Christopher Payan

Prevalence of rotavirus, adenovirus, norovirus, and astrovirus infections and coinfections among hospitalized children in northern France.

ABSTRACT From January to December 2007, 973 stool specimens were prospectively collected from children hospitalized for gastroenteritis signs or from neonates and premature cases who were born in two French hospital settings in the north of France. They were tested by rapid enzyme immunoassay (EIA) analyses for rotavirus and adenovirus and by two commercially available ELISA tests for the detection of norovirus and astrovirus. The overall rates of prevalence for rotavirus, norovirus, adenovirus, and astrovirus were 21, 13, 5, and 1.8%, respectively, and they did not significantly differ between the two hospital settings (P = 0.12). Mixed virus infections were detected in 32 (3.3%) of the 973 study children and were associated with norovirus in 21 (66%) infants, including 5 premature cases. From fall to spring, norovirus infections accounted for 52% of documented gastroenteritidis viral infections at a time when rotavirus was epidemic, resulting in mixed norovirus and rotavirus gastrointestinal tract infections. Of the 367 documented viral gastroenteritis cases, 15 (4.1%) were identified as nosocomial infections, 5 of which occurred in premature cases. These findings highlight the need to implement norovirus and astrovirus ELISA detection assays in association with rapid EIA rotavirus and adenovirus detection assays for the clinical diagnosis and the nosocomial prevention of gastroenteritis viral infections in pediatric departments.

Vascular Thrombosis and Acute Cytomegalovirus Infection in Immunocompetent Patients: Report of 2 Cases and Literature Review

Acute cytomegalovirus (CMV) infection in immunocompetent patients is common worldwide, with seroprevalence rates of 40%-100%, depending on the country, socioeconomic conditions, and the patients age. Infection is most often asymptomatic, but acute cytomegalovirus infection is occasionally revealed by prolonged fever, cervical lymphadenitis, and arthralgia, and it is more rarely revealed by pneumonia, myocarditis, pericarditis, colitis, and hemolytic anemia. Here, we report 2 cases of acute CMV infection in nonimmunocompromised adults that were complicated by venous thrombosis with pulmonary embolism. We also review previously reported cases of vascular thrombosis and discuss the propensity of CMV to induce vascular damage with associated thrombosis.

Human Papillomavirus Quantification in Urine and Cervical Samples by Using the Mx4000 and LightCycler General Real-Time PCR Systems

ABSTRACT During the last decade, growing efforts have focused on human papillomavirus (HPV) detection using liquid hybridization, conventional PCR, and real-time PCR-based methods to increase the overall proportion of patients participating in cervical cancer screening procedures. We proposed a new general HPV DNA real-time PCR on the Mx4000 (Stratagene) and LightCycler (Roche Diagnostics) systems usable for both cervical scrape specimens and urine samples. A linear range was obtained from 5 DNA copies to 8 log10 DNA copies/ml, and intra- and interassay variations were between 1.8 and 4%. Cervical carcinoma and HPV DNA screening was performed in 333 individual women referred for gynecological examination at the university hospitals of Angers and Brest and enrolled in the PapU study. Among cervical specimens (n = 333), 45% were positive for HPV DNA, with a mean viral load at 5.00 log/ml (± 1.73). Among urine samples (n = 177), 37% were positive with a significant 50-fold-lower mean viral load (3.77 ± 1.32 log/ml; P < 0.0001). Kappa agreement for HPV DNA between cervical and urine specimens was excellent (93%). Thus, we developed a highly sensitive and quantitative general HPV DNA real-time PCR method that allows mass screening of patients with HPV infection. The ongoing longitudinal and prospective multicenter PapU study should give us the opportunity to validate this method adapted to HPV DNA screening in urine samples in a larger population.

Rapid and early virological response to chronic hepatitis C treatment with IFN α2b or PEG-IFN α2b plus ribavirin in HIV/HCV co-infected patients

Background and aims: An algorithm based on a 2 log10 decline in hepatitis C virus (HCV) RNA at week (W) 12 has been proposed in US and European recommendations for the management of patients with chronic hepatitis C treated with pegylated-interferon and ribavirin. Methods: We examined rapid virological response (RVR; at W2 and W4 after the initiation of therapy) in HIV/HCV co-infected patients. Using HCV RNA measurements (Versant HCV RNA 3.0, Cobas Amplicor HCV 2.0), RVR was studied in 323 patients from the ANRS HC02 RIBAVIC trial, comparing interferon α2b 3 MU ×3/week with pegylated interferon α2b 1.5 μg/kg/week, each combined with ribavirin 800 mg/day over 48 weeks. Results: The best positive and negative predictive values of sustained virological response (SVR) were obtained with an undetectable HCV RNA at W4 (97%) and with more than a 2 log10 decrease at W12 (99%), respectively. Prediction of non-SVR was obtained in all patients by using HCV RNA cut-off levels above 460 000 IU/ml at W4 and above 39 000 UI/ml at W12 irrespective of the HCV genotype and arm of treatment. Conclusion: We propose a new algorithm based on RVR thresholds using HCV RNA that allows for excellent prediction of non-SVR as early as W4.

Influence of the HCV subtype on the virological response to pegylated interferon and ribavirin therapy.

The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95–0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7–5.0; P < 0.01), absence of HIV co‐infection (OR: 2.08; 95% CI = 1.2–3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2–2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0–2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1–3.8; P = 0.03). In conclusion, among difficult‐to‐treat genotypes, the subtype 1a is associated with a lower response to anti‐HCV therapy than subtypes 1b, 4a, and 4d. J. Med. Virol. 81:2029–2035, 2009.

Antiviral effect of ribavirin in early non-responders to interferon monotherapy assessed by kinetics of hepatitis C virus RNA and hepatitis C virus core antigen.

BACKGROUND/AIMS To evaluate the efficacy of ribavirin, given in second intention in non-responders to interferon alone, by studying viral kinetics. METHODS We conducted a trial including 203 patients with chronic hepatitis C, naïve of treatment. Patients were treated with interferon three times a week with or without ribavirin and amantadine according to response. Viral kinetics were assessed by serial measurements of HCV RNA (bDNA 3.0 and Monitor 2.0) and a new assay, trak-C, able to quantify total Hepatitis C virus (HCV) core antigen. RESULTS A significant initial drop in HCV RNA or HCV core antigen, under interferon alone, was associated with response to therapy, -4.85+/-1.33 log for HCV RNA in sustained responders versus -1.86+/-1.53 log for others groups, P<0.001. In patients receiving ribavirin in second intention, we also observed a similar drop in HCV RNA and HCV core antigen, predictive of sustained response, -2.67+/-1.26 log for HCV RNA in sustained responders versus -0.44+/-0.49 log in non-responders, P<0.001. CONCLUSIONS Ribavirin has probably an additional antiviral effect in interferon treated patients. Kinetics of HCV RNA and HCV core antigen under treatment are highly predictive of a sustained virological response.

Non-O1, non-O139 Vibrio cholerae bacteraemia in a cirrhotic patient.

Vibrio cholerae serogroups O1 or O139 are the aetiological agents of cholera. The pathogenicity of non-O1, non-O139 V. cholerae is less well known. These worldwide bacteria are responsible for gastrointestinal infections or, more rarely, bacteraemia in patients with an underlying disease, leading to life-threatening complications. We report a case of non-O1, non-O139 V. cholerae bacteraemia due to a haemolytic strain in a cirrhotic patient. Early antibiotherapy allowed a good outcome. The aim of this case report is to underline the virulence of non-choleragenic Vibrio strains, possibly linked to haemolysin production, and the potential danger of consuming undercooked seafood or exposing wounds to sea water in cirrhotic patients.

Fatal Case of Enterovirus 71 Infection, France, 2007

A fatal case of enterovirus 71 infection with pulmonary edema and rhombencephalitis occurred in Brest, France, in April 2007. The virus was identified as subgenogroup C2. This highly neurotropic enterovirus merits specific surveillance outside the Asia-Pacific region.

Mucosal humoral immune response to hepatitis C virus E1/E2 surface glycoproteins and HCV shedding in saliva and cervicovaginal fluids from chronically HCV-infected patients

BACKGROUND/AIMS We herein focused on identifying biological factors possibly involved in non-parenteral transmission of hepatitis C virus (HCV), such as HCV excretion patterns and antibody-based immunity to the virus in saliva and/or cervicovaginal secretions (CVS). METHODS Paired blood, saliva and cervicovaginal lavage samples were obtained from HCV-RNA plasma-positive hemoglobin (Hb) antigen and HIV-seronegative, HCV-seropositive males (n=13) and females (n=21). HCV-specific antibodies were detected by ELISA in paired samples, and HCV-RNA was detected in cell-free and cell-associated body fluids. RESULTS Antibodies to E1 HCV surface glycoprotein of the IgG and IgA isotypes showed similar, but less pronounced, profiles as IgG and IgA to E2. HCV-specific IgG and IgA in mucosal fluids likely originated predominantly from the systemic compartment, because HCV-specific mucosal immunoglobulins involved primarily monomeric antibodies, including monomeric IgA, and because their specific activities for HCV antigens in corporeal fluids were similar to those in paired serum (Se). Viral shedding in saliva or CVS was restricted to cell-associated, non-replicating strand((+)) HCV-RNA in 42% (12 out of 28) of saliva and in 19% (four out of 21) of cervicovaginal fluids. CONCLUSIONS The association in body fluids of HCV-specific IgG, and to a lesser extent IgA, directed to E1/E2 surface glycoproteins (which may block critical steps of virus-cell interactions), of undetectable free viral RNA, and of occasional non-replicating cell-associated HCV, suggests a resulting poor infectivity of saliva or cervicovaginal fluid in chronically HCV-infected individuals. Taken together, these observations provide the basis for the low risk of non-parenteral transmission of HCV infection.

Measures to improve microbial quality surveillance of gastrointestinal endoscopes.

BACKGROUND AND STUDY AIM Infectious outbreaks associated with the use of gastrointestinal endoscopes have increased in line with the spread of highly resistant bacteria. The aim of this study was to determine the measures required to improve microbial quality surveillance of gastrointestinal endoscopes. METHODS We reviewed the results of all microbiological surveillance testing of gastrointestinal endoscopes and automatic endoscope reprocessors (AERs) performed at Brest Teaching Hospital from 1 January 2008 to 1 June 2015. We analyzed the influence of the time of incubation on the rate of positive results using the Kaplan - Meier method. We also studied risk factors for gastrointestinal endoscope contamination using a multivariable logistic regression model. RESULTS Over the study period, 1100 microbiological tests of gastrointestinal endoscopes (n = 762) and AERs (n = 338) were performed. A total of 264 endoscope tests (34.6 %) showed a level of contamination higher than the target. After 2 days of incubation, contamination was apparent in only 55.5 % of the endoscopes that were later shown to be contaminated (95 % confidence interval [CI] 49.2 - 61.8). Multivariable analysis showed that the use of storage cabinets for heat-sensitive endoscopes significantly reduced the risk of endoscope contamination (odds ratio [OR] 0.23, 95 %CI 0.09 - 0.54; P  < 0.001) and that the use of endoscopes older than 4 years significantly increased this risk (OR ≥ 6 vs. < 2 years 2.92, 95 %CI 1.63 - 5.24; P < 0.001). CONCLUSIONS Microbiological culture technique, mainly incubation duration, strongly influenced the results of endoscope sampling. Samples should be cultured for more than 2 days to improve the detection of contaminated endoscopes. Particular attention should be paid to endoscopes older than 2 years and to those that are not stored in storage cabinets for heat-sensitive endoscopes.