Infectious Mononucleosis

Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for the characterisation of macrophage polarisation in situ. Furthermore, CD163 cannot be considered a reliable M2 marker when used on its own.

BackgroundGeneral practitioners encounter the vast majority of patients with Epstein-Barr virus-related disease, i.e. infectious mononucleosis in children and adolescents. With the expanding knowledge regarding the multifaceted role of Epstein-Barr virus in both benign and malignant disease we chose to focus this review on Epstein-Barr virus-related conditions with relevance to the general practitioners. A PubMed and Google Scholar literature search was performed using PubMed's MeSH terms of relevance to Epstein-Barr virus/infectious mononucleosis in regard to complications and associated conditions.Main textIn the present review, these included three early complications; hepatitis, splenic rupture and airway compromise, as well as possible late conditions; lymphoproliferative cancers, multiple sclerosis, rheumatoid arthritis, and chronic active Epstein-Barr virus infection. This review thus highlights recent advances in the understanding of Epstein-Barr virus pathogenesis, focusing on management, acute complications, referral indications and potentially associated conditions.ConclusionsHepatitis is a common and self-limiting early complication to infectious mononucleosis and should be monitored with liver tests in more symptomatic cases. Splenic rupture is rare. Most cases are seen within 3 weeks after diagnosis of infectious mononucleosis and may occur spontaneously. There is no consensus on the safe return to physical activities, and ultrasonic assessment of spleen size may provide the best estimate of risk. Airway compromise due to tonsil enlargement is encountered in a minority of patients and should be treated with systemic corticosteroids during hospitalization. Association between lymphoproliferative cancers, especially Hodgkin lymphoma and Burkitt lymphoma, and infectious mononucleosis are well-established. Epstein-Barr virus infection/infectious mononucleosis as a risk factor for multiple sclerosis has been documented and may be linked to genetic susceptibility. Chronic active Epstein-Barr virus infection is rare. However, a general practitioner should be aware of this as a differential diagnosis in patients with persisting symptoms of infectious mononucleosis for more than 3 months.

BackgroundInfectious mononucleosis (IM) is a common adverse presentation of primary infection with Epstein-Barr virus (EBV) in adolescence and later, but is rarely recognized in early childhood where primary EBV infection commonly occurs. It is not known what triggers IM, and also not why IM risk upon primary EBV infection (IM attack rate) seemingly varies between children and adolescents. IM symptoms may be severe and persist for a long time. IM also markedly elevates the risk of Hodgkin lymphoma and multiple sclerosis for unknown reasons. The way IM occurrence depends on age and sex is incompletely described and hard to interpret etiologically, because it depends on three quantities that are not readily observable: the prevalence of EBV-naϊve persons, the hazard rate of seroconverting and the attack rate, i.e. the fraction of primary EBV infections that is accompanied by IM. We therefore aimed to provide these quantities indirectly, to obtain epidemiologically interpretable measures of the dynamics of IM occurrence to provide etiological clues.Methods and findingsWe used joint modeling of EBV prevalence and IM occurrence data to provide detailed sex- and age-specific EBV infection rates and IM attack rates and derivatives thereof for a target population of all Danes age 0-29 years in 2006-2011. We demonstrate for the first time that IM attack rates increase dramatically rather precisely in conjunction to typical ages of puberty onset. The shape of the seroconversion hazard rate for children and teenagers confirmed a priori expectations and underlined the importance of what happens at age 0-2 years. The cumulative risk of IM before age 30 years was 13.3% for males and 22.4% for females. IM is likely to become more common through delaying EBV infection in years to come.ConclusionsThe change in attack rate at typical ages of puberty onset suggests that the immunologic response to EBV drastically changes over a relatively short age-span. We speculate that these changes are an integrated part of normal sexual maturation. Our findings may inform further etiologic research into EBV-related diseases and vaccine design. Our methodology is applicable to the epidemiological study of any infectious agent that establishes a persistent infection in the host and the sequelae thereof.

BackgroundDespite advances in HIV care, late diagnosis remains a major public health challenge in Europe, with nearly half of HIV diagnoses in the EU/EEA occurring at a late stage. In Poland, a substantial proportion of people living with HIV remain undiagnosed. Indicator condition-guided testing has been proposed as an effective strategy to reduce missed opportunities for earlier diagnosis.MethodsA prospective cohort study was conducted at the Emergency Department of the Hospital for Infectious Diseases in Warsaw, Poland, between May 2015 and March 2018, as part of the European OptTEST project. HIV DUO testing was offered to patients aged 18-65 years presenting with mononucleosis-like illness (MONO) or community-acquired pneumonia (CAP). We evaluated the prevalence of HIV infection and assessed linkage to HIV care among those testing positive. Confirmatory testing, CD4 cell counts at diagnosis, and linkage-to-care outcomes were collected.ResultsAmong 885 patients with indicator conditions (MONO: 794; CAP: 91), 636 (71.9%) accepted HIV testing. Twenty-two patients (3.5%) were confirmed HIV-positive. HIV prevalence was 2.6% among patients with MONO and 11.1% among those with CAP. Most HIV-positive patients were male (90.9%), with 59% identifying as men who have sex with men or bisexual. The median age was 32.5 years. The median CD4 cell count at diagnosis was 341 cells/µL overall and was lower in patients presenting with CAP than MONO (61 vs. 366.5 cells/µL). All patients diagnosed with HIV were linked to care, and 95.5% initiated antiretroviral therapy, with a median time to treatment of 8 days.ConclusionsHIV seroprevalence among patients presenting with MONO or CAP was higher than the national average, particularly among those with CAP. These findings support routine indicator condition-guided HIV testing in Emergency Departments to improve early HIV diagnosis and timely linkage to care.