Childcare attendance and risk of infectious mononucleosis: A population-based Danish cohort study.

BACKGROUND: The risk of infectious mononucleosis (IM) is affected both by crowding and by sibship structure, i.e., number and signed age differential between an index child and a sibling. Siblings provide protection against IM by pre-empting delayed primary Epstein-Barr virus infection with its associated high risk of IM. The association between childcare attendance and risk of IM, on the other hand, has never been studied in a large, well-characterized cohort. METHODS: Danish children born in July 1992 through 2016 with a completely known simple childcare attendance history before age 1.5 years (n = 908,866) were followed up for a hospital contact with an IM diagnosis at ages 1.5-26 years. Hazard ratios (HRs) of IM for an additional year of exposure were obtained from stratified Cox regression analyses, stratified by sex and year of birth, with age as the underlying time scale, adjusted for sibship structure, and sociodemographic variables including parental ethnicity and maternal age. RESULTS: An additional year of exclusively attending a daycare home (max 5 children) yielded HR = 0.90 (95% confidence interval 0.81-1.00), and similarly, each year of exclusively attending a childcare institution (e.g., crèche) yielded HR = 0.94 (0.84-1.06). CONCLUSIONS: Forwarding enrollment in childcare by a year lowers the risk of IM later in life much less than having an additional sibling of comparable age and has no practical public health implications. We find our results suggestive of a random threshold for successful Epstein-Barr virus infection that is more easily reached by a sibling than the collective of playmates in daycare homes or childcare institutions.

Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom.

BACKGROUND: Epstein-Barr Virus (EBV) is a ubiquitous gamma-herpesvirus with which ~ 95% of the healthy population is infected. EBV infection has been implicated in a range of haematological malignancies and autoimmune diseases. Delayed primary EBV infection increases the risk of subsequent complications. Contemporaneous seroepidemiological data is needed to establish best approaches for successful vaccination strategies in the future. METHODS: We conducted a sero-epidemiological survey using serum samples from 2325 individuals between 0 and 25 years old to assess prevalence of detectable anti-EBV antibodies. Second, we conducted a retrospective review of Hospital Episode Statistics to examine changes in Infectious Mononucleosis (IM) incidence over time. We then conducted a large case-control study of 6306 prevalent IM cases and 1,009,971 unmatched controls extracted from an East London GP database to determine exposures associated with IM. RESULTS: 1982/2325 individuals (85.3%) were EBV seropositive. EBV seropositivity increased more rapidly in females than males during adolescence (age 10-15). Between 2002 and 2013, the incidence of IM (derived from hospital admissions data) increased. Exposures associated with an increased risk of IM were lower BMI, White ethnicity, and not smoking. CONCLUSIONS: We report that overall EBV seroprevalence in the UK appears to have increased, and that a sharp increase in EBV seropositivity is seen in adolescent females, but not males. The incidence of IM requiring hospitalisation is increasing. Exposures associated with prevalent IM in a diverse population include white ethnicity, lower BMI, and never-smoking, and these exposures interact with each other. Lastly, we provide pilot evidence suggesting that antibody responses to vaccine and commonly encountered pathogens do not appear to be diminished among EBV-seronegative individuals. Our findings could help to inform vaccine study designs in efforts to prevent IM and late complications of EBV infection, such as Multiple Sclerosis.

Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post-transplant lymphoproliferative disease.

We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who underwent single-unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% [95% confidence interval (C.I.), 74-98%] with a median of 18 d (range, 10-48). CI of acute graft-versus-host disease (GvHD) grades II-IV was 30% (95% C.I., 17-44%), while the incidence of chronic GVHD was 42% (95% C.I., 23-77%). The non-relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13-46%) and 47% (95% C.I., 29-65%), respectively. EBV-related post-transplant lymphoproliferative disease (EBV-PTLD) accounted for more than one-third of transplant-related death, with an estimate incidence of 26% (95% C.I., 9-44). The incidence of relapse at 4 yr was 25% (95% C.I., 9-42%). Four-year event-free survival (EFS) and overall survival (OS) were 28% and 30%, respectively. Despite a high NRM and an unexpected high incidence of EBV-PTLD, UCBT in heavily pretreated HD patients is an option for patients lacking a suitable adult donor, provided the disease is not in refractory relapse.

O vírus Epstein-Barr e a mononucleose infecciosa / Epstein-Barr virus and infectious mononucleosis

JUSTIFICATIVA E OBJETIVOS: A mononucleose infecciosa (MI) é uma doença viral, contagiosa, causada pelo vírus Epstein-Barr (EBV). Apresenta distribuição universal e pode ocorrer em qualquer faixa etária. O presente estudo teve como objetivo descrever a interação entre o EBV e o Homo sapiens sapiens, no que diz respeito especialmente à MI. Para isso, realizou busca no Pubmed e no Scielo, bem como em livros-textos. Os artigos selecionados foram lidos e as informações organizadas de forma a contemplar os aspectos patogênicos - enfatizando o papel do EBV na doença -, epidemiológicos e diagnósticos dessa entidade. CONTEÚDO: A infecção do epitélio da orofaringe permite a replicação do vírus, o qual passa a ser eliminado na saliva, o que explica a transmissão pelo contato com tal fluido biológico. O período de incubação é de quatro a seis semanas. Manifesta-se do ponto de vista clínico, usualmente, com febre, faringite e linfadenomegalia generalizada de caráter agudo ou subagudo. As alterações laboratoriais incluem leucocitose, reações leucemoides, trombocitopenia e anemia hemolítica autoimune, além de aminotransferases elevadas e bilirrubina aumentada, destacando-se que a linfocitose atípica é habitualmente observada. O diagnóstico diferencial da MI abrange as demais causas de síndrome de mononucleose. O tratamento é sintomático, não havendo fármaco antiviral específico. Analgésicos habituais podem ser usados para a terapêutica da dor. CONCLUSÃO: Díspares grupos têm trabalhando no desenvolvimento de vacinas para o EBV, porém, a possibilidade de tumorigênese pelo vírus tem trazido inúmeras dificuldades para a confecção de imunoprofilaxia efetiva.

BACKGROUND AND OBJECTIVES: Infectious mononucleosis (IM) is a widespread viral disease caused by Epstein-Barr virus (EBV). It occurs worldwide and can reach any age group. This article aims at describing the interaction between EBV and Homo sapiens sapiens, regarding especially IM. Thus, a research on PubMed and Scielo was performed, as well as on books. The selected articles were read and the information was organized inorder to contain the pathological - emphasizing the role of EBV on the disease -, epidemiological aspects and its diagnosis. CONTENTS: The infection of the epithelium of the oropharynx leads to the replication of the virus, which is eliminated via saliva, and accounts for the transmission through contact with this biological fluid. The incubation period lasts from four to six weeks. Clinically, the classic symptoms are usually fever, faryngitis and generalized lymphadenopathy, which can be acute or subacute. The laboratorial changes include leukocytosis, leukemoid reactions, thrombocytopenia and severe autoimmune hemolytic anemia, besides high levels of transaminases and bilirubin; atypical lymphocytosis is usually observed. The differential diagnosis of IM includes the other causes of mononucleosis syndrome. Treatment is symptomatic and there is not a specific antiviral medicine. Common analgesics can be used to treat pain. CONCLUSION: Diverse groups have worked on the development of a vaccine for EBV; however, the possibility of tumorigenesis by the virus has brought up several difficulties to the production of an effective immunoprophylaxis.

[Genetic polymorphism of GST gene in children with infectious mononucleosis and acute lymphocytic leukemia].

OBJECTIVE: To study the relationship between glutathione S-transferase genes GSTT1 and GSTM1 polymorphisms and the susceptibility to infectious mononucleosis (IM) and acute lymphocytic leukemia (ALL) in children. METHODS: The case-control study involved 106 children with IM, 41 children with ALL and a control group of 100 children with non-hematologic and nontumorous diseases. The genetic polymorphisms of GSTT1 and GSTM1 were detected with multiplex polymerase chain reaction (PCR). Distribution of the genotypes in the children was analyzed. RESULTS: The frequency of GSTT1 null genotype in children with IM was significantly higher than in the control group (P<0.05). The risk of IM in children carrying GSTT1 null genotype was 2.186 times higher than in those carrying GSTT1 non-null genotype. The children carrying both GSTT1 and GSTM1 null genotype had a higher risk of suffering from IM compared to those carrying only one of the null genotypes (OR=4.937). The frequency of GSTM1 null genotype in children with ALL was significantly higher than in the control group (P<0.05). The risk of ALL in children carrying GSTM1 null genotype was 2.242 times higher than in those in carrying GSTT1 non-null genotype. Children carrying both GSTT1 and GSTM1 null genotype had a higher risk of suffering from ALL compared with those carrying only one of the null genotypes (OR=8.552). CONCLUSIONS: Children carrying GSTT1 or GSTM1 null genotype have a high risk of suffering from IM or ALL. Still more increased susceptibility to IM or ALL may occur in children who carry both GSTT1 and GSTM1 null genotype. GSTT1 and GSTM1 might play a potential role in the pathogenesis of both IM and ALL.

Infectious mononucleosis-like syndrome probably attributable to Coxsackie A virus infection.

Infectious mononucleosis (IM) is a clinical syndrome most often attributable to Epstein-Barr virus (EBV). Characteristic clinical features of EBV IM include bilateral upper lid edema, exudative or nonexudative pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly ± maculopapular rash. Laboratory features of EBV IM include atypical lymphocytes and elevated levels of serum transaminases. Leukopenia and thrombocytopenia are not uncommon. The syndrome of IM may also be attributable to other infectious diseases, eg, cytomegalovirus (CMV), human herpes virus-6 (HHV-6), or Toxoplasma gondii. Less commonly, viral hepatitis, leptospirosis, brucellosis, or parvovirus B(19) may present as an IM-like infection. To the best of our knowledge, only 2 cases of IM-like infections attributable to Coxsackie B viruses (B(3) and B(4)) have been reported. We present the first reported case of an IM-like syndrome with sore throat, fatigue, atypical lymphocytes, and elevated levels of serum transaminases likely due to Coxsackie A in an immunocompetent adult.

Reporte de una posible correlación entre la gingivitis ulceronecrotizante y la mononucleosis / Report a possible correlation between necrotizing ulcerative gingivitis and mononucleosis

Necrotizing ulcerative gingivitis is a relatively uncommon periodontal disease, characterized by ulceration, necrosis, pain and gingival bleeding. Factors often related to its occurrence include stress and systemic viral infections, such as those caused by cytomegalovirus and Epstein-Barr virus type 1, the latter being also considered the causative agent of infectious mononucleosis. This article aims to describe a clinical case of a female patient who presented with necrotizing ulcerative gingivitis associated with a clinical picture of infectious mononucleosis, as well as to review the literature concerning a possible correlation between these pathologies. This patient presented to our health care facility with necrotizing ulcerative gingivitis accompanied by lymphadenopathy, fever and prostration, after laboratory tests, Epstein-Barr virus type 1 infection was confirmed, as well as the co-occurrence of pathologies: necrotizing ulcerative gingivitis and infectious mononucleosis. Symptom remission in both disorders also occurred concomitantly, after instruction in plaque control measures and palliative medication for control of systemic symptoms. Therefore, although there is no scientific validation of an association between these two pathologies, it is imperative that all diagnostic alternatives be considered and investigated, in order to establish the therapeutic approach most appropriate to the patient(AU

La gingivitis ulcerativa necrótica es una enfermedad periodontal no común caracterizada por ulceración, necrosis, dolor y sangrado gingival. Los factores a menudo relacionados con su ocurrencia incluyen el estrés y las infecciones virales sistémicas como aquellas causadas por Cytomegalovirus y el virus Epstein-Barr tipo 1, donde este último es el agente causal de la mononuclerosis infecciosa. El objetivo de este trabajo fue describir el caso clínico de una mujer con gingivitis ulcerativa necrótica asociada a un cuadro clínico de mononucleosis infecciosa, así como hacer una revisión de la literatura concerniente a una posible correlación entre estas enfermedades. Esta paciente se presentó con una gingivitis ulcerativa necrótica acompañada de linfadenopatía, fiebre y postración después de las pruebas de laboratorio, donde se confirmó una infección por Epstein-Barr tipo 1 así como la ocurrencia conjunta de gingivitis ulcerativa necrótica y mononucleosis infecciosa. También se produjo una remisión concomitante de los síntomas en ambos trastornos después de la instrucción en medidas para el control de placas y una medicación paliativa para el control de los síntomas sistémicos. Por lo tanto, aunque no existió una validación científica de una asociación entre estas dos entidades, es imperativo que se consideren e investiguen todas las alternativas diagnósticas para establecer el enfoque terapéutico más apropiado para el paciente(AU)

[A young man with mononucleosis and swelling of the right eye]. / En ung mann med mononukleose og hevelse over høyre øye.

Treatment of acute infections in the upper airways comprises a significant part of direct healthcare expenditure and is a challenge for healthcare professionals. In Norway, 11,495 hospitalized days were recorded for acute infections (influenza and pneumonia excluded) in the upper airways in 2008. Acute bacterial rhinosinusitis (ABRS) is defined as inflammation of the nose and the paranasal sinuses characterized by both 1): symptoms of nasal blockage/obstruction/congestion or nasal discharge, and/or facial pain/pressure and 2): endoscopic signs of mucopurulent discharge from middle meatus and/or CT changes within the osteomeatal complex/sinuses. After 12 weeks of symptoms the definition changes to chronic rhinosinusitis. With antibiotic treatment of complicated ABRS we see fewer severe complications, but they still occur. Due to anatomical proximity of the orbit and intracranial structures a localized spread of the infection is especially unfortunate and potentially dangerous. We present a case report (with pan sinusitis and grave local complications) from the ear, nose and throat department in St. Olav's University Hospital in Trondheim, Norway.

Cytomegalovirus-induced infectious mononucleosis-like syndrome in a rheumatoid arthritis patient treated with methotrexate and infliximab.

We report a patient with rheumatoid arthritis (RA) who developed cytomegalovirus (CMV)-induced infectious mononucleosis-like syndrome (IMLS) while being treated with methotrexate and infliximab. She suddenly developed intermittent high fever and general fatigue with liver dysfunction, remarkable lymphocytosis and laboratory data suggestive of CMV reactivation. Her clinical symptoms quickly improved after the cessation of methotrexate and infliximab without the use of anti-viral drugs such as ganciclovir. CMV-induced IMLS might be a cause of persistent fever in RA patients, particularly when biologics are used for treatment.

Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development.

The lack of functional SAP protein, a consequence of mutation or deletion of the SH2D1A gene is the cause of X-linked lymphoproliferative disease (XLP). Others and we have shown that SAP can be involved in apoptosis. Activation induced apoptosis plays a pivotal role in the termination of the lymphocyte proliferation in infectious mononucleosis IM. This mechanism is inefficient in the XLP patients. Primary EBV infection of boys with XLP leads therefore to fulminant, often even fatal disease. In addition, the condition predisposes to considerably elevated incidence of lymphomas. Chromosomal translocation that juxtaposes one of the three immunoglobulin loci to the c-myc proto-oncogene is the hallmark of Burkitt lymphomas (BL), whether they carry the Epstein-Barr Virus (EBV) or not. Ig/myc translocations occur as rare accidents of normal B lymphocyte differentiation. The activated myc would drive the cells to proliferate, however unless protected, the cells become prone to apoptosis. Our results with BL derived cell lines suggest that the fate of the precursor cells is decided by the expression of the proapototic SAP and EBV infection. We found SAP expression in eight of ten EBV carrying, but none of nine EBV negative BL lines. Therefore it seems that the apoptosis prone Ig/myc translocation carrying EBV negative precursors of BL can grow into lymphomas only if they do not express the proapoptotic SAP while SAP expressor, but EBV positive cells can survive and proliferate. This is probably due to the antiapoptotic function of EBNA-1 and the proliferation induced by activated myc.

Enzymatic status of blood lymphocytes in young children with Epstein-Barr virus infection.

Activities of NAD(PH)-dependent dehydrogenases in peripheral blood lymphocytes were studied in children aged 1-3 years in the dynamics of the disease caused by Epstein-Barr virus. A relationship between changes in activities of the studied enzymes and disease period was revealed. The disorders of blood lymphocyte enzymatic status persisted during convalescence.

Epstein-Barr virus-induced infectious mononucleosis after two separate episodes of virus-associated hemophagocytic syndrome.

A 24-year-old man, who had suffered previous two episodes of non- Epstein-Barr virus (EBV)-associated hemophagocytic syndrome (HPS) at the ages of 16 and 18, developed EBV-induced infectious mononucleosis. His antibody pattern to EBV highlighted the initial infection. The disease took a self-limited course without developing into HPS. No reactivation of EBV infection was noted over the following 6 years. The patient may have attained immune competency in adulthood, which was somehow impaired during his adolescence.