Pain in adolescent chronic fatigue following Epstein-Barr virus infection.

Clinical symptoms and markers of disease mechanisms in adolescent chronic fatigue following Epstein-Barr virus infection: An exploratory cross-sectional study

S.16.03 Chronic fatigue syndrome

Predictors of chronic fatigue in adolescents six months after acute Epstein-Barr virus infection: A prospective cohort study

ObjectiveCognitive difficulties are among the most disruptive and disabling problems reported by chronic fatigue syndrome (CFS) sufferers. Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and CFS. The aim of this study was to investigate subjectively reported and objectively measured cognitive functioning in fatigued and non-fatigued adolescents six months after EBV infection. MethodsA total of 195 adolescents (12–19 years) with acute EBV infection were followed prospectively for six months, after which they were grouped as chronically fatigued (CF+) and non-fatigued (CF−) cases based on questionnaire score; the CF+-group was further subgrouped according to CFS diagnosis. A group of 70 healthy controls was also included. Groups were cross-sectionally compared on objective measures of processing speed, executive functions and memory, and subjective cognitive functioning. ResultsThere were no group differences regarding objective cognitive measures, but the CF+-group reported significantly (p < 0.001) more cognitive problems (cognitive symptoms sum score = 9.5) compared to the CF−-group (cognitive symptoms sum score = 5.3) and the healthy control group (cognitive symptoms sum score = 6.4). The CFS subgroup rated symptoms scores even higher but did not differ on cognitive performance tests. ConclusionSubjective experiences of cognitive difficulties characterize adolescents with CF and CFS six months after acute EBV infection, whereas objective measures of cognitive impairment are inconspicuous.

BackgroundCognitive–behavioural therapy (CBT) is effective in chronic fatigue (CF) syndrome. However, CBT has not been investigated in postinfectious CF, nor is it known whether addition of therapeutic elements from other...

Acute Epstein-Barr virus (EBV) infection is a trigger of prolonged fatigue. This study investigated baseline predictors of physical activity six months after an acute EBV infection. A total of 200 adolescents (12-20years old) with acute EBV infection were assessed for 149 possible baseline predictors and followed prospectively. In this exploratory study, we performed linear regression analysis to assess possible associations between baseline predictors and steps per day at six months. In the final multiple linear regression model, physical activity six months after acute EBV infection was significantly and independently predicted by baseline physical activity (steps per day), substance use (alcohol and illicit drugs) and human growth hormone (adjusted R2 =0.20). Baseline physical activity, substance use and plasma growth hormone are independent predictors of physical activity six months after an acute EBV infection in adolescents, whereas markers of the infection and associated immune response do not seem to be associated with physical activity six months later.

Chronic fatigue after Epstein-Barr virus (EBV) infection is a significant health problem among adolescents, yet its underlying mechanisms remain unclear. This study investigated whether preinfection hair cortisol levels predict chronic fatigue following acute EBV infection and examined the associations between hair cortisol and concurrent fatigue during acute infection, six months postinfection, and in healthy controls. This study is part of the CEBA project (Chronic Fatigue following Acute Epstein–Barr Virus Infection in Adolescents). Hair samples for cortisol measurements were obtained from 192 adolescents aged 12–20 years during acute EBV infection and again six months later, and from 66 age- and sex-matched healthy controls. Fatigue was measured by the total score on the Chalder Fatigue Questionnaire. Group comparisons were performed using nonparametric tests, and associations were examined with linear regression analyses. Adolescents with EBV infection had significantly higher preinfection hair cortisol levels (median 5.12, IQR: 3.27–8.76) compared with healthy controls did (median 3.90, IQR: 2.61–6.19) and with their own levels six months later (median 3.74, IQR: 2.46–6.52). A trend toward a positive association between preinfection hair cortisol and fatigue during acute infection, became significantly negative six months later. No associations were found among controls. Preinfection hair cortisol concentration did not predict chronic fatigue six months after acute EBV infection. Elevated preinfection hair cortisol may reflect stress-related vulnerability to infection, and the shifted from a positive to a negative association over time, suggests that HPA-axis alterations are more likely a consequence rather than a cause of chronic fatigue.

Primary infection with Epstein-Barr virus (EBV) is asymptomatic in children with immature immune systems but may manifest as infectious mononucleosis, a vigorous immune activation, in adolescents or adults with mature immune systems. Infectious mononucleosis and chronic immune activation are linked to increased risk for EBV-associated lymphoma. Here we show that EBV initiates progressive lytic infection by expression of BZLF-1 and the late lytic genes gp85 and gp350/220 in cord blood mononuclear cells (CBMC) but not in peripheral blood mononuclear cells (PBMC) from EBV-naive adults after EBV infection ex vivo. Lower levels of proinflammatory cytokines in CBMC, used to model a state of minimal immune activation and immature immunity, than in PBMC were associated with lytic EBV infection. Triggering the innate immunity specifically via Toll-like receptor-9 of B cells substantially suppressed BZLF-1 mRNA expression in acute EBV infection ex vivo and in anti-IgG-stimulated chronically latently EBV-infected Akata Burkitt lymphoma cells. This was mediated in part by IL-12 and IFN-gamma. These results identify immune activation as critical factor for the suppression of initiation of lytic EBV infection. We hypothesize that immune activation contributes to EBV-associated lymphomagenesis by suppressing lytic EBV and in turn promotes latent EBV with transformation potential.

Epstein Barr virus (EBV) infection causes asymptomatic liver-associated enzyme abnormalities in 80 to 90% of cases which are often unrecognized. Patients with acute EBV infections may also develop cholestatic hepatitis with associated jaundice and hepatitis with moderate elevations in the transaminase levels. Other gastrointestinal complications associated with EBV may include splenic rupture, liver failure due to acute and/or chronic EBV infection, and perhaps, autoimmune hepatitis and hepatocellular carcinoma. This article presents a case series of EBV infections with clinically significant hepatitis and reviews the literature on the gastrointestinal complications of EBV.

Primary Epstein Barr Virus (EBV) infection occurs during late adolescence and is characterized by the symptomatic manifestation of infectious mononucleosis (IM). Primary EBV infection in malaria-endemic areas often occurs in young children by the age of 2 and is generally asymptomatic. Acute EBV infection in children of this age results in humoral immune suppression to unrelated antigenic challenges for approximately 4 weeks. Whether acute EBV in infants similarly suppresses the development of antibody responses against Plasmodium falciparum (Pf) predisposing infants to severe malaria is unknown. We undertook a cross-sectional study of 195 infants aged 6-24 months in Cameroon. Infants were determined to be parasitaemic by microscopy or RDT, and their disease severity classified based on WHO criteria. The EBV infection status of each child was determined using a standard serological classification system, and the magnitude, breadth, and invasion blocking capacity of the anti- Pf antibody response were quantified. 26.7% of children were serologically positive for acute EBV infection, and the highest proportion of severe malaria cases was in children with primary acute EBV. An elevated magnitude and breadth of the antibody response with increased in vitro invasion-blocking capacity was observed in children with acute EBV but circulating parasitaemia in vivo was similar. Acute EBV infection is a risk factor for developing severe malaria in children 6-24 months. Targeting EBV infection in young children may be beneficial in protecting against the development of severe falciparum malaria in children living in malaria-endemic areas. Acute EBV infection in infants increases the risk of severe falciparum malaria. This does not appear to be due to an EBV-induced impairment of the anti- Plasmodium humoral immune response which is elevated in magnitude, breadth and function.

Acute Epstein-Barr virus (EBV) infection results in an unusually robust CD8(+) T cell response in young adults. Based on mouse studies, such a response would be predicted to result in attrition of preexisting memory to heterologous infections like influenza A (Flu) and cytomegalovirus (CMV). Furthermore, many studies have attempted to define the lymphocytosis that occurs during acute EBV infection in humans, but it is unclear whether bystander T cells contribute to it. To address these issues, we performed a longitudinal prospective study of primary EBV infection in humans. During acute EBV infection, both preexisting CMV- and Flu-specific memory CD8(+) T cells showed signs of bystander activation, including up-regulation of granzyme B. However, they generally did not expand, suggesting that the profound CD8(+) lymphocytosis associated with acute EBV infection is composed largely of EBV-specific T cells. Importantly, the numbers of CMV- and Flu-specific T cells were comparable before and after acute EBV infection. The data support the concept that, in humans, a robust CD8(+) T cell response creates a new memory CD8(+) T cell niche without substantially depleting preexisting memory for heterologous infections.

Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein–Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis

Reactivation ofHepatitis B virus (HBV) is not an uncommon condition. It is known to occur with immunosuppressive therapy. There are several viral infections that can trigger HBV reactivation, such as human immunodeficiency virus (HIV) infection. However, there is no reported case of HBV reactivation triggered by Epstein-Barr virus (EBV) infection in the literature. To our knowledge, we report the first case of reactivation of HBV secondary to acute Epstein-Barr virus (EBV) infection in the literature.A 47-year-old Caucasian male with a remote history of resolved acute Hepatitis B virus infection presented to our hospital with severe acute hepatitis, which manifested as epigastric pain, jaundice, dark urine, light-colored stools, hyperbilirubinemia, and transaminitis in the 1000s. Ultimately, the patient was diagnosed with reactivation of HBV triggered by acute EBV infection. After several days of supportive treatment, his hepatic function normalized. He was discharged with a scheduled follow-up at a hepatology clinic. In conclusion, EBV infection should be suspected as a trigger in cases with HBV reactivation, particularly when common etiologies are excluded.

X-linked lymphoproliferative disease: clinical, diagnostic and molecular perspective.

Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection.