[Non Hodgkin's and Hodgkin's lymphomas and HIV: frequency, outcome and immune response under HAART; Clermont-Ferrand University Hospital, 1991-2003]. / Lymphomes non hodgkiniens et hodgkiniens et infection VIH: fréquence, pronostic et reconstitution immune sous trithérapie antirétrovirale; CHU de Clermont-Ferrand, 1991-2003.

OBJECTIVES: The authors had for aim to identify cases of non Hodgkin's (NHL) and Hodgkin's (HL) lymphomas in HIV1-infected patients to assess 1) their incidence, before and after 1996, 2) the clinical features and outcome under treatment together with the survival rate of the patients, 3) the immune reconstitution of lymphoma-free patients under HAART. PATIENTS AND METHODS: A retrospective study was made of HIV1-infected patients managed at the Clermont-Ferrand University Hospital from 1991 to 2003 for the diagnosis and treatment of HIV1-related lymphomas. RESULTS: Forty-one patients were included: 35 NHL and 6 HL giving a cumulative incidence rate estimate from 2.4% between 1991 and 1996 to 3.4% between 1997 and 2003 while other opportunistic diseases were decreasing. A high proportion of aggressive and disseminated disease was observed among NHL cases. Complete remission was achieved in 17 (49%) and 5 (83%) NHL and HL cases respectively. The mean survival was 109+/-54 months and was correlated with CD4 cell count at lymphoma diagnosis (univariate analysis). Among responding patients, 5 died: 3 from opportunistic infections, 1 commited suicide, and 1 from hepatic carcinoma. For responding patients, the mean increase of CD4 cell count under HAART was 58/mm3 over a 2 year-period and 192/mm3 over a 5 year-period of follow-up. CONCLUSIONS: The incidence of lymphomas in HIV-infected patients has not decreased since the introduction of HAART. The immune status assessed by CD4 cell count on diagnosis is correlated with survival. Immune restoration in lymphoma-free patients under HAART is poor.

[Rapid diagnosis of rotavirus infections: comparative prospective study of two techniques for antigen detection in stool]. / Diagnostic rapide des infections à rotavirus: étude prospective comparative de deux techniques de détection d'antigènes dans les selles.

The ability of two commercially available diagnosis rapid assays in detecting rotavirus antigen was compared in a prospective study conducted from September 2002 to May 2003. Five hundred and twelve faecal specimens were studied by IDEIA Rotavirus enzyme immunoassay test (EIA) and Diarlex MB immunochromatographic test (ICG). Specimens giving discrepant results were examined by electron microscopy (EM) and clinical data reconsidered. Out of 512 stool specimens, 155 (30.3%) were positive and 332 (64.8%) negative with the two assays. Discrepant results were obtained for 25 (4.88%) specimens (24 children, 1 adult), with EIA giving more positive results. The retrospective examination by EM, possible for fifteen stools on the 25 that gave discrepant results, confirmed the presence of rotavirus in 7/14 stools which were positive only by EIA and in the stool specimen that was found positive only by ICG. The 25 clinical observations re-examination showed the presence of GEA signs in all cases. The statistical analysis shows an excellent concordance between the EIA and the ICG tests (kappa = 0.89, IC(95%) = [0.85-0.93]) in spite of the underestimation of ICG test in comparison with EIA test (P < 0.0001).

[From prospective molecular diagnosis of enterovirus meningitis...to the prevention of antibiotic resistance]. / Du diagnostic moléculaire initial prospectif des méningites à entérovirus...à la lutte contre l'antibiorésistance.

Meningitis initially presents with intense manifestations that are not generally specific to a given etiology. The first major question for the physician is to decide whether to initiate a probabilistic treatment. Enteroviruses are a major cause of aseptic meningitis, which is benign in immunocompetent patients. Molecular diagnosis is now becoming the gold standard and its prospective use at the time of patient admission, on the sole basis of clinical suspicion of meningitis, has yielded more reliable data. Cytological and biochemical data from CSF analyses are of low predictive value to influence the initial decision to treat with antibiotics. In addition, cases of meningitis during winter are not uncommon. Adults are concerned in about 25% of cases. Thus, if molecular diagnostic tools are not rapidly available, patient management may be inconsistent, leading to unnecessary scans, laboratory investigations and treatment (including overconsumption of antibiotics). Current progress in the automation and practicability of viral genomic detection yields the result within a few hours after admission. Rapid molecular viral diagnosis of a benign disease that does not require treatment but which is initially worrying is of unquestionable advantage. It is of benefit to both the patient and the community because of its input on health economics, the needless consumption of drugs and, as a result, resistance to antibiotics. The diagnosis of meningitis can no longer remain a retrospective diagnosis after elimination of all the possible causes, since not prescribing unnecessary laboratory tests and not treating are true therapeutic decisions.

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

[Acute myocarditis in children. Study of 11 clinical cases]. / Myocardites aiguës de l'enfant. Etude de 11 cas cliniques.

The diagnosis of acute myocarditis in children is based on histological criteria. Often viral in origin, it results in acute left ventricular dysfunction, the clinical manifestations of which are very variable. The potential severity of the disease is maximal in its initial phase, justifying rapid and intensive treatment. Long-term outcome is relatively good although there is a risk of chronic left ventricular dysfunction. This retrospective study is based on 11 cases of acute myocarditis admitted to the paediatric unit of Clermont-Ferrand University Hospital between February 1989 and March 1999. The initial symptoms were non-specific. Echocardiography was the key diagnostic procedure. Half of the patients had severe cardiac failure requiring admission to the intensive care unit. Four cases presented with a severe complication: two embolic events, one syncopal atrioventricular block and one cardiac arrest. The cardiac treatment was classical (digitalis, diuretics, angiotensin converting enzyme inhibitors, anticoagulants). The aetiology was established in 3 cases (toxoplasmosis, haemolytic and uraemic syndrome, Kawasaki) and a viral cause was suspected in 6 other cases (adenovirus in 3 cases, herpes virus, RSV and enterovirus in 1 case). There were no deaths in the acute phase. The long-term outcome was globally good: complete regression in 8 cases, 1 chronic left ventricular dysfunction and 2 late deaths due to intractable cardiac failure. This short series illustrates the often misleading presentation of acute myocarditis in childhood, the value of systematic investigation in the hope of a specific treatment becoming available in the near future for the often viral aetiology.

Genomic variations in echovirus 30 persistent isolates recovered from a chronically infected immunodeficient child and comparison with the reference strain.

Seven sequential isolates of echovirus type 30 (EV30) were recovered over 22 months from a child with severe combined immune deficiency syndrome. The nucleotide sequences of the 5' halves of the genomes (4,400 nucleotides) of the first (S1) and last (S7) isolates were determined and compared with that of the EV30 Bastianni reference strain, also determined in this study. In genome regions P1 and P2, 101 variations were identified between the two isolates. Synonymous differences far outnumbered nonsynonymous differences. Amino acid changes affected both capsid and nonstructural polypeptides (particularly 2B). The VP1 nucleotide sequences of the seven isolates were determined to analyze genome evolution during the chronic infection. In the phylogenetic tree, the seven isolates were directly related to the prototype strain in an individual monophyletic group, strongly suggesting that the chronic infection in the child arose from a single persistent EV30 isolate. Four lineages were observed in the persistent isolates. Isolates S2, S4, S5, and S6 were close relatives of one another, whereas isolates S1 and S3 formed individual lineages. Isolate S7, distantly related to all other isolates, formed the fourth lineage. These findings suggest the quasispecies nature of the genomes of the seven sequential EV30 isolates. Grouping of persistent isolates on the basis of replicative capacities was consistent with phylogenetic relationships. Overall, the results indicate that genetically related EV30 variants with different replicative capacities coexisted in a carrier state, probably in the gastrointestinal tract, during the infection of the child.

[Prospective comparative study of HCV serologic status in and AIDS population]. / Etude pronostique comparative d'une population SIDA en fonction du statut sérologique VHC.

OBJECTIVE: Study the influence of hepatitis C virus (HCV) serology on the course of HIV disease in AIDS patients. PATIENTS AND METHODS: A prospective study of survival prognosis in HIV infected patients who had reached the AIDS stage was conducted in the Saint-Etienne, Clermond-Ferrand and Lyons infectious disease centers to compare patients with positive and negative HCV serology. Data were collected using the clinico-epidemiological software DMI II. The effect of HCV ìco-infectionî defined by RIBA II or III confirmed seropositivity, was studied using Kaplan-Meier survival plots. RESULTS: Among the 1,005 HIV-infected subjects included in the study, 219 had AIDS and 43 of them (19.6%) were HCV positive. Survival curves in HIV/HCV positive patients with AIDS were not significantly different from those of HCV-negative AIDS patients (median 17.8 versus 18.6 months respectively, p = 0.93). This result was confirmed by univariate Kaplan-Meier analysis. Only 2 patients were treated with interferon and no deaths were attributed to liver disease. CONCLUSION: HCV positivity in AIDS patients does not appear to influence survival. The longer survival obtained with the new anti-retroviral treatments may have an effect on the HIV-HCV interaction.

[Geotrichum capitatum infection in a neutropenic patient. Apropos of a case and review of the literature]. / Infection à Geotrichum capitatum chez un patient neutropénique. A propos d'un cas et revue de la littérature.

INTRODUCTION: Geotrichum capitatum sepsis are rare, occurring exclusively in immunocompromised patients. EXEGESIS: We report the case of a patient with acute leukemia, presenting with chemotherapy-induced neutropenia and hospitalized in an intensive care unit for a severe sepsis. In spite of an antibiotic and antifungal treatment, the patient died of cardiorespiratory failure. Later on, blood cultures proved to be positive for Geotrichum capitatum. CONCLUSION: If fungal infections are common in neutropenic patients, Geotrichum capitatum sepsis remain exceptional. The portal of entry is digestive or respiratory, and the invasion is favored by immunodepression and suppression of the normal microbial flora. Induced lesions can be multiorganic. The treatment is not well established, and the association of either amphotericine B and 5-fluorocytosine or amphotericine B and itraconazole would lead to better results. Nevertheless, the prognosis is still unfavorable, with a mortality rate of approximately 75%.

Comparative sensitivities of Sabin and Mahoney poliovirus type 1 prototype strains and two recent isolates to low concentrations of glutaraldehyde.

Significant intratypic differences in the glutaraldehyde (GTA) sensitivity of echovirus isolates have been shown. While exploring ways to optimize the study of GTA sensitivity of enteroviruses, we also observed intratypic differences in poliovirus type 1 isolates collected in France. A suspension procedure was used for assessing the virucidal effect of GTA at low concentrations (< or = 0.10%) against purified viruses. Two recent isolates of poliovirus type 1 tested were first fully characterized by the PCR restriction fragment length polymorphism (RFLP) test. The RFLP pattern of clinical isolate 5617 was similar to that of poliovirus type 1 LS-c, 2ab (Sabin strain), confirming the vaccine origin of strain 5617. The RFLP pattern of strain 5915 recovered from sewage was different from that of the Mahoney strain, suggesting a genetic variation in this wild isolate. We then analyzed under the same controlled conditions the GTA sensitivities of both isolates and their respective prototype strains. The wild Mahoney and 5915 strains exhibited significantly lower sensitivities to GTA than did the vaccine Sabin and 5617 strains. The inactivation rates of clinical isolates 5617 and 5915 were very similar to those of their corresponding reference Sabin and Mahoney strains. Both the conformational structure of the capsid of each strain and the amino acid constitution of structural polypeptides could be involved in the variations observed. The relevance of our comparative sensitivity studies to standardization of virucidal tests is discussed.

[Seroprevalence of markers of viral hepatitis A, B and C in hospital personnel at the Clermont-Ferrand University Hospital Center]. / Séroprévalence des marqueurs des hépatites virales A, B et C, parmi le personnel hospitalier du centre hospitalo-universitaire de Clermont-Ferrand.

OBJECTIVES: Evaluate risk of hepatitis A, B and C infection and anti HBV vaccination policy in hospital personnel. METHODS: A sample of 440 health care workers (7.5% of the personnel at the Clermont-Ferrand University Hospital) representing 74.5% people directly involved in health care and 25.5% other workers were selected at random and stratified by work classification and age. A questionnaire was used to establish personal data on viral hepatitis status and blood samples were drawn for serological tests. RESULTS: Seroprevalence for hepatitis A was 52% with no significant difference between health care and other workers. For hepatitis B, 88.3% of the population had been vaccinated and anti-HBs titre was > or = 10 mIU/ml for 91.6% and > or = 50 mIU/ml for 86.1%. Seroprevalence for anti-HBc was 7% and none of the subjects were positive for HBs antigen. Anti-hepatic C antibodies were found in 2 health care workers (0.7%). CONCLUSION: These findings emphasize the need to persue further preventive actions against hepatitis A, B and C and the requirement for continued efforts in elementary hygiene.

Replication of echo virus type 25 JV-4 reference strain and wild type strains in MRC5 cells compared with that of poliovirus type 1.

In echo virus type 25/JV-4 the shut off of host cell protein synthesis took significantly longer and the kinetics of the synthesis of viral proteins and viral RNA occurred much later than in the poliovirus. However, these characteristics impaired neither polyprotein processing nor virus production in the JV-4 strain. In contrast the two wild strains M.1262 and Th.222 had a lower virus yield than strain JV-4. The presence of a high Mr protein in the pattern of viral proteins of wild strains suggested that a defect in the polyprotein processing was responsible for the decreased virus yield. The infectious cycle of strain Th.222 differed from that of strains JV-4 and M.1262 in the rapid inhibition of host cell translation and the extent of viral protein synthesis. The sensitivity to actinomycin D was also investigated. Strain M.1262 was found to be insensitive. The virus yield of strains JV-4 and Th.222 was three- and fourfold lower respectively in the presence of actinomycin D. This sensitivity to the antibiotic was observed during viral RNA synthesis in strain JV-4 and during viral protein synthesis in strain Th.222. These results suggest that cellular factors are involved in the replication of echo virus type 25 strains in MRC5 cells.

Activity of glutaraldehyde at low concentrations against capsid proteins of poliovirus type 1 and echovirus type 25.

The activity of glutaraldehyde (GTA) against capsid proteins of poliovirus type 1 and echovirus type 25 was studied to understand the mode of action of this reagent against enteroviruses. The viruses were treated with GTA concentrations ranging from 0.005 to 0.10%. In the poliovirus particles, high-molecular-weight products were formed by 0.05% GTA, whereas in the echovirus particles, they were formed at 0.005% GTA. These products consist of complexes composed essentially of VP1 and VP3. There seemed to be differences in the composition of the complexes in the two viruses. Cross-linkings between the two polypeptides of the poliovirus capsid may be due to the accessibility to GTA of lysine residues on the loops of VP1 and VP3, which twist out from the surface of the shell.

Heterogeneity of capsid proteins of echovirus type 25 wild-type strain and prototype strain, studied by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting were used to compare the capsid proteins of 19 antigenic variants of echovirus type 25 wild-type strains isolated in France between 1976 and 1987 with those of the prototype JV-4 reference strain isolated in 1957. Immunoblots were developed by using polyclonal sera from rabbits and mice immunized with the reference strain. Immunoblotting patterns revealed reactivity only against viral protein VP1 for sera from both animals. Comparative immunoblotting patterns showed differences in the electrophoretic mobilities of viral protein VP1, especially for the Montpellier 76.1262 wild-type strain. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of [35S]methioinine-labeled viral polypeptides revealed that the two variant strains, Montpellier 76.1262 and Thionville 86.222, exhibited significant and reproducible shifts in the relative mobilities of VP1 and VP3 and, to a lesser extent, in those of VP0 and VP2. The relative mobility of VP4 seemed very similar for the JV-4 reference strain and the two variants. Interestingly, the structural differences in VP1 and VP3 of Montpellier 76.1262 were not correlated with the pattern of neutralization by monoclonal antibodies, unlike in our previous study, in which this strain differed from the prototype strain in only two epitopes. We concluded that, in addition to the heterogeneity of their biological and antigenic properties that we observed previously, echovirus type 25 wild-type strains may exhibit differences in their structural proteins.

Activity of glutaraldehyde at low concentrations (less than 2%) against poliovirus and its relevance to gastrointestinal endoscope disinfection procedures.

The activity of glutaraldehyde (GTA) at low concentrations (less than 2%) against poliovirus was assessed by a suspension procedure. The inactivation kinetics showed that concentrations of less than or equal to 0.10% were effective against purified poliovirus at pH 7.2; a 1 log10 reduction was obtained in 70 min with 0.02% GTA, and a 3 log10 reduction was obtained in 30 min with 0.10% GTA. GTA activity at low concentrations was greatly enhanced at alkaline pH, but was completely abolished at acid pH. In contrast, the inactivation assays on poliovirus RNA showed that it was highly resistant to GTA at concentrations up to 1.0% at pH 7.2. At pH 8.3 a low inactivation was noticed with 1.0% GTA. Our results are of relevance to hospital practice in digestive endoscopy investigations because there has been an increasing tendency to use low concentrations of GTA and very short contact times in disinfection procedures.

[Acute diarrhea associated viruses : An update]. / Virus associés aux diarrhées aiguës. Actualités en 1991.

Viruses recovered in stools are either cultivable viruses (enteroviruses, adenoviruses excepted type 40 and 41), or "fastidious" non cultivable viruses (rotaviruses adenoviruses 40 and 41, Norwalk, calcivirus, astrovirus, SRSV and SRV). Non cultivable viruses have been associated with many cases of diarrhea. Norwalk, two strains of calicivirus and SRV/SRSV, appear to be capable of causing outbreak. Rotavirus, astrovirus and most fastidious adenoviruses are associated with endemic spread. Specific or catch-all methods are used for diagnosis. Among the latter, electron microscopy is the most commonly used when the virus is recognizable and present in sufficient quantities. Small spherical viruses in the range 20-35 nm present greater difficulties. Polyacrylamide gel electrophoresis gives interesting epidemiological results for rotavirus. Specific methods are latex agglutination and enzyme immunoassays essentially for rotavirus and adenoviruses (all types or only 40 and 41). False positive results are few with well-designed kits. False negative results are seen in atypical strains and antigenic variants. In an outbreak, it is essential to make electron microscopic examinations. In individual cases, if no electron microscope is available, it is possible to make the diagnosis of rotavirus - and perhaps adenovirus 40 and 41 with a commercial kit. However a small number of stools contain more than one virus and they may act in synergy. In contrast many asymptomatic children may carry viruses.

[A simple and rapid method to test the permeability of condoms to viruses]. / Une méthode simple et rapide de contrôle de l'imperméabilité aux virus des préservatifs.

phi x 174 and T7 coliphages can be used to find out if condoms are virus-proof. Protection against hepatitis B virus or papillomavirus contamination is not assured when T7, a 65 nm broad virus, leaks through the condom. The simple test can be used to establish a quality control norm for condoms.