Tag: Ablashi

Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome

Abstract:

BACKGROUND: The purpose of this study is to provide a case definition of chronic fatigue syndrome in an outbreak occurring in the Nevada-California region to evaluate candidate etiologic agents and observe the natural history of the illness.

METHODS: Patients diagnosed as having chronic fatigue syndrome were studied by repeated interviews, questionnaires, and blood collection over a 3-year period. Serum samples were tested for antibodies to Epstein-Barr virus, human herpesvirus-6, and human T-lymphotropic viruses I and II. Leukocytes from typical cases were also assayed for human T-lymphotropic viruses I and II.

RESULTS: Cases were defined as persons who had: (1) severe persistent fatigue following an acute illness appearing in an individual with no previous physical or psychological symptoms; (2) presenting signs and symptoms of an acute infection; (3) severe and persistent headache and/or myalgias; and (4) abrupt change in cognitive function or the appearance of a new mood disorder. After 3 years of follow-up, almost all study subjects were able to return to pre-illness activity. None of the viruses evaluated–human T-lymphotropic viruses I and II, Epstein-Barr virus, or human herpesvirus-6–could be etiologically linked to these outbreaks.

CONCLUSION: Clinical features of outbreaks of chronic fatigue syndrome differ sufficiently to suggest different etiologic agents. Giardiasis appears to have precipitated one of the four clusters in this study but the cause(s) of the other three outbreaks is as yet uncertain. The overall prognosis ofchronic fatigue syndrome is usually favorable.

Comment in: Human herpesvirus type 6 and chronic fatigue syndrome. [Arch Intern Med. 1993]

 

Source: Levine PH, Jacobson S, Pocinki AG, Cheney P, Peterson D, Connelly RR, Weil R, Robinson SM, Ablashi DV, Salahuddin SZ, et al. Clinical, epidemiologic, and virologic studies in four clusters of the chronic fatigue syndrome. Arch Intern Med. 1992 Aug;152(8):1611-6. http://www.ncbi.nlm.nih.gov/pubmed/1323246

 

A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection

Abstract:

OBJECTIVE: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset.

DESIGN: Cohort study with comparison to matched, healthy control subjects.

PATIENTS: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in.

MAIN OUTCOME MEASURES: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients’ lymphocytes with human herpesvirus type 6 (HHV-6).

MAIN RESULTS: Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P less than 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P less than 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-8], a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA.

CONCLUSIONS: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.

Comment in:

The chronic fatigue syndrome controversy. [Ann Intern Med. 1992]

The chronic fatigue syndrome controversy. [Ann Intern Med. 1992]

 

Source: Buchwald D, Cheney PR, Peterson DL, Henry B, Wormsley SB, Geiger A, Ablashi DV, Salahuddin SZ, Saxinger C, Biddle R, et al. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. Ann Intern Med. 1992 Jan 15;116(2):103-13. http://www.ncbi.nlm.nih.gov/pubmed/1309285

 

Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates

Abstract:

Fifteen human herpesvirus-6 (HHV-6) isolates from normal donors and patients with AIDS, systemic lupus erythematosis, chronic fatigue syndrome, collagen-vascular disease, leukopenia, bone marrow transplants, Exanthem subitum (roseola), and atypical polyclonal lymphoproliferation were studied for their tropism to fresh human cord blood mononuclear cells, growth in continuous T cell lines, reactivity to monoclonal antibodies, and by restriction enzyme banding patterns. All isolates replicated efficiently in human cord blood mononuclear cells, but mitogen stimulation of the cells prior to infection was required. The ability to infect continuous T-cell lines varied with the isolates. Isolates similar to GS prototype infected HSB2 and Sup T1 cells and did not infect Molt-3 cells, whereas isolates similar to Z-29 infected Molt-3 cells but not HSB2 and Sup T1 cells. Some of the monoclonal antibodies directed against the HHV-6 (GS) isolate showed reactivity with all isolates tested, but others only reacted with HHV-6 isolates similar to the GS isolate and not with those similar to Z-29 isolate. Restriction enzyme analysis using EcoRI, BamHI, and HindIII revealed that HHV-6 isolates from roseola, bone marrow transplant, leukopenia, and an HIV-1-positive AIDS patient from Zaire (Z-29) were closely related but distinct from GS type HHV-6 isolates. Based on the above findings, we propose that, like herpes simplex virus types 1 and 2, the 15 HHV-6 isolates analyzed can be divided into group A (GS type) and group B (Z-29 type).

 

Source: Ablashi DV, Balachandran N, Josephs SF, Hung CL, Krueger GR, Kramarsky B, Salahuddin SZ, Gallo RC. Genomic polymorphism, growth properties, and immunologic variations in human herpesvirus-6 isolates. Virology. 1991 Oct;184(2):545-52. http://www.ncbi.nlm.nih.gov/pubmed/1653487

 

Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis

Abstract:

Clinical infectious mononucleosis (IM) represents a benign self-limited form of lymphoproliferative disease which is usually caused by infection with Epstein-Barr virus (EBV). Microscopic characteristics of this lymphoproliferative disorder, however, are not ultimately specific for EBV infection, but can also be seen in infections with other lymphotropic viruses, especially of the herpesvirus family.

Human herpesvirus-6 (HHV-6) infection can apparently be associated with a number of diseases also seen in EBV infection. Also, postinfectious chronic fatigue syndrome (PICFS) which may follow IM is in more than 60% of the cases accompanied by persistent active HHV-6 infection.

We thus screened serologically 215 cases of acute IM for evidence for infection with EBV, HHV-6 and CMN. Patients were tentatively grouped into those having primary infection or reactivated (probably non-primary) infections. Cases were followed for two years to monitor changes in titers.

Of all 215 cases, 211 (98.1%) were positive for EBV, 137 (63.7%) for primary infections, 21 (9.8%) for reactivated infection, and 53 (24.6%) for latent EBV. Thirty-three (15.3%) cases had primary HHV-6 infection, 63 (29.3%) active or reactivated HHV-6 infection, and 71 (33.9%) latent HHV-6. Double active EBV and HHV-6 infection, including primary and reactivated infections, amounted to 89 (39.5%) cases. Cytomegalovirus (CMV) antibody titers were found in 81 (37%) cases, 48 (22.3%) of which indicated latent infection and 33 (15.3%) active infection. Only two cases had evidence of active CMV infection alone, 1 cases of active CMV and HHV-6 infection. Serologic titers in 12 (5.6%) cases indicated combined active infection with CMV, EBV and HHV-6.

(ABSTRACT TRUNCATED AT 250 WORDS)

 

Source: Bertram G, Dreiner N, Krueger GR, Ramon A, Ablashi DV, Salahuddin SZ, Balachandram N. Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis. In Vivo. 1991 May-Jun;5(3):271-9. http://www.ncbi.nlm.nih.gov/pubmed/1654150

 

Human herpesvirus-6 (HHV-6) (short review)

Abstract:

Human Herpesvirus-6 is the etiological agent of Roseola infantum and approximately 12% of heterophile antibody negative infectious mononucleosis. HHV-6 is T-lymphotropic, and readily infects and lyses CD4+ cells. The prevalence rate of HHV-6 in the general population is about 80% (as measured by IFA) with an IgG antibody titer of 1:80. A lower prevalence, however, is observed in some countries.

HHV-6 is reactivated in various malignant and non-malignant diseases as well as in Chronic Fatigue Syndrome and transplant patients. Furthermore, elevated antibody titers were also observed in lymphoproliferative disorders, auto-immune diseases and HIV-1 positive AIDS patients. There appears to be some strain variability in HHV-6 isolates.

The GS isolates of HHV-6 (prototype) was resistant to Acyclovir, Gancyclovir, but its replication was inhibited by Phosphonoacetic acid and Phosphoformic acid. HHV-7 isolated from healthy individuals showed, by restriction analysis, that 6 out of 11 probes derived from two strains of HHV-6, cross-hybridized with DNA fragments, derived from HHV-7.

 

Source: Ablashi DV, Salahuddin SZ, Josephs SF, Balachandran N, Krueger GR, Gallo RC. Human herpesvirus-6 (HHV-6) (short review). In Vivo. 1991 May-Jun;5(3):193-9. http://www.ncbi.nlm.nih.gov/pubmed/1654146

 

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

 

A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6

Abstract:

A 17-year-old, previously healthy woman developed an acute “mononucleosis-like” illness with an associated “atypical” pneumonitis, followed by years of debilitating chronic fatigue, fevers, a 10-kg weight loss, night sweats, and neurocognitive symptoms. Thereafter, her sister developed a similar but less severe illness.

The patient developed marked, chronic lymphadenopathy and splenomegaly, with associated persistent relative lymphocytosis and atypical lymphocytosis and with thrombocytopenia. After 3 years of illness, a splenectomy was performed, which resulted in some symptomatic improvement, prompt weight gain, and resolution of all hematologic abnormalities. Serial immunologic studies revealed a strikingly elevated number of activated B lymphocytes and a T lymphopenia, which improved but did not return to normal postsplenectomy. No causal association was found with any of several infectious agents that could produce such a lymphoproliferative illness.

However, both the patient and her sister had evidence of active infection with the recently discovered human herpesvirus-6. Seven years after the onset of the illness, the patient and her sister remain chronically ill.

 

Source:  Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, Hall CG, Ashley RL, Saxinger C, Balachandran N, et al. A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immunol. 1990 Nov;10(6):335-44. http://www.ncbi.nlm.nih.gov/pubmed/1964694