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PubMed1974

IgM antibodies specific for Epstein-Barr virus in infectious mononucleosis without heterophil antibodies.

IgM antibodies specific for Epstein-Barr (E.B.) virus were demonstrable in all but one out of 46 patients diagnosed as having infectious mononucleosis wihout heterophil antibodies; cytomegalovirus aetiology was excluded. In all but two cases the highest titre was found in the first sample. In 21 patients a significant decrease was seen within a few weeks. IgG antibodies to E.B. virus, mostly remaining at a constant level, were demonstrable in all cases. IgM antibodies to E.B. virus were found in only five out of 300 controls.The results suggest that in a disease similar to infectious mononucleosis without heterophil antibodies testing of transient E.B. virus-specific IgM antibodies makes a rapid aetiological diagnosis possible and that in clinically well-defined cases viruses other than E.B. virus and cytomegalovirus are unlikely to be causal agents.

Adolescent↗

PubMed1966

Studies on infectious mononucleosis: I. Cytopathic agents and immunofluorescence studies.

Viral studies were carried out on throat swabs, rectal swabs and washed white blood cells from 27 cases of infectious mononucleosis (positive Paul-Bunnell-David-sohn test), and from 22 controls.Four cytopathic agents were isolated in the test group, two of which were readily subcultured for at least three successive passages.Three cytopathic agents were recovered in the control group, two of which have been identified as adenovirus type 5 and adenovirus type 3. The unidentified agents tested so far are sensitive to ether and to pH 3. The results of acridine-orange staining and the immunofluorescence technique, using a conjugated control serum and two conjugated convalescent infectious mononucleosis sera, indicate that the isolated agent or agents in the test group are RNA-type agents with a cytoplasmic cycle of development. The overall results of this study lead the authors to suspect a respiratory syncytial-like myxovirus as the as yet unidentified agent which they recovered.

Adenoviridae↗

PubMed1985

Epstein-Barr virus infectious mononucleosis in children. I. Clinical and general laboratory findings.

Between 1976 and 1982, 113 children aged 6 months to 16 years with documented Epstein-Barr virus-induced infectious mononucleosis were studied prospectively, and in most instances serially. An unexpected finding was the large number of young children, less than 4 years old, with this disease. Children with infectious mononucleosis, in particular the very young, tended to have more rashes, significant neutropenia, abdominal pain (older children only), and possible hepatosplenomegaly than have been reported in adult patients. The intensity of the characteristic relative atypical lymphocytosis found in peripheral blood was age-related; it was less in the very young. Findings of failure to thrive, otitis media, and episodes of recurrent tonsillopharyngitis appeared to be unique or more closely associated with childhood disease. Complications such as thrombocytopenia with hemorrhagic manifestations, significant airway obstruction, and neurologic problems occurred more frequently whereas jaundice occurred less frequently than noted in adult patients. Six children, all less than 4 years old, developed pneumonia during the disease course. The increased availability of Epstein-Barr virus-specific testing should continue to expand our knowledge of this disease in children of all ages.

Adolescent↗

PubMed2002

Azithromycin-induced rash in infectious mononucleosis.

Antibiotic-induced skin eruption in the setting of infectious mononucleosis is a common and well-documented clinical scenario. The skin lesions are non-specific and the mechanisms causing them are unclear. Several reports have described this entity with different antibiotic classes, mainly penicillins. Only 1 case of azithromycin-induced skin eruption has previously been described in this setting. Herein, we report the second case.

Adult↗

PubMed1991

Epidemiological investigation of the association between infectious mononucleosis and multiple sclerosis.

By matching a cohort of 494 infectious mononucleosis (IM) cases with a multiple sclerosis (MS) register, 3 MS cases were retrieved. The interval between IM and MS was 12 years. This corresponds to a relative risk of 3.7 for MS to occur subsequent to IM (p = 0.05). This relationship between a manifestation of a relatively late Epstein-Barr virus infection and MS may indicate that a microbiologically shielded environment is important in the pathogenesis of MS.

Adolescent↗

PubMed1968

Bone marrow colony-stimulating activity of sera in infectious mononucleosis.

From 44 to 100% of sera from patients with infectious mononucleosis exhibited the capacity to stimulate colony formation in vitro by mouse bone marrow cells. The proportion of sera with colony-stimulating activity was highest in patients with a short fever period and developing low Paul-Bunnell titres. Patients with a more severe course of the disease generally displayed no, or only weak, colony-stimulating activity in their sera, and also had higher Paul-Bunnell titres. The level of serum colony-stimulating activity tended to fall in the convalescent stages of the disease.

Adult↗

PubMed1977

The complement system in infectious mononucleosis.

The complement system was investigated in 34 patients with infectious mononucleosis. Three had specific complications: one haemolytic anaemia, one severe arthralgia/myalgia and one proliferative glomerulonephritis. Complement changes consistent with classical pathway consumption were seen in ten of the uncomplicated group and the patients with haemolytic anaemia and arthralgia/myalgia. The patient with glomerulonephritis showed evidence of alternative pathway utilisation including C3 splitting activity and the deposition of properdin on renal biopsy. The complement findings suggest that circulating immune complexes are common in such patients and are likely to play a role in the pathogenesis of the complications. It is proposed that both complement pathways may be required for the effective clearance of viral material from the circulation.

Complement C1 Inactivator Proteins↗

PubMed1976

IgM and IgG antibody levels to ampicillin in patients with infectious mononucleosis.

By means of a sensitive radio-immunoassay an antibody-like activity against ampicillin was detected in both IgM and IgG immunoglobulin classes of patients with infectious mononucleosis, being fifteen times the level (for IgM) and six and a half times the level (for IgG) of control subjects. Such ampicillin antibody occurred without obvious relation to prior therapy with ampicillin. This antibody which may originate in a similar manner to Paul-Bunnell antibody was nevertheless immunologically unrelated. The possibility is discussed that the ampicillin rash in infectious mononucleosis results from a disseminated reaction of the small blood vessels to circulating ampicillin-antibody complexes.

Ampicillin↗

PubMed1978

Treatment of anginose infectious mononucleosis with metronidazole.

16 patients with the anginose type of infectious mononucleosis were treated with metronidazole, and another 3 patients were given clindamycin. Most of the patients had been given penicillin or erythromycin before admittance to hospital. Treatment with metronidazole had a favourable effect on the course of the disease; the body temperature was normalized, signs of tonsillitis disappeared and cervical lymph nodes decreased in size within 3 days in 10 patients and in the remaining 6 within 4 or 5 days. Difficulty in mastication and swallowing was usually relieved within 1 to 2 days of treatment. The period before normalization was significantly shorter than in 10 controls. Two of the 3 patients who were given clindamycin developed exanthems, but otherwise a similar favourable effect as in the metronidazole-treated patients was observed.

Adolescent↗

PubMed1984

Low secretory IgA concentrations in oral secretions during the acute phase of infectious mononucleosis.

Although the Epstein-Barr virus (EBV) relation to infectious mononucleosis (IM) has been well established, the question why IM is not compulsory during a primary EBV infection has yet to be solved. Assuming a possible oropharyngeal secretory immunoincompetence as an etiological component of IM, the secretory IgA concentrations in oral secretions during the acute phase of IM was investigated. Low concentrations of secretory IgA in IM patients (n = 18) were found, mean value 0.180 g/l as compared to those in healthy controls (n = 10), mean value 0.680 g/l. Furthermore, diminishing concentrations of secretory IgA were found during the acute phase of IM. There was no corresponding serum IgA decrease. The investigation also revealed that tinidazole, claimed to be beneficial in the treatment of anginous IM, did not affect the concentrations of spit secretory IgA.

Adolescent↗

PubMed1985

Anti-intermediate filament antibodies, antikeratin antibody, and antiperinuclear factor in rheumatoid arthritis and infectious mononucleosis.

Sera from patients with rheumatoid arthritis (RA), patients with infectious mononucleosis (IM), and blood donors were tested by indirect immunofluorescence for the presence of antikeratin antibody (AKA), antibody to cytoskeletal intermediate filaments of prekeratin or vimentin type (AIFA) and antiperinuclear factor (APF). In 81.9% of the RA sera and 92.5% of the IM sera AIFA of IgM class was found at titres up to and in some cases exceeding 1/160. In blood donors the incidence of AIFA was 26%, at titres not exceeding 1/20. AKA and APF, always of IgG class, were found in 54.2% and 73.6% of rheumatoid sera. A weak correlation was found in RA between the incidence of AIFA and APF. AKA was not present in either IM or blood donor sera, and APF was found in only 2.5% and 3.2% of IM or blood donors respectively.

Antibodies, Antinuclear↗

PubMed1992

Detection of Epstein-Barr virus in lymphoid tissues of patients with infectious mononucleosis by in situ hybridization.

Although the immunological response during infectious mononucleosis (IMN) has been studied in detail, little is known about the spread of Epstein-Barr virus (EBV) in lymphoid organs or the topographical distribution of the infected cells. In this study, EBV was detected in 11 lymph nodes, 4 tonsils, and 1 spleen of 16 patients with IMN. The predominant cell type positive for the EBV genome was identified as small lymphocytes localized chiefly within typical T areas, preferentially in perifollicular and interfollicular regions of the lymph node. A few endothelia of epithelioid venules were also found to be positive. Furthermore, a small number of sinus lining cells of lymph nodes exhibited labelling. Altogether, only a small number of cells, not exceeding 1 per cent of all cells, were infected with EBV. Our results show that only a small number of lymphocytes carry the EBV and that besides B lymphocytes, other cell constituents of lymphatic tissues are infected by EBV during IMN.

Autoradiography↗

PubMed1995

The significance of serum IgM IgA and IgG antibodies specific for Epstein-Barr virus as determined by immunoperoxidase assay in the rapid diagnosis of infectious mononucleosis.

The feasibility of using serum IgM, IgA and IgG antibodies specific to Epstein-Barr virus (EBV) viral capsid antigen (VCA), as determined by immunoperoxidase assay (IPA), for the early diagnosis of mononucleosis was evaluated in 65 patients with infectious mononucleosis (IMN). Control groups consisted of 104 healthy students and 15 cytomegalovirus-infected patients. In the first serum sample obtained upon admission, IgM antibodies (titer > or = 64) to EBV VCA were found in 64 of the 65 IMN patients (98%), while EBV-VCA IgA antibodies (titer > or = 32) were found in 32 patients (49%). In those particular titers, no EBV-VCA IgM or IgA antibodies were found in any of the control sera. EBV-VCA-specific IgM antibodies were also not detected in any of the 15 patients with cytomegalovirus infection. In sera obtained from IMN patients within 10 days of the onset of symptoms, 18 of 19 (95%) were IgM seropositive. This study demonstrates that serum EBV-VCA IgM antibodies (titer > or = 64) as determined by IPA are highly specific (100%) and highly sensitive (98%) and can be of value for the early and rapid diagnosis of EBV-IMN infection.

Adolescent↗

PubMed1977

Development of cell-mediated immunity to Epstein-Barr herpesvirus in infectious mononucleosis as shown by leukocyte migration inhibition.

Eight patients with infectious mononucleosis, aged between 8 and 24, were studied for cell-mediated immunity by the in vitro leukocyte migration inhibition test at acute and convalescent stages. Follow-up studies were also carried out at up to 4 months after clinical illness. Cell-mediated immunity to Epstein-Barr virus (EBV) in the peripheral leukocytes from these patients was absent or incipient in all cases during the acute phase, although it was present in lymphocytes from a biopsied lymph node obtained from one of the patients. In contrast, cell-mediated immunity to EBV was detected readily in peripheral leukocytes obtained during convalescence and in the follow-up studies. A blocking factor that abrogated leukocyte migration inhibition induced by EBV antigen was detected in acute and convalescent sera obtained from six of eight patients, whereas serum antinuclear autoantibodies were detected in the two patients whose sera failed to block leukocyte migration inhibition. When sera were fractionated, this blocking effect was observed only in the serum immunoglobulin G fractions. In follow-up studies, neither the blocking factor nor the antinuclear autoantibodies were found in the sera collected.

Adolescent↗

PubMed1987

Thymic lesions in fatal infectious mononucleosis.

Thymic lesions were studied in 35 patients with fatal infectious mononucleosis (FIM) including 21 males with the X-linked lymphoproliferative syndrome (XLP) and 14 non-XLP patients. Six patterns based on the lymphocyte content and status of Hassall's bodies were observed: massive lymphoproliferation effaced the architecture and Hassall's bodies (HB) in 6 cases. Epstein-Barr virus (EBV)-laden B cells surrounded by cytotoxic T cells and natural killer cells were found in one of these cases. Only 5 of the 35 thymuses contained normal-appearing HB. Seven showed a moderate reduction in HB. Rarely, multinucleated giant cells and hyaline globules were seen where one might expect HB to reside. Plasma cells and macrophages were generally abundant. Eight displayed a marked depletion of HB. In 7, no HB were recognized. Massive necrosis was seen in one of these cases. Stress involution was encountered in only two patients, both of whom had sporadic fatal IM. Thymic lesions and alterations were similar but less extensive in sporadic FIM. These morphological studies, taken in context with clinical and experimental reports, suggest that destruction of thymic epithelium may contribute to the progression of immune defects seen in XLP following EBV infection. The destruction of HB that we observed was similar in appearance to lesions in several other immune deficiency disorders.

Age Factors↗

PubMed1993

Infectious mononucleosis in lymphoid tissue. Histopathology, in situ hybridization, and differential diagnosis.

The histopathologic features of tissue specimens from 16 patients with acute Epstein-Barr virus-induced infectious mononucleosis, which was confirmed by clinical and serologic methods, are described. The clinical course was usually self-limited (14 patients), but it resulted in the death of two patients, one of whom (patient with renal transplantation) was immunosuppressed. Each lymphoid tissue specimen, including those obtained from the lymph nodes (n = 9), tonsils (n = 5), spleen (n = 1), and appendix (n = 1), showed a nonuniform expansion of nonfollicular areas by a polymorphous population of lymphocytes, including transformed lymphocytes and immunoblasts. In situ hybridization demonstrated Epstein-Barr virus-infected lymphocytes in four of eight tissue specimens that were studied. Other histologic features included Reed-Sternberg-like cells, plasma cells, histiocytes, frequent mitoses, abundance of postcapillary venules, and necrosis. These histologic features should suggest a diagnosis of infectious mononucleosis rather than other processes, either benign or malignant, that can mimic it.

Adolescent↗

PubMed1968

Infectious mononucleosis: immunoglobulin synthesis by cell lines.

Immunoglobulin synthesis by 16 long-term suspension cultures of mononuclear cells derived from peripheral blood of nine patients with heterophile-positive infectious mononucleosis (IM) has been demonstrated by radioimmunoelectrophoretic techniques. All cell lines synthesized molecules with IgG (gamma) heavy chain specificity. 14 cell lines produced molecules with IgM (mu) heavy chain specificity and 11 cell lines produced molecules with IgA (alpha) heavy chain specificity. No detectable synthesis of molecules with IgD (delta) heavy chain specificity was observed by these cell lines derived from peripheral blood of patients with IM. 13 cell lines produced molecules with type K (kappa) light chain specificity and 6 cell lines produced molecules with type L (lambda) light chain specificity. Of interest, 9 of 16 lines produced IgG (gamma), IgA (alpha), and IgM (mu) heavy chain molecules and 5 of these cell lines produced molecules with type K (kappa) and type L (lambda) light chain specificity as well. Further characterization by combined polyacrylamide gel filtration, immunodiffusion, and radioautography indicated the presence of newly synthesized immunoglobulin molecules with both heavy and light polypeptide chains in close association as well as free light polypeptide chain synthesis. Investigation of the localization of immunoglobulin in single cells by immunofluorescent techniques revealed that 5-22% of cells in these lines were strongly reactive with a fluorescein isothiocyanate-conjugated rabbit antisera directed against the antigenic determinants of human IgG and cross-reactive with the determinants common to IgA and IgM. No heterophile antibody, heteroagglutinin, or hemolytic antibody could be demonstrated in these cell lines derived from peripheral blood of patients with heterophile-positive infectious mononucleosis.

Adolescent↗

PubMed1996

Immunoglobulin-coated bacteria on the tonsillar surface during infectious mononucleosis.

Sequential bacterial samples were obtained from the tonsillar surface of 19 consecutive patients (12 females, seven males; mean age 16.1 years, range four to 24 years) suffering from infectious mononucleosis with membranous tonsillitis. The specimens were examined with respect to aerobes (culture on blood and chocolate agar plates) and proportions of bacteria coated with immunoglobulins (secretory IgA, IgG, IgM) by using an immunofluorescence assay. In the early stage of the membranous tonsillitis phase, attachment of secretory IgA (SIgA) and IgG to the bacteria was greatly suppressed, as compared with healthy controls. Coating with IgM was evident only late in the membranous tonsillitis phase but was contracted and still evident even after the clinical throat symptoms had abated. The findings suggest that the B-lymphotropic Epstein-Barr virus, causative agent of infectious mononucleosis, exerts a transient suppression of immunoglobulin-coating of bacteria harboured on the tonsillar surfaces, with consequent abundant bacterial attachment to the epithelial cells and massive bacterial colonization on the palatine tonsils.

Adolescent↗