.

Materials and methods: The study group included 198 patients,  aged 23 to 60 years, suffering from AChA-HVI. The control group (CG) consisted of 15 healthy persons, comparable by sex and age. Clinical methods were used: to assess the clinical status before and after treatment using  the created 5-point scale and the Mini- Mental State Examination (MSE) to assess cognitive functioning.  For detection of herpes viruses ELISA, PCR were used. The immunological tests included: ELISA, cytofluorimetry methods. The adequate methods of variation statistics were used.

Results:  Patients in SG had mixed ACh-HVI: EBV + CMV + HHV6 -  36.4%, HSV1 + EBV - 27.3%; EBV + CMV -18.2% of cases.  The post-viral CFS was diagnosed in 100% of cases. Mono-GVI - in 26% of cases. It was found that in patients with AChA-HVI, the incidence of aMCI was met in 68.3% of cases. The detection of base mechanisms  of  immune system (IS) have shown: the decrease in induced production of IFNα and IFNγ in 96.8%,  the decrease of number of  nature killers (NK), and/or subpopulations of T cells  (CD3⁺CD4⁺; CD3⁺CD8⁺; CD3⁺CD56⁺) in 89.5%, the functional defects of NG- 82.3% of cases. In patients of SG the number of NG with phenotype IFNα/βR1^dimIFNγR^midTLR4^mid   was in  24,4% versus in CG – in 2,5% of cases.

The program of 2-month course combine  immunotherapy was created which  was based  on immunopathogenesis of postviral CFS. This program included: 1) for restoration of IFN system: prolonged  systemic (suppositories of recombinant IFNα2b - 6 mln.IU in combination with very active antioxidants) and local application (gel recombinant  IFNα2b in combination with antioxidant); 2) for restoration NK and T lymphocytes:  14-day courses inosine pranobex in adequate doses; 3) 14-day courses of antiviral drug famciclovir in adequate doses. After treatment the  positive clinical and immunological dynamics were observed. It was shown the regression of postviral CFS and aMCI in 87% of cases, a significant decrease in the replicative activity of herpes viruses. The  improvement of the IS was shown in 85%, the restoration of the IFN system - in 67% of cases. The positive transformation of phenotype IFNα/βR1^dimIFNγR^midTLR4^mid??  was shown in  54,1% of cases. Two different active phenotypes of subset IFNα/βR1⁺IFNγR⁺TLR4⁺NG: IFNα/βR1^brightIFNγR^brightTLR4^dimNG in 40% and  IFNα/βR1^brightIFNγR^brightTLR4^brightNG in  60% of cases were appeared.

Conclusion: The immunopathogenesis of post-viral CFS associated with cognitive disorders in patients with AChA-HVI has been clarified. The developed program of combine IFN- and immunotherapy has demonstrated high clinical and immunological effectiveness

Biography:

Dr. Irina V. Nesterova studied Medical  Science  at  the  Kuban State Medical University, Krasnodar, Russia,  graduated as MS in 1973. She received her PhD degree in 1980 and Doctor of Science in 1993 at the same institution. She has published more than 200 research articles in SCI(E) journals. Science field- immunopathology, recurrent respiratory and herpesvirus infections, secondary immunodeficiency, antiviral immunity, interferonopathias, dysfunction of neutrophilic granulocytes, development different  programm of mono- and combine interferon- and immunomodulatory therapy.