Journal of Clinical Virology - Articles in Press

Differential resistance to antiviral drugs in an immunocompromised patient with cytomegalovirus encephalitis - Corrected Proof

2010-09-01

Human cytomegalovirus (HCMV) infection is usually inapparent in normal individuals but can cause life-threatening diseases including interstitial pneumonitis, retinitis and meningoencephalitis in immunocompromised hosts. Treatment of these HCMV-associated diseases in immunocompromised patients frequently requires long-term use of antiviral agents such as ganciclovir and foscarnet, which may be associated with the emergence of drug-resistant HCMV strains. Here, we describe a 17-year-old Japanese girl who developed refractory immune thrombocytopenic purpura at the age of 4 years. Despite a series of treatments including steroid, intravenous immunoglobulin, vincristine, vinblastine, cyclosporine, azathioprine, splenectomy, and rituximab, her platelet counts remained low, resulting in 2 episodes of intracranial hemorrhage at the age of 12 and in hemoperitoneum at the age of 13. Due to the immunosuppressive conditions, she developed chronic HCMV viremia and HCMV gastroenteritis leading to recurrent gastrointestinal bleeding at the age of 14, that required multiple and prolonged courses of ganciclovir therapy. At the age of 16, resistance to ganciclovir was clinically suspected because of persistent fever and lack of virologic responses, and foscarnet therapy was initiated. However, the patient showed continued high HCMV viral loads (>106copies/mL) in the serum, developed fatal HCMV encephalitis, and died at the age of 17 despite combined use of ganciclovir and foscarnet as well as intravenous immune globulin. The dose of intravenous ganciclovir was 300mg/day (4.5mg/kg twice daily) at the time of cerebrospinal fluid (CSF) sample collection.

Laboratory evaluation of the new Access® cytomegalovirus immunoglobulin IgM and IgG assays - Corrected Proof

Pol Carlier, Nawal Harika, Ronald Bailly, Guido Vranken — 2010-08-30

Abstract: Background: Reliable laboratory methods for detecting congenital CMV infection are valuable since CMV infections are asymptomatic and because early detection is important for correct management and counseling of expectant mothers.Objectives: Compare the Beckman Coulter Access® method for the Unicel® DxI 800 analyzer with the bioMérieux VIDAS® method for two serological markers: CMV IgG and CMV IgM.Study design: Precision was determined with CLSI EP5-A2 protocol. Linearity of the Access CMV IgG was evaluated using selected high positive samples. Performance was assessed by testing non-selected pregnant women, frozen negative and positive samples with recent and old infections. Kinetics of the anti-CMV antibodies response was studied using samples from pregnant women with a recent infection. In a prospective study, 3992 pregnant women were screened for determining prevalence of a primo-infection and CMV IgM non-specific rate.Results: Total CV is lower than 10% and 12% for Access CMV IgG and CMV IgM. The IgG method is linear (R2=0.999) with recoveries between 85% and 108%. Correlation between Access and VIDAS CMV IgG is highly significant (P<0.001). Observed agreement was 97.4% for CMV IgG and 93.7% for CMV IgM. Relative sensitivity and specificity was 97.2% and 100% for IgG and 100% and 97.4% for IgM. Kinetics of the antibody response measured with Access methods is significantly higher (P<0.02) when compared with VIDAS and probably easier to interpret. Prevalence of a recent infection was 0.85% and CMV IgM non-specific rate was 2.9%.Conclusion: Good sensitivity and specificity and pronounced anti-CMV antibody response make the Access CMV IgG and IgM tests suitable for screening prenatal CMV infections.

Antiviral treatment for severe EBV infections in apparently immunocompetent patients - Corrected Proof

2010-08-27

Abstract: Background: Infectious mononucleosis usually runs a mild self-limiting course. Complications arise rarely and when so, corticosteroids are the mainstay of their treatment. The role of antivirals in the management of severe EBV infections is debatable.Methods: We sought to review the usage of antivirals for severe EBV infection in apparently immunocompetent patients. For this reason a search in PubMed and Scopus was performed for the time period from 1982 to 2009.Results: 45 patients with severe manifestations of infectious mononucleosis received antivirals (as an adjunct to steroids in 26 of them). Specifically 21 patients with CNS involvement (meningoencephalitis, cerebellitis), 4 with peripheral nervous system involvement (Guillain-Barré, myeloradiculitis, facial nerve palsy), 5 with hepatitis and 15 with other afflictions (including adult respiratory distress syndrome, thrombocytopenia, aplastic anemia, acute renal failure, ulcerations, myocarditis, and frosted branch vasculitis) received antiviral medications. Thirty-nine out of these 45 patients had a favourable outcome (27 were cured and 12 showed clinical improvement) while 6 patients died. The most commonly prescribed antiviral regimen was acyclovir monotherapy (35 patients). Three patients received combinations of acyclovir with other antivirals and 1 received famciclovir. Three patients received ganciclovir monotherapy, 1 ganciclovir plus foscarnet, 1 foscarnet and 1 vidarabine.Conclusion: The available data derive from case reports and case series and thus the deduction of conclusions regarding the effect, if any, of antiviral treatment is debatable. However, physicians may consider using antiviral agents in severe manifestations of EBV infections in immunocompetent patients as an adjunct to steroid treatment.

Clinical features of echovirus 6 and 9 infections in children - Corrected Proof

2010-08-23

Abstract: Background: Clinical features of echovirus 6 and 9 infections in children have not been comprehensively evaluated, particularly for sporadic cases.Objective: To describe the clinical features of children with echovirus 6 or 9 infections.Study designs: From 2000 to 2008, 199 children with culture-proven echovirus 6 or 9 infections identified in a university-affiliated hospital were included. Data extracted from 174 inpatients were further analyzed.Results: Age ranged from 4 days to 15 years with a mean of 4.7 years. 123 (62%) were male. The disease spectrums were similar for echovirus 6 (n=100) and 9 (n=74) infections, with aseptic meningitis (49% and 51%, respectively) being the most common syndrome, followed by meningismus, upper respiratory tract infection, pneumonia, and herpangina. All 174 inpatients had fever but the duration of fever was significantly longer in patient with echovirus 9 infection than those with echovirus 6 infections (6.0 days vs. 3.8 days, p<0.001). The rate of leukocytosis (leukocyte count>15,000/μL) were significantly higher in patients with echovirus 6 infections than those with echovirus 9 infection (p<0.001). One neonate with echovirus 6 infection died from hepatic necrosis with coagulopathy, and one infant with echovirus 6 infection and one child with echovirus 9 infection died from brain involvement. Two children had long-term sequelae of seizure disorder. The remaining 169 children (97%) recovered uneventfully.Conclusion: For children with echovirus 6 or 9 infections requiring hospitalization, aseptic meningitis was the most common manifestation and fatal outcome or long-term sequel, though rare, might occur.

Multicentric evaluation of two chemiluminescent immunoassays for IgG and IgM antibodies towards Rubella virus - Corrected Proof

2010-08-23

Abstract: Background: Screening and diagnosis of Rubella virus infection rely on testing for specific IgG and IgM. Immunoassays may yield different IgG results especially at low values, with difficulties in the evaluation of protective immunity. IgM levels decrease until negative a few weeks or months after acute infection, but individual and assay-related variability is common.Objectives: To evaluate the performance characteristics of the automated immunoassay for Rubella IgG and IgM on the Abbott ARCHITECT.Study design: Twelve laboratories from 7 different Italian regions assayed 6268 routine specimens, comparing qualitative results for IgG and IgM and quantitative for IgG with other widespread immunoassays. Prevalence data for IgG were disaggregated by patients’ group and by age in order to evaluate vaccination coverage.Results: Qualitative concordance for IgG was 97.3% vs. Abbott AxSYM, 95.0% vs. DiaSorin Liaison and 97.7% vs. Behring Enzygnost; ARCHITECT was more sensitive than Liaison and equivalent to the other assays, with a good correlation of IU/mL values with AxSYM (r=0.89). IgG prevalence was 87.1% among pregnant women, indicating a sub-optimal vaccine coverage. IgM reactivity was 1%, except in one site due to an outbreak. IgM concordance was 97.5% vs. Abbott AxSYM, 97.9% vs. DiaSorin Liaison and 97.7% vs. Behring Enzygnost; ARCHITECT was more specific than AxSYM.Conclusions: Our study confirms that in Italy Rubella vaccination coverage among pregnant women is insufficient. The new Rubella IgG and IgM assays on the ARCHITECT analyzer showed a good performance in comparison with other commercial methods. The results obtained and the good precision, indicate their suitability for routine testing.

Human rhinovirus C infections mirror those of human rhinovirus A in children with community-acquired pneumonia - Corrected Proof

2010-08-23

Abstract: Background: Human rhinoviruses (HRVs) are among the most common causes of community-acquired pneumonia (CAP) in children. However, the differential roles of the three HRV species HRV-A, HRV-B, and HRV-C in pediatric CAP are not fully understood.Objective: To determine the distribution of HRV species and their roles in children hospitalized with CAP in Beijing, China.Study design: Nasopharyngeal aspirates were collected between April 2007 and March 2008 from 554 children with a primary diagnosis of CAP. HRVs in the clinical samples were detected by RT-PCR and by sequencing. Infections with other respiratory viruses were identified by PCR.Results: HRVs were detected in 99 patients (17.87%). Among these patients, 51.52% tested positive for HRV-A, 38.38% for HRV-C, and 10.10% for HRV-B. HRVs were detected throughout the study period. The monthly distribution of HRV infections varied with HRV species. Median age, gender, symptoms, severity, and duration of hospitalization for single HRV-C infections were similar to those observed for single HRV-A infections. Co-infections with other respiratory viruses were detected in 57.58% of the HRV-positive children. HRV/RSV dual infections were correlated with a higher frequency of shortness of breath (HRV-A group, P2tail=0.01; HRV-C group, P2tail=0.015) and lower median ages (HRV-A group, P2tail=0.049; HRV-C group, P2tail=0.009).Conclusion: Our study shows that HRV-C strains circulate at a prevalence intermediate between HRV-A and HRV-B. The severity of clinical manifestations for HRV-C is comparable to that for HRV-A in children with CAP. These findings point to an important role of both HRV-A and HRV-C in pediatric CAP.

Risk of fetal hydrops and non-hydropic late intrauterine fetal death after gestational parvovirus B19 infection - Corrected Proof

2010-08-23

Abstract: Background: Risk assessment of parvovirus B19 (B19)-associated fetal complications following gestational B19 infection remains controversial.Objectives: To determine the risk of fetal hydrops or non-hydropic late intrauterine fetal death following acute maternal B19 infection at defined gestational weeks.Study design: Observational cohort study of pregnant women with serologic evidence of acute B19 infection. If available, fetal or neonatal tissue samples from cases complicated by fetal loss or hydrops were investigated for the presence of B19 DNA by polymerase chain reaction (PCR) and/or in situ hybridization (ISH).Results: Of 236 women with known pregnancy outcome, 228 had a live birth and 8 a fetal loss. The observed rate of fetal hydrops for all pregnant women was 4.2% (10/236) (95% confidence interval [CI], 2.1–7.7) and 10.6% (10/94) (95% CI, 5.2–18.7) for those infected between 9 and 20 weeks gestation. Tissue samples from 8 hydrops cases were investigated by PCR or ISH and all were B19 DNA positive. Fetal death occurring during or after gestational week 22 was only observed in one case which was associated with B19-derived fetal hydrops.Conclusions: Our findings demonstrate that although adverse fetal outcome is a rare complication of gestational B19 infection, a relevant risk of fetal hydrops exists particularly for women infected between 9 and 20 weeks’ gestation. Cases of B19-derived non-hydropic late intrauterine fetal death were not observed in the present study.

Use of antisera directed against dsRNA to detect viral infections in formalin-fixed paraffin-embedded tissue - Corrected Proof

2010-08-23

Abstract: Background: The detection of viral infection in paraffin-embedded, formalin-fixed tissue is notoriously difficult and often requires inherent knowledge about the specific virus being sought. For this reason, there is an ongoing need for reagents and methods which can identify a range of different virus types in paraffin embedded tissue.Objectives: The aim of this study was to optimise and validate the use of antisera directed against dsRNA (>50bp in length) in paraffin-embedded formalin-fixed tissue samples.Study design: dsRNA antisera were optimised for use in a range of virally-infected tissue culture cells, Coxsackie-infected mice and human tissues. The specificity of labelling was confirmed by pre-adsorption of antisera with poly-IC and by digestion of dsRNA with RNaseIII.Results: Two different polyclonal dsRNA antisera (J2 and K1) were capable of recognising dsRNA encoded by all the multiple different viral types (including (+) ssRNA viruses, dsRNA viruses and DNA viruses) tested in paraffin-embedded formalin fixed infected cells and tissues. In contrast, the enteroviral vp1 antisera detected only a subset of the (+) ssRNA viruses tested. Staining was not seen in uninfected cells or in uninfected control tissues. Positive staining was ablated following incubation of antisera with poly-IC or by pre-treating sections with RNaseIII prior to staining.Conclusions: The dsRNA antisera J2 and K1 are useful for the detection of viral infection in formalin-fixed, paraffin-embedded, human tissue samples.

Jaundice complicated by an atypical form of Guillain-Barré syndrome - Corrected Proof

Pavel Chalupa, Michal Holub — 2010-08-23

A 65-year-old male was admitted for a loss of strength he had suddenly developed in his upper limbs and partially in his lower limbs, pain in both shoulders, subicterus, dark urine and elevated serum values (total bilirubin (37μmol/L; range 0–20), ALT (32.09μkat/L; range 0–0.8), AST (8.54μkat/L; range 0–0.65)). His cognition was normal, meningeal phenomena negative, and cranial nerves and skin sensation normal. A neurological examination revealed paresis in all four extremities with prevalence on the left side with pronounced paresis of the plexus brachialis (Duchenne-Erb). The reflexes of the upper extremities were markedly weakened on both sides; mild proximal weakness was present on the right, and moderate weakness was present on the left. The reflexes of the lower extremities were diminished and there was a mild proximal weakness on the left side. The Babinski sign was negative. The patient's gait was very wide-based, and he could not squat without help. An examination of cerebrospinal fluid (CSF) a week after his admission demonstrated only a slight increase in the protein level (0.70g/L; range 0.2–0.6) and a marginally elevated number of lymphocytes (7/μL; range 0–5). The patient was examined repeatedly by a neurologist and only physiotherapy with hydrotherapy was recommended. Nerve conduction studies in the limbs were performed, and the findings were consistent with polyradiculoneuropathy.What could be the cause of this clinical condition?What further tests were indicated?What are the characteristic symptoms of GBS?What other diagnostic tests should be performed to clear up persisted peripheral type of quadruparesis?

Genetic correlation between current circulating H1N1 swine and human influenza viruses - Corrected Proof

2010-08-23

Abstract: Background: H1N1 is the main subtype influenza A virus circulating in human and swine population, and has long been a threat to economy and public health.Objective: To explore the genetic correlation between current circulating H1N1 swine and human influenza viruses.Study design: Three new H1N1 swine influenza viruses (SIVs) were isolated and genomes sequencing were conducted followed by phylogenetic and molecular analysis of all swine and human H1N1 influenza viruses isolated in China in the past five years.Results: Homology and phylogenetic analysis revealed that the three isolates possessed different characteristics: the genome of A/Swine/Shandong/1112/2008 was closely related to that of classical H1N1 SIV, while A/Swine/Shandong/1123/2008 was a reassortant with NS gene from the human-like H3N2 influenza virus and other genes from the classical H1N1 SIV, and A/Swine/Fujian/0325/2008 fell into a lineage of seasonal human H1N1 influenza viruses. Genetically, 2009 H1N1 influenza A viruses (2009 H1N1) in China were contiguous to the SIV lineages rather than the seasonal H1N1 human influenza virus's lineage. Furthermore, molecular analysis among human and swine influenza viruses provided more detail information for understanding their genetic correlation.Conclusions: These results suggested that in China in the past five years, the classical, avian-like and human-like H1N1 SIV existed in swine herds and the reassortment between H1N1 swine and H3N2 human influenza viruses was identified. In addition, the present data showed no evidence to support a strong correlation between the 2009 H1N1 and the swine influenza virus circulating in China.

Epidemiology of hand, foot, and mouth disease and genotype characterization of Enterovirus 71 in Jiangsu, China - Corrected Proof

2010-08-18

Abstract: Background: In the spring of 2008, an EV71-caused hand, foot, and mouth disease (HFMD) outbreak occurred in Fuyang city, Anhui Province, China. Jiangsu Province that borders Auhui to the east is presumed as a key station for the spread of EV71 to other regions of the Yangtze River Delta.Objectives: To investigate the HFMD prevalence in Zhenjiang city of Jiangsu from May 2008 to October 2009, and the epidemic origin of EV71 circulating in Jiangsu.Study design: During May 2008 and October 2009, a total of 6324 HFMD cases in Zhenjiang, Jiangsu, were investigated. Sixty throat specimens were randomly selected from different patients, and 28 nucleotide sequences of EV71 VP1 regions were successfully determined by RT-nested-PCR and sequencing. EV71 genotypes were characterized by phylogenetic analyses.Results: The incidence rate of HFMD was highest in the period of March–July and in the 1–4 years old age groups. Intriguingly, there was a slight predominance for boys and for children living in rural areas in HFMD infection. Phylogenetic analyses indicated that all Jiangsu EV71 strains and most China strains belonged to subgenotype C4a.Conclusion: The C4a was the most prominent EV71 subgenotype circulating in China. Routine HFMD surveillance should be focused on the period of March–July, and more prevention efforts should be aimed at 1–4 years old children. Moreover, government efforts are urgently needed to improve public health condition and medical service quality in rural areas.

Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV–HCV coinfected patient - Corrected Proof

2010-08-16

Abstract: Introduction: The efficacy of antiviral therapy with pegylated interferon (PEGIFN) plus ribavirin (RBV) in patients with HIV and hepatitis C virus (HCV) coinfection is limited. Intravenous silibinin (ivSIL), a milk thistle extract with proven antiviral effects represents a novel therapeutic strategy for virological nonresponders.Methods: We report a case of an HIV–HCV coinfected patient, who has not responded to a prior course of PEGIFN-α2a (180μg/week/s.c.) and RBV (1000mg/day/p.o.). Testing for IL-28β small nucleotid polymorphism revealed the nonfavourable genotype T/T. Antiretroviral therapy was not prescribed because the patients presented with well-preserved CD4+ cell counts and low HIV-RNA levels. She received retreatment with ivSIL for two weeks followed by PEGIFN/RBV combination therapy starting at week 1.Results: After 2 weeks of ivSIL therapy both HCV-RNA and HIV-RNA become undetectable. On ivSIL monotherapy we noticed a trend towards an increase of CD4+ cell counts and a decrease of HIV-RNA. After 16 weeks PEGIFN+RBV was discontinued due to patients wish because of adverse events. HCV-RNA was still negative 24 weeks after cessation of therapy, while HIV-RNA returned to baseline levels.Conclusion: ivSIL may represent a potential treatment option for retreatment of HIV–HCV coinfected patients nonresponding to PEGIFN+RBV combination therapy. Further investigations on the possible beneficial effects of ivSIL on CD4+ cell counts and HIV-RNA levels are necessary.

Evaluation of four molecular assays for detection of pandemic influenza A (H1N1) 2009 virus in the routine diagnostic laboratory - Corrected Proof

Katharina T. Troppan, Michael Bozic, Brigitte I. Santner, Harald H. Kessler — 2010-08-16

Abstract: Background: Detection and differentiation of influenza A viral RNA and influenza A (H1N1) 2009 viral RNA have gained significance because of their widespread community transmission.Objective: To study the accuracy and the performance of four molecular assays for the detection and differentiation of influenza A viral RNA and influenza A (H1N1) 2009 viral RNA in the routine diagnostic laboratory.Study design: The accuracy of the molecular assays was determined with reference material. For evaluation of the performance, 104 clinical specimens were studied. Sample preparation was done on a fully automated extraction instrument. For amplification and detection of influenza RNA, all molecular assays evaluated were based on real-time PCR.Results: When the accuracy was tested, the majority of assays yielded results as expected. When clinical samples were analyzed, 94 samples gave concordant results with all assays. One of the assays showed one false-negative result and another assay 10 false-negatives.Conclusion: The majority of assays evaluated in this study proved suitable for the detection and differentiation of influenza A viral RNA and influenza A (H1N1) 2009 viral RNA. All assays are easy to handle and provide results rapidly.

Prevalence and clinical characteristics of human CoV-HKU1 in children with acute respiratory tract infections in China - Corrected Proof

2010-08-12

Abstract: Background: Human CoV-HKU1 (HCoV-HKU1) has been isolated from a 71-year-old man with pneumonia; however, the impact and role of emerging HCoV-HKU1 have not been defined in children with acute respiratory tract infection (ARTI).Objective: To investigate the Prevalence and clinical characteristics of HCoV-HKU1 in children with ARTI in Lanzhou, China.Study design: The reverse transcription polymerase chain reaction (RT-PCR) or PCR was employed to screen HCoV-HKU1 and other common respiratory viruses in 645 nasopharyngeal aspirate (NPA) specimens collected from children with ARTI from November 2006 to October 2008. All PCR positive products were sequenced. And the demographic and clinical data were collected for all patients.Results: Nineteen of 645 (2.95%) specimens tested positive for HCoV-HKU1, and all HCoV-HKU1 positive specimens were distributed in the winter and spring season. The HCoV-HKU1 co-infection rate with other respiratory viruses was 47.37% (9/19). There was no statistically significant difference in the detection rate between groups by age or gender, except between patients with and without underlying diseases. The phylogenetic analysis indicated that HCoV-HKU1 genotype B was circulating in the years 2007 and 2008 in children with ARTI in Lanzhou, China.Conclusions: HCoV-HKU1 is an uncommon virus existing among Chinese children with ARTI. Children with underlying diseases are more vulnerable to viral infection. Only HCoV-HKU1 genotype B circulated locally.

Clinical severity of respiratory adenoviral infection by serotypes in Korean children over 17 consecutive years (1991–2007) - Corrected Proof

Jina Lee, Eun Hwa Choi, Hoan Jong Lee — 2010-08-09

Abstract: Background: Human adenoviruses (HAdVs) are important causes of acute respiratory tract illness in children.Objectives: To evaluate the risk factors for severe respiratory HAdV infections and the temporal change in case-severity in relation to HAdV types.Study design: From January 1991 to December 2007, respiratory HAdV infections of Korean children requiring hospitalization or an emergency room visit were included. An episode of HAdV infection requiring an intensive care unit stay, use of mechanical ventilation and/or death was designated as a severe infection. The medical records were reviewed retrospectively.Results: A total of 428 respiratory HAdV infections were included in the clinical analysis. The mean age of patients was 2.6 years. The most frequent diagnosis was a lower respiratory tract infection (312/428, 72.9%), and 44% of respiratory HAdV infections occurred in patients with underlying co-morbidities. Fifteen percent of clinical events resulted in severe HAdV infections with a case-fatality rate of 5.1%. HAdV types 7 and 8 were associated with severe infections, after adjusting for co-morbidity and the age of patients (adjusted OR 8.5 and 15.1, respectively, by a logistic regression model). The case-severity of HAdV-7 associated with lower respiratory tract infections has decreased over time, coinciding with the decreasing size of subsequent epidemics after a large outbreak (P for trend=0.003).Conclusions: HAdV types 7 and 8 were independent risk factors for severe respiratory HAdV infections. In addition, the overall severity of HAdV-7 associated lower respiratory tract infections has shown a decreasing trend, which may reflect increasing level of herd immunity.

Single cytomegalovirus strain associated with fetal loss and then congenital infection of a subsequent child born to the same mother - Corrected Proof

2010-08-04

Abstract: Background: Intrauterine transmission of cytomegalovirus (CMV) can occur even in CMV-seropositive mothers. Previous studies demonstrated re-infection with a newly acquired CMV strain during pregnancy had a major role in such transmission. Although reactivation of latently infected CMV is another plausible cause, no direct evidence has been documented.Objectives: We sought to identify the route(s) and maternal risk factor of CMV infection that occurred in consecutive pregnancies and resulted in symptomatic congenital infections.Study design: A newborn identified with congenital CMV infection in our newborn screening program developed hearing loss and subsequent nystagmus. The mother had a history of an elective abortion due to a severe fetal CMV infection 32 months prior to delivery of this newborn. We analyzed maternal serological changes and compared CMV genomic sequences in specimens obtained from the aborted fetus and the present case. We also analyzed immunological functions of the mother.Results: Our major findings were as follows: (1) the aborted fetus and the present case were infected with the same strain. (2) The congenital infection that resulted in the abortion was due to a primary infection. (3) CMV DNA was undetectable in the mother's blood from 3 months after the abortion. These results strongly suggested that maternal viral reactivation caused the congenital infection in the present case. However, we could not find impairment of immunological functions in the mother.Conclusions: Viral reactivation in an apparently immunocompetent mother can cause symptomatic congenital CMV infection.

Hepatitis E virus excretion can be prolonged in patients with hematological malignancies - Corrected Proof

2010-08-03

Abstract: Background: Hepatitis E virus (HEV) is transmitted via the fecal–oral route and locally acquired sporadic hepatitis E can occur in Western countries. Chronic hepatitis E virus infections have been recently described in solid organ transplant recipients. There is little data on the evolution of hepatitis E in patients immunocompromised for other reasons.Objectives: The aim of this study was to evaluate the clinical course of hepatitis E in patients immunocompromised because of hematological malignancies.Study design: Starting on November 2003, all patients in the Toulouse University Hospital Hematology Department with unexplained elevated transaminases were tested for hepatitis E using viral RNA detection in serum or stools and serology.Results: Acute hepatitis E was diagnosed in six middle-aged hematology patients. All cases were autochthonous. HEV strains were genotype 3. All patients had a significant increase of transaminases (6–95 upper limit normal) and only two had HEV IgG. Five patients were asymptomatic and one had jaundice. Transmission of HEV occurred between two patients who had overlapping stays in the hematology ward. All five evaluable patients ultimately cleared their HEV but viremia was prolonged over 6 months in three patients and specific treatment had to be postponed in two patients.Conclusion: Screening for HEV should be carried out routinely in hematology patients with elevated transaminases, and patient-to-patient transmission is a concern. Further studies are required to determine whether management of malignancy, particularly stem-cell transplantation should be adapted to HEV status.

Antiviral agents: To treat or not to treat? An old dilemma revisited in light of new data from the 2009 influenza A(H1N1) pandemic - Corrected Proof

Juan Martínez Hernández, Victoria López-Rodas, Eduardo Costas — 2010-08-02

Antiviral agents are essential tools in the control of influenza outbreaks. However, mass treatment with antivirals increases the frequency of resistant viruses. Consequently, considerable debate has arisen about the mass use of oseltamivir during the most recent influenza pandemic. The five most populated European countries followed different strategies. Germany and France prescribed mass treatment with oseltamivir, whereas the United Kingdom and Spain did not. The countries that prescribed the most antivirals showed significantly less mortality from pandemic influenza (). In spite of possible differences in the severity of the pandemic among these countries, was the mass use of oseltamivir the best option to prevent fatal cases?

Molecular analysis of human group A rotavirus G10P[14] genotype in Slovenia - Corrected Proof

2010-08-02

Abstract: Background: Rotavirus G10 genotype is one of the main rotaviruses circulating in cattle throughout the world but is also found in asymptomatic and symptomatic infections in children, and thought to be acquired through zoonotic transmission.Objectives: To determine the genetic diversity of G10P[14] rotavirus strains detected in various regions in Slovenia during a study on the molecular epidemiology of rotaviruses conducted in 2007.Study design: Five G10P[14] rotavirus strains detected in Slovenia in 2007 were subjected to sequencing and phylogenetic analysis of the genes encoding VP7, NSP4 and partial VP4 (VP8*) and VP6 rotavirus proteins.Results: Sequence and phylogenetic analysis of the four genes analyzed revealed a significant genetic diversity. Overall, the Slovenian G10P[14] are divided into two phylogenetic lineages.Conclusions: These results suggest that the G10P[14] strains found in Slovenian children did not emerge from a common source but possibly result of at least two independent zoonotic transmissions. Phylogenetic analysis and comparison with sequence data available in GenBank points towards a bovine origin to these strains.

Chikungunya fever in Singapore: Acute clinical and laboratory features, and factors associated with persistent arthralgia - Corrected Proof

M.K. Win, A. Chow, F. Dimatatac, C.J. Go, Y.S. Leo — 2010-08-02

Abstract: Background: In Singapore, the first local outbreak of chikungunya was reported in January 2008, followed by a larger outbreak occurred in August 2008. During the initial outbreak period, a strict containment strategy was adopted and all chikungunya PCR-confirmed cases were isolated and hospitalised at the designated national outbreak management centre.Objectives: To detail daily clinical and laboratory features of chikungunya cases during acute illness, and determine factors associated with persistent arthralgia at week 6.Study design: Prospective cohort study of patients with PCR-confirmed chikungunya infection and hospitalised within 5 days of illness onset, from 1st August to 10th November 2008. Post-hospital discharge, patients were followed up at the specialist outpatient clinic, and assessed for arthralgia at week 6 of illness.Results: Of the 97 patients in the study, the most common presenting symptoms were fever (89.7%) and arthralgia (87.6%). Mean nadir leukocyte and platelet counts were 3.5(SD 1.9)×109/L and 165(SD 42)×109/L respectively. Of the 39 patients who were evaluated at week 6, 14 (35.9%) had persistent arthralgia. Those with persistent arthralgia tended to be females (p=0.003), and had a lower peak creatinine level (p=0.036) than those without. Peak viral load (p=0.664), and duration of fever (p=0.056) and viremia (p=0.55) respectively, were not significantly different between those with persistent arthralgia and those without.Conclusions: This study details the daily clinical and laboratory features of chikungunya patients during acute illness. Those with persistent arthralgia tended to be females, who had significantly lower peak creatinine level.

Evaluation of the Xpert Flu A Panel nucleic acid amplification-based point-of-care test for influenza A virus detection and pandemic H1 subtyping - Corrected Proof

Shireen L. Jenny, Yaobi Hu, Pieter Overduin, Adam Meijer — 2010-08-02

Abstract: Background: Influenza antigenic point-of-care (POC) tests are too insensitive for individual reliable diagnosis of influenza virus infections without additional laboratory confirmation. Molecular POC tests could be a valuable alternative.Objectives: To evaluate the first influenza molecular POC test commercially available, the Cepheid Xpert Flu A Panel designed to simultaneously detect influenza A virus and subtype A(H1N1) 2009 pandemic virus, and compare it with in-house real-time RT-PCR (qRT-PCR).Study design: Clinical specimens positive for influenza virus and influenza virus isolates with different viral loads and of different type and subtype were used to determine the analytical reactivity and sensitivity. A panel of pathogen negative specimens and isolates of 19 different respiratory pathogens were used to determine the analytical specificity.Results: Except A(H9N2) virus the Xpert Flu A Panel detected A(H1N1) seasonal and 2009 pandemic, A(H3N2), A(H5N2), A(H5N1) and A(H7N7) viruses and correctly subtyped A(H1N1) 2009 virus. Analytical sensitivity was similar to qRT-PCR in the range of 400–5000 viral particles per ml. However, of most subtypes some specimens with cycle threshold values greater than 30 in qRT-PCR and A(H1N1) 2009 specimens with inconsistent results in the qRT-PCR due to primer or probe mismatches were not detected in the Xpert Flu A Panel. Analytical specificity was 100%.Conclusions: The Xpert Flu A Panel is the first commercially available POC molecular test for detection of influenza A virus and determination of the H1 2009 subtype and is analytically reasonable sensitive compared with qRT-PCR and highly specific and therefore a welcome alternative to antigenic POC tests.

Transmission of pandemic influenza A (H1N1) 2009 within households: Edmonton, Canada - Corrected Proof

2010-07-30

Abstract: Background: In April 2009, a novel influenza A, subtype H1N1, now referred to as the Pandemic (H1N1) 2009 virus (pH1N1), began circulating in countries around the world. Describing the transmission characteristics of this novel influenza A virus is important to predict current, and future, disease spread. The Public Health response to the first wave of pH1N1 in Alberta focused on the identification and management of secondary cases within households.Objectives: The purpose of this study was to describe transmission characteristics of pH1N1 in households in Edmonton, the capital city of Alberta, during the first wave, and to identify the serial interval and secondary attack rate (SAR) in this setting.Study Design: This is a prospective analysis of pH1N1 household transmission within 87 urban Canadian households between April 30 and June 9, 2009; with each household having at least one laboratory-confirmed case. The secondary attack rate was calculated in the 262 household contacts using a weighted average by number of susceptible individuals in each household. The serial interval, or time to illness in secondary cases, was analyzed using survival analysis with a Weibull model.Results: Within the 87 households, 42 (48.3%) had no secondary cases develop; 25 (28.7%) had one secondary case develop; and 20 (22.9%) had more than one secondary case develop. The secondary attack rate did not decrease with increasing household size and households with two members exhibited the lowest secondary attack rate at 14.1%. Children under the age of 19, and individuals with an underlying medical condition, were at increased risk (p<0.05) of becoming a secondary case. The overall secondary attack rate among the 262 susceptible household contacts was 30.2% (95% CI: 12.6–52.2). The median serial interval for pH1N1 transmission was 3.4 days (95% CI: 2.9–3.9).Conclusions: The identified transmission characteristics of pH1N1 among Canadian households differ slightly from other previously reported North American estimates, but are in keeping with historical transmission rates of pandemic influenza viruses.

A comparative study of Merkel cell, BK and JC polyomavirus infections in renal transplant recipients and healthy subjects - Corrected Proof

Mohamed I. Husseiny, Bishoy Anastasi, Jennifer Singer, Simon F. Lacey — 2010-07-28

Abstract: Background: Merkel cell carcinoma (MCC) is a rare skin cancer associated with immunosuppression and the integration of Merkel cell polyomavirus (MCPyV) DNA into the tumor cell genome. Little is known about the natural history of MCPyV infection.Objectives: To investigate the presence of MCPyV, BK and JC polyomaviruses in serum and urine from immunosuppressed kidney transplant patients (KTx) and a control group of normal volunteers.Study design: Quantitative real-time PCR (q-PCR) was used to assess MCPyV, BKV and JCV viral load in urine and serum samples collected from normal donors (Group A), prospectively enrolled KTx patients (Group B) and from KTx with documented BK reactivation and/or nephropathy (Group C).Results: Low levels of MCPyV viruria was seen in 15% of the subjects in Group A, 30% of Group B, and was not detected in Group C. No individuals in the study developed MCPyV viremia. BK viruria was seen in 5% of Group A, 30% of Group B, and 100% of Group C. Consistent with previous reports, the mean BKV urinary load was significantly higher in immunosuppressed patients compared to non-immunosuppressed controls and also higher in urine compared to serum samples.Conclusions: Like BKV and JCV, MCPyV is likely a common infection in adult humans. Low level shedding of MCPyV in urine was similar in immunosuppressed organ transplant recipients to non-immunosuppressed subjects. However, MCPyV was not detected and JCV was infrequent in samples from KTx patients with clinical BKV reactivation.

Chikungunya and dengue virus antibodies in a traveller with severe arthralgia returning from India - Corrected Proof

2010-06-21

A 42-year-old Caucasian woman presented to a travel clinic in Germany with sore throat, fatigue, myalgia, and severe arthralgia of the hands, elbows, shoulders, hips, knees, and feet. Swellings of the hands and feet had developed () and the patient was barely able to walk upright. She had returned 1 day before from a 2-week stay in Bangalore, India, where she had worked as a teacher. Headache and fever had been the first symptoms 11 days before, which had been followed by myalgia, joint pain and a rash 1 and 2 days later, respectively. The maculo-papular rash had initially covered the legs, and later the trunk and arms. By the time of presentation to the travel clinic the rash was no longer visible, and headache and fever had disappeared (). There was unilateral submandibular lymphadenopathy, and the throat looked slightly inflamed. C-reactive protein (CRP) level was 0.70mg/dl (normal level <0.5mg/dl), lactate dehydrogenase level was 293U/l (normal <248U/l). Full blood count showed a normal leukocyte count of 6600cells/μl with 23% lymphocytes (normal 25–50%), 11% monocytes, and 64% granulocytes. Liver function tests revealed normal gamma-GT and GPT activities, but GOT levels were elevated (35U/l, normal <27U/l). Serum electrophoresis showed no abnormalities, and tests for cryoglobulinaemia were negative (paired cold and warm ESR, and agglutination). Indirect immunofluorescence assay (IFA) for dengue virus immunoglobulin (Ig) G was positive with a titer of 1:10,240 (cut-off 1:20), and dengue virus IgM-ELISA was negative. Qualitative ELISA specific for chikungunya virus IgG and IgM (Novatec, Dietzenbach, Germany) was positive and quantitative IFA for chikungunya virus IgG and IgM was also positive with a titer of 1:1280 and 1:640, respectively.Acute chikungunya virus infection and/or dengue fever was suspected here.What is your interpretation of the test results?

The importance of being earnest: Following up a low level hepatitis B surface antigen (HBsAg) result - Corrected Proof

2010-06-07

A 24 yr old Lithuanian woman (LA) resident in Ireland presented to the antenatal service of her local (regional) hospital for the first time at 36 weeks gestation in July 2008. Blood was drawn (sample date 08/07) and sent to the National Virus Reference Laboratory (NVRL) for antenatal screening for evidence of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). The sample was weakly positive in the HBsAg Abbott Architect (reading/cut-off: 0.29/0.05) and was confirmed by neutralization in the Abbott Murex HBsAg assay. No other marker of HBV infection (including HBV e antigen (HBeAg), e antibody (anti-HBe), HBcIgM, and anti-HBc) was detected. HIV and HCV serological results were negative.What is your interpretation of these results?What further investigations are indicated?How would you treat this lady's newborn baby?

Transmitted drug resistance and type of infection in newly diagnosed HIV-1 individuals in Honduras - Corrected Proof

2010-04-23

Abstract: Background: Transmitted drug resistance (TDR) reduces the efficacy of antiretroviral treatment and is a public health concern.Objectives: To gain insight in the epidemiology of TDR in Honduras by evaluating the amount of TDR in a representative sample of newly diagnosed individuals and by determining whether these are recent or established infections.Study design: Two hundred treatment-naïve, newly diagnosed HIV-positive individuals representing different population groups (general population, Garifunas ethnic group, female sex workers and men who have sex with men) and different geographic regions were enrolled during April 2004–April 2007. The HIV-1 pol gene was sequenced to identify drug-resistant mutations and TDR was scored as recommended by the WHO. Infections were classified as recent or established using the BED assay.Results: Among 200 samples analyzed from Honduran patients the prevalence of TDR was 7% (95% CI: 3.9–11.5%), 5% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3% for nucleoside reverse transcriptase inhibitors (NRTIs) and 0.5% for protease inhibitors (PIs). Testing of these samples with the BED assay revealed that 12% of the patients were recently infected. TDR was significantly more common in patients with recent infection (21%) than established infection (5%) (p=0.016).Conclusions: The prevalence of TDR in Honduras was moderate (7%). The percentage of patients who were recently infected was low (12%), suggesting that late HIV diagnosis is common. The TDR prevalence was higher in recent than in established infections, which may indicate that TDR is increasing over time. The higher prevalence of NNRTI and NRTI mutations as compared to PI mutations is probably due to a broader and longer use of these drugs in Honduras.

WITHDRAWN: Viral Hepatitis: global goals for vaccination - Corrected Proof

Daniel Lavanchy — 2009-07-06

This article has been withdrawn at the request of the author. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.