Frédéric Morinet

Resistant Herpes Simplex Virus Type 1 Infection: An Emerging Concern after Allogeneic Stem Cell Transplantation

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Advances in Human B19 Erythrovirus Biology

ABSTRACT Since its discovery, human parvovirus B19 (B19V), now termed erythrovirus, has been associated with many clinical situations (neurological and myocardium infections, persistent B19V DNAemia) in addition to the prototype clinical manifestations, i.e., erythema infectiosum and erythroblastopenia crisis. In 2002, the use of new molecular tools led to the characterization of three different genotypes of human B19 erythrovirus. Although the genomic organization is conserved, the geographic distribution of the different genotypes varies worldwide, and the nucleotidic divergences can impact the molecular diagnosis of B19 virus infection. The cell cycle of the virus remains partially unresolved; however, recent studies have shed light on the mechanism of cell entry and the interactions of B19V proteins with apoptosis pathways.

Usefulness of the Cytomegalovirus (CMV) Antigenemia Assay for Predicting the Occurrence of CMV Disease and Death in Patients with AIDS

A cohort study of 214 human immunodeficiency virus (HIV)-infected patients was performed to assess the usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death. Multivariate analysis revealed that only positive baseline CMV antigenemia assays (relative risk [RR], 7.2; 95% confidence interval [CI], 3.7-14.2; P = .0001) and CD4 cell counts (RR, 0.98; 95% CI, 0.97-0.99; P = .009) were associated with CMV disease. A positive baseline CMV antigenemia assay was also associated with death by multivariate analysis (RR, 2.2; 95% CI, 1.5-3.4; P = .0003). Increasing levels of CMV antigenemia during follow-up were associated with increased risks of CMV disease and death. A positive CMV antigenemia assay that showed > 10 cells per 2 x 10(5) polymorphonuclear leukocytes during follow-up was 91% sensitive and 84% specific for predicting a diagnosis of CMV disease; the negative predictive value for this positive test was high (97%). Therefore, the CMV antigenemia assay appears to be a simple, rapid, and inexpensive test for predicting the occurrence of CMV disease and death in patients with advanced HIV infection.

Establishment of a cell line expressing human parvovirus B19 non-structural protein from an inducible promoter

Human parvovirus B19 non-structural (NS) protein is supposed to play a major role in B19 replication and transcription, and therefore in B19 pathogenicity. Constitutive expression of NS protein in stable cell lines has failed so far, presumably because of its cytotoxicity. To avoid this cytotoxic effect, we have cloned the NS gene in an Epstein-Barr virus episomal vector under the control of a steroid inducible promoter (5xGRE) and transfected this construction into HeLa cells. We obtained stable cell lines inducibly expressing high level of NS protein, with 50% of the cells demonstrating specific nucleo-cytoplasmic staining. In Western blot analysis, three B19 NS proteins (72, 68 and 60 kDa) were found but a unique NS transcript was detected by Northern blotting. The NS protein expressed in HeLa cell lines was demonstrated to be functional as it trans-activates the B19 P6 promoter. These cell lines might be major tools for further study and characterization of B19 NS protein.

Human B19 Erythrovirus In Vitro Replication: What's New?

Human B19 erythrovirus (B19) tropism is almost restricted to erythroid progenitor cells and mediated by receptor and coreceptor interactions: i.e., P antigen ([2][1], [3][2]), α5β1 integrin complex ([20][3]), and Ku80 antigen ([11][4]). Few in vitro models allow production of B19 infectious

Health-care access for migrants in France

1704 www.thelancet.com Vol 382 November 23, 2013 the relatives in a safe and prepared environment. There are good reasons for this attitude to be the standard. However, there is also sometimes a need for time to understand the unforeseen. Sometimes, there is a need to face the sad and the painful. Sometimes, there is a need to fall down deep to recover. And always, there is a need to let people decide what they think the good is for them. There is obviously no miracle solution to face traumatic loss. Each of us needs to continuously fi nd our own, when possible. These parents are just telling us that keeping their breastfed child has been constructive for their bereavement. It helped them to enter into their cruel new reality and, later on, move toward their renewed life. The process of going through a period of mourning includes looking back trying to understand what happened. Unprepared doctors might sometimes underestimate how difficult it is to simply face the reality and restart from there. In both hospital and community settings, taking away a body might happen under many circumstances and under the cover of relatively obvious or fairly hypocritical reasons. Questions such as the acceptable delay for necropsy and the postmortem samples that need to be taken immediately should be clarifi ed and handled according to evidence-based priorities. Meanwhile, the next time you accompany the relatives of your deceased patient, these parents would be very grateful if you could sincerely ask yourself if you are not stealing the body in any way.

An in situ hybridization technique for the study of B19 human parvovirus replication in bone marrow cell cultures

An in situ hybridization technique using digoxigenin labelling was developed to study B19 infection. By using appropriate DNA probes, transcription of structural and non-structural genes was detected in bone marrow cell cultures. Such a simple system is useful to the study of B19-cell interactions in non-permissive cell lines.