Serological Response of the EBV Antibodies in Pediatric Cases of Infectious Mononucleosis and in Their Contacts

The EBV antibodies were measured in 378 sera from a group of 129 pediatric and older cases of infectious mononucleosis and from 117 family and social contacts. Cases of infectious mononucleosis with only one exception were EBV seropositive in acute and/or convalescent sera. Fourteen cases, however, from whom no convalescent serum was available were EBV seronegative. A rise in EBV antibodies of two dilutions or more was demonstrated in 15 of the 129 cases. The prevalence of these antibodies in contacts reached 50 to 70% in each of four age groups. A significant antibody rise was encountered in only four cases, one of whom was found to have infectious mononucleosis simultaneously with the index case and one after an interdisease period of 10 months. The infectivity of the EB virus (and of infectious mononucleosis if causally related) and its horizontal transmission seem to be as low in nature as they appear to be experimentally in the laboratory.     

Epstein-Barr virus serology

Because of the ubiquitous nature of EBV, most people are infected with this virus by the time they are adults. People acquire the virus at an early age, earlier in developing countries and in socioeconomically deprived areas of the United States, where about 80% of 5-year-old children are seropositive. In economically privileged areas, only about 40–50% of children are seropositive by age 5. Infections during childhood are usually asymptomatic. In contrast, 50% of adolescents who become infected with EBV develop the fatigue, fever, pharyngitis, and atypical lymphocytosis characteristic of acute infectious mononucleosis (IM). Heterophil antibodies, which are the basis for screening tests for IM, usually appear in the serum of these patients. However, approximately 10% of patients (more commonly children) with EBV induced IM do not develop heterophil antibodies. For this reason, tests for specific antibody-mediated immune responses to EBV may be necessary for diagnosis.     

Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children

It is well known that Epstein-Barr virus (EBV) is excreted from oral regions in the patients with infectious mononucleosis. We analyzed the prevalence of EBV in saliva and throat washings from healthy people in Japan by the polymerase chain reaction assay. EBV DNA was detected in 43 (90%) of the 48 throat washings from healthy adults (21 to 57 years old) and in 35 (38%) of the 93 salivas from healthy children (0 to 6 years old). The percentages of the EBV DNA-positive ratio in salivas increased in proportion relative to the increase of the children's ages. EBV type 1 was predominant and was detected in 86 and 94% of adults and children, respectively. Umbilical cord lymphocytes were transformed by some throat washings from EBV seropositive donors. EBV DNA was detected in throat washings from two healthy adults whose EBV antibody was not detected. In both cases, higher amounts of EBV DNA were detected in their peripheral blood mononuclear cells than in those of other, EBV antibody-positive donors. These results demonstrated the incidence of EBV excretion in oral regions of healthy individuals in Japan and defined a novel type of EBV infection in healthy adults.     

Serological Studies in Infectious Mononucleosis

Serological investigations performed on 27 patients with illnesses resembling infectious mononucleosis showed a significant increase in high antibody titres (more than 1:40) to EB virus in 11 of the 12 who developed heterophile antibodies. Two of these patients, however, had a significant increase in antibody titre to cytomegalovirus and rubella virus, respectively. Of 15 patients who failed to develop heterophile antibodies, one had a high antibody titre to EB virus, the others generally having undetectable or low antibody titres. The insidious onset of the illness in many patients together with the fact that EB virus antibodies rose to high titres rapidly reduced the value of this investigation diagnostically.EB virus antibody was still present in the sera of five patients who had had well-authenticated heterophile-antibody-positive infectious mononucleosis some four to seven years previously. Twenty-seven out of 70 (39%) healthy nurses had antibody at a level of more than 1:10 to EB virus. The presence of EB virus antibody in different population groups appears to be related to such factors as age and socioeconomic status.     

Studies on the presence of antibodies to EB virus and other herpesviruses in normal children and in infectious mononucleosis.

Children free from infectious disease have been examined by indirect immunofluorescence for the presence of antibodies to the intracellular capsid antigen of Epstein-Barr virus (EBV). In the first year of life 46%, between 2 and 6 years of age 66%, and between 7 and 14 years 91%, of the children proved positive. The corresponding percentages for the presence of antibodies to cytomegalovirus (CMV) and herpes simplex virus were about 50%, irrespective of the children's age. Serum samples from 69 patients suffering from infectious mononucleosis (IM) were tested for anti-EBV antibodies. Of the 29 Paul-Bunnell-positive patients 22 had antibodies, 11 of them in high titres (greater than 1 : 80). Of the 40 Paul-Bunnell-negative cases only 21 had antibodies, 8 in high titres. Of the Paul-Bunnell-negative cases, 73% were found to have anti-CMV antibodies, 32% in high titre. The respective percentages for the Paul-Bunnell-positive cases were 42% and 10%.     

Clinical efficacy of cycloferon in complex therapy of infectious mononucleosis in pediatrics

The results of the cycloferon use in therapy of 80 children at the age of 1 to 15 years with infectious mononucleosis are presented. The children were divided by chance sampling into two comparable groups of 40 subjects each. In the first group the children in addition to the standard therapy were treated with cycloferon for 10 days, intramuscularly or orally depending on the age. The reference group included the patients under the standard therapy alone. The efficacy of the drug was evaluated by reduction and more rapid disappearance of the main clinical symptoms of the disease. The improvement of certain laboratory indices, including those of the liver protein synthesis function were recorded, that allowed to reduce the hospitalization term. No side effects of the cycloferon use were observed.     

A Large-Scale Seroprevalence of Epstein-Barr Virus in Taiwan

Background

Epstein-Barr virus (EBV) causes a variety of clinical manifestations from asymptomatic infection to acute infectious mononucleosis in human. Moreover, the EBV infection is associated with malignancies. The large-scale EBV seroepidemiology across all age groups has been lacking in Taiwan.

Methods

A total of 1411 serum samples were tested to examine the seroprevalence of EBV in 2007. The samples were collected during an island-wide seroepidemiological survey of vaccine preventable diseases in Taiwan. The enzyme-linked immunosorbent assay was performed to detect anti-EBV viral capsid IgG in sera. Demographic and personal health data were obtained by questionnaires.

Results

The overall weighted seropositive rate of EBV was 88.5% (95% CI, 86.7%–90.1%). The seropositive rate of EBV reached 52.8% (95% CI, 44.0%–61.6%) in children aged 2 years, rapidly rose to 88.7% (95% CI, 79.0%–95.1%) in those aged 5–7 years and 93.0% (95%CI, 83.0%-98.1%) for those aged 14–16 years. Age and higher educational level were associated with the increased EBV seropositive rate.

Conclusion

In Taiwan, people had the EBV infection early in life. Children under 7 years should be the primary target popution of public health measures in the future.     

EBV与HCMV传染性单核细胞增多症患儿的实验室指标比较

目的观察EB病毒（EBV）与人类巨细胞病毒（HCMV）感染所致的传染性单核细胞增多症（IM）患儿超敏C-反应蛋白（hs-CRP）、白细胞（WBC）计数、嗜中性粒细胞比值（N）、异常淋巴细胞（异淋）、嗜异性抗体和血清酶的变化。方法选择70例确诊有EBV病毒感染且具备传染性单核细胞增多症临床特点的患儿（A组）进行实验室检测指标分析及总结;并与37例HCMV相关传染性单核细胞增多症患儿（B组）进行比较。结果与EB组（A组）比较,HCMV组（B组）感染患儿hs-CRP水平、肌酸激酶同功酶（CK-MB）、丙氨酸氨基转移酶（ALT）、外周血WBC计数、异型淋巴细胞增高程度较低（P〈0.05）,嗜异性抗体常为阴性,两组N值差异无统计学意义（P〉0.05）。结论 EBV与HCMV感染所致的传染性单核细胞增多症患儿的实验室指标变化不同,应重视IM患儿的实验室检查以辅助诊断。     

Cytomegalovirus in the mononucleosis syndrome in children

In 7 children aged 18 months to 7 years isolated from a group of 128 children with infectious mononucleosis the cytomegalovirus infection was found. Infection was diagnosed by determination of antibodies against immediate early and late CMV antigen by means of the ELISA test. Besides that, antibodies were determined against the capsid antigen and early antigen of EB virus by the method of indirect immunofluorescence. In four children only cytomegalovirus infection was found and three had a mixed infection with both viruses and the diagnosis in these cases was: infectious mononucleosis (due to EBV) with coexistent or following CMV infection. In the sera of two children with cytomegalovirus mononucleosis changes were observed in the antibodies against EBV which is explained as a result of interactions between CMV and EBV in the organism of the host.     

Toxoplasma gondii antibody titers in sera of children admitted to the Seoul National University Children's Hospital

A total of 542 children under 10 years of age, admitted to the Seoul National University Children's Hospital, was examined for antibody titers of Toxoplasma gondii using indirect latex agglutination (ILA) test. Among them, 7.7% showed positive titers higher than 1:32, without significant difference between males (7.3%) and females (8.5%). The seropositive rate increased with age although the statistical significance was negligible (0.05 < P < 0.1). By residential areas, the prevalence appeared higher among children from southern provinces (Kyongsang-do and Cholla do) than those from other areas, but the statistical significance was also very low (0.05 < P < 0.1). When the seropositive cases were analyzed by coincidental diseases, the prevalence was significantly higher in patients with congenital diseases than in patients with non-congenital diseases (P < 0.05). The results showed that the seropositive rate of toxoplasmosis in children examined was not high compared with other endemic countries. Some correlations are suggested between toxoplasmosis and congenital anomalies in Korea.     

Infectious mononucleosis at the United States Military Academy. A prospective study of a single class over four years

A prospective study of EB virus infections was initiated in July, 1969 in the entering class of 1401 cadets, at the U.S. Military Academy at West Point, N.Y. and continued over 4 yr. On entry 63.5% possessed EBV antibody and 36.5 lacked EBV antibody. The rate of antibody prevalence varied with the geographic area from which the cadet originated.Except in two cadets already ill on first bleeding no evidence of clinical infectious mononucleosis (I.M.) occurred over the 4 yr period in the 890 cadets entering the Academy with EBV antibody. Among 437 cadets without antibody on entry, 54 or 12.4% were infected (seroconverted) in the freshman year; 15 of these had clinical I.M., 12 had suggestive I.M., and 39 had no known mono-like illness. The annual infection rates in susceptible cadets in the second, third, and fourth years were 24.4, 15.1, and 30.8 per 100, respectively. Of 201 cadets infected with EBV over 4 yr only 26.4% were manifested by heterophile positive clinical infectious mononucleosis. Overall, 46% of the 437 cadets entering without EBV antibody became infected over 40 mo of serologic observation; definite clinical infectious mononucleosis developed in 53 cadets, a clinical attack rate of 12.1 per 100 for 4 yr. The EBV infection rate among exposed and susceptible roommates of known cases was no higher than in roommates not so exposed.Elevations of EBV-specific and total IgM occurred during acute illness and disappeared in late convalescence. Total IgG and IgA levels were less commonly elevated. EBV-specific-IgM antibody was demonstrable during the acute illness but was absent 12 mo later. Analysis of EBV infection rates revealed no difference among persons of different ABO blood groups.     

Epidemiologic and clinical features of infectious hepatitis in children against a background of massive prevention of the disease with microdoses of gamma-globulin]

The authors analyzed epidemiological and clinical peculiarities of infectious hepatitis in children aged under 11 years in conditions of mass-gamma-globulin prophylaxis in microdoses the last 5 years in Voronezh. It appeared that the incidence of the disease fell and that its clinical course became milder. In connection with reduction of the incidence of infectious hepatitis in the age group of under 10 years, the incidence of the disease was relatively higher in children aged from 10 to 14 years, with a tendency to levelling-out the periodic autumno-winter elevations among preschool children. Introduction of decreased gamma-globulin dose for hepatitis prophylaxis led to a lesser expenditure of the preparation and thus permitted to vaccinate more children.     

以儿童呼吸道感染为主的非典型EBV感染报道

目的报道儿童EBV感染所致的临床疾病谱与年龄特点,以进一步提高对EBV感染诊治水平.方法回顾性分析了EBV-VCA-IgM或EBV-DNA-PCR诊断的690例儿童EBV感染的疾病分布和年龄分布特点.结果EBV感染儿童非典型传染性单核细胞增多症患儿422例,占61.16%,非典型EBV感染268例,占38.84%.非典型EBV感染中以呼吸道感染最为多见,为191例,占非典型EBV感染的71.27%.其他为皮炎或口炎、血小板减少性紫癜、腹泻病、川畸病、肠系膜或颈淋巴结炎、肾炎或肾病和CNS感染等.EBV感染致传染性单核细胞增多症和呼吸道感染在各年龄组的分布差异无显著性,EBV感染男女比为1.79：1.结论儿童EBV感染所致疾病多样,累及系统多,非典型表现以呼吸道感染为主.传染性单核细胞增多症和呼吸道感染在各年龄组间差异无显著性.     

Impaired cellular immunecompetence in infectious mononucleosis as assessed by a local graft-versus-host reaction in rats and restoration of the immunecompetence by trypsin.

Lymphocytes from 11 patients with acute infectious mononucleosis were tested for functional capacity by means of a local graft-versus-host reaction (GVHR) and for T lymphocyte markers by the spontaneous rosette-formation test (E rosette). All of the patients showed an increased percentage (49–75%) and high absolute numbers (2078–8736/mm³) of E rosette-forming cells but no functional activity, i.e., a negative GVHR. Repeated examinations performed in four patients at intervals up to 6 months after the initial test showed a significant drop in the number of E rosette-forming cells although the GVHR remained negative. Trypsinization of lymphocytes performed in nine of the 11 patients resulted in recovery of immunecompetence of the T lymphocytes in five; in contrast, trypsinization of normal control lymphocyte abolished their ability to mount a normal GVHR. In view of the number of cases in which infectious mononucleosis has been followed by lymphoproliferative diseases, the importance of long-term follow-up in patients who have undergone an episode of infectious mononucleosis is stressed.     

Hepatitis C virus and Epstein-Barr virus: dual infection or atypical antibody response

Positive serological reactions against hepatitis C virus (HCV) appeared in the course of Epstein-Barr virus (EBV) infectious mononucleosis. In 429 consecutive patients with high levels of transaminases, 28 patients with EBV primary infection were found. The presence of anti-HCV antibodies and HCV RNA was studied in these subjects. In seven patients anti-HCV antibodies (C33 and C22c RIBA bands) were detected, but all were polymerase chain reaction (PCR) negative. These results may have been due solely to a HCV infection or were an atypical response to HCV in the course of infectious mononucleosis.     

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.     

The prevalence of helicobacteriosis in regions of Siberia based on serological study data

687 adults in 5 regions of Siberia and 79 children and young persons in Novosibirsk were examined. IgG antibodies to H. pylori in their blood sera were determined with the use the enzyme immunoassay. The detection rate of antibodies among the adult population varied within 70-87%, depending on the region, being somewhat lower among the population north of latitude 60 degrees (75%) in comparison with the population residing south of this latitude (86%, p < 0.001). In Novosibirsk the number of seropositive persons was found to be unrelated to sex, age and clinical manifestations of digestive tract diseases. A high detection rate of antibodies to H. pylori was registered in persons aged 25-34 years with a minor increase in older age groups. In children the detection rate increased with age: 29% in children of 5-10 years old and 56% in children 11-14 years old. By the age of 15 more than a half of the children had antibodies.     

EB virus antibody at different ages

In relation to the study of infectious mononucleosis a survey of the prevalence of antibody to EB virus was made on the sera of persons of varying age from several different areas in England by the indirect immunofluorescence technique. About half those tested were found to have acquired antibody by the age of 4 years and there was a further significant increase in the proportion of those positive between the ages of 15 and 24 years. The finding of seroconversion in two patients who developed infectious mononucleosis provides further support for an association between EB virus and this condition.     

Varicella morbidity in Czechoslovakia

Data are presented on varicella and herpes zoster morbidity notified in Czechoslovakia in the years 1970 to 1978. The notified varicella incidence is compared with serologically confirmed varicella incidence among the selected groups of children up to the age of 12 from the North-Moravia region. Comparative analysis revealed a considerable difference between the notified and serologically detected cases of varicella. The highest rate of notified varicella was recorded in children of 3 and 4 years of age, while the highest incidence of seropositive cases was detected among the 2-year-old children. The cumulative notified morbidity involved about 35% of 6-year-old and 45% of 12-year-old children, whereas specific antibodies against the varicella-zoster virus were found in about 60% of 6-year-old and 90% of 12-year-old children. The titres of virus-specific antibodies were determined by the method of indirect hemagglutination reaction. No serological methods are applicable for herpes zoster morbidity studies in the population.     

Infectious Mononucleosis and its Relationship to EB Virus Antibody: A JOINT INVESTIGATION BY UNIVERSITY HEALTH PHYSICIANS AND P.H.L.S. LABORATORIES

In October 1969 tests made on 1,457 students entering English universities and colleges showed that 57% already possessed antibody to EB virus. The students without antibody in these initial tests were retested seven months later and by then 12% had acquired antibody. In about one-third of them the acquisition of antibody was not associated with any illness. In about 20% respiratory and other illness had occurred, but these symptoms were almost equally frequent in students who had not acquired antibody. Nearly half had developed infectious mononucleosis. In students in whom the acquisition of EB virus antibody was associated with the clinical and haematological manifestations of infectious mononucleosis the Paul-Bunnell test was almost invariably positive. In contrast, when these manifestations were not associated with the acquisition of EB virus antibody the Paul-Bunnell test was always negative.Tests for cytomegalovirus antibody were also made on the students at entry. The proportion of students with this antibody was much less (30%) and only a small proportion (1·4%) of those without antibody had acquired cytomegalovirus antibody seven months later. In the only patient in whom the acquisition of cytomegalovirus antibody alone was associated with the clinical and haematological features of infectious mononucleosis the Paul-Bunnell test was negative.