Category: Viruses

Clinical and pathogenetic observations on children with chronic mononucleosis

Abstract:

Epstein-Barr virus is seldom the causative agent of a prolonged atypical illness, known as chronic mononucleosis syndrome, characterized by a persistent pattern of clinical manifestations and by a defective immune response to specific viral antigens. This paper refers about 6 children for whom clinical and serological findings suggest the chronic Epstein-Barr virus infection. The authors believe that this chronic state might be explained by the unusual antibody pattern to EBV virus, with the persistent presence of anti-EA and the absence of anti-EBNA titers, expression of a reduced EBV-specific cytotoxic T cell activity.

 

Source: Cataldo F, Ammatuna P, Bellia L, Sammartano F, Violante M, Albeggiani A. Clinical and pathogenetic observations on children with chronic mononucleosis. Pediatr Med Chir. 1991 Sep-Oct;13(5):489-94. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/1664943

 

Antibodies to Epstein-Barr virus in patients with chronic fatigue

Abstract:

To clarify the role of Epstein-Barr virus (EBV) infection and the value of EBV antibody testing in evaluating patients with chronic fatigue, we studied 200 consecutive patients with chronic fatigue (mean duration, 9 years).

Complete EBV serologic panels were obtained for 154 patients, 35 (23%) of whom met serologic or clinical criteria for chronic or reactivated EBV infection. We compared these patients with chronic EBV infection (CEBV cases) to 35 age- and sex-matched patients who were selected from the same cohort of fatigued patients but who did not meet the criteria (CEBV control subjects).

We found few differences between groups in demographic characteristics, clinical features, and symptoms; CEBV cases were more likely to meet criteria for the proposed chronic fatigue syndrome (14% vs 0%), and to report that they suffered from an influenza-like illness at the onset of their fatigue syndrome (34% vs 12%), that they lost their job because of their fatigue (37% vs 11%), and that their fatigue was improved by recreational activity (26% vs 3%).

Physical examination and laboratory testing showed few abnormalities in either group. Psychiatric morbidity was common in both groups, including mood disorders (63% of CEBV cases vs 54% of CEBV controls), anxiety (11% vs 9%) and somatization disorder (9% in each group).

We conclude that EBV serologic patterns have little clinical usefulness in evaluating patients with chronic fatigue.

 

Source: Matthews DA, Lane TJ, Manu P. Antibodies to Epstein-Barr virus in patients with chronic fatigue. South Med J. 1991 Jul;84(7):832-40. http://www.ncbi.nlm.nih.gov/pubmed/1648795

 

Chronic fatigue syndrome: lack of association with hepatitis C virus infection

Abstract:

Chronic fatigue syndrome (CFS) is a debilitating heterogeneous disorder lacking consistent, objective physical or laboratory abnormalities. Among the hypothetical etiologies for CFS are chronic viral infections. The present controlled seroprevalence study found that, among typical CFS patients, evidence of hepatitis C virus (HCV) infection is uncommon. Only one of 36 patients and none of 14 controls were anti-HCV positive. The positive patient had persistent aminotransferase elevations and prior posttransfusion hepatitis. Thus HCV infection is not a common feature of CFS and should not be routinely sought.

 

Source: Dale JK, Di Bisceglie AM, Hoofnagle JH, Straus SE. Chronic fatigue syndrome: lack of association with hepatitis C virus infection. J Med Virol. 1991 Jun;34(2):119-21. http://www.ncbi.nlm.nih.gov/pubmed/1653818

 

Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany

Abstract:

Thirty-five patients with chronic fatigue syndrome according to the criteria of Holmes were followed for periods of up to eight years. The most frequent symptoms were severe fatigue, arthralgias and myalgias, recurrent oropharyngitis and various psychiatric disorders.

More than half of the patients suffered from neuropathy, lymphadenopathy, gastrointestinal complaints and recurrent low-grade fever. Recurrent or persistent activity of human herpesvirus -6 infection was seen in 73% of the patients and of Epstein-Barr virus in 34.4%. In addition, various other infections were diagnosed at lower frequency.

Initial routine immunologic screening revealed various types of deficiencies, these were yet inconsistent and variable when different patients were compared with each other. Tentative treatments included in immunoglobulins, nonspecific immunostimulation and virostatic drugs. No consistently positive results were obtained with any treatment schedule although immunoglobulins appeared the most efficient measure. In addition, psychologic care of the patients is indicated, since disturbances in the psycho-neuroimmunologic regulation may play a significant role in the pathogenesis of the disease.

 

Source: Hilgers A, Krueger GR, Lembke U, Ramon A. Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany. In Vivo. 1991 May-Jun;5(3):201-5. http://www.ncbi.nlm.nih.gov/pubmed/1893076

 

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

 

Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome

Abstract:

Chronic fatigue immune dysfunction syndrome (CFIDS) is a recently recognized illness characterized by debilitating fatigue as well as immunological and neurological abnormalities [Straus, S.E. (1988) J. Inf. Dis. 157, 405-412]. Once thought to be caused by Epstein-Barr virus, it is now thought to have a different but unknown etiology.

We evaluated 30 adult and pediatric CFIDS patients from six eastern states for the presence of human T-lymphotropic virus (HTLV) types I and II by Western immunoblotting, polymearse chain reaction, and in situ hybridization of blood samples.

The majority of patients were positive for HTLV antibodies by Western blotting and for HTLV-II gag sequences by polymerase chain reaction and in situ hybridization. Twenty nonexposure healthy controls were negative in all assays. These data support an association between an HTLV-II-like virus and CFIDS.

 

Source: DeFreitas E, Hilliard B, Cheney PR, Bell DS, Kiggundu E, Sankey D, Wroblewska Z, Palladino M, Woodward JP, Koprowski H. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2922-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC51352/ (Full article)

 

Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up

Abstract:

During a 2-year period, 23 patients (14 girls, 9 boys) with chronic fatigue were referred to the Pediatric Infectious Disease Clinic of a tertiary care center, representing 19% of all out-patients seen in that clinic during that time. The median age was 14 years and the median duration of symptoms before referral was 6 months; 65% had missed at least 2 weeks of school and 30% required a home tutor.

There were few positive physical findings and no elevation of white blood cell count (median, 7000/mm3) or erythrocyte sedimentation rate (median, 5 mm/hour). Twenty-five percent had no evidence of Epstein-Barr virus infection, 15% had current or recent infection and 60% had past infection; 33% of the latter had detectable antibody to early antigen but the titers were low. Human herpesvirus 6 titers in 8 patients were similar to those in age- and sex-matched controls.

Of 17 patients contacted after a median of 26 months, 76% reported definite improvement, although 38% of these still experienced occasional symptoms. In this referral population chronic fatigue was a common presenting complaint, was associated with marked degrees of dysfunction and bore no relationship to Epstein-Barr virus or human herpesvirus 6 infection. In most children the disorder was self-limited, although a minority were persistently or severely affected.

 

Source: Marshall GS, Gesser RM, Yamanishi K, Starr SE. Chronic fatigue in children: clinical features, Epstein-Barr virus and human herpesvirus 6 serology and long term follow-up. Pediatr Infect Dis J. 1991 Apr;10(4):287-90. http://www.ncbi.nlm.nih.gov/pubmed/1648198

 

Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome

Abstract:

OBJECTIVE: To determine the presence of enteroviral sequences in muscle of patients with the postviral fatigue syndrome.

DESIGN: Detection of sequences with the polymerase chain reaction in a well defined group of patients with the syndrome and controls over the same period.

SETTING: Institute of Neurological Sciences, Glasgow.

SUBJECTS: 60 consecutive patients admitted to the institute with the postviral fatigue syndrome who had undergone extensive investigation to exclude other conditions. 41 controls from the same catchment area without evidence of fatigue, all undergoing routine surgery.

MAIN OUTCOME MEASURES: Routine investigations, serological screen for antibodies to a range of viruses, and presence of enteroviral RNA sequences in muscle biopsy specimens.

RESULTS: 15 (25%) patients and 10 (24.4%) controls had important serological findings. 12 patients had neutralising antibody titres of greater than or equal to 256 to coxsackieviruses B1-5 (six positive for enteroviral RNA sequences, six negative); three were positive for Epstein-Barr virus specific IgM (two positive, one negative). Six controls had similar neutralising antibody titres to coxsackieviruses (all negative); one was positive for Epstein-Barr virus specific IgM (negative); and three had titres of complement fixing antibody greater than or equal to 256 to cytomegalovirus (all negative). Overall, significantly more patients than controls had enteroviral RNA sequences in muscle (32/60, 53% v 6/41, 15%; odds ratio 6.7, 95% confidence interval 2.4 to 18.2). This was not correlated with duration of disease, patient and age, or to raised titres of antibodies to coxsackieviruses B1-5.

CONCLUSIONS: Persistent enteroviral infection of muscle may occur in some patients with postviral fatigue syndrome and may have an aetiological role.

Comment in: Postviral fatigue syndrome. [BMJ. 1991]

 

Source: Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. BMJ. 1991 Mar 23;302(6778):692-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669122/ (Full article)

 

Coxsackie B virus and postviral fatigue syndrome

Comment on: Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome. [BMJ. 1991]

 

SIR,-Dr N A Miller and colleagues highlight the difficulty of associating a virus (coxsackie B virus) with a disease (postviral fatigue syndrome) when the virus in question is common in the general population.’ In a recent serological survey of the family members of children with insulin dependent diabetes mellitus we also found a high prevalence of IgM antibody specific to enterovirus: 14% of children with recently diagnosed insulin dependent diabetes mellitus, 8% of unaffected siblings, and 18% of parents had the antibody at the time of entry into the study. Serum samples were collected between 1985 and 1987. These seroprevalence figures are higher than those reported among control populations in earlier studies in the United Kingdom-5 5% in children during 19822 and 3-5% in adults during 1979-80.3 Because the assay used in these studies was the same as that used by Dr Miller and colleagues this indicates that enterovirus was endemic during 1985-7, which covers the period of the study of Dr Miller and colleagues.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1675464/pdf/bmj00117-0062c.pdf

 

Source: Muir P, Nicholson F, Banatvala JE, Bingley PJ. Coxsackie B virus and postviral fatigue syndrome. BMJ. 1991 Mar 16;302(6777):658-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1675464/