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[Severe leukopenia and thrombocytopenia and transient acquired hypogammaglobulinemia in a patient with infectious mononucleosis].

A 30-year-old male with infectious mononucleosis by the Epstein-Barr virus who presented severe neutropenia and thrombocytopenia and type IgG acquired transitory hypogammaglobulinemia as complications during the acute period of the disease is presented. Although the etiopathogenesis of these phenomena is usually associated with an autoimmune basis, the antiplatelet and antileukocyte antibodies were negative. A bibliographic revision of the hematologic alterations of this disease was carried out and it was observed that the combination of the complications described has not been previously referred, thus, the present case may be the first observation with these characteristics.

Adult↗

False positive infectious mononucleosis serology in epilepsy.

Positive serum tests for infectious mononucleosis (IM) unaccompanied by the clinical syndrome or blood changes characteristic of the disease were detected in 39/177 (22%) mentally subnormal patients investigated with three different commercially available IM slide tests. Slide positively was still detectable six months later in 27/35 (77%) positive reactors. Positive IM slide tests were significantly associated with anticonvulsant, primarily phenobarbitone therapy and with concomitant elevations of immunoglobulins IgG and IgM. Epstein Barr virus antibodies were not detectable in the sera of 8/38 (21%) positive slide reactors. The implications of these observations are discussed and attention is drawn to the variations in sensitivity, specificity, and comparability of different IM slide tests.

Adolescent↗

[Infectious mononucleosis in childhood].

We present 42 cases of infectious mononucleosis caused by the Epstein-Barr virus in children. Patients were divided into two groups: those less than 4 years old and those 4 to 16 years of age. Splenomegaly was more frequent in young patients. Treatment with amoxicillin was associated with cutaneous rash. Heterophil antibodies were more frequent in patients older than four years of age. In 93% of the cases anticapside antibodies of IgM class were present. Complications were rarely encountered. Pneumonia and haemolytic anemia were present. We believe that anticapside antibodies of the IgM class should always be determined in patient younger than four years of age. If heterophil antibodies (Paul-Bunnell) and IgM are negative, we recommend that other specific serology related to the Epstein-Barr virus be determined in any age group.

Adolescent↗

Differences in EBV-specific antibody patterns at onset of infectious mononucleosis.

The EBV-specific antibody patterns of infectious mononucleosis (IM) patients were analyzed in relation to the onset of symptoms and clinical parameters during the acute phase of the disease. The antibody patterns varied considerably on admission. Three groups of patients were identified: one had not yet attained peak antibody titers, the second was at the peak and the third had passed the peak pattern. Patients with a "peak" current pattern had significantly higher lymphocyte counts, ASAT, ALAT, serum IgG and serum IgA concentrations than patients of the third group. Unexpectedly, there was no difference between the groups with regard to duration of sore throat and general malaise before admission. It thus seems that the lymphocyte proliferation during IM closely parallels the course of the EBV-specific antibody responses, whereas the onset of IM does not closely correlate to a specific stage of the antibody pattern.

Adolescent↗

Evaluation of latex-based heterophile antibody assay for diagnosis of acute infectious mononucleosis.

The diagnosis of an acute episode of infectious mononucleosis (IM) is made on the basis of clinical symptoms and serological evidence for development of heterophile antibodies. In an effort to obtain a very sensitive and specific assay for diagnosis of IM, we have developed MERISTAR:IM. The MERISTAR assay uses latex beads coated with purified bovine heterophile antigen. We compared the sensitivity and specificity and performance characteristics of the latex-based test to those of the commercially available erythrocyte-based Monospot test with serum samples from 363 suspected-IM patients and controls. A total of 28 samples from patients with confirmed IM were positive with the MERISTAR assay, while only 23 of the samples were positive with the Monospot assay. The two assays had equal specificity, as each test gave two false-positive results. In the technical performance of the assay, the MERISTAR assay was simpler and faster to perform than the Monospot assay.

Acute Disease↗

Anti-cardiolipin antibodies in infectious mononucleosis react with the membrane of activated lymphocytes.

To elucidate the mechanisms of autoantibody induction in infectious mononucleosis (IM), we have studied sera from 35 patients with IM with enzyme-linked immunosorbent assays using purified antigens. In the IM group 37% had IgM antibodies to cardiolipin above the normal range (mean plus 2 standard deviations of control sera). Significantly elevated frequencies of antibodies to actin (26%) and cytoskeletal antigens (97% versus 29% in normal sera) were also found, but levels of IgM rheumatoid factors, IgM antibodies to single-stranded DNA and antibodies to ribonucleoproteins (nRNP/Sm, Sm and La) were normal. Affinity purified anti-cardiolipin antibodies reacted with the cell membrane of transformed lymphocytes but not with resting cells, suggesting that cell activation was required for the expression of antigenic epitopes. Our data suggest that the autoantibody response in IM is restricted to two classes of autoantigens: cytoskeletal and cell membrane antigens. The appearance of antigenic epitopes on EBV-transformed lymphocytes could be a mechanism for the generation of anti-cardiolipin antibodies in infectious mononucleosis. Similar mechanisms could operate in autoimmune rheumatic disease.

Actins↗

Encephalitis in infectious mononucleosis: diagnostic considerations.

Four atypical cases of presumed infectious mononucleosis (IM) encephalitis are presented. To establish an etiologic diagnosis, Paul-Bunnell-Davidsohn heterophil titers (PBD), antibody titers to the antigens of the Epstein-Barr virus (EBV), and oropharyngeal excretion of EBV were determined. Criteria for a primary EBV infection are (1) an antiviral capsid antigen titer of 1:160 or greater, (2) the presence of antibody to the diffuse component of the early antigen, (3) absence of antibody to the nuclear antigen, and (4) excretion of the virus from the oropharynx. Three of the four cases met these criteria; of the three, one did not have a positive heterophil titer. The fourth case turned out not to be IM; there was a positive PBD heterophil, but there was no evidence of primary EBV infection. Although the PBD heterophil is usually a reliable test to diagnosis IM, it is not always present in children, and it is sometimes nonspecifically elevated. Some EBV titers can be nonspecifically elevated as well; however, the above criteria are diagnostic of primary EBV infection.

Adolescent↗

Viral antibodies in infectious mononucleosis.

Patients with Epstein-Barr virus (EBV) infectious mononucleosis (IM) usually develop heterophilic antibodies and some autoantibodies. Antibodies to rubella, measles, adeno-, entero-, herpes simplex, cytomegalo- and varicella-zoster viruses were titrated in sera from IM patients and matched healthy controls using the complement fixation test (CFT) and the haemagglutination inhibition test. Except for herpes simplex virus and cytomegalovirus, the IM sera had significantly higher arithmetical and geometrical mean antibody titres and showed in most cases higher antibody prevalences in the CFT. The titre rise was most pronounced for rubella and measles antibodies, between 2- and 3-fold. There were no cases of very high titres occasionally seen in IM. The IM sera had higher total IgG serum levels than the controls, 17.27 g/l and 11.8 g/l, respectively (P < 0.001). The present data show that in addition to previously reported high levels of some autoantibodies and of heterophilic antibodies, there is a more general increase in IgG antibodies to commonly occurring viruses. This increase is most likely due to the polyclonal activation of B-lymphocytes following the binding of EBV to the complement receptor CR2 (CD21). When due consideration is given to the possible occasional occurrence of a false positive rubella IgM test, the raised antibody-titres will most likely not interfere with routine diagnostics.

Antibodies, Viral↗

[Role of the B lymphocytes in children with infectious mononucleosis caused by Epstein-Barr Virus].

OBJECTIVE: Infectious mononucleosis (IM) is a lymphoproliferative disease caused primarily by the Epstein-Barr virus (EBV) infection. The initial viral infection by EBV occurs in B lymphocytes and is followed by an extensive proliferation of T lymphocytes. Previous studies on immunity to EBV (including IM) have mainly focused on activation of peripheral blood T cells, which are responsible for the lymphocytosis in blood during acute IM. B cells, regarding CD23 as their activation marker, are the target cells of EBV infection. There are few reports on their effect in patients with IM. The role of them during acute IM is not known yet. The present study aimed to explore the action of B cells in patients with IM. METHODS: In a prospective trial, a group of subjects comprised 22 patients with IM (14 boys and 8 girls) with mean age of 3.48 +/- 0.81 years (range 7 months to 8 years). Clinical diagnosis of IM was confirmed based on fever, lymphadenopathy, splenomegaly, lymphocytosis (> 50%), atypical lymphocytes (> 10%) in blood smears and the elevated levels of IgM antibody against EBV capsid antigen. The day of onset of fever was recognized as day 1 of illness. Blood samples taken during acute (3 - 5 days) and convalescent phase (about 15 days) were analyzed for expressions of CD19, CD19(+)/CD23(+) on PBMC by flow cytometry (FCM) and was compared with those of control group. The number of the days with fever was recorded. RESULTS: (1) The levels of CD19 and CD19(+)/CD23(+) expressions were markedly decreased in acute stage [CD19 (5.63 +/- 2.91)%, (387 +/- 178)/mm(3), CD19(+)/CD23(+) (2.45 +/- 1.87)%, (160 +/- 99)/mm(3)] and in convalescent stage [CD19 (12.49 +/- 5.70)%, (428 +/- 156)/mm(3), CD19(+)/CD23(+) (5.05 +/- 2.79)%, (172 +/- 78)/mm(3)] in patients with IM as compared with those of the healthy controls [CD19 (16.20 +/- 2.80)%, (545 +/- 150)/mm(3); CD19(+)/CD23(+) (7.08 +/- 2.78)%, (249 +/- 136)/mm(3)]. The earlier the specimens were taken after onset, the lower the expressed levels were. (2) There was a positive correlation of the expressions of CD19 and CD19(+)/CD23(+) between acute and convalescent stage (P < 0.01);there was also a positive correlation between the expressions of CD19 and CD19(+)/CD23(+) during acute and convalescent stage (P < 0.01). (3) A negative correlation was found between the duration of fever and the level of CD19 and CD19(+)/CD23(+) in acute stage (P < 0.01). CONCLUSION: The results indicate that B cells and CD23(+) B cells were significantly inhibited during the onset of IM in the patients, that with the recovery of the disease, the condition was gradually improved, and that the more evidently the CD19 and CD19(+)/CD23(+) decreased, the more serious the clinical symptoms were and the longer time the recovery needed. The levels of CD19 and CD19(+)/CD23(+) expressions may be useful in diagnosis and predicting the severity.

Antigens, CD19↗

Infectious mononucleosis associated with rhabdomyolysis and renal failure.

Acute rhabdomyolysis and renal failure occurred in a 16-year-old boy with infectious mononucleosis; recovery was complete. Renal failure is a rare complication of infectious mononucleosis. Rhabdomyolysis has been reported only once in association with the Epstein-Barr virus, but has frequently been associated with influenza virus infections. Prospective studies measuring creatine phosphokinase enzymes should establish the frequency of rhabdomyolysis in viral infections.

Acute Disease↗

Infectious mononucleosis in the case of two elderly (80 and 57 years old age) patients.

There are reported two cases of infectious mononucleosis in elderly. In the first case (80 years; probably the oldest in the geriatric literature) the infection provoked a very serious illness and the patient deceased three months after dimission, because of diminished resistance. In the second case the mononucleosis induced an autoimmune haemolytic anemia. The patient's daughter and granddaughter must be treated for complications of an infectious mononucleosis too.

Age Factors↗

Comparative evaluation of nine kits for rapid diagnosis of infectious mononucleosis and Epstein-Barr virus-specific serology.

Rapid diagnosis of Epstein-Barr virus (EBV)-associated infectious mononucleosis was compared by using nine kits and EBV-specific serology. Specific antibodies indicative of primary EBV infection were detected in 46 of 108 (43%) serum samples of infectious mononucleosis patients. The sensitivities and specificities of the rapid kits varied from 63 to 84% and 84 to 100%, respectively.

Adolescent↗

Complement-dependent, Epstein-Barr virus-neutralizing antibody appearing early in the sera of patients with infectious mononucleosis.

The first serum specimens obtained after onset of illness and those obtained later from patients with infectious mononucleosis were examined for neutralization of P3HR-1-derived Epstein-Barr virus (EBV). Without complement, viral neutralization indices of sera obtained soon after onset were all less than 0.2, and those of sera obtained later were less than 0.5. In contrast, sera from EBV-seropositive, healthy adults had neutralization indices of 0.45-1.0. Sera from EBV-seronegative adults showed no evidence of viral neutralization. The addition of complement from EBV antibody-negative human serum to 31 early and 34 late serum samples from 34 patients with infectious mononucleosis yielded neutralization indices of greater than or equal to 0.95. Complement-dependent neutralizing antibodies were also demonstrated in sera from EBV-seropositive, healthy adults. In contrast, sera from EBV-seronegative adults failed to neutralize EBV after the addition of complement. Heat inactivation destroyed the capacity of complement to induce additional neutralization of EBV by sera from patients with mononucleosis. The early appearance of complement-dependent neutralizing antibodies in the course of mononucleosis is consistent with a role in recovery from acute EBV infection.

Antibodies, Viral↗

Case report: Infectious mononucleosis in a 41-year-old man.

A 41-year-old man was found to have infectious mononucleosis, a disease frequently overlooked in patients of this age group. The symptoms and signs observed in this patient are seen in less than 10% of patients with this disease: arthralgia, epistaxis, jaundice, skin rash, and pneumonitis. Although mildly depressed platelet counts are common in patients with infectious mononucleosis, the count in this patient was markedly depressed.

Adult↗

The rapid diagnosis of infectious mononucleosis using an ELISA that detects IgM antibody to a peptide component of Epstein-Barr virus nuclear antigen.

An enzyme-linked immunosorbent assay (ELISA) that detects IgM antibody to a peptide component of the Epstein-Barr virus (EBV) nuclear antigen (EBNA-1) was compared with a conventional rapid heterophil antibody method for the rapid diagnosis of infectious mononucleosis. Discrepancies between the two methods were further analyzed using an indirect immunofluorescence assay to detect antibodies to EBV antigens. We evaluated 298 cases of suspected infectious mononucleosis. The ELISA was very sensitive (98.7%) and able to detect some cases (seven (9%) of 75 confirmed positives) that were negative by the rapid heterophil antibody test, but confirmed by immunofluorescence. However, approximately 17% of all positive tests could not be confirmed by EBV-specific immunofluorescence; thus, the overall positive predictive value was 83%; negative predictive value was 99.5%; and specificity was 93%. The high rate of false-positive tests makes this rapid ELISA unsuitable for the diagnosis of infectious mononucleosis.

Adolescent↗

Heterophile reactive antigen in infectious mononucleosis.

Specific heterophile reactive antigen has been localized by means of indirect immunofluorescence in 12 of 13 kidney biopsy specimens obtained during the acute phase of infectious mononucleosis. I feel that this may represent the identification of infectious agent antigen. Evidence is also presented for the possible existence of two different strains of the agent of infectious mononucleosis.

Antigens↗

Heterophile antigen detectable by infectious mononucleosis sera on bone marrow cells.

By means of mixed agglutination test and indirect immunofluorescence test, reactions of infectious mononucleosis sera with bone marrow cells were investigated. Positive reactions were observed with bovine, murine and rat bone marrow cells, but negative results were obtained with cells of monkeys and guinea pigs. Absorption studies demonstrated that the observed reactions are due to interaction of the Paul-Bunnell antigen on bone marrow cells with its corresponding antibodies in infectious mononucleosis sera. Whereas all cells of bovine bone marrow gave positive results, only 50% of murine or rat cells were positive and these cells were shown to be neutrophilic granulocytes. Evidence was also presented that the Paul-Bunnell antigen and Fc receptor are present, apart from each other, on murine neutrophilic granulocytes.

Animals↗

Infectious mononucleosis, Epstein-Barr virus, and chronic fatigue syndrome: a prospective case series.

Epstein-Barr viral infection, specifically infectious mononucleosis, typically has a more protracted course than other acute viral illnesses. Some recent observers have additionally suggested the possibility that Epstein-Barr virus (EBV) is the etiologic infectious agent in chronic fatigue syndrome, based on the finding of higher proportions of elevated antibodies to the EBV early antigen in some patients complaining of chronic fatigue. Straus et al reported on 23 patients with chronic fatigue, 83% of whom exhibited persistently elevated antibodies in modest titer to the early antigen. Ten of these patients had never fully recovered from an episode of acute infectious mononucleosis. Other studies had noted similar associations between persistently elevated antibodies to EBV-specific antigens and chronic symptoms in patients who presented with chronic symptoms after mononucleosis. Three important antigen complexes, demonstrable by immunofluorescence procedures, are expressed in EBV-infected cells. The early antigen is thought to function perhaps in early replication of viral DNA. A late antigenic complex, the viral capsid antigen, may represent, in addition to structural capsid proteins, components of the viral enzymatic machinery for late phases of replication or transformation. The Epstein-Barr nuclear antigen is felt to function in viral transformation of host cells.

Adolescent↗