Molecular approaches to epidemiologic evaluation of viruses as risk factors for patients who have chronic fatigue syndrome

Abstract:

One approach to understanding the chronic fatigue syndrome might be to carry out prospective studies of fatigue that occurs following infection with viral diseases of known etiology, such as influenza, hepatitis, and infectious mononucleosis. Among the viral parameters that should be evaluated are virus burden, variation of virus strain, sites of viral replication, and the state of the viral life cycle (e.g., latent or replicative). Immunologic studies should focus on the humoral and cellular responses to defined viral gene products to identify subtle, individual variations in immune recognition of specific viral subcomponents.

 

Source: Miller G. Molecular approaches to epidemiologic evaluation of viruses as risk factors for patients who have chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S119-22. http://www.ncbi.nlm.nih.gov/pubmed/1850537

 

Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera

Abstract:

Proteins of human herpesvirus 6 (HHV-6) eliciting human antibody responses were examined in serum from healthy adults and patients with AIDS, chronic fatigue syndrome, Hodgkin’s disease, and Sjögren’s syndrome.

HHV-6 IgG antibody titers measured by immunofluorescence (IF) ranged from 1:10 to 1:1280. Lysates of HHV-6-infected and uninfected cells labeled with [35S]methionine, [3H]glucosamine, and 125I were immunoprecipitated with sera and analyzed electophoretically. Sera with IF titers greater than or equal to 1:20 immunoprecipitated greater than 20 [35S]methionine-labeled HHV-6 polypeptides of approximately 26-180 kDa.

At least 10 HHV-6 glycoproteins and 8 HHV-6 polypeptides associated with the surfaces of infected cells were recognized by human sera. The approximate molecular masses of glycoproteins immunoprecipitated by human sera were similar to those immunoprecipitated by monoclonal antibodies.

The labeling intensity of HHV-6 protein bands increased with increasing IF titer, and the effect was most prominent for HHV-6 glycopolypeptides. No reactivities with specific HHV-6 polypeptide(s) were characteristic of a given patient group.

These findings suggest that HHV-6 glycoproteins are good targets for human antibody responses.

 

Source: Balachandran N, Tirawatnapong S, Pfeiffer B, Ablashi DV, Salahuddin SZ. Electrophoretic analysis of human herpesvirus 6 polypeptides immunoprecipitated from infected cells with human sera. J Infect Dis. 1991 Jan;163(1):29-34. http://www.ncbi.nlm.nih.gov/pubmed/1845808

 

Analysis of clinical, epidemiologic, and laboratory data on chronic fatigue syndrome

Abstract:

Much of the research conducted on chronic fatigue syndrome (CFS) is exploratory. The researchers’ overall goal is to use clinical, epidemiologic, and laboratory data to provide clues about the etiology of this syndrome. In preparation for this symposium, a review of numerous publications on CFS has indicated that the literature generally does not reflect the application of optimal statistical methods for exploration of data.

Whenever the researchers’ aim is to generate hypotheses, modern methods designed specifically for exploratory data analysis are likely to provide greater insights into any patterns of data than are the traditional approaches to hypothesis testing. In addition, the use of formal methods of data synthesis for ongoing and future research on CFS is a means of strengthening collaborative efforts and of improving the ability of researchers to interpret the evidence available that relates to specific etiologic factors. The inclusion on the research team of experienced biostatisticians, who would oversee the statistical methods and the development of innovative analyses, is recommended.

 

Source: Redmond CK. Analysis of clinical, epidemiologic, and laboratory data on chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S90-3. http://www.ncbi.nlm.nih.gov/pubmed/1826967

 

The chronic fatigue syndrome: a reappraisal and unifying hypothesis

Abstract:

The chronic fatigue syndrome is one of the most common medical problems in Western countries. Research work in virology, immunology, metabolic medicine and psychiatry in this area is reviewed and a disease model proposed. The chronic fatigue syndrome can be considered as a continuum ranging from cases with chronic viraemia on the one hand to instances of frank psychiatric illness on the other. In the majority of patients the fully evolved syndrome may involve an interaction of premorbid factors (psychological, immunological), environmental trigger factors (virus) and enhancing factors (emotional response to illness). A Venn diagram is a convenient way of expressing this concept.

 

Source: Byrne E. The chronic fatigue syndrome: a reappraisal and unifying hypothesis. Clin Exp Neurol. 1991;28:128-38. http://www.ncbi.nlm.nih.gov/pubmed/1821821

 

Natural killer cells and the post viral fatigue syndrome

Abstract:

60 patients were referred with a diagnosis of post viral fatigue syndrome (PVFS), but only 50 fulfilled strict criteria for this illness. Many lymphocyte subpopulations were normal, but there was a spectrum of natural killer (NK) cell results: 20/50 (40%) were raised; 8/50 (16%) were low;, 5/50 (10%) were low initially but normal on repeat testing; 17/50 (34%) were normal.

When patients were categorised on their NK cell results, there were significant differences in the two groups with raised or low NK cells compared to the “Not PVFS” group: the CD8 cells were increased (p less than 0.001, p less than 0.02) and the CD4/CD8 ratio was reduced (p less than 0.05) but the CD4 cells were normal.

Clinical data showed that the “Not PVFS” group were older, with less severe illness, less muscle pain and less virological evidence of infection. It is postulated that patients have low NK cells initially and then progress to normal or raised levels dependent on factors such as stress, other infections and behaviour.

 

Source: Ho-Yen DO, Billington RW, Urquhart J. Natural killer cells and the post viral fatigue syndrome. Scand J Infect Dis. 1991;23(6):711-6. http://www.ncbi.nlm.nih.gov/pubmed/1815333

 

Mitochondrial abnormalities in the postviral fatigue syndrome

Abstract:

We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid.

On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected.

The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.

 

Source: Behan WM1, More IA, Behan PO. Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol. 1991;83(1):61-5. http://www.ncbi.nlm.nih.gov/pubmed/1792865

 

Dual infections of the immune system in patients with chronic active Epstein-Barr virus infection mimicking chronic fatigue syndrome

Abstract:

The etiologic bases of CFS are undetermined at the present time. It is very important to distinguish the patients with CFS as defined by the Centers for Disease Control (CDC) case definition of Holmes et al. from patients with physical and laboratory findings suggesting dual infections and/or underlying immunodeficiency. Particularly fruitful might be a longitudinal immunovirologic study of patients who exhibit CFS following a well-documented viral infection.

 

Source: Purtilo DT. Dual infections of the immune system in patients with chronic active Epstein-Barr virus infection mimicking chronic fatigue syndrome. Can Dis Wkly Rep. 1991 Jan;17 Suppl 1E:29-32. http://www.ncbi.nlm.nih.gov/pubmed/1669350

 

Infectious mononucleosis-like syndrome caused by Cytomegaloviruses

Abstract:

The detailed clinical, hematological, and biochemical analysis performed in 332 patients in whom infectious mononucleosis had been diagnosed or suspected revealed the mononucleosis-like syndrome due to Cytomegalovirus infection in 4.5%. This diagnosis was confirmed by the presence of specific antibodies in the ELISA methods (most frequent titres 1:1600 and 1:3200) and or by the CFT (mostly 1:64 and 1:128). The diagnosis of infectious mononucleosis was confirmed in the Paul-Bunnell-Davidsohn test in the titre was greater than or equal to 1:56.

Attention is drawn to the differences regarding the clinical signs as well as the clinical and biochemical parameters between the mononucleosis-like syndrome and the infectious mononucleosis. The clinical diagnosis of this syndrome is difficult however possible, if kept, in mind and if all the parameters are properly analysed. This diagnosis has to be always confirmed by serologic test.

 

Source: Janeczko J. Infectious mononucleosis-like syndrome caused by Cytomegaloviruses. Przegl Epidemiol. 1991;45(4):257-61. [Article in Polish] http://www.ncbi.nlm.nih.gov/pubmed/1668699

 

Life insurance MDs sceptical when chronic fatigue syndrome diagnosed

Comment on: Life insurance MDs sceptical when chronic fatigue syndrome diagnosed. [CMAJ. 1990]

 

As a physician with chronic fatigue syndrome (CFS) since the early days of the Lake Tahoe, Calif., outbreak, in 1984, I read Olga Lechky’s report (Can MedAssoc J 1990; 143: 413- 415) with particular interest. It was refreshing to hear Dr. Richard Proschek, assistant medical director of Mutual Life of Canada, admit that the industry’s attitude to CFS is one of hostility. Unfortunately for the thousands of severely debilitated patients with the condition this scepticism and hostility are not restricted to that industry, which in many instances has behaved with compassion and responsibility toward its clients. The hostile viewpoint is also widely prevalent in the medical profession and is often freely communicated to patients.

To hold that CFS is not a real disease it is necessary to imagine that in 1984 people of all ages began to manufacture a condition with clearly defined symptoms that begins as a flu-like illness, persists and evolves. How many diseases fit this description? When, before 1984, did depression present so? Can it be true that thousands of our brightest citizens, including children, Olympic aspirants, several members of some families, alarming numbers of teachers, 50% of a symphony orchestra and 10% of the population of Incline Village, Nev., abruptly and concurrently elected to drop out of life, then continued to complain in the face of widespread scepticism, hostility, marital breakdown and, frequently, isolation? What, other than an infectious agent, could cause this?

Proschek’s bias arises from his position. Physicians in practice, however, see many CFS patients who have no insurance or are quite wealthy. The degree to which imagination must extend to accommodate a diagnosis of secondary gain in these people is beyond belief. Many physicians lament the lack of a blood test for CFS. What, pray, is the test for malingering, a diagnosis we seem to have no difficulty making?

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1452931/pdf/cmaj00229-0013.pdf

 

Source: Sean J. O’Sullivan, MD. Life insurance MDs sceptical when chronic fatigue syndrome diagnosed. CMAJ. 1990 Dec 15;143(12):1283-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1452931/

 

Is chronic fatigue syndrome synonymous with effort syndrome?

Abstract:

Chronic fatigue syndrome (CFS), including myalgic encephalomyelitis (ME) and postviral syndrome (PVS), is a term used today to describe a condition of incapacity for making and sustaining effort, associated with a wide range of symptoms. None of the reviews of CFS has provided a proper consideration of the effort syndrome caused by chronic habitual hyperventilation.

In 100 consecutive patients, whose CFS had been attributed to ME or PVS, the time course of their illness and the respiratory psychophysiological studies were characteristic of chronic habitual hyperventilation in 93.

It is suggested that the labels ‘CFS’, ‘ME’ or ‘PVS’ should be withheld until chronic habitual hyperventilation – for which conventional rehabilitation is available – has been definitively excluded.

 

Source: Rosen SD, King JC, Wilkinson JB, Nixon PG. Is chronic fatigue syndrome synonymous with effort syndrome? J R Soc Med. 1990 Dec;83(12):761-4. http://www.ncbi.nlm.nih.gov/pubmed/2125315