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oorzaak of gevolg

van ME en CVS

(studies Agliari,

Chapenko en Montoya)?








Recent zijn er drie relevante studies m.b.t. de rol van infecties (in ME en CVS) verschenen.


Volgens een studie van Agliari en collega's zou (cellulaire en humorale) immuunactivatie

het gevolg kunnen zijn van (langdurige) blootstelling aan het Epstein-Barr-virus.

Het afweersysteem is blijvend actief zelfs lang nadat EBV uit het systeem verdwenen is.


Een studie van Chapenko en collega's laat zien dat

bij ca. 65% van de ME/CVS-patiënten sprake is van

één of meer actieve virale infecties: HHV-6 (A en B), HHV-7 en/of parvo B19, en

er wellicht sprake is van een verband tussen specifieke infecties en specifieke symptomen

en tussen specifieke infecties en specifieke proinflammatoire cytokines (TNF-α en IL-6).


Een studie van Montoya en collega's naar het effect van antivirale middelen

bij twee mensen met chromosaal geintegreerde HHV6 (HHV6 geïntegreerd in het DNA)

toont aan dat deze medicijnen wel effectief zijn, maar dat dit effect niet blijvend is.




Can persistent Epstein-Barr virus infection induce chronic fatigue syndrome

as a Pavlov reflex of the immune response?

J Biol Dyn. 2012 Mar;6(2):740-62. doi: 10.1080/17513758.2012.704083.

Agliari E, Barra A, Vidal KG, Guerra F.





Chronic fatigue syndrome is a protracted illness condition (lasting even years)

appearing with strong flu symptoms and systemic defiances by the immune system.


Here, by means of statistical mechanics techniques,

we study the most widely accepted picture for its genesis,

namely a persistent acute mononucleosis infection, and

we show how such infection may drive the immune system

towards an out-of-equilibrium metastable state

displaying chronic activation of both humoral and cellular responses

(a state of full inflammation without a direct 'causes-effect' reason).


By exploiting a bridge with a neural scenario,

we mirror killer lymphocytes T(K) and B cells to neurons and helper lymphocytes

[Formula: see text] and [Formula: see text] to synapses,

hence showing that

the immune system may experience the Pavlov conditional reflex phenomenon:

if the exposition to a stimulus (Epstein-Barr virus antigens) lasts for too long,

strong internal correlations among B,T(K) and T(H) may develop

ultimately resulting in a persistent activation

even though the stimulus itself is removed.


These outcomes are corroborated by several experimental findings.



PMID: 22873615




Association of active human herpesvirus-6, -7 and parvovirus B19 infection with clinical outcomes in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Advances in Virology. Volume 2012 (2012), Article ID 205085.

Svetlana Chapenko, Angelika Krumina, Inara Logina, Santa Rasa, Maksims Chistjakovs, Alina Sultanova, Ludmila Viksna, Modra Murovska



Frequency of active

human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection

and its association with clinical course of ME/CFS was evaluated.


108 ME/CFS patients and

90 practically healthy persons

were enrolled in the study.


Viral genomic sequences were detected by

PCR, virus-specific antibodies and cytokine levels - by ELISA,

HHV-6 variants - by restriction analysis.


Active viral infection including concurrent infection was found

in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons.


Increase in peripheral blood leukocyte DNA HHV-6 load

as well as in proinflammatory cytokines' levels

was detected in patients during active viral infection.


Definite relationship was observed

between active betaherpesvirus infection and

subfebrility, lymphadenopathy and malaise after exertion, and

between active B19 infection and multijoint pain.


Neuropsychological disturbances were detected in all patients.


The manifestation of symptoms

was of more frequent occurrence

in patients with concurrent infection.


The high rate of active HHV-6, HHV-7 and B19 infection/coinfection

with the simultaneous increase in plasma proinflammatory cytokines' level

as well as the association between active viral infection and

distinctive types of clinical symptoms

shows necessity of simultaneous study of these viral infections

for identification of possible subsets of ME/CFS.




Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction.

J Clin Virol. 2012 Sep;55(1):40-5. doi:10.1016/j.jcv.2012.05.016.

Montoya JG, Neely MN, Gupta S, Lunn MR, Loomis KS, Pritchett JC, Polsky B, Medveczky PG.





Human herpesvirus (HHV-6) is a neurotropic virus implicated in

central nervous system (CNS) dysfunction, multiple sclerosis, seizures and encephalitis.


Inherited or "chromosomally integrated" HHV-6 (CIHHV-6)

is a condition characterized by high DNA loads and

germ line transmission of HHV-6 genomes, which are integrated into the telomere.





We previously reported that

integrated HHV-6 can be reactivated by trichostatin A in vitro.


Therefore, we hypothesized that

a broad array of neurological symptoms of CIHHV-6 patients

may respond to antiviral drug treatment.





The patients have been treated with antiviral drugs and

monitored for viral load, late mRNA, and clinical improvement.





Antiviral therapy of two CIHHV patients resulted in successful clinical resolution.


However, both patients relapsed on multiple occasions

within 4-6 months of cessation of antiviral therapy.





Successful antiviral drug treatment suggests that

clinical symptoms of these patients

were due to symptomatic reactivation of CIHHV-6.



some CIHHV-6 patients may have a reduced resistance to community-acquired HHV-6 strains

due to tolerance leading to persistent infections.



PMID: 22770640