Science.gov

Sample records for acute rsv infection

  1. RSV molecular characterization and specific antibody response in young children with acute lower respiratory infection.

    PubMed

    Baumeister, Elsa G; Hünicken, Diego S; Savy, Vilma L

    2003-05-01

    The presence of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) were studied in 254 hospitalized Argentinean children with acute lower respiratory infection tract (ALRI). The specific humoral immune response and partial sequences of the G protein gene were studied in a subset of 22 children with RSV confirmed infection. The RSV IgM detection and the RSV IgG titration were made by immunofluorescence assay (IFA) in pairs of sera. The partial RSV G gene sequences were obtained by an RT-PCR amplification directly from de NPAs. RSV was present in 44.5% of the children. The RSV IgM was detected in 22.7 and 68.8% of the first and second sera, respectively. The IgG geometric mean titers of the acute and convalescent sera were 8 and 589. The RSV IgG titration was able to define 86.4% of the RSV confirmed cases. The percentage of coincidence between RSV IgM detection in the second sera and diagnosis by RSV IgG titration was 72.7% and no significant differences were observed. The nucleotide sequence of one group A and three group B viruses were identified. The first one was related with circulating viruses in Madrid, Montevideo and Mozambique during 1992, 1989 and 1999, respectively. The three sequences identified as group B viruses were closely related with circulating viruses in 1998 from South Africa and Canada during 1999 and 2000. The data obtained in our study provide the first approach at the molecular level (nucleotide) of the RSV circulating strains in Argentina and the lack of genotype patterns previously determined make necessary a continuous molecular surveillance in order to contribute to the understanding of the behavior of this virus in our community.

  2. Association of RSV-A ON1 genotype with Increased Pediatric Acute Lower Respiratory Tract Infection in Vietnam

    PubMed Central

    Yoshihara, Keisuke; Le, Minh Nhat; Okamoto, Michiko; Wadagni, Anita Carolle Akpeedje; Nguyen, Hien Anh; Toizumi, Michiko; Pham, Enga; Suzuki, Motoi; Nguyen, Ai Thi Thuy; Oshitani, Hitoshi; Ariyoshi, Koya; Moriuchi, Hiroyuki; Hashizume, Masahiro; Dang, Duc Anh; Yoshida, Lay-Myint

    2016-01-01

    Since the initial discovery of RSV-A ON1 in Canada in 2010, ON1 has been reported worldwide, yet information regarding its clinical impact and severity has been controversial. To investigate the clinical relevance of RSV-A ON1,acute respiratory infection (ARI) cases enrolled to our population-based prospective pediatric ARI surveillance at Khanh Hoa General Hospital, Central Vietnam from January 2010 through December 2012 were studied. Clinical-epidemiological information and nasopharyngeal samples were collected. Multiplex PCR assays were performed for screening 13 respiratory viruses. RSV-positive samples were further tested for subgroups (A/B) and genotypes information by sequencing the G-glycoprotein 2nd hypervariable region. Statistical analysis was performed to evaluate the clinical-epidemiological characteristics of RSV-A ON1. A total of 1854 ARI cases were enrolled and 426 (23.0%) of them were RSV-positive. During the study period, RSV-A and B had been co-circulating. NA1 was the predominant RSV-A genotype until the appearance of ON1 in 2012. RSV-related ARI hospitalization incidence significantly increased after the emergence of ON1. Moreover, multivariate analysis revealed that risk of lower respiratory tract infection was 2.26 (95% CI: 1.37–3.72) times, and radiologically-confirmed pneumonia was 1.98 (95% CI: 1.01–3.87) times greater in ON1 compared to NA1 cases. Our result suggested that ON1 ARI cases were clinically more severe than NA1. PMID:27306333

  3. Association of RSV-A ON1 genotype with Increased Pediatric Acute Lower Respiratory Tract Infection in Vietnam.

    PubMed

    Yoshihara, Keisuke; Le, Minh Nhat; Okamoto, Michiko; Wadagni, Anita Carolle Akpeedje; Nguyen, Hien Anh; Toizumi, Michiko; Pham, Enga; Suzuki, Motoi; Nguyen, Ai Thi Thuy; Oshitani, Hitoshi; Ariyoshi, Koya; Moriuchi, Hiroyuki; Hashizume, Masahiro; Dang, Duc Anh; Yoshida, Lay-Myint

    2016-01-01

    Since the initial discovery of RSV-A ON1 in Canada in 2010, ON1 has been reported worldwide, yet information regarding its clinical impact and severity has been controversial. To investigate the clinical relevance of RSV-A ON1,acute respiratory infection (ARI) cases enrolled to our population-based prospective pediatric ARI surveillance at Khanh Hoa General Hospital, Central Vietnam from January 2010 through December 2012 were studied. Clinical-epidemiological information and nasopharyngeal samples were collected. Multiplex PCR assays were performed for screening 13 respiratory viruses. RSV-positive samples were further tested for subgroups (A/B) and genotypes information by sequencing the G-glycoprotein 2nd hypervariable region. Statistical analysis was performed to evaluate the clinical-epidemiological characteristics of RSV-A ON1. A total of 1854 ARI cases were enrolled and 426 (23.0%) of them were RSV-positive. During the study period, RSV-A and B had been co-circulating. NA1 was the predominant RSV-A genotype until the appearance of ON1 in 2012. RSV-related ARI hospitalization incidence significantly increased after the emergence of ON1. Moreover, multivariate analysis revealed that risk of lower respiratory tract infection was 2.26 (95% CI: 1.37-3.72) times, and radiologically-confirmed pneumonia was 1.98 (95% CI: 1.01-3.87) times greater in ON1 compared to NA1 cases. Our result suggested that ON1 ARI cases were clinically more severe than NA1. PMID:27306333

  4. Influence of meteorological conditions on RSV infection in Portugal

    NASA Astrophysics Data System (ADS)

    Oliveira-Santos, M.; Santos, J. A.; Soares, J.; Dias, A.; Quaresma, M.

    2016-04-01

    Acute viral bronchiolitis is a common cause for infant hospital admissions. Of all etiological agents, respiratory syncytial virus (RSV) is commonly the most frequent. The present study assesses relationships between atmospheric factors and RSV infections in under 3-year-old patients admitted to the Inpatient Paediatric Service of Vila Real (North of Portugal). For this purpose, (1) clinical files of children admitted with a diagnosis of acute bronchiolitis from September 2005 to December 2015 (>10 years) were scrutinised and (2) local daily temperature/precipitation series, as well as six weather types controlling meteorological conditions in Portugal, were used. Fifty-five percent of all 770 admitted children were effectively infected with a given virus, whilst 48 % (367) were RSV+, i.e. 87 % of virus-infected children were RSV+. The bulk of incidence is verified in the first year of age (82 %, 302), slightly higher in males. RSV outbreaks are typically from December to March, but important inter-annual variability is found in both magnitude and shape. Although no clear connections were found between monthly temperatures/precipitation and RSV outbreaks apart from seasonality, a linkage to wintertime cold spells is apparent on a daily basis. Anomalously low minimum temperatures from the day of admittance back to 10 days before are observed. This relationship is supported by anomalously high occurrences of the E and AA weather types over the same period, which usually trigger dry and cold weather. These findings highlight some predictability in the RSV occurrences, revealing potential for modelling and risk assessments.

  5. Genetic delivery of an anti-RSV antibody to protect against pulmonary infection with RSV.

    PubMed

    Skaricic, Davor; Traube, Chani; De, Bishnu; Joh, Ju; Boyer, Julie; Crystal, Ronald G; Worgall, Stefan

    2008-08-15

    Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infections. Protection against infection with RSV can be achieved by monthly administration of the humanized monoclonal antibody palivizumab. The present study analyzes if genetic delivery of a murine version of palivizumab by single administration would achieve high-level and sustained antibody expression to protect mice against pulmonary infection with RSV. A murine version of the palivizumab antibody was constructed by replacing the human sequences with sequences from the constant region of a murine IgG1 antibody, while preserving the complementarity-determining region. As a proof-of-principle to test the validity of the strategy, the coding sequence for the heavy and light chains were cloned into a replication-defective serotype 5 human adenovirus vector (AdalphaRSV). Antibody expression and specificity for RSV was confirmed by Western analysis. To determine if AdalphaRSV would mediate production of anti-RSV antibodies in vivo, 5x10(10) particle units of AdalphaRSV or a control vector without transgene (AdNull), were administered intravenously to BALB/c mice. RSV neutralizing antibodies were detected in the serum after 4 days in mice receiving AdalphaRSV but not in AdNull-infected or naive mice (p<0.05). The mice that had received AdalphaRSV had at least 5.4-fold lower RSV titers in the lung 4 days following intranasal challenge with RSV compared to the AdNull or naive group (p<0.01). To evaluate long-term protection, the antibody construct was expressed in a non-human primate serotype rh.10 adeno-associated virus vector (AAVrh.10alphaRSV). RSV neutralizing antibodies were detected in serum and bronchoalveolar lavage fluid for up to 21 wk following intrapleural administration of AAVrh.10alphaRSV, but not with a control AAV vector expressing an unrelated transgene (AAVrh.10alpha1AT). Following challenge with RSV at 7 or 21 wk, 14.3-fold and 10.6-fold lower RSV titers were

  6. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled or is ... school or childcare. They can then transmit the virus to other members of the family. RSV can ...

  7. Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

    PubMed Central

    Sharma, Anurag; Wu, Wenzhu; Sung, Biin; Huang, Jing; Tsao, Tiffany; Li, Xiangming; Gomi, Rika; Tsuji, Moriya

    2016-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4+ T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. IMPORTANCE Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and

  8. RSV infection in the adult population.

    PubMed

    Ramirez, Julio A

    2008-11-01

    RSV is a significant and unrecognized cause of seasonal RTIs in adults, accounting for as much as 25 percent of excess wintertime mortality usually attributed to influenza. Nearly 80 percent of RSV-associated underlying respiratory and circulatory deaths occur among the elderly, and RSV is estimated to account for about 180,000 hospital admissions each year at a cost exceeding $1 billion. RSV also is recognized as an important cause of viral pneumonia in adults. Preventive measures, such as hand washing, are paramount, especially in hospitals and nursing homes where many immunocompromised patients reside. When RSV is circulating, it is advisable to minimize contact between high-risk patients and children.

  9. ROLE OF MONOCYTES IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION.

    EPA Science Inventory

    ROLE OF MONOCYTES IN RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION.
    Joleen M. Soukup and Susanne Becker, National Health and Environmental Effects Research
    Laboratory, US EPA, Research Traingle Park, NC USA.

    RSV infection in airway epithelial cells (EC) results i...

  10. Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection

    PubMed Central

    Jordan, Robert; Shao, Matt; Mackman, Richard L.; Perron, Michel; Cihlar, Tomas; Lewis, Sandy A.; Eisenberg, Eugene J.; Carey, Anne; Strickley, Robert G.; Chien, Jason W.; Anderson, Mark L.; McEligot, Heather A.; Behrens, Nicole E.

    2015-01-01

    Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV. PMID:26055364

  11. Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection.

    PubMed

    de Waal, L; Koopman, L P; van Benten, I J; Brandenburg, A H; Mulder, P G H; de Swart, R L; Fokkens, W J; Neijens, H J; Osterhaus, A D M E

    2003-06-01

    Respiratory syncytial virus (RSV) infections are a major cause of severe respiratory disease in infants. It has been shown that there is an increased frequency of childhood wheezing in ex-bronchiolitic preteen children. This was postulated to be mediated by a vigorous virus-specific Th2 response influencing the further development of the immune system. Little is known about the possible role of the immune response to clinically mild RSV infections in this respect. We have studied the RSV-specific cellular immune response in infants with a laboratory-confirmed RSV upper respiratory tract infection (URTI; n = 13, mean age 12 months, range 2-22 months) in comparison with infants with non-RSV mediated URTI (n = 9, mean age 9.3 months, range 4-18 months) or infants with severe RSV bronchiolitis (n = 11, mean age 2.3 months, range 1-6 months). RSV-specific cytokine-producing cells were enumerated using the ELISPOT method in peripheral blood mononuclear cells and nasal brush T-cells, collected during the acute and convalescent phase of the infection. Mixed Th1 (IFN-gamma) and Th2 (IL-4 and IL-13) responses were detected in all three groups. Frequencies of RSV-specific T-cells were lower in both URTI groups than in the RSV bronchiolitis group, and not significantly different between the RSV URTI and the non-RSV URTI group. The absence of vigorous virus-specific Th2 responses upon mild RSV infection does not support the hypothesis that these infections influence the development of the immune system and that they predispose for the development of atopic disease. PMID:12696123

  12. Rapamycin increases RSV RNA levels and survival of RSV-infected dendritic cell depending on T cell contact.

    PubMed

    do Nascimento de Freitas, Deise; Gassen, Rodrigo Benedetti; Fazolo, Tiago; Souza, Ana Paula Duarte de

    2016-10-01

    The macrolide rapamycin inhibits mTOR (mechanist target of rapamycin) function and has been broadly used to unveil the role of mTOR in immune responses. Inhibition of mTOR on dendritic cells (DC) can influence cellular immune response and the survival of DC. RSV is the most common cause of hospitalization in infants and is a high priority candidate to vaccine development. In this study we showed that rapamycin treatment on RSV-infected murine bone marrow-derived DC (BMDC) decreases the frequency of CD8(+)CD44(high) T cells. However, inhibition of mTOR on RSV-infected BMDC did not modify the activation phenotype of these cells. RSV-RNA levels increase when infected BMDC were treated with rapamycin. Moreover, we observed that rapamycin diminishes apoptosis cell death of RSV-infected BMDC co-culture with T cells and this effect was abolished when the cells were co-cultured in a transwell system that prevents cell-to-cell contact or migration. Taken together, these data indicate that rapamycin treatment present a toxic effect on RSV-infected BMDC increasing RSV-RNA levels, affecting partially CD8 T cell differentiation and also increasing BMDC survival in a mechanism dependent on T cell contact. PMID:27466155

  13. Rapamycin increases RSV RNA levels and survival of RSV-infected dendritic cell depending on T cell contact.

    PubMed

    do Nascimento de Freitas, Deise; Gassen, Rodrigo Benedetti; Fazolo, Tiago; Souza, Ana Paula Duarte de

    2016-10-01

    The macrolide rapamycin inhibits mTOR (mechanist target of rapamycin) function and has been broadly used to unveil the role of mTOR in immune responses. Inhibition of mTOR on dendritic cells (DC) can influence cellular immune response and the survival of DC. RSV is the most common cause of hospitalization in infants and is a high priority candidate to vaccine development. In this study we showed that rapamycin treatment on RSV-infected murine bone marrow-derived DC (BMDC) decreases the frequency of CD8(+)CD44(high) T cells. However, inhibition of mTOR on RSV-infected BMDC did not modify the activation phenotype of these cells. RSV-RNA levels increase when infected BMDC were treated with rapamycin. Moreover, we observed that rapamycin diminishes apoptosis cell death of RSV-infected BMDC co-culture with T cells and this effect was abolished when the cells were co-cultured in a transwell system that prevents cell-to-cell contact or migration. Taken together, these data indicate that rapamycin treatment present a toxic effect on RSV-infected BMDC increasing RSV-RNA levels, affecting partially CD8 T cell differentiation and also increasing BMDC survival in a mechanism dependent on T cell contact.

  14. Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection

    PubMed Central

    Bird, Gregory H.; Boyapalle, Sandhya; Wong, Terianne; Opoku-Nsiah, Kwadwo; Bedi, Raminder; Crannell, W. Christian; Perry, Alisa F.; Nguyen, Huy; Sampayo, Viviana; Devareddy, Ankita; Mohapatra, Subhra; Mohapatra, Shyam S.; Walensky, Loren D.

    2014-01-01

    Respiratory syncytial virus (RSV) infection accounts for approximately 64 million cases of respiratory disease and 200,000 deaths worldwide each year, yet no broadly effective prophylactic or treatment regimen is available. RSV deploys paired, self-associating, heptad repeat domains of its fusion protein, RSV-F, to form a fusogenic 6-helix bundle that enables the virus to penetrate the host cell membrane. Here, we developed hydrocarbon double-stapled RSV fusion peptides that exhibit stabilized α-helical structure and striking proteolytic resistance. Pretreatment with double-stapled RSV peptides that specifically bound to the RSV fusion bundle inhibited infection by both laboratory and clinical RSV isolates in cells and murine infection models. Intranasal delivery of a lead double-stapled RSV peptide effectively prevented viral infection of the nares. A chitosan-based nanoparticle preparation markedly enhanced pulmonary delivery, further preventing progression of RSV infection to the lung. Thus, our results provide a strategy for inhibiting RSV infection by mucosal and endotracheal delivery of double-stapled RSV fusion peptides. PMID:24743147

  15. Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation

    PubMed Central

    Feng, Qiuqin; Su, Zhonglan; Song, Shiyu; Xu, Hui; Zhang, Bin; Yi, Long; Tian, Man; Wang, Hongwei

    2016-01-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS-2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro-inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of RSV infection

  16. Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation.

    PubMed

    Feng, Qiuqin; Su, Zhonglan; Song, Shiyu; Χu, Hui; Zhang, Bin; Yi, Long; Tian, Man; Wang, Hongwei

    2016-09-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS‑2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro‑inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of

  17. Inflammatory damage on respiratory and nervous systems due to hRSV infection.

    PubMed

    Bohmwald, Karen; Espinoza, Janyra A; Becerra, Daniela; Rivera, Katherine; Lay, Margarita K; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2015-10-01

    The exacerbated inflammatory response elicited by human Respiratory Syncytial Virus (hRSV) in the lungs of infected patients causes a major health burden in the pediatric and elderly population. Since the discovery of hRSV, the exacerbated host immune-inflammatory response triggered by this virus has been extensively studied. In this article, we review the effects on the airways caused by immune cells and cytokines/chemokines secreted during hRSV infection. While molecules such as interferons contribute at controlling viral infection, IL-17 and others produce damage to the hRSV-infected lung. In addition to affecting the airways, hRSV infection can cause significant neurologic abnormalities in the host, such as seizures and encephalopathy. Although the origin of these symptoms remains unclear, studies from patients suffering neurological alteration suggest an involvement of the inflammatory response against hRSV.

  18. Recombinant low-seroprevalent adenoviral vectors Ad26 and Ad35 expressing the respiratory syncytial virus (RSV) fusion protein induce protective immunity against RSV infection in cotton rats.

    PubMed

    Widjojoatmodjo, Myra N; Bogaert, Lies; Meek, Bob; Zahn, Roland; Vellinga, Jort; Custers, Jerome; Serroyen, Jan; Radošević, Katarina; Schuitemaker, Hanneke

    2015-10-01

    RSV is an important cause of lower respiratory tract infections in children, the elderly and in those with underlying medical conditions. Although the high disease burden indicates an urgent need for a vaccine against RSV, no licensed RSV vaccine is currently available. We developed an RSV vaccine candidate based on the low-seroprevalent human adenovirus serotypes 26 and 35 (Ad26 and Ad35) encoding the RSV fusion (F) gene. Single immunization of mice with either one of these vectors induced high titers of RSV neutralizing antibodies and high levels of F specific interferon-gamma-producing T cells. A Th1-type immune response was indicated by a high IgG2a/IgG1 ratio of RSV-specific antibodies, strong induction of RSV-specific interferon-gamma and tumor necrosis factor-alpha cytokine producing CD8 Tcells, and low RSV-specific CD4 T-cell induction. Both humoral and cellular responses were increased upon a boost with RSV-F expressing heterologous adenovirus vector (Ad35 boost after Ad26 prime or vice versa). Both single immunization and prime-boost immunization of cotton rats induced high and long-lasting RSV neutralizing antibody titers and protective immunity against lung and nasal RSV A2 virus load up to at least 30 weeks after immunization. Cotton rats were also completely protected against challenge with a RSV B strain (B15/97) after heterologous prime-boost immunization. Lungs from vaccinated animals showed minimal damage or inflammatory infiltrates post-challenge, in contrast to animals vaccinated with formalin-inactivated virus. Our results suggest that recombinant human adenoviral Ad26 and Ad35 vectors encoding the RSV F gene have the potential to provide broad and durable protection against RSV in humans, and appear safe to be investigated in infants.

  19. Resistance to Human Respiratory Syncytial Virus (RSV) Infection Induced by Immunization of Cotton Rats with a Recombinant Vaccinia Virus Expressing the RSV G Glycoprotein

    NASA Astrophysics Data System (ADS)

    Elango, Narayanasamy; Prince, Gregory A.; Murphy, Brian R.; Venkatesan, Sundararajan; Chanock, Robert M.; Moss, Bernard

    1986-03-01

    A cDNA copy of the G glycoprotein gene of human respiratory syncytial virus (RSV) was placed under control of a vaccinia virus promoter and inserted into the thymidine kinase locus of the vaccinia virus genome. The recombinant vaccinia virus retained infectivity and expressed a 93-kDa protein that migrated with the authentic RSV G glycoprotein upon polyacrylamide gel electrophoresis. Glycosylation of the expressed protein and transport to the cell surface were demonstrated in the absence of other RSV proteins. Cotton rats that were inoculated intradermally with the infectious recombinant virus produced serum antibody to the G glycoprotein that neutralized RSV in vitro. Furthermore, the vaccinated animals were resistant to lower respiratory tract infection upon intranasal inoculation with RSV and had reduced titers of RSV in the nose.

  20. A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection

    PubMed Central

    Ciencewicki, Jonathan M.; Wang, Xuting; Marzec, Jacqui; Serra, M. Elina; Bell, Douglas A.; Polack, Fernando P.; Kleeberger, Steven R.

    2014-01-01

    Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infection during childhood and causes severe symptoms in some patients, which may cause hospitalization and death. Mechanisms for differential responses to RSV are unknown. Our objective was to develop an in vitro model of RSV infection to evaluate interindividual variation in response to RSV and identify susceptibility genes. Populations of human-derived HapMap lymphoblastoid cell lines (LCLs) were infected with RSV. Compared with controls, RSV-G mRNA expression varied from ∼1- to 400-fold between LCLs. Basal expression of a number of gene transcripts, including myxovirus (influenza virus) resistance 1 (MX1), significantly correlated with RSV-G expression in HapMap LCLs. Individuals in a case-control population of RSV-infected children who were homozygous (n=94) or heterozygous (n=172) for the predicted deleterious A allele in a missense G/A SNP in MX1 had significantly greater risk for developing severe RSV disease relative to those with the major allele (n=108) (χ2=5.305, P=0.021; OR: 1.750, 95% CI: 1.110, 2.758, P=0.021). We conclude that genetically diverse human LCLs enable identification of susceptibility genes (e.g., MX1) for RSV disease severity in children, providing insight for disease risk.—Ciencewicki, J. M., Wang, X., Marzec, J., Serra, M. E., Bell, D. A., Polack, F. P., Kleeberger, S. R. A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection. PMID:24421397

  1. Antibodies enhance CXCL10 production during RSV infection of infant and adult immune cells.

    PubMed

    Vissers, Marloes; Schreurs, Inge; Jans, Jop; Heldens, Jacco; de Groot, Ronald; de Jonge, Marien I; Ferwerda, Gerben

    2015-12-01

    Respiratory syncytial virus (RSV) bronchiolitis is a major burden in infants below three months of age, when the primary immune response is mainly dependent on innate immunity and maternal antibodies. We investigated the influence of antibodies on innate immunity during RSV infection. PBMCs from infants and adults were stimulated with live RSV and inactivated RSV in combination with antibody-containing and antibody-depleted serum. The immune response was determined by transcriptome analysis and chemokine levels were measured using ELISA and flow cytometry. Microarray data showed that CXCL10 gene transcription was RSV dependent, whereas CXCL11 and IFNα were upregulated in an antibody-dependent manner. Although the presence of antibodies reduces RSV infection rate, it enhances the innate immune response. In adult immune cells, antibodies enhance CXCL10, CXCL11, IFNα and IFNγ production in response to RSV infection. Contrary, in infant immune cells only CXCL10 was enhanced in an antibody-dependent manner. Monocytes are the main source of CXCL10 and they produce CXCL10 in both an antibody- and virus-dependent manner. This study shows that antibodies enhance CXCL10 production in infant immune cells. CXCL10 has been implicated in exuberating the inflammatory response during viral infections and antibodies could therefore play a role in the pathogenesis of RSV infections.

  2. In Vitro Modeling of RSV Infection and Cytopathogenesis in Well-Differentiated Human Primary Airway Epithelial Cells (WD-PAECs).

    PubMed

    Broadbent, Lindsay; Villenave, Remi; Guo-Parke, Hong; Douglas, Isobel; Shields, Michael D; Power, Ultan F

    2016-01-01

    The choice of model used to study human respiratory syncytial virus (RSV) infection is extremely important. RSV is a human pathogen that is exquisitely adapted to infection of human hosts. Rodent models, such as mice and cotton rats, are semi-permissive to RSV infection and do not faithfully reproduce hallmarks of RSV disease in humans. Furthermore, immortalized airway-derived cell lines, such as HEp-2, BEAS-2B, and A549 cells, are poorly representative of the complexity of the respiratory epithelium. The development of a well-differentiated primary pediatric airway epithelial cell models (WD-PAECs) allows us to simulate several hallmarks of RSV infection of infant airways. They therefore represent important additions to RSV pathogenesis modeling in human-relevant tissues. The following protocols describe how to culture and differentiate both bronchial and nasal primary pediatric airway epithelial cells and how to use these cultures to study RSV cytopathogenesis. PMID:27464691

  3. [Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso].

    PubMed

    Ouédraogo Yugbaré, S O; Ouédraogo, R; Nenebi, A; Traoré, B; Congo, L; Yonli, F; Kima, D; Bonané, P; Yé, D; Plantier, J-C; Vabret, A; Marguet, C; Gueudin, M

    2016-02-01

    Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.

  4. Recombinant Human Respiratory Syncytial Virus (RSV) Monoclonal Antibody Fab is Effective Therapeutically when Introduced Directly into the Lungs of RSV-Infected Mice

    NASA Astrophysics Data System (ADS)

    Crowe, James E., Jr.; Murphy, Brian R.; Chanock, Robert M.; Williamson, R. Anthony; Barbas, Carlos F., III; Burton, Dennis R.

    1994-02-01

    Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), were evaluated for therapeutic efficacy in infected mice just before or at the time of peak virus replication in the lungs. Fab 19, which neutralized RSV infectivity with high efficiency in tissue culture, was effective therapeutically when delivered directly into the lungs by intranasal instillation under anesthesia. In contrast, RSV Fab 126, which failed to neutralize virus in cell culture, did not exhibit a therapeutic effect under these conditions. The amount of Fab 19 required to effect a 5000- to 12,000-fold reduction in titer of RSV in the lungs within 24 hr was rather small. In four separate experiments, a single instillation of 12.9-50 μg of RSV Fab 19 was sufficient to achieve such a reduction in pulmonary virus in a 25g mouse. The use of Fabs instead of the whole immunoglobulin molecules from which they are derived reduced the protein content of a therapeutic dose. This is important because the protein load that can be delivered effectively into the lungs is limited. The therapeutic effect of a single treatment with Fab 19 was not sustained, so that a rebound in pulmonary virus titer occurred on the 2nd day after treatment. This rebound in pulmonary RSV titer could be prevented by treating infected mice with a single dose of Fab 19 daily for 3 days. These observations suggest that human monoclonal Fabs grown in Escherichia coli may prove useful in the treatment of serious RSV disease as well as diseases caused by other viruses where replication in vivo is limited primarily to the lumenal lining of the respiratory tract.

  5. Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward.

    PubMed

    Jensen, Tomas Ostergaard; Stelzer-Braid, Sacha; Willenborg, Christiana; Cheung, Carol; Andresen, David; Rawlinson, William; Clezy, Kate

    2016-10-01

    We describe an outbreak of respiratory syncytial virus (RSV) infection on a hematology ward without allogeneic stem cell transplant patients. Twelve patients and one staff member infected with RSV were identified from the laboratory database. Five patients had lower respiratory tract infection, seven had upper respiratory tract infection, one was asymptomatic, and there were two (15.4%) deaths. Most patients had overlapping periods of potential infectiousness on the ward. Sequencing was possible on eight specimens and five of these had identical sequences. Results were consistent with transmission occurring both on the ward and by introduction of RSV from the community. J. Med. Virol. 88:1827-1831, 2016. © 2016 Wiley Periodicals, Inc.

  6. Health care utilisation of prematurely born, preschool children related to hospitalisation for RSV infection

    PubMed Central

    Greenough, A; Alexander, J; Burgess, S; Bytham, J; Chetcuti, P; Hagan, J; Lenney, W; Melville, S; Shaw, N; Boorman, J; Coles, S; Turner, J; Pang, F

    2004-01-01

    Background: In prematurely born infants with chronic lung disease (CLD), RSV hospitalisation is associated with increased health service utilisation and costs in the first two years after birth. Aims: To determine whether RSV hospitalisation in the first two years was associated with chronic respiratory morbidity during the preschool years in prematurely born children who had had CLD. Methods: Retrospective review of readmissions, outpatient attendances, and community care in years 2–4 and, at age 5 years, assessment of the children's respiratory status and their health related quality of life. Comparison was made of the results of children who had had at least one hospitalisation in the first two years after birth for RSV infection (RSV group) to those of the rest of the cohort. Participants were 190 of an original cohort of 235 infants with CLD and a median gestational age 27 (range 22–33) weeks. Results: The 33 children in the RSV group, compared to the rest of the cohort, had a greater duration of hospital stay and more outpatient appointments. The RSV group had required more prescriptions for all treatments and respiratory medications, and more had used an inhaler. The cost of care of the RSV group was higher (median £2630 [€4000, US$4800], range £124–18 091 versus £1360 [€2500, US$3000], range £5–18 929) and their health related quality of life was lower. Conclusion: In prematurely born children who had developed CLD, RSV hospitalisation in the first two years was associated with chronic respiratory morbidity and increased cost of care. PMID:15210503

  7. Immunogenicity of RSV F DNA Vaccine in BALB/c Mice

    PubMed Central

    2016-01-01

    Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections. PMID:27688769

  8. Immunogenicity of RSV F DNA Vaccine in BALB/c Mice

    PubMed Central

    2016-01-01

    Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections.

  9. Immunogenicity of RSV F DNA Vaccine in BALB/c Mice.

    PubMed

    Eroglu, Erdal; Singh, Ankur; Bawage, Swapnil; Tiwari, Pooja M; Vig, Komal; Pillai, Shreekumar R; Dennis, Vida A; Singh, Shree R

    2016-01-01

    Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths among the infant and elderly populations worldwide. There is no vaccine or a less effective drug available against RSV infections. Natural RSV infection stimulates the Th1 immune response and activates the production of neutralizing antibodies, while earlier vaccine trials that used UV-inactivated RSV exacerbated the disease due to the activation of the allergic Th2 response. With a focus on Th1 immunity, we developed a DNA vaccine containing the native RSV fusion (RSV F) protein and studied its immune response in BALB/c mice. High levels of RSV specific antibodies were induced during subsequent immunizations. The serum antibodies were able to neutralize RSV in vitro. The RSV inhibition by sera was also shown by immunofluorescence analyses. Antibody response of the RSV F DNA vaccine showed a strong Th1 response. Also, sera from RSV F immunized and RSV infected mice reduced the RSV infection by 50% and 80%, respectively. Our data evidently showed that the RSV F DNA vaccine activated the Th1 biased immune response and led to the production of neutralizing antibodies, which is the desired immune response required for protection from RSV infections. PMID:27688769

  10. The cytolytic activity of pulmonary CD8+ lymphocytes, induced by infection with a vaccinia virus recombinant expressing the M2 protein of respiratory syncytial virus (RSV), correlates with resistance to RSV infection in mice.

    PubMed Central

    Kulkarni, A B; Connors, M; Firestone, C Y; Morse, H C; Murphy, B R

    1993-01-01

    Previous studies demonstrated that the pulmonary resistance to respiratory syncytial virus (RSV) challenge induced by immunization with a recombinant vaccinia virus expressing the M2 protein of RSV (vac-M2) was significantly greater 9 days after immunization than at 28 days and was mediated predominantly by CD8+ T cells. In this study, we have extended these findings and sought to determine whether the level of CD8+ cytotoxic T-lymphocyte (CTL) activity measured in vitro correlates with the resistance to RSV challenge in vivo. Three lines of evidence documented an association between the presence of pulmonary CTL activity and resistance to RSV challenge. First, vac-M2 immunization induced pulmonary CD8+ CTL activity and pulmonary resistance to RSV infection in BALB/c (H-2d) mice, whereas significant levels of pulmonary CTL activity and resistance to RSV infection were not seen in BALB.K (H-2k) or BALB.B (H-2b) mice. Second, pulmonary CD8+ CTL activity was not induced by infection with other vaccinia virus-RSV recombinants that did not induce resistance to RSV challenge. Third, the peak of pulmonary CTL activity correlated with the peak of resistance to RSV replication (day 6), with little resistance being observed 45 days after immunization. An accelerated clearance of virus was not observed when mice were challenged with RSV 45 days after immunization with vac-M2. The results indicate that resistance to RSV induced by immunization with vac-M2 is mainly mediated by primary pulmonary CTLs and that this resistance decreases to very low levels within 2 months following immunization. The implications for inclusion of CTL epitopes into RSV vaccines are discussed in the context of these observations. PMID:8419638

  11. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice

    PubMed Central

    Shi, Hengfei; Ren, Ke; Lv, Baojie; Zhang, Wei; Zhao, Ying; Tan, Ren Xiang; Li, Erguang

    2016-01-01

    The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC50) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect. PMID:27767097

  12. Titanium dioxide nanoparticles exacerbate pneumonia in respiratory syncytial virus (RSV)-infected mice.

    PubMed

    Hashiguchi, Seiko; Yoshida, Hiroki; Akashi, Toshi; Komemoto, Keiji; Ueda, Tomoyuki; Ikarashi, Yoshiaki; Miyauchi, Aki; Konno, Katsuhiko; Yamanaka, Sayoko; Hirose, Akihiko; Kurokawa, Masahiko; Watanabe, Wataru

    2015-03-01

    To reveal the effects of TiO2 nanoparticles, used in cosmetics and building materials, on the immune response, a respiratory syncytial virus (RSV) infection mouse model was used. BALB/c mice were exposed once intranasally to TiO2 at 0.5mg/kg and infected intranasally with RSV five days later. The levels of IFN-γ and chemokine CCL5, representative markers of pneumonia, in the bronchoalveolar lavage fluids of RSV-infected mice had increased significantly in TiO2-exposed mice compared with the control on day 5 post-infection, but not in uninfected mice. While pulmonary viral titers were not affected by TiO2 exposure, an increase in the infiltration of lymphocytes into the alveolar septa in lung tissues was observed. Immunohistochemical analysis revealed aggregation of TiO2 nanoparticles near inflammatory cells in the severely affected region. Thus, a single exposure to TiO2 nanoparticles affected the immune system and exacerbated pneumonia in RSV-infected mice.

  13. Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

    PubMed Central

    Larios Mora, Alejandro; Detalle, Laurent; Van Geelen, Albert; Davis, Michael S.; Stohr, Thomas; Gallup, Jack M.; Ackermann, Mark R.

    2015-01-01

    Rationale Respiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions. Methods Newborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses. Results Lambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and

  14. ROLE OF MONOCYTES AND EOSINOPHILS IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION

    EPA Science Inventory

    Role of Monocytes and Eosinophils
    in Respiratory Syncytial Virus (RSV) Infection

    Joleen M. Soukup and Susanne Becker

    US Environmental Protection Agency, National Health and Environmental
    Effects Research Laboratory, Research Triangle Park, NC 27711;
    ...

  15. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    SciTech Connect

    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-03-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with /sup 3/H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P < 0.01) enhanced by prior RSV infection. The degree of adherence was directly related to the amount of viral antigen expressed on the cell surface. The adherence was temperature dependent, with maximal adherence observed at 37/sup 0/C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP.

  16. Immunopathology of RSV infection: prospects for developing vaccines without this complication.

    PubMed

    van Drunen Littel-van den Hurk, S; Mapletoft, J W; Arsic, N; Kovacs-Nolan, J

    2007-01-01

    Respiratory syncytial virus is the most important cause of lower respiratory tract infection in infants and young children. RSV clinical disease varies from rhinitis and otitis media to bronchiolitis and pneumonia. An increased incidence of asthma later in life has been associated with the more severe lower respiratory tract infections. Despite its importance as a pathogen, there is no licensed vaccine against RSV. This is due to a number of factors complicating the development of an effective and safe vaccine. The immunity to natural RSV infection is incomplete as re-infections occur in all age groups, which makes it challenging to design a protective vaccine. Second, the primary target population is the newborn infant, which has a relatively immature immune system and maternal antibodies that can interfere with vaccination. Finally, some vaccines have resulted in a predisposition for exacerbated pulmonary disease in infants, which was attributed to an imbalanced Th2-biased immune response, although the exact cause has not been elucidated. This makes it difficult to proceed with vaccine testing in infants. It is likely that an effective and safe vaccine needs to elicit a balanced immune response, including RSV-specific neutralising antibodies, CD8 T-cells, Th1/Th2 CD4 T-cells and preferably secretory IgA. Subunit vaccines formulated with appropriate adjuvants may be adequate for previously exposed individuals. However, intranasally delivered genetically engineered attenuated or vectored vaccines are currently most promising for newborns, as they are expected to induce a balanced immune response similar to that elicited to natural infection and not be subject to interference from maternal antibodies. Maternal vaccination may be the optimal strategy to protect the very young infants. PMID:17004293

  17. TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection

    SciTech Connect

    Dey, Nilay; Liu Tianshuang; Garofalo, Roberto P.; Casola, Antonella

    2011-09-30

    Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases. Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.

  18. [Update of recommendations on the use of palivizumab as prophylaxis in RSV infections].

    PubMed

    Figueras Aloy, J; Carbonell Estrany, X

    2015-03-01

    The Standards Committee of the Spanish Neonatology Society (SENeo) considers that the new document from the American Academy of Pediatrics, including recommendations for palivizumab use to prevent serious infections produced by the Respiratory Syncytial Virus (RSV), provides no new scientific evidence which would justify the modification of the current recommendations of the SENeo. However, some adjustments to the criteria of the existing recommendations are proposed to reduce the cost of the drug by its correct and judicious management.

  19. Acute upper airway infections.

    PubMed

    West, J V

    2002-01-01

    Upper respiratory tract infections are common and important. Although rarely fatal, they are a source of significant morbidity and carry a considerable economic burden. Numerous therapies for the common cold have no effect on symptoms or outcome. Complications such as cough are not improved by over-the-counter preparations, while labelling cough alone as a symptom of asthma may result in unnecessary use of inhaled steroid treatment. Clinical presentation of sore throat does not accurately predict whether the infection is viral or bacterial, while throat culture and rapid antigen tests do not significantly change prescribing practice. Antibiotics have only a limited place in the management of recurrent sore throat due to group A beta-haemolytic streptococcal infection. Routine use of antibiotics in upper respiratory infection enhances parent belief in their effectiveness and increases the likelihood of future consultation in primary care for minor self-limiting illness. Respiratory viruses play a major role in the aetiology of acute otitis media (AOM); prevention includes the use of influenza or RSV vaccination, in addition to reducing other risk factors such as early exposure to respiratory viruses in day-care settings and to environmental tobacco smoke. The use of ventilation tubes (grommets) in secretory otitis media (SOM) remains controversial with conflicting data on developmental outcome and quality of life in young children. New conjugate pneumococcal vaccines appear safe in young children and prevent 6-7% of clinically diagnosed AOM.

  20. A Respiratory Syncytial Virus (RSV) Anti-G Protein F(ab′)2 Monoclonal Antibody Suppresses Mucous Production and Breathing Effort in RSV rA2-line19F-Infected BALB/c Mice

    PubMed Central

    Boyoglu-Barnum, Seyhan; Gaston, Kelsey A.; Todd, Sean O.; Boyoglu, Cemil; Chirkova, Tatiana; Barnum, Thomas R.; Jorquera, Patricia; Haynes, Lia M.; Tripp, Ralph A.; Moore, Martin L.

    2013-01-01

    Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Increased airway resistance and increased airway mucin production are two manifestations of RSV infection in children. RSV rA2-line19F infection induces pulmonary mucous production and increased breathing effort in BALB/c mice and provides a way to assess these manifestations of RSV disease in an animal model. In the present study, we investigated the effect of prophylactic treatment with the F(ab′)2 form of the anti-G protein monoclonal antibody (MAb) 131-2G on disease in RSV rA2-line19F-challenged mice. F(ab′)2 131-2G does not affect virus replication. It and the intact form that does decrease virus replication prevented increased breathing effort and airway mucin production, as well as weight loss, pulmonary inflammatory-cell infiltration, and the pulmonary substance P and pulmonary Th2 cytokine levels that occur in mice challenged with this virus. These data suggest that the RSV G protein contributes to prominent manifestations of RSV disease and that MAb 131-2G can prevent these manifestations of RSV disease without inhibiting virus infection. PMID:23885067

  1. Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge.

    PubMed

    Etchart, Nathalie; Baaten, Bas; Andersen, Svein Rune; Hyland, Lisa; Wong, Simon Y C; Hou, Sam

    2006-05-01

    We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSV-specific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection. PMID:16619288

  2. Peroxisome-proliferator-activated receptor-{gamma} agonists inhibit the release of proinflammatory cytokines from RSV-infected epithelial cells

    SciTech Connect

    Arnold, Ralf . E-mail: ralf.arnold@medizin.uni-magdeburg.de; Koenig, Wolfgang

    2006-03-15

    The epithelial cells of the airways are the target cells for respiratory syncytial virus (RSV) infection and the site of the majority of the inflammation associated with the disease. Recently, peroxisome-proliferator-activated receptor {gamma} (PPAR{gamma}), a member of the nuclear hormone receptor superfamily, has been shown to possess anti-inflammatory properties. Therefore, we investigated the role of PPAR{gamma} agonists (15d-PGJ{sub 2}, ciglitazone and troglitazone) on the synthesis of RSV-induced cytokine release from RSV-infected human lung epithelial cells (A549). We observed that all PPAR{gamma} ligands inhibited dose-dependently the release of TNF-{alpha}, GM-CSF, IL-1{alpha}, IL-6 and the chemokines CXCL8 (IL-8) and CCL5 (RANTES) from RSV-infected A549 cells. Concomitantly, the PPAR{gamma} ligands diminished the cellular amount of mRNA encoding for IL-6, CXCL8 and CCL5 and the RSV-induced binding activity of the transcription factors NF-{kappa}B (p65/p50) and AP-1 (c-fos), respectively. Our data presented herein suggest a potential application of PPAR{gamma} ligands in the anti-inflammatory treatment of RSV infection.

  3. Host Factors Modulating RSV Infection: Use of Small Interfering RNAs to Probe Functional Importance.

    PubMed

    Caly, Leon; Li, Hong-Mei; Jans, David

    2016-01-01

    Although respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants and the elderly worldwide [1], the protein-protein interactions between the host cell and virus remain poorly understood. We have used a focused small interfering RNA (siRNA) approach to knock-down and examine the role(s) of various host cell proteins. Here, we describe approaches for casein kinase 2α (CK2α) as a key example. We show how to study the effect of host gene (CK2α) knockdown using siRNA on cell-associated and released virus titers, using both quantitative RT-PCR, which measures the level of viral RNA, and plaque assay, which measures infectious virus directly. Both assays identified reduced viral titers with CK2α gene knock-down, indicating that it is likely required for efficient viral assembly and/or release. Effects were confirmed in RSV infected cells using the specific CK2α inhibitor 4,5,6,7-tetrabromobenzotriazole, revealing a similar reduction in viral titers as CK2α specific siRNA. This demonstrates that siRNA can be used to characterize critical host cell-RSV protein-protein interactions, and establishes CK2α as a future druggable target. PMID:27464690

  4. The RSV F and G glycoproteins interact to form a complex on the surface of infected cells

    SciTech Connect

    Low, Kit-Wei; Tan, Timothy; Ng, Ken; Tan, Boon-Huan; Sugrue, Richard J.

    2008-02-08

    In this study, the interaction between the respiratory syncytial virus (RSV) fusion (F) protein, attachment (G) protein, and small hydrophobic (SH) proteins was examined. Immunoprecipitation analysis suggested that the F and G proteins exist as a protein complex on the surface of RSV-infected cells, and this conclusion was supported by ultracentrifugation analysis that demonstrated co-migration of surface-expressed F and G proteins. Although our analysis provided evidence for an interaction between the G and SH proteins, no evidence was obtained for a single protein complex involving all three of the virus proteins. These data suggest the existence of multiple virus glycoprotein complexes within the RSV envelope. Although the stimulus that drives RSV-mediated membrane fusion is unknown, the association between the G and F proteins suggest an indirect role for the G protein in this process.

  5. [Methodological aspects of economic evaluation in pediatrics: illustration by RSV infection prophylaxis in the French setting].

    PubMed

    Hascoet, J-M; Fagnani, F; Charlemagne, A; Vieux, R; Rozé, J-C; Bendjenana, H

    2008-12-01

    The methodological approach of the economic evaluation of drugs in pediatrics is illustrated by the case study of the prophylaxis for RSV infections using palivizumab in the French setting. The indications for the reimbursement of this treatment have been restricted to premature children with bronchopulmonary dysplasia (BPD) or hemodynamically significant congenital-heart disease. A model was developed primarily using the results of the pivotal clinical studies on palivizumab. Unit costs were estimated (2006 values) in both societal and payer's perspectives. An assumption was made and discussed on the benefits of the prophylaxis on mortality. Based on the different data available and the estimated costs and benefits, different cost-effectiveness ratios (CERs) were estimated from both the society's and payer's points of view. A discount rate of 3% was applied to benefit. The CER obtained in the most unfavorable case is considered acceptable for the innovative-medical technologies in the French-healthcare system. Some of the parameters used by the model will be illustrated from the EPIPAGE study data from 2 of the 9 regions involved in this study: this evaluation suggests that the children not having an RSV infection during their 1st year of life will continue to require significantly fewer hospitalizations in the following years. These additional evaluations also suggest that the model overestimates the costs of the treatment with regard to the true medical situation. This could be explained by the model not using the children's exact weight or the real number of injections because the children had been discharged from the maternity ward based on their date of birth and the epidemic period. In spite of these factors, RSV prophylaxis using palivizumab in premature children with BPD or hemodynamically significant congenital-heart disease can be considered cost-effective in France. PMID:18990549

  6. GROWTH REGULATION IN RSV INFECTED CHECKEN EMBRYO FIBROBLASTS: THE ROLE OF THE src GENE

    SciTech Connect

    Parry, G.; Bartholomew, J.C.; Bissell, M.J.

    1980-03-01

    The relationship between growth regulation and cell transformation has been studied in many cultured cell lines transformed by a range of oncogenic agents. The main conclusion derived from these investigations is that the nature of the growth regulatory lesion in transformed cells is a function of the agent used to induce transformation. For example, when 3T3 fibroblasts are rendered stationary by serum deprivation, normal cells accumulate in G{sub 1} but SV40 transformed cells are arrested at all stages of the cell cycle. In contrast, 3T3 cells transformed with Rous sarcoma virus B77, accumulate in G{sub 1} upon serum deprivation. This is also true when mouse sarcoma virus (MSV) is used as the transforming agent. MSV-transformed cells accumulate in G{sub 1}, just as do normal cells. In this letter we report a detailed study of the mechanisms leading to loss of growth control in chicken embryo fibroblasts transformed by Rous sarcoma virus (RSV). We have been particularly concerned with the role of the src gene in the process, and have used RSV mutants temperature sensitive (ts) for transformation to investigate the nature of the growth regulatory lesion. Two principal findings have emerged: (a) the stationary phase of the cell cycle (G{sub 1}) in chick embryo fibroblasts has two distinct compartments, (for simplicity referred to as G{sub 1} and G{sub 0} states), (b) when rendered stationary at 41.5{sup o} by serum deprivation, normal cells enter a G{sub 0}-like state, but cells infected with the ts-mutant occupy a G{sub 1} state, even though a known src gene product, a kinase, should be inactive at this temperature. The possibility is discussed that viral factors other than the active src protein kinase influence growth control.

  7. Respiratory syncytial virus, adenoviruses, and mixed acute lower respiratory infections in children in a developing country.

    PubMed

    Rodríguez-Martínez, Carlos E; Rodríguez, Diego Andrés; Nino, Gustavo

    2015-05-01

    There is growing evidence suggesting greater severity and worse outcomes in children with mixed as compared to single respiratory virus infections. However, studies that assess the risk factors that may predispose a child to a mixture of respiratory syncytial virus (RSV) and adenoviral infections, are scarce. In a retrospective cohort study, the study investigated the epidemiology of RSV and adenovirus infections and predictors of mixed RSV-adenoviral infections in young children hospitalized with acute lower respiratory infection in Bogota, Colombia, South America, over a 2-year period 2009-2011. Of a total of 5,539 children admitted with a diagnosis of acute lower respiratory infection, 2,267 (40.9%) who were positive for RSV and/or adenovirus were selected. Out the total number of cases, 1,416 (62.5%) infections occurred during the 3-month period from March to May, the first rainy season of Bogota, Colombia. After controlling for gender, month when the nasopharyngeal sample was taken, and other pre-existing conditions, it was found that an age greater than 6 months (OR:1.74; CI 95%:1.05-2.89; P = 0.030) and malnutrition as a comorbidity (OR:9.92; CI 95%:1.01-100.9; P = 0.049) were independent predictors of mixed RSV-adenoviral infections in the sample of patients. In conclusion, RSV and adenovirus are significant causes of acute lower respiratory infection in infants and young children in Bogota, Colombia, especially during the first rainy season. The identified predictors of mixed RSV-adenoviral infections should be taken into account when planning intervention, in order to reduce the burden of acute lower respiratory infection in young children living in the country.

  8. IL-4 induction in RSV-infected macrophages: examining the role of NFAT family members

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Respiratory Syncytial Virus (RSV) is the leading cause of respiratory illness in infants, causing severe bronchiolitis and pneumonia. In the lung, alveolar macrophages are important antigen presenting cells responsible for pathogen clearance, antigen presentation and cytokine production. The effec...

  9. Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins

    PubMed Central

    Fuentes, Sandra; Coyle, Elizabeth M.; Beeler, Judy; Golding, Hana; Khurana, Surender

    2016-01-01

    Respiratory Syncytial Virus (RSV) is the major cause of pneumonia among infants. Here we elucidated the antibody repertoire following primary RSV infection and traced its evolution through adolescence and adulthood. Whole genome-fragment phage display libraries (GFPDL) expressing linear and conformational epitopes in the RSV fusion protein (F) and attachment protein (G) were used for unbiased epitope profiling of infant sera prior to and following RSV infection. F-GFPDL analyses demonstrated modest changes in the anti-F epitope repertoires post-RSV infection, while G-GFPDL analyses revealed 100-fold increase in number of bound phages. The G-reactive epitopes spanned the N- and C-terminus of the G ectodomain, along with increased reactivity to the central conserved domain (CCD). Panels of F and G antigenic sites were synthesized to evaluate sera from young children (<2 yr), adolescents (14–18 yr) and adults (30–45 yr) in SPR real-time kinetics assays. A steady increase in RSV-F epitope repertoires from young children to adults was observed using peptides and F proteins. Importantly, several novel epitopes were identified in pre-fusion F and an immunodominant epitope in the F-p27. In all age groups, antibody binding to pre-fusion F was 2–3 folds higher than to post-fusion form. For RSV-G, antibody responses were high following early RSV infection in children, but declined significantly in adults, using either G proteins or peptides. This study identified unlinked evolution of anti-F and anti G responses and supportive evidence for immune pressure driven evolution of RSV-G. These findings could help development of effective countermeasures including vaccines. PMID:27100289

  10. Inosine-containing RNA is a novel innate immune recognition element and reduces RSV infection.

    PubMed

    Liao, Jie-ying; Thakur, Sheetal A; Zalinger, Zachary B; Gerrish, Kevin E; Imani, Farhad

    2011-01-01

    During viral infections, single- and double-stranded RNA (ssRNA and dsRNA) are recognized by the host and induce innate immune responses. The cellular enzyme ADAR-1 (adenosine deaminase acting on RNA-1) activation in virally infected cells leads to presence of inosine-containing RNA (Ino-RNA). Here we report that ss-Ino-RNA is a novel viral recognition element. We synthesized unmodified ssRNA and ssRNA that had 6% to16% inosine residues. The results showed that in primary human cells, or in mice, 10% ss-Ino-RNA rapidly and potently induced a significant increase in inflammatory cytokines, such as interferon (IFN)-β (35 fold), tumor necrosis factor (TNF)-α (9.7 fold), and interleukin (IL)-6 (11.3 fold) (p<0.01). Flow cytometry data revealed a corresponding 4-fold increase in influx of neutrophils into the lungs by ss-Ino-RNA treatment. In our in vitro experiments, treatment of epithelial cells with ss-Ino-RNA reduced replication of respiratory syncytial virus (RSV). Interestingly, RNA structural analysis showed that ss-Ino-RNA had increased formation of secondary structures. Our data further revealed that extracellular ss-Ino-RNA was taken up by scavenger receptor class-A (SR-A) which activated downstream MAP Kinase pathways through Toll-like receptor 3 (TLR3) and dsRNA-activated protein kinase (PKR). Our data suggests that ss-Ino-RNA is an as yet undescribed virus-associated innate immune stimulus.

  11. A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism

    PubMed Central

    Krarup, Anders; Truan, Daphné; Furmanova-Hollenstein, Polina; Bogaert, Lies; Bouchier, Pascale; Bisschop, Ilona J. M.; Widjojoatmodjo, Myra N.; Zahn, Roland; Schuitemaker, Hanneke; McLellan, Jason S.; Langedijk, Johannes P. M.

    2015-01-01

    Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion RSV F elicits neutralizing antibodies in cotton rats and induces complete protection against viral challenge. Moreover, the structural and biochemical analysis of the prefusion variants suggests a function for p27, the excised segment that precedes the fusion peptide in the polypeptide chain. PMID:26333350

  12. MicroRNA Profiling from RSV-Infected Biofluids, Whole Blood, and Tissue Samples.

    PubMed

    Anderson, Lydia; Jorquera, Patricia A; Tripp, Ralph A

    2016-01-01

    Several studies have shown that respiratory syncytial virus (RSV) can modulate the host innate immune response by dysregulation of host microRNAs (miRNAs) related to the antiviral response, a feature that also affects the memory immune response to RSV (Thornburg et al. MBio 3(6), 2012). miRNAs are small, endogenous, noncoding RNAs that function in posttranscriptional gene regulation. Here, we explain a compilation of methods for the purification, quantification, and characterization of miRNA expression profiles in biofluids, whole blood samples, and tissue samples obtained from in vivo studies. In addition, this chapter describes methods for the isolation of exosomal miRNA populations. Understanding alterations in miRNA expression profiles and identifying miRNA targets genes, and their contribution to the pathogenesis of RSV, may help elucidate novel mechanism of host-virus interaction (Rossi et al., Pediatr Pulmonol, 2015). PMID:27464696

  13. RSV-encoded NS2 promotes epithelial cell shedding and distal airway obstruction

    PubMed Central

    Liesman, Rachael M.; Buchholz, Ursula J.; Luongo, Cindy L.; Yang, Lijuan; Proia, Alan D.; DeVincenzo, John P.; Collins, Peter L.; Pickles, Raymond J.

    2014-01-01

    Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease. PMID:24713657

  14. Evidence that maturation of the N-linked glycans of the respiratory syncytial virus (RSV) glycoproteins is required for virus-mediated cell fusion: The effect of {alpha}-mannosidase inhibitors on RSV infectivity

    SciTech Connect

    McDonald, Terence P.; Jeffree, Chris E.; Li, Ping; Rixon, Helen W. McL.; Brown, Gaie; Aitken, James D.; MacLellan, Kirsty; Sugrue, Richard J. . E-mail: rjsugrue@ntu.edu.sg

    2006-07-05

    Glycan heterogeneity of the respiratory syncytial virus (RSV) fusion (F) protein was demonstrated by proteomics. The effect of maturation of the virus glycoproteins-associated glycans on virus infectivity was therefore examined using the {alpha}-mannosidase inhibitors deoxymannojirimycin (DMJ) and swainsonine (SW). In the presence of SW the N-linked glycans on the F protein appeared in a partially mature form, whereas in the presence of DMJ no maturation of the glycans was observed. Neither inhibitor had a significant effect on G protein processing or on the formation of progeny virus. Although the level of infectious virus and syncytia formation was not significantly affected by SW-treatment, DMJ-treatment correlated with a one hundred-fold reduction in virus infectivity. Our data suggest that glycan maturation of the RSV glycoproteins, in particular those on the F protein, is an important step in virus maturation and is required for virus infectivity.

  15. Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

    PubMed

    Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

    2015-12-01

    Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of <24 months during anti-tumor therapy from April 2006 to March 2009 were investigated by sending a questionnaire to all member institutions of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

  16. RSV fusion (F) protein DNA vaccine provides partial protection against viral infection.

    PubMed

    Wu, Hongzhuan; Dennis, Vida A; Pillai, Shreekumar R; Singh, Shree R

    2009-10-01

    The present study was conducted to investigate the feasibility and efficacy of a RSV F DNA vaccine incorporated with a mucosal adjuvant. Two DNA vaccine vectors (DRF-412 and DRF-412-P) were developed containing residues 412-524 of the RSV F gene. These antigenic regions were cloned into the phCMV1 DNA vaccine vector. One of the DNA vaccine vectors, DRF-412, contained the ctxA(2)B region of the cholera toxin gene as a mucosal adjuvant. The in vitro expressions of these DNA vectors were confirmed in Cos-7 cells by indirect immunofluorescence and Western blot analyses. In vivo expression of the cloned gene was further confirmed in mouse muscle tissue by immunohistological analysis. The active transcription of the RSV F gene in mouse muscle cells was confirmed by RT-PCR. The purified DRF-412 and DRF-412-P DNA vectors were used to immunize mice by intramuscular injections. Our results indicated that DRF-412 and DRF-412-P vaccine vectors were as effective as live RSV in inducing neutralization antibody, systemic Ab (IgG, IgG1, IgG2a, and IgG2b) responses, and mucosal antibody responses (Ig A). The Th1 (TNF-alpha, IL-12p70, IFN-gamma, IL-2) and Th2 (IL-10, IL-6) cytokine profiles were analyzed after stimulation of spleen cells from mice immunized with purified RF-412 protein. We observed that mice inoculated with vector DRF-412 induced a higher mixed Th1/Th2 cytokine immune response than DRF-412-P. Reverse transcriptase and quantitative real-time PCR (qRT-PCR) revealed that mice immunized with the DRF-412 vector contained less viral RNA in lung tissue and the lung immunohistology study confirmed that mice immunized with DRF-412 had better protection than those immunized with the DRF-412-P vector. These results indicate that the RSV DRF-412 vaccine vector, which contains the cholera toxin subunit ctxA2B as a mucosal adjuvant may provide a better DNA vaccination strategy against RSV. PMID:19540885

  17. Ear infection - acute

    MedlinePlus

    ... Risk factors for acute ear infections include: Attending day care (especially centers with more than 6 children) Changes ... hands and toys often. If possible, choose a day care that has 6 or fewer children. This can ...

  18. Screening for Respiratory Syncytial Virus and Isolation Strategies in Children Hospitalized With acute Respiratory Tract Infection

    PubMed Central

    Pfeil, Johannes; Tabatabai, Julia; Sander, Anja; Ries, Markus; Grulich-Henn, Jürgen; Schnitzler, Paul

    2014-01-01

    Abstract Nosocomial infection with respiratory syncytial virus (RSV) is an important health risk in pediatric care but is largely preventable by efficient infection control measures. Commonly applied rapid antigen detection tests (RADTs) miss a considerable number of RSV-infected patients. The objective of our analysis was to evaluate whether readily available host parameters are associated with false-negative RADT, and to assess how these parameters could be applied in an optimized RSV isolation strategy. We retrospectively analyzed a cohort of 242 children under the age of 2 years hospitalized with acute respiratory tract infection to identify host parameters associated with false-negative RADT test result. We subsequently simulated the outcome of different isolation strategies based on RADT result and host parameters in view of the overall isolation efficacy. Out of 242 hospitalized patients, 134 (55%) patients were found RSV-positive by RT-PCR, whereas 108 (45%) patients were tested negative. The performance of the RADT was compared with the result obtained by reverse transcription polymerase chain reaction on the identical nasopharyngeal wash. Overall, we found that 85 patients (35%) were tested true positive, 108 (45%) were tested true negative, whereas a false-negative test result was obtained in 49 patients (20%). Duration of respiratory symptoms for >3 days and a respiratory admission diagnosis are associated with false-negative RADT result. In comparison with RADT alone, consideration of these clinical parameters and RADT result can decrease the rate of nonisolated RSV-infected patients from approximately 24% to 8% (65% RSV pretest probability). Consideration of both RADT and clinical parameters associated with false-negative RADT can result in an optimized RSV infection control policy. PMID:25437026

  19. Cytokine polymorphisms predict the frequency of otitis media as a complication of rhinovirus and RSV infections in children.

    PubMed

    Alper, Cuneyt M; Winther, Birgit; Hendley, J Owen; Doyle, William J

    2009-02-01

    Previous studies suggested that the otitis media (OM) complication rate of viral upper respiratory infection (vURI) is conditioned by genes affecting cytokine production. Two hundred and thirty children (114 male; 187 White, 25 Black; aged 1-9.3 years, average=3.6+/-1.6 years) were prospectively followed over the typical cold season for cold-like illness and OM. Nasopharyngeal secretion samples collected during cold-like illness and OM were assayed for upper respiratory viruses and buccal samples were assayed for TNFalpha (-308), IL-10(-1082, -819, -592), IL-6 (-174) and IFN-gamma (+874) polymorphisms. Logistic regression was used to identify genotypes that predict OM coincident with RSV and rhinovirus (RV) infection. Of the 157 children with RV detection (79 male; 132 White, 13 Black, 12 Other; aged 3.6+/-1.5 years), simple logistic regression identified age (B= -0.34, Z= -2.8, P<0.01, OR=0.71), IL-6 (B= -0.76, Z= -3.3, P<0.01, OR=0.47) and IL-10 (B=0.49, Z=2.0, P=0.05, OR=1.6) as significant predictors of OM coincidence. A more complex logistic regression model for RV detection that included selected OM risk factors identified these factors as well as the TNFalpha genotype, OM history, breastfeeding history and daily environment as significant predictors of OM coincidence. Of the 43 children with RSV detection (21 male; 35 White, 5 Black, 3 Other, aged 3.9+/-1.7 years), logistic regression identified IL-10 (B=1.05, Z=2.0, P=0.05, OR=2.9) as a significant predictor of OM coincidence. New OM episodes coincident with evidence of RSV and RV infection were significantly more frequent in children with high production IL-10 phenotypes. The low production IL-6 and high production TNFalpha phenotypes also contributed to OM risk during RV detection. Cytokine polymorphisms may be one of an expectedly large number of genetic factors contributing to the known heritability of OM.

  20. Evolution and Transmission of Respiratory Syncytial Group A (RSV-A) Viruses in Guangdong, China 2008–2015

    PubMed Central

    Zou, Lirong; Yi, Lina; Wu, Jie; Song, Yingchao; Huang, Guofeng; Zhang, Xin; Liang, Lijun; Ni, Hanzhong; Pybus, Oliver G.; Ke, Changwen; Lu, Jing

    2016-01-01

    Respiratory syncytial viruses (RSVs) including subgroups A (RSV-A) and B (RSV-B) are an important cause of acute respiratory tract infections worldwide. RSV-A include major epidemic strains. Fundamental questions concerning the evolution, persistence and transmission of RSV-A are critical for disease control and prevention, yet remain unanswered. In this study, we generated 64 complete G gene sequences of RSV-A strains collected between 2008 and 2015 in Guangdong, China. Phylogenetic analysis was undertaken by incorporating 572 publicly available RSV-A sequences. Current data indicate that genotypes GA1, GA4, and GA5 are endemic with limited epidemic activity. In contrast, the GA2 genotype which likely originated in 1980 has spread rapidly and caused epidemics worldwide. By analyzing GA2 genotype sequences across epidemic seasons within Guangdong, we find that RSV-A epidemics in Guangdong are caused by a combination of virus importation and local persistence, although the magnitude of the latter is likely overestimated due to infrequent sampling in other regions. Our results provide new insights into RSV-A evolution and transmission at global and local scales and highlights the rapid and wide spread of genotype GA2 compared to other genotypes. In order to control RSV transmission and outbreak, both local persistence and external introduction should be taken into account when designing optimal strategies. PMID:27574518

  1. Evolution and Transmission of Respiratory Syncytial Group A (RSV-A) Viruses in Guangdong, China 2008-2015.

    PubMed

    Zou, Lirong; Yi, Lina; Wu, Jie; Song, Yingchao; Huang, Guofeng; Zhang, Xin; Liang, Lijun; Ni, Hanzhong; Pybus, Oliver G; Ke, Changwen; Lu, Jing

    2016-01-01

    Respiratory syncytial viruses (RSVs) including subgroups A (RSV-A) and B (RSV-B) are an important cause of acute respiratory tract infections worldwide. RSV-A include major epidemic strains. Fundamental questions concerning the evolution, persistence and transmission of RSV-A are critical for disease control and prevention, yet remain unanswered. In this study, we generated 64 complete G gene sequences of RSV-A strains collected between 2008 and 2015 in Guangdong, China. Phylogenetic analysis was undertaken by incorporating 572 publicly available RSV-A sequences. Current data indicate that genotypes GA1, GA4, and GA5 are endemic with limited epidemic activity. In contrast, the GA2 genotype which likely originated in 1980 has spread rapidly and caused epidemics worldwide. By analyzing GA2 genotype sequences across epidemic seasons within Guangdong, we find that RSV-A epidemics in Guangdong are caused by a combination of virus importation and local persistence, although the magnitude of the latter is likely overestimated due to infrequent sampling in other regions. Our results provide new insights into RSV-A evolution and transmission at global and local scales and highlights the rapid and wide spread of genotype GA2 compared to other genotypes. In order to control RSV transmission and outbreak, both local persistence and external introduction should be taken into account when designing optimal strategies. PMID:27574518

  2. Influenza A virus among the hospitalized young children with acute respiratory infection. Is influenza A co infected with respiratory syncytial virus?

    PubMed Central

    Alavi, Seyed Mohammad; Makvandi, Manoochehr; Najafi-Fard, Saied; Alavi, Leila

    2012-01-01

    Background: Both influenza A virus (IAV) and respiratory syncytial virus (RSV) cause acute respiratory infection (ARI) in infants and young children. This study was conducted to determine Influenza A virus and its co infection with RSV among the hospitalized children with ARI. Methods: A total of 153 throat samples of the hospitalized young children aged between below one year and 5 years with the clinical signs of ARI were collected from the different hospitals in Khuzestan from June 2009 to April 2010. The samples were tested for Influenza A viruses by real time PCR. Positive IAV samples were tested for influenza A sub type H1N1 and for RSV by the nested PCR. Results: In this study, from the total 153 samples, 35 samples (22.9%) including 15 (42.8%) females and 20 (57.2%) males were positive for influenza A viruses. From the 35 positive samples for IAV, 14 were positive for swine H1N1 subtype. All the positive samples for influenza showed negative for RSV infection which revealed no coinfection with RSV. The prevalence of influenza A among age/sex groups was not significant. Conclusion: Influenza A is a prevalent viral agent isolated from young children with ARI. Influenza A subtype H1N1 was accounted for the 40 percent all laboratory-proven diagnoses of influenza in 2009. No evidence of coinfection of influenza A and RSV has been observed in the present study. PMID:24009929

  3. Human bocavirus infection in young children with acute respiratory tract infection in Lanzhou, China.

    PubMed

    Zheng, Li-shu; Yuan, Xin-hui; Xie, Zhi-ping; Jin, Yu; Gao, Han-chun; Song, Jing-rong; Zhang, Rong-fang; Xu, Zi-qian; Hou, Yun-de; Duan, Zhao-jun

    2010-02-01

    Human bocavirus (HBoV) is a recognized human parvovirus associated with acute respiratory tract infection. However, HBoV has yet to be established as a causative agent of respiratory disease. In this study, the epidemiological and virological characteristics of HBoV infection were studied in children with acute respiratory tract infection in China. In total, 406 children younger than 14 years of age with acute respiratory tract infection were included in this prospective 1-year study. HBoV was detected in 29 (7.1%) of the 406 children. No clear seasonal fluctuation was observed in infection rates of HBoV. Of the 29 children infected with HBoV, 16 (55.2%) were coinfected with other respiratory viruses, most commonly respiratory syncytial virus (RSV). Viral coinfection with HBoV did not affect the severity of the respiratory disease (P = 0.291). The number of HBoV genome copies ranged from 5.80 x 10(2) to 9.72 x 10(8) copies/ml in nasopharyngeal aspirates among HBoV-positive specimens by real-time PCR, and neither coinfection nor the severity of disease correlated with the viral load (P = 0.148, P = 0.354, respectively). The most common clinical features were cough and acute upper respiratory infection, and acute bronchopneumonia. Additionally, the NP-1 gene of HBoV showed minimal sequence variation. These data suggest that HBoV is frequent in young children with acute respiratory tract infection in Lanzhou, China, and RSV is the most common coinfecting virus. There was no apparent association between the viral load of HBoV and coinfection or disease severity. The NP-1 gene was highly conserved in HBoV. PMID:20029808

  4. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection

    PubMed Central

    Jozwik, Agnieszka; Habibi, Maximillian S.; Paras, Allan; Zhu, Jie; Guvenel, Aleks; Dhariwal, Jaideep; Almond, Mark; Wong, Ernie H. C.; Sykes, Annemarie; Maybeno, Matthew; Del Rosario, Jerico; Trujillo-Torralbo, Maria-Belen; Mallia, Patrick; Sidney, John; Peters, Bjoern; Kon, Onn Min; Sette, Alessandro; Johnston, Sebastian L.; Openshaw, Peter J.; Chiu, Christopher

    2015-01-01

    In animal models, resident memory CD8+ T (Trm) cells assist in respiratory virus elimination but their importance in man has not been determined. Here, using experimental human respiratory syncytial virus (RSV) infection, we investigate systemic and local virus-specific CD8+ T-cell responses in adult volunteers. Having defined the immunodominance hierarchy, we analyse phenotype and function longitudinally in blood and by serial bronchoscopy. Despite rapid clinical recovery, we note surprisingly extensive lower airway inflammation with persistent viral antigen and cellular infiltrates. Pulmonary virus-specific CD8+ T cells display a CD69+CD103+ Trm phenotype and accumulate to strikingly high frequencies into convalescence without continued proliferation. While these have a more highly differentiated phenotype, they express fewer cytotoxicity markers than in blood. Nevertheless, their abundance before infection correlates with reduced symptoms and viral load, implying that CD8+ Trm cells in the human lung can confer protection against severe respiratory viral disease when humoral immunity is overcome. PMID:26687547

  5. Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus

    PubMed Central

    Richter, Jan; Panayiotou, Christakis; Tryfonos, Christina; Koptides, Dana; Koliou, Maria; Kalogirou, Nikolas; Georgiou, Eleni; Christodoulou, Christina

    2016-01-01

    In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections. PMID:26761647

  6. Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus.

    PubMed

    Richter, Jan; Panayiotou, Christakis; Tryfonos, Christina; Koptides, Dana; Koliou, Maria; Kalogirou, Nikolas; Georgiou, Eleni; Christodoulou, Christina

    2016-01-01

    In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections. PMID:26761647

  7. Respiratory syncytial virus (RSV)

    MedlinePlus

    ... RSV often spreads quickly in crowded households and day care centers. The virus can live for a half ... The following increase the risk for RSV: Attending day care Being near tobacco smoke Having school-aged brothers ...

  8. Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

    PubMed Central

    McGill, Jodi L.; Rusk, Rachel A.; Guerra-Maupome, Mariana; Briggs, Robert E.; Sacco, Randy E.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and γδ T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing γδ T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and γδ T cells in the pathogenesis of BRDC. PMID:26942409

  9. Respiratory Syncytial Virus (RSV) RNA loads in peripheral blood correlates with disease severity in mice

    PubMed Central

    2010-01-01

    Background Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Methods Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. Results RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. Conclusions RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease. PMID:20843364

  10. Acute cytomegalovirus (CMV) infection

    MedlinePlus

    CMV mononucleosis; Cytomegalovirus (CMV) ... Infection with cytomegalovirus (CMV) is very common. The infection is spread by: Blood transfusions Organ transplants Respiratory droplets Saliva Sexual contact ...

  11. Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

    PubMed Central

    Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

    2015-01-01

    Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

  12. Comparative evaluation of real-time PCR and conventional RT-PCR during a 2 year surveillance for influenza and respiratory syncytial virus among children with acute respiratory infections in Kolkata, India, reveals a distinct seasonality of infection.

    PubMed

    Agrawal, Anurodh S; Sarkar, Mehuli; Chakrabarti, Sekhar; Rajendran, K; Kaur, Harpreet; Mishra, Akhilesh C; Chatterjee, Mrinal K; Naik, Trailokya N; Chadha, Mandeep S; Chawla-Sarkar, Mamta

    2009-12-01

    Acute respiratory tract infections (ARTIs) are one of the most common causes of morbidity and mortality in young children worldwide. Influenza virus and respiratory syncytial virus (RSV) are the predominant aetiological agents during seasonal epidemics, and thus rapid and sensitive molecular tests for screening for such agents and timely identification of epidemics are required. This study compared real-time quantitative PCR (qPCR) with conventional RT-PCR for parallel identification of influenza A virus (IAV) or influenza B virus (IBV) and RSV. A total of 1091 respiratory samples was examined from children with suspected ARTIs between January 2007 and December 2008. Of these, 275 (25.21 %) were positive for either influenza or RSV by qPCR compared with 262 (24 .01%) positive by RT-PCR. Overall, IAV, IBV and RSV were detected in 121 (11.09 %), 59 (5.41 %) and 95 (8.71 %) samples, respectively. In spite of overlapping clinical symptoms, RSV and influenza virus showed distinct seasonal peaks. IAV correlated positively and RSV negatively with rainfall and temperature. No distinct seasonality was observed in IBV infections. This is, to the best of our knowledge, the first report of a systemic surveillance of respiratory viruses with seasonal correlation and prevalence rates from eastern India. This 2 year comparative analysis also confirmed the feasibility of using qPCR in developing countries, which will not only improve the scope for prevention of epidemics, but will also provide crucial epidemiological data from tropical regions.

  13. [Differentiation of influenza (Flu) type A, type B, and respiratory syncytial virus (RSV) by QuickNavi™-Flu+RSV].

    PubMed

    Kohiyama, Risa; Miyazawa, Takashi; Shibano, Nobuko; Inano, Koichi

    2014-01-01

    Because it is not easy to differentiate Influenza virus (Flu) from RS virus (RSV) just by clinical symptoms, to accurately diagnose those viruses in conjunction with patient's clinical symptoms, rapid diagnostic kits has been used separately for each of those viruses. In our new study, we have developed a new rapid diagnostic kit, QuickNavi™-Flu+RSV. The kit can detect Flu A, Flu B, and RSV antigens with a single sample collection and an assay. Total of 2,873 cases (including nasopharyngeal swabs and nasopharyngeal aspirates specimens) in 2010/2011 and 2011/2012 seasons were evaluated with QuickNavi™-Flu+RSV and a commercially available kit. Sensitivity, specificity, and accuracy of Flu type A, type B, and RSV were above 95% when compared to commercially available kits (QuickNavi™-Flu and QuickNavi™-RSV) and considered to be equivalent to the commercially available kits. In 2011/2012 season, RSV infections increased prior to Flu season and continued during the peak of the Flu season. The kit can contribute to accurate diagnosis of Flu and RSV infections since co-infection cases have also been reported during the 2011/2012 season. QuickNavi™-Flu+RSV is useful for differential diagnosis of respiratory infectious diseases since it can detect Flu type A, type B, and RSV virus antigens with a single sample collection.

  14. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection.

    PubMed

    Pettigrew, Melinda M; Gent, Janneane F; Pyles, Richard B; Miller, Aaron L; Nokso-Koivisto, Johanna; Chonmaitree, Tasnee

    2011-11-01

    Acute otitis media (AOM) is a common complication of upper respiratory tract infection whose pathogenesis involves both viruses and bacteria. We examined risks of acute otitis media associated with specific combinations of respiratory viruses and acute otitis media bacterial pathogens. Data were from a prospective study of children ages 6 to 36 months and included viral and bacterial culture and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and human metapneumovirus. Repeated-measure logistic regression was used to assess the relationship between specific viruses, bacteria, and the risk of acute otitis media complicating upper respiratory tract infection. In unadjusted analyses of data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were significantly associated with AOM (P < 0.05 by χ(2) test). Children with high respiratory syncytial virus loads (≥3.16 × 10(7) copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with high RSV viral load with Streptococcus pneumoniae (odds ratio [OR], 4.40; 95% confidence interval [CI], 1.90 and 10.19) and Haemophilus influenzae (OR, 2.04; 95% CI, 1.38 and 3.02). The risk was higher for the presence of bocavirus and H. influenzae together (OR, 3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.

  15. Severe acute malnutrition and infection

    PubMed Central

    Jones, Kelsey D J; Berkley, James A

    2014-01-01

    Severe acute malnutrition (SAM) is associated with increased severity of common infectious diseases, and death amongst children with SAM is almost always as a result of infection. The diagnosis and management of infection are often different in malnourished versus well-nourished children. The objectives of this brief are to outline the evidence underpinning important practical questions relating to the management of infectious diseases in children with SAM and to highlight research gaps. Overall, the evidence base for many aspects covered in this brief is very poor. The brief addresses antimicrobials; antipyretics; tuberculosis; HIV; malaria; pneumonia; diarrhoea; sepsis; measles; urinary tract infection; nosocomial Infections; soil transmitted helminths; skin infections and pharmacology in the context of SAM. The brief is structured into sets of clinical questions, which we hope will maximise the relevance to contemporary practice. PMID:25475887

  16. Use of Minigenome Systems to Study RSV Transcription.

    PubMed

    Teng, Michael N; Tran, Kim C

    2016-01-01

    Minigenome assays have been essential tools in the understanding of viral transcription and RNA replication for respiratory syncytial virus (RSV). Here, we describe the RSV minigenome assay for determining transcription by the viral polymerase in the absence of infection. We detail two different methods of detecting viral RNA synthesis: a firefly luciferase assay for rapid and sensitive measurement of RSV polymerase activity; and a real-time quantitative PCR method for determination of specific effects on the transcription of individual viral genes and the polar transcription gradient of RSV. PMID:27464693

  17. Viral etiology of acute lower respiratory tract infections in hospitalized young children in a children's referral hospital in Iran.

    PubMed

    Pourakbari, Babak; Mahmoudi, Shima; Movahedi, Zahra; Halimi, Shahnaz; Momeni, Shervin; Hosseinpour-Sadeghi, Reihaneh; Mamishi, Setareh

    2014-01-01

    Viruses are considered major causes of acute respiratory tract infections among children under 5 years old. In this study we investigated the prevalence of three respiratory viruses--respiratory syncytial virus (RSV), influenza virus (INF) and adenovirus (ADV)--among hospitalized children with acute viral lower respiratory tract infections (LRTIs). Nasopharyngeal aspirates were collected from children under five who had been hospitalized for LRTIs. The clinical data, including demographic data (age and sex), vital symptoms and signs at admission, duration of fever, duration of hospitalization, chest X-ray findings and outcome were considered. All inpatient specimens were tested by reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and the INF-A, INF-B and parainfluenza viruses and by polymerase chain reaction (PCR) for ADV. Out of those from 232 patients, 58 (25%) specimens were positive for either RSV, INF or ADV. The most predominant pathogens were RSV (40 cases, 17.2%), followed by INF (10 cases, 4%; including 8 type A and 2 type B) and ADV (8 cases, 3.4%). A total of 32 (55.1%) viral cases were identified in the spring, followed by 19 (32.7%) in the autumn and 7 (12%) in the winter. There was no significant correlation between clinical symptoms and the individual virus detected. In our study, RSV and INF were the two most common causes of LRTIs. These data are helpful for guiding the development of further vaccines as well as the use of antiviral drugs. Further studies will be needed to investigate other respiratory viruses such as parainfluenza, human metapneumovirus and rhinovirus. PMID:25818953

  18. Targeting RSV with Vaccines and Small Molecule Drugs

    PubMed Central

    Costello, Heather M.; Ray, William C.; Chaiwatpongsakorn, Supranee; Peeples, Mark E.

    2012-01-01

    Respiratory syncytial virus (RSV) is the most significant cause of pediatric respiratory infections. Palivizumab (Synagis®), a humanized monoclonal antibody, has been used successfully for a number of years to prevent severe RSV disease in at-risk infants. However, despite intense efforts, there is no approved vaccine or small molecule drug for RSV. As an enveloped virus, RSV must fuse its envelope with the host cell membrane, which is accomplished through the actions of the fusion (F) glycoprotein, with attachment help from the G glycoprotein. Because of their integral role in initiation of infection and their accessibility outside the lipid bilayer, these proteins have been popular targets in the discovery and development of antiviral compounds and vaccines against RSV. This review examines advances in the development of antiviral compounds and vaccine candidates. PMID:22335496

  19. Modulation of host adaptive immunity by hRSV proteins

    PubMed Central

    Espinoza, Janyra A; Bohmwald, Karen; Céspedes, Pablo F; Riedel, Claudia A; Bueno, Susan M; Kalergis, Alexis M

    2014-01-01

    Globally, the human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infections (LRTIs) in infants and children younger than 2 years old. Furthermore, the number of hospitalizations due to LRTIs has shown a sustained increase every year due to the lack of effective vaccines against hRSV. Thus, this virus remains as a major public health and economic burden worldwide. The lung pathology developed in hRSV-infected humans is characterized by an exacerbated inflammatory and Th2 immune response. In order to rationally design new vaccines and therapies against this virus, several studies have focused in elucidating the interactions between hRSV virulence factors and the host immune system. Here, we discuss the main features of hRSV biology, the processes involved in virus recognition by the immune system and the most relevant mechanisms used by this pathogen to avoid the antiviral host response. PMID:25513775

  20. Viruses as Sole Causative Agents of Severe Acute Respiratory Tract Infections in Children

    PubMed Central

    Moesker, Fleur M.; van Kampen, Jeroen J. A.; van Rossum, Annemarie M. C.; de Hoog, Matthijs; Koopmans, Marion P. G.; Osterhaus, Albert D. M. E.; Fraaij, Pieter L. A.

    2016-01-01

    Background Respiratory syncytial virus (RSV) and influenza A viruses are known to cause severe acute respiratory tract infections (SARIs) in children. For other viruses like human rhinoviruses (HRVs) this is less well established. Viral or bacterial co-infections are often considered essential for severe manifestations of these virus infections. Objective The study aims at identifying viruses that may cause SARI in children in the absence of viral and bacterial co-infections, at identifying disease characteristics associated with these single virus infections, and at identifying a possible correlation between viral loads and disease severities. Study Design Between April 2007 and March 2012, we identified children (<18 year) with or without a medical history, admitted to our paediatric intensive care unit (PICU) with SARI or to the medium care (MC) with an acute respiratory tract infection (ARTI) (controls). Data were extracted from the clinical and laboratory databases of our tertiary care paediatric hospital. Patient specimens were tested for fifteen respiratory viruses with real-time reverse transcriptase PCR assays and we selected patients with a single virus infection only. Typical bacterial co-infections were considered unlikely to have contributed to the PICU or MC admission based on C-reactive protein-levels or bacteriological test results if performed. Results We identified 44 patients admitted to PICU with SARI and 40 patients admitted to MC with ARTI. Twelve viruses were associated with SARI, ten of which were also associated with ARTI in the absence of typical bacterial and viral co-infections, with RSV and HRV being the most frequent causes. Viral loads were not different between PICU-SARI patients and MC-ARTI patients. Conclusion Both SARI and ARTI may be caused by single viral pathogens in previously healthy children as well as in children with a medical history. No relationship between viral load and disease severity was identified. PMID:26964038

  1. RSV604, a Novel Inhibitor of Respiratory Syncytial Virus Replication▿

    PubMed Central

    Chapman, Joanna; Abbott, Elizabeth; Alber, Dagmar G.; Baxter, Robert C.; Bithell, Sian K.; Henderson, Elisa A.; Carter, Malcolm C.; Chambers, Phil; Chubb, Ann; Cockerill, G. Stuart; Collins, Peter L.; Dowdell, Verity C. L.; Keegan, Sally J.; Kelsey, Richard D.; Lockyer, Michael J.; Luongo, Cindy; Najarro, Pilar; Pickles, Raymond J.; Simmonds, Mark; Taylor, Debbie; Tyms, Stan; Wilson, Lara J.; Powell, Kenneth L.

    2007-01-01

    Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease. PMID:17576833

  2. Demographic, Clinical and Hematological Profile of Children with Bronchiolitis: A Comparative Study between Respiratory Synctial Virus [RSV] and [Non RSV] Groups

    PubMed Central

    Brow, Edin; Mannu, Alexander; Vasudevan, Jaishree; Umadevi, Lala

    2016-01-01

    Introduction Acute bronchiolitis is one of major disease affecting the lower airways in infants and children with Respiratory Syncitial Virus (RSV) being most common causative organism accounting for 50%-80% of bronchiolitis cases. Aim To analyse the demographic characteristics, clinical features and haematological profile of children with Bronchiolitis. To compare the findings of demographic characteristics, clinical features and haematological profile between RSV and Non –RSV bronchiolitis. Materials and Methods This is a prospective study, conducted in a teritiary care center for 1 year period from Jan 2015 to Dec 2015. The demographic characteristics, clinical features and haematological profile of children aged between 1 month to 3 years who fulfilled the inclusion criteria were noted in predesigned proforma, nasopharyngeal swab was sent for RSV analysis and then the findings of the parameters were compared between the two groups of RSV bronchiolitis and Non RSV bronchiolitis. Results Among 80 cases with 40 in each group, children below the age of 1year were affected more in RSV group, with male preponderance. Among the clinical features except that 89.7% of RSV cases had wheeze that was statistically significant with no difference in other features. Investigations showed no much difference in both the groups. Percentage of Non RSV subjects who received nebulisation with bronchodilators, steroid and antibiotic therapy were higher than RSV subjects. The hospital stay was significantly higher in RSV cases and none of the study participants met with mortality. Conclusion Children with RSV bronchiolitis had prolonged hospital stay compared to Non RSV group. Need for nebulisation with bronchodilators, steroids and antibiotic therapy was more in Non RSV group. PMID:27656520

  3. Defining the timing of respiratory syncytial virus (RSV) outbreaks: an epidemiological study

    PubMed Central

    Terletskaia-Ladwig, Elena; Enders, Gisela; Schalasta, Gunnar; Enders, Martin

    2005-01-01

    Background Seasonal RSV infections occur every year and affect particularly children under six months of age. Passive immunoprophylaxis with monoclonal antibody Palivizumab is recommended in the period with high risk of RSV infection. This study aims to define the period for the southern part of Germany (Stuttgart area). Methods Epidemiological analysis of the RSV situation in southern Germany from 1996 to 2004 and comparison of results with literature was made. The respiratory tract specimens were sent in for the detection of RSV mainly by paediatric clinics. Detection of RSV was carried out mainly by real-time RT-PCR or by ELISA "Pathfinder". RSV outbreaks were depicted as an absolute number and as a percentage of RSV diagnoses in a month. Onsets, offsets, peaks, duration and severity of RSV seasons were defined and analysed. Results An early season with strong RSV activity (early-high phase) was followed by a weaker late season (late-low phase) in a regular biennial rhythm. However, onsets, offsets and durations of outbreaks varied significantly from year to year. RSV epidemics in southern Germany were found to oscillate in an antiphase with RSV epidemics in Finland and Sweden. Conclusion The long-term regular biennial rhythm allows predicting whether the next outbreak will be late or early and whether RSV activity will be strong or weak. Not foreseeable, however, is the precise time of increase and decrease of RSV activity. Moreover, the regular seasonal pattern may be disrupted by irregular outbreaks. Thus, activity of RSV has to be monitored every year to define the period with high risk of infection. PMID:15801975

  4. Structure and Function of RSV Surface Glycoproteins

    PubMed Central

    McLellan, Jason S.; Ray, William C.; Peeples, Mark E.

    2014-01-01

    The two major glycoproteins on the surface of the RSV virion, the attachment glycoprotein (G) and the fusion (F) glycoprotein, control the initial phases of infection. G targets the ciliated cells of the airways, and F causes the virion membrane to fuse with a target cell membrane. The F protein is the major target for antiviral drug development, and both G and F glycoproteins are the antigens targeted by neutralizing antibodies induced by infection. In this chapter we review the structure and function of the RSV surface glycoproteins, including recent X-ray crystallographic data of the F glycoprotein in its pre- and postfusion conformations, and discuss how this information informs antigen selection and vaccine development. PMID:24362685

  5. Stress and acute respiratory infection

    SciTech Connect

    Graham, N.M.; Douglas, R.M.; Ryan, P.

    1986-09-01

    To examine the relationship between stress and upper respiratory tract infection, 235 adults aged 14-57 years, from 94 families affiliated with three suburban family physicians in Adelaide, South Australia, participated in a six-month prospective study. High and low stress groups were identified by median splits of data collected from the Life Events Inventory, the Daily Hassles Scale, and the General Health Questionnaire, which were administered both before and during the six months of respiratory diary data collection. Using intra-study stress data, the high stress group experienced significantly more episodes (mean of 2.71 vs. 1.56, p less than 0.0005) and symptom days (mean of 29.43 vs. 15.42, p = 0.005) of respiratory illness. The two groups were almost identical with respect to age, sex, occupational status, smoking, passive smoking, exposure to air pollution, family size, and proneness to acute respiratory infection in childhood. In a multivariate model with total respiratory episodes as the dependent variable, 21% of the variance was explained, and two stress variables accounted for 9% of the explained variance. Significant, but less strong relationships were also identified between intra-study stress variables and clinically definite episodes and symptom days in both clinically definite and total respiratory episodes. Pre-study measures of stress emphasized chronic stresses and were less strongly related to measures of respiratory illness than those collected during the study. However, significantly more episodes (mean of 2.50 vs. 1.75, p less than 0.02) and symptom days (mean of 28.00 vs. 17.06, p less than 0.03) were experienced in the high stress group. In the multivariate analyses, pre-study stress remained significantly associated with total respiratory episodes nd symptom days in total and ''definite'' respiratory episodes.

  6. Recent advances in the development of subunit-based RSV vaccines.

    PubMed

    Jaberolansar, Noushin; Toth, Istvan; Young, Paul R; Skwarczynski, Mariusz

    2016-01-01

    Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections causing pneumonia and bronchiolitis in infants. RSV also causes serious illness in elderly populations, immunocompromised patients and individuals with pulmonary or cardiac problems. The significant morbidity and mortality associated with RSV infection have prompted interest in RSV vaccine development. In the 1960s, a formalin-inactivated vaccine trial failed to protect children, and indeed enhanced pathology when naturally infected later with RSV. Hence, an alternative approach to traditional killed virus vaccines, which can induce protective immunity without serious adverse events, is desired. Several strategies have been explored in attempts to produce effective vaccine candidates including gene-based and subunit vaccines. Subunit-based vaccine approaches have shown promising efficacy in animal studies and several have reached clinical trials. The current stage of development of subunit-based vaccines against RSV is reviewed in this article.

  7. Role of respiratory syncytial virus in acute otitis media: implications for vaccine development.

    PubMed

    Patel, Janak A; Nguyen, Dang T; Revai, Krystal; Chonmaitree, Tasnee

    2007-02-19

    We summarize herein the results of various virologic studies of acute otitis media (AOM) conducted at our site over a 10-year period. Among 566 children with AOM, respiratory syncytial virus (RSV) was the most common virus identified in either middle ear fluid or nasal wash; it was found in 16% of all children and 38% of virus-positive children. Seventy-one percent of the children with RSV were 1 year of age or older, which was significantly older than all other viruses combined (P=0.045). RSV infection was associated with the common bacterial pathogens causing AOM. Past efforts to develop vaccines for RSV have emphasized prevention of lower respiratory tract infection in infants, which is a more serious problem but less common than AOM. Our results suggest that RSV vaccines that work only against infection in older children may have value in preventing AOM, the most common pediatric disease.

  8. Current Therapy in Acute Mouth Infections

    ERIC Educational Resources Information Center

    Goldfarb, George; Burnstein, Irwin L.

    1970-01-01

    Until a dental department is added to a college health service, a physician or nurse can give treatment for acute oral infections. Treatment excludes the use of caustic, escharotic chemicals in favor of more benign agents. (Author)

  9. Experimental evidence and molecular modeling of the interaction between hRSV-NS1 and quercetin.

    PubMed

    Gomes, Deriane Elias; Caruso, Ícaro Putinhon; de Araujo, Gabriela Campos; de Lourenço, Isabella Otenio; de Melo, Fernando Alves; Cornélio, Marinônio Lopes; Fossey, Marcelo Andrés; de Souza, Fátima Pereira

    2016-04-01

    Human Respiratory Syncytial Virus is one of the major causes of acute respiratory infections in children, causing bronchiolitis and pneumonia. Non-Structural Protein 1 (NS1) is involved in immune system evasion, a process that contributes to the success of hRSV replication. This protein can act by inhibiting or neutralizing several steps of interferon pathway, as well as by silencing the hRSV ribonucleoproteic complex. There is evidence that quercetin can reduce the infection and/or replication of several viruses, including RSV. The aims of this study include the expression and purification of the NS1 protein besides experimental and computational assays of the NS1-quercetin interaction. CD analysis showed that NS1 secondary structure composition is 30% alpha-helix, 21% beta-sheet, 23% turn and 26% random coils. The melting temperature obtained through DSC analysis was around 56°C. FRET analysis showed a distance of approximately 19Å between the NS1 and quercetin. Fluorescence titration results showed that the dissociation constant of the NS1-quercetin interaction was around 10(-6)M. In thermodynamic analysis, the enthalpy and entropy balanced forces indicated that the NS1-quercetin interaction presented both hydrophobic and electrostatic contributions. The computational results from the molecular modeling for NS1 structure and molecular docking regarding its interaction with quercetin corroborate the experimental data.

  10. Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana

    PubMed Central

    2012-01-01

    Background Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. Method Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. Results Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2%) were positive for one or more viruses. Respiratory Syncytial Virus (RSV) was detected in 18(14.1%, 95%CI: 8.5% to 21.3%) patients followed by Adenoviruses (AdV) in 13(10.2%, 95%CI: 5.5% to 16.7%), Parainfluenza (PIV type: 1, 2, 3) in 4(3.1%, 95%CI: 0.9% to 7.8%) and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3). Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36) of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. Conclusion The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection. PMID:22490115

  11. Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.

    PubMed

    Song, Weifeng; Yu, Zhihong; Doran, Stephen F; Ambalavanan, Namasivayam; Steele, Chad; Garantziotis, Stavros; Matalon, Sadis

    2015-08-01

    Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments.

  12. TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

    PubMed Central

    Caballero, Mauricio T.; Serra, M. Elina; Acosta, Patricio L.; Marzec, Jacqui; Gibbons, Luz; Salim, Maximiliano; Rodriguez, Andrea; Reynaldi, Andrea; Garcia, Alejandro; Bado, Daniela; Buchholz, Ursula J.; Hijano, Diego R.; Coviello, Silvina; Newcomb, Dawn; Bellabarba, Miguel; Ferolla, Fausto M.; Libster, Romina; Berenstein, Ada; Siniawaski, Susana; Blumetti, Valeria; Echavarria, Marcela; Pinto, Leonardo; Lawrence, Andrea; Ossorio, M. Fabiana; Grosman, Arnoldo; Mateu, Cecilia G.; Bayle, Carola; Dericco, Alejandra; Pellegrini, Mariana; Igarza, Ignacio; Repetto, Horacio A.; Grimaldi, Luciano Alva; Gudapati, Prathyusha; Polack, Norberto R.; Althabe, Fernando; Shi, Min; Ferrero, Fernando; Bergel, Eduardo; Stein, Renato T.; Peebles, R. Stokes; Boothby, Mark; Kleeberger, Steven R.; Polack, Fernando P.

    2015-01-01

    While 30%–70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-γ ratio in respiratory secretions. The IL-4/IFN-γ ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-γ ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention. PMID:25555213

  13. Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats.

    PubMed

    Lu, Chia-Chen; Lai, Hsin-Chih; Hsieh, Shang-Chen; Chen, Jan-Kan

    2008-04-01

    Serratia marcescens is an important nosocomial pathogen, which has been especially problematic as a cause of hospital-acquired pneumonia in the past two decades. Treatment of S. marcescens-related infections has been limited by emergence of multiple drug-resistant strains. Thus, the development of alternative agents for the prevention and treatment of Serratia infection is urgently needed. Resveratrol (RSV) is a compound with diverse biological effects including anti-cancer, anti-inflammation, anti-diabetes, and cancer chemoprevention. Whether RSV has in vivo prophylactic or therapeutic potential against infection remains uncharacterized. In the present study, we used a murine acute pneumonia model initiated by intratracheal application of S. marcescens to evaluate whether RSV possesses anti-infection properties. We showed that pretreatment with RSV for 3 days markedly increased alveolar macrophage infiltration, elevated NK cell activity, and decreased bacterial burden in the infected lung with a subsequent decrease in mortality. These effects were associated with significantly less-severe inflammatory phenotypes in lung tissue and bronchoalveolar lavage fluid, including reduced neutrophil infiltration of the lungs, reduced phagocytosis activity, and reduced secretion of cytokines such as TNF-alpha, IL-1beta, and IL-6. To further characterize the underlying mechanism responsible for these effects of RSV, LPS derived from S. marcescens was used to induce acute pneumonia in rats, with or without RSV pretreatment. RSV was shown to ameliorate acute pneumonia via inhibition of the NF-kappaB signaling pathway, including inhibition of IkappaBalpha phosphorylation and subsequent NF-kappaB activation. These findings suggest that RSV might be beneficial as a prophylactic treatment in patients at risk of an episode of S. marcescens-induced acute pneumonia.

  14. Tsutsugamushi infection-associated acute rhabdomyolysis and acute renal failure.

    PubMed

    Young, Park Chi; Hae, Chung Choon; Lee, Kim Hyun; Hoon, Chung Jong

    2003-12-01

    Rhabdomyolysis is a rare complication that emerges in a variety of infectious diseases, such as tsutsugamushi infection. In this study, we report a 71-year-old female patient with tsutsugamushi infection who exhibiting rhabdomyolysis and acute renal failure. On admission, an eschar, which is characteristic of tsutsugamushi infection, was found on her right flank area. Moreover, her tsutsugamushi antibody titer was 1:40960. The elevated values of serum creatinine phosphokinase (CPK), aldolase, creatinine and dark brown urine secondary to myoglobinuria are consistent with indications of rhabdomyolysis and acute renal failure due to tsutsugamushi infection. Her health improved without any residual effects after treatment with doxycyclin and hydration with normal saline. PMID:14717236

  15. Acute otitis media and respiratory virus infections.

    PubMed

    Ruuskanen, O; Arola, M; Putto-Laurila, A; Mertsola, J; Meurman, O; Viljanen, M K; Halonen, P

    1989-02-01

    We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.

  16. Respiratory Syncytial Virus (RSV): Treatment

    MedlinePlus

    ... Treatment To treat RSV is to treat its symptoms. Drinking electrolyte-replacing fluids—not sugary sodas or sports drinks—regularly will prevent dehydration (abnormal loss of body fluids). Acetaminophen (Tylenol, for ...

  17. Temporal association between the influenza virus and respiratory syncytial virus (RSV): RSV as a predictor of seasonal influenza.

    PubMed

    Míguez, A; Iftimi, A; Montes, F

    2016-09-01

    Epidemiologists agree that there is a prevailing seasonality in the presentation of epidemic waves of respiratory syncytial virus (RSV) infections and influenza. The aim of this study is to quantify the potential relationship between the activity of RSV, with respect to the influenza virus, in order to use the RSV seasonal curve as a predictor of the evolution of an influenza virus epidemic wave. Two statistical tools, logistic regression and time series, are used for predicting the evolution of influenza. Both logistic models and time series of influenza consider RSV information from previous weeks. Data consist of influenza and confirmed RSV cases reported in Comunitat Valenciana (Spain) during the period from week 40 (2010) to week 8 (2014). Binomial logistic regression models used to predict the two states of influenza wave, basal or peak, result in a rate of correct classification higher than 92% with the validation set. When a finer three-states categorization is established, basal, increasing peak and decreasing peak, the multinomial logistic model performs well in 88% of cases of the validation set. The ARMAX model fits well for influenza waves and shows good performance for short-term forecasts up to 3 weeks. The seasonal evolution of influenza virus can be predicted a minimum of 4 weeks in advance using logistic models based on RSV. It would be necessary to study more inter-pandemic seasons to establish a stronger relationship between the epidemic waves of both viruses. PMID:27165946

  18. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

    PubMed Central

    Pierantoni, Angiolo; Esposito, Maria Luisa; Ammendola, Virginia; Napolitano, Federico; Grazioli, Fabiana; Abbate, Adele; del Sorbo, Mariarosaria; Siani, Loredana; D’Alise, Anna Morena; Taglioni, Alessandra; Perretta, Gemma; Siccardi, Antonio; Soprana, Elisa; Panigada, Maddalena; Thom, Michelle; Scarselli, Elisa; Folgori, Antonella; Colloca, Stefano; Taylor, Geraldine; Cortese, Riccardo; Nicosia, Alfredo; Capone, Stefania; Vitelli, Alessandra

    2015-01-01

    Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing. PMID:26015988

  19. Health plan medical director: considerations for prevention and management of RSV disease.

    PubMed

    Tzeel, Albert

    2008-11-01

    At Humana, our intent is to provide RSV immunoprophylaxis to all our members who need it quickly and efficiently. Humana's CareHub is a collaborative guidance model that fully engages our members and their health care providers, and allows us to leverage technology to develop a comprehensive clinical profile for each member and to share information. This clinical profile provides many ways in which we can identify those children who are at high risk of severe RSV infection, allowing us to implement RSV treatment and management quickly and effectively before the RSV season begins.

  20. Multiple CD4+ T cell subsets produce immunomodulatory interleukin-10 during respiratory syncytial virus infection

    PubMed Central

    Weiss, Kayla A.; Christiaansen, Allison F.; Fulton, Ross B.; Meyerholz, David K.; Varga, Steven M.

    2011-01-01

    The host immune response is believed to contribute to the severity of pulmonary disease induced by acute respiratory syncytial virus (RSV) infection. Because RSV-induced pulmonary disease is associated with immunopathology, we evaluated the role of IL-10 in modulating the RSV-specific immune response. We found that IL-10 protein levels in the lung were increased following acute RSV infection with maximum production corresponding to the peak of the virus-specific T cell response. The majority of IL-10 producing cells in the lung during acute RSV infection were CD4+ T cells. The IL-10-producing CD4+ T cells included Foxp3+Tregs, Foxp3− CD4+ T cells that co-produce IFN-γ, and Foxp3− CD4+ T cells that do not co-produce IFN-γ. RSV infection of IL-10-deficient mice resulted in more severe disease, as measured by increased weight loss and airway resistance, as compared to control mice. We also observed an increase in the magnitude of the RSV-induced CD8+ and CD4+ T cell response that correlated with increased disease severity in the absence of IL-10 or following IL-10R blockade. Interestingly, IL-10R blockade during acute RSV infection altered CD4+ T cell subset distribution, resulting in a significant increase in IL-17A-producing CD4+ T cells and a concomitant decrease in Foxp3+ regulatory T cells. These results demonstrate that IL-10 plays a critical role in modulating the adaptive immune response to RSV by limiting T-cell-mediated pulmonary inflammation and injury. PMID:21844390

  1. [Consensus conference on acute bronchiolitis (v): prevention of acute bronchiolitis. Review of scientific evidence].

    PubMed

    González de Dios, J; Ochoa Sangrador, C

    2010-05-01

    A review of the evidence on prevention of acute bronchiolitis is presented. Acute bronchiolitis prevention arises from three basic approaches: preventive treatment to reduce recurrent wheezing following an episode of acute bronchiolitis, preventive treatment to reduce the frequency and severity of RSV bronchiolitis in the population at risk (prematurity, bronchopulmonary dysplasia, congenital heart disease, etc.), and general preventive measures to reduce nosocomial infection with RSV. There is sufficient evidence on the lack of efficacy of inhaled corticosteroids, oral corticosteroids and montelukast. Intravenous RSV immunoglobulin has an unfavorable risk-benefit balance, particularly with the availability of monoclonal antibodies. Palivizumab is effective as preventive treatment of RSV infection in risk populations (high risk preterm infants and hemodynamically significant congenital heart disease), but not in the frequency and severity (ICU admission, need for mechanical ventilation and mortality) of the acute bronchiolitis. The benefits of palivizumab (less admissions) seem to be worth the adverse effects, but we do not know the cost-benefit ratio. The control and prevention measures of nosocomial transmission of RSV infection (isolation, hand washing, use of mask, gloves, cap and shoes) are based on indirect evidence.

  2. When to consider acute HIV infection in the differential diagnosis.

    PubMed

    Grimes, Richard M; Hardwicke, Robin L; Grimes, Deanna E; DeGarmo, D Sean

    2016-01-16

    Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection. PMID:26678418

  3. Predictors of RSV LRTI Hospitalization in Infants Born at 33 to 35 Weeks Gestational Age: A Large Multinational Study (PONI)

    PubMed Central

    Saliba, Elie; Kosma, Paraskevi; Posfay-Barbe, Klara; Yunis, Khalid; Farstad, Teresa; Unnebrink, Kristina; van Wyk, Jean; Wegzyn, Colleen; Notario, Gerard; Kalus, Stefanie; Campbell, Fiona J.

    2016-01-01

    Background Preterm infants are at high risk of developing respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI). This observational epidemiologic study evaluated RSV disease burden and risk factors for RSV-associated LRTI hospitalization in preterm infants 33 weeks+0 days to 35 weeks+6 days gestational age not receiving RSV prophylaxis. Methods Preterm infants ≤6 months of age during RSV season (1 October 2013–30 April 2014) were followed at 72 sites across 23 countries from September 2013–July 2014 (study period). RSV testing was performed according to local clinical practice. Factors related to RSV-associated hospitalization for LRTI were identified using multivariable logistic regression with backward selection. Results Of the 2390 evaluable infants, 204 and 127 were hospitalized for LRTI during the study period and RSV season, respectively. Among these subjects, 64/204 and 46/127, respectively, were hospitalized for confirmed RSV LRTI. Study period and RSV season normalized RSV hospitalization rates (per 100 infant years) were 4.1 and 6.1, respectively. Factors associated with an increased risk of RSV-related LRTI hospitalization in multivariable analyses were smoking of family members (P<0.0001), non-hemodynamically significant congenital heart disease diagnosis (P = 0.0077), maternal age of ≤25 years at delivery (P = 0.0009), low maternal educational level (P = 0.0426), household presence of children aged 4 to 5 years (P = 0.0038), age on 1 October ≤3 months (P = 0.0422), and presence of paternal atopy (P<0.0001). Conclusions During the 2013–2014 RSV season across 23 countries, for preterm infants 33–35 weeks gestation ≤6 months old on 1 October not receiving RSV prophylaxis, confirmed RSV LRTI hospitalization incidence was 4.1 per 100 infant years during the study period and 6.1 per 100 infant years during the RSV season. This study enhances the findings of single-country studies of common risk factors for

  4. Peritoneal infection in acute intermittent peritoneal dialysis.

    PubMed

    Sharma, Raj Kumar; Kumar, Jitendra; Gupta, Amit; Gulati, Sanjeev

    2003-11-01

    A prospective study was done to evaluate the incidence and microbiological trend of peritoneal infection in patients undergoing acute intermittent peritoneal dialysis (PD). Complete sterile procedure was ensured and at the completion of the procedure PD fluid was sent for bacteriological culture, sensitivity, and total and differential cell count. During the period September 2000 to February 2001 a total of 100 patients were evaluated. Male female ratio was 72:28. Mean age was 43.17 +/- 17.2 years. In 26 patients cyclers were used. Bacterial culture was positive in total of 30 cases (30%). Gram positive, Gram negative and mixed infection was found in 10%, 15%, and 5% respectively. Number of exchanges (31.61 +/- 7.7 vs. 31.3 +/- 6, p = 0.8) were similar and number of repositioning was significantly more in the infected group (23.3% vs. 11.4%, p < 0.01). Total cell count was significantly higher in infected group (274.3 +/- 502 vs. 31.25 +/- 79.34, p < 0.01). Among Gram +ve organisms Staphylococcus was found in 7, Enterococcus faecalis in 4 and Coryne bacterium sps. in 2 cases. Among Gram -ve organisms, E. coli was found in 4, Enterobacter in 3, Klebsiella 1, Pseudomonas 1, Acinetobacter arinatus 5, Acinetobacter baumani 3, and Citrobacter freundii 3. Mixed flora comprised of Enterococcus faecalis 3, Enterobacter 1, Staphlococcus 1, E. coli 3, Citrobacter 1, Acinobacter baumani 1. Although with the cyclers using collapsible bags, staphylococcus was not isolated, the total incidence of infection (11/26 cases) was not decreased with the use of cyclers. We conclude that in acute intermittent peritoneal dialysis the incidence of bacterial infection is 30% with preponderance of Gram -ve over Gram +ve organisms and organism of fecal origin being commoner than those of skin origin. Use of cycler-assisted over manual PD do not improve the incidence of infection. Repositioning of the stiff catheter significantly increases the incidence of infection.

  5. Exploring the dynamics of respiratory syncytial virus (RSV) transmission in children.

    PubMed

    Hogan, Alexandra B; Glass, Kathryn; Moore, Hannah C; Anderssen, Robert S

    2016-08-01

    Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in children. Whilst highly seasonal, RSV dynamics can have either one-year (annual) or two-year (biennial) cycles. Furthermore, some countries show a 'delayed biennial' pattern, where the epidemic peak in low incidence years is delayed. We develop a compartmental model for RSV infection, driven by a seasonal forcing function, and conduct parameter space and bifurcation analyses to document parameter ranges that give rise to these different seasonal patterns. The model is sensitive to the birth rate, transmission rate, and seasonality parameters, and can replicate RSV dynamics observed in different countries. The seasonality parameter must exceed a threshold for the model to produce biennial cycles. Intermediate values of the birth rate produce the greatest delay in these biennial cycles, while the model reverts to annual cycles if the duration of immunity is too short. Finally, the existence of period doubling and period halving bifurcations suggests robust model dynamics, in agreement with the known regularity of RSV outbreaks. These findings help explain observed RSV data, such as regular biennial dynamics in Western Australia, and delayed biennial dynamics in Finland. From a public health perspective, our findings provide insight into the drivers of RSV transmission, and a foundation for exploring RSV interventions. PMID:27155294

  6. Superinfection between influenza and RSV alternating patterns in San Luis Potosí State, México.

    PubMed

    Velasco-Hernández, Jorge Xicoténcatl; Núñez-López, Mayra; Comas-García, Andreu; Cherpitel, Daniel Ernesto Noyola; Ocampo, Marcos Capistrán

    2015-01-01

    The objective of this paper is to explain through the ecological hypothesis superinfection and competitive interaction between two viral populations and niche (host) availability, the alternating patterns of Respiratory Syncytial Virus (RSV) and influenza observed in a regional hospital in San Luis Potosí State, México using a mathematical model as a methodological tool. The data analyzed consists of community-based and hospital-based Acute Respiratory Infections (ARI) consultations provided by health-care institutions reported to the State Health Service Epidemiology Department from 2003 through 2009.

  7. Superinfection between Influenza and RSV Alternating Patterns in San Luis Potosí State, México

    PubMed Central

    Velasco-Hernández, Jorge Xicoténcatl; Núñez-López, Mayra; Comas-García, Andreu; Cherpitel, Daniel Ernesto Noyola; Ocampo, Marcos Capistrán

    2015-01-01

    The objective of this paper is to explain through the ecological hypothesis superinfection and competitive interaction between two viral populations and niche (host) availability, the alternating patterns of Respiratory Syncytial Virus (RSV) and influenza observed in a regional hospital in San Luis Potosí State, México using a mathematical model as a methodological tool. The data analyzed consists of community-based and hospital-based Acute Respiratory Infections (ARI) consultations provided by health-care institutions reported to the State Health Service Epidemiology Department from 2003 through 2009. PMID:25803450

  8. Acute focal infections of dental origin.

    PubMed

    Olsen, Ingar; van Winkelhoff, Arie J

    2014-06-01

    This article describes the most important pus-producing acute oral infections (dental infections) that can spread extra-orally. Most of these infections are spread by bacteria entering the bloodstream. However, dental infections have a number of other pathways for dissemination. By forming abscesses or phlegmon they can reach facial spaces that communicate with each other and then spread downwards to the mediastinum or upwards to the brain. In such cases dental infections can become, if not properly treated, life-threatening. It seems that early diagnosis and treatment are imperative, and potentially infectious foci should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental biofilm formation are important measures to reduce the risk of these calamities. The more compromised the host defense is, the more importance should be put on these measures. Although commensal bacteria are often involved in these infections, attention should also be paid to specific periodontal pathogens, and a proper microbial diagnosis, obtained using molecular methods plus bacterial sensitivity testing, can provide the patient with optimal care. Drainage of pus must be established where possible so that the optimal effect of antibiotics can be achieved. Penicillin is still the drug of first choice in settings where suspicion of methicillin-resistant Staphylococcus aureus is low.

  9. Acute focal infections of dental origin.

    PubMed

    Olsen, Ingar; van Winkelhoff, Arie J

    2014-06-01

    This article describes the most important pus-producing acute oral infections (dental infections) that can spread extra-orally. Most of these infections are spread by bacteria entering the bloodstream. However, dental infections have a number of other pathways for dissemination. By forming abscesses or phlegmon they can reach facial spaces that communicate with each other and then spread downwards to the mediastinum or upwards to the brain. In such cases dental infections can become, if not properly treated, life-threatening. It seems that early diagnosis and treatment are imperative, and potentially infectious foci should be traced and eliminated. Dental hygiene and prophylaxis to prevent dental biofilm formation are important measures to reduce the risk of these calamities. The more compromised the host defense is, the more importance should be put on these measures. Although commensal bacteria are often involved in these infections, attention should also be paid to specific periodontal pathogens, and a proper microbial diagnosis, obtained using molecular methods plus bacterial sensitivity testing, can provide the patient with optimal care. Drainage of pus must be established where possible so that the optimal effect of antibiotics can be achieved. Penicillin is still the drug of first choice in settings where suspicion of methicillin-resistant Staphylococcus aureus is low. PMID:24738592

  10. Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults

    PubMed Central

    Green, C A; Scarselli, E; Voysey, M; Capone, S; Vitelli, A; Nicosia, A; Cortese, R; Thompson, A J; Sande, C S; de Lara, Catherine; Klenerman, P; Pollard, A J

    2015-01-01

    Introduction Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults. Methods and analysis Heterologous and homologous ‘prime’/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18–50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60–75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK. Ethics and dissemination RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere

  11. Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells

    PubMed Central

    Guo, Xuancheng; Liu, Taixiang; Shi, Hengfei; Wang, Jingjing; Ji, Ping; Wang, Hongwei; Hou, Yayi; Tan, Ren Xiang

    2015-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract viral infection in infants, causing bronchiolitis and pneumonia. The host antiviral response to RSV acts via retinoic acid-inducible gene I (RIG-I). We show here that RSV infection upregulates major histocompatibility complex class I (MHC-I) expression through the induction of NLRC5, a NOD-like, CARD domain-containing intracellular protein that has recently been identified as a class I MHC transactivator (CITA). RSV infection of A549 cells promotes upregulation of NLRC5 via beta interferon (IFN-β) production, since the NLRC5-inducing activity in a conditioned medium from RSV-infected A549 cells was removed by antibody to IFN-β, but not by antibody to IFN-γ. RSV infection resulted in RIG-I upregulation and induction of NLRC5 and MHC-I. Suppression of RIG-I induction significantly blocked NLRC5, as well as MHC-I, upregulation and diminished IRF3 activation. Importantly, Vero cells deficient in interferon production still upregulated MHC-I following introduction of the RSV genome by infection or transfection, further supporting a key role for RIG-I. A model is therefore proposed in which the host upregulates MHC-I expression during RSV infection directly via the induction of RIG-I and NLRC5 expression. Since elevated expression of MHC-I molecules can sensitize host cells to T lymphocyte-mediated cytotoxicity or immunopathologic damage, the results have significant implications for the modification of immunity in RSV disease. IMPORTANCE Human respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants and young children worldwide. Infection early in life is linked to persistent wheezing and allergic asthma in later life, possibly related to upregulation of major histocompatibility class I (MHC-I) on the cell surface, which facilitates cytotoxic T cell activation and antiviral immunity. Here, we show that RSV infection of lung epithelial

  12. Central nervous system alterations caused by infection with the human respiratory syncytial virus.

    PubMed

    Bohmwald, Karen; Espinoza, Janyra A; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2014-11-01

    Worldwide, the human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization because of acute respiratory tract infections, including severe bronchiolitis and pneumonia. Despite intense research, to date there is neither vaccine nor treatment available to control hRSV disease burden globally. After infection, an incubation period of 3-5 days is usually followed by symptoms, such as cough and low-grade fever. However, hRSV infection can also produce a larger variety of symptoms, some of which relate to the individual's age at infection. Indeed, infants can display severe symptoms, such as dyspnea and chest wall retractions. Upon examination, crackles and wheezes are also common features that suggest infection by hRSV. Additionally, infection in infants younger than 1 year is associated with several non-specific symptoms, such as failure to thrive, periodic breathing or apnea, and feeding difficulties that usually require hospitalization. Recently, neurological symptoms have also been associated with hRSV respiratory infection and include seizures, central apnea, lethargy, feeding or swallowing difficulties, abnormalities in muscle tone, strabismus, abnormalities in the CSF, and encephalopathy. Here, we discuss recent findings linking the neurological, extrapulmonary effects of hRSV with infection and functional impairment of the CNS.

  13. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovi...

  14. Suppression of NS3 and MP Is Important for the Stable Inheritance of RNAi-Mediated Rice Stripe Virus (RSV) Resistance Obtained by Targeting the Fully Complementary RSV-CP Gene

    PubMed Central

    Park, Hyang-Mi; Choi, Man-Soo; Kwak, Do-Yeon; Lee, Bong-Choon; Lee, Jong-Hee; Kim, Myeong-Ki; Kim, Yeon-Gyu; Shin, Dong-Bum; Park, Soon-Ki; Kim, Yul-Ho

    2012-01-01

    Rice stripe virus (RSV) is a viral disease that seriously impacts rice production in East Asia, most notably in Korea, China, and Japan. Highly RSV-resistant transgenic japonica rice plants were generated using a dsRNAi construct designed to silence the entire sequence region of the RSV-CP gene. Transgenic rice plants were inoculated with a population of viruliferous insects, small brown planthoppers (SBPH), and their resistance was evaluated using ELISA and an infection rate assay. A correlation between the expression of the RSV-CP homologous small RNAs and the RSV resistance of the transgenic rice lines was discovered. These plants were also analyzed by comparing the expression pattern of invading viral genes, small RNA production and the stable transmission of the RSV resistance trait to the T3 generation. Furthermore, the agronomic trait was stably transmitted to the T4 generation of transgenic plants. PMID:22134721

  15. Thrombosis associated with acute cytomegalovirus infection: a narrative review

    PubMed Central

    Sherman, Shany; Eytan, Ori

    2014-01-01

    Thrombosis associated with acute cytomegalovirus infection has been reported many times in the literature since the mid 1980s – mainly in case reports and in small case series, but also in four controlled studies. Still, many physicians are unaware of this association although acute cytomegalovirus infection diagnosis in a thrombosis patient may warrant antiviral therapy and may affect anticoagulation therapy duration. Accordingly, the clinical characteristics of patients with thrombosis and acute cytomegalovirus infection are reviewed, and the current knowledge concerning this unique association is presented herein. We believe it is time to add acute cytomegalovirus infection to the list of thrombosis triggers. PMID:25624857

  16. Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein

    PubMed Central

    Tang, Aimin; Callahan, Cheryl; Pristatsky, Pavlo; Swoyer, Ryan; Cejas, Pedro; Nahas, Debbie; Galli, Jennifer; Cosmi, Scott; DiStefano, Daniel; Hoang, Van M.; Bett, Andrew; Casimiro, Danilo

    2016-01-01

    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis® (palivizumab) is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD® phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs) against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction. PMID:27258388

  17. Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein.

    PubMed

    Chen, Zhifeng; Zhang, Lan; Tang, Aimin; Callahan, Cheryl; Pristatsky, Pavlo; Swoyer, Ryan; Cejas, Pedro; Nahas, Debbie; Galli, Jennifer; Cosmi, Scott; DiStefano, Daniel; Hoang, Van M; Bett, Andrew; Casimiro, Danilo; Vora, Kalpit A

    2016-01-01

    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis® (palivizumab) is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD® phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs) against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction. PMID:27258388

  18. Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels

    PubMed Central

    Fuentes, Sandra; Coyle, Elizabeth M.; Golding, Hana

    2015-01-01

    ABSTRACT New efforts are under way to develop a vaccine against respiratory syncytial virus (RSV) that will provide protective immunity without the potential for vaccine-associated disease enhancement such as that observed in infants following vaccination with formalin-inactivated RSV vaccine. In addition to the F fusion protein, the G attachment surface protein is a target for neutralizing antibodies and thus represents an important vaccine candidate. However, glycosylated G protein expressed in mammalian cells has been shown to induce pulmonary eosinophilia upon RSV infection in a mouse model. In the current study, we evaluated in parallel the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain (amino acids 67 to 298) expressed in Escherichia coli (REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model. Vaccination with REG generated neutralizing antibodies against RSV A2 in 7/11 BALB/c mice, while RMG did not elicit neutralizing antibodies. Total serum binding antibodies against the recombinant proteins (both REG and RMG) were measured by surface plasmon resonance (SPR) and were found to be >10-fold higher for REG- than for RMG-vaccinated animals. Reduction of lung viral loads to undetectable levels after homologous (RSV-A2) and heterologous (RSV-B1) viral challenge was observed in 7/8 animals vaccinated with REG but not in RMG-vaccinated animals. Furthermore, enhanced lung pathology and elevated Th2 cytokines/chemokines were observed exclusively in animals vaccinated with RMG (but not in those vaccinated with REG or phosphate-buffered saline [PBS]) after homologous or heterologous RSV challenge. This study suggests that bacterially produced unglycosylated G protein could be developed alone or as a component of a protective vaccine against RSV disease. IMPORTANCE New efforts are under way to develop vaccines against RSV that will provide protective immunity without the potential

  19. Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

    PubMed Central

    Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

    2015-01-01

    Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

  20. Challenges and opportunities in RSV vaccine development: Meeting report from FDA/NIH workshop.

    PubMed

    Roberts, Jeffrey N; Graham, Barney S; Karron, Ruth A; Munoz, Flor M; Falsey, Ann R; Anderson, Larry J; Marshall, V; Kim, Sonnie; Beeler, Judy A

    2016-09-22

    Respiratory syncytial virus (RSV) is the most common cause of serious acute lower respiratory illness in infants and young children and a significant cause of disease burden in the elderly and immunocompromised. There are no licensed RSV vaccines to address this significant public health need. While advances in vaccine technologies have led to a recent resurgence in RSV vaccine development, the immune correlates of protection against RSV and the immunology of vaccine-associated enhanced respiratory disease (ERD) remain poorly understood. FDA's Center for Biologics Evaluation and Research (CBER) and NIH's National Institute of Allergy and Infectious Diseases (NIAID) organized and co-sponsored an RSV Vaccines Workshop in Bethesda, Maryland on June 1 and 2, 2015. The goal of the conference was to convene scientists, regulators, and industry stakeholders to discuss approaches to RSV vaccine development within the context of three target populations - infants and children, pregnant women, and individuals >60years of age. The agenda included topics related to RSV vaccine development in general, as well as considerations specific to each target population, such as clinical and serological endpoints. The meeting focused on vaccine development for high income countries (HIC), because issues relevant to vaccine development for low and middle income countries (LMIC) have been discussed in other forums. This manuscript summarizes the discussion of clinical, scientific, and regulatory perspectives, research gaps, and lessons learned. PMID:27566900

  1. Challenges and opportunities in RSV vaccine development: Meeting report from FDA/NIH workshop.

    PubMed

    Roberts, Jeffrey N; Graham, Barney S; Karron, Ruth A; Munoz, Flor M; Falsey, Ann R; Anderson, Larry J; Marshall, V; Kim, Sonnie; Beeler, Judy A

    2016-09-22

    Respiratory syncytial virus (RSV) is the most common cause of serious acute lower respiratory illness in infants and young children and a significant cause of disease burden in the elderly and immunocompromised. There are no licensed RSV vaccines to address this significant public health need. While advances in vaccine technologies have led to a recent resurgence in RSV vaccine development, the immune correlates of protection against RSV and the immunology of vaccine-associated enhanced respiratory disease (ERD) remain poorly understood. FDA's Center for Biologics Evaluation and Research (CBER) and NIH's National Institute of Allergy and Infectious Diseases (NIAID) organized and co-sponsored an RSV Vaccines Workshop in Bethesda, Maryland on June 1 and 2, 2015. The goal of the conference was to convene scientists, regulators, and industry stakeholders to discuss approaches to RSV vaccine development within the context of three target populations - infants and children, pregnant women, and individuals >60years of age. The agenda included topics related to RSV vaccine development in general, as well as considerations specific to each target population, such as clinical and serological endpoints. The meeting focused on vaccine development for high income countries (HIC), because issues relevant to vaccine development for low and middle income countries (LMIC) have been discussed in other forums. This manuscript summarizes the discussion of clinical, scientific, and regulatory perspectives, research gaps, and lessons learned.

  2. Respiratory syncytial virus infection: denominator-based studies in Indonesia, Mozambique, Nigeria and South Africa.

    PubMed Central

    Robertson, Susan E.; Roca, Anna; Alonso, Pedro; Simoes, Eric A. F.; Kartasasmita, Cissy B.; Olaleye, David O.; Odaibo, Georgina N.; Collinson, Mark; Venter, Marietjie; Zhu, Yuwei; Wright, Peter F.

    2004-01-01

    OBJECTIVE: To assess the burden of respiratory syncytial virus (RSV)-associated lower respiratory infections (LRI) in children in four developing countries. METHODS: A WHO protocol for prospective population-based surveillance of acute respiratory infections in children aged less than 5 years was used at sites in Indonesia, Mozambique, Nigeria and South Africa. RSV antigen was identified by enzyme-linked immunosorbent assay performed on nasopharyngeal specimens from children meeting clinical case definitions. FINDINGS: Among children aged < 5 years, the incidence of RSV-associated LRI per 1000 child-years was 34 in Indonesia and 94 in Nigeria. The incidence of RSV-associated severe LRI per 1000 child-years was 5 in Mozambique, 10 in Indonesia, and 9 in South Africa. At all study sites, the majority of RSV cases occurred in infants. CONCLUSION: These studies demonstrate that RSV contributes to a substantial but quite variable burden of LRI in children aged < 5 years in four developing countries. The possible explanations for this variation include social factors, such as family size and patterns of seeking health care; the proportion of children infected by human immunodeficiency syndrome (HIV); and differences in clinical definitions used for obtaining samples. The age distribution of cases indicates the need for an RSV vaccine that can protect children early in life. PMID:15654405

  3. Acute neuromuscular weakness associated with dengue infection

    PubMed Central

    Hira, Harmanjit Singh; Kaur, Amandeep; Shukla, Anuj

    2012-01-01

    Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK) were tested. In addition, two patients underwent nerve conduction velocity (NCV) test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2nd to 4th day of illness in 11 of 12 patients. In one patient, it developed on 10th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients. PMID:22346188

  4. In silico structure-based design and synthesis of novel anti-RSV compounds.

    PubMed

    Cancellieri, Michela; Bassetto, Marcella; Widjaja, Ivy; van Kuppeveld, Frank; de Haan, Cornelis A M; Brancale, Andrea

    2015-10-01

    Respiratory syncytial virus (RSV) is the major cause for respiratory tract disease in infants and young children. Currently, no licensed vaccine or a selective antiviral drug against RSV infections are available. Here, we describe a structure-based drug design approach that led to the synthesis of a novel series of zinc-ejecting compounds active against RSV replication. 30 compounds, sharing a common dithiocarbamate moiety, were designed and prepared to target the zinc finger motif of the M2-1 protein. A library of ∼ 12,000 small fragments was docked to explore the area surrounding the zinc ion. Among these, seven ligands were selected and used for the preparation of the new derivatives. The results reported here may help the development of a lead compound for the treatment of RSV infections. PMID:26259810

  5. Programmatic Implications of Acute and Early HIV Infection.

    PubMed

    Suthar, Amitabh B; Granich, Reuben M; Kato, Masaya; Nsanzimana, Sabin; Montaner, Julio S G; Williams, Brian G

    2015-11-01

    Human immunodeficiency virus (HIV) infection includes acute, early, chronic, and late stages. Acute HIV infection lasts approximately 3 weeks and early HIV infection, which includes acute HIV infection, lasts approximately 7 weeks. Many testing and blood screening algorithms detect HIV antibodies about 3 weeks after HIV infection. Incidence estimates are based on results of modeling, cohort studies, surveillance, and/or assays. Viral load is the key modifiable risk factor for HIV transmission and peaks during acute and early HIV infection. Empirical evidence characterizing the impact of acute and early HIV infection on the spread of the HIV epidemic are limited. Time trends of HIV prevalence collected from concentrated and generalized epidemics suggest that acute and early HIV infection may have a limited role in population HIV transmission. Collectively, these data suggest that acute and early HIV infection is relatively short and does not currently require fundamentally different programmatic approaches to manage the HIV/AIDS epidemic in most settings. Research and surveillance will inform which epidemic contexts and phases may require tailored strategies for these stages of HIV infection.

  6. Dose Determination for Acute Salmonella Infection in Pigs

    PubMed Central

    Loynachan, A. T.; Harris, D. L.

    2005-01-01

    Pigs were exposed to various levels of Salmonella enterica subsp. enterica serovar Typhimurium by either intranasal inoculation or by subjecting them to a contaminated environment. More than 103 salmonellae were required to induce acute Salmonella infection. These results indicate that intervention against acute Salmonella infection in lairage may be more readily achieved than previously thought. PMID:15870368

  7. RSV neutralization by palivizumab, but not by monoclonal antibodies targeting other epitopes, is augmented by Fc gamma receptors.

    PubMed

    van Mechelen, Lenny; Luytjes, Willem; de Haan, Cornelis A M; Wicht, Oliver

    2016-08-01

    Palivizumab efficiently blocks respiratory syncytial virus (RSV) infection in vitro. However, virus neutralization assays generally omit Fc region-mediated effects. We investigated the neutralization activity of RSV-specific monoclonal antibodies on cells with Fc receptors. Subneutralizing concentrations of antibodies resulted in antibody-dependent enhancement of RSV infection in monocytic cells. Contrary to antibodies targeting other epitopes, the neutralization by palivizumab was augmented in cells with Fc receptors. This unrecognized characteristic of palivizumab may be relevant for its performance in vivo.

  8. RSV neutralization by palivizumab, but not by monoclonal antibodies targeting other epitopes, is augmented by Fc gamma receptors.

    PubMed

    van Mechelen, Lenny; Luytjes, Willem; de Haan, Cornelis A M; Wicht, Oliver

    2016-08-01

    Palivizumab efficiently blocks respiratory syncytial virus (RSV) infection in vitro. However, virus neutralization assays generally omit Fc region-mediated effects. We investigated the neutralization activity of RSV-specific monoclonal antibodies on cells with Fc receptors. Subneutralizing concentrations of antibodies resulted in antibody-dependent enhancement of RSV infection in monocytic cells. Contrary to antibodies targeting other epitopes, the neutralization by palivizumab was augmented in cells with Fc receptors. This unrecognized characteristic of palivizumab may be relevant for its performance in vivo. PMID:27185625

  9. Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

    PubMed

    Ananworanich, Jintanat; Datta, Anandita A; Fletcher, James Lk; Townamchai, Natavudh; Chomchey, Nitiya; Kroon, Eugene; Sereti, Irini; Valcour, Victor; Kim, Jerome H

    2014-01-01

    We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion.

  10. Acute pancreatitis, ascites, and acute renal failure in Plasmodium vivax malaria infection, a rare complication.

    PubMed

    Lakhotia, Manoj; Pahadiya, Hans Raj; Kumar, Harish; Singh, Jagdish; Sangappa, Jainapur Ravi; Choudhary, Prakash Kumar

    2015-01-01

    A 22-year-old male presented with 6 days history of intermittent fever with chills, 2 days history of upper abdomen pain, distension of abdomen, and decreased urine output. He was diagnosed to have Plasmodium vivax malaria, acute pancreatitis, ascites, and acute renal failure. These constellations of complications in P. vivax infection have never been reported in the past. The patient responded to intravenous chloroquine and supportive treatment. For renal failure, he required hemodialysis. Acute pancreatitis, ascites, and acute renal failure form an unusual combination in P. vivax infection. PMID:26629455

  11. Acute hemiplegia with lacunar infarct after varicella infection in childhood.

    PubMed

    Eda, I; Takashima, S; Takeshita, K

    1983-01-01

    We report 4 cases of acute hemiplegia and a small low-density lesion on computerized tomography (CT) after varicella infection. In 3 of them, CT in the acute hemiplegic stage, and later, reveals the development of lacunar infarct around the internal capsule. Focal low density may be caused by occlusive vascular lesions of the penetrating arteries. Varicella infection may play an important role as one of the causes of acute hemiplegia in childhood producing lacunar infarct, as well as delayed hemiplegia, reported previously in herpes zoster ophthalmicus. PMID:6660422

  12. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2016-10-14

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  13. Multicenter evaluation of BD Veritor System and RSV K-SeT for rapid detection of respiratory syncytial virus in a diagnostic laboratory setting.

    PubMed

    Jonckheere, Stijn; Verfaillie, Charlotte; Boel, An; Van Vaerenbergh, Kristien; Vanlaere, Elke; Vankeerberghen, Anne; De Beenhouwer, Hans

    2015-09-01

    The recently introduced BD Veritor System RSV laboratory kit (Becton Dickinson, Sparks, MD, USA) with automatic reading was evaluated and compared with the RSV K-SeT (Coris BioConcept, Gembloux, Belgium) for the detection of respiratory syncytial virus (RSV) using 248 nasopharyngeal aspirates of children younger than 6 years old with respiratory tract infection. Compared to reverse transcriptase polymerase chain reaction as gold standard, both tests had an identical sensitivity of 78.1% and a specificity of 96.8% and 95.8% for the BD Veritor System and RSV K-SeT, respectively. Both antigen tests can be used to reliably confirm RSV in young children. However, a negative result does not definitively exclude the presence of RSV.

  14. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  15. Respiratory Syncytial Virus (RSV): Neutralizing Antibody, a Correlate of Immune Protection.

    PubMed

    Piedra, Pedro A; Hause, Anne M; Aideyan, Letisha

    2016-01-01

    Assays that measure RSV-specific neutralizing antibody activity are very useful for evaluating vaccine candidates, performing seroprevalence studies, and detecting infection. Neutralizing antibody activity is normally measured by a plaque reduction neutralization assay or by a microneutralization assay with or without complement. These assays measure the functional capacity of serum (or other fluids) to neutralize virus infectivity in cells as compared to ELISA assays that only measure the binding capacity against an antigen. This chapter discusses important elements in standardization of the RSV-specific microneutralization assay for use in the laboratory. PMID:27464689

  16. Roflumilast Inhibits Respiratory Syncytial Virus Infection in Human Differentiated Bronchial Epithelial Cells

    PubMed Central

    Mata, Manuel; Martinez, Isidoro; Melero, Jose A.; Tenor, Herman; Cortijo, Julio

    2013-01-01

    Respiratory syncytial virus (RSV) causes acute exacerbations in COPD and asthma. RSV infects bronchial epithelial cells (HBE) that trigger RSV associated lung pathology. This study explores whether the phosphodiesterase 4 (PDE4) inhibitor Roflumilast N-oxide (RNO), alters RSV infection of well-differentiated HBE (WD-HBE) in vitro. WD-HBE were RSV infected in the presence or absence of RNO (0.1-100 nM). Viral infection (staining of F and G proteins, nucleoprotein RNA level), mRNA of ICAM-1, ciliated cell markers (digital high speed videomicroscopy, β-tubulin immunofluorescence, Foxj1 and Dnai2 mRNA), Goblet cells (PAS), mRNA of MUC5AC and CLCA1, mRNA and protein level of IL-13, IL-6, IL-8, TNFα, formation of H2O2 and the anti-oxidative armamentarium (mRNA of Nrf2, HO-1, GPx; total antioxidant capacity (TAC) were measured at day 10 or 15 post infection. RNO inhibited RSV infection of WD-HBE, prevented the loss of ciliated cells and markers, reduced the increase of MUC5AC and CLCA1 and inhibited the increase of IL-13, IL-6, IL-8, TNFα and ICAM-1. Additionally RNO reversed the reduction of Nrf2, HO-1 and GPx mRNA levels and consequently restored the TAC and reduced the H2O2 formation. RNO inhibits RSV infection of WD-HBE cultures and mitigates the cytopathological changes associated to this virus. PMID:23936072

  17. Clinical role of respiratory virus infection in acute otitis media.

    PubMed

    Arola, M; Ruuskanen, O; Ziegler, T; Mertsola, J; Näntö-Salonen, K; Putto-Laurila, A; Viljanen, M K; Halonen, P

    1990-12-01

    The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media. Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis. Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected. Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently. The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media. Ninety-four percent of the children had symptoms of upper respiratory tract infection. Fever was reported in 55% and earache in 47% of cases. Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients. No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis. Most patients respond well to antimicrobial therapy despite the coexisting viral infection. If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients.

  18. Evaluation of Four Commercial Multiplex Molecular Tests for the Diagnosis of Acute Respiratory Infections

    PubMed Central

    Salez, Nicolas; Vabret, Astrid; Leruez-Ville, Marianne; Andreoletti, Laurent; Carrat, Fabrice; Renois, Fanny; de Lamballerie, Xavier

    2015-01-01

    Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden’s index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86–1.00; PPV:78.95–100.00; Sp:97.32–100.00] & B [YI:0.44–1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50–0.99; PPV:85.71–100.00; Sp:99.38–100.00], hMPV [YI:0.71–1.00; PPV:83.33–100.00; Sp:99.37–100.00], EV/hRV [YI:0.62–0.82; PPV:93.33–100.00; Sp:94.48–100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20–0.80; PPV:57.14–100.00; Sp:98.14–100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections. PMID:26107509

  19. Recombinant Bovine/Human Parainfluenza Virus Type 3 (B/HPIV3) Expressing the Respiratory Syncytial Virus (RSV) G and F Proteins Can Be Used To Achieve Simultaneous Mucosal Immunization against RSV and HPIV3

    PubMed Central

    Schmidt, Alexander C.; McAuliffe, Josephine M.; Murphy, Brian R.; Collins, Peter L.

    2001-01-01

    Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3. PMID:11312329

  20. RSV Growth and Quantification by Microtitration and qRT-PCR Assays.

    PubMed

    Caidi, Hayat; Harcourt, Jennifer L; Haynes, Lia M

    2016-01-01

    Defective interfering viral particles have been reported as important determinants of the course of viral infection, and they can markedly temper the virulence of the infection. Here, we describe a simple method, based on limiting dilution, for the removal of defective interfering particles from RSV. This method results in a high-titer viral preparation from both HEp-2 and Vero cell lines. We evaluated two concentrations of sucrose to stabilize the virus preparation, and demonstrate that RSV is stable when prepared and stored in 25 % sucrose at -152 °C. In addition, this chapter describes some commonly used methods of RSV titration, detection using microtitration and quantitative real-time RT-PCR, and the use of immunostaining for antigenic characterization.

  1. RSV Growth and Quantification by Microtitration and qRT-PCR Assays.

    PubMed

    Caidi, Hayat; Harcourt, Jennifer L; Haynes, Lia M

    2016-01-01

    Defective interfering viral particles have been reported as important determinants of the course of viral infection, and they can markedly temper the virulence of the infection. Here, we describe a simple method, based on limiting dilution, for the removal of defective interfering particles from RSV. This method results in a high-titer viral preparation from both HEp-2 and Vero cell lines. We evaluated two concentrations of sucrose to stabilize the virus preparation, and demonstrate that RSV is stable when prepared and stored in 25 % sucrose at -152 °C. In addition, this chapter describes some commonly used methods of RSV titration, detection using microtitration and quantitative real-time RT-PCR, and the use of immunostaining for antigenic characterization. PMID:27464684

  2. Influenza and RSV make a modest contribution to invasive pneumococcal disease incidence in the UK

    PubMed Central

    Nicoli, Emily J.; Trotter, Caroline L.; Turner, Katherine M.E.; Colijn, Caroline; Waight, Pauline; Miller, Elizabeth

    2013-01-01

    Summary Objectives The common seasonality of incidence of invasive pneumococcal disease (IPD) and viral respiratory infections has long been recognized, however, the extent to which this affects the association between the pathogens is unknown. We have analysed weekly surveillance data of IPD, influenza and respiratory syncytial virus (RSV), using ambient temperature and hours of sunshine as measures of seasonality. Methods Reported cases of influenza, IPD and RSV, were collected in England and Wales, from week 1 (January) 1996 to week 23 (June) 2009. The associations between IPD and respiratory viral infections were analysed using several statistical methods, including correlation coefficients and both additive and multiplicative regression models. Results 6–7.5% of cases of IPD are attributable to influenza and 3–4% attributable to RSV. Correlation coefficients reported considerably stronger associations between IPD and the viral infections compared to regression models. Conclusions A small but potentially important percentage of IPD may be attributable to influenza and RSV when adjusted for seasonality by temperature. Jointly these viral infections may lead to over 10% of IPD cases. Therefore, prevention of viral respiratory infections may offer some additional benefit in reducing invasive pneumococcal infections. PMID:23473714

  3. A Chimeric Pneumovirus Fusion Protein Carrying Neutralizing Epitopes of Both MPV and RSV.

    PubMed

    Wen, Xiaolin; Pickens, Jennifer; Mousa, Jarrod J; Leser, George P; Lamb, Robert A; Crowe, James E; Jardetzky, Theodore S

    2016-01-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are paramyxoviruses that are responsible for substantial human health burden, particularly in children and the elderly. The fusion (F) glycoproteins are major targets of the neutralizing antibody response and studies have mapped dominant antigenic sites in F. Here we grafted a major neutralizing site of RSV F, recognized by the prophylactic monoclonal antibody palivizumab, onto HMPV F, generating a chimeric protein displaying epitopes of both viruses. We demonstrate that the resulting chimeric protein (RPM-1) is recognized by both anti-RSV and anti-HMPV F neutralizing antibodies indicating that it can be used to map the epitope specificity of antibodies raised against both viruses. Mice immunized with the RPM-1 chimeric antigen generate robust neutralizing antibody responses to MPV but weak or no cross-reactive recognition of RSV F, suggesting that grafting of the single palivizumab epitope stimulates a comparatively limited antibody response. The RPM-1 protein provides a new tool for characterizing the immune responses resulting from RSV and HMPV infections and provides insights into the requirements for developing a chimeric subunit vaccine that could induce robust and balanced immunity to both virus infections. PMID:27224013

  4. A Chimeric Pneumovirus Fusion Protein Carrying Neutralizing Epitopes of Both MPV and RSV

    PubMed Central

    Wen, Xiaolin; Pickens, Jennifer; Mousa, Jarrod J.; Leser, George P.; Lamb, Robert A.; Crowe, James E.; Jardetzky, Theodore S.

    2016-01-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are paramyxoviruses that are responsible for substantial human health burden, particularly in children and the elderly. The fusion (F) glycoproteins are major targets of the neutralizing antibody response and studies have mapped dominant antigenic sites in F. Here we grafted a major neutralizing site of RSV F, recognized by the prophylactic monoclonal antibody palivizumab, onto HMPV F, generating a chimeric protein displaying epitopes of both viruses. We demonstrate that the resulting chimeric protein (RPM-1) is recognized by both anti-RSV and anti-HMPV F neutralizing antibodies indicating that it can be used to map the epitope specificity of antibodies raised against both viruses. Mice immunized with the RPM-1 chimeric antigen generate robust neutralizing antibody responses to MPV but weak or no cross-reactive recognition of RSV F, suggesting that grafting of the single palivizumab epitope stimulates a comparatively limited antibody response. The RPM-1 protein provides a new tool for characterizing the immune responses resulting from RSV and HMPV infections and provides insights into the requirements for developing a chimeric subunit vaccine that could induce robust and balanced immunity to both virus infections. PMID:27224013

  5. Viral antibodies in the CSF after acute CNS infections.

    PubMed

    Cappel, R; Thiry, L; Clinet, G

    1975-09-01

    Viral antibodies were measured in the cerebrospinal fluid (CSF) and serum from 25 patients having acute viral central nervous system (CNS) infections, and from 39 control patients. The results, collected two weeks after the clinical onset, revealed the presence of antibodies in nine of 13 (69%) CSF specimens from patients suffering from encephalitis of myelitis, and in only one of nine (11%) of the CSF samples of those presenting a viral meningitis infection. This difference was statistically significant and suggests that the titration of viral antibodies in the CSF can be helpful in establishing the diagnosis of viral CNS infection. Our data also suggest that localized production of antibodies occurs during the course of acute CNS infections, and that the respiratory syncytial virus can be associated with CNS infections in man.

  6. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection

    PubMed Central

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  7. Acute Myopericarditis Likely Secondary to Disseminated Gonococcal Infection.

    PubMed

    Bunker, Daniel; Kerr, Leslie Dubin

    2015-01-01

    Disseminated gonococcal infection (DGI) is a rare complication of primary infection with Neisseria gonorrhoeae. Cardiac involvement in this condition is rare, and is usually limited to endocarditis. However, there are a number of older reports suggestive of direct myocardial involvement. We report a case of a 38-year-old male with HIV who presented with chest pain, pharyngitis, tenosynovitis, and purpuric skin lesions. Transthoracic echocardiogram showed acute biventricular dysfunction. Skin biopsy showed diplococci consistent with disseminated gonococcal infection, and treatment with ceftriaxone improved his symptoms and ejection fraction. Though gonococcal infection was never proven with culture or nucleic acid amplification testing, the clinical picture and histologic findings were highly suggestive of DGI. Clinicians should consider disseminated gonococcal infection when a patient presents with acute myocarditis, especially if there are concurrent skin and joint lesions. PMID:26246922

  8. Role of dystrophin in acute Trypanosoma cruzi infection.

    PubMed

    Malvestio, Lygia M; Celes, Mara R N; Milanezi, Cristiane; Silva, João S; Jelicks, Linda A; Tanowitz, Herbert B; Rossi, Marcos A; Prado, Cibele M

    2014-09-01

    Previous studies have demonstrated loss/reduction of dystrophin in cardiomyocytes in both acute and chronic stages of experimental Trypanosoma cruzi (T. cruzi) infection in mice. The mechanisms responsible for dystrophin disruption in the hearts of mice acutely infected with T. cruzi are not completely understood. The present in vivo and in vitro studies were undertaken to evaluate the role of inflammation in dystrophin disruption and its correlation with the high mortality rate during acute infection. C57BL/6 mice were infected with T. cruzi and killed 14, 20 and 26 days post infection (dpi). The intensity of inflammation, cardiac expression of dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability were evaluated. Cultured neonatal murine cardiomyocytes were incubated with serum, collected at the peak of cytokine production and free of parasites, from T. cruzi-infected mice and dystrophin, calpain-1, and NF-κB expression analyzed. Dystrophin disruption occurs at the peak of mortality and inflammation and is associated with increased expression of calpain-1, TNF-α, NF-κB, and increased sarcolemmal permeability in the heart of T. cruzi-infected mice at 20 dpi confirmed by in vitro studies. The peak of mortality occurred only when significant loss of dystrophin in the hearts of infected animals occurred, highlighting the correlation between inflammation, dystrophin loss and mortality.

  9. Detection of RSV Antibodies in Human Plasma by Enzyme Immunoassays.

    PubMed

    Jadhao, Samadhan J; Anderson, Larry J

    2016-01-01

    Enzyme immunoassays (EIAs) to detect and quantify antibodies against respiratory syncytial virus (RSV) and RSV proteins in human plasma or sera are described. The first EIA uses RSV lysate antigens produced in HEp-2 cell line. The second EIA uses RSV F or G gene-expressed antigen in HEp-2 cells. The third EIA uses 30-amino acid synthetic peptides from central conserved region of G protein of RSV A2 or RSV B1 virus and a peptide from the SARS CoV nucleoprotein as a negative control peptide. All three EIAs have been evaluated for detecting and quantifying the respective antibodies in human sera or plasma. PMID:27464686

  10. Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells

    PubMed Central

    Céspedes, Pablo F.; Bueno, Susan M.; Ramírez, Bruno A.; Gomez, Roberto S.; Riquelme, Sebastián A.; Palavecino, Christian E.; Mackern-Oberti, Juan Pablo; Mora, Jorge E.; Depoil, David; Sacristán, Catarina; Cammer, Michael; Creneguy, Alison; Nguyen, Tuan H.; Riedel, Claudia A.; Dustin, Michael L.; Kalergis, Alexis M.

    2014-01-01

    Human respiratory syncytial virus (hRSV) is the leading cause of bronchiolitis and pneumonia in young children worldwide. The recurrent hRSV outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. Although several mouse- and human cell-based studies have shown that hRSV infection prevents naïve T-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains unknown. Here, we show that the hRSV nucleoprotein (N) could be at least partially responsible for inhibiting T-cell activation during infection by this virus. Early after infection, the N protein was expressed on the surface of epithelial and dendritic cells, after interacting with trans-Golgi and lysosomal compartments. Further, experiments on supported lipid bilayers loaded with peptide-MHC (pMHC) complexes showed that surface-anchored N protein prevented immunological synapse assembly by naive CD4+ T cells and, to a lesser extent, by antigen-experienced T-cell blasts. Synapse assembly inhibition was in part due to reduced T-cell receptor (TCR) signaling and pMHC clustering at the T-cell−bilayer interface, suggesting that N protein interferes with pMHC−TCR interactions. Moreover, N protein colocalized with the TCR independently of pMHC, consistent with a possible interaction with TCR complex components. Based on these data, we conclude that hRSV N protein expression at the surface of infected cells inhibits T-cell activation. Our study defines this protein as a major virulence factor that contributes to impairing acquired immunity and enhances susceptibility to reinfection by hRSV. PMID:25056968

  11. Differential Diagnosis and Treatment Proposal for Acute Endodontic Infection.

    PubMed

    Keine, Kátia Cristina; Kuga, Milton Carlos; Pereira, Kamila Figueiredo; Diniz, Ana Carolina Soares; Tonetto, Mateus Rodrigues; Galoza, Marina Oliveira Gonçalves; Magro, Miriam Graziele; de Barros, Yolanda Benedita Abadia Martins; Bandéca, Matheus Coelho; de Andrade, Marcelo Ferrarezi

    2015-12-01

    The objective of this study was to describe the main lesions that simulate clinically and propose a treatment protocol for acute endodontic infection. Signs and clinical symptoms of periodontal abscess, gingival abscess, odontoma, herpes simplex, pericoronitis, acute pulpitis and necrotizing ulcerative gingivitis/periodontitis (NUG/NUP) were described and compared with acute endodontic infections. A treatment protocol was described by optimizing the procedures in access cavity, microbial decontamination and detoxification of the root canal, apical debridement, intracanal and systemic medication and surgical drainage procedures. The convenience of the use of 5.25% sodium hypochlorite, root canal instrumentation using a crown-down technique, intracanal medication with 2% chlorhexidine or triple antibiotic paste and the convenience of the use of antibiotics, analgesics, and surgical drainage to solve cases of acute dentoalveolar abscess was discussed.

  12. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  13. Imaging in acute renal infection in children

    SciTech Connect

    Sty, J.R.; Wells, R.G.; Starshak, R.J.; Schroeder, B.A.

    1987-03-01

    Infection is the most common disease of the urinary tract in children, and various imaging techniques have been used to verify its presence and location. On retrospective analysis, 50 consecutive children with documented upper urinary tract infection had abnormal findings on renal cortical scintigraphy with 99mTc-glucoheptonate. The infection involved the renal poles only in 38 and the poles plus other renal cortical areas in eight. Four had abnormalities that spared the poles. Renal sonograms were abnormal in 32 of 50 children. Excretory urograms were abnormal in six of 23 children in whom they were obtained. Vesicoureteral reflux was found in 34 of 40 children in whom voiding cystourethrography was performed. These data show the high sensitivity of renal cortical scintigraphy with 99mTc-glucoheptonate in documenting upper urinary tract infection. The location of the abnormalities detected suggests that renal infections spread via an ascending mode and implies that intrarenal reflux is a major contributing factor.

  14. Pathophysiology of Clinical Symptoms in Acute Viral Respiratory Tract Infections.

    PubMed

    Kuchar, E; Miśkiewicz, K; Nitsch-Osuch, Aneta; Szenborn, L

    2015-01-01

    In this article we discuss the pathophysiology of common symptoms of acute viral respiratory infections (e.g., sneezing, nasal discharge, sore throat, cough, muscle pains, malaise, and mood changes). Since clinical symptoms are not sufficient to determine the etiology of viral respiratory tract infections, we believe that the host defense mechanisms are critical for the symptomatology. Consequently, this review of literature is focused on the pathophysiology of respiratory symptoms regardless of their etiology. We assume that despite a high prevalence of symptoms of respiratory infection, their pathogenesis is not widely known. A better understanding of the symptoms' pathogenesis could improve the quality of care for patients with respiratory tract infections.

  15. Lower respiratory tract illness and RSV prophylaxis in very premature infants

    PubMed Central

    Lacaze-Masmonteil, T; Truffert, P; Pinquier, D; Daoud, P; Goldfarb, G; Vicaut, E; Fauroux, B

    2004-01-01

    Aims: To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis. Methods: Multicentre prospective longitudinal cohort study of 2813 infants, born between April 2000 and December 2000 at less than 33 weeks of gestational age, and followed until the end of the epidemic season. Results: Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were readmitted at least once for any reason during the epidemic season; 15.1% and 7.2% were readmitted at least once for any LRTI and RSV related LRTI, respectively. Children born at less than 31 weeks' gestation, having an intrauterine growth restriction, or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI. Of the 376 children submitted to prophylaxis, 28.2% were readmitted at least once for any LRTI and 6.1% for RSV related LRTI. Conclusion: One out of four children who had received no prophylaxis, was born very prematurely, and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was readmitted at least once for any reason. Roughly 50% and 20% of these readmissions were related to a LRTI and an RSV infection, respectively. Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population. PMID:15155404

  16. Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

    PubMed Central

    Flieger, Robert Rainer; Mankertz, Annette; Yilmaz, Kadir; Roepke, Torsten Kai

    2016-01-01

    Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade.

  17. IKK{epsilon} modulates RSV-induced NF-{kappa}B-dependent gene transcription

    SciTech Connect

    Bao Xiaoyong; Indukuri, Hemalatha; Liu Tianshuang; Liao Suiling; Tian, Bing; Brasier, Allan R.; Garofalo, Roberto P.; Casola, Antonella

    2010-12-20

    Respiratory syncytial virus (RSV), a negative-strand RNA virus, is the most common cause of epidemic respiratory disease in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B). In this study we have investigated the role of the non canonical I{kappa}B kinase (IKK){epsilon} in modulating RSV-induced NF-{kappa}B activation. Our results show that inhibition of IKK{epsilon} activation results in significant impairment of viral-induced NF-{kappa}B-dependent gene expression, through a reduction in NF-{kappa}B transcriptional activity, without changes in nuclear translocation or DNA-binding activity. Absence of IKK{epsilon} results in a significant decrease of RSV-induced NF-{kappa}B phosphorylation on serine 536, a post-translational modification important for RSV-induced NF-{kappa}B-dependent gene expression, known to regulate NF-{kappa}B transcriptional activity without affecting nuclear translocation. This study identifies a novel mechanism by which IKK{epsilon} regulates viral-induced cellular signaling.

  18. Innate and adaptive cellular phenotypes contributing to pulmonary disease in mice after respiratory syncytial virus immunization and infection.

    PubMed

    Lee, Young-Tae; Kim, Ki-Hye; Hwang, Hye Suk; Lee, Youri; Kwon, Young-Man; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Kang, Sang-Moo

    2015-11-01

    Respiratory syncytial virus (RSV) is the major leading cause of infantile viral bronchiolitis. However, cellular phenotypes contributing to the RSV protection and vaccine-enhanced disease remain largely unknown. Upon RSV challenge, we analyzed phenotypes and cellularity in the lung of mice that were naïve, immunized with formalin inactivated RSV (FI-RSV), or re-infected with RSV. In comparison with naïve and live RSV re-infected mice, the high levels of eosinophils, neutrophils, plasmacytoid and CD11b(+) dendritic cells, and IL-4(+) CD4(+) T cells were found to be contributing to pulmonary inflammation in FI-RSV immune mice despite lung viral clearance. Alveolar macrophages appeared to play differential roles in protection and inflammation upon RSV infection of different RSV immune mice. These results suggest that multiple innate and adaptive immune components differentially contribute to RSV disease and inflammation.

  19. Characterization of acute rat parvovirus infection by in situ hybridization.

    PubMed

    Gaertner, D J; Jacoby, R O; Johnson, E A; Paturzo, F X; Smith, A L; Brandsma, J L

    1993-04-01

    In situ hybridization and virus titration were used to characterize early stages of rat virus (RV) infection of rat pups after oronasal inoculation. Results suggest that virus enters through the lung and that early viremia leads rapidly to pantropic infection. Cells derived from all three germ layers were infected with RV, but those of endodermal and mesodermal origin were the predominant targets. Infection of vascular endothelium was widespread and was associated with hemorrhage and infarction in the brain. Convalescence from acute infection was accompanied by mononuclear cell infiltrates at sites containing RV DNA. Viral DNA was also detected in endothelium, fibroblasts and smooth muscle myofibers four weeks after inoculation. Further examination of these cells as potential sites of persistent infection is warranted.

  20. Emergency Department Management Of Acute Infective Endocarditis.

    PubMed

    Schauer, Steven G; Pfaff, James A; Cuenca, Peter John

    2014-11-01

    Infective endocarditis has a high rate of mortality, and most patients suspected of having the disease will require hospital admission. This review examines the literature as it pertains specifically to emergency clinicians who must maintain vigilance for risk factors and obtain a thorough history, including use of intravenous drugs, in order to guide the workup and treatment. Properly obtained cultures are critical during the evaluation, as they direct the course of antibiotic therapy. Although transthoracic echocardiography is widely available in United States emergency departments, it is not sensitive or specific enough to rule out a diagnosis of infective endocarditis. In high-risk patients, transesophageal echocardiography should be considered.

  1. The role of respiratory syncytial virus and other viral pathogens in acute otitis media.

    PubMed

    Klein, B S; Dollete, F R; Yolken, R H

    1982-07-01

    We utilized recently developed enzyme immunoassay techniques to examine the role of selected viruses in the etiology of acute otitis media. Viral pathogens were found in middle ear fluids obtained from 13 (24%) of 53 children with acute otitis media; respiratory syncytial virus accounted for ten of the 13 viral agents identified. In addition, respiratory syncytial viral antigen was found in nasopharyngeal washings obtained from 15 of the 53 children. Seven of these children had RSV identified as the sole middle ear pathogen, whereas six children had otitis caused by Streptococcus pneumoniae as either the sole middle ear pathogen or in combination with RSV. Similarly, all three children with respiratory infections caused by influenza virus had ear infections caused by bacterial pathogens, either alone or in combination with influenza virus. These findings suggest that, in patients with viral respiratory infection, coexisting acute otitis media may be associated with the recovery of either viruses or bacteria from the middle ear exudates.

  2. Predicting development of infected necrosis in acute necrotizing pancreatitis.

    PubMed

    Dambrauskas, Zilvinas; Pundzius, Juozas; Barauskas, Giedrius

    2006-01-01

    The incidence of severe acute pancreatitis is about 30 cases per 100,000 inhabitants, and it carries an overall mortality rate of 10-15%. Infection of pancreatic necrosis occurs in 20-30% of patients with severe acute pancreatitis and triples the mortality rate. Therefore, early prediction and diagnosis of infection in necrotizing pancreatitis are extremely important. The aim of the studies included in this review was to investigate the potential of specific prognostic factors to predict the development of secondary pancreatic infection in severe acute pancreatitis. This is seen as an important tool allowing to perform a computed tomography- or ultrasound-guided fine needle aspiration for bacteriological sampling at the right moment, to confirm the diagnosis, and, finally, to select the subgroup of patients who would benefit from the antibiotic prophylaxis. Precise patients' selection could possibly result in more rational use of antibiotics in patients with acute necrotizing pancreatitis and reduction of multi-resistant bacteria. Recent studies show that C-reactive protein is an important prognostic marker of pancreatic necrosis with the highest sensitivity and negative prognostic value in this respect. Procalcitonin alone or in combination with interleukin-6 best identifies patients not at risk for infection. However, a review of the clinical studies suggests that we still do not have an optimal model, thus there is a need for new more reliable biochemical and/or clinical predictive systems.

  3. Acute Borrelia infection inducing an APMPPE-like picture.

    PubMed

    Al Mousa, Munjid; Koch, Frank

    2016-12-01

    Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an uncommon disorder of unknown etiology affecting the retina, the retinal pigment epithelium, and the choroid. Although several etiological factors have been suggested, none has been confirmed. We report a case of APMPPE associated with acute infection of Borreliosis. A 30-year-old man presented with a decrease in vision in the right eye of about 1-week duration. His visual acuity in the right eye was 6/36. Fundus exam revealed the presence of multiple placoid creamy retinal/subretinal lesions in the right eye. Fundus fluorescein angiography supported the diagnosis of APMPPE. Blood tests revealed the presence of concomitant acute Borreliosis infection, as confirmed by IgM. The patient received oral prednisone therapy and amoxicillin. Six weeks later, the visual acuity returned to 6/6, and the patient was symptom free. Borreliosis can have several manifestations in the eye. One of the less common presentations is an APMPPE-like picture. The clinician should suspect acute Borreliosis infection in patients presenting with APMPPE, especially when there is a history of a tick bite, when the patient has systemic symptoms, or when living in/visiting endemic areas. This may help in the prompt management of APMPPE, avoiding complications due to the condition itself, or systemic involvement secondary to the Borreliosis infection. PMID:27294731

  4. Immunochromatography-based Diagnosis of Rotavirus Infection in Acute Diarrhea.

    PubMed

    Vashishtha, Vipin M; Thacker, Sandeep; Namjoshi, Gajanan Sudhir

    2016-07-01

    Documentation of rotavirus diarrhea in a rural, resource-poor setting is a difficult task. We analyzed stool samples of 103 children admitted for acute diarrhea in a pediatric hospital in Bijnor, UP, India, using a simple bedside immunochromatography kit. Rotavirus infection was detected in 47 out of total of 103 children (45.6%). PMID:27508549

  5. RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets

    PubMed Central

    Knudson, Cory J.; Hartwig, Stacey M.; Meyerholz, David K.; Varga, Steven M.

    2015-01-01

    There is no currently licensed vaccine for respiratory syncytial virus (RSV) despite being the leading cause of lower respiratory tract infections in children. Children previously immunized with a formalin-inactivated RSV (FI-RSV) vaccine exhibited enhanced respiratory disease following natural RSV infection. Subsequent studies in animal models have implicated roles for CD4 T cells, eosinophils and non-neutralizing antibodies in mediating enhanced respiratory disease. However, the underlying immunological mechanisms responsible for the enhanced respiratory disease and other disease manifestations associated with FI-RSV vaccine-enhanced disease remain unclear. We demonstrate for the first time that while CD4 T cells mediate all aspects of vaccine-enhanced disease, distinct CD4 T cell subsets orchestrate discrete and specific disease parameters. A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. In contrast, the Th1-associated cytokine TNF-α was necessary to mediate airway obstruction and weight loss. Our data demonstrate that individual disease manifestations associated with FI-RSV vaccine-enhanced disease are mediated by distinct subsets of CD4 T cells. PMID:25769044

  6. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  7. Sentinel Surveillance of HIV-1 Transmitted Drug Resistance, Acute Infection and Recent Infection

    PubMed Central

    Truong, Hong-Ha M.; Kellogg, Timothy A.; McFarland, Willi; Louie, Brian; Klausner, Jeffrey D.; Philip, Susan S.; Grant, Robert M.

    2011-01-01

    Background HIV-1 acute infection, recent infection and transmitted drug resistance screening was integrated into voluntary HIV counseling and testing (VCT) services to enhance the existing surveillance program in San Francisco. This study describes newly-diagnosed HIV cases and characterizes correlates associated with infection. Methodology/Principal Findings A consecutive sample of persons presenting for HIV VCT at the municipal sexually transmitted infections (STI) clinic from 2004 to 2006 (N = 9,868) were evaluated by standard enzyme-linked immunoassays (EIA). HIV antibody-positive specimens were characterized as recent infections using a less-sensitive EIA. HIV-RNA pooled testing was performed on HIV antibody-negative specimens to identify acute infections. HIV antibody-positive and acute infection specimens were evaluated for drug resistance by sequence analysis. Multivariable logistic regression was performed to evaluate associations. The 380 newly-diagnosed HIV cases included 29 acute infections, 128 recent infections, and 47 drug-resistant cases, with no significant increases or decreases in prevalence over the three years studied. HIV-1 transmitted drug resistance prevalence was 11.0% in 2004, 13.4% in 2005 and 14.9% in 2006 (p = 0.36). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) was the most common pattern detected, present in 28 cases of resistance (59.6%). Among MSM, recent infection was associated with amphetamine use (AOR = 2.67; p<0.001), unprotected anal intercourse (AOR = 2.27; p<0.001), sex with a known HIV-infected partner (AOR = 1.64; p = 0.02), and history of gonorrhea (AOR = 1.62; p = 0.03). Conclusions New HIV diagnoses, recent infections, acute infections and transmitted drug resistance prevalence remained stable between 2004 and 2006. Resistance to NNRTI comprised more than half of the drug-resistant cases, a worrisome finding given its role as the backbone of first

  8. Safety and Immunogenicity of a Live Attenuated RSV Vaccine in Healthy RSV-Seronegative Children 5 to 24 Months of Age

    PubMed Central

    Malkin, Elissa; Yogev, Ram; Abughali, Nazha; Sliman, Joseph; Wang, C. Kathy; Zuo, Fengrong; Yang, Chin-Fen; Eickhoff, Mark; Esser, Mark T.; Tang, Roderick S.; Dubovsky, Filip

    2013-01-01

    Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in

  9. Nematode infection: A rare mimic of acute appendicitis

    PubMed Central

    Hotchen, Andrew; Chin, Kian; Raja, Mahzar

    2014-01-01

    INTRODUCTION Acute appendicitis is a common condition seen in all surgical units. One rare condition that can mimic acute appendicitis is a nematode infection of the bowel. There have been few reported cases of nematode infection within the appendix and none that have been accompanied by intra-operative pictures. PRESENTATION OF CASE A 16-year-old female presented with a 12 h history of right iliac fossa pain and mild pyrexia. Bloods showed a neutrophilia and normal C-reactive protein. Laparoscopy was performed which revealed a non-inflamed appendix. The appendix was dissected and a live nematode was visualised exiting the base of the appendix. Anti-helminthics were given and the infection resolved. DISCUSSION Nematode infection is most commonly seen in Africa, Asia and South America. When seen within the United Kingdom (UK), it is seen most commonly within high-risk populations. Testing for these infections is not routine within the UK and when they are performed, the results take a considerable amount of time to return. These tests should be considered within high-risk populations so that unnecessary surgery can be avoided. CONCLUSION This case highlights the importance of considering rare causes of right iliac fossa pain including nematode infection in a young patient. The case highlights this by giving intra-operative pictures of live nematodes upon dissection of the appendix. PMID:25024022

  10. Vitamin D Binding Protein Haplotype is Associated with Hospitalization for RSV Bronchiolitis

    PubMed Central

    Randolph, Adrienne G.; Yip, Wai-Ki; Falkenstein-Hagander, Kathy; Weiss, Scott T.; Janssen, Riny; Keisling, Shannon; Bont, Louis

    2014-01-01

    Background Between 75,000–125,000 U.S. infants are hospitalized for respiratory syncytial virus (RSV) bronchiolitis each year. Up to half will be diagnosed with asthma in later childhood. Vitamin D deficiency has been associated with susceptibility to asthma and respiratory infections. Measured vitamin D is largely bound to vitamin D binding protein (VDBP); VDBP levels are influenced by its gene (GC) haplotype. Objective We assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma. Methods We retrospectively recruited 198 otherwise healthy children (93% White) hospitalized for severe RSV bronchiolitis in Boston and 333 parents into a follow up study to assess asthma diagnosis. Data were analyzed using family-based genetic association tests. We independently validated our results in 465 White children hospitalized with RSV bronchiolitis and 930 White population controls from the Netherlands. Results The rs7041_C allele (denoting haplotype GC1s) was overtransmitted (P=0.02, additive model) in the entire Boston cohort, and in Whites (P=0.03), and in those subsequently diagnosed with asthma (P=0.006). The GC1f haplotype was undertransmitted in the White and asthma subgroups (both P=0.05). The rs7041_C allele was also more frequent in the RSV bronchiolitis group compared to controls (OR 1.12, 95% CI 1.02, 1.4, P=0.03) in the Netherlands; especially in mechanically ventilated patients (P=0.009). Conclusion and Clinical Relevance GC1s haplotype carriage may increase the risk of RSV bronchiolitis in infancy and subsequent asthma development. The GC1s haplotype is associated with higher VDBP levels, resulting in less freely-available vitamin D. PMID:24447085

  11. Vaccine prevention of acute otitis media.

    PubMed

    Greenberg, D P; Hoberman, A

    2001-07-01

    The incidence of acute otitis media (AOM) in infants and young children has increased dramatically in recent years in the United States. AOM often follows upper respiratory tract infections due to pathogens such as respiratory syncytial virus (RSV), influenza virus, and parainfluenza virus (PIV). These viruses cause eustachian tube dysfunction that is critical to the pathogenesis of AOM. Vaccines against these viruses would likely reduce the incidence of AOM. In three previous studies, influenza virus vaccines reduced the incidence of AOM by 30% to 36%. Vaccines to prevent infections with RSV and PIV type 3 are undergoing clinical testing at this time. Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the three most common AOM pathogens. Heptavalent pneumococcal conjugate vaccine is effective in preventing invasive disease and AOM caused by serotypes contained in the vaccine. Vaccine candidates for NTHi and M. catarrhalis are under development.

  12. Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective

    PubMed Central

    Rawlinson, William; Snelling, Thomas L.; Jaffe, Adam

    2014-01-01

    Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups. PMID:25548575

  13. Pooled Sequencing of Candidate Genes Implicates Rare Variants in the Development of Asthma Following Severe RSV Bronchiolitis in Infancy.

    PubMed

    Torgerson, Dara G; Giri, Tusar; Druley, Todd E; Zheng, Jie; Huntsman, Scott; Seibold, Max A; Young, Andrew L; Schweiger, Toni; Yin-Declue, Huiqing; Sajol, Geneline D; Schechtman, Kenneth B; Hernandez, Ryan D; Randolph, Adrienne G; Bacharier, Leonard B; Castro, Mario

    2015-01-01

    Severe infection with respiratory syncytial virus (RSV) during infancy is strongly associated with the development of asthma. To identify genetic variation that contributes to asthma following severe RSV bronchiolitis during infancy, we sequenced the coding exons of 131 asthma candidate genes in 182 European and African American children with severe RSV bronchiolitis in infancy using anonymous pools for variant discovery, and then directly genotyped a set of 190 nonsynonymous variants. Association testing was performed for physician-diagnosed asthma before the 7th birthday (asthma) using genotypes from 6,500 individuals from the Exome Sequencing Project (ESP) as controls to gain statistical power. In addition, among patients with severe RSV bronchiolitis during infancy, we examined genetic associations with asthma, active asthma, persistent wheeze, and bronchial hyperreactivity (methacholine PC20) at age 6 years. We identified four rare nonsynonymous variants that were significantly associated with asthma following severe RSV bronchiolitis, including single variants in ADRB2, FLG and NCAM1 in European Americans (p = 4.6x10-4, 1.9x10-13 and 5.0x10-5, respectively), and NOS1 in African Americans (p = 2.3x10-11). One of the variants was a highly functional nonsynonymous variant in ADRB2 (rs1800888), which was also nominally associated with asthma (p = 0.027) and active asthma (p = 0.013) among European Americans with severe RSV bronchiolitis without including the ESP. Our results suggest that rare nonsynonymous variants contribute to the development of asthma following severe RSV bronchiolitis in infancy, notably in ADRB2. Additional studies are required to explore the role of rare variants in the etiology of asthma and asthma-related traits following severe RSV bronchiolitis.

  14. Modeling inoculum dose dependent patterns of acute virus infections.

    PubMed

    Li, Yan; Handel, Andreas

    2014-04-21

    Inoculum dose, i.e. the number of pathogens at the beginning of an infection, often affects key aspects of pathogen and immune response dynamics. These in turn determine clinically relevant outcomes, such as morbidity and mortality. Despite the general recognition that inoculum dose is an important component of infection outcomes, we currently do not understand its impact in much detail. This study is intended to start filling this knowledge gap by analyzing inoculum dependent patterns of viral load dynamics in acute infections. Using experimental data for adenovirus and infectious bronchitis virus infections as examples, we demonstrate inoculum dose dependent patterns of virus dynamics. We analyze the data with the help of mathematical models to investigate what mechanisms can reproduce the patterns observed in experimental data. We find that models including components of both the innate and adaptive immune response are needed to reproduce the patterns found in the data. We further analyze which types of innate or adaptive immune response models agree with observed data. One interesting finding is that only models for the adaptive immune response that contain growth terms partially independent of viral load can properly reproduce observed patterns. This agrees with the idea that an antigen-independent, programmed response is part of the adaptive response. Our analysis provides useful insights into the types of model structures that are required to properly reproduce observed virus dynamics for varying inoculum doses. We suggest that such models should be taken as basis for future models of acute viral infections.

  15. Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection.

    PubMed

    Shinoda, Koji; Asahara, Hideaki; Uehara, Taira; Miyoshi, Katsue; Suzuki, Satoshi O; Iwaki, Toru; Kira, Jun-ichi

    2015-02-01

    We report the first case of an occurrence of multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection with no rash and long-term increased titers of serum anti-rubella IgM in a 17-year-old male who had no history of rubella vaccination. He suffered from at least six clinical exacerbations with disseminated hyperintense lesions on FLAIR MR images during the course of 18 months. Repeated methylprednisolone pulse therapy and intravenous immunoglobulin therapy resolved the exacerbations. In patients with multiphasic ADEM of unknown etiology, clinicians should also consider the possibility of preceding infection with rubella virus.

  16. Detection of Acute HIV-1 Infection by RT-LAMP.

    PubMed

    Rudolph, Donna L; Sullivan, Vickie; Owen, S Michele; Curtis, Kelly A

    2015-01-01

    A rapid, cost-effective diagnostic test for the detection of acute HIV-1 infection is highly desired. Isothermal amplification techniques, such as reverse-transcription loop-mediated isothermal amplification (RT-LAMP), exhibit characteristics that are ideal for the development of a rapid nucleic acid amplification test (NAAT) because they are quick, easy to perform and do not require complex, dedicated equipment and laboratory space. In this study, we assessed the ability of the HIV-1 RT-LAMP assay to detect acute HIV infection as compared to a representative rapid antibody test and several FDA-approved laboratory-based assays. The HIV-1 RT-LAMP assay detected seroconverting individuals one to three weeks earlier than a rapid HIV antibody test and up to two weeks earlier than a lab-based antigen/antibody (Ag/Ab) combo enzyme immunoassay (EIA). RT-LAMP was not as sensitive as a lab-based qualitative RNA assay, which could be attributed to the significantly smaller nucleic acid input volume. To our knowledge, this is the first demonstration of detecting acute HIV infection using the RT-LAMP assay. The availability of a rapid NAAT, such as the HIV-1 RT-LAMP assay, at the point of care (POC) or in laboratories that do not have access to large platform NAAT could increase the percentage of individuals who receive an acute HIV infection status or confirmation of their HIV status, while immediately linking them to counseling and medical care. In addition, early knowledge of HIV status could lead to reduced high-risk behavior at a time when individuals are at a higher risk for transmitting the virus. PMID:25993381

  17. Pteropine orthoreovirus infection among out-patients with acute upper respiratory tract infection in Malaysia.

    PubMed

    Voon, Kenny; Tan, Yeh Fong; Leong, Pooi Pooi; Teng, Cheong Lieng; Gunnasekaran, Rajasekaran; Ujang, Kamsiah; Chua, Kaw Bing; Wang, Lin-Fa

    2015-12-01

    This study aims to assess the incidence rate of Pteropine orthreovirus (PRV) infection in patients with acute upper respiratory tract infection (URTI) in a suburban setting in Malaysia, where bats are known to be present in the neighborhood. Using molecular detection of PRVs directly from oropharyngeal swabs, our study demonstrates that PRV is among one of the common causative agents of acute URTI with cough and sore throat as the commonest presenting clinical features. Phylogenetic analysis on partial major outer and inner capsid proteins shows that these PRV strains are closely related to Melaka and Kampar viruses previously isolated in Malaysia. Further study is required to determine the public health significance of PRV infection in Southeast Asia, especially in cases where co-infection with other pathogens may potentially lead to different clinical outcomes.

  18. Infection in acute leukemia patients receiving oral nonabsorable antibiotics.

    PubMed

    Hahn, D M; Schimpff, S C; Fortner, C L; Smyth, A C; Young, V M; Wiernik, P H

    1978-06-01

    During a 20-month period all acute nonlymphocytic patients (87 patient trials) receiving cytotoxic chemotherapy were placed on an oral nonabsorbable antibiotic regimen consisting of gentamicin, vancomycin, and nystatin in addition to an intensive program of infection prevention aimed at reducing exogenously acquired and body-surface potential pathogens. Although side effects of anorexia, diarrhea, and nausea were common, gentamicin-vancomycin-nystatin was ingested 80% of the study time. Microbial growth in gingival and rectal cultures was substantially reduced. The incidence of bacteremias and other serious infections was low. Pseudomonas aeruginosa, other gram-negative bacilli, and Candida species caused few infections along the alimentary canal, whereas infections of the skin (especially Staphylococcus aureus) were not reduced compared with those occurring in former years. A total of the 104 acquired gram-negative bacilli were gentamicin resistant; 5 subsequently caused infection. Thus, despite certain definite drawbacks, the use of oral nonabsorbable antibiotics to suppress alimentary tract microbial flora in combination with other infection prevention techniques in granulocytopenic cancer patients has proven feasible and tolerable and has been associated with a low order of life-threatening infections. PMID:98107

  19. Endogenous IL-21 regulates pathogenic mucosal CD4 T-cell responses during enhanced RSV disease in mice

    PubMed Central

    Dodd, J S; Clark, D; Muir, R; Korpis, C; Openshaw, P J M

    2013-01-01

    A role for interleukin-21 (IL-21) has recently been found in several diseases, but contribution to mucosal defences has not been described. In BALB/c mice infected with respiratory syncytial virus (RSV), IL-21 depletion had little effect in primary infection. However, depletion of mice during priming with recombinant vaccinia expressing RSV G protein (which primes RSV-specific T helper type 2 cells and causes lung eosinophilia during RSV infection) further exacerbated pathology during RSV challenge, with reduced viral clearance and impaired virus-specific serum antibody responses. This enhancement was accompanied by lymphocyte, neutrophil, and antigen-presenting cell recruitment to the lungs, with increased bronchoalveolar lavage interferon-γ and IL-17 levels. Adoptive transfer of splenic CD4 T cells from depleted mice into naive recipients replicated these effects, indicating that IL-21 mediates its effects via CD4 T cells. Endogenous IL-21, therefore, has potent and specific effects on mucosal antiviral responses, assisting viral clearance, regulating pulmonary T- and B-cell responses, and inhibiting IL-17 production. PMID:23168836

  20. A Golden Hamster Model for Human Acute Nipah Virus Infection

    PubMed Central

    Wong, K. Thong; Grosjean, Isabelle; Brisson, Christine; Blanquier, Barissa; Fevre-Montange, Michelle; Bernard, Arlette; Loth, Philippe; Georges-Courbot, Marie-Claude; Chevallier, Michelle; Akaoka, Hideo; Marianneau, Philippe; Lam, Sai Kit; Wild, T. Fabian; Deubel, Vincent

    2003-01-01

    A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153–2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection. PMID:14578210

  1. Pediatric Asthma and Viral Infection.

    PubMed

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma. PMID:26766408

  2. Pediatric Asthma and Viral Infection.

    PubMed

    Garcia-Garcia, M Luz; Calvo Rey, Cristina; Del Rosal Rabes, Teresa

    2016-05-01

    Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. Bronchiolitis is the most common acute respiratory infection in children under 1year of age, and the most common cause of hospitalization in this age group. RSV accounts for approximately 70% of all these cases, followed by rhinovirus, adenovirus, metapneumovirus and bocavirus. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In any case, sufficient evidence is available to corroborate the existence of this association, which is particularly strong when the causative agent of bronchiolitis is rhinovirus. The pathogenic role of respiratory viruses as triggers for exacerbations in asthmatic patients has not been fully characterized. However, it is clear that respiratory viruses, and in particular rhinovirus, are the most common causes of exacerbation in children, and some type of respiratory virus has been identified in over 90% of children hospitalized for an episode of wheezing. Changes in the immune response to viral infections in genetically predisposed individuals are very likely to be the main factors involved in the association between viral infection and asthma.

  3. Acute haematogenous infection of a closed vertebral fracture.

    PubMed

    Marshman, Laurence A G; Allison, Dale; Molloy, Cynthia J

    2009-12-01

    Acute haematogenous infection of a closed fractures is rare. A 68-year-old diabetic male sustained a burst fracture of a lumbar vertebra (L2) after a fall onto his back. After 5 days of conservative management, he developed a chest infection and amoxicillin was commenced empirically. However, after 6 days his previously moderate focal L2 back pain had become more severe. Pyrexia and systemic inflammatory markers continued to rise despite administration of antibiotics. Blood cultures and a CT-guided biopsy of L2 both revealed Staphylococcus aureus which was sensitive to flucloxacillin. The patient's symptoms and signs gradually normalised following administration of flucloxacillin for 6 weeks, and the use of a cast brace. We conclude that haematogenous infection can be successfully managed non-operatively.

  4. Telaprevir in the Treatment of Acute Hepatitis C Virus Infection in HIV-Infected Men

    PubMed Central

    Fierer, Daniel S.; Dieterich, Douglas T.; Mullen, Michael P.; Branch, Andrea D.; Uriel, Alison J.; Carriero, Damaris C.; van Seggelen, Wouter O.; Hijdra, Rosanne M.; Cassagnol, David G.; Akil, Bisher; Bailey, Juan; Bellman, Paul; Bowers, Daniel; Bungay, Krisczar; Burger, Susanne; Carpenter, Ward; Chavez, Robert; Chow, Rita; Cohen, Robert; Dalton, Patrick; Dellosso, John; Demidont, Adrian; Dillon, Stephen; Donlon, Eileen; Farrow, Terry; Gardenier, Donald; Guadron, Rodolfo; Haber, Stuart; Higgins, Lawrence; Hitzeman, Lawrence; Hsu, Ricky; Huprikar, Shirish; Inada, Victor; Jacob, Sneha; Johnson, Livette; Johnston, Barbara; Kaminsky, Donald; Klein, Oscar; Kwong, Jeffrey; Lares-Guia, Jose; Leach, Eric; Levine, Randy; Linetskaya, Irina; Litvinova, Larisa; Malhotra, Amisha; Mandell, William; Markowitz, Martin; Mayer, Gal; Meraz, Eddie; Mortensen, Erik; Ng, Michel; Olivieri, Joseph; Paolino, Charles; Photangtham, Punyadech; Psevdos, George; Radix, Anita; Rapaport, Steven; Rodriguez-Caprio, Gabriela; Shay, William; Somasundaram, Nirupama; Sorra, Lembitu; Stivala, Alicia; Tran, Richie; Urbina, Antonio; Vail, Rona; Wallach, Francis; Wang, Wen; Weiss, Susan; Wiener, Melissa

    2014-01-01

    Background. There is an international epidemic of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)–infected men who have sex with men. Sustained virologic response (SVR) rates with pegylated interferon and ribavirin treatment are higher in these men during acute HCV than during chronic HCV, but treatment is still lengthy and SVR rates are suboptimal. Methods. We performed a pilot study of combination therapy with telaprevir, pegylated interferon, and ribavirin in acute genotype 1 HCV infection in HIV-infected men. Men who were treated prior to the availability of, or ineligible for, telaprevir were the comparator group. The primary endpoint was SVR12, defined as an HCV viral load <5 IU/mL at least 12 weeks after completing treatment. Results. In the telaprevir group, 84% (16/19) of men achieved SVR12 vs 63% (30/48) in the comparator group. Among men with SVR, median time to undetectable viral load was week 2 in the telaprevir group vs week 4 in the comparator group, and 94% vs 53% had undetectable viral loads at week 4. Most patients (81%) who achieved SVR in the telaprevir group received ≤12 weeks of treatment and there were no relapses after treatment. The overall safety profile was similar to that known for telaprevir-based regimens. Conclusions. Incorporating telaprevir into treatment of acute genotype 1 HCV in HIV-infected men halved the treatment duration and increased the SVR rate. Larger studies should be done to confirm these findings. Clinicians should be alert to detect acute HCV infection of HIV-infected men to take advantage of this effective therapy and decrease further transmission in this epidemic. PMID:24336914

  5. ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE

    PubMed Central

    Bradley, G. Mary; Spink, Wesley W.

    1959-01-01

    When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed. PMID:13803714

  6. Performance Characteristics of Xpert Flu/RSV XC Assay.

    PubMed

    Popowitch, Elena B; Miller, Melissa B

    2015-08-01

    The Xpert Flu/RSV XC assay was compared to laboratory-developed tests (LDTs) (n = 207) and the Xpert Flu assay (n = 147) using archived nasopharyngeal swabs. The percentages of positive agreements with LDTs were 97.8% for influenza A, 97.2% for influenza B, and 89.3% for RSV. The sensitivity of influenza detection was improved with the Xpert Flu/RSV XC assay compared to the Xpert Flu assay.

  7. Human Bocavirus: Passenger or Pathogen in Acute Respiratory Tract Infections?

    PubMed Central

    Schildgen, Oliver; Müller, Andreas; Allander, Tobias; Mackay, Ian M.; Völz, Sebastian; Kupfer, Bernd; Simon, Arne

    2008-01-01

    Summary: Human bocavirus (HBoV) is a newly identified virus tentatively assigned to the family Parvoviridae, subfamily Parvovirinae, genus Bocavirus. HBoV was first described in 2005 and has since been detected in respiratory tract secretions worldwide. Herein we review the literature on HBoV and discuss the biology and potential clinical impact of this virus. Most studies have been PCR based and performed on patients with acute respiratory symptoms, from whom HBoV was detected in 2 to 19% of the samples. HBoV-positive samples have been derived mainly from infants and young children. HBoV DNA has also been detected in the blood of patients with respiratory tract infection and in fecal samples of patients with diarrhea with or without concomitant respiratory symptoms. A characteristic feature of HBoV studies is the high frequency of coinciding detections, or codetections, with other viruses. Available data nevertheless indicate a statistical association between HBoV and acute respiratory tract disease. We present a model incorporating these somewhat contradictory findings and suggest that primary HBoV infection causes respiratory tract symptoms which can be followed by prolonged low-level virus shedding in the respiratory tract. Detection of the virus in this phase will be facilitated by other infections, either simply via increased sample cell count or via reactivation of HBoV, leading to an increased detection frequency of HBoV during other virus infections. We conclude that the majority of available HBoV studies are limited by the sole use of PCR diagnostics on respiratory tract secretions, addressing virus prevalence but not disease association. The ability to detect primary infection through the development of improved diagnostic methods will be of great importance for future studies seeking to assign a role for HBoV in causing respiratory illnesses. PMID:18400798

  8. Actinomyces infection causing acute right iliac fossa pain

    PubMed Central

    Govindarajah, Narendranath; Hameed, Waseem; Middleton, Simon; Booth, Michael

    2014-01-01

    This is a case of a 75-year-old man being admitted to the on-call surgical department with acute abdominal pain. On arrival he was clinically dehydrated and shocked with localised pain over McBurney's point and examination findings were suggestive of appendiceal or other colonic pathology. Full blood testing revealed a white cell count of 38×109/L and a C reactive protein (CRP) of 278 mg/L. A CT scan revealed a gallbladder empyema that extended into the right iliac fossa. This case highlights the potential for a hyperdistended gallbladder empyema to present as acute right iliac fossa pain with blood tests suggestive of complicated disease. Further analysis confirmed Actinomyces infection as the underlying aetiology prior to a laparoscopic subtotal cholecystectomy. This case serves to remind clinicians of this as a rare potential cause of atypical gallbladder pathology. PMID:24872493

  9. The Diagnosis, Evaluation and Treatment of Acute and Recurrent Pediatric Urinary Tract Infections

    PubMed Central

    Becknell, Brian; Schober, Megan; Korbel, Lindsey; Spencer, John David

    2015-01-01

    Urinary tract infection is one of the most common bacterial infections encountered by pediatricians. Currently, the diagnosis and management of acute urinary tract infection and recurrent urinary tract infection in children remains controversial. Recently published guidelines and large clinical trials have attempted to clarify UTI diagnostic and management strategies. In this manuscript, we review the diagnosis and management of acute and recurrent urinary tract infection in the pediatric population. PMID:25421102

  10. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection.

    PubMed

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets.

  11. Proteomic Profiling of Mouse Liver following Acute Toxoplasma gondii Infection

    PubMed Central

    He, Jun-Jun; Ma, Jun; Elsheikha, Hany M.; Song, Hui-Qun; Zhou, Dong-Hui; Zhu, Xing-Quan

    2016-01-01

    Toxoplasma gondii remains a global public health problem. However, its pathophysiology is still not-completely understood particularly the impact of infection on host liver metabolism. We performed iTRAQ-based proteomic analysis to evaluate early liver protein responses in BALB/c mice following infection with T. gondii PYS strain (genotype ToxoDB#9) infection. Our data revealed modification of protein expression in key metabolic pathways, as indicated by the upregulation of immune response and downregulation of mitochondrial respiratory chain, and the metabolism of fatty acids, lipids and xenobiotics. T. gondii seems to hijack host PPAR signaling pathway to downregulate the metabolism of fatty acids, lipids and energy in the liver. The metabolism of over 400 substances was affected by the downregulation of genes involved in xenobiotic metabolism. The top 10 transcription factors used by upregulated genes were Stat2, Stat1, Irf2, Irf1, Sp2, Egr1, Stat3, Klf4, Elf1 and Gabpa, while the top 10 transcription factors of downregulated genes were Hnf4A, Ewsr1, Fli1, Hnf4g, Nr2f1, Pparg, Rxra, Hnf1A, Foxa1 and Foxo1. These findings indicate global reprogramming of the metabolism of the mouse liver after acute T. gondii infection. Functional characterization of the altered proteins may enhance understanding of the host responses to T. gondii infection and lead to the identification of new therapeutic targets. PMID:27003162

  12. Acute viral bronchiolitis in South Africa: Strategies for management and prevention.

    PubMed

    Zar, H J; Madhi, S A; White, D A; Masekela, R; Risenga, S; Lewis, H; Feldman, C; Morrow, B; Jeena, P

    2016-04-01

    Management of acute viral bronchiolitis is largely supportive. There is currently no proven effective therapy other than oxygen for hypoxic children. The evidence indicates that there is no routine benefit from inhaled, rapid short-acting bronchodilators, adrenaline or ipratropium bromide for children with acute viral bronchiolitis. Likewise, there is no demonstrated benefit from routine use of inhaled or oral corticosteroids, inhaled hypertonic saline nebulisation, montelukast or antibiotics. The last should be reserved for children with severe disease, when bacterial co-infection is suspected. Prevention of respiratory syncytial virus (RSV) disease remains a challenge. A specific RSV monoclonal antibody, palivizumab, administered as an intramuscular injection, is available for children at risk of severe bronchiolitis, including premature infants, young children with chronic lung disease, immunodeficiency, or haemodynamically significant congenital heart disease. Prophylaxis should be commenced at the start of the RSV season and given monthly during the season. The development of an RSV vaccine may offer a more effective alternative to prevent disease, for which the results of clinical trials are awaited. Education of parents or caregivers and healthcare workers about diagnostic and management strategies should include the following: bronchiolitis is caused by a virus; it is seasonal; it may start as an upper respiratory tract infection with low-grade fever; symptoms are cough and wheeze, often with fast breathing; antibiotics are generally not needed; and the condition is usually self limiting, although symptoms may occur for up to four weeks in some children. PMID:27303780

  13. Serum amyloid A protein in acute viral infections.

    PubMed Central

    Miwata, H; Yamada, T; Okada, M; Kudo, T; Kimura, H; Morishima, T

    1993-01-01

    Concentrations of serum amyloid A protein (SAA) were measured in 254 children with viral diseases, including measles, varicella, rubella, mumps, echo-30 meningitis, chronic hepatitis B and C, and in eight with Kawasaki disease. Latex agglutination nephelometric immunoassay was used for assaying SAA. In 191 out of 195 patients (98%), SAA concentrations became markedly raised in the acute phase of the viral disease: measles (97%), varicella (100%), mumps (95%), and echo-30 meningitis (99%) with mean titres of 82.4, 80.5, 60.2, 75.2, and 101.1 micrograms/ml respectively. This increase in SAA was followed by a rapid return to normal concentrations (< 5 micrograms/ml) during convalescence. Remarkably higher concentrations of SAA (mean 1630 micrograms/ml) were detected in the acute phase of patients with Kawasaki disease, but in most of the children with chronic hepatitis B or C, the titres of SAA remained normal. There was no close correlation between SAA and serum concentrations for alpha 1-acid glycoprotein, beta 2-microglobulin, transferrin, and IgG. There was a clear correlation between SAA and C reactive protein concentrations, although SAA showed a greater incremental change than C reactive protein in the acute phase. In the acute phase of these viral diseases, 56% of the patients had raised SAA concentrations (> or = 5 micrograms/ml) with normal C reactive protein concentrations (< 5 micrograms/ml). These results indicate that SAA could be useful as an inflammatory marker in children with acute viral infections. PMID:8481043

  14. Biochemical Effect of Resistance Mutations against Synergistic Inhibitors of RSV RNA Polymerase

    PubMed Central

    Fung, Amy; Stevens, Sarah K.; Jordan, Paul C.; Gromova, Tatiana; Taylor, Joshua S.; Hong, Jin; Meng, Jia; Wang, Guangyi; Dyatkina, Natalia; Prhavc, Marija; Symons, Julian A.; Beigelman, Leo

    2016-01-01

    ALS-8112 is the parent molecule of ALS-8176, a first-in-class nucleoside analog prodrug effective in the clinic against respiratory syncytial virus (RSV) infection. The antiviral activity of ALS-8112 is mediated by its 5'-triphosphate metabolite (ALS-8112-TP, or 2'F-4'ClCH2-cytidine triphosphate) inhibiting the RNA polymerase activity of the RSV L-P protein complex through RNA chain termination. Four amino acid mutations in the RNA-dependent RNA polymerase (RdRp) domain of L (QUAD: M628L, A789V, L795I, and I796V) confer in vitro resistance to ALS-8112-TP by increasing its discrimination relative to natural CTP. In this study, we show that the QUAD mutations specifically recognize the ClCH2 group of ALS-8112-TP. Among the four mutations, A789V conferred the greatest resistance phenotype, which was consistent with its putative position in the active site of the RdRp domain. AZ-27, a non-nucleoside inhibitor of RSV, also inhibited the RdRp activity, with decreased inhibition potency in the presence of the Y1631H mutation. The QUAD mutations had no effect on the antiviral activity of AZ-27, and the Y1631H mutation did not significantly increase the discrimination of ALS-8112-TP. Combining ALS-8112 with AZ-27 in vitro resulted in significant synergistic inhibition of RSV replication. Overall, this is the first mechanistic study showing a lack of cross-resistance between mutations selected by different classes of RSV polymerase inhibitors acting in synergy, opening the door to future potential combination therapies targeting different regions of the L protein. PMID:27163448

  15. Biochemical Effect of Resistance Mutations against Synergistic Inhibitors of RSV RNA Polymerase.

    PubMed

    Deval, Jerome; Fung, Amy; Stevens, Sarah K; Jordan, Paul C; Gromova, Tatiana; Taylor, Joshua S; Hong, Jin; Meng, Jia; Wang, Guangyi; Dyatkina, Natalia; Prhavc, Marija; Symons, Julian A; Beigelman, Leo

    2016-01-01

    ALS-8112 is the parent molecule of ALS-8176, a first-in-class nucleoside analog prodrug effective in the clinic against respiratory syncytial virus (RSV) infection. The antiviral activity of ALS-8112 is mediated by its 5'-triphosphate metabolite (ALS-8112-TP, or 2'F-4'ClCH2-cytidine triphosphate) inhibiting the RNA polymerase activity of the RSV L-P protein complex through RNA chain termination. Four amino acid mutations in the RNA-dependent RNA polymerase (RdRp) domain of L (QUAD: M628L, A789V, L795I, and I796V) confer in vitro resistance to ALS-8112-TP by increasing its discrimination relative to natural CTP. In this study, we show that the QUAD mutations specifically recognize the ClCH2 group of ALS-8112-TP. Among the four mutations, A789V conferred the greatest resistance phenotype, which was consistent with its putative position in the active site of the RdRp domain. AZ-27, a non-nucleoside inhibitor of RSV, also inhibited the RdRp activity, with decreased inhibition potency in the presence of the Y1631H mutation. The QUAD mutations had no effect on the antiviral activity of AZ-27, and the Y1631H mutation did not significantly increase the discrimination of ALS-8112-TP. Combining ALS-8112 with AZ-27 in vitro resulted in significant synergistic inhibition of RSV replication. Overall, this is the first mechanistic study showing a lack of cross-resistance between mutations selected by different classes of RSV polymerase inhibitors acting in synergy, opening the door to future potential combination therapies targeting different regions of the L protein. PMID:27163448

  16. Central venous catheter infection in adults in acute hospital settings.

    PubMed

    Jones, Clare A

    As well as the human cost, central venous catheter (CVC)-related bloodstream infections significantly inflate hospital costs, mainly through increased length of stay in hospital, particularly in intensive care. This literature review appraises recent research on measures used to minimize CVC-related infection and compares it with current best practice. Randomized controlled trials and systematic reviews published on the subject between 2000 and 2005 were reviewed, concentrating on non-tunnelled, short-term CVCs in the acute hospital setting. The new evidence mainly backs up current best practice. However, skin disinfection could be improved by using alcoholic chlorhexidine followed by aqueous povidone-iodine before CVC insertion. Also, alcoholic chlorhexidine is the preferred solution for cleaning the hubs/connectors before accessing the CVC. Good hand hygiene and quality control and education programmes are vital to improve patient care. More research is needed to clarify the effectiveness of certain interventions and technologies, such as antimicrobial CVCs.

  17. Antibiotic use in acute upper respiratory tract infections.

    PubMed

    Zoorob, Roger; Sidani, Mohamad A; Fremont, Richard D; Kihlberg, Courtney

    2012-11-01

    Upper respiratory tract infections account for millions of visits to family physicians each year in the United States. Although warranted in some cases, antibiotics are greatly overused. This article outlines the guidelines and indications for appropriate antibiotic use for common upper respiratory infections. Early antibiotic treatment may be indicated in patients with acute otitis media, group A beta-hemolytic streptococcal pharyngitis, epiglottitis, or bronchitis caused by pertussis. Persistent cases of rhinosinusitis may necessitate the use of antibiotics if symptoms persist beyond a period of observation. Antibiotics should not be considered in patients with the common cold or laryngitis. Judicious, evidence-based use of antibiotics will help contain costs and prevent adverse effects and drug resistance.

  18. Nutritional Predictors of Acute Respiratory Infections Among Children Born to HIV-Infected Women in Tanzania

    PubMed Central

    Spiegelman, Donna; Hertzmark, Ellen; Duggan, Christopher; Msamanga, Gernard; Aboud, Said; Fawzi, Wafaie

    2013-01-01

    We prospectively determined the association between undernutrition and incidence of acute respiratory infections (ARIs) among 711 children born to HIV-infected women. Overall, underweight was associated with a 58% increased risk of ARI. Similarly, wasting (54%), very low birth weight (88%) and child HIV infection (62%) were significantly associated with increased risk of ARI during the first 2 years. Breastfeeding was associated with 52% reduction in risk of ARI only during the first 12 months of life. Among HIV-exposed, but uninfected, children, underweight, wasting and stunting were associated with 73%, 61% and 33% increased risk of ARI, respectively. Very low birthweight and advanced maternal disease stage were also associated with increased risk of ARI. Similar results were observed among HIV-infected children, except for stunting and very low birth weight. Prevention of child undernutrition could have major impact in reducing child ARI morbidity in settings of high HIV prevalence. PMID:23400399

  19. RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis In Vivo.

    PubMed

    Ptaschinski, Catherine; Mukherjee, Sumanta; Moore, Martin L; Albert, Mareike; Helin, Kristian; Kunkel, Steven L; Lukacs, Nicholas W

    2015-06-01

    Respiratory syncytial virus (RSV) infection can result in severe disease partially due to its ability to interfere with the initiation of Th1 responses targeting the production of type I interferons (IFN) and promoting a Th2 immune environment. Epigenetic modulation of gene transcription has been shown to be important in regulating inflammatory pathways. RSV-infected bone marrow-derived DCs (BMDCs) upregulated expression of Kdm5b/Jarid1b H3K4 demethylase. Kdm5b-specific siRNA inhibition in BMDC led to a 10-fold increase in IFN-β as well as increases in IL-6 and TNF-α compared to control-transfected cells. The generation of Kdm5bfl/fl-CD11c-Cre+ mice recapitulated the latter results during in vitro DC activation showing innate cytokine modulation. In vivo, infection of Kdm5bfl/fl-CD11c-Cre+ mice with RSV resulted in higher production of IFN-γ and reduced IL-4 and IL-5 compared to littermate controls, with significantly decreased inflammation, IL-13, and mucus production in the lungs. Sensitization with RSV-infected DCs into the airways of naïve mice led to an exacerbated response when mice were challenged with live RSV infection. When Kdm5b was blocked in DCs with siRNA or DCs from Kdm5bfl/fl-CD11c-CRE mice were used, the exacerbated response was abrogated. Importantly, human monocyte-derived DCs treated with a chemical inhibitor for KDM5B resulted in increased innate cytokine levels as well as elicited decreased Th2 cytokines when co-cultured with RSV reactivated CD4+ T cells. These results suggest that KDM5B acts to repress type I IFN and other innate cytokines to promote an altered immune response following RSV infection that contributes to development of chronic disease. PMID:26083387

  20. RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis In Vivo

    PubMed Central

    Ptaschinski, Catherine; Mukherjee, Sumanta; Moore, Martin L.; Albert, Mareike; Helin, Kristian; Kunkel, Steven L.; Lukacs, Nicholas W.

    2015-01-01

    Respiratory syncytial virus (RSV) infection can result in severe disease partially due to its ability to interfere with the initiation of Th1 responses targeting the production of type I interferons (IFN) and promoting a Th2 immune environment. Epigenetic modulation of gene transcription has been shown to be important in regulating inflammatory pathways. RSV-infected bone marrow-derived DCs (BMDCs) upregulated expression of Kdm5b/Jarid1b H3K4 demethylase. Kdm5b-specific siRNA inhibition in BMDC led to a 10-fold increase in IFN-β as well as increases in IL-6 and TNF-α compared to control-transfected cells. The generation of Kdm5bfl/fl-CD11c-Cre+ mice recapitulated the latter results during in vitro DC activation showing innate cytokine modulation. In vivo, infection of Kdm5bfl/fl-CD11c-Cre+ mice with RSV resulted in higher production of IFN-γ and reduced IL-4 and IL-5 compared to littermate controls, with significantly decreased inflammation, IL-13, and mucus production in the lungs. Sensitization with RSV-infected DCs into the airways of naïve mice led to an exacerbated response when mice were challenged with live RSV infection. When Kdm5b was blocked in DCs with siRNA or DCs from Kdm5bfl/fl-CD11c-CRE mice were used, the exacerbated response was abrogated. Importantly, human monocyte-derived DCs treated with a chemical inhibitor for KDM5B resulted in increased innate cytokine levels as well as elicited decreased Th2 cytokines when co-cultured with RSV reactivated CD4+ T cells. These results suggest that KDM5B acts to repress type I IFN and other innate cytokines to promote an altered immune response following RSV infection that contributes to development of chronic disease. PMID:26083387

  1. Acute Arboviral Infections in Guinea, West Africa, 2006

    PubMed Central

    Jentes, Emily S.; Robinson, Jaimie; Johnson, Barbara W.; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M. Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G.

    2010-01-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region. PMID:20682888

  2. Acute arboviral infections in Guinea, West Africa, 2006.

    PubMed

    Jentes, Emily S; Robinson, Jaimie; Johnson, Barbara W; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G; Bryan, Juliet

    2010-08-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region.

  3. Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Martinón-Sánchez, José María; Justicia-Grande, Antonio; Rivero-Calle, Irene; Pinnock, Elli; Salas, Antonio; Fink, Colin

    2016-01-01

    Background The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases. PMID:26872131

  4. Atomic force microscopic investigation of respiratory syncytial virus infection in HEp-2 cells.

    PubMed

    Tiwari, P M; Eroglu, E; Boyoglu-Barnum, S; He, Q; Willing, G A; Vig, K; Dennis, V A; Singh, S R

    2014-01-01

    Respiratory syncytial virus (RSV) primarily causes bronchiolitis and pneumonia in infants. In spite of intense research, no safe and effective vaccine has been developed yet. For understanding its pathogenesis and development of anti-RSV drugs/therapeutics, it is indispensable to study the RSV-host interaction. Although, there are limited studies using electron microscopy to elucidate the infection process of RSV, to our knowledge, no study has reported the morphological impact of RSV infection using atomic force microscopy. We report the cytoplasmic and nuclear changes in human epidermoid cell line type 2 using atomic force microscopy. Human epidermoid cell line type 2 cells, grown on cover slips, were infected with RSV and fixed after various time periods, processed and observed for morphological changes using atomic force microscopy. RSV infected cells showed loss of membrane integrity, with degeneration in the cellular content and cytoskeleton. Nuclear membrane was disintegrated and nuclear volume was decreased. The chromatin of the RSV infected cells was condensed, progressing towards degeneration via pyknosis and apoptosis. Membrane protrusions of ~150-200 nm diameter were observed on RSV infected cells after 6 h, suggestive of prospective RSV budding sites. To our knowledge, this is the first study of RSV infection process using atomic force microscopy. Such morphological studies could help explore viral infection process aiding the development of anti-RSV therapies.

  5. Identification of gene biomarkers for respiratory synctial virus infection in a bronchical epithelial cell line

    EPA Science Inventory

    Abstract: Respiratory syncytial virus (RSV) infection involves complex virus-host interplay. In this study, we analyzed gene expression in RSV-infected BEAS-2B cells to discover novel signaling pathways and biomarkers. We hybridized RNAs from RSV- or vehicle-treated BEAS-2B to ...

  6. Airway microbiota and acute respiratory infection in children

    PubMed Central

    Hasegawa, Kohei; Camargo, Carlos A.

    2016-01-01

    Summary Acute respiratory infection (ARI), such as bronchiolitis and pneumonia, is the leading cause of hospitalization for U.S. infants. While the incidence and severity of ARI can vary widely among children, the reasons for these differences are not fully explained by traditional risk factors (e.g., prematurity, viral pathogens). The recent advent of molecular diagnostic techniques has revealed the presence of highly functional communities of microbes inhabiting the human body (i.e., microbiota) that appear to influence development of local and systemic immune response. We propose a “risk and resilience” model in which airway microbiota are associated with an increased (risk microbiota) or decreased (resilience microbiota) incidence and severity of ARI in children. We also propose that modulating airway microbiota (e.g., from risk to resilience microbiota) during early childhood will optimize airway immunity, and thereby decrease ARI incidence and severity in children. PMID:25961472

  7. Exposure to cold and acute upper respiratory tract infection.

    PubMed

    Eccles, R; Wilkinson, J E

    2015-06-01

    The incidence of acute upper respiratory tract viral infections (URTI) is directly correlated to air temperature with most URTI occurring seasonally in cold weather. This review looks at four types of cold exposure and examines the evidence and possible mechanisms for any relationship to URTI. The effects of cold are discussed as: 1) Chilling of the nose and upper respiratory tract by breathing cold air, 2) Chilling of the mouth and upper digestive tract by ingestion of cold drinks and food, 3) Acute chilling of the body surface, and, 4) Chilling of the body as a whole with a fall in body temperature, hypothermia. Some studies were found to support a relationship between breathing cold air and chilling the body surface with the development of URTI, although this area is controversial. No evidence was found in the literature to support any relationship between ingestion of cold drinks and food and URTI, and similarly no evidence was found to link hypothermia and URTI. PMID:26030031

  8. Infection of mice with respiratory syncytial virus during neonatal life primes for enhanced antibody and T cell responses on secondary challenge.

    PubMed

    Tasker, L; Lindsay, R W B; Clarke, B T; Cochrane, D W R; Hou, S

    2008-08-01

    Primary neonatal immune responses to infection or vaccines are weak when compared with those of adults. In addition, memory responses of neonatally primed animals may be absent, weak or T helper type 2 (Th2)-biased. Respiratory syncytial virus (RSV) is an important pathogen of human infants and infection during the neonatal period has been linked to the development of asthma in later life. Here we report that acute intranasal infection of neonatal mice with RSV induces significant RSV-specific antibody and CD8 T cell responses. These responses were boosted after RSV rechallenge during adulthood, demonstrating the establishment of memory after neonatal priming. Primary infection during neonatal life was associated, following rechallenge, with limited viral replication in the lung. Recall responses of both spleen and lymph node cells from neonatally primed and adult-primed mice were associated with interferon-gamma secretion, indicative of a Th1-type response. However, interleukin (IL)-4 and IL-5 secretion were enhanced only in spleen and lymph node cells from neonatally primed mice. Rechallenge of neonatally primed mice was also associated with increased concentrations of chemokines monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and regulated upon activation normal T cell expressed and secreted in the lung. These may play a role in the enhanced inflammatory cell recruitment and immunopathology induced following RSV reinfection. Our results demonstrate therefore that immunity to RSV can be established during neonatal life and, importantly, that the quality of the subsequent response is dependent upon the age of first infection. PMID:18549446

  9. Trypanosoma cruzi Entrance through Systemic or Mucosal Infection Sites Differentially Modulates Regional Immune Response Following Acute Infection in Mice

    PubMed Central

    de Meis, Juliana; Barreto de Albuquerque, Juliana; Silva dos Santos, Danielle; Farias-de-Oliveira, Désio Aurélio; Berbert, Luiz Ricardo; Cotta-de-Almeida, Vinícius; Savino, Wilson

    2013-01-01

    Acute Chagas disease is characterized by a systemic infection that leads to the strong activation of the adaptive immune response. Outbreaks of oral contamination by the infective protozoan Trypanosoma cruzi are frequent in Brazil and other Latin American countries, and an increased severity of clinical manifestations and mortality is observed in infected patients. These findings have elicited questions about the specific responses triggered after T. cruzi entry via mucosal sites, possibly modulating local immune mechanisms, and further impacting regional and systemic immunity. Here, we provide evidence for the existence of differential lymphoid organ responses in experimental models of acute T. cruzi infection. PMID:23898334

  10. Viral Infection in Adults with Severe Acute Respiratory Infection in Colombia

    PubMed Central

    Remolina, Yuly Andrea; Ulloa, María Mercedes; Vargas, Hernán; Díaz, Liliana; Gómez, Sandra Liliana; Saavedra, Alfredo; Sánchez, Edgar; Cortés, Jorge Alberto

    2015-01-01

    Objectives To identify the viral aetiology in adult patients with severe acute respiratory infection (SARI) admitted to sentinel surveillance institutions in Bogotá in 2012. Design A cross-sectional study was conducted in which microarray molecular techniques for viral identification were used on nasopharyngeal samples of adult patients submitted to the surveillance system, and further descriptions of clinical features and relevant clinical outcomes, such as mortality, need for critical care, use of mechanical ventilation and hospital stay, were obtained. Setting Respiratory infections requiring hospital admission in surveillance centres in Bogotá, Colombia. Participants Ninety-one adult patients with acute respiratory infection (55% were female). Measurements Viral identification, intensive care unit admission, hospital stay, and mortality. Results Viral identification was achieved for 63 patients (69.2%). Comorbidity was frequently identified and mainly involved chronic pulmonary disease or pregnancy. Influenza, Bocavirus and Adenovirus were identified in 30.8%, 28.6% and 18.7% of the cases, respectively. Admission to the intensive care unit occurred in 42.9% of the cases, while mechanical ventilation was required for 36.3%. The average hospital stay was 9.9 days, and mortality was 15.4%. Antibiotics were empirically used in 90.1% of patients. Conclusions The prevalence of viral aetiology of SARI in this study was high, with adverse clinical outcomes, intensive care requirements and high mortality. PMID:26576054

  11. Primary Epstein-Barr-virus infections in acute neurologic diseases.

    PubMed

    Grose, C; Henle, W; Henle, G; Feorino, P M

    1975-02-20

    Infectious mononucleosis has been associated with Guillain--Barré syndrome, Bell's palsy, meningoencephalitis and transverse myelitis. Since it is not known that many children with infectious mononucleosis do not develop heterophil antibodies, we looked for evidence of current or recent Epstein-Barr virus infection in young patients with these neurologic diseases by using serodiagnostic procedures for detection and titration of antibodies to various antigens related to Epstein-Barr virus. Seven of 24 cases with Guillain-Barre syndrome and three of 16 with facial palsy were definitely associated with primary infection with Epstein-Barr virus as were two cases each of the other two neurologic diseases. Only one of these patients had obvious clinical infectious mononucleosis, and only a few demonstrated heterophil agglutinins. It is evident that the virus must be considered in the diagnosis of various acute neurologic diseases affecting children and young adults, even in the absence of heterophil-antibody response or other signs of infectious mononucleosis.

  12. Surveillance for hospitalized acute respiratory infection in Guatemala.

    PubMed

    Verani, Jennifer R; McCracken, John; Arvelo, Wences; Estevez, Alejandra; Lopez, Maria Renee; Reyes, Lissette; Moir, Juan Carlos; Bernart, Chris; Moscoso, Fabiola; Gray, Jennifer; Olsen, Sonja J; Lindblade, Kim A

    2013-01-01

    Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to

  13. Surveillance for Hospitalized Acute Respiratory Infection in Guatemala

    PubMed Central

    Verani, Jennifer R.; McCracken, John; Arvelo, Wences; Estevez, Alejandra; Lopez, Maria Renee; Reyes, Lissette; Moir, Juan Carlos; Bernart, Chris; Moscoso, Fabiola; Gray, Jennifer; Olsen, Sonja J.; Lindblade, Kim A.

    2013-01-01

    Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to

  14. Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co-Infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses

    PubMed Central

    Rubio-Guerri, Consuelo; Karlsson, Oskar E.; Kukielka, Deborah; Belák, Sándor; Sánchez-Vizcaíno, José Manuel

    2013-01-01

    The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and “unknown”, emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees. PMID:23460860

  15. Respiratory Syncytial Virus Infections in Infants Affected by Primary Immunodeficiency

    PubMed Central

    Capretti, Maria Grazia; Lazzarotto, Tiziana; Faldella, Giacomo

    2014-01-01

    Primary immunodeficiencies are rare inherited disorders that may lead to frequent and often severe acute respiratory infections. Respiratory syncytial virus (RSV) is one of the most frequent pathogens during early infancy and the infection is more severe in immunocompromised infants than in healthy infants, as a result of impaired T- and B-cell immune response unable to efficaciously neutralize viral replication, with subsequent increased viral shedding and potentially lethal lower respiratory tract infection. Several authors have reported a severe clinical course after RSV infections in infants and children with primary and acquired immunodeficiencies. Environmental prophylaxis is essential in order to reduce the infection during the epidemic season in hospitalized immunocompromised infants. Prophylaxis with palivizumab, a humanized monoclonal antibody against the RSV F protein, is currently recommended in high-risk infants born prematurely, with chronic lung disease or congenital heart disease. Currently however the prophylaxis is not routinely recommended in infants with primary immunodeficiency, although some authors propose the extension of prophylaxis to this high risk population. PMID:25089282

  16. Prevention of acute otitis media by prophylaxis and treatment of influenza virus infections.

    PubMed

    Glezen, W P

    2000-12-01

    Human experimental challenge studies with influenza virus infection and controlled intervention trials have demonstrated beyond doubt the role of influenza virus infection in the pathogenesis of acute otitis media. Influenza virus infections not only disrupt eustachian tube function, but also impair recovery from infection and facilitate attachment of bacterial pathogens to respiratory epithelial cells. Immunization of young children with either inactivated or live, attenuated influenza vaccine will significantly reduce the incidence of acute otitis media. Early treatment of influenza with antiviral medication will reduce eustachian tube dysfunction that results from influenza virus infection. Influenza produces high morbidity in children that could be averted by universal immunization with attenuated nasal spray vaccine.

  17. Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells.

    PubMed

    Hirakawa, Satoshi; Kojima, Takashi; Obata, Kazufumi; Okabayashi, Tamaki; Yokota, Shin-Ichi; Nomura, Kazuaki; Obonai, Toshimasa; Fuchimoto, Jun; Himi, Tetsuo; Tsutsumi, Hiroyuki; Sawada, Norimasa

    2013-12-01

    Respiratory syncytial virus (RSV) is an important pathogen of bronchiolitis, asthma, and severe lower respiratory tract disease in infants and young children. Matrix metalloproteinases (MMPs) play key roles in viral infection, inflammation and remodeling of the airway. However, the roles and regulation of MMPs in human nasal epithelial cells (HNECs) after RSV infection remain unclear. To investigate the regulation of MMP induced after RSV infection in HNECs, an RSV-infected model of HNECs in vitro was used. It was found that mRNA of MMP-10 was markedly increased in HNECs after RSV infection, together with induction of mRNAs of MMP-1, -7, -9, and -19. The amount of MMP-10 released from HNECs was also increased in a time-dependent manner after RSV infection as was that of chemokine RANTES. The upregulation of MMP-10 in HNECs after RSV infection was prevented by inhibitors of NF-κB and pan-PKC with inhibition of RSV replication, whereas it was prevented by inhibitors of JAK/STAT, MAPK, and EGF receptors without inhibition of RSV replication. In lung tissue of an infant with severe RSV infection in which a few RSV antibody-positive macrophages were observed, MMP-10 was expressed at the apical side of the bronchial epithelial cells and alveolar epithelial cells. In conclusion, MMP-10 induced by RSV infection in HNECs is regulated via distinct signal transduction pathways with or without relation to RSV replication. MMP-10 may play an important role in the pathogenesis of RSV diseases and it has the potential to be a novel marker and therapeutic target for RSV infection.

  18. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

    PubMed Central

    Messacar, Kevin; Pastula, Daniel M.; Robinson, Christine C.; Leshem, Eyal; Sejvar, James J.; Nix, W. Allan; Oberste, M. Steven; Feikin, Daniel R.; Dominguez, Samuel R.

    2016-01-01

    During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  19. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

    PubMed

    Aliabadi, Negar; Messacar, Kevin; Pastula, Daniel M; Robinson, Christine C; Leshem, Eyal; Sejvar, James J; Nix, W Allan; Oberste, M Steven; Feikin, Daniel R; Dominguez, Samuel R

    2016-08-01

    During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  20. Acute middle East respiratory syndrome coronavirus infection in livestock Dromedaries, Dubai, 2014.

    PubMed

    Wernery, Ulrich; Corman, Victor M; Wong, Emily Y M; Tsang, Alan K L; Muth, Doreen; Lau, Susanna K P; Khazanehdari, Kamal; Zirkel, Florian; Ali, Mansoor; Nagy, Peter; Juhasz, Jutka; Wernery, Renate; Joseph, Sunitha; Syriac, Ginu; Elizabeth, Shyna K; Patteril, Nissy Annie Georgy; Woo, Patrick C Y; Drosten, Christian

    2015-06-01

    Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother-calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.

  1. Should teeth be extracted immediately in the presence of acute infection?

    PubMed

    Johri, Ankur; Piecuch, Joseph F

    2011-11-01

    Immediate extraction of teeth in the setting of an acute infection has shown to be beneficial for many reasons. It results in faster resolution of the infection, decreased pain, and earlier return of function and oral intake. The risk of seeding the infection into deeper spaces by performing immediate extraction is low.

  2. Three atypical lethal cases associated with acute Zika virus infection in Suriname.

    PubMed

    Zonneveld, Rens; Roosblad, Jimmy; Staveren, Jan Willem van; Wilschut, Jan C; Vreden, Stephen G S; Codrington, John

    2016-01-01

    Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks.

  3. Three atypical lethal cases associated with acute Zika virus infection in Suriname.

    PubMed

    Zonneveld, Rens; Roosblad, Jimmy; Staveren, Jan Willem van; Wilschut, Jan C; Vreden, Stephen G S; Codrington, John

    2016-01-01

    Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks. PMID:27630820

  4. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  5. Acute otitis media and respiratory viruses.

    PubMed

    Bulut, Yunus; Güven, Mehmet; Otlu, Bariş; Yenişehirli, Gülgün; Aladağ, Ibrahim; Eyibilen, Ahmet; Doğru, Salim

    2007-03-01

    The present study was performed to elucidate the clinical outcome, and etiology of acute otitis media (AOM) in children based on virologic and bacteriologic tests. The study group consisted of 120 children aged 6 to 144 months with AOM. Middle ear fluid (MEF) was tested for viral pathogens by reverse transcriptase polymerase chain reaction (RT-PCR) and for bacteria by gram-staining and culture. Clinical response was assessed on day 2 to 4, 11 to 13, 26 to 28. Respiratory viruses were isolated in 39 patients (32.5%). Respiratory syncytial virus (RSV) (46.5%) was the most common virus identified in MEF samples, followed by human rhinovirus (HRV) (25.6%), human coronavirus (HCV) (11.6%), influenza (IV) type A (9.3%), adenovirus type sub type A (AV) (4%), and parainfluenza (PIV) type -3 (2%) by RT-PCR. In total 69 bacterial species were isolated from 65 (54.8%) of 120 patients. Streptococcus pneumoniae (S. pneumoniae) was the most frequently isolated bacteria. Viral RNA was detected in 31 (56.3%) of 55 bacteria-negative specimens and in 8 (12.3%) of 65 bacteria-positive MEF samples. No significant differences were found between children representing viral infection alone, combined viral and bacterial infection, bacterial infection alone, and neither viral nor bacterial infection, regarding clinical cure, relapse and reinfection rates. A significantly higher rate of secretory otitis media (SOM) was observed in alone or combined RSV infection with S. pneumonia or Haemophilus influenzae (H. influenzae) than in other viruses infection. Conclusion. This study provides information about etiologic agents and diagnosis of AOM in Turkish children. The findings highlight the importance of common respiratory viruses and bacterial pathogens, particularly RSV, HRV, S. pneumoniae and H. influenzae, in predisposing to and causing AOM in children.

  6. Acute respiratory infections in Pakistan: have we made any progress?

    PubMed

    Khan, Tauseef Ahmad; Madni, Syed Ali; Zaidi, Anita K M

    2004-07-01

    Acute respiratory infections (ARI) are the leading cause of death in young children in Pakistan, responsible for 20-30% of all child deaths under age 5 years. This paper summarizes the research and technical development efforts over the last 15 years which have contributed to improving the effectiveness of the case management strategy to reduce mortality from pneumonia in children in Pakistan. Community intervention is viable, effective and practical. Rising antimicrobial resistance among commonly used and low-cost oral agents is of significant concern. Appropriate monitoring and evaluation of the impact of the ARI control programme is lacking. Lack of funding for programmatic activities, lack of coordination with other child survival programs, inadequate training for community health workers and general practitioners in the private sector, lack of public awareness about seeking timely and appropriate care, and insufficient planning and support for ARI programmatic activities at provincial and district levels are major hindrances in decreasing the burden of ARI in the country. The recent introduction of the community-based Lady Health Worker (LHW) Programme and WHO and UNICEF-sponsored integrated management of childhood illness initiative present ideal opportunities for re-emphasizing early case detection and appropriate case management of ARI. Ultimately, focusing on preventive strategies such as improving nutrition, reducing indoor pollution, improving mass vaccination, as well as introduction of new vaccines effective against important respiratory pathogens will likely have the most impact on reducing severe ARI and deaths from severe disease. PMID:15279753

  7. Induction and Antagonism of Antiviral Responses in Respiratory Syncytial Virus-Infected Pediatric Airway Epithelium

    PubMed Central

    Villenave, Rémi; Broadbent, Lindsay; Douglas, Isobel; Lyons, Jeremy D.; Coyle, Peter V.; Teng, Michael N.; Tripp, Ralph A.; Heaney, Liam G.; Shields, Michael D.

    2015-01-01

    ABSTRACT Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well-differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda 1 (IFN-λ1)/interleukin-29 (IL-29). In contrast, type I IFNs were not detected following RSV infection of WD-PBECs. IFN responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV nonstructural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic. IMPORTANCE Most respiratory viruses target airway epithelium for infection and replication, which is central to causing disease. However, for most human viruses we have a poor understanding of their interactions with human airway epithelium. Respiratory syncytial virus (RSV) is the most important viral pathogen of young infants. To help understand RSV interactions with pediatric

  8. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  9. Acute Necrotizing Pancreatitis Associated with Mycoplasma pneumoniae Infection in a Child.

    PubMed

    Yang, Aram; Kang, Ben; Choi, So Yoon; Cho, Joong Bum; Kim, Yae-Jean; Jeon, Tae Yeon; Choe, Yon Ho

    2015-09-01

    Mycoplasma pneumoniae is responsible for approximately 20% to 30% of community-acquired pneumonia, and is well known for its diverse extrapulmonary manifestations. However, acute necrotizing pancreatits is an extremely rare extrapulmonary manifestation of M. pneumoniae infection. A 6-year-old girl was admitted due to abdominal pain, vomiting, fever, and confused mentality. Acute necrotizing pancreatitis was diagnosed according to symptoms, laboratory test results, and abdominal computed tomography scans. M. pneumoniae infection was diagnosed by a 4-fold increase in antibodies to M. pneumoniae between acute and convalescent sera by particle agglutination antibody assay. No other etiologic factors or pathogens were detected. Despite the occurrence of a large infected pseudocyst during the course, the patient was able to discharge without morbidity by early aggressive supportive care. This is the first case in Korea of a child with acute necrotizing pancreatitis associated with M. pneumoniae infection. PMID:26473143

  10. Enhancing the detection and management of acute hepatitis C virus infection.

    PubMed

    Martinello, Marianne; Matthews, Gail V

    2015-10-01

    Acute HCV infection refers to the 6-month period following infection acquisition, although this definition is somewhat arbitrary. While spontaneous clearance occurs in approximately 25%, the majority will develop chronic HCV infection with the potential for development of cirrhosis, end stage liver disease and hepatocellular carcinoma. Detection of acute HCV infection has been hampered by its asymptomatic or non-specific presentation, lack of specific diagnostic tests and the inherent difficulties in identifying and following individuals at highest risk of transmitting and acquiring HCV infection, such as people who inject drugs (PWID). However, recognition of those with acute infection may have individual and population level benefits and could represent an ideal opportunity for intervention. Despite demonstration that HCV treatment is feasible and successful in PWID, treatment uptake remains low with multiple barriers to care at an individual and systems level. Given the burden of HCV-related disease among PWID, strategies to enhance HCV assessment, treatment and prevention in this group are urgently needed. As the therapeutic landscape of chronic HCV management is revolutionised by the advent of simple, highly effective directly-acting antiviral (DAA) therapy, similar opportunities may exist in acute infection. This review will discuss issues surrounding improving the detection and management of acute HCV infection, particularly in PWID. PMID:26254495

  11. Acute respiratory infections: the forgotten pandemic. Communiqué from the International Conference on Acute Respiratory Infections, held in Canberra, Australia, 7-10 July 1997.

    PubMed

    1998-01-01

    Acute respiratory infections kill 4 million children every year in developing countries, and most of these deaths are caused by pneumonia. This huge loss of life goes virtually unnoticed, despite the fact that we have two very effective ways of preventing many of the deaths from pneumonia: Haemophilus influenzae type b vaccine, and standardised antibiotic treatment regimens. Although H. influenzae type b vaccine has virtually eliminated diseases caused by this organism in children in developed countries, failure to appreciate the importance of this organism and the high cost of the vaccine has meant that it has not been used in developing countries; urgent steps need to be taken to ensure that children in developing countries receive H. influenzae vaccine. Streptococcus pneumoniae is a major cause of fatal pneumonia in developing countries. Controlled trials are needed to define the role of unconjugated 23-valent S. pneumoniae vaccine, and the new conjugate vaccine must be made available to children in developing countries soon after it is licensed. The World Health Organization has developed simple and effective guidelines for the treatment of pneumonia which have been incorporated into its Integrated Management of Childhood Illness strategy, and this programme should be strongly supported. In developed countries, acute respiratory infections are the leading cause of morbidity. The cost of these infections is enormous, because of lost earnings and the cost of treatment. There is an urgent need for systematic evaluation of existing knowledge about acute respiratory infections in developed countries, so that this knowledge can be applied to prevention and treatment. Approximately 75% of antibiotics are prescribed for acute respiratory infections, and many of these prescriptions are unnecessary. Unnecessary use of antibiotics is very expensive, and it has contributed to the rapid increase in resistance which has already made some bacteria resistant to all antibiotics

  12. Disseminated fungal infection complicated with pulmonary haemorrhage in a case of acute myeloid leukaemia

    PubMed Central

    Thulkar, S; Sharma, S; Das, P; Kumar, L

    2000-01-01

    Pulmonary haemorrhage is a common necropsy finding in acute leukaemia, however, it is rarely diagnosed during life. A man with acute myeloid leukaemia is reported who presented with disseminated fungal infection, anaemia, thrombocytopenia, and subconjuctival and petechial haemorrhages. During the course of the patient's illness, the chest infection was complicated with bilateral pulmonary haemorrhage. The diagnosis of pulmonary haemorrhage was based on characteristic clinical and radiological findings. The patient improved on treatment.


Keywords: leukaemia; pulmonary infiltrate; haemorrhage PMID:11060145

  13. A duplex recombinant viral nucleoprotein microbead immunoassay for simultaneous detection of seroresponses to human respiratory syncytial virus and metapneumovirus infections.

    PubMed

    Zhang, Yange; Brooks, W Abdullah; Goswami, Doli; Rahman, Mustafizur; Luby, Stephen P; Erdman, Dean D

    2014-09-01

    Serologic diagnosis of human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) infections has been shown to complement virus detection methods in epidemiologic studies. Enzyme immunoassays (EIAs) using cultured virus lysate antigens are often used to diagnose infection by demonstration of a ≥4-fold rises in antibody titer between acute and convalescent serum pairs. In this study, hRSV and hMPV nucleocapsid (recN) proteins were expressed in a baculovirus system and their performance compared with virus culture lysate antigen in EIAs using paired serum specimens collected from symptomatic children. The recN proteins were also used to develop a duplex assay based on the Luminex microbead-based suspension array technology, where diagnostic rises in antibody levels could be determined simultaneously at a single serum dilution. Antibody levels measured by the recN and viral lysate EIAs correlated moderately (hRSV, r(2)=0.72; hMPV, r(2)=0.76); the recN EIAs identified correctly 35 of 37 (94.6%) and 48 of 50 (96%) serum pairs showing diagnostic antibody rises by viral lysate EIAs. Purified recN proteins were then coupled to microbeads and serum pairs were tested at a single dilution on a Luminex MAGPIX(®) analyzer. The duplex recN assay identified correctly 33 of 39 (85%) and 41 of 47 (86.7%) serum pairs showing diagnostic rises to hRSV and hMPV, respectively. The recN assay permits simultaneous testing for acute hRSV and hMPV infections and offers a platform for expanded multiplexing of other respiratory virus assays.

  14. Lipschütz acute vulval ulcers associated with primary cytomegalovirus infection.

    PubMed

    Martín, José M; Godoy, Rosa; Calduch, Luis; Villalon, Guillermo; Jordá, Esperanza

    2008-01-01

    A previously healthy 16-year-old girl presented with painful acute genital ulcers that appeared in the context of a primary cytomegalovirus infection. Complementary examinations ruled out both venereal disease and other usual causes of genital ulcerations, and the lesions resolved in < 2 weeks with no sequelae or later recurrences. Cytomegalovirus disease should be considered in the screening of acute vulval ulcers.

  15. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

    PubMed Central

    2013-01-01

    Background Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Methods Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient’s condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Results Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. Discussion In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Conclusion Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission. PMID:24180319

  16. A qualitative study of patients' perceptions of acute infective conjunctivitis.

    PubMed Central

    Everitt, Hazel; Kumar, Satinder; Little, Paul

    2003-01-01

    BACKGROUND: Acute infective conjunctivitis is a self-limiting condition that commonly presents to primary care. Patients' understanding of conjunctivitis, their reasons for attendance, and their responses to different management strategies, are unknown. AIM: To explore patients' understanding of conjunctivitis and its management. DESIGN OF STUDY: Qualitative study using semi-structured one-to-one interviews. SETTING: Three general practices in Hampshire and Wiltshire. METHOD: Twenty-five patients presenting with conjunctivitis at their general practices were interviewed. Main outcome measures were patients' perceptions of conjunctivities, their experience and knowledge of the disease, beliefs regarding treatment, and their responses to different management strategies and a patient information leaflet. RESULTS: Patients regarded conjunctivitis as a minor illness, although some considered it might become more serious if not treated. Nearly all were confident at recognising conjunctivitis. They stated a preference for not taking medication, but believed that conjunctivitis would not clear up without treatment. However, they were open to alternative management approaches; for example, the delayed prescription approach, because they trusted their general practitioners' (GPs') judgement. Once they were aware of the self-limiting nature of conjunctivitis, patients felt they would prefer to wait a few days to see if the condition improved before seeking medical advice, even if this resulted in a few more days of symptoms. CONCLUSION: Patients who attend their general practices with conjunctivitis present for treatment because they are not aware of its self-limiting nature. Providing patients with this information may enable patients, enhance self-management, and reduce the use of topical antibiotics and the demand for urgent general practice appointments. PMID:12564275

  17. Pancreatitis and cholecystitis in primary acute symptomatic Epstein-Barr virus infection - Systematic review of the literature.

    PubMed

    Kottanattu, Lisa; Lava, Sebastiano A G; Helbling, Rossana; Simonetti, Giacomo D; Bianchetti, Mario G; Milani, Gregorio P

    2016-09-01

    Acute pancreatitis and acalculous cholecystitis have been occasionally reported in primary acute symptomatic Epstein-Barr virus infection. We completed a review of the literature and retained 48 scientific reports published between 1966 and 2016 for the final analysis. Acute pancreatitis was recognized in 14 and acalculous cholecystitis in 37 patients with primary acute symptomatic Epstein-Barr virus infection. In all patients, the features of acute pancreatitis or acalculous cholecystitis concurrently developed with those of primary acute symptomatic Epstein-Barr virus infection. Acute pancreatitis and acalculous cholecystitis resolved following a hospital stay of 25days or less. Acalculous cholecystitis was associated with Gilbert-Meulengracht syndrome in two cases. In conclusion, this thorough analysis indicates that acute pancreatitis and acalculous cholecystitis are unusual but plausible complications of primary acute symptomatic Epstein-Barr virus infection. Pancreatitis and cholecystitis deserve consideration in cases with severe abdominal pain. These complications are usually rather mild and resolve spontaneously without sequelae. PMID:27434148

  18. Co-immunization with virus-like particle and DNA vaccines induces protection against respiratory syncytial virus infection and bronchiolitis

    PubMed Central

    Hwang, Hye Suk; Kwon, Young-Man; Lee, Jong Seok; Yoo, Si-Eun; Lee, Yu-Na; Ko, Eun-Ju; Kim, Min-Chul; Cho, Min-Kyoung; Lee, Young-Tae; Jung, Yu-Jin; Lee, Ji-Yun; Li, Jian Dong; Kang, Sang-Moo

    2014-01-01

    This study demonstrates that immunization with non-replicating virus-like particle (FFG VLP) containing RSV F and G glycoproteins together with RSV F DNA induced T helper type 1 antibody responses to RSV F similar to live RSV infection. Upon RSV challenge 21 weeks after immunization, FFG VLP vaccination induced protection against RSV infection as shown by clearance of lung viral loads, and the absence of eosinophil infiltrates, and did not cause lung pathology. In contrast, formalin-inactivated RSV (FI-RSV) vaccination showed significant pulmonary eosinophilia, severe mucus production, and extensive histopathology resulting in a hallmark of pulmonary pathology. Substantial lung pathology was also observed in mice with RSV re-infections. High levels of systemic and local inflammatory cytokine-secreting cells were induced in mice with FI-RSV but not with FFG VLP immunization after RSV challenge. Therefore, the results provide evidence that recombinant RSV FFG VLP vaccine can confer long-term protection against RSV without causing lung pathology. PMID:25110201

  19. Cryptosporidiosis in rhesus macaques challenged during acute and chronic phases of SIV infection.

    PubMed

    Singh, Inderpal; Carville, Angela; Tzipori, Saul

    2011-09-01

    The intestinal immune dysfunction due to loss of mucosal and peripheral CD4(+) T cells in individuals with HIV/AIDS is presumably responsible for the establishment of persistent cryptosporidiosis. Simian immunodeficiency virus (SIV)-infected macaques were used to investigate the phase/timing in SIV infection, which permits a self-limiting Cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. Two groups of SIV-infected macaques were challenged with C. parvum; one was challenged during the acute SIV infection phase (2 weeks post-SIV infection) and the second was challenged during the chronic SIV phase (CD4 counts 200-500 cells/μl of blood). Samples (fecal, blood, biopsy, and necropsy) were collected at different time points after infection to correlate the progression of disease with the immune status of the animals. All seven SIV-infected macaques challenged during the acute phase of SIV infection became persistently infected and excreted oocysts for 1-4 months. However, four of the six in the chronic SIV phase became infected with cryptosporidiosis, of which one survived 2 weeks and one became naturally infected. Sequential analysis of CD4(+) in blood and intestines of coinfected macaques exhibited pronounced losses of CD4 T cells during the first 2 weeks after SIV infection, followed by transient rebound of CD4 T cells in the gut after C. parvum infection, and then a gradual loss over subsequent months. Persistent cryptosporidiosis was more consistently induced during the acute SIV phase indicating that profound viral damage to gut lymphoid tissue during the acute phase was more conducive, compared with the chronic phase, to establishing persistent cryptosporidiosis than low circulating CD4 T cells.

  20. 78 FR 63220 - Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... drugs to treat acute bacterial skin and skin structure infections (ABSSSI). This guidance finalizes...

  1. Chikungunya virus infection amongst the acute encephalitis syndrome cases in West Bengal, India.

    PubMed

    Taraphdar, D; Roy, B K; Chatterjee, S

    2015-02-01

    Chikungunya virus (CHIKV) infection from the acute encephalitis syndrome cases is an uncommon form and has been observed in the year 2010-11 from West Bengal, India. The case-1 and case-2 had the acute encephalitis syndrome; case-3 was of acute disseminated encephalomyelitis whereas the case-4 had the symptoms of meningo-encephalopathy with bulbar involvement. We are reporting four cases with neurological complications involving central nervous system (CNS) due to CHIKV infection from this state for the first time. The virus has spread almost every districts of this state rapidly. At this stage, these cases are public health threat.

  2. Large-scale seroprevalence analysis of human metapneumovirus and human respiratory syncytial virus infections in Beijing, China

    PubMed Central

    2011-01-01

    Background Human metapneumovirus (hMPV), a recently identified virus, causes acute respiratory tract infections (ARTIs) in infants and children. However, studies on the seroepidemeology of hMPV are very limited in China. To assess the seroprevalence of hMPV infection in China, we tested a total of 1,156 serum specimens for the presence of anti-hMPV IgG antibody in children and adults free of acute respiratory illness in Beijing, China by using hMPV nucleocapsid (N) protein as an antigen. As a control, we used the human serum antibody against the N protein of human respiratory syncytial virus (hRSV), the most important viral agent responsible for ARIs in children. Results The seropositive rate for hMPV increased steadily with age from 67% at 1-6 mo to 100% at age 20. However, the rate dropped slightly between 6 mo and 1 yr of age. The seropositive rate for hRSV also increased steadily with age from 71% at 1-6 mo to 100% at age 20. In children aged six months to six years, the seropositive rates for the anti-hRSV IgG antibody were significantly higher than those for hMPV. Additionally, IgG antibody titers to hMPV and hRSV were significantly higher in adults than in young children. Consistent with the seropositive rates, the geometric mean titer of anti-hMPV IgG antibody was lower than that of anti-hRSV IgG antibody in children aged six months to six years. Conclusions Our results indicate that similar to hRSV, exposure to hMPV is ubiquitous in the Beijing population. However, the seroprevalence of anti-hMPV IgG antibody is lower than that of hRSV in children between six months and six years old, which suggests a different number of repeat infections or a different response to infections. PMID:21310026

  3. Respiratory syncytial virus infection in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory syncytial virus (bRSV) is a cause of respiratory disease in cattle world-wide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bRSV infection can predispose calves to secondary bacterial infection by org...

  4. Enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis in 7 dogs from Saskatchewan.

    PubMed

    Kjaergaard, Astrid B; Carr, Anthony P; Gaunt, M Casey

    2016-09-01

    Seven dogs diagnosed with enteropathogenic Escherichia coli (EPEC) infection in association with acute gastroenteritis are described. Disease severity ranged from mild in adults to fatal disease in young dogs. Enteropathogenic E. coli infection should be considered as a possible differential diagnosis in dogs with diarrhea. PMID:27587889

  5. Development of Chronic and Acute Golden Syrian Hamster Infection Models with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several species of Leptospira. Onset of an acute, lethal infection following infection with several pathogenic Leptospira species has been widely adopted for vaccine testing. An important exceptio...

  6. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

    PubMed Central

    O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  7. Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

    PubMed

    Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

    2016-01-01

    Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

  8. Acute hepatitis C virus infection related to capillary blood glucose meter

    PubMed Central

    Inayat, Faisal; Rai, Aitzaz BinSultan

    2016-01-01

    Hepatitis C virus (HCV) infects an estimated 130-150 million people worldwide, becoming the major cause of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver transplantation. There are various preventable modes of transmission of HCV infection, including needlestick and sharps injuries. However, HCV infection secondary to needlestick injury by a capillary blood glucose meter (CBGM) lancet has not been previously well reported. We describe an unusual case of a 25-year-old male medical student, acquiring acute HCV infection with a lancing device of CBGM. The source patient was a 54-year-old diabetic male with positive anti-HCV test results. In our patient, after 3 months of initial exposure, a standard set of investigations confirmed the diagnosis of acute HCV infection with the same genotype (3a) as the source. The CBGM, as in our case, may have a role in the transmission of HCV infection warranting radical advancements in diabetes screening and monitoring technology. PMID:26739982

  9. Impact of early cART in the gut during acute HIV infection

    PubMed Central

    Deleage, Claire; Schuetz, Alexandra; Alvord, W. Gregory; Johnston, Leslie; Hao, Xing-Pei; Morcock, David R.; Rerknimitr, Rungsun; Fletcher, James L.K.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Dewar, Robin; McCune, Joseph M.; Robb, Merlin; Kim, Jerome H.; Schacker, Timothy W.; Hunt, Peter; Lifson, Jeffrey D.; Ananworanich, Jintanat

    2016-01-01

    Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (Mx1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART. PMID:27446990

  10. Impact of early cART in the gut during acute HIV infection

    PubMed Central

    Deleage, Claire; Schuetz, Alexandra; Alvord, W. Gregory; Johnston, Leslie; Hao, Xing-Pei; Morcock, David R.; Rerknimitr, Rungsun; Fletcher, James L.K.; Puttamaswin, Suwanna; Phanuphak, Nittaya; Dewar, Robin; McCune, Joseph M.; Sereti, Irini; Robb, Merlin; Kim, Jerome H.; Schacker, Timothy W.; Hunt, Peter; Lifson, Jeffrey D.; Ananworanich, Jintanat; Estes, Jacob D.

    2016-01-01

    Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART. PMID:27446990

  11. Routine Laboratory Screening for Acute and Recent HIV Infection in Lima, Peru

    PubMed Central

    Clark, Jesse L.; Segura, Eddy R.; Montano, Silvia M.; Leon, Segundo R.; Kochel, Tadeusz; Salvatierra, Hector J.; Alcantara, Jorge; Cáceres, Carlos F.; Coates, Thomas J.; Klausner, Jeffrey D.

    2011-01-01

    Background Prior to implementing screening programs for acute HIV infection in developing countries, key issues including cost, feasibility, and public health impact must be determined. We compared fourth-generation enzyme immunoassay (EIA) with pooled HIV-1 RNA assays for the detection of acute and early HIV infection in counseling and testing populations in Lima, Peru. Methods Adults presenting for HIV testing at designated clinics in Lima-Callao, Peru were offered additional screening for acute HIV infection. All serum samples were tested with fourth-generation Ag/Ab EIA and confirmed by line immunoassay (LIA). Negative specimens were combined into 50-sample pools for HIV-1 RNA screening by PCR analysis in standard pooling algorithms. RNA-positive samples were re-tested with a third-generation EIA to evaluate the relative sensitivity of standard testing procedures. Results Between 2007 and 2008 we recruited 1,191 participants. The prevalence of HIV infection was 3.2% (38/1191; 2.2-4.2%) overall and 10.6% (25/237; CI=6.6-14.5%) among men who reported sex with men (MSM). The prevalence of acute or recent HIV infection was 0.2% (CI=0-0.4%) overall and 0.8% (CI=0-2.0%) among MSM. Compared with third generation EIA testing, both fourth generation EIA and RNA PCR increased the rate of HIV case identification by 5.6% overall and by 8.0% within the subpopulation of MSM. Conclusions Screening for acute HIV infection within Peru's resource-limited public health system was acceptable and detected a high prevalence of acute and recent HIV infection among MSM. Additional efforts are needed to screen for and prevent transmission of HIV among MSM in Peru during the acute seroconversion stage. PMID:21113069

  12. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    PubMed

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  13. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  14. Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

    PubMed Central

    Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

    2015-01-01

    Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (dacute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0

  15. The use of health economics to guide drug development decisions: Determining optimal values for an RSV-vaccine in a model-based scenario-analytic approach.

    PubMed

    Bos, J M; Rietveld, E; Moll, H A; Steyerberg, E W; Luytjes, W; Wilschut, J C; de Groot, R; Postma, M J

    2007-09-28

    Health-economic modelling is useful for assessing the clinical requirements and impact of new vaccines. In this study, we estimate the impact of potential vaccination for respiratory syncytial virus (RSV) of infants in the Netherlands. A decision analysis model was employed using seasonal data from a cohort of children (1996-1997 through 1999-2000) to assess hospitalisation, costs and impact of vaccination. Yearly, an estimated 3670 infants are hospitalised with RSV-infection in the Netherlands, vaccination protecting infants from 3 months of life onwards could prevent approximately 1000-3000 hospitalisations, depending on the effectiveness of the potential vaccine. Additionally, vaccination could prevent a major share of RSV-related costs. Comparison of the calculated break-even prices with the average price of recently introduced vaccines indicates that pricing for a potential RSV-vaccine most likely allows for only a single dose vaccination or several doses at a relatively low price per dose in order to achieve cost savings. However, if evidence on relevant RSV-related mortality would become available, higher pricing would be justified, while still remaining below accepted thresholds for cost-effectiveness.

  16. Epidemiology of viral infections in Singapore.

    PubMed

    Doraisingham, S; Goh, K T; Ling, A E

    1987-04-01

    As Singapore is a densely populated island, and also a major air and sea port, the importation and dissemination of viral infections is facilitated. Respiratory viral infections have the highest prevalence rates, influenza and respiratory syncytial virus (RSV) being the most important ones. Seasonal variation occurs with influenza, RSV and parainfluenza virus type 1 infections. The age distribution and clinical picture associated with infections due to the various respiratory viruses are similar to those reported in other countries. Carrier rates for hepatitis B are high, but differ in the three major ethnic groups, vertical transmission from infected mothers being an important mode of transmission. Outbreaks of hepatitis A have been associated with the consumption of inadequately cooked shellfish. Cytomegalovirus and Epstein-Barr virus infections are acquired early in life and herpes simplex, more slowly. Genital herpes is increasing in incidence. Coxsackievirus A24 and enterovirus 70 have caused major epidemics of acute haemorrhagic conjunctivitis at 5-10 year intervals. Outbreaks of hand, foot and mouth disease due to coxsackievirus A16 have also occurred. With the declining incidence of dengue haemorrhagic fever, the percentage of susceptible individuals in children under 10 years, has increased markedly. Epidemics of rubella which occurred during the past decade, together with immunisation, have increased herd immunity to this virus. PMID:2825585

  17. Epidemiology of viral infections in Singapore.

    PubMed

    Doraisingham, S; Goh, K T; Ling, A E

    1987-04-01

    As Singapore is a densely populated island, and also a major air and sea port, the importation and dissemination of viral infections is facilitated. Respiratory viral infections have the highest prevalence rates, influenza and respiratory syncytial virus (RSV) being the most important ones. Seasonal variation occurs with influenza, RSV and parainfluenza virus type 1 infections. The age distribution and clinical picture associated with infections due to the various respiratory viruses are similar to those reported in other countries. Carrier rates for hepatitis B are high, but differ in the three major ethnic groups, vertical transmission from infected mothers being an important mode of transmission. Outbreaks of hepatitis A have been associated with the consumption of inadequately cooked shellfish. Cytomegalovirus and Epstein-Barr virus infections are acquired early in life and herpes simplex, more slowly. Genital herpes is increasing in incidence. Coxsackievirus A24 and enterovirus 70 have caused major epidemics of acute haemorrhagic conjunctivitis at 5-10 year intervals. Outbreaks of hand, foot and mouth disease due to coxsackievirus A16 have also occurred. With the declining incidence of dengue haemorrhagic fever, the percentage of susceptible individuals in children under 10 years, has increased markedly. Epidemics of rubella which occurred during the past decade, together with immunisation, have increased herd immunity to this virus.

  18. Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

    PubMed Central

    McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

    2011-01-01

    Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

  19. Regulatory T cells are decreased in acute RHDV lethal infection of adult rabbits.

    PubMed

    Teixeira, Luzia; Marques, Raquel M; Aguas, Artur P; Ferreira, Paula G

    2012-08-15

    Rabbit hemorrhagic disease virus (RHDV) is the etiologic agent of rabbit hemorrhagic disease (RHD), an acute lethal infection that kills 90% of adult rabbits due to severe acute liver inflammation. Interestingly, young rabbits are naturally resistant to RHDV infection. Here, we have compared naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) between young and adult rabbits after infection by RHDV. The number and frequency of Tregs was decreased in the spleen of adult rabbits 24h after the RHDV infection; this was in contrast with the unchanged number and frequency of splenic Tregs found in young rabbits after the same infection. Also, serum levels of IL-10 and TGF-β were enhanced in the infected adult rabbits whereas no alteration was observed in infected young rabbits. However, this increase is accompanied by a burst of pro-inflammatory cytokines, but seems not able to prevent the death of the animals with severe acute liver inflammation in few days after infection. Since Tregs downregulate inflammation, we conclude that their decrease may contribute to the natural susceptibility of adult rabbits to RHDV infection.

  20. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  1. Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

    PubMed Central

    Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Justicia, Antonio; Rivero-Calle, Irene; Sumner, Edward; Fink, Colin

    2016-01-01

    Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. PMID:27096199

  2. Severe Plasmodium falciparum infection mimicking acute myocardial infarction.

    PubMed

    Sulaiman, Helmi; Ismail, Muhammad Dzafir; Jalalonmuhali, Maisarah; Atiya, Nadia; Ponnampalavanar, Sasheela

    2014-08-30

    This case report describes a case of presumed acute myocardial infarction in a returned traveler who was later diagnosed to have severe malaria. Emergency coronary angiography was normal and subsequent peripheral blood film was positive for Plasmodium falciparum.

  3. Enzyme-linked immunosorbent assay for detection of respiratory syncytial virus infection: development and description.

    PubMed Central

    Hendry, R M; McIntosh, K

    1982-01-01

    An indirect enzyme-linked immunosorbent assay for detection of respiratory syncytial virus (RSV) antigens was developed, using commercially available antisera. Horse anti-RSV and calf antiserum to bovine RSV were used as capture and detector antibodies, respectively. The assay could detect as few as 50 PFU of unpurified RSV per ml in infected cell culture supernatant fluids and as little as 10 ng of affinity-purified RSV antigen per ml. No cross-reactions were observed with heterologous virus types. Freeze-thaw treatment had no effect on RSV enzyme-linked immunosorbent assay titers, but viral transport medium inhibited RSV enzyme-linked immunosorbent assay titers from 10- to 100-fold. The assay can be easily performed in 24 h and is a sensitive and specific method for the detection of RSV antigens. PMID:6749894

  4. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    PubMed Central

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection. PMID:27621819

  5. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    PubMed Central

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection.

  6. Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru

    PubMed Central

    Wu, Andrew; Budge, Philip J.; Williams, John; Griffin, Marie R.; Edwards, Kathryn M.; Johnson, Monika; Zhu, Yuwei; Hartinger, Stella; Verastegui, Hector; Gil, Ana I.; Lanata, Claudio F.; Grijalva, Carlos G.

    2015-01-01

    Introduction The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. Materials and Methods We conducted a prospective, household-based cohort study of children aged <3 years living in remote rural highland communities in San Marcos, Cajamarca, Peru. Acute respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), were monitored through weekly household visits from March 2009 through September 2011. Nasal swabs collected during ARI/LRTI were tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. Incidence rates and rate ratios were calculated using mixed effects Poisson regression. Results Among 892 enrolled children, incidence rates of RSV and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. The proportions of RSV and MPV ARI that presented as LRTI were 12.5% and 8.9%, respectively. Clinic visits for ARI and hospitalizations were significantly more frequent (all p values <0.05) among children with RSV (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when compared with other viral infections (23% and 0.7%) and infections without virus detected (24% and 0.6%). In multivariable analysis, risk factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). Conclusion In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional

  7. The acute phase response in parasite infection. Nippostrongylus brasiliensis in the mouse.

    PubMed Central

    Lamontagne, L R; Gauldie, J; Befus, A D; McAdam, K P; Baltz, M L; Pepys, M B

    1984-01-01

    Systemic inflammatory reactions are a prominent feature of many parasitic infections and the cellular and humoral components of the acute phase reaction may have an impact on the host-parasite relationship. We examined serum changes of four acute phase reactants: alpha 1-proteinase inhibition (alpha 1Pi); complement C3; serum amyloid A protein (SAA); and serum amyloid P component (SAP), in mice undergoing a primary infection with Nippostrongylus brasiliensis. SAA and SAP showed changes within the first 2 days of infection indicating the presence of an acute phase response associated with inflammation in the lung. Alpha 1Pi and C3 serum levels were not altered. However, all four acute phase reactants were synthesized in greater amounts by primary cultures of hepatocytes taken from infected animals at this time. Subsequently, as parasite-mediated inflammatory changes occur in the gut, both serum and hepatocyte cultures demonstrate an acute inflammatory response in all four reactants. It is proposed that the early reaction between parasites and macrophage/monocyte lead to the release of a mediator of inflammation which initiates the hepatocyte response. In this infection, at least one of the APR is shown to localize to the site of inflammation influencing the host-parasite relationship. Images Figure 2 Figure 3 PMID:6204934

  8. NITROTYROSINE ATTENUATES RSV-INDUCED INFLAMMATION IN AIRWAY EPITHELIAL CELLS

    EPA Science Inventory

    Nitrotyrosine attenuates RSV-induced inflammation in airway epithelial cells. Joleen Soukup, Zuowei Li, Susanne Becker and Yuh-Chin Huang. NHEERL, ORD, USEPA, RTP, North Carolina, CEMALB, University of North Carolina, Chapel Hill, North Carolina

    Nitrotyrosine (NO2Tyr) is a...

  9. Hospital Epidemiology and Infection Control in Acute-Care Settings

    PubMed Central

    Sydnor, Emily R. M.; Perl, Trish M.

    2011-01-01

    Summary: Health care-associated infections (HAIs) have become more common as medical care has grown more complex and patients have become more complicated. HAIs are associated with significant morbidity, mortality, and cost. Growing rates of HAIs alongside evidence suggesting that active surveillance and infection control practices can prevent HAIs led to the development of hospital epidemiology and infection control programs. The role for infection control programs has grown and continues to grow as rates of antimicrobial resistance rise and HAIs lead to increasing risks to patients and expanding health care costs. In this review, we summarize the history of the development of hospital epidemiology and infection control, common HAIs and the pathogens causing them, and the structure and role of a hospital epidemiology and infection control program. PMID:21233510

  10. Prevalence of antibiotic use for pediatric acute upper respiratory tract infections in Korea.

    PubMed

    Shin, Sun Mi; Shin, Ju-Young; Kim, Mi Hee; Lee, Shin Haeng; Choi, Sohyun; Park, Byung-Joo

    2015-05-01

    This study was conducted to estimate the prevalence of antimicrobial prescribing for acute upper respiratory tract infections (URI) among pediatric outpatients and to identify the national patterns of its use from 2009 to 2011 in Korea. Using National Patients Sample database from 2009 to 2011, we estimated the frequency of antibiotics prescribing for URI in pediatric outpatients with diagnoses of acute nasopharyngitis (common cold), acute sinusitis, acute pharyngitis, acute tonsillitis, acute laryngitis/tracheitis, acute obstructive laryngitis/epiglottitis, and acute upper respiratory infections of multiple and unspecified sites. The proportions of each antibiotic class were calculated by year and absolute and relative differences were estimated. Also, we investigated daily amount of prescribed antibiotics per defined population according to the type of medical care institution, physician specialty, and geographic region. The overall antibiotic prescribing proportion was 58.7% and its annual proportion slightly decreased (55.4% in 2011 vs. 60.5% in 2009; adjusted odds ratio, 0.82; 95% confidence interval, 0.82-0.83). Variations by the type of medical care institution were observed. Tertiary hospitals (45.0%) were less likely to prescribe antibiotics than primary care clinics (59.4%), hospitals (59.0%), and general hospitals (61.2%); they showed different tendencies in choosing antibiotics. Variations by physician specialty and region were also observed. Prevalence of antimicrobial prescribing for pediatric URI is still considered higher than that of western countries and varies by the type of medical care institution, physician specialty, and geographic region.

  11. Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection

    PubMed Central

    2005-01-01

    Background Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection. Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm. Case report We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation. Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids. Conclusion This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis. PMID:16164756

  12. Epidemiology of acute infections among patients with chronic kidney disease.

    PubMed

    Dalrymple, Lorien S; Go, Alan S

    2008-09-01

    The objectives of this review were (1) to review recent literature on the rates, risk factors, and outcomes of infections in patients who had chronic kidney disease (CKD) and did or did not require renal replacement therapy; (2) to review literature on the efficacy and use of selected vaccines for patients with CKD; and (3) to outline a research framework for examining key issues regarding infections in patients with CKD. Infection-related hospitalizations contribute substantially to excess morbidity and mortality in patients with ESRD, and infection is the second leading cause of death in this population. Patients who have CKD and do not require renal replacement therapy seem to be at higher risk for infection compared with patients without CKD; however, data about patients who have CKD and do not require dialysis therapy are very limited. Numerous factors potentially predispose patients with CKD to infection: advanced age, presence of coexisting illnesses, vaccine hyporesponsiveness, immunosuppressive therapy, uremia, dialysis access, and the dialysis procedure. Targeted vaccination seems to have variable efficacy in the setting of CKD and is generally underused in this population. In conclusion, infection is a primary issue when caring for patients who receive maintenance dialysis. Very limited data exist about the rates, risk factors, and outcomes of infection in patients who have CKD and do not require dialysis. Future research is needed to delineate accurately the epidemiology of infections in these populations and to develop effective preventive strategies across the spectrum of CKD severity. PMID:18650409

  13. Neurological complications of acute and persistent Epstein-Barr virus infection in paediatric patients.

    PubMed

    Häusler, Martin; Ramaekers, Vincent Thomas; Doenges, Martin; Schweizer, Klaus; Ritter, Klaus; Schaade, Lars

    2002-10-01

    Neurological complications of Epstein-Barr virus (EBV) have been reported almost exclusively in the course of acute primary infections. The role of EBV in paediatric neurological disease was investigated prospectively over a 2-year period, searching for acute primary, chronic, and reactivated EBV infections. Active EBV infections were diagnosed in 10/48 patients, including two with acute primary EBV infections (cranial neuritis and cerebellitis), one with chronic active infection (T/NK cell lymphoma with cranial neuritis), and seven with reactivated infections. Among these seven patients, three showed "Alice in Wonderland" syndrome, one facial nerve palsy, one progressive macrocephaly, and two prolonged encephalitic illness. The prognosis was good except for the patient with lethal T/NK cell lymphoma and the two girls with encephalitic illness. Despite steroid treatment, these girls suffered prolonged cognitive impairment and epileptic seizures. Both developed left-sided hippocampal atrophy, and one of them hippocampal sclerosis. Like primary infections, reactivated EBV infections cause neurological complications in a considerable number of paediatric patients, lead to serious long-term complications, and may contribute to the pathogenesis of hippocampal lesions. PMID:12210416

  14. The effect of cytomegalovirus infection on acute rejection in kidney transplanted patients

    PubMed Central

    Hasanzamani, Boshra; Hami, Maryam; Zolfaghari, Vajihe; Torkamani, Mahtab; Ghorban Sabagh, Mahin; Ahmadi Simab, Saiideh

    2016-01-01

    Introduction: It is known that cytomegalovirus (CMV) infection is a common problem among kidney transplant patients. This infection can be increased morbidity and decreased graft survival. This problem has been associated with acute rejection too. Patients and Methods: One hundred and thirty renal transplant patients were included in a prospective, case-control study. The renal transplant patients were divided into two groups; patients group with CMV infection and control group without CMV infection. Serum CMV-IgG in all patients was positive (donor and recipients). None of patients had received anti-thymocyte-globulin and thymoglobulin. CMV infection was diagnosed by quantitative CMV-PCR (polymerase chain reaction) test (more than 500 copies/μg). Rejection episode was defined by kidney isotope scan or biopsy. Results: In the group of 66 CMV infection patients (41 male [62.1%] and 25 female [37.9%]) the incidence of graft rejection was 36%, however in the group of 64 control patients the incidence of graft rejection was 9.4 % (P < 0.005). Conclusion: CMV infection is important predisposing factor for acute allograft rejection after kidney transplantation. The results of this study suggests that the control of CMV infection could decrease episodes of acute kidney rejection. PMID:27471740

  15. Endovascular intervention for acute stroke due to infective endocarditis: case report.

    PubMed

    Dababneh, Haitham; Hedna, V Shushrutha; Ford, Jenna; Taimeh, Ziad; Peters, Keith; Mocco, J; Waters, Michael F

    2012-02-01

    The overall incidence of neurological complications due to infective endocarditis is as high as 40%, with embolic infarcts more common than hemorrhagic strokes. The standard of care for typical strokes does not apply to infective endocarditis because there is a substantial risk of hemorrhage with thrombolysis. In the last decade there have been multiple case reports of intravenous and intraarterial thrombolysis with successful outcomes for acute strokes with related infective endocarditis, but successful endovascular interventions for acute strokes associated with infective endocarditis are rarely reported. To the authors' knowledge, this report is the first case in the literature to use a mechanical retrieval device in successful vegetation retrieval in an infective endocarditis acute stroke. Although an interventional approach for treatment of acute stroke related to infective endocarditis is a promising option, it is controversial and a cautious clinical decision should be made on a case-by-case basis. The authors conclude that this approach can be tested in a case series with matched controls, because this condition is rare and a randomized clinical trial is not a realistic option.

  16. Whole-body protein kinetics in marasmus and kwashiorkor during acute infection.

    PubMed

    Manary, M J; Broadhead, R L; Yarasheski, K E

    1998-06-01

    Marasmus and kwashiorkor are clinically distinct manifestations of severe malnutrition. This study tested the hypothesis that rates of whole-body protein synthesis and breakdown are higher in marasmus than in kwashiorkor during acute infection. We measured whole-body protein kinetics using stable isotope tracers in eight children with marasmus and acute infection (pneumonia or malaria) to determine the rate of appearance of urea and leucine in plasma. Serum concentrations of total protein, albumin, and C-reactive protein were also measured. These findings were compared with those reported previously for 13 children with kwashiorkor (including marasmic kwashiorkor) and acute infection who were studied with the same methods. HIV infection was present in 10 of 21 children. Rates of protein breakdown and synthesis were higher in marasmus than in kwashiorkor (227 +/- 59 compared with 103 +/- 30 micromol leucine x kg(-1) x h(-1) and 216 +/- 60 compared with 97 +/- 30 micromol leucine x kg(-1) x h(-1), P < 0.001). The concentration of globulin (total protein minus albumin) was higher in marasmus than kwashiorkor (40 +/- 17 compared with 25 +/- 7 g/L, P < or = 0.01), but C-reactive protein was not different (73 +/- 79 compared with 83 +/- 89 mg/L). HIV infection and body composition did not explain the differences between marasmus and kwashiorkor. The accelerated rate of protein turnover in children with marasmus and acute infection requires further investigation.

  17. Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

    PubMed Central

    Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

    2015-01-01

    Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

  18. The host response and molecular pathogenesis associated with respiratory syncytial virus infection

    PubMed Central

    Oshansky, Christine M; Zhang, Wenliang; Moore, Elizabeth; Tripp, Ralph A

    2009-01-01

    Since the isolation of respiratory syncytial virus (RSV) in 1956, its significance as an important human pathogen in infants, the elderly and the immunocompromised has been established. Many important mechanisms contributing to RSV infection, replication and disease pathogenesis have been uncovered; however, there is still insufficient knowledge in these and related areas, which must be addressed to facilitate the development of safe and effective vaccines and therapeutic treatments. A better understanding of the molecular pathogenesis of RSV infection, particularly the host-cell response and transcription profiles to RSV infection, is required to advance disease intervention strategies. Substantial information is accumulating regarding how RSV proteins modulate molecular signaling and regulation of cytokine and chemokine responses to infection, molecular signals regulating programmed cell death, and innate and adaptive immune responses to infection. This review discusses RSV manipulation of the host response to infection and related disease pathogenesis. PMID:19327115

  19. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  20. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    PubMed

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

  1. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques

    PubMed Central

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L.; Frank, Daniel N.; Ma, Dongzhu; Policicchio, Benjamin B.; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S.; Trichel, Anita; Ribeiro, Ruy M.; Tracy, Russell; Wilson, Cara; Landay, Alan L.; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab–infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection. PMID:26764484

  2. Cell fusion assay by expression of respiratory syncytial virus (RSV) fusion protein to analyze the mutation of palivizumab-resistant strains.

    PubMed

    Yasui, Yosuke; Yamaji, Yoshiaki; Sawada, Akihito; Ito, Takashi; Nakayama, Tetsuo

    2016-05-01

    Respiratory syncytial virus (RSV) consists of fusion (F), glyco (G), and small hydrophobic (SH) proteins as envelope proteins, and infects through cell fusion. F protein is expressed on the surface of infected cells, and induces cell fusion. In the present report, expression plasmids of the F, G and SH proteins were constructed and cell fusion activity was investigated under T7 RNA polymerase. F protein alone induced cell fusion at a lower concentration than previously reported, and co-expression of F and SH proteins induced cell fusion more efficiently than F protein alone. Palivizumab is the only prophylactic agent against RSV infection. Palivizumab-resistant strains having mutations of the F protein of K272E and S275F were reported. These mutations were introduced into an F-expression plasmid, and exhibited no inhibition of cell fusion with palivizumab. Among the RSV F protein mutants, N276S has been reported to have partial resistance against palivizumab, but the F expression plasmid with the N276S mutation showed a reduction in cell fusion in the presence of palivizumab, showing no resistance to palivizumab. The present expression system was useful for investigating the mechanisms of RSV cell fusion. PMID:26794681

  3. Peroxisome proliferator-activated receptor-{gamma} agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells

    SciTech Connect

    Arnold, Ralf . E-mail: ralf.arnold@medizin.uni-magdeburg.de; Koenig, Wolfgang

    2006-07-05

    We have previously shown that peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) agonists inhibited the inflammatory response of RSV-infected human lung epithelial cells. In this study, we supply evidence that specific PPAR{gamma} agonists (15d-PGJ{sub 2}, ciglitazone, troglitazone, Fmoc-Leu) efficiently blocked the RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp-2). All PPAR{gamma} agonists under study markedly inhibited the cell surface expression of the viral G and F protein on RSV-infected A549 cells. This was paralleled by a reduced cellular amount of N protein-encoding mRNA determined by real-time RT-PCR. Concomitantly, a reduced release of infectious progeny virus into the cell supernatants of human lung epithelial cells (A549, normal human bronchial epithelial cells (NHBE)) was observed. Similar results were obtained regardless whether PPAR{gamma} agonists were added prior to RSV infection or thereafter, suggesting that the agonists inhibited viral gene expression and not the primary adhesion or fusion process.

  4. [Clinical analysis of acute invasive fungal sinusitis with orbital infection].

    PubMed

    Chen, Feifei; Hu, Haiwen; Li, Jin

    2014-10-01

    The clinical manifestation of acute invasive fungal sinusitis was associated with facial pain,altered sense of smell, blindness and headache. Physical examinations show that dark brown nasal secretions with bone resorption in paranasal sinus. Radiographi parameters showed uneven density in paranasal sinus and intraorbital extension. Fungus smears and pathological examination can make a definitive diagnosis.

  5. Platelets from thrombocytopenic ponies acutely infected with equine infectious anemia virus are activated in vivo and hypofunctional.

    PubMed

    Russell, K E; Perkins, P C; Hoffman, M R; Miller, R T; Walker, K M; Fuller, F J; Sellon, D C

    1999-06-20

    Thrombocytopenia is a consistent finding and one of the earliest hematological abnormalities in horses acutely infected with equine infectious anemia virus (EIAV), a lentivirus closely related to human immunodeficiency virus. Multifactorial mechanisms, including immune-mediated platelet destruction and impaired platelet production, are implicated in the pathogenesis of EIAV-associated thrombocytopenia. This study was undertaken to investigate whether regenerative thrombopoiesis and platelet destruction occurred in ponies acutely infected with EIAV. Circulating large, immature platelets were increased in ponies acutely infected with EIAV late in the infection when platelet count was at a nadir. Morphometric analysis of bone marrow from acutely infected ponies revealed significant increased in megakaryocyte area and megakaryocyte nuclear area. A trend toward increased numbers of megakaryocytes was also observed. Platelets from acutely infected ponies had increased surface-bound fibrinogen and ultrastructural changes consistent with in vivo platelet activation. Platelets also had hypofunctional aggregation responses to three agonists in vitro. We conclude that thrombocytopenia in ponies acutely infected with EIAV is regenerative and suggest that bone marrow platelet production is not severely compromised in these ponies. Our findings reveal that in vivo platelet activation occurs in ponies acutely infected with EIAV, and as a result platelets are hypofunctional in vitro. Activation of platelets in vivo may cause platelet degranulation or formation of platelet aggregates, which would result in removal of these damages platelets from circulation. This may represent a form of nonimmune-mediated platelet destruction in ponies acutely infected with EIAV.

  6. Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

    NASA Astrophysics Data System (ADS)

    Walshe, R.; Ruskin, H. J.; Callaghan, A.

    Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

  7. Viral load and acute otitis media development after human metapneumovirus upper respiratory tract infection.

    PubMed

    Nokso-Koivisto, Johanna; Pyles, Richard B; Miller, Aaron L; Patel, Janak A; Loeffelholz, Michael; Chonmaitree, Tasnee

    2012-07-01

    The role of human metapneumovirus (hMPV) in acute otitis media complicating upper respiratory tract infection (URI) was studied. Nasopharyngeal specimens from 700 URI episodes in 200 children were evaluated; 47 (7%) were positive for hMPV, 25 (3.6%) with hMPV as the only virus. Overall, 24% of URI episodes with hMPV only were complicated by acute otitis media, which was the lowest rate compared with other respiratory viruses. hMPV viral load was significantly higher in children with fever, but there was no difference in viral load in children with hMPV-positive URI with or without acute otitis media complication.

  8. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  9. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    PubMed

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P < 0.05) as a consequence of lower iron levels. Ferritin and transferrin levels were higher in both phases (acute and subclinical) of the disease. The AOPP and FRAP levels increased in infected animals on the acute phase; however, the opposite occurred in the subclinical phase. We concluded that dogs naturally infected by E. canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology. PMID:26724737

  10. [Epidemiologic features of acute viral respiratory infections in familial foci].

    PubMed

    Lidina, P V; Mironovskaia, A V

    1977-03-01

    A study was made of the epidemiological peculiarities of viral respiratory infections of various etiology in the familial foci with the use of a methodical approach permitting to detect the true spread of infection in the familial foci, with consideration to the subclinical forme fruste of the disease and "carrier state". It appeared that in the familial foci the infectiousness of the majority of respiratory viral infections was greater than in the closed collective bodies uniting persons of the same age. The age composition of the family influences the manifestness (particularly in parainfluenza infection) and the intensity of the epidemic process characterized by the coefficient of the secondary affections. The type of the apartment, the floor on which it is located, and the number of persons residing in it had no significant influence on the spread of the viral infections in the familial foci. A definite role in this process is played by the level of specific serum antibodies in the members of the family surrounding the patient. The association of morbidity level with the antibody level proved to be the most distinct in children with influenza and adenoviral infection; this association was less significant in adults. PMID:193325

  11. Strategies to Prevent Surgical Site Infections in Acute Care Hospitals: 2014 Update

    PubMed Central

    Anderson, Deverick J.; Podgorny, Kelly; Berríos-Torres, Sandra I.; Bratzler, Dale W.; Dellinger, E. Patchen; Greene, Linda; Nyquist, Ann-Christine; Saiman, Lisa; Yokoe, Deborah S.; Maragakis, Lisa L.; Kaye, Keith S.

    2014-01-01

    PURPOSE Previously published guidelines are available that provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their surgical site infection (SSI) prevention efforts. This document updates “Strategies to Prevent Surgical Site Infections in Acute Care Hospitals,”1 published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA) and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise. The list of endorsing and supporting organizations is presented in the introduction to the 2014 updates.2 PMID:24799638

  12. Pulmonary C Fibers Modulate MMP-12 Production via PAR2 and Are Involved in the Long-Term Airway Inflammation and Airway Hyperresponsiveness Induced by Respiratory Syncytial Virus Infection

    PubMed Central

    Zang, Na; Zhuang, Jianguo; Deng, Yu; Yang, Zhimei; Ye, Zhixu; Xie, Xiaohong; Ren, Luo; Fu, Zhou; Luo, Zhengxiu; Xu, Fadi

    2015-01-01

    ABSTRACT Children with acute respiratory syncytial virus (RSV) infection often develop sequelae of persistent airway inflammation and wheezing. Pulmonary C fibers (PCFs) are involved in the generation of airway inflammation and resistance; however, their role in persistent airway diseases after RSV is unexplored. Here, we elucidated the pathogenesis of PCF activation in RSV-induced persistent airway disorders. PCF-degenerated and intact mice were used in the current study. Airway inflammation and airway resistance were evaluated. MMP408 and FSLLRY-NH2 were the selective antagonists for MMP-12 and PAR2, respectively, to investigate the roles of MMP-12 and PAR2 in PCFs mediating airway diseases. As a result, PCF degeneration significantly reduced the following responses to RSV infection: augmenting of inflammatory cells, especially macrophages, and infiltrating of inflammatory cells in lung tissues; specific airway resistance (sRaw) response to methacholine; and upregulation of MMP-12 and PAR2 expression. Moreover, the inhibition of MMP-12 reduced the total number of cells and macrophages in bronchiolar lavage fluid (BALF), as well infiltrating inflammatory cells, and decreased the sRaw response to methacholine. In addition, PAR2 was upregulated especially at the later stage of RSV infection. Downregulation of PAR2 ameliorated airway inflammation and resistance following RSV infection and suppressed the level of MMP-12. In all, the results suggest that PCF involvement in long-term airway inflammation and airway hyperresponsiveness occurred at least partially via modulating MMP-12, and the activation of PAR2 might be related to PCF-modulated MMP-12 production. Our initial findings indicated that the inhibition of PCF activity would be targeted therapeutically for virus infection-induced long-term airway disorders. IMPORTANCE The current study is critical to understanding that PCFs are involved in long-term airway inflammation and airway resistance after RSV infection

  13. Low-level Circulation of Enterovirus D68–Associated Acute Respiratory Infections, Germany, 2014

    PubMed Central

    Reiche, Janine; Böttcher, Sindy; Diedrich, Sabine; Buchholz, Udo; Buda, Silke; Haas, Walter; Schweiger, Brunhilde

    2015-01-01

    We used physician sentinel surveillance to identify 25 (7.7%) mild to severe infections with enterovirus D68 (EV-D68) in children and adults among 325 outpatients with acute respiratory infections in Germany during August–October 2014. Results suggested low-level circulation of enterovirus D68 in Germany. Viruses were characterized by sequencing viral protein (VP) 1 and VP4/VP2 genomic regions. PMID:25898320

  14. The association between obesity and outpatient visits for acute respiratory infections in Ontario, Canada

    PubMed Central

    Campitelli, Michael A.; Rosella, Laura C.; Kwong, Jeffrey C.

    2016-01-01

    Objectives Recent evidence suggests that obesity increases the risk of severe outcomes following respiratory infection. It is less clear whether obesity is associated with the risk of being infected with influenza or other respiratory pathogens. Therefore, we examined the association between obesity and outpatient visits for acute respiratory infections. Design We conducted a retrospective cohort study over 13 years on 104,665 individuals in Ontario, Canada who responded to population health surveys and agreed to linkage with health administrative data. Individuals aged 18–64 years who responded to a survey within 5 years prior to the start of an influenza season were included. Poisson regression, with adjustment for relevant confounders, was used to measure the association between self-reported BMI and outpatient visits coded as acute respiratory infection. We conducted numerous sensitivity analyses to assess the robustness of our findings. Results We observed higher rates of outpatient visits for ARI during influenza season periods compared with normal weight individuals for those who were overweight (BMI 25–29.9) (Rate Ratio [RR] 1.10; 95% Confidence Interval [95% CI] 1.07–1.13), obese class I (BMI 30–34.9) (RR 1.17; 95% CI 1.13–1.22), and obese class II or III (BMI ≥35) (RR 1.19; 95% CI 1.12–1.25) Associations of a similar magnitude were observed during non-influenza season periods. Obesity was a greater risk factor for acute respiratory infections managed in emergency departments than physician offices. Conclusions Obese individuals are at an increased risk of outpatient visits for acute respiratory infection during both influenza and non-influenza season periods, suggesting that the effect of obesity on the risk of respiratory infections is not limited to influenza. Interventions designed to reduce the prevalence of obesity may have the added benefit reducing the population burden of respiratory infections. PMID:23670219

  15. West Nile virus infection in a teenage boy with acute lymphocytic leukemia in remission.

    PubMed

    Hindo, Heather; Buescher, E Stephen; Frank, L Matthew; Pettit, Dee; Dory, Christopher; Byrd, Rebecca

    2005-12-01

    West Nile Virus (WNV) infection is an important cause of encephalitis. Although the medical literature contains examples of WNV encephalitis in susceptible, mainly elderly, immunocompromised hosts, few case reports have described pediatric cases. The authors describe an adolescent with acute lymphocytic leukemia and WNV encephalitis. Surveillance studies indicate an increase in WNV activity. Physicians need to be aware of WNV activity in their community and consider WNV as a potential source of infection.

  16. Characterization of hospital and community-acquired respiratory syncytial virus in children with severe lower respiratory tract infections in Ho Chi Minh City, Vietnam, 2010

    PubMed Central

    Tuan, Tran Anh; Thanh, Tran Tan; Hai, Nguyen thi Thanh; Tinh, Le Binh Bao; Kim, Le thi Ngoc; Do, Lien Anh Ha; Chinh B'Krong, Nguyen thi Thuy; Tham, Nguyen thi; Hang, Vu thi Ty; Merson, Laura; Farrar, Jeremy; Thuong, Tang Chi; de Jong, Menno D; Schultsz, Constance; van Doorn, H Rogier

    2015-01-01

    Background Human respiratory syncytial virus (RSV) is an important community and nosocomial pathogen in developed countries but data regarding the importance of RSV in developing countries are relatively scarce. Methods During a 1-year surveillance study in 2010, we took serial samples from children admitted to the Emergency Unit of the Respiratory Ward of Children's Hospital 1 in Ho Chi Minh City, Vietnam. RSV was detected within 72 hours of admission to the ward in 26% (376/1439; RSV A: n = 320; RSV B: n = 54; and RSV A and B: n = 2). Among those negative in the first 72 hours after admission, 6·6% (25/377) acquired nosocomial RSV infection during hospitalization (RSV A: n = 22; and RSV B: n = 3). Results Children with nosocomial RSV infection were younger (P = 0·001) and had a longer duration of hospitalization (P < 0·001). The rate of incomplete recovery among children with nosocomial RSV infection was significantly higher than among those without (P < 0·001). Phylogenetic analysis of partial G gene sequences obtained from 79% (316/401) of positive specimens revealed the co-circulation of multiple genotypes with RSV A NA1 being predominant (A NA1: n = 275; A GA5: n = 5; B BA3: n = 3; B BA9: n = 26; and B BA10: n = 7). The RSV A GA5 and RSV B BA3 genotypes have not been reported from Vietnam, previously. Conclusion Besides emphasizing the importance of RSV as a cause of respiratory infection leading to hospitalization in young children and as a nosocomial pathogen, data from this study extend our knowledge on the genetic diversity of RSV circulating in Vietnam. PMID:25702707

  17. [Gemifloxacin for the treatment of uncomplicated urinary infections (acute cystitis)].

    PubMed

    Blondeau, Joseph M; Tillotson, Glenn S

    2009-12-01

    Uncomplicated urinary infections are a significant and growing cause of morbidity amongst young women. Commonly these infections are caused by Escherichia coil or Staphylococcus saprophyticus. Escherichia coil is resistant to several empirical antibiotics: amoxicilin, trimetoprima-sulfametozaxol and, more recently, to some more old flouroquinolons. Gemifloxacin is a flouroquinolon with an excellent in vitro activity against many community acquired bacteria which cause respiratory or urinary infections. This antibiotic has a very unique and dual action mechanism directed against girasa and topoisomerasa II DNA, which grants minimum low inhibitory concentrations against Escherichia coil, Klebsiella and S. saprophyticus species and others attacking respiratory system. Young women with uncomplicated urinary infections were evaluated in two random clinical studies; they were treated with 320 mg gemifloxacin once a day for three days. Gemifloxacin was compared to ofloxacin or ciprofloxacin in approved doses and durations and it proved to be useful with clinical success rates of 95% or more in both studies. Gemifloxacin showed to be safe and well tolerated. A dose a day is a safe and useful alternative amongst current empirical options to treat patients with uncomplicated urinary infections.

  18. Acute phase proteins: a potential approach for diagnosing chronic infection by Trypanosoma vivax.

    PubMed

    Almeida, Katyane de Sousa; Costa, Alinny Ferreira; Silva, Paulo Cesar da; Fagliari, José Jurandir; Machado, Rosangela Zacarias; Nascimento, Adjair Antonio do

    2012-01-01

    The present study aimed to assess potential changes in acute phase proteins in sheep experimentally infected with Trypanosoma vivax. There were studied eight male sheep, four used as controls and four infected with 10(5) T. vivax trypomastigotes. Blood samples were collected at two points times before infection and then at 5,7, 9, 11, 13, 15, 20, 30, 45, 60, 75, 90, 105 and 120 days post-infection (dpi). Blood samples were centrifuged and allotted, and acute phase proteins were then separated by electrophoresis on acrylamide gel containing sodium dodecyl sulfate. Protein concentrations were determined by computer-assisted densitometry. Total protein was determined by colorimetric biuret method. Trypanosomes were counted daily using a 5 mL aliquot of blood smear on a glass slide under a 22 × 22 mm coverslip. Parasites were counted in 100 microscopic fields (40× magnification), and then multiplied by a correction factor. The results were expressed as parasites per mL of blood. For statistical analyses, we used the Wilcoxon test at 5% significance level. There was found a reduction in several acute phase proteins and increase in antitrypsin and transferrin. This finding can be used for the diagnosis of T. vivax infection, especially in chronic infection.

  19. EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression

    PubMed Central

    Stobart, Christopher C.; Hotard, Anne L.; Villenave, Remi; Meng, Jia; Pretto, Carla D.; Shields, Michael D.; Nguyen, Minh Trang; Todd, Sean O.; Chi, Michael H.; Hammonds, Jason; Krumm, Stefanie A.; Spearman, Paul; Plemper, Richard K.; Sakamoto, Kaori; Peebles, R. Stokes; Power, Ultan F.; Moore, Martin L.

    2016-01-01

    Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2–20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2–20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2–20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2–20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from “mucogenic” strains. RSV 2–20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease. PMID:27152417

  20. EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression.

    PubMed

    Currier, Michael G; Lee, Sujin; Stobart, Christopher C; Hotard, Anne L; Villenave, Remi; Meng, Jia; Pretto, Carla D; Shields, Michael D; Nguyen, Minh Trang; Todd, Sean O; Chi, Michael H; Hammonds, Jason; Krumm, Stefanie A; Spearman, Paul; Plemper, Richard K; Sakamoto, Kaori; Peebles, R Stokes; Power, Ultan F; Moore, Martin L

    2016-05-01

    Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease. PMID:27152417

  1. Risk Factors for the Development of Intra-Abdominal Fungal Infections in Acute Pancreatitis

    PubMed Central

    Schwender, Brian J.; Gordon, Stuart R.; Gardner, Timothy B.

    2015-01-01

    Objectives Intra-abdominal fungal infections (AFI) complicating acute pancreatitis arise in the context of pancreatic necrosis. Our goal was to determine which risk factors contribute to AFI in patients with acute pancreatitis. Methods Records were reviewed from 479 non-transfer patients admitted to our medical center with acute pancreatitis from 1985–2009. Using multivariable regression models, risk factors for AFI were identified. Results Out of 479 patients admitted with acute pancreatitis, 17 patients were subsequently found to have an AFI and 3 of these patients expired. The mean length of stay for patients with an AFI was 24 days and 76% were admitted to the intensive care unit. Patients with AFI were more likely to have received prophylactic antibiotics on admission (OR 1.7, 95% C.I. 1.2–2.3), TPN within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7) or to have necrosis on CT scan within 7 days of admission (OR 1.4, 95% C.I. 1.1–1.7). Multivariable regression models identified admission antibiotic use (OR 1.6, 95% C.I. 1.4–1.8) as the strongest predictor of AFI. Conclusion Admission antibiotics are the biggest risk factor for the development of intra-abdominal fungal infections in acute pancreatitis. Prophylactic antibiotics to prevent infected necrosis should therefore be discouraged. PMID:25872170

  2. Acute Neurological Illness in a Kidney Transplant Recipient Following Infection With Enterovirus-D68: An Emerging Infection?

    PubMed

    Wali, R K; Lee, A H; Kam, J C; Jonsson, J; Thatcher, A; Poretz, D; Ambardar, S; Piper, J; Lynch, C; Kulkarni, S; Cochran, J; Djurkovic, S

    2015-12-01

    We report the first case of enterovirus-D68 infection in an adult living-donor kidney transplant recipient who developed rapidly progressive bulbar weakness and acute flaccid limb paralysis following an upper respiratory infection. We present a 45-year-old gentleman who underwent pre-emptive living-donor kidney transplantation for IgA nephropathy. Eight weeks following transplantation, he developed an acute respiratory illness from enterovirus/rhinovirus that was detectable in nasopharyngeal (NP) swabs. Within 24 h of onset of respiratory symptoms, the patient developed binocular diplopia which rapidly progressed to multiple cranial nerve dysfunctions (acute bulbar syndrome) over the next 24 h. Within the next 48 h, asymmetric flaccid paralysis of the left arm and urinary retention developed. While his neurological symptoms were evolving, the Centers for Disease Control reported that the enterovirus strain from the NP swabs was, in fact, Enterovirus-D68 (EV-D68). Magnetic resonance imaging of the brain demonstrated unique gray matter and anterior horn cell changes in the midbrain and spinal cord, respectively. Constellation of these neurological symptoms and signs was suggestive for postinfectious encephalomyelitis (acute disseminated encephalomyelitis [ADEM]) from EV-D68. Treatment based on the principles of ADEM included intensive physical therapy and other supportive measures, which resulted in a steady albeit slow improvement in his left arm and bulbar weakness, while maintaining stable allograft function. PMID:26228743

  3. RAM simulation model for SPH/RSV systems

    SciTech Connect

    Schryver, J.C.; Primm, A.H.; Nelson, S.C.

    1995-12-31

    The US Army`s Project Manager, Crusader is sponsoring the development of technologies that apply to the Self-Propelled Howitzer (SPH), formerly the Advanced Field Artillery System (AFAS), and Resupply Vehicle (RSV), formerly the Future Armored Resupply Vehicle (FARV), weapon system. Oak Ridge National Laboratory (ORNL) is currently performing developmental work in support of the SPH/PSV Crusader system. Supportive analyses of reliability, availability, and maintainability (RAM) aspects were also performed for the SPH/RSV effort. During FY 1994 and FY 1995 OPNL conducted a feasibility study to demonstrate the application of simulation modeling for RAM analysis of the Crusader system. Following completion of the feasibility study, a full-scale RAM simulation model of the Crusader system was developed for both the SPH and PSV. This report provides documentation for the simulation model as well as instructions in the proper execution and utilization of the model for the conduct of RAM analyses.

  4. Knowledge of Acute Human Immnuodeficiency Virus Infection among Gay and Bisexual Male College Students

    ERIC Educational Resources Information Center

    Grin, Benjamin; Chan, Philip A.; Operario, Don

    2013-01-01

    Objective: To examine human immunodeficiency virus (HIV)-related knowledge, attitudes, and behaviors in at-risk college men who have sex with men (MSM), focusing on knowledge about acute HIV infection (AHI). Participants and Methods: A one-time anonymous survey was administered to college students attending a lesbian, gay, bisexual, transgender,…

  5. Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009.

    PubMed

    Tohme, Rania A; Drobeniuc, Jan; Sanchez, Roger; Heseltine, Gary; Alsip, Bryan; Kamili, Saleem; Hu, Dale J; Guerra, Fernando; Teshale, Eyasu H

    2011-10-01

    Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. PMID:21896699

  6. Cutaneous Infection Caused by Macrophomina phaseolina in a Child with Acute Myeloid Leukemia▿

    PubMed Central

    Srinivasan, Ashok; Wickes, Brian L.; Romanelli, Anna M.; Debelenko, Larisa; Rubnitz, Jeffrey E.; Sutton, Deanna A.; Thompson, Elizabeth H.; Fothergill, Annette W.; Rinaldi, Michael G.; Hayden, Randall T.; Shenep, Jerry L.

    2009-01-01

    We report a case of Macrophomina phaseolina skin infection in an immunocompromised child with acute myeloid leukemia, which was treated successfully with posaconazole without recurrence after a hematopoietic stem cell transplant. The fungus was identified by DNA sequencing using both the internal transcribed spacer and D1/D2 region of the 28S ribosomal DNA gene. PMID:19386841

  7. Disseminated Infection Caused by Scedosporium prolificans in a Patient with Acute Multilineal Leukemia

    PubMed Central

    de Batlle, J.; Motjé, M.; Balanzà, R.; Guardia, R.; Ortiz, R.

    2000-01-01

    In this report, we describe a case of disseminated infection caused by Scedosporium prolificans (S. inflatum) in a patient affected by chemotherapy-induced acute multilineal leukemia and neutropenia. For the fungus isolated in four blood cultures, high MICs of currently available antifungal agents were found. Postmortem examination revealed multiorgan involvement. PMID:10747173

  8. Development of Hamster Models for Acute and Chronic Infections with Leptospira borgpetersenii serovar Hardjo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Golden Syrian hamster is frequently used as a small animal model to study acute leptospirosis. However, use of this small animal model to study Leptospira borgpetersenii serovar Hardjo infections has not been well documented. Cattle are the normal maintenance hosts of L. borgpetersenii serovar...

  9. Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening.

    PubMed

    Hoenigl, Martin; Green, Nella; Camacho, Martha; Gianella, Sara; Mehta, Sanjay R; Smith, Davey M; Little, Susan J

    2016-03-01

    We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program that offered universal HIV-1 nucleic acid amplification testing. Forty-seven (52%) patients reported ongoing signs or symptoms at the time of testing. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing.

  10. Comparative analysis of the acute response of zebrafish Danio rerio skin to two different bacterial infections.

    PubMed

    Lü, Aijun; Hu, Xiucai; Wang, Yi; Shen, Xiaojing; Zhu, Aihua; Shen, Lulu; Ming, Qinglei; Feng, Zhaojun

    2013-12-01

    Skin is an important innate immune organ in fish; however, little is known about the skin's immune response to infectious pathogens. We conducted a comparative analysis of the acute immune response of Zebrafish Danio rerio skin against gram-positive (Staphylococcus chromogenes) and gram-negative (Citrobacter freundii) bacterial infections. Gene expression profiles induced from the two different infections were identified by microarray hybridization, with many genes demonstrating an acute immune response in the skin. Differentially expressed genes were mainly involved in response to stress and stimulus, complement activation, acute-phase response, and defense and immune response. Compared with transcription patterns of skin from the two infections, a similar innate immunity (e.g., transferrin, coagulation factor, complements, and lectins) was observed but with different acute-phase genes (e.g., ceruloplasmin, alpha-1-microglobulin, vitellogenin, and heat shock protein). These results suggest that the skin of fish plays an important role in the innate immune responses to bacterial infection. PMID:24341765

  11. Capgras-like syndrome in a patient with an acute urinary tract infection

    PubMed Central

    Salviati, Massimo; Bersani, Francesco Saverio; Macrì, Francesco; Fojanesi, Marta; Minichino, Amedeo; Gallo, Mariana; De Michele, Francesco; Chiaie, Roberto Delle; Biondi, Massimo

    2013-01-01

    Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%–40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder. PMID:23355784

  12. Infective endocarditis caused by Scedosporium prolificans infection in a patient with acute myeloid leukemia undergoing induction chemotherapy.

    PubMed

    Ochi, Yotaro; Hiramoto, Nobuhiro; Takegawa, Hiroshi; Yonetani, Noboru; Doi, Asako; Ichikawa, Chihiro; Imai, Yukihiro; Ishikawa, Takayuki

    2015-06-01

    Disseminated Scedosporium prolificans infection occurs mainly in immunocompromised patients. The mortality rate is high, as the fungus is resistant to most antifungal agents. Here, we present the case of a 66-year-old female with acute myeloid leukemia who developed infective endocarditis caused by S. prolificans infection during induction chemotherapy. Her 1,3-β-D-glucan levels were elevated and computed tomography revealed bilateral sinusitis and disseminated small nodular masses within the lungs and spleen; it nonetheless took 6 days to identify S. prolificans by blood culture. The patient died of multi-organ failure despite the combined use of voriconazole and terbinafine. Autopsy revealed numerous mycotic emboli within multiple organs (caused by mitral valve vegetation) and endocarditis (caused by S. prolificans). The geographic distribution of this infection is limited to Australia, the United States, and southern Europe, particularly Spain. The first Japanese case was reported in 2011, and four cases have been reported to date, including this one. Recently, the incidence of S. prolificans-disseminated infection in immunocompromised patients has increased in Japan. Therefore, clinicians should consider S. prolificans infection as a differential diagnosis when immunocompromised patients suffer disseminated infections with elevated 1,3-β-D-glucan levels.

  13. Magnetic Resonance Imaging of Acute Head and Neck Infections.

    PubMed

    Thayil, Neil; Chapman, Margaret N; Saito, Naoko; Fujita, Akifumi; Sakai, Osamu

    2016-05-01

    This article discusses the use of MR imaging in various acute infectious diseases of the head and neck, with particular emphasis on situations where MR imaging provides additional information that can significantly impact treatment decisions and outcomes. MR imaging findings of various disease processes are discussed, based on the head and neck compartments from which they originate. Specifically, infectious entities of the orbit, paranasal sinuses, pharynx, oral cavity (including periodontal disease), salivary glands, temporal bone, and lymph nodes are described in detail. PMID:27150323

  14. Screening for Host Factors Directly Interacting with RSV Protein: Microfluidics.

    PubMed

    Kipper, Sarit; Avrahami, Dorit; Bajorek, Monika; Gerber, Doron

    2016-01-01

    We present a high-throughput microfluidics platform to identify novel host cell binding partners of respiratory syncytial virus (RSV) matrix (M) protein. The device consists of thousands of reaction chambers controlled by micro-mechanical valves. The microfluidic device is mated to a microarray-printed custom-made gene library. These genes are then transcribed and translated on-chip, resulting in a protein array ready for binding to RSV M protein.Even small viral proteome, such as that of RSV, presents a challenge due to the fact that viral proteins are usually multifunctional and thus their interaction with the host is complex. Protein microarrays technology allows the interrogation of protein-protein interactions, which could possibly overcome obstacles by using conventional high throughput methods. Using microfluidics platform we have identified new host interactors of M involved in various cellular pathways. A number of microfluidics based assays have already provided novel insights into the virus-host interactome, and the results have important implications for future antiviral strategies aimed at targets of viral protein interactions with the host. PMID:27464694

  15. Apoptosis of Hippocampal Pyramidal Neurons Is Virus Independent in a Mouse Model of Acute Neurovirulent Picornavirus Infection

    PubMed Central

    Buenz, Eric J.; Sauer, Brian M.; LaFrance-Corey, Reghann G.; Deb, Chandra; Denic, Aleksandar; German, Christopher L.; Howe, Charles L.

    2009-01-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler’s murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non–cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  16. Apoptosis of hippocampal pyramidal neurons is virus independent in a mouse model of acute neurovirulent picornavirus infection.

    PubMed

    Buenz, Eric J; Sauer, Brian M; Lafrance-Corey, Reghann G; Deb, Chandra; Denic, Aleksandar; German, Christopher L; Howe, Charles L

    2009-08-01

    Many viruses, including picornaviruses, have the potential to infect the central nervous system (CNS) and stimulate a neuroinflammatory immune response, especially in infants and young children. Cognitive deficits associated with CNS picornavirus infection result from injury and death of neurons that may occur due to direct viral infection or during the immune responses to virus in the brain. Previous studies have concluded that apoptosis of hippocampal neurons during picornavirus infection is a cell-autonomous event triggered by direct neuronal infection. However, these studies assessed neuron death at time points late in infection and during infections that lead to either death of the host or persistent viral infection. In contrast, many neurovirulent picornavirus infections are acute and transient, with rapid clearance of virus from the host. We provide evidence of hippocampal pathology in mice acutely infected with the Theiler's murine encephalomyelitis picornavirus. We found that CA1 pyramidal neurons exhibited several hallmarks of apoptotic death, including caspase-3 activation, DNA fragmentation, and chromatin condensation within 72 hours of infection. Critically, we also found that many of the CA1 pyramidal neurons undergoing apoptosis were not infected with virus, indicating that neuronal cell death during acute picornavirus infection of the CNS occurs in a non-cell-autonomous manner. These observations suggest that therapeutic strategies other than antiviral interventions may be useful for neuroprotection during acute CNS picornavirus infection. PMID:19608874

  17. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    SciTech Connect

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  18. Effect of Brazilian Propolis on Exacerbation of Respiratory Syncytial Virus Infection in Mice Exposed to Tetrabromobisphenol A, a Brominated Flame Retardant

    PubMed Central

    Takeshita, Tomomi; Toyama, Satomi; Hayashi, Yuya; Honda, Shiori; Sakamoto, Shuichi; Matsuoka, Sayuri; Hidaka, Muneaki; Tsutsumi, Shigetoshi; Yasukawa, Ken; Park, Yong Kun

    2013-01-01

    Tetrabromobisphenol A (TBBPA), a brominated flame retardant, has been found to exacerbate pneumonia in respiratory syncytial virus- (RSV-) infected mice. We examined the effect of Brazilian propolis (AF-08) on the exacerbation of RSV infection by TBBPA exposure in mice. Mice were fed a powdered diet mixed with 1% TBBPA alone, 0.02% AF-08 alone, or 1% TBBPA and 0.02% AF-08 for four weeks and then intranasally infected with RSV. TBBPA exposure increased the pulmonary virus titer and level of IFN-γ, a representative marker of pneumonia due to RSV infection, in the lungs of infected mice without toxicity. AF-08 was significantly effective in reducing the virus titers and IFN-γ level increased by TBBPA exposure. Also, AF-08 significantly reduced proinflammatory cytokine (TNF-α and IL-6) levels in the lungs of RSV-infected mice with TBBPA exposure, but Th2 cytokine (IL-4 and IL-10) levels were not evidently increased. Neither TBBPA exposure nor AF-08 treatment affected the anti-RSV antibody production in RSV-infected mice. In flow cytometry analysis, AF-08 seemed to be effective in reducing the ratio of pulmonary CD8a+ cells in RSV-infected mice with TBBPA exposure. TBBPA and AF-08 did not exhibit anti-RSV activity in vitro. Thus, AF-08 probably ameliorated pneumonia exacerbated by TBBPA exposure in RSV-infected mice by limiting excess cellular immune responses. PMID:24250719

  19. Serious Infection Following Acute Myocardial Infarction: Incidence, Clinical Features, and Outcomes

    PubMed Central

    Truffa, Adriano A. M.; Granger, Christopher B.; White, Kyle R.; Newby, L. Kristin; Mehta, Rajendra H.; Hochman, Judith S.; Patel, Manesh R.; Pieper, Karen S.; Al-Khalidi, Hussein R.; Armstrong, Paul W.; Lopes, Renato D.

    2013-01-01

    Background Little is known about the incidence, location, etiologic organisms, and outcomes of infection in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Objectives To address this knowledge gap using the database of the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial. We also assessed the association between serious infections and 90-day death or death/MI. Methods We analyzed data from 5745 STEMI patients enrolled in the APEX-AMI trial. Detailed information on infection was collected on all patients. We describe characteristics of patients according to infection and details of infection. Cox proportional hazards models were used to assess 90-day outcomes among patients with and without infections after adjusting for associated clinical variables and using infection as a time-dependent covariate. Results Overall, 138 patients developed a serious infection (2.4%), most of whom presented with a single-site infection. The median (25th, 75th percentile) time until diagnosis of infection was 3 (1, 6) days. The most commonly identified organism was Staphylococcus aureus, and the main location of infection was the bloodstream. These patients had more comorbidities and lower procedural success at index PCI than those without infections. Serious infection was associated with significantly higher rates of 90-day death (adjusted hazard ratio [HR] 5.6; 95% confidence interval [CI] 3.8-8.4) and death or MI (adjusted HR 4.9; 95% CI 3.4-7.1). Conclusion Infections complicating the course of patients with STEMI are uncommon but associated with markedly worse 90-day clinical outcomes. Mechanisms for early identification of these high-risk patients, as well as design of strategies to reduce their risk of infection, are warranted. PMID:22814783

  20. An examination of co-infection in acute gastroenteritis and histo-blood group antigens leading to viral infection susceptibility

    PubMed Central

    FURUYA, KENTA; NAKAJIMA, HITOSHI; SASAKI, YOUSUKE; URITA, YOSHIHISA

    2016-01-01

    The aim of the present study was to evaluate co-infection in the gastrointestinal tract in terms of viruses, bacteria and the ABO blood group. We hypothesized that a combination of norovirus (NV) and bacteria in the gastrointestinal tract could affect the likelihood of an individual to contracting NV. Histo-blood group antigens (HBGAs) are considered to act as receptors that can lead to NV susceptibility. In addition to genetics, co-infection in the gastrointestinal tract may be associated with this mechanism. A total of 370 patients with acute gastroenteritis presenting with diarrhea (14–89 years) were recruited. The male/female ratio was 20/17. Single infection (bacteria or virus), co-infection with two viruses, and co-infection with one virus and one bacterium were statistically analyzed. In total, 88 of the 376 subjects (23.4%) were positive for one virus, and 50 (13.3%) were positive for one bacterium. Co-transfection with bacteria and a virus were detected in 46 (47.9%) of the 96 bacterial gastroenteritis cases. Statistical analysis revealed that co-infection of bacteria and NV was not significant in all viral infections (P=0.768). In terms of the ABO histo-blood group type and NV infection, the frequency in the O type was not significantly increased (P=0.052). Co-infection of bacteria and a virus occurred frequently in the gastrointestinal tract. The ABO blood phenotype expression was not a significant factor in NV infection in the present case series and the results did not suggest an affinity of NV for specific bacteria. PMID:26998270

  1. Urinary tract infections in patients admitted to rehabilitation from acute care settings: a descriptive research study.

    PubMed

    Romito, Diane; Beaudoin, JoAnn M; Stein, Patricia

    2011-01-01

    The use of an indwelling urinary catheter comes with associated risks. At a hospital in southern California, nurses on the acute rehabilitation unit suspected their patients were arriving from acute care with undiagnosed urinary tract infections (UTIs). This descriptive research study quantified the incidence of UTI on admission to a rehabilitation unit and correlations with catheter use. During the study period, 132 patients were admitted to acute rehabilitation from an acute care setting, and 123 met criteria to participate in the study. Among participants, 12% had a UTI upon admission. Questionnaires examined nursing attitudes toward appropriate urinary catheter use and proactive catheter removal. The data revealed that nurses want to be involved in decisions about urinary catheter use and that medical/surgical and rehabilitation nurses agree strongly about advocating for patients with indwelling urinary catheters.

  2. Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

    PubMed Central

    Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

    2012-01-01

    Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

  3. Recent advances in the management of acute bronchiolitis

    PubMed Central

    Ravaglia, Claudia

    2014-01-01

    Acute bronchiolitis is characterized by acute wheezing in infants or children and is associated with signs or symptoms of respiratory infection; it is rarely symptomatic in adults and the most common etiologic agent is respiratory syncytial virus (RSV). Usually it does not require investigation, treatment is merely supportive and a conservative approach seems adequate in the majority of children, especially for the youngest ones (<3 months); however, clinical scoring systems have been proposed and admission in hospital should be arranged in case of severe disease or a very young age or important comorbidities. Apnea is a very important aspect of the management of young infants with bronchiolitis. This review focuses on the clinical, radiographic, and pathologic characteristics, as well as the recent advances in management of acute bronchiolitis. PMID:25580257

  4. Does virus-bacteria coinfection increase the clinical severity of acute respiratory infection?

    PubMed

    Damasio, Guilherme A C; Pereira, Luciane A; Moreira, Suzana D R; Duarte dos Santos, Claudia N; Dalla-Costa, Libera M; Raboni, Sonia M

    2015-09-01

    This retrospective cohort study investigated the presence of bacteria in respiratory secretions of patients hospitalized with acute respiratory infections and analyzed the impact of viral and bacterial coinfection on severity and the mortality rate. A total of 169 patients with acute respiratory infections were included, viruses and bacteria in respiratory samples were detected using molecular methods. Among all samples, 73.3% and 59.7% were positive for viruses and bacteria, respectively; 45% contained both virus and bacteria. Bacterial coinfection was more frequent in patients infected by community respiratory viruses than influenza A H1N1pdm (83.3% vs. 40.6%). The most frequently bacteria detected were Streptococcus pneumoniae and Haemophilus influenzae. Both species were co-detected in 54 patients and identified alone in 22 and 21 patients, respectively. Overall, there were no significant differences in the period of hospitalization, severity, or mortality rate between patients infected with respiratory viruses alone and those coinfected by viruses and bacteria. The detection of mixed respiratory pathogens is frequent in hospitalized patients with acute respiratory infections, but its impact on the clinical outcome does not appear substantial. However, it should be noted that most of the patients received broad-spectrum antibiotic therapy, which may have contributed to this favorable outcome.

  5. A cluster of acute hepatitis E infection in United Nations Bangladeshi peacekeepers in Haiti.

    PubMed

    Drabick, J J; Gambel, J M; Gouvea, V S; Caudill, J D; Sun, W; Hoke, C H; Innis, B L

    1997-10-01

    In the fall of 1995, within a month of deployment to Haiti for peacekeeping duty, four Bangladeshi soldiers developed acute icteric hepatitis in rapid succession. Hepatitis E virus (HEV) was found to be the etiology by demonstrating HEV genomic sequences in serum samples by the polymerase chain reaction (PCR) and serologically by the detection of elevated IgM titers to HEV. No case had serologic evidence of acute hepatitis A or C infection. The soldiers had probably acquired their infection while living in a cantonment area outside Dhaka, Bangladesh for one month prior to deployment. Cloning and sequencing of amplified PCR products demonstrated a single strain suggestive of a common source of infection. Furthermore, high genomic identity with Asian strains of HEV and dissimilarity with the Mexican strain was demonstrated, verifying that the strain had indeed been imported. Human waste management from the Bangladesh camp in Haiti was strictly controlled and no secondary cases were observed. A convenience sample of 105 (12%) soldiers from the Bangladesh battalion (850 men) revealed anicteric or asymptomatic HEV infection in seven (7%) of 105. This report contains the first demonstration of acute hepatitis E in natives of Bangladesh and demonstrates the power of the PCR in the rapid diagnosis and epidemiologic analysis of HEV infection. More importantly, this cluster demonstrates the importation of an important infectious disease by multinational peacekeepers to a potentially susceptible host country.

  6. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep

    PubMed Central

    2014-01-01

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development. PMID:24475786

  7. Placental thrombosis in acute phase abortions during experimental Toxoplasma gondii infection in sheep.

    PubMed

    Castaño, Pablo; Fuertes, Miguel; Ferre, Ignacio; Fernández, Miguel; Ferreras, Maria del Carmen; Moreno-Gonzalo, Javier; González-Lanza, Camino; Katzer, Frank; Regidor-Cerrillo, Javier; Ortega-Mora, Luis Miguel; Pérez, Valentín; Benavides, Julio

    2014-01-29

    After oral administration of ewes during mid gestation with 2000 freshly prepared sporulated oocysts of T. gondii isolate M4, abortions occurred between days 7 and 11 in 91.6% of pregnant and infected ewes. Afterwards, a further infection was carried out at late gestation in another group of sheep with 500 sporulated oocysts. Abortions happened again between days 9 and 11 post infection (pi) in 58.3% of the infected ewes. Classically, abortions in natural and experimental ovine toxoplasmosis usually occur one month after infection. Few experimental studies have reported the so-called acute phase abortions as early as 7 to 14 days after oral inoculation of oocysts, and pyrexia was proposed to be responsible for abortion, although the underline mechanism was not elucidated. In the present study, all placentas analysed from ewes suffering acute phase abortions showed infarcts and thrombosis in the caruncullar villi of the placentomes and ischemic lesions (periventricular leukomalacia) in the brain of some foetuses. The parasite was identified by PCR in samples from some placentomes of only one sheep, and no antigen was detected by immunohistochemical labelling. These findings suggest that the vascular lesions found in the placenta, and the consequent hypoxic damage to the foetus, could be associated to the occurrence of acute phase abortions. Although the pathogenesis of these lesions remains to be determined, the infectious dose or virulence of the isolate may play a role in their development.

  8. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam.

    PubMed

    Phuong, Hoang Lan; Nga, Tran T T; van Doornum, Gerard J; Groen, Jan; Binh, Tran Q; Giao, Phan T; Hung, Le Q; Nams, Nguyen V; Kager, P A; de Vries, Peter J

    2010-09-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control program. Serum was collected on first presentation (t0) and after 3 weeks (t3) for serology. After exclusion of acute dengue infection, acute and convalescent serum samples from 606 patients were using enzyme-linked immunoassays to detect IgA, as well as IgM and IgG antibodies against common respiratory viruses. Paired sera showed the following infections: human parainfluenza virus (HPIV, 4.7%), influenza B virus (FLUBV, 2.2%), influenza A virus (FLUAV, 1.9%) and human respiratory syncytial virus (HRSV, 0.6%). There was no association between type of infection and age, sex or seasonality; some inter-annual differences were observed for influenza. Antibody prevalence, indicative of previous infections, was relatively low: HPV, 56.8%, FLUBV, 12.1%; FLUAV, 5.9% and HRSV, 6.8%.

  9. Fatal systemic adenoviral infection superimposed on pulmonary mucormycosis in a child with acute leukemia

    PubMed Central

    Seo, Yu Mi; Hwang-Bo, Seok; Kim, Seong koo; Han, Seung Beom; Chung, Nack-Gyun; Kang, Jin Han

    2016-01-01

    Abstract Background: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. Case summary: We report a case of a 15-year-old boy with a fatal systemic ADV infection. He had received reinduction chemotherapy for relapsed acute lymphoblastic leukemia under continuing antifungal therapy for previously diagnosed fungal pneumonia. He complained of fever and right shoulder pain 4 days after completing the reinduction chemotherapy. In spite of appropriate antibiotic and antifungal therapy, pneumonia was aggravated and gross hematuria was accompanied. A multiplex polymerase chain reaction test for respiratory viruses was positive for ADV in a blood sample, and a urine culture was positive for ADV. He received oral ribavirin, intravenous immunoglobulin, and intravenous cidofovir therapy; however, he eventually died. Relapsed leukemia, concurrent fungal pneumonia, and delayed cidofovir administration were considered the cause of the grave outcome in this patient. Conclusion: ADV may cause severe infections not only in allogeneic hematopoietic cell transplant recipients, but also in patients undergoing chemotherapy for acute leukemia. The risk factors for severe ADV infection in patients undergoing chemotherapy should be determined in the future studies, and early antiviral therapy should be administered to immune compromised patients with systemic ADV infection. PMID:27749571

  10. New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media

    PubMed Central

    Leino, Tuija; Kilpi, Terhi

    2016-01-01

    For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2–24 months at scheduled visits and at visits during respiratory infection in 1994–97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media. PMID:27257789

  11. Bench-to-bedside review: Rare and common viral infections in the intensive care unit – linking pathophysiology to clinical presentation

    PubMed Central

    Stollenwerk, Nicholas; Harper, Richart W; Sandrock, Christian E

    2008-01-01

    Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus. PMID:18671826

  12. Is accounting for acute care beds enough? A proposal for measuring infection prevention personnel resources.

    PubMed

    Gase, Kathleen A; Babcock, Hilary M

    2015-02-01

    There is still little known about how infection prevention (IP) staffing affects patient outcomes across the country. Current evaluations mainly focus on the ratio of IP resources to acute care beds (ACBs) and have not strongly correlated with patient outcomes. The scope of IP and the role of the infection preventionist in health care have expanded and changed dramatically since the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) recommended a 1 IP resource to 250 ACB ration in the 1980s. Without a universally accepted model for accounting for additional IP responsibilities, it is difficult to truly assess IP staffing needs. A previously suggested alternative staffing model was applied to acute care hospitals in our organization to determine its utility.

  13. Pathogenesis of acute murine cytomegalovirus infection in resistant and susceptible strains of mice.

    PubMed

    Mercer, J A; Spector, D H

    1986-02-01

    We have characterized the progress of acute murine cytomegalovirus (MCMV) infection in the spleen, liver, and salivary gland of susceptible (BALB/c) and resistant (C3H) strains of mice after intraperitoneal inoculation. Viral replication was analyzed by virus titration, infectious-center assays, and in situ cytohybridization with cloned subgenomic fragments of the MCMV genome. The most striking differences between strains were observed in the spleen. At 24 h postinfection (p.i.), both strains had a similar number of infected spleen cells. At 48 h p.i., BALB/c mice showed marked dissemination of the splenic infection which continued until 96 h p.i. In contrast, the number of infected C3H spleen cells did not increase from the 24-h level but declined later on. This early block in dissemination of MCMV infection in C3H mouse spleens was not a result of the H-2k haplotype, as BALB.K (H-2k) mice, which show an intermediate level of resistance to MCMV infection, exhibited dissemination of the infection between 24 and 48 h p.i., albeit at a reduced level. However, between 72 and 96 h p.i., we observed a decline in the number of infected spleen cells in BALB.K mice similar to that observed in C3H mice. We also demonstrated by Southern blot analysis of DNA from the infected spleen cells that the termini of the MCMV genome fuse after in vivo infection.

  14. Prevalence of Astrovirus Infection among Chilean Children with Acute Gastroenteritis

    PubMed Central

    Gaggero, Aldo; O’Ryan, Miguel; Noel, Jacqueline S.; Glass, Roger I.; Monroe, Stephan S.; Mamani, Nora; Prado, Valeria; Avendaño, Luis F.

    1998-01-01

    The frequency of astrovirus infection in 456 Chilean children with diarrhea was determined by enzyme-linked immunosorbent assay, reverse transcriptase PCR, and cell culture. Astrovirus was detected in 16.5% of rotavirus-negative and 7% of rotavirus-positive samples obtained from emergency rooms or hospitals and in 11% of samples from day care centers. HAst-1 was the predominant serotype identified. PMID:9817899

  15. Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

    PubMed Central

    Zhai, Yijie; Franco, Luis M.; Atmar, Robert L.; Quarles, John M.; Arden, Nancy; Bucasas, Kristine L.; Wells, Janet M.; Niño, Diane; Wang, Xueqing; Zapata, Gladys E.; Shaw, Chad A.; Belmont, John W.; Couch, Robert B.

    2015-01-01

    To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates. PMID:26070066

  16. Knowledge and Awareness of Acute Human Immunodeficiency Virus Infection Among Mobile App-Using Men Who Have Sex With Men: A Missed Public Health Opportunity

    PubMed Central

    Siegler, Aaron J.; Sanchez, Travis; Sineath, R. Craig; Grey, Jeremy; Kahle, Erin; Sullivan, Patrick S.

    2015-01-01

    In a national online survey, we assessed awareness and knowledge of acute human immunodeficiency virus (HIV) infection manifestation among 1748 men who have sex with men (MSM). Only 39% of respondents were aware that acute HIV infection may be accompanied by symptoms. Education and increased access to acute HIV testing may facilitate MSM to appropriately seek acute HIV testing. PMID:26034766

  17. Methods for monitoring dynamics of pulmonary RSV replication by viral culture and by real-time reverse transcription-PCR in vivo: Detection of abortive viral replication.

    PubMed

    Boukhvalova, Marina S; Yim, Kevin C; Prince, Gregory A; Blanco, Jorge C G

    2010-03-01

    Viral infection is normally detected either by viral culture or by PCR methods. Rarely is a combination of the two techniques used in the same study. Yet, when applied simultaneously, viral culture and PCR may reveal important features of viral biology, such as an abortive replication, as in the case of respiratory syncytial virus (RSV) infection. In this unit, we describe methods for detecting abortive RSV replication in a cotton rat model by using the plaque-forming unit assay and the real-time reverse-transcription PCR (qRT-PCR) assay. All steps of the process of monitoring viral replication in vivo are described, starting from the design of animal infection protocols. We continue on to the methods for extracting and processing lung samples for viral culture and RNA extraction, and finish with the actual methods of viral titration by the qRT-PCR and the plaque-forming unit assays.

  18. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    PubMed

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed. PMID:27084183

  19. Acute compartment syndrome of the forearm secondary to infection within the space of Parona.

    PubMed

    Jamil, Wiqqas; Khan, Irfan; Robinson, Paul; Thalava, Ramesh

    2011-09-01

    The deep midpalmar space of the hand communicates with the space of Parona in the forearm. Infection of these deep spaces can be difficult to diagnose. This article presents the first reported case of acute compartment syndrome of the forearm secondary to infection within the space of Parona. This article discusses the anatomy of the space of Parona, highlighting its communicating spaces and the importance of recognizing a deep-space infection of the hand as a possible cause of compartment syndrome of the forearm. This article also suggests a method of clinical examination to aid in the diagnosis of infection within the space of Parona to allow more specific planning of surgical intervention through early decompressive surgery, with surgical exploration to exclude and drain infection when no other clear cause for the rise in pressure within the osteofascial compartment is apparent. PMID:21902163

  20. Acute compartment syndrome of the forearm secondary to infection within the space of Parona.

    PubMed

    Jamil, Wiqqas; Khan, Irfan; Robinson, Paul; Thalava, Ramesh

    2011-09-09

    The deep midpalmar space of the hand communicates with the space of Parona in the forearm. Infection of these deep spaces can be difficult to diagnose. This article presents the first reported case of acute compartment syndrome of the forearm secondary to infection within the space of Parona. This article discusses the anatomy of the space of Parona, highlighting its communicating spaces and the importance of recognizing a deep-space infection of the hand as a possible cause of compartment syndrome of the forearm. This article also suggests a method of clinical examination to aid in the diagnosis of infection within the space of Parona to allow more specific planning of surgical intervention through early decompressive surgery, with surgical exploration to exclude and drain infection when no other clear cause for the rise in pressure within the osteofascial compartment is apparent.

  1. Imported Case of Acute Respiratory Tract Infection Associated with a Member of Species Nelson Bay Orthoreovirus

    PubMed Central

    Sakai, Kouji; Singh, Harpal; Himeji, Daisuke; Kikuchi, Ikuo; Ueda, Akira; Yamamoto, Seigo; Miura, Miho; Shioyama, Yoko; Kawano, Kimiko; Nagaishi, Tokiko; Saito, Minako; Minomo, Masumi; Iwamoto, Naoyasu; Hidaka, Yoshio; Sohma, Hirotoshi; Kobayashi, Takeshi; Kanai, Yuta; Kawagishi, Takehiro; Nagata, Noriyo; Fukushi, Shuetsu; Mizutani, Tetsuya; Tani, Hideki; Taniguchi, Satoshi; Fukuma, Aiko; Shimojima, Masayuki; Kurane, Ichiro; Kageyama, Tsutomu; Odagiri, Takato; Saijo, Masayuki; Morikawa, Shigeru

    2014-01-01

    A Japanese man suffered from acute respiratory tract infection after returning to Japan from Bali, Indonesia in 2007. Miyazaki-Bali/2007, a strain of the species of Nelson Bay orthoreovirus, was isolated from the patient's throat swab using Vero cells, in which syncytium formation was observed. This is the sixth report describing a patient with respiratory tract infection caused by an orthoreovirus classified to the species of Nelson Bay orthoreovirus. Given the possibility that all of the patients were infected in Malaysia and Indonesia, prospective surveillance on orthoreovirus infections should be carried out in Southeast Asia. Furthermore, contact surveillance study suggests that the risk of human-to-human infection of the species of Nelson Bay orthoreovirus would seem to be low. PMID:24667794

  2. Viral upper respiratory tract infections in young children with emphasis on acute otitis media.

    PubMed

    Nokso-Koivisto, Johanna; Hovi, Tapani; Pitkäranta, Anne

    2006-08-01

    Viral upper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications (e.g. acute otitis media (AOM)) are a burden for children, their families and society. Over the past decade, our knowledge on the significance of respiratory viruses has broadened remarkably. Viruses cause large variety of respiratory diseases and cause alone diseases, which previously have been assumed to be bacterial only (e.g. AOM and pneumonia). Methods for detection analysis of respiratory viruses are developing making both the diagnosis and epidemiological investigations of respiratory infections easier. Accurate diagnosis of respiratory infections and awareness of possible viral etiology could reduce the use of antibiotics. Etiologic studies of viral infections are becoming increasingly important, with the emergence of new antiviral drugs and vaccines.

  3. Establishment of a Persistent Escherichia coli Reservoir during the Acute Phase of a Bladder Infection

    PubMed Central

    Mulvey, Matthew A.; Schilling, Joel D.; Hultgren, Scott J.

    2001-01-01

    The vast majority of urinary tract infections are caused by strains of uropathogenic Escherichia coli that encode filamentous adhesive organelles called type 1 pili. These structures mediate both bacterial attachment to and invasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a urinary tract infection is unknown. Here we show that type 1-piliated uropathogens can invade the superficial epithelial cells that line the lumenal surface of the bladder and subsequently replicate, forming massive foci of intracellular E. coli termed bacterial factories. In response to infection, superficial bladder cells exfoliate and are removed with the flow of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within the bladder mucosa that may serve as a source for recurrent acute infections. These observations suggest that urinary tract infections are more chronic and invasive than generally assumed. PMID:11402001

  4. Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection

    PubMed Central

    Eller, Michael A.; Goonetilleke, Nilu; Tassaneetrithep, Boonrat; Eller, Leigh Anne; Costanzo, Margaret C.; Johnson, Susan; Betts, Michael R.; Krebs, Shelly J.; Slike, Bonnie M.; Nitayaphan, Sorachai; Rono, Kathleen; Tovanabutra, Sodsai; Maganga, Lucas; Kibuuka, Hannah; Jagodzinski, Linda; Peel, Sheila; Rolland, Morgane; Marovich, Mary A.; Kim, Jerome H.; Michael, Nelson L.; Robb, Merlin L.

    2016-01-01

    ABSTRACT Attrition within the CD4+ T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8+ T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8+ T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38+ CD27− CD8+ T cells characterized by the low expression of the CD8 receptor (CD8dim). Interestingly, while high frequencies of HIV-specific CD8+ T cell responses occur within the CD38+ CD27− CD8dim T cell population, the minority populations of CD8bright T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8dim T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8dim T cells, and the size of this population inversely correlates with the acute loss of CD4+ T cells. These data indicate, for the first time, that early CD4+ T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8dim T cell population less efficient in controlling HIV viremia. IMPORTANCE A distinct population of activated CD8+ T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8+ T cell dysfunction during acute infection. PMID:26842474

  5. Knowledge, attitude and practices regarding acute respiratory infections.

    PubMed

    Kapoor, S K; Reddaiah, V P; Murthy, G V

    1990-01-01

    One hundred and six mothers in a rural area were interviewed to determine as to how they recognise pneumonia in children, what therapies they practice with mild acute respiratory illnesses and pneumonias and the feeding practices they adopt. Most mothers recognised pneumonia by noticing fast respiratory rate and difficulty in breathing. More severe cases were recognised by these signs among a higher percentage of mothers. As regards management of mild ARI episodes, more than half the mothers preferred not to give any treatment or use only home remedies. In pneumonias, a majority of them preferred to consult a qualified doctor. Nearly a third of them were of the opinion that they would take the child to hospital if the disease was severe. Regarding feeding practices, most of them stated that they would continue feeding, fluids and breast feeds. Only 10% desired to stop and another 15% would decrease the amounts.

  6. The effect of dietary bovine colostrum on respiratory syncytial virus infection and immune responses following the infection in the mouse.

    PubMed

    Xu, Mei Ling; Kim, Hyoung Jin; Wi, Ga Ram; Kim, Hong-Jin

    2015-09-01

    Human respiratory syncytial virus (hRSV) is the most common cause of respiratory tract infection among young children because of immature T cell immunity of them against hRSV. CD8 T cells play a pivotal role in clearing hRSV and preventing subsequent infection. We examined the effects of dietary bovine colostrum on virus infection and CD8 T cell responses following hRSV infection in the mouse model. Mice received bovine colostrum for 14 days prior to hRSV challenge, and lung indexes (severity of symptom) and lung virus titers were analyzed. In addition, the activation of CD8 T cells in the bronchoalveolar lavage fluids (BALFs) of mice receiving bovine colostrum were compared with those in the BALFs of mice receiving phosphate-buffered saline (PBS) or ribavirin, post virus challenge. The severity of infection and lung virus titers were reduced in the mice receiving bovine colostrum, compared to those receiving PBS. Moreover CD8 T cell responses were selectively enhanced in the former. Our results suggest that dietary bovine colostrum exerts the effects to inhibit hRSV and ameliorate the symptom by hRSV infection, and enhances the CD8 T cell response during the hRSV infection. PMID:26310306

  7. Estimating the impact of vaccination in acute SHIV-SIV infection

    SciTech Connect

    Ribeiro, Ruy

    2008-01-01

    Human Immunodeficiency Virus (HIV) infects approxmately 0.5% of the world population, and is a major cause of morbidity and mortality worldwide. A vaccine for HIV is urgently required, and a variety of vaccine modalities have been tested in animal models of infection. A number of these studies have shown protection in monkey models of infection, although the ability of the vaccine to protect appears to vary with the viral strain and animal model used. The recent failure of a large vaccine study in humans suggests that further understanding of the basic dynamics of infection and impact of vaccination are required, in order to understand the variable efficacy of vaccination in different infections. The dynamics of HIV infection have been studied in humans and in a variety of animal models. The standard model of infection has been used to estimate the basic reproductive ratio (R{sub 0}) of the virus, calculated from the growth rate of virus in acute infection. This method has not been useful in studying the effects of vaccination, since, in the vaccines developed so far, early growth rates of virus do not differ between control and vaccinated animals. Here, we use the standard model of viral dynamics to derive the reproductive ratio from the peak viral load and nadir of target cell numbers in acute infection. We apply this method to data from studies of vaccination in Simian Human Immunodeficiency Virus (SHIV) and Simian Immunodeficiency Virus (SIV) infection and demonstrate that vaccination can reduce the reproductive ratio by 2.3 and 2 fold respectively. This method allows the comparison of vaccination efficacy amongst different viral strains and animal models in vivo.

  8. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.

    PubMed

    Kløverpris, Henrik N; Kazer, Samuel W; Mjösberg, Jenny; Mabuka, Jenniffer M; Wellmann, Amanda; Ndhlovu, Zaza; Yadon, Marisa C; Nhamoyebonde, Shepherd; Muenchhoff, Maximilian; Simoni, Yannick; Andersson, Frank; Kuhn, Warren; Garrett, Nigel; Burgers, Wendy A; Kamya, Philomena; Pretorius, Karyn; Dong, Krista; Moodley, Amber; Newell, Evan W; Kasprowicz, Victoria; Abdool Karim, Salim S; Goulder, Philip; Shalek, Alex K; Walker, Bruce D; Ndung'u, Thumbi; Leslie, Alasdair

    2016-02-16

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction. PMID:26850658

  9. Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection.

    PubMed

    Guglietta, Silvia; Garbuglia, Anna Rosa; Pacciani, Valentina; Scottà, Cristiano; Perrone, Maria Paola; Laurenti, Luca; Spada, Enea; Mele, Alfonso; Capobianchi, Maria Rosaria; Taliani, Gloria; Folgori, Antonella; Vitelli, Alessandra; Ruggeri, Lionello; Nicosia, Alfredo; Piccolella, Enza; Del Porto, Paola

    2005-09-01

    Cellular immune responses are induced during hepatitis C virus (HCV) infection and acute-phase CD8+ T cells are supposed to play an important role in controlling viral replication. In chimpanzees, failure of CD8+ T cells to control HCV replication has been associated with acquisition of mutations in MHC class I-restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8(+ T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi-species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute-phase CD8+ T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage. PMID:16114108

  10. An unusual case of infective endocarditis presenting as acute myocardial infarction.

    PubMed

    Chen, Zhong; Ng, Francesca; Nageh, Thuraia

    2007-06-01

    A 39-year-old Zimbabwean man presented with a 1 week history of fever, general malaise and acute-onset chest pain. He had a urethral stricture, which had been managed with an indwelling supra-pubic catheter. The electrocardiography on admission showed inferior ST-T segments elevation. His chest pain and electrocardiography changes resolved subsequent to thrombolysis, and he remained haemodynamically stable. The 12-h troponin I was increased at 10.5 microg/l (NR <0.04 microg/l). Echocardiography confirmed severe mitral regurgitation and a flail anterior mitral valve leaflet with an independently oscillating mobile vegetation. Enterococci faecalis were grown on blood cultures. A diagnosis of enterococci infective endocarditis with concomitant acute myocardial infarction due to possible septic emboli was made. Despite the successful outcome from thrombolysis in the setting of acute myocardial infarction with infective endocarditis, the case highlights the current lack of definitive data on the optimal acute management of such an unusual clinical scenario. Although there is serious concern that thrombolytic treatment for myocardial infarction in the setting of infective endocarditis may be associated with higher risk of cerebral haemorrhage, there is little documented evidence supporting the safety of primary percutaneous coronary intervention with these patients. PMID:17513553

  11. Acute transverse myelitis and subacute thyroiditis associated with dengue viral infection: A case report and literature review

    PubMed Central

    Mo, Zhiming; Dong, Yaxian; Chen, Xiaolian; Yao, Huiyan; Zhang, Bin

    2016-01-01

    Acute transverse myelitis is a rare manifestation of dengue infection. To the best of our knowledge, only 6 cases of acute transverse myelitis as a manifestation of dengue infection have been reported thus far. The present study described a case of acute transverse myelitis complicated with subacute thyroiditis 6 days after the onset of dengue viral infection. In addition, the available literature was searched to identify similar previous cases. Treatment with intravenous pulse methylprednisolone immunoglobulin plasmapheresis and physiotherapy resulted in partial recovery at 3 months post-infection. In conclusion, the involvement of dengue infection should be considered in patients who develop central nervous system manifestations during or after the recovery period of dengue infection. Furthermore, since methylprednisolone and immunoglobulin are effective during the active phase of the infection, prompt diagnosis and initiation of treatment are crucial. PMID:27703498

  12. Undernutrition, the Acute Phase Response to Infection, and Its Effects on Micronutrient Status Indicators12

    PubMed Central

    Bresnahan, Kara A.; Tanumihardjo, Sherry A.

    2014-01-01

    Infection and undernutrition are prevalent in developing countries and demonstrate a synergistic relation. Undernutrition increases infection-related morbidity and mortality. The acute phase response (APR) is an innate, systemic inflammatory reaction to a wide array of disruptions in a host’s homeostasis, including infection. Released from immune cells in response to deleterious stimuli, proinflammatory cytokines act on distant tissues to induce behavioral (e.g., anorexia, weakness, and fatigue) and systemic effects of the APR. Cytokines act to increase energy and protein requirements to manifest fever and support hepatic acute phase protein (APP) production. Blood concentrations of glucose and lipid are augmented to provide energy to immune cells in response to cytokines. Additionally, infection decreases intestinal absorption of nutrients and can cause direct loss of micronutrients. Traditional indicators of iron, zinc, and vitamin A status are altered during the APR, leading to inaccurate estimations of deficiency in populations with a high or unknown prevalence of infection. Blood concentrations of APPs can be measured in nutrition interventions to assess the time stage and severity of infection and correct for the APR; however, standardized cutoffs for nutrition applications are needed. Protein-energy malnutrition leads to increased gut permeability to pathogens, abnormal immune cell populations, and impaired APP response. Micronutrient deficiencies cause specific immune impairments that affect both innate and adaptive responses. This review describes the antagonistic interaction between the APR and nutritional status and emphasizes the need for integrated interventions to address undernutrition and to reduce disease burden in developing countries. PMID:25398733

  13. Microorganisms Causing Community-Acquired Acute Bronchitis: The Role of Bacterial Infection

    PubMed Central

    Park, Ji Young; Park, Sunghoon; Lee, Sun Hwa; Lee, Myung Goo; Park, Yong Bum; Oh, Kil Chan; Lee, Jae-Myung; Kim, Do Il; Seo, Ki-Hyun; Shin, Kyeong-Cheol; Yoo, Kwang Ha; Ko, Yongchun; Jang, Seung Hun; Jung, Ki-Suck; Hwang, Yong Il

    2016-01-01

    Background Although acute bronchitis is quite common, there is relatively limited information regarding the microorganisms that are involved in this illness. Methods We performed a prospective study of acute bronchitis at 31 hospitals and clinics in Korea from July 2011 to June 2012. Sputum specimens were collected for polymerase chain reaction (PCR) and culture of microorganisms. Results Of the 811 enrolled patients, 291 had acceptable sputum specimens that were included for analysis of the etiologic distribution. With multiplex PCR testing, viruses were identified in 36.1% (105/291), most commonly rhinovirus (25.8%) and coronavirus (3.8%). Typical bacteria were isolated in 126/291 (43.3%) patients. Among these patients Haemophilus influenzae (n = 39) and Streptococcus pneumoniae (n = 30) were isolated most commonly; atypical bacteria were identified in 44 (15.1%) patients. Bacteria-only, virus-only, and mixed infections (bacteria plus virus) accounted for 36.7% (98/291), 17.2% (50/291), and 18.9% (55/291) of infections, respectively. In particular, 52.4% of patients with viral infection had a concurrent bacterial infection, and rhinovirus was the most common virus in mixed infections (40/55). Additionally, infections with typical bacteria were more common in patients with chronic lung disease (p = 0.029), and typical bacterial infections showed a trend towards a higher prevalence with older age (p = 0.001). Conclusions Bacteria were associated with almost half of community-acquired acute bronchitis cases. Additional studies are required to further illuminate the role of bacteria and to identify patient groups most likely to benefit from antibiotic treatment. PMID:27788254

  14. A Pediatric Case of Acute Generalized Pustular Eruption without Streptococcal Infection.

    PubMed

    Tabata, Nobuko; Yoshizawa, Hideka

    2016-01-01

    Generalized pustular lesions characterized by acute onset with fever occur in pustulosis acuta generalisata, acute generalized exanthematous pustulosis, and generalized pustular psoriasis. In the present report, we describe a pediatric case of generalized pustular eruption that was not completely consistent with clinical features. Our patient had no evidence of a post-streptococcal infection. We observed scattered symmetric eruption of discrete pustules with an inflammatory halo on normal skin. The eruption was absent on her palms and soles of the feet. To the best of our knowledge, there are no reports in the English literature of cases with clinical features similar to those of our patient. PMID:27462226

  15. Patterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study

    PubMed Central

    Hajarizadeh, Behzad; Grady, Bart; Page, Kimberly; Kim, Arthur Y.; McGovern, Barbara H.; Cox, Andrea L.; Rice, Thomas M.; Sacks-Davis, Rachel; Bruneau, Julie; Morris, Meghan; Amin, Janaki; Schinkel, Janke; Applegate, Tanya; Maher, Lisa; Hellard, Margaret; Lloyd, Andrew R.; Prins, Maria; Dore, Gregory J.; Grebely, Jason

    2015-01-01

    Background Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. Methods Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels≤120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. Results Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P=0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). Conclusions Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex

  16. Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013

    PubMed Central

    Wang, Changbing; Zhao, Mingqi; Deng, Li; Zhong, Jiayu; Zhang, Yingying; Ye, Jun; Jing, Shuping; Cheng, Zetao; Guan, Yongxin; Ma, Yi; Sun, Yuanyuan; Zhu, Bing; Zhang, Qiwei

    2016-01-01

    Background Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Methods Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. Results Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups <1, 1–3, 3–6 and 6–14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0%). The most common co-infection pathogens with HAdV were MP (57.1%) and Human Bocavirus (HBoV) (16.7%). The majority of HAdV infected patients were totally recovered (96.9%, 480/495); However, four (0.8%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%), followed by HAdV-7 (28%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the

  17. Distinct surveillance pathway for immunopathology during acute infection via autophagy and SR-BI

    PubMed Central

    Pfeiler, Susanne; Khandagale, Avinash B.; Magenau, Astrid; Nichols, Maryana; Heijnen, Harry F. G.; Rinninger, Franz; Ziegler, Tilman; Seveau, Stephanie; Schubert, Sören; Zahler, Stefan; Verschoor, Admar; Latz, Eicke; Massberg, Steffen; Gaus, Katharina; Engelmann, Bernd

    2016-01-01

    The mechanisms protecting from immunopathology during acute bacterial infections are incompletely known. We found that in response to apoptotic immune cells and live or dead Listeria monocytogenes scavenger receptor BI (SR-BI), an anti-atherogenic lipid exchange mediator, activated internalization mechanisms with characteristics of macropinocytosis and, assisted by Golgi fragmentation, initiated autophagic responses. This was supported by scavenger receptor-induced local increases in membrane cholesterol concentrations which generated lipid domains particularly in cell extensions and the Golgi. SR-BI was a key driver of beclin-1-dependent autophagy during acute bacterial infection of the liver and spleen. Autophagy regulated tissue infiltration of neutrophils, suppressed accumulation of Ly6C+ (inflammatory) macrophages, and prevented hepatocyte necrosis in the core of infectious foci. Perifocal levels of Ly6C+ macrophages and Ly6C− macrophages were unaffected, indicating predominant regulation of the focus core. SR-BI-triggered autophagy promoted co-elimination of apoptotic immune cells and dead bacteria but barely influenced bacterial sequestration and survival or inflammasome activation, thus exclusively counteracting damage inflicted by immune responses. Hence, SR-BI- and autophagy promote a surveillance pathway that partially responds to products of antimicrobial defenses and selectively prevents immunity-induced damage during acute infection. Our findings suggest that control of infection-associated immunopathology can be based on a unified defense operation. PMID:27694929

  18. Increased frequencies of CD4+CD25high regulatory T cells in acute dengue infection

    PubMed Central

    Lühn, Kerstin; Simmons, Cameron P.; Moran, Edward; Dung, Nguyen Thi Phuong; Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thao, Le Thi Thu; Van Ngoc, Tran; Dung, Nguyen Minh; Wills, Bridget; Farrar, Jeremy; McMichael, Andrew J.; Dong, Tao; Rowland-Jones, Sarah

    2007-01-01

    Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4+CD25highFoxP3+ T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease. PMID:17452519

  19. HIV-1-Specific CD8 T Cells Exhibit Limited Cross-Reactivity during Acute Infection.

    PubMed

    Du, Victor Y; Bansal, Anju; Carlson, Jonathan; Salazar-Gonzalez, Jesus F; Salazar, Maria G; Ladell, Kristin; Gras, Stephanie; Josephs, Tracy M; Heath, Sonya L; Price, David A; Rossjohn, Jamie; Hunter, Eric; Goepfert, Paul A

    2016-04-15

    Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, most of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen. PMID:26983786

  20. HIV-1-specific CD8 T cells exhibit limited cross-reactivity during acute infection

    PubMed Central

    Du, Victor Y.; Bansal, Anju; Carlson, Jonathan; Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Ladell, Kristin; Gras, Stephanie; Josephs, Tracy M.; Heath, Sonya; Price, David A.; Rossjohn, Jamie; Hunter, Eric; Goepfert, Paul A.

    2016-01-01

    Prior work has demonstrated that HIV-1-specific CD8 T cells can cross-recognize variant epitopes. However, the majority of these studies were performed in the context of chronic infection, where the presence of viral quasispecies makes it difficult to ascertain the true nature of the original antigenic stimulus. To overcome this limitation, we evaluated the extent of CD8 T-cell cross-reactivity in patients with acute HIV-1 clade B infection. In each case, we determined the transmitted founder virus sequence to identify the autologous epitopes restricted by individual HLA class I molecules. Our data show that cross-reactive CD8 T cells are infrequent during the acute phase of HIV-1 infection. Moreover, in the uncommon instances where cross-reactive responses were detected, the variant epitopes were poorly recognized in cytotoxicity assays. Molecular analysis revealed that similar antigenic structures could be cross-recognized by identical CD8 T-cell clonotypes mobilized in vivo, yet even subtle differences in a single TCR-accessible peptide residue were sufficient to disrupt variant-specific reactivity. These findings demonstrate that CD8 T cells are highly specific for autologous epitopes during acute HIV-1 infection. Polyvalent vaccines may therefore be required to provide optimal immune cover against this genetically labile pathogen. PMID:26983786

  1. Enzyme-linked immunosorbent assay for acute adenovirus infection.

    PubMed

    Roggendorf, M; Wigand, R; Deinhardt, F; Frösner, G G

    1982-02-01

    An enzyme-linked immunosorbent assay (ELISA) is described for demonstrating antibodies to the hexone antigen of adenoviruses. The antigen-coated, flat-bottomed microtiter plates are incubated sequentially with dilutions of patients' sera (2 h at 37 degrees C) and peroxidase-coupled anti-human IgG (2 h at 37 degrees C). After a final washing, orthophenylenediamine is added to the plates, and the absorbance (A) measured 30 min later. The ELISA was found to be a hundred-fold more sensitive than complement fixation. An evaluation methods for determining antibody concentration is described which correlates the absorbance of sera diluted 10(-3) to the absorbance of a reference serum containing an arbitrary value (100) of antibody. This methods avoids titration of sera and day-to-day assay variations by different background reactions. A significant increase in antibody concentration of acute-phase serum over that of convalescent phase serum is observed. The ability to test sera in a single dilution and the automatic reading of results and their evaluation by computer make this assay suitable for diagnostic laboratories.

  2. Titration of hepatitis B virus infectivity in the sera of pre-acute and late acute phases of HBV infection: transmission experiments to chimeric mice with human liver repopulated hepatocytes.

    PubMed

    Tabuchi, Ayako; Tanaka, Junko; Katayama, Keiko; Mizui, Masaaki; Matsukura, Harumichi; Yugi, Hisao; Shimada, Takashi; Miyakawa, Yuzo; Yoshizawa, Hiroshi

    2008-12-01

    Studies of hepatitis B virus (HBV) infection in non-human primates such as chimpanzees are no longer possible due to ethical considerations and the endangered status of chimpanzees since April 2007 in Japan. A human hepatocyte transplanted chimeric mouse was used to characterize HBV infectivity in serial stages of acute infection. Chimeric mice were inoculated intravenously with serum samples obtained from an experimentally infected chimpanzee with HBV. Sera from the pre-acute phases (i.e., rump-up viremia prior to anti-HBc) and late acute phases (i.e., declining phase of HBsAg and anti-HBcAb positive) were collected from the chimpanzees 57 and 244 days after inoculation. These sera contained 2.6 x 10(6) and 2.8 x 10(6) copies/ml of HBV DNA, respectively. Three chimeric mice inoculated intravenously with 100 microl of pre-acute serum (equivalent to 10(0) copy of HBV DNA) developed an HBV infection. The three chimeric mice that received 100 microl of pre-acute serum (equivalent to 10(1) copies of HBV DNA), developed high levels of serum HBV DNA. None of the three chimeric mice inoculated with 100 microl of 1:10(4) dilution (equivalent to 10(1) copies of HBV DNA) of late-acute serum was infected, while only one of three chimeric mice inoculated with 100 microl of 1:10(3) dilution (equivalent to 10(2) copies of HBV DNA) of late-acute serum developed an HBV infection. Based on these results, chimeric mice can be used as animal models for the study of HBV infectivity, pathogenesis and control. The results show that pre-acute phase HBV serum is about 100-times more infectious than late acute phase serum.

  3. Bone marrow is a major site of long-term antibody production after acute viral infection.

    PubMed Central

    Slifka, M K; Matloubian, M; Ahmed, R

    1995-01-01

    Antiviral antibody production is often sustained for long periods after resolution of an acute viral infection. Despite extensive documentation of this phenomenon, the mechanisms involved in maintaining long-term antibody production remain poorly defined. As a first step towards understanding the nature of long-term humoral immunity, we examined the anatomical location of antibody-producing cells during acute viral infection. Using the lymphocytic choriomeningitis virus (LCMV) model, we found that after resolution of the acute infection, when antiviral plasma cells in the spleen decline, a population of virus-specific plasma cells appears in the bone marrow and constitutes the major source of long-term antibody production. Following infection of adult mice, LCMV-specific antibody-secreting cells (ASC) peaked in the spleen at 8 days postinfection but were undetectable in the bone marrow at that time. The infection was essentially cleared by 15 days, and the ASC numbers in the spleen rapidly declined while an increasing population of LCMV-specific ASC began to appear in the bone marrow. Compared with the peak response at 8 days postinfection, time points from 30 days to more than 1 year later demonstrated greater-than-10-fold reductions in splenic ASC. In contrast, LCMV-specific plasma cell numbers in the bone marrow remained high and correlated with the high levels of antiviral serum antibody. The presence of LCMV-specific plasma cells in the bone marrow was not due to persistent infection at this site, since the virus was cleared from both the spleen and bone marrow with similar kinetics as determined by infectivity and PCR assays. The immunoglobulin G subclass profile of antibody-secreting cells derived from bone marrow and the spleen correlated with the immunoglobulin G subclass distribution of LCMV-specific antibody in the serum. Upon rechallenge with LCMV, the spleen exhibited a substantial increase in virus-specific plasma cell numbers during the early phase

  4. Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia.

    PubMed

    Hogan, Alexandra B; Anderssen, Robert S; Davis, Stephanie; Moore, Hannah C; Lim, Faye J; Fathima, Parveen; Glass, Kathryn

    2016-09-01

    Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics. PMID:27294794

  5. IL-13 is associated with reduced illness and replication in primary respiratory syncytial virus infection in the mouse

    PubMed Central

    Zhou, Weisong; Hashimoto, Koichi; Moore, Martin L.; Elias, Jack A.; Zhu, Zhou; Durbin, Joan; Colasurdo, Giuseppe; Rutigliano, John A.; Chiappetta, Constance L.; Goleniewska, Kasia; O’Neal, Jamye F.; Graham, Barney S.; Peebles, R. Stokes

    2007-01-01

    The role of IL-13 in respiratory syncytial virus (RSV) immunopathogenesis is incompletely described. To assess the effect of IL-13 on primary RSV infection, transgenic mice which either overexpress IL-13 in the lung (IL-13 OE) or nontransgenic littermates (IL-13 NT) were challenged intranasally with RSV. IL-13 OE mice had significantly decreased peak viral titers four days after infection compared to non-transgenic littermates. In addition, the IL-13 OE mice had significantly lower RSV-induced weight loss and reduced lung IFN-γ protein expression compared with IL-13 NT mice. In contrast, primary RSV challenge of IL-13 deficient mice resulted in a small, but statistically significant increase in viral titers on day four after infection, no difference in RSV-induced weight loss compared to wild type mice, and augmented IFN-γ production on day 6 after infection. In STAT1-deficient (STAT1 KO) mice, where primary RSV challenge produced high levels of IL-13 production in the lungs, treatment with an IL-13 neutralizing protein resulted in greater peak viral titers both four and six days after RSV and greater RSV-induced weight loss compared to mice treated with a control protein. These results suggest that IL-13 modulates illness from RSV-infection. PMID:17110149

  6. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy

    PubMed Central

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-01-01

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research. PMID:27468190

  7. Quantitative Proteomics Identifies Host Factors Modulated during Acute Hepatitis E Virus Infection in the Swine Model

    PubMed Central

    Rogée, Sophie; Le Gall, Morgane; Chafey, Philippe; Bouquet, Jérôme; Cordonnier, Nathalie; Frederici, Christian

    2014-01-01

    ABSTRACT Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic

  8. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.

    PubMed

    Yang, Chin-Fen; Wang, C Kathy; Malkin, Elissa; Schickli, Jeanne H; Shambaugh, Cindy; Zuo, Fengrong; Galinski, Mark S; Dubovsky, Filip; Tang, Roderick S

    2013-06-10

    MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to <24 months of age demonstrated an acceptable safety profile at the following doses: 10(4), 10(5) and 10(6)TCID50. After 3 doses of MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study.

  9. Acute Hepatitis C Virus Infection Induces Consistent Changes in Circulating MicroRNAs That Are Associated with Nonlytic Hepatocyte Release

    PubMed Central

    El-Diwany, Ramy; Wasilewski, Lisa N.; Witwer, Kenneth W.; Bailey, Justin R.; Page, Kimberly; Ray, Stuart C.; Cox, Andrea L.; Thomas, David L.

    2015-01-01

    ABSTRACT Plasma microRNAs (miRNAs) change in abundance in response to disease and have been associated with liver fibrosis severity in chronic hepatitis C virus (HCV) infection. However, the early dynamics of miRNA release during acute HCV infection are poorly understood. In addition, circulating miRNA signatures have been difficult to reproduce among separate populations. We studied plasma miRNA abundance during acute HCV infection to identify an miRNA signature of early infection. We measured 754 plasma miRNAs by quantitative PCR array in a discovery cohort of 22 individuals before and during acute HCV infection and after spontaneous resolution (n = 11) or persistence (n = 11) to identify a plasma miRNA signature. The discovery cohort derived from the Baltimore Before and After Acute Study of Hepatitis. During acute HCV infection, increases in miR-122 (P < 0.01) and miR-885-5p (Pcorrected < 0.05) and a decrease in miR-494 (Pcorrected < 0.05) were observed at the earliest time points after virus detection. Changes in miR-122 and miR-885-5p were sustained in persistent (P < 0.001) but not resolved HCV infection. The circulating miRNA signature of acute HCV infection was confirmed in a separate validation cohort that was derived from the San Francisco-based You Find Out (UFO) Study (n = 28). As further confirmation, cellular changes of signature miRNAs were examined in a tissue culture model of HCV in hepatoma cells: HCV infection induced extracellular release of miR-122 and miR-885-5p despite unperturbed intracellular levels. In contrast, miR-494 accumulated intracellularly (P < 0.05). Collectively, these data are inconsistent with necrolytic release of hepatocyte miRNAs into the plasma during acute HCV infection of humans. IMPORTANCE MicroRNAs are small noncoding RNA molecules that emerging research shows can transmit regulatory signals between cells in health and disease. HCV infects 2% of humans worldwide, and chronic HCV infection is a major cause of severe

  10. Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity

    PubMed Central

    Bryant, Juliet E.; Tran, Anh Tuan; Nguyen, Bach Hue; Tran, Thi Thu Loan; Tran, Quynh Huong; Vo, Quoc Bao; Tran Dac, Nguyen Anh; Trinh, Hong Nhien; Nguyen, Thi Thanh Hai; Le Binh, Bao Tinh; Le, Khanh; Nguyen, Minh Tien; Thai, Quang Tung; Vo, Thanh Vu; Ngo, Ngoc Quang Minh; Dang, Thi Kim Huyen; Cao, Ngoc Huong; Tran, Thu Van; Ho, Lu Viet; Farrar, Jeremy; de Jong, Menno; van Doorn, H. Rogier

    2016-01-01

    Background Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. Methods A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. Results Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. Conclusion We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity. PMID:27500954

  11. Invasive fungal infection of the central nervous system in a patient with acute myeloid leukaemia

    PubMed Central

    Janik-Moszant, Anna; Matyl, Aleksander; Rurańska, Iwona; Machowska-Majchrzak, Agnieszka; Kluczewska, Ewa; Szczepański, Tomasz

    2012-01-01

    Summary Background: Although the new intensive chemotherapeutic programs introduced recently into hematooncological therapies have led to a higher number of recoveries, persistent neutropenia favours the spread of severe infections, frequently fungal infections. Systemic fungal infections in patients treated for proliferative diseases of the hematopoietic system are characterised by a severe, progressing course and high morbidity. Case Reports: We present a case report that demonstrates the diagnostic problem of lesions in the central nervous system which developed following the fourth block of chemotherapy in an eight-year-old boy treated for acute myeloid leukaemia. The risk factors, high values of the inflammatory parameters and imaging results enabled us to diagnose a fungal infection of the central nervous system. Results: A fast improvement in the clinical condition of the patient after the applied antifungal therapy and the regression of lesions in the central nervous system shown in the imaging studies confirmed our final diagnosis. PMID:22802867

  12. Depletion of alveolar macrophages prolongs survival in response to acute pneumovirus infection

    PubMed Central

    Rigaux, Peter; Killoran, Kristin E.; Qiu, Zhijun; Rosenberg, Helene F.

    2011-01-01

    Alveolar macrophages are immunoregulatory effector cells that interact directly with respiratory virus pathogens in vivo. We examined the role of alveolar macrophages in acute infection with pneumonia virus of mice (PVM), a rodent pneumovirus that replicates the clinical sequelae of severe human respiratory syncytial virus disease. We show that PVM replicates in primary mouse macrophage culture, releasing infectious virions and proinflammatory cytokines. Alveolar macrophages isolated from PVM-infected mice express activation markers Clec43 and CD86, cytokines TNFα, IL-1, IL-6, and numerous CC and CXC chemokines. Alveolar macrophage depletion prior to PVM infection results in small but statistically significant increases in virus recovery but paradoxically prolonged survival. In parallel, macrophage depleted PVM-infected mice exhibit enhanced NK cell recruitment and increased production of IFNγ by NK, CD4+ and CD8+ T cells. These results suggest a protective, immunomodulatory role for IFNγ, as overproduction secondary to macrophage depletion may promote survival despite increased virus recovery. PMID:22129848

  13. Analysis of reference gene stability after Israeli acute paralysis virus infection in bumblebees Bombus terrestris.

    PubMed

    Niu, Jinzhi; Cappelle, Kaat; de Miranda, Joachim R; Smagghe, Guy; Meeus, Ivan

    2014-01-01

    To date, there are no validated internal reference genes for the normalization of RT-qPCR data from virus infection experiments with pollinating insects. In this study we evaluated the stability of five candidate internal reference genes: elongation factor-1-alpha (ELF1α), peptidylprolyl isomerase A (PPIA), 60S ribosomal protein L23 (RPL23), TATA-binding protein (TBP) and polyubiquitin (UBI), in relation to Israeli acute paralysis virus (IAPV) infection of Bombus terrestris. We investigated the stability of these genes: in whole bodies and individual body parts, as well as in whole bodies collected at different time intervals after infection with IAPV. Our data identified PPIA as the single, most-optimal internal reference gene and the combination of PPAI-RPL23-UBI as a fully-sufficient multiple internal reference genes set for IAPV infection experiments in B. terrestris.

  14. Anemia and mechanism of erythrocyte destruction in ducks with acute Leucocytozoon infections

    USGS Publications Warehouse

    Kocan, R.M.

    1968-01-01

    In the anemia which accompanies infection by Leucocytozoon simondi in Pekin ducks there was a far greater loss of erythrocytes than could be accounted for as a result of direct physical rupture by the parasite. Erythrocyte loss began at the same time the 1st parasites appeared in the blood and was severest just prior to maximum parasitemia. Blood replacement and parasite loss occurred simultaneously. Examination of the spleen and bone marrow revealed that erythrophagocytosis was not the cause of anemia as reported for infections of Plasmodium, Babesia and Anaplasma. An anti-erythrocyte (A-E) factor was found in the serum of acutely infected ducks which agglutinated and hemolyzed normal untreated duck erythrocytes as well as infected cells. This A-E factor appeared when the 1st red cell loss was detected and reached its maximum titer just prior to the greatest red cell loss. Titers of the A-E factor were determined using normal uninfected erythrocytes at temperatures between 4 and 42 C. Cells agglutinated below 25 C and hemolyzed at 37 and 42 C. These results indicated that the A-E factor could be responsible for loss of cells other than those which were infected and could thus produce an excess loss of red cells. Attempts to implicate the A-E factor as an autoantibody were all negative. The A-E factor was present in the gamma fraction of acute serum but no anamnestic response could be detected when recovered ducks were reinfected. Anemia was never as severe in reinfections as in primary infections. The A-E factor also never reached as high a titer and was removed from the circulation very rapidly in reinfected ducks. It is concluded that red cell loss in ducks with acute Leucocytozoon disease results from intravascular hemolysis rather than erythrophagocytosis. The A-E factor responsible for hemolysis is more likely a parasite product rather than autoantibody.

  15. [Acute encephalitis. Neuropsychiatric manifestations as expression of influenza virus infection].

    PubMed

    Moreno-Flagge, Noris; Bayard, Vicente; Quirós, Evelia; Alonso, Tomás

    2009-01-01

    The aim is to review the encephalitis in infants and adolescents as well as its etiology, clinical manifestation, epidemiology, physiopathology, diagnostic methods and treatment, and the neuropsyquiatric signs appearing an influenza epidemy. Encephalitis is an inflammation of the central nervous system (CNS) which involves the brain. The clinical manifestations usually are: headache, fever and confusional stage. It could also be manifested as seizures, personality changes, or psiqyiatric symptoms. The clinical manifestations are related to the virus and the cell type affected in the brain. A meningitis or encephalopathy need to be ruled out. It could be present as an epidemic or isolated form, beeing this the most frequent form. It could be produced by a great variety of infections agents including virus, bacterias, fungal and parasitic. Viral causes are herpesvirus, arbovirus, rabies and enterovirus. Bacterias such as Borrelia burgdorferi, Rickettsia and Mycoplasma neumoniae. Some fungal causes are: Coccidioides immitis and Histoplasma capsulatum. More than 100 agents are related to encephalitis. The diagnosis of encephalitis is a challenge for the clinician and its infectious etiology is clear in only 40 to 70% of all cases. The diagnosis of encephalitis can be established with absolute certainty only by the microscopic examination of brain tissue. Epidemiology is related to age of the patients, geographic area, season, weather or the host immune system. Early intervention can reduce the mortality rate and sequels. We describe four patients with encephalitis and neuropsychiatric symptoms during an influenza epidemic.

  16. Saving the limb in diabetic patients with ischemic foot lesions complicated by acute infection.

    PubMed

    Clerici, Giacomo; Faglia, Ezio

    2014-12-01

    Ischemia and infection are the most important factors affecting the prognosis of foot ulcerations in diabetic patients. To improve the outcome of these patients, it is necessary to aggressively treat 2 important pathologies--namely, occlusive arterial disease affecting the tibial and femoral arteries and infection of the ischemic diabetic foot. Each of these 2 conditions may lead to major limb amputation, and the presence of both critical limb ischemia (CLI) and acute deep infection is a major risk factor for lower-extremity amputation. Thus, the management of diabetic foot ulcers requires specific therapeutic approaches that vary significantly depending on whether foot lesions are complicated by infection and/or ischemia. A multidisciplinary team approach is the key to successful treatment of a diabetic foot ulcer: ischemic diabetic foot ulcers complicated by acute deep infection pose serious treatment challenges because high levels of skill, organization, accuracy, and timing of intervention are required to maximize the chances of limb salvage: these complex issues are better managed by a multidisciplinary clinical group.

  17. Perceived social support among adults seeking care for acute respiratory tract infections in US EDs.

    PubMed

    Levin, Sara K; Metlay, Joshua P; Maselli, Judith H; Kersey, Ayanna S; Camargo, Carlos A; Gonzales, Ralph

    2009-06-01

    Emergency departments (EDs) provide a disproportionate amount of care to disenfranchised and vulnerable populations. We examined social support levels among a diverse population of adults seeking ED care for acute respiratory tract infections. A convenience sample of adults seeking care in 1 of 15 US EDs was telephone interviewed 1 to 6 weeks postvisit. The Multidimensional Scale of Perceived Social Support (7-point Likert) assessed social support across 3 domains: friends, family, and significant others. Higher scores indicate higher support. Of 1104 subjects enrolled, 704 (64%) completed the follow-up interview. Factor analysis yielded 3 factors. Mean social support score was 5.54 (SD 1.04). Female sex, greater household income, and better health status were independently associated with higher levels of social support. Social support levels among adults seeking care in the ED for acute respiratory tract infections are similar to general population cohorts, suggesting that social support is not a strong determinant of health care seeking in EDs.

  18. Influenza Virus-Associated Fatal Acute Necrotizing Encephalopathy: Role of Nonpermissive Viral Infection?

    PubMed Central

    Mungaomklang, Anek; Chomcheoy, Jiraruj; Wacharapluesadee, Supaporn; Joyjinda, Yutthana; Jittmittraphap, Akanitt; Rodpan, Apaporn; Ghai, Siriporn; Saraya, Abhinbhen; Hemachudha, Thiravat

    2016-01-01

    In 2014, two unusual peaks of H1N1 influenza outbreak occurred in Nakhon Ratchasima Province, in Thailand. Among 2,406 cases, one of the 22 deaths in the province included a 6-year-old boy, who initially presented with acute necrotizing encephalopathy. On the other hand, his sibling was mildly affected by the same influenza virus strain, confirmed by whole-genome sequencing, with one silent mutation. Absence of acute necrotizing encephalopathy and other neurological illnesses in the family and the whole province, with near identical whole viral genomic sequences from the two siblings, and an absence of concomitant severe lung infection (cytokine storm) at onset suggest nonpermissive infection as an alternative pathogenetic mechanism of influenza virus. PMID:27812294

  19. Management of acute respiratory infections by community health volunteers: experience of Bangladesh Rural Advancement Committee (BRAC).

    PubMed Central

    Hadi, Abdullahel

    2003-01-01

    OBJECTIVE: To assess the role of management practices for acute respiratory infections (ARIs) in improving the competency of community health volunteers in diagnosing and treating acute respiratory infections among children. METHODS: Data were collected by a group of research physicians who observed the performance of a sample of 120 health volunteers in 10 sub-districts in Bangladesh in which Bangladesh Rural Advancement Committee (BRAC) had run a community-based ARI control programme since mid-1992. Standardized tests were conducted until the 95% interphysician reliability on the observation of clinical examination was achieved. FINDINGS:The sensitivity, specificity, and overall agreement rates in diagnosing and treating ARIs were significantly higher among the health volunteers who had basic training and were supervised routinely than among those who had not. CONCLUSION: Diagnosis and treatment of ARIs at the household level in developing countries are possible if intensive basic training and the close supervision of service providers are ensured. PMID:12764514

  20. Capacity of a natural strain of woodchuck hepatitis virus, WHVNY, to induce acute infection in naive adult woodchucks.

    PubMed

    Freitas, Natalia; Lukash, Tetyana; Dudek, Megan; Litwin, Sam; Menne, Stephan; Gudima, Severin O

    2015-07-01

    Woodchuck hepatitis virus (WHV) is often used as surrogate to study mechanism of HBV infection. Currently, most infections are conducted using strains WHV7 or WHV8 that have very high sequence identity. This study focused on natural strain WHVNY that is more genetically distant from WHV7. Three naive adult woodchucks inoculated with WHVNY developed productive acute infection with long lasting viremia. However, only one of two woodchucks infected with WHV7 at the same multiplicity demonstrated productive liver infection. Quantification of intracellular WHV RNA and DNA replication intermediates; percentages of core antigen-positive hepatocytes; and serum relaxed circular DNA showed that strains WHVNY and WHV7 displayed comparable replication levels and capacities to induce acute infection in naive adult woodchucks. Strain WHVNY was therefore validated as valuable reagent to analyze the mechanism of hepadnavirus infection, especially in co- and super-infection settings, which required discrimination between two related virus genomes replicating in the same liver. PMID:25979221

  1. Best practice in the prevention and management of paediatric respiratory syncytial virus infection

    PubMed Central

    Green, Christopher A.; Sande, Charles J.

    2016-01-01

    Respiratory syncytial virus (RSV) infection is ubiquitous with almost all infants having been infected by 2 years of age and lifelong repeated infections common. It is the second largest cause of mortality, after malaria, in infants outside the neonatal period and causes up to 200,000 deaths per year worldwide. RSV results in clinical syndromes that include upper respiratory tract infections, otitis media, bronchiolitis (up to 80% of cases) and lower respiratory tract disease including pneumonia and exacerbations of asthma or viral-induced wheeze. For the purposes of this review we will focus on RSV bronchiolitis in infants in whom the greatest disease burden lies. For infants requiring hospital admission, the identification of the causative respiratory virus is used to direct cohorting or isolation and infection control procedures to minimize nosocomial transmission. Nosocomial RSV infections are associated with poorer clinical outcomes, including increased mortality, the need for mechanical ventilation and longer length of hospital stay. Numerous clinical guidelines for the management of infants with bronchiolitis have been published, although none are specific for RSV bronchiolitis. Ribavirin is the only licensed drug for the specific treatment of RSV infection but due to drug toxicity and minimal clinical benefit it has not been recommended for routine clinical use. There is currently no licensed vaccine to prevent RSV infection but passive immunoprophylaxis using a monoclonal antibody, palivizumab, reduces the risk of hospitalization due to RSV infection by 39–78% in various high-risk infants predisposed to developing severe RSV disease. The current management of RSV bronchiolitis is purely supportive, with feeding support and oxygen supplementation until the infant immune system mounts a response capable of controlling the disease. The development of a successful treatment or prophylactic agent has the potential to revolutionize the care and outcome for

  2. Acute Shunt Malfunction Caused by Percutaneous Endoscopic Gastrostomy without Shunt Infection

    PubMed Central

    Choi, Jingyu; Ki, Seung Seog

    2014-01-01

    Percutaneous endoscopic gastrostomy tube placement is often performed in patients with a ventriculoperitoneal shunt and it has been accepted as a safe procedure. The authors report a case of a 50-year-old male who developed acute exacerbation of the hydrocephalus immediately after the percutaneous endoscopic gastrostomy tube placement without any signs of shunt infection, which has not been reported until now. After revision of the intraperitoneal shunt catheter, the sizes of the intracranial ventricles were normalized. PMID:25371790

  3. Adenovirus type 7 associated with severe and fatal acute lower respiratory infections in Argentine children

    PubMed Central

    Carballal, Guadalupe; Videla, Cristina; Misirlian, Alicia; Requeijo, Paula V; Aguilar, María del Carmen

    2002-01-01

    Background Adenoviruses are the second most prevalent cause of acute lower respiratory infection of viral origin in children under four years of age in Buenos Aires, Argentina. The purpose of this study was to analyze the clinical features and outcome of acute lower respiratory infection associated with different adenovirus genotypes in children. Methods Twenty-four cases of acute lower respiratory infection and adenovirus diagnosis reported in a pediatric unit during a two-year period were retrospectively reviewed. Adenovirus was detected by antigen detection and isolation in HEp-2 cells. Adenovirus DNA from 17 isolates was studied by restriction enzyme analysis with Bam HI and Sma I. Results Subgenus b was found in 82.3% of the cases, and subgenus c in 17.7%. Within subgenus b, only genotype 7 was detected, with genomic variant 7h in 85.7% (12/14) and genomic variant 7i in 14.3% (2/14). Mean age was 8.8 ±; 6 months, and male to female ratio was 3.8: 1. At admission, pneumonia was observed in 71% of the cases and bronchiolitis in 29%. Malnutrition occurred in 37% of the cases; tachypnea in 79%; chest indrawing in 66%; wheezing in 58%; apneas in 16%; and conjunctivitis in 29%. Blood cultures for bacteria and antigen detection of other respiratory viruses were negative. During hospitalization, fatality rate was 16.7% (4 /24). Of the patients who died, three had Ad 7h and one Ad 7i. Thus, fatality rate for adenovirus type 7 reached 28.6% (4/14). Conclusions These results show the predominance of adenovirus 7 and high lethality associated with the genomic variants 7h and 7i in children hospitalized with acute lower respiratory infection. PMID:12184818

  4. Complete Genome Sequence of a Novel Human WU Polyomavirus Isolate Associated with Acute Respiratory Infection

    PubMed Central

    Dehority, Walter N.; Schwalm, Kurt C.; Young, Jesse M.; Gross, Stephen M.; Schroth, Gary P.; Young, Stephen A.

    2016-01-01

    We report here the complete genome sequence of a WU polyomavirus (WUPyV) isolate, NM040708, collected from a patient with an acute respiratory infection in New Mexico. The double-stranded DNA (dsDNA) genome of NM040708 is 5,229 bp in length and differs from the WUPyV reference with accession no. NC_009539 by 6 nucleotides and 2 amino acids. PMID:27151782

  5. Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase

    PubMed Central

    Cheung, Michael B.; Sampayo-Escobar, Viviana; Green, Ryan; Moore, Martin L.; Mohapatra, Subhra; Mohapatra, Shyam S.

    2016-01-01

    Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal stem cells (MSCs) but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts. RSV-infected MSCs showed differentially altered expression of cytokines and chemokines such as IL-1β, IL6, IL-8 and SDF-1 compared to epithelial cells. Notably, RSV-infected MSCs exhibited significantly increased expression of IFN-β (~100-fold) and indoleamine-2,3-dioxygenase (IDO) (~70-fold) than in mock-infected MSCs. IDO was identified in cytosolic protein of infected cells by Western blots and enzymatic activity was detected by tryptophan catabolism assay. Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their proliferation in a dose dependent manner. This effect on PBMC activation was reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated knockout of IDO in MSCs. Neutralizing IFN-β prevented IDO expression and activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a specific inhibitor of the TLR3/dsRNA complex, prevented IFN-β and IDO expression. Together, these results suggest that RSV infection of MSCs alters their immune regulatory function by upregulating IFN-β and IDO, affecting immune cell proliferation, which may account for the lack of protective RSV immunity and for chronicity of RSV-associated lung diseases such as asthma and COPD. PMID:27695127

  6. HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh.

    PubMed

    Mamun-Al-Mahtab; Rahman, Salimur; Khan, Mobin; Karim, Fazal

    2009-02-01

    Acute hepatitis is seen sporadically round the year in Bangladesh. The incidence of acute viral hepatitis E increases after floods as this allows sewerage contamination of piped and groundwater. The aim of this retrospective study was to assess the burden of hepatitis E virus (HEV infection) in Bangladesh. Patients attending the Hepatology Unit III of the Bangabandhu Sheikh Mujib Medical University, during June 2004-December 2006, were included in the study. All viral markers were tested by enzyme-linked immunosorbent assay. The study population was divided in four groups. Group 1 included 144 patients with acute viral hepatitis. The inclusion criteria were: nausea and/or vomiting, loss of appetite, serum bilirubin >200 micromol/L, raised serum transaminases, and prothrombin time >3 seconds prolonged beyond control value. In Group 2, there were 31 pregnant women with acute viral hepatitis. All the patients had prodrome, icterus, raised serum bilirubin and raised serum transaminase levels. Group 3 included 23 patients presenting with fulminant hepatic failure. In Group 4, 69 patients with cirrhosis of liver were included. They presented with features of decompensation for the first time. The inclusion criteria were: patients with established cirrhosis with jaundice and/or ascites and/or hepatic encephalopathy. In Group 1, 58.33% of the 144 patients had acute viral hepatitis E. In Group 2, 45.16% of the pregnant women also had acute viral hepatitis E. HEV was responsible for 56.52% cases of fulminant hepatic failure in Group 3. In 21.7% cases in Group 4, decompensation of cirrhosis was due to HEV. Acute viral hepatitis E in the third trimester of pregnancy and HEV-induced fulminant hepatic failure were associated with 80% of mortality despite the best possible care. In this clinical context, acute viral hepatitis E is the leading cause of wide spectrum of liver disease ranging from severe acute viral hepatitis, fulminant hepatic failure, to decompensation of liver in

  7. Respiratory virus infection as a cause of prolonged symptoms in acute otitis media.

    PubMed

    Arola, M; Ziegler, T; Ruuskanen, O

    1990-05-01

    We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy. The mean duration of preenrollment antimicrobial therapy was 4.8 days. For comparison we studied 66 children with newly diagnosed acute otitis media. Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05). Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group. Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy. All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection. Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection. Resistant bacteria seem to be a less common cause of failure of the initial treatment.

  8. Levofloxacin in the treatment of complicated urinary tract infections and acute pyelonephritis

    PubMed Central

    McGregor, Jessina C; Allen, George P; Bearden, David T

    2008-01-01

    Levofloxacin is a widely used fluoroquinolone approved for the treatment of complicated urinary tract infections and acute pyelonephritis. A comprehensive review of the medical literature identified five publications evaluating levofloxacin for the treatment of either complicated urinary tract infections or acute pyelonephritis. All trials, although variable in their inclusion criteria and levofloxacin dosing strategies, reported microbiologic, clinical, and safety-related outcomes. High microbiologic eradication rates, ranging from 79.8% to 95.3%, were observed in all studies. Escherichia coli was the most commonly isolated uropathogen. Data on levofloxacin resistance, both at baseline and after therapy, were limited. Clinical success was observed to range from 82.6% to 93% when measured after the completion of therapy. These clinical and microbiologic results were comparable to the fluoroquinolone comparators in all trials. Insufficient data are available to evaluate the outcomes in any meaningful patient subgroups, including catheterized patients, and those with other specific complicating factors. Levofloxacin was well tolerated in these studies, with headache, gastrointenstinal effects, and dizziness being the most commonly reported adverse events. The published data support the use of levofloxacin in complicated urinary tract infections and acute pyelonephritis. Further trials are necessary to evaluate levofloxacin within specific patient sub-populations. PMID:19209267

  9. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    PubMed Central

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  10. Antiviral Activity of TMC353121, a Respiratory Syncytial Virus (RSV) Fusion Inhibitor, in a Non-Human Primate Model

    PubMed Central

    Ispas, Gabriela; Koul, Anil; Verbeeck, Johan; Sheehan, Jennifer; Sanders-Beer, Brigitte; Roymans, Dirk; Andries, Koen; Rouan, Marie-Claude; De Jonghe, Sandra; Bonfanti, Jean-François; Vanstockem, Marc; Simmen, Kenneth; Verloes, Rene

    2015-01-01

    Background The study assessed the antiviral activity of TMC353121, a respiratory syncytial virus (RSV) fusion inhibitor, in a preclinical non-human primate challenge model with a viral shedding pattern similar to that seen in humans, following continuous infusion (CI). Methods African green monkeys were administered TMC353121 through CI, in 2 studies. Study 1 evaluated the prophylactic and therapeutic efficacy of TMC353121 at a target plasma level of 50 ng/mL (n=15; Group 1: prophylactic arm [Px50], 0.033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 24 hours pre-infection to 10 days; Group 2: therapeutic arm [Tx50], 0.033mg/mL TMC353121 from 24 hours postinfection to 8 days; Group 3: control [Vh1] vehicle, 24 hours post-infection to 8 days). Study 2 evaluated the prophylactic efficacy of TMC353121 at target plasma levels of 5 and 500 ng/mL (n=12; Group 1: prophylactic 5 arm [Px5], 0.0033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 72 hours pre-infection to 14 days; Group 2: prophylactic 500 arm [Px500], 0.33 mg/mL TMC353121; Group 3:control [Vh2] vehicle, 14 days). Bronchoalveolar lavage fluid and plasma were collected every 2 days from day 1 postinfection for pharmacokinetics and safety analysis. Findings TMC353121 showed a dose-dependent antiviral activity, varying from 1log10 reduction of peak viral load to complete inhibition of the RSV replication. Complete inhibition of RSV shedding was observed for a relatively low plasma exposure (0.39 μg/mL) and was associated with a dose-dependent reduction in INFγ, IL6 and MIP1α. TMC353121 administered as CI for 16 days was generally well-tolerated. Conclusion TMC353121 exerted dose-dependent antiviral effect ranging from full inhibition to absence of antiviral activity, in a preclinical model highly permissive for RSV replication. No new safety findings emerged from the study. PMID:26010881

  11. Rapid Development of gp120-Focused Neutralizing B Cell Responses during Acute Simian Immunodeficiency Virus Infection of African Green Monkeys

    PubMed Central

    Amos, Joshua D.; Himes, Jonathon E.; Armand, Lawrence; Gurley, Thaddeus C.; Martinez, David R.; Colvin, Lisa; Beck, Krista; Overman, R. Glenn; Liao, Hua-Xin; Moody, M. Anthony

    2015-01-01

    ABSTRACT The initial phases of acute human immunodeficiency virus type 1 (HIV-1) infection may be critical for development of effective envelope (Env)-specific antibodies capable of impeding the establishment of the latent pool of HIV-1-infected CD4+ T cells, preventing virus-induced immune hyperactivation to limit disease progression and blocking vertical virus transmission. However, the initial systemic HIV-1 Env-specific antibody response targets gp41 epitopes and fails to control acute-phase viremia. African-origin, natural simian immunodeficiency virus (SIV) hosts do not typically progress to AIDS and rarely postnatally transmit virus to their infants, despite high milk viral loads. Conversely, SIV-infected rhesus macaques (RMs), Asian-origin nonnatural SIV hosts, sustain pathogenic SIV infections and exhibit higher rates of postnatal virus transmission. In this study, of acute SIV infection, we compared the initial systemic Env-specific B cell responses of AGMs and RMs in order to probe potential factors influencing the lack of disease progression observed in AGMs. AGMs developed higher-magnitude plasma gp120-specific IgA and IgG responses than RMs, whereas RMs developed more robust gp140-directed IgG responses. These gp120-focused antibody responses were accompanied by rapid autologous neutralizing responses during acute SIV infection in AGMs compared to RMs. Moreover, acute SIV infection elicited a higher number of circulating Env-specific memory B cells in peripheral blood of AGMs than in the blood of RMs. These findings indicate that AGMs have initial systemic Env-specific B cell responses to SIV infection distinct from those of a nonnatural SIV host, resulting in more functional SIV-specific humoral responses, which may be involved in impairing pathogenic disease progression and minimizing postnatal transmission. IMPORTANCE Due to the worldwide prevalence of HIV-1 infections, development of a vaccine to prevent infection or limit the viral reservoir

  12. Immunoglobulin G antibody response in children and adults with acute dengue 3 infection.

    PubMed

    Vazquez, Susana; Acosta, Nadia; Ruiz, Didye; Calzada, Naifi; Alvarez, Angel M; Guzman, Maria G

    2009-07-01

    Using a serological test, different criteria have been established for classifying a case as primary or secondary dengue virus infection. Considering the dengue epidemiological situation in Cuba, IgG antibody response to dengue virus infection in serum samples from children and adults with a dengue 3 infection, in Havana city during the 2001-2002 epidemic was evaluated. Samples were collected on days 5-7 of fever onset and tested by an ELISA inhibition. A total of 713 serum samples positive for IgM antibody, 93 from children and 620 from adult patients were studied. Serum samples collected from healthy blood donors and patients not infected with dengue were included as controls. An IgG primary infection pattern was observed in sera collected from children, with titers of < or =20 in the 89.3% of the patients, while both, a primary and secondary patterns were observed in sera collected from adult patients with titers of < or =20 (13.4%) and > or =1280 (83.9%), respectively. These results permitted the definition of a primary or secondary case of dengue virus infection in serum samples collected during the acute phase of dengue virus infection.

  13. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection.

    PubMed

    Page, Carly; Goicochea, Lindsay; Matthews, Krystal; Zhang, Yong; Klover, Peter; Holtzman, Michael J; Hennighausen, Lothar; Frieman, Matthew

    2012-12-01

    Infection with severe acute respiratory syndrome coronavirus (SARS-CoV) causes acute lung injury (ALI) that often leads to severe lung disease. A mouse model of acute SARS-CoV infection has been helpful in understanding the host response to infection; however, there are still unanswered questions concerning SARS-CoV pathogenesis. We have shown that STAT1 plays an important role in the severity of SARS-CoV pathogenesis and that it is independent of the role of STAT1 in interferon signaling. Mice lacking STAT1 have greater weight loss, severe lung pathology with pre-pulmonary-fibrosis-like lesions, and an altered immune response following infection with SARS-CoV. We hypothesized that STAT1 plays a role in the polarization of the immune response, specifically in macrophages, resulting in a worsened outcome. To test this, we created bone marrow chimeras and cell-type-specific knockouts of STAT1 to identify which cell type(s) is critical to protection from severe lung disease after SARS-CoV infection. Bone marrow chimera experiments demonstrated that hematopoietic cells are responsible for the pathogenesis in STAT1(-/-) mice, and because of an induction of alternatively activated (AA) macrophages after infection, we hypothesized that the AA macrophages were critical for disease severity. Mice with STAT1 in either monocytes and macrophages (LysM/STAT1) or ciliated lung epithelial cells (FoxJ1/STAT1) deleted were created. Following infection, LysM/STAT1 mice display severe lung pathology, while FoxJ1/STAT1 mice display normal lung pathology. We hypothesized that AA macrophages were responsible for this STAT1-dependent pathology and therefore created STAT1/STAT6(-/-) double-knockout mice. STAT6 is essential for the development of AA macrophages. Infection of the double-knockout mice displayed a lack of lung disease and prefibrotic lesions, suggesting that AA macrophage production may be the cause of STAT1-dependent lung disease. We propose that the control of AA

  14. Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus

    PubMed Central

    2012-01-01

    Background Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer’s Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined. Results Plasma IgA level was reduced by 46% by 28 days post infection (dpi), and no IgA plasma cells were found within germinal centers of Peyer’s Patches and isolated lymphoid follicles. This lack of a T-dependent IgA response occurs although germinal centers remained functional with no sign of follicular damage, while a prolonged survival of follicular CD4+ T-cells and normal generation of IgG plasma cells is observed. Whereas the average plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to 1.9-fold more numerous in the lamina propria, the relative proportion of IgA plasma cells in this effector site was reduced by 19% (duodemun) to 35% (ileum) at 28 dpi. Conclusion Our data provide evidence that SIV is unable to initiate a T-dependent IgA response during the acute phase of infection and favors the production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA plasma cells. Therefore, an early and generalized default in IgA production takes place during the acute of phase of HIV/SIV infection, which might impair not only the virus-specific antibody response but also IgA responses to other pathogens and

  15. Validating a decision tree for serious infection: diagnostic accuracy in acutely ill children in ambulatory care

    PubMed Central

    Verbakel, Jan Y; Lemiengre, Marieke B; De Burghgraeve, Tine; De Sutter, An; Aertgeerts, Bert; Bullens, Dominique M A; Shinkins, Bethany; Van den Bruel, Ann; Buntinx, Frank

    2015-01-01

    Objective Acute infection is the most common presentation of children in primary care with only few having a serious infection (eg, sepsis, meningitis, pneumonia). To avoid complications or death, early recognition and adequate referral are essential. Clinical prediction rules have the potential to improve diagnostic decision-making for rare but serious conditions. In this study, we aimed to validate a recently developed decision tree in a new but similar population. Design Diagnostic accuracy study validating a clinical prediction rule. Setting and participants Acutely ill children presenting to ambulatory care in Flanders, Belgium, consisting of general practice and paediatric assessment in outpatient clinics or the emergency department. Intervention Physicians were asked to score the decision tree in every child. Primary outcome measures The outcome of interest was hospital admission for at least 24 h with a serious infection within 5 days after initial presentation. We report the diagnostic accuracy of the decision tree in sensitivity, specificity, likelihood ratios and predictive values. Results In total, 8962 acute illness episodes were included, of which 283 lead to admission to hospital with a serious infection. Sensitivity of the decision tree was 100% (95% CI 71.5% to 100%) at a specificity of 83.6% (95% CI 82.3% to 84.9%) in the general practitioner setting with 17% of children testing positive. In the paediatric outpatient and emergency department setting, sensitivities were below 92%, with specificities below 44.8%. Conclusions In an independent validation cohort, this clinical prediction rule has shown to be extremely sensitive to identify children at risk of hospital admission for a serious infection in general practice, making it suitable for ruling out. Trial registration number NCT02024282. PMID:26254472

  16. Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

    PubMed Central

    Coelho, Ana Maria M.; Sampietre, Sandra; Patzina, Rosely; Jukemura, Jose; Cunha, Jose Eduardo M.; Machado, Marcel C.C.

    2007-01-01

    Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy. PMID:18345325

  17. Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1.

    PubMed Central

    Cantin, E M; Hinton, D R; Chen, J; Openshaw, H

    1995-01-01

    This study was initiated to evaluate a role for gamma interferon (IFN-gamma) in herpes simplex virus type 1 (HSV-1) infection. At the acute stage of infection in mice, HSV-1 replication in trigeminal ganglia and brain stem tissue was modestly but consistently enhanced in mice from which IFN-gamma was by ablated monoclonal antibody treatment and in mice genetically lacking the IFN-gamma receptor (Rgko mice). As determined by reverse transcriptase PCR, IFN-gamma and tumor necrosis factor alpha transcripts were present in trigeminal ganglia during both acute and latent HSV-1 infection. CD4+ and CD8+ T cells were detected initially in trigeminal ganglia at day 5 after HSV-1 inoculation, and these cells persisted for 6 months into latency. The T cells were focused around morphologically normal neurons that showed no signs of active infection, but many of which expressed HSV-1 latency-associated transcripts. Secreted IFN-gamma was present up to 6 months into latency in areas of the T-cell infiltration. By 9 months into latency, both the T-cell infiltrate and IFN-gamma expression had cleared, although there remained a slight increase in macrophage levels in trigeminal ganglia. In HSV-1-infected brain stem tissue, T cells and IFN-gamma expression were present at 1 month but were gone by 6 months after infection. Our hypothesis is that the persistence of T cells and the sustained IFN-gamma expression occur in response to an HSV-1 antigen(s) in the nervous system. This hypothesis is consistent with a new model of HSV-1 latency which suggests that limited HSV-1 antigen expression occurs during latency (M. Kosz-Vnenchak, J. Jacobson, D.M. Coen, and D.M. Knipe, J. Virol. 67:5383-5393, 1993). We speculate that prolonged secretion of IFN-gamma during latency may modulate a reactivated HSV-1 infection. PMID:7609058

  18. The Effect of Statins Use on the Risk and Outcome of Acute Bacterial Infections in Adult Patients

    PubMed Central

    Ghorbani, Raheb; Afshar, Reza Kiaee

    2015-01-01

    Background Beyond their lipid-lowering abilities, statins have anti-inflammatory and immunomodulatory properties. In view of these effects, a growing interest has emerged in the possible role of statins, in preventing or decreasing morbidity and mortality from infection. Objectives The aim of this study was to determine whether previous statin use is associated with reduced risk of acute bacterial infections and better outcome of these infections. Materials and Methods In this historical cohort study, consecutive adult patients admitted with acute bacterial infection were enrolled. Control group were selected from adult outpatient and without history of acute bacterial infections. Acute bacterial infections included in this study were; pneumonia, acute pyelonephritis, cellulitis and sepsis with unknown origin. Data about baseline characteristics, co-morbidities and statins use of two groups was obtained. Results Finally 144 patients met inclusion criteria and were enrolled. Same numbers of controls were selected. Two groups were matched based on most baseline characteristics and co-morbidities. The patients’ categories were as follows: pneumonia 42.3%, acute pyelonephritis 23.6%, cellulitis 16% and sepsis 18%. From all participants 29.9% of patients and 45.8% controls were statin users. There was significant association between previous statin use and reduced risk of acute bacterial infections (Mantel Haenszel Weighted Odds Ratio=0.51, 95% CI: 0.30-0.85, p=0.009). Duration of hospitalization was significantly shorter in statin users (p=0.002). Hospital mortality rate was lower (14.6%) in statins users when compared with non-users (18.8%) with significant difference (p=0.028). Conclusion Prior therapy with statins is associated with considerably reduced onset of acute bacterial infections and better outcome in adult patients. PMID:26676277

  19. Virological Characteristics of Acute Hepatitis B in Eastern India: Critical Differences with Chronic Infection

    PubMed Central

    Sarkar, Neelakshi; Pal, Ananya; Das, Dipanwita; Saha, Debraj; Biswas, Avik; Bandopadhayay, Bhaswati; Chakraborti, Mandira; Ghosh, Mrinmoy; Chakravarty, Runu

    2015-01-01

    Hepatitis B Virus (HBV) manifests high genetic variability and is classifiable into ten genotypes (A-J). HBV infection can lead to variable clinical outcomes, ranging from self-limiting acute hepatitis to active chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study characterizes HBV strains circulating among patients with acute (AHB) and chronic HBV infection (CHB). Among a total of 653 HBsAg positive cases, 40 manifested acute infection. After sequencing the surface(S), basal core promoter/pre-core(BCP/PC) and the X gene regions, phylogenetic tree was constructed using MEGA4 by neighbor-joining method. Statistical robustness was established with bootstrap analysis. Nucleotide diversity was determined by Shannon entropy per site using the Entropy program of the Los Alamos National Laboratories. Analyses of acute patients revealed that HBV/D2 is the major circulating sub-genotype and commonly associated with sexual promiscuity and the age group between15-30 years. Comparison of AHB and CHB patients revealed that HBeAg positivity, ALT levels and genotype D were significantly high in AHB, whereas CHB patients were predominantly male, had a high viral load, and were commonly associated with genotype C. The frequencies of mutations in the S, BCP/PC, and X gene were low in AHB as compared to CHB. Drug resistant mutations were not detectable in the polymerase gene of AHB. Average nucleotide diversity in AHB was considerably low as compared to CHB. Further, the highest average ΔH (average difference in entropy between chronic and acute infection) was observed in the BCP/PC region implying that this region was most vulnerable to mutations upon HBV persistence, especially in case of genotype C. Additionally, among all substitutions, the A1762T and G1764A BCP mutations were the strongest indicators of chronicity. In conclusion, the study exhibits a general portrait of HBV strains circulating among acute hepatitis B patients in Eastern India and their

  20. [Interaction of the Siberian and Far Eastern subtypes of tick-borne encephalitis virus in mammals with mixed infection. Competition of the subtypes in acute and inapparent infection].

    PubMed

    Gerasimov, S G; Pogodina, V V; Koliasnikova, N M; Karan', L S; Malenko, G V; Levina, L S

    2011-01-01

    Long-term monitoring of natural tick-borne encephalitis virus (TBEV) populations could reveal the change of TBEV subtypes, the displacement of the Far Eastern (FE) subtype, and its substitution for the Siberian (Sib) subtype. Acute and inapparent mixed infections were studied in Syrian hamsters to understand this phenomenon. The animals were inoculated with the Sib subtype and then with the FE one of TBEV (JQ845440-YaroslavI-Aver-08 and Fj214132-Kemerovo-Phateev-1954 strains). The inapparent form developed more frequently in mixed infection. Viral progeny was genotyped by reverse transcription polymerase chain reaction and hybridization fluorescence detection using genotype-specific probes. Independent reproduction of strains in the brain gave way to competition. The FE subtype dominated in hamster youngsters with acute infection. The Sib subtype had selective benefits in asymptomatic infection (adult hamsters infected intracerebrally and subcutaneously and youngsters infected subcutaneously). The competition of the subtypes was imperfect.

  1. In vivo infection of IgG-containing cells by Jembrana disease virus during acute infection

    SciTech Connect

    Desport, Moira; Tenaya, I.W. Masa; McLachlan, Alexander; McNab, Tegan J.; Rachmat, Judhi; Hartaningsih, Nining; Wilcox, Graham E.

    2009-10-25

    Jembrana disease virus (JDV) is an unusual bovine lentivirus which causes a non-follicular proliferation of lymphocytes, a transient immunosuppression and a delayed humoral response in infected Bali cattle in Indonesia. A double-immunofluorescent labeling method was developed to identify the subset of mononuclear cells in which the viral capsid protein could be detected. Viral antigen was present in pleomorphic centroblast-like cells which were identified as IgG-containing cells, including plasma cells, in lymphoid tissues. There was no evidence of infection of CD3{sup +} T-cells or MAC387{sup +} monocytes in tissues but large vacuolated cells with a macrophage-like morphology in the lung were found to contain viral antigen although they could not be shown conclusively to be infected. The tropism of JDV for mature IgG-containing cells may be relevant to understanding the pathogenesis of Jembrana disease, the delayed antibody responses and the genetic composition of this atypical lentivirus.

  2. Norovirus Antagonism of B cell Antigen Presentation Results in Impaired Control of Acute Infection

    PubMed Central

    Zhu, Shu; Jones, Melissa K.; Hickman, Danielle; Han, Shuhong; Reeves, Westley; Karst, Stephanie M.

    2016-01-01

    Human noroviruses are a leading cause of gastroenteritis so vaccine development is desperately needed. Elucidating viral mechanisms of immune antagonism can provide key insight into designing effective immunization platforms. We recently revealed that B cells are targets of norovirus infection. Because noroviruses can regulate antigen presentation by infected macrophages and B cells can function as antigen presenting cells, we tested whether noroviruses regulate B cell-mediated antigen presentation and the biological consequence of such regulation. Indeed, murine noroviruses could prevent B cell expression of antigen presentation molecules and this directly correlated with impaired control of acute infection. In addition to B cells, acute control required MHC class I molecules, CD8+ T cells, and granzymes, supporting a model whereby B cells act as antigen presenting cells to activate cytotoxic CD8+ T cells. This immune pathway was active prior to the induction of antiviral antibody responses. As in macrophages, the minor structural protein VP2 regulated B cell antigen presentation in a virus-specific manner. Commensal bacteria were not required for activation of this pathway and ultimately only B cells were required for clearance of viral infection. These findings provide new insight into the role of B cells in stimulating antiviral CD8+ T cell responses. PMID:27007673

  3. A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates

    PubMed Central

    Yokoe, Deborah S.; Anderson, Deverick J.; Berenholtz, Sean M.; Calfee, David P.; Dubberke, Erik R.; Ellingson, Katherine D.; Gerding, Dale N.; Haas, Janet P.; Kaye, Keith S.; Klompas, Michael; Lo, Evelyn; Marschall, Jonas; Mermel, Leonard A.; Nicolle, Lindsay E.; Salgado, Cassandra D.; Bryant, Kristina; Classen, David; Crist, Katrina; Deloney, Valerie M.; Fishman, Neil O.; Foster, Nancy; Goldmann, Donald A.; Humphreys, Eve; Jernigan, John A.; Padberg, Jennifer; Perl, Trish M.; Podgorny, Kelly; Septimus, Edward J.; VanAmringe, Margaret; Weaver, Tom; Weinstein, Robert A.; Wise, Robert; Maragakis, Lisa L.

    2014-01-01

    Since the publication of “A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals” in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS). PMID:25026611

  4. A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection

    PubMed Central

    Rossi, Fernanda C.; Angerami, Rodrigo N.; de Paula, Erich V.; Orsi, Fernanda L.; Shang, Dezhi; del Guercio, Vânia M.; Resende, Mariângela R.; Annichino-Bizzacchi, Joyce M.; da Silva, Luiz J.; Zheng, X. Long; Castro, Vagner

    2011-01-01

    BACKGROUND Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue. PMID:19788513

  5. A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates.

    PubMed

    Yokoe, Deborah S; Anderson, Deverick J; Berenholtz, Sean M; Calfee, David P; Dubberke, Erik R; Ellingson, Katherine D; Gerding, Dale N; Haas, Janet P; Kaye, Keith S; Klompas, Michael; Lo, Evelyn; Marschall, Jonas; Mermel, Leonard A; Nicolle, Lindsay E; Salgado, Cassandra D; Bryant, Kristina; Classen, David; Crist, Katrina; Deloney, Valerie M; Fishman, Neil O; Foster, Nancy; Goldmann, Donald A; Humphreys, Eve; Jernigan, John A; Padberg, Jennifer; Perl, Trish M; Podgorny, Kelly; Septimus, Edward J; VanAmringe, Margaret; Weaver, Tom; Weinstein, Robert A; Wise, Robert; Maragakis, Lisa L

    2014-08-01

    Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS).

  6. Genomic and functional analysis of the host response to acute simian varicella infection in the lung

    PubMed Central

    Arnold, Nicole; Girke, Thomas; Sureshchandra, Suhas; Nguyen, Christina; Rais, Maham; Messaoudi, Ilhem

    2016-01-01

    Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host. PMID:27677639

  7. A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates.

    PubMed

    Yokoe, Deborah S; Anderson, Deverick J; Berenholtz, Sean M; Calfee, David P; Dubberke, Erik R; Ellingson, Katherine D; Gerding, Dale N; Haas, Janet P; Kaye, Keith S; Klompas, Michael; Lo, Evelyn; Marschall, Jonas; Mermel, Leonard A; Nicolle, Lindsay E; Salgado, Cassandra D; Bryant, Kristina; Classen, David; Crist, Katrina; Deloney, Valerie M; Fishman, Neil O; Foster, Nancy; Goldmann, Donald A; Humphreys, Eve; Jernigan, John A; Padberg, Jennifer; Perl, Trish M; Podgorny, Kelly; Septimus, Edward J; VanAmringe, Margaret; Weaver, Tom; Weinstein, Robert A; Wise, Robert; Maragakis, Lisa L

    2014-08-01

    Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS).

  8. Cost-effective Screening for Acute Hepatitis C Virus Infection in HIV-Infected Men Who Have Sex With Men

    PubMed Central

    Linas, Benjamin P.; Wong, Angela Y.; Schackman, Bruce R.; Kim, Arthur Y.; Freedberg, Kenneth A.

    2012-01-01

    Background. We used a Monte Carlo computer simulation to estimate the effectiveness and cost-effectiveness of screening for acute hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)–infected men who have sex with men. Methods. One-time screening for prevalent HCV infection was performed at the time of enrollment in care, followed by either symptom-based screening, screening with liver function tests (LFTs), HCV antibody (Ab) screening, or HCV RNA screening in various combinations and intervals. We considered both treatment with pegylated interferon and ribavirin (PEG/RBV) alone and with an HCV protease inhibitor. Outcome measures were life expectancy, quality-adjusted life expectancy, direct medical costs, and cost-effectiveness, assuming a societal willingness to pay $100 000 per quality-adjusted life-year (QALY) gained. Results. All strategies increased life expectancy (from 0.49 to 0.94 life-months), quality-adjusted life expectancy (from 0.47 to 1.00 quality-adjusted life-months), and costs (from $1900 to $7600), compared with symptom-based screening. The incremental cost-effectiveness ratio of screening with 6-month LFTs and a 12-month HCV Ab test, compared with symptom-based screening, was $43 700/QALY (for PEG/RBV alone) and $57 800/QALY (for PEG/RBV plus HCV protease inhibitor). The incremental cost-effectiveness ratio of screening with 3-month LFTs, compared with 6-month LFTs plus a 12-month HCV Ab test, was $129 700/QALY (for PEG/RBV alone) and $229 900/QALY (for PEG/RBV plus HCV protease inhibitor). With HCV protease inhibitor–based therapy, screening with 6-month LFTs and a 12-month HCV Ab test was the optimal strategy when the HCV infection incidence was ≤1.25 cases/100 person-years. The 3-month LFT strategy was optimal when the incidence was >1.25 cases/100 person-years. Conclusions. Screening for acute HCV infection in HIV-infected MSM prolongs life expectancy and is cost-effective. Depending on incidence

  9. Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

    PubMed Central

    Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

    2016-01-01

    The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

  10. Acute Acalculous Cholecystitis by Epstein-Barr Virus Infection: A Rare Association

    PubMed Central

    Vieira, Maria; Couto, Cristiana; Coelho, Maria D.; Laranjeira, Carla

    2015-01-01

    Acute acalculous cholecystitis (AAC) is a rare complication of Epstein Barr virus (EBV) infection, with only a few cases reported among pediatric population. This clinical condition is frequently associated with a favorable outcome and, usually, a surgical intervention is not required. We report a 16-year-old girl who presented with AAC following primary EBV infection. The diagnosis of AAC was documented by clinical and ultrasonographic examination, whereas EBV infection was confirmed serologically. A conservative treatment was performed, with a careful monitoring and serial ultrasonographic examinations, which led to the clinical improvement of the patient. Pediatricians should be aware of the possible association between EBV and AAC, in order to offer the patients an appropriate management strategy. PMID:26753086

  11. Cutaneous Infection Caused by Cylindrocarpon lichenicola in a Patient with Acute Myelogenous Leukemia

    PubMed Central

    Iwen, Peter C.; Tarantolo, Stefano R.; Sutton, Deanna A.; Rinaldi, Michael G.; Hinrichs, Steven H.

    2000-01-01

    Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been associated with human disease. We report the first case of localized invasive cutaneous infection caused by this fungus in a 53-year-old male from the rural midwestern United States with relapsed acute myelogenous leukemia. On admission for induction chemotherapy, the patient was noted to have an abrasive laceration between the fourth and fifth metacarpophalangeal joints and on the dorsum of the right hand, which progressed to frank ulceration following chemotherapy. A biopsy provided an initial diagnosis of an invasive fungal infection consistent with aspergillosis based on the histopathological appearance of the mold in tissue. Multiple positive fungal cultures which were obtained from the biopsied tissue were subsequently identified by microscopic and macroscopic characteristics to be C. lichenicola. The infection resolved following marrow regeneration, aggressive debridement of the affected tissue, and treatment with amphotericin B. This case extends the conditions associated with invasive disease caused by C. lichenicola. PMID:10970386

  12. Mixed Pulmonary Infection with Penicillium notatum and Pneumocystis jiroveci in a Patient with Acute Myeloid Leukemia

    PubMed Central

    Tehrani, Shabnam; Hemmatian, Marjan

    2016-01-01

    Penicillium notatum is a fungus that widely exists in the environment and is often non-pathogenic to humans. However, in immunocompromised hosts it may be recognized as a cause of systemic mycosis. A 44-year-old man with acute myeloid leukemia (AML) was admitted to our hospital with fever and neutropenia. Due to no improvement after initial treatment, he underwent bronchoscopy. The patient was found to have P. notatum and Pneumocystis jiroveci infection, and therefore was given voriconazole, primaquine and clindamycin. The patient was successfully treated and suffered no complications. Conclusion: This case highlights P. notatum as a cause of infection in immunocompromised patients. To the best of our knowledge, mixed lung infection with P. notatum and P. jiroveci in a patient with AML has not been previously reported. PMID:27403180

  13. Pseudomonas aeruginosa forms biofilms in acute infection independent of cell-to-cell signaling.

    PubMed

    Schaber, J Andy; Triffo, W Jeffrey; Suh, Sang Jin; Oliver, Jeffrey W; Hastert, Mary Catherine; Griswold, John A; Auer, Manfred; Hamood, Abdul N; Rumbaugh, Kendra P

    2007-08-01

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 h of infection in thermally injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections as well. Using light, electron, and confocal scanning laser microscopy, P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild-type and QS-deficient P. aeruginosa strains formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independently of QS.

  14. Outdoor air pollution and acute respiratory infections among children in developing countries.

    PubMed

    Romieu, Isabelle; Samet, Jonathan M; Smith, Kirk R; Bruce, Nigel

    2002-07-01

    Acute respiratory infections (ARIs) are the most common cause of illness and death in children in the developing world. This review focuses on outdoor air pollutants associated with pediatric ARI mortality and morbidity. Studies were identified using MEDLINE and other electronic databases. Four studies showed an increase in infant mortality in relation to outdoor air pollution. Short-term follow-up and time-series studies suggest that air pollutants act as risk factors for respiratory infection. Air pollution exposure increases the incidence of upper- and lower-respiratory infections in children. Because complex pollution mixtures are present in the studied urban areas, pollutant levels at which ARI risk would be expected to increase cannot be determined. Children may be at greater risk, given the poor environmental and nutritional conditions prevalent in developing countries.

  15. Inhibiting platelets aggregation could aggravate the acute infection caused by Staphylococcus aureus.

    PubMed

    Zhang, Xin; Liu, Yu; Gao, Yaping; Dong, Jie; Mu, Chunhua; Lu, Qiang; Shao, Ningsheng; Yang, Guang

    2011-01-01

    Several fibrinogen binding proteins (Fibs) play important roles in the pathogenesis of Staphylococcus aureus (S. aureus). Most Fibs can promote the aggregation of platelets during infection, but the extracellular fibrinogen-binding protein (Efb) is an exception. It is reported that Efb can specifically bind fibrinogen and inhibit the aggregation of platelet with its N terminal. However, the biological significance of platelet aggregation inhibition in the infection caused by S. aureus is unclear until now. Here, we demonstrated that the persistence and aggregation of platelets were important for killing S. aureus in whole blood. It was found that the N terminal of Efb (EfbN) and platelets inhibitors could increase the survival of S. aureus in whole blood. The study in vivo also showed that EfbN and platelets inhibitors could reduce the killing of S. aureus and increase the lethality rate of S. aureus in the acute infection mouse model.

  16. Viral Etiology of Respiratory Tract Infections in Children at the Pediatric Hospital in Ouagadougou (Burkina Faso)

    PubMed Central

    Ouédraogo, Solange; Traoré, Blaise; Nene Bi, Zah Ange Brice; Yonli, Firmin Tiandama; Kima, Donatien; Bonané, Pierre; Congo, Lassané; Traoré, Rasmata Ouédraogo; Yé, Diarra; Marguet, Christophe; Plantier, Jean-Christophe; Vabret, Astrid; Gueudin, Marie

    2014-01-01

    Background Acute respiratory infections (ARIs) are a major cause of morbidity and mortality in children in Africa. The circulation of viruses classically implicated in ARIs is poorly known in Burkina Faso. The aim of this study was to identify the respiratory viruses present in children admitted to or consulting at the pediatric hospital in Ouagadougou. Methods From July 2010 to July 2011, we tested nasal aspirates of 209 children with upper or lower respiratory infection for main respiratory viruses (respiratory syncytial virus (RSV), metapneumovirus, adenovirus, parainfluenza viruses 1, 2 and 3, influenza A, B and C, rhinovirus/enterovirus), by immunofluorescence locally in Ouagadougou, and by PCR in France. Bacteria have also been investigated in 97 samples. Results 153 children (73.2%) carried at least one virus and 175 viruses were detected. Rhinoviruses/enteroviruses were most frequently detected (rhinovirus n = 88; enterovirus n = 38) and were found to circulate throughout the year. An epidemic of RSV infections (n = 25) was identified in September/October, followed by an epidemic of influenza virus (n = 13), mostly H1N1pdm09. This epidemic occurred during the period of the year in which nighttime temperatures and humidity were at their lowest. Other viruses tested were detected only sporadically. Twenty-two viral co-infections were observed. Bacteria were detected in 29/97 samples with 22 viral/bacterial co-infections. Conclusions This study, the first of its type in Burkina Faso, warrants further investigation to confirm the seasonality of RSV infection and to improve local diagnosis of influenza. The long-term objective is to optimize therapeutic management of infected children. PMID:25360527

  17. Analysis of Serum Th1/Th2 Cytokine Levels in Patients with Acute Mumps Infection

    PubMed Central

    Malaiyan, Jeevan; Ramanan, Padmasani Venkat; Subramaniam, Dinesh; Menon, Thangam

    2016-01-01

    Background: The mumps virus is frequently the causative agent of parotitis. There has been no study on serum cytokine levels of acute mumps parotitis except for a few which document cytokine levels in cerebrospinal fluid of mumps meningitis. It is with this notion, our study aimed to find Th1/Th2 cytokine levels from patients with acute mumps parotitis. Materials and Methods: Concentrations of mumps-specific IgM, mumps, measles, rubella-specific IgG antibody, and Th1/Th2 cytokines, namely interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-10 were measured simultaneously in serum from 74 patients (42 pediatric and 32 adult cases), 40 healthy subjects (20 pediatric and 20 adults) and in the supernatant of peripheral blood mononuclear cells stimulated with mumps virus genotype C which served as the positive control. Statistical significance was analyzed between each group by means of Mann–Whitney U-test, Kruskal–Wallis test, and Spearman's rank correlation coefficient test. Results: IgM positivity confirmed acute infection in all 74 patients and of these 67 were vaccinated cases; however, very few of them (10/67) were positive for mumps IgG. We found that IFN-γ, IL-2, and IL-10 showed a statistically significant increase in both pediatric and adult patients with acute mumps infection when compared to healthy controls and values were comparable to the positive control. Conclusion: The Th1 cells play important roles during the acute phase of mumps parotitis. PMID:27293364

  18. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation.

    PubMed

    Ballen, Karen; Woo Ahn, Kwang; Chen, Min; Abdel-Azim, Hisham; Ahmed, Ibrahim; Aljurf, Mahmoud; Antin, Joseph; Bhatt, Ami S; Boeckh, Michael; Chen, George; Dandoy, Christopher; George, Biju; Laughlin, Mary J; Lazarus, Hillard M; MacMillan, Margaret L; Margolis, David A; Marks, David I; Norkin, Maxim; Rosenthal, Joseph; Saad, Ayman; Savani, Bipin; Schouten, Harry C; Storek, Jan; Szabolcs, Paul; Ustun, Celalettin; Verneris, Michael R; Waller, Edmund K; Weisdorf, Daniel J; Williams, Kirsten M; Wingard, John R; Wirk, Baldeep; Wolfs, Tom; Young, Jo-Anne H; Auletta, Jeffrey; Komanduri, Krishna V; Lindemans, Caroline; Riches, Marcie L

    2016-09-01

    Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n= 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P < .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P < .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P < .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and <.0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥ 90% but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes.

  19. Global reemergence of enterovirus D68 as an important pathogen for acute respiratory infections.

    PubMed

    Imamura, Tadatsugu; Oshitani, Hitoshi

    2015-03-01

    We previously detected enterovirus D68 (EV-D68) in children with severe acute respiratory infections in the Philippines in 2008-2009. Since then, the detection frequency of EV-D68 has increased in different parts of the world, and EV-D68 is now recognized as a reemerging pathogen. However, the epidemiological profile and clinical significance of EV-D68 is yet to be defined, and the virological characteristics of EV-D68 are not fully understood. Recent studies have revealed that EV-D68 is detected among patients with acute respiratory infections of differing severities ranging from mild upper respiratory tract infections to severe pneumonia including fatal cases in pediatric and adult patients. In some study sites, the EV-D68 detection rate was higher among patients with lower respiratory tract infections than among those with upper respiratory tract infections, suggesting that EV-D68 infections are more likely to be associated with severe respiratory illnesses. EV-D68 strains circulating in recent years have been divided into three distinct genetic lineages with different antigenicity. However, the association between genetic differences and disease severity, as well as the occurrence of large-scale outbreaks, remains elusive. Previous studies have revealed that EV-D68 is acid sensitive and has an optimal growth temperature of 33 °C. EV-D68 binds to α2,6-linked sialic acids; hence, it is assumed that it has an affinity for the upper respiratory track where these glycans are present. However, the lack of suitable animal model constrains comprehensive understanding of the pathogenesis of EV-D68.

  20. Progress in Treatment of Viral Infections in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Moschovi, Maria; Adamaki, Maria; Vlahopoulos, Spiros A.

    2016-01-01

    In children, the most commonly encountered type of leukemia is acute lymphoblastic leukemia (ALL). An important source of morbidity and mortality in ALL are viral infections. Even though allogeneic transplantations, which are often applied also in ALL, carry a recognized risk for viral infections, there are multiple factors that make ALL patients susceptible to viral infections. The presence of those factors has an influence in the type and severity of infections. Currently available treatment options do not guarantee a positive outcome for every case of viral infection in ALL, without significant side effects. Side effects can have very serious consequences for the ALL patients, which include nephrotoxicity. For this reason a number of strategies for personalized intervention have been already clinically tested, and experimental approaches are being developed. Adoptive immunotherapy, which entails administration of ex vivo grown immune cells to a patient, is a promising approach in general, and for transplant recipients in particular. The ex vivo grown cells are aimed to strengthen the immune response to the virus that has been identified in the patients’ blood and tissue samples. Even though many patients with weakened immune system can benefit from progress in novel approaches, a viral infection still poses a very significant risk for many patients. Therefore, preventive measures and supportive care are very important for ALL patients. PMID:27471584

  1. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys.

    PubMed Central

    Yasutomi, Y; Reimann, K A; Lord, C I; Miller, M D; Letvin, N L

    1993-01-01

    To assess the possible role of cytotoxic T lymphocytes (CTLs) in containing the spread of human immunodeficiency virus in acutely infected individuals, the temporal evolution of the virus-specific CD8+ lymphocyte response was defined in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. A brief period of SIVmac plasma antigenemia was seen 9 to 16 days following intravenous infection with SIVmac, ending as the absolute number of CD8+ peripheral blood lymphocytes (PBLs) increased. In a prospective assessment of the ability of CD8+ lymphocytes of these monkeys to suppress SIVmac replication in autologous PBLs, inhibitory activity was detected as early as 4 days, with a more pronounced effect 12 to 16 days following infection. SIVmac Gag- and Nef-specific CD8+ effector cell activities were demonstrable in PBLs of animals by 2 weeks following virus inoculation. In fact, SIVmac-specific CTL precursors were documented in the PBLs of rhesus monkeys 4 to 6 days after SIVmac infection. These studies indicate that AIDS virus-specific CD8+ CTLs are present in PBLs within days of infection and may play an important role in containing the early spread of virus. PMID:8437240

  2. Transcriptome Analysis of the Initial Stage of Acute WSSV Infection Caused by Temperature Change

    PubMed Central

    Sun, Yumiao; Li, Fuhua; Sun, Zheng; Zhang, Xiaojun; Li, Shihao; Zhang, Chengsong; Xiang, Jianhai

    2014-01-01

    White spot syndrome virus (WSSV) is the most devastating virosis threatening the shrimp culture industry worldwide. Variations of environmental factors in shrimp culture ponds usually lead to the outbreak of white spot syndrome (WSS). In order to know the molecular mechanisms of WSS outbreak induced by temperature variation and the biological changes of the host at the initial stage of WSSV acute infection, RNA-Seq technology was used to analyze the differentially expressed genes (DEGs) in shrimp with a certain amount of WSSV cultured at 18°C and shrimp whose culture temperature were raised to 25°C. To analyze whether the expression changes of the DEGs were due to temperature rising or WSSV proliferation, the expression of selected DEGs was analyzed by real-time PCR with another shrimp group, namely Group T, as control. Group T didn’t suffer WSSV infection but was subjected to temperature rising in parallel. At the initial stage of WSSV acute infection, DEGs related to energy production were up-regulated, whereas most DEGs related to cell cycle and positive regulation of cell death and were down-regulated. Triose phosphate isomerase, enolase and alcohol dehydrogenase involved in glycosis were up-regulated, while pyruvate dehydrogenase, citrate synthase and isocitrate dehydrogenase with NAD as the coenzyme involved in TCA pathway were down-regulated. Also genes involved in host DNA replication, including DNA primase, DNA topoisomerase and DNA polymerase showed down-regulated expression. Several interesting genes including crustin genes, acting binding or inhibiting protein genes, a disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) gene and a GRP 78 gene were also analyzed. Understanding the interactions between hosts and WSSV at the initial stage of acute infection will not only help to get a deep insight into the pathogenesis of WSSV but also provide clues for therapies. PMID:24595043

  3. Respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants

    PubMed Central

    2013-01-01

    Background Respiratory Syncytial Virus (RSV) is the most important cause of severe respiratory infections in infants with seasonal epidemics. Environmental factors (temperature, humidity, air pollution) could influence RSV epidemics through their effects on virus activity and diffusion. Methods We conducted a retrospective study on a paediatric population who referred to our Paediatric Emergency Unit in order to analyze the correlation between weekly incidence of RSV positive cases during winter season in Bologna and meteorological factors and air pollutants concentration. Results We observed a significant correlation between the incidence of RSV infections and the mean minimum temperature registered during the same week and the previous weeks. The weekly number of RSV positive cases was also correlated to the mean PM10 concentration of the week before. Conclusions RSV epidemic trend in Bologna (Italy) is related to the mean minimum temperature, and the mean PM10 concentration. PMID:23311474

  4. Acute phase response in two consecutive experimentally induced E. coli intramammary infections in dairy cows

    PubMed Central

    Suojala, Leena; Orro, Toomas; Järvinen, Hanna; Saatsi, Johanna; Pyörälä, Satu

    2008-01-01

    Background Acute phase proteins haptoglobin (Hp), serum amyloid A (SAA) and lipopolysaccharide binding protein (LBP) have suggested to be suitable inflammatory markers for bovine mastitis. The aim of the study was to investigate acute phase markers along with clinical parameters in two consecutive intramammary challenges with Escherichia coli and to evaluate the possible carry-over effect when same animals are used in an experimental model. Methods Mastitis was induced with a dose of 1500 cfu of E. coli in one quarter of six cows and inoculation repeated in another quarter after an interval of 14 days. Concentrations of acute phase proteins haptoglobin (Hp), serum amyloid A (SAA) and lipopolysaccharide binding protein (LBP) were determined in serum and milk. Results In both challenges all cows became infected and developed clinical mastitis within 12 hours of inoculation. Clinical disease and acute phase response was generally milder in the second challenge. Concentrations of SAA in milk started to increase 12 hours after inoculation and peaked at 60 hours after the first challenge and at 44 hours after the second challenge. Concentrations of SAA in serum increased more slowly and peaked at the same times as in milk; concentrations in serum were about one third of those in milk. Hp started to increase in milk similarly and peaked at 36–44 hours. In serum, the concentration of Hp peaked at 60–68 hours and was twice as high as in milk. LBP concentrations in milk and serum started to increase after 12 hours and peaked at 36 hours, being higher in milk. The concentrations of acute phase proteins in serum and milk in the E. coli infection model were much higher than those recorded in experiments using Gram-positive pathogens, indicating the severe inflammation induced by E. coli. Conclusion Acute phase proteins would be useful parameters as mastitis indicators and to assess the severity of mastitis. If repeated experimental intramammary induction of the same animals

  5. Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection

    PubMed Central

    Ren, Peijun; Sheng, Jun; Yan, Huajie; Zhang, Jing; Lin, Xin; Wang, Yongjin; Delpeyroux, Francis; Deubel, Vincent

    2009-01-01

    Background Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5′ untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. Methodology/Findings We cloned and sequenced a 924-nt fragment that covered part of the 5′UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5′ UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3′UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. Conclusion Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was

  6. Diagnostic challenge: bilateral infected lumbar facet cysts - a rare cause of acute lumbar spinal stenosis and back pain

    PubMed Central

    2010-01-01

    Symptomatic synovial lumbar facet cysts are a relatively rare cause of radiculopathy and spinal stenosis. This case and brief review of the literature, details a patient who presented with acutely symptomatic bilateral spontaneously infected synovial facet (L4/5) cysts. This report highlights diagnostic clues for identifying infection of a facet cyst. PMID:20205727

  7. The effect of feeding endophyte-infected fescue on the acute phase response to lipopolysaccharide in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angus heifers (n = 22; 292 ± 9.0 kg body weight) were paired by body weight and randomly placed on either an endophyte-infected (E+) or endophyte-free (E-) diet for 10 days to determine the influence of feeding endophyte-infected fescue on the physiological and acute phase responses of beef heifers ...

  8. Transient elevation of triiodothyronine caused by triiodothyronine autoantibody associated with acute Epstein-Barr-virus infection.

    PubMed

    Shimon, Ilan; Pariente, Clara; Shlomo-David, Jaffa; Grossman, Zehava; Sack, Joseph

    2003-02-01

    A unique 16-year old female patient presented after acute Epstein-Barr virus (EBV) infection with severe primary hypothyroidism. Her thyroid test results were thyrotropin level (TSH) of 198 mU/L (normal, 0.4-4 mU/L), free thyroxine [FT(4)], 2.5 pmol/L (normal, 10-25 pmol/L), total triiodothyronine (TT(3)) > 19.5 nmol/L (normal, 1.3-2.7 nmol/L), and free triiodothyronine (FT(3)), 0.77 pmol/L (normal, 3.3-6.3 pmol/L). She had high titers of thyroglobulin and thyroid peroxidase autoantibodies. In vitro triiodothyronine (T(3))-binding measured by radioimmunoprecipitation was 86% (normal, up to 8.5%) and thyroxine (T(4))-binding 8.2% (normal, 6.4%). Serum immunoglobulin G (IgG) absorption, achieved by protein-G Sepharose beads, decreased TT(3) toward normal. Levothyroxine treatment normalized the low baseline FT(4) and FT(3) values, and suppressed TSH to normal. However, TT(3) remained highly elevated and returned to normal after 20 months, while T(3 )binding gradually decreased. Thus, her severe hypothyroidism was masked by this unusual phenomenon. Thirty-four patients with EBV infection (15 with acute disease and 19 with previous infection) were tested for thyroid hormone levels. EBV antibodies (early antigen immunoglobulin M [IgM] and IgG and anti-Epstein-Barr virus nuclear antigen [EBNA] IgG) were measured by enzyme-linked immunosorbent assay (ELISA). In 15 patients with acute EBV the mean TT(3) level was 2.47 +/- 0.39 nmol/L (5 had TT(3) values above normal) compared to a mean TT(3) of 1.70 +/- 0.53 nmol/L in 19 subjects with previous infection (p < 0.0005; only 1 had a TT(3) result above normal), with no differences in FT(4) and TSH concentrations between the two groups. Acute EBV infection may be associated with transient mild to severe TT(3) elevation as a result of assay interference by anti-T(3) autoantibodies.

  9. Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays.

    PubMed

    Wesolowski, Laura G; Nasrullah, Muazzam; Coombs, Robert W; Rosenberg, Eric; Ethridge, Steven F; Hutchinson, Angela B; Dragavon, Joan; Rychert, Jennifer; Nolte, Frederick S; Madory, James E; Werner, Barbara G

    2016-01-01

    Background.  To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods.  We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results.  From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions.  Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT.

  10. Acute Infections, Cost per Infection and Turnaround Time in Three United States Hospital Laboratories Using Fourth-Generation Antigen-Antibody Human Immunodeficiency Virus Immunoassays.

    PubMed

    Wesolowski, Laura G; Nasrullah, Muazzam; Coombs, Robert W; Rosenberg, Eric; Ethridge, Steven F; Hutchinson, Angela B; Dragavon, Joan; Rychert, Jennifer; Nolte, Frederick S; Madory, James E; Werner, Barbara G

    2016-01-01

    Background.  To improve clinical and public health outcomes through early human immunodeficiency virus (HIV) detection, fourth-generation antigen/antibody immunoassay (4IA) and supplemental testing results must be returned rapidly. Methods.  We examined HIV testing data at Harborview Medical Center (HMC), Massachusetts General Hospital (MGH), and the Medical University of South Carolina (MUSC), which used 4IA and supplemental antibody and nucleic acid tests (NATs). At MGH and MUSC, HIV-1 Western blot (WB) and HIV-2 testing were conducted at a reference laboratory. We compared time from specimen collection to laboratory result for established (positive WB) and acute infections (reactive 4IA, negative/indeterminate WB, detectable NAT), and we calculated testing cost per positive-test result. Results.  From 3731 (MUSC) to 19 774 (MGH) tests were conducted; 0.01% (MGH) to 0.05% (HMC) were acute infections. Each laboratory had reactive 4IA, WB-negative, or indeterminate specimens without NAT (ie, potential acute infections). Time to result was 1.5 (HMC) to 5.2 days (MGH) for acute and 1.0 (HMC) to 5.2 days (MGH) for established infections. Costs were $1054 (MGH) to $1521 (MUSC). Conclusions.  Conducting supplemental testing in-house lowered turnaround times, which may be further reduced with rapid HIV-1/HIV-2 differentiation tests. Hospitals may benefit from quantitative NATs not requiring physician orders, so all potential acute infections receive NAT. PMID:26798766

  11. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi

    PubMed Central

    Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo

    2013-01-01

    Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243

  12. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization.

  13. Current and future trends in antibiotic therapy of acute bacterial skin and skin-structure infections.

    PubMed

    Russo, A; Concia, E; Cristini, F; De Rosa, F G; Esposito, S; Menichetti, F; Petrosillo, N; Tumbarello, M; Venditti, M; Viale, P; Viscoli, C; Bassetti, M

    2016-04-01

    In 2013 the US Food and Drug Administration (FDA) issued recommendations and guidance on developing drugs for treatment of skin infection using a new definition of acute bacterial skin and skin-structure infection (ABSSSI). The new classification includes cellulitis, erysipelas, major skin abscesses and wound infection with a considerable extension of skin involvement, clearly referring to a severe subset of skin infections. The main goal of the FDA was to better identify specific infections where the advantages of a new antibiotic could be precisely estimated through quantifiable parameters, such as improvement of the lesion size and of systemic signs of infection. Before the spread and diffusion of methicillin-resistant Staphylococcus aureus (MRSA) in skin infections, antibiotic therapy was relatively straightforward. Using an empiric approach, a β-lactam was the preferred therapy and cultures from patients were rarely obtained. With the emergence of MRSA in the community setting, initial ABSSSI management has been changed and readdressed. Dalbavancin, oritavancin and tedizolid are new drugs, approved or in development for ABSSSI treatment, that also proved to be efficient against MRSA. Dalbavancin and oritavancin have a long half-life and can be dosed less frequently. This in turn makes it possible to treat patients with ABSSSI in an outpatient setting, avoiding hospitalization or potentially allowing earlier discharge, without compromising efficacy. In conclusion, characteristics of long-acting antibiotics could represent an opportunity for the management of ABSSSI and could profoundly modify the management of these infections by reducing or in some cases eliminating both costs and risks of hospitalization. PMID:27125562

  14. ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation

    PubMed Central

    González-Sanz, Rubén; Mata, Manuel; Bermejo-Martín, Jesús; Álvarez, Amparo; Cortijo, Julio; Melero, José A.

    2016-01-01

    ABSTRACT Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15−/−) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control. PMID:26763998

  15. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report

    PubMed Central

    Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  16. Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case Report.

    PubMed

    Vitaliti, Giovanna; Falsaperla, Raffaele; Giunta, Leandra; Spataro, Giuseppina; Rapisarda, Venerando; Velardita, Mario; Nunnari, Giuseppe; Pavone, Piero

    2013-01-01

    Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. PMID:23970901

  17. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection

    PubMed Central

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  18. [Bocavirus in infants under 5 years with acute respiratory infection. Chaco Province, Argentina, 2014].

    PubMed

    Deluca, Gerardo D; Urquijo, María Cecilia; Passarella, Carolina; Picón, César; Picón, Dimas; Acosta, María; Rovira, Carina; Marín, Héctor M

    2016-01-01

    Acute respiratory infection (ARI) is the most frequent pathology along human life, being the most common cause of morbidity and mortality in children under 5 years. The aim of this study was to determine the frequency of bocavirus (BoV) in infants under 5 years with symptoms of ARI from north Argentina (Chaco province). The study was performed on nasopharyngeal aspirates from 488 patients, in the period of January-December 2014. The samples were tested by real time PCR and 36 positive BoV cases (7.4%) were detected. The period with the highest detection rate was June-September with 28 cases (77.8%), of which 26 (72.2%) were infants between 6-18 moths of life. In half of BoV positive cases this virus was detected as single infection of the upper respiratory tract, and in the remaining 50%, as concomitant infection with other microorganisms. To our knowledge, this would be the first study on molecular epidemiology of BoV in northern Argentina. We emphasize the importance of investigating these new viruses capable of generating acute respiratory disease and also to disseminate awareness on their circulation within the community.

  19. [Bocavirus in infants under 5 years with acute respiratory infection. Chaco Province, Argentina, 2014].

    PubMed

    Deluca, Gerardo D; Urquijo, María Cecilia; Passarella, Carolina; Picón, César; Picón, Dimas; Acosta, María; Rovira, Carina; Marín, Héctor M

    2016-01-01

    Acute respiratory infection (ARI) is the most frequent pathology along human life, being the most common cause of morbidity and mortality in children under 5 years. The aim of this study was to determine the frequency of bocavirus (BoV) in infants under 5 years with symptoms of ARI from north Argentina (Chaco province). The study was performed on nasopharyngeal aspirates from 488 patients, in the period of January-December 2014. The samples were tested by real time PCR and 36 positive BoV cases (7.4%) were detected. The period with the highest detection rate was June-September with 28 cases (77.8%), of which 26 (72.2%) were infants between 6-18 moths of life. In half of BoV positive cases this virus was detected as single infection of the upper respiratory tract, and in the remaining 50%, as concomitant infection with other microorganisms. To our knowledge, this would be the first study on molecular epidemiology of BoV in northern Argentina. We emphasize the importance of investigating these new viruses capable of generating acute respiratory disease and also to disseminate awareness on their circulation within the community. PMID:27295701

  20. Serum Galectin-9 and Galectin-3-Binding Protein in Acute Dengue Virus Infection.

    PubMed

    Liu, Kuan-Ting; Liu, Yao-Hua; Chen, Yen-Hsu; Lin, Chun-Yu; Huang, Chung-Hao; Yen, Meng-Chi; Kuo, Po-Lin

    2016-01-01

    Dengue fever is a serious threat for public health and induces various inflammatory cytokines and mediators, including galectins and glycoproteins. Diverse immune responses and immunological pathways are induced in different phases of dengue fever progression. However, the status of serum galectins and glycoproteins is not fully determined. The aim of this study was to investigate the serum concentration and potential interaction of soluble galectin-1, galectin-3, galectin-9, galectin-3 binding protein (galectin-3BP), glycoprotein 130 (gp130), and E-, L-, and P-selectin in patients with dengue fever in acute febrile phase. In this study, 317 febrile patients (187 dengue patients, 150 non-dengue patients that included 48 patients with bacterial infection and 102 patients with other febrile illness) who presented to the emergency department and 20 healthy controls were enrolled. Our results showed the levels of galectin-9 and galectin-3BP were significantly higher in dengue patients than those in healthy controls. Lower serum levels of galectin-1, galectin-3, and E-, L-, and P-selectin in dengue patients were detected compared to bacteria-infected patients, but not to healthy controls. In addition, strong correlation between galectin-9 and galectin-3BP was observed in dengue patients. In summary, our study suggested galectin-9 and galectin-3BP might be critical inflammatory mediators in acute dengue virus infection. PMID:27240351

  1. [Evaluation of an immunochromatographic fourth generation test for the rapid diagnosis of acute HIV infection].

    PubMed

    Kawahata, Takuya; Nagashima, Mami; Sadamasu, Kenji; Kojima, Yoko; Mori, Haruyo

    2013-07-01

    The early diagnosis of human immunodeficiency virus (HIV) infection is important to provide effective antiviral treatment and to prevent transmission of HIV. One of the key issues to achieve this goal is to shorten the so-called "diagnostic window period" when the humoral immune response toward the virus is not fully developed during the acute phase of HIV-1 infection. In 2008, the Espline HIV Ag/Ab test kit (E4G, Fujirebio Inc. Japan) was marketed in Japan belonging to the fourth generation of HIV test kits characterized by its ability to detect both viral antigens (Ag) and anti-HIV-1/2 antibodies (Ab). E4G is the first and only fourth generation immunochromatographic HIV test kit approved in Japan at present. To evaluate its performance to diagnose acute HIV infection (AHI), E4G was compared with fourth generation Ag/Ab ELISA test kits, a third generation PA test kit, WB and real-time PCR for the testing of 25 AHI clinical specimens. E4G detected HIV infection in 18/25 specimens (sensitivity : 72.0%), of which the viral Ag was detected in only 2 specimens (8.0%) bearing a viral load > 10 million copies/mL. No spesimens were simultaneously reactive to both Ag and Ab against HIV. The third generation PA achieved a positive score of 17/ 25 specimens (68.0%), which was almost the same as the E4G figure. In contrast the fourth generation Ag/ Ab ELISA scored all the 25 AHI specimens positive (sensitivity : 100%). Overall, although having the merit of offering a rapid diagnostic test for HIV infection, E4G does not provide a sensitivity in AHI diagnosis superior to test kits currently available.

  2. Two Ocular Infections during Conventional Chemotherapy in a Patient with Acute Lymphoblastic Leukemia: A Case Report

    PubMed Central

    Taha, Ruba; Al Hijji, Ibrahim; El Omri, Halima; Al-Laftah, Fareed; Negm, Riham; Yassin, Mohammed; El Ayoubi, Hanadi

    2010-01-01

    Viral retinitis due to cytomegalovirus (CMV) infection is rare in patients with acute leukemia who did not receive hematopoietic stem cell transplantation. We report a case of CMV retinitis that developed in a 49-year-old patient with acute lymphoblastic leukemia. The patient was treated with salvage chemotherapy using a hyper-CVAD regimen and did not receive hematopoietic stem cell transplantation. The incidence of CMV retinitis in this subgroup of patients is not described in literature. He had a very complicated course during chemotherapy but was successfully treated, with preservation of visual acuity, and to date he is in complete remission. Interestingly, prior to CMV retinitis, the patient had been diagnosed with and treated for candida retinitis. This case shows the importance of eye examination and care in patients diagnosed with hematological malignancies. PMID:20740203

  3. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    PubMed

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  4. Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model

    SciTech Connect

    Guillaume, Vanessa; Wong, K. Thong; Looi, R.Y.; Georges-Courbot, Marie-Claude; Barrot, Laura; Buckland, Robin; Wild, T. Fabian; Horvat, Branka

    2009-05-10

    Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses. We have analysed here the pathogenesis of the acute HeV infection using the new animal model, golden hamster (Mesocricetus auratus), which is highly susceptible to HeV infection. HeV-specific RNA and viral antigens were found in multiple organs and virus was isolated from different tissues. Dual pathogenic mechanism was observed: parenchymal infection in various organs, including the brain, with vasculitis and multinucleated syncytia in many blood vessels. Furthermore, monoclonal antibodies specific for the NiV fusion protein neutralized HeV in vitro and efficiently protected hamsters from HeV if given before infection. These results reveal the similarities between HeV and NiV pathogenesis, particularly in affecting both respiratory and neuronal system. They demonstrate that hamster presents a convenient novel animal model to study HeV infection, opening new perspectives to evaluate vaccine and therapeutic approaches against this emergent infectious disease.

  5. Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections

    PubMed Central

    Braido, F; Tarantini, F; Ghiglione, V; Melioli, G; Canonica, G W

    2007-01-01

    Respiratory tract infections (RTIs) represent a serious problem because they are one of the most common cause of human death by infection. The search for the treatment of those diseases has therefore a great importance. In this study we provide an overview of the currently available treatments for RTIs with particular attention to chronic obstructive pulmonary diseases exacerbations and recurrent respiratory infections therapy and a description of bacterial lysate action, in particular making reference to the medical literature dealing with its clinical efficacy. Those studies are based on a very large number of clinical trials aimed to evaluate the effects of this drug in maintaining the immune system in a state of alert, and in increasing the defences against microbial infections. From this analysis it comes out that bacterial lysates have a protective effect, which induce a significant reduction of the symptoms related to respiratory infections. Those results could be very interesting also from an economic point of view, because they envisage a reduction in the number of acute exacerbations and a shorter duration of hospitalization. The use of bacterial lysate could therefore represent an important means to achieve an extension of life duration in patients affected by respiratory diseases. PMID:18229572

  6. Use of Noninvasive Parameters to Evaluate Swiss Webster Mice During Trypanosoma cruzi Experimental Acute Infection.

    PubMed

    Campos, Jerônimo D S; Hoppe, Luanda Y; Duque, Thabata L A; de Castro, Solange Lisboa; Oliveira, Gabriel M

    2016-04-01

    Until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. The aim of this work is to use noninvasive methods to evaluate clinical signs in Swiss Webster mice that were experimentally infected with the Y strain of Trypanosoma cruzi during acute phase (Inf group). Infected mice showed evident clinical changes beginning in the second week of infection (wpi) when compared to the noninfected group (NI): (1) animals in hunched postures, closed eyes, lowered ears, peeling skin, increased piloerection, prostration, and social isolation; (2) significant decrease in body weight (Inf: 26.2 ± 2.6 g vs. NI: 34.2 ± 2.5 g) and in chow (1.5 ± 0.3 vs. 6.3 ± 0.5 mg) and water (2.4 ± 0.5 vs. 5.8 ± 0.7 ml) intake; (3) significant decrease of spontaneous activity as locomotor parameters: distance (0.64 ± 0.06 vs. 1.8 ± 0.13 m), velocity (1.9 ± 0.3 vs. 6.7 ± 1.5 cm/sec), and exploratory behavior by frequency (1.0 ± 0.5 vs. 5.7 ± 1.0 events) and duration (1.4 ± 0.3 vs. 5.1 ± 0.5 sec in central arena region); (4) significant increase in the PR (41.7 ± 8.7 vs. 27.6 ± 1.9 msec) and QT intervals (39.7 ± 2.0 vs. 27.5 ± 4.0 msec), and a decreased cardiac frequency (505 ± 52.8 vs. 774 ± 17.8 msec), showing a marked sinus bradycardia and an atrioventricular block. At 3 and 4 wpi, the surviving animals showed a tendency of recovery in body weight, food intake, locomotor activity, and exploratory interest. Through the use of noninvasive parameters, we were able to monitor the severity of the infection in individuals prior to death. Our perspective is the application of noninvasive methods to describe clinical signs over the course of acute infection complementing the preclinical evaluation of new agents, alone or in combination with benznidazole.

  7. Use of Noninvasive Parameters to Evaluate Swiss Webster Mice During Trypanosoma cruzi Experimental Acute Infection.

    PubMed

    Campos, Jerônimo D S; Hoppe, Luanda Y; Duque, Thabata L A; de Castro, Solange Lisboa; Oliveira, Gabriel M

    2016-04-01

    Until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. The aim of this work is to use noninvasive methods to evaluate clinical signs in Swiss Webster mice that were experimentally infected with the Y strain of Trypanosoma cruzi during acute phase (Inf group). Infected mice showed evident clinical changes beginning in the second week of infection (wpi) when compared to the noninfected group (NI): (1) animals in hunched postures, closed eyes, lowered ears, peeling skin, increased piloerection, prostration, and social isolation; (2) significant decrease in body weight (Inf: 26.2 ± 2.6 g vs. NI: 34.2 ± 2.5 g) and in chow (1.5 ± 0.3 vs. 6.3 ± 0.5 mg) and water (2.4 ± 0.5 vs. 5.8 ± 0.7 ml) intake; (3) significant decrease of spontaneous activity as locomotor parameters: distance (0.64 ± 0.06 vs. 1.8 ± 0.13 m), velocity (1.9 ± 0.3 vs. 6.7 ± 1.5 cm/sec), and exploratory behavior by frequency (1.0 ± 0.5 vs. 5.7 ± 1.0 events) and duration (1.4 ± 0.3 vs. 5.1 ± 0.5 sec in central arena region); (4) significant increase in the PR (41.7 ± 8.7 vs. 27.6 ± 1.9 msec) and QT intervals (39.7 ± 2.0 vs. 27.5 ± 4.0 msec), and a decreased cardiac frequency (505 ± 52.8 vs. 774 ± 17.8 msec), showing a marked sinus bradycardia and an atrioventricular block. At 3 and 4 wpi, the surviving animals showed a tendency of recovery in body weight, food intake, locomotor activity, and exploratory interest. Through the use of noninvasive parameters, we were able to monitor the severity of the infection in individuals prior to death. Our perspective is the application of noninvasive methods to describe clinical signs over the course of acute infection complementing the preclinical evaluation of new agents, alone or in combination with benznidazole. PMID:26741817

  8. [Stress effects of imidacloprid on RSV in rice plants].

    PubMed

    Wang, Shuang; Fu, Hong-wei; Yang, Yi-zhong

    2014-12-01

    The rice stripe disease is a viral disease transmitted by small brown planthopper, Laodelphax striatellus, which outbroke a few years ago in the Yangtze River basin, especially Jiangsu region, China. To study the effects of imidacloprid stress on rice stripe virus (RSV) in rice plants, the rice seedlings were treated with imidacloprid 1, 2, 3 and 4 times (B1, B2, B3 and B4), respectively, after artificial inoculation by L. striatellus for 48 h, and the expression levels of relative genes including RSV NS3, CP, SP and NSvc4, as well as the protein concentrations of CP and SP were detected at different stages by real-time PCR and Western blotting. The results showed that the effects of imidacloprid treatment on the expression levels of four genes were gene-specific and correlated with application frequencies of imidacloprid. The expression levels of NS3 gene were upregulated in three treatments, and the highest expression level (10.86) was observed 16 days after inoculation in B4 treatment, but a significant down-regulation of NS3 gene was found in all other treatments. The expression levels of CP, SP and NSvc4 genes were down-regulated significantly (0-0.74) in almost all B2 and B3 treatments, while a significant up-regulation was found in half of B1 and B4 treatments, and the highest expression levels of SP gene were observed 16 days after inoculation in B1 (258.89) and B4 (730.54) treatment, respectively. On the other hand, the effects of imidacloprid stress on the expression patterns of CP and SP genes were different from those of CP and SP proteins. For example, the expression level of CP gene was almost no expression (0) 19 days after inoculation in B1 treatment, while significantly up-regulated (23.08) was observdd for CP protein. PMID:25876413

  9. Prevalence of adenovirus and rotavirus infection in immunocompromised patients with acute gastroenteritis in Portugal

    PubMed Central

    Ribeiro, Joana; Ferreira, Delfim; Arrabalde, Célia; Almeida, Sandra; Baldaque, Inês; Sousa, Hugo

    2015-01-01

    AIM: To characterize the prevalence of rotavirus (RV) and adenovirus (AdV) infections in immunocompromised patients with acute gastroenteritis. METHODS: The presence of RV and AdV (serotypes 40 and 41) was evaluated in 509 stool samples obtained between January 2009 and December 2010 from 200 immunocompromised patients (83 females and 117 males; median age 21 years old, range 0-72. The diagnosis of infection was performed as a routine procedure and the presence of RV and AdV (serotypes 40 and 41) was determined by immunochromatography using the RIDA® Quick Rota-Adeno-Kombi kit (r-Biopharm, Darmstadt, Germany). The data analysis and description of seasonal frequencies were performed using computer software IBM® SPSS® (Statistical Package for Social Sciences) Statistics version 20.0 for Mac. The frequencies of infection were compared into different age and gender groups by χ2 test. RESULTS: The study revealed 12.4% AdV positive samples and 0.8% RV positive samples, which correspond to a prevalence of 6.5% and 1.5%, respectively. AdV was more frequent between October 2009 and April 2010, while RV was identified in April 2010 and July 2010. The stool analysis revealed that from the 509 samples, 63 (12.4%) were positive for AdV and 4 (0.8%) positive for RV, which by resuming the information of each patient, lead to an overall prevalence of AdV and RV of 6.5% (13/200 patients) and 1.5% (3/200 patients), respectively. The stratification of the analysis regarding age groups showed a tendency to an increased prevalence of infection in paediatric patients between 0-10 years old. Considering the seasonal distribution of these infections, our study revealed that AdV infection was more frequent between October 2009 and April 2010, while RV infection was characterized by two distinct peaks (April 2010 and July 2010). CONCLUSION: The overall prevalence of AdV and RV infection in immunocompromised patients with acute gastroenteritis was 8% and AdV was the most prevalent agent

  10. Burkholderia pseudomallei Colony Morphotypes Show a Synchronized Metabolic Pattern after Acute Infection

    PubMed Central

    Steinmetz, Ivo; Lalk, Michael

    2016-01-01

    Background Burkholderia pseudomallei is a water and soil bacterium and the causative agent of melioidosis. A characteristic feature of this bacterium is the formation of different colony morphologies which can be isolated from environmental samples as well as from clinical samples, but can also be induced in vitro. Previous studies indicate that morphotypes can differ in a number of characteristics such as resistance to oxidative stress, cellular adhesion and intracellular replication. Yet the metabolic features of B. pseudomallei and its different morphotypes have not been examined in detail so far. Therefore, this study aimed to characterize the exometabolome of B. pseudomallei morphotypes and the impact of acute infection on their metabolic characteristics. Methods and Principal Findings We applied nuclear magnetic resonance spectroscopy (1H-NMR) in a metabolic footprint approach to compare nutrition uptake and metabolite secretion of starvation induced morphotypes of the B. pseudomallei strains K96243 and E8. We observed gluconate production and uptake in all morphotype cultures. Our study also revealed that among all morphotypes amino acids could be classified with regard to their fast and slow consumption. In addition to these shared metabolic features, the morphotypes varied highly in amino acid uptake profiles, secretion of branched chain amino acid metabolites and carbon utilization. After intracellular passage in vitro or murine acute infection in vivo, we observed a switch of the various morphotypes towards a single morphotype and a synchronization of nutrient uptake and metabolite secretion. Conclusion To our knowledge, this study provides first insights into the basic metabolism of B. pseudomallei and its colony morphotypes. Furthermore, our data suggest, that acute infection leads to the synchronization of B. pseudomallei colony morphology and metabolism through yet unknown host signals and bacterial mechanisms. PMID:26943908

  11. Infection related renal impairment: a major cause of acute allograft dysfunction.

    PubMed

    Nampoory, Mangalathillam R N; Johny, Kaivilayil V; Costandy, Jamal N; Nair, Madhavan P; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, Mustafa

    2003-06-01

    We prospectively analyzed the impact of post-transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40+14 years). During the follow-up period, 52 patients expired and 64 lost on followup. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100+90.2) than that of acute rejection (166+127.1), but was more than that in cyclosporine toxicity (50+42.2). Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=or<0.01). Ecoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR. PMID:15859909

  12. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

    PubMed

    Tan, Petrina; Lye, David C; Yeo, Tun Kuan; Cheung, Carol Y; Thein, Tun-Linn; Wong, Joshua G; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C; Leo, Yee-Sin; Teoh, Stephen C

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.

  13. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells.

    PubMed

    Rochford, Kevin; Chen, Feng; Waguespack, Yan; Figliozzi, Robert W; Kharel, Madan K; Zhang, Qiaojuan; Martin-Caraballo, Miguel; Hsia, S Victor

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  14. Volatile Organic Compound Gamma-Butyrolactone Released upon Herpes Simplex Virus Type -1 Acute Infection Modulated Membrane Potential and Repressed Viral Infection in Human Neuron-Like Cells

    PubMed Central

    Waguespack, Yan; Figliozzi, Robert W.; Kharel, Madan K.; Zhang, Qiaojuan; Martin-Caraballo, Miguel

    2016-01-01

    Herpes Simplex Virus Type -1 (HSV-1) infections can cause serious complications such as keratitis and encephalitis. The goal of this study was to identify any changes in the concentrations of volatile organic compounds (VOCs) produced during HSV-1 infection of epithelial cells that could potentially be used as an indicator of a response to stress. An additional objective was to study if any VOCs released from acute epithelial infection may influence subsequent neuronal infection to facilitate latency. To investigate these hypotheses, Vero cells were infected with HSV-1 and the emission of VOCs was analyzed using two-dimensional gas chromatograph/mass spectrometry (2D GC/MS). It was observed that the concentrations of gamma-butyrolactone (GBL) in particular changed significantly after a 24-hour infection. Since HSV-1 may establish latency in neurons after the acute infection, GBL was tested to determine if it exerts neuronal regulation of infection. The results indicated that GBL altered the resting membrane potential of differentiated LNCaP cells and promoted a non-permissive state of HSV-1 infection by repressing viral replication. These observations may provide useful clues towards understanding the complex signaling pathways that occur during the HSV-1 primary infection and establishment of viral latency. PMID:27537375

  15. Fungal infection intensity and zoospore output of Atelopus zeteki, a potential acute chytrid supershedder.

    PubMed

    Direnzo, Graziella V; Langhammer, Penny F; Zamudio, Kelly R; Lips, Karen R

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population declines throughout its range, rapidly and exponentially increases skin Bd infection intensity, achieving intensities that are several orders of magnitude greater than most other species reported. We experimentally infected individuals that were never exposed to Bd (n = 5) or previously exposed to an attenuated Bd strain (JEL427-P39; n = 3). Within seven days post-inoculation, the average Bd infection intensity was 18,213 zoospores (SE: 9,010; range: 0 to 66,928). Both average Bd infection intensity and zoospore output (i.e., the number of zoospores released per minute by an infected individual) increased exponentially until time of death (t50 = 7.018, p<0.001, t46 = 3.164, p = 0.001, respectively). Mean Bd infection intensity and zoospore output at death were 4,334,422 zoospores (SE: 1,236,431) and 23.55 zoospores per minute (SE: 22.78), respectively, with as many as 9,584,158 zoospores on a single individual. The daily percent increases in Bd infection intensity and zoospore output were 35.4% (SE: 0.05) and 13.1% (SE: 0.04), respectively. We also found that Bd infection intensity and zoospore output were positively correlated (t43 = 3.926, p<0.001). All animals died between 22 and 33 days post-inoculation (mean: 28.88; SE: 1.58). Prior Bd infection had no effect on survival, Bd infection intensity, or zoospore output. We conclude that A. zeteki, a highly susceptible amphibian species, may be an acute supershedder. Our results can inform epidemiological models to estimate Bd outbreak probability, especially as they relate to

  16. Fungal Infection Intensity and Zoospore Output of Atelopus zeteki, a Potential Acute Chytrid Supershedder

    PubMed Central

    DiRenzo, Graziella V.; Langhammer, Penny F.; Zamudio, Kelly R.; Lips, Karen R.

    2014-01-01

    Amphibians vary in their response to infection by the amphibian-killing chytrid fungus, Batrachochytrium dendrobatidis (Bd). Highly susceptible species are the first to decline and/or disappear once Bd arrives at a site. These competent hosts likely facilitate Bd proliferation because of ineffective innate and/or acquired immune defenses. We show that Atelopus zeteki, a highly susceptible species that has undergone substantial population