WorldWideScience

Sample records for human enterovirus infection

  1. Seroepidemiology of Human Enterovirus 71 Infection among Children, Cambodia

    Science.gov (United States)

    Horwood, Paul F.; Andronico, Alessio; Tarantola, Arnaud; Salje, Henrik; Duong, Veasna; Mey, Channa; Ly, Sovann; Dussart, Philippe; Cauchemez, Simon

    2016-01-01

    Enterovirus 71 is reported to have emerged in Cambodia in 2012; at least 54 children with severe encephalitis died during that outbreak. We used serum samples collected during 2000–2011 to show that the virus had been widespread in the country for at least a decade before the 2012 outbreak. PMID:26690000

  2. Characterization of a monoclonal antibody against the 3D polymerase of enterovirus 71 and its use for the detection of human enterovirus A infection.

    Science.gov (United States)

    Kiener, Tanja K; Lim, Xiao Fang; Jia, Qiang; Meng, Tao; Chow, Vincent Tak Kwong; Kwang, Jimmy

    2012-03-01

    Over the last decade, frequent epidemic outbreaks of hand, foot and mouth disease have been observed in the Asia-Pacific region. Hand, foot and mouth disease is caused by different viruses from the enterovirus family, mainly coxsackievirus A16 and enterovirus 71 (EV71) from the human enterovirus A family. Severe disease and neurological complications are associated more often with EV71 infection, and can lead occasionally to fatal brain stem encephalitis in young children. The rapid progression and high mortality of severe hand, foot and mouth disease makes the direct detection of antigens early in infection essential. The best method for virus detection is the use of specific monoclonal antibodies. The generation and characterization of a monoclonal antibody specific for the 3D polymerase of human enterovirus A and the development of a virus detection dot blot assay are described. A recombinant 3CD protein from EV71 C4 strain was used as an immunogen to generate monoclonal antibodies (MAbs). Screening of hybridoma cells led to the isolation of monoclonal antibody 4B12 of the immunoglobulin IgG1 isotype. MAb 4B12 recognizes the linear epitope DFEQALFS close to the active site of the 3D polymerase, corresponding to amino acid positions 53-60 of 3D and 1784-1791 of enterovirus 71 polyprotein. The presence of 3D polymerase and its precursor 3CD proteinase in purified virus particles was confirmed. MAb 4B12 was used successfully to detect all enterovirus 71 subgenotypes in a denaturing dot blot assay with a sensitivity of 10 pg of 3D protein and 10(4) tissue culture infective dose of virus particles. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Epidemiology of neonatal enterovirus infection.

    Science.gov (United States)

    Jenista, J A; Powell, K R; Menegus, M A

    1984-05-01

    During a typical enterovirus season in Rochester, New York, none of 666 neonates or 629 mothers were found to be excreting nonpolio enteroviruses within 1 day of delivery. No enteroviruses were isolated from weekly cultures of the 23 infants who died or remained hospitalized during the first month of life. After discharge, culture specimens were obtained in 586 infants at one to four weekly home visits until 1 month of age. The incidence of acquisition of nonpolio enterovirus infection was 12.8%, and the overall prevalence of enterovirus excretion was 5.3%. Risk of virus infection was associated only with lower socioeconomic status (P less than 0.0001) and lack of breast-feeding (P less than 0.0001). Four percent of all infants and 21% of infants in whom cultures for enterovirus were positive were readmitted to the hospital in the first month of life; 79% of infants with positive enterovirus cultures were asymptomatic. We conclude that enterovirus infection during the first month of life is very common in the late summer and early fall. Most infants are asymptomatic, but the risk of hospitalization is high. Breast-feeding may be associated with protection from infection.

  4. Genetic Determinants of Enterovirus Infections

    DEFF Research Database (Denmark)

    Witsø, Elisabet; Cinek, Ondrej; Tapia, German

    2015-01-01

    Enteroviruses have been suggested as triggers of type 1 diabetes (T1D). We aimed to assess whether established T1D susceptibility single nucleotide polymorphisms (SNPs) and candidate SNPs in innate immune genes were associated with the frequency of enterovirus infection in otherwise healthy child...

  5. Differential Susceptibility and Response of Primary Human Myeloid BDCA1(+) Dendritic Cells to Infection with Different Enteroviruses

    NARCIS (Netherlands)

    Schulte, B.M.; Kers-Rebel, E.D.; Prosser, A.C; Galama, J.M.D.; Kuppeveld, F.J.M. van; Adema, G.J.

    2013-01-01

    Coxsackie B viruses (CVBs) and echoviruses (EVs) form the Human Enterovirus-B (HEV-B) species within the family Picornaviridae. HEV-B infections are widespread and generally cause mild disease; however, severe infections occur and HEV-B are associated with various chronic diseases such as

  6. Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

    Directory of Open Access Journals (Sweden)

    Qin Chuan

    2011-10-01

    Full Text Available Abstract Human enterovirus 71 (EV71 infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE on rhabdomyosarcoma (RD cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.

  7. Enterovirus D68 Infection

    NARCIS (Netherlands)

    Esposito, Susanna; Bosis, Samantha; Niesters, Hubert; Principi, Nicola

    2015-01-01

    First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many

  8. Focal encephalitis with enterovirus infections.

    Science.gov (United States)

    Modlin, J F; Dagan, R; Berlin, L E; Virshup, D M; Yolken, R H; Menegus, M

    1991-10-01

    We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.

  9. Retrospective Surveillance of Wastewater To Examine Seasonal Dynamics of Enterovirus Infections.

    Science.gov (United States)

    Brinkman, Nichole E; Fout, G Shay; Keely, Scott P

    2017-01-01

    Enteroviruses are RNA viruses that are responsible for both mild gastroenteritis and mild respiratory illnesses as well as debilitating diseases such as meningitis and myocarditis. The disease burden of enteroviruses in the United States is difficult to assess because most infections are not recorded. Since infected individuals shed enterovirus in feces and urine, surveillance of municipal wastewater can reveal the diversity of enteroviruses circulating in human populations. Therefore, monthly municipal wastewater samples were collected for 1 year and enteroviruses were quantified by reverse transcriptase quantitative PCR and identified by next-generation, high-throughput sequencing. Enterovirus concentrations ranged from 3.8 to 5.9 log10 equivalent copies/liter in monthly samples. From the mean monthly concentration, it can be estimated that 2.8% of the contributing population was shedding enterovirus daily. Sequence analysis showed that Enterovirus A and Enterovirus B alternate in predominance, with Enterovirus B comprising over 80% of the reads during the summer and fall months and Enterovirus A accounting for >45% of the reads in spring. Enterovirus C was observed throughout the year, while Enterovirus D was present intermittently. Principal-component analysis further supported the date corresponding to enterovirus seasonal trends as CVA6 (Enterovirus A) was predominant in the spring months; CVB3, CVB5, and E9 (Enterovirus B) were predominant in the summer and fall months; and CVA1, CVA19, and CVA22 (Enterovirus C) and EV97 (Enterovirus B) were predominant in winter. Rhinoviruses were also observed. Wastewater monitoring of human enterovirus provided improved insight into the seasonal patterns of enteroviruses circulating in communities and can contribute to understanding of enterovirus disease burden. IMPORTANCE Enterovirus infections are often not tracked or reported to health officials. This makes it hard to know how many people in a community are infected

  10. ENTEROVIRUS INFECTION: VARIETY OF ETIOLOGICAL FACTORS AND CLINICAL MANIFESTATIONS

    Directory of Open Access Journals (Sweden)

    O. I. Kanaeva

    2014-01-01

    Full Text Available Abstract. Enteroviruses are widely distributed human infectious pathogens. In spite of infection a disease does not manifest in majority number of cases. However, in some infected persons the different kind of symptoms can be observed; from common cold signs up to  aseptic (serous meningitis and myocarditis. Severe enteroviral cases with lethal outcomes are rarely reported. Ability of enteroviruses to cause large outbreaks and even epidemic distribution is very significant for health care systems. Taking in account a high genetic diversity of enteroviruses it is possible appearance of new highly pathogenic strains in the future. In some countries including the Russian Federation the permanent surveillance for enteroviral infections is provided besides of WHO polio elimination program. The laboratory diagnostics of enterovirus infections is complicated by numerous of pathogen serotypes. Thus, classical virological methods should be supported by molecular-biological tools to sequence pathogen genome and to define phylogenetic relations between different enterovirus strains.

  11. The Autophagic Machinery in Enterovirus Infection

    Directory of Open Access Journals (Sweden)

    Jeffrey K. F. Lai

    2016-01-01

    Full Text Available The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL. The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field.

  12. Human enterovirus and rhinovirus infections are associated with otitis media in a prospective birth cohort study.

    Science.gov (United States)

    Seppälä, Elina; Sillanpää, Saara; Nurminen, Noora; Huhtala, Heini; Toppari, Jorma; Ilonen, Jorma; Veijola, Riitta; Knip, Mikael; Sipilä, Markku; Laranne, Jussi; Oikarinen, Sami; Hyöty, Heikki

    2016-12-01

    Human enteroviruses (HEVs) and rhinoviruses (HRVs) have been linked to acute otitis media (AOM). The present study evaluates the aforementioned association in a birth cohort setting. The cohort included 286 healthy infants (191 boys) followed from birth up to the age of 2 years in the Type 1 Diabetes Prediction and Prevention study in Finland. Stool samples were collected monthly and analyzed for the presence of HRV and HEV RNA using RT-PCR. Clinical symptoms were recorded by a questionnaire every 3-6 months. Altogether 610 AOM episodes were reported during the follow-up. 9.8% of the stool samples were positive for HRV and 6.8% for HEV. HRV positivity peaked at the age of 3-6 months declining gradually after this age, whereas HEV positivity peaked later, at the age of 12-24 months. The risk of AOM was increased in children who were HEV positive at least once at the age of 6-12 months (OR 2.2 [95%CI 1.1-4.2], P=0.023) or who were HRV positive at least once at the age of 18-24 months (OR 2.3 [95%CI 1.0-5.2], P=0.042). Having an older sibling, short breast-feeding and maternal smoking during pregnancy were also significantly associated with AOM. HRV and HEV infections are frequent during the first months of life. The observed trend for increased risk of AOM in HRV and HEV positive children is in line with the results from hospital series suggesting that these viruses may play an independent role in the pathogenesis of AOM. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Global quantitative proteomic analysis of human glioma cells profiled host protein expression in response to enterovirus type 71 infection.

    Science.gov (United States)

    Zhang, Lei-Ke; Lin, Tao; Zhu, Sheng-Lin; Xianyu, Ling-Zhi; Lu, Song-Ya

    2015-11-01

    Enterovirus 71 (EV71) is one of the leading causes of hand, foot and mouth disease with neurological complications in some cases. To study the pathogenesis of EV71 infection, large-scale analyses of EV71 infected cells have been performed. However, most of these studies employed rhabdomyosarcoma (RD) cells or used transcriptomic strategy. Here, we performed SILAC-based quantitative proteomic analysis of EV71-infected U251 cells, a human glioma cell line. A total of 3125 host proteins were quantified, in which 451 were differentially regulated as a result of EV71 infection at 8 or 20 hpi or both. Gene Ontology analysis indicates the regulated proteins were enriched in "metabolic process", "biological regulation" and "cellular process", implying that these biological processes were affected by EV71 infection. Furthermore, functional study indicated that TRAF2 and TRAF6 among the up-regulated proteins could inhibit the replication of EV71 at the early phase post infection, and the anti-EV71 function of both proteins was independent of interferon β. Our study not only provided an overview of cellular response to EV71 infection in a human glioma cell line, but also found that TRAF2 and TRAF6 might be potential targets to inhibit the replication of EV71. All MS data have been deposited in the ProteomeXchange with identifier PXD002454 (http://proteomecentral.proteomexchange.org/dataset/PXD002454). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Cellular receptors for human enterovirus species A

    Directory of Open Access Journals (Sweden)

    Yorihiro eNishimura

    2012-03-01

    Full Text Available Human enterovirus species A (HEV-A is one of the four species of HEV in the genus Enterovirus in the family Picornaviridae. Among HEV-A, coxsackievirus A16 (CVA16 and enterovirus 71 (EV71 are the major causative agents of hand, foot, and mouth disease (HFMD. Some other types of HEV-A are commonly associated with herpangina. Although HFMD and herpangina due to HEV-A are common febrile diseases among infants and children, EV71 can cause various neurological diseases, such as aseptic meningitis and fatal encephalitis.Recently, two human transmembrane proteins, P-selectin glycoprotein ligand-1 (PSGL-1 and scavenger receptor class B, member 2 (SCARB2, were identified as functional receptors for EV71 and CVA16. In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and SCARB2 could be responsible for the specific receptors for EV71 and CVA16. However, the involvement of both receptors in the in vitro and in vivo infections of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse array of the clinical outcome of HEV-A-associated diseases, the identification and characterization of HEV-A receptors may provide useful information in understanding the HEV-A pathogenesis at a molecular level.

  15. NONPOLIO ENTEROVIRUSES WHICH CAUSED THE RISE OF ENTEROVIRUS INFECTION ON SOME TERRITORIES OF RUSSIA IN 2016

    Directory of Open Access Journals (Sweden)

    N. I. Romanenkova

    2017-01-01

    Full Text Available Aim: Characteristics of the peculiarities and the etiological factor of enterovirus infection on some territories of Russia in 2016. Materials and methods: We investigated 2138 samples from the patients with enterovirus infection. The isolation and identification of enteroviruses were conducted by the virological method and by partial sequencing of the genome region VP1. Phylogenic trees were constructed according to the method of Bayesian Monte Carlo Markov Chain. Results: Epidemic peaks of enterovirus infection were fixed on some territories of Russia. In Saratov region the morbidity index of enterovirus infection in 2016 was twice as high as the median morbidity index over previous years. The morbidity level of enterovirus meningitis – 3, 21 for 100000 of the population (77% from all the cases of enterovirus infection was higher than on the other territories. In Kostroma region the morbidity index of enterovirus infection in 2016 was 11 times higher than the index of the previous year. On both territories the rise of morbidity depends on the active circulation of enterovirus ЕСНО30. Enteroviruses ECHO30 from Saratov region belonged to two phylogenic groups of genotype h. To one of them belonged viruses ECHO30 from Kostroma region. In Murmansk and Leningrad regions in 2016 most cases of enterovirus infection were represented by hand, foot and mouth disease (HFMD. The grouped foci of infection were registered in some preschool institutions. The etiological factor of this clinical form was Coxsackieviruses A6 belonging to different genetic variants. Conclusion: Epidemic peaks of enterovirus infection with the prevalence of different clinical forms of the disease were provoked by different etiological factors. On territories where enterovirus meningitis prevailed strains of enterovirus ECHO30 belonging to different variants of genotype h were detected. In patients with clinical picture of HFMD from territories where this form was leading

  16. Differential susceptibility and response of primary human myeloid BDCA1(+ dendritic cells to infection with different Enteroviruses.

    Directory of Open Access Journals (Sweden)

    Barbara M Schulte

    Full Text Available Coxsackie B viruses (CVBs and echoviruses (EVs form the Human Enterovirus-B (HEV-B species within the family Picornaviridae. HEV-B infections are widespread and generally cause mild disease; however, severe infections occur and HEV-B are associated with various chronic diseases such as cardiomyopathy and type 1 diabetes. Dendritic cells (DCs are the professional antigen-presenting cells of our immune system and initiate and control immune responses to invading pathogens, yet also maintain tolerance to self-antigens. We previously reported that EVs, but not CVBs, can productively infect in vitro generated monocyte-derived DCs. The interactions between HEV-B and human myeloid DCs (mDCs freshly isolated from blood, however, remain unknown. Here, we studied the susceptibility and responses of BDCA1(+ mDC to HEV-B species and found that these mDC are susceptible to EV, but not CVB infection. Productive EV7 infection resulted in massive, rapid cell death without DC activation. Contrary, EV1 infection, which resulted in lower virus input at the same MOI, resulted in DC activation as observed by production of type I interferon-stimulated genes (ISGs, upregulation of co-stimulatory and co-inhibitory molecules (CD80, CD86, PDL1 and production of IL-6 and TNF-α, with a relative moderate decrease in cell viability. EV1-induced ISG expression depended on virus replication. CVB infection did not affect DC viability and resulted in poor induction of ISGs and CD80 induction in part of the donors. These data show for the first time the interaction between HEV-B species and BDCA1(+ mDCs isolated freshly from blood. Our data indicate that different HEV-B species can influence DC homeostasis in various ways, possibly contributing to HEV-B associated pathology.

  17. An elaborate landscape of the human antibody repertoire against enterovirus 71 infection is revealed by phage display screening and deep sequencing.

    Science.gov (United States)

    Chen, Zhe; Ren, Xianwen; Yang, Jian; Dong, Jie; Xue, Ying; Sun, Lilian; Zhu, Yafang; Jin, Qi

    Enterovirus 71 (EV71) causes outbreaks of hand, foot and mouth disease (HFMD), primarily in the Asia-Pacific area, that are often associated with complications of severe to fatal neurological symptoms. There are currently no anti-viral therapies or vaccines available for the treatment of EV71 infection. Illustrating human antibody responses neutralizing EV71 infection could potentially provide valuable information for the development of effective therapies and vaccines. Here, we constructed a comprehensive phage display library based on peripheral blood of eight EV71-infected donors and identified 27 EV71-specific human antibodies, of which four have neutralizing activity in in vitro experiments. Deep sequencing analysis of the antibody heavy chains at the transcript level of another three independent EV71-infected donors and three controls demonstrates that heavy chains of the EV71-specific antibodies are conserved among EV71-infected individuals but absent in controls, suggesting convergent evolution of human antibodies against EV71.

  18. Severe neonatal parechovirus infection and similarity with enterovirus infection

    NARCIS (Netherlands)

    Verboon-Maciolek, Malgorzata A.; Krediet, Tannette G.; Gerards, Leo J.; de Vries, Linda S.; Groenendaal, Floris; van Loon, Anton M.

    Background: Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae. Less is known about severe neonatal infection caused by the parechoviruses (PeV) of which type 1 (PeV1) and type 2

  19. Divergent Requirement for a DNA Repair Enzyme during Enterovirus Infections

    Directory of Open Access Journals (Sweden)

    Sonia Maciejewski

    2015-12-01

    Full Text Available Viruses of the Enterovirus genus of picornaviruses, including poliovirus, coxsackievirus B3 (CVB3, and human rhinovirus, commandeer the functions of host cell proteins to aid in the replication of their small viral genomic RNAs during infection. One of these host proteins is a cellular DNA repair enzyme known as 5′ tyrosyl-DNA phosphodiesterase 2 (TDP2. TDP2 was previously demonstrated to mediate the cleavage of a unique covalent linkage between a viral protein (VPg and the 5′ end of picornavirus RNAs. Although VPg is absent from actively translating poliovirus mRNAs, the removal of VPg is not required for the in vitro translation and replication of the RNA. However, TDP2 appears to be excluded from replication and encapsidation sites during peak times of poliovirus infection of HeLa cells, suggesting a role for TDP2 during the viral replication cycle. Using a mouse embryonic fibroblast cell line lacking TDP2, we found that TDP2 is differentially required among enteroviruses. Our single-cycle viral growth analysis shows that CVB3 replication has a greater dependency on TDP2 than does poliovirus or human rhinovirus replication. During infection, CVB3 protein accumulation is undetectable (by Western blot analysis in the absence of TDP2, whereas poliovirus protein accumulation is reduced but still detectable. Using an infectious CVB3 RNA with a reporter, CVB3 RNA could still be replicated in the absence of TDP2 following transfection, albeit at reduced levels. Overall, these results indicate that TDP2 potentiates viral replication during enterovirus infections of cultured cells, making TDP2 a potential target for antiviral development for picornavirus infections.

  20. Phagocytosis of enterovirus-infected pancreatic beta-cells triggers innate immune responses in human dendritic cells.

    NARCIS (Netherlands)

    Schulte, B.M.; Kramer, M.; Ansems, M.; Lanke, K.H.W.; Doremalen, N. van; Piganelli, J.D.; Bottino, R.; Trucco, M.; Galama, J.M.D.; Adema, G.J.; Kuppeveld, F.J.M. van

    2010-01-01

    OBJECTIVE: Type 1 diabetes is a chronic endocrine disorder in which enteroviruses, such as coxsackie B viruses and echoviruses, are possible environmental factors that can trigger or accelerate disease. The development or acceleration of type 1 diabetes depends on the balance between autoreactive

  1. Viremia in hospitalized children with enterovirus infections.

    Science.gov (United States)

    Dagan, R; Jenista, J A; Prather, S L; Powell, K R; Menegus, M A

    1985-03-01

    In a prospective study during the summer and fall of 1982, enterovirus was isolated from 48 hospitalized children; in 29 (60%) enterovirus was isolated from CSF or blood, and in 19 (40%) only a presumptive diagnosis was established. Blood was positive in 21 (44%) and was the only positive specimen in two children. A presumptive diagnosis was provided within 4 days of admission in 38 (80%) and within 48 hours in 19 (40%) of the children from whom enterovirus was isolated. Viremia was most often detected in febrile infants younger than 3 months of age with a clinical picture simulating bacterial sepsis. The presence of viremia was inversely related to the presence of CSF pleocytosis and to virus isolation from CSF. The diagnosis of diseases caused by enterovirus is more accurate when blood culture is added to CSF stool and throat cultures.

  2. Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa.

    Science.gov (United States)

    Phyu, Win Kyaw; Ong, Kien Chai; Kong, Chee Kwan; Alizan, Abdul Khalil; Ramanujam, Tindivanam Muthurangam; Wong, Kum Thong

    2017-03-21

    Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion.

  3. Neurologic Manifestations of Enterovirus 71 Infection in Korea.

    Science.gov (United States)

    Lee, Kyung Yeon; Lee, Myoung Sook; Kim, Dong Bin

    2016-04-01

    Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.

  4. Animal models of enterovirus 71 infection: applications and limitations.

    Science.gov (United States)

    Wang, Ya-Fang; Yu, Chun-Keung

    2014-04-17

    Human enterovirus 71 (EV71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the Asia-Pacific region over the past 15 years. Appropriate animal models are needed to understand EV71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. Non-human primate models have been used to characterize and evaluate the neurovirulence of EV71 after the early outbreaks in late 1990s. However, these models were not suitable for assessing the neurovirulence level of the virus and were associated with ethical and economic difficulties in terms of broad application. Several strategies have been applied to develop mouse models of EV71 infection, including strategies that employ virus adaption and immunodeficient hosts. Although these mouse models do not closely mimic human disease, they have been applied to determine the pathogenesis of and treatment and prevention of the disease. EV71 receptor-transgenic mouse models have recently been developed and have significantly advanced our understanding of the biological features of the virus and the host-parasite interactions. Overall, each of these models has advantages and disadvantages, and these models are differentially suited for studies of EV71 pathogenesis and/or the pre-clinical testing of antiviral drugs and vaccines. In this paper, we review the characteristics, applications and limitation of these EV71 animal models, including non-human primate and mouse models.

  5. Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yu-Ting Liao

    Full Text Available Enterovirus 71 (EV71 infections may be associated with neurological complications, including brainstem encephalitis (BE. Severe EV71 BE may be complicated with autonomic nervous system (ANS dysregulation and/or pulmonary edema (PE. ANS dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.The aims of this study were to explore the effects of catecholamines on severe EV71 infection and to investigate the changes in the percentages of EV71-infected cells, virus titer, and cytokine production on the involvement of catecholamines.Plasma levels of norepinephrine (NE and epinephrine (EP in EV71-infected patients were measured using an enzyme-linked immunoassay. The expression of adrenergic receptors (ADRs on RD, A549, SK-N-SH, THP-1, Jurkat and human peripheral blood mononuclear cells (hPBMCs were detected using flow cytometry. The percentages of EV71-infected cells, virus titer, and cytokine production were investigated after treatment with NE and EP.The plasma levels of NE and EP were significantly higher in EV71-infected patients with ANS dysregulation and PE than in controls. Both α1A- and β2-ADRs were expressed on A549, RD, SK-N-SH, HL-60, THP-1, Jurkat cells and hPBMCs. NE treatment elevated the percentages of EV71-infected cells to 62.9% and 22.7% in THP-1 and Jurkat cells, respectively. Via treatment with EP, the percentages of EV71-infected cells were increased to 64.6% and 26.9% in THP-1 and Jurkat cells. The percentage of EV71-infected cells increased upon NE or EP treatment while the α- and β-blockers reduced the percentages of EV71-infected cells with NE or EP treatment. At least two-fold increase in virus titer was observed in EV71-infected A549, SK-N-SH and hPBMCs after treatment with NE or EP. IL-6 production was enhanced in EV71-infected hPBMCs at a concentration of 102 pg/mL NE.The plasma levels of NE and EP elevated in EV71-infected patients with ANS

  6. Clinical Efficacy of Therapy with Recombinant Human Interferon α1b in Hand, Foot, and Mouth Disease with Enterovirus 71 Infection.

    Directory of Open Access Journals (Sweden)

    Xueyong Huang

    Full Text Available A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-α1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-α1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD.Chinese Clinical Trial Registry ChiCTR-TRC-14005153.

  7. Evolutionary trajectory of the VP1 gene of human enterovirus 71 genogroup B and C viruses

    NARCIS (Netherlands)

    S.M.G. van der Sanden (Sabine); H.G.A.M. van der Avoort (Harrie); P. Lemey (Philippe); G. Uslu (Gökhan); M.P.G. Koopmans D.V.M. (Marion)

    2010-01-01

    textabstractFrom 1963 to 1986, human enterovirus 71 (HEV71) infections in the Netherlands were successively caused by viruses of subgenogroups B0, B1 and B2. A genogroup shift occurred in 1987, after which viruses of subgenogroups C1 and C2 were detected exclusively. This is in line with HEV71

  8. Neonatal enterovirus infections reported to the national enterovirus surveillance system in the United States, 1983-2003.

    Science.gov (United States)

    Khetsuriani, Nino; Lamonte, Ashley; Oberste, M Steven; Pallansch, Mark

    2006-10-01

    Neonatal enterovirus (EV) infections lead to a wide range of clinical manifestations, from mild febrile illness to severe, sometimes fatal, sepsislike disease. To determine the relationship of EV serotypes with the risk of neonatal infection and its fatal outcome, we analyzed data reported to the National Enterovirus Surveillance System (NESS) during 1983-2003. Of the 26,737 EV detections reported during this period, neonates accounted for 2544 (11.4% of those with known age). Serotypes most commonly isolated from neonates included echovirus (E) 11 (14.0% of EV with known serotype), coxsackievirus (CV) B2 (8.9%), CVB5 (7.5%), E6, E9 and CVB4 (6.8% each). CVB1-4, E11, and E25 were significantly more common, whereas CVA16, E4, E9, E21, E30, and human parechovirus 1 (formerly E22) were less common among neonates than among persons aged > or =1 month. Fatal outcome was noted for 3.3% of reports, with neonates at a higher risk of death than persons aged > or =1 month (11.5% versus 2.5%; odds ratio [OR] 5.1; 95% confidence interval [CI] = 3.3-7.8). Neonates infected with CVB4 were at a higher risk of death (OR 6.5; 95% CI = 2.4-17.7) than those infected with other EV. EV are important neonatal pathogens associated with high risk of infection and death. Because of the limitations of the NESS (incomplete reporting, limited clinical data, bias towards more severe and younger cases), additional studies are needed to better evaluate the role of different EV in neonatal infections.

  9. Virucidal activity of Virkon S on human enterovirus.

    Science.gov (United States)

    Chan, Y F; Abu Bakar, S

    2005-06-01

    The efficacy of Virkon S, a commercial disinfectant as a virucidal spray against human enterovirus 71 (HEV71), the causative agent of the fatal form of hand, foot and mouth disease was examined. At least one log10 reduction of HEV71 titer was achieved when one spray of Virkon (1% or 2%) with ten minutes of contact time was applied. The infectivity was completely lost when four sprays of 1% or 2% Virkon were applied, suggesting that at least four sprays of 1% Virkon to the surface bound HEV71 was necessary to completely inactivate the virus. These findings suggest that Virkon S at the proper concentration is suitable to be used as an effective and easy to use disinfectant against HEV71.

  10. ENTEROVIRUS INFECTION IN CHILDREN: CLINICAL AND EPIDEMIOLOGICAL FEATURES AT THE CURRENT STAGE

    Directory of Open Access Journals (Sweden)

    G. P. Martynova

    2016-01-01

    Full Text Available The article presents the current clinical and epidemiological features of enterovirus infection in children of Krasnoyarsk Territory. A retrospective analysis of the incidence of enterovirus infection and enterovirus meningitis in the period 2014—2015 according to the forms of state statistical reporting №2 «Information on infectious and parasitic diseases». Clinical and epidemiological analysis of enterovirus infection in 454 children who were treated at MBUZ «City Children's Infectious Hospital №1» in the period of seasonal rise of morbidity in 2014 revealed a prevalence of etiological structure of enteroviruses Coxsackie B, Coxsackie B5, Coxsackie B3, Coxsackie B4. The region recorded the different clinical forms of enterovirus infection (rash, myalgia, diarrhea, gerpangina, the structure of which is still, aseptic meningitis prevails.

  11. Epidemiology of Enterovirus 71 Infections in Taiwan

    Directory of Open Access Journals (Sweden)

    Min-Yuan Chia

    2014-08-01

    Full Text Available Enterovirus 71 (EV71 was first described in USA in 1969 but retrospective studies in The Netherlands further detected EV71 in the clinical specimens collected in 1963. EV71 has one single serotype measured by using hyperimmune animal antisera but can be phylogenetically classified into three genogroups (A, B, and C including 11 genotypes (A, B1–B5, C1–C5. In Taiwan, EV71 caused a large-scale nationwide epidemic in 1998. Retrospective studies further detected EV71 in clinical specimens collected from hand–foot–mouth disease patients in 1980 and 1986. Therefore, EV71 may have circulated in Taiwan prior to 1980. Since 1998, EV71 has cyclically caused nationwide epidemics with different predominant genotypes in 1998 (genotype C2, 2000–2001 (B4, 2005 (C4, 2008 (B5, and 2012 (B5. Phylogenetic analysis revealed that C4 viruses isolated in 2005 were probably from China, B5 viruses isolated in 2008 were probably from South Eastern Asia, and B5 viruses isolated in 2012 were probably from Xiamen, China. Several studies have collected postinfection sera from children to measure cross-reactive neutralizing antibody titers against different EV71 genotypes and found that antigenic differences between genogroup B and C viruses did not have a clear pattern but that genotype A virus was antigenically different from genogroup B and C viruses. In conclusion, EV71 cyclically caused nationwide epidemics through international importations. EV71 surveillance in Taiwan should combine genetic and serological methods.

  12. Human Enteroviruses isolated during acute flaccid paralysis ...

    African Journals Online (AJOL)

    All 28 isolates from L20B were characterized by rRT-PCR as Sabin-like polioviruses. No wild poliovirus or VDPV was found. However from the microneutralisation assay, six different enteroviruses were characterized. Among these, Coxsackie B viruses were most predominant followed by Echovirus. Three children from ...

  13. [Group enterovirus infection due to coxsackievirus A16 in Northwestern Russia].

    Science.gov (United States)

    Bichurina, M A; Romanenkova, N I; Novikova, N A; Golitsyna, L N; Rozaeva, N R; Kanaeva, O I; Ermakova, M V; Kamynina, L S; Madoian, A G; Valdaĭtseva, N V; Leonova, N P; Ivanova, T G

    2014-01-01

    Study features of epidemic process and etiology of oral cavity and limb enterovirus exanthema group diseases in a number of territories of Northwestern Russia. Isolation and identification of non-poliomyelitis enteroviruses from material of patients was carried out according to WHO recommendations. Phenotyping and phylogenetic analysis of enteroviruses was carried out. In 3 territories of Northwestern Russia oral cavity and limb enterovirus group diseases were registered. Children aged less than 14 years, predominately aged less than 3 years, were shown to be involved in the epidemic process. Coxsackie A16 enteroviruses from 27 samples of patients were isolated in cell cultures and identified by using specific sera. Coxsackie A16 enteroviruses from 16 samples were identified by using partial sequencing of VP1 genome area. Phylogenetic analysis has shown that the identified Coxsackie A16 viruses distributed among 2 phylogenetic groups. Coxsackie A16 enteroviruses that had never been detected in the region previously were established to be the etiologic factor of oral cavity and limb enterovirus exanthema group disease in the 3 territories of Northwestern Russia. The data obtained give evidence on the necessity of epidemiologic and virological control for enterovirus infection with the aim of obtaining novel information on the circulation of non-poliomyelitis enteroviruses in the population and the establishment of development patterns for epidemic process of this infection.

  14. Proactive approach to containment of enterovirus infection in the nursery.

    Science.gov (United States)

    Fuchs, Inbal; Golan, Agneta; Borer, Abraham; Shemer-Avni, Yonat; Dagan, Ron; Greenberg, David

    2013-07-01

    Administration of prophylactic intravenous immunoglobulins to contacts of infants actively shedding enterovirus during a hospital nursery outbreak may attenuate severity of disease in those contacts and aid in containment of the outbreak. Four cases of neonatal enteroviral disease were treated in our hospital nursery in July and August 2011; 3 were presumed or proven vertical transmission cases and 1 was a presumed horizontal transmission. We aimed to prevent development of severe illness in contacts of affected neonates following a ministry of health advisory during the summer of 2011 warning of increased neonatal enteroviral morbidity and mortality in Israel. Strict infection control measures were implemented, including meticulous decontamination of the nursery environment and administration of intravenous immunoglobulin prophylaxis to contacts. No further horizontal transmission occurred after infection control interventions. Immunoglobulin prophylaxis to control enteroviral infection in the nursery should be considered as an auxiliary infection control intervention during a nursery outbreak.

  15. Survey of enterovirus infections from hand, foot and mouth disease outbreak in china, 2009

    Directory of Open Access Journals (Sweden)

    Yang Fan

    2011-11-01

    Full Text Available Abstract Background In China, a rapid expansion of Hand, foot, and mouth disease (HFMD outbreaks has occurred since 2004 and HFMD has become an important issue for China. However, people are still only concerned with human enterovirus 71(HEV-71 and coxsackie virus A16 (CV-A16. Much of what is known about the other enterovirus infections relies on fractional evidence and old epidemic data, with little knowledge concerning their distribution. To alert potential threatens of the other enteroviruses, our study genetically characterized specimens from different regions of China and yielded novel information concerning the circulating and phylogenetic characteristics of enteroviral strains from HFMD cases. Findings A total of 301 clinical throat swabs were randomly obtained from patients suffering from HFMD from the southern, northern and central regions of China during outbreaks in 2009. 266 of 301 (88.4% HFMD cases were found positive for HEV and seven genotypes, HEV-71, CV-A16, -B5, -A4, -A6, -A10, and -A12, were detected. Conclusions The HFMD pathogen compositions in the different regions of China were significantly different. HFMD epidemics might persist for a long time in China due to the multiple pathogen compositions, the enteroviral characteristic of recombination and co-infection, the ever-increasing travel and migration and the deficiency of effective vaccine. Our study deserves the attention on HFMD control and vaccine development.

  16. Deferoxamine Compensates for Decreases in B Cell Counts and Reduces Mortality in Enterovirus 71-Infected Mice

    Directory of Open Access Journals (Sweden)

    Yajun Yang

    2014-07-01

    Full Text Available Enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. No vaccine or antiviral therapy is currently available. In this work, we found that the number of B cells was reduced in enterovirus 71-infected mice. Deferoxamine, a marine microbial natural product, compensated for the decreased levels of B cells caused by enterovirus 71 infection. The neutralizing antibody titer was also improved after deferoxamine treatment. Furthermore, deferoxamine relieved symptoms and reduced mortality and muscle damage caused by enterovirus 71 infection. This work suggested that deferoxamine has the potential for further development as a B cell-immunomodulator against enterovirus 71.

  17. Enterovirus infection in children attending two outpatient clinics in Zhejiang Province, China.

    Science.gov (United States)

    Cai, Jian; Lv, Huakun; Lin, Junfen; Chen, Zhiping; Fang, Chunfu; Han, Jiankang

    2014-09-01

    Enteroviruses are responsible for hand, foot, and mouth disease, and have caused many deaths in China during recent years. But the natural history of enterovirus infection in children, especially asymptomatic children, is not yet clear. From April 2011 to May 2012, 505 stool and throat swab samples of children attending outpatients clinics in two hospitals were collected weekly to test for Enterovirus 71, Coxsackievirus A16, and other enterovirus nucleic acids by real-time RT-PCR. Two hundred sixty-four patients were enterovirus positive, the positive rate was 52.3%, 27.5% (22/80) in children without a rash and 56.9% (242/425) in children with a rash. Coxsackievirus A16 positive rate of male (24%, 61/254) was higher than that of female (15.2%, 26/171) (χ(2)  = 4.87, P = 0.027). The highest positive rate of enterovirus infection was 63.5% in the 2-year-old age group. Comparing children with and without a rash, within the same age groups, no statistical difference was found (P > 0.05). The seasonal distribution of Enterovirus 71 had only one peak in May, but Coxsackievirus A16 had two peaks in April and October. In patients with a rash, the frequency of Enterovirus 71 was relatively high before July, and then that of Coxsackievirus A16 increased gradually. In the case of Enterovirus 71 and Coxsackievirus A16, stool specimens had a higher positive rate than throat swab specimens' (χ(2)  = 3.88, P = 0.05; χ(2)  = 15.13, P < 0.001). Enterovirus infection was more frequent in males 2-3 year-old children, with the implicated virus varying by season. Targeted prevention and control measures should be carried out. © 2014 Wiley Periodicals, Inc.

  18. [Prevalence of enterovirus infection in infants in Armenia, Colombia, 2009].

    Science.gov (United States)

    González, María Mercedes; Giraldo, Alejandra María; Quintero, Liliana; Padilla, Leonardo; Sarmiento, Luis; Castaño, Jhon Carlos

    2011-01-01

    Despite world wide circulation of enteroviruses, little information has accumulated on the circulation of enteroviruses in Colombia. The prevalence of enterovirus circulation was examined in children under 1 year to identify the most common enterovirus serotypes. Fecal samples were collected from 320 children under 1 year of age who attended a first-level health center in the city of Armenia, Colombia, in 2009. Enterovirus detection was performed by reverse transcription reaction and nested polymerase chain reaction (RT-N-PCR) using generic enterovirus primers. Samples testing positive in the RT-N-PCR were inoculated into cell cultures susceptible to enterovirus. All isolates were typed by seroneutralization with Lim-Benyesh-Melnick antiserum pools. Overall, enteroviral RNA was detected in 43 of 320 (13.3%; 95% CI: 9.7 to 17.1) fecal samples by RT-N-PCR. Viral isolation was possible in 26 of 43 (60.4%) of the positive samples. Of these, 15 were Coxsackievirus B (eight CVB1, two CVB2, five CVB5) and 11 Echovirus (six E6 and five E30). The enteroviral circulation in a population on newly bornes up to 1 year old was 13.3%;the most frequent enterovirus was the same as those serotypes most commonly isolated in other parts of the world. The use of RT-N-PCR was demonstrably feasible as a tool to monitor the presence of enterovirus in stool samples.

  19. Enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.

    Science.gov (United States)

    Tan, Soon Hao; Ong, Kien Chai; Wong, Kum Thong

    2014-11-01

    Enterovirus 71 (EV71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. We investigated EV71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. Enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. Harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. In unimmunized mice, viral antigen and RNA were detected within 24 hours after infection only in ipsilateral cranial nerves, motor trigeminal nucleus, reticular formation, and facial nucleus; viral titers were significantly higher in the brainstem than in the spinal cord samples. Mice given preinfection hyperimmune serum showed a marked reduction of ipsilateral viral antigen/RNA and viral titers in the brainstem in a dose-dependent manner. With optimum hyperimmune serum given after infection, brainstem infection was significantly reduced in a time-dependent manner. A delay in disease onset and a reduction of disease severity and mortality were also observed. Thus, EV71 can directly infect the brainstem, including the medulla, via cranial nerves, most likely by retrograde axonal transport. This may explain the sudden cardiorespiratory collapse in human patients with fatal encephalomyelitis. Moreover, our results suggest that passive immunization may still benefit EV71-infected patients who have neurologic complications.

  20. African Non-Human Primates Host Diverse Enteroviruses.

    Directory of Open Access Journals (Sweden)

    Illich Manfred Mombo

    Full Text Available Enteroviruses (EVs belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP. Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas. The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations.

  1. A novel enterovirus species identified from severe diarrheal goats.

    Directory of Open Access Journals (Sweden)

    Mingyue Wang

    Full Text Available The Enterovirus genus of the family of Picornaviridae consists of 9 species of Enteroviruses and 3 species of Rhinoviruses based on the latest virus taxonomy. Those viruses contribute significantly to respiratory and digestive disorders in human and animals. Out of 9 Enterovirus species, Enterovirus E-G are closely related to diseases affecting on livestock industry. While enterovirus infection has been increasingly reported in cattle and swine, the enterovirus infections in small ruminants remain largely unknown.Virology, molecular and bioinformatics methods were employed to characterize a novel enterovirus CEV-JL14 from goats manifesting severe diarrhea with morbidity and mortality respectively up to 84% and 54% in China.CEV-JL14 was defined and proposed as a new Enterovirus species L within the genus of Enterovirus of the family Picornaviridae. CEV-JL14 had a complete genome sequence of 7461 nucleotides with an ORF encoding 2172 amino acids, and shared 77.1% of genomic sequence identity with TB4-OEV, an ovine enterovirus. Comparison of 5'-UTR and structural genes of CEV-JL14 with known Enterovirus species revealed highly genetic variations among CEV-JL14 with known Enterovirus species. VP1 nucleotide sequence identities of CEV-14 were 51.8%-53.5% with those of Enterovirus E and F, 30.9%-65.3% with Enterovirus G, and 43.8-51. 5% with Enterovirus A-D, respectively. CEV-JL14 was proposed as a novel species within the genus of Enterovirus according to the current ICTV demarcation criteria of enteroviruses.CEV-JL14 clustered phylogenetically to neither Enterovirus E and F, nor to Enterovirus G. It was defined and proposed as novel species L within the genus of Enterovirus. This is the first report of caprine enterovirus in China, the first complete genomic sequence of a caprine enterovirus revealed, and the unveiling of significant genetic variations between ovine enterovirus and caprine enterovirus, thus broadening the current understanding of

  2. The absence of exanthema is related with death and illness severity in acute enterovirus infection.

    Science.gov (United States)

    Zhou, Hong-Tao; Guo, Yong-Hui; Tang, Pei; Zeng, Lei; Pan, Yu-Xian; Ding, Xi-Xia; Wen, Kun; Tao, Shao-Hua; Chen, Man-Jun; Wang, Bin; Yu, Nan; Che, Xiao-Yan

    2014-11-01

    To clarify whether exanthema is related to illness severity in acute enterovirus infection in children. The data of pediatric inpatients at Zhujiang Hospital during 2009-2012 with an acute enterovirus infection were reviewed retrospectively. Enterovirus infection was determined by real-time reverse transcription PCR. Clinical data were summarized and compared between cases with and without exanthema. A total of 780 pediatric inpatients with an acute enterovirus infection were included in this study, of whom 83 (10.6%) presented no exanthema. The percentage of deaths in the group of patients without exanthema was significantly higher than that in the group with exanthema (7.2% vs. 1.1%; p = 0.002). Central nervous system involvement (41.0% vs. 30.0%; p = 0.041), severe central nervous system (CNS) involvement (21.7% vs. 11.0%; p = 0.005), severe CNS involvement with cardiopulmonary failure (9.6% vs. 2.3%; p = 0.002), an altered level of consciousness (15.7% vs. 7.6%; p = 0.013), and convulsions (14.4% vs. 6.3%; p = 0.007) occurred significantly more frequently in the group without exanthema. A considerable proportion of children with an acute enterovirus infection in Guangdong Province, China during 2009-2012 presented no exanthema, and the absence of exanthema was found to be related to death and illness severity for these acute enterovirus infections. Clinicians in China should consider enterovirus as the possible pathogen when treating children with an acute pathogen infection without exanthema.

  3. Frequency of isolation of polioviruses and non polio enteroviruses from patients with acute flaccid paralysis, enterovirus infection and children from groups at risk

    Directory of Open Access Journals (Sweden)

    N. I. Romanenkova

    2012-01-01

    Full Text Available The article describes the frequency of isolation of polioviruses and non polio enteroviruses from different categories of the investigated children. The percentage of detection of polioviruses from the patients with acute flaccid paralysis was lower than that from the children from groups at risk. Among the patients with the enterovirus infection the polioviruses were rarely revealed. The frequency of isolation of non polio enteroviruses from these patients was significantly higher than that from the other categories of investigated persons. The improvement of poliomyelitis surveillance and the reinforcement of virological surveillance of children from groups at risk and those with enterovirus infection will provide the important data for Global Polio Eradication Initiative and the maintenance of polio free status of the Russian Federation.

  4. Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71

    Directory of Open Access Journals (Sweden)

    Lianfeng Zhang

    2013-05-01

    Full Text Available Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50 of 12.5 μg/mL. The utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to efficiently reduce mortality and relieve clinical symptoms through the inhibition of viral replication. Chebulagic acid may represent a potential therapeutic agent to control infections to enterovirus 71.

  5. Enterovirus 71 infection: An experience in Korea, 2009

    Directory of Open Access Journals (Sweden)

    Kyung Hyo Kim

    2010-05-01

    Full Text Available Enterovirus 71 (EV71 has been recognized as a frequent cause of epidemics of hand-foot-and-mouth disease (HFMD associated with severe neurological symptoms. In the spring of 2009, HFMD was epidemic in Korea. Severe cases with complication, including death, have been reported and it has become a public health issue. Most symptomatic EV71 infections commonly result in HFMD or herpangina. These clinical manifestations can be associated with neurologic syndromes frequently. Neurologic syndromes observed in EV71 include meningitis, meningoencephalomyelitis, poliomyelitis-like paralytic disease, Guillain-Barr&eacute; syndrome, transverse myelitis, cerebellar ataxia, opsoclonus-myoclonus syndrome, benign intracranial hypertension, and brainstem encephalitis. Examinations for EV 71 were performed from the stools, respiratory secretion or CSF of the children by realtime PCR. Gene analysis showed that most of them were caused by EV71 subgenotype C4a which was prevalent in China, 2008. Public health measures including personal and environmental hygiene, must to target daycare centers, kindergartens, and schools where highly susceptible children congregate. To prevent the spread of infection, preschools where transmission persists for more than 2 incubation periods, have been recommended for closure, and trigger criteria for voluntary closure was instituted. During closure, operators are to thoroughly clean the centers before they are allowed to reopen. In addition, parents are advised to ensure that their children adopt a high standard of personal hygiene and to keep the infected child at home until full recovery. Because the outbreaks occur in a cyclical pattern, surveillance system to predict next outbreaks and adequate public health measures to control need to be planned for future. Control of EV71 epidemics through surveillance and public health intervention needs to be maintained in Korea. Future research should focus on understanding of EV71

  6. Molecular identification of 13 new enterovirus types, EV79-88, EV97, and EV100-101, members of the species Human Enterovirus B.

    Science.gov (United States)

    Oberste, M Steven; Maher, Kaija; Nix, William A; Michele, Suzanne M; Uddin, Moyez; Schnurr, David; al-Busaidy, Suleiman; Akoua-Koffi, Chantal; Pallansch, Mark A

    2007-09-01

    Molecular methods have enabled the rapid identification of new enterovirus (EV) serotypes that are untypeable using existing neutralizing antisera. As a result, sequencing of the VP1 capsid gene has been developed as a surrogate for antigenic typing to distinguish enterovirus types. In this study, 17 enterovirus isolates from four countries were identified as members of 13 new types within the species Human Enterovirus B (HEV-B) by complete genome sequencing. Members of each of these new types are at least 75% identical to one another (91% amino acid identity) in VP1, but members of different types differ from one another and from other enteroviruses by at least 27% in nucleotide sequence (26% amino acid sequence difference). The complete P1 (capsid) sequences of the new types are at least 17% different from those of all other enterovirus serotypes (14.5% amino acid sequence difference), but they are highly conserved within a type (93% amino acid identity), confirming that the 17 new strains belong to HEV-B. We propose that these 17 isolates be classified as members of 13 new human enterovirus types, enteroviruses 79-88, 97, and 100-101.

  7. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    Science.gov (United States)

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  8. High seroprevalence of enterovirus infections in apes and old world monkeys.

    Science.gov (United States)

    Harvala, Heli; McIntyre, Chloe L; Imai, Natsuko; Clasper, Lucy; Djoko, Cyrille F; LeBreton, Matthew; Vermeulen, Marion; Saville, Andrew; Mutapi, Francisca; Tamoufé, Ubald; Kiyang, John; Biblia, Tafon G; Midzi, Nicholas; Mduluza, Takafira; Pépin, Jacques; Njouom, Richard; Njoum, Richard; Smura, Teemu; Fair, Joseph N; Wolfe, Nathan D; Roivainen, Merja; Simmonds, Peter

    2012-02-01

    To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.

  9. Molecular Epidemiology of Human Rhinoviruses and Enteroviruses Highlights Their Diversity in Sub-Saharan Africa.

    Science.gov (United States)

    L'Huillier, Arnaud G; Kaiser, Laurent; Petty, Tom J; Kilowoko, Mary; Kyungu, Esther; Hongoa, Philipina; Vieille, Gaël; Turin, Lara; Genton, Blaise; D'Acremont, Valérie; Tapparel, Caroline

    2015-12-08

    Human rhinoviruses (HRVs) and enteroviruses (HEVs) belong to the Enterovirus genus and are the most frequent cause of infection worldwide, but data on their molecular epidemiology in Africa are scarce. To understand HRV and HEV molecular epidemiology in this setting, we enrolled febrile pediatric patients participating in a large prospective cohort assessing the causes of fever in Tanzanian children. Naso/oropharyngeal swabs were systematically collected and tested by real-time RT-PCR for HRV and HEV. Viruses from positive samples were sequenced and phylogenetic analyses were then applied to highlight the HRV and HEV types as well as recombinant or divergent strains. Thirty-eight percent (378/1005) of the enrolled children harboured an HRV or HEV infection. Although some types were predominant, many distinct types were co-circulating, including a vaccinal poliovirus, HEV-A71 and HEV-D68. Three HRV-A recombinants were identified: HRV-A36/HRV-A67, HRV-A12/HRV-A67 and HRV-A96/HRV-A61. Four divergent HRV strains were also identified: one HRV-B strain and three HRV-C strains. This is the first prospective study focused on HRV and HEV molecular epidemiology in sub-Saharan Africa. This systematic and thorough large screening with careful clinical data management confirms the wide genomic diversity of these viruses, brings new insights about their evolution and provides data about associated symptoms.

  10. Therapeutic Use of Native and Recombinant Enteroviruses.

    Science.gov (United States)

    Ylä-Pelto, Jani; Tripathi, Lav; Susi, Petri

    2016-02-23

    Research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. Many of these "viral" receptors are overexpressed in cancer cells. Receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e., disruption of the cells. Viral tropism and cytolytic properties thus make native enteroviruses prime candidates for oncolytic virotherapy. Copy DNA cloning and modification of enterovirus genomes have resulted in the generation of enterovirus vectors with properties that are useful in therapy or in vaccine trials where foreign antigenic epitopes are expressed from or on the surface of the vector virus. The small genome size and compact particle structure, however, set limits to enterovirus genome modifications. This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy.

  11. Therapeutic Use of Native and Recombinant Enteroviruses

    Directory of Open Access Journals (Sweden)

    Jani Ylä-Pelto

    2016-02-01

    Full Text Available Research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. Many of these “viral” receptors are overexpressed in cancer cells. Receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e., disruption of the cells. Viral tropism and cytolytic properties thus make native enteroviruses prime candidates for oncolytic virotherapy. Copy DNA cloning and modification of enterovirus genomes have resulted in the generation of enterovirus vectors with properties that are useful in therapy or in vaccine trials where foreign antigenic epitopes are expressed from or on the surface of the vector virus. The small genome size and compact particle structure, however, set limits to enterovirus genome modifications. This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy.

  12. Identification and typing of human enterovirus: a genomic barcode approach.

    Directory of Open Access Journals (Sweden)

    Chengguo Wei

    Full Text Available Identification and typing of human enterovirus (HEVs are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-mer based barcode image for each genome, HEV or other human viruses, for a fixed k, 1human viruses and 395 HEV sequences. The tree shows a clear separation of the HEV viruses from all the non-HEV viruses with 100% accuracy and a separation of the HEVs into four distinct clads with 93.4% consistency with a multiple sequence alignment-based phylogeny. Our detailed analyses of the HEVs having different typing results by the two methods indicate that our results are in better agreement with known information about the HEVs.

  13. Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence.

    Science.gov (United States)

    Chia, J; Chia, A; Voeller, M; Lee, T; Chang, R

    2010-02-01

    Enteroviruses are well-known causes of acute respiratory and/or gastrointestinal infections and non-specific flu-like illness. Although enterovirus protein, RNA and non-cytopathic viruses have been demonstrated in the stomach biopsies of patients with myalgia encephalomyelitis/chronic fatigue syndrome (ME/CFS), causality for chronic diseases is difficult to establish without having well-documented cases of acute enterovirus infections. The aim of this study was to link acute enteroviral infection to viral persistence in patients with ME/CFS. Patients admitted to the hospital with acute febrile illnesses were screened for enteroviral infections. Acutely infected patients were followed longitudinally, and those who developed symptoms of ME/CFS underwent oesophagogastroduodenoscopy and biopsies of the antrum to document viral persistence by immunoperoxidase staining for viral protein and viral RNA assay. Three representative patients with different manifestations of acute enterovirus infections progressed to have chronic symptoms of ME/CFS. Persistent viral infection was demonstrated in the antrum years later. After acute infections, enteroviruses can persist in patients resulting in manifestation of ME/CFS. Chronic enterovirus infection in an immunocompetent host may be an example of a stalemate between attenuated, intracellular viruses and an ineffective immune response.

  14. Antiviral activity of punicalagin toward human enterovirus 71 in vitro and in vivo.

    Science.gov (United States)

    Yang, Yajun; Xiu, Jinghui; Zhang, Lianfeng; Qin, Chuan; Liu, Jiangning

    2012-12-15

    Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children and has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available currently in the clinic. In this work, we investigated the antiviral effect of punicalagin on enterovirus 71 both in vitro and in vivo. The results showed that punicalagin reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC₅₀) value of 15 μg/ml. Moreover, punicalagin treatment of mice challenged with a lethal dose of enterovirus 71 resulted in a reduction of mortality and relieved clinical symptoms by inhibiting viral replication. Our work suggested that punicalagin have the potential for further development as antiviral agents against enterovirus 71. Copyright © 2012 Elsevier GmbH. All rights reserved.

  15. Differential gene expressions of the MAPK signaling pathway in enterovirus 71-infected rhabdomyosarcoma cells

    Directory of Open Access Journals (Sweden)

    Weifeng Shi

    Full Text Available BACKGROUND: Mitogen-activated protein kinase (MAPK signaling pathway plays an important role in response to viral infection. The aim of this study was to explore the function and mechanism of MAPK signaling pathway in enterovirus 71 (EV71 infection of human rhabdomyosarcoma (RD cells. METHODS: Apoptosis of RD cells was observed using annexin V-FITC/PI binding assay under a fluorescence microscope. Cellular RNA was extracted and transcribed to cDNA. The expressions of 56 genes of MAPK signaling pathway in EV71-infected RD cells at 8 h and 20 h after infection were analyzed by PCR array. The levels of IL-2, IL-4, IL-10, and TNF-α in the supernatant of RD cells infected with EV71 at different time points were measured by ELISA. RESULTS: The viability of RD cells decreased obviously within 48 h after EV71 infection. Compared with the control group, EV71 infection resulted in the significantly enhanced releases of IL-2, IL-4, IL-10 and TNF-α from infected RD cells (p < 0.05. At 8 h after infection, the expressions of c-Jun, c-Fos, IFN-i, MEKK1, MLK3 and NIK genes in EV71-infected RD cells were up-regulated by 2.08-6.12-fold, whereas other 19 genes (e.g. AKT1, AKT2, E2F1, IKK and NF-κB1 exhibited down-regulation. However, at 20 h after infection, those MAPK signaling molecules including MEKK1, ASK1, MLK2, MLK3, NIK, MEK1, MEK2, MEK4, MEK7, ERK1, JNK1 and JNK2 were up-regulated. In addition, the expressions of AKT2, ELK1, c-Jun, c-Fos, NF-κB p65, PI3K and STAT1 were also increased. CONCLUSION: EV71 infection induces the differential gene expressions of MAPK signaling pathway such as ERK, JNK and PI3K/AKT in RD cells, which may be associated with the secretions of inflammatory cytokines and host cell apoptosis.

  16. Passive protection effect of chicken egg yolk immunoglobulins on enterovirus 71 infected mice.

    Science.gov (United States)

    Liou, Jenn-Fa; Chang, Chih-Wei; Tailiu, Jui-jane; Yu, Chun-Keung; Lei, Huan-Yao; Chen, Lih-Ren; Tai, Chein

    2010-11-29

    The objective of this study is to evaluate the passive protective efficiency of immunoglobulin in yolk (IgY) specific against human enterovirus type 71 (EV71). The antibody was raised by intramuscular immunization to 10 White Leghorn hens, with inactivated human EV71 serving as the antigen. The titer and specificity of the antibody were analyzed from purified IgY in the egg yolks of immunized hens. Results indicate that the titer of IgY specific against EV71 increased from the third week after the first immunization. The content of total IgY was 190 ± 26 mg/yolk, with an average concentration of specific IgY of 6.34 ± 3.38 mg/yolk in the eggs from 3 to 18 wk after immunization. The results of the neutralization effect of specific IgY in EV71-challenged mice demonstrate that the EV71-specific IgY, either by intraperitoneal injection or oral administration, was able to significantly reduce the morbidity and mortality in EV71 infected mice pups. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Development of a sensitive and specific epitope-blocking ELISA for universal detection of antibodies to human enterovirus 71 strains.

    Directory of Open Access Journals (Sweden)

    Fang He

    Full Text Available BACKGROUND: Human Enterovirus 71 (EV71 is a common cause of hand, foot and mouth disease (HFMD in young children. It is often associated with severe neurological diseases and mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no efficient universal antibody test available to detect EV71 infections. METHODOLOGY/PRINCIPAL FINDING: In the present study, an epitope-blocking ELISA was developed to detect specific antibodies to human EV71 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (Mab 1C6 that specifically binds to capsid proteins in whole EV71 viruses without any cross reaction to any EV71 capsid protein expressed alone. The sensitivity and specificity of the epitope-blocking ELISA for EV71 was evaluated and compared to microneutralization using immunized animal sera to multiple virus genotypes of EV71 and coxsackieviruses. Further, 200 serum sample from human individuals who were potentially infected with EV71 viruses were tested in both the blocking ELISA and microneutralization. Results indicated that antibodies to EV71 were readily detected in immunized animals or human sera by the epitope blocking ELISA whereas specimens with antibodies to other enteroviruses yielded negative results. This assay is not only simpler to perform but also shows higher sensitivity and specificity as compared to microneutralization. CONCLUSION: The epitope-blocking ELISA based on a unique Mab 1C6 provided highly sensitive and 100% specific detection of antibodies to human EV71 viruses in human sera.

  18. Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

    Directory of Open Access Journals (Sweden)

    Huang Szu-Wei

    2011-11-01

    Full Text Available Abstract Background Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71 strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE, was not evident. Methods To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection. Results After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS. While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only. Conclusions Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.

  19. Human rhino- and enteroviruses in children with respiratory symptoms in Luanda, Angola.

    Science.gov (United States)

    Taipale, Anni; Pelkonen, Tuula; Roivainen, Merja; Kaijalainen, Svetlana; Bernardino, Luis; Peltola, Heikki; Pitkäranta, Anne

    2014-05-01

    The role of human rhinoviruses (HRV) and human enteroviruses (HEV) in common colds, as well as their seasonality, remains largely unknown in tropical environments. The study aimed to define the frequency and clinical features of HRV and HEV in children with respiratory symptoms in tropical Africa during autumn and winter. Clinical data and PCR assays of nasopharyngeal swabs (NPS) were collected from 67 (66%) children with and 35 (34%) children without chronic illnesses who were attending different outpatient clinics at a paediatric tertiary-care hospital in Luanda, Angola. Thirty-six (35%) children had HIV infection, and 27 (26%) were malnourished. Thirty-seven (36%) out of 102 NPS specimens were virus-positive: 34 (33%) for HRV and 10 (10%) for HEV. Seven (7%) had co-infection. The highest HRV-positivity rate (47%) occurred in July (P = 0·02), a mid-winter month with high relative humidity but no precipitation. Virus positivity was associated with younger age (median 36 vs 52 months, P = 0·02) but not with specific symptoms or findings. HRVs play a major role in young children's respiratory infections in urban tropical Angola during autumn and winter. A better understanding is required of the seasonality and clinical outcomes of these viruses in children living in resource-poor tropical countries.

  20. Maternal Enterovirus Infection during Pregnancy as a Risk Factor in Offspring Diagnosed with Type 1 Diabetes between 15 and 30 Years of Age

    Directory of Open Access Journals (Sweden)

    Maria Elfving

    2008-01-01

    Full Text Available Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM antibodies and enterovirus genome (RNA, and compared to a control group. Among the index mothers, 9/30 (30% were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16% were enterovirus IgM-positive, and 4/90 (4% were positive for enterovirus RNA (n.s.. Boys of enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22–17.6, as compared to boys of IgM-negative mothers (P<.025. These results suggest that gestational enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.

  1. Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenjing; Tao, Junyan; Yang, Xiaoping [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Zhuliang [Key Laboratory of Biodiversity and Biogeography, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201 (China); Zhang, Li; Liu, Hongsheng [Department of Academy of Sciences, Liaoning University, Shenyang 110036 (China); Wu, Kailang [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wu, Jianguo, E-mail: jwu@whu.edu.cn [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China)

    2014-07-04

    Highlights: • Triterpenoids GLTA and GLTB display anti-EV71 activities without cytotoxicity. • The compounds prevent EV71 infection by blocking adsorption of the virus to the cells. • GLTA and GLTB bind to EV71 capsid at the hydrophobic pocket to block EV71 uncoating. • The two compounds significantly inhibit the replication of EV71 viral RNA. • GLTA and GLTB may be used as potential therapeutic agents to treat EV71 infection. - Abstract: Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential

  2. Detection and distribution of culturable Human Enteroviruses through environmental surveillance in Milan, Italy.

    Science.gov (United States)

    Pellegrinelli, L; Binda, S; Chiaramonte, I; Primache, V; Fiore, L; Battistone, A; Fiore, S; Gambino, M; Bubba, L; Barbi, M

    2013-11-01

    Human Enteroviruses (HEVs) infections have a significant impact on public health, being implicated in outbreaks of meningitis, encephalitis, hand-foot-mouth disease and other acute and chronic manifestation. In the strategic plan for poliomyelitis eradication, the environmental surveillance of poliovirus (PV) has been identified by the World Health Organization (WHO) as an activity that can complement the surveillance of polio. Having wastewater samples available for PV surveillance allows us to study nonpolio enteroviruses (NPEVs) circulating in the study population, which are widely spread. This study was carried out according to the WHO guidelines for environmental surveillance of PV and analysed the circulation of PV and NPEVs through the isolation of viruses in cell cultures in Milan area; from 2006 to 2010, 321 wastewater samples were collected, regularly over time, at the inlet of three diverse waste water treatment plants (WWTPs). Culturable HEVs were isolated in 80% of sewage samples: all isolates belonged to the HEV-B group and those circulating more intensely were CVB5 and Echo 6, while CVB4 was the predominant serotype found in 2010. In this study, two type 2 PVs were isolated, both characterized as Sabin like. Environmental monitoring of HEVs in Milan has proved to be an interesting tool to investigate the circulation and distribution of viruses. The detection of PV and other NPEV could be predictive of possible re-emergence of these viruses with an impact on public health. NPEV monitoring could also be a powerful public health tool to investigate the possible role of NPEV in different clinical manifestations. © 2013 The Society for Applied Microbiology.

  3. Estimation of contamination sources of human enteroviruses in a wastewater treatment and reclamation system by PCR-DGGE.

    Science.gov (United States)

    Ji, Zheng; Wang, Xiaochang C; Xu, Limei; Zhang, Chongmiao; Funamizu, Naoyuki; Okabe, Satoshi; Sano, Daisuke

    2014-06-01

    A polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) method was employed to estimate the contamination sources of human enteroviruses and understand how their dominant strains vary in a wastewater treatment and reclamation system consisting of sewage collection, wastewater treatment with membrane bioreactor and open lakes for reclaimed water storage and reuse. After PCR-DGGE using a selected primer set targeting enteroviruses, phylogenetic analysis of acquired enterovirus gene sequences was performed. Enteroviruses identified from the septic tank were much more diverse than those from grey water and kitchen wastewater. Several unique types of enterovirus different from those in wastewater samples were dominant in a biological wastewater treatment unit. Membrane filtration followed by chlorination was proved effective for physically eliminating enteroviruses; however, secondary contamination likely occurred as the reclaimed water was stored in artificial lakes. Enterovirus 71 (EV71), a hand-foot-and-mouth disease (HFMD) viral pathogen, was detected mainly from the artificial lakes, implying that wastewater effluent was not the contamination source of EV71 and that there were unidentified non-point sources of the contamination with the HFMD viral pathogen in the reclaimed water stored in the artificial lakes. The PCR-DGGE targeting enteroviruses provided robust evidence about viral contamination sources in the wastewater treatment and reclamation system.

  4. Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions.

    Science.gov (United States)

    Lukashev, Alexander N; Lashkevich, Vasilii A; Ivanova, Olga E; Koroleva, Galina A; Hinkkanen, Ari E; Ilonen, Jorma

    2005-12-01

    The complete nucleotide sequences of eight Human enterovirus B (HEV-B) strains were determined, representing five serotypes, E6, E7, E11, CVB3 and CVB5, which were isolated in the former Soviet Union between 1998 and 2002. All strains were mosaic recombinants and only the VP2-VP3-VP1 genome region was similar to that of the corresponding prototype HEV-B strains. In seven of the eight strains studied, the 2C-3D genome region was most similar to the prototype E30, EV74 and EV75 strains, whilst the remaining strain was most similar to the prototype E1 and E9 strains in the non-structural protein genome region. Most viruses also bore marks of additional recombination events in this part of the genome. In the 5' non-translated region, all strains were more similar to the prototype E9 than to other enteroviruses. In most cases, recombination mapped to the VP4 and 2ABC genome regions. This, together with the star-like topology of the phylogenetic trees for these genome regions, identified these genome parts as recombination hot spots. These findings further support the concept of independent evolution of enterovirus genome fragments and indicate a requirement for more advanced typing approaches. A range of available phylogenetic methods was also compared for efficient detection of recombination in enteroviruses.

  5. Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

    Science.gov (United States)

    Tao, Zexin; Wang, Haiyan; Li, Yan; Liu, Guifang; Xu, Aiqiang; Lin, Xiaojuan; Song, Lizhi; Ji, Feng; Wang, Suting; Cui, Ning; Song, Yanyan

    2014-01-01

    Human enteroviruses (HEVs) are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification) and phylogenetic analysis were performed. A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2%) and were identified into 17 serotypes. The nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant pathogens for the hand, foot, and mouth disease-is currently an important concern in mainland China.

  6. Increased Risk of Tics in Children Infected with Enterovirus: A Nationwide Population-Based Study.

    Science.gov (United States)

    Lin, Jiun-Nong; Lin, Cheng-Li; Yen, Hung-Rong; Yang, Chi-Hui; Lai, Chung-Hsu; Lin, Hsi-Hsun; Kao, Chia-Hung

    2017-05-01

    Both tics and enterovirus (EV) infections are common in children. The association between EV infections and tics has been seldom evaluated. The aim of this study was to evaluate the risk of diagnosed tics after EV infections in children. A nationwide retrospective cohort study was conducted to determine the risk of tics after EV infections by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged tics, death, loss to follow-up, withdrawal from the insurance system, or December 31, 2008. A total of 282,321 EV-infected and 282,317 non-EV-infected children were included in this study. The mean age was 2.39 years in both cohorts. The overall incidences of tics were 9.12 and 6.21 per 10,000 person-years in the EV-infected and non-EV-infected cohorts, respectively. Children with EV infection were significantly associated with an increased risk of tics compared with those without EV infection (adjusted hazard ratio, 1.38; 95% confidence interval, 1.27-1.5). Multivariable analyses showed that boys, children living in urbanized areas, children whose parents had white-collar jobs, and children with allergic rhinitis or bronchial asthma exhibited a significantly increased risk of tics. This study revealed an increased risk of tics after EV infection in children.

  7. Detection of enterovirus RNA in cerebrospinal fluid : Comparison of two molecular assays

    NARCIS (Netherlands)

    de Crom, S. C. M.; Obihara, C. C.; van Loon, A. M.; Argilagos-Alvarez, A. A.; Peeters, M. F.; van Furth, A. M.; Rossen, J. W. A.

    Enterovirus (EV) and human parechovirus (HPeV) are a major cause of infection in childhood. A rapid diagnostic test may improve the management of patients with EV and HPeV infection. The aim of this study is to evaluate the performance of the GeneXpert enterovirus assay (GXEA) for detection of EV

  8. Seroprevalence of human enterovirus 71 and coxsackievirus A16 in Guangdong, China, in pre- and post-2010 HFMD epidemic period.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available BACKGROUND: Human Enterovirus 71 and Coxsackie A16 have caused many outbreaks in the last decade in mainland China, resulting in thousands of fatal cases. Seroepidemiology which provides important information to document population immunity is rare in China. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study of Enterovirus 71 (EV71 and Coxsackie A16 (CA16 seroprevalence was carried out in Guangdong, China, pre- and post- the 2010 hand, foot and mouth disease (HFMD epidemic period. The levels of EV71 and CA16 specific antibodies were evaluated by a microneutralization test and the geometric mean titer (GMT was calculated and compared. Our results indicated frequent infection by EV71 and CA16 in Guangdong before the 2010 epidemic. Only EV71 neutralizing antibody but not CA16 seroprevalence was significantly increased after the 2010 HFMD epidemic. Children less than 3 years old especially those aged 2 years showed the lowest positive rates for EV71 and CA16 NA before epidemic and the most significantly increased EV71 seroprevalence after epidemic. CA16 GMT values declined after the 2010 epidemic. CONCLUSIONS: These results indicate EV71 was the major pathogen of HFMD in Guangdong during the 2010 epidemic. The infection occurs largely in children less than 3 years, who should have first priority to receive an EV71 vaccine.

  9. Neurotropism In Vitro and Mouse Models of Severe and Mild Infection with Clinical Strains of Enterovirus 71

    Directory of Open Access Journals (Sweden)

    Pin Yu

    2017-11-01

    Full Text Available Enterovirus 71 (EV71 is a common etiological agent of hand, foot, and mouth disease and fatal neurological diseases in children. The neuropathogenicity of severe EV71 infection has been documented, but studies comparing mouse models of severe and mild EV71 infection are lacking. The aim of the study was to investigate the neurovirulence of EV71 strains and the differences in serum cytokine and chemokine levels in mouse models of severe and mild EV71 infection. Nine EV71 isolates belonging to the C4 subgenogroup (proposed as genotype D displayed infectivity in human neuroblastoma SK-N-SH cells; moreover, ultrastructural observation confirmed viral particle replication. The survival rate of the severe model was 71.43% (5/7, and 60% (3/5 of the surviving severe model mice displayed sequelae of paralysis, whereas the only symptom in mild model mice was ruffled fur. Dynamic detection of serum cytokine and chemokine levels demonstrated that interleukin (IL-5, IL-13, IL-6, monocyte chemotactic protein 1 (MCP-1, and chemokine (C-C motif ligand 5 (also called Regulated upon Activation, Normal T-cell Expressed, and Secreted (CCL5/RANTES were significantly up-regulated at the early period of infection, indicating that these factors might herald a severe outcome. Our findings suggest that elevated cytokines and chemokines may have potential value as prognostic markers in mouse models.

  10. Acute Flaccid Paralysis by Enterovirus D68 Infection: First Italian Description in Adult Patient and Role of Electrophysiology

    Directory of Open Access Journals (Sweden)

    Marco Ceccanti

    2017-11-01

    Full Text Available A Peruvian woman was admitted to the Emergency Department, due to an acute flaccid paralysis (AFP of the upper limbs that progressively involved also lower limbs and respiratory muscles. She previously suffered from non-Hodgkin’s lymphoma and had to undergo hematopoietic stem cell transplantation. A magnetic resonance imaging showed a T2 hyperintensity in the anterior and central region of the cervical segment with an elective involvement of gray matter. This finding, combined with other clinical, laboratory, and electrophysiological data, led to a diagnosis of AFP. Enterovirus D68 was isolated in the patient’s cerebrospinal fluid, plasma, and throat swab. To our knowledge, this is the first Italian case of AFP by Enterovirus D68 infection in an adult. The diagnostic assessment and management of AFP by Enterovirus D68 are discussed.

  11. CLINICAL AND LABORATORY CHARACTERISTICS OF THE INFECTION CAUSED BY ENTEROVIRUS-71

    Directory of Open Access Journals (Sweden)

    E. N. Simovanyan

    2014-01-01

    Full Text Available Adverse course of enterovirus-71 infection (EVI-71 in children, frequent development of the nervous system pathology determine the need for early disease diagnosis. The study included 139 children aged 6 months to 13 years. Modern EVI-71 features is a frequent defeat of children aged from 3 to 7 years, attending organized groups, the priority development of combined moderate severity forms without nervous system pathology. EVI-71 is characterized by cyclical course, appearance in the first two disease days fever, murrain-like, catarrhal, lymphoproliferative syndromes, conjunctivitis, headaches. The second stage of the disease (3— 6 days in 37.9% children accompanied by attaching of meningitis and meningoencephalitis symptoms (common cerebral, meningeal and encephalic syndromes, changes in cerebrospinal fluid. In the EVI-71 diagnosis must be observed epidemiological history, clinical and laboratory parameters, detection of enterovirus-71 and its RNA from feces, oropharyngeal mucus and cerebrospinal fluid. Patients with EVI-71 need for combined treatment, including causal agents and pathogenetic therapy. 

  12. Efficacy of alcohols and alcohol-based hand disinfectants against human enterovirus 71.

    Science.gov (United States)

    Chang, S-C; Li, W-C; Huang, K-Y; Huang, Y-C; Chiu, C-H; Chen, C-J; Hsieh, Y-C; Kuo, C-Y; Shih, S-R; Lin, T-Y

    2013-04-01

    Human enterovirus 71 (HEV71) infections are a significant public health threat in the Asia-Pacific region and occasionally cause severe neurological complications and even death in children. Although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against HEV71 are still lacking. To investigate the virucidal activity of alcohols and alcohol-based hand disinfectants against HEV71. A common alcohol-based hand disinfectant (0.5% chlorhexidine gluconate + 70% isopropanol) as well as different concentrations of isopropanol and ethanol were tested for virucidal activity against HEV71 using the suspension and the fingerpad tests. In suspension tests, 85% and 95% ethanol achieved a mean log10 reduction factor in HEV71 titre of >3 and nearly 6, respectively, within 10 min. By contrast, 70% and 75% ethanol and any concentration of isopropanol (70-95%) produced a factor of 4, while both 75% ethanol and a chlorhexidine gluconate-containing formula were ineffective against HEV71 with a mean log10 reduction factor of alcohol-based hand disinfectants based on 70% ethanol or isopropanol have poor effectiveness against HEV71. Ninety-five percent ethanol is the most effective concentration, but still cannot fully inactivate HEV71 and may be impractical for use in many instances. Hand hygiene with alcohol-based hand disinfectants alone is not recommended for preventing HEV71 transmission. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  13. The Preferential Infection of Astrocytes by Enterovirus 71 Plays a Key Role in the Viral Neurogenic Pathogenesis.

    Science.gov (United States)

    Feng, Min; Guo, Sujie; Fan, Shengtao; Zeng, Xiaofeng; Zhang, Ying; Liao, Yun; Wang, Jianbin; Zhao, Ting; Wang, Lichun; Che, Yanchun; Wang, Jingjing; Ma, Na; Liu, Longding; Yue, Lei; Li, Qihan

    2016-01-01

    The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection.

  14. The association between enterovirus 71 infections and meteorological parameters in Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsiao-Ling Chang

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 infections are a significant cause of neurological disorder and death in children worldwide. Seasonal variations in EV71 infections have been recognized, but the mechanisms responsible for this phenomenon remain unknown. The purpose of this study was to examine the relationship between meteorological parameters and EV71 infection. METHODS AND FINDINGS: We analyzed the number of EV71 infections and daily climate data collected in Taiwan between 1998 and 2008 and used Poisson regression analysis and case-crossover methodology to evaluate the association between weather variability and the incidence of EV71 infection. A total of 1,914 EV71-infected patients were reported between 1998 and 2008. The incidence of EV71 infections reflected significant summertime seasonality (for oscillation, p<0.001. The incidence of EV71 infections began to rise at temperatures above 13°C (r(2 = 0.76, p<0.001; at temperatures higher than approximately 26°C (r(2 = 0.94, p<0.05, the incidence began to decline, producing an inverted V-shaped relationship. The increase in the incidence with increasing relative humidity was positive and linear (r(2 = 0.68, p<0.05. EV71 infection was most highly correlated with temperature and relative humidity in the period that likely preceded the infection. CONCLUSION: Our study provides quantitative evidence that the rate of EV71 infection increased significantly with increasing mean temperature and relative humidity in Taiwan.

  15. [Mitochondrial injury in enterovirus 71-infected Vero cells and its mechanism].

    Science.gov (United States)

    Lin, Peixin; Shen, Hong; Gao, Lulu; Huang, Yeen; Zhang, Yaozhong; Chen, Qing

    2015-06-01

    To investigate the mitochondrial injury in enterovirus 71 (EV71)-infected Vero cells and explore the possible mechanism. A clinical isolate of EV71 was inoculated to Vero cells and the EV71 antigen was detected by immunofluorescence assay. The morphological changes of Vero cells were observed using optical microscopy and transmission electron microscopy. The diameter and area density of the viral particles and the ratio and area density of vacuolated mitochondria in the cells were measured on the ultrastructural images. EV71-infected Vero cells underwent obvious changes and to a spherical morphology followed by cell death EV71 particles were detected in the cytoplasm by immunofluorescence. Ultrastructurally, the infected cells contained a large number of viral particles in the cytoplasm, with a clustered distribution and lattice-like arrangement. The diameter of the particles were 16.3 nm and the mean area density was 38.3%. Most of the mitochondria presented with swelling, vacuoles and degeneration. The ratio of the vacuolated mitochondria was 90.9% with a mean area density of 89.2%. Viral particles were also found in some mitochondria. EV71 proliferates in the cytoplasm and invades the mitochondria of infected Vero cells leading to mitochondrial injury and cell death, suggesting that mitochondria are the targets for EV71 infection.

  16. Identification and Structure-Activity Relationships of Diarylhydrazides as Novel Potent and Selective Human Enterovirus Inhibitors.

    Science.gov (United States)

    Han, Xin; Sun, Ningyuan; Wu, Haoming; Guo, Deyin; Tien, Po; Dong, Chune; Wu, Shuwen; Zhou, Hai-Bing

    2016-03-10

    Enterovirus 71 (EV71) plays an important role in hand-foot-and-mouth disease. In this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of SAR led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an EC50 value of 0.02 μM against EV71. It is very interesting that this class of diarylhydrazides exhibits activities against a series of human enteroviruses at the picomolar level, including EV71 and Coxsackieviruses B1 (CVB1), CVB2, CVB3, CVB4, CVB5, and CVB6 (EC50 as low as 0.5 nM). Compared with the reference antienterovirus drug 1 (enviroxime) and known inhibitor 5 (WIN 51711), the four highly selective compounds 15, 27, 41 and 47 inhibited EV71 replication with EC50 values of 0.17-0.02 μM and SI values in a range of 978.4-12338. A preliminary mechanistic study indicated that VP1 might be the target site for this type of compound.

  17. Molecular Epidemiology of Human Enterovirus Associated with Aseptic Meningitis in Shandong Province, China, 2006–2012

    Science.gov (United States)

    Liu, Guifang; Xu, Aiqiang; Lin, Xiaojuan; Song, Lizhi; Ji, Feng; Wang, Suting; Cui, Ning; Song, Yanyan

    2014-01-01

    Background Human enteroviruses (HEVs) are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. Objectives To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. Study Design Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification) and phylogenetic analysis were performed. Results A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2%) and were identified into 17 serotypes. The nine main serotypes were echovirus (E) 30 (27.4%), EV71 (13.1%), coxsackievirus (CV) B1 (9.5%), CVB3 (7.1%), CVB5 (7.1%), E6 (7.1%), E9 (7.1%), CVA9 (6.0%), and CVA10 (3.6%). Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. Conclusions Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses–the predominant pathogens for the hand, foot, and mouth disease–is currently an important concern in mainland China. PMID:24587020

  18. Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

    Directory of Open Access Journals (Sweden)

    Zexin Tao

    Full Text Available BACKGROUND: Human enteroviruses (HEVs are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. OBJECTIVES: To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. STUDY DESIGN: Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification and phylogenetic analysis were performed. RESULTS: A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2% and were identified into 17 serotypes. The nine main serotypes were echovirus (E 30 (27.4%, EV71 (13.1%, coxsackievirus (CV B1 (9.5%, CVB3 (7.1%, CVB5 (7.1%, E6 (7.1%, E9 (7.1%, CVA9 (6.0%, and CVA10 (3.6%. Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. CONCLUSIONS: Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant pathogens for the hand, foot, and mouth disease-is currently an important concern in mainland China.

  19. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Science.gov (United States)

    McAllister, Shane C; Schleiss, Mark R; Arbefeville, Sophie; Steiner, Marie E; Hanson, Ryan S; Pollock, Catherine; Ferrieri, Patricia

    2015-01-01

    Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  20. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Directory of Open Access Journals (Sweden)

    Shane C McAllister

    Full Text Available Enterovirus D68 (EV-D68 is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3% were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA compared to HRV (129.7 nA. Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  1. A dominant EV71-specific CD4+ T cell epitope is highly conserved among human enteroviruses.

    Directory of Open Access Journals (Sweden)

    Ruicheng Wei

    Full Text Available CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD, has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine.

  2. Recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice.

    Science.gov (United States)

    Li, Yue-Xiang; Zhao, Hui; Cao, Rui-Yuan; Deng, Yong-Qiang; Han, Jian-Feng; Zhu, Shun-Ya; Ma, Jie; Liu, Long; Qin, E-De; Qin, Cheng-Feng

    2014-05-06

    Human Enterovirus 71 (EV71) has emerged as the leading cause of viral encephalitis in children, especially in the Asia-Pacific regions. EV71 vaccine development is of high priority at present, and neutralization antibodies have been documented to play critical roles during in vitro and in vivo protection against EV71 infection. In this study, a novel strategy to produce EV71 vaccine candidate based on recombinant multiple tandem linear neutralizing epitopes (mTLNE) was proposed. The three well identified EV71 linear neutralizing epitopes in capsid proteins, VP1-SP55, VP1-SP70 and VP2-SP28, were sequentially linked by a Gly-Ser linker ((G4S)3), and expressed in E.coli in fusion with the Trx and His tag at either terminal. The recombinant protein mTLNE was soluble and could be purified by standard affinity chromatography. Following three dosage of immunization in adult mice, EV71-specific IgG and neutralization antibodies were readily induced by recombinant mTLNE. IgG subtyping demonstrated that lgG1 antibodies dominated the mTLNE-induced humoral immune response. Especially, cytokine profiling in spleen cells from the mTLNE-immunized mice revealed high production of IL-4 and IL-6. Finally, in vivo challenge experiments showed that passive transfer with anti-mTLNE sera conferred full protection against lethal EV71 challenge in neonatal mice. Our results demonstrated that this rational designed recombinant mTLNE might have the potential to be further developed as an EV71 vaccine in the future.

  3. Broad protection with an inactivated vaccine against primary-isolated lethal enterovirus 71 infection in newborn mice.

    Science.gov (United States)

    Chang, Junliang; Li, Jingliang; Liu, Xin; Liu, Guanchen; Yang, Jiaxin; Wei, Wei; Zhang, Wenyan; Yu, Xiao-Fang

    2015-07-15

    Circulating enterovirus 71 (EV-A71)-associated hand, foot, and mouth disease is on the rise in the Asian-Pacific region. Although animal models have been developed using mouse-adapted EV-A71 strains, mouse models using primary EV-A71 isolates are scarce. Lethal animal models with circulating EV-A71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation. In this study, we established a lethal mouse model using primary EV-A71 isolates from patients infected with serotypes that are currently circulating in humans. We also characterized the dose-dependent virulence and pathologic changes of circulating EV-A71 in this mouse model. Most importantly, we have established this mouse model as a suitable system for EV-A71 vaccine evaluation. An inactivated EV-A71 vaccine candidate offered complete protection from death induced by various circulating EV-A71 viruses to neonatal mice that were born to immunized female mice. The sera of the immunized dams and their pups showed higher neutralization titers against multiple circulating EV-A71 viruses. Thus, our newly established animal model using primary EV-A71 isolates is helpful for future studies on viral pathogenesis and vaccine and drug development.

  4. Galectin-3 and Its Genetic Variation rs4644 Modulate Enterovirus 71 Infection.

    Science.gov (United States)

    Huang, Wen-Chan; Chen, Hung-Lin; Chen, Huan-Yuan; Peng, Kuan-Po; Lee, Yungling; Huang, Li-Min; Chang, Luan-Yin; Liu, Fu-Tong

    2016-01-01

    Galectin-3, a chimeric type β-galactoside-binding protein, is known to modulate viral infection; however, its role in enterovirus 71 (EV71) infection has not been investigated. We generated galectin-3 null rhabdomyosarcoma (RD) cells and evaluated whether EV71 infection would be affected. In galectin-3 null cells, the released and intracellular EV71 viral loads were suppressed after 24 h of infection, and cell death rates were significantly lower, while cell proliferation remained unaltered. In addition, RD cells expressing a nonsynonymous genetic variant of galectin-3, rs4644 (LGALS3 +191C/A, P64H), produced lower virus titers than those with wild-type galectin-3 (C allele). To clarify whether the in vitro viral load reduction correlates with clinical severity, we enrolled children with laboratory-confirmed EV71 infection. Since hyperglycemia is an indicator of severe EV71 infection in children, 152 of 401 enrolled children had glucose examinations at admission, and 59 subjects had serum glucose levels ≥ 150 mg/dL. In comparison to the rs4644 AA genotype (2.2 ± 0.06 log10 mg/dL), serum glucose levels during EV71 infection were higher in patients with CC (2.4 ± 0.17 log10 mg/dL, p = 0.03) and CA (2.4 ± 0.15 log10 mg/dL, p = 0.02) genotypes, respectively. These findings suggest that the rs4644 AA genotype of galectin-3 might exert a protective effect. In summary, galectin-3 affects EV71 replication in our cellular model and its variant, rs4644, is associated with hyperglycemia in the clinical setting. The underlying mechanism and its potential therapeutic application warrant further investigation.

  5. Confirmed enterovirus encephalitis with associated steroid-responsive acute disseminated encephalomyelitis: an overlapping infection and inflammation syndrome.

    Science.gov (United States)

    Pillai, Sekhar; Tantsis, Esther; Prelog, Kristina; Ramanathan, Sudarshini; Webster, Richard; Ouvrier, Robert A; Kesson, Alison; Brilot, Fabienne; Dale, Russell C

    2015-03-01

    Inflammatory disorders of the central nervous system have generally been separated into infectious or immune-mediated aetiologies. However, there are emerging examples of confirmed infectious viral infection of the brain followed by secondary inflammation or autoimmunity that is amenable to immune suppressive therapies. We report four children with confirmed enterovirus encephalitis (CSF enterovirus PCR positivity), who had MRI evidence of inflammatory demyelination compatible with ADEM. Two patients had a monophasic course, whereas two had a biphasic course. Serum myelin oligodendrocyte glycoprotein antibodies were negative in two tested patients, although all patients had mirrored CSF and serum oligoclonal bands. All four patients only improved with introduction of immune therapy (corticosteroids in three, corticosteroid and intravenous immunoglobulin in one). These cases provide a further example of the overlap between CNS infection and immune mediated CNS disease. Randomised controlled trials investigating immune therapies in encephalitis are required. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. Enterovirus infection induces cytokine and chemokine expression in insulin-producing cells.

    Science.gov (United States)

    Nair, Sandhya; Leung, Kin-Chuen; Rawlinson, William D; Naing, Zin; Craig, Maria E

    2010-11-01

    Despite evidence supporting an association between enterovirus (EV) infection and type 1 diabetes, the etiological mechanism(s) for EV-induced beta cell destruction is(are) not well understood. In this study, the effects of Coxsackievirus B (CVB) 1-6 on cell lysis and cytokine/chemokine expression in the insulinoma-1 (INS-1) beta cell line were investigated. Cytolysis was assessed using tissue culture infectious dose 50 (TCID(50)). Quantitative RT-PCR was used to measure viral RNA and mRNA of cytokines interferon (IFN)-α, IFN-β, IFN-γ, tumor necrosis factor (TNF)-α, and chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) in infected INS-1 cells. CVB2, 4, 5, and 6 lysed and replicated in INS-1 cells; TCID(50) was lowest for CVB5 and highest for CVB6. IFN-γ, CXCL10, and CCL5 mRNA levels all increased significantly following infection with CVB2, 4, 5, and 6 (PCVB5 infection (P<0.05), while TNF-α mRNA and IFN-β mRNA (P<0.001) increased with CVB2 infection. Dose-dependent effects of infection on cytokine mRNA levels were observed for all (P<0.01) except IFN-γ. Following inoculation of INS-1 cells with CVB1 and 3, viral RNA was not detected and cytokine/chemokine mRNA levels were unchanged. In conclusion, CVB2, 4, 5, and 6 induce dose-dependent cytokine and chemokine mRNA production from INS-1 cells suggesting that pro-inflammatory cytokine and chemokine secretion by beta cells is a potential mechanism for EV-induced beta cell damage in type 1 diabetes. © 2010 Wiley-Liss, Inc.

  7. The clinical correlation of regulatory T cells and cyclic adenosine monophosphate in enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    Full Text Available Brainstem encephalitis (BE and pulmonary edema (PE are notable complications of enterovirus 71 (EV71 infection.This study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment.Patients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD or BE group, and the autonomic nervous system (ANS dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP levels, and the regulatory T cell (Tregs profiles of the patients were determined.Patients with ANS dysregulation or PE exhibited significantly low frequency of CD4(+CD25(+Foxp3+ and CD4(+Foxp3(+ T cells compared with patients with HFMD or BE. The expression frequency of CD4-CD8- was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment.These findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels.

  8. The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore

    Directory of Open Access Journals (Sweden)

    James Lyn

    2011-10-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997. Methods The survey involved the prospective collection of 1,200 residual sera from Singapore residents aged 1-17 years in two hospitals. Neutralizing antibodies to EV71 were detected by the microneutralization test. The geometric mean titer (GMT of EV71 antibodies and 95% confidence intervals (CI were calculated and compared by age groups. Statistical significance was taken as P Results The overall EV71 antibody prevalence was 26.9% (95% CI: 24.5-29.5%. It increased significantly from 14.3% in children aged 1-6 years to 27.8% in those aged 7-12 years, and reached 38.8% in adolescents aged 13-17 years. The seroconversion rate differed by about 12% between the consecutive age groups. The GMT of EV71 antibodies was higher among primary school children aged 7-12 years in our study than that among the 6-12 year age group in the 1996-1997 study. Conclusions Higher antibody titers were observed in children aged 1-6 years than those in the other two age groups, indicating that most of the infections had been acquired during early childhood. EV71 infection is common among children and adolescents in Singapore, with 39% infected by the time they are in secondary school (13-17 years of age.

  9. Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30.

    Science.gov (United States)

    McWilliam Leitch, E C; Cabrerizo, M; Cardosa, J; Harvala, H; Ivanova, O E; Kroes, A C M; Lukashev, A; Muir, P; Odoom, J; Roivainen, M; Susi, P; Trallero, G; Evans, D J; Simmonds, P

    2010-09-01

    The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated. These marked differences in recombination dynamics matched epidemiological patterns of periodic epidemic cycles of 2 to 3 (E9) and 5 to 6 (E30) years and the longer-term endemic pattern of E11 infections. Phylotemporal analysis using a Bayesian Markov chain Monte Carlo method, which placed recombination events within the evolutionary reconstruction of VP1, showed a close relationship with VP1 lineage expansion, with defined recombination events that correlated with their epidemiological periodicity. Whether recombination events contribute directly to changes in transmissibility that drive epidemic behavior or occur stochastically during periodic population bottlenecks is an unresolved issue vital to future understanding of enterovirus molecular epidemiology and pathogenesis.

  10. Evolutionary Dynamics and Temporal/Geographical Correlates of Recombination in the Human Enterovirus Echovirus Types 9, 11, and 30▿

    Science.gov (United States)

    McWilliam Leitch, E. C.; Cabrerizo, M.; Cardosa, J.; Harvala, H.; Ivanova, O. E.; Kroes, A. C. M.; Lukashev, A.; Muir, P.; Odoom, J.; Roivainen, M.; Susi, P.; Trallero, G.; Evans, D. J.; Simmonds, P.

    2010-01-01

    The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated. These marked differences in recombination dynamics matched epidemiological patterns of periodic epidemic cycles of 2 to 3 (E9) and 5 to 6 (E30) years and the longer-term endemic pattern of E11 infections. Phylotemporal analysis using a Bayesian Markov chain Monte Carlo method, which placed recombination events within the evolutionary reconstruction of VP1, showed a close relationship with VP1 lineage expansion, with defined recombination events that correlated with their epidemiological periodicity. Whether recombination events contribute directly to changes in transmissibility that drive epidemic behavior or occur stochastically during periodic population bottlenecks is an unresolved issue vital to future understanding of enterovirus molecular epidemiology and pathogenesis. PMID:20610722

  11. An epidemic of encephalitis associated with human enterovirus B in Uttar Pradesh, India, 2008.

    Science.gov (United States)

    Kumar, Arvind; Shukla, Deepti; Kumar, Rashmi; Idris, Mohammad Z; Misra, Usha K; Dhole, Tapan N

    2011-06-01

    Human enteroviruses (HEVs) are a rare cause of encephalitis, presenting in endemic or epidemic form. The aim of the study is to identify and characterise the causative agent of the encephalitis epidemic, which occurred in Uttar Pradesh, India during the summer of 2008. A total of 90 cerebrospinal fluid (CSF) specimens were collected between June and October 2008 from children with symptoms of encephalitis admitted to Chhatrapati Shahuji Maharaj Medical University and Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Conventional and molecular methods were used to identify and characterise the viral agent associated with the epidemic. Enterovirus RNA was detected in 37 (41.11%) of 90 CSF samples by real-time polymerase chain reaction (PCR). Seroneutralisation, amplification and sequencing of the 3'-end of the VP1 region of EV isolates revealed coxsackievirus B5 (CBV) and echovirus 19 (ECV) as the main serotypes causing this epidemic. Phylogenetic analysis showed that sequence divergence among the same serotypes was 0-4% at the nucleotide level. This is the first report suggesting that CBV 5 and ECV 19 may be responsible for an epidemic of encephalitis in India. These serotypes were variant and evolved within the studied area. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Non-rhinovirus enteroviruses associated with respiratory infections in Peru (2005-2010).

    Science.gov (United States)

    Huaman, Jose L; Carrion, Gladys; Ampuero, Julia S; Gomez, Jorge; Ocaña, Victor; Paz, Irmia; Gomez, Elizabeth; Chavez, Edward; Sarmiento, Favio; Pozo, Edward; Laguna-Torres, V Alberto; Halsey, Eric S

    2014-09-22

    Enteroviruses (EVs) are a common cause of respiratory tract infections and are classified into seven species (EVA-D and rhinoviruses [RHVs] A-C) with more than 200 different serotypes. Little is known about the role of non-RHV EVs in respiratory infections in South America. The aim of this study was to describe the epidemiology of non-RHV EVs detected in patients with influenza-like illness enrolled in a passive surveillance network in Peru. Throat swabs and epidemiological data were collected from participants after obtaining verbal consent. Viral isolation was performed in cell culture and identified by immunofluorescence assay. Serotype identification of EV isolates was performed using commercial monoclonal antibodies. Identification of non-serotypeable isolations was carried out by reverse transcriptase-PCR, followed by sequencing. Between 2005 and 2010, 24,239 samples were analyzed, and 9,973 (41.1%) possessed at least one respiratory virus. EVs were found in 175 samples (0.7%). Our results revealed a clear predominance of EVB species, 90.9% (159/175). No EVDs were isolated. The mean and median ages of EV-positive subjects were 9.1 and 4.0 years, respectively, much younger than the population sampled, 17.6 and 12.0 years. Sixteen serotypes were identified, four EVA, 11 EVB, and one EVC species. The most common serotypes were coxsackievirus B1, coxsackievirus B2, coxsackievirus B5, and coxsackievirus B3. This study provides data about the serotypes of EVs circulating in Peru and sets the need for further studies.

  13. Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone.

    Directory of Open Access Journals (Sweden)

    Hongjie Xia

    2015-07-01

    Full Text Available RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71, which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3'-to-5' unwinds RNA helices in an adenosine triphosphate (ATP-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16, another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings

  14. Inhibition of enterovirus 71 (EV-71 infections by a novel antiviral peptide derived from EV-71 capsid protein VP1.

    Directory of Open Access Journals (Sweden)

    Chee Wah Tan

    Full Text Available Enterovirus 71 (EV-71 is the main causative agent of hand, foot and mouth disease (HFMD. In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50 values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.

  15. Inhibition of Enterovirus 71 (EV-71) Infections by a Novel Antiviral Peptide Derived from EV-71 Capsid Protein VP1

    Science.gov (United States)

    Tan, Chee Wah; Chan, Yoke Fun; Sim, Kooi Mow; Tan, Eng Lee; Poh, Chit Laa

    2012-01-01

    Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC50 values ranging from 6–9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71. PMID:22563456

  16. Molecular epidemiology of enterovirus 71 infection in the central region of Taiwan from 2002 to 2012.

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wu

    Full Text Available Enterovirus 71 (EV71, a causative agent of hand, foot, and mouth disease can be classified into three genotypes and many subtypes. The objectives of this study were to conduct a molecular epidemiological study of EV71 in the central region of Taiwan from 2002-2012 and to test the hypothesis that whether the alternative appearance of different EV71 subtypes in Taiwan is due to transmission from neighboring countries or from re-emergence of pre-existing local strains. We selected 174 EV71 isolates and used reverse transcription-polymerase chain reaction to amplify their VP1 region for DNA sequencing. Phylogenetic analyses were conducted using Neighbor-Joining, Maximum Likelihood and Bayesian methods. We found that the major subtypes of EV71 in Taiwan were B4 for 2002 epidemic, C4 for 2004-2005 epidemic, B5 for 2008-2009 epidemic, C4 for 2010 epidemic and B5 for 2011-2012 epidemic. Phylogenetic analysis demonstrated that the 2002 and 2008 epidemics were associated with EV71 from Malaysia and Singapore; while both 2010 and 2011-2012 epidemics originated from different regions of mainland China including Shanghai, Henan, Xiamen and Gong-Dong. Furthermore, minor strains have been identified in each epidemic and some of them were correlated with the subsequent outbreaks. Therefore, the EV71 infection in Taiwan may originate from pre-existing minor strains or from other regions in Asia including mainland China. In addition, 101 EV71 isolates were selected for the detection of new recombinant strains using the nucleotide sequences spanning the VP1-2A-2B region. No new recombinant strain was found. Analysis of clinical manifestations showed that patients infected with C4 had significantly higher rates of pharyngeal vesicles or ulcers than patients infected with B5. This is the first study demonstrating that different EV 71 genotypes may have different clinical manifestations and the association of EV71 infections between Taiwan and mainland China.

  17. [Genotype distribution of human enteroviruses isolated from swage in Shanghai during year 2013-2014].

    Science.gov (United States)

    Li, Y Y; Lu, J; Wang, X Z; Yang, Y Y; Fei, J; Zhang, L P; Li, Z; Li, C S; Zuo, Y

    2017-02-06

    Objective: To explore the time and genotype distribution of human enterovirus (HEV) isolated from sewage in Shanghai in 2013-2014. Methods: One sewage sample each was collected from two local sewage plants located in Minhang District and Jiading District on the same day at the day 24-28 of every month from 2013 to 2014. Each sample weighed 1 L. The specimens were concentrated by anionic membrane absorption, eluted with beef extract solution, and then used to inoculate RD, HEp-2, and L20B cell lines. A total of 249 enterovirus strains were isolated from sewage samples during the study period, including 185 non-polio enterovirus (NPEV) and 64 poliovirus (PV) strains, which were identified as vaccine strains. RT-PCR and Sanger sequencing were performed to identify HEV genotypes. Homologous analysis of VP1 sequences was conducted using BioEdit (version 7.0.0). Phylogenetic analysis was performed using the neighbor-joining method based on the alignment of VP1 gene sequences using MEGA (version 4.0.2). Results: Among 185 NPEV strains, 178 strains were successfully sequenced and classified into 15 genotypes, including coxsackievirus group B (CVB) 2, 3, and 5; enteric cytopathic human orphan (ECHO) virus 1, 3, 6, 7, 11, 13, 19, 20, 24, 25, and 30; and coxsackievirus group A 4. CVB5 and ECHO6 genotypes accounted for 33.5% (56 strains) and 24.9% (43 strains) of NPEV isolates, respectively. During the study period, HEV isolates were mainly isolated in summer and autumn in Minhang District. ECHO6 strains were frequently isolated from June 2013 to July 2014. Thereafter, the number of ECHO6 strains gradually reduced in the second half of 2014. CVB5 strains demonstrated scattered distribution from 2013 to the first half of 2014 and gradually increased in the second half of 2014. The distribution of ECHO6 and CVB5 strains in Jiading District was similar to that in Minhang District. In 2013-2014, CVB5 strains comprised C6 and C8 subgenotypes, which belong to two transmission chains

  18. Microchip, reverse transcription-polymerase chain reaction and culture methods to detect enterovirus infection in pediatric patients.

    Science.gov (United States)

    Tsao, Lon-Yen; Lin, Chi-Yung; Yu, Ya-Yan; Wang, Bao-Tyan

    2006-02-01

    Enterovirus infection usually presents with mild and self-limited illness in children. However, Enterovirus type 71 can be characterized by neurotropism and may cause severe illness or even sudden death. Early detection of the virus will allow a physician to provide intensive or aggressive intervention. The purpose of the present study was to compare sensitivity of two innovative laboratory methods, that is, the DR.EV microchip method (DR. Chip Biotechnology, Shin-Tsu, Taiwan) and the reverse transcription-polymerase chain reaction (RT-PCR) method following conventional virus culture in detecting enterovirus infection in pediatric patients with herpangina or hand-foot-mouth disease. A total of 87 children (age range: 1-8 years) were enrolled because of typical clinical findings of herpangina and hand-foot-mouth disease. Two hundred children selected after a careful clinical history review and physical examinations, were included as controls. All of these children had at least throat swab and rectal swab specimens taken and tested for evidence of enterovirus infection by microchip, RT-PCR and virus culture methods. In addition, 21 patients also had cerebrospinal fluid (CSF) specimens taken to test for possible central nervous system involvement. The test results obtained from the 200 healthy kindergarten children were all negative for enteroviral infection by these three methods. Among the 87 test patients, the positive rates for throat swab, rectal swab and CSF by DR.EV chip, RT-PCR and virus culture were 71%, 68%, and 45% (throat swab); 66%, 61%, and 33% (rectal swab); and 52%, 29%, and 5% (CSF), respectively. There was no significant difference in the positive rates between the DR.EV chip and the RT-PCR methods (P > 0.1) on all types of specimens. However, statistically significant differences in positive rates were noted between the DR.EV chip and the conventional virus culture methods on all types of specimens (P < 0.001). Sensitivity of the microchip, RT

  19. DETECTION OF HUMAN ENTEROVIRUS AND ADENOVIRUS IN SHELLFISH COLLECTED IN MOROCCO MEDITERRANEAN COAST

    Directory of Open Access Journals (Sweden)

    Laila Benabbes

    2013-10-01

    Full Text Available The aim of this study was the screening for the presence of enteric human virus in shellfish (clam and cockle collected from two production area in Moroccan Mediterranean coast. Between October 2006 and April 2008, forty four samples were collected and tested for viral contamination using cell culture (HEp-2 and Vero cells and integrated cell culture PCR. Overall, 88.6 % of all analysed samples were contaminated by at least one of the studied viruses, Adenovirus was detected in 52.3 % of the samples and Enterovirus in 36.3%. The presence of viruses in shellfish production area can represent a potential health risk by causing gastroenteritis. The procedure used in this study may be a tool for monitoring shellfish viral contamination in Morocco.

  20. Neutralizing antibodies to non-polio enteroviruses in human immune serum globulin.

    Science.gov (United States)

    Dagan, R; Prather, S L; Powell, K R; Menegus, M A

    1983-01-01

    Neutralizing antibodies to selected non-polio enteroviruses were found in three lots of human immune serum globulin (ISG) prepared from the sera of persons from different geographic regions. Reciprocal titers to coxsackieviruses B3 and B4 ranged from 400 to greater than or equal to 2000, whereas titers to coxsackievirus A9 and ECHO viruses 5 and 9 ranged from 100 to 400 in all three lots of ISG. The presence of neutralizing antibodies to commonly occurring (coxsackieviruses B1 to B5 and A9 and ECHO viruses 3, 4 and 9) and infrequently encountered (ECHO viruses 5 and 13) serotypes, coupled with the increasing evidence that antibodies are an important factor in preventing illness, support recommending the administration of ISG to those at high risk for serious disease.

  1. Serum cholinesterase: a potential assistant biomarker for hand, foot, and mouth disease caused by enterovirus 71 infection.

    Science.gov (United States)

    Cheng, Bang-Ning; Jin, Yu-Lian; Chen, Bi-Quan; Zhu, Li-Yan; Xu, Zi-Cheng; Shen, Tao

    2016-03-29

    Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) is a potentially life-threatening infectious disease that commonly occurs in children. Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD. Serum cholinesterase (SChE) activity has frequently been reported as a potential biomarker for solid central nervous system tumors, chronic heart failure, and liver cirrhosis. However, its potential value in the diagnosis of neurotropic virus infections, such as HFMD caused by EV71, remains to be determined. In our study, 220 children hospitalized with HFMD caused by EV71, 34 inpatients infected with coxsackievirus A16 (CVA16), and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children's Hospital between January 2011 and December 2012. SChE activity was measured. The non-parametric Mann-Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls (p  0.05). An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase (p < 0.001). Elevated SChE activity was observed in patients with severe HFMD caused by EV71. Therefore, SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.

  2. Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections.

    Science.gov (United States)

    Ihekwaba, Ugo K; Kudesia, Goura; McKendrick, Michael W

    2008-09-15

    In this retrospective study, our objective was to review the epidemiology of viral meningitis and to compare clinical features associated with enterovirus, herpes simplex virus (HSV), and varicella zoster virus (VZV) infections in immunocompetent adults. Data on cerebrospinal fluid (CSF) samples submitted to the Trust Virology Laboratory (Sheffield, UK) from April 2004 through April 2007 were reviewed. Notes on immunocompetent adults who were polymerase chain reaction (PCR) positive for enterovirus, HSV type 2, or VZV and who had presented to local clinical departments were scrutinized (4 patients were positive for HSV type 1 and did not meet the inclusion criteria). A total of 2045 samples were analyzed for viral pathogens during the 3-year period. Of the 109 PCR-positive samples, 38 (35%) were from immunocompetent adults, of whom 22 were infected with enterovirus, 8 were infected with HSV type 2, and 8 were infected with VZV. The median ages were 32 years (range, 16-39 years), 39 years (range, 22-53 years), and 47.5 years (range, 26-80 years), respectively. Rash occurred after the meningitis symptoms in 5 patients infected with VZV (median time from meningitis symptoms to rash, 6 days). Protein levels were significantly higher in CSF samples from patients infected with HSV type 2 (median, 1205 mg/L) and in samples from those infected with VZV (median, 974 mg/L) than in samples from those infected with enterovirus (median, 640 mg/L; P = .001 and P = .01, respectively). White blood cell counts were significantly higher in CSF samples from patients infected with HSV type 2 (median, 240 x 10(6) cells/L) than in samples from those infected with enterovirus (median, 51 x 10(6) cells/L; P = .01). Enterovirus infection was the most common cause of viral meningitis in immunocompetent adults in this study. White blood cell counts and protein levels were significantly higher in CSF samples from patients infected with HSV type 2 than in samples from patients with enterovirus

  3. Tyrosine sulfation of the amino terminus of PSGL-1 is critical for enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Yorihiro Nishimura

    Full Text Available Enterovirus 71 (EV71 is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1 as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1-P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1-EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1-selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1-EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes.

  4. Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child

    NARCIS (Netherlands)

    Esposito, Susanna; Chidini, Giovanna; Cinnante, Claudia; Napolitano, Luisa; Giannini, Alberto; Terranova, Leonardo; Niesters, Hubert; Principi, Nicola; Calderini, Edoardo

    2017-01-01

    Background: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. Case presentation: A previously healthy 4-year-old boy presented with sudden

  5. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Q.; Langereis, M.A.; Lork, M.; Nguyen, M.H.; Hato, S.V.; Lanke, K.H.W.; Emdad, L.; Bhoopathi, P.; Fisher, P.B.; Lloyd, R.E.; Kuppeveld, F.J.M. van

    2014-01-01

    RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress

  6. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A|info:eu-repo/dai/nl/304823597; Lork, Marie; Nguyen, Mai; Hato, Stanleyson V; Lanke, Kjerstin; Emdad, Luni; Bhoopathi, Praveen; Fisher, Paul B; Lloyd, Richard E; van Kuppeveld, Frank J M|info:eu-repo/dai/nl/156614723

    2014-01-01

    UNLABELLED: RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses

  7. Phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in European countries.

    Science.gov (United States)

    Mirand, A; Schuffenecker, I; Henquell, C; Billaud, G; Jugie, G; Falcon, D; Mahul, A; Archimbaud, C; Terletskaia-Ladwig, E; Diedrich, S; Huemer, H P; Enders, M; Lina, B; Peigue-Lafeuille, H; Bailly, J-L

    2010-09-01

    Human enterovirus 71 (EV-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. Uncertainty persists regarding the circulation of virus populations in several geographical areas and the timescale of their dissemination. We determined EV-71 sequences at loci 1D (VP1 capsid protein) and 3CD (non-structural proteins) in 86 strains recovered in Austria, France and Germany and performed an evolutionary genetic study of extant virus populations. Phylogenetic analyses positioned 78 of the 86 sequences within two clades among subgenogroups C1 and C2. A minor sequence cluster was assigned to subgenogroup C4. Analyses incorporating the available sequences estimated the substitution rate in genogroup C at 3.66 x 10(-3) and 4.46 x 10(-3) substitutions per site year(-1) for loci 1D and 3CD, respectively, assuming a relaxed molecular-clock model for sequence evolution. Most of the 'European' strains belonged to clades C1b and C2b, which originated in 1994 [95 % confidence interval (CI), 1992.7-1995.8] and 2002 (95 % CI, 2001.6-2003.8), respectively. Estimates of divergence times for locus 3CD were consistent with those measured for locus 1D. Intertwining between clades representing EV-71 subgenogroups and clades corresponding to other enterovirus types (notably early coxsackievirus A prototype strains) in the 3CD phylogeny is highly indicative of ancestral recombination events. Incongruent phylogenetic patterns estimated for loci 1D and 3CD show that a single tree cannot model the epidemic history of circulating EV-71 populations. The evolutionary timescale of genogroup C estimated for both loci was measured only in decades, indicating recent dissemination.

  8. Display of VP1 on the surface of baculovirus and its immunogenicity against heterologous human enterovirus 71 strains in mice.

    Directory of Open Access Journals (Sweden)

    Tao Meng

    Full Text Available Human Enterovirus 71 (EV71 is a common cause of hand, foot and mouth disease (HFMD in young children. It is often associated with severe neurological diseases and has caused high mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no effective vaccine and antiviral agents available against EV71 infections. VP1 is one of the major immunogenic capsid protein of EV71 and plays a crucial role in viral infection. Antibodies against VP1 are important for virus neutralization.In the present study, infectious EV71 viruses were generated from their synthetic complementary DNA using the human RNA polymerase I reverse genetics system. Secondly, the major immunogenic capsid protein (VP1 of EV71-Fuyang (subgenogroup C4 was displayed on the surface of recombinant baculovirus Bac-Pie1-gp64-VP1 as gp64 fusion protein under a novel White Spot Syndrome Virus (WSSV immediate early ie1 promoter. Baculovirus expressed VP1 was able to maintain its structural and antigenic conformity as indicated by immunofluorescence assay and western blot analysis. Interestingly, our results with confocal microscopy revealed that VP1 was able to localize on the plasma membrane of insect cells infected with recombinant baculovirus. In addition, we demonstrated with transmission electron microscopy that baculovirus successfully acquired VP1 from the insect cell membrane via the budding process. After two immunizations in mice, Bac-Pie1-gp64-VP1 elicited neutralization antibody titer of 1∶64 against EV71 (subgenogroup C4 in an in vitro neutralization assay. Furthermore, the antisera showed high cross-neutralization activities against all 11 subgenogroup EV71 strains.Our results illustrated that Bac-Pie1-gp64-VP1 retained native epitopes of VP1 and acted as an effective EV71 vaccine candidate which would enable rapid production without any biosafety concerns.

  9. Detection of human enterovirus 71 and coxsackievirus A16 in children with hand, foot and mouth disease in China.

    Science.gov (United States)

    Chen, Ling; Mou, Xiaozhou; Zhang, Qiong; Li, Yifei; Lin, Jian; Liu, Fanlong; Yuan, Li; Tang, Yiming; Xiang, Charlie

    2012-04-01

    The aims of the present study were to investigate the genetic characteristics of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) strains in China and to evaluate the relationship between the genotypes of CVA16 and EV71 and their geographical distribution. A total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (HFMD) in Zhejiang Province. The presence of enteroviruses was determined using reverse transcription-semi-nested PCR targeted to the VP1 gene of all human enteroviruses and DNA sequencing. EV71 and CVA16, the major etiological agents of HFMD, were detected in 38.4% (38/99) and 35.4% (35/99) of HEV-A species-positive cases, respectively. Based on the phylogenetic analysis of the VP1 gene, EV71 strains identified in this study belong to subgenotype C4, and CVA16 strains herein were classified into clusters B2a and B2b within the genotype B2. Taking into consideration other published data, we conclude that the genetic characteristics of enteroviruses in China reflect the pattern of the endemic circulation of the subgenotype C4 to EV71 and clusters B2a and B2b within genotype B2 to CVA16, which have been continuously circulating in China since 1997. This observation indicates that the genetic characteristics of enteroviruses in China seem to depend on their special geographical and climatical features allowing them to be sustained with little external effect.

  10. Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child.

    Science.gov (United States)

    Esposito, Susanna; Chidini, Giovanna; Cinnante, Claudia; Napolitano, Luisa; Giannini, Alberto; Terranova, Leonardo; Niesters, Hubert; Principi, Nicola; Calderini, Edoardo

    2017-01-11

    Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5 °C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm 3 , 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24 h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4 weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained

  11. Re-analysis of metagenomic sequences from acute flaccid myelitis patients reveals alternatives to enterovirus D68 infection [v2; ref status: indexed, http://f1000r.es/5mz

    Directory of Open Access Journals (Sweden)

    Florian P. Breitwieser

    2015-07-01

    Full Text Available Metagenomic sequence data can be used to detect the presence of infectious viruses and bacteria, but normal microbial flora make this process challenging. We re-analyzed metagenomic RNA sequence data collected during a recent outbreak of acute flaccid myelitis (AFM, caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68, one patient had clear evidence of infection with Haemophilus influenzae, and a second patient had a severe Staphylococcus aureus infection caused by a methicillin-resistant strain. Neither of these bacteria were identified in the original study. These observations may have relevance in cases that present with flaccid paralysis because bacterial infections, co-infections or post-infection immune responses may trigger pathogenic processes that may present as poliomyelitis-like syndromes and may mimic AFM.  A separate finding was that large numbers of human sequences were present in each of the publicly released samples, although the original study reported that human sequences had been removed before deposition.

  12. Enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated Enterovirus A71 vaccine in Jiangsu, China, 2012-2013.

    Science.gov (United States)

    Yao, Xin; Bian, Lian-Lian; Lu, Wei-Wei; Li, Jing-Xin; Mao, Qun-Ying; Wang, Yi-Ping; Gao, Fan; Wu, Xing; Ye, Qiang; Xu, Miao; Li, Xiu-Ling; Zhu, Feng-Cai; Liang, Zheng-Lun

    2015-12-01

    Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in Jiangsu Province from 2012 to 2013. Fifty-nine infants were randomly selected from 522 non-EV-A71/CV-A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT-PCR was used to amplify 5'-UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty-one non-EV-A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non-EV-A71/CV-A enteroviruses among infants were CV-B3, CV-A10, CV-A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co-infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co-infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD. © 2015 Wiley Periodicals, Inc.

  13. Coxsackievirus A 16 infection does not interfere with the specific immune response induced by an enterovirus 71 inactivated vaccine in rhesus monkeys.

    Science.gov (United States)

    Wang, Jingjing; Qi, Sudong; Zhang, Xiaolong; Zhang, Ying; Liu, Longding; Che, Yanchun; He, Zhanlong; Zhao, Yuan; Lu, Shuaiyao; Yu, Wenhai; Li, Qihan

    2014-07-31

    Hand, foot and mouth disease is usually caused by enterovirus 71 (EV71) and coxsackievirus A 16 (CA16), which are members of the Picornaviridae family. In the present study, the characteristics of the immune response induced by an EV71 inactivated vaccine (made from human diploid cells) were explored in the presence of CA16 infection, based on the previously established neonatal rhesus monkey model. The typical clinical manifestations, including body temperature, viral viremia and virus shedding in the mouth, pharynx and feces, were characterized. A specific neutralizing antibody assay showed that the specific immune response induced by the EV71 inactivated vaccine was active against EV71 but not against CA16. No remarkable fluctuation in proinflammatory cytokine release was identified in the serum of immunized monkeys with EV71 vaccine and CA16 infections subsequently. The results showed that the specific immune response induced by the EV71 inactivated vaccine is effective against EV71 infection but is not affected by CA16 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

    Directory of Open Access Journals (Sweden)

    Xiaohua Ye

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3 of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2, the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

  15. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

    Science.gov (United States)

    Han, Jun; Wang, Ying; Gan, Xing; Song, Juan; Sun, Peng; Dong, Xiao-Ping

    2014-08-01

    Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1β, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients. © 2014 Wiley Periodicals, Inc.

  16. Characterization of Enteroviruses from non-human primates in cameroon revealed virus types widespread in humans along with candidate new types and species.

    Directory of Open Access Journals (Sweden)

    Serge Alain Sadeuh-Mba

    Full Text Available Enteroviruses (EVs infecting African Non-Human Primates (NHP are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases.

  17. Characterization of Enteroviruses from Non-Human Primates in Cameroon Revealed Virus Types Widespread in Humans along with Candidate New Types and Species

    Science.gov (United States)

    Sadeuh-Mba, Serge Alain; Bessaud, Maël; Joffret, Marie-Line; Endegue Zanga, Marie-Claire; Balanant, Jean; Mpoudi Ngole, Eitel; Njouom, Richard; Reynes, Jean-Marc; Delpeyroux, Francis; Rousset, Dominique

    2014-01-01

    Enteroviruses (EVs) infecting African Non-Human Primates (NHP) are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases. PMID:25079078

  18. Simultaneous detection and differentiation of human rhino- and enteroviruses in clinical specimens by real-time PCR with locked nucleic Acid probes.

    Science.gov (United States)

    Osterback, Riikka; Tevaluoto, Tuire; Ylinen, Tiina; Peltola, Ville; Susi, Petri; Hyypiä, Timo; Waris, Matti

    2013-12-01

    Human rhinoviruses (HRVs) and human enteroviruses (HEVs) are significant respiratory pathogens. While HRV infections are restricted to the respiratory tract, HEV infections may spread to secondary target organs. The method of choice for sensitive specific detection of these viruses is reverse transcription (RT)-PCR with primers targeting the conserved 5' noncoding region of the viral RNA. On the other hand, sequence similarities between HRVs and HEVs complicate their differential detection. In this study, we describe the use of locked nucleic acid (LNA) analogues in short double-dye probes which contained only two selectively HRV- or HEV-specific bases. The double-stranded DNA dye BOXTO (4-[6-(benzoxazole-2-yl-(3-methyl-)-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)]-1-methyl-quinolinium chloride) was used with the LNA probes in a tricolor real-time PCR assay to allow specific detection of HRVs (probes labeled with 6-carboxyfluorescein [FAM] [green]) and HEVs (Cy5 [red]) with additional melting curve analysis (BOXTO [yellow]). The functionality of the probes was validated in PCR and RT-PCR assays using plasmids containing viral cDNA, quantified viral RNA transcripts, cultivated rhino- and enterovirus prototypes, and clinical specimens. Of 100 HRV and 63 HEV prototypes, the probes correctly identified all HEVs except one that produced only a BOXTO signal. Among 118 clinical specimens with sequencing results, concordant results were obtained for 116 specimens. Two specimens were reactive with both probes, but sequencing yielded only a single virus. Real-time PCR with LNA probes allowed sensitive group-specific identification of HRVs and HEVs and would enable relative copy number determination. The assay is suitable for rapid and accurate differential detection of HRVs and HEVs in a diagnostic laboratory setting.

  19. Population dynamics and genetic diversity of C4 strains of human enterovirus 71 in Mainland China, 1998-2010.

    Directory of Open Access Journals (Sweden)

    Dawei Guan

    Full Text Available BACKGROUND: Since 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD. Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71 belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high. METHODOLOGY/PRINCIPAL FINDINGS: To gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010. CONCLUSIONS: EV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate

  20. Molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in Spain.

    Science.gov (United States)

    Cabrerizo, María; Díaz-Cerio, María; Muñoz-Almagro, Carmen; Rabella, Núria; Tarragó, David; Romero, María Pilar; Pena, María José; Calvo, Cristina; Rey-Cao, Sonia; Moreno-Docón, Antonio; Martínez-Rienda, Inés; Otero, Almudena; Trallero, Gloria

    2017-03-01

    The epidemiology and clinical association of enterovirus (EV) and parechovirus (HPeV) infections, as well as the type-distribution-according-to-age, were determined during a 4-year study period in Spain. During 2010-2013, a total of 21,832 clinical samples were screened for EV and the detection frequency was 6.5% (1,430). Of the total EV-negative samples, only 1,873 samples from 2011 to 2013 were available for HPeV testing. HPeV was detected in 42 (2%) of them. Positive samples were genotyped using PCR and sequencing. EV infections occurred in all age groups of patients: neonates (17%), children 28 days to 2 years (29%), children 2-14 years (40%), and adults (14%). Thirty-four different EV types were identified. HPeV infections were detected exclusively in infants 2 years and adults (P < 0.05). Clinically, meningitis was associated with EV (P < 0.01) whereas, encephalitis was more frequent in HPeV-infected patients. CV-B types were associated with myocarditis (90%; P < 0.05) and EV species A with hand-foot-mouth-disease/atypical exanthema (88%; P < 0.05). J. Med. Virol. 89:435-442, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Prevalence and Phylogenetic Characterization of Enterovirus D68 in Pediatric Patients with Acute Respiratory Tract Infection in Thailand.

    Science.gov (United States)

    Thongpan, Ilada; Wanlapakorn, Nasamon; Vongpunsawad, Sompong; Linsuwanon, Piyada; Theamboonlers, Apiradee; Payungporn, Sunchai; Poovorawan, Yong

    2016-09-21

    Enterovirus D68 (EV-D68) is associated with severe lower respiratory tract infection and neurological abnormalities including acute myelitis and cranial nerve dysfunction. To determine whether an increased incidence of EV-D68 occurs in Southeast Asia, we retrospectively tested specimens collected from Thai pediatric patients who were less than 5 years of age and presented with acute respiratory tract infections between 2012 and 2014. Reverse transcription-polymerase chain reaction and nucleotide sequencing of the 5'-UTR/VP2 region were used to identify EV-D68. We also examined the epidemiological pattern of EV-D68 since 2009, when it was first identified in Thailand, and compiled records of clinical manifestations in children with confirmed EV-D68 infection. From 837 samples, 5 samples (0.6%) tested positive for EV-D68. All patients presented with viral pneumonia and required hospitalization. Phylogenetic analysis of the VP4/VP2 regions revealed that EV-D68 strains circulating in Thailand between 2012 and 2014 were closely related to strains reported in Japan, United Kingdom, China, and France. Continued surveillance of probable EV-D68-associated severe respiratory tract infection and the development of a rapid diagnostic test for EV-D68 are essential in supporting awareness and facilitating disease prevention and control.

  2. Characterization of human enterovirus71 virus-like particles used for vaccine antigens.

    Directory of Open Access Journals (Sweden)

    Dandan Zhao

    Full Text Available Human enterovirus 71 (EV71 is a major causative pathogen of hand, foot and mouth disease (HFMD and has caused outbreaks with significant mortality among young children in the Asia-Pacific region in recent years. Towards developing a vaccine for this disease, we have expressed and purified EV71 virus-like particles (VLPs, which resemble the authentic virus in appearance, capsid structure and protein sequence, from insect cells (Sf9 using a multistep chromatography process. We demonstrated intracellular localization of the VLPs in host cells by in situ immunogold detection, electron microscopy and immunofluorescence. Characteristics of these EV71 VLPs were studied using a variety of immunological and physicochemical techniques, which aimed to reveal that the purified EV71 VLPs have good morphology and structure consistent with natural EV71 empty capsids. Results of the amino acid analysis, SDS-PAGE, Western blotting and high-performance liquid chromatography confirmed the high purity of the EV71 VLPs. However the sedimentation coefficient of the VLPs showed that they were smaller than that of secreted EV71 VLPs purified by discontinuous cesium chloride density gradients, they were similar to the empty capsids of natural EV71 virions reported previously. Combined with the previous study that EV71 VLPs purified by a multistep chromatography process were able to elicit strong humoral immune responses in mice, our results further supported the conclusion that our EV71 VLPs had well-preserved molecular and structural characteristics. The EV71 VLPs produced from the baculovirus expression system and purified by a multistep chromatography process displayed key structural and immunological features, which would contribute to their efficacy as a HFMD vaccine.

  3. Implications of Age-Dependent Immune Responses to Enterovirus 71 Infection for Disease Pathogenesis and Vaccine Design.

    Science.gov (United States)

    Gantt, Soren; Yao, Lena; Kollmann, Tobias R; Casper, Corey; Zhang, Jing; Self, Steven G

    2013-06-01

    Epidemics of enterovirus serotype 71 (EV71) infection in Asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. Efforts are underway to develop an effective EV71 vaccine. However, the immunologic correlates of protection against EV71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. Severe disease and death typically occur only in young children, which is likely due in part to a lack of EV71-specific adaptive immunity but possibly also due to age-dependent hyperactive innate immune responses. Infants are the primary targets of EV71 vaccination strategies. Therefore, studies are needed to understand the interplay between age, immunopathology, and severity of EV71 infection to distinguish protective from harmful immune responses and to guide the development of effective EV71 vaccines. This review summarizes our current understanding and outlines the next steps forward. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. [Identification and genetic characterization of human enterovirus type 73, 75, and 97 strains of specie B isolated in Shandong province].

    Science.gov (United States)

    Tao, Ze-Xin; Wang, Hai-Yan; Xu, Ai-Qiang; Song, Li-Zhi; Li, Yan; Liu, Gui-Fang; Liu, Yao; Fan, Qing-Ying

    2010-01-01

    Molecular typing was conducted for three human enteroviruses (HEV) isolated from acute flaccid paralysis (AFP) cases in Shandong province, China. RNAs from virus supernatants were extracted and complete VP1 genes were amplified by RT-PCR and sequenced. Genotypes of these isolates were identified as HEV type 73, 75 and 97, respectively by BLAST program. Homology and phylogenetic tree analyses were performed. Sequence analysis of VP1 gene showed significant variation compared with prototype strains. This study presents the genetic characteristics of HEV 73, 75 and 97 of specie B in Shandong Province, and the first report of HEV97 in China.

  5. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells.

    Directory of Open Access Journals (Sweden)

    Cong Haolong

    Full Text Available Enterovirus 71 (EV71 is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human.

  6. Enterovirus 71 VP1 Activates Calmodulin-Dependent Protein Kinase II and Results in the Rearrangement of Vimentin in Human Astrocyte Cells

    Science.gov (United States)

    Haolong, Cong; Du, Ning; Hongchao, Tian; Yang, Yang; Wei, Zhang; Hua, Zhang; Wenliang, Zhang; Lei, Song; Po, Tien

    2013-01-01

    Enterovirus 71 (EV71) is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II) which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human. PMID:24073199

  7. A novel RT-multiplex PCR for detection of Aichi virus, human parechovirus, enteroviruses, and human bocavirus among infants and children with acute gastroenteritis.

    Science.gov (United States)

    Pham, Ngan Thi Kim; Trinh, Quang Duy; Chan-It, Wisoot; Khamrin, Pattara; Shimizu, Hideaki; Okitsu, Shoko; Mizuguchi, Masashi; Ushijima, Hiroshi

    2010-10-01

    A novel reverse transcription-multiplex polymerase chain reaction assay was developed to detect Aichi virus, human parechovirus, enteroviruses, and human bocavirus. A mixture of four pairs of published specific primers, 6261 and 6779, ev22(+) and ev22(-), F1 and R1, 188F and 542R, was used to amplify the viral genomes and specifically generate four different amplicon sizes of 519, 270, 440, and 354 bp for Aichi virus, human parechovirus, enteroviruses, and human bocavirus, respectively. A total of 247 fecal specimens previously screened for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus-negative, collected from infants and children with acute gastroenteritis in Japan from July 2007 to June 2008, were tested further for the presence of the four viruses, Aichi virus, human parechovirus, enteroviruses, and human bocavirus, by RT-multiplex PCR. The total detection rate of these viruses was 26.7% (66 out of 247 samples). Of these, HPeV, EVs, and HBoV were identified in 20, 41, and 5 specimens. No Aichi virus was found among these subjects. The sensitivity and specificity of RT-multiplex PCR were assessed and demonstrated a strong validation against RT-monoplex PCR. This is the first report of detecting these types of viruses in fecal samples from infants and children with acute gastroenteritis by RT-multiplex PCR. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Enterovirus and herpesviridae family as etiologic agents of lymphomonocytary meningitis, Southern Brazil

    Directory of Open Access Journals (Sweden)

    Luine Rosele Renaud Vidal

    2011-06-01

    Full Text Available Viral meningitis is a common infectious disease of the central nervous system (CNS that occurs worldwide. The aim of this study was to identify the etiologic agent of lymphomonocytary meningitis in Curitiba, PR, Brazil. During the period of July 2005 to December 2006, 460 cerebrospinal fluid (CSF samples with lymphomonocytary meningitis were analyzed by PCR methodologies. Fifty nine (12.8% samples were positive. Enteroviruses was present in 49 (83% samples and herpes virus family in 10 (17%, of these 6 (10% herpes simplex virus, 1 (2% Epstein Barr virus, 2 (3% human herpes virus type 6 and 1 (2% mixed infection of enterovirus and Epstein Barr virus. As conclusion enterovirus was the most frequent virus, with circulation during summer and was observed with higher frequency between 4 to 17 years of age. PCR methodology is an important method for rapid detection of RNA enterovirus and DNA herpesvirus in CSF.

  9. Challenges to licensure of enterovirus 71 vaccines.

    Directory of Open Access Journals (Sweden)

    Min-Shi Lee

    Full Text Available Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71, which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD. A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design.

  10. Association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis in hospitalized infants with enterovirus infection.

    Science.gov (United States)

    Dagan, R; Jenista, J A; Menegus, M A

    1988-12-01

    One hundred eight hospitalized infants with enteroviral infections were studied to determine the association of clinical presentation, laboratory findings, and virus serotypes with the presence of meningitis. Of 108 infants, 55 (51%) had meningitis. Clinical manifestations on admission did not distinguish between infants with and those without meningitis. Echoviruses 30 and 11 and coxsackie virus B were frequently associated with meningitis (34/38; 90%) whereas echoviruses 18, 24, and 25 were not (5/35; 4%). The virus isolation rate was directly proportional to the number of leukocytes in cerebrospinal fluid: 5 of 58 (9%) when up to 9 cells/mm3 were found, 10 of 21 (48%) when 10 to 99/mm3 cells were found, and 25 of 29 (86%) when greater than equal to 100 cells/mm3 were found. Meningitis is often unsuspected in children hospitalized with enterovirus infection. The frequency of meningitis among hospitalized infants is serotype dependent and is most frequently, but not exclusively, found with pleocytosis of the cerebrospinal fluid.

  11. Combining cell lines to optimize isolation of human enterovirus from clinical specimens: report of 25 years of experience.

    Science.gov (United States)

    Prim, Núria; Rodríguez, Graciela; Margall, Núria; Del Cuerpo, Margarita; Trallero, Gloria; Rabella, Núria

    2013-01-01

    Cell culture is still the gold standard for the diagnosis of human enteroviruses (HEVs) although molecular techniques are required for detection of some serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to all serotypes, and several lines are required to optimize the isolation of HEVs. In this study, the results of HEV isolation during the last 25 years are reported. A total of 1,192 HEVs were isolated and isolation rates varied depending on the cell line used. MRC5 cells yielded the best results (70.7%), followed by A549 cells (52.6%), RD cells (37.5%), and HEp-2 cells (29.7%). A total of 521 HEVs were characterized, and HEV-B was the most frequent species (81%). Polioviruses (PV) and HEV-A were isolated less frequently (17% and 1%, respectively). None of the cell lines detected all the enteroviruses. MRC5 cells were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%), whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD cells and HEp2 cells, respectively. Although A549 cells did not achieve the best performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs. In view of these results, MRC5 cells, A549 cells, and RD cells should be combined to optimize isolation of HEVs. Copyright © 2012 Wiley Periodicals, Inc.

  12. Excretion of enterovirus 71 in persons infected with hand, foot and mouth disease

    Directory of Open Access Journals (Sweden)

    Li Jie

    2013-01-01

    Full Text Available Abstract Background Hand, foot and mouth disease (HFMD is a common illness in young children. It also can be seen in adults occasionally. Enterovirus 71 (EV71, a pathogen that causes not only HFMD but also neurological complications and even death, has caused many HFMD outbreaks in China. However, till now the data about the duration of EV71 shedding is very limited. Results A total of 136 throat swabs and fecal samples were collected from 27 children and 3 adults, which includs 7 close contacts, 9 mild cases and 14 severe cases,. The participants were divided into three groups namely, severe case group, mild case group and close contact group. All the samples were assayed with real-time polymerase chain reaction (PCR. Kruskal-Wallis Test was employed to compare the difference in duration of viral RNA shedding among three groups. The results showed that significant difference in duration of EV71 shedding was found among three groups (P  Conclusions HFMD is characterized by extended excretion of EV71. Our results suggest that the duration of EV71 shedding is correlated with the severity of the disease. EV71 shedding through feces can persist more than 54 days. Prolonged virus shedding is a potential risk factor of proliferating HFMD epidemic.

  13. Evaluation of methods using celite to concentrate norovirus, adenovirus and enterovirus from wastewater

    Science.gov (United States)

    Enteroviruses, noroviruses and adenoviruses are among the most common viruses infecting humans worldwide. These viruses are shed in the feces of infected individuals and can accumulate in wastewater. Therefore, wastewater is a source of a potentially diverse group of enteric viru...

  14. Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia.

    Science.gov (United States)

    Duong, Veasna; Mey, Channa; Eloit, Marc; Zhu, Huachen; Danet, Lucie; Huang, Zhong; Zou, Gang; Tarantola, Arnaud; Cheval, Justine; Perot, Philippe; Laurent, Denis; Richner, Beat; Ky, Santy; Heng, Sothy; Touch, Sok; Sovann, Ly; van Doorn, Rogier; Tan Tran, Thanh; Farrar, Jeremy J; Wentworth, David E; Das, Suman R; Stockwell, Timothy B; Manuguerra, Jean-Claude; Delpeyroux, Francis; Guan, Yi; Altmeyer, Ralf; Buchy, Philippe

    2016-09-21

    Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.

  15. Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus).

    Science.gov (United States)

    Patel, Mira C; Wang, Wei; Pletneva, Lioubov M; Rajagopala, Seesandra V; Tan, Yi; Hartert, Tina V; Boukhvalova, Marina S; Vogel, Stefanie N; Das, Suman R; Blanco, Jorge C G

    2016-01-01

    In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68) among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs) and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus). Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49), along with the historical prototype Fermon strain (ATCC), to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA) upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines against EV-D68

  16. Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus.

    Directory of Open Access Journals (Sweden)

    Mira C Patel

    Full Text Available In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68 among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus. Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49, along with the historical prototype Fermon strain (ATCC, to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines

  17. Identification of a Common Epitope between Enterovirus 71 and Human MED25 Proteins Which May Explain Virus-Associated Neurological Disease

    Directory of Open Access Journals (Sweden)

    Peihu Fan

    2015-03-01

    Full Text Available Enterovirus 71 (EV71 is a major causative pathogen of hand, foot and mouth disease with especially severe neurologic complications, which mainly account for fatalities from this disease. To date, the pathogenesis of EV71 in the central neurons system has remained unclear. Cytokine-mediated immunopathogenesis and nervous tissue damage by virus proliferation are two widely speculated causes of the neurological disease. To further study the pathogenesis, we identified a common epitope (co-epitope between EV71 VP1 and human mediator complex subunit 25 (MED25 highly expressed in brain stem. A monoclonal antibody (2H2 against the co-epitope was prepared, and its interaction with MED25 was examined by ELISA, immunofluorescence assay and Western blot in vitro and by live small animal imaging in vivo. Additionally, 2H2 could bind to both VP1 and MED25 with the affinity constant (Kd of 10−7 M as determined by the ForteBio Octet System. Intravenously injected 2H2 was distributed in brain stem of mice after seven days of EV71 infection. Interestingly, 2H2-like antibodies were detected in the serum of EV71-infected patients. These findings suggest that EV71 infection induces the production of antibodies that can bind to autoantigens expressed in nervous tissue and maybe further trigger autoimmune reactions resulting in neurological disease.

  18. MRI of Enterovirus 71 myelitis with monoplegia

    Energy Technology Data Exchange (ETDEWEB)

    Shen, W.C. [Department of Radiology, and School of Medicine, China Medical College, China Medical College Hospital, Taiwan (Taiwan); Tsai, C.H. [Department of Paediatrics, and School of Medicine, China Medical College, China Medical College Hospital, Taiwan (Taiwan); Chiu, H.H. [Department of Paediatrics, China Medical College Hospital, No. 2 Yuh-Der Road, 407 Taichung, Taiwan (Taiwan); Chow, K.C. [Department of Medical Research, China Medical College Hospital, Taichung, Taiwan (Taiwan)

    2000-02-01

    We report two boys diagnosed as having herpangina and hand-foot-mouth disease complicated by monoplegia during the outbreak enterovirus infection in Taiwan in 1998. Enterovirus 71 was identified in the stool and throat swab; neither polio nor Coxsackie viruses was identified. MRI showed unilateral lesions in the anterior horns of the spinal cord at T11-12 and C2-5. Although the MRI findings and sites of these lesions were similar to those of poliovirus-associated poliomyelitis, the virological data indicated that these boys were infected with enterovirus type 71. (orig.)

  19. Correlation of symptomatic enterovirus infection and later risk of allergic diseases via a population-based cohort study.

    Science.gov (United States)

    Lee, Zon-Min; Huang, Ying-Hsien; Ho, Shu-Chen; Kuo, Ho-Chang

    2017-01-01

    Infants who are exposed to the rhinovirus or respiratory syncytial virus are at a higher risk of subsequently developing wheezing or asthma. This study aims to determine whether preschoolers with a history of symptomatic enterovirus infection are at an increased risk of developing allergic diseases or not.We used data from the Taiwan National Health Insurance Research Database from 1999 to 2006 for this nationwide population-based cohort study. The subsequent risks for allergic diseases, which included asthma (International Classification of Diseases [ICD]-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between herpangina (ICD-9: 074.0) and hand, foot, and mouth disease (HFMD; ICD-9: 074.3) throughout the follow-up period using the Cox proportional hazards model.In this database, 12,016 neonates were born between January 1999 and December 1999. Among them, we further evaluated 8337 subjects; 3267 children infected with either herpangina or HFMD served as the study cohort, and the other 5070 children made up the comparison cohort. Children in the herpangina group had a higher risk of developing AR and AD, with adjusted hazard ratios of 1.15 (1.02-1.30, 95% CI) and 1.38 (1.17-1.63. 95% CI), respectively, while children suffered from HFMD had decreased risks of asthma, with an adjusted hazard ratio of 0.76 (0.63-0.93, 95% CI).Children who previously suffered from herpangina experienced an increased risk of subsequently developing AD and AR. Meanwhile, children who had suffered from HFMD experienced a decrease in the subsequent occurrence of asthma compared to the general population.

  20. Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children

    NARCIS (Netherlands)

    de Crom, S. C. M.; Rossen, J. W. A.; de Moor, R. A.; Veldkamp, E. J. M.; van Furth, A. M.; Obihara, C. C.

    Background: Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children.

  1. Clinical features, outcomes, and cerebrospinal fluid findings in adult patients with central nervous system (CNS) infections caused by varicella-zoster virus: comparison with enterovirus CNS infections.

    Science.gov (United States)

    Hong, Hyo-Lim; Lee, Eun Mi; Sung, Heungsup; Kang, Joong Koo; Lee, Sang-Ahm; Choi, Sang-Ho

    2014-12-01

    Varicella-zoster virus (VZV) is known to be associated with central nervous system (CNS) infections in adults. However, the clinical characteristics of VZV CNS infections are not well characterized. The aim of this study was to compare the clinical manifestations, outcomes, and cerebrospinal fluid (CSF) findings in patients with VZV CNS infections with those in patients with enterovirus (EV) CNS infections. This retrospective cohort study was performed at a 2,700-bed tertiary care hospital. Using a clinical microbiology computerized database, all adults with CSF PCR results positive for VZV or EV that were treated between January 1999 and February 2013 were identified. Thirty-eight patients with VZV CNS infection and 68 patients with EV CNS infection were included in the study. Compared with the EV group, the median age in the VZV group was higher (VZV, 35 years vs. EV, 31 years; P = 0.02), and showed a bimodal age distribution with peaks in the third and seventh decade. Encephalitis was more commonly encountered in the VZV group (VZV, 23.7% vs. EV, 4.4%; P = 0.01). The median lymphocyte percentage in the CSF (VZV, 81% vs. EV, 36%; P < 0.001) and the CSF protein level (VZV, 100 mg/dl vs. EV, 46 mg/dl; P < 0.001) were higher in the VZV group. Compared with patients with EV CNS infection, patients with VZV CNS infection developed encephalitis more often and exhibited more intense inflammatory reaction. Nevertheless, both VZV and EV CNS infections were associated with excellent long-term prognosis. © 2014 Wiley Periodicals, Inc.

  2. Enterovirus Infection in Young Infants: Prevalence, Clinical and Laboratory Characteristics in Columbus, Ohio

    Science.gov (United States)

    Feister, John; Medoro, Alexandra; Souverbielle, Cristina Tomatis; Campbell, Jason; Akkoc, Gulsen; Ramilo, Octavio; Salamon, Douglas; Leber, Amy; Erdem, Guliz

    2017-01-01

    Abstract Background All infants under two months of age evaluated for fever or sepsis undergo routine work up at Nationwide Children’s Hospital that includes blood, CSF, and mucosal site PCRs for enteroviruses (EV). We sought to determine the local EV prevalence, clinical characteristics and viral correlates of disease severity in this large population. Methods EMRs of all infants 4–60 days of age evaluated for fever or sepsis from January 2015 to September 2016 were reviewed. An in-house developed real-time PCR was used for EV detection. We analyzed cycle threshold values for positive samples. Results Of the 713 patients tested, 151 (21%) patients were positive for EV in at least one site. Majority of the patients (76%) presented between the months of June and October. Median age was 24 days (IQR 16–37). Median length of stay (LOS) was 40.82 hours (IQR 33.4–47.5). 122 (81%) had fever and 27 (18%) had a rash on admission. Median duration of antibiotic treatment was 2 days (IQR 1.5–2) and median hospital charges were 13,169 USD. CBC values and transaminases were normal. 75 (49%) patients had EV PCR positive in CSF, 120 (79%) in superficial sites, and 109 (72%) in blood and 51 (34%) patients had positive EV PCR in all three sites. 5 patients were admitted to PICU (3.3%), of which 2 had EV detected in CSF. Two patients required pressor support and 3 had seizures. All patients recovered and had no complications at discharge. Among CSF positive patients, median CSF WBC count was 50 (IQR 5–360 cells/µl). Median PCR cycle threshold (Ct) values were: 35.88 (IQR 34.1–37.5) for CSF, 32.54 (IQR 30–36.42) for blood, and 34.58 (31.96–37.36) for superficial sites. CSF and blood Ct values in PICU patients were not significantly different. Ct values in CSF or blood had no significant correlation with length of stay. 55 patients (36%) had coinfections – 53 viral (parechovirus, parainfluenza and rhinovirus/EV [these cannot be distinguished by testing method

  3. A retrospective overview of enterovirus infection diagnosis and molecular epidemiology in the public hospitals of Marseille, France (1985-2005.

    Directory of Open Access Journals (Sweden)

    Charlene Y Q Tan

    Full Text Available Human enteroviruses (HEV are frequent human pathogens and, associated in particular with large outbreaks of aseptic meningitis. Here, we have compiled a database of clinical HEV isolates from the Public Hospitals of Marseille, from 1985 to 2005. Amongst 654 isolates that could be characterized by complete sequencing of the VP1 gene, 98% belonged to species HEV-B; the most frequently isolated serotypes were Echovirus E30, E11, E7, E6 and E4. The high incidence of E30 and the recent emergence of E13 are consistent with reports worldwide and peak HEV isolation occurred mostly in the late spring and summer months. The proportion of echoviruses has decreased across the years, while that of coxsackieviruses has increased. Stool (the most frequent sample type allowed detection of all identified serotypes. MRC5 (Human lung fibroblasts cell line was the most conducive cell line for HEV isolation (84.9% of 10 most common serotype isolates, 96.3% in association with BGM (Buffalo green monkey kidney cells. Previous seroneutralization-based serotype identification demonstrated 55.4% accuracy when compared with molecular VP1 analysis. Our analysis of a large number of clinical strains over 20 years reinforced the validity of VP1 serotyping and showed that comparative p-distance scores can be coupled with phylogenetic analysis to provide non-ambiguous serotype identification. Phylogenetic analysis in the VP1, 2C and 3D regions also provided evidence for recombination events amongst clinical isolates. In particular, it identified isolates with dissimilar VP1 but almost identical nonstructural regions.

  4. Relationship between serologic response and clinical symptoms in children with enterovirus 71-infected hand-foot-mouth disease.

    Science.gov (United States)

    Shen, Jun; Zhao, Chao; Cao, Ping; Shi, Peng; Cao, Lingfeng; Zhu, Qirong

    2015-01-01

    This study aimed to explore the correlation between clinical symptoms, including rash and fever, and serum antibody reaction to enterovirus 71 (EV71) infection in children hospitalized due to hand-foot-mouth disease (HFMD). From May 2014 to July 2014, a total of 547 children hospitalized due to HFMD in Children's Hospital of Fudan University were enrolled retrospectively. RNA levels of EV71 and CA16 in fecal, serum, and cerebrospinal fluid specimens were measured using quantitative real-time RT-PCR, and EV71-IgM antibody in the serum was detected using immune colloidal gold assays. Of the 547 fecal specimens, 296 were EV71 RNA positive, 109 were CA16 RNA positive, and 8 were positive for both EV71 RNA and CA16 RNA. The total positive rate for either EV71 or CA16 in feces was 72.58% (397/547). Additionally, 544 serum specimens were collected, and 409 were EV71-IgM positive (75.18%). The duration of rash and fever was found to be correlated to the positive rate of serum EV71-IgM, and the positive rate of serum EV71-IgM plus EV71 RNA in feces. The positive rates of serum EV71-IgM and serum EV71-IgM plus EV71 RNA in fecal collected at day 3 of fever were 79.7% and 52.8%, respectively. In conclusion, EV71 and CA16 were found to be the major pathogens responsible for the epidemics of HFMD in children during May to July 2014 in Shanghai, China. There is a close relationship between the positive rate of serum EV71-IgM and the duration of fever and rash.

  5. The isolation of nonpolio enteroviruses from serum.

    Science.gov (United States)

    Prather, S L; Jenista, J A; Menegus, M A

    1984-09-01

    Enteroviruses were isolated from 14 of 31 frozen serum specimens obtained from hospitalized patients with enterovirus infection, which had been previously documented by recovery of virus from stool, throat, or cerebrospinal fluid (CSF). Virus was detected in 71% of the positive sera within 3 days of specimen inoculation and serum virus titers ranged from 1.0 X 10(1) to 9.2 X 10(3) plaque-forming units/ml. The data suggest that blood cultures may be useful in the diagnosis of acute enterovirus disease and that use of RD and BGM cells may improve the speed and rate of virus recovery.

  6. Hydrophobic pocket targeting probes for enteroviruses

    Science.gov (United States)

    Martikainen, Mari; Salorinne, Kirsi; Lahtinen, Tanja; Malola, Sami; Permi, Perttu; Häkkinen, Hannu; Marjomäki, Varpu

    2015-10-01

    Visualization and tracking of viruses without compromising their functionality is crucial in order to understand virus targeting to cells and tissues, and to understand the subsequent subcellular steps leading to virus uncoating and replication. Enteroviruses are important human pathogens causing a vast number of acute infections, and are also suggested to contribute to the development of chronic diseases like type I diabetes. Here, we demonstrate a novel method to target site-specifically the hydrophobic pocket of enteroviruses. A probe, a derivative of Pleconaril, was developed and conjugated to various labels that enabled the visualization of enteroviruses under light and electron microscopes. The probe mildly stabilized the virus particle by increasing the melting temperature by 1-3 degrees, and caused a delay in the uncoating of the virus in the cellular endosomes, but could not however inhibit the receptor binding, cellular entry or infectivity of the virus. The hydrophobic pocket binding moiety of the probe was shown to bind to echovirus 1 particle by STD and tr-NOESY NMR methods. Furthermore, binding to echovirus 1 and Coxsackievirus A9, and to a lesser extent to Coxsackie virus B3 was verified by using a gold nanocluster labeled probe by TEM analysis. Molecular modelling suggested that the probe fits the hydrophobic pockets of EV1 and CVA9, but not of CVB3 as expected, correlating well with the variations in the infectivity and stability of the virus particles. EV1 conjugated to the fluorescent dye labeled probe was efficiently internalized into the cells. The virus-fluorescent probe conjugate accumulated in the cytoplasmic endosomes and caused infection starting from 6 hours onwards. Remarkably, before and during the time of replication, the fluorescent probe was seen to leak from the virus-positive endosomes and thus separate from the capsid proteins that were left in the endosomes. These results suggest that, like the physiological hydrophobic content

  7. Epidemiological survey enterovirus infection in of neonatal non-polio the Netherlands

    NARCIS (Netherlands)

    Verboon-Maciolek, MA; Krediet, TG; van Loon, AM; Kaan, J; Galama, JMD; Gerards, LJ; Fleer, A

    The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1

  8. Epidemiological survey of neonatal non-polio enterovirus infection in the Netherlands.

    NARCIS (Netherlands)

    Verboom-Maciolek, M.A.; Krediet, T.G.; Loon, A.M. van; Kaan, J.A.; Galama, J.M.D.; Gerards, L.J.; Fleer, A.

    2002-01-01

    The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1

  9. [Molecular diagnosis of respiratory enterovirus infections: Use of PCR and molecular identification for a best approach of the main circulating strains during 2008].

    Science.gov (United States)

    Petitjean-Lecherbonnier, J; Dina, J; Nguyen, E; Gouarin, S; Lebigot, E; Vabret, A

    2011-04-01

    The PCR assays are currently used in diagnosis of enterovirus (EV) meningitis. Nevertheless, the use of molecular diagnosis of EV should be investigated in respiratory tract infections (RTI). To perform enterovirus molecular diagnostic tools, PCR and genotyping, in nasal samples for diagnostic and epidemiologic purposes. During 2008, 3612 nasal specimen (NS) were studied by IFD and MRC5 culture. Next, we realised successively viral isolation on HuH7 culture (for NS negative by IFD assay) and a duplex PCR enterovirus-rhinovirus for the 816 HuH7 positive supernatants. Furthermore, 327 NS collected from neonates were systematically tested by a real-time RT-PCR. This assay was used in routine for EV diagnosis setting in cerebrospinal fluid. Enterovirus genotyping was then performed for the 68 positive supernatants. Thirty-five NS (0.97%) were positive for EV by culture (MRC5). A combination of both PCR assays, PEVRV and PEV, allowed an additional identification of 41 EV, eight EV-RV and 12 RV, increasing the number of positive to 96 NS (2.6%). Among the neonates, 32 NS (11.3%) were positive for EV by PEV. Of the 98 NS tested by the two PCR assays (PEV and PEVRV), 27 were positive and we detected 10 EV, five EV-RV and 12 RV. From January to December 2008, the circulation of EV showed the usual peak in June-July when a small outbreak of aseptic meningitis occurred and an additional autumnal peak corresponding to respiratory tract infections. Five main serotypes were isolated: 19 EV68 (29.7%), 12 CB3 (18.7%), nine E3 (14,1%), six CA9 (9.4%) and six CB1 (9.4%); the 19 EV68 were isolated in October-November and 17/19 (89.5%) of positive patients were hospitalised for severe respiratory diseases. The use of molecular screening techniques (PCR assays and genotyping) on nasal samples collected from patients with respiratory infections allowed a prospective, effective and precise identification of circulating strains. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  10. Global emergence of enterovirus D68

    DEFF Research Database (Denmark)

    Holm-Hansen, Charlotte Carina; Midgley, Sofie Elisabeth; Fischer, Thea Kølsen

    2016-01-01

    on enterovirus D68 to estimate its global epidemiology and its ability to cause respiratory infections and neurological damage in children. We extracted data from 70 papers to report on prevalence, symptoms, hospitalisation and mortality, and complications of enterovirus D68, both before and during the large......Since its discovery in California in 1962, reports of enterovirus D68 have been infrequent. Before 2014, infections were confirmed in only 699 people worldwide. In August, 2014, two paediatric hospitals in the USA reported increases in the number of patients with severe respiratory illness......, with an over-representation in children with asthma. Shortly after, the authorities recognised a nationwide outbreak, which then spread to Canada, Europe, and Asia. In 2014, more than 2000 cases of enterovirus D68 were reported in 20 countries. Concurrently, clusters of children with acute flaccid paralysis...

  11. Infecciones del sistema nervioso central por enterovirus en niños atendidos en un hospital de Lima, Perú Enteroviral central nervous system infections in children treated at a hospital in Lima, Peru

    Directory of Open Access Journals (Sweden)

    Iván O Espinoza

    2011-12-01

    Full Text Available Objetivos. Determinar la frecuencia y las características clínicas de las infecciones del sistema nervioso central por enterovirus en niños atendidos en el Hospital Nacional Cayetano Heredia de Lima, Perú. Materiales y métodos. Se realizó un estudio prospectivo y descriptivo desde abril 2008 hasta marzo 2010. Se enrolaron pacientes de un mes a 14 años con diagnóstico clínico de encefalitis o meningitis asépticas. Se investigó la presencia de enterovirus, virus herpes simple 1 (VHS-1, virus herpes simple 2 (VHS-2 y virus varicela-zoster (VZV mediante reacción en cadena de polimerasa (PCR. Resultados. Se enrolaron 97 pacientes de los cuales 69 % presentaron encefalitis aguda y 31 % meningitis aguda. Se identificó enterovirus en 52,6 % del total de infecciones agudas no bacterianas del sistema nervioso central; encontrándose en 83,3 % de las meningitis y en 38,8 % de las encefalitis. No hubo casos de infección por VHS-1, VHS-2 ni VZV. Las infecciones por enterovirus alcanzaron el 82,9 % en los meses cálidos de noviembre a enero y el 28,6 % en los meses fríos de mayo a julio. Conclusiones. Los enterovirus fueron los principales agentes etiológicos en las encefalitis y meningitis asépticas agudas en pacientes pediátricos de Lima, Perú. Los enterovirus tienen un comportamiento epidemiológico estacional con un claro aumento del número de casos en los meses de verano. Resulta útil tener disponible un método de diagnóstico rápido, como una ayuda para el manejo de las infecciones agudas del sistema nervioso.Objectives. To determine the frequency and clinical features of central nervous system infections caused by enterovirus in children treated at the Hospital Nacional Cayetano Heredia in Lima, Peru. Materials and methods. A prospective, descriptive study was performed from April 2008 to March 2010. Patients aged 1 month - 14 years with clinical diagnosis of encephalitis or aseptic meningitis were included. We investigated the

  12. Breastfeeding, previous Epstein-Barr virus infection, Enterovirus 71 infection, and rural residence are associated with the severity of hand, foot, and mouth disease.

    Science.gov (United States)

    Li, Yaping; Dang, Shuangsuo; Deng, Huiling; Wang, Wenjun; Jia, Xiaoli; Gao, Ning; Li, Mei; Wang, Jun

    2013-05-01

    Severe hand, foot, and mouth disease (HFMD) is likely to develop critical complications such as brainstem encephalitis, acute pulmonary edema, and circulatory failure, which cause child mortality during outbreaks. This study aims to investigate factors that predict the severity of HFMD. One hundred sixteen in-patient children with severe HFMD and 202 with mild HFMD were retrospectively enrolled. Potential factors were collected for each child including sex, age, residence, modes of delivery, birth weight, virus types causing HFMD, and virus exposure history. Univariate and multivariable logistic regression were used to determine which factors were associated with HFMD severity. In the univariate analysis, breastfeeding (OR 0.514, 95 % CI 0.309-0.856), rural residence (OR 1.971, 95 % CI 1.239-3.137), current Enterovirus 71 (EV71) infection (OR 2.539, 95 % CI 1.504-4.287), and previous Epstein-Barr virus (EBV) exposure (OR 3.136, 95 % CI 1.863-5.278) were each associated with the severity of HFMD. In the multivariate model, breastfeeding (OR 0.570, 95 % CI 0.332-0.980), rural residence (OR 1.973, 95 % CI 1.202-3.237), current EV71 infection (OR 2.290, 95 % CI 1.315-3.987), and previous EBV exposure (OR 2.550, 95 % CI 1.470-4.422) remained independently associated with the severity of HFMD. In conclusion, previous EBV exposure, EV71 infection, and rural residence are risk factors for severe HFMD; breastfeeding is a protective factor.

  13. Assessment of the risks for human health of adenoviruses, hepatitis A virus, rotaviruses and enteroviruses in the Buffalo River and three source water dams in the Eastern Cape.

    Science.gov (United States)

    Chigor, Vincent N; Sibanda, Timothy; Okoh, Anthony I

    2014-06-01

    Buffalo River is an important water resource in the Eastern Cape Province of South Africa. The potential risks of infection constituted by exposure to human enteric viruses in the Buffalo River and three source water dams along its course were assessed using mean values and static quantitative microbial risk assessment (QMRA). The daily risks of infection determined by the exponential model [for human adenovirus (HAdV) and enterovirus (EnV)] and the beta-Poisson model (for hepatitis A virus (HAV) and rotavirus (RoV)) varied with sites and exposure scenario. The estimated daily risks of infection values at the sites where the respective viruses were detected, ranged from 7.31 × 10(-3) to 1 (for HAdV), 4.23 × 10(-2) to 6.54 × 10(-1) (RoV), 2.32 × 10(-4) to 1.73 × 10(-1) (HAV) and 1.32 × 10(-4) to 5.70 × 10(-2) (EnV). The yearly risks of infection in individuals exposed to the river/dam water via drinking, recreational, domestic or irrigational activities were unacceptably high, exceeding the acceptable risk of 0.01% (10(-4) infection/person/year), and the guideline value used as by several nations for drinking water. The risks of illness and death from infection ranged from 6.58 × 10(-5) to 5.0 × 10(-1) and 6.58 × 10(-9) to 5.0 × 10(-5), respectively. The threats here are heightened by the high mortality rates for HAV, and its endemicity in South Africa. Therefore, we conclude that the Buffalo River and its source water dams are a public health hazard. The QMRA presented here is the first of its kinds in the Eastern Cape Province and provides the building block for a quantitatively oriented local guideline for water quality management in the Province.

  14. Inactivated Enterovirus 71 Vaccine Produced by 200-L Scale Serum-Free Microcarrier Bioreactor System Provides Cross-Protective Efficacy in Human SCARB2 Transgenic Mouse.

    Directory of Open Access Journals (Sweden)

    Chia-Ying Wu

    Full Text Available Epidemics and outbreaks caused by infections of several subgenotypes of EV71 and other serotypes of coxsackie A viruses have raised serious public health concerns in the Asia-Pacific region. These concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. In this report, we present a platform for the large-scale production of a vaccine based on the inactivated EV71(E59-B4 virus. The viruses were produced in Vero cells in a 200 L bioreactor with serum-free medium, and the viral titer reached 10(7 TCID50/mL 10 days after infection when using an MOI of 10(-4. The EV71 virus particles were harvested and purified by sucrose density gradient centrifugation. Fractions containing viral particles were pooled based on ELISA and SDS-PAGE. TEM was used to characterize the morphologies of the viral particles. To evaluate the cross-protective efficacy of the EV71 vaccine, the pooled antigens were combined with squalene-based adjuvant (AddaVAX or aluminum phosphate (AlPO4 and tested in human SCARB2 transgenic (Tg mice. The Tg mice immunized with either the AddaVAX- or AlPO4-adjuvanted EV71 vaccine were fully protected from challenges by the subgenotype C2 and C4 viruses, and surviving animals did not show any degree of neurological paralysis symptoms or muscle damage. Vaccine treatments significantly reduced virus antigen presented in the central nervous system of Tg mice and alleviated the virus-associated inflammatory response. These results strongly suggest that this preparation results in an efficacious vaccine and that the microcarrier/bioreactor platform offers a superior alternative to the previously described roller-bottle system.

  15. Antigenic and genetic diversity of human enterovirus 71 from 2009 to 2012, Taiwan.

    Directory of Open Access Journals (Sweden)

    Yuan-Pin Huang

    Full Text Available Different subgenogroups of enterovirus 71 (EV-71 have caused numerous outbreaks of hand, foot, and mouth disease worldwide, especially in the Asia-Pacific region. During the development of a vaccine against EV-71, the genetic and antigenic diversities of EV-71 isolates from Taiwan were analyzed by phylogenetic analyses and neutralization tests. The results showed that the dominant genogroups had changed twice, from B to C and from C to B, between 2009 and 2012. The subgenogroup B5 (B5b cluster was dominant in 2008-2009 but was replaced by subgenogroup C4 in 2010-2011. From the end of 2011 to 2012, the re-emerging subgenogroup B5 (B5c cluster was identified as the dominant subgenogroup of EV-71 outbreaks, and subgenogroups C2 and C4 were detected in sporadic cases. Interestingly, the amino acid substitution at position 145 in the VP1 gene was observed in some strains isolated from patients with acute flaccid paralysis. Furthermore, thirty-five strains and their corresponding serum samples were used to analyze the cross-protections and antigenic diversities among different subgenogroups (C4a, C5, B4, B5b, B5c, and C2-like of EV-71. Evident antigenic diversity existed only for the C2-like subgenogroup, which was not effectively neutralized by other serum samples. In contrast, the anti-C2-like serum sample showed broad cross-reactivity against all other subgenogroups. Therefore, these results may provide valuable information for the selection of EV-71 vaccine candidates and the evolution of EV-71 subgenogroups in Taiwan from 2009 to 2012.

  16. Potential biosentinels of human waste in marine coastal waters: bioaccumulation of human noroviruses and enteroviruses from sewage-polluted waters by indigenous mollusks.

    Science.gov (United States)

    Asahina, Audrey Y; Lu, Y; Wu, C; Fujioka, R S; Loh, P C

    2009-06-01

    A major problem of existing methods to monitor for viral pathogens in large bodies of water (i.e., coastal waters) is in the initial viral recovery and concentration of these viruses. In this report, the indigenous filter-feeding bivalve mollusk, Isognomon sp., ubiquitous in the Indo-Pacific area, has been used successfully in this critical initial sequence (virus recovery) to bioaccumulate human enteropathogenic viruses from seawater seeded experimentally with either raw sewage or human norovirus-positive stool samples. Characteristic amplicons representing the human noroviruses (213 bp) and enteroviruses (196 bp) were detected by reverse transcription polymerase chain reaction (RT-PCR) employing specific primers. The data indicate the high feasibility of employing these mollusks to serve as practical biosentinels of waters contaminated with sewage in coastal and island communities.

  17. Molecular identification and analysis of human enteroviruses isolated from healthy children in Shenzhen, China from 2010 to 2011.

    Directory of Open Access Journals (Sweden)

    Wei Wu

    Full Text Available OBJECTIVE: To determine the prevalence and distribution of human enteroviruses (HEVs among healthy children in Shenzhen, China. METHOD: Clinical specimens were obtained from 320 healthy children under 5 years old in Shenzhen, China from 2010 to 2011. The specimens were evaluated using real-time PCR and cell cultures. The positive specimens were further tested using reverse transcription-seminested PCR (RT-snPCR. Molecular typing and phylogenetic analysis were based on the sequence determined. RESULTS: Among the 320 samples, 34 were tested positive for HEVs (10.6% and 22 different serotypes were identified using RT-snPCR. PV1 and PV2 were also detected. The predominant serotype observed was EV71 (17.6%, followed by CV-B4 (14.7%. HEV-B was detected most frequently, with an overall prevalence of 47.1%. HEV-A and HEV-C were found in 32.3% and 20.6% of the samples, respectively. No HEV-D was identified. Molecular phylogeny indicated that all EV71 strains were of C4 genotype. CONCLUSION: Although a variety of HEVs was detected in healthy children, HEV-B was relatively more prevalent than other HEV species. Considering HEV-A is more prevalent than HEV-B among patients with hand-foot-mouth disease, additional long-term surveillance of HEV is warranted in both asymptomatic and symptomatic populations.

  18. Dermatophilus congolensis human infection.

    Science.gov (United States)

    Towersey, L; Martins, E de C; Londero, A T; Hay, R J; Soares Filho, P J; Takiya, C M; Martins, C C; Gompertz, O F

    1993-08-01

    Four cases of human dermatophilosis observed in Rio de Janeiro, Brazil, are reported. Data that suggest nail infection by Dermatophilus congolensis are presented. The clinical spectrum of the disease ranged from an asymptomatic infection to a pustular eruption. Our findings suggest that epidermal Langerhans cells play a role in the pathogenesis of the infection.

  19. Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease.

    Directory of Open Access Journals (Sweden)

    Lunbiao Cui

    Full Text Available Altered circulating microRNA (miRNA profiles have been noted in patients with microbial infections. We compared host serum miRNA levels in patients with hand-foot-and-mouth disease (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 as well as in other microbial infections and in healthy individuals. Among 664 different miRNAs analyzed using a miRNA array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. Expression levels of ten candidate miRNAs were further evaluated by quantitative real-time PCR assays. A receiver operating characteristic (ROC curve analysis revealed that six miRNAs (miR-148a, miR-143, miR-324-3p, miR-628-3p, miR-140-5p, and miR-362-3p were able to discriminate patients with enterovirus infections from healthy controls with area under curve (AUC values ranged from 0.828 to 0.934. The combined six miRNA using multiple logistic regression analysis provided not only a sensitivity of 97.1% and a specificity of 92.7% but also a unique profile that differentiated enterovirial infections from other microbial infections. Expression levels of five miRNAs (miR-148a, miR-143, miR-324-3p, miR-545, and miR-140-5p were significantly increased in patients with CVA16 versus those with EV71 (p<0.05. Combination of miR-545, miR-324-3p, and miR-143 possessed a moderate ability to discrimination between CVA16 and EV71 with an AUC value of 0.761. These data indicate that sera from patients with different subtypes of enteroviral infection express unique miRNA profiles. Serum miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping enteroviral HFMD infections.

  20. An enzyme-linked immuno focus assay for rapid detection and enumeration, and a newborn mouse model for human non-polio enteroviruses associated with acute diarrhea.

    Science.gov (United States)

    Rao, C Durga; Reddy, Harikrishna; Naidu, Jagadish R; Raghavendra, A; Radhika, N S; Karande, Anjali

    2015-11-01

    We have recently reported significant association of non-polio enteroviruses (NPEVs) with acute and persistent diarrhea (18-21% of total diarrheal cases), and non-diarrheal Increased Frequency of Bowel Movements (IFoBM-ND) (about 29% of the NPEV infections) in children and that the NPEV-associated diarrhea was as significant as rotavirus diarrhea. However, their diarrhea-causing potential is yet to be demonstrated in an animal model system. Since the determination of virus titers by the traditional plaque assay takes 4-7 days, there is a need for development of a rapid method for virus titer determination to facilitate active clinical research on enterovirus-associated diarrhea. The goal of this study is to develop a cell-based rapid detection and enumeration method and to demonstrate the diarrhea-inducing potential of purified and characterized non-polio enteroviruses, which were isolated from diarrheic children. Here we describe generation of monoclonal and polyclonal antibodies against purified strains belonging to different serotypes, and development of an enzyme-linked immuno focus assay (ELIFA) for detection and enumeration of live NPEV particles in clinical and purified virus samples, and a newborn mouse model for NPEV diarrhea. Plaque-purified NPVEs, belonging to different serotypes, isolated from children with diarrhea, were grown in cell culture and purified by isopycnic CsCl density gradient centrifugation. By ELIFA, NPEVs could be detected and enumerated within 12h post-infection. Our results demonstrated that Coxsackievirus B1 (CVB1) and CVB5 strains, isolated from diarrheic children, induced severe diarrhea in orally-inoculated 9-12 day-old mouse pups, fulfilling Koch's postulates. The methods described here would facilitate studies on NPEV-associated gastrointestinal disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Ku

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear. METHODS/FINDINGS: In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs. Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment. CONCLUSIONS: Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.

  2. Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of enterovirus-71 infection in Chinese Han children.

    Science.gov (United States)

    Tan, Yuxia; Yang, Tingting; Liu, Peipei; Chen, Liping; Tian, Qingwu; Guo, Ya; He, Hongfang; Liu, Yedan; Chen, Zongbo

    2017-08-01

    The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein that plays an important role in the antiviral action of IFN, with OAS3 being one of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several infectious viral diseases has been reported; however, a study of the effect of OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with susceptibility and severity of EV71 infection. We investigated 370 Chinese Han children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while 156 were severe). An improved multiplex ligation detection reaction (iMLDR) technique was carried out to examine the genotype. The AA genotype distribution (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p polymorphism is associated with the severity of EV-71 infection, and that the A allele is a risk factor for the development of severe EV71 infection.

  3. Fungi that Infect Humans.

    Science.gov (United States)

    Köhler, Julia R; Hube, Bernhard; Puccia, Rosana; Casadevall, Arturo; Perfect, John R

    2017-06-01

    Fungi must meet four criteria to infect humans: growth at human body temperatures, circumvention or penetration of surface barriers, lysis and absorption of tissue, and resistance to immune defenses, including elevated body temperatures. Morphogenesis between small round, detachable cells and long, connected cells is the mechanism by which fungi solve problems of locomotion around or through host barriers. Secretion of lytic enzymes, and uptake systems for the released nutrients, are necessary if a fungus is to nutritionally utilize human tissue. Last, the potent human immune system evolved in the interaction with potential fungal pathogens, so few fungi meet all four conditions for a healthy human host. Paradoxically, the advances of modern medicine have made millions of people newly susceptible to fungal infections by disrupting immune defenses. This article explores how different members of four fungal phyla use different strategies to fulfill the four criteria to infect humans: the Entomophthorales, the Mucorales, the Ascomycota, and the Basidiomycota. Unique traits confer human pathogenic potential on various important members of these phyla: pathogenic Onygenales comprising thermal dimorphs such as Histoplasma and Coccidioides; the Cryptococcus spp. that infect immunocompromised as well as healthy humans; and important pathogens of immunocompromised patients-Candida, Pneumocystis, and Aspergillus spp. Also discussed are agents of neglected tropical diseases important in global health such as mycetoma and paracoccidiomycosis and common pathogens rarely implicated in serious illness such as dermatophytes. Commensalism is considered, as well as parasitism, in shaping genomes and physiological systems of hosts and fungi during evolution.

  4. Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis.

    Science.gov (United States)

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2017-07-12

    Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 10 4 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.

  5. [Evolution and prognosis of the acute flaccid paralysis associated with enterovirus 71 infection evaluated through a clinical and magnetic resonance imaging follow-up study].

    Science.gov (United States)

    Peng, Bing-wei; Du, Zhi-hong; Li, Xiao-jing; Lin, Hai-sheng; Liu, Hong-sheng; Chen, Wen-xiong; Mai, Jian-ning; Liang, Hui-ci

    2012-04-01

    To explore the development and prognosis of the acute flaccid paralysis (AFP) associated with enterovirus 71 (EV71) infection through clinical follow-up study for clinical and magnetic resonance imaging (MRI) features based on the research progress of virology and pathology. Sixteen children with HFMD associated with AFP in hospital from May 1, 2011 to August 31, 2011 were investigated and the patients received intensive rehabilitation training. The 16 cases were divided into two groups (the recovery or the sequela) by if the muscle strength recovered to level 4 after intensive rehabilitation. The MRI findings of 15 children were analyzed and among them, 6 patients were reexamined after one month. The clinical markers were compared between groups including course of disease, WBC, WBC in cerebrospinal fluid (CSF), ventilator support, therapy, the worst muscle strength, the initial tendon reflex, the muscle atrophy, and multi-limb paralysis. The data were analyzed by t test and χ2 test with SPSS10.0. All the 16 children were infected with enterovirus 71 (EV71). The myodynamia of 7 children were level 0, 4 children had serious upper limbs paralysis. The neck muscle in 3 cases and the brain stem motor ruckus in 4 cases were involved. The ankle clonus of non-completely paralyzed limbs in 14 cases occurred during rehabilitation. Eight children had the better prognosis, the other 8 children had sequela. 0 level muscle strength (0 case vs. 7 cases, χ2=12.4), the initial tendon reflex (2 cases vs. 8 cases, χ2=9.6), obvious muscle atrophy (0 case vs. 8 cases, χ2=16), were significantly different in the children with the recovery when compared to the sequela (Pparalysis had the worse prognosis than the severe lower limbs paralysis. MR imaging showed signs of spinal nerve root inflammation and the bilateral hyperintense lesions, symmetrical in the posterior portions of the medulla, pons, and asymmetrical in the ventral horns of cervical spinal cord. Signal enhancement

  6. [Infection by human cytomegalovirus].

    Science.gov (United States)

    Sanbonmatsu Gámez, Sara; Ruiz, Mercedes Pérez; Navarro Marí, José María

    2014-02-01

    Prevalence of human cytomegalovirus infection is very high worldwide. Following primary infection, the virus remains latent, being able to cause recurrences either by reinfection with a new strain or by reactivation of the replication of the latent virus. The most severe disease is seen in congenital infection and in immunosuppressed patients, in whom the virus act as an opportunistic pathogen. Serological techniques are the methods of choice in primary infection and to determine the immune status against CMV in organ donor and receptor. Although well-standardized studies are lacking, the recent commercial availability of methods that measure cellular immune response are promising to predict the risk of CMV disease in immunosuppressed individuals. Molecular assays, that have gradually been substituting viral culture and/or antigen detection, are the most widely used methods for the diagnosis and control of CMV infection. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  7. Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction

    Directory of Open Access Journals (Sweden)

    Xiaobo Lei

    2016-01-01

    Full Text Available Enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (EV A71, EV-D68 and rhinovirus. Infection with EVs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. EVs, which are positive-sense single-stranded RNA viruses, trigger activation of the host antiviral innate immune responses through pathogen recognition receptors such as retinoic acid-inducible gene (RIG-I-likeand Toll-like receptors. In turn, EVs have developed sophisticated strategies to evade host antiviral responses. In this review, we discuss the interplay between the host innate immune responses and EV infection, with a primary focus on host immune detection and protection against EV infection and viral strategies to evade these antiviral immune responses.

  8. Enterovirus D68

    Science.gov (United States)

    ... Hygiene Viral Conjunctivitis Hand, Foot, and Mouth Disease Viral Meningitis What is Polio? Enterovirus D68 Language: English (US) ... Hygiene Viral Conjunctivitis Hand, Foot, and Mouth Disease Viral Meningitis What is Polio? Language: English (US) Español ( ...

  9. Replication and Inhibitors of Enteroviruses and Parechoviruses

    NARCIS (Netherlands)

    van der Linden, Lonneke; Wolthers, Katja C.; van Kuppeveld, Frank J. M.

    2015-01-01

    The Enterovirus (EV) and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV). They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases

  10. Non-polio enteroviruses serotypes circulating in Nigeria.

    Science.gov (United States)

    Oyero, O G; Adu, F D

    2010-12-01

    Enteroviruses is one of the most common group of human pathogens, causing a wide range of acute symptoms involving the cardiac and skeletal muscles, central nervous system, pancreas,skin and mucous membranes. In spite of the success recorded in polio eradication globally, infections with other enteroviruses remain frequent and sometimes very serious, requiring hospitalization. In this study we determined the various circulating serotypes of non-polio enteroviruses (NPEVs) with a view to providing information on the activity of these viruses among the Nigerian children, who usually are the most affected. Stool samples were obtained from hospitalized children at two major secondary community hospitals in Ibadan and acute flaccid paralysis (AFP) cases from 26 states ofNigeria. A presumptive identification of NPEVs was based on growth in RD cells. Isolates were identified by neutralization assay using sera obtained from the Institute for Public Health and the Environment, the Netherlands. The problems associated with this assay prompted the use of genotypic method developed at the Centers for Disease Control, Atlanta, USA for the final identification of isolates. Neutralization assay identified the 138 isolates into echoviruses (43.5%), coxsackie B viruses (29.7%) and untypeable isolates (26.8%). Finally genotyping identified echoviruses (E3, E6, E7, E11, E12, E13, E14, E19, E20, E21, E24, E29, E30, E33), coxsackieviruses (CVA3, CVA4, CVA6, CVA17, CVB3, CVB5, CVB6) and enteroviruses (EV69, EV71). The causal association of isolates with different diseases was also established. Majority of the isolates belonged to the human enterovirus gropup B (HEV-B) specie, followed by 4 and 1 in the HEV-A and HEV-C species respectively. This study forms the basis of molecular epidemiology of NPEVs being established for the first time in Nigeria. The implication of the presence of neurotropic serotypes (E3, E6, E7, E11, E14, E20, E24, E29, E30, EV71, CVB3 and CVB5) is that AFP may

  11. An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

    Directory of Open Access Journals (Sweden)

    Sun Junling

    2010-05-01

    Full Text Available Abstract Hand, foot and mouth disease (HFMD, a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71 with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50% were hospitalized, 353 (5.8% were severe and 22 (0.36% were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16, resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.

  12. Human Parechoviruses

    DEFF Research Database (Denmark)

    Fischer, Thea Kølsen; Harvala, Heli; Midgley, Sofie

    2017-01-01

    Infections with human parechoviruses (HPeV) are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. The clinical presentation of HPeV infection is often indistinguishable from that of enterovirus (EV) infection and may vary from mild disease...

  13. Enterovirus A71 Meningoencephalitis Outbreak, Rostov-on-Don, Russia, 2013.

    Science.gov (United States)

    Akhmadishina, Ludmila V; Govorukhina, Marina V; Kovalev, Evgeniy V; Nenadskaya, Svetlana A; Ivanova, Olga E; Lukashev, Alexander N

    2015-08-01

    Seventy-eight cases of enterovirus infection, including 25 neuroinfections, occurred in Rostov-on-Don, Russia, during May-June 2013. The outbreak was caused by an enterovirus A type 71 (EV-A71) subgenotype C4 lineage that spread to neighboring countries from China ≈3 years earlier. Enterovirus associated neuroinfection may emerge in areas with a preceding background circulation of EV-A71 with apparently asymptomatic infection.

  14. Clinical severity of pediatric respiratory illness with enterovirus D68 compared with rhinovirus or other enterovirus genotypes.

    Science.gov (United States)

    Mertz, Dominik; Alawfi, Abdulsalam; Pernica, Jeffrey M; Rutherford, Candy; Luinstra, Kathy; Smieja, Marek

    2015-11-17

    Enterovirus D68 (EV-D68) resulted in a reported increase in the number of children needing hospital or critical care admission because of respiratory insufficiency during 2014. It remains unclear, however, whether EV-D68 infections were more severe than rhinovirus or non-EV-D68 enterovirus infections. We evaluated consecutive children presenting to a pediatric hospital between Aug. 1 and Oct. 31, 2014, with positive nasopharyngeal swabs for rhinovirus or enterovirus that were sent automatically for EV-D68 testing. We compared characteristics and outcomes of patients with EV-D68 with those with rhinovirus or non-EV-D68 enterovirus in a matched cohort study. A total of 93/297 (31.3%) of rhinovirus or enterovirus samples tested positive for EV-D68, and it was possible to compare 87 matched pairs. Children with EV-D68 infection were more likely to have difficulty breathing (odds ratio [OR] 3.00, 95% confidence interval [CI] 1.47-6.14). There was no significant difference in admission to the critical care unit or death among children with EV-D68 infection compared with those with other rhinovirus or enterovirus infections (adjusted OR 1.47, 95% CI 0.61-3.52). Children with EV-D68 infection were more often admitted to hospital, but not significantly so (adjusted OR 2.29, 95% CI 0.96-5.46). Enterovirus D68 seems to be a more virulent pulmonary pathogen than rhinovirus or non-EV-D68 enterovirus, but we did not find a significant difference in death or need for critical care. © 2015 Canadian Medical Association or its licensors.

  15. Acute Disseminated Encephalomyelitis After Human Parechovirus Infection.

    Science.gov (United States)

    Obermeier, Patrick E; Karsch, Katharina; Hoppe, Christian; Seeber, Lea; Schneider, Joanna; Mühlhans, Susann; Chen, Xi; Tief, Franziska; Kaindl, Angela M; Weschke, Bernhard; Böttcher, Sindy; Diedrich, Sabine; Rath, Barbara

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory, demyelinating disease occurring several weeks after viral infection. Enteroviruses have been described as potential triggers of ADEM, but the closely related parechoviruses have not. The objective of the study is to assess the prevalence and disease presentation of ADEM after parechovirus infection in a syndromic surveillance program for pediatric infection/inflammation of the central nervous system (CNS). The surveillance was conducted at the Charité Department of Pediatrics in Berlin, Germany, from November 2010 to November 2014. All hospitalized children meeting predefined case criteria underwent highly standardized prospective clinical assessments based on the published case definitions, including for ADEM. Stool samples were independently analyzed by enterovirus and parechovirus real-time polymerase chain reaction at the Robert Koch Institute. Of 105,557 patients screened, 774 (0.7%) fulfilled entry criteria for CNS infection/inflammation, with 114 cases ascertained as ADEM. Parechoviruses were detected in 2.5% of patients with CNS infection/inflammation, including 1 case fulfilling ADEM case criteria with the highest level of diagnostic certainty. We report a first case of ADEM after parechovirus infection in a 5-year-old female presenting with acute hemiparesis 2 weeks after a respiratory illness. Parechovirus disease should be included in the differential diagnosis of ADEM.

  16. Risk factors of enterovirus 71 infection and associated hand, foot, and mouth disease/herpangina in children during an epidemic in Taiwan.

    Science.gov (United States)

    Chang, Luan-Yin; King, Chwan-Chuen; Hsu, Kuang-Hung; Ning, Hsiao-Chen; Tsao, Kuo-Chien; Li, Chung-Chen; Huang, Yhu-Chering; Shih, Shin-Ru; Chiou, Shu-Ti; Chen, Po-Yen; Chang, Hong-Jen; Lin, Tzou-Yien

    2002-06-01

    In 1998, an enterovirus 71 (EV71) epidemic in Taiwan was associated with hand, foot, and mouth disease (HFMD)/herpangina and involved 78 fatal cases. We measured EV71 seroprevalence rates before and after the epidemic and investigated risk factors associated with EV71 infection and illness. Neutralizing antibodies to EV71 were assayed for 539 people before the epidemic and 4619 people of similar ages after the epidemic. Questionnaires, which were completed during household interviews after the epidemic, solicited demographic variables, exposure history, and clinical manifestations. A total of 129 106 cases of HFMD were reported during the epidemic. Age-specific pre-epidemic EV71 seroprevalence rates were inversely related to age-specific periepidemic mortality rates (r = -0.82) or severe case rates (r = -0.93). Higher postepidemic EV71 seropositive rates among children who were younger than 3 years positively correlated with higher mortality rates in different areas (r = 0.88). After the epidemic, 51 (56%) of 91 younger siblings of elder siblings who were EV71-seropositive were EV71-seropositive; otherwise, 2.2% (4 of 186) of younger siblings were EV71-seropositive (matched odds ratio [OR]: 10; 95% confidence interval [CI]: 3.4-29). Stepwise multiple logistic regression revealed other factors associated with EV71 infection to be older age (adjusted OR: 2.5; 95% CI: 1.9-3.4), attendance at kindergartens/child care centers (adjusted OR: 1.8; 95% CI: 1.3-2.5), contact with HFMD/herpangina (adjusted OR: 1.6; 95% CI: 1.2-2.1), greater number of children in a family (adjusted OR: 1.4; 95% CI: 1.1-1.7), and rural residence (adjusted OR: 1.4; 95% CI: 1.2-1.6). Twenty-nine percent of preschool children who were infected with EV71 developed HFMD/herpangina. Younger age and contact with HFMD/herpangina were significant factors for the development of EV71-related HFMD/herpangina in these children. An increased incidence of EV71 infection in young children occurred more often

  17. Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC

    Science.gov (United States)

    Royston, Léna; Tapparel, Caroline

    2016-01-01

    Rhinoviruses (RVs) and respiratory enteroviruses (EVs) are leading causes of upper respiratory tract infections and among the most frequent infectious agents in humans worldwide. Both are classified in the Enterovirus genus within the Picornaviridae family and they have been assigned to seven distinct species, RV-A, B, C and EV-A, B, C, D. As viral infections of public health significance, they represent an important financial burden on health systems worldwide. However, the lack of efficient antiviral treatment or vaccines against these highly prevalent pathogens prevents an effective management of RV-related diseases. Current advances in molecular diagnostic techniques have revealed the presence of RV in the lower respiratory tract and its role in lower airway diseases is increasingly reported. In addition to an established etiological role in the common cold, these viruses demonstrate an unexpected capacity to spread to other body sites under certain conditions. Some of these viruses have received particular attention recently, such as EV-D68 that caused a large outbreak of respiratory illness in 2014, respiratory EVs from species C, or viruses within the newly-discovered RV-C species. This review provides an update of the latest findings on clinical and fundamental aspects of RV and respiratory EV, including a summary of basic knowledge of their biology. PMID:26761027

  18. Comparative analysis of viral shedding in pediatric and adult subjects with central nervous system-associated enterovirus infections from 2013 to 2015 in Switzerland.

    Science.gov (United States)

    Cordey, S; Schibler, M; L'Huillier, A G; Wagner, N; Gonçalves, A R; Ambrosioni, J; Asner, S; Turin, L; Posfay-Barbe, K M; Kaiser, L

    2017-04-01

    Several enterovirus (EV) genotypes can result in aseptic meningitis, but their routes of access to the central nervous system remain to be elucidated and may differ between the pediatric and adult populations. To assess the pattern of viral shedding in pediatric and adult subjects with acute EV meningitis and to generate EV surveillance data for Switzerland. All pediatric and adult subjects admitted to the University Hospitals of Geneva with a diagnosis of EV meningitis between 2013 and 2015 were enrolled. A quantitative EV real-time reverse transcriptase (rRT)-PCR was performed on the cerebrospinal fluid (CSF), blood, stool, urine and respiratory specimens to assess viral shedding and provide a comparative analysis of pediatric and adult populations. EV genotyping was systematically performed. EV positivity rates differed significantly between pediatric and adult subjects; 62.5% of pediatric cases (no adult case) were EV-positive in stool and blood for subjects for whom these samples were all collected. Similarly, the EV viral load in blood was significantly higher in pediatric subjects. Blood C-reactive protein levels were lower and the number of leucocytes/mm3 in the CSF were higher in non-viremic than in viremic pediatric subjects, respectively. A greater diversity of EV genotypes was observed in pediatric cases, with a predominance of echovirus 30 in children ≥3 years old and adults. In contrast to adults, EV-disseminated infections are predominant in pediatric subjects and show different patterns of EV viral shedding. This observation may be useful for clinicians and contribute to modify current practices of patient care. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  19. Characterization of a novel enterovirus serotype and an enterovirus EV-B93 isolated from acute flaccid paralysis patients.

    Directory of Open Access Journals (Sweden)

    Shahzad Shaukat

    Full Text Available Non-polio enteroviruses (NPEVs are among the most common viruses infecting humans worldwide. Most of these infections are asymptomatic but few can lead to systemic and neurological disorders like Acute Flaccid Paralysis (AFP. Acute Flaccid Paralysis is a clinical syndrome and NPEVs have been isolated frequently from the patients suffering from AFP but little is known about their causal relationship. The objective of this study was to identify and characterize the NPEV serotypes recovered from 184 stool samples collected from AFP patients in Federally Administered Tribal Areas (FATA in north-west of Pakistan. Overall, 44 (95.6 % isolates were successfully typed through microneutralization assay as a member of enterovirus B species including echovirus (E-2, E-3, E-4, E-6, E-7, E-11, E-13, E-14, E-21 and E-29 while two isolates (PAK NIH SP6545B and PAK NIH SP1202B remained untypeable. The VP1 and capsid regions analysis characterized these viruses as EV-B93 and EV-B106. Phylogenetic analysis confirmed that PAK NIH isolates had high genetic diversity and represent distinct genotypes circulating in the country. Our findings highlight the role of NPEVs in AFP cases to be thoroughly investigated especially in high disease risk areas, with limited surveillance activities and health resources.

  20. [Infection status of enterovirus 71 and coxsackievirus A16 among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice].

    Science.gov (United States)

    Wang, Xiaoli; Lin, Changying; Zhang, Haiyan; Ma, Jianxin; Li, Chao; Li, Jie; Jia, Lei; Yang, Yang; Du, Yiwei; Liang, Zhichao; Wang, Quanyi; He, Xiong

    2015-07-01

    To understand the infection status of enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) among children receiving health examination for child care setting entrance in Beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease (HFMD). Serological survey was conducted in the local children receiving health examination for child care setting entrance. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-EV71 and anti-Cox A16 IgG and IgM. A total of 813 children were surveyed (mean age: 3.5 ± 1.0 year old). The seropositive rate was 61.9% and 4.4% for anti-Cox A16 IgG and IgM. The seropositive rate was 9.3% and 1.1% for anti-EV71 IgG and IgM. No significant difference was observed in sex specific seropositive rate (P > 0.05). However, significant differences were found in seropositive rate among different age groups (P < 0.05). Among the children who were anti-Cox A16 positive, 7.8% had ever had rashes on their hands and feet, mouth or buttocks (HFMD-like rashes). Among the children who were anti-EV71 positive, 10.7% had ever had HFMD-like rashes. For the children who were anti-Cox A16 or anti-EV71 positive, only 7.1% were brought to see doctors by their parents. However, among the seropositive children with rashes, 80.5% were brought to see doctors. In the healthy children at the age to go to child care setting in Beijing, most had ever infected with Cox A16. The anti-EV71 positive rate was much lower than the anti-Cox A16 positive rate. It was necessary to strengthen the prevention and control of EV71 infection in child cares settings.

  1. Discovery of a bovine enterovirus in alpaca.

    Directory of Open Access Journals (Sweden)

    Shasta D McClenahan

    Full Text Available A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. Genomic sequence data of the alpaca isolate was obtained and compared with sequences of known viruses. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs, viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Because bovine enteroviruses have not been previously reported in U.S. alpaca, we suspect that this type of infection is fairly rare, and in this case appeared not to spread beyond the original outbreak. The capsid sequence of the detected virus had greatest homology to Enterovirus F type 1 (indicating that the virus should be considered a member of serotype 1, but the virus had greater homology in 2A protease sequence to type 3, suggesting that it may have been a recombinant. Identifying pathogens that infect a new host species for the first time can be challenging. As the disease in a new host species may be quite different from that in the original or natural host, the pathogen may not be suspected based on the clinical presentation, delaying diagnosis. Although this virus replicated in MDBK cells, existing standard culture and molecular methods could not identify it. In this case, a highly sensitive generic PCR-based pathogen-detection method was used to identify this pathogen.

  2. Discovery of a bovine enterovirus in alpaca.

    Science.gov (United States)

    McClenahan, Shasta D; Scherba, Gail; Borst, Luke; Fredrickson, Richard L; Krause, Philip R; Uhlenhaut, Christine

    2013-01-01

    A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from lung tissue of alpaca that died of a severe respiratory infection. To identify the virus, the infected cell culture supernatant was enriched for virus particles and a generic, PCR-based method was used to amplify potential viral sequences. Genomic sequence data of the alpaca isolate was obtained and compared with sequences of known viruses. The new alpaca virus sequence was most similar to recently designated Enterovirus species F, previously bovine enterovirus (BEVs), viruses that are globally prevalent in cattle, although they appear not to cause significant disease. Because bovine enteroviruses have not been previously reported in U.S. alpaca, we suspect that this type of infection is fairly rare, and in this case appeared not to spread beyond the original outbreak. The capsid sequence of the detected virus had greatest homology to Enterovirus F type 1 (indicating that the virus should be considered a member of serotype 1), but the virus had greater homology in 2A protease sequence to type 3, suggesting that it may have been a recombinant. Identifying pathogens that infect a new host species for the first time can be challenging. As the disease in a new host species may be quite different from that in the original or natural host, the pathogen may not be suspected based on the clinical presentation, delaying diagnosis. Although this virus replicated in MDBK cells, existing standard culture and molecular methods could not identify it. In this case, a highly sensitive generic PCR-based pathogen-detection method was used to identify this pathogen.

  3. Prevalence and molecular characterizations of enterovirus D68 among children with acute respiratory infection in China between 2012 and 2014.

    Science.gov (United States)

    Xiao, Qiuyan; Ren, Luo; Zheng, Shouyan; Wang, Lili; Xie, Xiaohong; Deng, Yu; Zhao, Yao; Zhao, Xiaodong; Luo, Zhengxiu; Fu, Zhou; Huang, Ailong; Liu, Enmei

    2015-11-16

    EV-D68 is associated with respiratory tract infections (RTIs). Since its first isolation, EV-D68 has been detected sporadically. However, the US and Canada have experienced outbreaks of EV-D68 infections between August and December 2014. This study aimed to investigate the molecular epidemiology and clinical characteristics of EV-D68 in Chongqing, Southwestern China. From January 2012 to November 2014, 1876 nasopharyngeal aspirate specimens (NPAs) were collected from hospitalized children with RTIs. Among the 1876 NPAs, EV-D68 was detected in 19 samples (1.0%, 19/1876). Of these, 13 samples were detected in September and October 2014 (9.8%, 13/132). Phylogenetic analysis showed that all 13 strains detected in the 2014 Chongqing had high homology with the main strains of the 2014 US outbreak. Among the children with EV-D68 infection, 13 (68%) had a history of recurrent wheezing. A total of 13 children had a discharge diagnosis of asthma. Of these, 11 children were diagnosed with acute asthma exacerbation. EV-D68 was the predominant pathogen that evoked asthma exacerbation in September and October 2014. In conclusion, our results found that a history of recurrent wheezing may be a risk factor for the detection of EV-D68 and viral-induced asthma exacerbation may be a clinical feature of EV-D68 infection.

  4. An RNA replication-center assay for high content image-based quantifications of human rhinovirus and coxsackievirus infections

    Directory of Open Access Journals (Sweden)

    Lötzerich Mark

    2010-10-01

    Full Text Available Abstract Background Picornaviruses are common human and animal pathogens, including polio and rhinoviruses of the enterovirus family, and hepatits A or food-and-mouth disease viruses. There are no effective countermeasures against the vast majority of picornaviruses, with the exception of polio and hepatitis A vaccines. Human rhinoviruses (HRV are the most prevalent picornaviruses comprising more than one hundred serotypes. The existing and also emerging HRVs pose severe health risks for patients with asthma or chronic obstructive pulmonary disease. Here, we developed a serotype-independent infection assay using a commercially available mouse monoclonal antibody (mabJ2 detecting double-strand RNA. Results Immunocytochemical staining for RNA replication centers using mabJ2 identified cells that were infected with either HRV1A, 2, 14, 16, 37 or coxsackievirus (CV B3, B4 or A21. MabJ2 labeled-cells were immunocytochemically positive for newly synthesized viral capsid proteins from HRV1A, 14, 16, 37 or CVB3, 4. We optimized the procedure for detection of virus replication in settings for high content screening with automated fluorescence microscopy and single cell analysis. Our data show that the infection signal was dependent on multiplicity, time and temperature of infection, and the mabJ2-positive cell numbers correlated with viral titres determined in single step growth curves. The mabJ2 infection assay was adapted to determine the efficacy of anti-viral compounds and small interfering RNAs (siRNAs blocking enterovirus infections. Conclusions We report a broadly applicable, rapid protocol to measure infection of cultured cells with enteroviruses at single cell resolution. This assay can be applied to a wide range of plus-sense RNA viruses, and hence allows comparative studies of viral infection biology without dedicated reagents or procedures. This protocol also allows to directly compare results from small compound or siRNA infection screens

  5. A prospective, comparative study of severe neurological and uncomplicated hand, foot and mouth forms of paediatric enterovirus 71 infections.

    Science.gov (United States)

    Crabol, Yoann; Pean, Polidy; Mey, Channa; Duong, Veasna; Richner, Beat; Laurent, Denis; Santy, Ky; Sothy, Heng; Dussart, Philippe; Tarantola, Arnaud; Buchy, Philippe; Horwood, Paul F

    2017-06-01

    In this study, we document the clinical characteristics and investigated risk factors for uncomplicated and severe forms of EV-A71 disease in Cambodian children. From March to July 2014 inclusive, all patients with suspicion of EV-A71 infection presenting to Kantha Bopha Hospitals in Phnom Penh and Siem Reap and confirmed by the Virology Unit at the Institut Pasteur du Cambodge were prospectively enrolled in this study. Throat swabs, rectal swabs and serum samples were collected from all consecutive patients with suspected EV-A71 infection. In addition, CSF was also collected from patients with suspected EV-A71 associated encephalitis. A total of 122 patients (29 with uncomplicated disease and 93 with severe disease) with confirmed EV-A71 infection with all available demographic and clinical data for clinical classification and further analysis were included in the study. In this prospective EV-A71 study in Cambodia, we confirmed the previously reported association of male gender and absence of mouth or skin lesions with severe disease. We also highlighted the strong association of neutrophils in blood, but also in CSF in patients with pulmonary oedema. More importantly, we identified new putative nutrition-related risk factors for severe disease. EV-A71 is an important cause of encephalitis in the Asia-Pacific region. Further studies to determine the risk factors associated with severe EV-A71 disease are needed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  6. Seroprevalence of enterovirus 71 and no evidence of crossprotection of enterovirus 71 antibody against the other enteroviruses in kindergarten children in Taipei city.

    Science.gov (United States)

    Huang, Wen-Chan; Huang, Li-Min; Kao, Chuan-Liang; Lu, Chun-Yi; Shao, Pei-Lan; Cheng, Ai-Ling; Fan, Tsui-Yien; Chi, Hsin; Chang, Luan-Yin

    2012-04-01

    Enterovirus 71 (EV71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. This study is to investigate the seroprevalence and seroconversion of EV71, and the crossprotection of EV71 antibody against other enteroviruses among kindergarteners. Overall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in Taipei, Taiwan and we measured their EV71 neutralizing antibody. When the participants had herpangina; hand, foot and mouth disease (HFMD); febrile illness or respiratory symptoms, throat swabs were sampled and processed for viral culture and enterovirus real-time reverse transcriptase polymerase chain reaction (RT-PCR). Questionnaires, completed by the participants' guardians, surveyed the history of allergy and annual incidence of symptoms related to enterovirus infection. Seropositive rates of EV71 were 20% (32/163) in 2006 and 6% (4/65) in 2007. The rate of EV71 seropositivity increased with age (p < 0.01) in 2006 but it did not differ between genders (p = 0.14). No seroconversion was observed from 2006 to 2007. Herpangina occurred in 64% of children with EV71 seropositivity and 48% of those without EV71 antibodies (p = 0.12). Non-71 enterovirus infection, confirmed by viral study, occurred in 53% (19/36) of the EV71-seropositive children and in 53% (102/192) of EV71-seronegative children (p = 0.89). No participants had EV71 infection during the study period. EV71 did not frequently circulate in Taipei City from September 2006 to June 2008. Presence of EV71 neutralizing antibody was not associated with lower incidence of enterovirus infection caused by non-71 serotypes. Copyright © 2011. Published by Elsevier B.V.

  7. Prevalence of rotavirus, norovirus and enterovirus in diarrheal diseases in Himachal Pradesh, India.

    Science.gov (United States)

    Jain, Swapnil; Thakur, Nutan; Grover, Neelam; Vashistt, Jitendraa; Changotra, Harish

    2016-03-01

    Diarrheal diseases are responsible for a significant proportion of mortality and morbidity all around the globe. The contribution of viruses to gastroenteritis incidences in humans is well established. In the present study, we have studied the prevalence of rotavirus, norovirus and enterovirus in Himachal Pradesh, a north Indian state. A total of 287 (111 children and 176 adults) stool samples of gastroenteritis patients were screened for the viruses using RT-PCR method. 34.5 % samples were positive for the viral pathogens of gastroenteritis. Rotavirus was the predominant virus detected in the study with 49.5 and 14.8 % positivity in children and adults, respectively. Enterovirus was present in 5.6 % cases whereas norovirus had least prevalence (1.4 %). Co infection (rotavirus and enterovirus) was witnessed at the prevalence rate of 0.6 %. Among different age groups, the prevalence of studied viruses was highest in the children belonging to the age groups of Rotavirus infections were found to be significantly associated with vomiting and trend of higher rates of fever and dehydration was seen in children along with diarrhea. Seasonal distribution shows circulation of diarrheagenic viruses throughout the year. This is the first report of prevalence of various diarrheagenic viruses circulating in this region. The outcome of the study from this cohort provides a baseline data which can be used to design the preventive strategies in the otherwise unexplored state of Himachal Pradesh.

  8. Detection of human adenovirus, rotavirus and enterovirus in water samples collected on dairy farms from Tenente Portela, Northwest of Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Fernando Rosado Spilki

    2013-09-01

    Full Text Available Viral gastroenteritis and other waterborne diseases are a major concern for health in Brazil. A number of studies were conducted about the presence of viruses on water samples from Brazilian areas. However, the knowledge about the occurrence of viral contamination of drinking water sources in rural settings of the country is insufficient. On the present work, 15 samples from 5 dairy farms located at the municipality of Tenente Portela were collected and analysed for the presence of human adenoviruses (HAdV, as well as human enteroviruses (EV and rotaviruses (RV. HAdV was present on 66.66% of the water samples, and have been found in all samples from artesian wells and springs, which are used as sources of drinking water for the individuals inhabiting those farms. EV and RV found only in one sample each. The detection rates of HAdV on the water from these dairy farms are alarming and point towards a situation of elevated environmental contamination by fecal microorganisms of human origin and poor basic sanitation conditions.

  9. Detection of human adenovirus, rotavirus and enterovirus in water samples collected on dairy farms from Tenente Portela, Northwest of Rio Grande do Sul, Brazil.

    Science.gov (United States)

    Spilki, Fernando Rosado; da Luz, Roger Bordin; Fabres, Rafael Bandeira; Soliman, Mayra Cristina; Kluge, Mariana; Fleck, Juliane Deise; Rodrigues, Manoela Tressoldi; Comerlato, Juliana; Cenci, Alexander; Cerva, Cristine; Dasso, Maurício Gautério; Roehe, Paulo Michel

    2013-01-01

    Viral gastroenteritis and other waterborne diseases are a major concern for health in Brazil. A number of studies were conducted about the presence of viruses on water samples from Brazilian areas. However, the knowledge about the occurrence of viral contamination of drinking water sources in rural settings of the country is insufficient. On the present work, 15 samples from 5 dairy farms located at the municipality of Tenente Portela were collected and analysed for the presence of human adenoviruses (HAdV), as well as human enteroviruses (EV) and rotaviruses (RV). HAdV was present on 66.66% of the water samples, and have been found in all samples from artesian wells and springs, which are used as sources of drinking water for the individuals inhabiting those farms. EV and RV found only in one sample each. The detection rates of HAdV on the water from these dairy farms are alarming and point towards a situation of elevated environmental contamination by fecal microorganisms of human origin and poor basic sanitation conditions.

  10. Isolation of an imported subgenotype B5 strain of human enterovirus A71 in Chongqing City, China, 2014.

    Science.gov (United States)

    Yang, Qian; Zhang, Yong; Yan, Dongmei; Zhu, Shuangli; Wang, Dongyan; Ji, Tianjiao; Huang, Wei; An, Hongqiu; Xu, Wenbo

    2016-06-29

    Enterovirus A71 (EV-A71) is the main pathogen responsible for large outbreaks of hand, foot, and mouth disease (HFMD) in mainland China, and the dominant EV-A71 strains belong to subgenotype C4. To date, only one imported subgenotype B5 of EV-A71 has been reported in Xiamen City Fujian Province, 2009. Here, we report on another imported subgenotype B5 of EV-A71 isolated from a HFMD patient in Chongqing City in 2014 (strain CQ2014-86/CQ/CHN/2014, hereafter refer as CQ2014-86). The VP1 coding sequence and the whole genome sequence revealed that strain CQ2014-86 shares the high nucleotide identity with Vietnamese strains isolated in 2011-2013, suggesting that strain CQ2014-86 may have been imported from Vietnam. In the 5'UTR, P2 and P3 regions, recombination events were found between strain CQ2014-86 and other EV-A, such as coxsackievirus A4 (CV-A4), CV-A5, CV-A14 and CV-A16. This is the second report on importation of subgenotype B5 of EV-A71 in China, implying that we need to pay more attention to the importation of different subgenotypes of EV-A71.

  11. Recommendations for enterovirus diagnostics and characterisation within and beyond Europe

    NARCIS (Netherlands)

    Harvala, Heli; Broberg, Eeva; Benschop, Kimberley; Berginc, Natasa; Ladhani, Shamez; Susi, Petri; Christiansen, Claus; McKenna, James; Allen, David; Makiello, Phoebe; McAllister, Georgina; Carmen, Mirabelli; Zakikhany, Katherina; Dyrdak, Robert; Nielsen, Xiaohui; Madsen, Tina; Paul, Joel; Moore, Catherine; von Eije, Karin; Piralla, Antonio; Carlier, Mieke; Vanoverschelde, Laura; Poelman, Randy; Anton, Andrés; López-Labrador, F. Xavier; Pellegrinelli, Laura; Keeren, Kathrin; Maier, Melanie; Cassidy, Hayley; Derdas, Stavros; Savolainen-Kopra, Carita; Diedrich, Sabine; Nordbø, Svein; Buesa, Javier; Bailly, Jean-Luc; Baldanti, Fausto; MacAdam, Andrew; Mirand, Audrey; Dudman, Susanne; Schuffenecker, Isabelle; Kadambari, Seilesh; Neyts, Johan; Griffiths, Michael J.; Richter, Jan; Margaretto, Cristina; Govind, Sheila; Morley, Ursula; Adams, Ortwin; Krokstad, Sidsel; Dean, Jonathan; Pons-Salort, Margarita; Prochazka, Birgit; Cabrerizo, Maria; Majumdar, Manasi; Nebbia, Gaia; Wiewel, Maryse; Cottrell, Simon; Coyle, Peter; Martin, Javier; Moore, Catrin; Midgley, Sofie; Horby, Peter; Wolthers, Katja; Simmonds, Peter; Niesters, Hubert; Fischer, Thea K.

    2018-01-01

    Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European

  12. Impact of Enterovirus Testing on Resource Use in Febrile Young Infants: A Systematic Review.

    Science.gov (United States)

    Wallace, Sowdhamini S; Lopez, Michelle A; Caviness, A Chantal

    2017-02-01

    Enterovirus infection commonly causes fever in infants aged 0 to 90 days and, without testing, is difficult to differentiate from serious bacterial infection. To determine the cost savings of routine enterovirus testing and identify subgroups of infants with greater potential impact from testing among infants 0 to 90 days old with fever. Studies were identified systematically from published and unpublished literature by using Embase, Medline, the Cochrane database, and conference proceedings. Inclusion criteria were original studies, in any language, of enterovirus infection including the outcomes of interest in infants aged 0 to 90 days. Standardized instruments were used to appraise each study. The evidence quality was evaluated using Grading of Recommendations Assessment, Development, and Evaluation criteria. Two investigators independently searched the literature, screened and critically appraised the studies, extracted the data, and applied the Grading of Recommendations Assessment, Development, and Evaluation criteria. Of the 257 unique studies identified and screened, 32 were completely reviewed and 8 were included. Routine enterovirus testing was associated with reduced hospital length of stay and cost savings during peak enterovirus season. Cerebrospinal fluid pleocytosis was a poor predictor of enterovirus meningitis. The studies were all observational and the evidence was of low quality. Enterovirus polymerase chain reaction testing, independent of cerebrospinal fluid pleocytosis, can reduce length of stay and achieve cost savings, especially during times of high enterovirus prevalence. Additional study is needed to identify subgroups that may achieve greater cost savings from testing to additionally enhance the efficiency of testing. Copyright © 2017 by the American Academy of Pediatrics.

  13. Magnesium lithospermate B and rosmarinic acid, two compounds present in Salvia miltiorrhiza, have potent antiviral activity against enterovirus 71 infections.

    Science.gov (United States)

    Chung, Yi-Ching; Hsieh, Feng-Chia; Lin, Ying-Ju; Wu, Tzong-Yuan; Lin, Cheng-Wen; Lin, Ching-Ting; Tang, Nou-Ying; Jinn, Tzyy-Rong

    2015-05-15

    The aim of this study was to identify the active ingredients responsible for the anti-EV71 activity produced by Salvia miltiorrhiza extracts. A pGS-EV71 IRES-based bicistronic reporter assay platform was used for rapid analysis of compounds that could specifically inhibit EV71 viral IRES-mediated translation. The analysis identified 2 caffeic acid derivatives, magnesium lithospermate B (MLB) and rosmarinic acid (RA), which suppressed EV71 IRES-mediated translation at concentrations of 30μg/ml. We also found that MLB and RA inhibited EV71 infection when they were added to RD cells during the viral absorption stage. MLB had a low IC50 value of 0.09mM and a high TI value of 10.52. In contrast, RA had an IC50 value of 0.50mM with a TI value of 2.97. MLB and RA (100µg/ml) also reduced EV71 viral particle production and significantly decreased VP1 protein production. We propose that these two derivatives inhibit EV71 viral entry into cells and viral IRES activity, thereby reducing viral particle production and viral RNA expression and blocking viral VP1 protein translation. This study provides useful information for the development of anti-EV71 assays and reagents by demonstrating a convenient EV71 IRES-based bicistronic assay platform to screen for anti-EV71 IRES activity, and also reports 2 compounds, MLB and RA, which are responsible for the anti-EV71 activity of S. miltiorrhiza. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71.

    Science.gov (United States)

    McWilliam Leitch, E C; Cabrerizo, M; Cardosa, J; Harvala, H; Ivanova, O E; Koike, S; Kroes, A C M; Lukashev, A; Perera, D; Roivainen, M; Susi, P; Trallero, G; Evans, D J; Simmonds, P

    2012-03-01

    Enterovirus 71 (EV71) is responsible for frequent large-scale outbreaks of hand, foot, and mouth disease worldwide and represent a major etiological agent of severe, sometimes fatal neurological disease. EV71 variants have been classified into three genogroups (GgA, GgB, and GgC), and the latter two are further subdivided into subgenogroups B1 to B5 and C1 to C5. To investigate the dual roles of recombination and evolution in the epidemiology and transmission of EV71 worldwide, we performed a large-scale genetic analysis of isolates (n = 308) collected from 19 countries worldwide over a 40-year period. A series of recombination events occurred over this period, which have been identified through incongruities in sequence grouping between the VP1 and 3Dpol regions. Eleven 3Dpol clades were identified, each specific to EV71 and associated with specific subgenogroups but interspersed phylogenetically with clades of coxsackievirus A16 and other EV species A serotypes. The likelihood of recombination increased with VP1 sequence divergence; mean half-lives for EV71 recombinant forms (RFs) of 6 and 9 years for GgB and GgC overlapped with those observed for the EV-B serotypes, echovirus 9 (E9), E30, and E11, respectively (1.3 to 9.8 years). Furthermore, within genogroups, sporadic recombination events occurred, such as the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization.

  15. Impact and seasonality of human rhinovirus infection in hospitalized patients for two consecutive years.

    Science.gov (United States)

    Leotte, Jaqueline; Trombetta, Hygor; Faggion, Heloisa Z; Almeida, Bernardo M; Nogueira, Meri B; Vidal, Luine R; Raboni, Sonia M

    To report epidemiological features, clinical characteristics, and outcomes of human rhinovirus (HRV) infections in comparison with other community acquired respiratory virus (CRV) infections in patients hospitalized for two consecutive years. This was a cross-sectional study. Clinical, epidemiological, and laboratory data of patients hospitalized with acute respiratory syndrome in a tertiary care hospital from 2012 to 2013 were reviewed. HRV was the most common CRV observed (36%, 162/444) and was present in the majority of viral co-detections (69%, 88/128), mainly in association with human enterovirus (45%). Most HRV-infected patients were younger than 2 years (57%). Overall, patients infected with HRV had a lower frequency of severe acute respiratory infection than those infected with other CRVs (60% and 84%, respectively, p=0.006), but had more comorbidities (40% and 27%, respectively; p=0.043). However, in the adjusted analysis this association was not significant. The mortality rate within the HRV group was 3%. Detection of HRV was more prevalent during autumn and winter, with a moderately negative correlation between viral infection frequency and temperature (r=-0.636, p<0.001) but no correlation with rainfall (r=-0.036, p=0.866). HRV is usually detected in hospitalized children with respiratory infections and is often present in viral co-detections. Comorbidities are closely associated with HRV infections. These infections show seasonal variation, with predominance during colder seasons. Copyright © 2016. Published by Elsevier Editora Ltda.

  16. CLINICAL EPIDEMIOLOGICAL PECULIARITIES OF ENTEROVIRUS COXSACKIEVIRUS A16 GROUP MORBIDITY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L. A. Lityaeva

    2013-01-01

    Full Text Available Federal Service on Customers' Rights Protection and Human Well-Being Surveillance in Orenburg Region, Orenburg The authors presented the results of the clinical and epidemiological analysis of enterovirus coxsackievirus A-16 group morbidity among kindergarten children in the Orenburg region occurring in the form of the syndrome of ≪hand-foot-mouth≫ with exantem. 20 children were involved in the epidemic process, 72,2% of the children are 1—2 years old, they became a source of infection to other groups of children. The disease had a mild course and did not require special treatment.

  17. [Listeria monocytogenes in human infections].

    Science.gov (United States)

    Kołakowska, Agnieszka; Madajczak, Grzegorz

    2011-01-01

    The Listeria genus is distinguished into six species from which just one--Listeria monocytogenes is pathogenic for humans. The main route of acquisition of Listeria is through the ingestion of contaminated food products. An important element of the L. monocytogenes pathogenesis infection is affiliation with high-risk group of immunocompromised patients, infants or pregnant women, who infected by this microorganism can lead to miscarriage. Listeriosis can appear in the form of sepsis, infection of the nervous system or local abscesses. Another form of listeriosis is gastrointestinal tract infection--noticed in case of food poisoning outbreak.

  18. Targeting Persistent Human Papillomavirus Infection.

    Science.gov (United States)

    Shanmugasundaram, Srinidhi; You, Jianxin

    2017-08-18

    While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.

  19. Prevalence of human coronaviruses in adults with acute respiratory tract infections in Beijing, China.

    Science.gov (United States)

    Ren, Lili; Gonzalez, Richard; Xu, Jin; Xiao, Yan; Li, Yongjun; Zhou, Hongli; Li, Jianguo; Yang, Qingqing; Zhang, Jing; Chen, Lan; Wang, Wei; Vernet, Guy; Paranhos-Baccalà, Gláucia; Wang, Zhong; Wang, Jianwei

    2011-02-01

    Human coronaviruses (HCoVs) are a common etiological agent of acute respiratory tract infections. HCoV infections, especially those caused by the two HCoVs identified most recently, NL63 and HKU-1, have not been characterized fully. To evaluate the prevalence and clinical presentations of HKU1 and NL63 in adults with acute respiratory tract infections, an investigation of HCoV infections in Beijing, China from 2005 to 2009 was performed by using reverse transcriptase PCR assays and sequencing analysis. Among 8,396 respiratory specimens studied, 87 (1%) clinical samples were positive for HCoVs, of which 50 samples (0.6% of the total) were positive for HCoV-OC43, 15 (0.2%) for HCoV-229E, 14 (0.2%) for HCoV-HKU1, and 8 (0.1%) for HCoV-NL63. The prevalence of HCoV infection in adults exhibited distinct seasonal fluctuations during the study period. In addition, patients positive for HCoV-229E infections were more likely to be co-infected with other respiratory viruses. Enterovirus, rhinovirus, and parainfluenza virus type 3 were the most common viruses found in patients with HCoV infections. The demographic and clinical data present in this study of HCoV infections in adults with acute respiratory tract infections should improve our understanding of the pathogenesis of HCoVs. 2010 Wiley-Liss, Inc.

  20. Human infection with Dermatophilus congolensis.

    Science.gov (United States)

    Kaminski, G W; Suter, I I

    1976-03-27

    Dermatophilosis is a skin disease in animals and humans caused by the actinomycete Dermatophilus congolensis. This microorganism causes the skin disease in sheep commonly referred to in Australia as "lumpy wool" or mycotic dermatitis. One proven case of human dermatophilosis and two cases with features which are clinically highly suggestive of the disease from South Australia are described. There has been only one previous report of human infection caused by D. congolensis, which was from the United States in 1961. A brief account of the history, characteristics and life cycle of D. congolensis is given. Human infection in Australia may be not uncommon. A diagnosis can be made by direct microscopy of scab material from the lesions. For this purpose, dry scabs should be sent to the laboratory.

  1. Avian Influenza infection in Human

    Directory of Open Access Journals (Sweden)

    Mohan. M

    2008-08-01

    Full Text Available Outbreaks caused by the H5N1 strain are presently of the greatest concern for human health. In assessing risks to human health, it is important to know exactly which avian virus strains are causing the outbreaks in birds.All available evidence points to an increased risk of transmission to humans when outbreaks of highly pathogenic avian H5N1 influenza are widespread in poultry. There is mounting evidence that this strain has a unique capacity to jump the species barrier and cause severe disease, with high mortality, in humans. There is no evidence, to date that efficient human to human transmission of H5N1 strain has occurred and very often. Efficient transmission among humans is a key property of pandemic strains and a property that the avian H5N1 and H9N2 viruses apparently lacked. The biological and molecular basis for effective aerosol transmission among humans is not known. The virus can improve its transmissibility among humans via two principal mechanisms. The first is a “reassortment” event, in which genetic material is exchanged between human and avian viruses during co-infection of a human or pig.Reassortment could result in a fully transmissible pandemic virus, announced by a sudden surge of cases with explosive spread. The second mechanism is a more gradual process of adaptive mutation, whereby the capability of the virus to bind to human cells increases during subsequent infections of humans. Adaptive mutation, expressed initially as small clusters of human cases with some evidence of human-to-human transmission, would probably give the world some time to take defensive action, if detected sufficiently early. As the number of human infections grows, the risk increases that a new virus subtype could emerge, triggering an influenza pandemic. Humans as well as swine must now be considered a potential mixing vessel for the generation of such a virus. This link between widespread infection in poultry and increased risk of human

  2. Enterovirus 71 in Taiwan

    Directory of Open Access Journals (Sweden)

    Luan-Yin Chang

    2008-08-01

    Full Text Available The enterovirus 71 (EV71 outbreak in Taiwan in 1998 proved fatal in many children. A seroepidemiological study performed prior to the 1998 outbreak showed pre-epidemic (1997 EV71 seroprevalence rates to be about 60–70% in adults and children older than 6 years of age. A retrospective case review carried out from 1980–81 identified 16 cases of hand, foot and mouth disease associated with central nervous system involvement, two of whom died soon after hospitalization. There were 405 severe cases and 78 deaths reported in the 1998 epidemic, and dozens of fatal EV71 cases were still reported from 2000 to 2002. A stage-based management strategy was developed to reduce fatality, but most survivors of brainstem encephalitis with cardio pulmonary failure have neurologic sequelae and impaired cognition. Continuous clinical and laboratory surveillance of EV71 disease is required to enable earlier implementation of control and prevention measures. Development of EV71-specific antiviral therapy, a novel class of imidazolidinones, and development of a vaccine are ongoing.

  3. Epidemics and Frequent Recombination within Species in Outbreaks of Human Enterovirus B-Associated Hand, Foot and Mouth Disease in Shandong China in 2010 and 2011.

    Directory of Open Access Journals (Sweden)

    Ting Zhang

    Full Text Available The epidemiology and molecular characteristics of human enterovirus B (HEV-B associated with hand, foot and mouth disease (HFMD outbreaks in China are not well known. In the present study, we tested 201 HEV isolates from 233 clinical specimens from patients with severe HFMD during 2010-2011 in Linyi, Shandong, China. Of the 201 isolates, 189 were fully typed and 18 corresponded to HEV-B species (six serotypes CVA9, CVB1, CVB4, Echo 6, Echo 25 and Echo 30 using sensitive semi-nested polymerase chain reaction analysis of VP1 gene sequences. Phylogenetic analysis based on the VP1 region showed that eight E30SD belonged to a novel sub-genogroup D2; E25SD belonged to a novel sub-genogroup D6; E6SD belonged to sub-lineage C6 and five CVB1SD belonged to subgroup 4C; and B4SD belonged sub-lineage D2. The full viral genomes of the CVB1SD, E6SD, E25SD and E30SD isolates were sequenced. Analysis of phylogenetic and similarity plots indicated that E25SD recombined with E25-HN-2, E30FDJS03 and E4AUS250 at noncontiguous P2A-P3D regions, while E30SD, E30FDJ03, E25-HN-2 and E9 DM had shared sequences in discrete regions of P2 and P3. Both E6SD and B1SD shared sequences with E1-HN, B4/GX/10, B5-HN, and A9-Alberta in contiguous regions of most of P2 and P3. Genetic algorithm recombination detection analysis further confirmed the existence of multiple potential recombination points. In conclusion, analysis of the complete genomes of E25SD, E30SD, CVB1SD and E6SD isolated from HFMD patients revealed that they formed novel subgenogroup. Given the prevalence and recombination of these viruses in outbreaks of HFMD, persistent surveillance of HFMD-associated HEV-B pathogens is required to predict potential emerging viruses and related disease outbreaks.

  4. Human genetic susceptibility to Candida infections

    NARCIS (Netherlands)

    Plantinga, T.S.; Johnson, M.D.; Scott, W.K.; Joosten, L.A.B.; Meer, J.W. van der; Perfect, J.R.; Kullberg, B.J.; Netea, M.G.

    2012-01-01

    Infections with Candida spp. have different manifestations in humans, ranging from mucosal to bloodstream and deep-seated disseminated infections. Immunocompromised patients have increased susceptibility to these types of infections, due to reduced capacity to elicit effective innate or adaptive

  5. Structure determination of enterovirus 71

    Energy Technology Data Exchange (ETDEWEB)

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G. (Purdue); (Sentinext)

    2013-02-20

    Enterovirus 71 is a picornavirus that causes hand, foot and mouth disease but may induce fatal neurological illness in infants and young children. Enterovirus 71 crystallized in a body-centered orthorhombic space group with two particles in general orientations in the crystallographic asymmetric unit. Determination of the particle orientations required that the locked rotation function excluded the twofold symmetry axes from the set of icosahedral symmetry operators. This avoided the occurrence of misleading high rotation-function values produced by the alignment of icosahedral and crystallographic twofold axes. Once the orientations and positions of the particles had been established, the structure was solved by molecular replacement and phase extension.

  6. Development of Novel Vaccines against Enterovirus-71

    Directory of Open Access Journals (Sweden)

    Pinn Tsin Isabel Yee

    2015-12-01

    Full Text Available The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71 and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1 vaccine and virus-like particles (VLPs. The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design.

  7. Avian Influenza A Virus Infections in Humans

    Science.gov (United States)

    ... Pandemic Other Avian Influenza A Virus Infections in Humans Language: English (US) Español Recommend on Facebook Tweet ... A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses usually do not ...

  8. High frequency of enterovirus serotype circulation in a densely populated area of India.

    Science.gov (United States)

    Kumar, Arvind; Shukla, Deepti; Srivastava, Shalini; Idris, Mohammad Z; Dhole, Tapan N

    2013-06-15

    In the state of Uttar Pradesh in India, enteroviruses are a significant cause of infection presenting in endemic or epidemic forms. The present study aimed to use molecular methods to identify enterovirus serotypes in clinical specimens to determine their circulation in the community. A total of 320 clinical specimens were collected between January 2009 and December 2010 from children younger than 15 year of age in northern India. Reverse- transcription (RT) real time PCR and semi-nested RT PCR targeting the 5'untranslated region and VP1 region was used for the detection and identification of enterovirus serotypes. The enterovirus genome was detected in 79 (24.7%) of 320 clinical specimens by real time PCR. Central nervous system syndrome (CNS) was the most common clinical manifestation (n=32, 62.74%), followed by respiratory tract infection (n=8, 15.69%), acute febrile illness (n=7, 13.73%), and gastrointestinal disease (n=4, 7.84%). A total of 32 different serotypes were identified with the predominance of coxsackievirus B5 and echovirus 6. Phylogenetic analysis of partial VP1 gene sequences from this study showed that many enterovirus serotypes showed good similarity with strains from America and Europe in comparison to neighbouring Asian countries. To our knowledge this is the first study of enterovirus prevalence from northern India based on unbiased molecular methods which leads to the identification of fifteen different enterovirus serotypes. The high frequency of enterovirus B species serotypes circulation may be an important cause of CNS infection in the children of this region.

  9. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Robert Y.L., E-mail: yuwang@mail.cgu.edu.tw [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Kuo, Rei-Lin [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Ma, Wei-Chieh [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Hsing-I [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yu, Jau-Song [Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yen, Sih-Min [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Chi-Ruei [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Shih, Shin-Ru [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China)

    2013-09-01

    Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone. - Highlights: • Hsp90β is associated with EV71 virion and is secreted with the release virus. • Hsp90β effects on the correct assembly of viral particles. • Viral titer of cultured medium was reduced in the presence of geldanamycin. • Viral titer was also reduced when Hsp90β was suppressed by siRNA treatment. • The extracellular Hsp90β was also observed in other RNA viruses-infected cells.

  10. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    Directory of Open Access Journals (Sweden)

    Win Kyaw Phyu

    Full Text Available Enterovirus A71 (EV-A71 causes self-limiting, hand-foot-and-mouth disease (HFMD that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia, acinar cells (salivary gland, lacrimal gland, lymphoid cells (lymph node, spleen, and muscle fibres (skeletal, cardiac and smooth muscles, liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  11. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    Science.gov (United States)

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  12. Molecular epidemiology of human rhinovirus infections in the pediatric emergency department.

    Science.gov (United States)

    Martin, Emily K; Kuypers, Jane; Chu, Helen Y; Lacombe, Kirsten; Qin, Xuan; Strelitz, Bonnie; Bradford, Miranda; Jones, Charla; Klein, Eileen J; Englund, Janet A

    2015-01-01

    Human rhinovirus (HRV) infections are highly prevalent, genetically diverse, and associated with both mild upper respiratory tract and more severe lower tract illnesses (LRTI). To characterize the molecular epidemiology of HRV infections in young children seeking acute medical care. Nasal swabs collected from symptomatic children FilmArray(®)) for multiple viruses including HRV/enterovirus. HRV-positive results were confirmed by laboratory-developed real-time reverse transcription PCR (LD-PCR). Clinical data were collected by chart review. A subset of samples was selected for sequencing using the 5' noncoding region. Associations between LRTI and HRV species and genotypes were estimated using logistic regression analysis. Of 595 samples with HRV/enterovirus detected by FilmArray, 474 (80%) were confirmed as HRV by LD-PCR. 211 (96%) of 218 selected samples were sequenced; HRV species A, B, and C were identified in 133 (63%), 6 (3%), and 72 (34%), respectively. LRTI was more common in HRV-C than HRV-A illness episodes (adjusted OR [95% CI] 2.35[1.03-5.35). Specific HRV-A and HRV-C genotypes detected in multiple patients were associated with a greater proportion of LRTI episodes. In 18 patients with >1 HRV-positive illness episodes, a distinct genotype was detected in each. Diverse HRV genotypes circulated among symptomatic children during the study period. We found an association between HRV-C infections and LRTI in this patient population and evidence of association between specific HRV genotypes and LRTI. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome

    Directory of Open Access Journals (Sweden)

    Hongbin Wang

    2015-07-01

    Full Text Available Enterovirus 71 (EV71 is the major etiological agent of hand, foot, and mouth disease (HFMD. Early studies showed that EV71-infected patients with severe complications exhibited elevated plasma levels of IL-1β, indicating that EV71 may activate inflammasomes. Our current study demonstrates that the NLRP3 inflammasome plays a protective role against EV71 infection of mice in vivo. EV71 replication in myeloid cells results in the activation of the NLRP3 inflammasome and secretion of IL-1β. Conversely, EV71 counteracts inflammasome activation through cleavage of NLRP3 by viral proteases 2A and 3C, which cleave NLRP3 protein at the G493-L494 or Q225-G226 junction, respectively. Moreover, EV71 3C interacts with NLRP3 and inhibits IL-1β secretion when expressed in mammalian cells. These results thus reveal a set of reciprocal regulations between enterovirus 71 and the NLRP3 inflammasome.

  14. Seroprevalence of Enterovirus A71 and Coxsackievirus A16 in Healthy People in Shandong Province, China.

    Directory of Open Access Journals (Sweden)

    Jian-Xing Wang

    Full Text Available Hand, foot, and mouth disease has become very common in mainland of China in recent years, and enterovirus A71 and coxsackievirus A16 are its major etiologic factors. Here we investigated the seroprevalence of enterovirus A71 and coxsackievirus A16 based on a large group of healthy individuals in Shandong province, China.A total of 1378 healthy individuals were tested for serum neutralizing antibodies against enterovirus A71 and coxsackievirus A16 using a micro neutralization test.The overall seroprevalence of enterovirus A71 neutralizing antibodies was 74.75%. It increased significantly from 48.84% in children aged 0-1 years old to 88.64% in those aged 20-29 years (p 40 years old with a significant gender-specific difference (p 40 years without a gender-specific difference. Nearly 50% of the children <1 year were susceptible to enterovirus A71 infection versus 40% to coxsackievirus A16 infection. Sample collection time and place also played a role in the enterovirus A71 and coxsackievirus A16 positive rates. The overall rates in January were significantly lower than those in April and August (p < 0.01; enterovirus A71 positive rates in Jinan city (capital city of Shandong province were lower than those in Jining city and Zibo city (p < 0.05; and oxsackievirus A16 positive rates in Jining city were significantly higher than those in Jinan city and Zibo city (p < 0.01.There were significant differences among age groups, locations, and time points in the seroprevalence rates of enterovirus A71 and coxsackievirus A16 neutralizing antibodies in healthy people in Shandong province.

  15. 21 CFR 866.3225 - Enterovirus nucleic acid assay.

    Science.gov (United States)

    2010-04-01

    ... meningitis or meningoencephalitis. The detection of enterovirus RNA, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of viral meningitis caused by enterovirus. (b...

  16. Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.

    Science.gov (United States)

    Smee, Donald F; Evans, W Joseph; Nicolaou, K C; Tarbet, E Bart; Day, Craig W

    2016-07-01

    Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents (enviroxime, guanidine HCl, pirodavir, pleconaril, and rupintrivir), nucleobase/nucleoside analogs (3-deazaguanine and ribavirin), and three novel epidithiodiketopiperazines (KCN-2,2'-epi-19, KCN-19, and KCN-21). Of these, rupintrivir was the most potent, with 50% inhibition of viral cytopathic effect (EC50) and 90% inhibition (EC90) of virus yield at 0.0022-0.0053 μM against EV-D68. Enviroxime, pleconaril and the KCN compounds showed efficacy at 0.01-0.3 μM; 3-deazaguanine and pirodavir inhibited EV-D68 at 7-13 μM, and guanidine HCl and ribavirin were inhibitory at 80-135 μM. Pirodavir was active against EV-71 (EC50 of 0.78 μM) but not against RV-87 or EV-D68, and all other compounds were less effective against EV-71 than against RV-87 and EV-D68. The most promising compound inhibiting both virus infections at low concentrations was rupintrivir. Antiviral activity was confirmed for the ten compounds in virus yield reduction (VYR) assays in RD cells, and for enviroxime, guanidine HCl, and pirodavir by cytopathic effect (CPE) assays in A549, HeLa-Ohio-1, and RD cells. These studies may serve as a basis for further pre-clinical discovery of anti-enterovirus inhibitors. Furthermore, the antiviral profiles and growth characteristics observed herein support the assertion that EV-D68 should be classified together with RV-87. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Seroepidemiology and molecular epidemiology of enterovirus 71 in Russia.

    Science.gov (United States)

    Akhmadishina, Ludmila V; Eremeeva, Tatiana P; Trotsenko, Olga E; Ivanova, Olga E; Mikhailov, Mikhail I; Lukashev, Alexander N

    2014-01-01

    Enterovirus 71 (EV71) is an emerging human pathogen causing massive epidemics of hand, foot and mouth disease with severe neurological complications in Asia. EV71 also circulates in Europe, however it does not cause large outbreaks. The reason for distinct epidemiological patterns of EV71 infection in Europe and Asia and the risk of EV71 epidemic in Europe and Russia remain unknown. Seroepidemiology of EV71 and molecular epidemiology of occasional EV71 isolates were studied to explore circulation of EV71 in Russia. In six regions of Russian Federation, seroprevalence of EV71 in sera collected in 2008 ranged from 5% to 20% in children aged 1-2 years and from 19% to 83% in children aged 3-5 years. The seroprevalence among elder children was significantly higher (41-83% vs. 19-27%) in Asian regions of Russia. EV71 strains identified in Russia in 2001-2011 belonged to subtypes C1 and C2, while genotype C4 that was causing epidemics in Asia since 1998 emerged in 2009 and became dominant in 2013.

  18. Properties of Two Enterovirus Antibodies that are Utilized in Diabetes Research.

    Science.gov (United States)

    Maccari, Giuseppe; Genoni, Angelo; Sansonno, Silvia; Toniolo, Antonio

    2016-04-19

    Human enteroviruses (EVs) comprise >100 different types. Research suggests a non-chance association between EV infections and type 1 diabetes. Immunohistochemical studies with the anti-EV antibody 5D-8.1 have shown that the EV capsid antigen is present in pancreatic islet cells of diabetic subjects. When it was noticed that 5D-8.1 may cross-react with human proteins, doubt was casted on the significance of the above histopathologic findings. To address this issue, properties of EV antibodies 5D-8.1 and 9D5 have been investigated using peptide microarrays, peptide substitution scanning, immunofluorescence of EV-infected cells, EV neutralization assays, bioinformatics analysis. Evidence indicates that the two antibodies bind to distinct non-neutralizing linear epitopes in VP1 and are specific for a vast spectrum of EV types (not for other human viruses). However, their epitopes may align with a few human proteins at low expected values. When tested by immunofluorescence, high concentrations of 5D-8.1 yelded faint cytoplasmic staining in uninfected cells. At reduced concentrations, both antibodies produced dotted staining only in the cytoplasm of infected cells and recognized both acute and persistent EV infection. Thus, the two monoclonals represent distinct and independent probes for hunting EVs in tissues of patients with diabetes or other endocrine conditions.

  19. Infecciones del sistema nervioso central por enterovirus en niños atendidos en un hospital de Lima, Perú Enteroviral central nervous system infections in children treated at a hospital in Lima, Peru

    OpenAIRE

    Iván O Espinoza; Theresa J Ochoa; Susan Mosquito; Francesca Barletta; Roger Hernández; María del Pilar Medina; María Luisa Stiglich; Claudia Ugarte; Daniel Guillén

    2011-01-01

    Objetivos. Determinar la frecuencia y las características clínicas de las infecciones del sistema nervioso central por enterovirus en niños atendidos en el Hospital Nacional Cayetano Heredia de Lima, Perú. Materiales y métodos. Se realizó un estudio prospectivo y descriptivo desde abril 2008 hasta marzo 2010. Se enrolaron pacientes de un mes a 14 años con diagnóstico clínico de encefalitis o meningitis asépticas. Se investigó la presencia de enterovirus, virus herpes simple 1 (VHS-1), virus h...

  20. Human papillomavirus type 13 infecting the conjunctiva.

    Science.gov (United States)

    Benevides dos Santos, Paulo José; Borborema dos Santos, Cristina Maria; Rufino Mendonça, Rosângela; Vieira do Carmo, Maria Auxiliadora; Astofi-Filho, Spartaco

    2005-09-01

    Focal epithelial hyperplasia (FEH) is a rare infection caused by human papillomavirus (HPV) types 13 or 32 believed to infect exclusively oral mucosa. This report illustrates a case of multiple conjunctival papillomas similar to oral FEH caused by HPV-13, consisting in the first description of its infection outside the oral mucosa in a healthy patient.

  1. Outbreak of Enterovirus - 71 Meningitis in Calicut

    Directory of Open Access Journals (Sweden)

    CK Sasidharan

    2016-04-01

    Full Text Available Objective: Enterovirus 71(EV 71 causes wide spectrum of infections ranging from asymptomatic conditions to clinical syndromes like diarrhea, rash, hand-foot-and mouth disease (HFMD, herpangina, aseptic meningitis, encephalitis, myocarditis, acute flaccid paralysis, bulbar and brainstem encephalitis Guillain Barre syndrome, pulmonary haemorrhage. This study deals with an outbreak of aseptic meningitis in children caused by EV 71 virus. Methods: The authors report an outbreak of aseptic meningitis in children in and around Calicut in June 2008. Clinical and laboratory study was done in collaboration with National Centre for Disease Control, New Delhi. 149 children with aseptic meningitis were studied and followed up from June 2008 to May 2009. Result: All children had clinical features suggestive of aseptic meningitis and serology showed the rising antibody titre against EV 71 virus infection. CSF analysis also showed four fold rise in antibodies in one and ≥ 1:2 neutralising antibodies titer against EV- 71 in four samples indicating meningitis due to EV-71. Conclusion: EV 71 was identified as the causative agent of the outbreak of aseptic meningitis in the study and the fact that the EV 71 infection has evolved from minor illness like HFMD to major illness like aseptic meningitis from the same locality is truly alarming.

  2. Human Infections and Detection of Plasmodium knowlesi

    Science.gov (United States)

    Daneshvar, Cyrus

    2013-01-01

    SUMMARY Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection. PMID:23554413

  3. Ocorrência de infecção por enterovírus em recém-nascidos internados em maternidade no município de São Paulo, Brasil (1980 Occurrence of enterovirus infection in new-born children admitted to maternity ward in São Paulo municipality, Brazil (1980

    Directory of Open Access Journals (Sweden)

    Eliseu Alves Waldman

    1984-02-01

    Full Text Available Pesquisou-se infecção intestinal por enterovirus em 300 crianças, aparentemente normais, nascidas de parto hospitalar, com a mediana das idades de 2 dias, estudadas antes da alta hospitalar. Essas crianças foram divididas em três grupos de igual número, sendo que o primeiro grupo foi examinado no período que precedeu o 1.º Dia Nacional de Vacinação Contra a Poliomielite, efetuado em 1980, o segundo logo após a realização dessa imunização em massa e o terceiro posteriormente ao 2º Dia Nacional de Vacinação Contra a Poliomielite levado a efeito no mesmo ano. A pesquisa de enterovirus foi feita a partir de uma única amostra de fezes, colhida de cada criança por meio de Swab retal. Obteve-se o isolamento de poliovírus em 13 (4,3% dos 300 recém-nascidos estudados, sendo que 8 deles pertenciam ao primeiro grupo e os outros 5 ao segundo. Das crianças infectadas, 12 eliminavam poliovírus lei poliovírus 3. Não foram isolados outros enterovirus. Discute-se a possibilidade da infecção por esses poliovírus ter ocorrido por transmissão transplacentária, via canal de parto ou ainda por infecção cruzada no próprio ambiente hospitalar.The occurrence of intestinal infection with enterovirus was investigated in 300 healthy children of median age of two days old, born in hospital; the children were analysed before being discharged from hospital. For the investigation, these children were divided into three groups, and each group was composed by equal number of cases. The first group was examined during the period preceding The First National Day for Poliomyelitis Vaccination held in 1980; the second group was analysed soon after this mass immunization and the third after The Second National Day for Poliomyelitis Vaccination, which was achieved in the same year. On purpose of enterovirus investigation, it was analysed the single faeces sample obtained from every child by means of rectal swab. In 300 newborn children analysed, it

  4. Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

    Directory of Open Access Journals (Sweden)

    Zhu Liye

    2011-06-01

    Full Text Available Abstract Enterovirus 71 (EV71 has emerged as a significant pathogen causing large outbreaks in China for the past 3 years. Developing an EV71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to EV71 infection remains unclear. We examined the neutralizing antibody titers in HFMD patients and compared them to those of asymptomatic healthy children and young adults. We found that 80% of HFMD patients became positive for neutralizing antibodies against EV71 (GMT = 24.3 one day after the onset of illness. The antibody titers in the patients peaked two days (GMT = 79.5 after the illness appeared and were comparable to the level of adults (GMT = 45.2. Noticeably, the antibody response was not correlated with disease severity, suggesting that cellular immune response, besides neutralizing antibodies, could play critical role in controlling the outcome of EV71 infection in humans.

  5. The Spectrum of Fungi That Infects Humans

    Science.gov (United States)

    Köhler, Julia R.; Casadevall, Arturo; Perfect, John

    2015-01-01

    Few among the millions of fungal species fulfill four basic conditions necessary to infect humans: high temperature tolerance, ability to invade the human host, lysis and absorption of human tissue, and resistance to the human immune system. In previously healthy individuals, invasive fungal disease is rare because animals’ sophisticated immune systems evolved in constant response to fungal challenges. In contrast, fungal diseases occur frequently in immunocompromised patients. Paradoxically, successes of modern medicine have put increasing numbers of patients at risk for invasive fungal infections. Uncontrolled HIV infection additionally makes millions vulnerable to lethal fungal diseases. A concerted scientific and social effort is needed to meet these challenges. PMID:25367975

  6. Toxoplasma gondii infection in humans in China

    Directory of Open Access Journals (Sweden)

    He Shenyi

    2011-08-01

    Full Text Available Abstract Toxoplasmosis is a zoonotic infection of humans and animals, caused by the opportunistic protozoan Toxoplasma gondii, a parasite belonging to the phylum Apicomplexa. Infection in pregnant women may lead to abortion, stillbirth or other serious consequences in newborns. Infection in immunocompromised patients can be fatal if not treated. On average, one third of people are chronically infected worldwide. Although very limited information from China has been published in the English journals, T. gondii infection is actually a significant human health problem in China. In the present article, we reviewed the clinical features, transmission, prevalence of T. gondii infection in humans in China, and summarized genetic characterizations of reported T. gondii isolates. Educating the public about the risks associated with unhealthy food and life style habits, tracking serological examinations to special populations, and measures to strengthen food and occupational safety are discussed.

  7. Infection and Coinfection of Human Rhinovirus C in Stem Cell Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Filippo Canducci

    2013-01-01

    Full Text Available In 54 adult stem cell transplant recipients, the presence and persistence of human rhinoviruses (including the novel lineage C were evaluated by molecular detection and phylogenetic analysis, independently from respiratory symptoms. In the same group of patients, the presence of other coinfecting respiratory pathogens, including the novel enterovirus 109, was also evaluated.

  8. Oral Manifestations of Human Immunodeficiency Virus Infection

    OpenAIRE

    Epstein, Joel B.; Mathias, Richard G.

    1988-01-01

    The AIDS epidemic continues. All health-care workers, including physicians and dental personnel, may be instrumental in recognizing risk factors associated with Acquired Immunodeficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) infection. Oral signs and symptoms of HIV infection may be the first presentation of the disease or may develop during the course of the disease and require management. Knowledge of the signs, symptoms and associated infections and tumours is needed to as...

  9. Chlamydophila psittaci infection of birds and humans

    OpenAIRE

    Bülent Baş; Gökçen Dinç

    2015-01-01

    Psittacosis is a systemic infection with high morbidity caused by Chlamydophila psittaci in domestic and wild birds. It shows zoonotic characteristic. C. psittaci leads an infection in over of 470 bird species worldwide has been known. This is a fact that people have a close relationship both with wild and pet birds and this has paved the way for infection in humans of. C. psittaci Gram negative, obligate and intracellular bacterium with biphasic growth cycle. It is transmitted by respiratory...

  10. Human Immunodeficiency Virus Infection among Psychiatric ...

    African Journals Online (AJOL)

    Background: Psychiatric patients are considered high risked group for Human immunodeficiency virus (HIV) infection. This has been found to be as a result of poor judgment and irrationality associated with some of the disorders. However, there is dearth of literature on the prevalence of HIV infection among psychiatric ...

  11. Inhibition of enterovirus 71 entry by transcription factor XBP1

    Energy Technology Data Exchange (ETDEWEB)

    Jheng, Jia-Rong; Lin, Chiou-Yan [Department of Biochemistry and Research Center for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa First Road, Kweishan, Taoyuan 333, Taiwan (China); Horng, Jim-Tong, E-mail: jimtong@mail.cgu.edu.tw [Department of Biochemistry and Research Center for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa First Road, Kweishan, Taoyuan 333, Taiwan (China); Lau, Kean Seng [Department of Biochemistry and Research Center for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa First Road, Kweishan, Taoyuan 333, Taiwan (China)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer IRE1 was activated but no XBP1 splicing was detected during enterovirus 71 infection. Black-Right-Pointing-Pointer XBP1 was subject to translational shutoff by enterovirus 71-induced eIF4G cleavage. Black-Right-Pointing-Pointer The uptake of UV-irradiated virus was decreased in XBP1-overexpressing cells. -- Abstract: Inositol-requiring enzyme 1 (IRE1) plays an important role in the endoplasmic reticulum (ER), or unfolded protein, stress response by activating its downstream transcription factor X-box-binding protein 1 (XBP1). We demonstrated previously that enterovirus 71 (EV71) upregulated XBP1 mRNA levels but did not activate spliced XBP1 (XBP1s) mRNA or its downstream target genes, EDEM and chaperones. In this study, we investigated further this regulatory mechanism and found that IRE1 was phosphorylated and activated after EV71 infection, whereas its downstream XBP1s protein level decreased. We also found that XBP1s was not cleaved directly by 2A{sup pro}, but that cleavage of eukaryotic translation initiation factor 4G by the EV71 2A{sup pro} protein may contribute to the decrease in XBP1s expression. Knockdown of XBP1 increased viral protein expression, and the synthesis of EV71 viral protein and the production of EV71 viral particles were inhibited in XBP1-overexpressing RD cells. When incubated with replication-deficient and UV-irradiated EV71, XBP1-overexpressing RD cells exhibited reduced viral RNA levels, suggesting that the inhibition of XBP1s by viral infection may underlie viral entry, which is required for viral replication. Our findings are the first indication of the ability of XBP1 to inhibit viral entry, possibly via its transcriptional activity in regulating molecules in the endocytic machinery.

  12. Enterovirus and Norovirus Monitoring under UCMR3

    Science.gov (United States)

    This presentation describes the Unregulated Contaminant Monitoring Rule round 3 (UCMR3) monitoring program for enterovirus and norovirus in groundwater. It provides the data on microbial indicators and virus occurrence during the monitoring period. Enteric virus occurrence was ab...

  13. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    Poelman, Randy; Schuffenecker, Isabelle; Van Leer-Buter, Coretta; Josset, Laurence; Niesters, Hubert G. M.; Lina, Bruno

    2015-01-01

    Background: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory

  14. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    R. Poelman (Randy); I. Schuffenecker (Isabelle); C. Van Leer-Buter (Coretta); L. Josset (Laurence); H.G.M. Niesters (Bert); B. Lina (Bruno)

    2015-01-01

    textabstractBackground: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen

  15. Evaluation of the enterovirus laboratory surveillance system in Denmark, 2010 to 2013

    DEFF Research Database (Denmark)

    Condell, Orla; Midgley, Sofie; Christiansen, C B

    2016-01-01

    The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus-transmission...

  16. Increased Intracranial Pressure in the Setting of Enterovirus and Other Viral Meningitides

    Directory of Open Access Journals (Sweden)

    Jules C. Beal

    2017-01-01

    Full Text Available Increased intracranial pressure due to viral meningitis has not been widely discussed in the literature, although associations with Varicella and rarely Enterovirus have been described. Patients with increased intracranial pressure and cerebrospinal fluid analysis suggestive of a viral process are sometimes classified as having atypical idiopathic intracranial hypertension (IIH. However, a diagnosis of IIH requires normal cerebrospinal fluid, and therefore in these cases an infection with secondary intracranial hypertension may be a more likely diagnosis. Here seven patients are presented with elevated intracranial pressure and cerebrospinal fluid suggestive of viral or aseptic meningitis. Of these, 1 had Enterovirus and the remainder were diagnosed with nonspecific viral meningitis. These data suggest that viral meningitis may be associated with elevated intracranial pressure more often than is commonly recognized. Enterovirus has previously been associated with increased intracranial pressure only in rare case reports.

  17. High degree of genetic diversity of non-polio enteroviruses identified in Georgia by environmental and clinical surveillance, 2002-2005.

    Science.gov (United States)

    Khetsuriani, N; Kutateladze, T; Zangaladze, E; Shutkova, T; Peñaranda, S; Nix, W A; Pallansch, M A; Oberste, M S

    2010-11-01

    Enterovirus surveillance data are useful for establishing temporal and geographical patterns of circulation and for virus characterization to determine phylogenetic relationships between strains. Almost no information is available on circulating enteroviruses in Georgia and the surrounding region. To describe enterovirus circulation in Georgia, determine relationships with previously characterized strains and assess the role of environmental and clinical enterovirus surveillance, this study analysed a total of 112 non-polio enterovirus isolates identified during 2002-2005 from sewage and human stool samples. Viruses were isolated in cell culture using standard methods and typed by partial sequencing of the VP1 gene. A total of 20 different non-polio enterovirus serotypes were identified over the 4-year period. The most commonly detected enteroviruses included echovirus (E) 6 (21 isolates; 18.8 %), E20, E3 and E7 (11 isolates each; 9.8 %), E11, coxsackievirus (CV) B4 and CVB5 (seven isolates each; 6.3 %), and E13, E19 and E30 (six isolates each; 5.4 %). Phylogenetic analysis showed that many serotypes were represented by more than one genetic lineage. The present study showed a very high degree of enterovirus diversity in Georgia and demonstrated the added value of environmental enterovirus surveillance, particularly in settings with limited clinical surveillance. Several serotypes would not have been detected without having both clinical and environmental surveillance in place. Several serotypes detected in Georgia were among those rarely reported in the USA and Europe (e.g. E3, E20 and E19). As the emergence of new genetic lineages of enterovirus in a particular area is often associated with large-scale outbreaks, continued monitoring of enterovirus strains by both environmental and clinical surveillance and genetic characterization should be encouraged.

  18. Replication and Inhibitors of Enteroviruses and Parechoviruses

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden

    2015-08-01

    Full Text Available The Enterovirus (EV and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV. They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.

  19. An outbreak of enterovirus 71 in a nursery.

    Science.gov (United States)

    Huang, Fang-Liang; Chen, Chao-Huei; Huang, Shui-King; Chen, Po-Yen

    2010-08-01

    In this article we report a nosocomial outbreak of enterovirus 71 (EV71) in a newborn nursery and describe the clinical presentations of infected infants. Community outbreaks of EV71 are quite common in epidemic areas, but a nosocomial outbreak of EV71 is a rare occurrence. A total of 7 out of 19 infants (37%) had symptoms. All infants had poor activity, 6 (86%) had fever, 4 (57%) had drowsiness, 3 (43%) had diarrhoea, and 2 (29%) had oral ulcers. Four infants (57%) suffered from encephalitis. There were no deaths. EV71 was isolated from 3 (43%) of the young infants, while all were positive when tested for EV71 using a reverse transcription polymerase chain reaction. A sequence analysis of the EV71 partial gene revealed a 98.6-100% nucleotide similarity. Control measures included staff hand washing, disinfecting all materials exposed to potentially infected biological fluid, increasing staff hygiene precautions in the kitchen, and using a different basin for bathing each baby. We conclude that it is difficult to diagnose EV71 infection in young infants by clinical presentation alone and, similar to other enteroviruses, EV71 can spread efficiently amongst young infants in a nursery unit.

  20. Saffold virus infection associated with human myocarditis

    DEFF Research Database (Denmark)

    Nielsen, Trine Skov; Nielsen, Alex Yde; Banner, Jytte

    2016-01-01

    BACKGROUND: Saffold virus was described in 2007 as one of the first human viruses within the genus cardioviruses. Cardioviruses may cause severe infections of the myocardium in animals, and several studies have associated saffold virus with human disease. As a result, saffold virus has been...... in the myocardium, lung tissue and blood of one child and was accompanied by histopathological inflammation in the heart and lungs, which was supportive of a viral infection. These findings suggest that cardioviruses may be associated with myocarditis in humans....

  1. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

    Directory of Open Access Journals (Sweden)

    Alexandr Krasota

    2016-01-01

    Full Text Available Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1% patients compared with 75 (47.2%, 53 (33.3% and 31 (19.5% achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14, E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71 in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

  2. Clinical and molecular epidemiology of human rhinovirus infections in patients with hematologic malignancy.

    Science.gov (United States)

    Jacobs, Samantha E; Lamson, Daryl M; Soave, Rosemary; Guzman, Brigitte Huertas; Shore, Tsiporah B; Ritchie, Ellen K; Zappetti, Dana; Satlin, Michael J; Leonard, John P; van Besien, Koen; Schuetz, Audrey N; Jenkins, Stephen G; George, Kirsten St; Walsh, Thomas J

    2015-10-01

    Human rhinoviruses (HRVs) are common causes of upper respiratory tract infection (URTI) in hematologic malignancy (HM) patients. Predictors of lower respiratory tract infection (LRTI) including the impact of HRV species and types are poorly understood. This study aims to describe the clinical and molecular epidemiology of HRV infections among HM patients. From April 2012-March 2013, HRV-positive respiratory specimens from symptomatic HM patients were molecularly characterized by analysis of partial viral protein 1 (VP1) or VP4 gene sequence. HRV LRTI risk-factors and outcomes were analyzed using multivariable logistic regression. One hundred and ten HM patients presented with HRV URTI (n=78) and HRV LRTI (n=32). Hypoalbuminemia (OR 3.0; 95% CI, 1.0-9.2; p=0.05) was independently associated with LRTI, but other clinical and laboratory markers of host immunity did not differ between patients with URTI versus LRTI. Detection of bacterial co-pathogens was common in LRTI cases (25%). Among 92 typeable respiratory specimens, there were 58 (64%) HRV-As, 12 (13%) HRV-Bs, and 21 (23%) HRV-Cs, and one Enterovirus 68. LRTI rates among HRV-A (29%), HRV-B (17%), and HRV-C (29%) were similar. HRV-A infections occurred year-round while HRV-B and HRV-C infections clustered in the late fall and winter. HRVs are associated with LRTI in HM patients. Illness severity is not attributable to specific HRV species or types. The frequent detection of bacterial co-pathogens in HRV LRTIs further substantiates the hypothesis that HRVs predispose to bacterial superinfection of the lower airways, similar to that of other community-acquired respiratory viruses. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Whole Genome Sequencing of Enterovirus species C Isolates by High-throughput Sequencing: Development of Generic Primers

    Directory of Open Access Journals (Sweden)

    Maël Bessaud

    2016-08-01

    Full Text Available Enteroviruses are among the most common viruses infecting humans and can cause diverse clinical syndromes ranging from minor febrile illness to severe and potentially fatal diseases. Enterovirus species C (EV-C consists of more than 20 types, among which the 3 serotypes of polioviruses, the etiological agents of poliomyelitis, are included. Biodiversity and evolution of EV-C genomes are shaped by frequent recombination events. Therefore, identification and characterization of circulating EV-C strains require the sequencing of different genomic regions.A simple method was developed to sequence quickly the entire genome of EV-C isolates. Four overlapping fragments were produced separately by RT-PCR performed with generic primers. The four amplicons were then pooled and purified prior to be sequenced by high-throughput technique.The method was assessed on a panel of EV-Cs belonging to a wide-range of types. It can be used to determine full-length genome sequences through de novo assembly of thousands of reads. It was also able to discriminate reads from closely related viruses in mixtures.By decreasing the workload compared to classical Sanger-based techniques, this method will serve as a precious tool for sequencing large panels of EV-Cs isolated in cell cultures during environmental surveillance or from patients, including vaccine-derived polioviruses.

  4. Enterovirus related metabolic myopathy: a postviral fatigue syndrome

    OpenAIRE

    Lane, R; Soteriou, B; Zhang, H; Archard, L

    2003-01-01

    Objective: To detect and characterise enterovirus RNA in skeletal muscle from patients with chronic fatigue syndrome (CFS) and to compare efficiency of muscle energy metabolism in enterovirus positive and negative CFS patients.

  5. Can Helicobacter pylori infection influence human reproduction?

    Science.gov (United States)

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-05-21

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermatozoa, conceivably hampering the oocyte/sperm fusion. Infection by CagA positive organisms enhances the risk of preeclampsia, which is a main cause of foetus death. These findings are supported by the results of experimental infections of pregnant mice, which may cause reabsorption of a high number of foetuses and alter the balance between Th1 and Th2 cell response. Infected men have decreased sperm motility, viability and numbers of normally shaped sperm and augmented systemic levels of inflammatory cytokines, such as tumor necrosis factor-α, which may damage spermatozoa. In countries where parasitic infestation is endemic, detrimental effects of infection upon spermatozoa may not occur, because the immune response to parasites could determine a switch from a predominant Th1 type to Th2 type lymphocytes, with production of anti-inflammatory cytokines. In conclusion, the evidences gathered until now should be taken into consideration for future studies aiming to explore the possible role of H. pylori infection on human reproduction.

  6. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  7. Human Infection in Wild Mountain Gorillas

    Centers for Disease Control (CDC) Podcasts

    2011-04-25

    This podcast discusses a study about the transmission of Human Metapneumovirus Infection to wild mountain gorillas in Rwanda in 2009, published in the April 2011 issue of Emerging Infectious Diseases. Dr. Ian Lipkin, Director of the Center for Infection and Immunity and Dr. Gustavo Palacios, investigator in the Center of Infection & Immunity share details of this study.  Created: 4/25/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 5/2/2011.

  8. Peptide inhibition of human cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  9. Update on human Campylobacter jejuni infections.

    Science.gov (United States)

    Kirkpatrick, Beth D; Tribble, David R

    2011-01-01

    The present review will update the reader to the clinical, epidemiological and immunologic advances in the field of human campylobacteriosis. New advances in human campylobacteriosis include an increased appreciation of the role of Campylobacter jejuni in postinfectious sequelae, a broadened understanding of Campylobacter-associated disease burden and the interplay between host immunity and bacterial factors. Antibiotic management has also become more complex: C. jejuni has undergone a rapid increase in resistance to the fluoroquinolone antibiotics and concurrently, postinfectious irritable bowel syndrome has been associated with a longer duration of untreated infection. In anticipation of new candidate C. jejuni vaccines, progress in understanding human immune responses to infection has been made via human experimental infections. These tightly controlled studies have also increased our understanding of the natural history of campylobacteriosis as well as observations of recrudescent infection following treatment with C. jejuni-sensitive antibiotics. As one of the most common agents of bacterial gastroenteritis and a major health burden for both developing world and industrialized nations, Campylobacter infections remain a high priority for research efforts to improve prevention and management. Priorities for the future include vaccine development, pathogen-specific immunity and identification of risk factors for postinfectious sequelae.

  10. A Study of Brucella Infection in Humans

    Directory of Open Access Journals (Sweden)

    Hasanjani Roushan Mohammad Reza

    2014-07-01

    Full Text Available Objective: Brucellosis is the most usual zoonotic disease around the world especially in the Middle East, Mediterranean and Indian sub-continent areas. This bacterium has ten species that Brucella melitensis among them recognized as the most important cause of human brucellosis. This infection transfer ways to human include of wounds, bacteria inhalation and consumption of septic dairy such as raw milk, cream and butter. Brucellosis as a systemic disease can involve more organs of patients that have symptoms such as fever, night sweating, and backache. This infection can be divided as acute, sub-acute and chronic forms according to the manner of clinical presentation. Materials and Methods: This research is a review study and conducted by reviewing of the literature, which is related to this issue and also visiting, PubMed, and other linked websites. Results: In human brucellosis domestic animals are the main natural reservoir of infection. Whenever incidence rate of this infection in domestic and wild animals is reduced on the other hand incidence rate in human also will reduce. Conclusion: Blood cultures, serological tests and molecular tests are common laboratory methods of this infection. Diminution of relapse and therapeutic failure rates are as most important aim, which is researcher’s regards.

  11. Mycobacterium caprae infection in humans.

    Science.gov (United States)

    Prodinger, Wolfgang M; Indra, Alexandra; Koksalan, Orhan K; Kilicaslan, Zeki; Richter, Elvira

    2014-12-01

    Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, causes tuberculosis (TB) in man and animals. Some features distinguish M. caprae from its epidemiological twin, Mycobacterium bovis: M. caprae is evolutionarily older, accounts for a smaller burden of zoonotic TB and is not globally distributed, but primarily restricted to European countries. M. caprae occurs only in a low proportion of human TB cases and this proportion may even decrease, if progress toward eradication of animal TB in Europe continues. So why bother, if M. caprae is not an enigma for diagnostic TB tests and if resistance against first-line drugs is a rarity with M. caprae? This 'European' pathogen of zoonotic TB asks interesting questions regarding the definition of a species. The latter, seemingly only an academic question, particularly requires and challenges the collaboration between human and veterinary medicine.

  12. Cytomegalovirus infection presenting as acute periodontal infection in a patient infected with the human immunodeficiency virus.

    Science.gov (United States)

    Dodd, C L; Winkler, J R; Heinic, G S; Daniels, T E; Yee, K; Greenspan, D

    1993-04-01

    During childhood, many people acquire primary infection with cytomegalovirus (CMV), one of the herpes viruses. If they later become immunosuppressed, such as occurs with human immunodeficiency virus (HIV) infection, CMV is likely to become reactivated. Severe disease caused by CMV is life-threatening in the HIV-infected population. CMV retinitis, gastritis, colitis, pneumonia, encephalitis and hepatitis have all been reported, but oral lesions due to infection with CMV are rarely reported. We report a case of oral CMV infection which at first was clinically indistinguishable from HIV-associated periodontal disease.

  13. Atypical human infections by animal trypanosomes.

    Directory of Open Access Journals (Sweden)

    Philippe Truc

    Full Text Available The two classical forms of human trypanosomoses are sleeping sickness due to Trypanosoma brucei gambiense or T. brucei rhodesiense, and Chagas disease due to T. cruzi. However, a number of atypical human infections caused by other T. species (or sub-species have been reported, namely due to T. brucei brucei, T. vivax, T. congolense, T. evansi, T. lewisi, and T. lewisi-like. These cases are reviewed here. Some infections were transient in nature, while others required treatments that were successful in most cases, although two cases were fatal. A recent case of infection due to T. evansi was related to a lack of apolipoprotein L-I, but T. lewisi infections were not related to immunosuppression or specific human genetic profiles. Out of 19 patients, eight were confirmed between 1974 and 2010, thanks to improved molecular techniques. However, the number of cases of atypical human trypanosomoses might be underestimated. Thus, improvement, evaluation of new diagnostic tests, and field investigations are required for detection and confirmation of these atypical cases.

  14. Thrombocytopenia in Children Infected with the Human ...

    African Journals Online (AJOL)

    Background: Human immunodeficiency virus (HIV) infection is associated with a myriad of hematopoietic abnormalities, of which thrombocytopenia (TP) is a common complication. The condition could predispose to life-threatening hemorrhage. Objectives: To determine the prevalence of thrombocytopenia among HIV- ...

  15. Human Immunodeficiency Virus Infection Occupational Post ...

    African Journals Online (AJOL)

    opsig

    potentially infected body fluids so that they can present themselves rapidly for risk assessment and commencement of ART if necessary in the event of an occupational exposure to HIV. INTRODUCTION. Human Immunodeficiency Virus (HIV) is the virus that causes Acquired Immune Deficiency Syndrome. (AIDS). It can be ...

  16. Human immunodeficiency virus infection among migrant fishermen ...

    African Journals Online (AJOL)

    Background: People migrate from place to place for diverse reasons chief among which is economic. Migrant fishermen like other migrant population lead high risk sexual lifestyle and are therefore, predisposed to Human immunodeficiency virus (HIV) infection. Aim: To determine the prevalence of HIV among migrant ...

  17. Human Diphyllobothrium nihonkaiense Infection in Washington State

    Science.gov (United States)

    Billman, Zachary P.; Wallis, Carolyn K.; Abbott, April N.; Olson, John C.; Dhanireddy, Shireesha; Murphy, Sean C.

    2015-01-01

    A patient in Washington State harbored a fish tapeworm most likely acquired from eating raw salmon. Diphyllobothrium nihonkaiense was identified by cox1 sequence analysis. Although this is the first documented human D. nihonkaiense infection in the United States, the parasite may have been present earlier but misidentified as Diphyllobothrium latum. PMID:25609724

  18. HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

    NARCIS (Netherlands)

    Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio

    Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we

  19. Infecciones del sistema nervioso central por enterovirus en niños atendidos en un hospital de Lima, Perú

    OpenAIRE

    Espinoza, Iván O.; Universidad Peruana Cayetano Heredia. Lima, Perú. Hospital Nacional Cayetano Heredia. Lima, Perú. Médico neurólogo pediatra.; Ochoa, Theresa J.; Universidad Peruana Cayetano Heredia. Lima, Perú University of Texas School of Public Health. Texas, EE. UU.; Mosquito, Susan; Universidad Peruana Cayetano Heredia. Lima, Perú. Microbiólogo.; Barletta, Francesca; Universidad Peruana Cayetano Heredia. Lima, Perú. Biólogo molecular.; Hernández, Roger; Universidad Peruana Cayetano Heredia. Lima, Perú. Hospital Nacional Cayetano Heredia. Lima, Perú. Grupo Peruano de Investigación en Neumococo (GPIN). Lima, Perú. Médico infectólogo pediatra.; Medina, María del Pilar; Universidad Peruana Cayetano Heredia. Lima, Perú. Instituto Nacional Materno Perinatal. Lima, Perú. Médico neurólogo pediatra.; Stiglich, María Luisa; Universidad Peruana Cayetano Heredia. Lima, Perú. Hospital Nacional Docente Madre Niño San Bartolomé. Lima, Perú. Médico neurólogo pediatra.; Ugarte, Claudia; Universidad Peruana Cayetano Heredia. Lima, Perú. Hospital Nacional Cayetano Heredia. Lima, Perú. Médico pediatra.; Guillén, Daniel; Universidad Peruana Cayetano Heredia. Lima, Perú. Hospital Nacional Cayetano Heredia. Lima, Perú. Médico neurólogo pediatra.

    2014-01-01

    Objectives. To determine the frequency and clinical features of central nervous system infections caused by enterovirus in children treated at the Hospital Nacional Cayetano Heredia in Lima, Peru. Materials and methods. A prospective, descriptive study was performed from April 2008 to March 2010. Patients aged 1 month – 14 years with clinical diagnosis of encephalitis or aseptic meningitis were included. We investigated the presence of enterovirus, herpes simplex virus 1 (HSV-1), herpes s...

  20. Adenovirus, enterovirus and thermotolerant coliforms in recreational waters from Lake Guaíba beaches, Porto Alegre, Brazil.

    Science.gov (United States)

    Maurer, C P; Simonetti, A B; Staggemeier, R; Rigotto, C; Heinzelmann, L S; Spilki, F R

    2015-12-01

    In the present study, molecular detection of human adenoviruses (HAdV) and enteroviruses (EV) was performed in surface water samples collected from beaches Ipanema and Lami, located on the shores of Lake Guaíba, city of Porto Alegre, RS, southern Brazil. Furthermore, water safety was evaluated by counting thermotolerant coliforms (TC), following local government regulations. A total of 36 samples were collected monthly from six different sites along the beaches. Viral genomes were found in 30 (83.3%) samples. The higher detection rate was observed for HAdV (77.8%), followed by EV (22.2%). Although low concentrations of TC have been found, the occurrence of viral genomes in water samples was frequent and may pose a potential risk of infection for people bathing in these beaches.

  1. QUANTIFICATION OF ENTEROVIRUS AND HEPATITIS A VIRUSES IN WELLS AND SPRINGS IN EAST TENNESSEE USING REAL-TIME REVERSE TRANSCIPTION PCR

    Science.gov (United States)

    This project involves development, validation testing and application of a fast, efficient method of quantitatively measuring occurrence and concentration of common human viral pathogens, enterovirus and hepatitis A virus, in ground water samples using real-time reverse transcrip...

  2. Cryptic diversity in hymenolepidid tapeworms infecting humans.

    Science.gov (United States)

    Nkouawa, Agathe; Haukisalmi, Voitto; Li, Tiaoying; Nakao, Minoru; Lavikainen, Antti; Chen, Xingwang; Henttonen, Heikki; Ito, Akira

    2016-04-01

    An adult hymenolepidid tapeworm was recovered from a 52-year-old Tibetan woman during a routine epidemiological survey for human taeniasis/cysticercosis in Sichuan, China. Phylogenetic analyses based on sequences of nuclear 28S ribosomal DNA and mitochondrial cytochrome c oxidase subunit 1 showed that the human isolate is distinct from Hymenolepis diminuta and Hymenolepis nana, the common parasites causing human hymenolepiasis. Proglottids of the human isolate were unfortunately unsuitable for morphological identification. However, the resultant phylogeny demonstrated the human isolate to be a sister species to Hymenolepis hibernia from Apodemus mice in Eurasia. The present data clearly indicate that hymenolepidid tapeworms causing human infections are not restricted to only H. diminuta and H. nana. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. [Development of a GeXP based multiplex RT-PCR assay for simultaneous differentiation of nine human hand food mouth disease pathogens].

    Science.gov (United States)

    Hu, Xiu-Mei; Zhang, Yong; Xu, Bang-Lao; Yang, Meng-Jie; Wang, Miao; Zhang, Chen; Li, Jin; Bai, Ru-Yin; Zhou, Xiao-Mian; Xu, Wen-Bo; Ma, Xue-Jun

    2011-07-01

    A multiplex RT-PCR assay based on GeXP system was developed in order to detect simultaneously human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) and other coxsackieviruses (CVA4, 5, 9 and 10, CVB1, 3 and 5). Enterovirus detection was performed with a mixture of 12 pairs of oligonucleotide primers including one pair of published primers for amplifying all known pan-enterovirus genomes and eleven primer pairs specific for detection of the VP1 genes of EV71, C A16, CVA4, CVA5, CVA9, CVA10, CVB1, CVB3 and CVB5, respectively. The specificity of multiplex RT-PCR system was examined using enterovirus cell cultures and positive strains identified previously from hand-foot-and-mouth disease (HFMD) patients. Serial dilution of titrated EV71 and C A16 cell cultures and in vitro transcripted RNA of enterovirus VP1 regions were used to detect the sensitivity of the multiplex RT-PCR system. The limit of detection for this multiplex RT-PCR system was 10(0.5) TCID50/microL for EV71 and C A16 cell cultures and 1000 copies for in vitro transcripted RNA of nine viruses per assay. This multiplex RT-PCR assay is a rapid, sensitive and specific assay for the diagnosis of common enterovirus infection in cases of HFMD outbreak and is also potentially useful for molecular epidemiological investigation.

  4. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?

    Science.gov (United States)

    Jain, Sonia P; Gulhane, Sachin; Pandey, Neha; Bisne, Esha

    2015-01-01

    Psoriasis is an autoimmune chronic inflammatory skin disease known to be triggered by streptococcal and HIV infections. However, human papilloma virus infection (HPV) as a triggering factor for the development of psoriasis has not been reported yet. We, hereby report a case of plaque type with inverse psoriasis which probably could have been triggered by genital warts (HPV infection) and discuss the possible pathomechanisms for their coexistence and its management.

  5. Virus infection and human cancer: an overview.

    Science.gov (United States)

    Schiller, John T; Lowy, Douglas R

    2014-01-01

    It is now estimated that approximately 10 % of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. Oncogenic viruses include various classes of DNA and RNA viruses and induce cancer by a variety of mechanisms. A unifying theme is that cancer develops in a minority of infected individuals and only after chronic infection of many years duration. The viruses associated with the greatest number of cancer cases are the human papillomaviruses (HPVs), which cause cervical cancer and several other epithelial malignancies, and the hepatitis viruses HBV and HCV, which are responsible for the majority of hepatocellular cancer. Other oncoviruses include Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). Identification of the infectious cause has led to several interventions that may reduce the risk of developing these tumors. These include preventive vaccines against HBV and HPV, HPV-based testing for cervical cancer screening, anti-virals for the treatment of chronic HBV and HCV infection, and screening the blood supply for the presence of HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may lead to further insight into etiology and pathogenesis as well as to new approaches for therapeutic and prophylactic intervention.

  6. Rhinovirus genome evolution during experimental human infection.

    Directory of Open Access Journals (Sweden)

    Samuel Cordey

    Full Text Available Human rhinoviruses (HRVs evolve rapidly due in part to their error-prone RNA polymerase. Knowledge of the diversity of HRV populations emerging during the course of a natural infection is essential and represents a basis for the design of future potential vaccines and antiviral drugs. To evaluate HRV evolution in humans, nasal wash samples were collected daily for five days from 15 immunocompetent volunteers experimentally infected with a reference stock of HRV-39. In parallel, HeLa-OH cells were inoculated to compare HRV evolution in vitro. Nasal wash in vivo assessed by real-time PCR showed a viral load that peaked at 48-72 h. Ultra-deep sequencing was used to compare the low-frequency mutation populations present in the HRV-39 inoculum in two human subjects and one HeLa-OH supernatant collected 5 days post-infection. The analysis revealed hypervariable mutation locations in VP2, VP3, VP1, 2C and 3C genes and conserved regions in VP4, 2A, 2B, 3A, 3B and 3D genes. These results were confirmed by classical sequencing of additional samples, both from inoculated volunteers and independent cell infections, and suggest that HRV inter-host transmission is not associated with a strong bottleneck effect. A specific analysis of the VP1 capsid gene of 15 human cases confirmed the high mutation incidence in this capsid region, but not in the antiviral drug-binding pocket. We could also estimate a mutation frequency in vivo of 3.4x10(-4 mutations/nucleotides and 3.1x10(-4 over the entire ORF and VP1 gene, respectively. In vivo, HRV generate new variants rapidly during the course of an acute infection due to mutations that accumulate in hot spot regions located at the capsid level, as well as in 2C and 3C genes.

  7. Enterovirus Migration Patterns between France and Tunisia.

    Science.gov (United States)

    Othman, Ines; Mirand, Audrey; Slama, Ichrak; Mastouri, Maha; Peigue-Lafeuille, Hélène; Aouni, Mahjoub; Bailly, Jean-Luc

    2015-01-01

    The enterovirus (EV) types echovirus (E-) 5, E-9, and E-18, and coxsackievirus (CV-) A9 are infrequently reported in human diseases and their epidemiologic features are poorly defined. Virus transmission patterns between countries have been estimated with phylogenetic data derived from the 1D/VP1 and 3CD gene sequences of a sample of 74 strains obtained in France (2000-2012) and Tunisia (2011-2013) and from the publicly available sequences. The EV types (E-5, E-9, and E-18) exhibited a lower worldwide genetic diversity (respective number of genogroups: 4, 5, and 3) in comparison to CV-A9 (n = 10). The phylogenetic trees estimated with both 1D/VP1 and 3CD sequence data showed variations in the number of co-circulating lineages over the last 20 years among the four EV types. Despite the low number of genogroups in E-18, the virus exhibited the highest number of recombinant 3CD lineages (n = 10) versus 4 (E-5) to 8 (E-9). The phylogenies provided evidence of multiple transportation events between France and Tunisia involving E-5, E-9, E-18, and CV-A9 strains. Virus spread events between France and 17 other countries in five continents had high probabilities of occurrence as those between Tunisia and two European countries other than France. All transportation events were supported by BF values > 10. Inferring the source of virus transmission from phylogenetic data may provide insights into the patterns of sporadic and epidemic diseases caused by EVs.

  8. Infections caused by Kluyvera species in humans.

    Science.gov (United States)

    Sarria, J C; Vidal, A M; Kimbrough, R C

    2001-10-01

    Kluyvera is a relatively newly described genus in the family Enterobacteriaceae that infrequently causes infections in humans. The organism has been isolated from various clinical specimens, but its significance has not been clearly established. In fact, it has been regarded alternatively as saprophytic, opportunistic, or pathogenic. Since the redefinition of this genus in 1981, case reports of diverse clinical infections occurring under various host conditions have been published. Here we present a critical review of all Kluyvera infections reported in the literature, along with our experience involving 5 additional cases. Most patients received prompt antimicrobial treatment on the basis of susceptibility testing, and overall the clinical outcomes were good. Antimicrobial agents active against most Kluyvera strains include third-generation cephalosporins, fluoroquinolones, and aminoglycosides. In contrast, the resistance to ampicillin, extended-spectrum penicillins, and first- and second-generation cephalosporins is significant. Kluyvera is a potentially virulent pathogen that deserves aggressive treatment designed with an awareness of the organism's antimicrobial resistance patterns.

  9. HUMAN PARASITIC INFECTIONS IN BALI : A REVIEW

    Directory of Open Access Journals (Sweden)

    Putu Sutisna

    2012-09-01

    Full Text Available Parasitic infections in humans in Bali are well documented, especially in the population who lived in rural areas. The most common infections are those of the soil-transmitted helminthiasis which are caused by Ascaris lumbricoides, Trichuris trichiura and hookworm showing prevalence rates of 40 - 95%, 25 - 90% and 20 - 70% respectively. Enterobius vermicularis prevalence rate has been reported to be 18 - 53%. Taenniasis prevalence rate has been documented to be 0.8 - 23% in some villages, where Taenia saginata was found to be more prevalent than Taenia solium, and this might be due to the eating habit of the Balinese people who consumed both pork and beef lawar. Malaria is still found in Bali especially in regions along the coasts of some regencies, although generally the infection rate is low. The prevalence rates of intestinal protozoa such as Giardia lamblia, Entamoeba histolytica, Balantidium coli have been occasionally reported in low percentages.

  10. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells

    NARCIS (Netherlands)

    Heikkilä, Outi; Merilahti, Pirjo; Hakanen, Marika; Karelehto, Eveliina; Alanko, Jonna; Sukki, Maria; Kiljunen, Saija; Susi, Petri

    2016-01-01

    Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the

  11. Coxsackievirus B5 Infection Induces Dysregulation of microRNAs Predicted to Target Known Type 1 Diabetes Risk Genes in Human Pancreatic Islets.

    Science.gov (United States)

    Kim, Ki Wook; Ho, Andy; Alshabee-Akil, Ammira; Hardikar, Anandwardhan A; Kay, Thomas W H; Rawlinson, William D; Craig, Maria E

    2016-04-01

    Extensive research has identified enterovirus (EV) infections as key environmental triggers of type 1 diabetes. However, the underlying molecular mechanisms via which EVs contribute to the pathogenesis of type 1 diabetes remain unclear. Given that EVs dysregulate host microRNAs (miRNAs), which function as key regulators of β-cell biology, we investigated the impact of coxsackievirus B5 (CVB5) infection on the cellular expression of miRNAs within human islets. Using high-throughput quantitative PCR nanofluidics arrays, the expression of 754 miRNAs was examined in CVB5-infected human pancreatic islets. In total, 33 miRNAs were significantly dysregulated (≥ threefold difference) in the infected compared with control islets (P CVB5-infected human pancreatic islets. We propose that EVs disrupt the miRNA-directed suppression of proinflammatory factors within β-cells, thereby resulting in an exacerbated antiviral immune response that promotes β-cell destruction and eventual type 1 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Human Schistosome Infection and Allergic Sensitisation

    Directory of Open Access Journals (Sweden)

    Nadine Rujeni

    2012-01-01

    Full Text Available Several field studies have reported an inverse relationship between the prevalence of helminth infections and that of allergic sensitisation/atopy. Recent studies show that immune responses induced by helminth parasites are, to an extent, comparable to allergic sensitisation. However, helminth products induce regulatory responses capable of inhibiting not only antiparasite immune responses, but also allergic sensitisation. The relative effects of this immunomodulation on the development of protective schistosome-specific responses in humans has yet to be demonstrated at population level, and the clinical significance of immunomodulation of allergic disease is still controversial. Nonetheless, similarities in immune responses against helminths and allergens pose interesting mechanistic and evolutionary questions. This paper examines the epidemiology, biology and immunology of allergic sensitisation/atopy, and schistosome infection in human populations.

  13. [Human papillomavirus infection in male genitalia].

    Science.gov (United States)

    Cano Garfias, R; Villarreal Peral, C; Juárez Azpilcueta, A

    1995-10-01

    A prospective and transversal study in 100 patients since January to December of 1994, was done, to know the human papiloma virus infection prevalence in male genitals. The patients were studied by a clinical history, genital area colposcopic revision after acetic acid 5% application, biopsy of the lesion and histopathology study. The patients age was among 16 to 71 years old, with a media of 38.8 years old. The sexual activity beginning was from 12 to 27 years old, with an average of 18 years old. Forty one percent of the patients have had sexual relations with prostitutes, 26% have had sexually transmitted diseases, 9% of the patients referred only 1 sexual mate and 82% had human papiloma virus infection.

  14. Leishmania major infection in humanized mice induces systemic infection and provokes a nonprotective human immune response.

    Directory of Open Access Journals (Sweden)

    Anja Kathrin Wege

    Full Text Available BACKGROUND: Leishmania (L. species are the causative agent of leishmaniasis. Due to the lack of efficient vaccine candidates, drug therapies are the only option to deal with cutaneous leishmaniasis. Unfortunately, chemotherapeutic interventions show high toxicity in addition to an increased risk of dissemination of drug-resistant parasites. An appropriate laboratory animal based model is still missing which allows testing of new drug strategies in the context of human immune cells in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Humanized mice were infected subcutaneously with stationary phase promastigote L. major into the footpad. The human immune response against the pathogen and the parasite host interactions were analyzed. In addition we proved the versatility of this new model to conduct drug research studies by the inclusion of orally given Miltefosine. We show that inflammatory human macrophages get infected with Leishmania parasites at the site of infection. Furthermore, a Leishmania-specific human-derived T cell response is initiated. However, the human immune system is not able to prevent systemic infection. Thus, we treated the mice with Miltefosine to reduce the parasitic load. Notably, this chemotherapy resulted in a reduction of the parasite load in distinct organs. Comparable to some Miltefosine treated patients, humanized mice developed severe side effects, which are not detectable in the classical murine model of experimental leishmaniasis. CONCLUSIONS/SIGNIFICANCE: This study describes for the first time L. major infection in humanized mice, characterizes the disease development, the induction of human adaptive and innate immune response including cytokine production and the efficiency of Miltefosine treatment in these animals. In summary, humanized mice might be beneficial for future preclinical chemotherapeutic studies in systemic (visceral leishmaniasis allowing the investigation of human immune response, side effects of the drug

  15. Human alpha-defensins block papillomavirus infection.

    Science.gov (United States)

    Buck, Christopher B; Day, Patricia M; Thompson, Cynthia D; Lubkowski, Jacek; Lu, Wuyuan; Lowy, Douglas R; Schiller, John T

    2006-01-31

    Sexually transmitted human papillomaviruses (HPVs) are the primary cause of cervical cancer. Recent advances in techniques for production of papillomaviral vectors [known as pseudoviruses (PsVs)] have made it possible to perform high-throughput screens for compounds that might block the initial stages of papillomavirus infection. We have used PsVs to screen a variety of compounds that might function as inhibitors of HPV infection, with emphasis on human peptides previously implicated in innate antimicrobial immunity. Little is known about the possible activity of these peptides against nonenveloped viruses, such as HPVs. Our screen revealed that human alpha-defensins 1-3 [known as human neutrophil peptides (HNPs) 1-3] and human alpha-defensin 5 (HD-5) are potent antagonists of infection by both cutaneous and mucosal papillomavirus types. In contrast, human beta-defensins 1 and 2 displayed little or no anti-HPV activity. HD-5 was particularly active against sexually transmitted HPV types, with 50% inhibitory doses in the high ng/ml range. Microscopic studies of PsV inhibition by the alpha-defensins revealed that they block virion escape from endocytic vesicles but not virion binding or internalization. Consistent with this finding, PsVs remained susceptible to inhibition by alpha-defensins for many hours after initial binding to cells. HNPs 1-3 and HD-5 have been reported to be present in the female genital tract at levels that overlap those that inhibit HPVs in vitro, suggesting that they could present a natural barrier to the sexual transmission of HPV and could serve as the basis of a broad-spectrum topical microbicide.

  16. Epidemiology of virus infection and human cancer.

    Science.gov (United States)

    Chen, Chien-Jen; Hsu, Wan-Lun; Yang, Hwai-I; Lee, Mei-Hsuan; Chen, Hui-Chi; Chien, Yin-Chu; You, San-Lin

    2014-01-01

    The International Agency for Research on Cancer (IARC) has comprehensively assessed the human carcinogenicity of biological agents. Seven viruses including Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Kaposi's sarcoma herpes virus (KSHV), human immunodeficiency virus, type-1 (HIV-1), human T cell lymphotrophic virus, type-1 (HTLV-1), and human papillomavirus (HPV) have been classified as Group 1 human carcinogens by IARC. The conclusions are based on the findings of epidemiological and mechanistic studies. EBV, HPV, HTLV-1, and KSHV are direct carcinogens; HBV and HCV are indirect carcinogens through chronic inflammation; HIV-1 is an indirect carcinogen through immune suppression. Some viruses may cause more than one cancer, while some cancers may be caused by more than one virus. However, only a proportion of persons infected by these oncogenic viruses will develop specific cancers. A series of studies have been carried out to assess the viral, host, and environmental cofactors of EBV-associated nasopharyngeal carcinoma, HBV/HCV-associated hepatocellular carcinoma, and HPV-associated cervical carcinoma. Persistent infection and high viral load are important risk predictors of these virus-caused cancers. Risk calculators incorporating host and viral factors have also been developed for the prediction of long-term risk of hepatocellular carcinoma. These risk calculators are useful for the triage and clinical management of infected patients. Both clinical trials and national programs of immunization or antiviral therapy have demonstrated a significant reduction in the incidence of cancers caused by HBV, HCV, and HPV. Future researches on gene-gene and gene-environment interaction of oncogenic viruses and human host are in urgent need.

  17. A novel enterovirus and parechovirus multiplex one-step real-time PCR-validation and clinical experience

    DEFF Research Database (Denmark)

    Nielsen, A. C. Y.; Bottiger, B.; Midgley, S. E.

    2013-01-01

    testing and routine usage. During 15 months of routine use, from October 2008 to December 2009, we received and analysed 2187 samples (stool samples, cerebrospinal fluids, blood samples, respiratory samples and autopsy samples) were tested, from 1546 patients and detected enteroviruses and parechoviruses...... in 171 (8%) and 66(3%) of the samples, respectively. 180 of the positive samples could be genotyped by PCR and sequencing and the most common genotypes found were human parechovirus type 3, echovirus 9, enterovirus 71, Coxsackievirus A16, and echovirus 25. During 2009 in Denmark, both enterovirus...... and human parechovirus type 3 had a similar seasonal pattern with a peak during the summer and autumn. Human parechovirus type 3 was almost invariably found in children less than 4 months of age. In conclusion, a multiplex assay was developed allowing simultaneous detection of 2 viruses, which can cause...

  18. Human Respiratory Syncytial Virus: Infection and Pathology.

    Science.gov (United States)

    Bohmwald, Karen; Espinoza, Janyra A; Rey-Jurado, Emma; Gómez, Roberto S; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2016-08-01

    The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. Human Cytomegalovirus Manipulation of Latently Infected Cells

    Science.gov (United States)

    Sinclair, John H.; Reeves, Matthew B.

    2013-01-01

    Primary infection with human cytomegalovirus (HCMV) results in the establishment of a lifelong infection of the host which is aided by the ability of HCMV to undergo a latent infection. One site of HCMV latency in vivo is in haematopoietic progenitor cells, resident in the bone marrow, with genome carriage and reactivation being restricted to the cells of the myeloid lineage. Until recently, HCMV latency has been considered to be relatively quiescent with the virus being maintained essentially as a “silent partner” until conditions are met that trigger reactivation. However, advances in techniques to study global changes in gene expression have begun to show that HCMV latency is a highly active process which involves expression of specific latency-associated viral gene products which orchestrate major changes in the latently infected cell. These changes are argued to help maintain latent infection and to modulate the cellular environment to the benefit of latent virus. In this review, we will discuss these new findings and how they impact not only on our understanding of the biology of HCMV latency but also how they could provide tantalising glimpses into mechanisms that could become targets for the clearance of latent HCMV. PMID:24284875

  20. Experimental Campylobacter Jejuni Infection in Humans

    Science.gov (United States)

    1988-03-01

    Blaser MJI Black RE. Duncan DJ, Amer I. Campylobacter Clements ML, Robins-Brone R, Lim Y-L. Duration of jejuni -specific serum antibodies are elevated in...SUBTITLE 5 FUNDING •4UMBERS Experimental Campylobacter jejuni Infection 86PP6826 in Humans 61102A 30161102BS13 AB6. AUTHOR(S)DA328 Robert E. Black...SUPPLEMENTARY NOTES Contract Title: Studies of the Outer Membrane Proteins of Campylobacter Jejuni for Vaccine Development ൔa• DISTRIBUTION

  1. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    DEFF Research Database (Denmark)

    Poelman, Randy; Schuffenecker, Isabelle; Van Leer-Buter, Coretta

    2015-01-01

    BACKGROUND: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory...... sample screening for enterovirus detection and typing in cases with severe respiratory presentations. OBJECTIVES: To provide a detailed picture of EV-D68 epidemiology in Europe by conducting a retrospective and prospective laboratory analysis of clinical specimens. STUDY DESIGN: An initiative supported...... laboratories from 17 European countries, analyzed 17,248 specimens yielding 389 EV-D68 positive samples (2.26%) in 14 countries. The proportion of positive samples ranged between 0 and 25% per country. These infections resulted primarily in mild respiratory disease, mainly detected in young children presenting...

  2. Polymorphisms in the innate immune IFIH1 gene, frequency of enterovirus in monthly fecal samples during infancy, and islet autoimmunity

    DEFF Research Database (Denmark)

    Witsø, Elisabet; Tapia, German; Cinek, Ondrej

    2011-01-01

    autoimmunity reported in our previous study was not materially influenced by the IFIH1 SNPs.We conclude that the type 1 diabetes-associated IFIH1 polymorphisms have no, or only minor influence on the occurrence, quantity or duration of enterovirus infection in the gut. Its effect on the risk of diabetes...

  3. New approaches for enhanced detection of enteroviruses from Hawaiian environmental waters.

    Directory of Open Access Journals (Sweden)

    Christina Connell

    Full Text Available Health risks associated with sewage-contaminated recreational waters are of important public health concern. Reliable water monitoring systems are therefore crucial. Current recreational water quality criteria rely predominantly on the enumeration of bacterial indicators, while potentially dangerous viral pathogens often remain undetected. Human enteric viruses have been proposed as alternative indicators; however, their detection is often hindered by low viral concentrations present in the environment. Reported here are novel and effective laboratory protocols for viral concentration and highly sensitive and optimized RT-PCR for the efficient detection of enteroviruses, an important enteric virus subset, in Hawaiian environmental waters. Eighteen published enterovirus primer pairs were comparatively evaluated for detection sensitivity. The primer set exhibiting the lowest detection limit under optimized conditions, EQ-1/EQ-2, was validated in a field survey of 22 recreational bodies of water located around the island of Oahu, Hawaii. Eleven sites tested positive for enterovirus, indicating fecal contamination at these locations. As an additional means of viral concentration, shellfish were collected from 9 sample sites and subjected to dissection, RNA extraction, and subsequent RT-PCR. Shellfish tissue from 6 of 9 sites tested positive for enterovirus. The techniques implemented here are valuable resources to aid accurate reflection of microbial contamination in Hawaii's environmental waters.

  4. Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China.

    Directory of Open Access Journals (Sweden)

    Xiaomei Wang

    Full Text Available Human enterovirus 71 (EV71-associated hand, foot, and mouth disease (HFMD has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV. Classified as EV71 subtype C4 (EV71 C4, these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1 of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3 showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD.

  5. The Mathematical Biology of Human Infections

    Directory of Open Access Journals (Sweden)

    Martin A. Nowak

    1999-12-01

    Full Text Available Humans are constant victims of infectious diseases. Biomedical research during this century has led to important insights into the molecular details of immune defense. Yet, many questions relating to disease require a quantitative understanding of the complex systems that arise from the nonlinear interactions between populations of immune cells and infectious agents. Exploration of such questions has lead to a newly emerging field of mathematical biology describing the spread of infectious agents both within and between infected individuals. This essay will discuss simple and complex models of evolution, and the propagation of virus and prion infections. Such models provide new perspectives for our understanding of infectious disease and provide guidelines for interpreting experimental observation; they also define what needs to be measured to improve understanding.

  6. Dengue human infection models supporting drug development.

    Science.gov (United States)

    Whitehorn, James; Van, Vinh Chau Nguyen; Simmons, Cameron P

    2014-06-15

    Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  7. Actinomyces and related organisms in human infections.

    Science.gov (United States)

    Könönen, Eija; Wade, William G

    2015-04-01

    Actinomyces israelii has long been recognized as a causative agent of actinomycosis. During the past 3 decades, a large number of novel Actinomyces species have been described. Their detection and identification in clinical microbiology laboratories and recognition as pathogens in clinical settings can be challenging. With the introduction of advanced molecular methods, knowledge about their clinical relevance is gradually increasing, and the spectrum of diseases associated with Actinomyces and Actinomyces-like organisms is widening accordingly; for example, Actinomyces meyeri, Actinomyces neuii, and Actinomyces turicensis as well as Actinotignum (formerly Actinobaculum) schaalii are emerging as important causes of specific infections at various body sites. In the present review, we have gathered this information to provide a comprehensive and microbiologically consistent overview of the significance of Actinomyces and some closely related taxa in human infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Microbiological diagnosis of human papilloma virus infection.

    Science.gov (United States)

    Mateos-Lindemann, Maria Luisa; Pérez-Castro, Sonia; Rodríguez-Iglesias, Manuel; Pérez-Gracia, Maria Teresa

    2017-11-01

    Infection with human papillomavirus (HPV) is the leading cause of sexually transmitted infection worldwide. This virus generally causes benign lesions, such as genital warts, but persistent infection may lead to cervical cancer, anal cancer, vaginal cancer, and oropharyngeal cancer, although less frequently. Cervical cancer is a severe disease with a high mortality in some countries. Screening with cytology has been very successful in the last few years, but nowadays there are numerous studies that confirm that cytology should be replaced with the detection of HPV as a first line test in population based screening. There are several commercially available FDA approved tests for screening of cervical cancer. A new strategy, based on individual detection of the high risk genotypes HPV16 and HPV18, present in 70% of cervical cancer biopsies, has been proposed by some experts, and is going to be implemented in most countries in the future. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Human papilloma virus infection prior to coitarche.

    Science.gov (United States)

    Doerfler, Daniela; Bernhaus, Astrid; Kottmel, Andrea; Sam, Christine; Koelle, Dieter; Joura, Elmar A

    2009-05-01

    The aim of our study was to determine the prevalence and the natural course of anogenital human papilloma virus (HPV) infections in girls prior to coitarche attending an outpatient gynecological unit. Specimens were taken from the anogenital region of 114 unselected 4-15 year old girls who were referred consecutively for various gynecological problems. Four girls were excluded because of sexual abuse. Low-risk HPV-deoxyribonucleic acid (DNA) was detected in 4 girls (3.6%) and high-risk HPV DNA in 15 children (13.6%). Two girls testing positive for HPV DNA had clinical apparent warts. After 1 year, 2 children had persistent high-risk HPV DNA, and in 1 case we found a switch from high-risk to low-risk HPV DNA. Subclinical genital low- and high-risk HPV infections are common in girls without any history of sexual abuse or sexual activity. We found persistence of genital HPV infection in children, which could be a reservoir for HPV-associated diseases later in life.

  10. Human immunodeficiency virus infection and child sexual abuse

    African Journals Online (AJOL)

    Human immunodeficiency virus infection and child sexual abuse. Hendrik Simon Schaaf. Child sexual abuse (CSA) has not previously been regarded as important in the overall transmission of HIV infection to. childrenY However, with both CSA'·' and HIV infection on the increase, the risk of acquiring HIV infection through ...

  11. The isolation of enteroviruses from blood: a comparison of four processing methods.

    Science.gov (United States)

    Prather, S L; Dagan, R; Jenista, J A; Menegus, M A

    1984-01-01

    Blood from 28 children hospitalized with symptomatic enterovirus infections was processed by four different methods in an effort to define optimum conditions for detecting viremia. Enteroviremia was demonstrated in 11/28 children. Virus was isolated by method 1 (serum) in 7/11 children and by method 2 (mononuclear leukocytes) in 9/11, but in only 3/10 and 3/11 children by methods 3 and 4 (granulocytes and plasma-mixed leukocytes, respectively). In four children, the only blood isolate was from mononuclear leukocytes, and in two, serum was the only positive blood preparation. This suggests that viremia can be often detected in hospitalized children with enterovirus disease and shows that the methods used for processing blood may significantly influence the isolation rate.

  12. Humanized mouse model to study bacterial infections targeting the microvasculature.

    Science.gov (United States)

    Melican, Keira; Aubey, Flore; Duménil, Guillaume

    2014-04-01

    Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream.

  13. Sudden cardiac death in patients with human immunodeficiency virus infection

    National Research Council Canada - National Science Library

    Tseng, Zian H; Secemsky, Eric A; Dowdy, David; Vittinghoff, Eric; Moyers, Brian; Wong, Joseph K; Havlir, Diane V; Hsue, Priscilla Y

    2012-01-01

    ...) in patients with human immunodeficiency virus (HIV) infection. As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described...

  14. Human immunodeficiency virus infection and female lower genital tract malignancy.

    Science.gov (United States)

    Kuhn, L; Sun, X W; Wright, T C

    1999-02-01

    The risk of lower genital tract neoplasia is increased in women infected with HIV. This has been best demonstrated in cervical squamous intraepithelial lesions, but has also been observed in vulvar and perianal intraepithelial lesions in some studies. Alterations in the prevalence and natural history of human papillomavirus infections of the lower genital tract appear to account for much of the increase. HIV-infected women are approximately four times more likely to be infected with human papillomavirus (including infection with high oncogenic risk human papillomavirus types) than are HIV-uninfected women, and these infections are more likely to be persistent. Human papilomavirus-associated lesions may be more difficult to treat in HIV-infected women. These data highlight the need to develop effective cervical cancer prevention programs for HIV-infected women.

  15. Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein.

    Science.gov (United States)

    van der Schaar, H M; Melia, C E; van Bruggen, J A C; Strating, J R P M; van Geenen, M E D; Koster, A J; Bárcena, M; van Kuppeveld, F J M

    2016-01-01

    Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for

  16. A mouse model of paralytic myelitis caused by enterovirus D68.

    Directory of Open Access Journals (Sweden)

    Alison M Hixon

    2017-02-01

    Full Text Available In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68 respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch's postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.

  17. Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children.

    Science.gov (United States)

    Zhang, Ying; Wang, Lichun; Liao, Yun; Liu, Longding; Ma, Kaili; Yang, Erxia; Wang, Jingjing; Che, Yanchun; Jiang, Li; Pu, Jing; Guo, Lei; Feng, Min; Liang, Yan; Cui, Wei; Yang, Huai; Li, Qihan

    2015-11-17

    During the development of enterovirus 71 (EV71) inactivated vaccine for preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an effective animal model is presumed to be significant and necessary. Our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of HFMD, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during EV71 infection. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Human Immunodeficiency Virus Infection in Pregnancy

    Directory of Open Access Journals (Sweden)

    Yasemin Arikan

    1998-01-01

    Full Text Available The incidence and prevalence of human immunodeficiency virus (HIV infection in women of child-bearing age continue to increase both internationally and in Canada. The care of HIV-infected pregnant women is complex, and multiple issues must be addressed, including the current and future health of the woman, minimization of the risk of maternal-infant HIV transmission, and maintenance of the well-being of the fetus and neonate. Vertical transmission of HIV can occur in utero, intrapartum and postpartum, but current evidence suggests that the majority of transmission occurs toward end of term, or during labour and delivery. Several maternal and obstetrical factors influence transmission rates, which can be reduced by optimal medical and obstetrical care. Zidovudine therapy has been demonstrated to reduce maternal-infant transmission significantly, but several issues, including the short and long term safety of antiretrovirals and the optimal use of combination antiretroviral therapy in pregnancy, remain to be defined. It is essential that health care workers providing care to these women fully understand the natural history of HIV disease in pregnancy, the factors that affect vertical transmission and the management issues during pregnancy. Close collaboration among a multidisciplinary team of knowledgeable health professionals and, most importantly, the woman herself can improve both maternal and infant outcomes.

  19. New treatments for human papillomavirus infection.

    Science.gov (United States)

    Muñoz-Santos, C; Pigem, R; Alsina, M

    2013-12-01

    Human papillomavirus infection is very common. In this article, we review the latest developments in the treatment of lesions caused by this virus, with a particular focus on anogenital warts. Sinecatechins and new imiquimod formulations are among the most significant new developments. Others include photodynamic therapy and intralesional immunotherapy, but there is insufficient evidence to recommend their routine use. Finally, while therapeutic vaccines and inhibitory molecules appear to hold great promise, they are still in the early phases of investigation. More studies are needed, and these should have similar designs, larger samples, and sufficiently long follow-up periods to enable the direct comparison of the short-term and long-term effectiveness of different treatment options. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  20. Modeling human influenza infection in the laboratory

    Directory of Open Access Journals (Sweden)

    Radigan KA

    2015-08-01

    Full Text Available Kathryn A Radigan,1 Alexander V Misharin,2 Monica Chi,1 GR Scott Budinger11Division of Pulmonary and Critical Care Medicine, 2Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection.Keywords: mice, ferret, influenza, animal model, biosafety

  1. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

    Science.gov (United States)

    Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun Ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

    2016-01-01

    Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

  2. Pediatric Acute Flaccid Paralysis: Enterovirus D68-Associated Anterior Myelitis.

    Science.gov (United States)

    Yoder, James A; Lloyd, Michael; Zabrocki, Luke; Auten, Jonathan

    2017-07-01

    Enteroviral infections can cause acute flaccid paralysis secondary to anterior myelitis. Magnetic resonance imaging (MRI) is important in the diagnosis of this potentially devastating pediatric disease. Before the 2014 outbreak of Enterovirus D68 (EV-D68), the virus was considered a relatively benign disease. A fully immunized 8-year-old boy was brought to the emergency department complaining of a cough, headache, neck pain, and right arm pain and weakness. Deep tendon reflexes in the weak arm could not be elicited. MRI of the brain and cervical spine revealed anterior myelitis of the cervical spine. The patient was given intravenous antibiotics, acyclovir, and methylprednisolone with no initial improvement. He was then given intravenous immunoglobulin over 3 days with improvement in symptoms. Nasal swab polymerase chain reaction revealed EV-D68. Despite medical management, the child was left with long-term motor disability in the effected extremity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Acute flaccid paralysis is a potential devastating complication of enteroviral infections. Extremity complaints in the clinical setting of central nervous system infection should raise concern for encephalomyelitis. MRI is extremely helpful in establishing this diagnosis. Prevalence of non-polio enteroviral paralytic events is increasing in the United States. Potential EV-D68 cases should be reported to local health departments. Emergency medicine providers should consider this complication in the child with acute, unexplained significant respiratory illness with new neurologic complaints. Published by Elsevier Inc.

  3. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea

    OpenAIRE

    Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

    2016-01-01

    Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytol...

  4. Enterovirus Species B Bias of RD Cell Line and Its Influence on Enterovirus Diversity Landscape.

    Science.gov (United States)

    Faleye, Temitope Oluwasegun Cephas; Adeniji, Johnson Adekunle

    2015-12-01

    Despite its widespread use in poliovirus isolation, studies show that most RD cell line isolates are species B enteroviruses (EB), it was therefore employed to further catalogue the EB diversity in two different regions of Nigeria. Concentrates of 18 environmental samples were inoculated into RD cell line. Isolates were subjected to PCR assays to detect enteroviruses, species C and B members and partial VP1 gene which was subsequently sequenced and used for identification and phylogenetic analysis. Isolates were further passaged in L20B cell line to detect polioviruses. Sixty-eight isolates were recovered from the 18 concentrates, all of which were positive for the enterovirus 5'-UTR screen. Thirteen of the 68 isolates were positive for the species C screen and replicated in L20B cell line, eleven of which also contained species B enteroviruses. Some of the mixed isolates were successfully typed, but as species B members. In all, isolates recovered in this study were identified as CVB5, E6, E7, E11, E13, E19, E20, E33, EVB75 and WPV3, while some could not be typed. Alongside the ten different enterovirus serotypes confirmed, results of this study document for the first time in Nigeria, EVB75. It showed the EB bias of RD cell line might indicate something much more fundamental in its biology. Finally, the finding of WPV3 in a region considered low risk for poliovirus emphasizes the need to expand poliovirus environmental surveillance to enable early detection of poliovirus silent circulation before occurrence of clinical manifestations.

  5. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea

    Science.gov (United States)

    Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je

    2016-01-01

    Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour. Results A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM) and 68 from men who have sex with women (MSW). Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection. Conclusion Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age. PMID:27548632

  6. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71.

    Science.gov (United States)

    Zhang, Yu-Feng; Deng, Hui-Ling; Fu, Jia; Zhang, Yu; Wei, Jian-Qiang

    2016-02-14

    Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.

  7. Pathogenesis of Hendra and Nipah virus infection in humans.

    Science.gov (United States)

    Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry

    2013-04-17

    Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans.

  8. Hepatitis C Virus and Human Immunodeficiency Virus Co-Infection ...

    African Journals Online (AJOL)

    Background: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are major health problems worldwide. HCV/HIV co-infection has been shown to increase the frequency of liver disease and also maternal-fetal transmission of HCV. Little data exist on the prevalence of co-infection of these viruses in ...

  9. Human papillomavirus infection and disease in men: Impact of HIV ...

    African Journals Online (AJOL)

    There is growing evidence of a significant burden of human papillomavirus (HPV) infection and associated disease in men. High rates of HPV infection have been observed in men from sub-Saharan Africa where HIV prevalence is high. HIV infection increases HPV prevalence, incidence and persistence and is strongly ...

  10. Development of duplex real-time RT-PCR based on Taqman technology for detecting simultaneously the genome of pan-enterovirus and enterovirus 71.

    Science.gov (United States)

    Hwang, Seoyeon; Kang, Byunghak; Hong, Jiyoung; Kim, Ahyoun; Kim, Hyejin; Kim, Kisang; Cheon, Doo-Sung

    2013-07-01

    Human enterovirus (EV) 71 is the main etiological agent of hand, foot, and mouth disease (HFMD). It is associated with neurological complications, and caused fatalities during recent outbreaks in the Asia-Pacific region. Infections caused by EV71 could lead to many complications, ranging from brainstem encephalitis to pulmonary oedema, resulting in high mortality. In this study, a duplex real-time RT-PCR assay was developed in order to simultaneously detect pan-EV and EV71. EV71-specific primers and probes were designed based on the highly conserved VP1 region of EV71. Five EV71 strains were detected as positive, and no positive fluorescence signal was observed in the duplex real-time RT-PCR for other viral RNA, which showed 100% specificity for the selected panel, and no cross-reactions were observed in this duplex real-time RT-PCR. The EV71-specific duplex real-time RT-PCR was more sensitive than conventional RT-PCR, and detected viral titers that were 10-fold lower than those measured by the latter. Of the 381 HFMD clinical specimens, 196 (51.4%) cases were pan-EV-positive, of which 170 (86.7%) were EV71-positive when tested by pan-EV and EV71-specific duplex real-time RT-PCR. EV71-specific duplex real-time RT-PCR offers a rapid and sensitive method to detect EV71 from clinical specimens, and will allow quarantine measures to be taken more effectively during outbreaks. Copyright © 2013 Wiley Periodicals, Inc.

  11. Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina.

    Science.gov (United States)

    Zhou, Hong-Tao; Yi, Hai-Su; Guo, Yong-Hui; Pan, Yu-Xian; Tao, Shao-Hua; Wang, Bin; Chen, Man-Jun; Yang, Mei; Yu, Nan

    2016-03-16

    A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in hand, foot and mouth disease/herpangina (HFMD/HA). However, the complication of diarrhoea caused by enteroviruses has been neglected, and a summary of its clinical features and impact on HFMD/HA is unavailable. We included inpatients with HFMD/HA admitted to the Paediatric Department of Zhujiang Hospital during 2009-2012. We summarised and compared clinical data for cases with and without diarrhoea, and determined enterovirus serotypes by reverse transcriptase polymerase chain reaction and genotyping based on a partial-length fragment of viral protein 1 or the 5'-untranslated region. There were 804 inpatients with HFMD/HA and 28 (3.5%) presented with diarrhoea. Gastrointestinal symptoms were mild in most cases of diarrhoea (82.1%), with high prevalence of no dehydration (82.1%), short duration of diarrhoea (78.6%) and watery stools (75.0%). The prevalence of multi-organ dysfunction syndrome (10.7 vs 0.40%) (p = 0.001), hepatic injury (14.3 vs 3.4%) (p = 0.019), myocardial injury (21.4 vs 6.1%) (p = 0.002) and convulsion (21.4 vs 7.2%) (p = 0.016) was significantly higher in the diarrhoea than no diarrhoea group. There was no significant difference between the two groups regarding prevalence of death, altered consciousness, paralysis, central nervous system involvement, or acute respiratory infection. Most patients with diarrhoea caused by enteroviruses circulating in Guangdong Province in 2009-2012 had mild or moderate gastrointestinal symptoms. Although enterovirus-related diarrhoea caused additional multi-organ dysfunction syndrome, hepatic injury and myocardial injury in children with HFMD/HA, timely intervention efficiently reduced disease severity and improved outcome.

  12. Can Helicobacter pylori infection influence human reproduction?

    OpenAIRE

    Moretti, Elena; Figura, Natale; Collodel, Giulia; Ponzetto, Antonio

    2014-01-01

    Helicobacter pylori (H. pylori) infection could be associated with extra-digestive diseases. Here, we report the evidences concerning the decrease in reproductive potential occurring in individuals infected by H. pylori, especially by strains expressing CagA. This infection is more prevalent in individuals with fertility disorders. Infected women have anti-H. pylori antibodies in cervical mucus and follicular fluid that may decrease sperm motility and cross react immunologically with spermato...

  13. Enterovirus 71 Neutralizing Antibodies Seroepidemiological Research among Children in Guangzhou, China between 2014 and 2015: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Dingmei Zhang

    2017-03-01

    Full Text Available A hand-foot-mouth disease outbreak occurred in 2014 around Guangdong. The purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. Serum specimens were collected from children in communities from January 2014 to March 2015 in Guangzhou. A total of 197 serum samples from children 1–5 years old were collected for this cross-sectional study via non-probabilistic sampling from the database of Chinese National Science and Technique Major Project. Neutralization activity was measured via micro neutralization test in vitro. The positive rate of enterovirus 71 neutralizing antibodies was 59.4%, whereas the geometric mean titre was 1:12.7. A statistically significant difference in true positive rates was found between different age groups but not between different genders. Being the most susceptible population of hand–foot–mouth disease, children under 3 years of age are more likely to be infected with enterovirus 71, and the immunity of children increases with increasing age. Further cohort studies should be conducted, and measures for prevention and vaccination should be taken.

  14. Changes in microbiota during experimental human Rhinovirus infection

    NARCIS (Netherlands)

    Hofstra, J. J.; Matamoros, S.; van de Pol, M. A.; de Wever, B.; Tanck, M. W.; Wendt-Knol, H.; Deijs, M.; van der Hoek, L.; Wolthers, K. C.; Molenkamp, R.; Visser, C. E.; Sterk, P. J.; Lutter, R.; de Jong, M. D.

    2015-01-01

    Human Rhinovirus (HRV) is responsible for the majority of common colds and is frequently accompanied by secondary bacterial infections through poorly understood mechanisms. We investigated the effects of experimental human HRV serotype 16 infection on the upper respiratory tract microbiota. Six

  15. Arterial Disease in Patients With Human Immunodeficiency Virus Infection

    OpenAIRE

    Stein, James H.; Currier, Judith S.; HSUE, Priscilla Y

    2014-01-01

    With advances in antiretroviral therapy, individuals with human immunodeficiency virus (HIV) infection are living longer and increasingly die of non-HIV related diseases such as cardiovascular disease (CVD). Several observational studies suggest that HIV-infected patients on ART are at increased CVD risk; however, the precise mechanisms underlying the association between HIV infection and CVD risk are uncertain. Atherosclerosis and arterial disease in HIV-infected individuals is a multifactor...

  16. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes

    OpenAIRE

    Nigel Pereira; Kucharczyk, Katherine M.; Estes, Jaclyn L.; Rachel S. Gerber; Jovana P. Lekovich; Elias, Rony T.; Spandorfer, Steven D.

    2015-01-01

    The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apo...

  17. Perception of the Risks of Ebola, Enterovirus-E68 and Influenza Among Emergency Department Patients

    Directory of Open Access Journals (Sweden)

    Lauren K. Whiteside

    2016-06-01

    Full Text Available Introduction: Emerging infectious diseases often create concern and fear among the public. Ebola virus disease (EVD and enterovirus (EV-68 are uncommon viral illnesses compared to influenza. The objective of this study was to determine risk for these viral diseases and then determine how public perception of influenza severity and risk of infection relate to more publicized but less common emerging infectious diseases such as EVD and EV-68 among a sample of adults seeking care at an emergency department (ED in the United States. Methods: We included consenting adults who sought care in two different urban EDs in Seattle, WA in November 2014. Excluded were those who were not fluent in English, in police custody, had decreased level of consciousness, a psychiatric emergency, or required active resuscitation. Patients were approached to participate in an anonymous survey performed on a tablet computer. Information sought included demographics, medical comorbidities, risk factors for EVD and EV-68, and perceptions of disease likelihood, severity and worry for developing EVD, EV-68 or influenza along with subjective estimates of the number of people who have died of each virus over the year in the United States. Results: A total of 262 (88.5% participation rate patients participated in the survey. Overall, participants identified that they were more likely to get influenza compared to EVD (p<0.001 or EV-68 (p<0.001, but endorsed worry and concern about getting both EVD and EV-68 despite having little or no risk for these viral diseases. Nearly two-thirds (64% of participants had at-least one risk factor for an influenza-related complication. Most participants (64% believed they could get influenza in the next 12 months. Only 52% had received a seasonal influenza vaccine. Conclusion: Perception of risk for EVD, EV-68 and influenza is discordant with actual risk as well as self-reported use of preventive care. Influenza is a serious public health

  18. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J. B. M.; Bos, A. P.; Lutter, R.; Rossen, J. W. A.; Schuurman, R.

    2006-01-01

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  19. Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection

    NARCIS (Netherlands)

    van Woensel, J B M; Bos, A P; Lutter, R; Rossen, J W A; Schuurman, R

    It has been suggested that co-infection of human metapneumovirus (hMPV) in severe respiratory syncytial (RSV) virus bronchiolitis is very common. To evaluate the epidemiology of hMPV co-infection in children with severe lower respiratory tract infection caused by RSV virus. This was an observational

  20. Comparison analysis of microRNAs in response to EV71 and CA16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms.

    Science.gov (United States)

    Hu, Yajie; Song, Jie; Liu, Longding; Li, Jing; Tang, Beibei; Zhang, Ying; Wang, Jingjing; Wang, Lichun; Fan, Shengtao; Feng, Ming; Li, Qihan

    2017-01-15

    Hand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) infections which presented significantly different clinical manifestations. Nevertheless, the factors underlying these differences remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host interactions have been highlighted. Here, we performed comprehensive miRNA profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at multiple time points using high-throughput sequencing. The results showed that 154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the 56 known differentially expressed miRNAs by further screening for targets prediction. GO and pathway analysis of these targets demonstrated that 18 biological processes, 7 molecular functions, 1 cellular component and 123 pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt signalling pathway and angiogenesis showed significant alterations. The regulatory networks of these miRNAs with predicted targets, GOs, pathways and transcription factors were determined, which suggested that miRNAs displayed intricate regulatory mechanisms during the infection phase. Consequently, we specifically analysed the hierarchical GO categories of the predicted targets involved in adhesion. The results indicated that the distinct changes induced by EV71 and CA16 infection may be partly linked to airway epithelial barrier function. Taken together, our data provide useful insights that help elucidate the different host-pathogen interactions following EV71 and CA16 infection and might offer novel therapeutic targets for these infections. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. [Cerebral infarction in human immunodeficiency virus infection].

    Science.gov (United States)

    Blanche, P; Toulon, P; de La Blanchardière, A; Sicard, D

    1995-06-03

    Patients infected with the human immunodeficiency virus (HIV) appear to have a high risk of ischaemic cerebral events. We observed two cases of cerebral infarction in patients with acquired immune deficiency syndrome (AIDS). In the first case, a 38-year-old homosexual with no cardiovascular risk other than smoking presented with rapidly progressive hemiparesia. Brain CT-scan visualized two infarcts in the territory of the right sylvian artery and the arteriography an occlusion of the internal carotid artery. In the second, a 37-year-old homosexual, hospitalization was required for a left-sided pure sensitive epilepsy seizure. There was no cardiovascular risk other than smoking. Magnetic resonance imaging showed parietal ischaemia and thrombus in the left atrium without atrial hypertrophy was seen at transoesophageal echocardiography. In both cases, there was no evidence of endocarditis, dissection of the neck vessels or disseminated intravascular coagulation nor of associated viral or bacterial infectious complication of AIDS. Angiographic findings eliminated cerebral vascularitis. Among the perturbed haemostasis factors previously reported in HIV+ patients, we observed free proteins S deficiency (68 and 43%) and heparin cofactor II deficiency (54 and 40%). Serum albumin was 33 and 32 g/l respectively. Outcome was favourable in both cases with anticoagulant therapy. These coagulation anomalies would not appear sufficient to explain cerebral infarction. Other mechanisms including immune complexed deposition, direct HIV toxicity for endothelial cells or the effect of cytokines on smooth muscles fibres and fibroblasts are probably more important causal factors.

  2. Epidemiología de los enterovirus asociados a enfermedades neurológicas Epidemiology of enterovirus associated with neurologic diseases

    Directory of Open Access Journals (Sweden)

    Daniel M. Cisterna

    2007-04-01

    Full Text Available El presente estudio describe los resultados de la investigación de los enterovirus humanos (HEV mediante cultivo celular y reacción en cadena de la polimerasa y su tipificación molecular en 2167 casos de parálisis fláccida aguda, meningitis aséptica y encefalitis aguda, obtenidos entre 1991 y 1998 en la Argentina. La frecuencia de detección de HEV en parálisis fláccida aguda fue 19.5% (130/666 y de poliovirus Sabin 5.4% (36/666. La tasa de detección de HEV en los casos de meningitis fue 28.8% (231/801 y en encefalitis 3.0% (21/700. El grupo etario más afectado por las meningitis fue entre 1 y 9 años (75.3% y en los casos de parálisis fláccida aguda, de 1 a 4 años (58%. En muestras de brotes de meningitis se identificó echovirus (E 4, E9, E30 y E17, y en casos esporádicos virus coxsackie A (CAV 2, B (CBV 2 y CBV5, E7, E11, E19, E24 y E29, y enterovirus (EV 71. Finalmente, en casos de encefalitis se detectó E4, E7 y E24. En casos de parálisis fláccida aguda se identificaron 28 serotipos distintos de enterovirus no polio. En la Argentina y en otros países latinoamericanos existe escasa información acerca de la circulación de los HEV y su relación con diversas enfermedades neurológicas. Este estudio proporciona información que puede servir como base para posteriores investigaciones.This report describes the results of human enterovirus (HEV detection and characterization using cell culture, polymerase chain reaction and molecular typing in 2167 samples obtained from acute flaccid paralysis, aseptic meningitis and acute encephalitis patients, from 1991 to 1998 in Argentina. HEV were isolated in 130 out of 666 cases (19.5% and 36 out of 666 (5.4%. HEV RNA was detected in 28.8% (231/801 and 3.0% (21/700 of the patients with meningitis and encephalitis, respectively. Children with ages ranging from 1 to 9 years accounted for 75.3% of the meningitis cases and from 1 to 4 years for 58% of acute flaccid paralysis patients

  3. Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Christensen, JK; Eugen-Olsen, Jesper; Sørensen, M

    2000-01-01

    No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain rea...... TTV viremia (Psuspected to be an opportunistic pathogen with an independent influence on HIV progression....

  4. Human Infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013

    NARCIS (Netherlands)

    Memish, Ziad A.; Cotten, Matthew; Meyer, Benjamin; Watson, Simon J.; Alsahafi, Abdullah J.; Al Rabeeah, Abdullah A.; Corman, Victor Max; Sieberg, Andrea; Makhdoom, Hatem Q.; Assiri, Abdullah; Al Masri, Malaki; Aldabbagh, Souhaib; Bosch, Berend Jan|info:eu-repo/dai/nl/273306049; Beer, Martin; Müller, Marcel A.; Kellam, Paul; Drosten, Christian

    2014-01-01

    We investigated a case of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) after exposure to infected camels. Analysis of the whole human-derived virus and 15% of the camel-derived virus sequence yielded nucleotide polymorphism signatures suggestive of cross-species

  5. Variations in cerebrospinal fluid viral loads among enterovirus genotypes in patients hospitalized with laboratory-confirmed meningitis due to enterovirus.

    Science.gov (United States)

    Volle, Romain; Bailly, Jean-Luc; Mirand, Audrey; Pereira, Bruno; Marque-Juillet, Stéphanie; Chambon, Martine; Regagnon, Christel; Brebion, Amélie; Henquell, Cécile; Peigue-Lafeuille, Hélène; Archimbaud, Christine

    2014-08-15

    Acute enterovirus (EV) meningitis is a major cause of hospitalization among adults and children. It is caused by multiple EV genotypes assigned to 4 species (EV-A, EV-B, EV-C, and EV-D). We determined viral loads in the cerebrospinal fluid (CSF) of 156 patients of all ages with EV meningitis during a 5-year observational prospective study. The virus strains were genotyped, and their time origin was determined with Bayesian phylogenetic methods. The CSF viral loads ranged between 3.4 and 7.5 log10 copies/mL (median, 4.9 log10 copies/mL). They were higher in neonates than in infants and children (P = .02) but were comparable in adults. Viral loads were associated with EV genotypes (P viral loads (P viral loads were in meningitis cases caused by coxsackievirus A9, B4, and B5 genotypes. Most patients infected by a same genotype were infected by a major virus variant of recent emergence. The variations in CSF viral loads in patients at the onset of EV meningitis are related to genotypic differences in the virus strains involved. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Factors Associated with Acquisition of Human Infective and Animal Infective Trypanosome Infections in Domestic Livestock in Western Kenya

    Science.gov (United States)

    von Wissmann, Beatrix; Machila, Noreen; Picozzi, Kim; Fèvre, Eric M.; deC. Bronsvoort, Barend M.; Handel, Ian G.; Welburn, Susan C.

    2011-01-01

    Background Trypanosomiasis is regarded as a constraint on livestock production in Western Kenya where the responsibility for tsetse and trypanosomiasis control has increasingly shifted from the state to the individual livestock owner. To assess the sustainability of these localised control efforts, this study investigates biological and management risk factors associated with trypanosome infections detected by polymerase chain reaction (PCR), in a range of domestic livestock at the local scale in Busia, Kenya. Busia District also remains endemic for human sleeping sickness with sporadic cases of sleeping sickness reported. Results In total, trypanosome infections were detected in 11.9% (329) out of the 2773 livestock sampled in Busia District. Multivariable logistic regression revealed that host species and cattle age affected overall trypanosome infection, with significantly increased odds of infection for cattle older than 18 months, and significantly lower odds of infection in pigs and small ruminants. Different grazing and watering management practices did not affect the odds of trypanosome infection, adjusted by host species. Neither anaemia nor condition score significantly affected the odds of trypanosome infection in cattle. Human infective Trypanosoma brucei rhodesiense were detected in 21.5% of animals infected with T. brucei s.l. (29/135) amounting to 1% (29/2773) of all sampled livestock, with significantly higher odds of T. brucei rhodesiense infections in T. brucei s.l. infected pigs (OR = 4.3, 95%CI 1.5-12.0) than in T. brucei s.l. infected cattle or small ruminants. Conclusions Although cattle are the dominant reservoir of trypanosome infection it is unlikely that targeted treatment of only visibly diseased cattle will achieve sustainable interruption of transmission for either animal infective or zoonotic human infective trypanosomiasis, since most infections were detected in cattle that did not exhibit classical clinical signs of

  7. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    Science.gov (United States)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  8. Non-polio enteroviruses in acute flaccid paralysis children of India: vital assessment before polio eradication.

    Science.gov (United States)

    Dhole, Tapan N; Ayyagari, Archana; Chowdhary, Rashmi; Shakya, Akhalesh K; Shrivastav, Nikky; Datta, Tapas; Prakash, Vijay

    2009-01-01

    This study is an overview of non-polio enterovirus (NPEV) circulating in North India studied from the perspective of poliomyelitis eradication. Wild polio cases declined because of intensive oral polio vaccine immunization. As we approach global eradication of poliovirus (PV), NPEV causing acute flaccid paralysis (AFP) are equal cause of concern. A total of 46 653 AFP samples (World Health Organization) and apparently 1000 healthy contacts living in the same geographical area were studied (2004-2007). Serological identification of NPEV was done using RIVM-specific pools (The Netherlands). Untyped (UT)-NPEVs were sequenced directly from reverse transcription-polymerase chain reaction using pan-enterovirus (Pan-EV) primer (CDC, Atlanta, GA) targeting highly conserved 5'un-translated regions of the enterovirus. In this study, 12 513 NPEVs were isolated from the collected stool samples. Seroneutralization had identified 67% of NPEV isolates, whereas 32.6% remained as UT- NPEV. Of the typed NPEVs, Coxsackie-B accounted for 32.3%; followed by echoviruses-11, 12, 13, 7 between 8 and 28%. In sequencing few UT-NPEVs, some were identified also as echovirus-30, 11 and 18 which were probably present in mixtures as they remained UT-NPEV in ENT. Newly classified human enterovirus virus-86 (HEV) (EU079026), HEV-97(EU071767) and HEV-B isolate (EU071768) were isolated in AFP samples. This study provided definitive information about circulation, prevalence and new emerging NPEV in the polio-endemic region of India, hence they should be considered in AFP surveillance. This would help in adopting and planning new strategies in post-PV eradication era in the country. This is the right time to prepare for the future tasks while we head towards a polio-free region.

  9. Humanized chimeric mouse models of hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Suwan Sun

    2017-06-01

    Full Text Available Hepatitis B virus (HBV infection is associated with an increased risk of hepatic cirrhosis, hepatocellular carcinoma, fulminant hepatitis and end-stage hepatic failure. Despite the availability of anti-HBV therapies, HBV infection remains a major global public health problem. Developing an ideal animal model of HBV infection to clarify the details of the HBV replication process, the viral life cycle, the resulting immunoresponse and the precise pathogenesis of HBV is difficult because HBV has an extremely narrow host range and almost exclusively infects humans. In this review, we summarize and evaluate animal models available for studying HBV infection, especially focusing on humanized chimeric mouse models, and we discuss future development trends regarding immunocompetent humanized mouse models that can delineate the natural history and immunopathophysiology of HBV infection.

  10. Oesophageal Ulceration in Human Immunodeficiency Virus Infected ...

    African Journals Online (AJOL)

    Objective. To determine the aetiology of oesophageal ulceration in HIV-infected patients. Design. A retrospective clinical, endoscopic and histopathological analysis of patients with confirmed HIV infection and an oesophageal ulcer diagnosed on endoscopy. Setting. A tertiary referral, gastrointestinal clinic in Cape Town.

  11. Human cytomegalovirus infections in premature infants by ...

    African Journals Online (AJOL)

    Freezing breast milk may be protective for the preterm infant until the titer of CMV antibody increases. However clinical importance of CMV infection in premature infants by breast-feeding is still unclear. This minireview focuses on recent advances in the study of CMV infection in premature infants by breastfeeding.

  12. Laboratory diagnosis of persistent human chlamydial infection

    Directory of Open Access Journals (Sweden)

    Mirja ePuolakkainen

    2013-12-01

    Full Text Available Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data.

  13. Human immunodeficiency virus (HIV) infection in tuberculosis ...

    African Journals Online (AJOL)

    BACKGROUND: In a country with a rapidly spreading HIV epidemic information regarding HIV and TB Co-infection are lacking. OBJECTIVES: To determine the prevalence of HIV infection in a representative sample of sputum-positive tuberculosis patients. METHODS: A cross-sectional survey whereby blood sample was ...

  14. Enterovirus 71 Brainstem Encephalitis and Cognitive and Motor Deficits

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-12-01

    Full Text Available Follow-up studies were conducted in 63 previously healthy children with enterovirus 71 brainstem encephalitis (49 stage II, 7 stage Ilia, and 7 stage Illb at National Cheng Kung University Hospital, Tainan, Taiwan.

  15. Enterovirus species and serotype distributions in monthly municipal wastewater samples

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset contains the enterovirus genome copies measured per liter of sample and read counts obtained from amplicon sequencing of the VP1 and VP4 genes. This...

  16. Use of an Innovative Web-Based Laboratory Surveillance Platform to Analyze Mixed Infections Between Human Metapneumovirus (hMPV and Other Respiratory Viruses Circulating in Alberta (AB, Canada (2009–2012

    Directory of Open Access Journals (Sweden)

    Shamir Mukhi

    2012-11-01

    Full Text Available We investigated the proportions of mono vs. mixed infections for human metapneumovirus (hMPV as compared to adenovirus (ADV, four types of coronavirus (CRV, parainfluenza virus (PIV, RSV, and enterovirus/rhinovirus (ERV in Alberta, Canada. Using the Data Integration for Alberta Laboratories (DIAL platform, 26,226 respiratory specimens at ProvLab between 1 July 2009 and 30 June 2012 were selected and included in the study. Using the Respiratory Virus Panel these specimens tested positive for one or more respiratory virus and negative for influenza A and B. From our subset hMPV was the fourth most common virus (n=2,561 with 373 (15% identified as mixed infection using DIAL. Mixed infection with hMPV was most commonly found in infants less than 6 months old and ERV was most commonly found in mixed infection with hMPV (230/373, 56% across all age groups. The proportion of mixed-infection vs. mono-infection was highest for ADV (46%, followed by CRV 229E (32%, CRV HKU1 (31%, CRV NL63 (28%, CRV OC43 (23%, PIV (20%, RSV (17%, hMPV (15% and ERV (13%. hMPV was significantly more likely to be identified in mono infection as compared with ADV, CRV, PIV, and RSV with the exception of ERV [p < 0.05].

  17. Adaptation of enterovirus 71 to adult interferon deficient mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  18. Human muscle satellite cells as targets of Chikungunya virus infection.

    Directory of Open Access Journals (Sweden)

    Simona Ozden

    Full Text Available BACKGROUND: Chikungunya (CHIK virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells, and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. CONCLUSIONS/SIGNIFICANCE: This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans.

  19. Molecular evolution of enterovirus 68 detected in the Philippines.

    Directory of Open Access Journals (Sweden)

    Tadatsugu Imamura

    Full Text Available BACKGROUND: Detection of Enterovirus 68 (EV68 has recently been increased. However, underlying evolutionary mechanism of this increasing trend is not fully understood. METHODS: Nasopharyngeal swabs were collected from 5,240 patients with acute respiratory infections in the Philippines from June 2009 to December 2011. EV68 was detected by polymerase chain reaction (PCR targeting for 5' untranslated region (5'UTR, viral protein 1 (VP1, and VP4/VP2. Phylogenetic trees were generated using the obtained sequences. RESULTS: Of the 5,240 tested samples, 12 EV68 positive cases were detected between August and December in 2011 (detection rate, 0.23%. The detection rate was higher among inpatients than outpatients (p<0.0001. Among VP1 sequences detected from 7 patients in 2011, 5 in lineage 2 were diverged from those detected in the Philippines in 2008, however, 2 in lineage 3 were not diverged from strains detected in the Philippines in 2008 but closely associated with strains detected in the United States. Combined with our previous report, EV68 occurrences were observed twice in the Philippines within the last four years. CONCLUSIONS: EV68 detections might be occurring in cyclic patterns, and viruses might have been maintained in the community while some strains might have been newly introduced.

  20. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  1. Transient Oral Human Cytomegalovirus Infections Indicate Inefficient Viral Spread from Very Few Initially Infected Cells.

    Science.gov (United States)

    Mayer, Bryan T; Krantz, Elizabeth M; Swan, David; Ferrenberg, James; Simmons, Karen; Selke, Stacy; Huang, Meei-Li; Casper, Corey; Corey, Lawrence; Wald, Anna; Schiffer, Joshua T; Gantt, Soren

    2017-06-15

    Cytomegalovirus (CMV) is acquired by the oral route in children, and primary infection is associated with abundant mucosal replication, as well as the establishment of latency in myeloid cells that results in lifelong infection. The efficiency of primary CMV infection in humans following oral exposure, however, is unknown. We consistently detected self-limited, low-level oral CMV shedding events, which we termed transient CMV infections, in a prospective birth cohort of 30 highly exposed CMV-uninfected infants. We estimated the likelihood of transient oral CMV infections by comparing their observed frequency to that of established primary infections, characterized by persistent high-level shedding, viremia, and seroconversion. We developed mathematical models of viral dynamics upon initial oral CMV infection and validated them using clinical shedding data. Transient infections comprised 76 to 88% of oral CMV shedding events. For this high percentage of transient infections to occur, we identified two mathematical prerequisites: a very small number of initially infected oral cells (1 to 4) and low viral infectivity (<1.5 new cells infected/cell). These observations indicate that oral CMV infection in infants typically begins with a single virus that spreads inefficiently to neighboring cells. Thus, although the incidence of CMV infection is high during infancy, our data provide a mechanistic framework to explain why multiple CMV exposures are typically required before infection is successfully established. These findings imply that a sufficiently primed immune response could prevent CMV from establishing latent infection in humans and support the achievability of a prophylactic CMV vaccine. IMPORTANCE CMV infects the majority of the world's population and is a major cause of birth defects. Developing a vaccine to prevent CMV infection would be extremely valuable but would be facilitated by a better understanding of how natural human CMV infection is acquired. We

  2. Severe respiratory tract infections with human bocavirus in children

    Directory of Open Access Journals (Sweden)

    Halise Akça, Nilden Tuygun, Emine Polat, Can Demir Karacan

    2016-09-01

    Full Text Available Acute respiratory tract infection remains a major cause of childhood hospitalization and mortality in young children. Human bocavirus (HBoV is a virus belonging to the Parvoviridae family, which has been newly discovered to be associated with respiratory tract infection in children. Human bocavirus infection is usually seen as form of co-infection. The frequent associations of HBoV with other respiratory viruses might be explained by the persistence of HBoV in the respiratory tract. HBoV primary events generally associated with mild respiratory illness. Here, we reported three patients who developed an extremely severe acute life-threatening respiratory failure due to HBoV infection. J Microbiol Infect Dis 2016; 6(3: 145-147

  3. Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

    Directory of Open Access Journals (Sweden)

    Juliana Assis Silva Gomes

    2012-01-01

    Full Text Available In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV. Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans.

  4. No evidence for ape Plasmodium infections in humans in Gabon.

    Science.gov (United States)

    Délicat-Loembet, Lucresse; Rougeron, Virginie; Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.

  5. Neutralizing Antibodies to Enterovirus 71 in Belém, Brazil

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes C Gomes

    2002-01-01

    Full Text Available Non-polio enteroviruses (Coxsackievirus A, Coxsackievirus B, Echovirus and EV 68-72 which belong to the enterovirus (EV genus, Picornaviridae family, may be responsible for acute flaccid paralysis, aseptic meningitis, myocarditis, hepatitis, pleurodinia, neonatal sepsis, hand, foot and mouth disease (HFMD even though 50-80% of infections are asymptomatic. EV 71 has been responsible for outbreaks and epidemics of HFMD and acute neurologic disease justifying its study in our country. The aim of this study was to detect neutralizing antibodies (NtAb to EV 71 in individuals up to 15 years of age living in Belém, State of Pará, northern Brazil. Serum samples from 238 patients attending the Virology Sector of Evandro Chagas Institute in Belém, Brazil, were analyzed using microneutralization tests that included RD cells and BrCr strain. Overall 40.8% (97/238 of tested samples had NtAb to EV 71. Regarding the distribution per age group, 85.2% (92/108 of patients aged 0-3 years had no NtAb to this virus and 69.2% of those 12 to15 years of age were seropositive. These results confirm that EV 71 infection occurs in the city of Belém; and that a high rate of individuals in this study were infected aged 3 years and over and, when aged 15 years nearly 70% had EV 71 NtAb.

  6. Enterovirus-71 genotype C isolated in Peru between 2006 and 2009.

    Science.gov (United States)

    Huaman, Jose L; Carrion, Gladys; Ampuero, Julia S; Ocaña, Victor; Laguna-Torres, V Alberto; Hontz, Robert D

    2016-12-01

    Enterovirus-71 (EV71) was first isolated in California, United States in 1969, belongs to the genus Enterovirus, family Picornaviridae. Although infection normally causes mild, often undiagnosed illness, it can cause central nervous system infections that could turn fatal. Based on VP1 gene analysis, EV71 has been classified into six separate genotypes. Although the molecular epidemiology of EV71 has been well described via studies originating from Asia and Europe, it is mostly unknown in South America. From our study, four EV71 isolates from Peru were characterized using phylogenetic methods to determine their relationship with known reference strains. These four Peruvian EV71 isolates from between 2006 and 2009 were analyzed by RT-PCR using primers capable of amplifying the entire VP1 gene. Reference strains representing all six known genotypes were used to determine any recognizable phylogenetic relationships. In fact, all of our isolates clustered together within the genotype C1 lineage- separate from Asian, European, North American, and Australian strains. We present evidence that EV71 genotype C1 exists in Peru, and this is the first such report documenting EV71 genotype C1 circulating in South America. Gathering additional isolates will help elucidate a more complete global epidemiological picture of EV71 infections. Published by Elsevier B.V.

  7. Primary and secondary infection with human parvovirus B19 in ...

    African Journals Online (AJOL)

    Primary and secondary infection with human parvovirus. B19 in pregnant women in South Africa ... I Infection during pregnancy may lead to fetal loss, especially during the second trimester, because of severe ... IgG antibodies) with viruses such as rubella: cyto- megalovirus' and varicella." Subjects and methods. A total of 1 ...

  8. Human papillomavirus infection and disease in men: Impact of HIV

    African Journals Online (AJOL)

    2 London School of Hygiene and Tropical Medicine, London, United Kingdom. Corresponding author: S Delany-Moretlwe (sdelany@wrhi.ac.za). Human papillomavirus (HPV) is a common sexually transmitted infection (STI) affecting both men and women.[1] HPV infections can be classified as either low- (LR) or high-risk ...

  9. Knowledge of Human Papillomavirus Infection and Acceptability of ...

    African Journals Online (AJOL)

    Introduction: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and has been implicated in over 70% of cases of cervical cancer. This study assessed the knowledge of HPV infection and acceptability of HPV vaccination among nursing students in Benin City. Methodology: A ...

  10. Adenovirus infection reverses the antiviral state induced by human interferon.

    Science.gov (United States)

    Feduchi, E; Carrasco, L

    1987-04-06

    HeLa cells treated with human lymphoblastoid interferon do not synthesize poliovirus proteins. The antiviral state against poliovirus is reversed if cells are previously infected with adenovirus type 5. A late gene product seems to be involved in this reversion, since no effect is observed at early stages of infection or in the presence of aphidicolin.

  11. Cardiovascular implications from untreated human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Lundgren, Jens D

    2011-01-01

    Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk...

  12. malaria parasitaemia among febrile children infected with human

    African Journals Online (AJOL)

    2014-01-01

    Jan 1, 2014 ... MALARIA PARASITAEMIA AMONG FEBRILE CHILDREN INFECTED WITH. HUMAN IMMUNODEFICIENCY VIRUS IN THE CONTEXT OF PROPHYLACTIC. COTRIMOXAZOLE AS STANDARD OF CARE: A CROSS- SECTIONAL SURVEY. IN WESTERN KENYA. I. K. MARETE, M. MUTUGI, Z. LAGAT, ...

  13. Human immunodeficiency virus infection presenting as a fatal case ...

    African Journals Online (AJOL)

    MJP

    2015-06-25

    CMV), Epstein-. Barr virus (EBV), Hepatitis B and C virus,. Mycoplasma. Pneumoniae,. Haemophilus influenzae and Campylobacter jejuni have all been implicated in. GBS.[6]. Human immunodeficiency virus (HIV) infection has ...

  14. Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein

    Directory of Open Access Journals (Sweden)

    Kiener Tanja K

    2012-02-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 has emerged as a major causative agent of hand, foot and mouth disease in the Asia-Pacific region over the last decade. Hand, foot and mouth disease can be caused by different etiological agents from the enterovirus family, mainly EV71 and coxsackieviruses, which are genetically closely related. Nevertheless, infection with EV71 may occasionally lead to high fever, neurologic complications and the emergence of a rapidly fatal syndrome of pulmonary edema associated with brainstem encephalitis. The rapid progression and high mortality of severe EV71 infection has highlighted the need for EV71-specific diagnostic and therapeutic tools. Monoclonal antibodies are urgently needed to specifically detect EV71 antigens from patient specimens early in the infection process. Furthermore, the elucidation of viral epitopes will contribute to the development of targeted therapeutics and vaccines. Results We have identified the monoclonal antibody 7C7 from a screen of hybridoma cells derived from mice immunized with the EV71-B5 strain. The linear epitope of 7C7 was mapped to amino acids 142-146 (EDSHP of the VP2 capsid protein and was characterized in detail. Mutational analysis of the epitope showed that the aspartic acid to asparagine mutation of the EV71 subgenogroup A (BrCr strain did not interfere with antibody recognition. In contrast, the serine to threonine mutation at position 144 of VP2, present in recently emerged EV71-C4 China strains, abolished antigenicity. Mice injected with this virus strain did not produce any antibodies against the VP2 protein. Immunofluorescence and Western blotting confirmed that 7C7 specifically recognized EV71 subgenogroups and did not cross-react to Coxsackieviruses 4, 6, 10, and 16. 7C7 was successfully used as a detection antibody in an antigen-capture ELISA assay. Conclusions Detailed mapping showed that the VP2 protein of Enterovirus 71 contains a single, linear, non

  15. Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.

    Science.gov (United States)

    Zhong, Ting; Zhang, Li-Ying; Wang, Zeng-Yan; Wang, Yue; Song, Feng-Mei; Zhang, Ya-Hong; Yu, Jing-Hua

    2017-03-01

    Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

  16. RSV Infection in Human Macrophages Promotes CXCL10/IP-10 Expression during Bacterial Co-Infection

    Directory of Open Access Journals (Sweden)

    Daniela Machado

    2017-12-01

    Full Text Available Respiratory syncytial virus (RSV, a major etiologic agent of acute lower respiratory infection constitutes the most important cause of death in young children worldwide. Viral/bacterial mixed infections are related to severity of respiratory inflammatory diseases, but the underlying mechanisms remain poorly understood. We have previously investigated the intracellular mechanisms that mediate the immune response in the context of influenza virus/Streptococcus pneumoniae (Sp co-infection using a model of human monocyte-derived macrophages (MDMs. Here, we set up and characterized a similar model of MDMs to investigate different scenarios of RSV infection and co-infection with Sp. Our results suggest that Sp contributes to a faster and possibly higher level of CXCL10/IP-10 expression induced by RSV infection in human MDMs.

  17. A DNA Vaccine Protects Human Immune Cells against Zika Virus Infection in Humanized Mice

    Directory of Open Access Journals (Sweden)

    Guohua Yi

    2017-11-01

    Full Text Available A DNA vaccine encoding prM and E protein has been shown to induce protection against Zika virus (ZIKV infection in mice and monkeys. However, its effectiveness in humans remains undefined. Moreover, identification of which immune cell types are specifically infected in humans is unclear. We show that human myeloid cells and B cells are primary targets of ZIKV in humanized mice. We also show that a DNA vaccine encoding full length prM and E protein protects humanized mice from ZIKV infection. Following administration of the DNA vaccine, humanized DRAG mice developed antibodies targeting ZIKV as measured by ELISA and neutralization assays. Moreover, following ZIKV challenge, vaccinated animals presented virtually no detectable virus in human cells and in serum, whereas unvaccinated animals displayed robust infection, as measured by qRT-PCR. Our results utilizing humanized mice show potential efficacy for a targeted DNA vaccine against ZIKV in humans.

  18. Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells.

    Science.gov (United States)

    Laucirica, Daniel R; Triantis, Vassilis; Schoemaker, Ruud; Estes, Mary K; Ramani, Sasirekha

    2017-09-01

    Background: Oligosaccharides in milk act as soluble decoy receptors and prevent pathogen adhesion to the infant gut. Milk oligosaccharides reduce infectivity of a porcine rotavirus strain; however, the effects on human rotaviruses are less well understood. Objective: In this study, we determined the effect of specific and abundant milk oligosaccharides on the infectivity of 2 globally dominant human rotavirus strains. Methods: Four milk oligosaccharides-2'-fucosyllactose (2'FL), 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), and galacto-oligosaccharides-were tested for their effects on the infectivity of human rotaviruses G1P[8] and G2P[4] through fluorescent focus assays on African green monkey kidney epithelial cells (MA104 cells). Oligosaccharides were added at different time points in the infectivity assays. Infections in the absence of oligosaccharides served as controls. Results: When compared with infections in the absence of glycans, all oligosaccharides substantially reduced the infectivity of both human rotavirus strains in vitro; however, virus strain-specific differences in effects were observed. Compared with control infections, the maximum reduction in G1P[8] infectivity was seen with 2'FL when added after the onset of infection (62% reduction, P < 0.01), whereas the maximum reduction in G2P[4] infectivity was seen with the mixture of 3'SL + 6'SL when added during infection (73% reduction, P < 0.01). The mixture of 3'SL + 6'SL at the same ratio as is present in breast milk was more potent in reducing G2P[4] infectivity (73% reduction, P < 0.01) than when compared with 3'SL (47% reduction) or 6'SL (40% reduction) individually. For all oligosaccharides the reduction in infectivity was mediated by an effect on the virus and not on the cells. Conclusions: Milk oligosaccharides reduce the infectivity of human rotaviruses in MA104 cells, primarily through an effect on the virus. Although breastfed infants are directly protected, the addition of specific

  19. Molecular epidemiological study of enteroviruses associated with encephalitis in children from India.

    Science.gov (United States)

    Kumar, Arvind; Shukla, Deepti; Kumar, Rashmi; Idris, Mohammad Z; Misra, Usha K; Dhole, Tapan N

    2012-11-01

    Enteroviruses have been reported in encephalitis cases. However, clinical and epidemiological characteristics of enteroviruses in encephalitis are not fully established. We prospectively investigated 204 children with encephalitis over a period of 2 years (2009 to 2010) for enterovirus. Enterovirus was detected in 45 specimens (22.1%); of these, 40 were typed by seminested reverse transcription-PCR (RT-PCR) and sequencing of the VP1 gene. Molecular typing of enterovirus revealed the predominance of echovirus 21 associated with an epidemic during the rainy seasons of 2010 and the circulation of echovirus 1, coxsackievirus B1, enterovirus 75, enterovirus 76, coxsackievirus B5, and echovirus 19. The nucleotide divergence among echovirus 21 strains was 0 to 2% at the nucleotide level. This study suggests that enterovirus is an important cause of encephalitis in children from India. To our knowledge, this is the first report of echovirus 21 in encephalitis cases worldwide.

  20. Serodiagnosis of Helicobacter pylori infection in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Nielsen, H; Andersen, L P

    1995-01-01

    In contrast to the established role of Helicobacter pylori gastritis in gastritis and duodenal ulcer in general, conflicting results have been reported in patients with human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome. The seroprevalence during early HIV...

  1. Update on human immunodeficiency virus (HIV)-2 infection.

    Science.gov (United States)

    Campbell-Yesufu, Omobolaji T; Gandhi, Rajesh T

    2011-03-15

    Infection with human immunodeficiency virus type 2 (HIV-2) occurs mainly in West Africa, but an increasing number of cases have been recognized in Europe, India, and the United States. In this era of global integration, clinicians must be aware of when to consider the diagnosis of HIV-2 infection and how to test for this virus. Although there is debate regarding when therapy should be initiated and which regimen should be chosen, recent trials have provided important information on treatment options for HIV-2 infection. In this review, we present information on recent clinical advances in our understanding of HIV-2 infection and highlight remaining diagnostic and therapeutic challenges.

  2. Neopterin and human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Hofmann, B

    1993-01-01

    to predict the later development of AIDS. The increased neopterin concentrations show that the immune system is activated in HIV infection and demonstrate the presence of an interaction between the virus and the immune system. The most important future use of neopterin measurements may be in fast evaluation...

  3. Brucella neotomae Infection in Humans, Costa Rica.

    Science.gov (United States)

    Suárez-Esquivel, Marcela; Ruiz-Villalobos, Nazareth; Jiménez-Rojas, César; Barquero-Calvo, Elías; Chacón-Díaz, Carlos; Víquez-Ruiz, Eunice; Rojas-Campos, Norman; Baker, Kate S; Oviedo-Sánchez, Gerardo; Amuy, Ernesto; Chaves-Olarte, Esteban; Thomson, Nicholas R; Moreno, Edgardo; Guzmán-Verri, Caterina

    2017-06-01

    Several species of Brucella are known to be zoonotic, but B. neotomae infection has been thought to be limited to wood rats. In 2008 and 2011, however, B. neotomae was isolated from cerebrospinal fluid of 2 men with neurobrucellosis. The nonzoonotic status of B. neotomae should be reassessed.

  4. Avian Influenza Infection in Humans

    African Journals Online (AJOL)

    Pulmonology Unit, Department of Medicine,. University College Hospital, Ibadan. INTRODUCTION _ ... saliva, nasal secretions and faeces. Susceptible birds become infected when they have contact with con- .... ing and immunofluorescence[l4, 1 5]. Laboratory tests are required for specific identification of avian. influenza.

  5. Establishing China's national standards of antigen content and neutralizing antibody responses for evaluation of enterovirus 71 (EV71) vaccines.

    Science.gov (United States)

    Liang, Zhenglun; Mao, Qunying; Gao, Qiang; Li, Xiuling; Dong, Chenghong; Yu, Xiang; Yao, Xin; Li, Fengxiang; Yin, Weidong; Li, Qihan; Shen, Xinliang; Wang, Junzhi

    2011-12-06

    Enterovirus 71 (EV71) is a highly infectious agent that causes hand-foot-mouth disease (HFMD) in humans. Effective vaccination against EV71 infection is critically important, given the recent outbreak of HFMD in the Asia-Pacific region, where it has shown significant mortality and morbidity. There is currently no approved anti-viral therapy available to treat the disease. While several vaccine manufacturers are actively developing EV71 vaccines, there are no international reference standards available to conduct quality control on EV71 vaccines or to assess the effectiveness of EV71 vaccines in immunized populations. In the current report, antigen reference standard based on the C4 subtype of the EV71 vaccine strain was developed. In addition, neutralizing antibody (NTAb) reference panels were analyzed and standards with various neutralizing titers were selected. These reference antigens were used to calibrate vaccine samples from several producers and found that five EV71 antigens and the national reference standards showed good linearity and parallelism. Moreover, mice immunized with various vaccines at doses standardized by these national references showed comparable NTAb responses. Finally, the national NTAb reference panels were found to effectively reduce assay discrepancy between different labs. Taken together, these national reference standards are highly valuable for the standardization and evaluation of EV71 vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Genital human papillomavirus infection in Panama City prostitutes.

    Science.gov (United States)

    Reeves, W C; Arosemena, J R; Garcia, M; de Lao, S L; Cuevas, M; Quiroz, E; Caussy, D; Rawls, W E

    1989-10-01

    Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present.

  7. Laboratory and Clinical Aspects of Human Herpesvirus 6 Infections

    Science.gov (United States)

    Bonnafous, Pascale; Gautheret-Dejean, Agnès

    2015-01-01

    SUMMARY Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and

  8. Fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from Wenzhou, China.

    Science.gov (United States)

    Guo, Wen-Ping; Lin, Xian-Dan; Chen, Yi-Ping; Liu, Qi; Wang, Wen; Wang, Cai-Qiao; Li, Ming-Hui; Sun, Xiao-Yu; Shi, Mang; Holmes, Edward C; Zhang, Yong-Zhen

    2015-09-01

    Although hand, foot, and mouth disease (HFMD) is a major public concern in China, the prevalence and clinical symptoms associated with the different agents of HFMD in this country remain poorly understood. We investigated the clinical and molecular characteristics of enteroviruses in patients with HFMD from Wenzhou, China. Patients with laboratory-confirmed HFMD admitted to the Yuying Children's Hospital in Wenzhou, China during 2013 were included in this study. Viral RNA sequences were amplified using RT-PCR, determined by sequencing, and compared by phylogenetic analysis. A total of 955 clinically diagnosed HFMD cases were determined using PCR, with whole viral genomes obtained for each enterovirus type. 14 types of enterovirus belonging to two viral species were identified. Notably, Coxsackievirus A6 (CV-A6) was the most common species detected (77.8%), followed by EV-A71 (8.2%) and CV-A10 (8.1%). Phylogenetic analysis revealed multiple independent introductions of these viruses into Wenzhou. In addition, the enterovirus observed in Wenzhou had a recombinant history, with two or three recombination breakpoints. Although the illness associated with CV-A6 was milder than that of EV-A71, CV-A6 infection caused more widespread rash, larger blisters, and subsequent skin peeling and/or nail shedding. Our study revealed the co-circulation of 14 types of enteroviruses in a single location - Wenzhou, China - with CV-A6 virus the predominant agent of HFMD. This work highlights the need to perform larger-scale surveillance to fully understand the epidemiology of enteroviruses in China and the wider Asia-Pacific region. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Detection of enteroviruses ribonucleic acid sequences in endomyocardial tissue from adult patients with chronic dilated cardiomyopathy by a rapid RT-PCR and hybridization assay.

    Science.gov (United States)

    Rey, L; Lambert, V; Wattré, P; Andréoletti, L

    2001-06-01

    A rapid reverse transcription polymerase chain reaction (RT-PCR) and microwell capture hybridisation assay with general specificity for enteroviruses was developed and compared with an improved nested RT-PCR for the detection of enteroviral RNA sequences in endomyocardial tissue from patients with chronic dilated cardiomyopathy. This method could detect as few as 20 genomic RNA copies per 100 mg of heart tissue homogenate and results could be obtained within 8 hours. Of the 55 biopsy specimens aseptically collected from the explanted hearts of 55 patients, 21 (38.2%) were positive by RT-PCR microplate assay, whereas only 19 (34.5%) were positive by nested RT-PCR assay and none were positive by classical cell culture assays. No enterovirus was detectable by RT-PCR or classical cell culture assays in any of the 55 heart biopsy specimens taken from organ donors without any known heart disease. Moreover, the nucleotide sequences of EV nested RT-PCR products showed greatest similarity to group B Coxsackieviruses [CVB3 (n = 12) or CVB5 (n = 3)], but also to group A Coxsackieviruses (CVA21 (n = 1) or CVA9 ( n= 3)]. The described RT-PCR and microwell capture hybridisation assay can be applied to the virological diagnosis of human enteroviral cardiac infections. Moreover our findings suggest that group B and group A Coxsackieviruses can persist in heart tissue from patients with end-stage chronic cardiomyopathy, supporting the hypothesis that these viruses could be implicated in the etiology of idiopathic dilated cardiomyopathy. Copyright 2001 Wiley-Liss, Inc.

  10. PREVALENCE OF INFECTION WITH HUMAN HERPESVIRUS ...

    African Journals Online (AJOL)

    were tuberculosis suspects but had no active STD (25 women and 25 men), 50 patients with a proven STD, and 36 paediatric inpatients ~th a variety of .... Frottier J. Detection of human herpesvirus 8 DNA sequences before the appearance of Kaposi's sarcoma in human immunodeficiency virus (HIV}-positive subjects with a ...

  11. West Nile Virus: Biology, Transmission, and Human Infection

    Science.gov (United States)

    Colpitts, Tonya M.; Conway, Michael J.; Montgomery, Ruth R.

    2012-01-01

    Summary: West Nile Virus was introduced into the Western Hemisphere during the late summer of 1999 and has been causing significant and sometimes severe human diseases since that time. This article briefly touches upon the biology of the virus and provides a comprehensive review regarding recent discoveries about virus transmission, virus acquisition, and human infection and disease. PMID:23034323

  12. Human Dobrava-Belgrade hantavirus infection, Kosovo.

    Science.gov (United States)

    Emmerich, Petra; Müller, Nicole; Heinemann, Patrick; Rother, Enno; Jakupi, Xhevat; Günther, Stephan; Cadar, Daniel; Schmidt-Chanasit, Jonas

    2014-11-01

    Here we describe an acute Dobrava-Belgrade virus (DOBV) infection that presented as severe hemorrhagic fever with renal syndrome (HFRS) in an active-duty U.S. soldier. The infection was acquired in northern Kosovo in spring 2013. Amplification of DOBV genome segments directly from the patient's serum sample was successfully performed. Phylogenetic analysis demonstrated that the strain belong to DOBV genotype Dobrava and is closely related to strains circulating in Southeast Europe and Slovakia. Thus, our case confirms that DOBV genotype Dobrava is able to cause a severe form of HFRS, especially when compared to the other less pathogenic DOBV genotypes. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Four Human Cases of Diphyllobothrium latum Infection

    Science.gov (United States)

    Choi, Hee-Jung; Lee, Junghye

    2012-01-01

    Diphyllobothrium latum infections in 4 young Korean men detected from 2008 to 2012 are presented. Three were diagnosed based on spontaneously discharged strobila of the adult worm in their feces, and 1 case was diagnosed by finding the worm at colonoscopy examination in a local clinic. The morphologic characteristics of the gravid proglottid and eggs were consistent with D. latum. All patients were treated with praziquantel 15 mg/kg, and follow-up stool examinations were done at 2 months after the medication. The main clinical complaints were intermittent gastrointestinal troubles such as indigestion, abdominal distension, and spontaneous discharge of tapeworm's segments in their feces. The most probable source of infection was the flesh of salmon or trout according to a patient's past history. These are the 45th to 48th recorded cases diagnosed by the adult worm in the Republic of Korea since 1971. PMID:22711926

  14. Mycobacterium abscessus Complex Infections in Humans.

    Science.gov (United States)

    Lee, Meng-Rui; Sheng, Wang-Huei; Hung, Chien-Ching; Yu, Chong-Jen; Lee, Li-Na; Hsueh, Po-Ren

    2015-09-01

    Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that are responsible for a wide spectrum of skin and soft tissue diseases, central nervous system infections, bacteremia, and ocular and other infections. M. abscessus complex is differentiated into 3 subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. The 2 major subspecies, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense, have different erm(41) gene patterns. This gene provides intrinsic resistance to macrolides, so the different patterns lead to different treatment outcomes. M. abscessus complex outbreaks associated with cosmetic procedures and nosocomial transmissions are not uncommon. Clarithromycin, amikacin, and cefoxitin are the current antimicrobial drugs of choice for treatment. However, new treatment regimens are urgently needed, as are rapid and inexpensive identification methods and measures to contain nosocomial transmission and outbreaks.

  15. Salmonella, a cross-kingdom pathogen infecting humans and plants.

    Science.gov (United States)

    Hernández-Reyes, Casandra; Schikora, Adam

    2013-06-01

    Infections with non-typhoidal Salmonella strains are constant and are a non-negligible threat to the human population. In the last two decades, salmonellosis outbreaks have increasingly been associated with infected fruits and vegetables. For a long time, Salmonellae were assumed to survive on plants after a more or less accidental infection. However, this notion has recently been challenged. Studies on the infection mechanism in vegetal hosts, as well as on plant immune systems, revealed an active infection process resembling in certain features the infection in animals. On one hand, Salmonella requires the type III secretion systems to effectively infect plants and to suppress their resistance mechanisms. On the other hand, plants recognize these bacteria and react to the infection with an induced defense mechanism similar to the reaction to other plant pathogens. In this review, we present the newest reports on the interaction between Salmonellae and plants. We discuss the possible ways used by these bacteria to infect plants as well as the plant responses to the infection. The recent findings indicate that plants play a central role in the dissemination of Salmonella within the ecosystem. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  16. Potential Therapy for Neisseria Gonorrhoeae Infections With Human Chorionic Gonadotropin.

    Science.gov (United States)

    Rao, C V

    2015-12-01

    The scientific evidence suggests that Neisseria gonorrhoeae (NG) infects human fallopian tubes by molecular mimicry in which pathogens act like a ligand to bind to epithelial cell surface human chorionic gonadotrophin (hCG)/luteinizing hormone (LH) receptors. The hCG-like molecule has been identified as ribosomal protein L12 in NG coat surface. Human fallopian tube epithelial cells have been shown to contain functional hCG/LH receptors. As previously shown in human fallopian tube organ and cell culture studies, cellular invasion and infection can be prevented by exposing the cells to excess hCG, which would outnumber and outcompete NG for receptor binding. Based on these data, we suggest testing hCG in clinical trials on infected women. © The Author(s) 2015.

  17. Non-Human Primate Models of Orthopoxvirus Infections

    Directory of Open Access Journals (Sweden)

    Anne Schmitt

    2014-06-01

    Full Text Available Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV, the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

  18. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection.

    Science.gov (United States)

    de Repentigny, Louis; Lewandowski, Daniel; Jolicoeur, Paul

    2004-10-01

    Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4(+) cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8(+) T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal.

  19. Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates.

    Science.gov (United States)

    Lim, Pei-Yin; Hickey, Andrew C; Jamiluddin, Mohamad F; Hamid, Sharifah; Kramer, Joshua; Santos, Rosemary; Bossart, Katharine N; Cardosa, M Jane

    2015-11-04

    A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 μg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 2BC Non-Structural Protein of Enterovirus A71 Interacts with SNARE Proteins to Trigger Autolysosome Formation

    Directory of Open Access Journals (Sweden)

    Jeffrey K. F. Lai

    2017-07-01

    Full Text Available Viruses have evolved unique strategies to evade or subvert autophagy machinery. Enterovirus A71 (EV-A71 induces autophagy during infection in vitro and in vivo. In this study, we report that EV-A71 triggers autolysosome formation during infection in human rhabdomyosarcoma (RD cells to facilitate its replication. Blocking autophagosome-lysosome fusion with chloroquine inhibited virus RNA replication, resulting in lower viral titres, viral RNA copies and viral proteins. Overexpression of the non-structural protein 2BC of EV-A71 induced autolysosome formation. Yeast 2-hybrid and co-affinity purification assays showed that 2BC physically and specifically interacted with a N-ethylmaleimide-sensitive factor attachment receptor (SNARE protein, syntaxin-17 (STX17. Co-immunoprecipitation assay further showed that 2BC binds to SNARE proteins, STX17 and synaptosome associated protein 29 (SNAP29. Transient knockdown of STX17, SNAP29, and microtubule-associated protein 1 light chain 3B (LC3B, crucial proteins in the fusion between autophagosomes and lysosomes as well as the lysosomal-associated membrane protein 1 (LAMP1 impaired production of infectious EV-A71 in RD cells. Collectively, these results demonstrate that the generation of autolysosomes triggered by the 2BC non-structural protein is important for EV-A71 replication, revealing a potential molecular pathway targeted by the virus to exploit autophagy. This study opens the possibility for the development of novel antivirals that specifically target 2BC to inhibit formation of autolysosomes during EV-A71 infection.

  1. Anal Human Papillomavirus Infection among HIV-Infected Men in Korea.

    Directory of Open Access Journals (Sweden)

    Chang Hun Lee

    Full Text Available Little is known about the epidemiology on human papillomavirus (HPV infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea.A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytology and HPV genotyping. Factors associated with anal HPV infection were assessed using multivariable logistic regression, stratifying by sexual behaviour.A total of 201 HIV-infected men were included in the study: 133 were from men who have sex with men (MSM and 68 from men who have sex with women (MSW. Any anal HPV infection was detected in 82.7% of HIV-infected MSM and in 51.5% of HIV- infected MSW (P < 0.001. High-risk HPV (HR-HPV prevalence was higher among MSM (47.4% than MSW (25.0%; P = 0.002. The HR-HPV types identified most frequently were HPV 16 (11%, HPV 18 (9.9%, and HPV 58 (5% in MSM, and HPV 58(11% and HPV 16 (8.9% in MSW. Prevalence of any HPV types in 9-valent vaccine types was higher among MSM than MSW (47.4% vs 22.1%. P = 0.001. Abnormal anal cytology was more commonly detected in MSM than MSW (42.9% vs.19.1%, P < 0.001. In HIV-infected MSM, higher number of lifetime male sex partners was significantly associated with any anal HPV infection, but age was a significant risk factor associated with anal HR-HPV infection.Anal HPV infection was highly prevalent in HIV-infected MSM in Korea, and also commonly found in HIV-infected MSW. In HIV-infected MSM, the significant risk factor for being infected with any HPV infection was lifetime number of male sexual partners, and with anal oncogenic HPV infection was age.

  2. Aspergillus Sydowi Infection of Human Finger Nail

    Directory of Open Access Journals (Sweden)

    A K Barde

    1981-01-01

    Full Text Available A case of Aspergillus sydowi infection of left middle finger nail is described ′ The presence of fungal hypae with phialids and spores on direct microscopy as well as in culture, the colour of the sub-ungual mass of the nail resembling the colour of the fungus in, culture′ repeated isolations of A sydowi from the diseased tissue along with the absence of any established pathogenic species in the specimen are taken as evidences that this fungus was invading the nail tissue.

  3. Influenza A virus infection of human Schwann cells in vitro.

    Science.gov (United States)

    Levine, Joshua; Buchman, Craig A; Fregien, Nevis

    2003-01-01

    Sudden sensorineural hearing loss, vestibular neuronitis, vocal fold paralysis and Bell's palsy have been associated with a viral etiology, due to the infection of nerve cells. The goal of this research was to ascertain whether Schwann cells can support infection with human influenza A virus and thereby represent a plausible alternative site for virus-host interaction. Viral infection of Schwann cells may lead to secretion of inflammatory mediators, leukocyte recruitment, demyelination and nerve damage. Cultured human Schwann cells were exposed to human influenza A virus. Infection was assayed at various times post-inoculation (0, 24, 48 and 72 h) using light microscopy, immunocytochemistry and influenza A virus-specific reverse transcriptase polymerase chain reaction (RT-PCR). A group of unexposed cells served as controls. Following exposure to the virus, vacuolization, cellular expansion and detachment from the dish were seen as early as 24 h post-inoculation. The exposed cells demonstrated positive immunocytochemical staining for influenza A virus antigen at 24, 48 and 72 h. Using RT-PCR, a sharp rise in influenza A virus-specific mRNA was detected. Human Schwann cells can be infected with human influenza A virus. Further studies will assess the inflammatory response in this model.

  4. Growth in Agarose of Human Cells Infected with Cytomegalovirus

    Science.gov (United States)

    Lang, David J.; Montagnier, Luc; Latarjet, Raymond

    1974-01-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation. Images PMID:4367907

  5. Dynamics of the cellular metabolome during human cytomegalovirus infection.

    Directory of Open Access Journals (Sweden)

    Joshua Munger

    2006-12-01

    Full Text Available Viral replication requires energy and macromolecular precursors derived from the metabolic network of the host cell. Despite this reliance, the effect of viral infection on host cell metabolic composition remains poorly understood. Here we applied liquid chromatography-tandem mass spectrometry to measure the levels of 63 different intracellular metabolites at multiple times after human cytomegalovirus (HCMV infection of human fibroblasts. Parallel microarray analysis provided complementary data on transcriptional regulation of metabolic pathways. As the infection progressed, the levels of metabolites involved in glycolysis, the citric acid cycle, and pyrimidine nucleotide biosynthesis markedly increased. HCMV-induced transcriptional upregulation of specific glycolytic and citric acid cycle enzymes mirrored the increases in metabolite levels. The peak levels of numerous metabolites during infection far exceeded those observed during normal fibroblast growth or quiescence, demonstrating that HCMV markedly disrupts cellular metabolic homeostasis and institutes its own specific metabolic program.

  6. Immunopathogenesis of Oropharyngeal Candidiasis in Human Immunodeficiency Virus Infection

    OpenAIRE

    De Repentigny, Louis; Lewandowski, Daniel; Jolicoeur, Paul

    2004-01-01

    Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical i...

  7. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells.

    Science.gov (United States)

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang; Wang, Xiao; Zhang, Lujun; Liu, Siwen; Zhou, Jingjing; Li, Xin; He, Tieming; Cheng, Zhongyi; Xie, Peng

    2014-09-01

    Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. EBV Infection of Mice with Reconstituted Human Immune System Components.

    Science.gov (United States)

    Münz, Christian

    2015-01-01

    Epstein-Barr virus (EBV) was discovered 50 years ago as the first candidate human tumor virus. Since then, we have realized that this human γ-herpesvirus establishes persistent infection in the majority of adult humans, but fortunately causes EBV-associated diseases only in few individuals. This is an incredible success story of the human immune system, which controls EBV infection and its transforming capacity for decades. A better understanding of this immune control would not only benefit patients with EBV-associated malignancies, but could also provide clues how to establish such a potent, mostly cell-mediated immune control against other pathogens and tumors. However, the functional relevance of EBV-specific immune responses can only be addressed in vivo, and mice with reconstituted human immune system components (huMice) constitute a small animal model to interrogate the protective value of immune compartments during EBV infection, but also might provide a platform to test EBV-specific vaccines. This chapter will summarize the insights into EBV immunobiology that have already been gained in these models and provide an outlook into promising future avenues to develop this in vivo model of EBV infection and human immune responses further.

  9. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xia [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Fifth People' s Hospital of Shanghai, School of Medicine, Fudan University, Shanghai, 200240 (China); Zhao, Libo [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Department of Neurology, The Third People' s Hospital of Chongqing, 400014 (China); Yang, Yongtao [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Bode, Liv [Bornavirus Research Group affiliated to the Free University of Berlin, Berlin (Germany); Huang, Hua [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Liu, Chengyu [Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); Huang, Rongzhong [Department of Rehabilitative Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 (China); Zhang, Liang [Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016 (China); Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, 400016 (China); Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016 (China); and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  10. General Overview on Nontuberculous Mycobacteria, Biofilms, and Human Infection

    Directory of Open Access Journals (Sweden)

    Sonia Faria

    2015-01-01

    Full Text Available Nontuberculous mycobacteria (NTM are emergent pathogens whose importance in human health has been growing. After being regarded mainly as etiological agents of opportunist infections in HIV patients, they have also been recognized as etiological agents of several infections on immune-competent individuals and healthcare-associated infections. The environmental nature of NTM and their ability to assemble biofilms on different surfaces play a key role in their pathogenesis. Here, we review the clinical manifestations attributed to NTM giving particular importance to the role played by biofilm assembly.

  11. Human Metapneumovirus Infection and Acute Respiratory Distress Syndrome During Pregnancy.

    Science.gov (United States)

    Fuchs, Alina; McLaren, Rodney; Saunders, Paul; Karakash, Scarlett; Minkoff, Howard

    2017-09-01

    Human metapneumovirus has recently been recognized as an important cause of severe respiratory viral infections and of viral infections in patients admitted to intensive care units. Little is known about the course of this infection in pregnancy. A late-preterm primigravid woman was admitted to the intensive care unit for acute respiratory distress syndrome and subsequently diagnosed with human metapneumovirus. Because of worsening maternal respiratory status, she was intubated and a primary cesarean delivery was performed. The patient's respiratory status continued to decline postpartum, and she ultimately required extracorporeal membrane oxygenation. She was treated supportively until her respiratory status improved, at which time she was extubated and weaned off extracorporeal membrane oxygenation and subsequently discharged home. Human metapneumovirus can lead to severe respiratory illness during pregnancy.

  12. Expression of enterovirus 71 capsid protein VP1 in Escherichia coli and its clinical application

    Directory of Open Access Journals (Sweden)

    Mei Shi

    2013-12-01

    Full Text Available The VPl gene of enterovirus 71 (EV71 was synthesized, construct a recombinant plasmid pET15b/VP1 and expressed in E. coli BL21. The recombinant VP1 protein could specifically react with EV71-infected patient sera without the cross-reaction with serum antibodies of coxsackievirus A16 (CA16, A4, A5, B3 and B5 as well as echovirus 6. In acute and convalescent phases, IgM and IgG antibodies of 182 serum samples were detected by ELISA with recombinant VP1 protein as a coated antigen. The results showed that the sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV of IgM antibodies in serum samples for the diagnosis of EV71 infection were 90.1, 98.4, 98.8 and 88.7%, respectively; similarly, those of IgG antibodies in serum samples were 82.4, 89.1, 91.5 and 78.1%, respectively. Five of 80 samples (6.25% from CA16infected patients were detected positive by ELISA with recombinant VP1 protein in which indicated the cross reactions and 0 of 5 samples from patients infected with other enteroviruses including CA4, CA5, CB3, CB5 and echovirus 6. Therefore, the recombinant VP1 protein of EV7l may provide a theoretical reference for establishing an effective antibody screening of IgM for EV71-infected patients with clinically suspected hand, foot, and mouth disease (HFMD.

  13. A one-step, triplex, real-time RT-PCR assay for the simultaneous detection of enterovirus 71, coxsackie A16 and pan-enterovirus in a single tube.

    Directory of Open Access Journals (Sweden)

    Shiyin Zhang

    Full Text Available The recent, ongoing epidemic of hand, foot, and mouth disease (HFMD, which is caused by enterovirus infection, has affected millions of children and resulted in thousands of deaths in China. Enterovirus 71 (EV71 and coxsackie A16 (CA16 are the two major distinct pathogens for HFMD. However, EV71 is more commonly associated with neurologic complications and even fatalities. Therefore, simultaneously detecting and differentiating EV71 and CA16 specifically from other enteroviruses for diagnosing HFMD is important. Here, we developed a one-step, triplex, real-time RT-PCR assay for the simultaneous detection of EV71, CA16, and pan-enterovirus (EVs in a single tube with an internal amplification control. The detection results for the serially diluted viruses indicate that the lower limit of detection for this assay is 0.001-0.04 TCID50/ml, 0.02 TCID50/ml, and 0.001 TCID50/ml for EVs, EV71, and CA16, respectively. After evaluating known HFMD virus stocks of 17 strains of 16 different serotypes, this assay showed a favorable detection spectrum and no obvious cross-reactivity. The results for 141 clinical throat swabs from HFMD-suspected patients demonstrated sensitivities of 98.4%, 98.7%, and 100% for EVs, EV71, and CA16, respectively, and 100% specificity for each virus. The application of this one-step, triplex, real-time RT-PCR assay in clinical units will contribute to HFMD surveillance and help to identify causative pathogen in patients with suspected HFMD.

  14. Humanized mouse models for HIV-1 infection of the CNS.

    Science.gov (United States)

    Honeycutt, Jenna B; Sheridan, Patricia A; Matsushima, Glenn K; Garcia, J Victor

    2015-06-01

    Since the onset of the HIV epidemic, there has been a shift from a deadly diagnosis to the management of a chronic disease. This shift is the result of the development of highly effective drugs that are able to suppress viral replication for years. The availability of these regimens has also shifted the neurocognitive pathology associated with infection from potentially devastating to a much milder phenotype. As the disease outcome has changed significantly with the availability of antiretroviral therapy, there is an opportunity to re-evaluate the currently available models to address the neurocognitive pathology seen in suppressed patients. In the following, we seek to summarize the current literature on humanized mouse models and their utility in understanding how HIV infection leads to changes in the central nervous system (CNS). Also, we identify some of the unanswered questions regarding HIV infection of the CNS as well as the opportunities and limitations of currently existing models to address those questions. Finally, our conclusions indicate that the earlier humanized models used to study HIV infection in the CNS provided an excellent foundation for the type of work currently being performed using novel humanized mouse models. We also indicate the potential of some humanized mouse models that have not been used as of this time for the analysis of HIV infection in the brain.

  15. Malignant syphilis with human immunodeficiency virus infection

    Directory of Open Access Journals (Sweden)

    Jiby Rajan

    2011-01-01

    Full Text Available Malignant syphilis or Lues maligna, commonly reported in the pre-antibiotic era, has now seen a resurgence with the advent of human immunodeficiency virus (HIV. Immunosuppression and sexual promiscuity set the stage for this deadly association of HIV and Treponema pallidum that can manifest atypically and can prove to cause diagnostic problems. We report one such case in a 30-year-old female who responded favorably to treatment with penicillin.

  16. Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

    Science.gov (United States)

    Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

    2012-01-01

    Background Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. Principal Finding In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7–10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30–43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37°C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4°C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and

  17. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration, a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice

  18. Generation and maintenance of human memory cells during viral infection.

    Science.gov (United States)

    Halwani, Rabih; Doroudchi, Mehrnoosh; Yassine-Diab, Bader; Janbazian, Loury; Shi, Yu; Said, Elias A; Haddad, Elias K; Sékaly, Rafick-Pierre

    2006-11-01

    Long-term maintenance of memory T cell response is the hallmark of immune protection and hence the holy grail of most vaccine development studies. Persistent memory cells, developed after either viral infection or vaccination, ensure the generation of an antiviral response upon reexposure to the pathogen. During acute viral infections, as in the case of measles and influenza viruses, strong T cell effector functions, which eradicate the virus and protect patients against reexposure, are achieved by the generation of persistent protective memory cells. However, in chronic infections, T cells drastically lose effector functions before acquiring a memory phenotype. Chronic infections can be categorized into infections where viremia is controlled and protective memory cells are maintained as in the case of EBV and CMV infections, or where the virus persists and memory cells are exhausted and disrupted as in the case of human immunodeficiency virus infection. In this review, we will discuss the different phenotypical and functional characteristics of memory cells subsets, the importance of the role they play during acute and chronic infections, and the mechanisms behind their effectiveness and persistence.

  19. Obesity and human papillomavirus infection in perimenopausal women.

    Science.gov (United States)

    Liu, Su-Hsun; Rositch, Anne F; Viscidi, Raphael P; Silver, Michelle I; Burke, Anne E; Gravitt, Patti E

    2013-10-01

    Obesity is known to increase susceptibility to certain infections in men. It is unclear whether obesity increases women's risk for human papillomavirus (HPV) infection. In a prospective cohort of 696 perimenopausal women enrolled in 2008-2012, we sought to determine whether obesity predicted incident HPV detection or nondetection. Obesity was defined as body mass index (BMI) ≥ 30 kg/m(2). Baseline any type HPV prevalence was comparable between obese and nonobese women (18.7% vs 19.1%; P > .05). Over a median follow-up period of 17.9 months (interquartile range: 12.1-24.5), 187 new HPV detections occurred among 123 women, 60 of whom subsequently lost 76 detectable infections. When compared with nonobese participants, obese women had a similar rate of new HPV detection (7.1 vs 7.8 infections per 1000 infection-years; P > .05) or loss of detection (100.3 vs 85.8 infections per 100 infection-years; P > .05). Similar results were found after adjusting for age, menopausal status, smoking habit, and sexual exposure history. Results from the current analysis suggest little effect of obesity on HPV detection and loss of detection in mid-adult women. More research is needed to determine whether adipokines or cytokines better capture the potential immune modulating effects of obesity on HPV infection.

  20. Cytomegalovirus infection of the human placenta: an immunocytochemical study.

    Science.gov (United States)

    Mühlemann, K; Miller, R K; Metlay, L; Menegus, M A

    1992-11-01

    In congenital cytomegalovirus (CMV) infection histologic evaluation of the placenta is often unrevealing. In the present study immunocytochemistry to CMV immediate early and early nuclear antigens was used to characterize placental involvement in six cases of symptomatic intrauterine CMV infection. Histologic examination had demonstrated diagnostic viral inclusions in one placenta and non-specific villitis in another. However, immunocytochemistry revealed CMV infection in five of the six placentas, including three with no pathologic changes on routine histologic evaluation. Infected cells were located primarily in the villous stroma. In one case immunoperoxidase staining showed infection in the syncytiotrophoblast. Infected endothelial cells were demonstrated by double staining for CMV and factor VIII antigen. No double-stained cells were seen in tissue sections stained for CMV immediate early nuclear antigen or the human macrophage-associated CD68 antigen, which is expressed in Hofbauer cells. In conclusion, specific immunoperoxidase staining was more sensitive for demonstrating placental CMV infection than was histologic examination and it aided in the characterization of infected cells.

  1. Human bocavirus in children with acute respiratory infections in Vietnam.

    Science.gov (United States)

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

  2. Animal-associated opportunistic infections among persons infected with the human immunodeficiency virus.

    Science.gov (United States)

    Glaser, C A; Angulo, F J; Rooney, J A

    1994-01-01

    A number of animal-associated infections occur in persons infected with the human immunodeficiency virus (HIV), including those due to Toxoplasma gondii, Cryptosporidium, Microsporida, Salmonella, Campylo-bacter, Giardia, Rhodococcus equi, Rochalimaea, and Listeria monocytogenes. Most of these infections, with the exception of those due to Rochalimaea, appear to be acquired by the immunosuppressed individual from sources other than exposure to animals. Drs. Glaser and colleagues review our current understanding of the role of exposure to animals, especially pets, in the natural history of these opportunistic infections. They suggest that the risk of zoonotic transmission is small and offer practical suggestions designed to reduce this low risk. They conclude that the benefits of animal companionship outweigh the risks to patients and that prohibition of pet ownership by individuals infected with HIV is not warranted.

  3. Borna Disease Virus Infection, a Human Mental-Health Risk

    Science.gov (United States)

    Bode, Liv; Ludwig, Hans

    2003-01-01

    This article focuses on human Borna disease virus (BDV) infections, most notably on the development of valid diagnostic systems, which have arisen as a major research issue in the past decade. The significance of a novel modular triple enzyme-linked immunosorbent assay that is capable of specifically measuring anti-BDV antibodies as well as major structural proteins N (p40) and P (p24) in the blood, either as free antigens in the plasma or as antibody-bound circulating immune complexes (CICs), is explained. The impact of CICs and plasma antigen, which indicate periods of antigenemia in the course of BDV infection, along with other infection markers that are still in use is discussed. The review further provides new insight into possible links of BDV to human diseases, summarizing cross-sectional and longitudinal data which correlate acute depression with the presence and amount of antigen and CICs. Moreover, BDV prevalence in healthy people is reevaluated, suggesting that this was previously underestimated. Antiviral efficacy of amantadine, in vivo and in vitro, is outlined as well, with emphasis on wild-type (human and equine) versus laboratory strains. Finally, the pros and cons of the association of BDV with human disease, as detailed in the literature, are critically discussed and related to our data and concepts. This article supports existing correlative evidence for a pathogenic role of BDV infection in particular human mental disorders, in analogy to what has been proven for a variety of animal species. PMID:12857781

  4. Efficient replication of recombinant Enterovirus B types, carrying different P1 genes in the coxsackievirus B5 replicative backbone.

    Science.gov (United States)

    Jonsson, Nina; Sävneby, Anna; Gullberg, Maria; Evertsson, Kim; Klingel, Karin; Lindberg, A Michael

    2015-06-01

    Recombination is an important feature in the evolution of the Enterovirus genus. Phylogenetic studies of enteroviruses have revealed that the capsid genomic region (P1) is type specific, while the parts of the genome coding for the non-structural proteins (P2-P3) are species specific. Hence, the genome may be regarded as consisting of two modules that evolve independently. In this study, it was investigated whether the non-structural coding part of the genome in one type could support replication of a virus with a P1 region from another type of the same species. A cassette vector (pCas) containing a full-length cDNA copy of coxsackievirus B5 (CVB5) was used as a replicative backbone. The P1 region of pCas was replaced with the corresponding part from coxsackievirus B3 Nancy (CVB3N), coxsackievirus B6 Schmitt (CVB6S), and echovirus 7 Wallace (E7W), all members of the Enterovirus B species. The replication efficiency after transfection with clone-derived in vitro transcribed RNA was studied and compared with that of pCas. All the recombinant viruses replicated with similar efficiencies and showed threshold cycle (Ct) values, tissue culture infectivity dose 50 %, and plaque-forming unit titers comparable to viruses generated from the pCas construct. In addition to this, a clone without the P1 region was also constructed, and Western Blot and immunofluorescence staining analysis showed that the viral genome could be translated and replicated despite the lack of the structural protein-coding region. To conclude, the replicative backbone of the CVB5 cassette vector supports replication of intraspecies constructs with P1 regions derived from other members of the Enterovirus B species. In addition to this, the replicative backbone can be both translated and replicated without the presence of a P1 region.

  5. Human and bovine viruses and bacteria at three Great Lakes beaches: Environmental variable associations and health risk

    Science.gov (United States)

    Corsi, Steven R.; Borchardt, Mark A.; Carvin, Rebecca B.; Burch, Tucker R; Spencer, Susan K.; Lutz, Michelle A.; McDermott, Colleen M.; Busse, Kimberly M.; Kleinheinz, Gregory; Feng, Xiaoping; Zhu, Jun

    2016-01-01

    Waterborne pathogens were measured at three beaches in Lake Michigan, environmental factors for predicting pathogen concentrations were identified, and the risk of swimmer infection and illness was estimated. Waterborne pathogens were detected in 96% of samples collected at three Lake Michigan beaches in summer, 2010. Samples were quantified for 22 pathogens in four microbial categories (human viruses, bovine viruses, protozoa, and pathogenic bacteria). All beaches had detections of human and bovine viruses and pathogenic bacteria indicating influence of multiple contamination sources at these beaches. Occurrence ranged from 40 to 87% for human viruses, 65–87% for pathogenic bacteria, and 13–35% for bovine viruses. Enterovirus, adenovirus A, Salmonella spp., Campylobacter jejuni, bovine polyomavirus, and bovine rotavirus A were present most frequently. Variables selected in multiple regression models used to explore environmental factors that influence pathogens included wave direction, cloud cover, currents, and water temperature. Quantitative Microbial Risk Assessment was done for C. jejuni, Salmonella spp., and enteroviruses to estimate risk of infection and illness. Median infection risks for one-time swimming events were approximately 3 × 10–5, 7 × 10–9, and 3 × 10–7 for C. jejuni, Salmonella spp., and enteroviruses, respectively. Results highlight the importance of investigating multiple pathogens within multiple categories to avoid underestimating the prevalence and risk of waterborne pathogens.

  6. Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis.

    Directory of Open Access Journals (Sweden)

    Issac Horng Khit Too

    2018-01-01

    Full Text Available A close relative of poliovirus, enterovirus 71 (EV71 is regarded as an important neurotropic virus of serious public health concern. EV71 causes Hand, Foot and Mouth Disease and has been associated with neurological complications in young children. Our limited understanding of the mechanisms involved in its neuropathogenesis has hampered the development of effective therapeutic options. Here, using a two-dimensional proteomics approach combined with mass spectrometry, we have identified a unique panel of host proteins that were differentially and dynamically modulated during EV71 infection of motor-neuron NSC-34 cells, which are found at the neuromuscular junctions where EV71 is believed to enter the central nervous system. Meta-analysis with previously published proteomics studies in neuroblastoma or muscle cell lines revealed minimal overlapping which suggests unique host-pathogen interactions in NSC-34 cells. Among the candidate proteins, we focused our attention on prohibitin (PHB, a protein that is involved in multiple cellular functions and the target of anti-cancer drug Rocaglamide (Roc-A. We demonstrated that cell surface-expressed PHB is involved in EV71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB associates with the virus replication complex and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected neuronal cells reduced significantly virus yields. However, the inhibitory effect of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway as previously reported. Instead, Roc-A treated NSC-34 cells had lower mitochondria-associated PHB and lower ATP levels that correlated with impaired mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived longer than the vehicle-treated animals and had significantly lower virus loads in their spinal cord and brain, whereas virus titers in their limb muscles were comparable to controls. Together, this

  7. Zika Virus Infects Human Fetal Brain Microglia and Induces Inflammation.

    Science.gov (United States)

    Lum, Fok-Moon; Low, Donovan K S; Fan, Yiping; Tan, Jeslin J L; Lee, Bernett; Chan, Jerry K Y; Rénia, Laurent; Ginhoux, Florent; Ng, Lisa F P

    2017-04-01

    The unprecedented reemergence of Zika virus (ZIKV) has startled the world with reports of increased microcephaly in Brazil. ZIKV can infect human neural progenitors and impair brain growth. However, direct evidence of ZIKV infection in human fetal brain tissues remains elusive. Investigations were performed with brain cell preparations obtained from 9 donors. Virus infectivity was assessed by detection of virus antigen by flow cytometry together with various hematopoietic cell surface markers. Virus replication was determined by viral RNA quantification. Cytokine levels in supernatant obtained from virus-infected fetal brain cells were measured simultaneously in microbead-based immunoassays. We also show that ZIKV infection was particularly evident in hematopoietic cells with microglia, the brain-resident macrophage population being one of the main targets. Infection induces high levels of proinflammatory immune mediators such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and monocyte chemotactic protein 1 (MCP-1). Our results highlight an important role for microglia and neuroinflammation during congenital ZIKV pathogenesis.

  8. Microsphaeropsis olivacea as an etiological agent of human skin infection.

    Science.gov (United States)

    Guarro, J; Mayayo, E; Tapiol, J; Aguilar, C; Cano, J

    1999-04-01

    Microsphaeropsis olivacea is reported as the agent of a case of human skin infection in an otherwise healthy woman. This fungus has not been reported previously as causing disease in humans. It was identified on the basis of its production of pycnidia and conidial structures typical of the Coelomycetes, and by its light brown, ellipsoid to cylindrical and thick walled conidia. The in vitro inhibitory activity of amphotericin B, fluconazole, flucytosine, itraconazole, ketoconazole and miconazole was determined.

  9. Human dendritic cell culture and bacterial infection.

    Science.gov (United States)

    Jones, Hannah E; Klein, Nigel; Dixon, Garth L J

    2012-01-01

    Dendritic cells (DC) play a key role in the development of natural immunity to microbes. The DC form a bridge between the innate and adaptive immune system by providing key instructions particularly to antigen naïve T-cells. The interaction of DC with T lymphocytes involves three signals: (1) antigen processing and presentation in context of MHC Class I and/or II, (2) expression of T cell co-stimulatory molecules, and (3) cytokine production. Studying the interactions of DCs with specific pathogens allows for better understanding of how protective immunity is generated, and may be particularly useful for assessing vaccine components. In this chapter, we describe methods to generate human monocyte-derived DCs and assess their maturation, activation, and function, using interaction with the gram-negative bacterial pathogen Neisseria meningitidis as a model.

  10. Severe human Babesia divergens infection in Norway

    Directory of Open Access Journals (Sweden)

    K. Mørch

    2015-04-01

    Full Text Available Human babesiosis is a rare but potentially life-threatening parasitic disease transmitted by ixodid ticks, and has not previously been reported in Norway. We report a case of severe babesiosis that occurred in Norway in 2007. The patient had previously undergone a splenectomy. He was frequently exposed to tick bites in an area endemic for bovine babesiosis in the west of Norway. The patient presented with severe haemolysis and multiorgan failure. Giemsa-stained blood smears revealed 30% parasitaemia with Babesia spp. He was treated with quinine in combination with clindamycin, apheresis, and supportive treatment with ventilatory support and haemofiltration, and made a complete recovery. This is the first case reported in Norway; however Babesia divergens seroprevalence in cattle in Norway is high, as is the risk of Ixodes ricinus tick bite in the general population. Babesiosis should be considered in the differential diagnosis of unexplained febrile haemolytic disease.

  11. Controlled Human Malaria Infection: Applications, Advances, and Challenges.

    Science.gov (United States)

    Stanisic, Danielle I; McCarthy, James S; Good, Michael F

    2018-01-01

    Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of Plasmodium falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of Plasmodium vivax -specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration. Copyright © 2017 American Society for Microbiology.

  12. Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD. This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity. METHODOLOGY: Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined. PRINCIPAL FINDINGS: Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1 GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2 G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3 IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4 FACS analysis revealed that the frequency of CD19(+HLADR(+ mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.

  13. The effect of human papillomavirus infection on sperm cell motility.

    Science.gov (United States)

    Lai, Y M; Lee, J F; Huang, H Y; Soong, Y K; Yang, F P; Pao, C C

    1997-06-01

    To investigate the presence of human papillomavirus (HPV) in human sperm cells and to evaluate potential effects of HPV on the sperm functions. A descriptive clinical study. Specimens of semen were collected from 24 randomly selected patients who attended the fertility clinics at Chang Gung Memorial Hospital. The presence of HPV DNA and RNA were examined by polymerase chain reaction. Semen quality and sperm cell function were analyzed by computer-aided autoanalyzer. Human papillomavirus type 16 DNA and RNA were found in 6 (25%) and 2 (8%) of the sperm cells specimens, respectively. Human papillomavirus type 18 DNA and RNA were present in 11 (46%) and 5 (21%) of the same sperm cells specimens, respectively. Incidence of asthenozoospermia among patients infected with either HPV was significantly higher than in those without HPV in their sperm cells (75% versus 8%). Although performance of curvilinear velocity, straight-line velocity, and mean amplitude of lateral head displacement was significantly lower in HPV-infected specimens, the differences of linearity, beat cross frequency, and straightness were not statistically significant. These results suggest that human papillomavirus can be found in human sperm cells and that certain HPV-specific genes are actively transcribed. Sperm motility parameters seem to be affected by the presence of HPV in the sperm cells, and also the incidence of asthenozoospermia may be associated with HPV infection.

  14. Differential TLR7-mediated expression of proinflammatory and antiviral cytokines in response to laboratory and clinical enterovirus strains.

    Science.gov (United States)

    Chehadeh, Wassim; Alkhabbaz, Marwa

    2013-06-01

    Enteroviruses (EVs) are single stranded RNA viruses associated with many serious diseases. The exact mechanism by which an EV is able to evade innate immunity and cause tissue damage still remain unknown. Toll-like receptor 7 (TLR7) mediates the activation of type I interferon genes and the development of inflammatory cytokine response. The main aim of the study was to explore the antiviral activity and the pattern of cytokine expression in human embryonic kidney cells (HEK-293 cells) expressing TLR7 protein following challenging with laboratory and clinical EV strains. The TLR7 open reading frame was cloned into the pcDNA3.1/nV5-DEST™ expression vector, followed by transfection into HEK-293 cells. TLR7- and mock-transfected cells were infected with laboratory and clinical strains of CVB1 and CVB5. The levels of cytokines (IL-6, IL-8, TNF-α, IFN-α and IFN-β) were measured by ELISA. The EV RNA concentrations were measured by real-time RT-PCR, and normalized against GAPDH RNA concentrations. The clinical EV strains were more effective activators of cytokines production in TLR7-transfected cells than the laboratory EV strains. The inhibition of EV replication in TLR7-transfected cells was correlated to the production of type I IFNs. The cytopathic effects observed in TLR7-transfected cells were correlated to the levels of IL-6 and TNF-α. The results suggest a clear segregation between laboratory and clinical EV strains on the basis of their cytokine induction ability, and a possible role of TLR7-induced proinflammatory cytokines in the pathogenesis of EV infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Local Risk Factors in Genital Human Papilloma Virus Infection in ...

    African Journals Online (AJOL)

    Papdopoulus AG, Devaja O, Cason J, Raju KS. The clinical implications of human papilloma virus infection in cervical cancinogenesis and emerging therapies. In: Studd J, editor. Prorgess in Obstetrics and Gynaecology. Vol. 14. Edinburgh: Churchhill Livingstone Publications; 2000. p. 281‑93. 2. Ijaiya MA, Aboyeji PA, ...

  16. Declining Rate of Infection with Maternal Human Immunodeficiency ...

    African Journals Online (AJOL)

    Declining Rate of Infection with Maternal Human Immunodeficiency Virus at Delivery Units in North-Central Nigeria. GE Imade, AS Sagay, J Musa, AN Ocheke, DS Adeniyi, M Idighri, R Powl, A Sendeht, JP Ogwuche, M Elujoba, CO Egbodo, T Oyebode, PH Daru, O Agbaji, IC Pam, ST Meloni, P Okonkwo, PJ Kanki ...

  17. Age-specific prevalence of cervical human papillomavirus infection ...

    African Journals Online (AJOL)

    This cross-sectional study describes the age-specific prevalence of human papillomavirus (HPV) infection and cytological abnormalities among this urban and peri-urban population. Method. Over the period March 2009 - September 2011, 1 524 women attending public sector primary healthcare clinics were invited to

  18. Local Risk Factors in Genital Human Papilloma Virus Infection in ...

    African Journals Online (AJOL)

    cervical cancer and identified other risk factors. Molecular epidemiologic evidence clearly indicates that certain types of. HPV are the principal cause of invasive cancer and cervical intraepithelial neoplasia.[3]. Local Risk Factors in Genital Human Papilloma Virus. Infection in Cervical Smears. Ojiyi EC, Dike IE, Okeudo C, ...

  19. Autochthonous Nocardia cerradoensis Infection in Humans, Spain, 2011 and 2014

    Science.gov (United States)

    Ercibengoa, Maria; Pérez-Trallero, Emilio

    2016-01-01

    Nocardia cerradoensis was first isolated in 2003 in the El Cerrado region of Brazil; since then, only 2 human infections, in France and Spain, have been reported. We describe 3 autochthonous cases in residents of Spain during 2011 and 2014. Together these cases support the idea of an emerging global pathogenic microorganism. PMID:26691545

  20. Prevalence of human immunodeficiency virus (HIV) infection among ...

    African Journals Online (AJOL)

    Prevalence of human immunodeficiency virus (HIV) infection among pregnant women in an antenatal clinic in Port-Harcourt, Nigeria. ... 6, No 3 (2007) >. Log in or Register to get access to full text downloads. ... A total of 10,032 pregnant women were screened for the possible occurrence of HIV 1 and HIV 2 within the period.

  1. Awareness of Human Immunodeficiency Virus (HIV) infection among ...

    African Journals Online (AJOL)

    Objective: To determine the level of awareness of Human Immunodeficiency Virus (HIV) infection among antenatal clients in Nnewi Nigeria. Subjects and Methods: A cross sectional descriptive study of six hundred consecutive antenatal clients attending the Nnamdi Azikiwe University Teaching Hospital and five private ...

  2. Prevalence of human immunodeficiency virus infection among ...

    African Journals Online (AJOL)

    Prevalence of human immunodeficiency virus infection among tuberculosis suspect patients in Accra, Ghana, ... man immunodeficiency virus (HIV) and tuberculosis. (TB) is well known. A previous study showed a 16,8 % .... HIV~1 and HIV-(Z; Fujirebio Inc, TokyoJapan) and con-- firmed with the synthetic peptide based ...

  3. seroprevalence of human herpes virus 8 (hhv8) infection among ...

    African Journals Online (AJOL)

    Praise

    SEROPREVALENCE OF HUMAN HERPES VIRUS 8 (HHV8) INFECTION. AMONG COMMERCIAL SEX WORKERS IN JOS. Zakari1, H., Nimzing2, L., Agabi1, Y. A., Amagam3, P. and Dashen,1 M. M.. 1Department of Microbiology, Faculty of Natural Sciences, University o f Jos, Nigeria. 2Department of Medical Microbiology, ...

  4. Prevalence And Risk Factors For Human Pappiloma Virus Infection ...

    African Journals Online (AJOL)

    Human Pappiloma Virus (HPV) infection is a disease of global public health importance, culminating into a high risk of cervical cancer. Most of the risk factors are modifiable, thus making HPV itself preventable. Efforts towards community HPV prevention and vaccination have not yielded the desired results, most especially ...

  5. Health Disparity in Human Papilloma Virus Related Infections | Poku ...

    African Journals Online (AJOL)

    In spite of the volume of information of Human Papilloma Virus (HPV) and the HPV vaccines, there are racial and gender differences in the knowledge and awareness of HPV among Guyanese. The study aimed to assess the knowledge and attitude towards HPV infection, cervical cancer and HPV vaccines. The study was ...

  6. Prevalence of tonsillar human papillomavirus infections in Denmark

    DEFF Research Database (Denmark)

    Rusan, M; Klug, Tejs Ehlers; Henriksen, Jens-Jacob Mølby

    2014-01-01

    The incidence of tonsillar carcinomas associated with Human Papillomavirus (HPV) infection has increased dramatically over the last three decades. In fact, currently in Scandinavia, HPV-associated cases account for over 80 % of tonsillar carcinoma cases. Yet, the epidemiology and natural history...

  7. Human Papillomavirus Infection Among 2460 Men in Denmark

    DEFF Research Database (Denmark)

    Hebnes, Julie Buchholt; Munk, Christian; Nøhr, Bugge

    2015-01-01

    BACKGROUND: It is crucial to understand the epidemiology and natural history of human papillomavirus (HPV) infection in both men and women, to prevent the increasing HPV-related disease burden in men. Data on HPV prevalence among men in the general population are limited. In this cross...

  8. Nocardia brasiliensis: from microbe to human and experimental infections.

    Science.gov (United States)

    Salinas-Carmona, M C

    2000-09-01

    Nocardia brasiliensis is a Gram-positive bacterium that lives as a saprophyte in soil. In this article the physical properties, chemical composition and taxonomic position of this species is reviewed. Human infections and an experimental model of actinomycetoma in BALB/c mice as well as the host-immune response is described.

  9. Prevalence of Human Rhinovirus Infection in Children with Acute ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    Prevalence of Human Rhinovirus Infection in Children with. Acute Respiratory Symptoms in Ilorin, Nigeria. Olatunji Matthew Kolawole\\ Busayo Joseph Adeyemf1 and Aishat Abdulrahman. Gobir2. 1lnfectious Diseases and Environmental Health Research Group, Department of Microbiology,. Faculty of Life Sciences ...

  10. Campylobacter: animal reservoirs, human infections, and options for control

    NARCIS (Netherlands)

    Wagenaar, Jaap; Newell, D.G.; Kalupahana, R.S.; Mughini Gras, Lapo

    2015-01-01

    Campylobacteriosis is a frequently diagnosed disease in humans. Most infections are considered food-borne and are caused by Campylobacter jejuni and C. coli. The animal reservoirs of these Campylobacter, and the sources and routes of transmission, are described and discussed. Most warm-blooded

  11. Human skin Langerhans cells are targets of dengue virus infection

    NARCIS (Netherlands)

    Wu, SJL; Grouard-Vogel, G; Mascola, [No Value; Brachtel, E; Putvatana, R; Louder, MK; Filgueira, L; Marovich, MA; Wong, HK; Blauvelt, A; Murphy, GS; Robb, ML; Innes, BL; Birx, DL; Hayes, CG; Frankel, SS

    Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine(1,2). Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by

  12. Report of the first human case of Caulobacter sp. infection

    DEFF Research Database (Denmark)

    Justesen, Ulrik S; Holt, Hanne M; Thiesson, Helle

    2007-01-01

    A Caulobacter sp. isolate was recovered from the dialysis fluid of a patient undergoing peritoneal dialysis. Bacterial identification included electron microscopy and 16S rDNA sequencing. To our knowledge, this is the first report of human Caulobacter infection. Special growth requirements suggest...

  13. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes

    Directory of Open Access Journals (Sweden)

    Nigel Pereira

    2015-01-01

    Full Text Available The human papillomavirus (HPV is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.

  14. Human Immunodeficiency Virus Infection and Host Defense in the Lungs.

    Science.gov (United States)

    Charles, Tysheena P; Shellito, Judd E

    2016-04-01

    Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Human Papillomavirus Infection, Infertility, and Assisted Reproductive Outcomes.

    Science.gov (United States)

    Pereira, Nigel; Kucharczyk, Katherine M; Estes, Jaclyn L; Gerber, Rachel S; Lekovich, Jovana P; Elias, Rony T; Spandorfer, Steven D

    2015-01-01

    The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.

  16. Human Papillomavirus Infections in Primary Care

    Science.gov (United States)

    Ogunmodede, Folashade; Yale, Steven H.; Krawisz, Bruce; Tyler, Gregory C.; Evans, Anthony C.

    2007-01-01

    Cervical cancer continues to be a leading cause of mortality worldwide. The incidence and mortality associated with invasive cervical cancer have declined significantly in developed countries due to widespread availability of screening with the Papanicolaou (Pap) test. However, the incidence and prevalence of non-invasive cervical intraepithelial neoplasms and genital warts related to oncogenic and nononcogenic strains of human papilloma viruses (HPV) have remained relatively stable. Recent advances in molecular diagnostics have resulted in improved characterization of various HPV types and have led to changes in terminology of Pap test findings. Changes in nomenclature may lead to confusion among primary care providers regarding how best to further evaluate abnormal cytological results. This article provides a concise overview of the approach to the treatment of genital warts and management of abnormal cervical cytology based on guidelines from the American Society of Colposcopy and Cervical Pathology. It also reviews advances in HPV vaccine development and the new recombinant vaccine recently approved for use in the United States. PMID:18086908

  17. Phylogenetic evidence that two distinct Trichuris genotypes infect both humans and non-human primates.

    Directory of Open Access Journals (Sweden)

    Damiana F Ravasi

    Full Text Available Although there has been extensive debate about whether Trichuris suis and Trichuris trichiura are separate species, only one species of the whipworm T. trichiura has been considered to infect humans and non-human primates. In order to investigate potential cross infection of Trichuris sp. between baboons and humans in the Cape Peninsula, South Africa, we sequenced the ITS1-5.8S-ITS2 region of adult Trichuris sp. worms isolated from five baboons from three different troops, namely the Cape Peninsula troop, Groot Olifantsbos troop and Da Gama Park troop. This region was also sequenced from T. trichiura isolated from a human patient from central Africa (Cameroon for comparison. By combining this dataset with Genbank records for Trichuris isolated from other humans, non-human primates and pigs from several different countries in Europe, Asia, and Africa, we confirmed the identification of two distinct Trichuris genotypes that infect primates. Trichuris sp. isolated from the Peninsula baboons fell into two distinct clades that were found to also infect human patients from Cameroon, Uganda and Jamaica (named the CP-GOB clade and China, Thailand, the Czech Republic, and Uganda (named the DG clade, respectively. The divergence of these Trichuris clades is ancient and precedes the diversification of T. suis which clustered closely to the CP-GOB clade. The identification of two distinct Trichuris genotypes infecting both humans and non-human primates is important for the ongoing treatment of Trichuris which is estimated to infect 600 million people worldwide. Currently baboons in the Cape Peninsula, which visit urban areas, provide a constant risk of infection to local communities. A reduction in spatial overlap between humans and baboons is thus an important measure to reduce both cross-transmission and zoonoses of helminthes in Southern Africa.

  18. Enteroviruses as a possible cause of hypertension, dilated ...

    African Journals Online (AJOL)

    Objective: To assess the role of enteroviruses in the etiology of hypertension, DCM and HHF. Methods: We obtained stool specimens from 70 subjects comprising 65 patients and 5 controls and isolation was carried out on RD, L20B, HEp-2C and Vero cell lines and identified by neutralization with standard antisera (RIVM).

  19. Anti-Enterovirus 71 Agents of Natural Products

    Directory of Open Access Journals (Sweden)

    Liyan Wang

    2015-09-01

    Full Text Available This review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. It covers literature published from 2005–2015 and refers to compounds isolated from biogenic sources. In total, 58 naturally-occurring anti-EV71 compounds are recorded.

  20. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  1. Mechanism of Human Papillomavirus Binding to Human Spermatozoa and Fertilizing Ability of Infected Spermatozoa

    OpenAIRE

    Carlo Foresta; Cristina Patassini; Alessandro Bertoldo; Massimo Menegazzo; Felice Francavilla; Luisa Barzon; Alberto Ferlin

    2011-01-01

    Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm expos...

  2. Human Dirofilaria repens Infection in Romania: A Case Report

    Directory of Open Access Journals (Sweden)

    Ioana Popescu

    2012-01-01

    Full Text Available Human dirofilariasis is a zoonotic infectious disease caused by the filarial nematodes of dogs Dirofilaria repens and Dirofilaria immitis. Depending on the species involved, human infections usually manifest as one cutaneous or visceral larva migrans that forms a painless nodule in the later course of disease. Dirofilariae are endemic in the Mediterranean, particularly in Italy. They are considered as emerging pathogens currently increasing their geographical range. We present one of the few known cases of human dirofilariasis caused by D. repens in Romania. The patient developed unusual and severe clinical manifestations that mimicked pathological conditions like cellulitis or deep venous thrombosis.

  3. Human Trichinella infection outbreaks in Slovakia, 1980-2008.

    Science.gov (United States)

    Dubinský, Pavol; Antolová, Daniela; Reiterová, Katarína

    2016-03-01

    Trichinellosis, a parasitic zoonosis with world-wide distribution, causes serious health problems in humans and is also of economic importance. In Slovakia the most frequent species is T. britovi, causing disease mainly in wild life species. T. spiralis occurs less frequently and T. pseudospiralis only sporadically. The paper describes the epidemiology of six human Trichinella infection outbreaks recorded in Slovakia between 1980 and 2008. Before 1990 wild boar meat was the main source of infection. Later, risk farm practices, especially feeding of pigs with the wild animal´s offal contributed to the formation of synanthropic cycle and pig meat caused the epidemics in 1990, 2001 and 2008. Sausages prepared from pork and T. britovi infected dog meat and offered as a local food specialty on traditional folk festival in 1998 (Brezno district, Central Slovakia) were the source of the largest human outbreak recorded in Slovakia. The anti-Trichinella antibodies were detected in 336 event visitors. The main reason of repeated human epidemics in Slovakia has been the permanent circulation of Trichinella spp. in sylvatic cycle, especially in red foxes and wild boars. High population density of both animal species, persistent prevalence of trichinellosis in wild boars and even increasing positivity of red foxes suggest that the risk of human outbreaks in Slovakia persists.

  4. Infection prevention and control during prolonged human space travel.

    Science.gov (United States)

    Mermel, Leonard A

    2013-01-01

    Prolonged human spaceflight to another planet or an asteroid will introduce unique challenges of mitigating the risk of infection. During space travel, exposure to microgravity, radiation, and stress alter human immunoregulatory responses, which can in turn impact an astronaut's ability to prevent acquisition of infectious agents or reactivation of latent infection. In addition, microgravity affects virulence, growth kinetics, and biofilm formation of potential microbial pathogens. These interactions occur in a confined space in microgravity, providing ample opportunity for heavy microbial contamination of the environment. In addition, there is the persistence of aerosolized, microbe-containing particles. Any mission involving prolonged human spaceflight must be carefully planned to minimize vulnerabilities and maximize the likelihood of success.

  5. Relationship between cytomegalovirus infection and procoagulant changes in human immunodeficiency virus-infected patients

    NARCIS (Netherlands)

    Mulder, R.; Tichelaar, Y. I. G. V.; Sprenger, H. G.; Mulder, A. B.; Lijfering, W. M.

    P>Cytomegalovirus is associated with hypercoagulability, and is reported to increase the risk of venous thrombosis in human immunodeficiency virus (HIV)-infected patients. Progression to AIDS, however, is also associated with hypercoagulability and venous thrombosis, and may result in more

  6. Hepatitis C virus infection in the human immunodeficiency virus infected patient

    DEFF Research Database (Denmark)

    Clausen, Louise Nygaard; Lundbo, Lene Fogt; Benfield, Thomas

    2014-01-01

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and...

  7. Prevalence of human papilloma virus infection in patients with male accessory gland infection.

    Science.gov (United States)

    La Vignera, S; Vicari, E; Condorelli, R A; Franchina, C; Scalia, G; Morgia, G; Perino, A; Schillaci, R; Calogero, A E

    2015-04-01

    The frequency of human papillomavirus (HPV) infection in the semen of patients with male accessory gland infection (MAGI) was evaluated. One hundred infertile patients with MAGI were classified into group A: patients with an inflammatory MAGI (n = 48) and group B: patients with a microbial form (n = 52). Healthy age-matched fertile men (34.0 ± 4.0 years) made up the control group (n = 20). Amplification of HPV DNA was carried out by HPV-HS Bio nested polymerase chain reaction for the detection of HPV DNA sequences within the L1 ORF. Ten patients in group A (20.8%) and 15 patients in group B (28.8%) had a HPV infection; two controls (10.0%) had HPV infection. Patients with MAGI had a significantly higher frequency of HPV infection compared with controls; patients with a microbial MAGI had significantly higher frequency of HPV infection compared with patients with an inflammatory form (both P HPV had a slight, but significantly lower sperm progressive motility and normal morphology compared with patients with MAGI HPV-negative (P HPV infection occurred in patients with MAGI, suggesting that HPV should be investigated in the diagnostic work-up of these patients. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  8. Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients.

    Directory of Open Access Journals (Sweden)

    Kam Leng Aw-Yong

    Full Text Available Enterovirus A71 (EV-A71 is one of the main causative agents of hand, foot and mouth disease (HFMD. Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4, and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142-156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41-55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates.

  9. Human parasitic protozoan infection to infertility: a systematic review.

    Science.gov (United States)

    Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

    2016-02-01

    Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

  10. Disruption of the human gut microbiota following Norovirus infection.

    Directory of Open Access Journals (Sweden)

    Adam M Nelson

    Full Text Available The gut microbiota, the collection of all bacterial members in the intestinal tract, plays a key role in health. Disruption of the indigenous microbiota by a variety of stressors, including antibiotic therapy and intestinal infections, is associated with multiple health problems. We sought to determine if infection with Norovirus disrupts the gut microbiota. Barcoded pyrosequencing of the 16S rRNA-encoding gene was used to characterize the stool microbiota in Norovirus-infected human patients (n = 38. While the microbiota in most infected patients (n = 31 resembled that seen in uninfected healthy controls, a minority of patients (n = 7 possessed a significantly altered microbiota characterized by reduced relative numbers of Bacteriodetes and a corresponding increase in Proteobacteria. In these patients, the increase in Proteobacteria was due to a single operational taxonomic unit (OTU of Escherichia coli. We cultured E. coli from Norovirus-infected patients and characterized them using PCR-ribotyping and virulence factor analysis. Multiple ribotypes were encountered, but none possessed typical virulence factors commonly carried by enteropathogenic E. coli strains. Microbiota disruption and elevated Proteobacteria were not significantly correlated to patient age, gender, sampling time following illness onset, or overall gut inflammation. These results demonstrate that some patients have a disrupted microbiota following Norovirus infection, and therefore may be at elevated risk for long-term health complications.

  11. Human Hendra virus infection causes acute and relapsing encephalitis.

    Science.gov (United States)

    Wong, K T; Robertson, T; Ong, B B; Chong, J W; Yaiw, K C; Wang, L F; Ansford, A J; Tannenberg, A

    2009-06-01

    To study the pathology of two cases of human Hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis. Autopsy tissues were investigated by light microscopy, immunohistochemistry and in situ hybridization. In the patient with acute pulmonary syndrome but not clinical acute encephalitis, vasculitis was found in the brain, lung, heart and kidney. Occasionally, viral antigens were demonstrated in vascular walls but multinucleated endothelial syncytia were absent. In the lung, there was severe inflammation, necrosis and viral antigens in type II pneumocytes and macrophages. The rare kidney glomerulus showed inflammation and viral antigens in capillary walls and podocytes. Discrete necrotic/vacuolar plaques in the brain parenchyma were associated with antigens and viral RNA. Brain inflammation was mild although CD68(+) microglia/macrophages were significantly increased. Cytoplasmic viral inclusions and antigens and viral RNA in neurones and ependyma suggested viral replication. In the case of relapsing encephalitis, there was severe widespread meningoencephalitis characterized by neuronal loss, macrophages and other inflammatory cells, reactive blood vessels and perivascular cuffing. Antigens and viral RNA were mainly found in neurones. Vasculitis was absent in all the tissues examined. The case of acute Hendra virus infection demonstrated evidence of systemic infection and acute encephalitis. The case of relapsing Hendra virus encephalitis showed no signs of extraneural infection but in the brain, extensive inflammation and infected neurones were observed. Hendra virus can cause acute and relapsing encephalitis and the findings suggest that the pathology and pathogenesis are similar to Nipah virus infection.

  12. Human innate lymphoid cells (ILCs) in filarial infections.

    Science.gov (United States)

    Bonne-Année, S; Nutman, T B

    2018-02-01

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  13. [Transfer factor effectiveness patients with persistent genital human papillomavirus infection].

    Science.gov (United States)

    Morfin-Maciel, Blanca María; Sotelo-Ortiz, Julieta Margarita

    2012-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.

  14. De Novo Generated Human Red Blood Cells in Humanized Mice Support Plasmodium falciparum Infection.

    Directory of Open Access Journals (Sweden)

    Anburaj Amaladoss

    Full Text Available Immunodeficient mouse-human chimeras provide a powerful approach to study host specific pathogens like Plasmodium (P. falciparum that causes human malaria. Existing mouse models of P. falciparum infection require repeated injections of human red blood cells (RBCs. In addition, clodronate lipsomes and anti-neutrophil antibodies are injected to suppress the clearance of human RBCs by the residual immune system of the immunodeficient mice. Engraftment of NOD-scid Il2rg-/- mice with human hematopoietic stem cells leads to reconstitution of human immune cells. Although human B cell reconstitution is robust and T cell reconstitution is reasonable in the recipient mice, human RBC reconstitution is generally poor or undetectable. The poor reconstitution is mainly the result of a deficiency of appropriate human cytokines that are necessary for the development and maintenance of these cell lineages. Delivery of plasmid DNA encoding human erythropoietin and interleukin-3 into humanized mice by hydrodynamic tail-vein injection resulted in significantly enhanced reconstitution of erythrocytes. With this improved humanized mouse, here we show that P. falciparum infects de novo generated human RBCs, develops into schizonts and causes successive reinvasion. We also show that different parasite strains exhibit variation in their ability to infect these humanized mice. Parasites could be detected by nested PCR in the blood samples of humanized mice infected with P. falciparum K1 and HB3 strains for 3 cycles, whereas in other strains such as 3D7, DD2, 7G8, FCR3 and W2mef parasites could only be detected for 1 cycle. In vivo adaptation of K1 strain further improves the infection efficiency and parasites can be detected by microscopy for 3 cycles. The parasitemia ranges between 0.13 and 0.25% at the first cycle of infection, falls between 0.08 and 0.15% at the second cycle, and drops to barely detectable levels at the third cycle of infection. Compared to existing

  15. Diagnostic uncertainty of herpangina and hand-foot-and-mouth disease and its impact on national enterovirus syndromic monitoring.

    Science.gov (United States)

    Yang, T O; Huang, W-T; Chen, M-H; Chen, P-C

    2016-05-01

    The community burden of enterovirus is often monitored through syndromic monitoring systems based on reported cases of enterovirus-related infection (EVI) diagnoses. The extent to which this is affected by under- and over-diagnosis has not been reported. In Taiwan, children often make more than one healthcare visit during an episode of infection. We used change of diagnosis within an episode of infection as a guide of diagnostic uncertainty in a nationally representative cohort of Taiwanese children (n = 13 284) followed from birth to the 9th birthday through electronic health records. We conducted a nested case-control analysis and estimated cross-diagnosis ratios (CDRs) as the observed proportion of acute respiratory infection (ARI) diagnoses following an EVI diagnosis in excess of background ARI burdens. With 19 357 EVI diagnoses in this cohort, the CDR within 7 days was 1·51 (95% confidence interval 1·45-1·57), confirming a significant excess of ARI diagnoses within the week following an EVI diagnosis. We used age-specific CDRs to calibrate the weekly EVI burden in children aged 3-5 years in 2008, and the difference between observed and calibrated weekly EVI burdens was small. Therefore, there was evidence suggesting a small uncertainty in EVI diagnosis, but the observed EVI burdens through syndromic monitoring were not substantially affected by the small uncertainty.

  16. Non-polio enteroviruses from acute flaccid paralysis surveillance in Shandong Province, China, 1988-2013.

    Science.gov (United States)

    Tao, Zexin; Wang, Haiyan; Liu, Yao; Li, Yan; Jiang, Ping; Liu, Guifang; Lin, Xiaojuan; Li, Manshi; Wang, Suting; Ji, Feng; Feng, Lei; Xiong, Ping; Zhang, Yan; Feng, Yi; Fan, Qingying; Yang, He; Yang, Jing; Chen, Peng; Li, Wenfeng; Xu, Aiqiang; Song, Lizhi

    2014-08-22

    Enteroviruses (EVs) are important human pathogens associated with various clinical syndromes. This study represents an overview of non-polio enteroviruses (NPEVs) isolated from acute flaccid paralysis (AFP) surveillance in Shandong Province, China from 1988 to 2013. Altogether 792 and 170 NPEV isolates were isolated from stool specimens of 9263 AFP cases and 1059 contacts, respectively. Complete VP1 sequencing and typing on all 962 isolates revealed 53 NPEV types in which echovirus (E) 6 (7.6%), E14 (7.6%), E11 (7.4%), coxsackievirus (CV) B3 (7.4%), E25 (5.6%), CVB5 (4.9%), E7 (4.5%) and EV-A71 (4.4%) were the eight most commonly reported serotypes. Distinct summer-fall seasonality was observed, with June-October accounting for 79.3% of isolation from AFP cases with known month of specimen collection. Increase of isolation of EV-A71 and CVA--the predominant pathogens for the hand, foot, and mouth disease--was observed in recent years. Sequence analysis on VP1 coding region of EV-A71 and E6 suggested Shandong strains had great genetic divergence with isolates from other countries. The results described in this study provide valuable information on the circulation and emergence of different EV types in the context of limited EV surveillance in China.

  17. Non-Polio Enteroviruses from Acute Flaccid Paralysis Surveillance in Shandong Province, China, 1988–2013

    Science.gov (United States)

    Tao, Zexin; Wang, Haiyan; Liu, Yao; Li, Yan; Jiang, Ping; Liu, Guifang; Lin, Xiaojuan; Li, Manshi; Wang, Suting; Ji, Feng; Feng, Lei; Xiong, Ping; Zhang, Yan; Feng, Yi; Fan, Qingying; Yang, He; Yang, Jing; Chen, Peng; Li, Wenfeng; Xu, Aiqiang; Song, Lizhi

    2014-01-01

    Enteroviruses (EVs) are important human pathogens associated with various clinical syndromes. This study represents an overview of non-polio enteroviruses (NPEVs) isolated from acute flaccid paralysis (AFP) surveillance in Shandong Province, China from 1988 to 2013. Altogether 792 and 170 NPEV isolates were isolated from stool specimens of 9263 AFP cases and 1059 contacts, respectively. Complete VP1 sequencing and typing on all 962 isolates revealed 53 NPEV types in which echovirus (E) 6 (7.6%), E14 (7.6%), E11 (7.4%), coxsackievirus (CV) B3 (7.4%), E25 (5.6%), CVB5 (4.9%), E7 (4.5%) and EV-A71 (4.4%) were the eight most commonly reported serotypes. Distinct summer–fall seasonality was observed, with June–October accounting for 79.3% of isolation from AFP cases with known month of specimen collection. Increase of isolation of EV-A71 and CVA—the predominant pathogens for the hand, foot, and mouth disease—was observed in recent years. Sequence analysis on VP1 coding region of EV-A71 and E6 suggested Shandong strains had great genetic divergence with isolates from other countries. The results described in this study provide valuable information on the circulation and emergence of different EV types in the context of limited EV surveillance in China. PMID:25145609

  18. [Genotype distribution of enterovirus group B isolated in Shandong Province, China].

    Science.gov (United States)

    Wang, Hai-yan; Liu, Kun; Tao, Ze-xin; Li, Yan; Liu, Gui-fang; Liu, Yao; Feng, Lei; Fan, Qing-ying; Yang, He; Song, Li-zhi; Xu, Ai-qiang

    2010-09-01

    In order to explore the genotype distribution of human enterovirus group B (HEV-B) in Shandong Province and to study the correlation between HEV-B serotypes and disease outbreaks, we sequenced and analyzed the entire VP1 coding region of HEV-B isolated from acute flaccid parolysis (AFP) system and disease outbreaks in Shandong province during 1998-2008. All together twenty nine HEV-B serotypes were identified, including twenty Echovirus (ECHO) serotypes, five Coxsackievirus B (CVB1-5) serotypes, one Coxsackievirus A9(CVA9) serotype, and newer enteroviruses EV73, EV75, and EV97. E11, CVB3, E6, E14 and E25 were the five frequently isolated serotypes from AFP surveillance system. CVB3, CVB5 and ECHO30 were the major causative agent of aseptic meningitis in Shandong province. Comparison of nucleotide sequence homology showed 75.4%-99.6% inter-typic identities within Shandong strains, and 73.8%-85.2% identities with prototype strains. Amino acid sequence comparison showed the differentiation was not much. Our research showed different serotypes possessed distinct time-cycling pattern, and different sub-genotypes could be further classified according to the inter-typic genetic distance. Thereby the route and range of transmission of HEV could be determined.

  19. Human coronavirus and severe acute respiratory infection in Southern Brazil.

    Science.gov (United States)

    Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

    2016-05-01

    Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

  20. [Human intestinal parasitosis: role of Dientamoeba fragilis in human infections].

    Science.gov (United States)

    Crotti, D; D'Annibale, M L

    2007-01-01

    The Authors report prevalences of intestinal parasitosis among home children and adults during 2002-2004, as in O&P as in acute or prolonged diarrhoea, with particular attention to the role of Dientamoeba fragilis, because often undervalued. Among 3139 subjects, 116 cases of dientamoebiasis (3.7%) and 62 of giardiasis (2.0%) were observed; not typical pathogenic protozoa were reported in 71 cases (2.3%); helminths were identified only in 8 cases (0.5%). Particularly, inside O&P group D. fragilis prevailed in 5.2% of cases (7.8% in adults and 0.5% in children) and G. duodenalis in 2.7% (3.5% and 1.3% respectively); inside acute diarrhoeas D. fragilis prevailed in 1.6% (3.9% and 0.3%) and G. duodenalis in 0.6% (1.3% and 0. 1%); inside prolonged diarrhoeas D. fragilis prevailed in 3.5 % (2.6% and 5.4%) and G. duodenalis in 3.9% (5.8% in adults and never in children). D. fragilis was more often observed among adults (6.3% of all) than among children (0.6%), like G. duodenalis (3.1% versus 0.6%). So, 107 strains of D. fragilis (92.2%) and 53 strains of G. duodenalis (85.5%) were identified in adults. D. fragilis was more frequent among females (24/39 cases, 61.5%, in the last year) while G. duodenalis was more frequent in males (13/23 cases, 56.5%). The Authors conclude underlining the importance of a permanent stain, as Giemsa stain, for a good and complete diagnosis of protozoal intestinal infections, particularly for D. fragilis.

  1. Controlled human infection models for vaccine development: Zika virus debate.

    Science.gov (United States)

    Gopichandran, Vijayaprasad

    2017-10-31

    An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.

  2. Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

    Science.gov (United States)

    2018-01-21

    Streptococcus Pyogenes Pharyngitis; Streptococcus Pharyngitis; Strep Throat; Streptococcus Pyogenes Infection; Group A Streptococcus: B Hemolytic Pharyngitis; Group A Streptococcal Infection; Gram-Positive Bacterial Infections; Bacterial Infections

  3. Comparison of the genexpert enterovirus assay (GXEA) with real-time one step RT-PCR for the detection of enteroviral RNA in the cerebrospinal fluid of patients with meningitis.

    Science.gov (United States)

    Hong, JiYoung; Kim, Ahyoun; Hwang, Seoyeon; Cheon, Doo-Sung; Kim, Jong-Hyen; Lee, June-Woo; Park, Jae-Hak; Kang, Byunghak

    2015-02-13

    Enteroviruses (EVs) are the leading cause of aseptic meningitis worldwide. Detection of enteroviral RNA in clinical specimens has been demonstrated to improve the management of patient care, especially that of neonates and young children. To establish a sensitive and reliable assay for routine laboratory diagnosis, we compared the sensitivity and specificity of the GeneXpert Enterovirus Assay (GXEA) with that of the reverse transcription polymerase chain reaction (RT-PCR) based assay referred to as real-time one step RT-PCR (RTo-PCR). The sensitivity/specificity produced by GXEA and RTo-PCR were 100%/100% and 65%/100%, respectively. Both methods evaluated in this article can be used for detection of enterovirus in clinical specimens and these nucleic acid amplification methods are useful assays for the diagnosis of enteroviral infection.

  4. [Pulmonary complications in children with human immunodeficiency virus infection].

    Science.gov (United States)

    Brockmann V, Pablo; Viviani S, Támara; Peña D, Anamaría

    2007-08-01

    Pulmonary complications in children infected by human immunodeficiency virus (HIV) are common and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). The aim of our study was to review pulmonary diseases and complications in pediatric patients with HIV infection in a large tertiary hospital in Santiago, Chile. We performed a retrospective, descriptive analysis of 17 patients with HIV infection controlled at the Hospital Dr. Sótero del Rio. Respiratory complications/diseases were: overall pneumonia (n: 14), recurrent pneumonia (n: 10), citomegalovirus associated pneumonia (n: 4), Pneumocystis jiroveci associated pneumonia (n: 1) pulmonary tuberculosis (n: 1), lymphoid interstitial pneumonia (n: 3) and chronic pulmonary disease (n: 7). Microorganisms isolated were mostly atypical and frequently associated with severe and chronic pulmonary damage. A high degree of suspicion is required to detect atypical microorganisms promptly, in order to rapidly implement pathogen targeted therapy that could potentially decrease the possibility of sequelae.

  5. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes...... cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi......'s sarcoma are the most important parts of the differential diagnosis. An aggressive approach to the diagnosis of pulmonary disease in this patient population is indicated in order to provide optimal care and assess new therapies....

  6. Kluyvera cryocrescens finger infection: case report and review of eighteen Kluyvera infections in human beings.

    Science.gov (United States)

    West, B C; Vijayan, H; Shekar, R

    1998-11-01

    We report a case of soft tissue infection with Kluyvera cryocrescens and a critical review of Kluyvera infections. A 31-year-old diabetic man used a new chemical for stripping the floor with his bare hands. Two days later he developed a blister on a finger which progressed to tenosynovitis in spite of intravenous nafcillin therapy. After 11 days culture and sensitivity results dictated treatment with intravenous ticarcillin/clavulanic acid. The wound was debrided twice, and later a skin flap was done. Wound cultures became sterile after 7 days of treatment with ticarcillin/clavulanic acid, and he recovered. This case represents the fourth clinical infection with K. cryocrescens and the eighteenth of Kluyvera to be reported. Four others were K. ascorbata, and the remaining ten Kluyvera infections in humans were not identified beyond genus. Our case and review of the 17 previous cases emphasize that while Kluyvera rarely cause disease, these opportunistic Gram-negative bacilli may be virulent in a variety of sites under as yet poorly defined host conditions. Sites of infection varied, but the brain and meninges were not among them. Two patients had diabetes mellitus, none had AIDS, and four died. Once shown clinically to be the cause of an infection, Kluyvera deserve aggressive treatment which acknowledges their ampicillin resistance.

  7. Human Papillomavirus infection and cervical lesions in HIV infected women on antiretroviral treatment in Thailand.

    Science.gov (United States)

    Delory, Tristan; Ngo-Giang-Huong, Nicole; Rangdaeng, Samreung; Chotivanich, Nantasak; Limtrakul, Aram; Putiyanun, Chaiwat; Suriyachai, Pornnapa; Matanasarawut, Wanmanee; Jarupanich, Tapnarong; Liampongsabuddhi, Prateung; Heard, Isabelle; Jourdain, Gonzague; Lallemant, Marc; Le Coeur, Sophie

    2017-05-01

    To estimate the prevalence and factors associated with Human Papillomavirus (HPV) infection, HPV genotypes and cytological/histological high-grade (HSIL+/CIN2+) lesions. We conducted a cross-sectional study within a prospective cohort of HIV-infected women on combination antiretroviral therapy (cART). Cervical specimens were collected for cytology and HPV genotyping (Papillocheck®). Any women with High-Risk-HPV (HR-HPV), and/or potentially HR-HPV (pHR-HPV) and/or ASC-US or higher (ASC-US+) lesions were referred for colposcopy. Factors associated with HR-HPV infection and with HSIL+/CIN2+ lesions were investigated using mixed-effects logistic regression models. 829 women were enrolled: median age 40.4 years, on cART for a median of 6.9 years, median CD4 cell-count 536 cells/mm3, and 788 (96%) with HIV-viral loadwomen (9%) had ASC-US+ and 28 (3%) HSIL+/CIN2+ lesions. HR-HPV infection was independently associated with HSIL+/CIN2+ lesions. The prevalence of HPV infection and of cervical lesions was low. The HPV genotype distribution supports the use of 9-valent vaccine in Thailand. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  8. Natural Gastric Infection with Helicobacter pylori in Monkeys: A Model for Spiral Bacteria Infection in Humans

    Science.gov (United States)

    1994-01-01

    humans and by the persistently Infected and have gastrtis and elevated absence of an accepted animal model. specific IgG levels, all of which may... Gastrtis scoe H. pyon gG Time (mo) Corpus Antrum Corpus Antrum Corpus Antrum ratiod H. pylion-infected (n = 6) 0 1.8 ± 0.5 2.3 ± 0.4 0.7 ± 0.2 1.0...light microscopy)a H. pylon (culture)* Gastrtis score’ H. pylon lgG Time (mo) Corpus Antrum Corpus Antrum Corpus Antrum ratiow H. pyllon-nfected kn = 2

  9. The Pseudomonas aeruginosa opportunistic pathogen and human infections.

    Science.gov (United States)

    de Bentzmann, Sophie; Plésiat, Patrick

    2011-07-01

    Pseudomonas aeruginosa, a Gram-negative environmental species and an opportunistic microorganism, establishes itself in vulnerable patients, such as those with cystic fibrosis or hospitalized in intensive care units. It has become a major cause of nosocomial infections worldwide (about 10% of all such infections in most European Union hospitals) and a serious threat to Public Health. The overuse and misuse of antibiotics have also led to the selection of resistant strains against which very few therapeutic options exist. How an environmental species can cause human infections remains a key question that still needs elucidation despite the incredibly high progress that has been made in the P. aeruginosa biology over the past decades. The workshop belonging to Current trends in Biomedicine series, which was held under the sponsorship of the Universidad International de Andalucia between the 8th and the 10th November 2010 brought in the most recent advances in the environmental life of P. aeruginosa, the human P. aeruginosa infections, the new animal models to study Pseudomonas infections, the new genetic aspects including metabolomics, genomics and bioinformatics and the community lifestyle named biofilm that accounts for P. aeruginosa persistence in humans. This workshop organized by Soeren Molin (Danemark), Juan-Luis Ramos (Spain) and Sophie de Bentzmann (France) gathered 46 researchers coming from 11 European and American countries in a small format and was hosted in the 'Sede Antonio Machado' in Baeza. It was organized in seven sessions covering animal models for P. aeruginosa pathogenesis, resistance to drugs, regulatory potency including small RNA, two component systems, extracytoplasmic function sigma factors and trancriptional regulators, new therapies emerging from dissection of molecular mechanisms, and evolutionary mechanisms of P. aeruginosa strains in patients. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  10. Oral Human Papillomavirus Infection: Differences in Prevalence Between Sexes and Concordance With Genital Human Papillomavirus Infection, NHANES 2011 to 2014.

    Science.gov (United States)

    Sonawane, Kalyani; Suk, Ryan; Chiao, Elizabeth Y; Chhatwal, Jagpreet; Qiu, Peihua; Wilkin, Timothy; Nyitray, Alan G; Sikora, Andrew G; Deshmukh, Ashish A

    2017-10-17

    The burden of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is disproportionately high among men, yet empirical evidence regarding the difference in prevalence of oral HPV infection between men and women is limited. Concordance of oral and genital HPV infection among men is unknown. To determine the prevalence of oral HPV infection, as well as the concordance of oral and genital HPV infection, among U.S. men and women. Nationally representative survey. Civilian noninstitutionalized population. Adults aged 18 to 69 years from NHANES (National Health and Nutritional Examination Survey, 2011 to 2014). Oral rinse, penile swab, and vaginal swab specimens were evaluated by polymerase chain reaction followed by type-specific hybridization. The overall prevalence of oral HPV infection was 11.5% (95% CI, 9.8% to 13.1%) in men and 3.2% (CI, 2.7% to 3.8%) in women (equating to 11 million men and 3.2 million women nationwide). High-risk oral HPV infection was more prevalent among men (7.3% [CI, 6.0% to 8.6%]) than women (1.4% [CI, 1.0% to 1.8%]). Oral HPV 16 was 6 times more common in men (1.8% [CI, 1.3% to 2.2%]) than women (0.3% [CI, 0.1% to 0.5%]) (1.7 million men vs. 0.27 million women). Among men and women who reported having same-sex partners, the prevalence of high-risk HPV infection was 12.7% (CI, 7.0% to 18.4%) and 3.6% (CI, 1.4% to 5.9%), respectively. Among men who reported having 2 or more same-sex oral sex partners, the prevalence of high-risk HPV infection was 22.2% (CI, 9.6% to 34.8%). Oral HPV prevalence among men with concurrent genital HPV infection was fourfold greater (19.3%) than among those without it (4.4%). Men had 5.4% (CI, 5.1% to 5.8%) greater predicted probability of high-risk oral HPV infection than women. The predicted probability of high-risk oral HPV infection was greatest among black participants, those who smoked more than 20 cigarettes daily, current marijuana users, and those who reported 16 or more

  11. Infection

    Science.gov (United States)

    2010-09-01

    whether BMPs maintain their osteoinductive capability in infected human wounds. The authors are aware of only one series describing the use of BMP in an...et al. Osteogenic protein-1 induces bone formation in the presence of bacterial infection in a rat intramuscular osteoinduction model. J Orthop Trauma

  12. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections.

    Directory of Open Access Journals (Sweden)

    Ettie M Lipner

    Full Text Available Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects.

  13. Human giardiasis in Serbia: asymptomatic vs symptomatic infection*

    Science.gov (United States)

    Nikolić, A.; Klun, I.; Bobić, B.; Ivović, V.; Vujanić, M.; Živković, T.; Djurković-Djaković, O.

    2011-01-01

    Despite the public health importance of giardiasis in all of Europe, reliable data on the incidence and prevalence in Western Balkan Countries (Serbia, Bosnia and Herzegovina, Croatia, Montenegro and FYR Macedonia) are scarce, and the relative contribution of waterborne and food-borne, or person-to-person and/or animalto- person, transmission of human giardiasis is not yet clear. To provide baseline data for the estimation of the public health risk caused by Giardia, we here review the information available on the epidemiological characteristics of asymptomatic and symptomatic human infection in Serbia. Although asymptomatic cases of Giardia represent a major proportion of the total cases of infection, high rates of Giardia infection were found in both asymptomatic and symptomatic populations. No waterborne outbreaks of giardiasis have been reported, and it thus seems that giardiasis mostly occurs sporadically in our milieu. Under such circumstances, control measures to reduce the high prevalence of giardiasis in Serbia have focused on person-to-person transmission, encouraging proper hygiene, but for more targeted intervention measures, studies to identify other risk factors for asymptomatic and symptomatic infections are needed. PMID:21678797

  14. Nuclear domain 10 components upregulated via interferon during human cytomegalovirus infection potently regulate viral infection.

    Science.gov (United States)

    Ashley, Caroline L; Glass, Mandy S; Abendroth, Allison; McSharry, Brian P; Slobedman, Barry

    2017-07-01

    Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection. In this study, analysis of ND10 component transcription during HCMV infection demonstrated that PML and Sp100 were significantly upregulated whilst hDaxx expression remained unchanged. In cells engineered to block the production of, or response to, type I IFNs, upregulation of PML and Sp100 was not detected during HCMV infection. Furthermore, pre-treatment with an IFN-β neutralizing antibody inhibited upregulation of PML and Sp100 during both infection and treatment with HCMV-infected cell supernatant. The significance of ND10 components functioning as anti-viral ISGs during HCMV infection was determined through knockdown of PML, Sp100 and hDaxx. ND10 knockdown cells were significantly more permissive to HCMV infection, as previously described but, in contrast to control cells, could support HCMV plaque formation following IFN-β pre-treatment. This ability of HCMV to overcome the potently anti-viral effects of IFN-β in ND10 expression deficient cells provides evidence that ND10 component upregulation is a key mediator of the anti-viral activity of IFN-β.

  15. Hand foot and mouth disease due to enterovirus 71 in Malaysia.

    Science.gov (United States)

    Chua, Kaw Bing; Kasri, Abdul Rasid

    2011-08-01

    Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. The illness is caused by a number of enteroviruses with coxsackievirus A16 and enterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs to the species Human enterovirus A under the genus Enterovirus within the family Picornaviridae. EV71 has been associated with an array of clinical diseases including hand foot and mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like acute flaccid paralysis. A large outbreak of HFMD due to highly neurovirulent EV71 emerged in Malaysia in 1997, and caused 41 deaths amongst young children. In late 2000, a recurrence of an outbreak of HFMD occurred in Malaysia with 8 fatalities in peninsular Malaysia. Outbreak of HFMD due to EV71 recurred in 2003 with an unknown number of cases and mortalities. A similar outbreak of HFMD with 2 recorded deaths in young children occurred in peninsular Malaysia in late 2005 and this was followed by a larger outbreak in Sarawak (Malaysian Borneo) with 6 reported fatalities in the early part of 2006. The current on-going outbreak of HFMD started in peninsular Malaysia in epidemiological week 12 of 2010. As with other HFMD outbreaks in Malaysia, both EV71 and CA16 were the main aetiological viruses isolated. In similarity with the HFMD outbreak in 2005, the isolation of CA16 preceded the appearance of EV71. Based on the VP1 gene nucleotide sequences, 4 sub-genogroups of EV71 (C1, C2, B3 and B4) co-circulated and caused the outbreak of hand, foot and mouth disease in peninsular Malaysia in 1997. Two sub-genogroups (C1 and B4) were noted to cause the outbreak in 2000 in both peninsular Malaysia and Sarawak. EV71 of sub-genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak in 2003. In the 2005 outbreak

  16. Role of CD4 endocytosis in human immunodeficiency virus infection.

    Science.gov (United States)

    Pelchen-Matthews, A; Clapham, P; Marsh, M

    1995-12-01

    We have analyzed the role of CD4 endocytosis in human immunodeficiency virus (HIV) entry by measuring the infection of HeLa cells expressing various CD4 constructs with endocytosis rates of between 0.2 and 30%/min in a quantitative infectious focus assay. For a number of laboratory-adapted HIV-1 and HIV-2 strains, the highest levels of infection were found on cells with very limited CD4 endocytosis, while cells with efficient CD4 uptake were only poorly infectable, suggesting that CD4 internalization is not required for HIV entry. This was confirmed in a modified assay involving prebinding of HIV-1LAI to HeLa-CD4 cells at 4 degrees C, synchronized virus entry during warming to 37 degrees C, and neutralization of virions remaining at the cell surface with anti-V3 loop antibodies. Warming cells in hypertonic medium inhibited CD4 endocytosis but did not affect the rate or the extent of infection. These studies confirm that HIV infection does not require endocytosis and that laboratory-adapted virus strains can enter HeLa-CD4 cells by fusion at the plasma membrane.

  17. [Hematological changes associated with human immunodeficiency virus (HIV-1) infection].

    Science.gov (United States)

    Møller, T; Hasselbalch, H C

    1993-05-10

    Infection with human immunodeficiency virus type 1 (HIV-1) primarily involves a subgroup of T-lymphocytic cells, but other cell types are also invaded by the virus, including cell lines within the haematopoietic system. Together with infectious, inflammatory and neoplasic processes, invasion of haematopoietic tissue explains the haematological alterations which are seen during the course of infection with HIV-1. Anaemia develops in the large proportion of patients. Thrombocytopenia frequently occurs during the course of the disease, but may be seen in some patients already at the time of diagnosis, where the condition may be misdiagnosed as "idiopathic" thrombocytopenic purpura. Neutropenia is seen in all disease stages, but is most severe in patients with advanced disease. Bone marrow changes include varying degrees of dysplasia in one or more cell lines, which in some patients may mimic a myelodysplastic syndrome. The number of plasma cells is always increased. In many patients the bone marrow stroma exhibits an increased amount of reticular fibres. HIV-1 infection is associated with an increased risk of non-Hodgkin malignant lymphoma. Acute myelogenous leukaemia and myelomatosis have been described in patients with advanced disease. Treatment of the above mentioned haematological abnormalities aims primarily at reducing replication of HIV-1, thereby diminishing suppression of haematopoiesis by the virus infection, and at controlling the opportunistic infections during the course of the disease. Specific antiviral therapy (AZT) is most successful in correcting thrombocytopenia. The possibility of bone marrow suppression mediated by a toxic drug effect should always be considered in this patient group.

  18. Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

    Science.gov (United States)

    Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

    2013-06-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection.

  19. Human rhinovirus infection in young African children with acute wheezing

    Directory of Open Access Journals (Sweden)

    Zar Heather J

    2011-03-01

    Full Text Available Abstract Background Infections caused by human rhinoviruses (HRVs are important triggers of wheezing in young children. Wheezy illness has increasingly been recognised as an important cause of morbidity in African children, but there is little information on the contribution of HRV to this. The aim of this study was to determine the role of HRV as a cause of acute wheezing in South African children. Methods Two hundred and twenty children presenting consecutively at a tertiary children's hospital with a wheezing illness from May 2004 to November 2005 were prospectively enrolled. A nasal swab was taken and reverse transcription PCR used to screen the samples for HRV. The presence of human metapneumovirus, human bocavirus and human coronavirus-NL63 was assessed in all samples using PCR-based assays. A general shell vial culture using a pool of monoclonal antibodies was used to detect other common respiratory viruses on 26% of samples. Phylogenetic analysis to determine circulating HRV species was performed on a portion of HRV-positive samples. Categorical characteristics were analysed using Fisher's Exact test. Results HRV was detected in 128 (58.2% of children, most (72% of whom were under 2 years of age. Presenting symptoms between the HRV-positive and negative groups were similar. Most illness was managed with ambulatory therapy, but 45 (35% were hospitalized for treatment and 3 (2% were admitted to intensive care. There were no in-hospital deaths. All 3 species of HRV were detected with HRV-C being the most common (52% followed by HRV-A (37% and HRV-B (11%. Infection with other respiratory viruses occurred in 20/128 (16% of HRV-positive children and in 26/92 (28% of HRV-negative samples. Conclusion HRV may be the commonest viral infection in young South African children with acute wheezing. Infection is associated with mild or moderate clinical disease.

  20. Measuring serum antibody to human papillomavirus following infection or vaccination.

    Science.gov (United States)

    Frazer, Ian H

    2010-06-01

    The family of human papillomaviruses (HPVs) includes more than 130 genotypes, many of which infect the genital tract, and these can be classified as low risk or high risk for induction of genital neoplasia. Two prophylactic vaccines are currently available for the prevention of genital HPV infection: a quadrivalent (Gardasil); Merck & Co. Inc) and a bivalent (Cervarix; GlaxoSmithKline) vaccine. Protection against HPV infection and associated disease is observed for at least 6.4 years following immunization with the bivalent vaccine and for at least 8.5 years with the HPV 16L1 virus-like particle of the quadrivalent vaccine. HPV vaccines induce robust immune memory, as evidenced by recall of responses after revaccination, suggesting that immunization will afford long-lasting protection. An immunological marker for ongoing protection from infection would provide information to help establish best-practice deployment of these vaccines. However, while HPV-specific antibody is likely the major mechanism of protection against HPV infection following immunization, available serological assays provide only a partial characterization of immune status, and no measured immune response has been shown to define immediate or future protection against HPV infection or associated disease. Future research efforts should therefore be directed towards correlating measures of virus-specific immune memory with continued protection against infection with the HPV types in the available vaccines, and towards determining the duration of cross-protection afforded by these vaccines against HPV types other than those incorporated in the vaccines. Copyright (c) 2010. Published by Elsevier Inc.

  1. Serologic evidence of human orthopoxvirus infections in Sierra Leone.

    Science.gov (United States)

    Macneil, Adam; Abel, Jason; Reynolds, Mary G; Lash, Rr; Fonnie, Richard; Kanneh, Lansana D; Robert, Willie; Lungay, Victor K; Goba, Augustine; Moses, Lina M; Damon, Inger K; Karem, Kevin; Bausch, Daniel G

    2011-10-28

    Orthopoxviruses, including variola virus, vaccinia virus, and monkeypox virus, have previously been documented in humans in West Africa, however, no cases of human orthopoxvirus infection have been reported in the region since 1986. We conducted a serosurvey to determine whether human exposure to orthopoxviruses continues to occur in eastern Sierra Leone. To examine evidence of exposure to orthopoxviruses in the Kenema District of Sierra Leone, we collected and tested sera from 1596 persons by IgG ELISA and a subset of 313 by IgM capture ELISA. Eleven persons born after the cessation of smallpox vaccination had high orthopoxvirus-specific IgG values, and an additional 6 persons had positive IgM responses. No geographic clustering was noted. These data suggest that orthopoxviruses continue to circulate in Sierra Leone. Studies aimed at obtaining orthopoxvirus isolates and/or genetic sequences from rodents and symptomatic humans in the area are indicated.

  2. Serologic evidence of human orthopoxvirus infections in Sierra Leone

    Directory of Open Access Journals (Sweden)

    Goba Augustine

    2011-10-01

    Full Text Available Abstract Background Orthopoxviruses, including variola virus, vaccinia virus, and monkeypox virus, have previously been documented in humans in West Africa, however, no cases of human orthopoxvirus infection have been reported in the region since 1986. We conducted a serosurvey to determine whether human exposure to orthopoxviruses continues to occur in eastern Sierra Leone. Findings To examine evidence of exposure to orthopoxviruses in the Kenema District of Sierra Leone, we collected and tested sera from 1596 persons by IgG ELISA and a subset of 313 by IgM capture ELISA. Eleven persons born after the cessation of smallpox vaccination had high orthopoxvirus-specific IgG values, and an additional 6 persons had positive IgM responses. No geographic clustering was noted. Conclusions These data suggest that orthopoxviruses continue to circulate in Sierra Leone. Studies aimed at obtaining orthopoxvirus isolates and/or genetic sequences from rodents and symptomatic humans in the area are indicated.

  3. BioFire FilmArray Respiratory Panel for Detection of Enterovirus D68.

    Science.gov (United States)

    Shibib, Dena R; Matushek, Scott M; Beavis, Kathleen G; Gawel, Susan H; Charnot-Katsikas, Angella

    2016-02-01

    During the enterovirus D68 (EV-D68) outbreak of 2014, the BioFire FilmArray (FA) respiratory panel was used to detect rhinovirus/enterovirus in respiratory specimens; suspected EV-D68-positive specimens were sent to CDC for confirmation. Positive rhinovirus/enterovirus FA targets revealed patterns loosely associated with EV-D68 that may be useful for confirmation triaging. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. Defining cell culture conditions to improve human norovirus infectivity assays

    Energy Technology Data Exchange (ETDEWEB)

    Straub, Tim M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hutchison, Janine R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bartholomew, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Valdez, Catherine O. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Valentine, Nancy B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Dohnalkova, Alice [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Ozanich, Richard M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bruckner-Lea, Cindy J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-01-10

    Significant difficulties remain for determining whether human noroviruses (hNoV) recovered from water, food, and environmental samples are infectious. Three-dimensional tissue culture of human intestinal cells has shown promise in developing an infectivity assay, but reproducibility, even within a single laboratory, remains problematic. From the literature and our observations, we hypothesized that the common factors that leads to more reproducible hNoV infectivity in vitro requires that the cell line be 1) of human gastrointestinal origin, 2) expresses apical microvilli, and 3) be a positive secretor cell line. The C2BBe1 cell line, which is a brush-border producing clone of Caco-2, meets these three criteria. When challenged with Genogroup II viruses, we observed a 2 Log10 increase in viral RNA titer. A passage experiment with GII viruses showed evidence of the ability to propagate hNoV by both reverse transcription quantitative PCR (qRT-PCR) and microscopy. Using 3-D C2BBe1 cells improves reproducibility of the infectivity assay for hNoV, but the assay can still be variable. Two sources of variability include the cells themselves (mixed phenotypes of small and large intestine) and initial titer measurements using quantitative reverse transcription PCR (qRT-PCR) that measures all RNA vs. plaque assays that measure infectious virus.

  5. A highly conserved amino acid in VP1 regulates maturation of enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yong-Xin Zhang

    2017-09-01

    Full Text Available Enterovirus 71 (EV71 is the major causative agent of hand, foot and mouth disease (HFMD in children, causing severe clinical outcomes and even death. Here, we report an important role of the highly conserved alanine residue at position 107 in the capsid protein VP1 (VP1A107 in the efficient replication of EV71. Substitutional mutations of VP1A107 significantly diminish viral growth kinetics without significant effect on viral entry, expression of viral genes and viral production. The results of mechanistic studies reveal that VP1A107 regulates the efficient cleavage of the VP0 precursor during EV71 assembly, which is required, in the next round of infection, for the transformation of the mature virion (160S into an intermediate or A-particle (135S, a key step of virus uncoating. Furthermore, the results of molecular dynamic simulations and hydrogen-bond networks analysis of VP1A107 suggest that flexibility of the VP1 BC loop or the region surrounding the VP1107 residue directly correlates with viral infectivity. It is possible that sufficient flexibility of the region surrounding the VP1107 residue favors VP0 conformational change that is required for the efficient cleavage of VP0 as well as subsequent viral uncoating and viral replication. Taken together, our data reveal the structural role of the highly conserved VP1A107 in regulating EV71 maturation. Characterization of this novel determinant of EV71 virulence would promote the study on pathogenesis of Enteroviruses.

  6. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  7. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Science.gov (United States)

    2012-01-01

    Background Congenital human cytomegalovirus (HCMV) infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR) methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV), microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC). However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-6 (IL-6). Pericytes exposed to SBCMV elicited higher levels of IL-6

  8. Preclinical evaluation of the immunogenicity and safety of an inactivated enterovirus 71 candidate vaccine.

    Directory of Open Access Journals (Sweden)

    Shi-Hsia Hwa

    2013-11-01

    Full Text Available Human enterovirus 71 (EV71 is a significant cause of morbidity and mortality from Hand, Foot and Mouth Disease (HFMD and neurological complications, particularly in young children in the Asia-Pacific region. There are no vaccines or antiviral therapies currently available for prevention or treatment of HFMD caused by EV71. Therefore, the development of therapeutic and preventive strategies against HFMD is of growing importance. We report the immunogenic and safety profile of inactivated, purified EV71 preparations formulated with aluminum hydroxide adjuvant in preclinical studies in mice and rabbits. In mice, the candidate vaccine formulations elicited high neutralizing antibody responses. A toxicology study of the vaccine formulations planned for human use performed in rabbits showed no vaccine-related pathological changes and all animals remained healthy. Based on these preclinical studies, Phase 1 clinical testing of the EV71 inactivated vaccine was initiated.

  9. Incidence and persistence of carcinogenic genital human papillomavirus infections in young women with or without Chlamydia trachomatis co-infection

    NARCIS (Netherlands)

    Vriend, Henrike J.; Bogaards, Johannes A.; van Bergen, Jan E. A. M.; Brink, Antoinette A. T. P.; van den Broek, Ingrid V. F.; Hoebe, Christian J. P. A.; King, Audrey J.; van der Sande, Marianne A. B.; Wolffs, Petra F. G.; de Melker, Hester E.

    2015-01-01

    We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation

  10. Anti-enterovirus 71 activities of Melissa officinalis extract and its biologically active constituent rosmarinic acid.

    Science.gov (United States)

    Chen, Sin-Guang; Leu, Yann-Lii; Cheng, Mei-Ling; Ting, Siew Chin; Liu, Ching-Chuan; Wang, Shulhn-Der; Yang, Cheng-Hung; Hung, Cheng-Yu; Sakurai, Hiroaki; Chen, Kuan-Hsing; Ho, Hung-Yao

    2017-09-25

    Enterovirus 71 (EV71) infection is endemic in the Asia-Pacific region. No specific antiviral drug has been available to treat EV71 infection. Melissa officinalis (MO) is a medicinal plant with long history of usage in the European and Middle East. We i