HLH caused by an HSV-2 infection: a case report and review of the literature.

Haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory condition that can be triggered by infections, malignancies, or auto-immune diseases. Here, we present a patient with rapidly progressive HLH triggered by a herpes simplex virus type 2 (HSV-2) primary infection. The patient was successfully treated with intravenous high-dose acyclovir, immunoglobulins, and dexamethasone. This is the first report of HSV-2-associated HLH in an immunocompetent adult patient.

[Revised multidisciplinary guidelines 'Varicella'; broader indication for post-exposure prophylaxis]. / Herziene multidisciplinaire richtlijn 'Varicella'.

Post-exposure prophylaxis (PEP) with varicella zoster immunoglobulins (VZIG) should be administered as soon as possible after exposure to the virus, but always within ten days; in the previous guidelines this was within 96 hours. In cases of perinatal exposure, PEP with VZIG should be administered to neonates if the mother develops clinical chickenpox between seven days before delivery and seven days after delivery; in the previous guidelines this was between five days before delivery and two days after delivery. A new chapter on the treatment of chickenpox has been added to the guidelines.

A longitudinal and cross-sectional study ofEpstein-Barr virus DNA load: a possible predictor of AIDS-related lymphoma in HIV-infected patients.

INTRODUCTION: HIV-infected patients are more than 100-fold greater at risk for developing malignant AIDS-related lymphoma (ARL) compared to the general population. Most ARLs are EBV related. The main purpose of this study was to investigate whether a high peak EBV DNA load in HIV-infected patients is predictive of ARL, including classical Hodgkin lymphoma. METHODS: From an ongoing prospective HIV positive cohort study, we conducted a case-control study between 2004 and 2016 among patients from whom at least one EBV DNA load in serum or plasma was available. We compared peak EBV DNA load between patients with (49 cases) and without ARL (156 controls). RESULTS: The geometric mean of the peak EBV DNA load measured before diagnosis of malignant lymphoma was 52,565 IU/mL in EBER-positive lymphoma patients vs. 127 IU/mL in controls (p < .001). Patients with EBV DNA loads >100,000 IU/mL have an increased risk for diagnosis of malignant lymphoma compared to patients with EBV DNA loads ≤100,000 IU/mL (adjusted OR 12.53; 95%CI: 4.08; 38.42). In the longitudinal study, including 13 patients with at least three left-over plasma samples available for retesting, measurements of EBV-DNA during the preceding 12 months proved to be of poor value for predicting subsequent lymphoma diagnosis. CONCLUSIONS: A EBV DNA load >100,000 IU/mL can be useful in clinical setting to accelerate time to diagnosis and treatment. EBV-DNA loads in samples taken during the preceding year of ARL diagnosis showed to be of poor predictive value.

Diagnostic performance of influenza viruses and RSV rapid antigen detection tests in children in tertiary care.

BACKGROUND: Rapid antigen detection tests (RADTs) are increasingly used to detect influenza viruses and respiratory syncytial virus (RSV). However, their sensitivity and specificity are a matter of debate, challenging their clinical usefulness. OBJECTIVES: Comparing diagnostic performances of BinaxNow Influenza AB(®) (BNI) and BinaxNow RSV(®) (BNR), to those of real-time reverse transcriptase PCR (RT-PCR), virus isolation and direct immunofluorescence (D-IF) in paediatric patients. STUDY DESIGN: Between November 2005 and September 2013, 521 nasal washings from symptomatic children (age <5 years) attending our tertiary care centre were tested, with a combination of the respective assays using RT-PCR as gold standard. RESULTS: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BNI were 69% (confidence interval [CI] [51-83]), 96% [94-97], 55% [39-70] and 98% [96-99] respectively. Of eleven false-negative samples, RT-PCR Ct-values were higher than all RT-PCR positive test results (27 vs 22, p=0.012). Of twenty false-positive samples, none were culture positive and two tested positive in D-IF. Sensitivity, specificity, PPV and NPV for BNR were 79% [73-85], 98% [96-99], 97% [93-99] and 88% [84-91]. Of the 42 false-negative samples the median Ct-value was higher than that of all RT-PCR positive samples (31 vs 23, p<0.0001). Five false-positive samples were detected. Three of these tested positive for RSV in virus isolation and D-IF. CONCLUSIONS: RADTs have a high specificity with BNR being superior to BNI. However, their relative low sensitivity limits their usefulness for clinical decision making in a tertiary care paediatric hospital.

Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections.

Evaluation of the diagnostic work-up in children with myocarditis and idiopathic dilated cardiomyopathy.

The underlying etiology of dilated cardiomyopathy (DCM) in children varies, 14-22% is secondary to myocarditis, and the majority remains idiopathic. Etiology has prognostic value; however, 'a clinical diagnosis of myocarditis' has been frequently used because the gold standard [endomyocardial biopsy (EMB)] is often not performed. Therefore, a consistent diagnostic approach and interpretation is needed. In this multicenter study, we evaluated the diagnostic approach and interpretation of the viral results in children with myocarditis and idiopathic DCM. We included 150 children with DCM, of whom 103 were assigned the diagnosis myocarditis (n = 21) or idiopathic DCM (n = 82) by the attending physician. Viral tests were performed in 97/103 patients, in only 34% (n = 35) some of the tests were positive. Of those patients, we evaluated the probability of the assigned diagnosis using the viral test results. We classified viral test results as reflecting definite or probable myocarditis in 14 children and possible or unlikely myocarditis in 21 children. Based on this classification, 23% of patients were misclassified. We found that in children with DCM, the diagnostic approach varied and the interpretation was mainly based on viral results. Since a 'clinical diagnosis of myocarditis' has been frequently used in daily practice because of the lack of EMB results, a uniform protocol is needed. We propose to use viral test results in several steps (blood PCR, serology, PCR and/or cultures of the gastro-intestinal and respiratory tract, and EMB results) to estimate the probability of myocarditis.

Ebola virus disease: a review on epidemiology, symptoms, treatment and pathogenesis.

Currently, West Africa is facing the largest outbreak of Ebola virus disease (EVD) in history. The virus causing this outbreak, the Zaire Ebolavirus (EBOV), belongs to the genus Ebolavirus which together with the genus Marburgvirus forms the family of the Filoviridae. EBOV is one of the most virulent pathogens among the viral haemorrhagic fevers, and case fatality rates up to 90% have been reported. Mortality is the result of multi-organ failure and severe bleeding complications. By 18 September 2014, the WHO reported of 5335 cases (confirmed, suspected and probable) with 2622 deaths, resulting in a case fatality rate of around 50%. This review aims to provide an overview of EVD for clinicians, with the emphasis on pathogenesis, clinical manifestations, and treatment options.