Diagnosis Of Infectious Mononucleosis Research Articles

亜急性壊死性リンパ節炎の１例

Subacute necrotizing lymphadenitis (SNL) was first reported by Kikuchi (1972) and Fujimoto et al.SNL has a characteristic clinical pattern of fever, lymphadenopathy, and leukopenia; the prognosis is usually favorable. Eighty-five percent of the cases affected by the disease are under the age of 30 years.SNL may be a reactiton to a viral infection, such as that caused by the Epstein-Barr virus or Toxoplasma, but the etiology of this disorder remains obscure.We encountered a patient who was found to have a high elevation of antibody titer to E-B virus, and a positive Paul-Bunnell reaction. A diagnosis of infectious mononucleosis (IM) was considered highly likely, but histopathological findings revealed SNL.This case may be associated with the E-B virus. Case reports of infectious mononucleosis which lack some of the clinical and hematological features of the disease despite a high elevation of antibody titer to E-B virus and a positive Paul-Bunnell reaction, may found to include SNL if biopsy of the lymph nodes is carried out.

Cold Erythrocyte Agglutination and Infectious Mononucleosis

We detected cold agglutinin-induced erythrocyte agglutination by reading a characteristic pattern on a Technicon H-l (Technicon Instruments Corp, Tarrytown, NY) erythrocyte cytogram. We describe this pattern’s role in the diagnosis of infectious mononucleosis in a 22-year-old patient. Recognition of this characteristic erythrocyte cytogram pattern can be used as a screening tool for erythrocyte agglutinins, and can help avoid confusion with comparatively serious erythrocytic cellular abnormalities.

Patients treated in hospital for infectious mononucleosis and risk of cancer.

The risk of cancer was evaluated in a cohort of 1,234 patients with severe infectious mononucleosis between 1954 and 1983. The diagnosis of mononucleosis was confirmed by reviewing patient records. The observed numbers of cancer cases up to 1988 were obtained through record linkage from the Finnish Cancer Registry, which is nationwide and population-based. There were 11 cases of cancer in the cohort, as against 17.4 expected on the basis of the 24,288 person-years at risk and of incidence rates specific for age, sex and period in the area. This gives a standardized incidence ratio of 0.6 (95% confidence interval 0.3-1.1). There was only 1 lymphoma case. No malignancies were diagnosed during the first 5 years after infectious mononucleosis. The results indicate that infectious mononucleosis with severe symptoms does not imply an increased risk of cancer.

Serodiagnosis of infectious mononucleosis by using recombinant Epstein-Barr virus antigens and enzyme-linked immunosorbent assay technology

Four recombinant, diagnostically useful Epstein-Barr virus (EBV) proteins representative of the viral capsid antigen (p150), diffuse early antigen (p54), the major DNA-binding protein (p138), and the EBV nuclear antigen (p72) (W. Hinderer, H. Nebel-Schickel, H.H. Sonneborn, M. Motz, R. Kühbeck, and H. Wolf, J. Exp. Clin. Cancer Res. 7[Suppl.]:132, 1988) were used to set up individual enzyme-linked immunosorbent assays (ELISAs) for the qualitative and quantitative detection of immunoglobulin M (IgM) and IgG antibodies. In direct comparison with results obtained by standard immunofluorescence or immunoperoxidase assays, it was then shown that the recombinant EBV ELISAs provide the means for specific and sensitive serodiagnosis of infectious mononucleosis (IM) caused by EBV. The most useful markers in sera from such patients proved to be IgM antibodies against p54, p138, and p150. Additional positive markers for recent or ongoing IM apparently were IgG antibodies against p54 and p138. In contrast, anti-p72 IgG had a high preference for sera from healthy blood donors and, therefore, can be considered indicative of past exposure to the virus. Altogether, the individual ELISAs proved to be as specific and at least as sensitive for the diagnosis of IM as the currently available standard techniques are. Moreover, our findings suggest that, by combining individual test antigens, a workable ELISA system consisting of three assays (IgM against p54, p138, and p150; IgG against p54 and p138; and IgG against p72) can be established for the standardized rapid diagnosis of acute EBV infections.

Heterophile igm, iga, and ige antibodies in infectious mononucleosis

Fifty infectious mononucleosis (IM) and 150 non-infectious mononucleosis (non-IM) sera were tested by a hemadsorption immunocapture test (HIT) for the detection of heterophile antibodies of IgM, IgA, and IgE classes. The specificity of Paul-Bunnell (PB) antibodies was ascertained by a differential absorption test. IgM PB-antibodies were demonstrated in 100% of IM sera, IgA in 92%, and IgE in 88%. PB antibodies were present only in IM sera; but other heterophile antibodies of IgM (68%), IgA (6.7%), and IgE (9.3%) classes were demonstrated in non-IM sera. IgA and IgE heterophile antibodies were thus present, especially in IM sera. HIT was found to be more sensitive than Paul-Bunnell Davidsohn test (PBD test) and suitable for the diagnosis of infectious mononucleosis.

Hepatitis in fatal infectious mononucleosis

A detailed clinicopathologic analysis of 30 patients with sporadic fatal infectious mononucleosis and 31 males with fatal infectious mononucleosis and the X-linked lymphoproliferative syndrome was performed to determine the extent of hepatic dysfunction in these cases. At death, the median age of patients with sporadic infectious mononucleosis was 10.7 yr vs. 2.4 yr for X-linked lymphoproliferative syndrome. The median survival time was 8 wk for sporadic infectious mononucleosis and only 4 wk for X-linked lymphoproliferative syndrome. The male to female ratio was 3:2 in sporadic infectious mononucleosis; all patients with X-linked lymphoproliferative syndrome were males. Fever, sore throat, lymphadenopathy, hepatomegaly, and splenomegaly were prominent findings. Hepatic dysfunction was uniformly present and caused death in 13 of 30 sporadic infectious mononucleosis cases and 18 of 31 X-linked lymphoproliferative syndrome cases. Diagnosis of infectious mononucleosis was confirmed by heterophile antibody titers or Monospot, Epstein-Barr virus antibody studies, viral culture, molecular hybridization studies, clinical and histologic findings, and pedigree analysis.

Laboratory testing for infectious mononucleosis. Cautions to observe in interpreting results.

In the vast majority of cases, diagnosis of infectious mononucleosis is relatively simple and the illness is not serious. Performing tests for specific Epstein-Barr virus (EBV) antibodies in these cases is not necessary. However, when the clinical manifestations are atypical or unusually severe, especially when the heterophil antibody test is negative, specific EBV antibody tests may be needed. The EBV antibodies used in diagnosis are IgG antibodies to viral capsid antigen (VCA), IgM antibodies to VCA, and antibodies to early antigen (anti-D) and Epstein-Barr nuclear antigen (EBNA). The diagnosis of infectious mononucleosis may be made when IgG-VCA, IGM-VCA, and anti-D antibodies are present and EBNA antibodies are absent. EBNA antibodies appear later and, together with IgG-VCA antibodies, persist indefinitely. Still, infectious mononucleosis often cannot be diagnosed with certainty because of the difficulties in interpreting laboratory findings. The diagnosis must be made with caution and possible sources of error considered when test results are interpreted.

A case presenting symptoms of subacute necrotizing lymphadenitis following infectious mononucleosis

We treated a Japanese woman who presented symptoms of subacute necrotizing lymphadenitis (SNL), which occurred following an EB virus infection, i.e., infectious mononucleosis (IM). No such cases have been reported and the possibility that SNL may be induced by an EB virus infection has to be given attention.The patient was a 26 year-old Japanese woman who admitted to Kyushu University Hospital because of persistent fever and sore throat. Systemic lymphadenopathy, hepatomegaly, leukocytosis, an increased number of atypical lymphocytes and the elevation of serum EB VCA-IgM titer were evident and the diagnosis of IM was made. Two months after the onset of IM, she again had a high fever and marked swelling of the left submandibular lymph nodes accompanied by marked tenderness. Serum markers of EB virus showed evidence of the convalescent stage of IM. Leukocytopenia was present and she recovered 40 days later with no specific treatment. Though SNL was not histologically proven, the diagnosis of SNL was made. Immunological investigations showed that the ratio of OKT 4+ to OKT 8+ lymphocytes was decreased and the natural killer cell activity had deteriorated.

The Diagnosis of Mononucleosis in the Office Laboratory

Infectious mononucleosis has been known for a long time to be a common infection in young adults. It also infects children. In particular, children under the age of 2 years may not express the illness clinically. Diagnostic criteria vary but in young adults usually include the symptoms of fever, exudative tonsillitis, and cervical lymphadenopathy. Usually, there is a relative and absolute lymphocytosis, with 10 to 20 per cent or greater atypical lymphocytes. Rapid slide tests are accurate and economical and support the diagnosis when positive. False-positive results are known to occur with several other important disease processes; therefore, the clinical presentation and laboratory results must be interpreted in their appropriate context. Quality control is essential even for the rapid slide tests, and experienced examiners are required to review blood smears. The morphology of atypical lymphocytes varies greatly. In addition, morphology interpretation can be hampered by problems in preparation of slides or the holding of blood samples awaiting slide preparation. EBV-specific serodiagnosis has significantly enhanced our ability to study further and differentiate heterophil-negative syndromes that share clinical features with infectious mononucleosis. Acute, past, chronic, and no EBV infection can now be differentiated. Further diagnostic tests for other etiologic agents are necessary when all EBV tests are negative and the clinical situation requires appropriate diagnosis.

Serodiagnosis of infectious mononucleosis with a bovine erythrocyte glycoprotein.

A glycoprotein from bovine erythrocyte membrane was evaluated in two immunoassays as a reagent for the serodiagnosis of infectious mononucleosis (IM). We previously reported that a partially purified preparation of this glycoprotein, when attached to latex beads, agglutinated in the presence of IM heterophile antibody. In the present study, we used a highly purified form of the glycoprotein both as an agglutinating reagent, covalently bound to latex, and in a solid-phase sandwich-type radioimmunoassay (RIA) for IM antibody detection in a larger population of patients. We tested serum samples from college students with symptoms suggestive of IM with the latex reagent (143 samples) and with the RIA (245 samples). Correlation of these two tests, both with each other and with the classical differentially absorbed, agglutination tests for Paul-Bunnell antibody in IM sera, using fresh sheep or horse cells, was excellent (greater than 97% agreement). The new tests also corresponded in most cases with a rapid, unabsorbed preserved horse erythrocyte slide test. However, in this study of 245 samples, both apparent false-positives (5 samples) and apparent false-negatives (3 samples) were observed with this slide test. In conclusion, we found that the bovine glycoprotein as a reagent can facilitate the diagnosis of IM, giving results comparable to those with erythrocyte agglutination tests on differentially absorbed sera. The advantages are ease and speed of performance (latex test), potential for automation (RIA test), stability and uniformity of the glycoprotein reagent (latex and RIA tests), and most importantly, the ability to use unabsorbed sera (latex and RIA tests).

Beta-Hemolytic Streptococcal Pharyngitis

Infectious mononucleosis (IM) and beta-hemolytic streptococcal pharyngitis may present similar clinical pictures and may occur concurrently; however, recent studies have differed sharply with older ones that cited high rates of concurrent disease. Our study of 100 consecutive new patients meeting strict criteria for a diagnosis of IM found only 4% with positive throat cultures for group A beta-hemolytic streptococci at the time of diagnosis. Use of antibiotics for presumed streptococcal pharyngitis in patients with IM is unjustified. Only patients with positive cultures should be treated.

Limitations of available tests for diagnosis of infectious mononucleosis.

Among 500 students seen at a university health service for illnesses resembling infectious mononucleosis (IM), the diagnosis of IM was established in 124 (25%) on the basis of the initial presence or subsequent emergence of the spectrum of Epstein-Barr virus (EBV) antibodies characteristic of a primary EBV infection. Of these 124 patients, 113 had an EBV-specific antibody pattern in the initial serum indicative of current primary infection; however, 11 (9%) had no detectable immunoglobulin G antibodies to EBV-specific antigens in their first serum. The sensitivity of this panel of EBV antibody assays was 91% and the specificity was 100%. Initial sera had detectable heterophil antibodies for 107 (86%) of the 124 students with IM and for 2 with other illnesses. Among our patients, the Monospot (Ortho Diagnostics Inc.) test had a sensitivity of 86% and a specificity of 99%. Reliance on hematological criteria (lymphocyte count greater than or equal to 50% and atypical lymphocyte count greater than or equal to 10%) gave a sensitivity of only 39%, but a specificity of 99%. Students with IM who showed a delayed emergence of the spectrum of EBV-specific antibodies characteristic of an acute infection were compared with control patients who had such antibodies at the time of their initial visit to the health service. They were found to have a briefer duration of illness (P greater than 0.05), lower leukocyte (P less than 0.005), lymphocyte (P less than 0.005), and atypical lymphocyte (P less than 0.05) counts, and a less frequent occurrence of heterophil antibodies (P less than 0.05).

Infectious mononucleosis fifty years after the discovery of the Paul-Bunnell test.

The Paul-Bunnell test, now 50 years old, is still of fundamental importance in the diagnosis of infectious mononucleosis, even though various immunologic methods have been developed in clinical practice to identify constituents of the Epstein-Barr virus (EBV). The demonstration of sheep red cell agglutinins in infectious mononucleosis (Paul-Bunnell) was in fact the first observation of the presence of heterophil antibodies in this viral disease which was later shown to evoke a polyclonal antibody response to a wide spectrum of autoantigens as well. The selective tropism of EBV for B lymphocytes and the reactivity of T lymphocytes to these infected B lymphocytes are the pathophysiological elements characteristic of infectious mononucleosis, and are the reason for this massive antibody response.

EBV-IgA and new heterophile antibody tests in diagnosis of infectious mononucleosis.

An evaluation has been made of the EBV-IgA tests and the immune adherence hemagglutination assay (IAHA) as compared with standard diagnostic procedures in 119 serial sera from 22 clinical and 113 sera from 42 subclinical cases of EBV infectious mononucleosis. EBV-IgA antibody was demonstrable in 86.4 per cent of patients using EB3 cells as antigen and in 68.2 per cent with P3/HRIK cells. For heterophile antibody the IAHA test was more sensitive, gave higher titers, and was positive longer than the standard absorbed horse or sheep RBC tests in both clinical and subclinical EBV infections.

Two-dimensional analysis of human lymphocyte proteins. III. Preliminary report on a marker for the early detection and diagnosis of infectious mononucleosis.

Two-dimensional gel electrophoretic patterns of human peripheral blood leukocytes from 12 patients with infectious mononucleosis were prepared by use of the ISO-DALT system. Before the two-dimensional separation, the leukocytes were purified by Ficoll-Paque gradient centrifugation and labeled overnight with [35S]methionine. Quantitative increases in two proteins were detected in the patterns of infected leukocytes from the patients as compared with controls. Fluorescence-activated cell sorting of leukocytes from normal human peripheral blood before subsequent two-dimensional gel analysis revealed that the dramatic increase in one of these proteins (Inmono:2) could be due to shifts in the population ratios of lymphocytes, monocytes, and granulocytes (Willard et al., manuscript in preparation). In contrast, the appearance of the infected leukocytes of a second protein, Inmono:1, could not be accounted for by cell-population shifts. Increased amounts of these two proteins have been found in every patient studied who had clinically detectable infectious mononucleosis. In addition, a patient who displayed symptoms of infectious mononucleosis but who did not have a positive result in the MONOSPOT Test (Ortho) until three weeks after our analysis also demonstrated increased relative amounts of these proteins in his leukocyte pattern.

Beta 2-microglobulin serum levels in infectious mononucleosis in childhood.

A material of fifteen children aged 10 months to 15 years with infectious mononucleosis (IM) was investigated. The diagnosis was established by demonstration of Epstein-Barr virus (EBV) specific IgM antibodies. The serum concentrations of beta 2-microglobulin (beta 2-m) were significantly increased (p less than 0.01) in the first sample after onset of disease, compared to control groups of children with other infectious diseases and children without diseases. The serum concentration of beta 2-m decreased towards normal range within 3 weeks- 3 months. During the same period, IgM antibodies of EBV decreased to unmeasurable levels, and the IgG titers were almost constant. Serum beta -2m may be a parameter of value in the diagnosis of infectious mononucleosis in childhood, replacing tests for heterophile antibodies (Emni test and Paul-Bunnell test) which are often negative in children suffering from a primary EBV infection, or it may be used for assessment of disease activity.

Leukocyte response in childhood infectious mononucleosis. Caused by Epstein-Barr virus.

The usual leukocyte response in infectious mononucleosis (IM) has been established in adults but not in children. Previously, the diagnosis of IM often was difficult in childhood due to the lack of detectable heterophil antibody response in many patients. Using Epstein-Barr virus-specific serology, we have documented IM in 45 patients between 1 and 15 years of age. the mean and ranges for the total leukocytes, percent lymphocytes, and percent atypical lymphocytes are presented. These do not vary significantly with age and are similar to those reported for adolescents and adults with this illness.

Points: Diagnosis of infectious mononucleosis

Points: Diagnosis of infectious mononucleosis

Sudden Death Due to Spontaneous Rupture of the Spleen from Infectious Mononucleosis

An 18-year-old white male showing no external signs of trauma was discovered dead in his bathroom. A ten-day history of illness resulting in symptomatic treatment for viremia one day before death was elicited. Autopsy revealed splenic rupture, massive peritoneal hemorrhage, and atypical lymphocytes. Laboratory tests on postmortem samples confirmed the diagnosis of infectious mononucleosis.

Practical approach to diagnosis of infectious mononucleosis

This article, the first of two on laboratory aspects of mononucleosis, presents a simplified approach to diagnosis of acute infectious mononucleosis based on a rapid screening test for heterophil antibodies and analysis of a blood smear for atypical lymphocytes. Diagnosis of the cytomegalovirus-mononucleosis syndrome will be discussed next month.