High incidence of Epstein-Barr virus, cytomegalovirus and human herpesvirus 6 infections in children with cancer

BACKGROUND: A prospective single-center study was performed to study infection with lymphotropic herpesviruses (LH) Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) in children with cancer. METHODS: The group of 186 children was examined for the presence of LH before, during and 2 months after the end of anticancer treatment. Serology of EBV and CMV was monitored in all children, serology of HHV-6 and DNA analysis of all three LH was monitored in 70 children. RESULTS: At the time of cancer diagnosis (pre-treatment), there was no difference between cancer patients and age-matched healthy controls in overall IgG seropositivity for EBV (68.8% vs. 72.0%; p = 0.47) and CMV (37.6% vs. 41.7%; p = 0.36). During anticancer therapy, primary or reactivated EBV and CMV infection was present in 65 (34.9%) and 66 (35.4%) of 186 patients, respectively, leading to increased overall post-treatment IgG seropositivity that was significantly different from controls for EBV (86.6% vs. 72.0%; p = 0.0004) and CMV (67.7% vs. 41.7%; p < 0.0001). Overall pre-treatment IgG seropositivity for HHV-6 was significantly lower in patients than in controls (80.6% vs. 91.3%; p = 0.0231) which may be in agreement with Greaves hypothesis of protective effect of common infections in infancy to cancer development. Primary or reactivated HHV-6 infection was present in 23 (32.9%) of 70 patients during anticancer therapy leading to post-treatment IgG seropositivity that was not significantly different from controls (94.3% vs. 91.3%; p = 0.58). The LH infection occurred independently from leukodepleted blood transfusions given. Combination of serology and DNA analysis in detection of symptomatic EBV or CMV infection was superior to serology alone. CONCLUSION: EBV, CMV and HHV-6 infections are frequently present during therapy of pediatric malignancy

Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

BACKGROUND: Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known. METHODS AND FINDINGS: 200 adults with documented HIV-1 (n=194) or HIV-2 infection (n=6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2 was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2, Determine HIV 1-2, Determine HIV-1/2 Ag/Ab Combo and INSTI HIV-1/HIV-2. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p=0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level<200 cp/ml was significantly associated with a false-negative result (p=0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p=0.04; 100%, p=0.004; and 100%, p=0.02, respectively). CONCLUSION: When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum

Herpes-Virus Infection in Patients with Langerhans Cell Histiocytosis: A Case-Controlled Sero-Epidemiological Study, and In Situ Analysis

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that affects mainly young children, and which features granulomas containing Langerhans-type dendritic cells. The role of several human herpesviruses (HHV) in the pathogenesis of LCH was suggested by numerous reports but remains debated. Epstein-barr virus (EBV, HHV-4), & Cytomegalovirus (CMV, HHV-5) can infect Langerhans cells, and EBV, CMV and HHV-6 have been proposed to be associated with LCH based on the detection of these viruses in clinical samples. METHODOLOGY: We have investigated the prevalence of EBV, CMV and HHV-6 infection, the characters of antibody response and the plasma viral load in a cohort of 83 patients and 236 age-matched controls, and the presence and cellular localization of the viruses in LCH tissue samples from 19 patients. PRINCIPAL FINDINGS: The results show that prevalence, serological titers, and viral load for EBV, CMV and HHV-6 did not differ between patients and controls. EBV was found by PCR in tumoral sample from 3/19 patients, however, EBV small RNAs EBERs -when positive-, were detected by in situ double staining in bystander B CD20+ CD79a+ lymphocytes and not in CD1a+ LC. HHV-6 genome was detected in the biopsies of 5/19 patients with low copy number and viral Ag could not be detected in biopsies. CMV was not detected by PCR in this series. CONCLUSIONS/SIGNIFICANCE: Therefore, our findings do not support the hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans cell histiocytosis is accounted for by the infection of bystander B lymphocytes in LCH granuloma. The latter observation can be attributed to the immunosuppressive micro environment found in LCH granuloma

Evaluation de nouveaux tests de dépistage du VIH (trousses de diagnostic rapide)

PARIS-BIUP (751062107) / SudocSudocFranceF

Need for a better characterization of HHV‐6 infections and associated clinical impacts

International audienc

Fatal outcome after reactivation of inherited chromosomally integrated HHV-6A (iciHHV-6A) transmitted through liver transplantation

International audienceHHV-6A and HHV-6B are found as inherited and chromosomally integrated forms (iciHHV-6A and -6B) into all germinal and somatic cells and vertically transmitted in a Mendelian manner in about 1% of the population. They were occasionally shown to be horizontally transmitted through hematopoietic stem cell transplantation. Here, we present a clinical case of horizontal transmission of iciHHV-6A from donor to recipient through liver transplantation. Molecular analysis performed on three viral genes (7.2 kb) in the recipient and donor samples supports transmission of iciHHV-6A from the graft. Transmission was followed by reactivation, with high viral loads in several compartments. The infection was uncontrollable, leading to severe disease and death, despite antiviral treatments and the absence of resistance mutations. This case highlights the fact that physicians should be aware of the possible horizontal transmission of iciHHV-6 and its consequences in case of reactivation in immunocompromised patients

Utilization of Microsatellite Polymorphism for Differentiating Herpes Simplex Virus Type 1 Strains ▿ †

The herpes simplex virus type 1 (HSV-1) genome is a linear double-stranded DNA of 152 kpb. It is divided into long and short regions of unique sequences termed UL and US, respectively, and these are flanked by regions of inverted internal and terminal repeats. Microsatellites are short tandem repeats of 1- to 6-nucleotide motifs; they are often highly variable and polymorphic within the genome, which raises the question of whether they may be used as molecular markers for the precise differentiation of HSV-1 strains. In this study, 79 different microsatellites (mono-, di-, and trinucleotide repeats) in the HSV-1 complete genome were identified by in silico analysis. Among those microsatellites, 45 were found to be distributed in intergenic or noncoding inverted repeat regions, while 34 were in open reading frames. Length polymorphism analysis of the PCR products was used to investigate a set of 12 distinct HSV-1 strains and allowed the identification of 23 polymorphic and 6 monomorphic microsatellites, including two polymorphic trinucleotide repeats (CGT and GGA) within the UL46 and US4 genes, respectively. A multiplex PCR method that amplified 10 polymorphic microsatellites was then developed for the rapid and accurate genetic characterization of HSV-1 strains. Each HSV-1 strain was characterized by its own microsatellite haplotype, which proved to be stable over time in cell culture. This relevant innovative tool was successfully applied both to confirm the close relationship between sequential HSV-1 isolates collected from patients with multiple recurrent infections and to investigate putative nosocomial infections

Census and Analysis of Persistent False-Negative Results in Serological Diagnosis of Human Immunodeficiency Virus Type 1 Group O Infections▿

Human immunodeficiency viruses (HIV) have a high level of genetic diversity. The outlier variants of HIV type 1 (HIV-1) group O are distantly related to HIV-1 group M. Their divergence has an impact on serological diagnosis, with a risk of false-negative results. In this study, we report 20 failure cases, involving patients with primary or chronic infection, in France and Cameroon between 2001 and 2008. Our results indicate that some assays detected group O infection much less efficiently than others. Two major reasons for these false-negative results were identified: the presence or absence of a group O-specific antigen (and the designed sequence) for the detection of antibodies and the greater envelope variability of group O than of group M strains. This study highlights the complexity of screening for these divergent variants and the need to evaluate test performance with a large panel of strains, due to the extensive diversity of group O variants