Showing papers in "Journal of Medical Virology in 2014"
TL;DR: The serological test suggested the possible involvement of HCoV‐229E in the development of Kawasaki disease as well as immunofluorescence assays and virus neutralizing tests revealed no difference in seropositivity between the acute and recovery phases of patients with Kaw Osaka disease.
Abstract: Although human coronavirus (HCoV)-NL63 was once considered a possible causative agent of Kawasaki disease based on RT-PCR analyses, subsequent studies could not confirm the result. In this study, this possibility was explored using serological tests. To evaluate the role of HCoV infection in patients with Kawasaki disease, immunofluorescence assays and virus neutralizing tests were performed. Paired serum samples were obtained from patients with Kawasaki disease who had not been treated with γ-globulin. HCoV-NL63 and two antigenically different isolates of HCoV-229E (ATCC-VR740 and a new isolate, Sendai-H) were examined as controls. Immunofluorescence assays detected no difference in HCoV-NL63 antibody positivity between the patients with Kawasaki disease and controls, whereas the rate of HCoV-229E antibody positivity was higher in the patients with Kawasaki disease than that in controls. The neutralizing tests revealed no difference in seropositivity between the acute and recovery phases of patients with Kawasaki disease for the two HCoV-229Es. However, the Kawasaki disease specimens obtained from patients in recovery phase displayed significantly higher positivity for Sendai-H, but not for ATCC-VR740, as compared to the controls. The serological test supported no involvement of HCoV-NL63 but suggested the possible involvement of HCoV-229E in the development of Kawasaki disease.
78 citations
TL;DR: The detection of rare types of EVs are circulating in human populations inconspicuously and one of their transmission modes could be the consumption of contaminated oysters, indicating a high prevalence of NoV infection associated with the Consumption of raw or under‐cooked oysters.
Abstract: Enteric viruses are an important cause of viral food-borne disease. Shellfish, especially oysters, are well recognized as a source of food-borne diseases, and oyster-associated gastroenteritis outbreaks have on occasion become international occurrences. In this study, 286 fecal specimens from 88 oyster-associated gastroenteritis outbreaks were examined for the presence of 10 human enteric viruses using antigenic or genetic detection methods in order to determine the prevalence of these infections. All virus-positive patients were over 18 years old. The most common enteric virus in outbreaks (96.6%) and fecal specimens (68.9%) was norovirus (NoV), indicating a high prevalence of NoV infection associated with the consumption of raw or under-cooked oysters. Five other enteric viruses, aichiviruses, astroviruses, sapoviruses, enteroviruses (EVs), and rotavirus A, were detected in 30.7% of outbreaks. EV strains were characterized into three rare genotypes, coxsackievirus (CV) A1, A19, and EV76. No reports of CVA19 or EV76 have been made since 1981 in the Infectious Agents Surveillance Report by the National Infectious Diseases Surveillance Center, Japan. Their detection suggested that rare types of EVs are circulating in human populations inconspicuously and one of their transmission modes could be the consumption of contaminated oysters. Rapid identification of pathogens is important for the development of means for control and prevention. The results of the present study will be useful to establish an efficient approach for the identification of viral pathogens in oyster-associated gastroenteritis in adults.
72 citations
TL;DR: It is concluded that that the diagnosis of viral hepatitis should be based on clinical features, raised transaminases, serology, and confirmatory PCR testing, indicating that serology is unreliable in the diagnoses of acute viral hepatitis.
Abstract: Hepatitis E virus (HEV) infection is an important public health concern as a major cause of enterically-transmitted hepatitis worldwide. The detectable window of viraemia is narrow, and HEV IgM and IgG rise simultaneously in acute infection. Furthermore, previous investigators have shown HEV IgM false positive reactions occur against EBV, CMV and potentially hepatitis A. A retrospective analysis of HEV serology testing was performed at a London tertiary referral hospital over a 3-year period. A thousand four hundred and twenty three serum samples were tested for HEV serology, with 33 samples HEV IgM positive and 28 HEV IgM equivocal. One hundred and eleven samples were HEV IgG positive but IgM negative suggesting past infection. No patients with HEV IgM positivity had false positive reactions against hepatitis A. A high degree of EBV and CMV cross reactivity was noted, with 33.3% and 24.2% of HEV IgM positive samples also testing positive for EBV and CMV IgM, respectively. HEV RNA was detected in four HEV IgM positive samples, indicating true positivity, although three demonstrated cross reactivity against EBV. Only 13.3% of samples with positive HEV IgM were HEV PCR positive, highlighting a low positive predictive value of serology testing. Overall a high level of HEV, EBV and CMV IgM cross reactivity was demonstrated, indicating that serology is unreliable in the diagnosis of acute viral hepatitis. It is concluded that that the diagnosis of viral hepatitis should be based on clinical features, raised transaminases, serology, and confirmatory PCR testing.
67 citations
TL;DR: The findings revealed that acute phase of CHIKV infection is characterized by predominant inflammatory responses mediated by IL‐6, IL‐8, IP‐10, MCP‐1, and MIG, and these chemokines might serve as targets for theDevelopment of treatment to ameliorate the symptoms during the acute phase and prevent the development of chronic manifestations.
Abstract: Chikungunya (CHIKV) is an emerging arboviral infection of public health concern in India contributing to widespread morbidity. The precise molecular events occurring early in the infection have not been well understood. Cytokines/chemokines are suspected to play a key role in its pathogenesis. Very few studies have correlated the plasma levels of cytokines/chemokines with diagnostic markers such as viral loads and presence of CHIKV IgM antibodies. Understanding these dynamics in the early phase of CHIKV infection is likely to provide an insight into the evolution of the immune response, identify biomarkers for assessing severity, and for development of newer therapeutic strategies. This study was therefore undertaken to estimate the levels of various cytokines/chemokines in plasma samples of patients infected with CHIKV and correlate to viral load and CHIKV IgM antibodies. Cytokine/chemokine levels and viral loads in plasma were measured using cytometric bead array and TaqMan real time PCR assay, respectively. The findings revealed that acute phase of CHIKV infection is characterized by predominant inflammatory responses mediated by IL-6, IL-8, IP-10, MCP-1, and MIG (P < 0.003). Plasma levels of IL-6 (r = 0.53, P < 0.05) and MCP-1 (r = 0.83, P < 0.05) emerged as reliable biomarkers of high viral loads in Chikungunya patients. Further, presence of elevated levels of MCP-1 and MIG during the chronic phase of the disease suggests that these chemokines may contribute to perpetuation of symptoms. Hence, these chemokines might serve as targets for the development of treatment to ameliorate the symptoms during the acute phase and prevent the development of chronic manifestations. J. Med. Virol. 86:1393–1401, 2014. © 2014 Wiley Periodicals, Inc.
66 citations
TL;DR: Both NV and SMV were shed in stools for up to 3 weeks after the resolution of symptoms, but long shedding durations were more common in NV infections, and shedding titers and patterns were not correlated with subject demographics or clinical course.
Abstract: Norovirus is the most common cause of acute infectious gastroenteritis, causing approximately 21 million cases annually in the USA. The virus is highly contagious and resistant to decontamination, making outbreaks difficult to control. To facilitate the development of better control methods, this study characterized the viral shedding patterns in stools from subjects experimentally infected with genogroup I or II norovirus. Viral stool titers were determined by quantitative real-time RT-PCR for all stools produced in the first 7 days post-challenge and representative stools through day 35 post-challenge. The shedding titers and disease course were analyzed with respect to virus type, illness, and subject demographics. Infection with GII.2 Snow Mountain (SMV) resulted in more symptoms and a higher frequency of painful symptoms compared to GI.1 Norwalk (NV) infection. However, NV infection produced stool viral titers approximately 2 logs higher than those seen in SMV infections. Both NV and SMV were shed in stools for up to 3 weeks after the resolution of symptoms, but long shedding durations were more common in NV infections. For each challenge virus, shedding titers and patterns were not correlated with subject demographics or clinical course. This is the first study to report shedding dynamics in experimental GII norovirus infection.
66 citations
TL;DR: Sputum would benefit for the detection of respiratory viruses by nucleic acid amplification tests (NAATs) in patients who produce sputum, and further studies are needed to establish standardized RNA extraction methods from Sputum samples.
Abstract: Diagnostic tests for respiratory viral infections use traditionally either nasopharyngeal washes or swabs. Sputum is representative of the lower respiratory tract but is used rarely for viral testing. The aim of this study was to compare the detection rates of respiratory viruses from nasopharyngeal swabs and sputum using a multiplex real-time reverse transcription-polymerase chain reaction (RT-PCR). Adults who were admitted or presented to the clinics of Gil Medical Center with acute respiratory symptoms were recruited from 1 November 2012 to 31 March 2013. Paired specimens of nasopharyngeal swabs and sputum were obtained from 154 subjects, and RNA was extracted and tested for 16 different respiratory viruses using the Anyplex II RV16 Detection kit (Seegene, Seoul, Korea). The positive rate was 53% (81/154) for nasopharyngeal swabs and 68% (105/154) for sputum (P < 0.001). One hundred thirty-four viruses were identified for 107 illnesses. Influenza A virus, RSV A, HRV, coronavirus OC43, and adenovirus were detected more frequently in sputum samples than in nasopharyngeal swabs (P < 0.001). Importantly, 12 of 44 (27%) influenza A infections and 11 of 27 (41%) RSV infections were positive in only sputum samples. The detection rates of respiratory viruses from sputum samples were significantly higher than those from nasopharyngeal swabs in adults using real-time multiplex RT-PCR. These findings suggest that sputum would benefit for the detection of respiratory viruses by nucleic acid amplification tests (NAATs) in patients who produce sputum. Further studies are needed to establish standardized RNA extraction methods from sputum samples. J. Med. Virol. 86:2122–2127, 2014. © 2014 Wiley Periodicals, Inc.
61 citations
TL;DR: The present results indicated that the miR‐252 of Ae.
Abstract: The Asian tiger mosquito, Aedes albopictus isa major vector of dengue in mainland China. Dengue epidemics have spread from the southern coastal regions to the relatively northern and western regions since 1990s. Dengue has become an emerging public health problem in the southern coastal regions. microRNAs(miRNAs) are short non-coding RNAs that regulate gene expression at the post transcription allevel. A highly abundant miRNA, miR-252, was induced more than threefold after dengue virus serotype 2 (DENV-2) infection in the Ae. albopictus C6/36 cellline. Transfection with miR-252 inhibitor resulted in the increase of DENV-2 RNA copies and the up-regulation of DENV-2 envelop protein(E protein) expression, whereas over expression of miR-252 with its mimic decreased DENV RNA copies and the down-regulation of E protein expression. MiR-252 mimic reduced luciferase activity of a luciferase reporter that contained the predicted miR-252 target on the DENV-2 envelope gene sequence. The present results indicated that the miR-252 of Ae. albopictus could regulate the gene expression of DENV-2 E protein and may act asa cellular antiviral regulator in Ae. albopictus.
59 citations
TL;DR: Molecular technology significantly enhanced the identification of EV causing sporadic gastroenteritis in Alberta and followed a U‐shaped age distribution; positive samples were more common in children ≤5 years old and adults >60 years old.
Abstract: Viral gastroenteritis causes significant mortality and morbidity worldwide. Identifying the etiology of viral gastroenteritis is a challenge as most enteric viruses (EVs) are non-culturable. This study is to develop an EV testing panel using real-time PCR (EVPrtPCR) to simultaneously detect rotavirus, norovirus, sapovirus, astrovirus, and enteric adenovirus in stool samples. EVPrtPCR using universal amplification conditions was run in a single instrument run. EVPrtPCR was used to test 2,486 sporadic gastroenteritis samples submitted for EV testing using electron microscopy (EM) between July 2008 and July 2009. Retesting spiked negative stool samples and Salmon DNA as internal control were used to evaluate inhibition. EVPrtPCR detected viruses in significantly more samples: 748 (34%) as compared to 94 (3.8%) by EM. EM did not detect any norovirus, sapovirus, and mixed infection, and detected only 39% of rotavirus and 38.2% of enteric adenovirus positive samples. Four samples that tested positive for rotavirus and two for adenovirus and for small-round-structured viruses by EM were negative by EVPrtPCR. Norovirus was the most common virus detected (17.6%) with 92.4% as genogroup II, followed by rotavirus (6.8%), sapovirus (4.2%), astrovirus (2.0%), and enteric adenovirus (1.4%) with 9% samples positive for mixed infection. Overall, EV identification followed a U-shaped age distribution; positive samples were more common in children ≤5 years old and adults >60 years old. Norovirus, sapovirus and astrovirus showed winter predominance and rotavirus peaked in the spring. No inhibition was observed. Molecular technology significantly enhanced the identification of EV causing sporadic gastroenteritis in Alberta.
58 citations
TL;DR: The results suggest that gastrointestinal tract, a constituent member of the common mucosal immune system, is a potent candidate applicable as a DNA vaccine route against virus respiratory diseases.
Abstract: It is well accepted that vaccination by oral administration has many advantages over injected parenteral immunization. The present study focuses on whether oral vaccination with a DNA vaccine could induce protective immunity against respiratory challenge infection. The M1 gene of influenza A virus was used to construct DNA vaccine using pcDNA 3.1(+) plasmid, a eukaryotic expression vector. The cationic liposomes were used to deliver the constructed DNA vaccine. In vitro and in vivo expression of M1 gene was observed in the cell line and in the intestine of orally vaccinated C57BL/6 mice, respectively. It became clear that this type of oral DNA vaccination was capable of inducing both humoral and cellular immune responses, together with an augmentation of IFN-γ production. In addition, oral vaccination with liposome-encapsulated DNA vaccine could protect the mice against respiratory challenge infection. These results suggest that gastrointestinal tract, a constituent member of the common mucosal immune system, is a potent candidate applicable as a DNA vaccine route against virus respiratory diseases.
56 citations
TL;DR: Only type‐specific HPV persistence predicted recurrent or residual disease, and HPV genotyping appears useful to improve the specificity when using HPV testing in post‐treatment follow‐up, according to the aim of the present study.
Abstract: Human papillomavirus (HPV) infection is a necessary factor in the cervical cancer development. Also after treatment for cervical dysplasia, HPV can be present and promote the recurrence of cervical ...
52 citations
TL;DR: The aim of this review is to address the current data regarding the association and status of TGF‐β with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.
Abstract: Hepatitis B virus (HBV) which includes, fulminant, acute, chronic, asymptomatic, and occult HBV infection is the most prevalent virus that leads to human liver diseases. Chronic, asymptomatic, and occult infection can induce further sever diseases such as hepatocellular carcinoma (HCC) and cirrhosis of the liver. The underlying mechanisms that allow progression of the prolonged forms of the infection and subsequent HCC or cirrhosis of the liver are yet to be clarified. However, many researchers have suggested that immunological and genetic parameters may play important roles in the etiology of hepatitis B. Transforming growth factor beta (TGF-β) is an important cytokine with dual regulatory functions in the immune system and in the responses against viral infections. However, the pathways and mechanisms controlling these are not fully understood. The crucial roles of TGF-β in the development of Th17 and T regulatory lymphocytes, the main cell types involved in autoimmunity and destructive immune related diseases, have been documented and this provides insights into TGF-β function during hepatitis infection and subsequent HCC and cirrhosis of the liver. Recent findings also confirm that TGF-β directly alters hepatocyte function during hepatitis B, hence, the aim of this review is to address the current data regarding the association and status of TGF-β with hepatitis B infection and its related disorders including HCC and cirrhosis of the liver.
TL;DR: It is suggested that young subjects are more likely to be eligible for gene therapy based on AAV vectors delivered via an intravascular route because of the low prevalence of antibodies to AAV capsids.
Abstract: Pre-existing antibodies against adeno-associated virus (AAV), caused by natural AAV infections, interfere with recombinant AAV vector-mediated gene transfer. We studied the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 in healthy subjects (n = 85) and hemophilia patients (n = 59) in a Japanese population. For healthy subjects, the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 was 36.5%, 35.3%, 37.6%, 32.9%, and 36.5%, respectively, while that in hemophilia patients was 39.7%, 28.8%, 35.6%, 32.9%, and 27.4%, respectively. There was no difference in the prevalence of neutralizing antibody against each AAV serotype between the healthy subjects and the hemophilia patients. The prevalence of neutralizing antibodies against all AAV serotypes increased with age in both healthy subjects and hemophilia patients. High titers of neutralizing antibodies against AAV2 (≥1:224) and AAV8 (≥1:224) were more evident in older individuals (≥42 years old). Approximately 50% of all screened individuals were seronegative for neutralizing antibodies against each AAV tested, while approximately 25% of individuals were seropositive for each AAV serotype tested. The prevalence of seronegativity for all AAV serotypes was 67.0% (healthy subjects, 68.6%; hemophilia patients, 65.0%) and 18.6% (healthy subjects, 20.5%; hemophilia patients, 15.7%) in young (<42 years old) and older subjects (≥42 years old), respectively. The findings from this study suggested that young subjects are more likely to be eligible for gene therapy based on AAV vectors delivered via an intravascular route because of the low prevalence of antibodies to AAV capsids. J. Med. Virol. 86:1990–1997, 2014. © 2013 Wiley Periodicals, Inc.
TL;DR: Examination of genes involved in viral sensing and the development of innate immunity in isolated, highly purified, human islets found that Coxsackievirus B1 infection is consistent with the preferential β‐cell tropism of the virus.
Abstract: Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined wheth ...
TL;DR: Antigenic data suggested that low vaccine effectiveness was not associated with poor vaccine match among the A(H3) viruses, however, genetic analysis suggested nucleotide substitutions in antigenic sites.
Abstract: Vaccine effectiveness may wane with increasing time since vaccination. This analysis used the Victorian sentinel general practitioner (GP) network to estimate vaccine effectiveness for trivalent inactivated vaccines in the 2012 season. A test-negative design was used where patients presenting to GPs with influenza-like illness who tested positive for influenza were cases and noncases were those who tested negative. Vaccination status was recorded by GPs. Vaccine effectiveness was calculated as (1-odds ratio) × 100%. Estimates were compared early versus late in the season and by time since vaccination. Virus isolates were assessed antigenically by hemagglutination inhibition assay in a selection of positive samples and viruses from healthy adults who experienced a vaccine breakthrough were analyzed genetically. The adjusted vaccine effectiveness estimate for any type of influenza was 45% (95% CI: 8,66) and for influenza A(H3) was 35% (95% CI: −11,62). A non-significant effect of waning effectiveness by time since vaccination was observed for A(H3). For those vaccinated <93 days of presentation vaccine effectiveness was 37% (95% CI: −29,69), while for those vaccinated ≥93 days before presentation it was 18% (95% CI: −83,63). Comparison of early versus late in the season estimates was very sensitive to the cut off week chosen for analysis. Antigenic data suggested that low vaccine effectiveness was not associated with poor vaccine match among the A(H3) viruses. However, genetic analysis suggested nucleotide substitutions in antigenic sites. In 2012, the trivalent influenza vaccine provided moderate protection against influenza and showed limited evidence for waning effectiveness. Antigenic and genetic data can provide additional insight into understanding these estimates. J. Med. Virol. 86:1017–1025, 2014. © 2013 Wiley Periodicals, Inc.
TL;DR: Additional evidence is provided supporting a role of EV‐D68 in severe respiratory infection in pediatric patients and all the three EV‐ D68 clades circulating worldwide were identified in Italy in a 5‐year period of time.
Abstract: Enterovirus 68 (EV-D68) was associated with mild to severe respiratory infections. In the last 4 years, circulation of different EV-D68 strains has been documented worldwide. In this study, the phylogenetic characterization of nine EV-D68 strains identified in patients in the 2010–2012 period and 12 additional EV-D68 Italian strains previously identified in 2008 in Italy was described. From January 2010 to December 2012, a total of 889 respiratory specimens from 588 patients stayed or visited at the Fondazione IRCCS Policlinico San Matteo were positive for HRV or HEV. Extracted nucleic acids were amplified by one-step RT-PCR with primer specific for VP1 region of EV-D68 and purified positive PCR products were directly sequenced. Overall, 9/3736 (0.24%) patients were EV-D68 positive. Of these, 7/9 (77.8%) were pediatric and two (22.2%) were adults. Five out of seven (71.4%) pediatric patients had lower respiratory tract infection with oxygen saturation <94%. Four cases were detected from August through October 2010, while five other cases from September through December 2012. The Italian EV-D68 strains in 2008 belonged to clade A (n = 5) and clade C (n = 7). In 2010 all the Italian strains belonged to clade A (n = 4) and in 2012, four Italian strains belonged to clade B and one to clade A. In conclusion, we provide additional evidence supporting a role of EV-D68 in severe respiratory infection in pediatric patients. In addition, all the three EV-D68 clades circulating worldwide were identified in Italy in a 5-year period of time. J. Med. Virol. 86:1590–1593, 2014. © 2013 Wiley Periodicals, Inc.
TL;DR: The detection of different viruses in the CNS of patients with meningitis or encephalitis highlight the importance of maintaining an active laboratory monitoring diagnostics with rapid methodology of high sensitivity in areas of viral hyperendemicity that may assist in clinical decisions and in the choice of antiviral therapy.
Abstract: Acute infections of the central nervous system (CNS) can be caused by various pathogens. In this study, the presence of herpesviruses (HHV), enteroviruses (EVs), and arboviruses were investigated in CSF samples from 165 patients with suspected CNS viral infection through polymerase chain reaction (PCR) and reverse transcriptase PCR. The genomes of one or more viral agents were detected in 29.7% (49/165) of the CSF samples. EVs were predominant (16/49; 32.6%) followed by Epstein-Barr virus (EBV) (22.4%), Varicella-Zoster virus (VZV) (20.4%), Cytomegalovirus (CMV) (18.4%), herpes simplex virus (HSV-1) (4.1%), (HSV-2) (4.1%), and the arboviruses (14.3%). Four of the arboviruses were of dengue virus (DENV) and three of oropouche virus (OROV). The detection of different viruses in the CNS of patients with meningitis or encephalitis highlight the importance of maintaining an active laboratory monitoring diagnostics with rapid methodology of high sensitivity in areas of viral hyperendemicity that may assist in clinical decisions and in the choice of antiviral therapy.
TL;DR: It was observed a regular expression of IL‐18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury.
Abstract: Dengue infection is an important tropical disease worldwide. The host immune response has been studied in order to better understand lesion mechanisms. It was performed an immunohistochemical study in 14 specimens of liver from patients with dengue hemorrhagic fever (DHF) to characterize cytokines and some factors present in liver lesions and their possible role in the pathogenesis of hepatic injury. Portal tract and hepatic acinus presented high expression of TLR2, TLR3, IL6, and granzyme B. Hepatic acinus also presented iNOS, IL18, and TGF-beta. Cells expressing IL12, IL13, JAk1, STAT1, and NF-κB were rarely visualized. Treg cells foxp3+ were absent. TLR2 and TLR3 seem to participate in cellular activation and cytokine production. Cytotoxic response seems to play a role. Although TGF-beta promotes the activation of Foxp3+ regulatory T cells, IL6 can significantly suppresses their generation. The expression of Treg cells is diminished probably as a result of the high frequency of these cytokines. Both cytokines play a role in the increased vascular permeability and edema observed in dengue liver specimens, with consequent plasma leakage and severity of the disease. It was observed a regular expression of IL-18 in hepatocytes and lymphocytes of the inflammatory infiltrate in portal tract, which reflects the acute inflammatory response that occurs in the liver and contributes to hepatic injury. At least in part, the increased number of cells expressing IL-18 could play a role of "up" regulation of FasL and correlate to the phenomenon of apoptosis, a mechanism of destruction of hepatocytes in DHF.
TL;DR: Prevalence data suggest that patients infected with HIV can be considered a risk group for HEV infection and that chronic coinfection HEV‐HIV seems to be a very rare event.
Abstract: Hepatitis E virus is responsible for sporadic cases of acute, self-limited viral hepatitis not only in endemic but also in industrialized countries. In addition, some reports confirm that it can cause chronic infection and even cirrhosis in immunosuppressed and also in patients infected with HIV. There are few data about prevalence and incidence of HEV chronic infection in HIV-HEV coinfected individuals in Spain. The aim of this study is to investigate the prevalence of anti-HEV IgG in a representative sample of 448 patients infected with HIV and determine the role of age, gender, and CD4 counts in the detection of anti-HEV IgG antibodies in blood. In addition, the clinical features and ALT levels in relation to the presence of anti-HEV IgM and/or HEV-RNA in the blood of these patients were investigated. Anti-HEV IgG antibodies were detected in serum using a commercial enzyme immunoassay. All positive samples were studied further for the presence of anti-HEV IgM antibodies. In addition, HEV RNA was amplified by reverse transcriptase (RT)-nested PCR in all serum samples with IgM anti-HEV. The overall prevalence of anti-HEV IgG was 10.4% (45/448, 95% C.I. 7.2-12.8%). HEV-RNA was found in only one patient out of the 45 anti-HEV IgG positive samples studied. Regarding to gender and CD4 count, no difference in seroprevalence could be observed. This prevalence data suggest that patients infected with HIV can be considered a risk group for HEV infection and that chronic coinfection HEV-HIV seems to be a very rare event.
TL;DR: In this article, the authors investigated whether the single nucleotide polymorphism (SNP) upstream of the IL28B gene had any effect on the incidence rate and the features of active CMV infection in the Allogeneic stem cell transplantation setting.
Abstract: The current study was aimed at investigating whether the single nucleotide polymorphism (SNP) (rs12979860), upstream of the IL28B gene, had any effect on the incidence rate and the features of active CMV infection in the Allogeneic stem cell transplantation setting. This was a retrospective observational study including 151 patients undergoing T cell-replete Allo-SCT. Donor and recipient IL28 SNP genotype was determined by allele-specific real-time PCR. The incidence rate of active CMV infection was not significantly associated with either the donor or the recipient IL28B SNP genotype. Nevertheless, a trend towards a lower incidence of active CMV infection was noted in the donor T/T population with respect to the donor C/T and C/C population. The duration of first episodes of CMV DNAemia was significantly shorter in patients carrying the donor T/T genotype with respect to their C/C or C/T counterparts (P = 0.038). Peak CMV DNAmeia levels tended to be lower in patients carrying the T/T genotype (donor or recipient) than in C/C or C/T patients, although statistical significance was not reached. In conclusion the data presented pointed to a protective effect of the T allele (recessive genetic model) against CMV infection in the Allo-SCT setting. J. Med. Virol. 86:838–844, 2014. © 2013 Wiley Periodicals, Inc.
TL;DR: It was demonstrated by the first time the emergence of unusual genotype G3P[6] in the Amazon region of Brazil, which shares neither VP7 nor VP4 specificity with the used vaccine and may represent a challenge to vaccination strategies.
Abstract: Rotavirus A (RVA) is the most common cause of severe acute gastroenteritis in infants and young children worldwide, causing 453,000 deaths annually. In Brazil, the most frequent genotype identified was G1 during almost three decades in the pre-vaccination period; however, after anti-rotavirus vaccine introduction, there was a predominance of G2 genotype. The aim of this study was to determine the G and P genotypes of rotaviruses isolated from children under 5 years of age with acute gastroenteritis in the Northern region of Brazil, and discuss the emergence of G3P[6] genotype. A total of 783 stool specimens were obtained between January 2011 and March 2012. RVA antigen was detected in 33% (272/783) of samples using a commercial enzyme-linked immunosorbent assay and type-specificity was determined by reverse-transcription polymerase chain reaction. The most common binary combination was G2P[4], representing 41% of cases, followed by G3P[6] (15%), G1P[8] (8%), G3P[8] (4%), G9P[8] (3%), and G12P[6] (2%). G3P[6] strains were analyzed further and phylogenetic analysis of VP7 gene showed that G3 strains clustered into lineage I and showed a high degree of amino acid identity with vaccine strain RV3 (95.1-95.6%). For VP4 sequences, G3P[6] clustered into lineage Ia. It was demonstrated by the first time the emergence of unusual genotype G3P[6] in the Amazon region of Brazil. This genotype shares neither VP7 nor VP4 specificity with the used vaccine and may represent a challenge to vaccination strategies. A continuous monitoring of circulating strains is therefore needed during the post-vaccine era in Brazil.
TL;DR: A high prevalence of HCMV in glioblastoma multiforme samples is shown reinforcing a possible association between human cytomegalovirus infection and tumor development.
Abstract: Glioblastoma multiforme is the most prevalent and malignant tumor of the central nervous system. In the last few years, accumulating evidence has suggested an association between human cytomegalovirus (HCMV) infection and glioblastoma multiforme. In this study, tumor tissues and peripheral blood of patients with glioblastoma multiforme were examined for the presence of HCMV DNA. Twenty-two fresh surgical brain specimens and 20 peripheral blood samples were analyzed by real-time PCR (qPCR) and hemi-nested PCR (nPCR) for the presence of pp65 and (glycoprotein B) gB viral genomic regions, respectively. HCMV DNA was detected in the majority of the tumor samples analyzed (95% by qPCR and 91% by nPCR). About half of the patients with tumors positive for HCMV also had detectable viral DNA in their peripheral blood (47% by qPCR and 61% by nPCR). Genome copy numbers were determined and in the majority of the tumor samples cellular DNA outnumbers viral DNA (average of 1 infected cell in 33 cells). The gB genotypes were determined in HCMV-positive samples and gB2 was the most prevalent genotype in the tumor and blood samples. The results show a high prevalence of HCMV in glioblastoma multiforme samples reinforcing a possible association between HCMV infection and tumor development.
TL;DR: It was demonstrated that the strains with two different genotype constellations prevailed in the season, and the results suggest that the intergenogroup reassortants, considered generally unstable, can spread rapidly and become relevant.
Abstract: During a survey of human rotaviruses in Okayama Prefecture, Japan in the 2011-2012 rotavirus season (between September 2011 and August 2012), G3P[8] was found to be a predominant genotype overall. However, G1P[8] emerged in the latter half of the season. To clarify the genetic background of the G1P[8] strains, the VP7, VP4, VP6, NSP4, and NSP5/6 genes of the strains were sequenced and genotyped. As a result, it was demonstrated that the strains with two different genotype constellations (G1-P[8]-I1-E1-H1 and G1-P[8]-I2-E2-H2) prevailed in the season. The G1P[8] strains possessing the DS-1-like VP6, NSP4, and NSP5/6 genes (the DS-1-like G1P[8] strains), which should reveal a short electropherotype, were originated from possible intergenogroup reassortment events. The DS-1-like G1P[8] strains accounted for 74.1% of all G1P[8] strains and were detected continuously throughout the season but not in the preceding season, indicating the possibility of new introduction and rapid spreading of these strains in the 2011-2012 season. The results suggest that the intergenogroup reassortants, considered generally unstable, can spread rapidly and become relevant.
TL;DR: Real‐time TaqMan PCR should be made available widely as an adjunctive test for diagnosis of human rabies in high disease burden countries like India.
Abstract: Rabies, a fatal zoonotic viral encephalitis remains a neglected disease in India despite a high disease burden. Laboratory confirmation is essential, especially in patients with paralytic rabies who pose a diagnostic dilemma. However, conventional tests for diagnosis of rabies have several limitations. In the present study the utility of a real-time TaqMan PCR assay was evaluated for antemortem/postmortem diagnosis of rabies. Human clinical samples received for antemortem rabies diagnosis (CSF, saliva, nuchal skin biopsy, serum), and samples obtained postmortem from laboratory confirmed rabies in humans (brain tissue, CSF, serum) and animals (brain tissue) were included in the study. All CSF and sera were tested for rabies viral neutralizing antibodies (RVNA) by rapid fluorescent focus inhibition test (RFFIT) and all samples (except sera) were processed for detection of rabies viral RNA by real-time TaqMan PCR. All the 29 (100%) brain tissues from confirmed cases of human and animal rabies, and 11/14 (78.5%) CSF samples obtained postmortem from confirmed human rabies cases were positive by real-time TaqMan PCR. Rabies viral RNA was detected in 5/11 (45.4%) CSF samples, 6/10 (60%) nuchal skin biopsies, and 6/7 (85.7%) saliva samples received for antemortem diagnosis. Real-time TaqMan PCR alone could achieve antemortem rabies diagnosis in 11/13 (84.6%) cases; combined with RVNA detection in CSF antemortem rabies diagnosis could be achieved in all 13 (100%) cases. Real-time TaqMan PCR should be made available widely as an adjunctive test for diagnosis of human rabies in high disease burden countries like India.
TL;DR: It is found that consideration of HCC development is required in patients with coexistence of HBsAg and anti‐HBs, as well as age over 40 years, and cirrhosis, which increased in proportion to the number of the risk factors.
Abstract: The simultaneous detection of hepatitis B surface antigen (HBsAg) and antibody to hepatitis B surface (anti-HBs) is unusual in chronic hepatitis B virus (HBV) infection, but may be related with more advanced liver diseases. This retrospective long-term cohort study was aimed to investigate whether coexistence of HBsAg and anti-HBs may increase the risk of hepatocellular carcinoma (HCC) in chronic HBV infection. A total of 1,042 non-HCC patients were recruited and followed up for a median 4.3 years (range 1.0–22 years). Univariate and multivariate analyses were performed to identify the risk factors for HCC development. The prevalence of coexistence of HBsAg and anti-HBs was 7.0% (73/1,042). In univariate analysis, the 5-, 10-, and 15-year cumulative incidences of HCC were significantly higher in coexistence group than in HBsAg only group (12.7%, 23.4%, 69.4% vs. 4.9%, 13%, 20.6%, respectively; P = 0.008). In multivariate analysis, coexistence of HBsAg and anti-HBs [Hazard ratio (HR), 2.001; 95% confidence interval (CI), 1.023–3.912; P = 0.043] as well as male gender [HR, 1.898; 95% CI, 0.31–0.896; P = 0.018], age over 40 years [HR, 14.56; 95% CI, 4.499–47.08; P = 0.0001], and cirrhosis [HR, 7.995; 95% CI, 4.756–13.439; P = 0.0001] was identified as the independent factor for HCC development. Also, the cumulative incidence of HCC increased in proportion to the number of the risk factors. In conclusion, coexistence of HBsAg and anti-HBs may increase independently the risk of HCC development in chronic HBV infection. Therefore, consideration of HCC development is required in patients with coexistence of HBsAg and anti-HBs. J. Med. Virol. 86:124–130, 2014. © 2013 Wiley Periodicals, Inc.
Duke University1, University of Texas Southwestern Medical Center2, University of Washington3, University of California, San Francisco4, California Pacific Medical Center5, Yale University6, Icahn School of Medicine at Mount Sinai7, University of Nebraska–Lincoln8, Mayo Clinic9, Baylor University Medical Center10, University of Pittsburgh11, Northwestern University12, University of Oregon13, University of California, Los Angeles14, University of Michigan15, University of Alabama at Birmingham16, Harvard University17, Columbia University18, Washington University in St. Louis19, Medical University of South Carolina20, Yeshiva University21, University of Pennsylvania22, Virginia Commonwealth University23, University of California, Davis24, University of California, San Diego25
TL;DR: Serum levels in patients with chronic hepatitis C were compared to other forms of liver injury including patients with acute liver failure and healthy controls to evaluate whether circulating levels of miR‐122 are elevated in chronic‐HCV for a reason other than hepatic injury.
Abstract: MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis Additionally, six HIV–HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0001) Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 016 to 146, after sustained viral response Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure Eradication of HCV was associated with decreased miR-122 but not hgDNA An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed J Med Virol 86:1507–1514, 2014 © 2014 Wiley Periodicals, Inc
TL;DR: Significantly lower anti‐rubella IgG titre found in the youngest age groups highlights the need for continued antenatal screening, and a considerable increase in anti‐CMV‐IgG seropositivity rate was observed and might be associated with higher rate of breastfeeding and a higher percentage attending day‐care centres.
Abstract: Infections caused by cytomegalovirus (CMV), parvovirus B19 (B19), and rubella can lead to serious complications in pregnant women. The aim of this study was to determine the susceptibility to CMV, B19, and rubella antibodies in pregnant women in Norway. Consecutive sera samples were collected from pregnant women in two different regions in Norway. Sera were collected from age groups; ≤19, 20-24, 25-29, 30-34, 35-39, and ≥40 years old. Of the 2,000 pregnant women tested, anti-CMV IgG was positive in 62.8% anti-parvovirus B19 IgG in 59.7% and anti-rubella IgG in 94.4%. CMV IgG susceptibility has decreased in pregnant women less than 30 years of age, from 60% in a study conducted in 1973-1974 to 37.2% in present study. There was a significant difference in CMV IgG seropositivity rate between the two regions (58.6% and 67.1%). Serum levels of rubella IgG was lowest in age group 25-29 years with a positivity rate of 91.0%. Women born before vaccination with two doses of MMR started, had both a higher positivity rate and significantly higher levels of rubella antibody titre, 96.1% and 82.2 IU/ml compared to those born after 92.9% and 41.7 IU/ml. Significantly lower anti-rubella IgG titre found in the youngest age groups highlights the need for continued antenatal screening. A considerable increase in anti-CMV-IgG seropositivity rate was observed and might be associated with higher rate of breastfeeding and a higher percentage attending day-care centres.
TL;DR: Chronic HBV infection is a strong risk factor for hepatocellular carcinoma and also increases the risk of seven other cancers: cancers of the upper aerodigestive tract, lung, kidney, skin (squamous cell carcinoma), and thyroid gland, and lymphoma and leukemia.
Abstract: Hepatitis B virus (HBV) infection is one of most common viral infections worldwide. While chronic HBV infection has been shown consistently to be associated with hepatocellular carcinoma, data on associations with cancers at other sites are limited. In this study a total of 10,197 patients were diagnosed with chronic HBV infection in Sweden, and they were retrieved from the nationwide Swedish Hospital Discharge Register and Outpatient Register and linked to Cancer Registry data. Standardized incidence ratios (SIRs) for cancers were calculated for these patients in comparison with the population without HBV infection. Five hundred sixty-seven of whom developed cancer (SIR 1.82 (95% confidence interval (CI) 1.67-1.97)) during the study period. The SIR for hepatocellular carcinoma in patients with HBV infection was 40.58 (95% CI 30.50-50.07). In addition, a total of seven other cancer sites/types showed increased SIRs: cancers of the upper aerodigestive tract, lung, kidney, skin (squamous cell carcinoma), and thyroid gland, and lymphoma and leukemia. The risks of non-Hodgkin lymphoma and acute myeloid leukemia were increased in both Swedish- and foreign-born patients with HBV infection. In summary, chronic HBV infection is a strong risk factor for hepatocellular carcinoma and also increases the risk of seven other cancers. These findings illustrate the need for surveillance for cancers other than hepatocellular carcinoma in patients with HBV infection. J. Med. Virol. © 2013 Wiley Periodicals, Inc. (Less)
TL;DR: It is suggested that chronic HBV infection is likely to represent a significant cause of infertility and the impact of HBV on sperm parameters, ovarian stimulation, and outcomes of in vitro fertilization and embryo transfer is investigated.
Abstract: Whether hepatitis B virus (HBV) infection impairs human infertility is unclear. The present retrospective case–controlled study investigated the impact of HBV on sperm parameters, ovarian stimulation, and outcomes of in vitro fertilization (IVF) and embryo transfer. A total of 224 couples with at least one partner being HBsAg-seropositive undergoing their first IVF and embryo transfer cycle were identified, which included 77 couples with female partners being HBsAg-seropositive, 136 couples with male partners being HBsAg-seropositive, and 11 couples with both partners being HBsAg-seropositive. A total of 448 both HBsAg-seronegative couples served as controls. The percentage of normal sperm morphology was significantly lower in HBsAg-seropositive male partners than that in HBsAg-seronegative male partners (11.9 ± 9.4% vs. 19.0 ± 11.9%, P < 0.01). The duration of infertility was significantly prolonged in HBV-seropositive patients compared with HBV-seronegative patients (4.9 vs. 4.1 years, P < 0.01). Couples with female partners being HBsAg-seropositive had significantly lower top-quality embryo rate than control group (22.4% vs. 31.6%, P < 0.01). In addition, the fertilization rates in groups with male or female partners being HBsAg-seropositive were both significantly lower than the matched controls (80.2% vs. 82.8%, P < 0.05; 76.6% vs. 84.3%, P < 0.01, respectively). HBV infection was also found to be associated negatively with fertilization rate by logistic regression analysis (odds ratios: 0.410, 95% confidence interval: 0.186–0.906, P < 0.05). However, there was no significant difference in clinical pregnancy rates between HBsAg-seropositive and HBsAg-seronegative group. These results suggest that chronic HBV infection is likely to represent a significant cause of infertility. J. Med. Virol. 86:1099–1104, 2014. © 2014 Wiley Periodicals, Inc.
TL;DR: Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness, and a striking difference to infections caused by influenza A virus was the lack of fever.
Abstract: Due to the lack of rapid diagnostic tests, clinical features of Influenza C virus infections are poorly characterized Respiratory infections in military recruits in eastern Finland were monitored between July 2004 and December 2005 in order to study the epidemiology and clinical picture of infections caused by this virus Blood samples were obtained at entry and at the end of the military service, and during each episode of respiratory infection to measure antibody responses against 10 viral and 2 bacterial pathogens If possible, sputum samples were collected during the acute phase of respiratory infection episodes Symptoms of the episodes were recorded for comparison of the clinical picture caused by various infectious agents Infection with influenza C virus was detected in 38 of 892 young men during their service The virus usually caused a mild upper respiratory tract infection Most typical clinical features of influenza C virus infection were cough, rhinitis, and hoarseness A striking difference to infections caused by influenza A virus was the lack of fever Influenza C virus is an important cause of a respiratory tract infection in army conscripts Infections with this virus are usually mild but can be complicated in some cases
TL;DR: Overall, serum antibodies against MCPyV, JCV, and JCV were found in 63%, 57%, and 69%, respectively, of this population of the Czech Republic, and these rates were associated with age; the occurrence of antibodies against JCV was highest for those older than 59 years, while the occurrence against BKV was highest in those aged 10–19 years and 20–29 years.
Abstract: JC and BK polyomaviruses (JCV and BKV) infect humans and can cause severe illnesses in immunocompromised patients. Merkel cell polyomavirus (MCPyV) can be found in skin carcinomas. In this study, we assessed the occurrence of serum antibodies against MCPyV, BKV, and JCV polyomaviruses in a healthy population of the Czech Republic. Serum samples from 991 healthy individuals (age range: 6-64 years) were examined by enzyme-linked immunoassay (ELISA) using virus-like particles (VLPs) based on the major VP1 capsid proteins of these viruses. Overall, serum antibodies against MCPyV, JCV, and BKV were found in 63%, 57%, and 69%, respectively, of this population. For all three viruses, these rates were associated with age; the occurrence of antibodies against MCPyV and JCV was highest for those older than 59 years, while the occurrence of antibodies against BKV was highest in those aged 10-19 years and 20-29 years. This is the first large study to determine the seroprevalence rates for BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population.