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1
West, Cara, Florentina Rus, Ying Chen, Anni Kleino, Monique Gangloff, Don B. Gammon, and Neal Silverman. "IIV-6 Inhibits NF-κB Responses in Drosophila." Viruses 11, no. 5 (May 1, 2019): 409. http://dx.doi.org/10.3390/v11050409.
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The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-κB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur in IIV-6 infected cells, indicating that the mechanism of viral inhibition is farther downstream, at the level of Relish promoter binding or transcriptional activation. Additionally, flies co-infected with both IIV-6 and the Gram-negative bacterium, Erwinia carotovora carotovora, succumb to infection more rapidly than flies singly infected with either the virus or the bacterium. These findings demonstrate how pre-existing infections can have a dramatic and negative effect on secondary infections, and establish a Drosophila model to study confection susceptibility.
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Wysocki, Marc, Frederique Delatour, François Faurisson, Alain Rauss, Yves Pean, Benoit Misset, Frank Thomas, et al. "Continuous versus Intermittent Infusion of Vancomycin in Severe Staphylococcal Infections: Prospective Multicenter Randomized Study." Antimicrobial Agents and Chemotherapy 45, no. 9 (September 1, 2001): 2460–67. http://dx.doi.org/10.1128/aac.45.9.2460-2467.2001.
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ABSTRACT A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 ± 31 versus 51 ± 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 ± 2.2 versus 11.8 ± 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC24h) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg2/liter2/h2[P = 0.026] and 414 versus 818 g2[P = 0.057], respectively). The 10-day treatment cost per patient was $454 ± 137 in the IIV group and was 23% lower in the CIV group ($321 ± 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.
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Dakhlallah, Abe, Felice C. Adler-Shohet, Antonio Arrieta, and M. Tuan Tran. "Vancomycin (VAN) administered as continuous infusion (CIV) vs. intermittent infusion (IIV) in children with Methicillin-Resistant Staphylococcus aureus (MRSA) infections." Open Forum Infectious Diseases 4, suppl_1 (2017): S295. http://dx.doi.org/10.1093/ofid/ofx163.678.
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Abstract Background Guidelines for treatment of MRSA infections recommend VAN trough (TR) of 15–20 mg/L to achieve a 24-hour ratio of area-under-the-curve (AUC24) over minimum inhibitory concentration (MIC) ≥ 400, the primary pharmacodynamic (PD) parameter that predicts VAN efficacy. However, achieving this target TR in children is difficult in clinical settings and may not be necessary to achieve AUC24/MIC ≥ 400. Additionally, higher doses and TR >15 mg/L have been associated with increased risk for VAN nephrotoxicity. The use of CIV may lead to lower VAN exposure and subsequent toxicity while achieving the desired AUC24/MIC ratio. To our knowledge there are no reports exploring differences in VAN exposure, AUC24/MIC ratio and toxicity between CIV and IIV VAN in children. Methods We conducted a retrospective, cohort study between January 1, 2011–December 30, 2016. Children ages 3 months–18 years with an MRSA infection were included. Only the highest VAN level and total daily dose (TDD) within the first 72 hours of treatment were included for analysis. Patients with CrCl < 30 mL/minute/1.73m2 were excluded. Primary outcome was differences in TDD, AUC24 and AUC24/MIC. Secondary outcomes evaluated adverse events. Results Twenty-two patients were evaluated, 11 received IIV and 11 received CIV VAN. Median age, weight, gender, baseline serum creatinine, VAN clearance and volume of distribution were similar in both groups. Fewer patients in the IIV group received concomitant nephrotoxic drugs compared with CIV group (5/11 (45%) vs.. 10/11 (91%), P = 0.03). Patients in the IIV group received more VAN (median 85 mg/kg/day vs. 67 mg/kg/day, P = 0.08) and had higher AUC24 (723 mg*hours/L, (IQR 669–752) vs. 572 mg*hours/L, (IQR 459–633), P = 0.02) compared with CIV. Patients in IIV group had lower median TR (16 mg/L vs. 25 mg/L) that required longer time to attain (50.9 hours, (IQR 42–70) vs. 21.5 hours (IQR 17–34), P = 0.04) than serum levels in CIV. Both groups had a median VAN MIC 1 mg/L with a trend towards higher AUC24/MIC observed in IIV group (752 vs. 621, P = 0.07). More patients in IIV group experienced VAN-related adverse events (renal toxicity, infusion reactions, phlebitis) compared with CIV (7/11 (64%) vs. 1/11 (9%), P = 0.01). Conclusion In pediatric patients, CIV VAN achieved the recommended PD target in shorter time, and with fewer adverse events compared with IIV. Disclosures All authors: No reported disclosures.
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Lopez, Christopher E., and Kevin L. Legge. "Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine." Vaccines 8, no. 3 (August 3, 2020): 434. http://dx.doi.org/10.3390/vaccines8030434.
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Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection.
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Larke, RP Bryce. "Blood Borne Viral Infections in Transplantation: Hepatitis Viruses and Retroviruses." Canadian Journal of Infectious Diseases 4, suppl c (1993): 20–25. http://dx.doi.org/10.1155/1993/248042.
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Hepatitis viruses B (HBV), C (HCV) and D (HDV) and the retroviruses human immunodeficiency virus (HIV-1) and human T celllymphotropic virus type I (HTLV-1) and type ll (HTLV-11) have been transmitted from infected organ and tissue donors to allograft recipients. Ascertainment of personal risk factors by health questionnaire may exclude volunteer blood donors recently exposed to transmissible diseases who could be in the 'window period' of the infection, when routine serological screening tests are negative. Difficulty in obtaining historical evidence of possible recent exposure from a critically ill prospective organ donor may make the residual risk of infection slightly higher than the risk estimated per unit of transfused products from serologically screened volunteer blood donors. Current estimates of residual risk from transfusion based on United States data are: one in 200,000 units for HBV; one in 2000 to one in 6000 units for HCV; one in 40.000 lo one in 60,000 units for HIV-1; and one in 69,272 units for HTLV-1/11. Despite recent improvements in anti-HCV testing, current screening assays underestimate the incidence of transmission and prevalence of HCV infection among immunosuppressed organ recipients: evidence of ongoing HCV infection depends on detection of HCV RNA by polymerase chain reaction. Determination of I-IIV-1 p24 antigen may facilitate identification of prospective organ donors in ll1e window period of early infection and may enhance serological follow-up of allograft recipients al risk of transplantation-associated HIV-1 infection. Highly sensitive assays that can be completed very rapidly are needed to ensure greater safely for the recipient of an emergency organ transplant, where time to screen a prospective donor for infectious diseases may be extremely limited.
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Alonso-Moreno, Marta, Marta Mejías-Trueba, Laura Herrera-Hidalgo, Walter Alfredo Goycochea-Valdivia, and María Victoria Gil-Navarro. "Efficacy and Safety of Continuous Infusion of Vancomycin in Children: A Systematic Review." Antibiotics 10, no. 8 (July 26, 2021): 912. http://dx.doi.org/10.3390/antibiotics10080912.
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Vancomycin is used to treat a wide variety of infections within the pediatric population. In adults, continuous infusion of vancomycin (CIV) has been evaluated as an alternative to intermittent infusion of vancomycin (IIV) with potential advantages. In children, the use of CIV is increasing; however, data is currently limited. The objective is to provide efficacy and safety evidence for CIV within this population. The review was carried out following PRISMA guidelines. A bibliographic search was performed for studies on PubMed and EMBASE. Clinical trials and observational studies that reported clinical efficacy and/or target attainment of CIV in pediatrics were included. Articles were reviewed to assess their design and target population, characteristics of vancomycin treatment and the main findings in terms of safety and efficacy. A total of 359 articles were identified, of which seven met the inclusion criteria. All of them evaluated the target attainment, six assessed safety but only three assessed clinical efficacy. The best administration method for this antibiotic within the pediatric population is still unknown due to limited evidence. However, studies conducted thus far suggest pharmacokinetic advantages for CIV. Further investigation is required, in particular for studies comparing IIV with CIV for clinical efficacy and toxicity outcomes.
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Shore, Anna, Angela S. Rossney, Conor T. Keane, Mark C. Enright, and David C. Coleman. "Seven Novel Variants of the Staphylococcal Chromosomal Cassette mec in Methicillin-Resistant Staphylococcus aureus Isolates from Ireland." Antimicrobial Agents and Chemotherapy 49, no. 5 (May 2005): 2070–83. http://dx.doi.org/10.1128/aac.49.5.2070-2083.2005.
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ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in Irish hospitals between 1971 and 2002 were characterized using multilocus sequence typing (MLST) (n = 130) and SCCmec typing (n = 172). Where atypical SCCmec typing results were obtained, PCR amplification of entire SCCmec elements, analysis of amplimer mobility, and nucleotide sequencing were undertaken. MLST revealed that 129/130 isolates had the same genotypes as internationally spread MRSA clones, including ST239, ST247, ST250, ST5, ST22, ST36, and ST8. A novel genotype, ST496, was identified in one isolate. Half of the isolates (86/172) had SCCmec type I, IA, II, III, or IV. The remaining 86 isolates harbored novel SCCmec variants in three distinct genetic backgrounds: (i) 74/86 had genotype ST8 and either one of five novel SCCmec II (IIA, IIB, IIC, IID, and IIE) or one of two novel SCCmec IV (IVE and IVF) variants; (ii) 3/86 had genotype ST239 and a novel SCCmec III variant; (iii) 9/86 had a novel SCCmec I variant associated with ST250. SCCmec IVE and IVF were similar to SCCmec IVc and IVb, respectively, but differed in the region downstream of mecA. The five SCCmec II variants were similar to SCCmec IVb in the region upstream of the ccr complex but otherwise were similar to SCCmec II, except for the following regions: SCCmec IIA and IID had a novel mec complex, A.4 (ΔmecI-IS1182-ΔmecI-mecR1-mecA-IS431mec); SCCmec IIC and IIE had a novel mec complex, A.3 (IS1182-ΔmecI-mecR1-mecA-IS431mec); SCCmec IID and IIE lacked pUB110; SCCmec IIC and IIE lacked a region of DNA between Tn554 and the mec complex; and SCCmec IIB lacked Tn554. This study has demonstrated a hitherto-undescribed degree of diversity within SCCmec.
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Blanco-Lobo, Pilar, Aitor Nogales, Laura Rodríguez, and Luis Martínez-Sobrido. "Novel Approaches for The Development of Live Attenuated Influenza Vaccines." Viruses 11, no. 2 (February 22, 2019): 190. http://dx.doi.org/10.3390/v11020190.
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Influenza virus still represents a considerable threat to global public health, despite the advances in the development and wide use of influenza vaccines. Vaccination with traditional inactivate influenza vaccines (IIV) or live-attenuated influenza vaccines (LAIV) remains the main strategy in the control of annual seasonal epidemics, but it does not offer protection against new influenza viruses with pandemic potential, those that have shifted. Moreover, the continual antigenic drift of seasonal circulating influenza viruses, causing an antigenic mismatch that requires yearly reformulation of seasonal influenza vaccines, seriously compromises vaccine efficacy. Therefore, the quick optimization of vaccine production for seasonal influenza and the development of new vaccine approaches for pandemic viruses is still a challenge for the prevention of influenza infections. Moreover, recent reports have questioned the effectiveness of the current LAIV because of limited protection, mainly against the influenza A virus (IAV) component of the vaccine. Although the reasons for the poor protection efficacy of the LAIV have not yet been elucidated, researchers are encouraged to develop new vaccination approaches that overcome the limitations that are associated with the current LAIV. The discovery and implementation of plasmid-based reverse genetics has been a key advance in the rapid generation of recombinant attenuated influenza viruses that can be used for the development of new and most effective LAIV. In this review, we provide an update regarding the progress that has been made during the last five years in the development of new LAIV and the innovative ways that are being explored as alternatives to the currently licensed LAIV. The safety, immunogenicity, and protection efficacy profile of these new LAIVs reveal their possible implementation in combating influenza infections. However, efforts by vaccine companies and government agencies will be needed for controlled testing and approving, respectively, these new vaccine methodologies for the control of influenza infections.
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Lee, Jinhwa, Liping Wang, Rachel Palinski, Tim Walsh, Dongchang He, Yonghai Li, Rui Wu, et al. "Comparison of Pathogenicity and Transmissibility of Influenza B and D Viruses in Pigs." Viruses 11, no. 10 (September 27, 2019): 905. http://dx.doi.org/10.3390/v11100905.
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Influenza viruses are important pathogens causing respiratory disease in humans and animals. In contrast to influenza A virus (IAV) that can infect a wide range of animal species, other influenza viruses, including influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDV) have a limited host range. Swine can be infected with all four different genera of influenza viruses. IAV infection of pigs causes the well-known swine influenza that poses significant threats to human and animal health. However, influenza virus infection of pigs with IBV, ICV, and IDV are not well-characterized. Herein, we compared pathogenicity of IBV and IDV using intratracheal and intranasal infection of pigs, which are IAV seropositive, and commingled naïve pigs with the infected animals to determine their transmissibility. Both viruses caused fever and some lung lesions, replicated in the lungs of infected pigs, but only IDV transmitted to the contact animals. Although IBV and IDV displayed differing levels of replication in the respiratory tract of infected pigs, no significant differences in pathogenicity of both viruses were observed. These results indicate that both IBV and IDV can replicate, and are pathogenic in pigs.
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STRASSE, Karin Lye auf der, Carmen Mayanna JAMUR, Janaina MARQUES, Mirian Su Mi KIM, Ricardo Rasmussen PETTERLE, and Heda Maria Barska dos Santos AMARANTE. "IMMUNIZATION STATUS OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE." Arquivos de Gastroenterologia 56, no. 2 (June 2019): 124–30. http://dx.doi.org/10.1590/s0004-2803.201900000-26.
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ABSTRACT BACKGROUND: Treatment for inflammatory bowel disease (IBD) includes a variety of immunosuppressants and biological agents, which increase the risk of infections due to altered cellular and humoral immunity. Prevention of these infections can be done through vaccination, however, patients with IBD are usually under-immunized. OBJECTIVE: Analyze the immunization status of patients with IBD and confront it with the current recommendations to verify if the immunization guidelines are being followed correctly. METHODS: Analytical cross-sectional study including 239 IBD patients being regularly followed in the Gastroenterology Service from Hospital de Clínicas da Universidade Federal do Paraná, which were subjected to a survey about their relevant demographic data and immunization status. RESULTS: The amount of patients that declared being unaware of their immunization status is high - between 34.3% (Tdap) and 52% (meningococcal) - excepting IIV, hepatitis B and HPV. The vaccines with the largest rates of patients declaring to have taken it are inactivated influenza vaccine (72.4%), BCG (55.3%), hepatitis B (48.3%), measles, mumps and rubella vaccine (43.8%) and DTaP (43%). The vaccines with the lowest rates of patients declaring to have taken it are Haemophilus influenza type b (0.8%), herpes zoster (2.1%) and HPV (3.4%). Patients that are being treated or have been treated with biological therapy have the largest immunization coverage for inactivated influenza vaccine (81%) and PPSV23 (25.9%), also they have the largest awareness rates for those vaccines. CONCLUSION: Although being a specialized service linked to a university hospital, vaccination coverage and patients’ awareness rates proved to be below the desirable level. Vaccination and recovery of the immunization history is recommended immediately after the diagnosis of IBD, regardless of the use of biological agents. Those findings support the need of implementing hospital guidelines and constantly verifying its application by the multidisciplinary team in specialized services in IBD.
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Kozdrowski, Roland, Marcin Nowak, Monika Sikora, and Justyna Buczkowska. "Relationship between uterine biopsy score, endometrial infection and inflammation in the mare." Tierärztliche Praxis Ausgabe G: Großtiere / Nutztiere 44, no. 03 (2016): 158–63. http://dx.doi.org/10.15653/tpg-150581.
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Summary Objective: Endometrial biopsy score is an accepted marker of uterine health and predicted fertility, and it has been suggested that endometrial alternations are correlated with susceptibility to persistent infectious endometritis. The objective of this study was to investigate associations of endometrial biopsy score with: 1) presence of polymorphonuclear cells (PMNs) in the epithelium and stratum compactum in histopathology; 2) presence of PMNs in cytology and 3) presence of infection in microbiology. Materials and methods: The material for examination was collected from 69 mares suspected for subclinical endometritis (bred three or more times unsuccessfully in the same breeding season) and from 15 maiden mares. Samples were collected by endometrial biopsy and cytobrush technique. Results: Endometrial alterations (biopsy score IIA, IIB, III) were found in 64 of 82 mares (78%). There was an increase in PMN occurrence for grades IIA, IIB and III. When comparing grades and PMNs infiltration, we observed statistically significant differences between grades I and IIA (p = 0.222) and grades I and IIB (p = 0.042) in samples collected by endometrial biopsy. Statistically significant differences were found in microbiological examination (biopsy p = 0.036; cytobrush p = 0.189), cytological examination (biopsy p = 0.040; cytobrush p = 0.079) and PMN infiltration (p = 0.042) between mares with biopsy scores I and IIB. Furthermore, the highest percentage of infected mares was in grade IIA and IIB, and we found statistically significant differences between grades I and IIA (p = 0.043), and grades I and IIB (p = 0.036) in biopsy samples. We observed a tendency to higher prevalence of endometrial infection in mares with biopsy score IIA, IIB and III than with biopsy score I in samples collected using cytobrush technique. However, there were no statistical significant differences. Conclusion: Degenerative endometrial changes can predispose to uterine infection and inflammation. Our study shows that mares with endometrial score I are less predisposed to infection than mares with category IIA, IIB and III. Endometrial biopsy is a reliable diagnostic tool.
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Groopman, J. E., S. M. Hammer, S. E. Sallan, and J. D. Allan. "Human T-lymphotropic virus type III infection in previously immunocompromised hosts." Journal of Clinical Oncology 4, no. 4 (April 1986): 540–43. http://dx.doi.org/10.1200/jco.1986.4.4.540.
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The human T-lymphotropic virus type III (HTLV-III) is the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). HTLV-III infection in patients with prior underlying immune deficiency states such as cancer has not yet been studied. We report on the occurrence of clinically atypical opportunistic infections in previously immunocompromised patients that resulted from transfusion-acquired HTLV-III infection. Development of unusual infectious diseases in patients with neoplasms and other underlying immune deficiency disorders should lead to consideration of HTLV-III infection. Surveillance data should be obtained on these patients to accurately define the scope of HTLV-III infection.
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Bhuiyan, Md Safiul Alam, Zarina Amin, Ag Muhammad Sagaf Abu Bakar, Suryani Saallah, Noor Hydayaty Md Yusuf, Sharifudin Md Shaarani, and Shafiquzzaman Siddiquee. "Factor Influences for Diagnosis and Vaccination of Avian Infectious Bronchitis Virus (Gammacoronavirus) in Chickens." Veterinary Sciences 8, no. 3 (March 16, 2021): 47. http://dx.doi.org/10.3390/vetsci8030047.
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Infectious bronchitis virus (IBV) is a major economic problem in commercial chicken farms with acute multiple-system infection, especially in respiratory and urogenital systems. A live-attenuated and killed vaccine is currently immunized to control IBV infection; however, repeated outbreaks occur in both unvaccinated and vaccinated birds due to the choice of inadequate vaccine candidates and continuous emergence of novel infectious bronchitis (IB) variants and failure of vaccination. However, similar clinical signs were shown in different respiratory diseases that are essential to improving the diagnostic assay to detect IBV infections. Various risk factors involved in the failure of IB vaccination, such as various routes of application of vaccination, the interval between vaccinations, and challenge with various possible immunosuppression of birds are reviewed. The review article also highlights and updates factors affecting the diagnosis of IBV disease in the poultry industry with differential diagnosis to find the nature of infections compared with non-IBV diseases. Therefore, it is essential to monitor the common reasons for failed IBV vaccinations with preventive action, and proper diagnostic facilities for identifying the infective stage, leading to earlier control and reduced economic losses from IBV disease.
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Hatesuer, Bastian, Hang Thi Thu Hoang, Peggy Riese, Stephanie Trittel, Ingo Gerhauser, Husni Elbahesh, Robert Geffers, Esther Wilk, and Klaus Schughart. "Deletion of Irf3 and Irf7 Genes in Mice Results in Altered Interferon Pathway Activation and Granulocyte-Dominated Inflammatory Responses to Influenza A Infection." Journal of Innate Immunity 9, no. 2 (November 4, 2016): 145–61. http://dx.doi.org/10.1159/000450705.
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The interferon (IFN) pathway plays an essential role in the innate immune response following viral infections and subsequent shaping of adaptive immunity. Infections with influenza A viruses (IAV) activate the IFN pathway after the recognition of pathogen-specific molecular patterns by respective pattern recognition receptors. The IFN regulatory factors IRF3 and IRF7 are key players in the regulation of type I and III IFN genes. In this study, we analyzed the role of IRF3 and IRF7 for the host response to IAV infections in Irf3-/-, Irf7-/-, and Irf3-/-Irf7-/- knockout mice. While the absence of IRF3 had only a moderate impact on IFN expression, deletion of IRF7 completely abolished IFNα production after infection. In contrast, lack of both IRF3 and IRF7 resulted in the absence of both IFNα and IFNβ after IAV infection. In addition, IAV infection of double knockout mice resulted in a strong increase of mortality associated with a massive influx of granulocytes in the lung and reduced activation of the adaptive immune response.
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PHILLIPS, G., C. C. TAM, L. C. RODRIGUES, and B. LOPMAN. "Risk factors for symptomatic and asymptomatic norovirus infection in the community." Epidemiology and Infection 139, no. 11 (December 17, 2010): 1676–86. http://dx.doi.org/10.1017/s0950268810002839.
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SUMMARYThe objective of this study was to investigate risk factors for norovirus-associated infectious intestinal disease (IID) and asymptomatic norovirus infection. Individuals with IID and healthy controls were recruited in a community-based study in England (1993–1996). This is the first risk-factor study to use viral load measurements, generated by real-time RT–PCR, to identify cases of norovirus-associated IID and asymptomatic infections. Using multivariable logistic regression the main risk factor identified for norovirus-associated IID was contact with a person with IID symptoms. Infectious contacts accounted for 54% of norovirus cases in young children and 39% of norovirus cases in older children and adults. For young children, contacts outside the household presented the highest risk; for older children and adults, the highest risk was associated with child contacts inside the household. Foreign travel and consumption of shellfish increased the risk of norovirus-associated IID. Lifestyle and dietary factors were associated with a decreased risk of both norovirus-associated IID and asymptomatic infection. No risk factors were identified for asymptomatic norovirus infection.
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van Boven, Michiel, Frits R. Mooi, Joop F. P. Schellekens, Hester E. de Melker, and Mirjam Kretzschmar. "Pathogen adaptation under imperfect vaccination: implications for pertussis." Proceedings of the Royal Society B: Biological Sciences 272, no. 1572 (July 6, 2005): 1617–24. http://dx.doi.org/10.1098/rspb.2005.3108.
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Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity.
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Méndez-Martínez, S., M. García-Carrasco, E. A. Jiménez-Herrera, C. Mendoza-Pinto, I. Etchegaray-Morales, P. W. Barahona-Rubio, J. L. Gálvez-Romero, et al. "Factors of the epidemiological triad that influence the persistence of human papilloma virus infection in women with systemic lupus erythematosus." Lupus 27, no. 9 (May 6, 2018): 1542–46. http://dx.doi.org/10.1177/0961203318773176.
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We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ≥18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (≥2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ≥3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence.
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HUGHES, G. J., and R. GORTON. "Inequalities in the incidence of infectious disease in the North East of England: a population-based study." Epidemiology and Infection 143, no. 1 (March 18, 2014): 189–201. http://dx.doi.org/10.1017/s0950268814000533.
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SUMMARYThe objective of this study was to measure the association between deprivation and incidence of 21 infectious diseases in the North East of England (2007–2011). We used count regression models with the Index of Multiple Deprivation and population/landscape data for small areas (~1500 persons). Deprivation significantly predicted incidence (P < 0·05) for 17 infectious diseases. The direction of association was broadly consistent within groups: increased incidence with increased deprivation for all three bloodborne viruses, 2/3 invasive bacterial diseases, 4/5 sexually transmitted infections (STI) and tuberculosis (TB); decreased incidence with increased deprivation for 5/6 infectious intestinal diseases (IID) and 2/3 vaccine-preventable diseases. Associations were removed for all but one IID (E. coliO157 infection) after accounting for recent foreign travel. Hepatitis C virus, TB and STI are priority infections for reduction of inequalities associated with deprivation in the North East of England.
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Arii, Jun, Yoshitaka Hirohata, Akihisa Kato, and Yasushi Kawaguchi. "Nonmuscle Myosin Heavy Chain IIB Mediates Herpes Simplex Virus 1 Entry." Journal of Virology 89, no. 3 (November 26, 2014): 1879–88. http://dx.doi.org/10.1128/jvi.03079-14.
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ABSTRACTNonmuscle myosin heavy chain IIA (NMHC-IIA) has been reported to function as a herpes simplex virus 1 (HSV-1) entry coreceptor by interacting with viral envelope glycoprotein B (gB). Vertebrates have three genetically distinct isoforms of the NMHC-II, designated NMHC-IIA, NMHC-IIB, and NMHC-IIC. COS cells, which are readily infected by HSV-1, do not express NMHC-IIA but do express NMHC-IIB. This observation prompted us to investigate whether NMHC-IIB might associate with HSV-1 gB and be involved in an HSV-1 entry like NMHC-IIA. In these studies, we show that (i) NMHC-IIB coprecipitated with gB in COS-1 cells upon HSV-1 entry; (ii) a specific inhibitor of myosin light chain kinase inhibited cell surface expression of NMHC-IIB in COS-1 cells upon HSV-1 entry as well as HSV-1 infection, as reported with NMHC-IIA; (iii) overexpression of mouse NMHC-IIB in IC21 cells significantly increased their susceptibility to HSV-1 infection; and (iv) knockdown of NMHC-IIB in COS-1 cells inhibited HSV-1 infection as well as cell-cell fusion mediated by HSV-1 envelope glycoproteins. These results supported the hypothesis that, like NMHC-IIA, NMHC-IIB associated with HSV-1 gB and mediated HSV-1 entry.IMPORTANCEHerpes simplex virus 1 (HSV-1) was reported to utilize nonmuscle myosin heavy chain IIA (NMHC-IIA) as an entry coreceptor associating with gB. Vertebrates have three genetically distinct isoforms of NMHC-II. In these isoforms, NMHC-IIB is of special interest since it highly expresses in neuronal tissue, one of the most important cellular targets of HSV-1in vivo. In this study, we demonstrated that the ability to mediate HSV-1 entry appeared to be conserved in NMHC-II isoforms. These results may provide an insight into the mechanism by which HSV-1 infects a wide variety of cell typesin vivo.
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Vesole, David H., Martin M. Oken, Charles Heckler, Philip R. Greipp, Michael S. Katz, Susanna Jacobus, and Gary R. Morrow. "Oral Antibiotic Prophylaxis of Early Infection In Multiple Myeloma: A URCC/ECOG Phase III Study." Blood 116, no. 21 (November 19, 2010): 3017. http://dx.doi.org/10.1182/blood.v116.21.3017.3017.
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Abstract Abstract 3017 Introduction: Multiple myeloma (MM) is a malignancy of clonal plasma cells with resulting in an increase production of ineffective immunoglobulins with suppression of non-involved immunoglobulins. Patients with MM are at increased risk of infectious complications, particularly to those organisms in which opsonization is one of the key defense mechanisms, e.g. strep and staph infections. Treatment of MM is virtually always associated with further immunosuppression, at least in the immediate term, until the malignant clone is eradicated and normal immunoglobulins are produced. Rationale: Due to further compromise of an already incompetent immune system by initial chemotherapy and the previous suggestion (Oken et al Am J Med 1996; 100:624-628) that prophylactic antibiotics may reduce infectious complications, this study was designed to evaluate the impact of prophylactic antibiotics on the incidence of serious bacterial infections during the first two months of treatment. Methods: Pts with untreated MM receiving chemotherapy were randomized on a 1:1:1 basis to receive either a daily ciprofloxacin (C; 500 mg), trimetheprim-sulfamethoxazole (T; DS bid) or observation (O) for the first 2 months of treatment. Pts were evaluated for serious bacterial infection (grade 3 or 4) during the first two months of myelotoxic/suppressive therapy. Secondary endpoints (EP) included: incidence of non-bacterial infections, resistant organisms due to prophylaxis, the incidence of infection the third month OFF of antibiotic prophylaxis and whether protection against infection is associated with an improved response rate. Results: From July 1998 to January 2008, 212 untreated, symptomatic MM pts being treated with myelotoxic/suppressive chemotherapy were randomized to C (n=69), T (n=76) or O (n=67) for the first 2 months of treatment. The incidence of serious infection (> grade 3 ECOG toxicity criteria and/or hospitalization) was comparable among groups: C=10 (14.7%), T=5 (6.9%), O=9 (14.5%); p= 0.268 which was the primary EP. The incidence of any infection during the first 2 months was also comparable (20% vs 23% vs 22%, respectively, p=0.910). There were 25 grade 2 infections and 4 grade 3 infections involving respiratory (n =13), sepsis/bacteremia (n = 4), and urinary (n =3), joint/bone (n =2), unknown (n =2) or various GI tract (n = 5) and skin (n =1). Eight pts expired within the first 2 months: 2 from MM, 3 cardiac, 2 respiratory, 1 renal (unrelated to MM or Rx) occurring in the C (4), T (1), O (2). Secondary EPs failed to show a difference in the incidence of serious bacterial infection during the third month in the absence of prophylaxis (C=3%, T=4%, O=2%; p=0.874), development of resistant infections, initial response to therapy or overall survival. Conclusions: The use of prophylactic antibiotics did not decrease the incidence of serious infection (> grade 3 and/or hospitalization) nor of any infection within the first 2 months of treatment. Infection prophylaxis did not affect the incidence of infection upon completion of 2 months of therapy (nor, ultimately, at any time during the subsequent 2 years), the response to therapy or to overall survival. Incidentally, there were no documented cases of PCP despite the assumption that MM pts, with compromised immune systems, are more susceptible. The incidence of serious infections in this study, in which few patients received novel agents, is comparable to that observed in more modern regimens even in the presence of mandated/recommended prophylactic antibiotics. Utilizing either lenalidomide plus dexamethasone or clarithromycin, lenalidomide and dexamethasone resulted in > grade 3 infectious complications in 16.7% and 9.7%, respectively, as reported by the Mayo Clinic and Cornell groups, respectively (Gay et al Am J Hematol, in press). Furthermore, in the ECOG E4A03 randomized trial of lenalidomide plus either high dose dexamethasone (LD) or low dose dexamethasone (Ld) in which prophylactic antibiotics were recommended, the incidence of > grade 3 infectious complications were 9.4% and 6.4%, respectively (Rajkumar et al Lancet Oncol 2010; 11: 29–37). We conclude that routine use of prophylactic antibiotics should not be mandated for patients receiving induction chemotherapy. Prophylactic antibiotics should be considered on a case-by-case basis after analyzing the potential infection risk in individuals. Disclosures: No relevant conflicts of interest to declare.
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DOWD, J. B., A. E. AIELLO, and D. E. ALLEY. "Socioeconomic disparities in the seroprevalence of cytomegalovirus infection in the US population: NHANES III." Epidemiology and Infection 137, no. 1 (April 16, 2008): 58–65. http://dx.doi.org/10.1017/s0950268808000551.
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SUMMARYThere is a strong relationship between socioeconomic status (SES) and health outcomes in the United States, although the mechanisms are poorly understood. Increasing evidence points to links between lifelong exposure to infectious disease and subsequent chronic disease. Exposure and susceptibility to infections may be one way SES affects long-term health, although little population-based research to date has examined social patterning of infections in the United States. This paper tests the relationship between income, education, race/ethnicity and seroprevalence of cytomegalovirus (CMV) infection at different ages in a representative sample of the US population, and tests potential mediators for these relationships. The study finds significant racial and socioeconomic disparities in CMV seroprevalence beginning at early ages and persisting into middle age. Potential exposures do not explain the relationship between SES and CMV positivity. Because reactivation of latent CMV infections may contribute to chronic disease and immune decline later in life, future research should determine the exposure or susceptibility pathways responsible for these disparities in the prevalence of CMV infection.
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Nawar, Hesham F., Natalie D. King-Lyons, John C. Hu, Raymond C. Pasek, and Terry D. Connell. "LT-IIc, a New Member of the Type II Heat-Labile Enterotoxin Family Encoded by an Escherichia coli Strain Obtained from a Nonmammalian Host." Infection and Immunity 78, no. 11 (August 16, 2010): 4705–13. http://dx.doi.org/10.1128/iai.00730-10.
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ABSTRACT Two families of bacterial heat-labile enterotoxins (HLTs) have been described: the type I HLTs are comprised of cholera toxin (CT) of Vibrio cholerae, LT-I of Escherichia coli, and several related HLTs; the type II HLTs are comprised of LT-IIa and LT-IIb. Herein, we report LT-IIc, a new type II HLT encoded from an enterotoxigenic E. coli (ETEC) strain isolated from an avian host. Using a mouse Y1 adrenal cell bioassay, LT-IIc was shown to be less cytotoxic than CT, LT-IIa, or LT-IIb. Cytotoxicity of LT-IIc was partially neutralized by antisera recognizing LT-IIa or LT-IIb but not by anti-CT antiserum. Genes encoding putative A polypeptide and B polypeptides of LT-IIc were arranged in an operon which was flanked by potential prophage sequences. Analysis of the nucleotide and predicted amino acid sequences demonstrated that the A polypeptide of LT-IIc has moderate homology to the A polypeptides of CT and LT-I and high homology to the A polypeptides of LT-IIa and LT-IIb. The B polypeptide of LT-IIc exhibited no significant homology to the B polypeptides of CT and LT-I and only moderate homology to the B polypeptides of LT-IIa and LT-IIb. The binding pattern of LT-IIc for gangliosides was distinctive from that of either LT-IIa or LT-IIb. The data suggest that other types of the type II HLT subfamily are circulating in the environment and that host specificity of type II HLT is likely governed by changes in the B polypeptide which mediate binding to receptors.
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Donowitz, Gerald R., Dennis G. Maki, Christopher J. Crnich, Peter G. Pappas, and Kenneth V. I. Rolston. "Infections in the Neutropenic Patient— New Views of an Old Problem." Hematology 2001, no. 1 (January 1, 2001): 113–39. http://dx.doi.org/10.1182/asheducation-2001.1.113.
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Abstract Infection in the neutropenic patient has remained a major clinical challenge for over three decades. While diagnostic and therapeutic interventions have improved greatly during this period, increases in the number of patients with neutropenia, changes in the etiologic agents involved, and growing antibiotic resistance have continued to be problematic. The evolving etiology of infections in this patient population is reviewed by Dr. Donowitz. Presently accepted antibiotic regimens and practices are discussed, along with ongoing controversies. In Section II, Drs. Maki and Crnich discuss line-related infection, which is a major infectious source in the neutropenic. Defining true line-related bloodstream infection remains a challenge despite the fact that various methods to do so exist. Means of prevention of line related infection, diagnosis, and therapy are reviewed. Fungal infection continues to perplex the infectious disease clinician and hematologist/oncologist. Diagnosis is difficult, and many fungal infections will lead to increased mortality even with rapid diagnosis and therapy. In Section III, Dr. Pappas reviews the major fungal etiologies of infection in the neutropenic patient and the new anti-fungals that are available to treat them. Finally, Dr. Rolston reviews the possibility of outpatient management of neutropenic fever. Recognizing that neutropenics represent a heterogeneous group of patients, identification of who can be treated as an outpatient and with what antibiotics are discussed.
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Steyn, Angela, Sarah Keep, Erica Bickerton, and Mark Fife. "The Characterization of chIFITMs in Avian Coronavirus Infection In Vivo, Ex Vivo and In Vitro." Genes 11, no. 8 (August 10, 2020): 918. http://dx.doi.org/10.3390/genes11080918.
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The coronaviruses are a large family of enveloped RNA viruses that commonly cause gastrointestinal or respiratory illnesses in the infected host. Avian coronavirus infectious bronchitis virus (IBV) is a highly contagious respiratory pathogen of chickens that can affect the kidneys and reproductive systems resulting in bird mortality and decreased reproductivity. The interferon-inducible transmembrane (IFITM) proteins are activated in response to viral infections and represent a class of cellular restriction factors that restrict the replication of many viral pathogens. Here, we characterize the relative mRNA expression of the chicken IFITM genes in response to IBV infection, in vivo, ex vivo and in vitro using the pathogenic M41-CK strain, the nephropathogenic QX strain and the nonpathogenic Beaudette strain. In vivo we demonstrate a significant upregulation of chIFITM1, 2, 3 and 5 in M41-CK- and QX-infected trachea two days post-infection. In vitro infection with Beaudette, M41-CK and QX results in a significant upregulation of chIFITM1, 2 and 3 at 24 h post-infection. We confirmed a differential innate response following infection with distinct IBV strains and believe that our data provide new insights into the possible role of chIFITMs in early IBV infection.
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Krementsov, Dimitry N., Laure K. Case, Oliver Dienz, Abbas Raza, Qian Fang, Jennifer L. Ather, Matthew E. Poynter, Jonathan E. Boyson, Janice Y. Bunn, and Cory Teuscher. "Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection." Proceedings of the National Academy of Sciences 114, no. 13 (February 27, 2017): 3491–96. http://dx.doi.org/10.1073/pnas.1620889114.
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Males of many species, ranging from humans to insects, are more susceptible than females to parasitic, fungal, bacterial, and viral infections. One mechanism that has been proposed to account for this difference is the immunocompetence handicap model, which posits that the greater infectious disease burden in males is due to testosterone, which drives the development of secondary male sex characteristics at the expense of suppressing immunity. However, emerging data suggest that cell-intrinsic (chromosome X and Y) sex-specific factors also may contribute to the sex differences in infectious disease burden. Using a murine model of influenza A virus (IAV) infection and a panel of chromosome Y (ChrY) consomic strains on the C57BL/6J background, we present data showing that genetic variation in ChrY influences IAV pathogenesis in males. Specific ChrY variants increase susceptibility to IAV in males and augment pathogenic immune responses in the lung, including activation of proinflammatory IL-17–producing γδ T cells, without affecting viral replication. In addition, susceptibility to IAV segregates independent of copy number variation in multicopy ChrY gene families that influence susceptibility to other immunopathological phenotypes, including survival after infection with coxsackievirus B3. These results demonstrate a critical role for genetic variation in ChrY in regulating susceptibility to infectious disease.
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Terry, Karianne, Susan M. Williams, Lynn Connolly, and Karen M. Ottemann. "Chemotaxis Plays Multiple Roles during Helicobacter pylori Animal Infection." Infection and Immunity 73, no. 2 (February 2005): 803–11. http://dx.doi.org/10.1128/iai.73.2.803-811.2005.
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ABSTRACT Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as specific gastric cancers. H. pylori infects approximately 50% of the world's population, and infections can persist throughout the lifetime of the host. Motility and chemotaxis have been shown to be important in the infection process of H. pylori. We sought to address the specific roles of chemotaxis in infection of a mouse model system. We found that mutants lacking cheW, cheA, or cheY are all nonchemotactic and infect FVB/N mice with an attenuated phenotype after 2 weeks of infection. If infections proceeded for 6 months, however, this attenuation disappeared. Histological and culture analysis revealed that nonchemotactic mutants were found only in the corpus of the stomach, while the wild type occupied both the corpus and the antrum. Further analysis showed that nonchemotactic H. pylori isolates had an increased 50% infectious dose and were greatly outcompeted when coinfected with the wild type. If nonchemotactic mutants were allowed to establish an infection, subsequent infection with the wild type partially displaced the nonchemotactic mutants, indicating a role for chemotaxis in maintenance of infection. The data presented here support four roles for chemotaxis in H. pylori mouse infections: (i) establishing infection, (ii) achieving high-level infection, (iii) maintaining an infection when there are competing H. pylori present, and (iv) colonizing all regions of the stomach.
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EZE, J. I., E. M. SCOTT, K. G. POLLOCK, R. STIDSON, C. A. MILLER, and D. LEE. "The association of weather and bathing water quality on the incidence of gastrointestinal illness in the west of Scotland." Epidemiology and Infection 142, no. 6 (September 6, 2013): 1289–99. http://dx.doi.org/10.1017/s0950268813002148.
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SUMMARYThe associations with weather and bathing water quality on infectious intestinal disease (IID) were investigated using data from two Scottish NHS Board areas. Monthly counts of viral and non-viral gastrointestinal infections were modelled as a smooth function of temperature, relative humidity and average monthly counts of faecal indicator organisms, respectively, adjusting for season and long-term trend effects. Strong seasonal patterns were observed for each group of pathogens. Peak viral gastrointestinal infection was in May while that of non-viral gastrointestinal infections was in July. A statistically significant negative association existed between weather (temperature and humidity) and viral infection. Average levels of non-viral gastrointestinal infections increased as temperature and relative humidity increased. Increasing levels of faecal indicator organisms in bathing waters were also associated with an increase in the average number of viral and non-viral gastrointestinal infections at the ecological level. Future climate change and prolonged precipitation events may result in increasing levels of faecal indicator organisms in bathing waters leading to likely increases in IIDs.
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Echeverri, A., J. Naranjo-Escobar, I. Posso-Osorio, D. Aguirre-Valencia, D. Zambrano, G. L. Castaño, J. D. Martínez, C. A. Cañas, and G. J. Tobón. "Neutrophil CD64 expression, procalcitonin and presepsin are useful to differentiate infections from flares in SLE patients with SIRS." Lupus 27, no. 7 (March 14, 2018): 1130–39. http://dx.doi.org/10.1177/0961203318763740.
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Background/Objective Differentiating systemic lupus erythematosus (SLE) activity from infections in febrile patients is difficult because of similar initial clinical presentation. The aim of this study is to evaluate the usefulness of a number of biomarkers for differentiating infections from activity in SLE patients admitted with systemic inflammatory response (SIRS). Methods Patients with SLE and SIRS admitted to the emergency room were included in this study. Measurements of different markers including procalcitonin, neutrophil CD64 expression and presepsin, were performed. Infection was considered present when positive cultures and/or polymerase chain reaction were obtained. Sensitivity and specificity were calculated for all biomarkers. Results Twenty-seven patients were admitted, 23 women (82.5%), mean age 33.2 years. An infectious disease was confirmed in 12 cases. Markers for SLE activity including anti-DNA titers by IIF ( p = 0.041) and enzyme-linked immunosorbent assay ( p = 0.009) were used for differentiating SLE flares from infection. On the contrary, increased procalcitonin ( p = 0.047), neutrophil CD64 expression by flow cytometry ( p = 0.037) and presepsin ( p = 0.037) levels were observed in infected SLE patients. Conclusions High neutrophil CD64 expression, presepsin and procalcitonin levels are useful to differentiate infections from activity in SLE patients. In most cases, a positive bioscore that includes these three markers demonstrate the presence of an infectious disease.
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De Silva Senapathi, Upasama, Mohamed Abdul-Cader, Aruna Amarasinghe, Guido van Marle, Markus Czub, Susantha Gomis, and Mohamed Abdul-Careem. "The In Ovo Delivery of CpG Oligonucleotides Protects against Infectious Bronchitis with the Recruitment of Immune Cells into the Respiratory Tract of Chickens." Viruses 10, no. 11 (November 15, 2018): 635. http://dx.doi.org/10.3390/v10110635.
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The in ovo delivery of cytosine-guanosine (CpG) oligodeoxynucleotides (ODNs) protects chickens against many bacterial and viral infections, by activating the toll-like receptor (TLR)21 signaling pathway. Although the delivery of CpG ODNs in ovo at embryo day (ED) 18 has been shown to reduce infectious bronchitis virus (IBV) loads in embryonic chicken lungs pre-hatch, whether in ovo delivered CpG ODNs are capable of protecting chickens against a post-hatch challenge is unknown. Thus, our objectives were to determine the protective effect of the in ovo delivery of CpG ODNs at ED 18 against IBV infection encountered post-hatch and, then, to investigate the mechanisms of protection. We found significantly higher survival rates and reduced IBV infection in the chickens following the pre-treatment of the ED 18 eggs with CpG ODNs. At 3 days post infection (dpi), we found an increased recruitment of macrophages, cluster of differentiation (CD)8α+ and CD4+ T lymphocytes, and an up-regulation of interferon (IFN)-γ mRNA in the respiratory tract of the chickens. Overall, it may be inferred that CpG ODNs, when delivered in ovo, provide protection against IBV infection induced morbidity and mortality with an enhanced immune response.
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Qin, Zhen, Yuan Yang, Hongren Wang, Jun Luo, Xiaojun Huang, Jiangzhou You, Baoning Wang, and Mingyuan Li. "Role of Autophagy and Apoptosis in the Postinfluenza Bacterial Pneumonia." BioMed Research International 2016 (2016): 1–10. http://dx.doi.org/10.1155/2016/3801026.
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The risk of influenza A virus (IAV) is more likely caused by secondary bacterial infections. During the past decades, a great amount of studies have been conducted on increased morbidity from secondary bacterial infections following influenza and provide an increasing number of explanations for the mechanisms underlying the infections. In this paper, we first review the recent research progress that IAV infection increased susceptibility to bacterial infection. We then propose an assumption that autophagy and apoptosis manipulation are beneficial to antagonize post-IAV bacterial infection and discuss the clinical significance.
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Abdelaziz, Adel M., Mahmoud H. A. Mohamed, Mahmoud M. Fayez, Theeb Al-Marri, Ibrahim Qasim, and Abdul Aziz Al-Amer. "Molecular survey and interaction of common respiratory pathogens in chicken flocks (field perspective)." December-2019 12, no. 12 (December 2019): 1975–86. http://dx.doi.org/10.14202/vetworld.2019.1975-1986.
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Aim: The present study was designed for the detection of the most prevalent respiratory infections in chicken flocks and clarifying their interaction and impact on flock health. Materials and Methods: A total of 359 serum samples were collected from 55 backyard chickens and tested using commercial enzyme-linked immunosorbent assay kits to determine the seroprevalence of Newcastle disease virus (NDV), infectious bronchitis virus (IBV), influenza type A, Mycoplasma gallisepticum (MG), and Mycoplasma synoviae (MS). Molecular prevalence of NDV, IBV, low pathogenic avian influenza virus (LPAIV) H9N2, MG, and MS was carried out on swab, and tissue samples collected from 55 backyard flocks and 11 commercial broiler flocks suffered from respiratory infections using polymerase chain reaction (PCR) and reverse transcription-PCR. Results: Seroprevalence of NDV, IBV, Influenza type A virus, MG, and MS in chicken backyard flocks was 56.4%, 50.9%, 12.7%, 14.5%, and 3.6%, respectively. Specific antibodies against one or more respiratory viruses and mycoplasma were detected in 36.4% of backyard flocks, indicating concurrent viral infections. The molecular survey showed that 90.9% of chicken backyard flocks were infected with common respiratory viruses (NDV, IBV, and LPAIV H9N2) while 81.8% of commercial broiler flocks were infected. The molecular prevalence rate of NDV, IBV, and LPAIV H9N2 was 46.97%, 56.1%, and 19.7% in backyard flocks, respectively. Combined viral and bacterial infection represented 40% and 63.6% of the respiratory infections, resulting in enhanced pathogenicity and increased mortalities of up to 87.5% and 27.8% in backyard and commercial flocks, respectively. Mixed infection of IBV, LPAIV H9N2, and/or Escherichia coli is the most prevalent mixed infection in broiler flocks, inducing severe clinical outcomes. Avian pathogenic E. coli was, respectively, isolated from 40% of backyard flocks and 81.82% of broiler flocks. Staphylococcus aureus was isolated from three backyard chicken flocks mixed with other respiratory pathogens with elevated mortality. Mixed infection of E. coli and MG reported in 9.1% of broiler flock. MG was detected in 14.5% of backyard flocks and 9.1% of broiler flocks while MS was detected only in 3.6% of backyard chickens mixed with E. coli, and other viruses. Conclusion: Our results confirm that mixed infections are more commonly prevalent and associated with dramatic exacerbation in clinical outcomes than a single infection. Bidirectional synergistic interaction between these concurrently interacted respiratory pathogens explains the severe clinical impact and high mortality rate. The high prevalence of IBV (either as a single or combined infection) with LPAIV H9N2 and/or E. coli, in spite of intensive use of commercial vaccines, increases the need for revising vaccination programs and the application of standard biosecurity measures. Backyard chickens impose a great risk and threaten commercial flocks due to the high prevalence of viral respiratory pathogens.
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Chatterjee, Rudrarpan, Pankti Mehta, Vikas Agarwal, and Latika Gupta. "High burden of infections in Indian patients with Idiopathic Inflammatory Myopathy: validation of observations from the MyoCite dataset." Rheumatology 60, no. 9 (January 26, 2021): 4315–26. http://dx.doi.org/10.1093/rheumatology/keab015.
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Abstract Objective To determine the prevalence, profile and predictors of infections in an Indian cohort with idiopathic inflammatory myopathies (IIM). Methods We reviewed the records of a retrospective cohort with IIM enrolled from consecutive patients being followed up in the clinic, and these constituted the observation cohort. A newly diagnosed inception cohort with IIM were followed prospectively as the validation cohort for confirmation of observations and comparison with the observation cohort. Results Among the 68 patients in the observation cohort (average age 33.4 years, female:male 4.2:1), 37 (54.4%) experienced 54 infections between them; of these 54 infections, 21 (38.8%) were major and recurrent infections and they occurred in 11 patients (16.17%) over 3.08 years. Tuberculosis was the most common infection (12, 22.2%), with a predominance of extrapulmonary forms. Serum protein [odds ratio (OR) 0.44], platelets (0.44) at disease onset and daily steroid dose (1.04) predicted major infections on multivariate analysis. A higher daily dose of steroids at first infection correlated with number of recurrent infections. The infection-free 1-year survival was 73.8%. Of the 70 patients in the validation cohort (average age 35.7 years, female:male 3.7:1), 3 had myositis attributed to an infection. A similar proportion of the cohort experienced infections (22, 33.3%) with similar number of major (10, 45.4%) and recurrent (4, 18%) infections being recorded. The most common infection was community-acquired pneumonia, followed by tuberculosis, with serum albumin (OR 0.25) at disease onset being the only predictor. The one-year infection-free survival rate was 64.7%. Those who had a major infection had increased mortality at 1 year, with a survival rate of 60%, compared with 89.09% in those without. In both cohorts, a daily prednisone dose >6.25 mg predisposed to major infections. Conclusion Major and recurrent infections are common in Indian IIM patients and confer higher risk for future infections and lower survival. Respiratory and atypical bacterial infections such as tuberculosis occur throughout the disease course.
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Meningher, Tal, Musa Hindiyeh, Liora Regev, Hilda Sherbany, Ella Mendelson, and Michal Mandelboim. "Relationships between A(H1N1)pdm09 influenza infection and infections with other respiratory viruses." Influenza and Other Respiratory Viruses 8, no. 4 (April 4, 2014): 422–30. http://dx.doi.org/10.1111/irv.12249.
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Scherbo, S. N., D. S. Shcherbo, A. L. Tishchenko, M. I. Savina, and T. I. Turkina. "Genetic predisposition and resistance to certain infectious diseases. III. COVID 19." Medical alphabet, no. 13 (June 29, 2021): 7–12. http://dx.doi.org/10.33667/2078-5631-2021-13-7-12.
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The review discusses issues related to genetic predisposition and resistance to the new coronavirus infection including various factors: epidemiological, gender, ethnic and microbiome. The role of molecular genetic methods in the diagnosis of coronavirus infection is emphasized. The genetic factors largely determine the body’s susceptibility to various diseases, including infectious ones. The focus is on the genes associated with the production of interferons and enzymes that are responsible for anti-viral responses, as well as inflammatory reactions in the lungs. The first group includes genes IFNAR2 and OAS1, which control the production of antiviral proteins, while the second includes DPP9, TYK2 and CCR2, that control the behavior of monocytes. A number of other genetic polymorphisms responsible for resistance and susceptibility to infections and associated clinical consequences are discussed. The knowledge of molecular genetic biomarkers is necessary to identify risk groups, conduct predictive measures, including vaccination against COVID-19.
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Warren, Rachel, William Domm, Min Yee, Andrew Campbell, Jane Malone, Terry Wright, Margot Mayer-Pröschel, and Michael A. O’Reilly. "Ataxia-telangiectasia mutated is required for the development of protective immune memory after influenza A virus infection." American Journal of Physiology-Lung Cellular and Molecular Physiology 317, no. 5 (November 1, 2019): L591—L601. http://dx.doi.org/10.1152/ajplung.00031.2019.
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Ataxia-telangiectasia (A-T), caused by mutations in the A-T mutated ( ATM) gene, is a neurodegenerative disorder affecting ∼1 in 40,000–100,000 children. Recurrent respiratory infections are a common and challenging comorbidity, often leading to the development of bronchiectasis in individuals with A-T. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood. Here, we infect wild-type (WT) and Atm-null mice with influenza A virus (IAV; HKx31, H3N2) and interrogate the immune memory with secondary infections designed to challenge the B cell memory response with homologous infection (HKx31) and the T cell memory response with heterologous infection (PR8, H1N1). Although Atm-null mice survived primary and secondary infections, they lost more weight than WT mice during secondary infections. This enhanced morbidity to secondary infections was not attributed to failure to effectively clear virus during the primary IAV infection. Instead, Atm-null mice developed persistent peribronchial inflammation, characterized in part by clusters of B220+ B cells. Additionally, levels of select serum antibodies to hemagglutinin-specific IAV were significantly lower in Atm-null than WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection, implying that vaccination of children with A-T by itself may not be sufficiently protective against respiratory viral infections.
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Berg, Johanna, Katja Zscheppang, Diana Fatykhova, Mario Tönnies, Torsten T. Bauer, Paul Schneider, Jens Neudecker, et al. "Tyk2 as a target for immune regulation in human viral/bacterial pneumonia." European Respiratory Journal 50, no. 1 (July 2017): 1601953. http://dx.doi.org/10.1183/13993003.01953-2016.
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The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.We established a human lungex vivoco-infection model to investigate innate immune related mechanisms contributing to the susceptibility of secondary pneumococcal pneumonia.We revealed that type I and III interferon (IFN) inhibitsStreptococcus pneumoniae-induced interleukin (IL)-1β release. The lack of IL-1β resulted in the repression of bacterially induced granulocyte-macrophage colony-stimulating factor (GM-CSF) liberation. Specific inhibition of IFN receptor I and III-associated tyrosine kinase 2 (Tyk2) completely restored theS. pneumoniae-induced IL-1β–GM-CSF axis, leading to a reduction of bacterial growth. A preceding IAV infection of the human alveolus leads to a type I and III IFN-dependent blockade of the early cytokines IL-1β and GM-CSF, which are key for orchestrating an adequate innate immune response against bacteria. Their virally induced suppression may result in impaired bacterial clearance and alveolar repair.Pharmacological inhibition of Tyk2 might be a new treatment option to sustain beneficial endogenous GM-CSF levels in IAV-associated secondary bacterial pneumonia.
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Rathe, Jennifer A., Michael Gale Jr., and Megan Knoll. "2608. Restriction of Rhinovirus Infection Depends on Virus Sensing and Early IFN Induction." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S907. http://dx.doi.org/10.1093/ofid/ofz360.2286.
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Abstract Background Human rhinovirus (RV) infections are ubiquitous, underestimated, and costly. RV causes 3–12 infections per year per individual with a wide range of clinical presentations from mild upper respiratory infections to severe viral pneumonias (1). The virus-host interactions that control RV infection are poorly understood. Thus, there are no vaccines or antiviral medications available. RV infection begins at the airway epithelial surface where the virus first encounters the host cell immune defenses, including type I and III interferon (IFN). IFN actions are critical for defense against RV infection wherein interferon-stimulated genes (ISG)s direct antiviral actions to limit RV infection. Methods We hypothesized that the timing of IFN induction is a critical determinant of RV restriction by host innate immune defenses in the human respiratory tract. Thus, an immortalized bronchial epithelial cell line was infected with RV-14 with multiplicity of infection (MOI) ranging from 0.1 – 10 and under conditions of pre/post infection treatment with IFN-β or IFN-λ. Host and viral RNA, protein, and RV infectious particle levels were analyzed. Results We found that RV infection induces IFN-β and IFN-λ production and subsequent ISG induction, including expression of IFIT-1, OAS1, and MX1. RV-14 infection induced IFN-β and IFN-λ in a dose-dependent manner, with a maximum fold increase of IFN expression at 48hours post infection. ISGs were induced in a similar pattern to IFNs. Viral titers increased significantly over the first 24hours post infection and then plateaued through 96hours. IFN-β and IFN-λ pre- and posttreatment conditions significantly decreased maximum viral titers achieved but with continued viral plateaus 24–96 hours post infection. Conclusion Our observations demonstrate that RV induces innate immune activation and the production of type I and III IFN during acute infection of airway cells. Sustained viral titer plateaus, despite antiviral ISG induction, suggests viral blocking of IFN pathway mechanisms that can be overcome by early IFN induction to significantly restrict RV viral replication. 1. Royston L, Tapparel C. 2016. Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC. Viruses 8. Disclosures All authors: No reported disclosures.
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De Herdt, P., M. De Gussem, S. Van Gorp, and R. Currie. "Infectious bronchitis virus infections of chickens in Belgium: an epidemiological survey." Vlaams Diergeneeskundig Tijdschrift 85, no. 5 (October 28, 2016): 285–90. http://dx.doi.org/10.21825/vdt.v85i5.16319.
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Between April 2012 and July 2015, cloacal and/or tracheal swab samples were collected from four hundred and twenty-four Belgian chicken broiler, breeder and layer flocks. All flocks were kept for production purposes and presented clinical signs suggestive of an infectious bronchitis virus (IBV) infection. The samples were analyzed by real-time polymerase chain reaction (RT-qPCR) to detect the presence of ribonucleic acid (RNA) of IBV. When positive, approximately four hundred base pairs (bp) encoding for the hypervariable region of the IBV S1 protein were sequenced. Sequencing results, cycle threshold (Ct) values and vaccination history were used as criteria to try and distinguish vaccine strains from field strains. Of all samples examined, 22.4% was negative. In 16.4% of the samples that did contain RNA from IBV, the genotype could not be determined. In most cases, this was due to the recovery of RNA quantities below the lower limit of detection of the sequencing PCR. The remaining positive submissions predominantly revealed RNA from IBV strains that belonged to the 4/91–793B (46.8%), D388–QX (25.2%), D274-D207 (5.8%) and Massachusetts (4.0%) genotypes. Estimations indicated that approximately 58%, 11%, 37% and 46% of these detections, respectively, were vaccine strains. Infections with types CK/CH/Guandong/Xindadi/0903, Ukr/27/2011, NGA/295/2006 and Q1 were observed sporadically. The results indicate that IBV infections are highly prevalent in Belgian chickens and that at least eight different IBV types were circulating during the monitored period. This underlines the necessity of providing flocks with a strong and broad protective immunity against IBV.
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Ma, Zhong-Min, Mars Stone, Mike Piatak, Becky Schweighardt, Nancy L. Haigwood, David Montefiori, Jeffrey D. Lifson, Michael P. Busch, and Christopher J. Miller. "High Specific Infectivity of Plasma Virus from the Pre-Ramp-Up and Ramp-Up Stages of Acute Simian Immunodeficiency Virus Infection." Journal of Virology 83, no. 7 (January 7, 2009): 3288–97. http://dx.doi.org/10.1128/jvi.02423-08.
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ABSTRACT To define the ratio of simian immunodeficiency virus (SIV) RNA molecules to infectious virions in plasma, a ramp-up-stage plasma pool was made from the earliest viral RNA (vRNA)-positive plasma samples (collected approximately 7 days after inoculation) from seven macaques, and a set-point-stage plasma pool was made from plasma samples collected 10 to 16 weeks after peak viremia from seven macaques; vRNA levels in these plasma pools were determined, and serial 10-fold dilutions containing 1 to 1,500 vRNA copies/ml were made. Intravenous (i.v.) inoculation of a 1-ml aliquot of diluted ramp-up-stage plasma containing 20 vRNA copies infected 2 of 2 rhesus macaques, while for the set-point-stage plasma, i.v. inoculation with 1,500 vRNA copies was needed to transmit infection. Further, when the heat-inactivated set-point-stage plasma pool was mixed with ramp-up-stage virions, infection of inoculated macaques was blocked. Notably, 2 of 2 animals inoculated with 85 ml of a pre-ramp-up plasma pool containing <3 SIV RNA copies/ml developed SIV infections characterized by high levels of viral replication, demonstrating that “vRNA-negative” plasma collected from macaques in the pre-ramp-up stage is infectious. Furthermore, there is a high ratio of infectious virions to total virions in ramp-up-stage plasma (between 1:1 and 1:10) and a lower ratio in set-point-stage plasma (between 1:75 and 1:750). Heat-inactivated chronic-stage plasma can “neutralize” the highly infectious ramp-up-stage virions. These findings have implications for the understanding of the natural history of SIV and human immunodeficiency virus infection and transmission.
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Gavin, Giovannoni, Hartung Hans-Peter, Comi Giancarlo, de Seze Jérôme, Hemmer Bernhard, Kappos Ludwig, Montalban Xavier, Selmaj Krzysztof, Mairon Nicole, and Wolinsky Jerry. "WED 187 Infections in ocrelizumab recipients from phase III studies." Journal of Neurology, Neurosurgery & Psychiatry 89, no. 10 (September 13, 2018): A26.3—A27. http://dx.doi.org/10.1136/jnnp-2018-abn.92.
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BackgroundOcrelizumab Phase III study safety findings in relapsing (OPERA I/II [NCT01247324/NCT01412333]) and primary progressive multiple sclerosis (ORATORIO [NCT01194570]) were reported; infections and serious infections are reported here. Methods: Ocrelizumab patients received 600 mg intravenously every 24 weeks for 96 weeks (OPERA I/II) or ≥120 weeks (ORATORIO; 2 × 300 mg infusions 14 days apart every 24 weeks). Controls received interferon beta-1a 44 µg thrice weekly (IFNβ−1a; OPERA I/II) or placebo (ORATORIO). Infections were classified by MedDRA system organ class/preferred term.ResultsNon-serious infection rates in ocrelizumab-treated patients in OPERA were 58.4% (pooled analysis) and ORATORIO 69.8%; comparators were IFNβ−1a 52.4% and placebo 67.8%. Most infections were mild-to-moderate. Common infections (≥10% in either group) reported more in ocrelizumab treated patients were upper respiratory tract infections and either nasopharyngitis (OPERA) or influenza (ORATORIO);<1% of ocrelizumab-treated patients withdrew due to non-serious infections. Serious infections occurred in 1.3% (OPERA) and 6.2% (ORATORIO) of ocrelizumab-treated patients; comparators were IFNβ−1a 2.9% and placebo 5.9%. No infection-related deaths occurred in ocrelizumabtreated patients in OPERA; two deaths occurred in ORATORIO (aspiration pneumonia and pneumonia [unrelated per investigator, related per sponsor]). No opportunistic infections were reported.ConclusionSerious infection rates with ocrelizumab were numerically lower than with IFNβ−1a and similar compared with placebo.
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Luo, Min Hua, Philip H. Schwartz, and Elizabeth A. Fortunato. "Neonatal Neural Progenitor Cells and Their Neuronal and Glial Cell Derivatives Are Fully Permissive for Human Cytomegalovirus Infection." Journal of Virology 82, no. 20 (August 6, 2008): 9994–10007. http://dx.doi.org/10.1128/jvi.00943-08.
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ABSTRACT Congenital human cytomegalovirus (HCMV) infection causes central nervous system structural abnormalities and functional disorders, affecting both astroglia and neurons with a pathogenesis that is only marginally understood. To better understand HCMV's interactions with such clinically important cell types, we utilized neural progenitor cells (NPCs) derived from neonatal autopsy tissue, which can be differentiated down either glial or neuronal pathways. Studies were performed using two viral isolates, Towne (laboratory adapted) and TR (a clinical strain), at a multiplicity of infection of 3. NPCs were fully permissive for both strains, expressing the full range of viral antigens (Ags) and producing relatively large numbers of infectious virions. NPCs infected with TR showed delayed development of cytopathic effects (CPE) and replication centers and shed less virus. This pattern of delay for TR infections held true for all cell types tested. Differentiation of NPCs was carried out for 21 days to obtain either astroglia (>95% GFAP+) or a 1:5 mixed neuron/astroglia population (β-tubulin III+/GFAP+). We found that both of these differentiated populations were fully permissive for HCMV infection and produced substantial numbers of infectious virions. Utilizing a difference in plating efficiencies, we were able to enrich the neuron population to ∼80% β-tubulin III+ cells. These β-tubulin III+-enriched populations remained fully permissive for infection but were very slow to develop CPE. These infected enriched neurons survived longer than either NPCs or astroglia, and a small proportion were alive until at least 14 days postinfection. These surviving cells were all β-tubulin III+ and showed viral Ag expression. Surprisingly, some cells still exhibited extended processes, similar to mock-infected neurons. Our findings strongly suggest neurons as reservoirs for HCMV within the developing brain.
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Hill, Rachel D., Julia S. Gouffon, Arnold M. Saxton, and Chunlei Su. "Differential Gene Expression in Mice Infected with Distinct Toxoplasma Strains." Infection and Immunity 80, no. 3 (December 5, 2011): 968–74. http://dx.doi.org/10.1128/iai.05421-11.
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Toxoplasma gondiiis the causative agent of toxoplasmosis in human and animals. In a mouse model,T. gondiistrains can be divided into three groups, including the virulent, intermediately virulent, and nonvirulent. The clonal type I, II, and IIIT. gondiistrains belong to these three groups, respectively. To better understand the basis of virulence phenotypes, we investigated mouse gene expression responses to the infection of differentT. gondiistrains at day 5 after intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of mouse peritoneal cells showed that 1,927, 1,573, and 1,009 transcripts were altered more than 2-fold by type I, II, and III infections, respectively, and that the majority of altered transcripts were shared. Overall transcription patterns were similar in type I and type II infections, and both had greater changes than infection with type III. Quantification of parasite burden in mouse spleens showed that the burden with type I infection was 1,000 times higher than that of type II and that the type II burden was 20 times higher than that of type III. Fluorescence-activated cell sorting revealed that type I and II infections had comparable macrophage populations, and both were higher than the population with type III infection. In addition, type I infection had a higher percentage of neutrophils than type II and III infections. Taken together, these results suggested that there is a common gene expression response toT. gondiiinfection in mice. This response is further modified by parasite strain-specific factors that determine their distinct virulence phenotypes.
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Pirbonyeh, Neda, Amir Emami, Abdollah Bazargani, Fatemeh Javanmardi, Seyed Mohsen Hosseini, and Bahram Derakhshan. "Integron-Related Resistance in New Emerged Staphylococcus lugdunensis Infection in Burn Patients." Journal of Burn Care & Research 41, no. 3 (December 23, 2019): 598–603. http://dx.doi.org/10.1093/jbcr/irz211.
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Abstract Staphylococcus lugdunensis is a coagulase-negative Staphylococcus species that may cause various infections with unusual severity. In spite of the administration of various antibiotics, infections caused by such bacteria are become resistant significantly. Transmission of antibiotic resistance genes, especially by Integron structures, exacerbates the prevalence of resistant strains. To investigate the antibiotic susceptibility pattern of S. lugdunensis as a new emergence in burns, the presence of integron classes (I, II, III) was performed in recent study. Sampling for this study was carried out over a period of 13 months (January 2017 to February 2018) from Amir-Al-Momenin burn center of southwest of Iran, affiliated with Shiraz University of Medical Sciences. Twenty-eight isolates of S. lugdunensis were confirmed by phenotypic tests. The presence of integron classes was evaluated by PCR technique and specific primers. The majority of studied infectious agents were seen in ICU with 28.57%. The prevalence of class I and II integrons was 7 (25.00%) and 2 (7.14%), respectively, in S. lugdunensis isolates, whereas no integron III was found. No significant association was seen between antibiotic resistance and the present integrons (P > .05). Since the prevalence of S. lugdunensis strains as a new emergence infection is increasing in clinical settings especially burns, preventing drug resistance in these isolates is inevitable. So knowing the epidemiology pattern of new emerging infections and their resistant pattern is very helpful in infection control and save hospitalized patients life.
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Ng, Wy Ching, Sarah L. Londrigan, Najla Nasr, Anthony L. Cunningham, Stuart Turville, Andrew G. Brooks, and Patrick C. Reading. "The C-type Lectin Langerin Functions as a Receptor for Attachment and Infectious Entry of Influenza A Virus." Journal of Virology 90, no. 1 (October 14, 2015): 206–21. http://dx.doi.org/10.1128/jvi.01447-15.
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ABSTRACTIt is well established that influenza A virus (IAV) attachment to and infection of epithelial cells is dependent on sialic acid (SIA) at the cell surface, although the specific receptors that mediate IAV entry have not been defined and multiple receptors may exist. Lec2 Chinese hamster ovary (CHO) cells are SIA deficient and resistant to IAV infection. Here we demonstrate that the expression of the C-type lectin receptor langerin in Lec2 cells (Lec2-Lg) rendered them permissive to IAV infection, as measured by replication of the viral genome, transcription of viral mRNA, and synthesis of viral proteins. Unlike SIA-dependent infection of parental CHO cells, IAV attachment and infection of Lec2-Lg cells was mediated via lectin-mediated recognition of mannose-rich glycans expressed by the viral hemagglutinin glycoprotein. Lec2 cells expressing endocytosis-defective langerin bound IAV efficiently but remained resistant to IAV infection, confirming that internalization via langerin was essential for infectious entry. Langerin-mediated infection of Lec2-Lg cells was pH and dynamin dependent, occurred via clathrin- and caveolin-mediated endocytic pathways, and utilized early (Rab5+) but not late (Rab7+) endosomes. This study is the first to demonstrate that langerin represents an authentic receptor that binds and internalizes IAV to facilitate infection. Moreover, it describes a unique experimental system to probe specific pathways and compartments involved in infectious entry following recognition of IAV by a single cell surface receptor.IMPORTANCEOn the surface of host cells, sialic acid (SIA) functions as the major attachment factor for influenza A viruses (IAV). However, few studies have identified specific transmembrane receptors that bind and internalize IAV to facilitate infection. Here we identify human langerin as a transmembrane glycoprotein that can act as an attachment factor and abone fideendocytic receptor for IAV infection. Expression of langerin by an SIA-deficient cell line resistant to IAV rendered cells permissive to infection. As langerin represented the sole receptor for IAV infection in this system, we have defined the pathways and compartments involved in infectious entry of IAV into cells following recognition by langerin.
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Srivenkataramana, T., and C. Nagaraja Rao. "HIV Spread: Some Statistical Results." Mapana - Journal of Sciences 1, no. 1 (July 12, 2002): 28–39. http://dx.doi.org/10.12723/mjs.1.3.
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The spread of AIDS causative agent HIV has now entered the third decade. The infection was first noticed in 1981 in the USA. Within 2 decades, it has quickly grown to the level of an endemic. Unlike several other infectious diseases, AIDS endemiology is interdisciplinary, surrounded by many complex socio-economic, psychological, legal, behavioural and statistical issues. Knowledge of HIV incidence is important to formulate sensible intervention strategies aimed at its control. This article discusses: i) Important special features of the spread mechanism which render the syndrome a lethal and silent killer. ii) A method to evaluate probability of infection in a heterosexual relation. iii) A method for estimating HIV infections in perinatal transmissions, and iv) The Indian HIV perspective and makes a few suggestions to control the reckless spread of HIV across the country.
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Zav'yalov, Vladimir P., Heli Hämäläinen-Laanaya, Timo K. Korpela, and Tony Wahlroos. "Interferon-Inducible Myxovirus Resistance Proteins: Potential Biomarkers for Differentiating Viral from Bacterial Infections." Clinical Chemistry 65, no. 6 (June 1, 2019): 739–50. http://dx.doi.org/10.1373/clinchem.2018.292391.
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Abstract BACKGROUND In 2015, the 68th World Health Assembly declared that effective, rapid, low-cost diagnostic tools were needed for guiding optimal use of antibiotics in medicine. This review is devoted to interferon-inducible myxovirus resistance proteins as potential biomarkers for differentiating viral from bacterial infections. CONTENT After viral infection, a branch of the interferon (IFN)-induced molecular reactions is triggered by the binding of IFNs with their receptors, a process leading to the activation of mx1 and mx2, which produce antiviral Mx proteins (MxA and MxB). We summarize current knowledge of the structures and functions of type I and III IFNs. Antiviral mechanisms of Mx proteins are discussed in reference to their structural and functional data to provide an in-depth picture of protection against viral attacks. Knowing such a mechanism may allow the development of countermeasures and the specific detection of any viral infection. Clinical research data indicate that Mx proteins are biomarkers for many virus infections, with some exceptions, whereas C-reactive protein (CRP) and procalcitonin have established positions as general biomarkers for bacterial infections. SUMMARY Mx genes are not directly induced by viruses and are not expressed constitutively; their expression strictly depends on IFN signaling. MxA protein production in peripheral blood cells has been shown to be a clinically sensitive and specific marker for viral infection. Viral infections specifically increase MxA concentrations, whereas viruses have only a modest increase in CRP or procalcitonin concentrations. Therefore, comparison of MxA and CRP and/or procalcitonin values can be used for the differentiation of infectious etiology.
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Kang, Moon Cheol, Dong-Hoon Choi, Young Woo Choi, Seong Jeong Park, Hong Namkoong, Ki Seok Park, So-Shin Ahn, et al. "Intranasal Introduction of Fc-Fused Interleukin-7 Provides Long-Lasting Prophylaxis against Lethal Influenza Virus Infection." Journal of Virology 90, no. 5 (December 9, 2015): 2273–84. http://dx.doi.org/10.1128/jvi.02768-15.
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ABSTRACTInfluenza A virus (IAV) infection frequently causes hospitalization and mortality due to severe immunopathology. Annual vaccination and antiviral drugs are the current countermeasures against IAV infection, but they have a limited efficacy against new IAV variants. Here, we show that intranasal pretreatment with Fc-fused interleukin-7 (IL-7–mFc) protects mice from lethal IAV infections. The protective activity of IL-7–mFc relies on transcytosis via neonatal Fc receptor (FcRn) in the lung and lasts for several weeks. Introduction of IL-7–mFc alters pulmonary immune environments, leading to recruitment of T cells from circulation and their subsequent residency as tissue-resident memory-like T (TRM-like) cells. IL-7–mFc-primed pulmonary TRM-like cells contribute to protection upon IAV infection by dual modes. First, TRM-like cells, although not antigen specific but polyclonal, attenuate viral replication at the early phase of IAV infection. Second, TRM-like cells augment expansion of IAV-specific cytotoxic T lymphocytes (CTLs), in particular at the late phase of infection, which directly control viruses. Thus, accelerated viral clearance facilitated by pulmonary T cells, which are either antigen specific or not, alleviates immunopathology in the lung and mortality from IAV infection. Depleting a subset of pulmonary T cells indicates that both CD4 and CD8 T cells contribute to protection from IAV, although IL-7-primed CD4 T cells have a more prominent role. Collectively, we propose intranasal IL-7–mFc pretreatment as an effective means for generating protective immunity against IAV infections, which could be applied to a potential prophylaxis for influenza pandemics in the future.IMPORTANCEThe major consequence of a highly pathogenic IAV infection is severe pulmonary inflammation, which can result in organ failure and death at worst. Although vaccines for seasonal IAVs are effective, frequent variation of surface viral proteins hampers development of protective immunity. In this study, we demonstrated that intranasal IL-7–mFc pretreatment protected immunologically naive mice from lethal IAV infections. Intranasal pretreatment with IL-7–mFc induced an infiltration of T cells in the lung, which reside as effector/memory T cells with lung-retentive markers. Those IL-7-primed pulmonary T cells contributed to development of protective immunity upon IAV infection, reducing pulmonary immunopathology while increasing IAV-specific cytotoxic T lymphocytes. Since a single treatment with IL-7–mFc was effective in the protection against multiple strains of IAV for an extended period of time, our findings suggest a possibility that IL-7–mFc treatment, as a potential prophylaxis, can be developed for controlling highly pathogenic IAV infections.
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Delogu, Lucia Gemma, Silvia Deidda, Giuseppe Delitala, and Roberto Manetti. "Infectious diseases and autoimmunity." Journal of Infection in Developing Countries 5, no. 10 (October 11, 2011): 679–87. http://dx.doi.org/10.3855/jidc.2061.
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Introduction: Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. Methodology: We searched PubMed, Cochrane, and Scopus without time limits for relevant articles. Results: In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity. Conclusions: Besides genetic predisposition to autoimmunity, viral and bacterial infections are known to be involved in the initiation and promotion of autoimmune diseases. These studies suggest that pathogens can trigger autoimmunity through molecular mimicry and their adjuvant effects during initiation of disease, and can promote autoimmune responses through bystander activation or epitope spreading via inflammation and/or superantigens.
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Альбот, Вадим, Vadim Albot, Ирина Келешева, and Irina Kelesheva. "COMPARATIVE ANALYSIS OF THE SPECTRUM OF FORCES OF URINARY INFECTION OF THE DELIVERIES OF THE IRKUTSK REGION AND THE DYNAMICS OF BACTERIAL RESISTANCE In 2002-2004 and 2014-2016 years." Acta biomedica scientifica 2, no. 5 (January 18, 2018): 87–92. http://dx.doi.org/10.12737/article_5a3a0ddcb65a61.76013249.
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In the structure of diseases of the urinary system in children, microbial-inflammatory lesions of the kidneys and urinary
tract are 70–80 %. The prevalence of infections of urinary system in children in the Russian Federation is on average
18–22 per 1000 children’s population.
The aim of the study was to analyze the spectrum of infectious agents of urinary infection in children and to determine
the dynamics of bacterial resistance.
We analyzed 330 cases of urinary system infection in children aged from 2 months up to 18 years in two time peri-
ods – 2002–2004 and 2014–2016 (n = 114 and n = 216, respectively). Patients of both periods were divided into three groups: the first one – cystitis, the second one – pyelonephritis and the third group – a combination of pyelonephritis
and cystitis. An obligatory criterion for including the patient in the study was the presence of a pathogmonic combina-
tion of leukocyturia and bacteriuria, 10 5 KOE/ml, for the infection of the urinary system.
The main causative agent of urinary infection in children remains E. coli. An increase is marked in the specific gravity
of E. coli, Enterococcus spp. and Klebsiella spp., Pr. vulgaris.
The study revealed the growth of E. coli resistance to cephalosporins of II, III, IV generations; decreased resistance of
Enterococcus spp. to ampicillin and gentamicin. In the study of the sensitivity of Klebsiella spp. an increase was detected
in resistance to cephalosporins of the III generation.
We identified the main pathogens of infections of the urinary system and determined bacterial resistance.
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Park, Bum Ju, Man Seong Park, Jae Myun Lee, and Yoon Jae Song. "Specific Detection of Influenza A and B Viruses by CRISPR-Cas12a-Based Assay." Biosensors 11, no. 3 (March 19, 2021): 88. http://dx.doi.org/10.3390/bios11030088.
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A rapid and accurate on-site diagnostic test for pathogens including influenza viruses is critical for preventing the spread of infectious diseases. Two types of influenza virus, A and B cause seasonal flu epidemics, whereas type A can cause influenza pandemics. To specifically detect influenza A (IAV) and B (IBV) viruses, we developed a clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated (Cas) system-based assay. By coupling reverse transcription recombinase polymerase amplification (RT-RPA) and reverse transcription loop-mediated isothermal amplification (RT-LAMP), a CRISPR-Cas12a DNA endonuclease-targeted CRISPR trans-reporter (DETECTR) detected IAV and IBV titers as low as 1 × 100 plaque forming units (PFUs) per reaction without exhibiting cross-reactivity. Only 75 to 85 min were required to detect IAV and IBV, depending on isothermal nucleic acid amplification methods, and results were verified using a lateral flow strip assay that does not require additional analytic equipment. Taken together, our findings establish RT-RPA and RT-LAMP-coupled DETECTR-based diagnostic tests for rapid, specific and high-sensitivity detection of IAV and IBV using fluorescence and lateral flow assays. The diagnostic test developed in this study can be used to distinguish IAV and IBV infections, a capability that is necessary for monitoring and preventing the spread of influenza epidemics and pandemics.