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Journal articles on the topic 'Meningitis; Influenza virus'
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1
Shiomi, M., M. Togawa, H. Kurimasa, H. Kawawaki, K. Tomiwa, Y. Sawada, H. Shintaku, M. Asada, and R. Murata. "Neopterin Concentrations of Serum and Cerebrospinal Fluid in Febrile Convulsion, Aseptic Meningitis and Influenza Encephalopathy." Pteridines 10, no. 1 (February 1999): 35–38. http://dx.doi.org/10.1515/pteridines.1999.10.1.35.
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The concentration of total neopterin in serum and cerebrospinal fluid (CSF) was measured in cases of febrile convulsion, aseptic meningitis and influenza encephalopathy. In febrile convulsion except for exanthem subitum, the concentrations of CSF neopterin (26± 11, Mean±SD, n=6) were all within normal range while those of serum neopterin (66± 20, n=8) were significantly higher (p < 0.05). In aseptic meningitis, on the other hand, the concentrations of CSF neopterin (194± 130, n=13) were significantly higher than those of serum (33±23, n=11, p < 0.05). In influenza encephalopathy, both concentrations of serum neopterin (329±478, n=13) and CSF neopterin(179±131, n=11) were much higher than the control range. Our results indicate that the primary immunoreacting site is the central nervous system (CNS) for aseptic meningitis, the periphery for febrile convulsion except for exanthem subitum and both the periphery and the CNS for influenza encephalopathy. Measurements of neopterin concentrations in CSF as well as in serum may thus constitute an immediate aid for early differentiation of CNS infection from peripheral infection as well as for early detection of viral encephalopathy caused by viruses such as the influenza virus or the human herpes virus 6.
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Opatowski, Lulla, Emmanuelle Varon, Claire Dupont, Laura Temime, Sylvie van der Werf, Laurent Gutmann, Pierre-Yves Boëlle, Laurence Watier, and Didier Guillemot. "Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models." Proceedings of the Royal Society B: Biological Sciences 280, no. 1764 (August 7, 2013): 20130519. http://dx.doi.org/10.1098/rspb.2013.0519.
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Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001–2004 are analysed and used to assess four distinct virus–bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96–0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.
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Short, Kirsty R., Patrick C. Reading, Lorena E. Brown, John Pedersen, Brad Gilbertson, Emma R. Job, Kathryn M. Edenborough, et al. "Influenza-Induced Inflammation Drives Pneumococcal Otitis Media." Infection and Immunity 81, no. 3 (January 14, 2013): 645–52. http://dx.doi.org/10.1128/iai.01278-12.
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ABSTRACTInfluenza A virus (IAV) predisposes individuals to secondary infections with the bacteriumStreptococcus pneumoniae(the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.
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Moxon, E. Richard. "Bacterial variation, virulence and vaccines." Microbiology 155, no. 4 (April 1, 2009): 997–1003. http://dx.doi.org/10.1099/mic.0.024877-0.
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Research into Haemophilus influenzae, a commensal and pathogen of humans, has resulted in major scientific contributions to biology. The first endonucleases (restriction enzymes), which paved the way for the new genetics, and the DNA used to obtain the first complete genome sequence of a free-living organism were obtained from H. influenzae. Prevention of invasive bacterial infections of infants, such as meningitis, has been achieved using a novel class of vaccines, of which the glycoconjugates of H. influenzae were the first to be licensed. Originally fallaciously proposed to be the aetiological agent of epidemic influenza, now known to be caused by a virus, H. influenzae is a pathogen of global public health importance. Research into the pathogenesis of the infections it causes (for example, meningitis, septicaemia, pneumonia and otitis media) are case studies in understanding the molecular basis of the variation in gene expression and gene sequences that are critical to its commensal and virulence behaviour and for the strategies that can be pursued to prevent H. influenzae diseases through vaccines.
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Choi, Gwang-Jun, Ji Young Park, Joon-Sik Choi, Bitna Kim, Sae Rom Choi, Dong Sub Kim, Ji-Man Kang, et al. "724. Neurologic Complications in Hospitalized Pediatric Patients with Influenza Infection, A Multicenter Retrospective Study in Korea." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S260. http://dx.doi.org/10.1093/ofid/ofy210.731.
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Abstract Background The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea. Methods We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country. Results A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P < 0.0001). Conclusion IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases. Disclosures All authors: No reported disclosures.
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Nakayama, T., S. Sonoda, T. Urano, T. Yamada, and M. Okada. "Monitoring both serum amyloid protein A and C-reactive protein as inflammatory markers in infectious diseases." Clinical Chemistry 39, no. 2 (February 1, 1993): 293–97. http://dx.doi.org/10.1093/clinchem/39.2.293.
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Abstract We examined serum amyloid protein A (SAA) and C-reactive protein (CRP) as inflammatory markers of viral and bacterial infections. Both acute-phase reactants increased in the acute stage and thereafter decreased in the convalescent stage. In viral infections, the mean serum concentrations of SAA during the acute stage were 141 mg/L in infections with adenovirus, 77 mg/L with measles virus, 63 mg/L with influenza virus, 55 mg/L with parainfluenza virus, 31 mg/L with respiratory syncytial virus, and 31 mg/L in aseptic meningitis. The mean serum concentration of CRP was 19 mg/L for adenovirus infection and < 7 mg/L in all other viral infections. The SAA concentrations were 5- to 11-fold greater than the CRP concentrations. Both the SAA and the CRP concentrations were higher in bacterial infections than in viral infections. Changes in the concentrations of serum SAA paralleled those in serum CRP in bacterial infection; during the course of viral infection, however, serum SAA tended to disappear more quickly than CRP did. SAA appears to be a clinically useful marker of inflammation in acute viral infections, with or without significant changes in the CRP concentration.
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Malarski, Maya, Mateusz Hasso-Agopsowicz, Adam Soble, Wilson Mok, Sophie Mathewson, and Johan Vekemans. "Vaccine impact on antimicrobial resistance to inform Gavi, the Vaccine Alliance’s 2018 Vaccine Investment Strategy: report from an expert survey." F1000Research 8 (September 24, 2019): 1685. http://dx.doi.org/10.12688/f1000research.20100.1.
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Background: While the rise of antimicrobial resistance (AMR) has been recognised as a major public health problem, the value of vaccines to control AMR is poorly defined. This expert survey was launched with the aim of informing the 2018 Vaccine Investment Strategy through which Gavi, the Vaccine Alliance prioritises future vaccine funding. This exercise focused on both vaccines currently supported by Gavi and under consideration for future funding. Methods: The relative importance of pre-defined criteria as drivers of overall value of vaccines as a tool/ intervention to control AMR was assessed by 18 experts: prevention of mortality and morbidity due to resistant pathogens, antibiotic use prevented, societal impact, ethical importance and sense of urgency. For each vaccine, experts attributed scores reflecting the estimated value for each criterion, and overall value relative to AMR was derived from the value assigned to each criterion and their relative importance for each vaccine. Results: Mortality, morbidity due to targeted resistant pathogens, and antibiotic use prevented were considered the most important determinants of overall value. Pneumococcal, typhoid and malaria vaccines were assigned highest value relative to antimicrobial resistance. Intermediate value was estimated for specific rotavirus, cholera, respiratory syncytial virus (RSV), influenza, dengue, measles, meningitis and Haemophilus influenza type b- (Hib-) containing pentavalent vaccines. Lowest value relative to AMR was estimated for Japanese encephalitis, hepatitis A, yellow fever, rabies and human papilloma virus vaccine. Conclusions: In the future, more evidence-based, data-driven, robust methodologies should be developed to guide coordinated, rational decision making on priority actions aimed at strengthening the use of vaccines against AMR.
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Muñoz, Clara, Nazli Ayhan, Maria Ortuño, Juana Ortiz, Ernest A. Gould, Carla Maia, Eduardo Berriatua, and Remi N. Charrel. "Experimental Infection of Dogs with Toscana Virus and Sandfly Fever Sicilian Virus to Determine Their Potential as Possible Vertebrate Hosts." Microorganisms 8, no. 4 (April 20, 2020): 596. http://dx.doi.org/10.3390/microorganisms8040596.
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The sandfly-borne Toscana phlebovirus (TOSV), a close relative of the sandfly fever Sicilian phlebovirus (SFSV), is one of the most common causes of acute meningitis or meningoencephalitis in humans in the Mediterranean Basin. However, most of human phlebovirus infections in endemic areas either are asymptomatic or cause mild influenza-like illness. To date, a vertebrate reservoir for sandfly-borne phleboviruses has not been identified. Dogs are a prime target for blood-feeding phlebotomines and are the primary reservoir of human sandfly-borne Leishmania infantum. However, there are no definitive studies to assess whether dogs play a significant role as a reservoir host for human phlebovirus survival in the environment. Here, we have evaluated the susceptibility of domestic dogs to infection by TOSV and SFSV following the direct inoculation of the infectious virus. After experimental infection, the presence of viral RNA was investigated in plasma, urine, saliva, conjunctiva, faeces, semen, and bone marrow samples from 0 to 91 days postinoculation (dpi), as well as in plasma, saliva, and tears samples at 760 dpi. None of the challenged dogs developed clinical signs of infection with either TOSV or SFSV. SFSV RNA was never detected. TOSV RNA was not in any of the specimen types, except for plasma samples that showed low viral loads, although irregularly. None of the dogs developed detectable neutralizing antibodies after a single challenge dose of either TOSV or SFSV. However, a second challenge dose of virus given 56 days later elicited neutralizing antibodies, implying that the first inoculation of virus primed the animals for an anamnestic response following the second challenge. These results demonstrated that healthy domestic dogs are not highly susceptible to infection by TOSV or SFSV and do not develop significant viremia or excrete virus following infection. Consequently, dogs are unlikely natural reservoir hosts of infection and do not appear to play a significant role in phlebovirus transmission cycles.
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English, Abigail, Carol A. Ford, and John S. Santelli. "Clinical Preventive Services for Adolescents: Position Paper of the Society for Adolescent Medicine." American Journal of Law & Medicine 35, no. 2-3 (June 2009): 351–64. http://dx.doi.org/10.1177/009885880903500206.
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Over the past several years, new vaccines have become available to prevent serious illnesses and conditions in the adolescent population. Several have already been approved by the FDA for use in this age group; others are still in development. Recently, significant public attention has been focused on the availability of vaccines for several strains of HPV, to prevent both cervical cancer and genital warts. Prior to that, the vaccine for Hepatitis B was approved and recommended for the adolescent age group. Others currently available and recommended include vaccines for pertussis, meningitis, and influenza. In the future, additional vaccines are expected to become available for sexually transmitted and communicable diseases such as herpes simplex virus and HIV. Unfortunately, financial limitations and consent requirements can impede adolescents’ access to the vaccines that are recommended for their age group. However, a variety of policy options exist for overcoming the barriers and expanding access. These policy options are grounded both in international principles of human rights and in the existing framework of laws in the United States, and can be enhanced by attending to variations in age and developmental status among adolescents.
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Etna, Marilena P., Aurora Signorazzi, Daniela Ricci, Martina Severa, Fabiana Rizzo, Elena Giacomini, Andrea Gaggioli, Isabelle Bekeredjian-Ding, Anke Huckriede, and Eliana M. Coccia. "Human plasmacytoid dendritic cells at the crossroad of type I interferon-regulated B cell differentiation and antiviral response to tick-borne encephalitis virus." PLOS Pathogens 17, no. 4 (April 15, 2021): e1009505. http://dx.doi.org/10.1371/journal.ppat.1009505.
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The Tick-borne encephalitis virus (TBEV) causes different disease symptoms varying from asymptomatic infection to severe encephalitis and meningitis suggesting a crucial role of the human host immune system in determining the fate of the infection. There is a need to understand the mechanisms underpinning TBEV-host interactions leading to protective immunity. To this aim, we studied the response of human peripheral blood mononuclear cells (PBMC) to the whole formaldehyde inactivated TBEV (I-TBEV), the drug substance of Encepur, one of the five commercially available vaccine. Immunophenotyping, transcriptome and cytokine profiling of PBMC revealed that I-TBEV generates differentiation of a sub-population of plasmacytoid dendritic cells (pDC) that is specialized in type I interferon (IFN) production. In contrast, likely due to the presence of aluminum hydroxide, Encepur vaccine was a poor pDC stimulus. We demonstrated I-TBEV-induced type I IFN together with Interleukin 6 and BAFF to be critical for B cell differentiation to plasmablasts as measured by immunophenotyping and immunoglobulin production. Robust type I IFN secretion was induced by pDC with the concerted action of both viral E glycoprotein and RNA mirroring previous data on dual stimulation of pDC by both S. aureus and influenza virus protein and nucleic acid that leads to a type I IFN-mediated sustained immune response. E glycoprotein neutralization or high temperature denaturation and inhibition of Toll-like receptor 7 signalling confirmed the importance of preserving the functional integrity of these key viral molecules during the inactivation procedure and manufacturing process to produce a vaccine able to stimulate strong immune responses.
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Palacios, G., I. Casas, D. Cisterna, G. Trallero, A. Tenorio, and C. Freire. "Molecular Epidemiology of Echovirus 30: Temporal Circulation and Prevalence of Single Lineages." Journal of Virology 76, no. 10 (May 15, 2002): 4940–49. http://dx.doi.org/10.1128/jvi.76.10.4940-4949.2002.
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ABSTRACT Echovirus 30 (EV30) is one of the most frequently isolated EVs, causing extensive outbreaks of EV30 aseptic meningitis in temperate climates. EV30 is antigenically heterogeneous, and three major antigenic groups have been defined, although the basis for the antigenic differences is unknown. A reverse transcription-nested PCR which amplifies the 3′-terminal region of the VP1 gene directly from clinical samples was selected for studying EV30 molecular epidemiology, since the major antigenic sites in this region reflect the serotypic pattern of this virus. The different previous approaches to the genetic classification of EV30 were analyzed. A complete study of the EV30 strains was performed by analyzing the sequences from the 112 EV30 strains amplified in this work and the complete set of EV30 strains previously published. A total of 318 strains of EV30 were divided into two broad genotypes (I and II). This classification was supported by the phylogenetic trees obtained from amino acid sequences, and it correlated with the antigenic heterogeneity of the reference strains described in earlier studies. The genotypes could be further divided into subgroups, and these subgroups could be divided into lineages based on their nucleotide distances and levels of bootstrapping. On the other hand, the subgroups and lineages did not result in the same correlation between amino acid and nucleotide differentiation. The molecular epidemiology of EV30 can be compared to influenza virus epidemiology, where prevailing lineages displace the less established lineages on the basis of immune escape. This pattern of evolution is clearly different from that of other enteroviruses. A single lineage at a time appears to be circulating worldwide. This behavior may be related to the epidemic activity of EV30.
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Tobaiqy, Mansour, Ahmed H. Alhasan, Manal M. Shams, Samar A. Amer, Katie MacLure, Mohammed F. Alcattan, and Sami S. Almudarra. "Assessment of Preventative Measures Practice among Umrah Pilgrims in Saudi Arabia, 1440H-2019." International Journal of Environmental Research and Public Health 18, no. 1 (December 31, 2020): 257. http://dx.doi.org/10.3390/ijerph18010257.
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Background: Annually, approximately 10 million pilgrims travel to the Kingdom of Saudi Arabia (KSA) for Umrah from more than 180 countries. This event presents major challenges for the Kingdom’s public health sector, which strives to decrease the burden of infectious diseases and to adequately control their spread both in KSA and pilgrims home nations. The aims of the study were to assess preventative measures practice, including vaccination history and health education, among Umrah pilgrims in Saudi Arabia. Methods: A cross sectional survey was administered to pilgrims from February to April 2019 at the departure lounge at King Abdul Aziz International airport, Jeddah city. The questionnaire comprised questions on sociodemographic information (age, gender, marital status, level of education, history of vaccinations and chronic illnesses), whether the pilgrim had received any health education and orientation prior to coming to Saudi Arabia or on their arrival, and their experiences with preventative practices. Results: Pilgrims (n = 1012) of 41 nationalities completed the survey. Chronic diseases were reported among pilgrims (n = 387, 38.2%) with cardiovascular diseases being the most reported morbidity (n = 164, 42.3%). The majority of pilgrims had been immunized prior to travel to Saudi Arabia (n = 770, 76%). The most commonly reported immunizations were influenza (n = 514, 51%), meningitis (n = 418, 41%), and Hepatitis B virus vaccinations (n = 310, 31%). However, 242 (24%) had not received any vaccinations prior to travel, including meningitis vaccine and poliomyelitis vaccine, which are mandatory by Saudi Arabian health authorities for pilgrims coming from polio active countries. Nearly a third of pilgrims (n = 305; 30.1%) never wore a face mask in crowded areas during Umrah in 2019. In contrast, similar numbers said they always wore a face mask (n = 351, 34.6%) in crowded areas, while 63.2% reported lack of availability of face masks during Umrah. The majority of participants had received some form of health education on preventative measures, including hygiene aspects (n = 799, 78.9%), mostly in their home countries (n = 450, 44.4%). A positive association was found between receiving health education and practicing of preventative measures, such as wearing face masks in crowded areas (p = 0.04), and other health practice scores (p = 0.02). Conclusion: Although the experiences of the preventative measures among pilgrims in terms of health education, vaccinations, and hygienic practices were at times positive, this study identified several issues. These included the following preventative measures: immunizations, particularly meningitis and poliomyelitis vaccine, and using face masks in crowded areas. The recent COVID-19 pandemic highlights the need for further studies that focus on development of accessible health education in a form that engages pilgrims to promote comprehensive preventative measures during Umrah and Hajj and other religious pilgrimages.
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Di Maio, Nicoletta, Giovanna Russo, Susanna Barella, Gian Luca Forni, Raffaella Colombatti, Lucia Notarangelo, Giovanna Graziadei, et al. "Influenza Vaccination in Asplenia: Improving Quality of Care in Time of Coronavirus." Blood 136, Supplement 1 (November 5, 2020): 39–40. http://dx.doi.org/10.1182/blood-2020-142335.
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Introduction Asplenic patients are at high risk of potentially fatal invasive infections, such as sepsis, meningitis, and pneumonia. It has been shown that infection from influenza viruses can precede or increase the risk of bacterial infection and of serious complications of the underlying disease. International and national guidelines recommend annual influenza vaccination in asplenic subjects. Following the Covid-19 pandemic, the major government and medical-scientific institutions in the US and in Europe have been planning how to contain infection during the 2020-2021 influenza season. Extending influenza vaccination is the safest and most effective way to reduce the circulation of influenza virus and to promote the correct diagnosis and management of suspected cases of SARS-CoV-2. Influenza vaccination also reduces complications associated with the underlying disease and visits to Emergency Units. Our study aims to evaluate influenza vaccination in a large population of asplenic patients and explore the main causes for non-vaccination to identify critical areas for improvement in the vaccination programme in these at-risk patients for the 2020-2021 influenza season. Methods The Italian Network of Asplenia (INA) is made up of 88 doctors working in 50 clinical centers in 27 cities and 16 of the 20 regions of Italy. It aims to build a large, prospective cohort of asplenic patients throughout Italy through which to study the interaction between asplenia and its associated underlying conditions, collecting precise, accurate data also in cases of rarer diseases. The study also aims to improve the quality of healthcare for this at-risk population. The number of patients enrolled in the Network who had had at least one dose of influenza vaccine at the time of diagnosis of asplenia was retrieved from the INA database. All participating centers were asked to answer a questionnaire to report the main obstacles for influenza vaccination. Results At 1st August 2020, 1,670 patients had been enrolled in the INA (783 females; 887 males). All underlying causes of asplenia are shown in Table 1. Only 466 (28%) patients had had at least one influenza vaccination, while 1,204 (72%) had never been vaccinated since diagnosis of asplenia. Thirty-five (70%) of the 50 centers answered the questionnaire. Main causes of non-vaccination were physicians' ambivalence concerning vaccination and patients' inadequate awareness or logistical problems. Conclusions These data show very low seasonal influenza vaccination cover even though asplenic patients are considered at-risk of complications associated with infection from influenza viruses. Since the 2020-2021 influenza season could see influenza viruses in circulation with SARS-CoV-2, influenza vaccination must be expanded as widely as possible, in particular to subjects of all ages at high risk. These results reveal important areas of concern in the management of asplenic patients and the need to improve the quality of information to physicians and patients alike. The INA co-ordinating center will launch a campaign to provide information and organize ad hoc meetings to widen influenza vaccination coverage in asplenic patients and reduce the pressure on the national health service during the next influenza season. Disclosures Forni: Novartis: Membership on an entity's Board of Directors or advisory committees. Colombatti:Addmedica: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Giona:Sanofi Genzyme: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Novartis: Research Funding. Ferrero:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Research Funding, Speakers Bureau; Servier: Speakers Bureau. Perrotta:Novartis: Consultancy, Research Funding, Speakers Bureau. Casale:Novartis: Membership on an entity's Board of Directors or advisory committees.
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Read, Robert C., Linda Goodwin, M. Andrew Parsons, Paul Silcocks, Edward B. Kaczmarski, Andrew Parker, and Thomas J. Baldwin. "Coinfection with Influenza B Virus Does Not Affect Association ofNeisseria meningitidis with Human Nasopharyngeal Mucosa in Organ Culture." Infection and Immunity 67, no. 6 (June 1, 1999): 3082–86. http://dx.doi.org/10.1128/iai.67.6.3082-3086.1999.
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ABSTRACT There is an epidemiological association between influenza virus infection and meningococcal disease. Proposed mechanisms are the destruction of the normal epithelial barrier function of the upper respiratory tract by influenza virus or the expression of human or viral surface-exposed proteins that enhance bacterial adherence and/or invasion. To test these hypotheses, human nasopharyngeal mucosa specimens from a total of 19 individual donors were successfully infected with influenza B virus and then inoculated with serogroup B Neisseria meningitidis. Subsequent bacterial association with the epithelial surface was measured in three separate series of experiments by using transmission electron microscopy (n = 6), scanning electron microscopy (n = 6), and counting of viable bacteria within homogenates of explants (n = 7). Penetration of the mucosa was estimated by measuring the count of viable bacteria recovered from explants after exposure to sodium taurocholate. Bacterial association with the surface of explants was time dependent over 24 h of superinfection. Influenza virus did not positively or negatively influence bacterial attachment to or penetration of explant mucosa compared to those of uninfected controls, even when the period of preincubation with virus was extended to 7 days. When proteins were purified from mucosal epithelium and immobilized on nitrocellulose membranes, N. meningitidis attached predominantly to bands corresponding to proteins of 210 and 130 kDa. In the presence of influenza virus infection, these proteins were gradually lost over the course of 72 h. In conclusion, influenza B virus did not increase association of serogroup B N. meningitidis with human nasopharyngeal mucosa.
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Leber, Amy L., Kathy Everhart, Joan-Miquel Balada-Llasat, Jillian Cullison, Judy Daly, Sarah Holt, Paul Lephart, et al. "Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens." Journal of Clinical Microbiology 54, no. 9 (June 22, 2016): 2251–61. http://dx.doi.org/10.1128/jcm.00730-16.
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Rapid diagnosis and treatment of infectious meningitis and encephalitis are critical to minimize morbidity and mortality. Comprehensive testing of cerebrospinal fluid (CSF) often includes Gram stain, culture, antigen detection, and molecular methods, paired with chemical and cellular analyses. These methods may lack sensitivity or specificity, can take several days, and require significant volume for complete analysis. The FilmArray Meningitis/Encephalitis (ME) Panel is a multiplexedin vitrodiagnostic test for the simultaneous, rapid (∼1-h) detection of 14 pathogens directly from CSF specimens:Escherichia coliK1,Haemophilus influenzae,Listeria monocytogenes,Neisseria meningitidis,Streptococcus pneumoniae,Streptococcus agalactiae, cytomegalovirus, enterovirus, herpes simplex virus 1 and 2, human herpesvirus 6, human parechovirus, varicella-zoster virus, andCryptococcus neoformans/Cryptococcus gattii. We describe a multicenter evaluation of 1,560 prospectively collected CSF specimens with performance compared to culture (bacterial analytes) and PCR (all other analytes). The FilmArray ME Panel demonstrated a sensitivity or positive percentage of agreement of 100% for 9 of 14 analytes. Enterovirus and human herpesvirus type 6 had agreements of 95.7% and 85.7%, andL. monocytogenesandN. meningitidiswere not observed in the study. ForS. agalactiae, there was a single false-positive and false-negative result each, for a sensitivity and specificity of 0 and 99.9%, respectively. The specificity or negative percentage of agreement was 99.2% or greater for all other analytes. The FilmArray ME Panel is a sensitive and specific test to aid in diagnosis of ME. With use of this comprehensive and rapid test, improved patient outcomes and antimicrobial stewardship are anticipated.
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Rameix-Welti, Marie-Anne, Maria Leticia Zarantonelli, Dario Giorgini, Corinne Ruckly, Monica Marasescu, Sylvie van der Werf, Jean-Michel Alonso, Nadia Naffakh, and Muhamed-Kheir Taha. "Influenza A Virus Neuraminidase Enhances Meningococcal Adhesion to Epithelial Cells through Interaction with Sialic Acid-Containing Meningococcal Capsules." Infection and Immunity 77, no. 9 (June 15, 2009): 3588–95. http://dx.doi.org/10.1128/iai.00155-09.
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ABSTRACT The underlying mechanisms of the epidemiological association between influenza virus infections and Neisseria meningitidis invasive infections are not fully understood. Here we report that adhesion of N. meningitidis to human Hec-1-B epithelial cells is enhanced by influenza A virus (IAV) infection. A potential role of the viral neuraminidase (NA) in facilitating meningococcal adhesion to influenza virus-infected epithelial cells was examined. Expression of a recombinant IAV NA in Hec-1-B human epithelial cells increased the adhesion of strains of N. meningitidis belonging to the sialic acid-containing capsular serogroups B, C, and W135 but not to the mannosamine phosphate-containing capsular serogroup A. Adhesion enhancement was not observed with an inactive NA mutant or in the presence of an NA inhibitor (zanamivir). Furthermore, purified IAV NA was shown to cleave sialic acid-containing capsular polysaccharides of N. meningitidis. On the whole, our findings suggest that a direct interaction between the NA of IAV and the capsule of N. meningitidis enhances bacterial adhesion to cultured epithelial cells, most likely through cleavage of capsular sialic acid-containing polysaccharides. A better understanding of the association between IAV and invasive meningococcal infections should help to set up improved control strategies against these seasonal dual viral-bacterial infections.
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Gorgievski-Hrisoho, Meri, Jean-Daniel Schumacher, Nevenka Vilimonovic, Daniel Germann, and Lukas Matter. "Detection by PCR of Enteroviruses in Cerebrospinal Fluid during a Summer Outbreak of Aseptic Meningitis in Switzerland." Journal of Clinical Microbiology 36, no. 9 (1998): 2408–12. http://dx.doi.org/10.1128/jcm.36.9.2408-2412.1998.
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Enteroviruses (EV) are among the most common causes of aseptic meningitis. Standard diagnostic techniques are often too slow and lack sensitivity to be of clinical relevance. EV RNA can be detected within 5 h by a commercially available reverse transcription-PCR (RT-PCR) test kit. Cerebrospinal fluid (CSF) samples from 68 patients presenting with aseptic meningitis during a summer outbreak in Switzerland were examined in parallel with cell culture and commercial RT-PCR. RT-PCR was positive in all 16 CSF specimens positive by cell culture (100%). In addition, 42 of 52 (80%) CSF samples negative by cell culture were PCR positive. In 26 of these 42 (62%) patients, viral culture from other sites (throat swab or stool) was also positive. The CSF virus culture took 3 to 7 days to become positive. Echovirus 30 was the type most often isolated in this outbreak. The sensitivity of CSF RT-PCR based on clinical diagnosis during this aseptic meningitis outbreak in patients with negative bacterial culture results was 85%, i.e., considerably higher than the sensitivity of CSF virus culture (24%). We conclude that this commercial RT-PCR assay allows a positive diagnosis with minimal delay and may thus influence clinical decisions.
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Rabin, Karen R., Johann Hitzler, Vilmarie Rodriguez, Reuven Schore, Anne Angiolillo, Michael J. Burke, Wanda Salzer, et al. "Treatment-Related Mortality (TRM) in Children with Down Syndrome (DS) and B-Lymphoblastic Leukemia (B-ALL): An Interim Report from the Children's Oncology Group Trials AALL0932 and AALL1131." Blood 126, no. 23 (December 3, 2015): 2502. http://dx.doi.org/10.1182/blood.v126.23.2502.2502.
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Abstract Background: Children with DS and B-ALL have historically experienced excessive TRM, primarily from infection. Here we provide an interim report on TRM in children with DS and newly diagnosed B-ALL enrolled on Children's Oncology Group (COG) trials for NCI standard risk (SR) (AALL0932) and high risk (HR) B-ALL (AALL1131). Methods: As of 06/30/2015, 203 SR DS-ALL patients have completed Induction on AALL0932 with 146 receiving post-Induction treatment on AALL0932. Eighty-eight HR DS patients have completed Induction on AALL1131, with 80 receiving post-Induction treatment on AALL1131. An additional 26 SR DS patients with poor early response received post-Induction therapy on AALL1131. Adverse events were graded according to NCI CTCAE v4.0, with enhanced data collection for targeted toxicities including infectious toxicities, and enhanced supportive care recommendations. Results: Patient characteristics are summarized in Table 1. TRM on AALL0932 occurred during Induction in 2/203 (1.0%) and post-Induction in 3/146 (2.1%), compared to 17/5528 (0.3%) and 12/3119 (0.4%) in non-DS SR patients (Fisher exact p=0.14 for Induction and p=0.03 for post-Induction). TRM on AALL1131 occurred during Induction in 4/88 (4.5%) and post-Induction in 5/106 (4.7%), compared to 34/2116 (1.6%) and 13/1258 (1.0%) in non-DS AALL1131 patients (p=0.06 for Induction and p=0.01 for post-Induction). Timing, cause, and other circumstances surrounding TRM are provided in Table 2. Gram-negative organisms accounted for the majority of fatal bacterial infections in patients with HR DS-ALL. Conclusion: TRM continues to be higher on current COG trials for patients with DS-ALL compared to non-DS patients. Most of the toxic deaths occur during intensive treatment phases due to infection in the context of profound neutropenia. Patients with HR B-ALL have a higher incidence of toxic death, notably in patients over 15 years of age. Based on our findings, hospitalization and antimicrobial prophylaxis during intensive treatment phases should be considered in children with DS-ALL due to their increased risk of infection-related mortality. Table 1. Patient Characteristics AALL1131 AALL0932 DS-ALL Non-DS ALL DS-ALL Non-DS ALL N 117 2689 207 5619 Median Age at Diagnosis (Years) 10.5 10.3 4.8 4.5 Gender Male 62 1511 117 2981 Female 55 1178 90 2637 Table 2. Treatment-Related Mortality Case Characteristics Case Age Gender Treatment Phase Site of Infection Organism AALL1131 (High Risk) 1 15 F Induction D#29 (RER) Pneumonia, ARDS HMPV (pre-treatment) 2 21 F Induction D#29 (SER) Sepsis 3 17 F Induction D#22 (SER) Sepsis, typhlitis Escherichia coli 4 12 M Induction D#16 (RER) Sepsis, pneumonia (+baseline CHD, AV canal s/p repair 2003) Influenza B 5 19 M Consolidation D#18 Sepsis Citrobacter 6 2 F Delayed Intensification D#101 ARDS/capillary leak (+baseline CHD) Rhinovirus 7 15 F Delayed Intensification D#45 Sepsis, pneumonia Klebsiella, enterovirus, rhinovirus 8 27 M Delayed Intensification D#52 Sepsis Gram negative bacillus 9 14 M Delayed Intensification D#22 Sepsis AALL0932 (Standard Risk) 1 7.3 M Induction Febrile neutropenia, hypotension, cardiorespiratory failure None reported 2 3.0 F Induction Febrile neutropenia, sepsis, liver failure Viridans group Strepococcus coagulase negative staphylococcus HSV, EBV and HHV 3 3.4 M Consolidation Meningitis, brainstem infarction None reported 4 9.7 F Interim Maintenance I Sepsis, Stevens Johnson syndrome/TEN None reported 5 7.2 M Interim Maintenance II Death NOS None reported RER, rapid early responder; SER, slow early responder; CHD, congenital heart disease; AV, atrioventricular; ARDS, acute respiratory distress syndrome; HMPV, human metapneumovirus; TEN, toxic epidermal necrolysis; HSV, herpes simplex virus; EBV, Epstein-Barr virus; HHV, human herpesvirus. Disclosures Hunger: Sigma Tau: Consultancy; Jazz Pharmaceuticals: Consultancy; Merck: Equity Ownership; Spectrum Pharmaceuticals: Consultancy.
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Zykova, Anna A., Elena A. Blokhina, Roman Y. Kotlyarov, Liudmila A. Stepanova, Liudmila M. Tsybalova, Victor V. Kuprianov, and Nikolai V. Ravin. "Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide." Viruses 12, no. 10 (October 6, 2020): 1133. http://dx.doi.org/10.3390/v12101133.
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The highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to induce an efficient immune response. In this study, we obtained recombinant mosaic proteins containing tandem copies of M2e fused to a lipopeptide from Neisseria meningitidis surface lipoprotein Ag473 and alpha-helical linkers and analyzed their immunogenicity. Six fusion proteins, comprising four or eight tandem copies of M2e flanked by alpha-helical linkers, lipopeptides, or a combination of both of these elements, were produced in Escherichia coli. The proteins, containing both alpha-helical linkers and lipopeptides at each side of M2e repeats, formed nanosized particles, but no particulate structures were observed in the absence of lipopeptides. Animal study results showed that proteins with lipopeptides induced strong M2e-specific antibody responses in the absence of external adjuvants compared to similar proteins without lipopeptides. Thus, the recombinant M2e-based proteins containing alpha-helical linkers and N. meningitidis lipopeptide sequences at the N- and C-termini of four or eight tandem copies of M2e peptide are promising vaccine candidates.
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Morales-Aza, Begonia, Sarah J. Glennie, Tomaz Pereira Garcez, Victoria Davenport, Sarah L. Johnston, Neil A. Williams, and Robert S. Heyderman. "Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency." Blood 113, no. 18 (April 30, 2009): 4206–12. http://dx.doi.org/10.1182/blood-2008-08-171587.
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AbstractThe importance of T cells in the generation of antigen-specific B-cell immunity has been extensively described, but the role B cells play in shaping T-cell memory is uncertain. In healthy controls, exposure to Neisseria meningitidis in the upper respiratory tract is associated with the generation of memory T cells in the mucosal and systemic compartments. However, we demonstrate that in B cell–deficient subjects with X-linked agammaglobulinemia (XLA), naturally acquired T-cell memory responses to meningococcal antigens are reduced compared with healthy control patients. This difference is not found in T-cell memory to an obligate respiratory pathogen, influenza virus. Accordingly, we show that meningococcal antigens up-regulate major histocompatibility complex (MHC) class II, CD40, CD86/80 expression on mucosal and systemic associated B cells and that antigen presentation stimulates T-cell proliferation. A similar reduction in N meningitidis but not influenza antigen–specific T-cell memory was observed in subjects with X-linked hyper IgM syndrome (X-HIM), implicating the interaction of CD40-CD40L in this process. Together, these data implicate B cells in the induction and maintenance of T-cell memory to mucosal colonizing bacteria such as N meningitidis and highlight the importance of B cells beyond antibody production but as a target for immune reconstitution.
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Friedland, Leonard. "Vaccination in Older Adults: The Who and What." Innovation in Aging 4, Supplement_1 (December 1, 2020): 806. http://dx.doi.org/10.1093/geroni/igaa057.2927.
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Abstract Aging brings increased impact of infectious disease in terms of hospitalization, morbidity, and mortality. This increased susceptibility to infection results from immunosenescence, age-related changes in the immune system, anatomic and functional changes, and environmental exposure to infections. Adults age 65 and over are at increased risk of pertussis, shingles, influenza and pneumococcal disease, and evidence-based recommendations for vaccination are protect older adults against these diseases. Underlying medical conditions including end stage renal disease, chronic lung, heart and liver disease, diabetes and immunocompromised place adults age 65 and over at increased risk of infectious diseases, therefore evidence-based vaccine recommendations in older adults with additional risk factors are in place to protect against varicella, hepatitis A and B, meningococcal meningitidis and Haemophilus influenzae type b. Investigational vaccines are developed to protect against infectious diseases causing significant morbidity and mortality in older adults, for example, respiratory syncytial virus, to further promote healthy aging. Part of a symposium sponsored by the Health Behavior Change Interest Group.
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Chioato, A., E. Noseda, M. Stevens, N. Gaitatzis, A. Kleinschmidt, and H. Picaud. "Treatment with the Interleukin-17A-Blocking Antibody Secukinumab Does Not Interfere with the Efficacy of Influenza and Meningococcal Vaccinations in Healthy Subjects: Results of an Open-Label, Parallel-Group, Randomized Single-Center Study." Clinical and Vaccine Immunology 19, no. 10 (August 8, 2012): 1597–602. http://dx.doi.org/10.1128/cvi.00386-12.
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ABSTRACTOur objective was to evaluate the efficacy of influenza and meningococcal vaccinations in healthy subjects exposed to the anti-interleukin-17A (IL-17A) monoclonal antibody (MAb) secukinumab. We used an open-label, parallel-group, randomized single-center study of 50 healthy subjects. Subjects received a single 150-mg dose of secukinumab or no treatment, followed by vaccination with inactivated trivalent subunit influenza virus and conjugate group C meningococcal vaccine (Agrippal and Menjugate, respectively) 2 weeks later. Primary efficacy variables were responses of ≥4-fold increases in antibody titer (hemagglutination inhibition [HI; for influenza virus] and serum bactericidal assay [SBA; forNeisseria meningitides]) for meningococcus and influenza (at least two out of three serotypes), both at 4 weeks postvaccination. All subjects randomized to secukinumab (n= 25) or the control (n= 25) completed the study. Antibody responses to vaccinations measured at 4 weeks were comparable in both groups, with ≥4-fold increased responses following influenza virus vaccination of 20/25 (80%) for both groups and following meningococcal vaccination of 19/25 (76%) for the secukinumab group and 18/25 (72%) for the control group. Differences between groups were 0% (90% confidence intervals [CI], 19 and 19%) and 4% (90% CI, 16 and 24%) for influenza virus and meningococcal vaccines, respectively. Antibody responses were comparable between the 2 groups at different time points. Headache was the most frequently reported adverse effect. No deaths or serious adverse events were reported. Blockade of IL-17A by secukinumab does not appear to interfere with efficacy of influenza and meningococcal vaccinations, as assessed by the achievement of protective antibody levels. A protective (≥4-fold) immune response to both vaccinations at 4 weeks was achieved in 80 and 76% of subjects exposed to secukinumab and the control, respectively.
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Gitman, Melissa R., Michael D. Nowak, Allison Navis, and Emilia Mia. Sordillo. "2169. An Algorithm-Based Approach Reduces Overuse of Meningitis/Encephalitis Multiplex PCR Panel." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S736. http://dx.doi.org/10.1093/ofid/ofz360.1849.
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Abstract Background Syndromic molecular panels enable rapid diagnosis and optimized management of infections with significant morbidity and mortality, but may be overused without clear guidelines. A recent report indicated there was little clinical suspicion of infection in up to 1/3 of cases for which a FILMARRAY® Meningitis/Encephalitis Panel (ME Panel, bioMérieux) was ordered. We recently implemented the ME Panel in our multicenter health system. We assessed ME Panel use for the 6-month period following test implementation. Methods A testing algorithm was developed, vetted with our system-wide Infectious Diseases (ID) and Neuro-ID Services, and used as the basis for the education of the Emergency Medicine, Internal Medicine, Hospitalist, Pediatric, and Critical Care Medicine Services. Algorithm elements were embedded in the electronic medical record (EMR). Lab records and EMRs were reviewed for all patients tested by ME Panel or cerebrospinal (CSF) culture. Lab results, baseline demographic and underlying medical history, and results of singleplex viral PCR CSF tests and the multiplex NY State Encephalitis PCR Panel (NYS Panel, Wadsworth Laboratory, Albany, NY) were recorded. ME Panel results were compared with other findings. Results 115 ME Panels were performed, with 5 (4%) positives [1 N.meningitidis, 1 H.influenzae, 1 cytomegalovirus (CMV), 1 Herpes simplex virus type 1 (HSV1), and 1 varicella zoster virus (VZV)]. Other findings were consistent with true infection for the N. meningitis, HSV and VZV; the CMV was likely reactivation. Significance of the H. influenzae was unclear. There were 830 CSF cultures, with 38 (4%) positive; 5 of the 38 were ME Panel targets. 29 NYS Panels were sent [1 positive each for Human Herpesvirus 6 (HHV6) and Epstein Barr Virus (EBV)]. Finally, 7 singleplex PCRs were positive [5 HSV, 1 CMV and 1 HHV6], including one negative by ME Panel. Conclusion We did not find ME Panel overuse; rather, we found several cases for which the ME Panel could have given a more rapid diagnosis. We did identify areas for improvement in test ordering, such as minimizing duplicate testing (e.g., singleplex PCR) A multi-disciplinary approach engaging stakeholders in the lab, ID and Neuro-ID can assist appropriate test utilization and diagnostic stewardship. Disclosures All authors: No reported disclosures.
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A.L. Sidelkovsky, P.A. Fedorov, V.V. Marusichenko, and M.R. Ignatischev. "Damage to the nervous system associated with HIV infection (a clinical case)." INTERNATIONAL NEUROLOGICAL JOURNAL 16, no. 8 (March 10, 2021): 53–56. http://dx.doi.org/10.22141/2224-0713.16.8.2020.221963.
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In Eastern Europe, at least 130 thousand new cases of HIV infection have been registered, which undoubtedly reflects the urgency of this medical problem. In our country, the average rate of human immunodeficiency infection is 58 cases per 100 thousand people. It is known that the disease is caused by an RNA-containing human immunodeficiency virus. Two types of it have been studied — HIV-1 and HIV-2, which have many subtypes. An important clinical feature of this virus is its tropism to cells of the human nervous and immune systems. The main risk group for the disease is injecting drug users, blood recipients, and people with low social responsibility. The impairment of the nervous system in AIDS is represented by the AIDS-dementia complex, acute aseptic meningitis, HIV-associated myelopathy, pathology of the peripheral nervous system, as well as the influence of opportunistic infections and neoplasms. This article presents a clinical case of lesions of the nervous system associated with HIV infection and also considers the etiology, pathogenesis, features of the course, diagnosis, and treatment of patients with neuro-AIDS.
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Nansen, Anneline, Jan Pravsgaard Christensen, Susanne Ørding Andreasen, Christina Bartholdy, Jeanette Erbo Christensen, and Allan Randrup Thomsen. "The role of CC chemokine receptor 5 in antiviral immunity." Blood 99, no. 4 (February 15, 2002): 1237–45. http://dx.doi.org/10.1182/blood.v99.4.1237.
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The CC chemokine receptor CCR5 is an important coreceptor for human immunodeficiency virus (HIV), and there is a major thrust to develop anti-CCR5–based therapies for HIV-1. However, it is not known whether CCR5 is critical for a normal antiviral T-cell response. This study investigated the immune response to lymphocytic choriomeningitis virus in mice lacking CCR5 (CCR5−/− mice). This infection is a classical model for studying antiviral immunity, and influx of CCR5-expressing CD8+ T cells and macrophages is essential for both virus control and associated immunopathology. Results showed that the virus-induced clonal expansion of antigen-specific T cells was augmented in CCR5−/− mice especially with regard to the CD4+ subset. Despite absence of CCR5, intracerebral infection invariably resulted in lethal T cell-mediated meningitis, and quantitative and qualitative analysis of the inflammatory exudate cells did not reveal any significant differences between gene-targeted mice and wild-type controls. CCR5 was also found to be redundant regarding the ability to eliminate virus from internal organs. Using delayed-type hypersensitivity to evaluate CD8+ T cell-mediated inflammation, no significant influence of CCR5 was found, not even when viral peptide was used as local trigger instead of live virus. Finally, long-term CD8+ T cell-mediated immune surveillance was efficiently sustained in CCR5−/− mice. Taken together, these results indicate that expression of CCR5 is not critical for T cell-mediated antiviral immunity, and this molecule may therefore constitute a logic and safe target for anti-HIV therapies.
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Evans, Jared D., and Christoph Seeger. "Differential Effects of Mutations in NS4B on West Nile Virus Replication and Inhibition of Interferon Signaling." Journal of Virology 81, no. 21 (August 22, 2007): 11809–16. http://dx.doi.org/10.1128/jvi.00791-07.
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ABSTRACT West Nile virus (WNV) is a human pathogen that can cause symptomatic infections associated with meningitis and encephalitis. Previously, we demonstrated that replication of WNV inhibits the interferon (IFN) signal transduction pathway by preventing the accumulation of phosphorylated Janus kinase 1 (JAK1) and tyrosine kinase 2 (Tyk2) (J. T. Guo et al., J. Virol. 79:1343-1350, 2005). Through a genetic analysis, we have now identified a determinant on the nonstructural protein 4B (NS4B) that controls IFN resistance in HeLa cells expressing subgenomic WNV replicons lacking the structural genes. However, in the context of infectious genomes, the same determinant did not influence IFN signaling. Thus, our results indicate that NS4B may be sufficient to inhibit the IFN response in replicon cells and suggest a role for structural genes, or as yet unknown interactions, in the inhibition of the IFN signaling pathway during WNV infections.
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Bartholdy, C., A. Nansen, J. Erbo Christensen, O. Marker, and A. Randrup Thomsen. "Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology." Journal of General Virology 80, no. 11 (November 1, 1999): 2997–3005. http://dx.doi.org/10.1099/0022-1317-80-11-2997.
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By using mice with a targetted disruption in the gene encoding inducible nitric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) in lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protective immunity and immunopathology. The afferent phase of the T cell-mediated immune response was found to be unaltered in iNOS-deficient mice compared with wild-type C57BL/6 mice, and LCMV- induced general immunosuppression was equally pronounced in both strains. In vivo analysis revealed identical kinetics of virus clearance, as well as unaltered clinical severity of systemic LCMV infection in both strains. Concerning the outcome of intracerebral infection, no significant differences were found between iNOS-deficient and wild-type mice in the number or composition of mononuclear cells found in the cerebrospinal fluid on day 6 post-infection. Likewise, NO did not influence the up-regulation of proinflammatory cytokine/chemokine genes significantly, nor did it influence the development of fatal meningitis. However, a reduced virus-specific delayed-type hypersensitivity reaction was observed in iNOS-deficient mice compared with both IFN-γ-deficient and wild-type mice. This might suggest a role of NO in regulating vascular reactivity in the context of T cell-mediated inflammation. In conclusion, these findings indicate a minimal role for iNOS/NO in the host response to LCMV. Except for a reduced local oedema in the knockout mice, iNOS/NO seems to be redundant in controlling both the afferent and efferent phases of the T cell-mediated immune response to LCMV infection.
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Almeida, Sérgio Monteiro de, Sônia Mara Raboni, Meri Bordignon Nogueira, and Luine R. Renaud Vidal. "Red blood cells in cerebrospinal fluid as possible inhibitory factor for enterovirus RT-PCR." Arquivos de Neuro-Psiquiatria 74, no. 10 (October 2016): 810–15. http://dx.doi.org/10.1590/0004-282x20160119.
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ABSTRACT The presence of hemoglobin in samples are considered an important inhibitory factor for polymerase chain reaction (PCR). The aim of this study was to examine the influence of red blood cells (RBC)s in cerebrospinal fluid (CSF) as an inhibitory factor to reverse transcription polymerase chain reaction (RT-PCR) for enteroviruses (EV). Forty-four CSF samples from patients showing characteristics of viral meningitis were assessed for EV by RT-PCR. Viral RNA extracted with guanidine isothyocianate buffer and virus detection was performed by in-house nested PCR. Positivity for EV RT-PCR was higher in CSF samples without RBCs than in samples with RBCs: 13(26%) and 36(9.2%), p = 0.001. In the group with positive EV RT-PCR, the mean + SD CSF RBC was 37 ± 183 cell/mm3; the group with negative results had 580 + 2,890 cell/mm3 (p = 0.007). The acceptable upper limit for CSF RBCs that could not influence RT-PCR was 108 cells/mm3. CSF samples with negative results for EV RT-PCR have more erythrocytes.
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Onyango, Clayton O., Vladimir Loparev, Shirley Lidechi, Vinod Bhullar, D. Scott Schmid, Kay Radford, Michael K. Lo, et al. "Evaluation of a TaqMan Array Card for Detection of Central Nervous System Infections." Journal of Clinical Microbiology 55, no. 7 (April 12, 2017): 2035–44. http://dx.doi.org/10.1128/jcm.02469-16.
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ABSTRACT Infections of the central nervous system (CNS) are often acute, with significant morbidity and mortality. Routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-Saharan Africa. We developed a TaqMan array card (TAC) that detects multiple pathogens simultaneously from cerebrospinal fluid. The 21-pathogen CNS multiple-pathogen TAC (CNS-TAC) assay includes two parasites ( Balamuthia mandrillaris and Acanthamoeba ), six bacterial pathogens ( Streptococcus pneumonia e, Haemophilus influenzae , Neisseria meningitidis , Mycoplasma pneumoniae , Mycobacterium tuberculosis , and Bartonella ), and 13 viruses (parechovirus, dengue virus, Nipah virus, varicella-zoster virus, mumps virus, measles virus, lyssavirus, herpes simplex viruses 1 and 2, Epstein-Barr virus, enterovirus, cytomegalovirus, and chikungunya virus). The card also includes human RNase P as a nucleic acid extraction control and an internal manufacturer control, GAPDH (glyceraldehyde-3-phosphate dehydrogenase). This CNS-TAC assay can test up to eight samples for all 21 agents within 2.5 h following nucleic acid extraction. The assay was validated for linearity, limit of detection, sensitivity, and specificity by using either live viruses (dengue, mumps, and measles viruses) or nucleic acid material (Nipah and chikungunya viruses). Of 120 samples tested by individual real-time PCR, 35 were positive for eight different targets, whereas the CNS-TAC assay detected 37 positive samples across nine different targets. The CNS-TAC assays showed 85.6% sensitivity and 96.7% specificity. Therefore, the CNS-TAC assay may be useful for outbreak investigation and surveillance of suspected neurological disease.
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Hemmila, Erin, Claire Turbide, Melanie Olson, Serge Jothy, Kathryn V. Holmes, and Nicole Beauchemin. "Ceacam1a−/− Mice Are Completely Resistant to Infection by Murine Coronavirus Mouse Hepatitis Virus A59." Journal of Virology 78, no. 18 (September 15, 2004): 10156–65. http://dx.doi.org/10.1128/jvi.78.18.10156-10165.2004.
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ABSTRACT CEACAM1a glycoproteins are members of the immunoglobulin (Ig) superfamily and the carcinoembryonic antigen family. Isoforms expressing either two or four alternatively spliced Ig-like domains in mice have been found in a number of epithelial, endothelial, or hematopoietic tissues. CEACAM1a functions as an intercellular adhesion molecule, an angiogenic factor, and a tumor cell growth inhibitor. Moreover, the mouse and human CEACAM1a proteins are targets of viral or bacterial pathogens, respectively, including the murine coronavirus mouse hepatitis virus (MHV), Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis, as well as Moraxella catarrhalis in humans. We have shown that targeted disruption of the Ceacam1a (MHVR) gene resulting in a partial ablation of the protein in mice (p/p mice) led to reduced susceptibility to MHV-A59 infection of the modified mice in the BALB/c background. We have now engineered and produced a Ceacam1a −/− mouse that exhibits complete ablation of the CEACAM1a protein in every tissue where it is normally expressed. We report that 3-week-old Ceacam1a −/− mice in the C57BL/6 genetic background are fully resistant to MHV-A59 infection by both intranasal and intracerebral routes. Whereas virus-inoculated wild-type +/+ C57BL/6 mice showed profound liver damage and spinal cord demyelination under these conditions, Ceacam1a −/− mice displayed normal livers and spinal cords. Virus was recovered from liver and spinal cord tissues of +/+ mice but not of −/− mice. These results indicate that CEACAM1a is the sole receptor for MHV-A59 in both liver and brain and that its deletion from the mouse renders the mouse completely resistant to infection by this virus.
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Nansera, Denis, Irama Max, Kisakye Annet, and Bradford D. Gessner. "Bacterial meningitis among children under the age of 2 years in a high human immunodeficiency virus prevalence area after Haemophilus influenzae type b vaccine introduction." Journal of Paediatrics and Child Health 48, no. 4 (November 14, 2011): 324–28. http://dx.doi.org/10.1111/j.1440-1754.2011.02235.x.
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Upadhyayula, Shankar. "1823. Incidence of Meningoencephalitis in the Absence of CSF Pleocytosis." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S39. http://dx.doi.org/10.1093/ofid/ofz359.085.
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Abstract Background Cerebrospinal fluid (CSF) pleocytosis, defined here as ≥5 white blood cells (WBC)/high power field (HPF) suggests inflammation of brain parenchyma /meninges or both. However, the absence of pleocytosis does not rule out meningoencephalitis. The frequency with which infectious targets are identified in the absence of CSF pleocytosis is not well known. Traditional diagnostic methods based on culture and single target polymerase chain reaction (PCR) assay were inadequate to answer this question. However, the availability of multiplex (PCR) panels opens up the opportunity. Methods Starting June of 2016 Akron children’s hospital adopted the Biofire® Meningitis encephalitis panel (MEP). The panel is run routinely on all CSF specimens obtained from patients presenting with a clinical picture consistent with meningoencephalitis irrespective of their CSF biochemistry and cell count Results. We retrospectively collected laboratory data for all the MEP positive patients. The data were filtered based on CSF WBC count, pathogens identified as well as by patient age. Results A total of 133 positive results were identified from June 2016 to March 2019. Due to unclear significance, 22 positive Human herpes virus (HHV) 6 results were excluded, One VZV positive result was also excluded (Figure 1). Of the remaining 110 positives, 29% had CSF WBC count < 5/HPF. Parecho and Enterovirus were the most common. Three isolates were positive for Herpes simplex 1 (HSV 1) and one for Herpes simplex 2 (HSV 2). Haemophilus influenzae was detected in one patient (Figure 2). Conclusion Our observations suggest that viral meningoencephalitis may occur frequently in the absence of CSF pleocytosis. Bacterial meningitis seems less likely. Several centers have a policy to restrict multiplex PCR panel testing based on CSF WBC cut-offs, citing increased costs. However, this approach may lead to missed diagnosis. As a direct result of this additional investigations and/or treatment may be pursued leading to increased overall costs as well as exposing the patient to potential harm. Additionally making a diagnosis could lend itself to monitoring outcomes—an area where there is paucity of high-quality data. Disclosures All Authors: No reported Disclosures.
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Schmitt, Heinz-J., Gudrun Maechler, Pirmin Habermehl, Markus Knuf, Roland Saenger, Norman Begg, and Dominique Boutriau. "Immunogenicity, Reactogenicity, and Immune Memory after Primary Vaccination with a Novel Haemophilus influenzae-Neisseria meningitidis Serogroup C Conjugate Vaccine." Clinical and Vaccine Immunology 14, no. 4 (February 7, 2007): 426–34. http://dx.doi.org/10.1128/cvi.00377-06.
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ABSTRACT We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov ]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM197 plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (≥1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (≥0.15 μg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules.
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Zelano, Johan, and Gabriel Westman. "Epilepsy after brain infection in adults." Neurology 95, no. 24 (September 28, 2020): e3213-e3220. http://dx.doi.org/10.1212/wnl.0000000000010954.
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ObjectiveTo describe risk and risk factors of epilepsy after hospitalization for brain infection in adults in Sweden.MethodsThis was a matched retrospective cohort study based on the comprehensive National Patient and Cause of Death Registers. All individuals age >18 without prior epilepsy who received inpatient care in 2000–2010 for a brain infection were included, with 3 age- and sex-matched unexposed controls per exposed individual (n = 12,101 exposed and 36,228 controls). Kaplan-Meier risks of epilepsy after different brain infections were calculated and risk factors identified by Cox regression. Patients were followed until the end of 2017.ResultsThe 10-year risk of epilepsy was 5.9% (95% confidence interval [CI] 5.5–6.3) in cases and 1.2% (95% CI 1.0–1.4) in controls: 1.7% (95% CI 0.7–2.7) after tick-borne encephalitis, 4.1% (95% CI 3.3–4.9) after bacterial meningitis, 26.0% (95% CI 21.5–30.5) after herpes simplex virus encephalitis, and 30.2% (95% CI 27.1–33.3) after brain abscess. In Cox regression, seizure during the index admission and mechanical ventilation were epilepsy risk factors.ConclusionsEpilepsy is common after several types of brain infections in adults. The type of infection, its severity, and propensity to cause seizures in the acute phase influence the risk of subsequent epilepsy.Classification of evidenceThis study provides Class II evidence that in adults, brain infection is associated with an increased risk of subsequent epilepsy.
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Lee, C. K., K. Kono, E. Haas, K. S. Kim, K. M. Drescher, N. M. Chapman, and S. Tracy. "Characterization of an infectious cDNA copy of the genome of a naturally occurring, avirulent coxsackievirus B3 clinical isolate." Journal of General Virology 86, no. 1 (January 1, 2005): 197–210. http://dx.doi.org/10.1099/vir.0.80424-0.
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Group B coxsackieviruses (CVB) cause numerous diseases, including myocarditis, pancreatitis, aseptic meningitis and possibly type 1 diabetes. To date, infectious cDNA copies of CVB type 3 (CVB3) genomes have all been derived from pathogenic virus strains. An infectious cDNA copy of the well-characterized, non-pathogenic CVB3 strain GA genome was cloned in order to facilitate mapping of the CVB genes that influence expression of a virulence phenotype. Comparison of the sequence of the parental CVB3/GA population, derived by direct RT-PCR-mediated sequence analysis, to that of the infectious CVB3/GA progeny genome demonstrated that an authentic copy was cloned; numerous differences were observed in coding and non-coding sequences relative to other CVB3 strains. Progeny CVB3/GA replicated similarly to the parental strain in three different cell cultures and was avirulent when inoculated into mice, causing neither pancreatitis nor myocarditis. Inoculation of mice with CVB3/GA protected mice completely against myocarditis and pancreatitis induced by cardiovirulent CVB3 challenge. The secondary structure predicted for the CVB3/GA domain II, a region within the 5′ non-translated region that is implicated as a key site affecting the expression of a cardiovirulent phenotype, differs from those predicted for cardiovirulent and pancreovirulent CVB3 strains. This is the first report characterizing a cloned CVB3 genome from an avirulent strain.
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Blau, Dianna M., Claire Turbide, Michel Tremblay, Melanie Olson, Stéphanie Létourneau, Eva Michaliszyn, Serge Jothy, Kathryn V. Holmes, and Nicole Beauchemin. "Targeted Disruption of the Ceacam1(MHVR) Gene Leads to Reduced Susceptibility of Mice to Mouse Hepatitis Virus Infection." Journal of Virology 75, no. 17 (September 1, 2001): 8173–86. http://dx.doi.org/10.1128/jvi.75.17.8173-8186.2001.
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ABSTRACT The CEACAM1 glycoproteins (formerly called biliary glycoproteins; BGP, C-CAM, CD66a, or MHVR) are members of the carcinoembryonic antigen family of cell adhesion molecules. In the mouse, splice variants of CEACAM1 have either two or four immunoglobulin (Ig) domains linked through a transmembrane domain to either a short or a long cytoplasmic tail. CEACAM1 has cell adhesion activity and acts as a signaling molecule, and long-tail isoforms inhibit the growth of colon and prostate tumor cells in rodents. CEACAM1 isoforms serve as receptors for several viral and bacterial pathogens, including the murine coronavirus mouse hepatitis virus (MHV) and Haemophilus influenzae, Neisseria gonorrhoeae, andNeisseria meningitidis in humans. To elucidate the mechanisms responsible for the many biological activities of CEACAM1, we modified the expression of the mouse Ceacam1 gene in vivo. Manipulation of the Ceacam1 gene in mouse embryonic stem cells that contained the Ceacam1a allele yielded a partial knockout. We obtained one line of mice in which the insert in the Ceacam1a gene had sustained a recombination event. This resulted in the markedly reduced expression of the two CEACAM1a isoforms with four Ig domains, whereas the expression of the two isoforms with two Ig domains was doubled relative to that in wild-type BALB/c (+/+) mice. Homozygous (p/p)Ceacam1a-targeted mice (Ceacam1aΔ4D) had no gross tissue abnormalities and were viable and fertile; however, they were more resistant to MHV A59 infection and death than normal (+/+) mice. Following intranasal inoculation with MHV A59, p/p mice developed markedly fewer and smaller lesions in the liver than +/+ or heterozygous (+/p) mice. The titers of virus produced in the livers were 50- to 100-fold lower in p/p mice than in +/p or +/+ mice. p/p mice survived a dose 100-fold higher than the lethal dose of virus for +/+ mice. +/p mice were intermediate between +/+ and p/p mice in susceptibility to liver damage, virus growth in liver, and susceptibility to killing by MHV. Ceacam1a-targeted mice provide a new model to study the effects of modulation of receptor expression on susceptibility to MHV infection in vivo.
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Contreras-Yametti, Gloria, Custodio Haidee, and Hamayun Imran. "Prevalence of Severe Bacterial Infection in Febrile Children with Sickle CELL Disease in the Era of Pneumococcal Conjugate Vaccine 13." Blood 132, Supplement 1 (November 29, 2018): 3665. http://dx.doi.org/10.1182/blood-2018-99-111362.
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Abstract Introduction The incidence of invasive pneumococcal infections in patients with sickle cell disease (SCD) decreased after introduction of penicillin prophylaxis and pneumococcal conjugate vaccine (PCV). However, the decrease in pneumococcal infections alone may not necessarily mean an overall decrease in severe bacterial infections (SBI). In a previous publication, we reported a 0.4 % prevalence of pneumococcal bacteremia following introduction of PCV 13. In the current study, we aimed to define the prevalence of SBI and hospitalization in febrile patients in the same cohort in the later years. Methods We performed a retrospective study of patients with SCD <18 years old presenting with fever to University of South Alabama Children's and Women's Hospital from January 2014 to June 2017. SBI was defined as: bacteremia, pneumonia, pyelonephritis, meningitis, osteomyelitis and abscess (superficial and deep). Univariate analysis and multivariate logistic regression were used to determine factors associated with patient disposition as well as presence of SBI. Results There were 258 febrile events in 120 patients resulting in 187 (72%) admissions (figure 1). SBI was seen in 12% of admissions with uncomplicated community acquired pneumonia being the most common. The prevalence of bacteremia was 1.6% with single cases of pneumococcus, E. coli, and H. influenzae bacteremia. Younger age, high fever, and splenectomy were associated with hospitalization (p<0.05). However, only C reactive protein was associated with SBI (p<0.02). Viral infection was diagnosed in 80% of outpatients but 87% were given antibiotics. Among inpatients, all received parenteral antibiotics, and 67% were assessed to have viral illness, although only 23% had a virus identified. Pneumococcal vaccination status was satisfactory in 77% of our sample while compliance rate with penicillin prophylaxis was >85% in both inpatient and outpatient groups. Conclusion Although majority of febrile events were due to viral infections, 3 of four febrile episodes in our cohort resulted in hospitalization. A small proportion of patients had SBI and a much smaller proportion had bacteremia. These findings support early virus identification which can have implications on patient discharge disposition and antibiotic use. Further studies looking at risk stratification of febrile patients with SCD are needed to encourage outpatient management without compromising safety. Figure 1. Figure 1. Disclosures Imran: Novo Nordask: Speakers Bureau.
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Begum, N., MA Salam, MI Rahman, L. Akter, SM Asafudullah, I. Mahmood, and I. Ahmed. "Etiological Agents of Acute Meningo-Encephalitis Syndrome: Study of 75 Cases in Rajshahi Medical College Hospital." TAJ: Journal of Teachers Association 22, no. 2 (December 1, 2009): 216–22. http://dx.doi.org/10.3329/taj.v22i2.37727.
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Acute meningoencephalitis syndrome (AMES) is a life threatening condition of all ages caused by different microbial agents. Etiological diagnosis is imperative for introduction of appropriate antimicrobial agents to treat the condition. This cross sectional prospective study included seventy five (75) clinically suspected patients of AMES of different age and sex groups, who were admitted at Rajshahi Medical College Hospital (RMCH) during August, 2005 to Jun e, 2006. Cerebra spinal fluid (CSF) was studied by Gram-stained smear examination, bacterial culture, latex agglutination test (LAT), cytological and biochemical tests. The serum samples were also tested for qualitative C - reactive protein (CRP} by latex agglutination test and lgM anti body against Japanese Encephalitis (JE} virus by Enzyme-linked immunosorbent assay (ELISA). Direct microscopy on Gram-stained smears of CSF was found positive for 10 (13.33%) cases while bacterial culture was positive in 17(22.66%) cases. Culture yielded H. influenzae, S. pneumoniae N. meningitidis and Esch. coli in 07 (41.17%), 05 (29.41%), 04 (23.53%) and 01(5.88%) cases respectively. Higher rate of isolation was noted among 0-5 years age group. Out of 75 CSF samples, LAT could be done for randomly selected 45 cases with positive results observed in 18 (40%) cases. Good correlation of increase total white cell count and protein level and decrease glucose level was observed among culture-positive cases in cytological and biochemical analysis of CSF. Serum CRP was found positive in 21 (28.00%) cases and it had also excellent (94.11%) correlation with culture-positive cases. Among 75 patients, whose CSF samples were found apparently clear on physical examination, 40 of them were tested for serum lgM antibodies against JE virus with 4 (10%) cases as JE-positive in ELISA. All bacterial isolates were 100% sensitive to ceftriaxone and ciprofloxacin except S. pneumoniae which showed 80% sensitivity to ciprofloxacin in antimicrobial susceptibility testing. Variable sensitivity pattern was noted against penicillin, ampicillin, cotrimoxazole, gentamycin and erythromycin. This limited study has revealed that clinically suspected cases of AMES can have varying etiology with JE virus is an important cause detected among patients admitted in RMCH and Ceftriaxone is the drug of choice for bacterial meningitis.TAJ 2009; 22(1): 216-222
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Greenwood, Brian. "The epidemiology of pneumococcal infection in children in the developing world." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354, no. 1384 (April 29, 1999): 777–85. http://dx.doi.org/10.1098/rstb.1999.0430.
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Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100 000–500 000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio–economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing counties. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide–protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.
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Cassone, Antonio, and Rino Rappuoli. "Universal Vaccines: Shifting to One for Many." mBio 1, no. 1 (May 18, 2010). http://dx.doi.org/10.1128/mbio.00042-10.
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ABSTRACT Human vaccines, with their exquisite antigenic specificity, have greatly helped to eliminate or dramatically abate the incidence of a number of historical and current plagues, from smallpox to bacterial meningitis. Nonetheless, as new infectious agents emerge and the number of vaccine-preventable diseases increases, the practice and benefits of single-pathogen- or disease-targeted vaccination may be put at risk by constraints of timely production, formulation complexity, and regulatory hurdles. During the last influenza pandemic, extraordinary efforts by vaccine producers and health authorities have had little or no influence on disease prevention or mitigation. Recent research demonstrating the possibility of protecting against all influenza A virus types or even phylogenetically distant pathogens with vaccines based on highly conserved peptide or saccharide sequences is changing our paradigm. “Universal vaccine” strategies could be particularly advantageous to address protection from antibiotic-resistant bacteria and fungi for which no vaccine is currently available.
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Escribano-Romero, Estela, Nereida Jiménez de Oya, Esteban Domingo, and Juan Carlos Saiz. "Extinction of West Nile Virus by Favipiravir through Lethal Mutagenesis." Antimicrobial Agents and Chemotherapy 61, no. 11 (August 28, 2017). http://dx.doi.org/10.1128/aac.01400-17.
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ABSTRACT Favipiravir is an antiviral agent effective against several RNA viruses. The drug has been shown to protect mice against experimental infection with a lethal dose of West Nile virus (WNV), a mosquito-borne flavivirus responsible for outbreaks of meningitis and encephalitis for which no antiviral therapy has been licensed; however, the mechanism of action of the drug is still not well understood. Here, we describe the potent in vitro antiviral activity of favipiravir against WNV, showing that it decreases virus-specific infectivity and drives the virus to extinction. Two passages of WNV in the presence of 1 mM favipiravir—a concentration that is more than 10-fold lower than its 50% cytotoxic concentration (CC50)—resulted in a significant increase in mutation frequency in the mutant spectrum and in a bias toward A→G and G→A transitions relative to the population passaged in the absence of the drug. These data, together with the fact that the drug is already licensed in Japan against influenza virus and in a clinical trial against Ebola virus, point to favipiravir as a promising antiviral agent to fight medically relevant flaviviral infections, such as that caused by WNV.
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McEntire, Caleb R. S., Kun-Wei Song, Robert P. McInnis, John Y. Rhee, Michael Young, Erika Williams, Leah L. Wibecan, et al. "Neurologic Manifestations of the World Health Organization's List of Pandemic and Epidemic Diseases." Frontiers in Neurology 12 (February 22, 2021). http://dx.doi.org/10.3389/fneur.2021.634827.
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The World Health Organization (WHO) monitors the spread of diseases globally and maintains a list of diseases with epidemic or pandemic potential. Currently listed diseases include Chikungunya, cholera, Crimean-Congo hemorrhagic fever, Ebola virus disease, Hendra virus infection, influenza, Lassa fever, Marburg virus disease, Neisseria meningitis, MERS-CoV, monkeypox, Nipah virus infection, novel coronavirus (COVID-19), plague, Rift Valley fever, SARS, smallpox, tularemia, yellow fever, and Zika virus disease. The associated pathogens are increasingly important on the global stage. The majority of these diseases have neurological manifestations. Those with less frequent neurological manifestations may also have important consequences. This is highlighted now in particular through the ongoing COVID-19 pandemic and reinforces that pathogens with the potential to spread rapidly and widely, in spite of concerted global efforts, may affect the nervous system. We searched the scientific literature, dating from 1934 to August 2020, to compile data on the cause, epidemiology, clinical presentation, neuroimaging features, and treatment of each of the diseases of epidemic or pandemic potential as viewed through a neurologist's lens. We included articles with an abstract or full text in English in this topical and scoping review. Diseases with epidemic and pandemic potential can be spread directly from human to human, animal to human, via mosquitoes or other insects, or via environmental contamination. Manifestations include central neurologic conditions (meningitis, encephalitis, intraparenchymal hemorrhage, seizures), peripheral and cranial nerve syndromes (sensory neuropathy, sensorineural hearing loss, ophthalmoplegia), post-infectious syndromes (acute inflammatory polyneuropathy), and congenital syndromes (fetal microcephaly), among others. Some diseases have not been well-characterized from a neurological standpoint, but all have at least scattered case reports of neurological features. Some of the diseases have curative treatments available while in other cases, supportive care remains the only management option. Regardless of the pathogen, prompt, and aggressive measures to control the spread of these agents are the most important factors in lowering the overall morbidity and mortality they can cause.
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Bernardes, Bruno Gaia, and Marcelo Lancellotti. "Análise do efeito das nanopartículas de sílica mesoporosa SBA-15 e SBA-16 na detecção de Neisseria meningitidis e Haemophilus influenzae biotipo aegyptius por qPCR." Revista dos Trabalhos de Iniciação Científica da UNICAMP, no. 26 (December 12, 2018). http://dx.doi.org/10.20396/revpibic262018237.
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Ambos os patógenos são de grande importância para a epidemiologia global atualmente, uma vez que as meningites bacterianas são as causadoras de dezenas de milhares de mortes anualmente, sendo uma das bactérias causadoras de meningite a Neisseria meningitidis e a infecção de gestantes pelo Zika Virus (ZIKV) está relacionado com o nascimento de crianças com microcefalia (OMS, 2016), assim como possui relação com a síndrome de Guillain-Barré, bem como a possibilidade de infecção por troca de fluídos, como a amamentação, por exemplo.
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Jia, Xiaofang, Lvyin Hu, Min Wu, Yun Ling, Wei Wang, Hongzhou Lu, Zhenghong Yuan, Zhigang Yi, and Xiaonan Zhang. "A streamlined clinical metagenomic sequencing protocol for rapid pathogen identification." Scientific Reports 11, no. 1 (February 23, 2021). http://dx.doi.org/10.1038/s41598-021-83812-x.
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AbstractMetagenomic next-generation sequencing (mNGS) holds promise as a diagnostic tool for unbiased pathogen identification and precision medicine. However, its medical utility depends largely on assay simplicity and reproducibility. In the current study, we aimed to develop a streamlined Illumina and Oxford Nanopore-based DNA/RNA library preparation protocol and rapid data analysis pipeline. The Illumina sequencing-based mNGS method was first developed and evaluated using a set of samples with known aetiology. Its sensitivity for RNA viruses (influenza A, H1N1) was < 6.4 × 102 EID50/mL, and a good correlation between viral loads and mapped reads was observed. Then, the rapid turnaround time of Nanopore sequencing was tested by sequencing influenza A virus and adenoviruses. Furthermore, 11 respiratory swabs or sputum samples pre-tested for a panel of pathogens were analysed, and the pathogens identified by Illumina sequencing showed 81.8% concordance with qPCR results. Additional sequencing of cerebrospinal fluid (CSF) samples from HIV-1-positive patients with meningitis/encephalitis detected HIV-1 RNA and Toxoplasma gondii sequences. In conclusion, we have developed a simplified protocol that realizes efficient metagenomic sequencing of a variety of clinical samples and pathogen identification in a clinically meaningful time frame.
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Mantay, Kristi, Elin Armeau, and Thomas Parish. "Recognizing Guillain-Barré Syndrome in the Primary Care Setting." Internet Journal of Allied Health Sciences and Practice, 2007. http://dx.doi.org/10.46743/1540-580x/2007.1133.
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Purpose: Guillain-Barré Syndrome (GBS) is the most common cause of acute flaccid paralysis in adults and children in the United States. The purpose of this article is to educate Primary Care Practitioners (PCP) about GBS and the importance of its recognition in the acute care setting. Method: A review of literature examined epidemiology, pathophysiology, clinical features, and antecedent events related to primary care. Results: Studies show correlations between GBS and preceding viral-bacterial infections, and certain vaccines. However, a direct causation has not been proven. Antecedent events encountered in primary care include, but are not limited to, gastroenteritis, upper respiratory infection, cytomegalovirus, Epstein-Barr virus, and vaccinations against influenza, meningitis, and tetanus toxoid.Conclusion: PCPs should be able to recognize GBS and its triggers should a case present to their clinics. It is hoped that GBS mortality and sequela would be decreased if PCPs are more knowledgeable about this condition.
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Ruschil, Christoph, Gisela Gabernet, Gildas Lepennetier, Simon Heumos, Miriam Kaminski, Zsuzsanna Hracsko, Martin Irmler, et al. "Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses." Frontiers in Immunology 11 (December 18, 2020). http://dx.doi.org/10.3389/fimmu.2020.606338.
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Double negative (DN) (CD19+CD20lowCD27-IgD-) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barré syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with naïve B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway.
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Zbrzeźniak, Jakub, and Iwona Paradowska-Stankiewicz. "Meningitis and encephalitis in Poland in 2018." Przeglad Epidemiologiczny, 2021, 63–75. http://dx.doi.org/10.32394/pe.75.07.
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INTRODUCTION. Infectious diseases of the nervous system are most often manifested in the form of meningitis. We distinguish meningitis and/or encephalitis according to their etiology, i.e. bacterial and viral. The study discusses meningitis and encephalitis caused by: N. meningitidis, S. pneumoniae, H. influenzae and tick-borne encephalitis virus. This is due to the epidemiological surveillance of these diseases and the available prevention in the form of vaccinations against these diseases. AIM OF THE STUDY. The aim of the study is to assess the epidemiological situation of meningitis and encephalitis in Poland in 2018. MATERIAL AND METHODS. The epidemiological situation of meningitis and encephalitis in Poland was assessed on data from the annual bulletin “Infectious diseases and poisoning in Poland in 2018” and “Vaccinations in Poland in 2018”. RESULTS. In 2018, a total of 2406 cases of meningitis and/or encephalitis were registered in Poland. It is a 14.7% increase in incidence compared to 2017. An increase was recorded in the viral infections from 1212 to 1533 cases. In contrast, the number of infections with bacterial etiology decreased from 886 to 873 cases. Meningitis and/or encephalitis caused by pathogens specified in epidemiological surveillance have noticed a decreased incidence. The only exception is the increase in cases caused by S. pneumoniae, compared to 2017, from 177 to 212. This is an increase of 19.8% compared to the previous year. However, the number of cases of N. meningitidis showed a decrease of 16.4% during this period. Viral infections constituted 63.7% of all cases. Compared to 2017, it means an increase in the percentage of viral infections by 5.9 percentage points. Among laboratory confirmed cases of meningitis and/or encephalitis of known etiology, cases caused by Neisseria meningitidis (102 cases), Streptococcus pneumoniae (212 cases) and tick-borne encephalitis (197 cases) were predominant. SUMMARY AND CONCLUSION. There is a general increasing trend in the number of cases of viral meningitis and/or encephalitis. On the other hand, thanks to vaccinations, no significant increase was noted in H. influenzae, meningococcal and TBE infections. There is a chance to minimize the incidence of bacterial meningitis and/or encephalitis as in the H. influenzae infections. On the other hand, it should be seen that the problem of diagnosing cases of viral etiology should be considered. This is more related to the determination of the etiological factor than the diagnosis of viral meningitis and/or encephalitis. Difficulties in determining the etiological factor indicate that, meningitis and/or encephalitis remain a challenge for healthcare and epidemiological surveillance institutions.
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"Meningitis and encephalitis in Poland in 2017." Przeglad Epidemiologiczny, 2019, 417–27. http://dx.doi.org/10.32394/pe.73.39.
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ABSTRACT INTRODUCTION. Meningitis are the most common form of the nervous system infectious diseases. There are meningitis and/or encephalitis with bacterial and viral etiology. In epidemiological surveillance are highlighted meningitis and/or encephalitis caused by N. meningitidis, S. pneumoniae, H. influenzae and tick-borne encephalitis virus. Because vaccinations against these agents are common. AIM OF THE STUDY. The aim of the study is to assess the epidemiological situation of meningitis and encephalitis in Poland in 2017. MATERIAL AND METHODS. The epidemiological situation of meningitis and encephalitis in Poland was assessed on data from the annual bulletin “Infectious diseases and poisoning in Poland in 2017” and “Vaccinations in Poland in 2017”. (MP Czarkowski et al., Warsaw 2018, NIZP-PZH, GIS). RESULTS. In 2017 were registered 2 095 cases of meningitis and/or encephalitis in Poland. It means a 10.8% decrease in meningitis and/or encephalitis in Poland compared to 2016. With a general decrease in the number of infections of bacterial etiology, the number of cases of meningitis and/or encephalitis of S. pneumoniae, H. influenzae type B cases reported remains at the same level similar to last year. In contrast, the number of cases of etiology of N. meningitidis shows an increase of 25.4% compared to the previous year. Among all cases 57.9% were viral infections. In comparison to 2016 means a decrease in the percentage share of viral infections by 1.2 percentage points for bacterial infections. Among laboratory confirmed cases of neuroinfection with established etiology, the incidence caused by Neisseria miningitidis (122 cases), Streptococcus pneumoniae (171 cases) and tick-borne encephalitis (283 cases) are the most prevalent. SUMMARY AND CONCLUSION. There is a general downward trend in the number of meningitis and/or encephalitis cases, which may be due to introducing mandatory vaccination against S. pneumoniae. It can also mean an improvement in diagnostics given the decrease in unspecified meningitis and/or encephalitis. However meningitis and/or encephalitis remain a challenge for healthcare and epidemiological surveillance institutions.
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Manasatienkij, Wudtichai, Piyawan Chinnawirotpisan, Weerayuth Kittichotirat, Sriluck Simasathien, Louis R. Macareo, Damon W. Ellison, Supapon Cheevadhanarak, Wiriya Rutvisuttinunt, Stefan Fernandez, and Chonticha Klungthong. "Nuclease pre-treatment increases efficiency of whole genome sequencing of Influenza B virus in respiratory specimens." Asia Pacific Journal of Molecular Biology and Biotechnology, January 21, 2020, 1–13. http://dx.doi.org/10.35118/apjmbb.2020.028.1.01.
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The use of next generation sequencing (NGS) directly on respiratory specimens to obtain viral whole genome sequence (WGS) enhances the capability for rapid and unbiased viral characterization. One of the challenges of using NGS directly in influenza-like illness (ILI) respiratory specimens is the higher proportion of host and bacterial genome compared to viral genetic materials found, which reduces the likelihood of obtaining complete viral genome sequences. This study aims to evaluate nuclease pretreatments prior to sequencing of influenza B virus directly from ILI respiratory specimens. Sequence data were mapped to human, bacteria and influenza B viral genome. In the absence of any nuclease pretreatments, the sequence reads identified as Haemophilus influenzae, Haemophilus parainfluenzae, Neisseria meningitidis and Veillonella parvula were the most prominent genetic materials in respiratory specimens. Filtration followed by nuclease treatment reduced bacterial sequence reads by at least 70 folds in all 4 tested samples, supporting the direct application of NGS in ILI respiratory specimens. Although the pretreatment methods significantly reduced human genome sequences, the remaining human genome especially human rRNA still impact the number and proportion of the viral sequence reads.
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Oladele, Rita O., Alani S. Akanmu, Augustina O. Nwosu, Folasade T. Ogunsola, Malcolm D. Richardson, and David W. Denning. "Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence." Open Forum Infectious Diseases 3, no. 2 (2016). http://dx.doi.org/10.1093/ofid/ofw055.
Full textAbstract:
Abstract Background. Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. Sera were collected from 214 consenting HIV-infected participants with CD4+ counts <250 cells/mm3, irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results. Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4+ cell count was 160 cells/mm3 (interquartile range, 90–210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4+ cell counts <100 cells/mm3, 4 of 80 (5.0%) in the 100–200 group, and 9 of 73 (12.3%) in 200–250 cells/mm3 group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm3, which was unrelated to CrAg positivity (P = .018). Conclusions. We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend CrAg screening for HIV-infected patients, even for patients on ART.