Detection of African swine fever, classical swine fever, and foot-and-mouth disease viruses in swine oral fluids by multiplex reverse transcription real-time polymerase chain reaction.

PubMed

Grau, Frederic R; Schroeder, Megan E; Mulhern, Erin L; McIntosh, Michael T; Bounpheng, Mangkey A

2015-03-01

African swine fever (ASF), classical swine fever (CSF), and foot-and-mouth disease (FMD) are highly contagious animal diseases of significant economic importance. Pigs infected with ASF and CSF viruses (ASFV and CSFV) develop clinical signs that may be indistinguishable from other diseases. Likewise, various causes of vesicular disease can mimic clinical signs caused by the FMD virus (FMDV). Early detection is critical to limiting the impact and spread of these disease outbreaks, and the ability to perform herd-level surveillance for all 3 diseases rapidly and cost effectively using a single diagnostic sample and test is highly desirable. This study assessed the feasibility of simultaneous ASFV, CSFV, and FMDV detection by multiplex reverse transcription real-time polymerase chain reaction (mRT-qPCR) in swine oral fluids collected through the use of chewing ropes. Animal groups were experimentally infected independently with each virus, observed for clinical signs, and oral fluids collected and tested throughout the course of infection. All animal groups chewed on the ropes readily before and after onset of clinical signs and before onset of lameness or serious clinical signs. ASFV was detected as early as 3 days postinoculation (dpi), 2-3 days before onset of clinical disease; CSFV was detected at 5 dpi, coincident with onset of clinical disease; and FMDV was detected as early as 1 dpi, 1 day before the onset of clinical disease. Equivalent results were observed in 4 independent studies and demonstrate the feasibility of oral fluids and mRT-qPCR for surveillance of ASF, CSF, and FMD in swine populations. © 2015 The Author(s).

Timing and Predictors of Fever and Infection after Craniotomy for Epilepsy in Children

PubMed Central

Phung, Jennifer; Mathern, Gary W.; Krogstad, Paul

2013-01-01

Background Fevers and leukocytosis after pediatric craniotomy trigger diagnostic evaluation and antimicrobial therapy for possible brain infection. This study determined the incidence and predictors of infection in infants and children undergoing epilepsy neurosurgery. Methods We reviewed the postoperative course of 100 consecutive surgeries for pediatric epilepsy, comparing those with and without infections for clinical variables and daily maximum temperatures, blood WBC and differential, and cerebrospinal fluid (CSF) studies. Results Infections were the most common adverse events following these surgeries. Four patients (4%) had CSF infections and 12 had non-CSF infections (including one with distinct CSF and bloodstream infections). Most (88%) infections occurred before postoperative day 12 and were associated with larger resections involving ventriculostomies. Fevers (T ≥38.5°C) were observed in the first 12-days postsurgery in 43 % of cases, and were associated with patients undergoing hemispherectomy and multilobar resections. Fevers in the first three days postsurgery identified infections with 73% sensitivity, 69% specificity, and 70% accuracy; two (13%) patients with infections never developed fevers. Peripheral blood WBC >15,000 was found in 49% of patients and 5 cases of infections never had elevated WBC counts. WBC differential, CSF protein, RBC, WBC, and RBC/WBC ratios were poor predictors of infections. Longer hospital stays were associated with infections and hemispherectomy and multilobar resections. Patients with and without infections were equally likely to be seizure free after surgery. Conclusions Fevers and elevated blood WBC counts were common after pediatric epilepsy surgery, but CSF infections were uncommon. Positive cultures and other confirmatory microbiologic tests should drive changes in antimicrobial therapy after surgery. PMID:23348815

Intrathecal antibody production in two cases of yellow fever vaccine associated neurotropic disease in Argentina.

PubMed

Pires-Marczeski, Fanny Clara; Martinez, Valeria Paula; Nemirovsky, Corina; Padula, Paula Julieta

2011-12-01

During the period 2007-2008 several epizootics of Yellow fever with dead of monkeys occurred in southeastern Brasil, Paraguay, and northeastern Argentina. In 2008 after a Yellow fever outbreak an exhaustive prevention campaign took place in Argentina using 17D live attenuated Yellow fever vaccine. This vaccine is considered one of the safest live virus vaccines, although serious adverse reactions may occur after vaccination, and vaccine-associated neurotropic disease are reported rarely. The aim of this study was to confirm two serious adverse events associated to Yellow fever vaccine in Argentina, and to describe the analysis performed to assess the origin of specific IgM against Yellow fever virus (YFV) in cerebrospinal fluid (CSF). Both cases coincided with the Yellow fever vaccine-associated neurotropic disease case definition, being clinical diagnosis longitudinal myelitis (case 1) and meningoencephalitis (case 2). Specific YFV antibodies were detected in CSF and serum samples in both cases by IgM antibody-capture ELISA. No other cause of neurological disease was identified. In order to obtain a conclusive diagnosis of central nervous system (CNS) infection the IgM antibody index (AI(IgM) ) was calculated. High AI(IgM) values were found in both cases indicating intrathecal production of antibodies and, therefore, CNS post-vaccinal YFV infection could be definitively associated to YFV vaccination. Copyright © 2011 Wiley Periodicals, Inc.

Quantitative approach for the risk assessment of African swine fever and Classical swine fever introduction into the United States through legal imports of pigs and swine products.

PubMed

Herrera-Ibatá, Diana María; Martínez-López, Beatriz; Quijada, Darla; Burton, Kenneth; Mur, Lina

2017-01-01

The US livestock safety strongly depends on its capacity to prevent the introduction of Transboundary Animal Diseases (TADs). Therefore, accurate and updated information on the location and origin of those potential TADs risks is essential, so preventive measures as market restrictions can be put on place. The objective of the present study was to evaluate the current risk of African swine fever (ASF) and Classical swine fever (CSF) introduction into the US through the legal importations of live pigs and swine products using a quantitative approach that could be later applied to other risks. Four quantitative stochastic risk assessment models were developed to estimate the monthly probabilities of ASF and CSF release into the US, and the exposure of susceptible populations (domestic and feral swine) to these introductions at state level. The results suggest a low annual probability of either ASF or CSF introduction into the US, by any of the analyzed pathways (5.5*10-3). Being the probability of introduction through legal imports of live pigs (1.8*10-3 for ASF, and 2.5*10-3 for CSF) higher than the risk of legally imported swine products (8.90*10-4 for ASF, and 1.56*10-3 for CSF). This could be caused due to the low probability of exposure associated with this type of commodity (products). The risk of feral pigs accessing to swine products discarded in landfills was slightly higher than the potential exposure of domestic pigs through swill feeding. The identification of the months at highest risk, the origin of the higher risk imports, and the location of the US states most vulnerable to those introductions (Iowa, Minnesota and Wisconsin for live swine and California, Florida and Texas for swine products), is valuable information that would help to design prevention, risk-mitigation and early-detection strategies that would help to minimize the catastrophic consequences of potential ASF/CSF introductions into the US.

Quantitative approach for the risk assessment of African swine fever and Classical swine fever introduction into the United States through legal imports of pigs and swine products

PubMed Central

Herrera-Ibatá, Diana María; Martínez-López, Beatriz; Quijada, Darla; Burton, Kenneth

2017-01-01

The US livestock safety strongly depends on its capacity to prevent the introduction of Transboundary Animal Diseases (TADs). Therefore, accurate and updated information on the location and origin of those potential TADs risks is essential, so preventive measures as market restrictions can be put on place. The objective of the present study was to evaluate the current risk of African swine fever (ASF) and Classical swine fever (CSF) introduction into the US through the legal importations of live pigs and swine products using a quantitative approach that could be later applied to other risks. Four quantitative stochastic risk assessment models were developed to estimate the monthly probabilities of ASF and CSF release into the US, and the exposure of susceptible populations (domestic and feral swine) to these introductions at state level. The results suggest a low annual probability of either ASF or CSF introduction into the US, by any of the analyzed pathways (5.5*10−3). Being the probability of introduction through legal imports of live pigs (1.8*10−3 for ASF, and 2.5*10−3 for CSF) higher than the risk of legally imported swine products (8.90*10−4 for ASF, and 1.56*10−3 for CSF). This could be caused due to the low probability of exposure associated with this type of commodity (products). The risk of feral pigs accessing to swine products discarded in landfills was slightly higher than the potential exposure of domestic pigs through swill feeding. The identification of the months at highest risk, the origin of the higher risk imports, and the location of the US states most vulnerable to those introductions (Iowa, Minnesota and Wisconsin for live swine and California, Florida and Texas for swine products), is valuable information that would help to design prevention, risk-mitigation and early-detection strategies that would help to minimize the catastrophic consequences of potential ASF/CSF introductions into the US. PMID:28797058

Effect of pyrogen and antipyretics on prostaglandin activity in cisternal c.s.f. of unanaesthetized cats

PubMed Central

Feldberg, W.; Gupta, K. P.; Milton, A. S.; Wendlandt, Sabine

1973-01-01

1. Samples of cisternal cerebrospinal fluid (c.s.f.) were collected from unanaesthetized cats while rectal temperature was continuously recorded. From the same cat, samples were collected during normal body temperature, during pyrogen fever and when the fever was brought down by an I.P. injection of an antipyretic. Fever was produced by injection of the bacterial pyrogen of Shigella dysenteriae either into the third ventricle, cisterna magna or I.V. The samples of c.s.f. were assayed for PGE1-like activity on the rat stomach fundus strip preparation rendered insensitive to 5-HT. 2. In samples of c.s.f. collected during normal body temperature, usually either no PGE1-like activity was detected, or its activity was low. Higher values were obtained in only a few cats. 3. In each experiment the PGE1-like activity increased, often many-fold, in samples collected during the pyrogen fever, irrespective, of the route of administration of the pyrogen. However, on I.V. injection, about 1000 times larger doses of the pyrogen were required than on injection into the liquor space to produce fever and the increase in PGE1-like activity of cisternal c.s.f. 4. The antipyretic drugs indomethacin, paracetamol and aspirin, injected I.P. during the pyrogen fever, brought down temperature, and the PGE1-like activity of the cisternal c.s.f. again became low. 5. When samples of cisternal c.s.f. were subjected to thin layer chromatography the prostaglandin-like activity was solely or mainly found in the zone corresponding to the prostaglandins of the E series. 6. These findings support the theory that pyrogens produce fever by increasing synthesis and release of prostaglandin in the preoptic anterior hypothalamic area, and that antipyretics of the aspirin type bring down this fever because they inhibit this synthesis. 7. It is concluded that pyrogen increases prostaglandin synthesis not only in the preoptic anterior hypothalamic area. When injected into the liquor space increased synthesis of prostaglandin probably occurs in many regions near the surface of the brain stem, and when injected I.V. may occur in other parts of the C.N.S. as well. But to produce fever the prostaglandin has to act on the preoptic anterior hypothalamic area. PMID:4588122

The Relationship Between Monthdisease Incidence Rate and Climatic Factor of Classical Swine Fever

NASA Astrophysics Data System (ADS)

Wang, Hongbin; Xu, Danning; Xiao, Jianhua; Zhang, Ru; Dong, Jing

The Swine Fever is a kind of acute, highly infective epidemic disease of animals; it is name as Classical Swine Fever (CSF) by World animal Health organization. Meteorological factors such as temperature, air pressure and rainfall affect the epidemic of CSF significantly through intermediary agent and CSF viral directly. However there is significant difference among different region for mode of effects. Accordingly, the analyze must adopt different methods. The dependability between incidence rate each month of CSF and meteorological factors from 1999 to 2004 was analyzed in this paper. The function of meteorological factors on CSF was explored and internal law was expected to be discovered. The correlation between the incidence rate of Swine Fever and meteorological factors, thus the foundation analysis of the early warning and the decision-making was made, the result indicated that the incidence rate of CSF has negative correlation with temperature, rainfall, cloudage; relative humidity has positive correlation with disease; for air pressure, except average air pressure of one month, other air pressure factors have positive correlation with disease; for wind speed, except Difference among moths of wind speed and average temperature of one month. have positive correlation with disease, other wind speed factors has negative correlation with disease.

Serum Metabolomic Profiling of Piglets Infected with Virulent Classical Swine Fever Virus

PubMed Central

Gong, Wenjie; Jia, Junjie; Zhang, Bikai; Mi, Shijiang; Zhang, Li; Xie, Xiaoming; Guo, Huancheng; Shi, Jishu; Tu, Changchun

2017-01-01

Classical swine fever (CSF) is a highly contagious swine infectious disease and causes significant economic losses for the pig industry worldwide. The objective of this study was to determine whether small molecule metabolites contribute to the pathogenesis of CSF. Birefly, serum metabolomics of CSFV Shimen strain-infected piglets were analyzed by ultraperformance liquid chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) in combination with multivariate statistical analysis. In CSFV-infected piglets at days 3 and 7 post-infection changes were found in metabolites associated with several key metabolic pathways, including tryptophan catabolism and the kynurenine pathway, phenylalanine metabolism, fatty acid and lipid metabolism, the tricarboxylic acid and urea cycles, branched-chain amino acid metabolism, and nucleotide metabolism. Several pathways involved in energy metabolism including fatty acid biosynthesis and β-oxidation, branched-chain amino acid metabolism, and the tricarboxylic acid cycle were significantly inhibited. Changes were also observed in several metabolites exclusively associated with gut microbiota. The metabolomic profiles indicate that CSFV-host gut microbiome interactions play a role in the development of CSF. PMID:28496435

[Cytokines in cancer chemotherapy: present state and problems in use of G- and GM-CSF for solid tumors in Japan].

PubMed

Ogawara, M

1998-01-01

The present state and the problems of G and GM-CSF in cancer chemotherapy, especially for solid tumors in Japan, were reviewed. One of the problems is that adaptation is restricted to several tumors, and the other that recommended doses are about half or one-fourth as much as in North America or Europe. With G-CSF after dose-intensive chemotherapy in small-cell lung cancer, three studies showed G-CSF shortened the duration of neutropenia, and reduced the incidence of neutropenic fever, use of antibiotics and hospitalization, while they showed no advantages in terms of response rate and the incidence of infection-related death. Moreover, the effect on survival has not been proved. In afebrile neutropenic patients, G-CSF could accelerate recovery from neutropenia, but did not reduce the incidence of neutropenic fever. In febrile neutropenic patients with antibiotics, it could also accelerate recovery from neutropenia, but did not reduce neutropenic fever compared with no CSF except in some subsets. Our retrospective study showed the effects of G-CSF in grade 4 neutropenia were comparable with grade 3 neutropenia. The functions of neutrophils with G-CSF after chemotherapy were reported to be increased or maintained. Clinical benefits were only obtained in certain dose-intensive chemotherapy or in limited subsets. Additional clinical trials and a guideline like ASCO's should be planned.

Economic Analysis of Classical Swine Fever Surveillance in the Netherlands.

PubMed

Guo, X; Claassen, G D H; Oude Lansink, A G J M; Loeffen, W; Saatkamp, H W

2016-06-01

Classical swine fever (CSF) is a highly contagious pig disease that causes economic losses and impaired animal welfare. Improving the surveillance system for CSF can help to ensure early detection of the virus, thereby providing a better initial situation for controlling the disease. Economic analysis is required to compare the benefits of improved surveillance with the costs of implementing a more intensive system. This study presents a comprehensive economic analysis of CSF surveillance in the Netherlands, taking into account the specialized structure of Dutch pig production, differences in virulence of CSF strains and a complete list of possible surveillance activities. The starting point of the analysis is the current Dutch surveillance system (i.e. the default surveillance-setup scenario), including the surveillance activities 'daily clinical observation by the farmer', 'veterinarian inspection after a call', 'routine veterinarian inspection', 'pathology in AHS', 'PCR on tonsil in AHS', 'PCR on grouped animals in CVI' and 'confirmatory PCR by NVWA'. Alternative surveillance-setup scenarios were proposed by adding 'routine serology in slaughterhouses', 'routine serology on sow farms' and 'PCR on rendered animals'. The costs and benefits for applying the alternative surveillance-setup scenarios were evaluated by comparing the annual mitigated economic losses because of intensified CSF surveillance with the annual additional surveillance costs. The results of the cost-effectiveness analysis show that the alternative surveillance-setup scenarios with 'PCR on rendered animals' are effective for the moderately virulent CSF strain, whereas the scenarios with 'routine serology in slaughterhouses' or 'routine serology on sow farms' are effective for the low virulent strain. Moreover, the current CSF surveillance system in the Netherlands is cost-effective for both moderately virulent and low virulent CSF strains. The results of the cost-benefit analysis for the moderately virulent CSF strain indicate that the current surveillance system in the Netherlands is adequate. From an economic perspective, there is little to be gained from intensifying surveillance. © 2014 Blackwell Verlag GmbH.

9 CFR 94.24 - Restrictions on the importation of pork, pork products, and swine from the APHIS-defined European...

Code of Federal Regulations, 2014 CFR

2014-01-01

... pork, pork products, and swine from the APHIS-defined European CSF region. 94.24 Section 94.24 Animals..., NEWCASTLE DISEASE, HIGHLY PATHOGENIC AVIAN INFLUENZA, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE... Restrictions on the importation of pork, pork products, and swine from the APHIS-defined European CSF region...

The effect of vaccination with the PAV-250 strain classical swine fever (CSF) virus on the airborne transmission of CSF virus.

PubMed

Gonzalez, C; Pijoan, C; Ciprian, A; Correa, P; Mendoza, S

2001-09-01

The airborne transmission of Classical Swine Fever (CSF) virus to susceptible pigs, as well as the effect of vaccination with the CSF virus PAV-250 strain was investigated on this mode of transmission. Experiment I: four pigs were inoculated with the ALD CSFV strain (10(4.3) 50% TCID) by the intramuscular route, and at the onset of fever, they were introduced into an enclosed chamber. At the end of the experiment surviving pigs were sedated, anesthetized and euthanatized. Experiment II: four pigs were previously vaccinated with the CSF virus PAV-250 strain, and at 14 days post-vaccination they were challenged with the CSF virus ALD strain. In both experiments, four susceptible pigs were exposed to infectious aerosols by placing them in a chamber connected by a duct to the adjacent pen containing the infected animals and were kept there for 86 hs. In Experiment I, pigs exposed to contaminated air died as a result of infection with CSF virus on days 14, 21 and 28 post-inhalation. These four pigs seroconverted from day 12 post-inhalation. CSF virus was isolated from these animals, and the fluorescent antibody test on tonsils was positive. In Experiment II, a vaccinated pig exposed to contaminated air did not seroconvert, nor was CSF virus isolated from lymphoid tissues. However, mild fluorescence in tonsil sections from these pigs was observed. In conclusion, CSF virus was shown to be transmitted by air at a distance of 1 m to susceptible pigs. Vaccination with the PAV-250 CSF virus strain protected the pigs from clinical disease under the same conditions.

Surveillance of classical swine fever in wild boar in South Korea from 2010-2014.

PubMed

Kim, Yong Kwan; Lim, Seong-In; Kim, Jae-Jo; Cho, Yoon-Young; Song, Jae-Young; Cho, In-Soo; Hyun, Bang-Hun; Choi, Sung-Hyun; Kim, Seung-Hoe; Park, Eun-Hye; An, Dong-Jun

2016-01-01

Classical swine fever (CSF) is a highly contagious systemic hemorrhagic viral disease of pigs. Wild boar plays a crucial role in the epidemiology of CSF. Between 2010 and 2014, samples were collected nationwide from 6,654 wild boars hunted in South Korea. Anti-CSF antibodies were identified in 0.59% (39 of 6,654) of the wild boar samples using a virus neutralization test and were primarily detected in wild boars living close to the demilitarized zone and the area of the Taebaek Mountains surroundings. The CSF virus (subgroup 2.1b) was isolated from two wild boars captured in a nearby border area. The criteria used to define high-risk areas for targeted CSF surveillance in South Korea should be further expanded to include other regions nationwide.

The challenges of classical swine fever control: modified live and E2 subunit vaccines.

PubMed

Huang, Yu-Liang; Deng, Ming-Chung; Wang, Fun-In; Huang, Chin-Cheng; Chang, Chia-Yi

2014-01-22

Classical swine fever (CSF) is an economically important, highly contagious disease of swine worldwide. CSF is caused by classical swine fever virus (CSFV), and domestic pigs and wild boars are its only natural hosts. The two main strategies used to control CSF epidemic are systematic prophylactic vaccination and a non-vaccination stamping-out policy. This review compares the protective efficacy of the routinely used modified live vaccine (MLV) and E2 subunit vaccines and summarizes the factors that influence the efficacy of the vaccines and the challenges that both vaccines face to CSF control. Although MLV provide earlier and more complete protection than E2 subunit vaccines, it has the drawback of not allowing differentiation between infected and vaccinated animals (DIVA). The marker vaccine of E2 protein with companion discriminatory test to detect antibodies against E(rns) allows DIVA and is a promising strategy for future control and eradication of CSF. Maternal derived antibody (MDA) is the critical factor in impairing the efficacy of both MLV and E2 subunit vaccines, so the well-designed vaccination programs of sows and piglets should be considered together. Because of the antigen variation among various genotypes of CSFV, antibodies raised by either MLV or subunit vaccine neutralize genotypically homologous strains better than heterologous ones. However, although this is not a major concern for MLV as the induced immune responses can protect pigs against the challenge of various genotypes of CSFVs, it is critical for E2 subunit vaccines. It is thus necessary to evaluate whether the E2 subunit vaccine can completely protect against the current prevalent strains in the field. An ideal new generation of vaccine should be able to maintain the high protective efficiency of MLV and overcome the problem of antigenic variations while allowing for DIVA. Copyright © 2013 Elsevier B.V. All rights reserved.

Molecular Detection of Leptospira in Two Returned Travelers: Higher Bacterial Load in Cerebrospinal Fluid versus Serum or Plasma

PubMed Central

Waggoner, Jesse J.; Soda, Elizabeth A.; Seibert, Ryan; Grant, Philip; Pinsky, Benjamin A.

2015-01-01

Leptospirosis is a potentially severe illness in returned travelers. Patients often present with fever, headache, and neck pain, which may lead to a workup for meningitis including the acquisition of cerebrospinal fluid (CSF). Although Leptospira DNA has been detected in CSF by polymerase chain reaction (PCR), little data exist regarding the utility of testing CSF in addition to serum or plasma obtained on presentation. In this report, we present two cases of leptospirosis in returned travelers presenting with fever and headache. Our first patient had neutrophilic meningitis, and Leptospira was detectable only in CSF obtained on admission. The second patient had a normal CSF profile, but Leptospira was detected in CSF at a bacterial load 5- to 10-fold higher than that in plasma. CSF is an important specimen for the diagnosis of Leptospira by molecular methods and may yield an actionable diagnosis in the absence of leptospiremia. PMID:26033024

9 CFR 94.24 - Restrictions on the importation of pork, pork products, and swine from the APHIS-defined European...

Code of Federal Regulations, 2013 CFR

2013-01-01

... pork, pork products, and swine from the APHIS-defined European CSF region. 94.24 Section 94.24 Animals..., EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE... pork, pork products, and swine from the APHIS-defined European CSF region. (a) Pork and pork products...

9 CFR 94.24 - Restrictions on the importation of pork, pork products, and swine from the APHIS-defined European...

Code of Federal Regulations, 2012 CFR

2012-01-01

... pork, pork products, and swine from the APHIS-defined European CSF region. 94.24 Section 94.24 Animals..., EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE... pork, pork products, and swine from the APHIS-defined European CSF region. (a) Pork and pork products...

Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

PubMed Central

Tamura, Tomokazu; Yoshino, Fumi; Nomura, Takushi; Yamamoto, Naoki; Sato, Yuka; Okamatsu, Masatoshi; Ruggli, Nicolas; Kida, Hiroshi

2012-01-01

Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low-virulent and moderately virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE− was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE− vaccine virus was readapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE−/P-11 virus isolated from the tonsils after the 11th passage in vivo had acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studies in vitro indicated that the substitution in E2 influenced virus spreading and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiency in vitro and pathogenicity in pigs. PMID:22674973

A Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-terminal Domain.

PubMed

Li, Weiwei; Wu, Baixing; Soca, Wibowo Adian; An, Lei

2018-05-02

Classical swine fever virus (CSFV) is the ringleader of Classical swine fever (CSF). The non-structural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp) that is a key enzyme initiating viral RNA replication by a de novo mechanism. It is also an attractive target for the development of anti-CSFV drugs. To gain a better understanding on the mechanism of CSFV RNA synthesis, here we solved the first crystal structure of CSFV-NS5B. Our studies show that the CSFV-NS5B RdRp contains characteristic fingers, palm domain and thumb domain as well as a unique N-terminal domain (NTD) that had never been observed. Mutagenesis studies on NS5B validated the importance of NTD in the catalytic activity of this novel RNA-dependent RNA polymerase. Moreover, our results shed light on the understanding of CSFV infection. IMPORTANCE Pigs are important domestic animal. However, a highly contagious viral disease named Classical swine fever (CSF) causes devastating economic losses. Classical swine fever virus (CSFV) is the primary culprit of CSF, which is a positive-sense single-stranded RNA virus belonging to the Pestivirus genus, Flaviviridae family. Genome replication of CSFV depends on RNA-dependent RNA polymerase known as NS5B. However, the structure of CSFV-NS5B has never been reported, and the mechanism of CSFV replication is poorly understood. Here, we solved the first crystal structure of CSFV-NS5B, analyzed the function of characteristic fingers, palm, and thumb domains. Additionally, our structure also revealed the presence of a novel N-terminal domain (NTD). Biochemical studies demonstrated that the NTD of CSFV-NS5B is very important for RNA-dependent RNA polymerase (RdRp) activity. Collectively, our studies provide a structural basis for future rational design of anti-CSFV drugs which is critically important as no effective anti-CSFV drugs have been developed. Copyright © 2018 American Society for Microbiology.

9 CFR 94.10 - Swine from regions where classical swine fever exists.

Code of Federal Regulations, 2010 CFR

2010-01-01

...-defined EU CSF region is a single region of low-risk for CSF. (c) Except as provided in § 94.24 for the APHIS-defined EU CSF region, no swine that are moved from or transit any region where classical swine...

Incidence and persistence of classical swine fever in free-ranging wild boar (Sus scrofa).

PubMed

Rossi, S; Fromont, E; Pontier, D; Crucière, C; Hars, J; Barrat, J; Pacholek, X; Artois, M

2005-06-01

Although veterinary authorities aim to limit persistence of classical swine fever (CSF) in wild boar (Sus scrofa), to avoid potential transmission to pigs, factors influencing CSF transmission and persistence are not clearly understood. Here we analyse incidence and persistence in a CSF epidemic that occurred in the French Vosges Forest. Higher incidence was found in large forests compared to smaller isolated ones, being highest near the starting point of the epidemic, but poorly related to the local density. We hypothesize that the spatial and social structure of wild boar populations may be responsible for this variability of incidence over space. Persistence was highest near the starting point of the epidemic and where initial density was highest. We hypothesize that persistence was favoured by the abundance of young wild boar, itself encouraged by CSF. Our results allow us to propose management measures aimed at limiting CSF persistence.

Construction and immunological characterization of CD40L or GM-CSF incorporated Hantaan virus like particle

PubMed Central

Zhang, Xiaoxiao; Truax, Agnieszka D.; Ma, Ruixue; Liu, Ziyu; Lei, Yingfeng; Zhang, Liang; Ye, Wei; Zhang, Fanglin; Xu, Zhikai; Shang, Lei; Liu, Rongrong; Wang, Fang; Wu, Xingan

2016-01-01

Infection of Hantaan virus (HTNV) usually causes hemorrhagic fever with renal syndrome (HFRS). China has the worst epidemic incidence of HFRS as well as high fatality. Inactivated whole virus has been used for HFRS vaccination, however there are still problems such as safety concerns. CD40 ligand (CD40L) and granulocyte macrophage colony-stimulating factor (GM-CSF) are well-known immune stimulating molecules that can enhance antigen presenting, lymphocytes activation and maturation, incorporation of CD40L and GM-CSF to the surface of virus like particles (VLPs) can greatly improve the vaccination effect. We constructed eukaryotic vectors expressing HTNV M segment and S segment, as well as vectors expressing HTNV M segment with CD40L or GM-CSF, our results showed successful production of CD40L or GM-CSF incorporated HTNV VLPs. In vitro stimulation with CD40L or GM-CSF anchored HTNV VLP showed enhanced activation of macrophages and DCs. CD40L/GM-CSF incorporated VLP can induce higher level of HTNV specific antibody and neutralizing antibody in mice. Immunized mice splenocytes showed higher ability of secreting IFN-γ and IL-2, as well as enhancing CTL activity. These results suggest CD40L/GM-CSF incorporated VLP can serve as prospective vaccine candidate. PMID:27542281

New insights on the management of wildlife diseases using multi-state recapture models: the case of classical swine fever in wild boar.

PubMed

Rossi, Sophie; Toigo, Carole; Hars, Jean; Pol, Françoise; Hamann, Jean-Luc; Depner, Klaus; Le Potier, Marie-Frederique

2011-01-01

The understanding of host-parasite systems in wildlife is of increasing interest in relation to the risk of emerging diseases in livestock and humans. In this respect, many efforts have been dedicated to controlling classical swine fever (CSF) in the European Wild Boar. But CSF eradication has not always been achieved even though vaccination has been implemented at a large-scale. Piglets have been assumed to be the main cause of CSF persistence in the wild since they appeared to be more often infected and less often immune than older animals. However, this assumption emerged from laboratory trials or cross-sectional surveys based on the hunting bags. In the present paper we conducted a capture-mark-recapture study in free-ranging wild boar piglets that experienced both CSF infection and vaccination under natural conditions. We used multi-state capture recapture models to estimate the immunization and infection rates, and their variations according to the periods with or without vaccination. According to the model prediction, 80% of the infected piglets did not survive more than two weeks, while the other 20% quickly recovered. The probability of becoming immune did not increase significantly during the summer vaccination sessions, and the proportion of immune piglets was not higher after the autumn vaccination. Given the high lethality of CSF in piglets highlighted in our study, we consider unlikely that piglets could maintain the chain of CSF virus transmission. Our study also revealed the low efficacy of vaccination in piglets in summer and autumn, possibly due to the low palatability of baits to that age class, but also to the competition between baits and alternative food sources. Based on this new information, we discuss the prospects for the improvement of CSF control and the interest of the capture-recapture approach for improving the understanding of wildlife diseases.

9 CFR 94.10 - Swine from regions where classical swine fever exists.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Pacific Islands. (b) The APHIS-defined EU CSF region is a single region of low-risk for CSF. (c) Except as provided in § 94.24 for the APHIS-defined EU CSF region, no swine that are moved from or transit any region...

Vulnerability of the British swine industry to classical swine fever

PubMed Central

Porphyre, Thibaud; Correia-Gomes, Carla; Chase-Topping, Margo E.; Gamado, Kokouvi; Auty, Harriet K.; Hutchinson, Ian; Reeves, Aaron; Gunn, George J.; Woolhouse, Mark E. J.

2017-01-01

Classical swine fever (CSF) is a notifiable, highly contagious viral disease of swine which results in severe welfare and economic consequences in affected countries. To improve preparedness, it is critical to have some understanding of how CSF would spread should it be introduced. Based on the data recorded during the 2000 epidemic of CSF in Great Britain (GB), a spatially explicit, premises-based model was developed to explore the risk of CSF spread in GB. We found that large outbreaks of CSF would be rare and generated from a limited number of areas in GB. Despite the consistently low vulnerability of the British swine industry to large CSF outbreaks, we identified concerns with respect to the role played by the non-commercial sector of the industry. The model further revealed how various epidemiological features may influence the spread of CSF in GB, highlighting the importance of between-farm biosecurity in preventing widespread dissemination of the virus. Knowledge of factors affecting the risk of spread are key components for surveillance planning and resource allocation, and this work provides a valuable stepping stone in guiding policy on CSF surveillance and control in GB. PMID:28225040

Toward the development of a one-dose classical swine fever subunit vaccine: antigen titration, immunity onset, and duration of immunity

PubMed Central

Madera, Rachel F.; Wang, Lihua; Gong, Wenjie; Burakova, Yulia; Buist, Sterling; Nietfeld, Jerome; Henningson, Jamie; Cino-Ozuna, Ada G.; Tu, Changchun

2018-01-01

Highly contagious classical swine fever (CSF) remains a major trade and health problem in the pig industry, resulting in large economic losses worldwide. In CSF-endemic countries, attenuated CSF virus (CSFV) vaccines have been routinely used to control the disease. However, eradication of CSFV in a geographical area would require permanent reduction to zero presence of the virus. It is therefore of paramount importance to develop a safe, potent, and non-infectious CSF vaccine. We have previously reported on a cost-effective CSF E2 subunit vaccine, KNB-E2, which can protect against CSF symptoms in a single dose containing 75 µg of recombinant CSFV glycoprotein E2. In this study, we report on a series of animal studies undertaken to elucidate further the efficacy of KNB-E2. We found that pigs vaccinated with a single KNB-E2 dose containing 25 µg of recombinant CSFV glycoprotein E2 were protected from clinical symptoms of CSF. In addition, KNB-E2-mediated reduction of CSF symptoms was observed at two weeks post-vaccination and the vaccinated pigs continued to exhibit reduced CSF clinical signs when virus challenged at two months and four months post-vaccination. These results suggest that KNB-E2 effectively reduces CSF clinical signs, indicating the potential of this vaccine for safely minimizing CSF-related losses. PMID:29510474

9 CFR 94.9 - Pork and pork products from regions where classical swine fever exists.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the importation of swine and swine products. (b) The APHIS-defined EU CSF region is a single region of low-risk for CSF. (c) Except as provided in § 94.24 for the APHIS-defined EU CSF region, no fresh pork...

Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis.

PubMed

Choi, Jiwoon; Kim, Se Hoon

2018-01-01

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4-11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small.

Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal Meningitis

PubMed Central

Choi, Jiwoon; Kim, Se Hoon

2018-01-01

Cryptococcus neoformans is the most common microorganism found in cerebrospinal fluid (CSF) cytology and causes life-threatening infections in immunocompromised hosts. Although its cytomorphologic features in conventional smear cytology have been well described, those in liquid-based cytology have rarely been. A 73-year-old woman with diffuse large B-cell lymphoma presented with mental confusion and a spiking fever. To rule out infectious conditions, CSF examination was performed. A cytology slide that was prepared using the ThinPrep method showed numerous spherical yeast-form organisms with diameters of 4–11 μm and thick capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or pseudohyphae were observed. Gomori methenamine silver staining was positive. Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen test and culture. Liquid-based cytology allows for a clean background and additional slides for ancillary testing, facilitating the detection of microorganisms in CSF specimens, particularly when the number of organisms is small. PMID:29069886

Classical swine fever in pigs: recent developments and future perspectives.

PubMed

Chander, Vishal; Nandi, S; Ravishankar, C; Upmanyu, V; Verma, Rishendra

2014-06-01

Classical swine fever (CSF) is one of the most devastating epizootic diseases of pigs, causing high morbidity and mortality worldwide. The diversity of clinical signs and similarity in disease manifestations to other diseases make CSF difficult to diagnose with certainty. The disease is further complicated by the presence of a number of different strains belonging to three phylogenetic groups. Advanced diagnostic techniques allow detection of antigens or antibodies in clinical samples, leading to implementation of proper and effective control programs. Polymerase chain reaction (PCR)-based methods, including portable real-time PCR, provide diagnosis in a few hours with precision and accuracy, even at the point of care. The disease is controlled by following a stamping out policy in countries where vaccination is not practiced, whereas immunization with live attenuated vaccines containing the 'C' strain is effectively used to control the disease in endemic countries. To overcome the problem of differentiation of infected from vaccinated animals, different types of marker vaccines, with variable degrees of efficacy, along with companion diagnostic assays have been developed and may be useful in controlling and even eradicating the disease in the foreseeable future. The present review aims to provide an overview and status of CSF as a whole with special reference to swine husbandry in India.

The relevance of kalikrein-kinin system via activation of B2 receptor in LPS-induced fever in rats.

PubMed

Soares, Denis de Melo; Santos, Danielle R; Rummel, Christoph; Ott, Daniela; Melo, Míriam C C; Roth, Joachim; Calixto, João B; Souza, Glória E P

2017-11-01

This study evaluated the involvement of endogenous kallikrein-kinin system and the bradykinin (BK) B 1 and B 2 receptors on LPS- induced fever and the POA cells involved in this response. Male Wistar rats received either i.v. (1 mg/kg), i.c.v. (20 nmol) or i.h. (2 nmol) injections of icatibant (B 2 receptor antagonist) 30 or 60 min, respectively, before the stimuli. DALBK (B 1 receptor antagonist) was given either 15min before BK (i.c.v.) or 30 min before LPS (i.v.). Captopril (5 mg/kg, sc.,) was given 1 h prior LPS or BK. Concentrations of BK and total kininogenon CSF, plasma and tissue kallikrein were evaluated. Rectal temperatures (rT) were assessed by telethermometry. Ca ++ signaling in POA cells was performed in rat pup brain tissue microcultures. Icatibant reduced LPS fever while, captopril exacerbated that response, an effect abolished by icatibant. Icatibant (i.h.) reduced fever to BK (i.h.) but not that induced by LPS (i.v.). BK increased intracellular calcium concentration in neurons and astrocytes. LPS increased levels of bradykinin, tissue kallikrein and total kininogen. BK (i.c.v.) increased rT and decreased tail skin temperature. Captopril potentiated BK-induced fever an effect abolished by icatibant. DALBK reduced the fever induced by BK. BK (i.c.v.) increased the CSF PGE 2 concentration. Effect abolished by indomethacin (i.p.). LPS activates endogenous kalikrein-kinin system leading to production of BK, which by acting on B 2 -receptors of POA cells causes prostaglandin synthesis that in turn produces fever. Thus, a kinin B 2 -receptor antagonist that enters into the brain could constitute a new and interesting strategy to treat fever. Copyright © 2017 Elsevier Ltd. All rights reserved.

A 51-year-old man with intramedullary spinal cord abscess having a patent foramen ovale

PubMed Central

Higuchi, Kanako; Ishihara, Hiroyuki; Okuda, Shiho; Kanda, Fumio

2011-01-01

The authors report a case of a 51-year-old man with intramedullary spinal cord abscess (ISCA) having a patent foramen ovale (PFO). He developed fever and tetraplegia after a recent dental treatment. MRI showed ISCA with longitudinal swelling from the upper cervical to the lumbar spinal cord. Cerebrospinal fluid (CSF) analysis indicated bacterial meningitis, and the culture of CSF revealed Streptococcus viridans. Transoesophageal echocardiography revealed the existence of a PFO. We suspected another possibility other than systemic bacteraemia, that paradoxical bacteric embolisation through PFO after the dental treatment caused ISCA. While several reports of brain abscess with PFO are available, this is the first report of ISCA with PFO. PMID:22696715

Colchicine-induced leukopenia in a patient with familial Mediterranean fever: the cause and a possible approach.

PubMed

Ben-Chetrit, E; Navon, P

2003-01-01

A young patient with familial Mediterranean fever (FMF) developed leukopenia each time she took colchicine. However, when she discontinued the drug the white cell and the platelets counts increased but she experienced FMF attacks. Later it was found that the patient also had concomitant cytomegalovirus (CMV) infection. This complex situation posed several diagnostic and therapeutic issues concerning the real cause for the leukopenia and the possible approach to take in such conditions. We propose that when an essential drug (such as colchicine for FMF) causes leukopenia, one should look for concurrent CMV or another viral infection. If there is no such infection, it is suggested that the mechanism leading to leukopenia be clarified. In the case of bone marrow suppression, colchicine should be continued with injections of G-CSF, whereas if the bone marrow is hypercellular it is suggested to use steroids and colchicine concomitantly.

Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral particles as a non-transmissible bivalent marker vaccine candidate against CSF and JE infections

USDA-ARS?s Scientific Manuscript database

A trans-complemented CSF- JE chimeric viral replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The E2 gene of CSFV Alfort/187 strain was deleted and the resultant plasmid pA187delE2 was inserted by a fragment containing the region coding for a truncate...

Investigation of a pig herd with animals seropositive for classical swine fever and where porcine circovirus-associated disease had been diagnosed.

PubMed

Bingham, P C; McFadden, A M J; Wang, J; Kittelberger, R; Clough, R R; Tham, K M

2010-10-01

To investigate the cause of classical swine fever (CSF) virus-seropositive animals in a nucleus pig-breeding herd in New Zealand, where porcine circovirus-associated disease had been diagnosed. An exotic disease investigation was undertaken to exclude CSF and porcine reproductive and respiratory syndrome (PRRS) on a nucleus pig-breeding herd comprising approximately 300 breeding sows, 1,000 weaners, and 650 grower pigs. The herd was experiencing poor reproductive performance in sows, and breeding records showed a declining farrowing rate attributable to a single manager. The growing pigs (10-15 weeks old) were experiencing respiratory disease and wasting, and the mortality rate by pen varied between 9 and 20%. Post-mortem changes in affected grower pigs were consistent with circovirus-associated diseases. DIAGNOSTIC TESTING: Serological screening using an IDEXX-ELISA gave negative results for PRRS virus antibodies, but two grower pigs and one sow tested positive for CSF virus antibodies. These three seropositive animals remained positive to CSF virus, using three commercial ELISA test kits, over 27 weeks. A newly developed virus neutralisation test (VNT), using a New Zealand isolate of border disease (BD) virus, demonstrated that the seropositive pig sera had higher antibody titres to BD virus than to bovine viral diarrhoea (BVD) virus and CSF virus. PCR performed on tonsil, kidney, ileum and spleen gave negative results for CSF virus, and histopathology on lymph nodes, intestine, lung, kidney, liver and brain showed no evidence of the disease. Virus isolation performed on a number of samples was negative. The seropositive samples for CSF virus found in this investigation were likely to be a cross reaction to a pestivirus other than CSF virus. The finding of a possible endemic pestivirus capable of being transmitted between sheep and pigs on this farm may explain findings from previous serological survey work in New Zealand, and supports experience elsewhere, where BD virus was found to be the predominant ruminant pestivirus infecting pigs. The results show that pestivirus cross reactivity can result in unexpectedly high titres, and that testing with a full set of (local) pestiviruses is necessary to reach the correct conclusion. The investigation has direct relevance where pig herds with a low seroprevalence are encountered during surveillance for CSF.

CSF coccidioides complement fixation

MedlinePlus

... The name of this infection is coccidioidomycosis, or valley fever. When the infection involves the covering of the ... and the A.D.A.M. Editorial team. Valley Fever Read more NIH MedlinePlus Magazine Read more Health ...

Isolation and Characterization of a Moderately Virulent Classical Swine Fever Virus Emerging in China.

PubMed

Luo, Y; Ji, S; Liu, Y; Lei, J-L; Xia, S-L; Wang, Y; Du, M-L; Shao, L; Meng, X-Y; Zhou, M; Sun, Y; Qiu, H-J

2017-12-01

Classical swine fever (CSF) is a devastating infectious disease of pigs caused by classical swine fever virus (CSFV). In China, CSF has been under control owing to extensive vaccination with the lapinized attenuated vaccine (C-strain) since 1950s, despite sporadic or endemic in many regions. However, recently, CSF outbreaks occurred in a large number of swine herds in China. Here, we isolated 15 CSFV strains from diverse C-strain-vaccinated pig farms in China and characterized the genetic variations and antigenicity of the new isolates. The new strains showed unique variations in the E2 protein and were clustered to the subgenotype 2.1d of CSFV recently emerging in China in the phylogenetic tree. Cross-neutralization test showed that the neutralizing titres of porcine anti-C-strain sera against the new isolates were substantially lower than those against both the highly virulent Shimen strain and the subgenotype 2.1b strains that were isolated in China in 2006 and 2009, respectively. In addition, experimental animal infection showed that the HLJZZ2014 strain-infected pigs displayed lower mortality and less severe clinical signs and pathological changes compared with the Shimen strain-infected pigs. The HLJZZ2014 strain was defined to be moderately virulent based on a previously established assessment system for CSFV virulence evaluation, and the virus shedding and the viral load in various tissues of the CSFV HLJZZ2014 strain-infected pigs were significantly lower than those of the Shimen strain-infected pigs. Taken together, the subgenotype 2.1d isolate of CSFV is a moderately virulent strain with molecular variations and antigenic alterations. © 2016 Blackwell Verlag GmbH.

Complex Virus-Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview.

PubMed

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-07-05

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV-host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus-host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding.

Complex Virus–Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview

PubMed Central

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-01-01

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV–host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus–host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding. PMID:28678154

Recoding structural glycoprotein E2 in classical swine fever virus (CSFV) produces complete virus attenuation in swine and protects infected animals against disease

USDA-ARS?s Scientific Manuscript database

Controlling classical swine fever (CSF) involves vaccination in endemic regions and preemptive slaughter of infected swine herds during epidemics. Generally, live attenuated vaccines induce solid immunity. Using diverse approaches, reverse genetics has been useful in developing classical swine fever...

Detection of West Nile virus genome and specific antibodies in Iranian encephalitis patients.

PubMed

Chinikar, S; Javadi, A; Ataei, B; Shakeri, H; Moradi, M; Mostafavi, E; Ghiasi, S M

2012-08-01

West Nile virus (WNV) is a mosquito-borne flavivirus which circulates in birds, horses and humans. An estimated 80% of WNV infections are asymptomatic. Fewer than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. This study was conducted from January 2008 to June 2009 in Isfahan, Iran. Patients attending the emergency department with fever and loss of consciousness were consecutively included. Cerebrospinal fluids (CSF) were initially analysed through bacteriology and biochemistry examinations, resulting in those with evidence of meningitis being excluded. Patients' CSF and serum were diagnosed by serological and molecular assays. A total of 632 patients with fever and loss of consciousness were tested by CSF analyses. Samples of the remaining patients (39·4%) were referred for WNV investigation. Three (1·2%) of the patients were positive for both serum and CSF by RT-PCR, and six (2·4%) were positive only for IgG antibodies. History of insect bite, and blood transfusion and transplantation were risk factors for being positive by RT-PCR (P=0·048) and being IgG positive (P=0·024), respectively. The results of this study showed that the prevalence of West Nile fever is low in patients with encephalitis.

[Pleomorphic carcinoma of the lung with high serum granulocyte colony stimulating factor, suggested of pulmonary abscess by preoperative radiology; report of a case].

PubMed

Mizuno, Mikoto; Miyoshi, Tatsu; Nabeshima, Kazuki; Iwasaki, Akinori; Shirakusa, Takaho

2006-08-01

A 52-year-old man with a history of heavy smoking was hospitalized for evaluation of fever. Pulmonary abscess was initially suspected by computed tomography (CT) showing an ovoid, well-demarcated nodule of 61 mm in diameter with coarse calcification in S2a of the right lung. The patient was treated with antibiotics, but no improvement was seen in inflammatory reactions or lesion size. Marked leukocytosis and high level of granulocyte colony stimulating factor (G-CSF) was shown by laboratory examination. To improve patient condition and ensure correct diagnosis, right upper lobectomy of the lung was performed. Pleomorphic carcinoma of the lung was subsequently diagnosed. G-CSF producing tumor was suspected, since the normalization of serum G-CSF level followed by the improvement of both fever and inflammatory reaction was observed postoperatively. We also present herein a review of 22 Japanese cases of pleomorphic carcinoma producing G-CSF of the lung, characterized by leukocytosis.

Genetic and virulence characterization of classical swine fever viruses isolated in Mongolia from 2007 to 2015.

PubMed

Enkhbold, Bazarragchaa; Shatar, Munkhduuren; Wakamori, Shiho; Tamura, Tomokazu; Hiono, Takahiro; Matsuno, Keita; Okamatsu, Masatoshi; Umemura, Takashi; Damdinjav, Batchuluun; Sakoda, Yoshihiro

2017-06-01

Classical swine fever (CSF), a highly contagious viral disease affecting domestic and wild pigs in many developing countries, is now considered endemic in Mongolia, with 14 recent outbreaks in 2007, 2008, 2011, 2012, 2014, and 2015. For the first time, CSF viruses isolated from these 14 outbreaks were analyzed to assess their molecular epidemiology and pathogenicity in pigs. Based on the nucleotide sequences of their 5'-untranslated region, isolates were phylogenetically classified as either sub-genotypes 2.1b or 2.2, and the 2014 and 2015 isolates, which were classified as 2.1b, were closely related to isolates from China and Korea. In addition, at least three different viruses classified as 2.1b circulated in Mongolia. Experimental infection of the representative isolate in 2014 demonstrated moderate pathogenicity in 4-week-old pigs, with relatively mild clinical signs. Understanding the diversity of circulating CSF viruses gleans insight into disease dynamics and evolution, and may inform the design of effective CSF control strategies in Mongolia.

A multisystemic Acanthamoeba infection in a dog in Tenerife, Canary Islands, Spain.

PubMed

Valladares, María; Reyes-Batlle, María; Mora-Peces, Inmaculada; Martín-Navarro, Carmen M; López-Arencibia, Atteneri; Dorta-Gorrín, Alexis; Comyn-Afonso, Estefanía; Martínez-Carretero, Enrique; Maciver, Sutherland K; Piñero, José E; Valladares, Basilio; Lorenzo-Morales, Jacob

2014-10-15

A 22-month-old male Spanish water dog was hospitalized after its physical examination revealed fever and movement difficulty. After 24h, the dog was found to have a high fever (39.5 °C) and was treated empirically with doxycycline/ciprofloxacin. At 48 h, after submission the fever rose to 41 °C and the animal presented with a stiff neck and dehydration. Peripheral blood and cerebrospinal fluid (CSF) were sampled and trophozoites with an Acanthamoeba-like morphology were observed in the CSF. PCR specific for Acanthamoeba, Naegleria fowleri and Balamuthia mandrillaris were performed and the CSF sample found positive for Acanthamoeba. Lungs, kidney, liver and spleen samples were collected post mortem. All collected organ samples were positive for Acanthamoeba by PCR, thus confirming a multisystemic infection. Water samples taken at a suspected site of infection yielded an almost identical PCR fragment to those of the clinical samples, indicating that this was probably where the infection originated. This is the first report of a fatal case of Acanthamoeba disseminated infection in a dog in Spain. Copyright © 2014 Elsevier B.V. All rights reserved.

Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.

PubMed

Ravaud, A; Delaunay, M; Chevreau, C; Coulon, V; Debled, M; Bret-Dibat, C; Courbon, F; Gualde, N; Nguyen Bui, B

2001-11-16

The potential antitumoral effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 microg kg(-1), bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 microg kg(-1), bid, day 2 to day 19 every 21 days and DTIC: 800 mg m(-2), day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoral activity with subsequent toxicity.

Classical Swine Fever in Wild Hog: Report of its Prevalence in Northeast India.

PubMed

Barman, N N; Bora, D P; Khatoon, E; Mandal, S; Rakshit, A; Rajbongshi, G; Depner, K; Chakraborty, A; Kumar, S

2016-10-01

Classical swine fever virus (CSFV) is the causative agent of a highly contagious disease, hog cholera in pigs. The disease is endemic in many parts of the world and vaccination is the only way to protect the animals from CSFV infection. Wild hogs belong to the species Sus Scrofa Cristatus under the family Suidae are quite susceptible to CSFV infection. The epidemiological role concerning classical swine fever (CSF) in India is largely unknown. We report here the three isolated cases of CSF in wild hogs from three National parks, namely Kaziranga National Park, Manas National Park and Jaldapara National Park, from north-east part of India. The post-mortem and histopathological findings were clearly indicative for CSFV infection. The presence of CSFV genome was demonstrated in several organs and tissues collected from hogs died due to viral infection. In addition, CSF-specific antibodies were detected in two wild hogs as well as in eighteen feral pigs from the same locations. The phylogenetic analysis of the partial E2 protein gene and 5' untranslated region of CSFV isolates from the wild hog showed identities with genotype 2.2 of the Indian isolates. Occurrence of CSF in wild hogs may pose a potent threat in the epidemiology of the virus in Northeast part of India. To the best of our knowledge, the report presented in the manuscript is the first comprehensive report on CSF in wild hogs form Northeast India. The findings reported would help us to understand the epidemiology and biology of CSFV in wild animals. © 2014 Blackwell Verlag GmbH.

[Meningoencephalitis caused by West Nile virus in a renal transplant recipient].

PubMed

Ertilav, Muhittin; Ozkul, Aykut; Zeytinoğlu, Ayşın; Sen, Sait; Sipahi, Savaş; Töz, Hüseyin; Kitiş, Omer; Eraslan, Cenk

2014-10-01

West Nile virus (WNV) infection which is asymptomatic or mild in normal population, it may cause serious clinical conditions leading to death in eldery and immunosupressed patients. The virus is mainly transmitted by mosquito bites, however transfusion, transplantation, transplasental and nosocomial ways have also been reported to be responsible for viral transmission. It is known that WNV may cause life-threatining conditions such as central nervous system (CNS) infections especially in bone marrow and solid organ transplant recipients. In this report, the first case of WNV encephalitis in an immunosuppressed patient with renal transplant in Turkey was presented. A 25-year-old male patient admitted to our hospital with the complaints of generalized myalgia, nausea and vomiting, after the 24. day of renal transplantation from a live donor. Since he developed diffuse tonic clonic seizures during his follow up, he was diagnosed as meningoencephalitis with the results of cranial magnetic resonance imaging (MR) and cerebrospinal fluid (CSF) biochemistry. Bacterial and fungal cultures of blood and CSF yielded negative results. CMV antigenemia test and CMV IgM in blood, and nucleic acid tests for CMV, EBV, HSV-1/2, VZV, HHV-6, enterovirus and parvovirus in CSF were also negative. However, WNV RNA was detected in CSF by an in-house reverse transcriptase (RT) nested PCR method. The sequence analysis (GenBank BLAST) of the virus showed that it had 99% similarity with Lineage-1 WNV strains. To define the transmission way of the virus to the recipient, WNV-RNA was searched in the renal biopsy sample and found negative by RT nested PCR. The clinical condition of the patient was improved with supportive therapy and by the de-escalation of immunosuppressive drugs [Mycophenolate mofetil (MMF; 1 g/day), cyclosporin (1 mg/kg/day)]. However WNV meningoencephalitis recurred one month later. The patient presented with fever, myalgia, confusions, leukocytosis, anemia, and repeating WNV-RNA positivity in CSF. This time cyclosporin was stopped, MMF was given in low dose (1 g/day), and high dose parenteral acyclovir and intravenous immunoglobulin (400 mg/kg/day, 7 days) were initiated. The patient recovered completely after 10 days without any neurological abnormalities. In conclusion, especially in endemic areas, WNV should be considered in the differential diagnosis of CNS infections develop in solid organ transplant cases and patients with other immunodeficiencies who present with fever, generalized myalgia, gastrointestinal symptoms and/or neurological disorders.

Transmission of yellow fever vaccine virus through breast-feeding - Brazil, 2009.

PubMed

2010-02-12

In April, 2009, the state health department of Rio Grande do Sul, Brazil, was notified by the Cachoeira do Sul municipal health department of a case of meningoencephalitis requiring hospitalization in an infant whose mother recently had received yellow fever vaccine during a postpartum visit. The Field Epidemiology Training Program of the Secretariat of Surveillance in Health of the Brazilian Ministry of Health assisted state and municipal health departments with an investigation. This report summarizes the results of that investigation, which determined that the infant acquired yellow fever vaccine virus through breast-feeding. The mother reported 2 days of headache, malaise, and low fever occurring 5 days after receipt of yellow fever vaccine. The infant, who was exclusively breast-fed, was hospitalized at age 23 days with seizures requiring continuous infusion of intravenous anticonvulsants. The infant received antimicrobial and antiviral treatment for meningoencephalitis. The presence of 17DD yellow fever virus was detected by reverse transcription--polymerase chain reaction (RT-PCR) in the infant's cerebrospinal fluid (CSF); yellow fever--specific immunoglobulin M (IgM) antibodies also were present in serum and CSF. The infant recovered completely, was discharged after 24 days of hospitalization, and has had normal neurodevelopment and growth through age 6 months. The findings in this report provide documentation that yellow fever vaccine virus can be transmitted via breast-feeding. Administration of yellow fever vaccine to breast-feeding women should be avoided except in situations where exposure to yellow fever viruses cannot be avoided or postponed.

Two cases of dengue meningitis: a rare first presentation.

PubMed

Goswami, Rudra Prosad; Mukherjee, Arindam; Biswas, Tapan; Karmakar, Partha Sarathi; Ghosh, Alakendu

2012-02-13

Dengue, a mosquito-borne disease caused by a flavivirus, is recognized in over 120 countries with 3.6 billion people living in areas at risk. Neurological manifestations are infrequently reported as clinical consequences of dengue infection. Though severe dengue may be associated with meningoencephalitis, meningitis is a rare initial presentation of otherwise uncomplicated dengue fever. We report two adult patients who presented with fever, headache, and nuchal rigidity without the typical symptoms of dengue infection. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis in one and slight neutrophilic pleocytosis in the other with a normal glucose value and negative bacterial cultures. Dengue was suspected because thrombocytopenia was symptomatic in one patient and documented during the hospital course, and was confirmed by demonstration of IgM antibody in the cerebrospinal fluid samples specific for dengue in both cases. Our report demonstrates that meningitis with or without encephalitis can be the first manifestation of dengue infection. In endemic areas, dengue infection should be considered as a probable etiological agent of meningitis. Regular monitoring of platelet count can be an invaluable diagnostic screening tool. In appropriate clinical settings detection of anti-dengue IgM both in serum and in CSF may lead to correct diagnosis.

[Treatment of severe neutropenias in dogs and cats with filgrastim].

PubMed

Kraft, W; Kuffer, M

1995-12-01

The recombinant hG-CSF Filgrastim was used in severe cases of neutropenia in the dog caused by parvovirosis, hyperestrogenism, treatment with antineoplastic agents, an aplastic syndrome and in the cat in cases of infectious panleukopenia. Increases of the numbers of leukocytes were observed in all groups of diseases in the dog, but not in feline infectious panleukopenia. Filgrastim is indicated in neutropenias associated with disturbance of the general condition accompanied by fever, but not in cases of transitory leukopenias.

Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

PubMed

Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

2015-07-09

Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial

PubMed Central

Ravaud, A; Delaunay, M; Chevreau, C; Coulon, V; Debled, M; Bret-Dibat, C; Courbon, F; Gualde, N; Bui, B Nguyen

2001-01-01

The potential antitumoural effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 μg kg−1, bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 μg kg−1, bid, day 2 to day 19 every 21 days and DTIC: 800 mg m−2, day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoural activity with subsequent toxicity. © 2001 Cancer Research Campaign   http://www.bjcancer.com PMID:11720430

Treatment with interferon-alpha delays disease in swine infected with a highly virulent CSFV strain

USDA-ARS?s Scientific Manuscript database

Classical swine fever (CSF) is an economically significant, highly contagious swine disease. The etiological agent, CSF virus (CSFV), is an enveloped virus with a positive-sense, single-stranded RNA genome, classified as a member of the genus Pestivirus within the family Flaviviridae (Becher et al.,...

[Bacterial meningitis caused by beta-lactamase-negative, ampicillin-resistant nontypeable Haemophilus influenzae in a 1-year-old girl: a case report].

PubMed

Abe, Katsuaki; Hoshino, Tadashi; Imuta, Naoko; Nishi, Junichiro; Ishiwada, Naruhiko

2014-05-01

We present herein the case report of bacterial meningitis caused by nontypeable Haemophilus influenzae (NTHi) in a 1-year-7-month-old girl with no medically significant history. NTHi from cerebrospinal fluid (CSF) was the beta-lactamase non-producing ampicillin resistant strain (BLNAR). Some beta-lactams were administrated, but fever was prolonged. Finally, rifampicin seemed to be effective. In NTHi, compared with H. influenzae type b (Hib), the prevalence of BLNAR is high. Hence, complicated cases may increase in the near future if the use of the Hib vaccine becomes widespread, and meningitis caused by NTHi increases. It may be necessary to consider combination therapy or use of non-beta-lactams that have a different antimicrobial mechanism from beta-lactams. PCR analysis revealed the possibility that the CSF isolate lacked the P5 protein gene. Though deficiency of P5 fimbriae is known to reduce the affinity of NTHi for the human respiratory epithelium, determining whether P5 deficient NTHi induced meningitis will require further study.

A Promising Trigene Recombinant Human Adenovirus Vaccine Against Classical Swine Fever Virus.

PubMed

Li, Helin; Gao, Rui; Zhang, Yanming

2016-05-01

Classical swine fever (CSF) vaccine based on HAdV-5 had achieved an efficient protection in swine. Both classical swine fever virus (CSFV) E0 glycoprotein and E2 glycoprotein were the targets for neutralizing antibodies and related to immune protection against CSF. Interleukin-2 (IL2), as an adjuvant, also had been used in CSF vaccine research. In this study, coexpression of the CSFV E0, E2, and IL2 genes by HAdV-5 (rAdV-E0-E2-IL2) was constructed and immunized to evaluate its efficacy. Three expressed genes had been sequentially connected with foot-and-mouth disease virus 2A (FMDV 2A). The vaccine was administered by intramuscular inoculation to CSFV-free pigs (10(8) TCID50) twice at triweekly intervals. No adverse clinical signs were observed in any of the pigs after vaccination. The vaccine induced strong humoral and cellular responses that led to complete protection against clinical signs of lethal CSFV infection, viremia, and shedding of challenge virus. The rAdV-E0-E2-IL2 is a promising, efficient, and safe marker vaccine candidate against CSFV.

Virus load in pigs affected with different clinical forms of classical swine fever.

PubMed

Rout, M; Saikumar, G

2012-04-01

Classical swine fever (CSF) is an endemic disease in India, but the real magnitude of the problem is not known as only outbreaks of acute CSF are reported and many cases of chronic and clinically inapparent forms of the disease, which manifest a confusing clinical picture, remain undiagnosed. The real status of classical swine fever virus (CSFV) infection can only be known by testing pigs with highly specific and sensitive diagnostic assays. To obtain the baseline prevalence of CSFV infection among pigs in an endemic region where no vaccination was being performed, a real-time PCR assay was used to detect viral genetic material in tissue samples collected from a slaughterhouse in the northern state of Uttar Pradesh in India. In total, 1120 slaughtered pigs were examined for the presence of CSF suggestive pathological lesions and tissues from suspected cases were tested for the presence of CSFV antigen and nucleic acids by indirect immuno-peroxidase test and real-time PCR, respectively. Based on the detection of viral genetic material in the tonsils, the prevalence of CSFV infection among slaughtered pigs was found to be 7.67%. Pigs detected positive for viral genome by quantitative real-time PCR assay when categorized into different forms of CSF, depending upon the pathological lesions observed, the viral load in the tonsils of some of the pigs with chronic or clinically inapparent form of the disease was similar to that detected in pigs with acute CSF. The results of the study suggested that the risk posed by pigs with chronic disease or those infected but showing no clinical disease may be relatively higher as they can transmit the virus to new susceptible hosts over a longer period of time. © 2011 Blackwell Verlag GmbH.

Evaluation of the risk of classical swine fever (CSF) spread from backyard pigs to other domestic pigs by using the spatial stochastic disease spread model Be-FAST: the example of Bulgaria.

PubMed

Martínez-López, Beatriz; Ivorra, Benjamin; Ramos, Angel Manuel; Fernández-Carrión, Eduardo; Alexandrov, Tsviatko; Sánchez-Vizcaíno, José Manuel

2013-07-26

The study presented here is one of the very first aimed at exploring the potential spread of classical swine fever (CSF) from backyard pigs to other domestic pigs. Specifically, we used a spatial stochastic spread model, called Be-FAST, to evaluate the potential spread of CSF virus (CSFV) in Bulgaria, which holds a large number of backyards (96% of the total number of pig farms) and is one of the very few countries for which backyard pigs and farm counts are available. The model revealed that, despite backyard pigs being very likely to become infected, infections from backyard pigs to other domestic pigs were rare. In general, the magnitude and duration of the CSF simulated epidemics were small, with a median [95% PI] number of infected farms per epidemic of 1 [1,4] and a median [95% PI] duration of the epidemic of 44 [17,101] days. CSFV transmission occurs primarily (81.16%) due to indirect contacts (i.e. vehicles, people and local spread) whereas detection of infected premises was mainly (69%) associated with the observation of clinical signs on farm rather than with implementation of tracing or zoning. Methods and results of this study may support the implementation of risk-based strategies more cost-effectively to prevent, control and, ultimately, eradicate CSF from Bulgaria. The model may also be easily adapted to other countries in which the backyard system is predominant. It can also be used to simulate other similar diseases such as African swine fever. Copyright © 2013 Elsevier B.V. All rights reserved.

[Group B streptococcus meningitis and infection surrounding the spinal canal caused by bacterial transmission from rectal ulcer via Batson's plexus].

PubMed

Tsutsumi, Ryosuke; Saito, Masaaki; Yoshizawa, Toshihiro

2011-07-01

A 62-year-old man was admitted to our hospital because of fever and disturbed consciousness. He suffered from persistent constipation due to diabetic autonomic neuropathy. On admission, neck stiffness and weakness of the lower extremities were observed. Cerebrospinal fluid (CSF) pleocytosis and decreased CSF glucose concentration showed the presence of meningitis. Bacterial culture of CSF was negative. One week after admission, he suddenly suffered from massive bleeding from the rectum, where a hemorrhagic ulcer caused by severe persistent constipation was observed. Contrast-enhanced CT scans and gadolinium-enhanced MR scans demonstrated a lumbar spinal epidural abscess, paraspinal muscle abscess, and cervical osteomyelitis. Streptococcus agalactiae, a bacterial species belonging to the group B streptococci, was isolated from pus obtained by needle puncture of the paraspinal muscle abscess. His entire condition was treated successfully with ampicillin and cefotaxime. Group B streptococci normally colonize the mucous membrane of the genital or lower gastrointestinal regions and rarely cause a spinal epidural abscess. However, in this case, the existence of a rectal ulcer probably made it possible for S. agalactiae to cause an infection of the epidural space or paraspinal muscles via the spinal valveless venous system named Batson's plexus communicating with the sacral, pelvic, and prostatic venous plexus. Our case indicated the importance of Batson's plexus in group B streptococcus infections surrounding the spinal canal and the necessity to explore for intrapelvic lesions including a rectal ulcer.

Rhodotorula glutinis meningitis: a case report and review of literature.

PubMed

Menon, Sarala; Gupta, H R; Sequeira, R; Chavan, Shazia; Gholape, D; Amandeep, S; Bhilave, N; Chowdhary, A S

2014-07-01

Rhodotorula is ubiquitous saprophytic yeast belonging to phylum Basidiomycota. These encapsulated basidiomycetes are being increasingly recognised as important emerging human pathogens. There are scanty reports of meningitis caused by Rhodurorula spp in HIV infected patients. We present one such case of meningitis by Rhodutorula glutinis in HIV-infected patient. The patient also had a past history of abdominal tuberculosis. The diagnosis of Rhodotorula was confirmed by Gram staining and culture of the cerebrospinal fluid (CSF). Contamination was ruled out by repeated culturing of CSF from the same patient. Therapy with Amphotericin B showed good results. Patient was discharged from the hospital. However, in the seventh month of follow-up patient was readmitted with complaints of fever, breathlessness, altered sensorium, vomiting and succumbed to his illness. This time the CSF cultures remained negative for Rhodotorula, acid fast bacilli and other pyogenic organisms. Our last 11-year retrospective analysis of 8197 specimens received for mycological work-up showed that this is the first report of R. glutinis isolation from our institute. © 2014 Blackwell Verlag GmbH.

Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G

USDA-ARS?s Scientific Manuscript database

Prophylactic vaccination using live attenuated classical swine fever (CSF) vaccines has been a very effective method to control disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccina...

Surveillance strategies for Classical Swine Fever in wild boar – a comprehensive evaluation study to ensure powerful surveillance

PubMed Central

Schulz, Katja; Peyre, Marisa; Staubach, Christoph; Schauer, Birgit; Schulz, Jana; Calba, Clémentine; Häsler, Barbara; Conraths, Franz J.

2017-01-01

Surveillance of Classical Swine Fever (CSF) should not only focus on livestock, but must also include wild boar. To prevent disease transmission into commercial pig herds, it is therefore vital to have knowledge about the disease status in wild boar. In the present study, we performed a comprehensive evaluation of alternative surveillance strategies for Classical Swine Fever (CSF) in wild boar and compared them with the currently implemented conventional approach. The evaluation protocol was designed using the EVA tool, a decision support tool to help in the development of an economic and epidemiological evaluation protocol for surveillance. To evaluate the effectiveness of the surveillance strategies, we investigated their sensitivity and timeliness. Acceptability was analysed and finally, the cost-effectiveness of the surveillance strategies was determined. We developed 69 surveillance strategies for comparative evaluation between the existing approach and the novel proposed strategies. Sampling only within sub-adults resulted in a better acceptability and timeliness than the currently implemented strategy. Strategies that were completely based on passive surveillance performance did not achieve the desired detection probability of 95%. In conclusion, the results of the study suggest that risk-based approaches can be an option to design more effective CSF surveillance strategies in wild boar. PMID:28266576

Surveillance strategies for Classical Swine Fever in wild boar - a comprehensive evaluation study to ensure powerful surveillance.

PubMed

Schulz, Katja; Peyre, Marisa; Staubach, Christoph; Schauer, Birgit; Schulz, Jana; Calba, Clémentine; Häsler, Barbara; Conraths, Franz J

2017-03-07

Surveillance of Classical Swine Fever (CSF) should not only focus on livestock, but must also include wild boar. To prevent disease transmission into commercial pig herds, it is therefore vital to have knowledge about the disease status in wild boar. In the present study, we performed a comprehensive evaluation of alternative surveillance strategies for Classical Swine Fever (CSF) in wild boar and compared them with the currently implemented conventional approach. The evaluation protocol was designed using the EVA tool, a decision support tool to help in the development of an economic and epidemiological evaluation protocol for surveillance. To evaluate the effectiveness of the surveillance strategies, we investigated their sensitivity and timeliness. Acceptability was analysed and finally, the cost-effectiveness of the surveillance strategies was determined. We developed 69 surveillance strategies for comparative evaluation between the existing approach and the novel proposed strategies. Sampling only within sub-adults resulted in a better acceptability and timeliness than the currently implemented strategy. Strategies that were completely based on passive surveillance performance did not achieve the desired detection probability of 95%. In conclusion, the results of the study suggest that risk-based approaches can be an option to design more effective CSF surveillance strategies in wild boar.

Validation of two commercial real-time RT-PCR kits for rapid and specific diagnosis of classical swine fever virus.

PubMed

Le Dimna, M; Vrancken, R; Koenen, F; Bougeard, S; Mesplède, A; Hutet, E; Kuntz-Simon, G; Le Potier, M F

2008-01-01

Two real-time RT-PCR kits, developed by LSI (TaqVet CSF) and ADIAGENE (Adiavet CSF), obtained an agreement to be commercialised in France, subject to conditions, defined by the French Classical Swine Fever (CSF) National Reference Laboratory. The producers were asked to introduce an internal control to check the RNA extraction efficacy. The different criteria assessed were sensitivity, "pestivirus specificity", reproducibility and ease of handling, using 189 different samples. These samples were either CSFV inactivated strains or blood/serum/organs collected from CSFV experimentally infected pigs or naturally infected wild boars. The reproducibility of the assays was confirmed by the analysis of a batch-to-batch panel control that was used for inter-laboratory tests involving nine laboratories. The two kits were also tested for the use in mass diagnostics and the results proved the kits to be suited using pools of blood, serum and tonsils. Moreover, a field evaluation, carried out on spleen samples collected from the CSF surveillance of wild boars in an area known to be infected and from domestic pigs at a slaughterhouse, confirmed the high sensitivity and specificity of the two kits. This step-by-step evaluation procedure confirmed that the two commercial CSF real-time RT-PCR kits have a higher predictive value than the current diagnostic standard, Virus Isolation.

Meta-analysis of classical swine fever prevalence in pigs in India: A 5-year study

PubMed Central

Patil, S. S.; Suresh, K. P.; Saha, S.; Prajapati, A.; Hemadri, D.; Roy, P.

2018-01-01

Aim: The aim of the study was to determine the overall prevalence of classical swine fever (CSF) in pigs in India, through a systematic review and meta-analysis of published data. Materials and Methods: Consortium for e-Resources in Agriculture, India, Google Scholar, PubMed, annual reports of All India Coordinated Research Project on Animal Disease Monitoring and Surveillance, and All India Animal Disease database of NIVEDI (NADRES) were used for searching and retrieval of CSF prevalence data (seroprevalence, virus antigen, and virus nucleic acid detection) in India using a search strategy combining keywords and related database-specific subject terms from January 2011 to December 2015 in English only. Results: A total of 22 data reports containing 6,158 samples size from 18 states of India were used for the quantitative synthesis, and overall 37% (95% confidence interval [CI]=0.24, 0.51) CSF prevalence in India was estimated. The data were classified into 4 different geographical zones of the country: 20% (95% CI=0.05, 0.55), 31% (95% CI=0.18, 0.47), 55% (95% CI=0.32, 0.76), and 34% (95% CI=0.14, 0.62). CSF prevalence was estimated in northern, eastern, western, and southern regions, respectively. Conclusion: This study indicates that overall prevalence of CSF in India is much lower than individual published reports. PMID:29657420

Tick-borne encephalitis in a child with previous history of completed primary vaccination.

PubMed

Zlamy, Manuela; Haberlandt, Edda; Brunner, Jürgen; Dozcy, Ludwig; Rostasy, Kevin

2016-01-01

We report the case of a 13-year-old girl who presented with fever, headache, nausea and pain behind the right ear. Cerebrospinal fluid (CSF; leukocytes 227/μL), electroencephalogram and cerebral magnetic resonance imaging were indicative of meningoencephalitis. Despite intensive therapy the general condition worsened and the patient was admitted to the intensive care unit. Serological analysis of CSF and serum indicated acute tick-borne encephalitis virus (TBEV) infection (IgG and IgM positive). TBEV infection has been reported after incomplete and complete vaccination. TBEV vaccination breakthrough in childhood has been shown to cause severe disease. It has been suggested that immunized patients develop more severe disease due to altered immune response, but the exact mechanism is unknown. In the presence of typical symptoms and a history of vaccination, possible vaccination breakthrough or missing booster vaccination should be considered. © 2015 Japan Pediatric Society.

Further evidence implicating prostaglandin E sub 2 in the genesis of pyrogen fever

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coceani, F.; Lees, J.; Bishai, I.

1988-03-01

Conscious cats were used to study the effects of endotoxin and interleukin 1 (IL 1) on levels of prostaglandin (PG) E{sub 2} and thromboxane (TX) B{sub 2} (the stable TXA{sub 2} byproduct) in cerebrospinal fluid (CSF) from the third ventricle. Pyrogens were given intravenously or intraventricularly and prostanoids were measured by radioimmunoassay. PGE{sub 2} was normally less abundant than TXB{sub 2}, and its level increased severalfold during the sustained fever following intravenous endotoxin (bolus) or IL 1 (bolus plus infusion). PGE{sub 2} elevation preceded the fever and was maintained thereafter. Likewise, intraventricular pyrogens promoted PGE{sub 2} formation, and their effectmore » was also manifest during the latent period of the fever. The PGE{sub 2} metabolite, 13,14-dihydro-15-keto-PGE{sub 2}, was not measurable in CSF from either afebrile or febrile animals. Basal content of PGE{sub 2}, on the other hand, was higher in animals pretreated with probenecid, confirming the importance of transport processes in removing prostanoids from brain. Unlike PGE{sub 2}, TXB{sub 2} levels did not change during the fever to intravenous endotoxin. TXB{sub 2} rose instead in response to intraventricular endotoxin, although the elevation did not extend beyond fever uprise. Furthermore, a TXA{sub 2} analog had inconsistent effects on body temperature, while a TXA{sub 2} antagonist did not interfere with endotoxin fever. These findings strongly support a causative role for PGE{sub 2} in the onset and progression of pyrogen fever. No evidence of a similar role was obtained for TXA{sub 2}.« less

Evaluation of movement restriction zone sizes in controlling classical swine fever outbreaks

USDA-ARS?s Scientific Manuscript database

The objective of this study was to compare the movement restriction zone sizes of 3-km, 5-km, 9-km, and 11-km with that of 7-km in controlling a classical swine fever (CSF) outbreak. Three assumptions of compliance level were considered: baseline, baseline ±10%, and baseline ±15%. The compliance lev...

Detection of antibodies against classical swine fever virus in fecal samples from wild boar.

PubMed

Seo, Sang won; Sunwoo, Sun young; Hyun, Bang hoon; Lyoo, Young S

2012-12-28

Classical swine fever (CSF) is a contagious viral disease that affects pigs. Wild boars can play an important epidemiological role in CSF outbreaks. In the past decades, studies conducted in many countries have reported that the CSF virus (CSFV) may persist in wild boar populations. The existence of CSFV in the free-ranging wild boar populations was indirectly confirmed by determining the prevalence of antibodies against CSFV in the serum of hunted wild boars. However, analyzing sero-prevalence in hunted wild boars to study the risk of CSF outbreaks is difficult due to insufficient number of samples, limitation of hunting area and biased age distribution of hunted wild boars. To improve this survey method, we collected feces of wild boars from their habitat and tested them using CSFV antibody enzyme-linked immunosorbent assay (ELISA) and CSF virus neutralization (VN) test. In this study, ELISA was found to be highly sensitive for detecting antibodies against CSFV in fecal samples. Most of doubtful or positive results obtained in CSFV ELISA were confirmed by VN tests. Despite the high coincidence rate of antibody-positive samples between CSFV ELISA and VN test, the possibility of false positive reaction should be considered. In the regional distribution, a fact that antibody-positive fecal and serum samples were found in geographically close area was shown. Hence, presence of antibodies in fecal samples may provide vital information regarding the risk of CSF outbreaks in wild boar groups in geographical proximity. Copyright © 2012 Elsevier B.V. All rights reserved.

E. coli Multiresistant Meningitis after Transrectal Prostate Biopsy

PubMed Central

Alecsandru, Diana; Gestoso, Israel; Romero, Ana; Martinez, Alfonso; García, Ana; Lobo, Julio; Yagüe, M. Ruiz

2006-01-01

Escherichia coli meningitis is a frequent pathology in children younger than 3 years old, but is an uncommon disease in adults. E. coli infection is the main cause of intrahospital bacteremia as a consequence of the employment of different medical procedures. Our patient, male, 69 years old, presented with fever, progressive difficulty in breathing, and shivers 24 h after transrectal prostate biopsy, with an absence of any other symptoms. He received prophylactic treatment with ciprofloxacin and later empirical treatment with ampicillin and tobramicin. After that, the patient presented with fever, headache, behavioral changes, somnolence, disorientation, a fluctuating level of conscience, cutaneous widespread pallor, and acute urinary retention. On physical exploration, we observed generalized hypoventilation, Glasgow 10, stiffness of the neck, inconclusive Kernig; the remaining neurological exploration was normal. Systematic of blood: leukocytes = 8,510/mm3 (94.5% polymorphonuclear), platelet = 87,000/mm3, pH = 7.51, pCO2 = 28.8 mmHg, pO2 = 61 mmHg, O2 saturation = 93.8%, and remaining values were normal. Chest X- ray, cranial CT scan, urine cultures were normal. Blood culture: E. coli. CSF: glucose <0.4 g/l, total proteins = 3.05 g/l, PMN = 7 cells. Microscopic examination of the CSF: Gram-negative bacilli; CSF's culture: abundant E. coli. The case of acute meningitis by multiresistant E. coli after transrectal prostate biopsy presented demonstrates that antibiotic prevention with ciprofloxacin is not absolutely risk free. Besides the use of antibiotic prevention for multiresistant microorganisms, the urologist and other physicians involved in the procedure must not forget that the rate of major complications of transrectal prostate biopsy is 1%, especially when it is performed in patients who will not benefit from that biopsy. PMID:17619698

Npro of classical swine fever virus contributes to pathogenicity in pigs by preventing type I interferon induction at local replication sites.

PubMed

Tamura, Tomokazu; Nagashima, Naofumi; Ruggli, Nicolas; Summerfield, Artur; Kida, Hiroshi; Sakoda, Yoshihiro

2014-04-17

Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly contagious disease of pigs. The viral protein Npro of CSFV interferes with alpha- and beta-interferon (IFN-α/β) induction by promoting the degradation of interferon regulatory factor 3 (IRF3). During the establishment of the live attenuated CSF vaccine strain GPE-, Npro acquired a mutation that abolished its capacity to bind and degrade IRF3, rendering it unable to prevent IFN-α/β induction. In a previous study, we showed that the GPE- vaccine virus became pathogenic after forced serial passages in pigs, which was attributed to the amino acid substitutions T830A in the viral proteins E2 and V2475A and A2563V in NS4B. Interestingly, during the re-adaptation of the GPE- vaccine virus in pigs, the IRF3-degrading function of Npro was not recovered. Therefore, we examined whether restoring the ability of Npro to block IFN-α/β induction of both the avirulent and moderately virulent GPE--derived virus would enhance pathogenicity in pigs. Viruses carrying the N136D substitution in Npro regained the ability to degrade IRF3 and suppress IFN-α/β induction in vitro. In pigs, functional Npro significantly reduced the local IFN-α mRNA expression in lymphoid organs while it increased quantities of IFN-α/β in the circulation, and enhanced pathogenicity of the moderately virulent virus. In conclusion, the present study demonstrates that functional Npro influences the innate immune response at local sites of virus replication in pigs and contributes to pathogenicity of CSFV in synergy with viral replication.

Marker vaccine strategies and candidate CSFV marker vaccines.

PubMed

Dong, Xiao-Nan; Chen, Ying-Hua

2007-01-04

Classical swine fever (CSF) is an economically important highly contagious disease of swine worldwide. Classical swine fever virus (CSFV) is its etiological agent, and the only natural hosts are domestic pigs and wild boars. Although field CSFV strains vary in the virulence, they all result in serious losses in pig industry. Highly virulent field strains generally cause acute disease and high mortality; moderately virulent field strains raise subacute or chronic infections; postnatal infection by low virulent field strains produces subclinical infection and mortality in the new-born piglets. CSFV can cross the placental barrier, and this transplacental transmission usually results in mortality of fetuses and birth of congenitally infected pigs with a late-onset disease and death. Two main strategies to control CSF epidemic are systematic prophylactic vaccination with live attenuated vaccines (such as C-strain) and non-vaccination stamping-out policy. But neither of them is satisfying enough. Marker vaccine and companion serological diagnostic test is thought to be a promising strategy for future control and eradication of CSF. During the past 15 years, various candidate marker vaccines were constructed and evaluated in the animal experiments, including recombinant chimeric vaccines, recombinant deletion vaccines, DNA vaccines, subunit vaccines and peptide vaccines. Among them, two subunit vaccines entered the large scale marker vaccine trial of EU in 1999. Although they failed to fulfil all the demands of the Scientific Veterinary Committee, they successfully induced solid immunity against CSFV in the vaccinated pigs. It can be expected that new potent marker vaccines might be commercially available and used in systematic prophylactic vaccination campaign or emergency vaccination in the next 15 years. Here, we summarized current strategies and candidate CSFV marker vaccines. These strategies and methods are also helpful for the development of new-generation vaccines against other diseases.

Meningoencephalitis from Borrelia miyamotoi in an immunocompromised patient.

PubMed

Gugliotta, Joseph L; Goethert, Heidi K; Berardi, Victor P; Telford, Sam R

2013-01-17

Ixodes ticks serve as vectors for Borrelia burgdorferi, the agent of Lyme disease. Globally, these ticks often concurrently harbor B. miyamotoi, a spirochete that is classified within the relapsing-fever group of spirochetes. Although humans presumably are exposed to B. miyamotoi, there are limited data suggesting disease attributable to it. We report a case of progressive mental deterioration in an older, immunocompromised patient, and even though Koch's postulates were not met, we posit B. miyamotoi as the cause, owing to its direct detection in cerebrospinal fluid (CSF) with the use of microscopy and a polymerase-chain-reaction (PCR) assay. It is likely that B. miyamotoi is an underrecognized cause of disease, especially in sites where Lyme disease is endemic.

The European Classical Swine Fever Virus Database: Blueprint for a Pathogen-Specific Sequence Database with Integrated Sequence Analysis Tools

PubMed Central

Postel, Alexander; Schmeiser, Stefanie; Zimmermann, Bernd; Becher, Paul

2016-01-01

Molecular epidemiology has become an indispensable tool in the diagnosis of diseases and in tracing the infection routes of pathogens. Due to advances in conventional sequencing and the development of high throughput technologies, the field of sequence determination is in the process of being revolutionized. Platforms for sharing sequence information and providing standardized tools for phylogenetic analyses are becoming increasingly important. The database (DB) of the European Union (EU) and World Organisation for Animal Health (OIE) Reference Laboratory for classical swine fever offers one of the world’s largest semi-public virus-specific sequence collections combined with a module for phylogenetic analysis. The classical swine fever (CSF) DB (CSF-DB) became a valuable tool for supporting diagnosis and epidemiological investigations of this highly contagious disease in pigs with high socio-economic impacts worldwide. The DB has been re-designed and now allows for the storage and analysis of traditionally used, well established genomic regions and of larger genomic regions including complete viral genomes. We present an application example for the analysis of highly similar viral sequences obtained in an endemic disease situation and introduce the new geographic “CSF Maps” tool. The concept of this standardized and easy-to-use DB with an integrated genetic typing module is suited to serve as a blueprint for similar platforms for other human or animal viruses. PMID:27827988

Development of a duplex lateral flow assay for simultaneous detection of antibodies against African and Classical swine fever viruses.

PubMed

Sastre, Patricia; Pérez, Teresa; Costa, Sofia; Yang, Xiaoping; Räber, Alex; Blome, Sandra; Goller, Katja V; Gallardo, Carmina; Tapia, Istar; García, Julia; Sanz, Antonio; Rueda, Paloma

2016-09-01

Classical swine fever (CSF) and African swine fever (ASF) are both highly contagious diseases of domestic pigs and wild boar and are clinically indistinguishable. For both diseases, antibody detection is an integral and crucial part of prevention and control measures. The purpose of our study was to develop and initially validate a duplex pen-side test for simultaneous detection and differentiation of specific antibodies against CSF virus (CSFV) and ASF virus (ASFV). The test was based on the major capsid protein VP72 of ASFV and the structural protein E2 of CSFV, both considered the most immunogenic proteins of these viruses. The performance of the pen-side test was evaluated using a panel of porcine samples consisting of experimental, reference, and field sera, with the latter collected from European farms free of both diseases. The new lateral flow assay was able to detect specific antibodies to ASFV or CSFV, showing good levels of sensitivity and specificity. These preliminary data indicate the potential of the newly developed pen-side test for rapid differential detection of antibodies found in the 2 diseases, which is of particular importance in the field and in front-line laboratories where equipment and skilled personnel are limited and control of ASF and CSF is crucial. © 2016 The Author(s).

Implementation and validation of an economic module in the Be-FAST model to predict costs generated by livestock disease epidemics: Application to classical swine fever epidemics in Spain.

PubMed

Fernández-Carrión, E; Ivorra, B; Martínez-López, B; Ramos, A M; Sánchez-Vizcaíno, J M

2016-04-01

Be-FAST is a computer program based on a time-spatial stochastic spread mathematical model for studying the transmission of infectious livestock diseases within and between farms. The present work describes a new module integrated into Be-FAST to model the economic consequences of the spreading of classical swine fever (CSF) and other infectious livestock diseases within and between farms. CSF is financially one of the most damaging diseases in the swine industry worldwide. Specifically in Spain, the economic costs in the two last CSF epidemics (1997 and 2001) reached jointly more than 108 million euros. The present analysis suggests that severe CSF epidemics are associated with significant economic costs, approximately 80% of which are related to animal culling. Direct costs associated with control measures are strongly associated with the number of infected farms, while indirect costs are more strongly associated with epidemic duration. The economic model has been validated with economic information around the last outbreaks in Spain. These results suggest that our economic module may be useful for analysing and predicting economic consequences of livestock disease epidemics. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a new LAMP assay for the detection of CSFV strains from Cuba: a proof-of-concept study.

PubMed

Postel, Alexander; Pérez, Lester J; Perera, Carmen L; Schmeiser, Stefanie; Meyer, Denise; Meindl-Boehmer, Alexandra; Rios, Liliam; Austermann-Busch, Sophia; Frias-Lepoureau, Maria T; Becher, Paul

2015-06-01

Classical swine fever (CSF) is a devastating animal disease of great economic impact worldwide. In many countries, CSF has been endemic for decades, and vaccination of domestic pigs is one of the measures to control the disease. Consequently, differentiating infected from vaccinated animals by antibody ELISA screening is not applicable. In some countries, such as Cuba, lack of molecular techniques for sensitive, rapid and reliable detection of virus genomes is a critical point. To overcome this problem, an easy-to-use one-tube assay based on the loop-mediated isothermal amplification (LAMP) principle has been developed for detection of the genome of CSF virus (CSFV) of endemic Cuban genotype 1.4 isolates. The assay reliably detected recent isolates from three different regions of Cuba with an analytical sensitivity 10-100 times lower than that of quantitative reverse transcription RT-qPCR. Diagnostic test sensitivity was examined using reference sera from two groups of pigs experimentally infected with Cuban virulent strain CSF0705 "Margarita" and the recent field isolate CSF1058 "Pinar del Rio". Differences in pathogenicity of the two viruses were reflected in the clinical course of disease as well as in virus loads of blood samples. Low viral RNA loads in samples from pigs infected with the field isolate caused serious detection problems in RT-LAMP as well as in RT-qPCR. Thus, it will be necessary in future research to focus on targeted sampling of diseased animals and to restrict diagnosis to the herd level in order to establish LAMP as an efficient tool for diagnosing CSF under field conditions.

Novel rope-based sampling of classical swine fever shedding in a group of wild boar showing low contagiosity upon experimental infection with a classical swine fever field strain of genotype 2.3.

PubMed

Mouchantat, Susan; Globig, Anja; Böhle, Wolfgang; Petrov, Anja; Strebelow, Heinz-Günther; Mettenleiter, Thomas C; Depner, Klaus

2014-06-04

Several classical swine fever (CSF) epidemics in wild boar and domestic pigs in Europe during the last decades have been caused by CSF virus (CSFV) strains of genotype 2.3. This genotype is known to be virulent leading to high morbidity and mortality. We experimentally infected two eight months old wild boar with 10(5,5) TCID50 of CSFV genotype 2.3 and kept the animals together with five noninoculated wild boar of the same age. Our original purpose was to evaluate a non-invasive sampling method based on saliva collection using "rope-in-a-bait" sampling baits. While expecting high morbidity, high level of virus shedding and some mortality, we actually observed a subclinical course of infection with an unexpected low contagiosity. The two inoculated animals infected only three contact animals while two contact animals remained uninfected. These findings substantially add to our epidemiological understanding of CSFV circulation in wild boar populations. CSFV infected animals older than six months and in good condition may not shed sufficient virus to transmit infection to all seronegative in-contact animals. The contagiosity in relation to the animal's age is discussed. This supports the hypothesis of silent perpetuation of CSFV in wild boar populations for several months if the wild boar density is sufficiently high. The feasibility of the "rope-in-a-bait" sampling method could be proven during the short viraemic phase of infected animals during the second week of infection. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced protective immunity of the chimeric vector-based vaccine rAdV-SFV-E2 against classical swine fever in pigs by a Salmonella bacterial ghost adjuvant.

PubMed

Xia, Shui-Li; Lei, Jian-Lin; Du, Mingliang; Wang, Yimin; Cong, Xin; Xiang, Guang-Tao; Li, Lian-Feng; Yu, Shenye; Du, Enqi; Liu, Siguo; Sun, Yuan; Qiu, Hua-Ji

2016-06-14

Classical swine fever (CSF) is a highly contagious swine disease caused by classical swine fever virus (CSFV). Previously, we demonstrated that rAdV-SFV-E2, an adenovirus-delivered, Semliki Forest virus replicon-vectored marker vaccine against CSF, is able to protect pigs against lethal CSFV challenge. From an economical point of view, it will be beneficial to reduce the minimum effective dose of the vaccine. This study was designed to test the adjuvant effects of Salmonella enteritidis-derived bacterial ghosts (BG) to enhance the protective immunity of rAdV-SFV-E2 in pigs. Groups of 5-week-old pigs (n = 4) were immunized intramuscularly twice with 10(5) median tissue culture infective doses (TCID50) rAdV-SFV-E2 combined with 10(10) colony forming units (CFU) BG, 10(6) or 10(5) TCID50 rAdV-SFV-E2 alone or 10(10) CFU BG alone at an interval of 3 weeks, and challenged with the highly virulent CSFV Shimen strain at 1 week post-booster immunization. The results show that the pigs inoculated with 10(5) TCID50 rAdV-SFV-E2 plus BG or 10(6) TCID50 rAdV-SFV-E2 alone were completely protected from lethal CSFV challenge, in contrast with the pigs vaccinated with 10(5) TCID50 rAdV-SFV-E2 or BG alone, which displayed partial or no protection following virulent challenge. The data indicate that BG are a promising adjuvant to enhance the efficacy of rAdV-SFV-E2 and possibly other vaccines.

A sequence database allowing automated genotyping of Classical swine fever virus isolates.

PubMed

Dreier, Sabrina; Zimmermann, Bernd; Moennig, Volker; Greiser-Wilke, Irene

2007-03-01

Classical swine fever (CSF) is a highly contagious viral disease of pigs. According to the OIE classification of diseases it is classified as a notifiable (previously List A) disease, thus having the potential for causing severe socio-economic problems and affecting severely the international trade of pigs and pig products. Effective control measures are compulsory, and to expose weaknesses a reliable tracing of the spread of the virus is necessary. Genetic typing has proved to be the method of choice. However, genotyping involves the use of multiple software applications, which is laborious and complex. The implementation of a sequence database, which is accessible by the World Wide Web with the option to type automatically new CSF virus isolates once the sequence is available is described. The sequence to be typed is tested for correct orientation and, if necessary, adjusted to the right length. The alignment and the neighbor-joining phylogenetic analysis with a standard set of sequences can then be calculated. The results are displayed as a graph. As an example, the determination is shown of the genetic subgroup of the isolate obtained from the outbreaks registered in Russia, in 2005. After registration (Irene.greiser-wilke@tiho-hannover.de) the database including the module for genotyping are accessible under http://viro08.tiho-hannover.de/eg/eurl_virus_db.htm.

Five years' experience of classical swine fever polymerase chain reaction ring trials in France.

PubMed

Po, F; Le Dimna, M; Le Potier, M F

2011-12-01

Since 2004, the French National Reference Laboratory for classical swine fever (CSF) has conducted an annual proficiency test (PT) to evaluate the ability of local veterinary laboratories to perform real-time polymerase chain reaction (PCR) for CSF virus. The results of five years of testing (2004-2008) are described here. The PT was conducted under blind conditions on 20 samples. The same batch of samples was used for all five years. The number of laboratories that analysed the samples increased from four in 2004 to 13 in 2008. The results of the PT showed the following: cross-contamination between samples and deficiencies in RNA preparation can occur even in experienced laboratories; sample homogeneity should be checked carefully before selection; samples stored at-80 degrees C for several years remain stable; and poor shipment conditions do not damage the samples with regard to detection of CSF virus genome. These results will enable redesign of the panel to improve the overall quality of the PT, which will encourage laboratories to check and improve their PCR procedures and expertise. This is an excellent way to determine laboratory performance.

Co-expression of Erns and E2 genes of classical swine fever virus by replication-defective recombinant adenovirus completely protects pigs against virulent challenge with classical swine fever virus.

PubMed

Sun, Yongke; Yang, Yuai; Zheng, Huanli; Xi, Dongmei; Lin, Mingxing; Zhang, Xiaomin; Yang, Linfu; Yan, Yulin; Chu, Xiaohui; Bi, Baoliang

2013-04-01

The objective of this study was to construct a recombinant adenovirus for future CSFV vaccines used in the pig industry for the reduction of losses involved in CSF outbreaks. The Erns and E2 genes of classical swine fever virus (CSFV), which encode the two main protective glycoproteins from the "Shimen" strain of CSFV, were combined and inserted into the replication-defective human adenovirus type-5 and named the rAd-Erns-E2. Nine pigs were randomly assigned to three treatment groups (three pigs in each group) including the rAd-Erns-E2, hAd-CMV control and DMEM control. Intramuscular vaccination with 2×10(6) TCID(50) of the rAd-Erns-E2 was administered two times with an interval of 21 days. At 42 days post inoculation, pigs in all groups were challenged with a lethal dose of 1×10(3) TCID(50) CSFV "Shimen" strain. Observation of clinical signs was made and the existence of CSFV RNA was detected. Animals in the hAd-CMV and DMEM groups showed severe clinical CSF symptoms and were euthanized from 7 to 10 days after the challenge. However, no adverse clinical CSF signs were observed in vaccinated pigs after the administration of rAd-Erns-E2 and even after CSFV challenge. Neither CSFV RNA nor pathological changes were detected in the tissues of interest of the above vaccinated pigs. These results implied that the recombination adenovirus carrying the Erns-E2 genes could be used to prevent swine from classical swine fever. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of Oral Bait Vaccine Efficacy Against Classical Swine Fever in Village Backyard Pig Farms in Bhutan.

PubMed

Monger, V R; Stegeman, J A; Dukpa, K; Gurung, R B; Loeffen, W L A

2016-12-01

Control and eradication of classical swine fever (CSF) in countries with a high proportion of backyard holdings is a challenge. Conventional attenuated Chinese C-strain vaccines, though safe and effective, are difficult to use in backyard farms due to various practical reasons. The aim of this study was to evaluate the efficacy of the CSF oral bait vaccine in village backyard pig farms and to assess the farmers' knowledge on CSF and motivation on using oral vaccines. The pigs were fed the bait by the farmers themselves; one bait was given on day 0, followed by second bait on the next day. Seventy-three per cent (140 of 193 pigs) of vaccinated pigs had either a slight (2-fold-3-fold; 60 pigs) or significant (at least 4-fold; 80 pigs) increase of the antibody titre against CSFV. A significant increase of the antibody titres was mainly observed in pigs with no pre-vaccination titre (OR = 12, 95% CI = 4-40). The number of pigs with protective antibody titres (≥40) rose from 47 (24%) to 115 (60%) following vaccination. Only 30% of the farmers claimed to be familiar with CSF, although clinical signs they mentioned were rather unspecific and could relate to many other pig diseases. Most of the farmers claimed to be motivated to use oral vaccines if made available. The oral vaccine could be a substitute for the conventional attenuated CSF vaccines in areas where it is logistically difficult for veterinarians to visit. It may therefore be a useful tool to combat endemic CSF disease in regions where the disease continues to have a serious impact on the backyard farmers who depend on pig farming for their sustenance and livelihoods. © 2015 Blackwell Verlag GmbH.

Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis.

PubMed

Andrès, E; Kurtz, J E; Perrin, A E; Dufour, P; Schlienger, J L; Maloisel, F

2001-08-01

Drug-induced agranulocytosis (DIA) is often caused by antithyroid drugs. We retrospectively studied the use of granulocyte colony-stimulating factor (G-CSF) therapy in antithyroid-DIA. Data for 20 patients (10 treated with G-CSF) with antithyroid-DIA (neutrophil count <0.5x10(9)/l) were extracted from a cohort study of DIA patients (n=110). G-CSF (300 microg/day subcutaneously) was used where the neutrophil count was <0.1x10(9)/l, or the patient was aged >70 years, or there were severe features of infection or underlying disease. Mean patient age was 62 years (range 34-87); sex ratio (M/F) was 0.05. Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20-60) and 100 mg/day (range 50-150), respectively, for a mean of 37 days (range 31-90). Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6). Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3). Mean neutrophil count was 0.07+/-0.1x10(9)/l. No patient died. Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G-CSF: 6.8+/-4 days vs. 11.6+/-5; 7.5+/-3.8 days vs. 12+/-4.5; and 7.3+/-4.8 days vs. 13+/-6.1, respectively (all p<0.05). G-CSF induced flu-like symptoms in 30% of patients, but reduced overall costs.

Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge.

PubMed

Madera, Rachel; Gong, Wenjie; Wang, Lihua; Burakova, Yulia; Lleellish, Karen; Galliher-Beckley, Amy; Nietfeld, Jerome; Henningson, Jamie; Jia, Kaimin; Li, Ping; Bai, Jianfa; Schlup, John; McVey, Scott; Tu, Changchun; Shi, Jishu

2016-09-09

Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease. CSF endemic countries have to use routine vaccination with modified live virus (MLV) vaccines to prevent and control CSF. However, it is impossible to serologically differentiate MLV vaccinated pigs from those infected with CSF virus (CSFV). The aim of this study is to develop a one-dose E2-subunit vaccine that can provide protection against CSFV challenge. We hypothesize that a vaccine consisting of a suitable adjuvant and recombinant E2 with natural conformation may induce a similar level of protection as the MLV vaccine. Our experimental vaccine KNB-E2 was formulated with the recombinant E2 protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion based adjuvant. 10 pigs (3 weeks old, 5 pigs/group) were immunized intramuscularly with one dose or two doses (3 weeks apart) KNB-E2, and 10 more control pigs were administered normal saline solution only. Two weeks after the second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged with 5 × 10(5) TCID50 CSFV Honduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml intranasal). It was found that while control pigs infected with CSFV stopped growing and developed high fever (>40 °C), high level CSFV load in blood and nasal fluid, and severe leukopenia 3-14 days post challenge, all KNB-E2 vaccinated pigs continued to grow as control pigs without CSFV exposure, did not show any fever, had low or undetectable level of CSFV in blood and nasal fluid. At the time of CSFV challenge, only pigs immunized with KNB-E2 developed high levels of E2-specific antibodies and anti-CSFV neutralizing antibodies. Our studies provide direct evidence that pigs immunized with one dose KNB-E2 can be protected clinically from CSFV challenge. This protection is likely mediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.

Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy.

PubMed

Herbst, Christine; Naumann, Frauke; Kruse, Eva-Brigitta; Monsef, Ina; Bohlius, Julia; Schulz, Holger; Engert, Andreas

2009-01-21

Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life. We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications. Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care. Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia. There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.

Marker vaccines and companion diagnostic tests for classical swine fever.

PubMed

Floegel-Niesmann, G

2003-01-01

For Classical Swine Fever (CSF) a subunit vaccine consisting of the E2 protein is commercially available. The discriminatory ELISAs detect antibodies against another viral protein, the E(rns). As CSF has already been eradicated from many countries the use of a marker vaccine in these regions can only be contemplated as emergency vaccination after a new introduction of virus. Therefore, a Large Scale Marker Vaccine Trial was financed by the EU Commission and organised by the EU Reference Laboratory for CSF in 1999. When tested under the conditions of emergency vaccination, e.g. challenge before full immunity had developed, it was shown, that most CSF challenge infections took a subclinical course with reduced virus shedding. Transplacental transmission in pregnant sows could not be prevented after an application of a single vaccine dose. The most serious deficiencies have been found in the discriminatory ELISAs. Both available tests have shown deficiencies in sensitivity and specificity compared to conventional CSF antibody ELISAs. At the time, when the trial was performed, no confirmatory test was available to verify the results of the discriminatory ELISAs. Currently two new developments of marker vaccines for CSF are in progress. A chimaeric vaccine is based on infectious clones of the conventional live vaccine (C-strain) where a gene is replaced with the corresponding gene of the closely related pestivirus Bovine Viral Diarrhoea (BVD) virus. Conversely, the E2 gene of a BVD virus can be replaced by the E2 of a virulent CSF virus. The other principle is the construction of a DNA vaccine, expressing the E2 gene after entering the host cell. Deletion mutants of the E2 gene have also been constructed and tested for their induction of immunity. Both new developments are based on the same discriminatory tests as mentioned previously and developments of other principles for discrimination are rare.

An update on the diagnosis and treatment of chronic idiopathic neutropenia.

PubMed

Dale, David C; Bolyard, Audrey A

2017-01-01

Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia (CIN). CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Long-term observational studies in children indicate that the disease often lasts for 3-5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of antineutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune-mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however, for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, that is more than 0.5 × 10/l, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe, treatment with G-CSF is often beneficial.

An update on the diagnosis and treatment of chronic idiopathic neutropenia

PubMed Central

Dale, David C.; Bolyard, Audrey Anna

2017-01-01

Purpose of Review Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia. (CIN) CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Recent findings Long-term observational studies in children indicate that the disease often lasts for 3 to 5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of anti-neutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. Summary It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, i.e. > 0.5 × 109/L, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe treatment with G-CSF is often beneficial. PMID:27841775

CSF leak

MedlinePlus

... this makes symptoms go away. In rare cases, surgery is needed to repair the tear in the dura and stop the headache. If symptoms of infection ( fever , chills, change in mental status) are present, they need to be treated ...

Antigenic characterization of classical swine fever virus YC11WB isolates from wild boar.

PubMed

Lim, Seong-In; Kim, Yong Kwan; Lim, Ji-Ae; Han, Song-Hee; Hyun, Hee-Suk; Kim, Ki-Sun; Hyun, Bang-Hun; Kim, Jae-Jo; Cho, In-Soo; Song, Jae-Young; Choi, Sung-Hyun; Kim, Seung-Hoe; An, Dong-Jun

2017-06-30

Classical swine fever (CSF), a highly contagious disease that affects domestic pigs and wild boar, has serious economic implications. The present study examined the virulence and transmission of CSF virus strain YC11WB (isolated from a wild boar in 2011) in breeding wild boar. Virulence of strain YC11WB in domestic pigs was also examined. Based on the severe clinical signs and high mortality observed among breeding wild boar, the pathogenicity of strain YC11WB resembled that of typical acute CSF. Surprisingly, in contrast to strain SW03 (isolated from breeding pigs in 2003), strain YC11WB showed both acute and strong virulence in breeding pigs. None of three specific monoclonal antibodies (7F2, 7F83, and 6F65) raised against the B/C domain of the SW03 E2 protein bound to the B/C domain of strain YC11WB due to amino acid mutations ( 720 K→R and 723 N→S) in the YC11WB E2 protein. Although strains YC11WB and SW03 belong to subgroup 2.1b, they had different mortality rates in breeding pigs. Thus, if breeding pigs have not developed protective immunity against CSF virus, they may be susceptible to strain YC11WB transmitted by wild boar, resulting in severe economic losses for the pig industry.

Pre-Clinical Evaluation of a Real-Time PCR Assay on a Portable Instrument as a Possible Field Diagnostic Tool: Experiences from the Testing of Clinical Samples for African and Classical Swine Fever Viruses.

PubMed

Liu, L; Luo, Y; Accensi, F; Ganges, L; Rodríguez, F; Shan, H; Ståhl, K; Qiu, H-J; Belák, S

2017-10-01

African swine fever (ASF) and classical swine fever (CSF) are two highly infectious transboundary animal diseases (TADs) that are serious threats to the pig industry worldwide, including in China, the world's largest pork producer. In this study, a duplex real-time PCR assay was developed for the rapid detection and differentiation of African swine fever virus (ASFV) and classical swine fever virus (CSFV). The assay was performed on a portable, battery-powered PCR thermocycler with a low sample throughput (termed as 'T-COR4 assay'). The feasibility and reliability of the T-COR4 assay as a possible field method was investigated by testing clinical samples collected in China. When evaluated with reference materials or samples from experimental infections, the assay performed in a reliable manner, producing results comparable to those obtained from stationary PCR platforms. Of 59 clinical samples, 41 had results identical to a two-step CSFV real-time PCR assay. No ASFV was detected in these samples. The T-COR4 assay was technically easy to perform and produced results within 3 h, including sample preparation. In combination with a simple sample preparation method, the T-COR4 assay provides a new tool for the field diagnosis and differentiation of ASF and CSF, which could be of particular value in remote areas. © 2016 Blackwell Verlag GmbH.

Herpes Zoster Meningitis Presenting With a Cerebrospinal Fluid Leukemoid Reaction in an Adolescent With preB-ALL in Remission.

PubMed

Adachi, Kristina; Song, Sophie X; Kao, Roy L; Van Dyne, Elizabeth; Kempert, Pamela; Deville, Jaime G

2016-08-01

A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia.

Oral ezatiostat HCl (Telintra®, TLK199) and Idiopathic Chronic Neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor

PubMed Central

2011-01-01

Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 × 109/L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4-year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping G-CSF), clearing of fever, and healing of areas of infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to G-CSF, as an oral therapy alternative, or as an adjunct to G-CSF, and further studies are warranted. PMID:22047626

Generation and Efficacy Evaluation of a Recombinant Pseudorabies Virus Variant Expressing the E2 Protein of Classical Swine Fever Virus in Pigs.

PubMed

Wang, Yimin; Yuan, Jin; Cong, Xin; Qin, Hua-Yang; Wang, Chun-Hua; Li, Yongfeng; Li, Su; Luo, Yuzi; Sun, Yuan; Qiu, Hua-Ji

2015-10-01

Classical swine fever (CSF) is an economically important infectious disease of pigs caused by classical swine fever virus (CSFV). Pseudorabies (PR), which is caused by pseudorabies virus (PRV), is another important infectious disease of pigs and other animals. Coinfections of pigs with PRV and CSFV occur occasionally in the field. The modified live vaccine Bartha-K61 strain has played an important role in the control of PR in many countries, including China. Since late 2011, however, increasing PR outbreaks caused by an emerging PRV variant have been reported in Bartha-K61-vaccinated swine populations on many farms in China. Previously, we generated a gE/gI-deleted PRV (rPRVTJ-delgE) based on this PRV variant, which was shown to be safe and can provide rapid and complete protection against lethal challenge with the PRV variant in pigs. Here, we generated a new recombinant PRV variant expressing the E2 gene of CSFV (rPRVTJ-delgE/gI-E2) and evaluated its immunogenicity and efficacy in pigs. The results showed that rPRVTJ-delgE/gI-E2 was safe for pigs, induced detectable anti-PRV and anti-CSFV neutralizing antibodies, and provided complete protection against the lethal challenge with either the PRV TJ strain or the CSFV Shimen strain. The data indicate that rPRVTJ-delgE/gI-E2 is a promising candidate bivalent vaccine against PRV and CSFV coinfections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Enterovirus infection in febrile neonates: A hospital-based prospective cohort study.

PubMed

Lv, Xiao-Qing; Qian, Ling-He; Wu, Tai; Yuan, Tian-Ming

2016-08-01

This study aims to investigate clinical characteristics and microbiological results and to assess the predictors for enterovirus infection in febrile neonates. A prospective cohort study was conducted on 334 febrile patients (age: 0.33-28 days) in 2011-2012 years. Enterovirus RNA was detected by reverse transcription polymerase chain reaction on faeces or cerebrospinal fluid (CSF). Clinical characteristics were compared, and non-conditional logistic regression analysis was performed to determine independent predictors for enterovirus infection. There were 131 episodes of neonatal enterovirus infection (39.22%). Forty-eight (36.64%) developed respiratory symptoms, 69 (52.67%) had diarrhoea, 22 (16.79%) had poor feeding and 34 (25.95%) had rash. Eighteen (13.74%) had lower platelet counts, and CSF specimens were positive for enterovirus RNA in 44.27% (58/131) whose CSF revealed a mean white blood cell counts of 100.38 ± 147.97 cells/mm(3) (range: 2-668 cells/mm(3) ). The positivity of stool 38.92% (130/334) was significantly higher than that of CSF specimens 26.24% (58/221) for enterovirus RNA (P < 0.01). By logistic regression analysis, the following independently predicted enterovirus infection: abnormal CSF test (odds ratio (OR): 12.426, 95% confidence interval (CI): 5.633-27.413), thrombocytopenia (OR: 3.647, 95% CI: 1.312-10.136), duration of fever >3.25 (d) (OR: 2.293, 95% CI: 1.279-4.113), highest temperature >38.35 (°C) (OR: 2.094, 95% CI: 1.342-4.123) and negative bacterial culture (OR: 5.073, 95% CI: 1.504-17.114). Our data indicated that enteroviruses should be routinely considered in the differential diagnosis of febrile neonates. The factors, which may predict the risk of neonatal enterovirus infection, were abnormal CSF test, thrombocytopenia, duration of fever >3.25 (d), highest temperature >38.35 (°C) and negative bacterial culture. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Emergence of 2.1. subgenotype of classical swine fever virus in pig population of India in 2011.

PubMed

Rajkhowa, T K; Hauhnar, Lalthapui; Lalrohlua, Isaac; Mohanarao G, Jagan

2014-01-01

Limited studies are available on molecular epidemiology of classical swine fever virus (CSFV) in India and are restricted to domestic pigs. These studies show the presence of 1.1. genotype. The aim of the present study was to subgenotype four CSFV isolates, two each from the outbreaks of CSF in wild (Sus scrofa) and domestic pigs of Mizoram state, India, in 2011. CSFV isolates were subjected to nucleotide sequencing in E2 and NS5B genomic regions. Phylogenetic analysis of the isolates in both genomic regions was carried out with 39 Indian isolates (4 isolates from the present study of Mizoram state and 35 isolates from the other states of India) and 57 reference sequences retrieved from the GenBank database. Two of the 39 isolates from India were collected from wild boar and were subgenotyped as 2.1. Out of 37 isolates from domestic pigs, only two were subgenotyped as 2.1. The analysis revealed the emergence of 2.1. subgenotype of CSFV in both wild and domestic pigs in India. The isolates from domestic pigs of Mizoram state (CSF/MZ/KOL/73 and CSF/MZ/AIZ/115) were grouped in genotype 1 and subgenotype 1.1., thus confirming that the source of CSF outbreaks in domesticated pigs in Mizoram was not from wild pigs. The current study forms an essential step for better understanding of the epidemiology of 2.1 subgroup as well as the movement and spread of the disease in India.

African and classical swine fever situation in Ivory-Coast and neighboring countries, 2008-2013.

PubMed

Kouakou, K V; Michaud, V; Biego, H G; Gnabro, H P G; Kouakou, A V; Mossoun, A M; Awuni, J A; Minoungou, G L; Aplogan, G L; Awoumé, F K; Albina, E; Lancelot, R; Couacy-Hymann, E

2017-02-01

This study was conducted from 2008 to 2013 to determine the animal health status of Ivory Coast and neighboring countries (Burkina Faso, Ghana, Togo and Benin) for African swine fever (ASF) and classical swine fever (CSF), and to assess the risk factors for ASF introduction in Ivory Coast. Ivory Coast had probably been free from ASF from 1998 to 2014 when it was re-introduced in this country. However, the ASF virus was found in all neighboring countries. In contrast, no evidence of CSF infection was found so far in Ivory Coast and neighboring countries. To assess the risk of ASF reintroduction in Ivory Coast, we surveyed 59 modern pig farms, and 169 pig owners in 19 villages and in two towns. For the village livestock, the major risk factor was the high frequency of pig exchanges with Burkinabe villages. In the commercial sector, many inadequate management practices were observed with respect to ASF. Their identification should enable farmers and other stakeholders to implement a training and prevention program to reduce the introduction risk of ASF in their farms. Copyright © 2016 Elsevier B.V. All rights reserved.

A prospective study of the importance of enteric fever as a cause of non-malarial febrile illness in patients admitted to Chittagong Medical College Hospital, Bangladesh.

PubMed

Maude, Rapeephan R; Ghose, Aniruddha; Samad, Rasheda; de Jong, Hanna K; Fukushima, Masako; Wijedoru, Lalith; Hassan, Mahtab Uddin; Hossain, Md Amir; Karim, Md Rezaul; Sayeed, Abdullah Abu; van den Ende, Stannie; Pal, Sujat; Zahed, A S M; Rahman, Wahid; Karnain, Rifat; Islam, Rezina; Tran, Dung Thi Ngoc; Ha, Tuyen Thanh; Pham, Anh Hong; Campbell, James I; van Doorn, H Rogier; Maude, Richard J; van der Poll, Tom; Wiersinga, W Joost; Day, Nicholas P J; Baker, Stephen; Dondorp, Arjen M; Parry, Christopher M; Faiz, Md Abul

2016-10-13

Fever is a common cause of hospital admission in Bangladesh but causative agents, other than malaria, are not routinely investigated. Enteric fever is thought to be common. Adults and children admitted to Chittagong Medical College Hospital with a temperature of ≥38.0 °C were investigated using a blood smear for malaria, a blood culture, real-time PCR to detect Salmonella Typhi, S. Paratyphi A and other pathogens in blood and CSF and an NS1 antigen dengue ELISA. We enrolled 300 febrile patients with a negative malaria smear between January and June 2012: 156 children (aged ≤15 years) and 144 adults with a median (interquartile range) age of 13 (5-31) years and median (IQR) illness duration before admission of five (2-8) days. Clinical enteric fever was diagnosed in 52 patients (17.3 %), lower respiratory tract infection in 48 (16.0 %), non-specific febrile illness in 48 (16.0 %), a CNS infection in 37 patients (12.3 %), urinary sepsis in 23 patients (7.7 %), an upper respiratory tract infection in 21 patients (7.0 %), and diarrhea or dysentery in 21 patients (7.0 %). Malaria was still suspected in seven patients despite a negative microscopy test. S. Typhi was detected in blood by culture or PCR in 34 (11.3 %) of patients. Of note Rickettsia typhi and Orientia tsutsugamushi were detected by PCR in two and one patient respectively. Twenty-nine (9 %) patients died during their hospital admission (15/160 (9.4 %) of children and 14/144 (9.7 %) adults). Two of 52 (3.8 %) patients with enteric fever, 5/48 (10.4 %) patients with lower respiratory tract infections, and 12/37 (32.4 %) patients with CNS infection died. Enteric fever was confirmed in 11.3 % of patients admitted to this hospital in Bangladesh with non-malaria fever. Lower respiratory tract and CNS infections were also common. CNS infections in this location merit more detailed study due to the high mortality.

Laboratory diagnosis and genetic analysis of a family clustering outbreak of aseptic meningitis due to echovirus 30

PubMed Central

Ye, Hongyan; Yan, Juying; Xie, Guoliang; Cui, Dawei; Yu, Fei; Wang, Yiyin; Yang, Xianzhi; Zhou, Fangman; Zhang, Yanjun; Tian, Xueli; Chen, Yu

2016-01-01

Echovirus 30 (E30) is a major pathogen associated with aseptic meningitis. In the summer of 2014, a family clustering aseptic meningitis outbreak occurred in urban–rural fringe of Ningbo city in Zhejiang Province in China. To identify the etiologic agent, specimens were tested by cell culture and reverse transcriptase–polymerase chain reaction. Pathogenic examination confirmed that the outbreak is caused by E30. The first case is a 6-year-old child, who studied in kindergarten in local, suffered from headache and fever. Same symptoms appeared in his parents, aunts, and other six relatives continuously. Meanwhile, vomiting occurred in majority of the patients and diarrhea in parts of them. White blood cells in cerebrospinal fluid (CSF) exceeded normal range in all patients. Protein levels in CSF were above normal range in half of the patients. Glucose levels in CSF were within normal range in all patients. We isolated six strains E30 in the stool specimens of patients, and carried out sequencing analysis to VP1 region. Sequencing results showed that 100% sequence identity was seen in both nucleotide and amino acid levels. Phylogenetic analysis discovered that isolate in this study was grouped into sublineage D2 together with sequences isolated from other areas of China in the 2000s and 2010s. Our study is the first family clustering outbreak of aseptic meningitis caused by E30 in Zhejiang Province in China. It is essential to establish an enterovirus molecular surveillance system in China to prevent mass outbreaks in Zhejiang. PMID:27646838

Laboratory diagnosis and genetic analysis of a family clustering outbreak of aseptic meningitis due to echovirus 30.

PubMed

Zheng, Shufa; Ye, Hongyan; Yan, Juying; Xie, Guoliang; Cui, Dawei; Yu, Fei; Wang, Yiyin; Yang, Xianzhi; Zhou, Fangman; Zhang, Yanjun; Tian, Xueli; Chen, Yu

2016-09-01

Echovirus 30 (E30) is a major pathogen associated with aseptic meningitis. In the summer of 2014, a family clustering aseptic meningitis outbreak occurred in urban-rural fringe of Ningbo city in Zhejiang Province in China. To identify the etiologic agent, specimens were tested by cell culture and reverse transcriptase-polymerase chain reaction. Pathogenic examination confirmed that the outbreak is caused by E30. The first case is a 6-year-old child, who studied in kindergarten in local, suffered from headache and fever. Same symptoms appeared in his parents, aunts, and other six relatives continuously. Meanwhile, vomiting occurred in majority of the patients and diarrhea in parts of them. White blood cells in cerebrospinal fluid (CSF) exceeded normal range in all patients. Protein levels in CSF were above normal range in half of the patients. Glucose levels in CSF were within normal range in all patients. We isolated six strains E30 in the stool specimens of patients, and carried out sequencing analysis to VP1 region. Sequencing results showed that 100% sequence identity was seen in both nucleotide and amino acid levels. Phylogenetic analysis discovered that isolate in this study was grouped into sublineage D2 together with sequences isolated from other areas of China in the 2000s and 2010s. Our study is the first family clustering outbreak of aseptic meningitis caused by E30 in Zhejiang Province in China. It is essential to establish an enterovirus molecular surveillance system in China to prevent mass outbreaks in Zhejiang.

Modeling Classical Swine Fever Outbreak-Related Outcomes

PubMed Central

Yadav, Shankar; Olynk Widmar, Nicole J.; Weng, Hsin-Yi

2016-01-01

The study was carried out to estimate classical swine fever (CSF) outbreak-related outcomes, such as epidemic duration and number of infected, vaccinated, and depopulated premises, using defined most likely CSF outbreak scenarios. Risk metrics were established using empirical data to select the most likely CSF outbreak scenarios in Indiana. These scenarios were simulated using a stochastic between-premises disease spread model to estimate outbreak-related outcomes. A total of 19 single-site (i.e., with one index premises at the onset of an outbreak) and 15 multiple-site (i.e., with more than one index premises at the onset of an outbreak) outbreak scenarios of CSF were selected using the risk metrics. The number of index premises in the multiple-site outbreak scenarios ranged from 4 to 32. The multiple-site outbreak scenarios were further classified into clustered (N = 6) and non-clustered (N = 9) groups. The estimated median (5th, 95th percentiles) epidemic duration (days) was 224 (24, 343) in the single-site and was 190 (157, 251) and 210 (167, 302) in the clustered and non-clustered multiple-site outbreak scenarios, respectively. The median (5th, 95th percentiles) number of infected premises was 323 (0, 488) in the single-site outbreak scenarios and was 529 (395, 662) and 465 (295, 640) in the clustered and non-clustered multiple-site outbreak scenarios, respectively. Both the number and spatial distributions of the index premises affected the outcome estimates. The results also showed the importance of implementing vaccinations to accommodate depopulation in the CSF outbreak controls. The use of routinely collected surveillance data in the risk metrics and disease spread model allows end users to generate timely outbreak-related information based on the initial outbreak’s characteristics. Swine producers can use this information to make an informed decision on the management of swine operations and continuity of business, so that potential losses could be minimized during a CSF outbreak. Government authorities might use the information to make emergency preparedness plans for CSF outbreak control. PMID:26870741

Controlling disease outbreaks in wildlife using limited culling: modelling classical swine fever incursions in wild pigs in Australia.

PubMed

Cowled, Brendan D; Garner, M Graeme; Negus, Katherine; Ward, Michael P

2012-01-16

Disease modelling is one approach for providing new insights into wildlife disease epidemiology. This paper describes a spatio-temporal, stochastic, susceptible- exposed-infected-recovered process model that simulates the potential spread of classical swine fever through a documented, large and free living wild pig population following a simulated incursion. The study area (300 000 km2) was in northern Australia. Published data on wild pig ecology from Australia, and international Classical Swine Fever data was used to parameterise the model. Sensitivity analyses revealed that herd density (best estimate 1-3 pigs km-2), daily herd movement distances (best estimate approximately 1 km), probability of infection transmission between herds (best estimate 0.75) and disease related herd mortality (best estimate 42%) were highly influential on epidemic size but that extraordinary movements of pigs and the yearly home range size of a pig herd were not. CSF generally established (98% of simulations) following a single point introduction. CSF spread at approximately 9 km2 per day with low incidence rates (< 2 herds per day) in an epidemic wave along contiguous habitat for several years, before dying out (when the epidemic arrived at the end of a contiguous sub-population or at a low density wild pig area). The low incidence rate indicates that surveillance for wildlife disease epidemics caused by short lived infections will be most efficient when surveillance is based on detection and investigation of clinical events, although this may not always be practical. Epidemics could be contained and eradicated with culling (aerial shooting) or vaccination when these were adequately implemented. It was apparent that the spatial structure, ecology and behaviour of wild populations must be accounted for during disease management in wildlife. An important finding was that it may only be necessary to cull or vaccinate relatively small proportions of a population to successfully contain and eradicate some wildlife disease epidemics.

Controlling disease outbreaks in wildlife using limited culling: modelling classical swine fever incursions in wild pigs in Australia

PubMed Central

2012-01-01

Disease modelling is one approach for providing new insights into wildlife disease epidemiology. This paper describes a spatio-temporal, stochastic, susceptible- exposed-infected-recovered process model that simulates the potential spread of classical swine fever through a documented, large and free living wild pig population following a simulated incursion. The study area (300 000 km2) was in northern Australia. Published data on wild pig ecology from Australia, and international Classical Swine Fever data was used to parameterise the model. Sensitivity analyses revealed that herd density (best estimate 1-3 pigs km-2), daily herd movement distances (best estimate approximately 1 km), probability of infection transmission between herds (best estimate 0.75) and disease related herd mortality (best estimate 42%) were highly influential on epidemic size but that extraordinary movements of pigs and the yearly home range size of a pig herd were not. CSF generally established (98% of simulations) following a single point introduction. CSF spread at approximately 9 km2 per day with low incidence rates (< 2 herds per day) in an epidemic wave along contiguous habitat for several years, before dying out (when the epidemic arrived at the end of a contiguous sub-population or at a low density wild pig area). The low incidence rate indicates that surveillance for wildlife disease epidemics caused by short lived infections will be most efficient when surveillance is based on detection and investigation of clinical events, although this may not always be practical. Epidemics could be contained and eradicated with culling (aerial shooting) or vaccination when these were adequately implemented. It was apparent that the spatial structure, ecology and behaviour of wild populations must be accounted for during disease management in wildlife. An important finding was that it may only be necessary to cull or vaccinate relatively small proportions of a population to successfully contain and eradicate some wildlife disease epidemics. PMID:22243996

Safety and immunogenicity of a gE/gI/TK gene-deleted pseudorabies virus variant expressing the E2 protein of classical swine fever virus in pigs.

PubMed

Lei, Jian-Lin; Xia, Shui-Li; Wang, Yimin; Du, Mingliang; Xiang, Guang-Tao; Cong, Xin; Luo, Yuzi; Li, Lian-Feng; Zhang, Lingkai; Yu, Jiahui; Hu, Yonghao; Qiu, Hua-Ji; Sun, Yuan

2016-06-01

Classical swine fever (CSF) and pseudorabies (PR) are both major infectious diseases of pigs, causing enormous economic losses to the swine industry in many countries. A marker vaccine that enables differentiation of infected from vaccinated animals (DIVA) is highly desirable for control and eradication of these two diseases in endemic areas. Since late 2011, PR outbreaks have been frequently reported in many Bartha-K61-vaccinated pig farms in China. It has been demonstrated that a pseudorabies virus (PRV) variant with altered antigenicity and increased pathogenicity was responsible for the outbreaks. Previously, we showed that rPRVTJ-delgE/gI/TK, a gE/gI/TK-deleted PRV variant, was safe for susceptible animals and provided a complete protection against lethal PRV variant challenge, indicating that rPRVTJ-delgE/gI/TK can be used as an attractive vaccine vector. To develop a safe bivalent vaccine against CSF and PR, we generated a recombinant virus rPRVTJ-delgE/gI/TK-E2 expressing the E2 protein of classical swine fever virus (CSFV) based on rPRVTJ-delgE/gI/TK and evaluated its safety and immunogenicity in pigs. The results indicated that pigs (n=5) immunized with rPRVTJ-delgE/gI/TK-E2 of different doses did not exhibit clinical signs or viral shedding following immunization, the immunized pigs produced anti-PRV or anti-CSFV neutralizing antibodies and the pigs immunized with 10(6) or 10(5) TCID50 rPRVTJ-delgE/gI/TK-E2 were completely protected against the lethal challenge with either CSFV Shimen strain or variant PRV TJ strain. These findings suggest that rPRVTJ-delgE/gI/TK-E2 is a promising bivalent DIVA vaccine candidate against CSFV and PRV coinfections. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Remission induction of refractory anaemia with excess blasts in transformation by sole treatment with granulocyte colony-stimulating factor with persistent chromosomal abnormality.

PubMed

Kondo, Haruki; Kasahara, Yasunori; Mori, Akinori

2002-01-01

We report a patient with myelodysplastic syndrome (MDS), refractory anaemia with excess blasts in transformation, in whom complete remission (CR) was achieved with the administration of granulocyte colony-stimulating factor (G-CSF). The 76-year-old patient was admitted to our hospital with a fever and a productive cough; a diagnosis of pneumonia was thus made. Following treatment with antibiotics, the patient's condition improved, and MDS was diagnosed from peripheral blood and bone marrow examinations after the patient recovered from the infection. The patient achieved a sustained haematological CR that was confirmed by morphological and flow cytometric examination after treatment with G-CSF alone, although chromosomal abnormalities persisted. According to the literature, in almost all patients with acute myeloid leukaemia or MDS who were reported to achieve CR by G-CSF, the course was associated with infection, although our case did not have this complication during the course of G-CSF therapy. We suggest that patients with G-CSF alone without infection can achieve CR and that this may be related to a differentiation effect of G-CSF based on persistent chromosomal abnormality in this case. Copyright 2002 S. Karger AG, Basel

Porcine circovirus type 2 (PCV2) infection decreases the efficacy of an attenuated classical swine fever virus (CSFV) vaccine

PubMed Central

2011-01-01

The Lapinized Philippines Coronel (LPC) vaccine, an attenuated strain of classical swine fever virus (CSFV), is an important tool for the prevention and control of CSFV infection and is widely and routinely used in most CSF endemic areas, including Taiwan. The aim of this study was to investigate whether PCV2 infection affects the efficacy of the LPC vaccine. Eighteen 6-week-old, cesarean-derived and colostrum-deprived (CDCD), crossbred pigs were randomly assigned to four groups. A total of 105.3 TCID50 of PCV2 was experimentally inoculated into pigs through both intranasal and intramuscular routes at 0 days post-inoculation (dpi) followed by LPC vaccination 12 days later. All the animals were challenged with wild-type CSFV (ALD stain) at 27 dpi and euthanized at 45 dpi. Following CSFV challenge, the LPC-vaccinated pigs pre-inoculated with PCV2 showed transient fever, viremia, and viral shedding in the saliva and feces. The number of IgM+, CD4+CD8-CD25+, CD4+CD8+CD25+, and CD4-CD8+CD25+ lymphocyte subsets and the level of neutralizing antibodies against CSFV were significantly higher in the animals with LPC vaccination alone than in the pigs with PCV2 inoculation/LPC vaccination. In addition, PCV2-derived inhibition of the CSFV-specific cell proliferative response of peripheral blood mononuclear cells (PBMCs) was demonstrated in an ex vivo experiment. These findings indicate that PCV2 infection decreases the efficacy of the LPC vaccine. This PCV2-derived interference may not only allow the invasion of wild-type CSFV in pig farms but also increases the difficulty of CSF prevention and control in CSF endemic areas. PMID:22129109

THE CHALLENGE OF DETECTING CLASSICAL SWINE FEVER VIRUS CIRCULATION IN WILD BOAR (SUS SCROFA): SIMULATION OF SAMPLING OPTIONS.

PubMed

Sonnenburg, Jana; Schulz, Katja; Blome, Sandra; Staubach, Christoph

2016-10-01

Classical swine fever (CSF) is one of the most important viral diseases of domestic pigs ( Sus scrofa domesticus) and wild boar ( Sus scrofa ). For at least 4 decades, several European Union member states were confronted with outbreaks among wild boar and, as it had been shown that infected wild boar populations can be a major cause of primary outbreaks in domestic pigs, strict control measures for both species were implemented. To guarantee early detection and to demonstrate freedom from disease, intensive surveillance is carried out based on a hunting bag sample. In this context, virologic investigations play a major role in the early detection of new introductions and in regions immunized with a conventional vaccine. The required financial resources and personnel for reliable testing are often large, and sufficient sample sizes to detect low virus prevalences are difficult to obtain. We conducted a simulation to model the possible impact of changes in sample size and sampling intervals on the probability of CSF virus detection based on a study area of 65 German hunting grounds. A 5-yr period with 4,652 virologic investigations was considered. Results suggest that low prevalences could not be detected with a justifiable effort. The simulation of increased sample sizes per sampling interval showed only a slightly better performance but would be unrealistic in practice, especially outside the main hunting season. Further studies on other approaches such as targeted or risk-based sampling for virus detection in connection with (marker) antibody surveillance are needed.

Cryptococcal meningitis in HIV-infected patients at Chiang Mai University Hospital: a retrospective study.

PubMed

Chaiwarith, Romanee; Vongsanim, Surachet; Supparatpinyo, Khuanchai

2014-05-01

Cryptococcal meningitis (CM) is a common central nervous system infection in HIV-infected patients. This study aimed to determine treatment outcomes among HIV-infected patients who had cryptococcal meningitis and to determine predictors of death. We conducted a retrospective cohort study among HIV-infected patients receiving care at Chiang Mai University Hospital from January 1, 2005 to December 31, 2010. We studied 79 patients; 45 (57.0%) were male and the mean age was 35.1 +/- 7.2 years. Eleven patients (13.9%) had previous opportunistic infection. The most common presenting symptoms were headache (63 patients, 79.8%), fever (49 patients, 62.0%), and altered consciousness (21 patients, 26.6%). The median CD4+ cell count was 20 cells/mm3 [Interquartile range (IQR) 10, 53]. The in-hospital, 90-day, and 1-year mortality rates were 24.1%, 32.4%, and 52.2%, respectively. The CM attributable in-hospital, 90-day and 1-year mortality rates were 13.9%, 20.3%, and 23.2%, respectively. Predictors associated with a 1-year mortality were a high cerebrospinal (CSF) cryptococcal antigen titer (> 1:10,000) [Odds Ratio (OR) =7.08, 95% confidence interval (CI): 1.62-31.00, p = 0.009], and altered consciousness at presentation (OR = 5.27; 95% CI: 1.16-24.05; p = 0.032). Cryptococcal meningitis is an important cause of death in HIV-infected patients. HIV-infected patients with a low CD4+ cell count, a headache, fever and altered consciousness should be investigated for CM and those with a high CSF cryptococcal antigen titer are at high risk for mortality.

Role of the nitric oxide/cyclic GMP/Ca2+ signaling pathway in the pyrogenic effect of interleukin-1beta.

PubMed

Palmi, Mitri; Meini, Antonella

2002-04-01

Interleukin-1beta (IL-1beta) has a wide spectrum of inflammatory, metabolic, haemopoietic, and immunological properties. Because it produces fever when injected into animals and humans, it is considered an endogenous pyrogen. There is evidence to suggest that Ca2+ plays a critical role in the central mechanisms of thermoregulation, and in the intracellular signaling pathways controlling fever induced by IL-1beta and other pyrogens. Data from different labs indicate that Ca2+ and Na+ determine the temperature set point in the posterior hypothalamus (PH) of various mammals and that changes in Ca2+ and PGE2 concentrations in the cerebrospinal fluid (CSF) of these animals are associated with IL-1beta-induced fever. Antipyretic drugs such as acetylsalicylic acid, dexamethasone, and lipocortin 5-(204-212) peptide counteract IL-1beta-induced fever and abolish changes in Ca2+ and PGE2 concentrations in CSF. In vitro studies have established that activation of the nitric oxide (NO)/cyclic GMP (cGMP) pathway is part of the signaling cascade transducing Ca2+ mobilization in response to IL-1beta and that the ryanodine (RY)- and inositol-(1,4,5)-trisphosphate (IP3)-sensitive pools are the main source of the mobilized Ca2+. It is concluded that the NO/cGMP/Ca2+ pathway is part of the signaling cascade subserving some of the multiple functions of IL-1beta.

IL-23/IL-17/G-CSF pathway is associated with granulocyte recruitment to the lung during African swine fever.

PubMed

Karalyan, Z; Voskanyan, H; Ter-Pogossyan, Z; Saroyan, D; Karalova, E

2016-10-15

The interleukin (IL)-23/IL-17 pathway plays a crucial role in various forms of inflammation but its function in acute African swine fever (ASF) is not well understood. Thus, in this study, we aimed to find out whether IL-23/IL-17/G-CSF is released in acute ASF and what function it may have. The present study revealed that the production of IL-17 and IL-23 were significantly increased in the sera of ASFV infected pigs. Using ELISA, we found that the serum levels of IL-23 and IL-17 have overexpressed in ASF virus infected pigs compared with healthy controls. The levels of IL-17 and IL-23 increase in the early stages and the levels of G-CSF and C - reactive protein in the later stages of ASF. Simultaneously, with the increase of the levels of IL-23/IL-17 extravasation of granular leukocytes in the tissue (diapedesis) is observed. Diapedesis can explain the neutropenia that we identified previously in the terminal stages of ASF. The increase in serum levels of IL-23/IL-17 is preceded by enhanced migration of neutrophils in tissues, and the last one is preceded by neutropenia. The increase in serum levels of G-CSF has compensatory nature, directed on stimulation of proliferation of granulocytes. Taken together, our results revealed an overexpression of the IL-23/IL-17 axis in the ASF virus infected pigs, suggesting that it may be a crucial pathway in the diapedesis at ASF. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute human herpes virus 7 (HHV-7) encephalitis in an immunocompetent adult patient: a case report and review of literature.

PubMed

Riva, Nicoletta; Franconi, Iacopo; Meschiari, Marianna; Franceschini, Erica; Puzzolante, Cinzia; Cuomo, Gianluca; Bianchi, Alessandro; Cavalleri, Francesca; Genovese, Maurilio; Mussini, Cristina

2017-06-01

We report a case of an acute HHV-7 encephalitis involving the nucleus of the VI cranial nerve in an immunocompetent host. The patient was an adult male admitted to our Clinic with headache, diplopia, fever, nausea, vertigo, asthenia and general malaise. PCR for viral and bacterial genomes was run on both serum and cerebral spinal fluid (CSF) after performing lumbar puncture, resulting positive only for HHV-7 DNA on CSF. MRI showed hyperintensity in FLAIR signal in the dorsal pons, in the area of the VI cranial nerve nucleus. Empirical therapy with Acyclovir and Dexamethasone was started at the time of admission and was continued after the microbiology results. After three days of therapy diplopia, fever and other previous clinical manifestations improved and the patient recovered normal sight. Our case report contributes to a better understanding of the presentation, diagnosis and treatment of HHV-7 encephalitis in immunocompetent patients due to reactivation in adult age.

Risk score for identifying adults with CSF pleocytosis and negative CSF Gram stain at low risk for an urgent treatable cause.

PubMed

Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C; Khoury, Nabil; Hadi, Christiane M; van der Ende, Arie; Wootton, Susan H; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

2013-08-01

We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n = 193) and a retrospective validation (n = 567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high (≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95% CI 93.9-100.0%) in the validation cohort and 100.0% (95% CI 97.8-100.0%) in bacterial meningitis patients. The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

RISK SCORE FOR IDENTIFYING ADULTS WITH CSF PLEOCYTOSIS AND NEGATIVE CSF GRAM STAIN AT LOW RISK FOR AN URGENT TREATABLE CAUSE

PubMed Central

Hasbun, Rodrigo; Bijlsma, Merijn; Brouwer, Matthijs C; Khoury, Nabil; Hadi, Christiane M; van der Ende, Arie; Wootton, Susan H.; Salazar, Lucrecia; Hossain, Md Monir; Beilke, Mark; van de Beek, Diederik

2013-01-01

Background We aimed to derive and validate a risk score that identifies adults with cerebrospinal fluid (CSF) pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. Methods Patients with CSF pleocytosis and a negative CSF Gram stain were stratified into a prospective derivation (n=193) and a retrospective validation (n=567) cohort. Clinically related baseline characteristics were grouped into three composite variables, each independently associated with a set of predefined urgent treatable causes. We subsequently derived a risk score classifying patients into low (0 composite variables present) or high ( ≥ 1 composite variables present) risk for an urgent treatable cause. The sensitivity of the risk score was determined in the validation cohort and in a prospective case series of 214 adults with CSF-culture proven bacterial meningitis, CSF pleocytosis and a negative Gram stain. Findings A total of 41 of 193 patients (21%) in the derivation cohort and 71 of 567 (13%) in the validation cohort had an urgent treatable cause. Sensitivity of the dichotomized risk score to detect an urgent treatable cause was 100.0% (95%CI 93.9-100.0%) in the validation cohort and 100.0% (95%CI 97.8-100.0%) in bacterial meningitis patients. Interpretation The risk score can be used to identify adults with CSF pleocytosis and a negative CSF Gram stain at low risk for an urgent treatable cause. PMID:23619080

A serological survey on classical swine fever (CSF), Aujeszky's disease (AD) and porcine reproductive and respiratory syndrome (PRRS) virus infections in French wild boars from 1991 to 1998.

PubMed

Albina, E; Mesplède, A; Chenut, G; Le Potier, M F; Bourbao, G; Le Gal, S; Leforban, Y

2000-11-15

In early 1992, a CSF epizootic was clinically recognised in a wild boar population of approximately 1300 animals within an area of 250km(2) located in the east of France. In order to check the CSF situation in wild boars outside this area, a serological survey was carried out in the rest of France, for 8 consecutive years (1991-1998). This paper reports on the results obtained during this survey which included wild boars shot during the hunting period but also boars reared within fences. Around 1000-2700 sera a year were tested for the presence of antibodies to classical swine fever virus (CSFV) and also to Aujeszky's disease virus (ADV). Out of 12025 sera tested over the whole period, 80 wild boars were found positive for CSF antibodies. Sixty of them were collected on wild boars shot during the years 1992-1994 in the epizootic area located in east of France and 10 were collected in Corsica during the years 1994-1996. The last four positive samples were single reactors coming from areas or farms, which were thereafter confirmed to be serologically negative. These results together with the fact that no disease has been reported so far illustrate that the French wild boar population is probably not concerned by CSF infection (excepted in the east of France where the disease has now become enzootic). Two hundred and forty nine sera were initially detected as CSF positive but confirmed secondarily as positive for border disease (BD) antibodies. This finding shows that wild boars are also susceptible to infection by ruminant pestiviruses. Four hundred and twenty three wild boars have been found positive for ADV antibodies. In addition, from 1993 to 1995, 909 samples were tested for the presence of antibodies to porcine reproductive and respiratory syndrome virus (PRRSV). Thirty three of them were positive. The results on AD and PRRS antibody detection show that wild boars may constitute a reservoir for various infectious diseases of pigs.

A Simulation Model to Determine Sensitivity and Timeliness of Surveillance Strategies.

PubMed

Schulz, J; Staubach, C; Conraths, F J; Schulz, K

2017-12-01

Animal surveillance systems need regular evaluation. We developed an easily applicable simulation model of the German wild boar population to investigate two evaluation attributes: the sensitivity and timeliness (i.e. the ability to detect a disease outbreak rapidly) of a surveillance system. Classical swine fever (CSF) was used as an example for the model. CSF is an infectious disease that may lead to massive economic losses. It can affect wild boar as well as domestic pigs, and CSF outbreaks in domestic pigs have been linked to infections in wild boar. Awareness of the CSF status in wild boar is therefore vital. Our non-epidemic simulation model is based on real data and evaluates the currently implemented German surveillance system for CSF in wild boar. The results show that active surveillance for CSF fulfils the requirements of detecting an outbreak with 95% confidence within one year after the introduction of CSF into the wild boar population. Nevertheless, there is room for improved performance and efficiency by more homogeneous (active and passive) sampling of wild boar over the year. Passive surveillance alone is not sufficient to meet the requirements for detecting the infection. Although CSF was used as example to develop the model, it may also be applied to the evaluation of other surveillance systems for viral diseases in wild boar. It is also possible to compare sensitivity and timeliness across hypothetical alternative or risk-based surveillance strategies. © 2016 Blackwell Verlag GmbH.

[Nonspecific clinical signs in pigs and use of exclusion diagnosis for classical swine fever: a survey among pig farmers and veterinary practitioners].

PubMed

Elbers, A R W; Gorgievski-Duijvesteijn, M J; van der Velden, P G; Loeffen, W L A

2007-05-01

Outbreaks of Classical Swine Fever (CSF) occurred in spring 2006 in Germany close to the Dutch border. On 6th April Dutch pig farmers were given the possibility to submit blood samples directly via their veterinary practitioner to the National Reference Laboratory for CSF if their pigs had non-specific clinical symptoms or if pigs were being treated with antibiotics. The pig farm was not quarantined and was not visited by the veterinary authorities. Over a period of 9 weeks 156 pig farmers submitted whole blood samples via 50 different veterinary practices. All samples tested negative in the PCR test. These pig farmers and veterinary practitioners were asked to respond to a postal questionnaire with questions regarding their experience with this new diagnostic possibility, the distribution of the costs involved, a comparison with other instruments, such as official notification or use of a leukocyte count test, and their knowledge of clinical signs of CSF. 65 pig farmers (42%) and 33 veterinary practices (66%) returned the questionnaire. The main results indicated that pig farmers (72%) would use this type of exclusion diagnostics sooner than that they would approach the veterinary authorities (practitioners: 86%). Moreover the respondents considered the fact that the farm was not quarantined immediately to be an advantage (pig farmers, 79%; practitioners, 88%). 32 percent of the pig farmers were not aware that they were required to submit blood samples if pigs were being treated with antibiotics (practitioners: 11%). The majority of pig farmers and practitioners were not satisfied with the current distribution of the costs involved: in their opinion the costs of the PCR test, the costs of the veterinary practitioner and the costs for shipping the samples to the reference laboratory should be paid out of the Animal Health Fund (50% government and 50% industry) or by the government. If the current distribution of the costs is not changed, a large proportion of the pig farmers indicated that they would not use this form of exclusion diagnostics for CSF in the future. Pig farmers appeared to have a rather limited knowledge of the clinical signs of CSF: 33% of the pig farmers could mention maximally three clinical signs of CSF, and 7% could not mention a single clinical sign of CSF and said they were entirely dependent on the practitioners' ability to judge a CSF-suspect situation.

Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral replicon as a non-transmissible vaccine candidate against CSF and JE infections.

PubMed

Yang, Zhenhua; Wu, Rui; Li, Robert W; Li, Ling; Xiong, Zhongliang; Zhao, Haizhong; Guo, Deyin; Pan, Zishu

2012-04-01

A trans-complemented chimeric CSF-JE virus replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The CSFV E2 gene was deleted, and a fragment containing the region encoding a truncated envelope protein (tE, amino acid 292-402, domain III) of JE virus (JEV) was inserted into the resultant plasmid, pA187delE2, to generate the recombinant cDNA clone pA187delE2/JEV-tE. Porcine kidney 15 (PK15) cells that constitutively express the CSFV E2p7 proteins were then transfected with in vitro-transcribed RNA from pA187delE2/JEV-tE. As a result, the chimeric CSF-JE virus replicon particle (VRP), rv187delE2/JEV-tE, was rescued. In a mouse model, immunization with the chimeric CSF-JE VRP induced strong production of JEV-specific antibody and conferred protection against a lethal JEV challenge. Pigs immunized with CSF-JE VRP displayed strong anti-CSFV and anti-JEV antibody responses and protection against CSFV and JEV challenge infections. Our evidence suggests that E2-complemented CSF-JE VRP not only has potential as a live-attenuated non-transmissible vaccine candidate against CSF and JE but also serves as a potential DIVA (Differentiating Infected from Vaccinated Animals) vaccine for CSF in pigs. Together, our data suggest that the non-transmissible chimeric VRP expressing foreign antigenic proteins may represent a promising strategy for bivalent DIVA vaccine design. Copyright © 2012 Elsevier B.V. All rights reserved.

A Review of Classical Swine Fever Virus and Routes of Introduction into the United States and the Potential for Virus Establishment.

PubMed

Brown, Vienna R; Bevins, Sarah N

2018-01-01

Classical swine fever (CSF) is caused by CSF virus (CSFV) which can be the source of substantial morbidity and mortality events in affected swine. The disease can take one of several forms (acute, chronic, or prenatal) and depending on the virulence of the inoculating strain may result in a lethal infection irrespective of the form acquired. Because of the disease-free status of the United States and the high cost of a viral incursion, a summary of US vulnerabilities for viral introduction and persistence is provided. The legal importation of live animals as well as animal products, byproducts, and animal feed serve as a potential route of viral introduction. Current import regulations are described as are mitigation strategies that are commonly utilized to prevent pathogens, including CSFV, from entering the US. The illegal movement of suids and their products as well as an event of bioterrorism are both feasible routes of viral introduction but are difficult to restrict or regulate. Ultimately, recommendations are made for data that would be useful in the event of a viral incursion. Population and density mapping for feral swine across the United States would be valuable in the event of a viral introduction or spillover; density data could further contribute to understanding the risk of infection in domestic swine. Additionally, ecological and behavioral studies, including those that evaluate the effects of anthropogenic food sources that support feral swine densities far above the carrying capacity would provide invaluable insight to our understanding of how human interventions affect feral swine populations. Further analyses to determine the sampling strategies necessary to detect low levels of antibody prevalence in feral swine would also be valuable.

A Review of Classical Swine Fever Virus and Routes of Introduction into the United States and the Potential for Virus Establishment

PubMed Central

Brown, Vienna R.; Bevins, Sarah N.

2018-01-01

Classical swine fever (CSF) is caused by CSF virus (CSFV) which can be the source of substantial morbidity and mortality events in affected swine. The disease can take one of several forms (acute, chronic, or prenatal) and depending on the virulence of the inoculating strain may result in a lethal infection irrespective of the form acquired. Because of the disease-free status of the United States and the high cost of a viral incursion, a summary of US vulnerabilities for viral introduction and persistence is provided. The legal importation of live animals as well as animal products, byproducts, and animal feed serve as a potential route of viral introduction. Current import regulations are described as are mitigation strategies that are commonly utilized to prevent pathogens, including CSFV, from entering the US. The illegal movement of suids and their products as well as an event of bioterrorism are both feasible routes of viral introduction but are difficult to restrict or regulate. Ultimately, recommendations are made for data that would be useful in the event of a viral incursion. Population and density mapping for feral swine across the United States would be valuable in the event of a viral introduction or spillover; density data could further contribute to understanding the risk of infection in domestic swine. Additionally, ecological and behavioral studies, including those that evaluate the effects of anthropogenic food sources that support feral swine densities far above the carrying capacity would provide invaluable insight to our understanding of how human interventions affect feral swine populations. Further analyses to determine the sampling strategies necessary to detect low levels of antibody prevalence in feral swine would also be valuable. PMID:29556501

Classical Swine Fever-An Updated Review.

PubMed

Blome, Sandra; Staubach, Christoph; Henke, Julia; Carlson, Jolene; Beer, Martin

2017-04-21

Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries are mainly based on classical intervention measures; i.e., quarantine and strict culling of affected herds. In these countries, vaccination is only an emergency option. However, live vaccines are used for controlling the disease in endemically infected regions in Asia, Eastern Europe, the Americas, and some African countries. Here, we will provide a concise, updated review on virus properties, clinical signs and pathology, epidemiology, pathogenesis and immune responses, diagnosis and vaccination possibilities.

[Meningitis and white matter lesions due to Streptococcus mitis in a previously healthy child].

PubMed

Yiş, Reyhan; Yüksel, Ciğdem Nükhet; Derundere, Umit; Yiş, Uluç

2011-10-01

Streptococcus mitis, an important member of viridans streptococci, is found in the normal flora of the oropharynx, gastrointestinal tract, female genital tract and skin. Although it is of low pathogenicity and virulence, it may cause serious infections in immunocompromised patients. Meningitis caused by S.mitis has been described in patients with previous spinal anesthesia, neurosurgical procedure, malignancy, bacterial endocarditis with neurological complications and alcoholics, but it is rare in patients who are previously healthy. In this report, a rare case of meningoencephalitis caused by S.mitis developed in a previously healthy child has been presented. A previously healthy eight-year-old girl who presented with fever, altered state of consciousness, and headache was hospitalized in intensive care unit with the diagnosis of meningitis. Past history revealed that she was treated with amoxicillin-clavulanate for acute sinusitis ten days before her admission. Whole blood count revealed the followings: hemoglobin 13 g/dl, white blood cell count 18.6 x 109/L (90% neutrophils), platelet count 200 x 109/L and 150 leucocytes were detected on cerebrospinal fluid (CSF) examination. Protein and glucose levels of CSF were 80 mg/dl and 40 mg/dl (concomitant blood glucose 100 mg/dl), respectively. Brain magnetic resonance imaging (MRI) revealed widespread white matter lesions, and alpha-hemolytic streptococci were grown in CSF culture. The isolate was identified as S.mitis with conventional methods, and also confirmed by VITEK2 (bioMerieux, France) and API 20 STREP (bioMerieux, France) systems. Isolate was found susceptible to penicillin, erythromycin, clindamycin, tetracycline, cefotaxime, vancomycin and chloramphenicol. Regarding the etiology, echocardiography revealed no vegetation nor valve pathology, and peripheral blood smear showed no abnormality. Immunoglobulin and complement levels were within normal limits. Ongoing inflammation in maxillary sinuses detected in brain MRI suggested that meningitis could be related to previous sinus infection. After 14 days of ceftriaxone treatment, the patient was discharged from the hospital with cure. The aim of this case presentation was to emphasize that S.mitis may cause meningitis and white matter lesions in previously healthy children with concomitant sinusitis.

Efficacy evaluation of the C-strain-based vaccines against the subgenotype 2.1d classical swine fever virus emerging in China.

PubMed

Luo, Yuzi; Ji, Shengwei; Lei, Jian-Lin; Xiang, Guang-Tao; Liu, Yan; Gao, Yao; Meng, Xing-Yu; Zheng, Guanglai; Zhang, En-Yu; Wang, Yimin; Du, Ming-Liang; Li, Yongfeng; Li, Su; He, Xi-Jun; Sun, Yuan; Qiu, Hua-Ji

2017-03-01

Classical swine fever (CSF) is a devastating infectious disease of pigs caused by classical swine fever virus (CSFV). The disease has been controlled following extensive vaccination with the lapinized attenuated vaccine C-strain for decades in China. However, frequent CSF outbreaks occurred recently in a large number of C-strain-vaccinated pig farms in China and a new subgenotype 2.1d of CSFV has been reported to be responsible for the outbreaks. Here we analyzed the molecular variations and antigenic differences among the C-strain-based commercial vaccines of different origins from different manufacturers in China, and reevaluated the vaccines against the emerging subgenotype 2.1d strain of CSFV. The results showed that the C-strain adapted to the continuous ST cell line (C ST ) contain a unique M290K variation on the E2 protein, compared to those of primary BT cells (C BT ) or rabbit origin (C RT ) and the traditional C-strain sequences available in the GenBank database. Serum neutralization test revealed the antigenic differences between C ST and C BT or C RT . Notably, the neutralizing titers of porcine anti-C-strain sera against the CSFV isolate of subgenotype 2.1d were significantly lower than those against C-strain or Shimen strain. The C-strain-vaccinated, subgenotype 2.1d HLJZZ2014 strain-challenged pigs did not show any clinical signs and all survived. However, these pigs displayed mild pathological and histological lesions, and the CSFV viral RNA was detected in the various tissue and blood samples. Taken together, the C-strain-based vaccines of different origins showed molecular variations and antigenic differences, and could provide clinical but not pathological and virological protection against the subgenotype 2.1d CSFV emerging in China. Further investigation is needed to comprehensively assess the efficacy of C-strain of different doses against the subgenotype 2.1d CSFV. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

PubMed

Yoshida, M; Karasawa, M; Naruse, T; Fukuda, M; Hirashima, K; Oh, H; Ninomiya, H; Abe, T; Saito, K; Shishido, H; Moriyama, Y; Shibata, A; Motoyoshi, K; Nagata, N; Miura, Y

1999-02-01

The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts < 1.0 x 10(9)/l) were treated with flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children

PubMed Central

Anderson, B J; Holford, N H G; Woollard, G A; Chan, P L S

1998-01-01

Aims Paracetamol has a central action for both antipyresis and analgesia. Maximum temperature decrease and peak analgesia are reported at 1–2 h after peak plasma paracetamol concentration. We wished to determine the relationship between plasma and cerebrospinal fluid (CSF) pharmacokinetics in children. Methods Concentration-time profiles in plasma and CSF after nasogastric paracetamol 40 mg kg−1 were measured in nine children who had indwelling ventricular drains. Estimation of population pharmacokinetic parameters was made using both a standard two-stage population approach (MKMODEL) and a nonlinear mixed effect model (NONMEM). Results were standardized to a 70 kg person using an allometric power model. Results Both approaches gave similar estimates. NONMEM parameter estimates were clearance 10.2 l h−1 (CV 47%), volume of distribution 67.1 l (CV 58%) and absorption rate constant 0.77 h−1 (CV 49%). Cerebrospinal fluid concentrations lagged behind those of plasma. The equilibration half time was 0.72 h (CV 117%). The CSF/plasma partition coefficient was 1.18 (CV 8%). Conclusions Higher concentrations in the CSF probably reflect the lower free water volume of plasma. The CSF equilibration half time suggests that CSF kinetics approximate more closely to the effect compartment than plasma, but further time is required for paracetamol to exert its effects. Effect site concentrations equilibrate slowly with plasma. Paracetamol should be given 1–2 h before anticipated pain or fever in children. PMID:9764964

Human enteroviruses are not the cause of neurological impairments in children at the Korle-Bu Teaching Hospital.

PubMed

Tettey, Prudence; Badoe, Ebenezer; Adiku, Theophilus; Obodai, Eva; Odoom, John Kofi

2014-01-01

Convulsions associated with fever and acute onset of unknown aetiology with case fatalities have become a long observed medical condition at the Child Health Department of the Korle-Bu Teaching Hospital. Children admitted to the department with seizures of undetermined origin and fever has been a source of diagnostic confusion. Studies from the Asia Pacific region suggest a link with non-polio enteroviruses. The aim of the study was to investigate the association between non-polio enterovirus and acute encephalopathy causing neurological morbidity in children. One hundred and fifty cerebrospinal fluid (CSF), throat swab and serum samples were collected from participants at the Child Health Department of the Korle-Bu Teaching Hospital for virus isolation and characterization. Samples were cultured on cells and positive culture assayed by microneutralisation. Direct PCR as well as multiplex PCR were used to detect other viral agents present. Enterovirus isolation rate was approximately 0.67%. Intratypic differentiation by molecular characterization identified a poliovirus from vaccine origin. Further screening by real-time RT-PCR identified the virus as normal Sabin and not vaccine-derive poliovirus. No arbovirus was however detected. Non-polio enteroviruses and chikugunya virus were found not to be the etiologic agent responsible for the convulsion with neurologic morbidity observed in the Ghanaian children. Investigation for other viral agents is recommended.

Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis.

PubMed

Chavez-Tapia, Norberto C; Mendiola-Pastrana, Indira; Ornelas-Arroyo, Victoria J; Noreña-Herrera, Camilo; Vidaña-Perez, Desiree; Delgado-Sanchez, Guadalupe; Uribe, Misael; Barrientos-Gutierrez, Tonatiuh

2015-01-01

Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.

The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

PubMed

Chen, Shu-Huey; Yang, Shang-Hsien; Chu, Sung-Chao; Su, Yu-Chieh; Chang, Chu-Yu; Chiu, Ya-Wen; Kao, Ruey-Ho; Li, Dian-Kun; Yang, Kuo-Liang; Wang, Tso-Fu

2011-05-01

Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/μL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/μL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 μg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.

First molecular identification and characterization of classical swine fever virus isolates from Nepal.

PubMed

Postel, Alexander; Jha, Vijay C; Schmeiser, Stefanie; Becher, Paul

2013-01-01

Classical swine fever (CSF) is a major constraint to pig production worldwide, and in many developing countries, the epidemiological status is unknown. Here, for the first time, molecular identification and characterization of CSFV isolates from two recent outbreaks in Nepal are presented. Analysis of full-length E2-encoding sequences revealed that these isolates belonged to CSFV subgenotype 2.2 and had highest genetic similarity to isolates from India. Hence, for CSFV, Nepal and India should be regarded as one epidemiological unit. Both Nepalese isolates exhibited significant sequence differences, excluding a direct epidemiological connection and suggesting that CSFV is endemic in that country.

Rapid spontaneous cerebrospinal fluid leak detected in the gastrointestinal tract.

PubMed

Ma, Hong Yun; Sen, Papia; Stein, Evan G; Freeman, Leonard M

2014-02-01

There are many causes of cerebrospinal (CSF) leaks. Most cases are secondary to blunt trauma and iatrogenic trauma caused by postoperative sequelae. Occasionally, CSF leakage may occur from nontraumatic or "spontaneous" causes, such as benign intracranial hypertension and "empty sella syndrome." Mass effect due to an encephalocele or meningocele may also be seen. Radionuclide cisternography is a sensitive method of determining CSF leak when combined with intranasal cotton pledget placement and analysis. We present a spontaneous CSF fluid leak that was detected when scintigraphic activity appeared first in the gastrointestinal tract.

Longitudinal myelitis associated with yellow fever vaccination.

PubMed

Chaves, M; Riccio, P; Patrucco, L; Rojas, J I; Cristiano, E

2009-07-01

Severe adverse reaction to yellow fever (YF) vaccine includes the yellow fever vaccine-associated neurotropic disease. This terminology includes postvaccinal encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. The objective of this communication is to report a patient who received a YF vaccine in Argentina and subsequently developed longitudinal myelitis with a symptom that had previously gone unreported in the literature. A 56-year-old man began with progressive paraparesia, urinary retention, and constipation 48 h previous to admission. The patient received YF vaccine 45 days prior to the onset of the symptoms. There was no history of other immunization or relevant condition. MR of the spine showed longitudinal intramedullary hyperintense signal (D5-12) without gadolinium enhancement. A high concentration of YFV-specific IgM vaccine antibody was found in the cerebrospinal fluid (CSF). Serological tests for other flavivirus were negative. A diagnosis of longitudinal myelitis without encephalitis associated with YF vaccine was performed and symptoms improved 5 days later. This is the first report dealing with longitudinal myelitis as a serious adverse event associated with YF vaccination in which confirmation of the presence of antibodies in CSF was found. To date, it is also the first report with serological confirmation in Argentina and in South America. We consider that the present investigation will raise awareness in the region in the reporting of adverse events related to YF vaccine and improve our knowledge of adverse reactions to the vaccine.

A single dose of the novel chimeric subunit vaccine E2-CD154 confers early full protection against classical swine fever virus.

PubMed

Suárez, Marisela; Sordo, Yusmel; Prieto, Yanet; Rodríguez, María P; Méndez, Lídice; Rodríguez, Elsa M; Rodríguez-Mallon, Alina; Lorenzo, Elianet; Santana, Elaine; González, Nemecio; Naranjo, Paula; Frías, María Teresa; Carpio, Yamila; Estrada, Mario Pablo

2017-08-03

Classical swine fever is an economically important, highly contagious disease of swine worldwide. Subunit vaccines are a suitable alternative for the control of classical swine fever. However, such vaccines have as the main drawback the relatively long period of time required to induce a protective response, which hampers their use under outbreak conditions. In this work, a lentivirus-based gene delivery system is used to obtain a stable recombinant HEK 293 cell line for the expression of E2-CSFV antigen fused to porcine CD154 as immunostimulant molecule. The E2-CD154 chimeric protein was secreted into the medium by HEK293 cells in a concentration around 50mg/L in suspension culture conditions using spinner bottles. The E2-CD154 immunized animals were able to overcome the challenge with a high virulent CSF virus strain performed 7days after a unique dose of the vaccine without clinical manifestations of the disease. Specific anti-CSFV neutralizing antibodies and IFN-γ were induced 8days after challenge equivalent to 14days post-vaccination. The present work constitutes the first report of a subunit vaccine able to confer complete protection by the end of the first week after a single vaccination. These results suggest that the E2-CD154 antigen could be potentially used under outbreak conditions to stop CSFV spread and for eradication programs in CSF enzootic areas. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

PubMed

Dranitsaris, G; Altmayer, C; Quirt, I

1997-06-01

Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak

PubMed Central

2009-01-01

Background Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity. Methods We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD. Results Total duration of fever ≥ 3 days, peak temperature ≥ 38.5°C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (≥ 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79–6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature ≥ 38.5°C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of ≥ 2 risk factors predictive of CSF pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively. Conclusion Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for hospitalization and further investigation, including cerebrospinal fluid examination, and close monitoring for disease progression in children with HFMD. PMID:19152683

[Clinical experience and next-generation sequencing analysis of encephalitis caused by pseudorabies virus].

PubMed

Zhao, W L; Wu, Y H; Li, H F; Li, S Y; Fan, S Y; Wu, H L; Li, Y J; Lü, Y L; Han, J; Zhang, W C; Zhao, Y; Li, G L; Qiao, X D; Ren, H T; Zhu, Y C; Peng, B; Cui, L Y; Guan, H Z

2018-04-17

Objective: To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities. Methods: Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity. Results: The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)×10(6)/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up. Conclusions: PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.

Meningitis caused by Rhodotorula mucilaginosa in human immunodeficiency virus seropositive patient

PubMed Central

Baradkar, V. P.; Kumar, S.

2008-01-01

Rhodotorula species may be responsible for systemic infection in immunocompromised patients. Meningitis by Rhodotorula species in human immunodeficiency virus (HIV) infected persons has been reported previously. We report a case of meningitis caused by Rhodotorula mucilaginosa in a 36-year-old HIV seropositive male patient who presented with fever, altered sensorium and features of meningeal irritation i.e. neck rigidity. The Cerebrospinal fluid (CSF) cell counts were high, showing 150 cells/mm3, with 60% lymphocytes and 40% polymorphs, and protein content of 100 mg%; glucose was 60 mg%. The diagnosis was confirmed by culture on Sabouraud's Dextrose agar. The patient was treated successfully with intensive Amphotericin B (1 mg/kg), for two weeks, followed by oral Itraconazole (400 mg daily), for a period of two months. The patient was started on anti retroviral therapy. He did not show any relapse of the symptoms when the last follow up was done six months after the date of discharge. PMID:19893682

Cost Effectiveness of G:CSF in Chemotherapy and Transplant-related Neutropenia.

PubMed

Jacobs, P; Wood, L; Schall, R

1998-01-01

Sustained fever over 38°C is potentially lethal when neutrophil counts remain below 0.1 × 10(9)/L. To determine whether the addition of a haematopoietic stimulatory peptide to conventional supportive care and antibiotic management was cost-effective, 74 such episodes were analysed. Group I (5μg/kg G: CSF: n = 41); Group II (10 μg/kg: n = 19) and Group III (controls: n = 14): these were similar in respect of race, gender, age and body weight. The median days and range of neutrophil count below 0.1 × 10(9)/Lw as 6 (0-12), 7 (0-20) and 8 (0-20) and the corresponding figures for 0.5 × 10(9)/L were 8 (0-19), 8 (1-23) and 13.5 (3-30) days respectively, while the median hospital period was 26 (18-49), 30 (9-86) and 35 (13-44). Mean, standard deviation and range for bed costs in Group I was R9,528 (2125:6120-1660), the corresponding figures for Group II were Rll,453 (5570:3060-2924), and for Group III Rll,366 (2755: 4420-1496). The approximate fate of exchange is: Rl = US$5.87. When expenditure for growth factor was integrated these figures were approximately R26,071, R37,787 and R27,376. There were no advantages in 10 over 5 μg/kg G: CSF. More red cell transfusions were needed in Group III. The days requiring antimicrobial therapy were 14, 16 and 20 respectively. It is concluded from this study, carried out in reverse isolation at a University Teaching Hospital, that duration of neutropenic fever was significantly shortened on G: CSF but there was no benefit in using the higher dose. Additionally, at equivalent cost, there was a shorter period of hospitalisation thereby reducing risk of acquiring nosocomial infections. Finally, there was concurrently a decreased exposure to potentially nephrotoxic antibiotics. Accordingly, this regimen can be justified in the routine management of this category of patient.

Diagnosis and Treatment of Central Nervous System Infections in the Emergency Department

PubMed Central

Dorsett, Maia

2016-01-01

Central nervous system (CNS) infections, including meningitis, encephalitis, and brain abscess, are rare but time-sensitive emergency department (ED) diagnoses. Patients with CNS infection can present to the ED with a host of non-specific signs and symptoms, including headache, fever, altered mental status, and behavioral changes. In meningitis, the classic triad of fever, neck stiffness, and altered mental status occurs in only a minority of patients. Classic physical examination maneuvers, such Kernig’s and Brudzinski’s signs, are relatively insensitive although specific for predicting cerebrospinal fluid (CSF) pleocytosis. Patients with parenchymal involvement, as occurs with encephalitis and brain abscess, may also have focal neurologic deficits or seizures. Neuroimaging and CSF fluid analysis can appear benign early in the course of meningitis and encephalitis, and clinicians should not be falsely reassured. Delaying antibiotic and antiviral therapies negatively impacts outcomes, particularly with bacterial meningitis and herpes simplex virus encephalitis. As with other rare, life-threatening diagnoses encountered in emergency medicine, the diagnosis and treatment of CNS infections requires vigilance and a high index of suspicion based on the history and physical examination which must be confirmed with appropriate imaging and laboratory evaluation. PMID:27741995

Real-time laboratory exercises to test contingency plans for classical swine fever: experiences from two national laboratories.

PubMed

Koenen, F; Uttenthal, A; Meindl-Böhmer, A

2007-12-01

In order to adequately and efficiently handle outbreaks of contagious diseases such as classical swine fever (CSF), foot and mouth disease or highly pathogenic avian influenza, competent authorities and the laboratories involved have to be well prepared and must be in possession of functioning contingency plans. These plans should ensure that in the event of an outbreak access to facilities, equipment, resources, trained personnel, and all other facilities needed for the rapid and efficient eradication of the outbreak is guaranteed, and that the procedures to follow are well rehearsed. It is essential that these plans are established during 'peace-time' and are reviewed regularly. This paper provides suggestions on how to perform laboratory exercises to test preparedness and describes the experiences of two national reference laboratories for CSF. The major lesson learnt was the importance of a well-documented laboratory contingency plan. The major pitfalls encountered were shortage of space, difficulties in guaranteeing biosecurity and sufficient supplies of sterile equipment and consumables. The need for a standardised laboratory information management system, that is used by all those involved in order to reduce the administrative load, is also discussed.

Competitive replication kinetics and pathogenicity in pigs co-infected with historical and newly invading classical swine fever viruses.

PubMed

Huang, Yu-Liang; Deng, Ming-Chung; Tsai, Kuo-Jung; Liu, Hsin-Meng; Huang, Chin-Cheng; Wang, Fun-In; Chang, Chia-Yi

2017-01-15

Classical swine fever (CSF), an economically important and highly contagious disease of pigs, is caused by classical swine fever virus (CSFV). In Taiwan, CSFVs from field outbreaks belong to two distinct genotypes. The historical genotype 3.4 dominated from the 1920s to 1996, and since 1996, the newly invading genotype 2.1 has dominated. To explain the phenomenon of this virus shift in the field, representative viruses belonging to genotypes 2.1 and 3.4 were either inoculated alone (single infection) or co-inoculated (co-infection), both in vivo and in vitro, to compare the virus replication and pathogenesis. In pigs co-infected with the genotype 2.1 TD/96/TWN strain and the genotype 3.4 94.4/IL/94/TWN strain, the newly invading genotype 2.1 was detected earlier in the blood, oral fluid, and feces, and the viral loads were consistently and significantly higher than that of the historical genotype 3.4. In cell cultures, the ratio of secreted virus to cell-associated virus of the genotype 2.1 strain was higher than that of the genotype 3.4 strain. This study is the first to demonstrate a possible explanation of virus shift in the field, wherein the newly invading genotype 2.1 replicates more efficiently than did genotype 3.4 and outcompetes the replication and pathogenicity of genotype 3.4 in pigs in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

Cryptococcal meningitis with secondary cutaneous involvement in an immunocompetent host.

PubMed

Tabassum, Saadia; Rahman, Atiya; Herekar, Fivzia; Masood, Sadia

2013-09-16

Cryptococcosis is a potentially fatal fungal disease caused by variants of Cryptococcus neoformans species.  The respiratory tract is the usual portal of entry, with a peculiar predilection to invade the central nervous system.  The skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation.  The disease is mostly seen in immunodeficiency states.  The diagnosis is frequently unsuspected in immunocompetent patients. We report a case of disseminated cryptococcal meningitis in an immunocompetent young adult. The cutaneous eruption prompted the accurate diagnosis.  The patient, a 20-year-old female, had fever, cough, headache and intractable vomiting for the past two months and was being managed as a case of tuberculous meningitis. Two weeks after starting antituberculous treatment she developed umbilicated papules on the head and neck region. Necessary laboratory workup identified C. neoformans in cerebrospinal fluid (CSF) and skin specimens.  The titers of cryptococcal antigen were measured in CSF and serum for diagnostic and prognostic purposes.  Anti-fungal treatment resulted in regression of the cutaneous lesions and resolution of systemic complaints. The case highlights the need for high degree of suspicion, especially in healthy young adults, in the diagnosis of cryptococcosis. The cutaneous eruptions can be the first manifestation or a diagnostic clue of enormous significance.

Prevalence and predictors of bacterial meningitis in young infants with fever without a source.

PubMed

Martinez, Elena; Mintegi, Santiago; Vilar, Begoña; Martinez, Maria Jesus; Lopez, Amaia; Catediano, Estibaliz; Gomez, Borja

2015-05-01

Classical criteria differ when performing cerebrospinal fluid (CSF) analysis in infants younger than 90 days with fever without a source (FWS). Our objectives were to analyze the prevalence and microbiology of bacterial meningitis in this group and its prevalence in relation to clinical and laboratory risk factors. This is a substudy of a prospective registry including all infants of this age with FWS seen between September 2003 and August 2013 in a Pediatric Emergency Department of a Tertiary Teaching Hospital. Lumbar puncture was performed in 639 (27.0%) of the 2362 infants with FWS seen, the rate being higher in not well-appearing infants [60.9% vs. 25.7%; odds ratio (OR), 4.49] and in those ≤21 days old (70.1% vs. 20.4%; OR, 9.14). Eleven infants were diagnosed with bacterial meningitis: 9 were ≤21 days old (prevalence 2.8% vs. 0.1%; OR, 30.42) and 5 were not well-appearing infants (5.7% vs. 0.2%; OR, 23.06). Bacteria isolated were Streptococcus agalactiae (3), Escherichia coli (3), Listeria monocytogenes (3), Streptococcus pneumoniae (1) and Neisseria meningitidis (1). None of the 1975 well-appearing infants >21 days old were diagnosed with bacterial meningitis, regardless of whether biomarkers were altered. In infants younger than 90 days with FWS, performing CSF analysis for ruling out bacterial meningitis must be strongly considered in not well-appearing infants and in those ≤21 days old. The recommendation of systematically performing CSF analysis in well-appearing infants 22-90 days of age on the basis of analytical criteria alone must be reevaluated.

Lack of causal association between spontaneous intracranial hypotension and cranial cerebrospinal fluid leaks.

PubMed

Schievink, Wouter I; Schwartz, Marc S; Maya, M Marcel; Moser, Franklin G; Rozen, Todd D

2012-04-01

Spontaneous intracranial hypotension is an important cause of headaches and an underlying spinal CSF leak can be demonstrated in most patients. Whether CSF leaks at the level of the skull base can cause spontaneous intracranial hypotension remains a matter of controversy. The authors' aim was to examine the frequency of skull base CSF leaks as the cause of spontaneous intracranial hypotension. Demographic, clinical, and radiological data were collected from a consecutive group of patients evaluated for spontaneous intracranial hypotension during a 9-year period. Among 273 patients who met the diagnostic criteria for spontaneous intracranial hypotension and 42 who did not, not a single instance of CSF leak at the skull base was encountered. Clear nasal drainage was reported by 41 patients, but a diagnosis of CSF rhinorrhea could not be established. Four patients underwent exploratory surgery for presumed CSF rhinorrhea. In addition, the authors treated 3 patients who had a postoperative CSF leak at the skull base following the resection of a cerebellopontine angle tumor and developed orthostatic headaches; spinal imaging, however, demonstrated the presence of a spinal source of CSF leakage in all 3 patients. There is no evidence for an association between spontaneous intracranial hypotension and CSF leaks at the level of the skull base. Moreover, the authors' study suggests that a spinal source for CSF leakage should even be suspected in patients with orthostatic headaches who have a documented skull base CSF leak.

Simulation of Cross-border Impacts Resulting from Classical Swine Fever Epidemics within the Netherlands and Germany.

PubMed

Hop, G E; Mourits, M C M; Oude Lansink, A G J M; Saatkamp, H W

2016-02-01

The cross-border region of the Netherlands (NL) and the two German states of North Rhine Westphalia (NRW) and Lower Saxony (LS) is a large and highly integrated livestock production area. This region increasingly develops towards a single epidemiological area in which disease introduction is a shared veterinary and, consequently, economic risk. The objectives of this study were to examine classical swine fever (CSF) control strategies' veterinary and direct economic impacts for NL, NRW and LS given the current production structure and to analyse CSF's cross-border causes and impacts within the NL-NRW-LS region. The course of the epidemic was simulated by the use of InterSpread Plus, whereas economic analysis was restricted to calculating disease control costs and costs directly resulting from the control measures applied. Three veterinary control strategies were considered: a strategy based on the minimum EU requirements, a vaccination and a depopulation strategy based on NL and GER's contingency plans. Regardless of the veterinary control strategy, simulated outbreak sizes and durations for 2010 were much smaller than those simulated previously, using data from over 10 years ago. For example, worst-case outbreaks (50th percentile) in NL resulted in 30-40 infected farms and lasted for two to four and a half months; associated direct costs and direct consequential costs ranged from €24.7 to 28.6 million and €11.7 to 26.7 million, respectively. Both vaccination and depopulation strategies were efficient in controlling outbreaks, especially large outbreaks, whereas the EU minimum strategy was especially deficient in controlling worst-case outbreaks. Both vaccination and depopulation strategies resulted in low direct costs and direct consequential costs. The probability of cross-border disease spread was relatively low, and cross-border spread resulted in small, short outbreaks in neighbouring countries. Few opportunities for further cross-border harmonization and collaboration were identified, including the implementation of cross-border regions (free and diseased regions regardless of the border) in case of outbreaks within close proximity of the border, and more and quicker sharing of information across the border. It was expected, however, that collaboration to mitigate the market effects of an epidemic will create more opportunities to lower the impact of CSF outbreaks in a cross-border context. © 2014 Blackwell Verlag GmbH.

Candida meningitis in an immunocompetent patient detected through (1→3)-beta-d-glucan.

PubMed

Farrugia, Mark K; Fogha, Evan P; Miah, Abdul R; Yednock, Joel; Palmer, H Carl; Guilfoose, John

2016-10-01

A 44-year-old female presented with a 3-month history of headache, dizziness, nausea, and vomiting. Her past medical history was significant for long-standing intravenous drug abuse. Shortly after admission, the patient became hypertensive and febrile, with fever as high as 38.8°C. The lumbar puncture profile supported an infectious process; however multiple cultures of blood and cerebrospinal fluid (CSF) did not initially show growth of organisms. Finally after 9 days of incubation, a CSF culture showed evidence of a few colonies of Candida albicans. To confirm the diagnosis, preserved CSF from that sample was tested for (1→3)-β-d-glucan, showing levels >500pg/ml. This report illustrates a rare complication of intravenous drug use in an immunocompetent patient and demonstrates the utility of (1→3)-β-d-glucan testing in possible Candida meningitis. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Spontaneous spinal cerebrospinal fluid leak as a cause of coma after craniotomy for clipping of an unruptured intracranial aneurysm.

PubMed

Schievink, Wouter I; Palestrant, David; Maya, M Marcel; Rappard, George

2009-03-01

Spontaneous spinal CSF leaks are best known as a cause of orthostatic headache, but may also be the cause of coma. The authors encountered a unique case of a spontaneous spinal CSF leak causing coma 2 days after craniotomy for clipping of an unruptured aneurysm. This 44-year-old woman with autosomal dominant polycystic kidney disease underwent an uneventful craniotomy for an incidental anterior choroidal artery aneurysm. No intraoperative spinal CSF drainage was used. Two days after surgery the patient became comatose with a left oculomotor nerve palsy. Computed tomography scanning revealed a right extraceberal hematoma and loss of gray-white matter differentiation. The hematoma was evacuated and a diagnosis of hemodialysis disequilibrium syndrome was made. Continuous hemodialysis and hyperosmolar therapy were instituted without any improvement. The CT scans were then reinterpreted as showing sagging of the brain, and the patient was placed in the Trendelenburg position which resulted in prompt improvement in her level of consciousness. A CT myelogram demonstrated an upper thoracic CSF leak that eventually required surgical correction. The patient made a complete neurological recovery. Neurological deterioration after craniotomy may be caused by brain sagging caused by a spontaneous spinal CSF leak, similar to intracranial hypotension due to intraoperative lumbar CSF drainage.

Ultrafast dynamic computed tomography myelography for the precise identification of high-flow cerebrospinal fluid leaks caused by spiculated spinal osteophytes.

PubMed

Thielen, Kent R; Sillery, John C; Morris, Jonathan M; Hoxworth, Joseph M; Diehn, Felix E; Wald, John T; Rosebrock, Richard E; Yu, Lifeng; Luetmer, Patrick H

2015-03-01

Precise localization and understanding of the origin of spontaneous high-flow spinal CSF leaks is required prior to targeted treatment. This study demonstrates the utility of ultrafast dynamic CT myelography for the precise localization of high-flow CSF leaks caused by spiculated spinal osteophytes. This study reports a series of 14 patients with high-flow CSF leaks caused by spiculated spinal osteophytes who underwent ultrafast dynamic CT myelography between March 2009 and December 2010. There were 10 male and 4 female patients, with an average age of 49 years (range 37-74 years). The value of ultrafast dynamic CT myelography in depicting the CSF leak site was qualitatively assessed. In all 14 patients, ultrafast dynamic CT myelography was technically successful at precisely demonstrating the site of the CSF leak, the causative spiculated osteophyte piercing the dura, and the relationship of the implicated osteophyte to adjacent structures. Leak sites included 3 cervical, 11 thoracic, and 0 lumbar levels, with 86% of the leaks occurring from C-5 to T-7. Information obtained from the ultrafast dynamic CT myelogram was considered useful in all treated CSF leaks. Spinal osteophytes piercing the dura are a more frequent cause of high-flow CSF leaks than previously recognized. Ultrafast dynamic CT myelography adds value beyond standard dynamic myelography or digital subtraction myelography in the diagnosis and anatomical characterization of high-flow spinal CSF leaks caused by these osteophytes. This information allows for appropriate planning for percutaneous or surgical treatment.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

PubMed

Mhaskar, Rahul; Clark, Otavio Augusto Camara; Lyman, Gary; Engel Ayer Botrel, Tobias; Morganti Paladini, Luciano; Djulbegovic, Benjamin

2014-10-30

Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results. The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.

Comparative analyses of host responses upon infection with moderately virulent classical swine fever virus in domestic pigs and wild boar.

PubMed

Petrov, Anja; Blohm, Ulrike; Beer, Martin; Pietschmann, Jana; Blome, Sandra

2014-07-29

Classical swine fever (CSF) is one of the most important viral diseases of pigs. Clinical signs may vary from almost inapparent infection to a hemorrhagic fever like illness. Among the host factors leading to different disease courses are age, breed, and immune status. The aim of this study was to compare host responses of different pig breeds upon infection with a recent moderately virulent CSF virus (CSFV) strain, and to assess their impact on the clinical outcome and the efficiency of immune responses. To this means, two domestic pig types (German Landrace and hybrids), were compared to European wild boar. Along with clinical and pathological assessments and routine virological and serological methods, kinetics of immune-cellular parameters were evaluated. All animals were susceptible to infection and despite clinical differences, virus could be detected in all infected animals to similar amounts. All but one animal developed an acute disease course, two landrace animals recovered after a transient infection. One wild boar got chronically infected. Changes in the percentages of lymphocyte subsets in peripheral blood did not show a clear correlation with the clinical outcome. High and early titers of neutralizing antibodies were especially detected in wild boar and German Landrace pigs. While differences among breeds did not have the expected impact on course and outcome of CSFV infection, preload with facultative pathogens and even small differences in age seemed to be more relevant. Future studies will target the characterization of responses observed during different disease courses including cytokine reactions and further analyses of lymphocyte subsets.

Comparing actual and perceived causes of fever among community members in a low malaria transmission setting in northern Tanzania

PubMed Central

Hertz, Julian T.; Munishi, O. Michael; Sharp, Joanne P.; Reddy, Elizabeth A.; Crump, John A.

2013-01-01

Objective To compare actual and perceived causes of fever in northern Tanzania. Methods In a standardized survey, heads of households in 30 wards in Moshi, Tanzania, were asked to identify the most common cause of fever for children and for adults. Responses were compared to data from a local hospital-based fever etiology study that used standard diagnostic techniques. Results Of 810 interviewees, the median (range) age was 48 (16, 102) years and 62.8% were females. Malaria was the most frequently identified cause of fever, cited by 56.7% and 43.6% as the most common cause of fever for adults and children, respectively. In contrast, malaria accounted for 2.0% of adult and 1.3% of pediatric febrile admissions in the fever etiology study. Weather was the second-most frequently cited cause of fever. Participants who identified a non-biomedical explanation such as weather as the most common cause of fever were more likely to prefer a traditional healer for treatment of febrile adults (OR 2.7, p<0.001). Bacterial zoonoses were the most common cause of fever among inpatients, but no interviewees identified infections from animal contact as the most common cause of fever for adults; 0.2% identified these infections as the most common cause of fever for children. Conclusions Malaria is perceived to be a much more common cause of fever than hospital studies indicate whereas other important diseases are under-appreciated in northern Tanzania. Belief in non-biomedical explanations of fever is common locally and has important public health consequences. PMID:24103083

Case of Mycobacterium tuberculosis meningitis: Gram staining as a useful initial diagnostic clue for tuberculous meningitis.

PubMed

Kawakami, Sayoko; Kawamura, Yasuyosi; Nishiyama, Kyouhei; Hatanaka, Hiroki; Fujisaki, Ryuichi; Ono, Yasuo; Miyazawa, Yukihisa; Nishiya, Hajime

2012-12-01

A 32-year-old man was admitted to our hospital because of fever, headache, and loss of consciousness. Four days before admission, he had had difficulty speaking. On the day of admission, his colleague had found him to be unconscious and lying on his back. He was admitted to our hospital. The temperature at the eardrum was 35.2°C. Neurologic evaluation was negative. Computed tomography (CT) scan of the brain showed slight ventricular enlargement bilaterally. An X-ray film of the chest showed no abnormality. On the second hospital day, neck stiffness was noted. The cerebrospinal fluid (CSF) contained 870 white cells/μl, most of which were neutrophils; the glucose level in the CSF was 10 mg/dl, and the protein level was 140 mg/dl. Stained smears of the CSF, including Gram staining and India-ink preparations, disclosed no microorganisms. Capsular antigen tests for several bacteria were negative. Antimicrobial agents were started. However, by changing the microscope focus slightly while viewing Gram stains of the CSF, we could see brightened and Gram-positive bacilli that had been phagocytosed by neutrophils. This finding suggested the presence of Mycobacterium tuberculosis. Ziehl-Neelsen staining of the CSF and gastric juice revealed anti-acid bacilli. Polymerase chain reaction for M. tuberculosis in the gastric juice was positive. This case showed that Gram staining could be useful as an initial adjunct for the diagnosis of tuberculous meningitis, particularly when the CSF shows predominantly neutrocytic pleocytosis, but no other evidence of bacterial meningitis.

Yellow fever vaccine-associated neurotropic disease (YEL-AND) - A case report.

PubMed

Florczak-Wyspiańska, Jolanta; Nawotczyńska, Ewa; Kozubski, Wojciech

Yellow fever (YF) is a mosquito-borne viral hemorrhagic fever, which is a serious and potentially fatal disease with no specific antiviral treatment that can be effectively prevented by an attenuated vaccine (YEL). Despite the long history of safe and efficacious YF vaccination, sporadic case reports of serious adverse events (SAEs) have been reported, including yellow fever vaccine-associated neurotropic disease (YEL-AND). YEL-AND usually appears within one month of YF vaccination, manifesting as meningoencephalitis, Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM). We report a case of YEL-AND with meningitis presentation in a 39-year-old Caucasian man without evidence of significant risk factors, which was confirmed by the presence of the YF virus and specific immunoglobulin G (IgG) antibodies in the cerebrospinal fluid (CSF). In conclusion, we should stress the importance of balancing the risk of SAEs associated with the vaccine and the benefits of YF vaccination for each patient individually. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Estimating the scale of adverse animal welfare consequences of movement restriction and mitigation strategies in a classical swine fever outbreak.

PubMed

Yadav, Shankar; Weng, Hsin-Yi

2017-04-04

The study aim was to quantify the impact of movement restriction on the well-being of pigs and the associated mitigation responses during a classical swine fever (CSF) outbreak. We developed a stochastic risk assessment model and incorporated Indiana swine industry statistics to estimate the timing and number of swine premises that would encounter overcrowding or feed interruption resulting from movement restriction. Our model also quantified the amount of on-farm euthanasia and movement of pigs to slaughter plants required to alleviate those conditions. We simulated various single-site (i.e., an outbreak initiated from one location) and multiple-site (i.e., an outbreak initiated from more than one location) outbreak scenarios in Indiana to estimate outputs. The study estimated that 14% of the swine premises in Indiana would encounter overcrowding or feed interruption due to movement restriction implemented during a CSF outbreak. The number of premises that would experience animal welfare conditions was about 2.5 fold of the number of infected premises. On-farm euthanasia needed to be performed on 33% of those swine premises to alleviate adverse animal welfare conditions, and more than 90% of on-farm euthanasia had to be carried out within 2 weeks after the implementation of movement restriction. Conversely, movement of pigs to slaughter plants could alleviate 67% of adverse animal welfare conditions due to movement restriction, and only less than 1% of movement of pigs to slaughter plants had to be initiated in the first 2 weeks of movement restrictions. The risk of secondary outbreaks due to movement of pigs from movement restriction areas to slaughter plants was low and only seven pigs from each shipment needed to be tested for CSF infection to prevent a secondary outbreak. We found that the scale of adverse animal welfare consequences of movement restriction during a CSF outbreak in Indiana was substantial, and controlled movement of pigs to slaughter plants was an efficient and low-risk alternative mitigation response to on-farm euthanasia. The output estimates generated from this study provide empirical evidence for decision makers to properly incorporate required resources for mitigating adverse animal welfare conditions in CSF outbreak management strategic planning.

Drug eruption caused by recombinant human G-CSF.

PubMed

Sasaki, O; Yokoyama, A; Uemura, S; Fujino, S; Inoue, Y; Kohno, N; Hiwada, K

1994-10-01

Two types of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are available, and equally used for mitigation of neutropenia. One is a glycosylated natural product from mammalian cells, and the other a non-glycosylated form from Escherichia coli. Though only minimal adverse effects have been reported for both, we treated two patients with rhG-CSF-induced systemic eruption. Based on these patients, the following should be noted: 1) drug eruption may occur in both types of rhG-CSF without detectable antibodies, 2) intradermal test is useful for determination of the causal drug, and 3) if one rhG-CSF product causes eruption, the alternative one may possibly be safe and effective.

[Successful treatment of Candida meningitis with miconazole].

PubMed

Fukui, S; Tabata, H; Hayashi, H; Matsushima, Y

1990-09-01

This paper presents a case of successful treatment of candida meningitis with miconazole. A 55-year-old woman was admitted due to high fever, vomiting and urinary incontinence on November 11, 1986. Four months prior to this episode, she had been treated for a ruptured aneurysm with neck-clipping and V-P shunt for NPH. Candida albicans was cultured from her CSF. The shunt system was immediately removed and an Ommaya's reservoir was installed for external drainage and intrathecal administrations. Combination therapy (amphotericin B and flucytosine) was initiated. However, it was discontinued after ten days because of high fever and chills after intrathecal injection of amphotericin B. Treatment with miconazole intrathecally (10-90 mg/week, total 565 mg) and intravenously (200-1200 mg/day, total 70.4 g) was begun on November 23. Clinical and CSF findings were improved soon. No side effect of miconazole was observed. After V-P shunt revision, she was discharged without neurological deficit on March 12, 1987. Reports of mycosis in central nervous system are recently increasing, especially for candidosis. Cryptococcosis is noted frequently as an opportunistic infection of AIDS. The administration of amphotericin B and flucytosine has been the main therapy for mycotic meningitis. Unfortunately, however, Amphotericin B has many toxic effects, including renal dysfunction, and flucytosine can induce the emergent resistance. Miconazole has been used to successfully treat cryptococcosis, aspergillosis or coccidiosis, and was effective in our case of candida meningitis. Few side effects have been reported with its use. The intrathecal injection of miconazole is recommended for meningitis, because the drug is taken up minimally into CSF space after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)

How to survey classical swine fever in wild boar (Sus scrofa) after the completion of oral vaccination? Chasing away the ghost of infection at different spatial scales.

PubMed

Saubusse, Thibault; Masson, Jean-Daniel; Le Dimma, Mireille; Abrial, David; Marcé, Clara; Martin-Schaller, Regine; Dupire, Anne; Le Potier, Marie-Frédérique; Rossi, Sophie

2016-01-25

Oral mass vaccination (OMV) is considered as an efficient strategy for controlling classical swine fever (CSF) in wild boar. After the completion of vaccination, the presence of antibodies in 6-12 month-old hunted wild boars was expected to reflect a recent CSF circulation. Nevertheless, antibodies could also correspond to the long-lasting of maternal antibodies. This paper relates an experience of surveillance which lasted 4 years after the completion of OMV in a formerly vaccinated area, in north-eastern France (2010-2014). First, we conducted a retrospective analysis of the serological data collected in 6-12 month-old hunted wild boars from 2010 up to 2013, using a spatial Bayesian model accounting for hunting data autocorrelation and heterogeneity. At the level of the whole area, seroprevalence in juvenile boars decreased from 28% in 2010-2011 down to 1% in 2012-2013, but remained locally high (above 5%). The model revealed the existence of one particular seroprevalence hot-spot where a longitudinal survey of marked animals was conducted in 2013-2014, for deciphering the origin of antibodies. Eleven out of 107 captured piglets were seropositive when 3-4 months-old, but their antibody titres progressively decreased until 6-7 months of age. These results suggest piglets were carrying maternal antibodies, few of them carrying maternal antibodies lasting until the hunting season. Our study shows that OMV may generate confusion in the CSF surveillance several years after the completion of vaccination. We recommend using quantitative serological tools, hunting data modelling and capture approaches for better interpreting serological results after vaccination completion. Surveillance perspectives are further discussed.

CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses

PubMed Central

2013-01-01

The conventional C-strain vaccine induces early protection against classical swine fever (CSF), but infected animals cannot be distinguished from vaccinated animals. The CP7_E2alf marker vaccine, a pestivirus chimera, could be a suitable substitute for C-strain vaccine to control CSF outbreaks. In this study, single oral applications of CP7_E2alf and C-strain vaccines were compared for their efficacy to induce protection against a CSF virus (CSFV) challenge with the moderately virulent Bas-Rhin isolate, in pigs as early as two days post-immunization. This work emphasizes the powerful potential of CP7_E2alf vaccine administered orally by a rapid onset of partial protection similar to that induced by the C-strain vaccine. Furthermore, our results revealed that both vaccinations attenuated the effects induced by CSFV on production of the pig major acute phase protein (PigMAP), IFN-α, IL-12, IL-10, and TGF-β1 cytokines. By this interference, several cytokines that may play a role in the pathogeny induced by moderately virulent CSFV strains were revealed. New hypotheses concerning the role of each of these cytokines in CSFV pathogeny are discussed. Our results also show that oral vaccination with either vaccine (CP7_E2alf or C-strain) enhanced CSFV–specific IgG2 production, compared to infection alone. Interestingly, despite the similar antibody profiles displayed by both vaccines post-challenge, the production of CSFV-specific IgG1 and neutralizing antibodies without challenge was lower with CP7_E2alf vaccination than with C-strain vaccination, suggesting a slight difference in the balance of adaptive immune responses between these vaccines. PMID:23398967

Concurrent Cryptococcal and Pneumocystis Pneumonia along with Pulmonary Tuberculosis in an HIV-Positive Patient: Lessons Learned for Early Management.

PubMed

Kaur, Ravinder; Gautam, Hitender; Maheshwari, Megha; Goyal, Ritu; Bhalla, Preena; Dewan, Richa

2011-01-01

We are presenting a 50-year-old patient of pulmonary tuberculosis, on anti-tuberculosis therapy (ATT) for last 2 months who presented with fever, cough, breathlessness, anorexia, and weight loss. The case was found to be HIV reactive. His sputum sample showed Candida albicans and Pneumocystis jirovecii. Fluconazole and cotrimoxazole + sulphamethoxazole were added. The index case did not respond to the treatment and his clinical condition started to deteriorate and he developed headache, vomiting, and dysphagia. Repeat sputum sample and cerebrospinal fluid (CSF) showed Cryptococcus neoformans which was found to be sensitive to Amphotericin B. Amphotericin B was added to the treatment and patient clinically responded to treatment. In conclusion, emphasis should be given to correct etiological identification, allowing appropriate treatment and decreasing the morbidity and mortality in these patients as concomitant opportunistic infections may cause diagnostic problems.

High mobility group box 1 in patients with 2009 pandemic H1N1 influenza-associated encephalopathy.

PubMed

Momonaka, Hiroshi; Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Kajimoto, Madoka; Okada, Seigo; Nakatsuka, Kenji; Morishima, Tsuneo; Ichiyama, Takashi

2014-06-01

Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have been reported in Japan. The most common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously highlighted the cytokine profile of pIE; our results suggest that proinflammatory cytokines play an important role in the pathogenesis. High mobility group box 1 (HMGB1) protein is a late mediator of inflammation or sepsis. However, there are few reports regarding the serum and cerebrospinal fluid (CSF) levels of HMGB1 in pIE patients. We measured serum and CSF levels of HMGB1 in the following: pIE patients with poor outcomes, pIE patients without neurological sequelae, influenza patients without pIE, and control subjects. Serum HMGB1 levels were significantly higher in pIE patients with poor outcomes compared to those without neurological sequelae. In contrast, there was no difference in CSF HMGB1 levels among all groups. Regarding pIE patients, we found a significant positive correlation between HMGB1 levels and IL-6 in the serum but not in the CSF. Our results suggest that HMGB1 protein may be involved in the pathogenesis of pIE and that a high serum, but not CSF, level of inflammatory cytokines plays an important role in the severity of pIE. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The effect of macrophage colony-stimulating factor on haemopoietic recovery after autologous bone marrow transplantation.

PubMed

Khwaja, A; Yong, K; Jones, H M; Chopra, R; McMillan, A K; Goldstone, A H; Patterson, K G; Matheson, C; Ruthven, K; Abramson, S B

1992-06-01

Macrophage colony-stimulating factor (M-CSF) is active in the late stages of monocyte maturation, activates mature monocyte-macrophages and enhances their production of various other cytokines. We have examined the effects of a 21 d course of escalating doses of M-CSF purified from human urine (hM-CSF) on recovery following autologous bone marrow transplantation (ABMT) in 20 patients with malignant lymphomas. Four patients were treated at each dose level of 4, 8, 16, 32 and 64 x 10(6) U/m2/d and results compared to 46 concurrent controls. There was no significant difference in recovery to an absolute neutrophil count (ANC) of 0.5 x 10(9)/l (median 20 d in hM-CSF group versus 22 in controls) or in recovery of platelets to 50 x 10(9)/l (32 d versus 39 d, 0.05 less than P less than 0.1); hM-CSF patients received a median of 81 platelet units following ABMT (controls 112 units, P = NS). hM-CSF patients had a median of 5.5 d with fever greater than 37.5 degrees C (control 8, P = NS), received parenteral antibiotics for 14.5 d (control 17, P = NS) and had a 50% incidence of bacteraemia (control 48%). hM-CSF treated patients were discharged by a median of day 29 following transplantation (control 33, P less than 0.05). Platelet and neutrophil recovery correlated significantly with the number of marrow mononuclear cells (MNC) reinfused in the hM-CSF group (P = 0.05 and P = 0.014 respectively) but not in controls. Subgroup analysis showed that hM-CSF patients receiving greater than 2 x 10(8) MNC/kg body weight reached an ANC of 0.5 x 10(9)/l by a median of day 16.5 (control 18.5, NS), became platelet transfusion independent by day 17 (control 29, P less than 0.05) and reached a platelet count of 50 x 10(9)/l by day 21 (control 40, P less than 0.05). No significant toxicity attributable to hM-CSF treatment was seen. These results suggest that hM-CSF accelerates platelet recovery following ABMT and that relatively large marrow innocula are required to see this effect.

Electronegative L5-LDL induces the production of G-CSF and GM-CSF in human macrophages through LOX-1 involving NF-κB and ERK2 activation.

PubMed

Yang, Tzu-Ching; Chang, Po-Yuan; Kuo, Tzu-Ling; Lu, Shao-Chun

2017-12-01

Circulating levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) are associated with the severity of acute myocardial infarction (AMI). However, what causes increases in G-CSF and GM-CSF is unclear. In this study, we investigated whether L5-low-density lipoprotein (LDL), a mildly oxidized LDL from AMI, can induce G-CSF and GM-CSF production in human macrophages. L1-LDL and L5-LDL were isolated through anion-exchange chromatography from AMI plasma. Human macrophages derived from THP-1 and peripheral blood mononuclear cells were treated with L1-LDL, L5-LDL, or copper-oxidized LDL (Cu-oxLDL) and G-CSF and GM-CSF protein levels in the medium were determined. In addition, the effects of L5-LDL on G-CSF and GM-CSF production were tested in lectin-type oxidized LDL receptor-1 (LOX-1), CD36, extracellular signal-regulated kinase (ERK) 1, and ERK2 knockdown THP-1 macrophages. L5-LDL but not L1-LDL or Cu-oxLDL significantly induced production of G-CSF and GM-CSF in macrophages. In vitro oxidation of L1-LDL and L5-LDL altered their ability to induce G-CSF and GM-CSF, suggesting that the degree of oxidation is critical for the effects. Knockdown and antibody neutralization experiments suggested that the effects were caused by LOX-1. In addition, nuclear factor (NF)-κB and ERK1/2 inhibition resulted in marked reductions of L5-LDL-induced G-CSF and GM-CSF production. Moreover, knockdown of ERK2, but not ERK1, hindered L5-LDL-induced G-CSF and GM-CSF production. The results indicate that L5-LDL, a naturally occurring mild oxidized LDL, induced G-CSF and GM-CSF production in human macrophages through LOX-1, ERK2, and NF-κB dependent pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of blood contamination of cerebrospinal fluid on results of indirect fluorescent antibody tests for detection of antibodies against Sarcocystis neurona and Neospora hughesi.

PubMed

Finno, Carrie J; Packham, Andrea E; David Wilson, W; Gardner, Ian A; Conrad, Patricia A; Pusterla, Nicola

2007-05-01

The purpose of this study was to determine the effect of blood contamination of cerebrospinal fluid (CSF) on the results of indirect fluorescent antibody tests (IFATs) for Sarcocystis neurona and Neospora hughesi. The in vitro study used antibody-negative CSF collected from non-neurologic horses immediately after euthanasia and blood samples from 40 healthy horses that had a range of IFAT antibody titers against S. neurona and N. hughesi. Serial dilutions of whole blood were made in seronegative CSF to generate blood-contaminated CSF with red blood cell (RBC) concentrations ranging from 10 to 100,000 RBCs/microl. The blood-contaminated CSF samples were then tested for antibodies against both pathogens using IFAT. Blood contamination of CSF had no detectable effect on IFAT results for S. neurona or N. hughesi at any serologic titer when the RBC concentration in CSF was <10,000 RBCs/microl. At concentrations of 10,000-100,000 RBCs/microl of CSF, positive CSF results (IFAT titer >or=5) for S. neurona and N. hughesi were detected only when the corresponding serum titers were >or=160 and >or=80, respectively. The IFAT performed on CSF is reliable for testing horses for equine protozoal myeloencephalitis caused by S. neurona or N. hughesi, even when blood contamination causes the RBC concentration in CSF to be up to 10,000 RBCs/microl.

[Acute cerebellar ataxia associated with infectious mononucleosis--a case report and review of the literature].

PubMed

Yabuki, S; Kazahaya, Y; Ikeda, K

1983-04-01

A 20-year-old man, a college student, was admitted to Kochi Municipal Central Hospital with a month's history of slurring of speech and unsteadiness of gait. He had developed fever, sore throat and cervical lymphadenopathy. On admission, the throat was mildly injected, and enlarged lymph nodes were palpable in the lateral cervical regions. His speech was slightly slurred. Bilateral dysmetria, dyssynergia and intention tremor were noted in both extremities. The gait was grossly ataxic. Plantar responses were extensor. Examination of his peripheral blood revealed atypical lymphocytes, and the titer of Paul-Bunnell was 1:16. The CSF protein was 25 mg/dl with normal cell count. Epstein-Barr virus (EBV) antibody titers by indirect immunofluorescence in the serum of the second hospital day were as follows: VCA-IgG was 1:640, VCA-IgM less than 1:10, EBV-EA 1:160, and EBNA less than 1:10, while the CSF-EBV antibody titer was negative. Treatment with prednisolone was started and within 7 days he began to recover. Six weeks after admission he was completely free of neurological symptoms and signs. We also reviewed 18 cases of acute cerebellar ataxia with infectious mononucleosis in the literature. It was postulated that the neurological symptoms complicating infectious mononucleosis were possibly caused by infectious and immuno-allergic mechanisms.

CSF Venous Fistulas in Spontaneous Intracranial Hypotension: Imaging Characteristics on Dynamic and CT Myelography.

PubMed

Kranz, Peter G; Amrhein, Timothy J; Gray, Linda

2017-12-01

The objective of this study is to describe the anatomic and imaging features of CSF venous fistulas, which are a recently reported cause of spontaneous intracranial hypotension (SIH). We retrospectively reviewed the records of patients with SIH caused by CSF venous fistulas who received treatment at our institution. The anatomic details of each fistula were recorded. Attenuation of the veins involved by the fistula was compared with that of adjacent control veins on CT myelography (CTM). Visibility of the CSF venous fistula on CTM and a modified conventional myelography technique we refer to as dynamic myelography was also compared. Twenty-two cases of CSF venous fistula were identified. The fistulas were located between T4 and L1. Ninety percent occurred without a concurrent epidural CSF leak. In most cases (82%), the CSF venous fistula originated from a nerve root sleeve diverticulum. On CTM, the abnormal veins associated with the CSF venous fistula were seen in a paravertebral location in 45% of cases, centrally within the epidural venous plexus in 32%, and lateral to the spine in 23%. Differences in attenuation between the fistula veins and the control veins was highly statistically significant (p < 0.0001), with a threshold of 70 HU perfectly discriminating fistulas from normal veins in our series. When both CTM and dynamic myelography were performed, the fistula was identified on both modalities in 88% of cases. CSF venous fistulas are an important cause of SIH that can be detected on both CTM and dynamic myelograph y and may occur without an epidural CSF leak. Familiarity with the imaging characteristics of these lesions is critical to providing appropriate treatment to patients with SIH.

[Streptococcus suis infection--clinical manifestations].

PubMed

Dragojlović, Julijana; Milosević, Branko; Sasić, Neda; Pelemis, Mijomir; Sasić, Milan

2005-01-01

Streptococcus suis is a bacterium causing a disease in pigs and rarely in humans. This zoonosis is mostly found as a sporadic disease in individuals that were in contact with the affected or infected pigs: farmers, veterinarians and workers engaged in fresh pork processing. It is assumed that the bacterium enters the body through a cut abrasion in the skin. Initially, the condition resembles a flu, followed by signs of bacteriemia and sepsis. The most frequent clinical manifestation of Streptococcus suis infection is meningitis, leading to hearing loss in over 75% of patients, and subsequent arthritis, endophtalmitis, endocarditis and pneumonia. Toxic shock syndrome with hemorhagic manifestations rarely develops. This study included five male patients aged 22 to 63 years treated in the Intensive Care Unit of the Institute of Infectious and Tropical Diseases in Belgrade, due to Streptococcus suis infection. The aim of this study was to point to the existence of this bacteria in our environment, to describe clinical manifestations of the disease and to point out the importance of its prevention. All patients had epidemiological evidence of being in contact with pork meat. There were no data about diseased pigs. The estimated incubation period was 4 to 8 days. All patients had meningeal signs. Clinical symptoms included shivering, fever, vomiting, headache, malaise, vertigo and tinitus. Three patients presented with alerterd level of awarrness. Four patients developed very severe bilateral hearing impairment, whereas one endophtalmtis and one developed endocarditis. The cerebrospinal fluid (CSF) was opalescent in four patients, and only one patient presented with clear CSF. CSF examination showed typical changes characteristic for bacterial meningitis. Streptoccocus suis was isolated in CSF in all patients, and in one patient the bacteria was isolated in blood as well. All patients underwent treatement with II and III generation cephalosporins and one with one aminoglycosides. All patients were cured, but 4 of them developed sequelae like permanent sensorineural deafness and mild ataxia. Streptococcus suis infection is present as a zoonosis in pigs, while humans are contracted occasionaly, most frequently related to occupational risk. In cases with bacterial meningitis with sepsis and hearing loss, Streptococcus suis infections must be suspected. Effective prevention requires collaboration between epidemiologists, veterinarians and human medicine physicians.

Differential diagnosis of scrub typhus meningitis from tuberculous meningitis using clinical and laboratory features.

PubMed

Valappil, Ashraf V; Thiruvoth, Sohanlal; Peedikayil, Jabir M; Raghunath, Praveenkumar; Thekkedath, Manojan

2017-12-01

The involvement of the central nervous system in the form of meningitis or meningoencephalitis is common in scrub typhus and is an important differential diagnosis of other lymphocytic meningitis like tuberculous meningitis (TBM). The aim of this study was to identify the clinical and laboratory parameters that may be helpful in differentiating scrub typhus meningitis from TBM. We compared of the clinical and laboratory features of 57 patients admitted with scrub typhus meningitis or TBM during a 3-year period. Patients who had abnormal cerebrospinal fluid (CSF) and positive scrub typhus enzyme-linked immunosorbent assay serology (n=28) were included in the scrub typhus meningitis group, while the TBM group included those who satisfied the consensus diagnostic criteria of TBM (n=29). Compared with the TBM group, the mean duration of symptoms was less in patients with scrub typhus meningitis, who also had a lower magnitude of neurological deficits, such as altered mental status and cranial nerve and motor deficits. Patients with scrub typhus meningitis had a lower CSF white blood-cell count (WBC) than the TBM group (130.8±213 195±175 cells/mm 3 , P=0.002), lower CSF protein elevation (125±120 vs. 195.2±108.2mg/dl, P=0.002), and higher CSF sugar (70.1±32.4 vs. 48.7±23.4mg/dl, P=0.006). Features predictive of the diagnosis of scrub typhus meningitis included the absence of neurological impairment at presentation, blood serum glutamic-oxaloacetic transaminase>40 international units (IU)/L, serum glutamic-pyruvic transaminase>60 IU/L, total blood leukocyte count>10,000/mm 3 , CSF protein<100mg/dl, CSF sugar>50mg/dl, CSF WBC<100 cells/mm 3 . All patients with scrub typhus meningitis recovered completely following doxycycline therapy CONCLUSIONS: This study suggests that, clinical features, including duration of fever, neurological deficits at presentation and laboratory parameters such as CSF pleocytosis,CSF protein elevation, CSF sugar levels and liver enzyme values are helpful in differentiating scrub typhus meningitis from tuberculous meningits. These features with scrub IgM serology may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis. Copyright © 2017 Elsevier B.V. All rights reserved.

Comprehensive Soldier Fitness (CSF) Experiment: Research Biases in the Development of the CSF

DTIC Science & Technology

2013-06-13

issues that Soldiers were having, mostly during or returning from deployments. Issues such as PTSD, depression , and suicide . Seligman helped the...argues that the domains that are being measured do not necessarily link themselves to the key stressors that cause PTSD, depression , or suicide (Eidelson...or lessen any one of the key of stressors that cause PTSD, depression , and suicidality , which was supposed to be the results of the CSF (Eidelson

Fever--an update.

PubMed

Becker, John H; Wu, Stephanie C

2010-01-01

Fever is an active yet nonspecific response of the body to infections and other insults that cause immune cells to release cytokines, resulting in a brain prostanoid-mediated rise in body temperature. The causes, types, clinical management, and postoperative consequences of fever are reviewed in this article. Physicians use fever as a clinical sign for diagnoses and prognoses, but "fevers of unknown origin" continue to be problematic. Fevers that arise 1 or 2 days after surgery are usually due to stress and trauma, but later postoperative fevers often have more serious causes and consequences, such as wound infection. Fever is commonly encountered by podiatric physicians and surgeons, and certain procedures with the lower extremity are more likely to eventuate in fever.

Hunters' acceptability of the surveillance system and alternative surveillance strategies for classical swine fever in wild boar - a participatory approach.

PubMed

Schulz, Katja; Calba, Clémentine; Peyre, Marisa; Staubach, Christoph; Conraths, Franz J

2016-09-06

Surveillance measures can only be effective if key players in the system accept them. Acceptability, which describes the willingness of persons to contribute, is often analyzed using participatory methods. Participatory epidemiology enables the active involvement of key players in the assessment of epidemiological issues. In the present study, we used a participatory method recently developed by CIRAD (Centre de Coopération Internationale en Recherche Agronomique pour le Développement) to evaluate the functionality and acceptability of Classical Swine Fever (CSF) surveillance in wild boar in Germany, which is highly dependent on the participation of hunters. The acceptability of alternative surveillance strategies was also analyzed. By conducting focus group discussions, potential vulnerabilities in the system were detected and feasible alternative surveillance strategies identified. Trust in the current surveillance system is high, whereas the acceptability of the operation of the system is medium. Analysis of the acceptability of alternative surveillance strategies showed how risk-based surveillance approaches can be combined to develop strategies that have sufficient support and functionality. Furthermore, some surveillance strategies were clearly rejected by the hunters. Thus, the implementation of such strategies may be difficult. Participatory methods can be used to evaluate the functionality and acceptability of existing surveillance plans for CSF among hunters and to optimize plans regarding their chances of successful implementation.

Normocellular CSF in herpes simplex encephalitis.

PubMed

Saraya, Abhinbhen W; Wacharapluesadee, Supaporn; Petcharat, Sininat; Sittidetboripat, Nuntaporn; Ghai, Siriporn; Wilde, Henry; Hemachudha, Thiravat

2016-02-15

Herpes simplex virus (HSV) is the most common cause of sporadic encephalitis worldwide. The high mortality rate (70-80 %) of herpes simplex encephalitis (HSE) can be reduced to 20-30 % by antiviral therapy. However, normocellular CSF can lure physicians to look for non-infectious causes, resulting in delayed treatment. This study aimed to investigate, characterize and differentiate HSE patients, with normocellular and pleocytosis CSF, according to neuroimaging patterns, underlying disease, CSF viral load and clinical outcome. Patients with proven (by PCR positive CSF) or presumed viral infections of the CNS admitted to King Chulalongkorn Memorial Hospital between January 2002 and 2011 were analyzed. HSV was detected in the CSF of 43 patients but only 23 patients had encephalitis. Among these 23 patients, 6 cases (26.1 %) had normal CSF WBC (<5 cells/mm(3)). One patient in this normocellular CSF group had HIV infection. Although this patient had low CD4 counts (<200 cells/mm(3)), the peripheral WBC counts showed only mild leukopenia. The CSF HSV viral load in the pleocytosis group was higher than the normocellular group, with an average of 12,200 vs 3027 copies/ml respectively. There was no correlation between the viral load and the clinical outcome. With respect to neuroimaging, 4 (66.7 %) patients in the normocellular group had unremarkable/non-specific results. Normocellular CSF in HSE is not rare, and can be seen in normal as well as immunocompromised hosts. Clinicians should not exclude CNS infection, especially HSE, merely based on the absence of CSF pleocytosis and/or unremarkable neuroimaging study.

A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids☆

PubMed Central

Ahmed, Rebekah; Guerreiro, Rita; Rohrer, Jonathan D.; Guven, Gamze; Rossor, Martin N.; Hardy, John; Fox, Nick C.

2013-01-01

We report a family with a novel CSF1R mutation causing hereditary diffuse leucoencephalopathy with axonal spheroids. Family members presented with neuropsychiatric and behavioural symptoms, with subsequent development of motor symptoms and gait disturbance. MRI brain showed extensive white matter change with a frontal predominance and associated atrophy in two members of the family. Genetic testing revealed a novel mutation c.2342C > T (p.A781V) in the CSF1R gene in two brothers of the family. This report highlights the difficulties in diagnosing HDLS and discusses the indications for testing for mutations in the CSF1R gene. PMID:23816250

Early awareness of cerebrospinal fluid hypovolemia after craniotomy for microsurgical aneurysmal clipping.

PubMed

Kawahara, Ichiro; Tsutsumi, Keisuke; Matsunaga, Yuki; Takahata, Hideaki; Ono, Tomonori; Toda, Keisuke; Baba, Hiroshi

2013-08-01

Mild cerebrospinal fluid (CSF) hypovolemia is a well-known clinical entity, but critical CSF hypovolemia that can cause transtentorial herniation is an unusual and rare clinical entity that occurs after craniotomy. We investigated CSF hypovolemia after microsurgical aneurysmal clipping for subarachnoid hemorrhage (SAH). This study included 144 consecutive patients with SAH. Lumbar drainage (LD) was inserted after general anesthesia or postoperatively as a standard perioperative protocol. CSF hypovolemia diagnosis was based on three criteria. Eleven patients (7.6%) were diagnosed with CSF hypovolemia according to diagnostic criteria in a postoperative range of 0-8 days. In all patients, signs or symptoms of CSF hypovolemia improved within 24 hours by clamping LD and using the Trendelenburg position. As a cause of acute clinical deterioration after aneurysmal clipping, CSF hypovolemia is likely under-recognized, and may actually be misdiagnosed as vasospasm or brain swelling. We should always take the etiology of CSF hypovolemia into consideration, and especially pay attention in patients with pneumocephalus and subdural fluid collection alongside brain sag on computed tomography. These patients are at higher risk developing of pressure gradients between their cranial and spinal compartments, and therefore, brain sagging after LD, than after ventricular drainage. We should be vigilant to strictly manage LD so as not to produce high pressure gradients.

Infections in the differential diagnosis of Bell's palsy: a plea for performing CSF analysis.

PubMed

Henkel, Katrin; Lange, Peter; Eiffert, Helmut; Nau, Roland; Spreer, Annette

2017-04-01

Peripheral facial nerve palsy (FP) is the most common single nerve affection. Most cases are idiopathic, but a relevant fraction is caused by potentially treatable aetiologies including infections. Not all current diagnosis and treatment guidelines recommend routine cerebrospinal fluid (CSF) analysis in the diagnostic workup of this symptom. In this study, we evaluated frequency of aetiologies and relevance of CSF analysis in an interdisciplinary cohort. We retrospectively analysed all cases of newly diagnosed FP treated at a German university medical centre in a 3-year period. Diagnostic certainty was classified for infectious aetiologies according to clinical and CSF parameters. 380 patients with FP were identified, 63 children and 317 adults. Idiopathic Bell´s palsy was predominant in 61 %. 25 % of FP was attributed to infections, and other causes were identified in 14 %. Clinical presentation alone was not conclusive for infectious aetiology, in almost half of patients with infection-attributed FP the reported symptoms or clinical signs did not differ from common symptoms of idiopathic Bell`s palsy. Determination of C-reactive protein or white blood cell count was not helpful in the identification of infectious causes, and radiological imaging was performed in a high proportion of adult patients without conclusive results. Nuchal rigidity was found only in 7 % of patients with CSF pleocytosis. The predominant infectious agents were Borrelia burgdorferi, VZV and HSV, and in most of these cases diagnosis relied on the findings of CSF analysis. This study outlines the importance of careful differential diagnosis to identify infectious causes of facial nerve palsy. The high incidence and frequent unspecific clinical presentation of infectious FP underlines the importance of including CSF analysis in the diagnostic routine workup of FP.

Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology

PubMed Central

Michael, Benedict D.; Griffiths, Michael J.; Granerod, Julia; Brown, David; Davies, Nicholas W. S.; Borrow, Ray; Solomon, Tom

2016-01-01

Background Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15–60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. Methods We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Results Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Conclusions Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation. PMID:26808276

Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

PubMed

Michael, Benedict D; Griffiths, Michael J; Granerod, Julia; Brown, David; Davies, Nicholas W S; Borrow, Ray; Solomon, Tom

2016-01-01

Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause. We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology. Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001). Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

Implantable Systems for Continuous Liquorpheresis and CSF Replacement

PubMed Central

2017-01-01

Liquorpheresis (cerebrospinal fluid filtration) comprises a therapeutical approach that has been proposed to treat several neurological conditions where antibodies, inflammatory mediators, or abnormal peptides are the cause or play an important role in the pathogenesis of the disease. Continuous or intermittent cerebrospinal fluid (CSF) replacement may be an alternative approach not explored thus far. Here, we review previous experiences in the use of liquorpheresis in autoimmune and degenerative neurological diseases. Then we describe previous technical reports  and provide some new innovations in order to design bidirectional CSF shunting systems that can be complemented either with a deposit of artificial CSF or with a filter of CSF, allowing CSF replacement or liquorpheresis respectively. Both options would lead to mechanical dilution of the patient’s CSF. PMID:28413734

Human T-cell lymphotropic virus (HTLV)-associated encephalopathy: an under-recognised cause of acute encephalitis? Case series and literature review.

PubMed

Crawshaw, Ania A; Dhasmana, Divya; Jones, Brynmor; Gabriel, Carolyn M; Sturman, Steve; Davies, Nicholas W S; Taylor, Graham P

2018-04-01

Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) is well described. Clinical features are predominantly consistent with cord pathology, though imaging and autopsy studies also demonstrate brain inflammation. In general, this is subclinical; however, six cases have previously been reported of encephalopathy in HTLV-1-infected patients, without alternative identified aetiology. We describe three further cases of encephalitis in the UK HAM cohort (n = 142), whereas the annual incidence of acute encephalitis in the general population is 0.07-12.6 per 100,000. Clinical features included reduced consciousness, fever/hypothermia, headaches, seizures, and focal neurology. Investigation showed: raised CSF protein; pleocytosis; raised CSF:peripheral blood mononuclear cell HTLV-1 proviral load ratio; and MRI either normal or showing white matter changes in brain and cord. Four of the six previous case reports of encephalopathy in HTLV-infected patients also had HAM. Histopathology, reported in three, showed perivascular predominantly CD8+ lymphocytic infiltrates in the brain. One had cerebral demyelination, and all had cord demyelination. We have reviewed the existing six cases in the literature, together with our three new cases. In all seven with HAM, the spastic paraparesis deteriorated sub-acutely preceding encephalitis. Eight of the nine were female, and four of the seven treated with steroids improved. We propose that HTLV-associated encephalopathy may be part of the spectrum of HTLV-1-induced central nervous system disease.

Aseptic meningitis in children: analysis of 506 cases.

PubMed

Michos, Athanasios G; Syriopoulou, Vassiliki P; Hadjichristodoulou, Christos; Daikos, George L; Lagona, Evagelia; Douridas, Panagiotis; Mostrou, Glykeria; Theodoridou, Maria

2007-08-01

Non-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored. A retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm(3) with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (P = 0.01). There were no serious complications or deaths. Enteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis.

Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after primary immunisation.

PubMed

Tarai, B; Ravishankar, N; Vohra, P; Das, P

2015-01-01

We report a 14-month-male child, who developed Hemophilus influenzae meningitis after three primary doses of the vaccine. The child presented with fever and seizures. H. influenzae was isolated from both cerebrospinal fluid (CSF) and blood. The child also had features of septicaemia. Procalcitonin (104 ng/ml) and C-reactive protein (CRP--42.6 mg/dl) were high. Appropriate antibiotics were given. The child made an uneventful recovery. This case highlights vaccine failure, especially after primary immunisation alone.

[Diagnostic difficulties in encephalitis: two case reports].

PubMed

Garlicki, A; Dereszak-Kozanecka, E; Pietruszewski, K; Krukowiecki, J

1997-01-01

The differential diagnosis of psychiatric symptoms in encephalitis, especially in the early phase of the disease may be very difficult. It is particularly hard to distinguish it from the classic psychosis. The diagnostic problems have been presented on the basis of analysis of two case reports of the acute encephalitis in young persons. The presence of fever and pathological changes in the CSF were the most important indicators that helped to establish the diagnosis of encephalitis during the phase of acute psychopathological disorders.

Intensive chemotherapy plus recombinant human granulocyte-colony stimulating factor support for distant metastatic nasopharyngeal carcinoma. A preliminary report.

PubMed

Wang, C H; Wang, H M; Chen, J S; Chang, W J; Lai, G M

1997-01-01

Nasopharyngeal carcinoma (NPC) has been shown to be highly responsive to chemotherapy. The major limiting toxicity was myelotoxicity. Recently, the role of granulocyte colony-stimulating factor (G-CSF) in reducing chemotherapy-induced neutropenic sepsis has been well established. In this study, we tested whether recombinant human G-CSF (rhG-CSF) could effectively support the bone marrow function in both previously untreated and pretreated metastatic NPC patients receiving intensive chemotherapy. Twelve patients with distant metastatic disease, 5 newly diagnosed (group A) and 7 pretreated patients (group B), were enrolled to receive BEC (bleomycin, epirubicin and cisplatin), followed by rhG-CSF support (50 microg/m2 s.c. daily for 10 days) every 4 weeks for two cycles. Four patients in group A completed the treatment as scheduled while only 2 patients in group B did. After the first treatment cycle, 6 patients (50%) had grade III-IV myelosuppression. Five of the patients were from group B. The mean values of the white cell count nadir were 2,680 (range 1,200-3,700) in group A and 1,343 (range 400-2,900) in group B (p = 0.0386). Neutropenia-associated fever occurred in 7 patients, 6 of whom had received previous treatment. There were 2 deaths due to toxicity, and both patients had liver metastases within 6 months following radiation. After 24 months of follow-up, only 1 patient is still alive. Our preliminary results suggest that in previously treated metastatic NPC patients, bone marrow suppression is still the major limiting toxic side effect of aggressive chemotherapy, especially for those patients with liver recurrences within 6 months after irradiation and despite rhG-CSF support.

Clinical utility of serum samples for human parechovirus type 3 infection in neonates and young infants: The 2014 epidemic in Japan.

PubMed

Aizawa, Yuta; Suzuki, Yuko; Watanabe, Kanako; Oishi, Tomohiro; Saitoh, Akihiko

2016-02-01

During the 2014 human parechovirus type 3 (HPeV3) epidemic in Niigata, Japan, this prospective observational study identified HPeV3 from 43/85 (51%) febrile young infants <4 months using PCR analysis of serum (n = 42) and/or cerebrospinal fluid (CSF) (n = 32) and genetic sequencing of the VP1 region of HPeV3. HPeV3-infected patients (median age, 32 days; range, 4-113 days) were diagnosed as having sepsis (79%), sepsis-like syndrome (19%), or encephalitis with septic shock (2%). Other than fever, mottled skin (67%) was significantly more frequent in HPeV3-infected patients than other virus-infected patients (P = 0.005). The rate of HPeV3 RNA detection in CSF without pleocytosis was high (88%; 28/32). Among the 32 patients whose serum and CSF samples were available, all patients were positive for serum PCR; however, 4 (12%) patients were negative for CSF PCR. Serum HPeV3 RNA level on admission was associated with younger age (P = 0.002), bad temper (P = 0.041), and grunting (P = 0.008). Among 6 patients with sequential data on serum HPeV3 RNA level, levels decreased rapidly without specific therapy. In conclusion, serum samples at disease onset are the most useful compared to CSF in detection of HPeV RNA and serum HPeV3 RNA level on admission was associated with important clinical manifestations in HPeV3-infected patients. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Tsutsugamushi Disease (Scrub Typhus) Meningoencephalitis in North Eastern India: A Prospective Study.

PubMed

Sharma, S R; Masaraf, H; Lynrah, K G; Lyngdoh, M

2015-01-01

Scrub typhus is rampant in northern, eastern, and southern India. Central nervous system involvement in the form of meningitis or meningoencephalitis is common in scrub typhus. As specific laboratory methods remain inadequate or inaccessible in developing countries, prompt diagnosis is often difficult. The aim of this study was to characterize neurological complications in scrub typhus from northeastern region of India. We did a prospective study of scrub meningoencephalitis at North Eastern Indira Gandhi Regional Institute of Medical Sciences among patients admitted to hospital between October 2009 and November 2011. The diagnosis was made based on the clinical pictures, presence of an eschar, and a positive Weil-Felix test (WFT) with a titer of >1:160 and if required a positive scrub IgM enzyme-linked immunosorbent assay. Lumbar puncture was performed in patients with headache, nuchal rigidity, altered sensorium or cranial nerve deficits, and magnetic resonance imaging (MRI) brain performed if needed. Twenty-three patients of scrub typhus meningitis that were serologically confirmed were included in the study. There were 13 males and 10 females. Fever ≥1 week was the most common manifestation (39.1%). Interestingly, none had an eschar. Median cerebrospinal fluid (CSF) cell count, lymphocyte percentage, CSF protein, CSF glucose/blood glucose, CSF ADA were 17 cells/μL, 90%, 86 mg/dL, 0.6605 and 3.6 U/mL, respectively. All patients were treated with doxycycline. There was no mortality in our study. Absence of Eschar does not rule out scrub typhus. Clinical features and CSF findings can mimic tuberculous meningitis so misdiagnosis may lead to unwarranted prolonged empirical antituberculous therapy in cases of lymphocytic meningoencephalitis. Delay in treatment can be potentially fatal. WFT still serves as a useful and affordable diagnostic tool for this disease in resource-poor countries.

Pathophysiology of Relapsing Fever: Interaction of Borrelia Spirochetes with Blood Mononuclear Leukocytes Causes Production of Leukocytic Pyrogen and Tissue Thromboplastin.

DTIC Science & Technology

1980-12-10

AD-A093 BN6 CASE WESTERN RESERVE UNIV CLEVELAND OH DEPT OF MEDICINE FIG 6/5 PAT1OPHYSIOLOGY OF RELAPSING FEVERS INTERACTION OF BORRELtA SPI-ETC(U...NUMBER 4 Pathophysiology of Relapsing Fever : Interaction of Borrelia Spirochetes 0 with Blood Mononuclear Leukocytes Causes Production of Leukocytic...Relapsing fever caused by Borrelia spirochetes is characterized by episodes of spirochetemia, fever , and disseminated intravascular coagu- lation (DIC

First report on the diagnosis and treatment of encephalic and urinary paracoccidioidomycosis in a cat.

PubMed

Gonzalez, Juan F; Montiel, Nestor A; Maass, Rodrigo L

2010-08-01

A male Persian cat was presented with persistent fever, anorexia, weakness, hypopyon, nystagmus, and intention tremors. The hemogram showed severe neutropenia and laboratory analysis on cerebrospinal fluid (CSF) smears revealed abundant yeast cells compatible with Paracoccidioides brasiliensis. Urinalysis demonstrated persistent funguria and an increased urine protein-to-creatinine ratio (UPC) in addition to mild azotemia. Long-term therapy with oral fluconazole was effective in controlling the nervous system signs. Funguria was resolved with subcutaneous administration of diluted amphotericin B in a large volume of saline solution for a period of 12 weeks during the second year after initial diagnosis. Throughout 5 years of treatment, no adverse effects were observed and tolerance to the drugs was normal. Due to development of progressive uremic syndrome the animal was euthanased. To the best of our knowledge, this report is the first clinical case described of a nervous and urinary system infection caused by the P brasiliensis in a cat. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Recombinant human granulocyte colony-stimulating factor administration in a case of neutropenia due to increased neutrophil sequestration.

PubMed

Carulli, G; Lazzeri, E; Lagomarsini, G; Zucca, A; Cannizzo, E; Riccioni, R; Petrini, M

2007-01-01

A 55-year-old female was admitted with fever which followed an episode of pseudomembranous colitis. Despite an accurate clinical investigation, there was no evidence for specific sites of infection. Remission of fever was not obtained with antibiotic therapy (gentamycin plus carbepenem) and progressive neutropenia was observed. Neutrophils fell to 0.3 x 10(9)/1. The diagnostic approach, including a bone marrow aspirate, excluded mechanisms leading to impaired neutrophil production, and in the suspect of increased neutrophil sequestration/destruction, whole-body scintigraphy with (99m)technetium-hexamethylpropyleneamineoxime ((99m)Tc-HMPAO)-labeled autologous leukocytes was performed. As a result, a site of leukocyte sequestration localized at the medium lobe of the right lung was detected. In an attempt to enhance neutrophil functions and achieve remission of infection, recombinant human granulocyte colony-stimulating factor (Filgrastim, Granulokine 30, Roche) at the dosage of 300 microg/day, subcutaneously, was added. As a results, fever disappeared in three days, but neutrophil recovery was slower, and normalization of the absolute neutrophil count (ANC) was obtained on day +7. The results obtained in this peculiar case of neutropenia, and the kinetics of both fever and ANC, suggest the possible combination of neutrophil function enhancement and an anti-inflammatory effect of rhG-CSF.

Simulating the spread of classical swine fever virus between a hypothetical wild-boar population and domestic pig herds in Denmark.

PubMed

Boklund, A; Goldbach, S G; Uttenthal, A; Alban, L

2008-07-15

Denmark has no free-range wild-boar population. However, Danish wildlife organizations have suggested that wild boar should be reintroduced into the wild to broaden national biodiversity. Danish pig farmers fear that this would lead to a higher risk of introduction of classical swine fever virus (CSFV), which could have enormous consequences in terms of loss of pork exports. We conducted a risk assessment to address the additional risk of introducing and spreading CSFV due to the reintroduction of wild boar. In this paper, we present the part of the risk assessment that deals with the spread of CSFV between the hypothetical wild-boar population and the domestic population. Furthermore, the economic impact is assessed taking the perspective of the Danish national budget and the Danish pig industry. We used InterSpreadPlus to model the differential classical swine fever (CSF) risk due to wild boar. Nine scenarios were run to elucidate the effect of: (a) presence of wild boar (yes/no), (b) locations for the index case (domestic pig herd/wild-boar group), (c) type of control strategy for wild boar (hunting/vaccination) and (d) presence of free-range domestic pigs. The presence of free-range wild boar was simulated in two large forests using data from wildlife studies and Danish habitat data. For each scenario, we estimated (1) the control costs borne by the veterinary authorities, (2) the control-related costs to farmers and (3) the loss of exports associated with an epidemic. Our simulations predict that CSFV will be transmitted from the domestic pig population to wild boar if the infected domestic pig herd is located close to an area with wild boar (<5 km). If an outbreak begins in the wild-boar population, the epidemic will last longer and will occasionally lead to several epidemics because of periodic transfer of virus from groups of infected wild boar to domestic pig herds. The size and duration of the epidemic will be reduced if there are no free-range domestic pig herds in the area with CSF-infected wild boar. The economic calculations showed that the total national costs for Denmark (i.e. the direct costs to the national budget and the costs to the pig industry) related to an outbreak of CSF in Denmark will be highly driven by the reactions of the export markets and in particular of the non-EU markets. Unfortunately, there is a substantial amount of uncertainty surrounding this issue. If hunting is used as a control measure, the average expenses related to a CSF outbreak will be 40% higher if wild boar are present compared with not present. However, a vaccination strategy for wild boar will double the total costs compared with a hunting strategy.

Aseptic meningitis in children--the Singapore experience.

PubMed

Tee, W S N; Choong, C T; Lin, R V T P; Ling, A E

2002-11-01

To study the incidence, aetiology, clinical characteristics and management of paediatric aseptic meningitis in a paediatric hospital in Singapore. Patients with cerebrospinal fluid (CSF) pleocytosis, a negative Gram stain and bacterial culture were reviewed retrospectively from 1 January to 31 December 2000. Eighty-seven patients who fulfilled the criteria for aseptic meningitis and without neurological deficits were studied. In addition, reverse transcriptase polymerase chain reaction (RT-PCR) using pan enterovirus primers was subsequently performed on 73 of these CSF specimens which were available for storage. The incidence of aseptic meningitis was approximately 37 cases per 10,000 admissions. Non-polio enteroviruses were isolated from 29 of 64 (45.3%) CSF and 38 of 52 (73.1%) stool samples. RT-PCR was positive in 43 (58.9%) of the archived CSF specimens. The aetiologies of the remaining cases were mostly unidentified. Their ages ranged from 5 days to 12 years (median, 2 months). All patients except 1 had fever. Vomiting or poor feeding occurred in 44.7%, cough or running nose in 35.3%, irritability was observed in 35.3%, seizures in 7.1%, a rash in 10.6% and diarrhoea in 5.9%. All patients recovered without sequelae. The median CSF white cell count was 212 cells/mm3 (range, 7 to 12,000). The median glucose concentration was 2.7 mmol/L (range, 1.6 to 4.4). The median CSF/blood glucose ratio was 0.52 (range, 0.23 to 0.73). Median length of stay was 7 days (range, 4 to 17). Eighty-four patients (96.6%) received antibiotics for a median of 5.5 days (range, 2 to 14). Enteroviruses were the most common aetiologic agent identified. A method of early diagnosis using RT-PCR for enteroviruses is necessary to reduce the current duration of antibiotic usage and to decrease the length of hospital stay.

Co-infection ZIKV and HSV-1 associated with meningoencephalitis: Case report and literature review.

PubMed

Araújo, Paulo S Ramos de; Silva Júnior, Mário L de Mélo; Tenório, Marli; Santos, Fabiana G Torreão Dos

2018-04-24

A man, 26years-old, presented fever, mental confusion and a progressively worsening headache 6days prior to admission. The CSF study was suggestive of meningoencephalitis, the PCR study revealed presence of HSV-1 and ZIKV, while other immunology tests were negative. ZIKV was also identified in serum. The MRI showed temporal lobe hyper-intensity in FLAIR-weight sequence with areas of contrast enhancement and the electroencephalogram showed slow wave activity in such region. Patient was treated with acyclovir and supportive measures and had good clinical outcome at evaluation after 6 months. Neurological spectrum of ZIKV manifestations is wide, but meningoencephalitis is not frequent. Co-infection HSV-1 plus ZIKV was not yet related in humans, but there is increased cellular damage caused by association of ZIKV and herpes virus family infection. ZIKV may facilitate infection or recrudescence by other viruses or cause concurrently neuronal injury by direct or indirect mechanisms. We suggest that clinicians attempt new manifestations related to ZIKV and include this agent in differential diagnosis of neurological diseases even when other agents were identified. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

PubMed Central

Piccoli, Luca; Campo, Ilaria; Fregni, Chiara Silacci; Rodriguez, Blanca Maria Fernandez; Minola, Andrea; Sallusto, Federica; Luisetti, Maurizio; Corti, Davide; Lanzavecchia, Antonio

2015-01-01

Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies. PMID:26077231

Combination chemotherapy containing mitoguazone, ifosfamide, methotrexate, etoposide (MIME) and G-CSF efficiently mobilize peripheral blood progenitor cells in heavily pre-treated relapsed lymphoma patients.

PubMed

Aurlien, E; Holte, H; Kvaløy, S; Jakobsen, E; Rusten, L S; Kvalheim, G

2001-07-01

In this study we explored whether a standard chemotherapy regimen consisting of mitoguazone, ifosfamide, methotrexate and etoposide (MIME) combined with 5 micrograms/kg or 10 micrograms/kg G-CSF was capable of mobilizing peripheral blood progenitor cells (PBPC) in lymphoma patients. Thirty-three patients with Hodgkin's disease (HD) and 108 patients with non-Hodgkin's lymphoma (NHL) were mobilized with MIME/G-CSF. Most patients were heavily treated with different chemotherapy regimens receiving a median of 11 cycles (range 3-40) of chemotherapy prior to mobilization. Eight of 141 patients failed to mobilize PBPC and bone marrow was harvested. In addition, 10 patients obtained a harvest of < 2.0 x 10(6) CD34+ cells/kg. More than 2.0 x 10(6) CD34+ cells/kg were achieved in all HD patients and in 83% of the NHL patients. Fifty-eight per cent of the patients harvested > or = 5 x 10(6) CD34+ cells/kg. Eleven per cent of the patients developed neutropenic fever during the mobilization and 3% had nadir platelet values below 20 x 10(9)/L. An inverse correlation was observed in high-grade NHL (H-NHL) patients between the number of chemotherapy cycles given before mobilization and yield of CD34+ cells. Such an association was not seen among patients with HD, transformed and low-grade NHL. When G-CSF 10 micrograms/kg was used in combination with MIME, this correlation was no longer seen in patients with H-NHL. There was also association between CD34+ cell yield and prior radiotherapy in patients with HD or transformed NHL or low-grade NHL. These results demonstrate that an ordinary salvage chemotherapy regimen, such as MIME combined with G-CSF, can be successfully used to mobilize PBPC. Although no significant effect of increased dose of G-CSF was found, our data suggest that MIME/G-CSF 10 micrograms/kg should preferentially be used to mobilize PBPC in H-NHL patients pre-treated with > or = 12 cycles of chemotherapy, in irradiated HD patients and in all low-grade and transformed lymphomas.

Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed.

PubMed

Dinarello, Charles A

2004-01-01

For many years, it was thought that bacterial products caused fever via the intermediate production of a host-derived, fever-producing molecule, called endogenous pyrogen (EP). Bacterial products and other fever-producing substances were termed exogenous pyrogens. It was considered highly unlikely that exogenous pyrogens caused fever by acting directly on the hypothalamic thermoregulatory center since there were countless fever-producing microbial products, mostly large molecules, with no common physical structure. In vivo and in vitro, lipopolysaccharides (LPSs) and other microbial products induced EP, subsequently shown to be interleukin-1 (IL-1). The concept of the 'endogenous pyrogen' cause of fever gained considerable support when pure, recombinant IL-1 produced fever in humans and in animals at subnanomolar concentrations. Subsequently, recombinant tumor necrosis factor-alpha (TNF-alpha), IL-6 and other cytokines were also shown to cause fever and EPs are now termed pyrogenic cytokines. However, the concept was challenged when specific blockade of either IL-1 or TNF activity did not diminish the febrile response to LPS, to other microbial products or to natural infections in animals and in humans. During infection, fever could occur independently of IL-1 or TNF activity. The cytokine-like property of Toll-like receptor (TLR) signal transduction provides an explanation by which any microbial product can cause fever by engaging its specific TLR on the vascular network supplying the thermoregulatory center in the anterior hypothalamus. Since fever induced by IL-1, TNF-alpha, IL-6 or TLR ligands requires cyclooxygenase-2, production of prostaglandin E2 (PGE2) and activation of hypothalamic PGE2 receptors provides a unifying mechanism for fever by endogenous and exogenous pyrogens. Thus, fever is the result of either cytokine receptor or TLR triggering; in autoimmune diseases, fever is mostly cytokine mediated whereas both cytokine and TLR account for fever during infection.

Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection.

PubMed

Hagberg, Lars; Cinque, Paola; Gisslen, Magnus; Brew, Bruce J; Spudich, Serena; Bestetti, Arabella; Price, Richard W; Fuchs, Dietmar

2010-06-03

HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients.In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays (<50 copies HIV RNA/mL), CSF neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued CNS infection and whether it causes continued indolent CNS injury.Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.

Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.

PubMed

Rothchild, Alissa C; Stowell, Britni; Goyal, Girija; Nunes-Alves, Cláudio; Yang, Qianting; Papavinasasundaram, Kadamba; Sassetti, Christopher M; Dranoff, Glenn; Chen, Xinchun; Lee, Jinhee; Behar, Samuel M

2017-10-24

Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF -/- ) are highly susceptible to infection with Mycobacterium tuberculosis , and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T cells also produce GM-CSF during M. tuberculosis infection. Early during infection, nonconventional iNKT cells and γδ T cells are the main source of GM-CSF, a role subsequently assumed by conventional CD4 + T cells as the infection progresses. M. tuberculosis -specific T cells producing GM-CSF are also detected in the peripheral blood of infected people. Under conditions where nonhematopoietic production of GM-CSF is deficient, T cell production of GM-CSF is protective and required for control of M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated protection in settings where GM-CSF is produced by other cell types. Finally, using an in vitro macrophage infection model, we demonstrate that GM-CSF inhibition of M. tuberculosis growth requires the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Thus, we identified GM-CSF production as a novel T cell effector function. These findings suggest that a strategy augmenting T cell production of GM-CSF could enhance host resistance against M. tuberculosis IMPORTANCE Mycobacterium tuberculosis is the bacterium that causes tuberculosis, the leading cause of death by any infection worldwide. T cells are critical components of the immune response to Mycobacterium tuberculosis While gamma interferon (IFN-γ) is a key effector function of T cells during infection, a failed phase IIb clinical trial and other studies have revealed that IFN-γ production alone is not sufficient to control M. tuberculosis In this study, we demonstrate that CD4 + , CD8 + , and nonconventional T cells produce GM-CSF during Mycobacterium tuberculosis infection in mice and in the peripheral blood of infected humans. Under conditions where other sources of GM-CSF are absent, T cell production of GM-CSF is protective and is required for control of infection. GM-CSF activation of macrophages to limit bacterial growth requires host expression of the transcription factor PPARγ. The identification of GM-CSF production as a T cell effector function may inform future host-directed therapy or vaccine designs. Copyright © 2017 Rothchild et al.

[No connection between scarlet fever and gouty fever. Historical analysis from Ytre Nordhordland during 1862-1884].

PubMed

Sandvik, H

1992-12-10

In 1987 there was an unexplained increase in severe streptococcal diseases in Norway and other western countries. In Norway this increase was not accompanied by a corresponding increase in acute rheumatic fever. This study investigated the occurrence of scarlet fever and acute rheumatic fever in a rural district (approximately 15,000 inhabitants) of western Norway during the years 1862-1884. Four epidemics of severe scarlet fever occurred during this period. The local doctor treated 1,155 patients (96% children), of whom 154 (13.3%) died. Acute glomerulonephritis with subsequent kidney failure seems to have been a major cause of death. During the same period 76 patients (96% adults) were treated for acute rheumatic fever. These cases were not related to the severe epidemics of scarlet fever. It is probable that different, co-circulating strains of streptococci caused the infections, which were followed by glomerulonephritis and rheumatic fever. It is possible that rheumatic fever was caused by the strain that induced the more benign "Angina tonsillaris".

Hemorrhagic Fevers

MedlinePlus

... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

Powassan encephalitis and Colorado tick fever.

PubMed

Romero, José R; Simonsen, Kari A

2008-09-01

This article discusses two tick-borne illnesses: Powassan encephalitis, a rare cause of central nervous system infection caused by the Powassan virus, and Colorado tick fever, an acute febrile illness caused by the Colorado tick fever virus common to the Rocky Mountain region of North America.

Yellow Fever Outbreak, Southern Sudan, 2003

PubMed Central

Onyango, Clayton O.; Grobbelaar, Antoinette A.; Gibson, Georgina V.F.; Sang, Rosemary C.; Sow, Abdourahmane; Swanepoel, Robert

2004-01-01

In May 2003, an outbreak of fatal hemorrhagic fever, caused by yellow fever virus, occurred in southern Sudan. Phylogenetic analysis showed that the virus belonged to the East African genotype, which supports the contention that yellow fever is endemic in East Africa with the potential to cause large outbreaks in humans. PMID:15498174

The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation.

PubMed

Cesaro, Simone; Marson, Piero; Gazzola, Maria Vittoria; De Silvestro, Giustina; Destro, Roberta; Pillon, Marta; Calore, Elisabetta; Messina, Chiara; Zanesco, Luigi

2002-08-01

Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in the medium term rhG-CSF is not associated with an excess of lymphoproliferative disorders. Currently, caution on the long-term safety of the use of rhG-CSF in healthy donor is still warranted but the data so far accumulated on allogeneic PBSC transplants are encouraging both as far as concerns the good short-medium tolerability profile of G-CSF-stimulation of the donor and the potential major efficacy in leukemia patients.

The Laminin Receptor Is a Cellular Attachment Receptor for Classical Swine Fever Virus

PubMed Central

Chen, Jianing; He, Wen-Rui; Shen, Liang; Dong, Hong; Yu, Jiahui; Wang, Xiao; Yu, Shaoxiong; Li, Yongfeng; Li, Su; Luo, Yuzi; Sun, Yuan

2015-01-01

ABSTRACT Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious, economically important viral disease in many countries. The Erns and E2 envelope glycoproteins are responsible for the binding to and entry into the host cell by CSFV. To date, only one cellular receptor, heparan sulfate (HS), has been identified as being involved in CSFV attachment. HS is also present on the surface of various cells that are nonpermissive to CSFV. Hence, there must be another receptor(s) that has been unidentified to date. In this study, we used a set of small interfering RNAs (siRNAs) against a number of porcine cell membrane protein genes to screen cellular proteins involved in CSFV infection. This approach resulted in the identification of several proteins, and of these, the laminin receptor (LamR) has been demonstrated to be a cellular receptor for several viruses. Confocal analysis showed that LamR is colocalized with CSFV virions on the membrane, and a coimmunoprecipitation assay indicated that LamR interacts with the CSFV Erns protein. In inhibition assays, anti-LamR antibodies, soluble laminin, or LamR protein significantly inhibited CSFV infection in a dose-dependent manner. Transduction of PK-15 cells with a recombinant lentivirus expressing LamR yielded higher viral titers. Moreover, an attachment assay demonstrated that LamR functions during virus attachment. We also demonstrate that LamR acts as an alternative attachment receptor, especially in SK6 cells. These results indicate that LamR is a cellular attachment receptor for CSFV. IMPORTANCE Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), an economically important viral disease affecting the pig industry in many countries. To date, only heparan sulfate (HS) has been identified to be an attachment receptor for CSFV. Here, using RNA interference screening with small interfering RNAs (siRNAs) against a number of porcine membrane protein genes, we identified the laminin receptor (LamR) to be another attachment receptor. We demonstrate the involvement of LamR together with HS in virus attachment, and we elucidate the relationship between LamR and HS. LamR also serves as an attachment receptor for many viral pathogens, including dengue virus, a fatal human flavivirus. The study will help to enhance our understanding of the life cycle of flaviviruses and the development of antiviral strategies for flaviviruses. PMID:25694590

Typhoid fever

MedlinePlus

Typhoid fever is an infection that causes diarrhea and a rash . It is most commonly caused due to ... in their stools for years, spreading the disease. Typhoid fever is common in developing countries. Most cases in ...

New concepts for the old challenge of African relapsing fever borreliosis.

PubMed

Cutler, S J; Abdissa, A; Trape, J-F

2009-05-01

Relapsing fever, caused by spirochaetes belonging to the genus Borrelia, was once the cause of worldwide epidemic disease. This was largely through infection with the louse-borne form of the disease, caused by Borrelia recurrentis (louse-borne relapsing fever (LBRF)). During the last century, we have witnessed the demise of this infection, largely owing to improved standards of living and the introduction of the insecticide DDT, resulting in a reduction in the incidence of the body louse, the vector for relapsing fever. In areas of extreme poverty this disease persists, causing a significant burden of disease. It is now looking probable that this infection is caused by a louse-adapted variant of Borrelia duttonii, transmitted by Ornithodoros moubata 'soft' ticks in East Africa. Like LBRF, infection still causes impact, particularly affecting young children and pregnant women. Over recent years, the true burden of relapsing fever caused by infection with the closely related Borrelia crocidurae, transmitted by Ornithodoros sonrai ticks, has only just begun to emerge. Here, the current state of knowledge concerning relapsing fever in Africa is reviewed.

A Low-Molecular-Weight Ferroxidase Is Increased in the CSF of sCJD Cases: CSF Ferroxidase and Transferrin as Diagnostic Biomarkers for sCJD

PubMed Central

Haldar, Swati; Beveridge, ’Alim J.; Wong, Joseph; Singh, Ajay; Galimberti, Daniela; Borroni, Barbara; Zhu, Xiongwei; Blevins, Janis; Greenlee, Justin; Perry, George; Mukhopadhyay, Chinmay K.; Schmotzer, Christine

2013-01-01

Abstract Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are surrogate in nature, and provide suboptimal sensitivity and specificity. Results: We report that CJD-associated brain iron dyshomeostasis is reflected in the cerebrospinal fluid (CSF), providing disease-specific diagnostic biomarkers. Analysis of 290 premortem CSF samples from confirmed cases of CJD, Alzheimer's disease, and other dementias (DMs), and 52 non-DM (ND) controls revealed a significant difference in ferroxidase (Frx) activity and transferrin (Tf) levels in sporadic Creutzfeldt-Jakob disease (sCJD) relative to other DM and ND controls. A combination of CSF Frx and Tf discriminated sCJD from other DMs with a sensitivity of 86.8%, specificity of 92.5%, accuracy of 88.9%, and area-under-the receiver-operating-characteristic (ROC) curve of 0.94. This combination provided a similar diagnostic accuracy in discriminating CJD from rapidly progressing cases who died within 6 months of sample collection. Surprisingly, ceruloplasmin and amyloid precursor protein, the major brain Frxs, displayed minimal activity in the CSF. Most of the Frx activity was concentrated in the <3-kDa fraction in normal and diseased CSF, and resisted heat and proteinase-K treatment. Innovation: (i) A combination of CSF Frx and Tf provides disease-specific premortem diagnostic biomarkers for sCJD. (ii) A novel, nonenzymatic, nonprotein Frx predominates in human CSF that is distinct from the currently known CSF Frxs. Conclusion: The underlying cause of iron imbalance is distinct in sCJD relative to other DMs associated with the brain iron imbalance. Thus, change in the CSF levels of iron-management proteins can provide disease-specific biomarkers and insight into the cause of iron imbalance in neurodegenerative conditions. Antioxid. Redox Signal. 19, 1662–1675. PMID:23379482

Detection of Classical swine fever virus infection by individual oral fluid of pigs following experimental inoculation.

PubMed

Petrini, Stefano; Pierini, Ilaria; Giammarioli, Monica; Feliziani, Francesco; De Mia, Gian Mario

2017-03-01

We evaluated the use of oral fluid as an alternative to serum samples for Classical swine fever virus (CSFV) detection. Individual oral fluid and serum samples were collected at different times post-infection from pigs that were experimentally inoculated with CSFV Alfort 187 strain. We found no evidence of CSFV neutralizing antibodies in swine oral fluid samples under our experimental conditions. In contrast, real-time reverse transcription-polymerase chain reaction could detect CSFV nucleic acid from the oral fluid as early as 8 d postinfection, which also coincided with the time of initial detection in blood samples. The probability of CSFV detection in oral fluid was identical or even higher than in the corresponding blood sample. Our results support the feasibility of using this sampling method for CSFV genome detection, which may represent an additional cost-effective tool for CSF control.

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin.

PubMed

Kast, Richard E; Hill, Quentin A; Wion, Didier; Mellstedt, Håkan; Focosi, Daniele; Karpel-Massler, Georg; Heiland, Tim; Halatsch, Marc-Eric

2017-05-01

Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain-be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation-increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration- and European Medicines Agency-approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF)

PubMed Central

2013-01-01

Background Myelosuppressive chemotherapy can lead to dose-limiting febrile neutropenia. Prophylactic use of recombinant human G-CSF such as daily filgrastim and once-per-cycle pegfilgrastim may reduce the incidence of febrile neutropenia. This comparative study examined the effect of pegfilgrastim versus daily filgrastim on the risk of hospitalization. Methods This retrospective United States claims analysis utilized 2004–2009 data for filgrastim- and pegfilgrastim-treated patients receiving chemotherapy for non-Hodgkin’s lymphoma (NHL) or breast, lung, ovarian, or colorectal cancers. Cycles in which pegfilgrastim or filgrastim was administered within 5 days from initiation of chemotherapy (considered to represent prophylaxis) were pooled for analysis. Neutropenia-related hospitalization and other healthcare encounters were defined with a “narrow” criterion for claims with an ICD-9 code for neutropenia and with a “broad” criterion for claims with an ICD-9 code for neutropenia, fever, or infection. Odds ratios (OR) for hospitalization and 95% confidence intervals (CI) were estimated by generalized estimating equation (GEE) models and adjusted for patient, tumor, and treatment characteristics. Per-cycle healthcare utilization and costs were examined for cycles with pegfilgrastim or filgrastim prophylaxis. Results We identified 3,535 patients receiving G-CSF prophylaxis, representing 12,056 chemotherapy cycles (11,683 pegfilgrastim, 373 filgrastim). The mean duration of filgrastim prophylaxis in the sample was 4.8 days. The mean duration of pegfilgrastim prophylaxis in the sample was 1.0 day, consistent with the recommended dosage of pegfilgrastim - a single injection once per chemotherapy cycle. Cycles with prophylactic pegfilgrastim were associated with a decreased risk of neutropenia-related hospitalization (narrow definition: OR = 0.43, 95% CI: 0.16–1.13; broad definition: OR = 0.38, 95% CI: 0.24–0.59) and all-cause hospitalization (OR = 0.50, 95% CI: 0.35–0.72) versus cycles with prophylactic filgrastim. For neutropenia-related utilization by setting of care, there were more ambulatory visits and hospitalizations per cycle associated with filgrastim prophylaxis than with pegfilgrastim prophylaxis. Mean per-cycle neutropenia-related costs were also higher with prophylactic filgrastim than with prophylactic pegfilgrastim. Conclusions In this comparative effectiveness study, pegfilgrastim prophylaxis was associated with a reduced risk of neutropenia-related or all-cause hospitalization relative to filgrastim prophylaxis. PMID:23298389

Chronic Q Fever in the Netherlands 5 Years after the Start of the Q Fever Epidemic: Results from the Dutch Chronic Q Fever Database

PubMed Central

Delsing, Corine E.; Groenwold, Rolf H. H.; Wegdam-Blans, Marjolijn C. A.; Bleeker-Rovers, Chantal P.; de Jager-Leclercq, Monique G. L.; Hoepelman, Andy I. M.; van Kasteren, Marjo E.; Buijs, Jacqueline; Renders, Nicole H. M.; Nabuurs-Franssen, Marrigje H.; Oosterheert, Jan Jelrik; Wever, Peter C.

2014-01-01

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P = 0.004 and 0.010), proven chronic Q fever (P = 0.020 and 0.002), vascular chronic Q fever (P = 0.024 and 0.005), acute presentation with chronic Q fever (P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever (P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively. PMID:24599987

Rat-bite fever

MedlinePlus

Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic erythema; Spirillary fever; Sodoku ... Rat-bite fever can be caused by either of 2 different bacteria, Streptobacillus moniliformis or Spirillum minus. Both of these are ...

Dengue fever (image)

MedlinePlus

Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.

PubMed

Wang, Wensheng; Wang, Hua; Zhou, Xichao; Li, Xing; Sun, Wen; Dellinger, Michael; Boyce, Brendan F; Xing, Lianping

2017-05-01

Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Prevalence of HHV-6 in cerebrospinal fluid of children younger than 2 years of age with febrile convulsion.

PubMed

Mamishi, Setareh; Kamrani, Laura; Mohammadpour, Masoud; Yavarian, Jila

2014-04-01

Febrile convulsion is a common disorder in children. Viral infections such as human herpes virus 6 (HHV-6) which results in roseola infantum may contribute to developing seizure. The objective of this study was to determine the prevalence of HHV-6 by detecting DNA in cerebrospinal fluid (CSF) of children with febrile convulsion and without any rash of roseola infantum. In this descriptive cross-sectional study, CSF of 100 children younger than 2 years of age with febrile convulsion was evaluated for detecting HHV-6 DNA by PCR. All of them were referred to emergency ward in Pediatric Medical Center from March 2010 to March 2011. General information, clinical manifestations, laboratory tests and outcomes were collected in the questionnaires. One hundred children including 59 males and 41 females were evaluated. HHV-6 was detected from CSF in six patients (6%) by PCR. Mean age was 8 months old. All children were younger than 12 months old. The most common primary manifestation was fever alone. None of them had rash. Majority of cases occurred in winter. All patients recovered without any encephalitis. These findings showed that primary infection with HHV-6 is frequently associated with febrile convulsion in infants which may be at risk for subsequent development of epilepsy.

Scrub Typhus: A Clinico-Laboratory Differentiation of Children with and without Meningitis.

PubMed

Bhat, Nowneet Kumar; Pandita, Neerul; Saini, Manju; Dhar, Minakshi; Ahmed, Sohaib; Shirazi, Nadia; Wasim, Sanober; Shirke, Rupali; Chandar, Vipan

2016-06-01

Neurological involvement in the form of meningitis or meningoencephalitis, although well documented in scrub typhus, has not been extensively studied in the pediatric population. We report the clinical and laboratory profile of 96 children with scrub typhus and compared those with and without meningitis. Twenty seven (28%) children had clinical and laboratory evidence of meningitis. The most frequent presenting features were fever (100%), meningeal signs (66.6%), nausea and vomiting (56.3%), seizures (55.5%) and altered sensorium (51.8%). The children with meningitis presented early and had significantly lower respiratory and renal impairments when compared with the non-meningitis group. Cerebrospinal fluid (CSF) analysis revealed elevated total leukocyte count (86.73 ± 94.50 cells/mm(3)), mononuclear pleocytosis (lymphocyte percentage of 76.85 ± 15.86), elevated proteins (108.33 ± 52.63 mg%) and normal CSF glucose (64.18 ± 15.92 mg%). We conclude that meningitis is a common and early complication of childhood scrub typhus. The CSF reveals a lymphocytic pleocytosis, raised proteins and a normal glucose level. These children respond promptly to appropriate antibiotics as do children without meningitis. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fever in Patients With Cancer.

PubMed

Pasikhova, Yanina; Ludlow, Steven; Baluch, Aliyah

2017-04-01

The definition of fever is flexible and depends on the clinical context. Fever is frequently observed in patients with cancer. Infectious and noninfectious causes of fever in patients with various oncological and hematological malignancies and the usefulness of biomarkers are discussed. To treat patients in a timely manner and to minimize morbidity and mortality, it is paramount that health care professionals determine the cause of fever. The usefulness of biomarkers in febrile patients with cancer continues to be controversial. Fever is frequently seen in patients with cancer and can be associated with a variety of infectious and noninfectious causes. The utility of acute-phase reactants, such as erythrocyte sedimentation rate, C-reactive protein, and procalcitonin, along with a nonsteroidal anti-inflammatory drug challenge should be further evaluated as adjunct tools for the workup of fever in patients with cancer.

[Hyperthyroid and acute tonsillitis in a 23-year-old woman].

PubMed

Beyer, G; Küster, I; Budde, C; Wilhelm, E; Hoene, A; Evert, K; Stracke, S; Friesecke, S; Mayerle, J; Steveling, A

2016-07-01

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G‑CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

GM-CSF modulates autoantibody production and skin blistering in experimental epidermolysis bullosa acquisita.

PubMed

Samavedam, Unni Krishna S R L; Iwata, Hiroaki; Müller, Susen; Schulze, Franziska S; Recke, Andreas; Schmidt, Enno; Zillikens, Detlef; Ludwig, Ralf J

2014-01-15

GM-CSF activates hematopoietic cells and recruits neutrophils and macrophages to sites of inflammation. Inhibition of GM-CSF attenuates disease activity in models of chronic inflammatory disease. Effects of GM-CSF blockade were linked to modulation of the effector phase, whereas effects on early pathogenic events, for example, Ab production, have not been identified. To evaluate yet uncharacterized effects of GM-CSF on early pathogenic events in chronic inflammation, we employed immunization-induced epidermolysis bullosa acquisita (EBA), an autoimmune bullous disease caused by autoantibodies to type VII collagen. Compared to wild-type mice, upon immunization, GM-CSF(-/-) mice produced lower serum autoantibody titers, which were associated with reduced neutrophil numbers in draining lymph nodes. The same effect was observed in neutrophil-depleted wild-type mice. Neutrophil depletion in GM-CSF(-/-) mice led to a stronger inhibition, indicating that GM-CSF and neutrophils have additive functions. To characterize the contribution of GM-CSF specifically in the effector phase of EBA, disease was induced by transfer of anti-type VII collagen IgG into mice. We observed an increased GM-CSF expression, and GM-CSF blockade reduced skin blistering. Additionally, GM-CSF enhanced reactive oxygen species release and neutrophil migration in vitro. In immunization-induced murine EBA, treatment with anti-GM-CSF had a beneficial effect on established disease. We demonstrate that GM-CSF modulates both autoantibody production and skin blistering in a prototypical organ-specific autoimmune disease.

Transition in the cause of fever from malaria to dengue, Northwestern Ecuador, 1990-2011.

PubMed

Cifuentes, Sara G; Trostle, James; Trueba, Gabriel; Milbrath, Meghan; Baldeón, Manuel E; Coloma, Josefina; Eisenberg, Joseph N S

2013-10-01

In tropical areas, the predominant cause of fever has historically been malaria. However by 2011, among febrile patients in northwestern Ecuador, dengue was identified in 42% and malaria in none. This finding suggests a transition in the cause of fever from malaria to other illnesses, such as dengue.

Hypertension from chronic central sodium chloride in mice is mediated by the ouabain-binding site on the Na,K-ATPase α2-isoform

PubMed Central

Dostanic, Iva; Lingrel, Jerry B.; Hou, Xiaohong; Wu, Hengwei

2011-01-01

A chronic increase in the concentration of sodium chloride in the cerebrospinal fluid (CSF) (↑CSF [NaCl]) appears to be critically important for the development of salt-dependent hypertension. In agreement with this concept, increasing CSF [NaCl] chronically by intracerebroventricular (icv) infusion of NaCl-rich artificial CSF (aCSF-HiNaCl) in rats produces hypertension by the same mechanisms (i.e., aldosterone-ouabain pathway in the brain) as that produced by dietary sodium in salt-sensitive strains. We first demonstrate here that icv aCSF-HiNaCl for 10 days also causes hypertension in wild-type (WT) mice. We then used both WT and gene-targeted mice to explore the mechanisms. In WT mice with a ouabain-sensitive Na,K-ATPase α2-isoform (α2S/S), mean arterial pressure rose by ∼25 mmHg within 2 days of starting aCSF-HiNaCl (0.6 nmol Na/min) and remained elevated throughout the study. Ouabain (171 pmol/day icv) increased blood pressure to a similar extent. aCSF-HiNaCl or ouabain given at the same rates subcutaneously instead of intracerebroventricularly had no effect on blood pressure. The pressor response to icv aCSF-HiNaCl was abolished by an anti-ouabain antibody given intracerebroventricularly but not subcutaneously, indicating that it is mediated by an endogenous ouabain-like substance in the brain. We compared the effects of icv aCSF-HiNaCl or icv ouabain on blood pressure in α2S/S versus knockout/knockin mice with a ouabain-resistant endogenous α2-subunit (α2R/R). In α2R/R, there was no pressor response to icv aCSF-HiNaCl in contrast to WT mice. The α2R/R genotype also lacked a pressor response to icv ouabain. These data demonstrate that chronic ↑CSF [NaCl] causes hypertension in mice and that the blood pressure response is mediated by the ouabain-like substance in the brain, specifically by its binding to the α2-isoform of the Na,K-ATPase. PMID:21856907

Clinical observation of the therapeutic effects of pegylated recombinant human granulocyte colony-stimulating factor in patients with concurrent chemoradiotherapy-induced grade IV neutropenia

PubMed Central

WU, FENG-PENG; WANG, JUN; WANG, HUI; LI, NA; GUO, YIN; CHENG, YUN-JIE; LIU, QING; YANG, XIANG-RAN

2015-01-01

The aim of the present study was to investigate the efficacy and side-effects of preventive treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on concurrent chemoradiotherapy-induced grade IV neutropenia and to provide a rational basis for its clinical application. A total of 114 patients with concurrent chemoradiotherapy-induced grade IV neutropenia were enrolled. A randomized approach was used to divide the patients into an experimental group and a control group. The experimental group included three subgroups, namely a P-50 group, P-100 group and P + R group. The P-50 group had 42 cases, which were given a single 50-μg/kg subcutaneous injection of PEG-rhG-CSF. The P-100 group had 30 cases, which received a single 100-μg/kg subcutaneous injection of PEG-rhG-CSF. The P + R group comprised 22 cases, which were given a single 50-μg/kg subcutaneous injection of PEG-rhG-CSF and rhG-CSF 5 μg/kg/day; when the absolute neutrophil count (ANC) was ≥2.0×109/l, the administration of rhG-CSF was stopped. The control group (RC group) comprised 20 patients, who received rhG-CSF 5 μg/kg/day by subcutaneous injection until the ANC was ≥2.0×109/l. Changes in the neutrophil proliferation rate and ANC values over time, the neutropenic symptom remission time and incidence of adverse drug reactions were analyzed statistically in each group of patients. In the experimental group, the neutrophil proliferation rate and ANC values were significantly higher than those in the control group; the clinical effects began 12–24 h after treatment in the experimental group, and indicated that the treatment improved neutropenia in ~48 h after treatment. There was no significant difference in the neutrophil proliferation rate and ANC values between the P-50 and P+R groups. In the experimental group, the remission time of neutropenia-induced fever and muscle pain after administration was significantly shorter than that in the control group, with a statistically significant difference (P<0.05). The adverse drug reaction rates showed no significant difference between the experimental group and the control group. PEG-rhG-CSF had good efficacy and safety in the treatment of concurrent chemotherapy-induced grade IV neutropenia. For the treatment of concurrent chemotherapy-induced grade IV neutropenia, a single subcutaneous injection of 50 μg/kg PEG-rhG-CSF is the recommended dose. The effects begin at 12–24 h; if the ANC values are not significantly improved during this time, no supplementary administration of rhG-CSF is necessary. PMID:25667625

Ectopic Prolactinoma Presenting as Bacterial Meningitis: A Diagnostic Conundrum.

PubMed

Akinduro, Oluwaseun O; Akinduro, Olutomi T; Gupta, Vivek; Reimer, Ronald; Olomu, Osarenoma

2018-04-01

Prolactinomas may rarely present with meningitis and cerebrospinal fluid (CSF) rhinorrhea secondary to erosion of the wall of the sella turcica. It is even more uncommon for this abnormal communication to be caused by an ectopic prolactinoma arising from the sphenoid sinus and eroding into the sella. This atypical growth pattern makes diagnosis very difficult because there may be no displacement of the normal pituitary gland. The first reported case of a patient with an ectopic prolactinoma originating within the sphenoid sinus presenting primarily with meningitis is presented, and the management strategy and surgical and nonsurgical treatment options are discussed. A 48-year-old woman presented with confusion, low-pressure headache, and fever. A lumbar puncture revealed Streptococcus pneumoniae meningitis, and she was placed on intravenous penicillin G. After initiation of antibiotics, she noticed salty tasting postnasal fluid leakage. Imaging was remarkable for bony erosion of the sphenoid sinus wall by a soft tissue mass growing from within the sinus, with no disruption of the normal pituitary gland. A biopsy was then performed with an endoscopic transnasal transsphenoidal approach, and the CSF leak was repaired with a pedicled nasoseptal flap. The final pathology was prolactinoma, and she was placed on cabergoline. Ectopic prolactinomas may rarely present as meningitis secondary to retrograde transmission of bacteria through a bony defect in the sphenoid sinus, and must be included in the differential diagnosis of any sphenoid sinus mass. Management should first address the infection, followed by surgical repair of the bony defect. Copyright © 2018 Elsevier Inc. All rights reserved.

[Community acquired bacterial meningitis in patients over 60].

PubMed

Mora Mora, Luis A; Arco Espinosa, Micke E de; Plumet, Javier; Micheli, Federico

2015-01-01

Acute bacterial meningitis has a global mortality rate of 135000 cases per year. In Argentina over the last 12 years, the annual incidence rate has been 5.5/100 000. About 20% of patients present neurological sequelae, which are more common in patients aged 60 or older. Our objective here is to determine the clinical characteristics, the most common causes and to measure evolution in patients over 60 years old diagnosed with meningitis and treated at the Hospital de Clinicas José de San Martín. This is a retrospective study based on a review of medical records from 2003 to 2013 that takes into account patients older than 60 who were diagnosed with acute bacterial meningitis acquired in the community by a microbiological diagnosis of CSF or those included due to a high suspicion of bacterial meningitis (pleocitosis > 2000 cells/mm3, proteins > 220 mg/dl, glycorrhachia < 34 mg/dl, glycorrhachia/glucose index < 0.23). Cases of TB meningitis, nosocomial, postoperative and other nonbacterial meningitis were excluded. Sixty nine patients were included, 45 (65%) were women with an average age of 78 ± 10.6 years. Only 40% had the triad of classical meningitis symptoms (stiff neck, fever and altered mental status). In 52% of the patients germs developed in the CSF, the most frequent being Streptococcus pneumoniae present in 47% of cases. Lethality rate was 41%, all of them by methicillin-sensitive Staphylococcus aureus. Only 24 (35%) cases were admitted into intensive care. The main sequelae present were motor disorders (12%) and hearing loss (5%).

Spinal cerebrospinal fluid leak as the cause of chronic subdural hematomas in nongeriatric patients.

PubMed

Beck, Jürgen; Gralla, Jan; Fung, Christian; Ulrich, Christian T; Schucht, Philippe; Fichtner, Jens; Andereggen, Lukas; Gosau, Martin; Hattingen, Elke; Gutbrod, Klemens; Z'Graggen, Werner J; Reinert, Michael; Hüsler, Jürg; Ozdoba, Christoph; Raabe, Andreas

2014-12-01

The etiology of chronic subdural hematoma (CSDH) in nongeriatric patients (≤ 60 years old) often remains unclear. The primary objective of this study was to identify spinal CSF leaks in young patients, after formulating the hypothesis that spinal CSF leaks are causally related to CSDH. All consecutive patients 60 years of age or younger who underwent operations for CSDH between September 2009 and April 2011 at Bern University Hospital were included in this prospective cohort study. The patient workup included an extended search for a spinal CSF leak using a systematic algorithm: MRI of the spinal axis with or without intrathecal contrast application, myelography/fluoroscopy, and postmyelography CT. Spinal pathologies were classified according to direct proof of CSF outflow from the intrathecal to the extrathecal space, presence of extrathecal fluid accumulation, presence of spinal meningeal cysts, or no pathological findings. The primary outcome was proof of a CSF leak. Twenty-seven patients, with a mean age of 49.6 ± 9.2 years, underwent operations for CSDH. Hematomas were unilateral in 20 patients and bilateral in 7 patients. In 7 (25.9%) of 27 patients, spinal CSF leakage was proven, in 9 patients (33.3%) spinal meningeal cysts in the cervicothoracic region were found, and 3 patients (11.1%) had spinal cysts in the sacral region. The remaining 8 patients (29.6%) showed no pathological findings. The direct proof of spinal CSF leakage in 25.9% of patients suggests that spinal CSF leaks may be a frequent cause of nongeriatric CSDH.

Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

PubMed

Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

2006-04-01

The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

Laboratory-based clinical audit as a tool for continual improvement: an example from CSF chemistry turnaround time audit in a South-African teaching hospital.

PubMed

Imoh, Lucius C; Mutale, Mubanga; Parker, Christopher T; Erasmus, Rajiv T; Zemlin, Annalise E

2016-01-01

Timeliness of laboratory results is crucial to patient care and outcome. Monitoring turnaround times (TAT), especially for emergency tests, is important to measure the effectiveness and efficiency of laboratory services. Laboratory-based clinical audits reveal opportunities for improving quality. Our aim was to identify the most critical steps causing a high TAT for cerebrospinal fluid (CSF) chemistry analysis in our laboratory. A 6-month retrospective audit was performed. The duration of each operational phase across the laboratory work flow was examined. A process-mapping audit trail of 60 randomly selected requests with a high TAT was conducted and reasons for high TAT were tested for significance. A total of 1505 CSF chemistry requests were analysed. Transport of samples to the laboratory was primarily responsible for the high average TAT (median TAT = 170 minutes). Labelling accounted for most delays within the laboratory (median TAT = 71 minutes) with most delays occurring after regular work hours (P < 0.05). CSF chemistry requests without the appropriate number of CSF sample tubes were significantly associated with delays in movement of samples from the labelling area to the technologist's work station (caused by a preference for microbiological testing prior to CSF chemistry). A laboratory-based clinical audit identified sample transportation, work shift periods and use of inappropriate CSF sample tubes as drivers of high TAT for CSF chemistry in our laboratory. The results of this audit will be used to change pre-analytical practices in our laboratory with the aim of improving TAT and customer satisfaction.

[Hydrocephalus Associated with Small Clinoidal Meningioma that Resolved after Tumor Removal:A Case Report].

PubMed

Fujiwara, Hidemoto; Aiba, Toyotaka; Watanabe, Toru; Hiraishi, Tetsuya; Fujii, Yukihiko

2016-12-01

Small meningiomas causing hydrocephalus without obstruction of the ventricular system are rare. Herein, we report a case of small clinoidal meningioma with communicating hydrocephalus, which resolved after tumor removal. A 70-year-old woman presented with a 1-month history of memory disturbance followed by gait disturbance. MR images revealed a right clinoidal meningioma, 2 cm in diameter, and dilatation of the ventricles suggesting communicating hydrocephalus. The cerebrospinal fluid(CSF)pressure was 130 mmH₂O, as determined via a lumbar puncture. High concentrations of protein(65mg/dL)were detected in the lumbar CSF. The tumor was completely removed via a frontotemporal craniotomy. Higher protein concentrations(94mg/dL)were detected in the CSF obtained intraoperatively from the sylvian cistern. The histopathological diagnosis was meningothelial meningioma. The patient's symptoms improved markedly after surgery. Postoperative MR images revealed resolution of the hydrocephalus. The lumbar CSF protein concentration returned to normal(43mg/dL). Neither tumor recurrence nor progression of hydrocephalus has been observed for 4 years. Communicating hydrocephalus, associated with a small meningioma at the supratentorial region, has not been described. Previous studies have shown that patients with meningioma may develop communicating hydrocephalus after tumor removal or stereotactic radiosurgery. Thus, it is interesting that the small supratentorial meningioma in our case developed communicating hydrocephalus without any therapeutic intervention. Considering the CSF protein concentration, we speculate that the hydrocephalus was the result of CSF malabsorption associated with high CSF protein concentration and CSF pathway obstruction at the suprasellar cistern caused by the tumor.

Neurotoxicity of cerebro-spinal fluid from patients with Parkinson's disease on mesencephalic primary cultures as an in vitro model of dopaminergic neurons.

PubMed

Kong, Ping; Zhang, Ben-Shu; Lei, Ping; Kong, Xiao-Dong; Zhang, Shi-Shuang; Li, Dai; Zhang, Yun

2015-08-01

Parkinson's disease is a degenerative disorder of the central nervous system. In spite of extensive research, neither the cause nor the mechanisms have been firmly established thus far. One assumption is that certain toxic substances may exist in the cerebro-spinal fluid (CSF) of Parkinson's disease patients. To confirm the neurotoxicity of CSF and study the potential correlation between neurotoxicity and the severity of Parkinson's disease, CSF was added to cultured cells. By observation of cell morphology, changes in the levels of lactate dehydrogenase, the ratio of tyrosine hydroxylase-positive cells, and the expression of tyrosine hydroxylase mRNA and protein, the differences between the two groups were shown. The created in vitro model of dopaminergic neurons using primary culture of mouse embryonic mesencephalic tissue is suitable for the study of neurotoxicity. The observations of the present study indicated that CSF from Parkinson's disease patients contains factors that can cause specific injury to cultured dopaminergic neurons. However, no obvious correlation was found between the neurotoxicity of CSF and the severity of Parkinson's disease.

Long-term survival in a dog with meningoencephalitis and epidural abscessation due to Actinomyces species.

PubMed

Song, Rachel B; Vitullo, Carina A; da Costa, Ronaldo C; Daniels, Joshua B

2015-07-01

A 2-year-old, female spayed Golden Retriever dog was presented to The Ohio State University Veterinary Medical Center for evaluation of ataxia, cervical pain, 1 episode of acute collapse, dull mentation, and inappetence. Physical examination revealed an elevated temperature of 39.7°C and severe cervical pain. Blood work revealed a mature neutrophilia. Cerebrospinal fluid (CSF) analysis revealed nondegenerative neutrophilic pleocytosis with no infectious agents. A presumptive diagnosis of steroid-responsive meningitis-arteritis was made, and corticosteroid therapy was started. The patient improved initially but experienced a vestibular episode characterized by falling and vertical nystagmus. A magnetic resonance imaging of the brain revealed an epidural abscess in the cervical vertebral canal and diffuse meningeal enhancement in the brain and cranial cervical spine. Abscess drainage revealed degenerate neutrophils and several filamentous, branching organisms. Culture of the initial CSF using an enrichment broth revealed growth of a Gram-positive organism 5 days after fluid collection. The isolate was identified by partial 16S ribosomal DNA sequencing as Actinomyces spp. The patient was successfully treated with long-term antibiotics. Our study reports the long-term survival after medical treatment of bacterial meningoencephalitis and epidural abscessation due to Actinomyces sp. infection in a dog. Bacterial meningoencephalitis should be included as a differential diagnosis in patients with cervical pain and fever, even when a nondegenerative neutrophilic pleocytosis is found on CSF analysis. Culture of the CSF with use of an enrichment broth should be considered in all cases of neutrophilic pleocytosis to rule out infections of the central nervous system. © 2015 The Author(s).

Regulation of Embryonic and Postnatal Development by the CSF-1 Receptor

PubMed Central

Chitu, Violeta; Stanley, E. Richard

2017-01-01

Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development. Outside the mononuclear phagocytic system, the CSF-1R directly regulates neuronal survival and differentiation, the development of intestinal Paneth cells and of preimplantation embryos, as well as trophoblast innate immune function. Consistent with the pleiotropic roles of the receptor during development, CSF-1R deficiency in most mouse strains causes embryonic or perinatal death and the surviving mice exhibit multiple developmental and functional deficits. The CSF-1R is activated by two dimeric glycoprotein ligands, CSF-1, and interleukin-34 (IL-34). Homozygous Csf1-null mutations phenocopy most of the deficits of Csf1r-null mice. In contrast, Il34-null mice have no gross phenotype, except for decreased numbers of Langerhans cells and microglia, indicating that CSF-1 plays the major developmental role. Homozygous inactivating mutations of the Csf1r or its ligands have not been reported in man. However, heterozygous inactivating mutations in the Csf1r lead to a dominantly inherited adult-onset progressive dementia, highlighting the importance of CSF-1R signaling in the brain. PMID:28236968

Regulation of Embryonic and Postnatal Development by the CSF-1 Receptor.

PubMed

Chitu, Violeta; Stanley, E Richard

2017-01-01

Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development. Outside the mononuclear phagocytic system, the CSF-1R directly regulates neuronal survival and differentiation, the development of intestinal Paneth cells and of preimplantation embryos, as well as trophoblast innate immune function. Consistent with the pleiotropic roles of the receptor during development, CSF-1R deficiency in most mouse strains causes embryonic or perinatal death and the surviving mice exhibit multiple developmental and functional deficits. The CSF-1R is activated by two dimeric glycoprotein ligands, CSF-1, and interleukin-34 (IL-34). Homozygous Csf1-null mutations phenocopy most of the deficits of Csf1r-null mice. In contrast, Il34-null mice have no gross phenotype, except for decreased numbers of Langerhans cells and microglia, indicating that CSF-1 plays the major developmental role. Homozygous inactivating mutations of the Csf1r or its ligands have not been reported in man. However, heterozygous inactivating mutations in the Csf1r lead to a dominantly inherited adult-onset progressive dementia, highlighting the importance of CSF-1R signaling in the brain. © 2017 Elsevier Inc. All rights reserved.

Scarlet fever is caused by a limited number of Streptococcus pyogenes lineages and is associated with the exotoxin genes ssa, speA and speC.

PubMed

Silva-Costa, Catarina; Carriço, Joao A; Ramirez, Mario; Melo-Cristino, Jose

2014-03-01

Several outbreaks of scarlet fever caused by Streptococcus pyogenes were recently reported. Scarlet fever is historically considered a toxin-mediated disease, dependent on the production of the exotoxins SpeA and SpeC, but a strict association between scarlet fever and these exotoxins is not always detected. The aims of this study were to characterize the scarlet fever bacterial isolates recovered from patients in a Lisbon hospital and to identify any distinctive characteristics of such isolates. We characterized a collection of 303 pharyngeal S. pyogenes collected between 2002 and 2008. One-hundred and one were isolated from scarlet fever patients and 202 were associated to a diagnosis of tonsillo-pharyngitis. Isolates were characterized by T and emm typing, pulsed field gel electrophoresis profiling and superantigen gene profiling. The diversity of the scarlet fever isolates was lower than that of the pharyngitis isolates. Specific lineages of emm87, emm4 and emm3 were overrepresented in scarlet fever isolates but only 1 pulsed field gel electrophoresis major lineage was significantly associated with scarlet fever. Multivariate analysis indicated associations of ssa, speA and speC with scarlet fever. In nonoutbreak conditions, scarlet fever is caused by a number of distinct genetic lineages. The lower diversity of these isolates and the association with specific exotoxin genes indicates that some lineages are more prone to cause this presentation than others even in nonoutbreak conditions.

Review of the etiologies of viral meningitis and encephalitis in a dengue endemic region.

PubMed

Soares, Cristiane N; Cabral-Castro, Mauro J; Peralta, José M; de Freitas, Marcos R G; Zalis, Mariano; Puccioni-Sohler, Marzia

2011-04-15

To evaluate the etiology of viral meningitis and encephalitis in adults and adolescents living in areas affected by dengue. Over two years, adults and adolescents with diagnoses of viral encephalitis or meningitis were selected for study in Brazil. PCRs for dengue, enterovirus, HSV1 and 2 and cytomegalovirus were performed in CSF samples. Serum and CSF samples were tested for the presence of anti-dengue IgM antibodies. The etiologies of encephalitis and meningitis were determined in 70% of cases (30/47). Dengue was the leading cause of encephalitis (47%) with normal CSF cellularity in 75% of these patients. HSV1 was found in 17.6% of the cases, two of which had mild encephalitis. Enterovirus was the most common cause of meningitis (50%), followed by HSV1 (15%), cytomegalovirus and dengue (10%, each). We identified the viral agents causing encephalitis and meningitis in a higher proportion of cases than has been reported in other studies. Dengue was the most frequent cause of encephalitis, which surpassed HSV. In endemic areas, dengue should be investigated as an important cause of encephalitis. Normal CSF cellularity should not exclude dengue encephalitis. Enterovirus is known to be the leading cause of meningitis in children, but here we found it was also the main cause of the disease in adults. HSV1 should be investigated in patients with mild forms of encephalitis and meningitis. Copyright © 2011 Elsevier B.V. All rights reserved.

CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients.

PubMed

Ghosh, Gopal Chandra; Sharma, Brijesh; Gupta, B B

2016-01-01

Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients.

Neonatal purulent meningitis in southern Tunisia: Epidemiology, bacteriology, risk factors and prognosis.

PubMed

Kamoun, Fatma; Dowlut, Mashuma Bibi; Ameur, Salma Ben; Sfaihi, Lamia; Mezghani, Senda; Chabchoub, Imen; Hammami, Adnen; Aloulou, Hajer; Hachicha, Mongia

2015-01-01

To study the epidemiological, clinical and bacteriological aspects and outcome of purulent neonatal meningitis (PNM). Retrospective analysis of 55 cases of PNM hospitalized in the pediatric ward of Hedi Chaker Hospital from 1990 to 2012. Infants less than 29 days of age were included. The diagnosis was made on either the presence of bacteria in the cerebrospinal fluid (CSF) or the combination of pleocytosis >30 cells/mm(3), protein level >1.3 g/l and glucose level <2.2 mmol/l or CSF/blood glucose ratio <0.4. The male:female sex ratio was 1.75. One or more maternal risk factors for infection were found in 24 cases. The main symptoms were fever and poor feeding. Soluble antigen was positive in four cases and cultures had isolated the bacteria in 28 cases. The mortality rate was 40%. The sequelae rate in the survivors was 16.4%. This study emphasizes the severity of PNM with high rates of mortality and neurological sequelae.

Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child.

PubMed

Almeida, Ana F; Trindade, Eunice; B Vitor, Artur; Tavares, Margarida

Invasive Haemophilus influenzae type b (Hib) disease decreased dramatically after the introduction of conjugate vaccine in routine immunization schedules. We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski's sign was positive. The cerebrospinal fluid (CSF) analysis showed pleocytosis and high protein level. Empiric intravenous antibiotics (ceftriaxone and vancomycin) were administered for suspected bacterial meningitis during 10 days. Serotyping of the Haemophilus influenzae strain found in CSF revealed a serotype b. After one year of follow-up no Hib meningitis sequelae were noted. Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure. Efforts to keep the low incidence of invasive Hib disease should be directed to the maintenance of high vaccination coverage rates, combined with the notification and surveillance strategies already implemented in each country. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

[Human African trypanosomiasis in children. A pediatrics service experience in Libreville, Gabon].

PubMed

Koko, J; Dufillot, D; Gahouma, D; Amblard, J; Kani, F

1997-01-01

During a period of six years (1/1/89-12/31/94), seven children with trypanosomiasis were admitted to the Department of Pediatrics of Owendo Pediatric Hospital-Libreville, Gabon. They were 5 boys and 2 girls, aged 4-17 years, five of them under 15 years. The main reasons of hospitalization were somnolence (4 cases), psychical disorders (5 cases), neurological disorders (4 cases), asthenia (3 cases), loss of weight (3 cases) and fever (3 cases). Increased sedimentation rate (5 cases) and hypergammaglobulinemia (6 cases) were the most important biological disturbances. Serodiagnosis (CATT, indirect immunofluorescence test) was positive in all cases. The parasite was detected in blood seven times, and four times in cerebrospinal fluid (CSF). According to CSF status, six children have been classified in second stage of the disease. Six patients were treated by melarsoprol, and one by eflornithine. Tolerance and response to treatment were good in six cases. Three children presented sequels when leaving hospital. No patient was seen again after the study.

Treatment with Botulinum Toxin for Refractory Fever Caused by Severe Spasticity: A Case Series.

PubMed

Lester, Jacobo; Alvarez-Resendiz, Gerardo Esteban; Klériga, Enrique; Videgaray, Fernando; Zambito, Gerardo

2018-06-01

Brain and spinal cord injuries may cause very severe spasticity that occasionally may be associated with persistent fever. We present 14 patients with spasticity and persistent fever, treated with botulinum toxin type A. Their spasticity improved and the fever resolved within a period no greater than 48 h. In all cases, infectious and other non-infectious causes were ruled out. When sustained tonic muscular activity is associated with a significant increase in body temperature and is refractory to the usual drugs used for hyperpyrexia, type A botulinum toxin may be an effective treatment option to control both spasticity and fever.

CXCL13 as a Cerebrospinal Fluid Marker for Neurosyphilis in HIV-infected Patients with Syphilis

PubMed Central

Marra, Christina M.; Tantalo, Lauren C.; Sahi, Sharon K.; Maxwell, Clare L.; Lukehart, Sheila A.

2010-01-01

Background Asymptomatic neurosyphilis is more difficult to diagnose in HIV-infected patients because HIV itself can cause cerebrospinal fluid (CSF) pleocytosis. The proportion of CSF lymphocytes that are B cells is elevated in neurosyphilis, suggesting that the CSF concentration of the B cell chemoattractant, chemokine (C-X-C motif) ligand 13 (CXCL13) concentration may also be elevated. Methods CSF and blood were collected from 199 HIV-infected patients with syphilis and neurosyphilis. Serum and CSF CXCL13 concentrations were determined. Results Patients with neurosyphilis had higher CSF and serum CXCL13 concentrations compared to patients with syphilis but not neurosyphilis. The odds of having symptomatic neurosyphilis were increased by 2.23 fold for every log increase in CSF CXCL13 concentration and were independent of CSF WBC and plasma HIV RNA concentrations, peripheral blood CD4+ T cell count and use of antiretroviral medications. A cut-off of 10 pg/mL CSF CXCL13 had high sensitivity and a cut-off of 250 pg/mL or evidence of intrathecal synthesis of CXCL13 had high specificity for diagnosis of both symptomatic and asymptomatic neurosyphilis. CSF concentrations of CXCL13 declined after treatment for neurosyphilis. Conclusions CSF CXCL13 concentration may be particularly useful for diagnosis of neurosyphilis in HIV-infected patients because it is independent of CSF pleocytosis and markers of HIV disease. PMID:20393380

Transition in the Cause of Fever from Malaria to Dengue, Northwestern Ecuador, 1990–2011

PubMed Central

Cifuentes, Sara G.; Trostle, James; Trueba, Gabriel; Milbrath, Meghan; Baldeón, Manuel E.; Coloma, Josefina

2013-01-01

In tropical areas, the predominant cause of fever has historically been malaria. However by 2011, among febrile patients in northwestern Ecuador, dengue was identified in 42% and malaria in none. This finding suggests a transition in the cause of fever from malaria to other illnesses, such as dengue. PMID:24047566

Medical Surveillance Monthly Report. olume 22, Number 1, January 2015

DTIC Science & Technology

2015-01-01

etiologic agents for enteric fever , the prototype of which is typhoid fever caused by S. Typhi.1 In the U.S., the most common serotypes isolated in...component of the U.S. Armed Forces, Sal- monella is a leading cause of acute gastroin- testinal illness.3 Typhoid fever , in contrast, is relatively...more than 20 million cases of typhoid fever occur annually and another 5.5 million cases of enteric fever are attributed to S. Paratyphi.1 Th e most

[Biochemical measurements of glucose metabolism in relation to cause of death and postmortem effects].

PubMed

Kernbach, G; Püschel, K; Brinkmann, B

1986-01-01

This study was performed to examine the relationship between postmortem biochemical values and cause of death. The follow samples were taken from 399 corpses: cerebrospinal fluid (CSF; n = 376, suboccipital), blood (n = 158, femoral vein), and urine (n = 101, at autopsy). (See Table 1 for causes of death) All samples were stored at -80 degrees C. A further 100 samples of blood were later taken and stored at +4 degrees C before testing. Biochemical determinations made were: glucose in CSF, blood, and urine (hexokinase method); lactate (LDH/GPT) and free acetone (HS-gas chromatography) in CSF; hemoglobin A1 in blood (microcolumn technique). In 34 cases fatal diabetic coma was considered verified by morphological and chemical findings. One hundred cases of sudden cardiac death were chosen as the main control group. In 32 of the 34 cases defined above, the value of the formula of Traub (glucose + lactate in CSF) exceeded 415 mg/dl. It is not influenced significantly by hyperglycemia or hyperlactatemia due to factors other than diabetes (i.e., carbon monoxide, asphyxia). After death the value rose till the 30th hpm, then remained stable for at least 1 week. Fatal coma was defined as the ketoacidotic form if free acetone in CSF ranged above 21 mg/l. In these cases, CSF glucose and free acetone correlated positively. Hemoglobin A1 remained stable after death. Its amount was independent from postmortem blood glucose, postmortem interval and total hemoglobin. Furthermore, the manner of storage (-80 degrees or +4 degrees C) had no significant influence on its values. In 29 of 34 cases of fatal coma, Hb A1 exceeded 12.1%. Analysis of urine glucose showed elevated levels (over 500 mg/dl) in diabetic comas. On conclusion, fatal diabetic coma seems indicated as the cause of death if measured values of postmortem biochemistry exceed the following limits: CSF-Traub 415 mg/dl, free acetone (CSF) 21 mg/l; Hb A1 12.1%; urine glucose 500 mg/dl. Most important are the Traub formula and hemoglobin A1. Usually, in fatal coma both values are elevated. If both of them are normal, diabetic coma can nearly be excluded. Combined evaluation of all values is absolutely necessary. Morphology must also always be taken into account. Consequently, a diagnosis of fatal coma can be obtained by a process of elimination.

Imaging review of cerebrospinal fluid leaks

PubMed Central

Vemuri, Naga V; Karanam, Lakshmi S P; Manchikanti, Venkatesh; Dandamudi, Srinivas; Puvvada, Sampath K; Vemuri, Vineet K

2017-01-01

Cerebrospinal fluid (CSF) leak occurs due to a defect in the dura and skull base. Trauma remains the most common cause of CSF leak; however, a significant number of cases are iatrogenic, and result from a complication of functional endoscopic sinus surgery (FESS). Early diagnosis of CSF leak is of paramount importance to prevent life-threatening complications such as brain abscess and meningitis. Imaging plays a crucial role in the detection and characterization of CSF leaks. Three-dimensional, isotropic, high resolution computed tomography (HRCT) accurately detects the site and size of the bony defect. CT cisternography, though invasive, helps accurately identify the site of CSF leak, especially in the presence of multiple bony defects. Magnetic resonance imaging (MRI) accurately detects CSF leaks and associated complications such as the encephaloceles and meningoceles. In this review, we emphasize the importance and usefulness of 3D T2 DRIVE MR cisternography in localizing CSF leaks. This sequence has the advantages of effective bone and fat suppression, decreased artefacts, faster acquisition times, three-dimensional capability, y and high spatial resolution in addition to providing very bright signal from the CSF. PMID:29379240

Imaging review of cerebrospinal fluid leaks.

PubMed

Vemuri, Naga V; Karanam, Lakshmi S P; Manchikanti, Venkatesh; Dandamudi, Srinivas; Puvvada, Sampath K; Vemuri, Vineet K

2017-01-01

Cerebrospinal fluid (CSF) leak occurs due to a defect in the dura and skull base. Trauma remains the most common cause of CSF leak; however, a significant number of cases are iatrogenic, and result from a complication of functional endoscopic sinus surgery (FESS). Early diagnosis of CSF leak is of paramount importance to prevent life-threatening complications such as brain abscess and meningitis. Imaging plays a crucial role in the detection and characterization of CSF leaks. Three-dimensional, isotropic, high resolution computed tomography (HRCT) accurately detects the site and size of the bony defect. CT cisternography, though invasive, helps accurately identify the site of CSF leak, especially in the presence of multiple bony defects. Magnetic resonance imaging (MRI) accurately detects CSF leaks and associated complications such as the encephaloceles and meningoceles. In this review, we emphasize the importance and usefulness of 3D T2 DRIVE MR cisternography in localizing CSF leaks. This sequence has the advantages of effective bone and fat suppression, decreased artefacts, faster acquisition times, three-dimensional capability, y and high spatial resolution in addition to providing very bright signal from the CSF.

Think fungus NOT just a crypto-meningitis in AIDS!

PubMed

Badiye, Amit; Patnaik, Mrinal; Deshpande, Alaka; Rajendran, C; Chandrashekara, K V

2012-12-01

Extrapulmonary cryptococcosis has been defined as AIDS defining illness in HIV infected people. Cryptococcal meningitis is the commonest meningitis with advanced immune deficiency. Therefore clinicians ask for tests only for detection of cryptococci which may be misleading. A prospective study of suspected fungal meningitis with CSF fungal culture is carried out. 70 ART naive cases of suspected fungal meningitis in HIV cases were subjected to CSF cytochemistry, smear exam and CSF fungal culture. The CSF culture was positive in 75.6% cases of these 21 were C. Neoformans as against 28 of Rhodotorula. In addition candida, aspergillus, geotrichum, trichosporon were isolated. Apart from c. neoformans, other fungi also cause meningitis. Each case of suspected fungal meningitis, may be subjected for CSF fungal culture for proper and adequate management. If facility for fungal culture is not available and if CSF smear shows evidence of fungal infection then standard therapy with Amphotericin may be instituted earlier to reduce mortality. This is the largest series isolating Rhodotorula from CSF in AIDS patients.

GM-CSF primes cardiac inflammation in a mouse model of Kawasaki disease

PubMed Central

McKenzie, Brent S.

2016-01-01

Kawasaki disease (KD) is the leading cause of pediatric heart disease in developed countries. KD patients develop cardiac inflammation, characterized by an early infiltrate of neutrophils and monocytes that precipitates coronary arteritis. Although the early inflammatory processes are linked to cardiac pathology, the factors that regulate cardiac inflammation and immune cell recruitment to the heart remain obscure. In this study, using a mouse model of KD (induced by a cell wall Candida albicans water-soluble fraction [CAWS]), we identify an essential role for granulocyte/macrophage colony-stimulating factor (GM-CSF) in orchestrating these events. GM-CSF is rapidly produced by cardiac fibroblasts after CAWS challenge, precipitating cardiac inflammation. Mechanistically, GM-CSF acts upon the local macrophage compartment, driving the expression of inflammatory cytokines and chemokines, whereas therapeutically, GM-CSF blockade markedly reduces cardiac disease. Our findings describe a novel role for GM-CSF as an essential initiating cytokine in cardiac inflammation and implicate GM-CSF as a potential target for therapeutic intervention in KD. PMID:27595596

Evaluation of fever in the emergency department.

PubMed

DeWitt, Sarah; Chavez, Summer A; Perkins, Jack; Long, Brit; Koyfman, Alex

2017-11-01

Fever is one of the most common complaints in the emergency department (ED) and is more complex than generally appreciated. The broad differential diagnosis of fever includes numerous infectious and non-infectious etiologies. An essential skill in emergency medicine is recognizing the pitfalls in fever evaluation. This review provides an overview of the complaint of fever in the ED to assist the emergency physician with a structured approach to evaluation. Fever can be due to infectious or non-infectious etiology and results from the body's natural response to a pyrogen. Adjunctive testing including C-reactive protein, erythrocyte sedimentation rate, and procalcitonin has been evaluated in the literature, but these tests do not have the needed sensitivity and specificity to definitively rule in a bacterial cause of fever. Blood cultures should be obtained in septic shock or if the results will change clinical management. Fever may not be always present in true infection, especially in elderly and immunocompromised patients. Oral temperatures suffer from poor sensitivity to diagnose fever, and core temperatures should be utilized if concern for fever is present. Consideration of non-infectious causes of elevated temperature is needed based on the clinical situation. Any fever evaluation must rigorously maintain a broad differential to avoid pitfalls that can have patient care consequences. Fever is complex and due to a variety of etiologies. An understanding of the pathophysiology, causes, and assessment is important for emergency physicians. Published by Elsevier Inc.

Observations on the site and mode of action of pyrogens in the rabbit brain

PubMed Central

Cooper, K. E.; Cranston, W. I.; Honour, A. J.

1967-01-01

1. Leucocyte pyrogen has been injected bilaterally into various parts of the rabbit brain. It caused fever when injected into the pre-optic area and the anterior hypothalamus, but not when injected into the posterior hypothalamus, the mid-brain, the pons, the cerebellum or the cerebral cortex. 2. The mean time which elapsed between a leucocyte pyrogen injection into the anterior hypothalamus and the onset of fever was 7·8 min. For similar injections of bacterial pyrogen the time lag was 24·8 min. The mean time lag between bilateral injections of noradrenaline into the anterior hypothalamus and the onset of fever was 7·4 min. 3. The amount of leucocyte pyrogen required to cause fever when injected into the anterior hypothalamus was less than 1/100 of that required to cause a similar fever on intravenous injection. The quantity of bacterial pyrogen injected into the hypothalamus was of the same order as that which would cause a similar fever on intravenous injection. 4. Control injections of saline, plasma, cerebrospinal fluid, heated leucocyte pyrogen and red cells into the anterior hypothalamus did not cause fever. 5. After attempts to deplete the hypothalamus of its monoamine stores by intraventricular injections of reserpine, the rabbit had fever as a result of an intravenous injection of bacterial pyrogen. 6. We conclude that the anterior hypothalamus and the pre-optic area are sites at which leucocyte pyrogen acts to cause fever in the rabbit. The mechanism of this febrile response is not clear, but it appears that part, at least, of the response could be mediated by a mechanism other than release of noradrenaline or failure to release 5-HT. ImagesPlate 1 PMID:6050108

Evaluation of Movement Restriction Zone Sizes in Controlling Classical Swine Fever Outbreaks

PubMed Central

Yadav, Shankar; Olynk Widmar, Nicole; Lay, Donald C.; Croney, Candace; Weng, Hsin-Yi

2017-01-01

The objective of this study was to compare the impacts of movement restriction zone sizes of 3, 5, 9, and 11 km with that of 7 km (the recommended zone size in the United States) in controlling a classical swine fever (CSF) outbreak. In addition to zone size, different compliance assumptions and outbreak types (single site and multiple site) were incorporated in the study. Three assumptions of compliance level were simulated: baseline, baseline ± 10%, and baseline ± 15%. The compliance level was held constant across all zone sizes in the baseline simulation. In the baseline ± 10% and baseline ± 15% simulations, the compliance level was increased for 3 and 5 km and decreased for 9 and 11 km from the baseline by the indicated percentages. The compliance level remained constant in all simulations for the 7-km zone size. Four single-site (i.e., with one index premises at the onset of outbreak) and four multiple-site (i.e., with more than one index premises at the onset of outbreak) CSF outbreak scenarios in Indiana were simulated incorporating various zone sizes and compliance assumptions using a stochastic between-premises disease spread model to estimate epidemic duration, percentage of infected, and preemptively culled swine premises. Furthermore, a risk assessment model that incorporated the results from the disease spread model was developed to estimate the number of swine premises under movement restrictions that would experience animal welfare outcomes of overcrowding or feed interruption during a CSF outbreak in Indiana. Compared with the 7-km zone size, the 3-km zone size resulted in a longer median epidemic duration, larger percentages of infected premises, and preemptively culled premises (P’s < 0.001) across all compliance assumptions and outbreak types. With the assumption of a higher compliance level, the 5-km zone size significantly (P < 0.001) reduced the epidemic duration and percentage of swine premises that would experience animal welfare outcomes in both outbreak types, whereas assumption of a lower compliance level for 9- and 11-km zone sizes significantly (P < 0.001) increased the epidemic duration and percentage of swine premises with animal welfare outcomes compared with the 7-km zone size. The magnitude of impact due to a zone size varied across the outbreak types (single site and multiple site). Overall, the 7-km zone size was found to be most effective in controlling CSF outbreaks, whereas the 5-km zone size was comparable to the 7-km zone size in some circumstances. PMID:28119920

The double-antigen ELISA concept for early detection of Erns -specific classical swine fever virus antibodies and application as an accompanying test for differentiation of infected from marker vaccinated animals.

PubMed

Meyer, D; Fritsche, S; Luo, Y; Engemann, C; Blome, S; Beyerbach, M; Chang, C-Y; Qiu, H-J; Becher, P; Postel, A

2017-12-01

Emergency vaccination with live marker vaccines represents a promising control strategy for future classical swine fever (CSF) outbreaks, and the first live marker vaccine is available in Europe. Successful implementation is dependent on a reliable accompanying diagnostic assay that allows differentiation of infected from vaccinated animals (DIVA). As induction of a protective immune response relies on virus-neutralizing antibodies against E2 protein of CSF virus (CSFV), the most promising DIVA strategy is based on detection of E rns -specific antibodies in infected swine. The aim of this study was to develop and to evaluate a novel E rns -specific prototype ELISA (pigtype CSFV E rns Ab), which may be used for CSF diagnosis including application as an accompanying discriminatory test for CSFV marker vaccines. The concept of a double-antigen ELISA was shown to be a solid strategy to detect E rns -specific antibodies against CSFV isolates of different genotypes (sensitivity: 93.5%; specificity: 99.7%). Furthermore, detection of early seroconversion is advantageous compared with a frequently used CSFV E2 antibody ELISA. Clear differences in reactivity between sera taken from infected animals and animals vaccinated with various marker vaccines were observed. In combination with the marker vaccine CP7_E2alf, the novel ELISA represents a sensitivity of 90.2% and a specificity of 93.8%. However, cross-reactivity with antibodies against ruminant pestiviruses was observed. Interestingly, the majority of samples tested false-positive in other E rns -based antibody ELISAs were identified correctly by the novel prototype E rns ELISA and vice versa. In conclusion, the pigtype CSFV E rns Ab ELISA can contribute to an improvement in routine CSFV antibody screening, particularly for analysis of sera taken at an early time point after infection and is applicable as a DIVA assay. An additional E rns antibody assay is recommended for identification of false-positive results in a pig herd immunized with the licensed CP7_E2alf marker vaccine. © 2017 Blackwell Verlag GmbH.

Repair of Spontaneous Cerebrospinal Fluid Otorrhea from Defect of Middle Cranial Fossa

PubMed Central

Goh, Young Bum; Han, Chi-Sung

2013-01-01

Spontaneous cerebrospinal fluid (CSF) otorrhea is defined as CSF otorrhea where there are no identifiable causes including previous trauma, surgery, infection, neoplasm or congenital anomaly. The condition is rare. The origin of CSF leak is commonly a defect in the tegmen of the middle cranial fossa. The pathophysiology of spontaneous CSF otorrhea is unclear. Two theories of the etiology of bony defects of the temporal bone are the congenital bony defect theory and arachnoid granulation theory. The authors experienced a case of a 49-year-old female patient admitted with the complaint of persistent right ear fullness. Computed tomography revealed a large defect of the middle fossa and suspicious CSF otorrhea through the defect of tegmen tympani. Repair was successful with multiple bone chips using the transmastoid approach. The postoperative course was good and there has been no recurrence of the CSF leakage. PMID:24653924

Laboratory-based clinical audit as a tool for continual improvement: an example from CSF chemistry turnaround time audit in a South-African teaching hospital

PubMed Central

Imoh, Lucius C; Mutale, Mubanga; Parker, Christopher T; Erasmus, Rajiv T; Zemlin, Annalise E

2016-01-01

Introduction Timeliness of laboratory results is crucial to patient care and outcome. Monitoring turnaround times (TAT), especially for emergency tests, is important to measure the effectiveness and efficiency of laboratory services. Laboratory-based clinical audits reveal opportunities for improving quality. Our aim was to identify the most critical steps causing a high TAT for cerebrospinal fluid (CSF) chemistry analysis in our laboratory. Materials and methods A 6-month retrospective audit was performed. The duration of each operational phase across the laboratory work flow was examined. A process-mapping audit trail of 60 randomly selected requests with a high TAT was conducted and reasons for high TAT were tested for significance. Results A total of 1505 CSF chemistry requests were analysed. Transport of samples to the laboratory was primarily responsible for the high average TAT (median TAT = 170 minutes). Labelling accounted for most delays within the laboratory (median TAT = 71 minutes) with most delays occurring after regular work hours (P < 0.05). CSF chemistry requests without the appropriate number of CSF sample tubes were significantly associated with delays in movement of samples from the labelling area to the technologist’s work station (caused by a preference for microbiological testing prior to CSF chemistry). Conclusion A laboratory-based clinical audit identified sample transportation, work shift periods and use of inappropriate CSF sample tubes as drivers of high TAT for CSF chemistry in our laboratory. The results of this audit will be used to change pre-analytical practices in our laboratory with the aim of improving TAT and customer satisfaction. PMID:27346964

Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

DTIC Science & Technology

2009-07-01

Microbiology. All Rights Reserved. Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever Kelly L. Warfield,* Steven B...mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV...cause severe hemorrhagic fevers in humans and non- human primates (27). The incubation time is estimated to be 3 to 21 days, with human case fatality

Detection and typing of enteroviruses from CSF specimens from patients diagnosed with meningitis/encephalitis.

PubMed

Tavakoli, Norma P; Wang, Heng; Nattanmai, Seela; Dupuis, Michelle; Fusco, Heather; Hull, Rene

2008-10-01

Human enteroviruses are the most common cause of viral meningitis. Rapid enterovirus detection and identification is important in order to ruleout other causes of disease, initiate appropriate patient management and to aid in epidemiological investigations. A 2-year study (2005-2006) of patients with symptoms of meningitis/encephalitis was performed in New York State (NYS) to determine the underlying enteroviral etiology. Reverse-transcription, followed by a sequential PCR strategy targeting the 5'-nontranslated and VP1 regions, were used to first detect and then type, these RNA viruses. From a total of 1374 specimens tested, enterovirus was detected in 67 specimens (4.9%); of these, 59 could subsequently be typed. Coxsackievirus B5 was found in 14 cases in 2005, but none in 2006. Overall, 14 enterovirus serotypes were detected. The most prevalent enteroviruses in this cohort were Coxsackievirus B5, and echoviruses 18, and 6 collectively accounting for 46%. 2005 was a period of high activity for Coxsackievirus B5 in NYS. A large majority of the enterovirus-positive patients suffered from headache and fever. In most cases, the cerebrospinal fluid profile was reported and generally showed elevated protein levels (>45mg/dl) and a higher than normal white blood cell count (>5mm(3)).

Naegleria fowleri That Induces Primary Amoebic Meningoencephalitis: Rapid Diagnosis and Rare Case of Survival in a 12-Year-Old Caucasian Girl.

PubMed

Dunn, Andrew L; Reed, Tameika; Stewart, Charlotte; Levy, Rebecca A

2016-05-01

Primary amoebic meningoencephalitis (PAM) is a rare and almost always fatal disease that is caused by Naegleria fowleri, a freshwater thermophilic amoeba. Our case involves an adolescent female who presented with fever of unknown origin. A lumbar puncture was performed, and the Wright-Giemsa and Gram stained cerebrospinal fluid (CSF) cytospin slides showed numerous organisms. Experienced medical technologists in the microbiology and hematology laboratories identified the organisms as morphologically consistent with Naegleria species. The laboratory made a rapid diagnosis and alerted emergency department care providers within 75 minutes. The patient was treated for PAM with amphotericin, rifampin, azithromycin, fluconazole and aggressive supportive therapy including dexamethasone. The Centers for Disease Control and Prevention (CDC) was contacted, and miltefosine, an investigational medication, was started. Additional treatment included an intraventricular shunt and controlled hypothermia in order to mitigate potential cerebral edema. Our patient is a rare success story, as she was diagnosed swiftly, successfully treated, and survived PAM. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

CSF Analysis

MedlinePlus

... one or more hours to avoid a potential post-test headache. The lumbar puncture procedure usually takes less ... in CSF with laboratory tests such as molecular tests or culture. Parasitic meningitis or encephalitis are rare and can be lethal. One example is an infection caused by the free-living ...

Management of Postoperative Fever in Adult Cardiac Surgical Patients.

PubMed

O'Mara, Susan K

Postoperative fever after cardiac surgery is a common occurrence. Most fevers are benign and self-limiting resulting from inflammation caused by surgical trauma and blood contact with cardiopulmonary bypass circuit resulting in the release of cytokines. Only a small percentage of time is postoperative fever due to an infection complicating surgery. The presence of fever frequently triggers a battery of diagnostic tests that are costly, could expose the patient to unnecessary risks, and can produce misleading or inconclusive results. It is therefore important that fever be evaluated in a systematic, prudent, clinically appropriate, and cost-effective manner. This article focuses on the current evidence regarding pathophysiology, incidence, causes, evaluation, and management of fever in postoperative adult cardiac surgical patients.

Direct numerical simulation of transitional hydrodynamics of the cerebrospinal fluid in Chiari I malformation: The role of cranio-vertebral junction.

PubMed

Jain, Kartik; Ringstad, Geir; Eide, Per-Kristian; Mardal, Kent-André

2017-09-01

Obstruction to the cerebrospinal fluid (CSF) outflow caused by the herniation of cerebellar tonsils as a result of Chiari malformation type I leads to altered CSF hydrodynamics. This contribution explores the minutest characteristics of the CSF hydrodynamics in cervical subarachnoid space (SAS) of a healthy subject and 2 Chiari patients by performing highly resolved direct numerical simulation. The lattice Boltzmann method is used for the simulations because of its scalability on modern supercomputers that allow us to simulate up to approximately 10 9 cells while resolving the Kolmogorov microscales. The results depict that whereas the complex CSF flow remains largely laminar in the SAS of a healthy subject, constriction of the cranio-vertebral junction in Chiari I patients causes manifold fluctuations in the hydrodynamics of the CSF. These fluctuations resemble a flow that is in a transitional regime rather than laminar or fully developed turbulence. The fluctuations confine near the cranio-vertebral junction and are triggered due to the tonsillar herniation, which perturbs the flow as a result of altered anatomy of the SAS. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluating the effect of hydrocephalus cause on the manner of changes in the effective parameters and clinical symptoms of the disease.

PubMed

Gholampour, Seifollah; Fatouraee, Nasser; Seddighi, Amir Saeed; Seddighi, Afsoun

2017-01-01

In the present study, the heads of 11 normal subjects and 21 patients affected by hydrocephalus due to three different causes were simulated using fluid-structure interaction (FSI). To validate the results, the calculated diagram of CSF velocity in aqueduct of Sylvius (AS) was compared with the similar velocity diagram measured using Cine PC-MRI for the same subject. After ensuring the agreement of results, other outputs such as CSF pressure were calculated non-invasively using FSI. The intracranial pressure and CSF pressure in AS and behind the optic nerve sheath were in patients 5-5.3 times the value in normal subjects and the ventricular system volume in patients was 10.2-11.1 times the value in normal subjects. However, the difference between the coefficient of variation and the maximum value of pressure and volume in different types of hydrocephalus was small. Furthermore, the difference between CSF stroke volumes in various types of hydrocephalus patients was less than 4.4%. Results showed that the intensity of clinical symptoms was similar in patients with similar CSF pressure and the cause of the hydrocephalus disease didn't have any significant effect on the intensity of patients' clinical symptoms and the manner of changes in effective parameters on disease. It was also found that the relation of CSF pressure and volume was 16.7% greater in patients with non-communicating hydrocephalus than in patients with communicating hydrocephalus. These results enhance the insight into hydrocephalus bio-mechanism and can help to choose the proper treatment method for hydrocephalus patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Example of Genetically Distinct HIV Type 1 Variants in Cerebrospinal Fluid and Plasma During Suppressive Therapy

PubMed Central

Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W.; Palmer, Sarah

2014-01-01

We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system. PMID:24338353

An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy.

PubMed

Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W; Palmer, Sarah

2014-05-15

We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system.

Detection of Bacterial Meningitis Pathogens by PCR-Mass Spectrometry in Cerebrospinal Fluid.

PubMed

Jing-Zi, Piao; Zheng-Xin, He; Wei-Jun, Chen; Yong-Qiang, Jiang

2018-06-01

Acute bacterial meningitis remains a life-threatening infectious disease with considerable morbidity and mortality. DNA-based detection methods are an urgent requisite for meningitis-causing bacterial pathogens for the prevention of outbreaks and control of infections. We proposed a novel PCR-mass spectrometry (PCR-Mass) assay for the simultaneous detection of four meningitis-causing agents, Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae, and Mycobacterium tuberculosis in the present study. A total of 138 cerebrospinal fluid (CSF) samples (including 56 CSF culture positive, 44 CSF culture negative, and 38 CSF control) were enrolled and analyzed by PCR/Mass. Results were compared to real-time PCR detection. These four targeting pathogens could be discriminated without cross-reaction by the accurate detection of the corresponding extension products with different masses. The limits of detection were 102 copies/reaction for S. pneumoniae, H. influenzae, and N. meningitidis and 103 for M. tuberculosis. The evaluation of the culture-positive CSF specimens from the meningitis patients provided an overall agreement rate of 85.7% with PCR-Mass and real-time PCR. The PCR-Mass was also able to detect the targeting pathogens from culture-negative CSF specimens from meningitis patients receiving early antibiotic treatment. PCR-Mass could be used for the molecular detection of bacterial meningitis and tuberculosis, especially when early antibiotic treatment has been administered to the suspected patients.

[Group A streptococcal meningitis: Streptococcus pneumoniae is not the only one to seep into the CSF fluid leak!].

PubMed

Zappella, N; Barrelet, A; Pangon, B; Laurent, V; Bruneel, F

2013-11-01

We reported a case of group A streptococcal meningitis in a patient with a CSF fluid leak. This case underlined several relevant points: (i) an unfrequent cause of bacterial meningitis; (ii) the main diagnosis to evoke when the direct examination of CSF shows Gram+ cocci with a negative pneumococcal antigen; (iii) that bacteria other than Streptococcus pneumoniae are possible in front of a meningitis associated with a CSF fluif leak. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Herpes simplex encephalitis presenting as stroke-like symptoms with atypical MRI findings and lacking cerebrospinal fluid pleocytosis.

PubMed

Tsuboguchi, Shintaro; Wakasugi, Takahiro; Umeda, Yoshitaka; Umeda, Maiko; Oyake, Mutsuo; Fujita, Nobuya

2017-07-29

A 73-year-old woman presented with sudden onset of right hemiparesis and was diagnosed as having cerebral infarction on the basis of diffusion-weighted brain MRI, which demonstrated lesions in the left parietal cortex. On the 3rd day, the patient developed right upper limb myoclonus, aphasia, and disturbance of consciousness with high fever. On the 6th day, she was transferred to our hospital with suspected viral encephalitis, and treatment with acyclovir was started. By the 6th day, the lesions detected by MRI had expanded to the gyrus cinguli, insula and thalamus, but not to the temporal lobe. At that time, the CSF cell count was 8/μl, and this later increased to 17/μl by the 13th day. Although herpes simplex virus DNA was detected in the CSF on the 6th day, there was no evidence of CSF pleocytosis or temporal lobe abnormalities demonstrable by brain MRI throughout the whole follow-up period. This was very atypical case of herpes simplex encephalitis characterized by a stroke-like episode, atypical MRI findings, and absence of cerebrospinal fluid pleocytosis. It is important to be mindful that herpes simplex encephalitis (HSE) can have an atypical presentation, and that sufficient acyclovir treatment should be initiated until HSE can be ruled out.

Coccidioidomycosis as a Common Cause of Community-acquired Pneumonia

PubMed Central

Valdivia, Lisa; Nix, David; Wright, Mark; Lindberg, Elizabeth; Fagan, Timothy; Lieberman, Donald; Stoffer, T'Prien; Ampel, Neil M.

2006-01-01

The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of valley fever may be underestimated by public health statistics. Therefore, we conducted a prospective observational study of adults with recent onset of a lower respiratory tract syndrome. Valley fever was serologically confirmed in 16 (29%) of 55 persons (95% confidence interval 16%–44%). Antimicrobial medications were used in 81% of persons with valley fever. Symptomatic differences at the time of enrollment had insufficient predictive value for valley fever to guide clinicians without specific laboratory tests. Thus, valley fever is a common cause of CAP after exposure in a disease-endemic region. If CAP develops in persons who travel or reside in Coccidioides-endemic regions, diagnostic evaluation should routinely include laboratory evaluation for this organism. PMID:16707052

Hybrid Monte Carlo-Diffusion Method For Light Propagation in Tissue With a Low-Scattering Region

NASA Astrophysics Data System (ADS)

Hayashi, Toshiyuki; Kashio, Yoshihiko; Okada, Eiji

2003-06-01

The heterogeneity of the tissues in a head, especially the low-scattering cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown to strongly affect light propagation in the brain. The radiosity-diffusion method, in which the light propagation in the CSF layer is assumed to obey the radiosity theory, has been employed to predict the light propagation in head models. Although the CSF layer is assumed to be a nonscattering region in the radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in the CSF layer in real heads. A novel approach, the hybrid Monte Carlo-diffusion method, is proposed to calculate the head models, including the low-scattering region in which the light propagation does not obey neither the diffusion approximation nor the radiosity theory. The light propagation in the high-scattering region is calculated by means of the diffusion approximation solved by the finite-element method and that in the low-scattering region is predicted by the Monte Carlo method. The intensity and mean time of flight of the detected light for the head model with a low-scattering CSF layer calculated by the hybrid method agreed well with those by the Monte Carlo method, whereas the results calculated by means of the diffusion approximation included considerable error caused by the effect of the CSF layer. In the hybrid method, the time-consuming Monte Carlo calculation is employed only for the thin CSF layer, and hence, the computation time of the hybrid method is dramatically shorter than that of the Monte Carlo method.

Hybrid Monte Carlo-diffusion method for light propagation in tissue with a low-scattering region.

PubMed

Hayashi, Toshiyuki; Kashio, Yoshihiko; Okada, Eiji

2003-06-01

The heterogeneity of the tissues in a head, especially the low-scattering cerebrospinal fluid (CSF) layer surrounding the brain has previously been shown to strongly affect light propagation in the brain. The radiosity-diffusion method, in which the light propagation in the CSF layer is assumed to obey the radiosity theory, has been employed to predict the light propagation in head models. Although the CSF layer is assumed to be a nonscattering region in the radiosity-diffusion method, fine arachnoid trabeculae cause faint scattering in the CSF layer in real heads. A novel approach, the hybrid Monte Carlo-diffusion method, is proposed to calculate the head models, including the low-scattering region in which the light propagation does not obey neither the diffusion approximation nor the radiosity theory. The light propagation in the high-scattering region is calculated by means of the diffusion approximation solved by the finite-element method and that in the low-scattering region is predicted by the Monte Carlo method. The intensity and mean time of flight of the detected light for the head model with a low-scattering CSF layer calculated by the hybrid method agreed well with those by the Monte Carlo method, whereas the results calculated by means of the diffusion approximation included considerable error caused by the effect of the CSF layer. In the hybrid method, the time-consuming Monte Carlo calculation is employed only for the thin CSF layer, and hence, the computation time of the hybrid method is dramatically shorter than that of the Monte Carlo method.

Successful treatment of methimazole-induced severe aplastic anemia by granulocyte colony-stimulating factor, methylprednisolone, and cyclosporin.

PubMed

Honda, Munehiro

2011-01-01

A 52-year-old Japanese woman was examined because of general malaise, weight loss and a lump in her left breast. She was diagnosed with cancer of the left breast and Graves' disease, and was administered methimazole (MMI). A left mastectomy was performed for the breast cancer. She presented with a high fever and peripheral blood examination revealed a severe pancytopenia. She was diagnosed with severe aplastic anemia, and administered G-CSF, however, the treatment was unsuccessful. Thus, oral methyprednisolone and cyclosporin were added. There was a remarkable improvement in the peripheral blood count.

Clinical characteristics of 15 cases of chronic subdural hematomas due to spontaneous intracranial hypotension with spinal cerebrospinal fluid leak.

PubMed

Wan, Yingfeng; Xie, Jixi; Xie, Dajiang; Xue, Zhaoliang; Wang, Yirong; Yang, Shuxu

2016-12-01

The etiology of chronic subdural hematoma (CSDH) in patients is diverse. The primary objective of this article was to discuss one of the causes, spontaneous intracranial hypotension with spinal cerebrospinal fluid (CSF) leak, which is usually neglected by the neurosurgeon. All the consecutive 15 patients who underwent operation for CSDHs between June 2012 and June 2014 at Sir Run Run Shaw Hospital of Zhejiang University were included in this retrospective cohort study. The clinical and imaging data of these patients with CSDHs due to spinal CSF leak were retrospectively studied. Fifteen patients, with a mean age of 53.8 ± 8.3 years, underwent operations for CSDH. Hematomas were unilateral in 4 patients and bilateral in 11 patients. Among these patients, eight patients had recurrence of hematomas after operation due to neglect of spinal CSF leak. All patients had fully recovery. Spinal CSF leak is a cause of cSDH, which is overlooked by the doctor.

Acute meningitis prognosis using cerebrospinal fluid interleukin-6 levels.

PubMed

Vázquez, Jorge Alejandro; Adducci, Maria del Carmen; Coll, Carlos; Godoy Monzón, Daniel; Iserson, Kenneth V

2012-08-01

Improved diagnostic tests would aid in diagnosing and treating community-acquired meningitis. To analyze the diagnostic value of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients presenting with symptoms of acute meningitis. In a 6-month prospective, observational, cross-sectional emergency department (ED) study, serum and CSF samples were obtained from all patients with a headache and fever in whom the physician suspected meningitis. Patients were excluded if computed tomography findings contraindicated a lumbar puncture, if they had bleeding disorders, or if their serum indicated bleeding. IL-6 levels were measured and compared in patients with (Group A) and without (Group B) bacterial meningitis. Samples were obtained from 53 patients, of whom 40 were ultimately found to have meningitis. These 40 patients averaged 49.6 ± 21.9 years, with number of men 18 (45%), hospitalizations 21 (52%), mortality 3 (.07%), and IL-6 average rating 491 (median: 14.5; range 0000-6000). Findings in the two groups were: Group A (with meningitis): n = 13, average IL-6 level: 1495 (median: 604; 25/75 percentiles: 232.5-2030; 95% confidence interval [CI] 371.7-2618.6; range 64-6000). Group B (with aseptic meningitis): n = 27, average IL-6 level: 7.34 (median: 5; 25/75 percentiles: 0.0/15.1; 95% CI 3.94-10.73; range 0-23.6). Mann-Whitney rank sum test: p < 0.0001. In patients with acute bacterial meningitis, CSF cytokine concentrations are elevated. Measuring CSF inflammatory cytokine levels in patients with acute meningitis could be a valuable ED diagnostic tool. Using this tool could improve the prognosis of patients with bacterial meningitis by allowing more rapid initiation of antibiotic treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shim, Ann Hye-Ryong; Chang, Rhoda Ahn; Chen, Xiaoyan

The ubiquitous EBV causes infectious mononucleosis and is associated with several types of cancers. The EBV genome encodes an early gene product, BARF1, which contributes to pathogenesis, potentially through growth-altering and immune-modulating activities, but the mechanisms for such activities are poorly understood. We have determined the crystal structure of BARF1 in complex with human macrophage-colony stimulating factor (M-CSF), a hematopoietic cytokine with pleiotropic functions in development and immune response. BARF1 and M-CSF form a high-affinity, stable, ring-like complex in both solution and the crystal, with a BARF1 hexameric ring surrounded by three M-CSF dimers in triangular array. The binding ofmore » BARF1 to M-CSF dramatically reduces but does not completely abolish M-CSF binding and signaling through its cognate receptor FMS. A three-pronged down-regulation mechanism is proposed to explain the biological effect of BARF1 on M-CSF:FMS signaling. These prongs entail control of the circulating and effective local M-CSF concentration, perturbation of the receptor-binding surface of M-CSF, and imposition of an unfavorable global orientation of the M-CSF dimer. Each prong may reduce M-CSF:FMS signaling to a limited extent but in combination may alter M-CSF:FMS signaling dramatically. The downregulating mechanism of BARF1 underlines a viral modulation strategy, and provides a basis for understanding EBV pathogenesis.« less

Production of Multiple Growth Factors by a Newly Established Human Thyroid Carcinoma Cell Line

PubMed Central

Yoshida, Yataro; Ohashi, Kensaku; Sano, Emiko; Kobayashi, Hisataka; Endo, Keigo; Naruto, Masanobu; Nakamura, Toru

1992-01-01

A multiple growth factor‐producing tumor cell line (NIM‐1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM‐1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM‐1‐conditioned medium (NIM‐1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony‐stimulating factor (CSF)‐dependent cell lines, NFS60‐KX and TF‐1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte‐CSF (G‐CSF), granulocyte/macrophage‐CSF (GM‐CSF) and interleukin(IL)‐6 mRNAs in NIM‐1 cells. Enzyme‐linked immunosorbent assays (ELISA) using NIM‐1CM also confirmed the production of IL‐la and a small amount of IL‐1β besides G‐CSF, GM‐CSF and IL‐6 in NIM‐1 cells. In addition, unexpected production of IL‐11 in NIM‐1 cells was detected by northern blot hybridization analysis and by bioassay using an IL‐11‐dependent cell line. Therefore, NIM‐1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM‐CSF, IL‐6 and IL‐11. PMID:1372885

ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells.

PubMed

Zhang, Hu; Zhang, Shuhong; Zhang, Jilin; Liu, Dongxin; Wei, Jiayi; Fang, Wengang; Zhao, Weidong; Chen, Yuhua; Shang, Deshu

2018-05-01

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

Clinical Profile of Scrub Typhus in Pregnancy in Sub-Himalayan Region.

PubMed

Kumar, Ritesh; Thakur, Surinder; Bhawani, Rajesh; Kanga, Anil; Ranjan, Asha

2016-10-01

Scrub typhus is rare in pregnancy, but it has now become an important cause of febrile illness in pregnancy in sub-Himalayan region of India. Only a few case reports have been published so far, and they show adverse maternal and fetal outcomes. No consensus has been reached till now regarding treatment. All the pregnant patients irrespective of period of gestation admitted with febrile illness with positive IgM ELISA for scrub typhus with or without eschar were included. The clinical profile was observed using a detailed history of symptoms, travel, recreation, agricultural activities, treatment record prior to admission, and a detailed examination, and the treatment outcome was noted. Fever workup including cultures, CXR, CSF analysis, serology for scrub was done. IgM scrub typhus was done by kit method manufactured by InBios Intertational, Inc. We observed in total 14 pregnant patients out of which eight were in the the second trimester and six were in the third trimester. The clinical features of the disease observed for pregnant females were the same as for nonpregnant females. There was no difference in the severity of scrub typhus between pregnant and nonpregnant women. No mortality was found in these patients. On follow-up, they had normal peripartum and postpartum periods. All were treated with azithromycin 500 mg once a day for 5 days. Although rare, scrub typhus should be considered in differential diagnosis of fever in pregnant patients especially in scrub season. Azithromycin should be the drug of choice in pregnancy as it has no adverse effect on fetus and pregnancy outcome.

Brucellosis With Multi-Organ Involvement in a Patient With History of Composite Aortic Graft and Hepatitis B.

PubMed

Dehghan Manshadi, Seyed Ali; Rezahosseini, Omid; Abdi Liaei, Zahra

2016-11-01

The brucellosis with multi-organ involvement in a patient with a history of the composite aortic graft (Bentall procedure) and Hepatitis B infection is rare. A 35-year-old man presented to us with fever and loss of consciousness. Four years ago, he was IDU and underwent cardiac surgery because of endocarditis. Recently lumbar spondylodiscitis was diagnosed. The Wright (1/320) and Coombs Wright tests (1/640) were positive. After CNS imaging, lumbar puncture was done. The CSF pleocytosis was lymphocyte dominant. In cardiac echocardiography, large vegetation on prosthetic aortic valve leaflets was seen. The brain MRI was reported abnormal. Treatment of brucellosis started with Ceftriaxone, Doxycycline, Rifampin and Gentamycin. After 4 days, he became oriented, and fever was disappeared then we continued the treatment for 16 days. The patient discharged and followed by daily phone calls. As symptoms of abdominal pain and jaundice were presented on the fifth day, he re-admitted. The patient expired because of hepatorenal and cardiac insufficiency. Drug side effects, activation of Hepatitis B and embolism of cardiac vegetation to other organs were suspected causes of death. We do not suggest medical therapy without cardiac surgery in such cases. When combination therapy is necessary for brucellosis in an HBsAg-positive patient, hepatitis virus activity should be assess by HBV-DNA PCR and the dose of drugs with known hepatotoxic effects such as rifampin and co-trimoxazole should be adjust. Combination therapy with quinolones instead of hepatoxic drugs is one of our suggustions.

Arthropod Borne Disease: The Leading Cause of Fever in Pregnancy on the Thai-Burmese Border

PubMed Central

McGready, Rose; Ashley, Elizabeth A.; Wuthiekanun, Vanaporn; Tan, Saw Oo; Pimanpanarak, Mupawjay; Viladpai-nguen, Samuel Jacher; Jesadapanpong, Wilarat; Blacksell, Stuart D.; Peacock, Sharon J.; Paris, Daniel H.; Day, Nicholas P.; Singhasivanon, Pratap; White, Nicholas J.; Nosten, François

2010-01-01

Background Fever in pregnancy is dangerous for both mother and foetus. In the 1980's malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented. Methodology Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded. Principal Findings Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests). Conclusion/Significance Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis. PMID:21103369

Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border.

PubMed

McGready, Rose; Ashley, Elizabeth A; Wuthiekanun, Vanaporn; Tan, Saw Oo; Pimanpanarak, Mupawjay; Viladpai-Nguen, Samuel Jacher; Jesadapanpong, Wilarat; Blacksell, Stuart D; Peacock, Sharon J; Paris, Daniel H; Day, Nicholas P; Singhasivanon, Pratap; White, Nicholas J; Nosten, François

2010-11-16

Fever in pregnancy is dangerous for both mother and foetus. In the 1980's malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented. Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded. Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests). Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis.

Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF) : A Review of its Pharmacological Properties and Prospective Role in the Management of Myelosuppression.

PubMed

Grant, Susan M; Heel, Rennie C

1992-04-01

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics. Endogenous GM-CSF is produced by T-lymphocytes, macrophages, fibroblasts and endothelial cells, and participates both in the complex regulation of blood cell formation and in activation of mature leucocytes. It is a polypeptide which is variably glycosylated in its native state although the carbohydrate content is not essential for its biological effects, and the 3 available recombinant forms (which differ in extent of glycosylation) are similarly active in vivo. Proliferative activity and priming of mature cells are manifest at similar picomolar concentrations of GM-CSF, and it is the programming of the cell which appears to determine the response to binding of GM-CSF to its cell surface receptor. In concert with other colony-stimulating factors, GM-CSF facilitates lineage commitment and subsequently supports or amplifies the clonogenic activity of lineage-restricted factors, with the strongest effect seen on the granulocyte-macrophage lineage. A biphasic response was seen when rGM-CSF was administered in doses up to 1000 µg/m 2 /day or 60 µg/kg/day by subcutaneous or intravenous routes in phase I/II trials. Peripheral blood leucocyte counts decreased rapidly and profoundly secondary to sequestration within the lungs. Re-entry of these cells into the circulation restores counts to baseline in 2 to 4 hours and thereafter an increase in the proliferative fraction of haematopoietic cells in bone marrow probably accounts for the progressive rise in the number of neutrophils, eosinophils and monocytes. This effect is dose-proportional. GM-CSF stimulates proliferation of leukaemic progenitors from patients with acute myeloid leukaemia without stimulating differentiation. In contrast, the abnormal clone from myelodysplastic patients can be induced with GM-CSF to differentiate in vitro although karyotype anomalies persist. In vitro studies suggest that stimulation of nonhaematological cancer cells at physiological concentrations of GM-CSF is unlikely. The priming effects of GM-CSF on mature leucocytes which include increased expression of other cytokines, secretion of granule contents, augmentation of antigen presentation, altered chemotaxis, and enhanced phagocytosis, oxidative metabolism and antibody dependent cell-mediated cytotoxicity probably serve to increase the host response to infection. Administration of murine rGM-CSF to mice injected with lethal inocula of, for example, Pseudomonas aeruginosa improved their survival relative to controls. There are several reports of refractory infection in seriously ill neutropenic patients resolving after addition of rGM-CSF to ongoing antimicrobial therapy and subsequent neutrophil recovery; however, the role of rGM-CSF in management of established infection in patients with neutropenia remains to be more thoroughly investigated. The pharmacokinetic properties of rGM-CSF depend on the route of administration. After intravenous administration, serum levels decline rapidly with a half-life of distribution (t 1/2α ) of 5 to 15 minutes and half-life of elimination (t 1/2β ) of 1.5 to 2 hours. Maximum serum concentrations are reached 2 hours after subcutaneous injection, then decline with a t 1/2β of 3 hours. Serum levels of rGM-CSF increase with dose and a proposed therapeutic target level of 1 µg/L is maintained for 8 to 22 and 16 hours after administration of 15 µg/kg of rGM-CSF by intravenous bolus and subcutaneous injection, respectively. The correlation between duration and severity of neutropenia and incidence of serious infection is well established. Administration of rGM-CSF to bone marrow transplant recipients is aimed at reducing morbidity in the early post-transplant period by shortening the duration of agranulocytosis. Intravenous administration of rGM-CSF up to 16 µg/kg/day (approximately 640 µg/m 2 /day) is well tolerated, and when begun within 24 hours of autologous marrow infusion produces the earlier appearance of > 0.5 × 10 9 /L neutrophils in the peripheral circulation as compared with historical controls. Early studies indicate that treated patients have a lower incidence of culture-proven bacteraemia, and recent reports, some preliminary, of placebo-controlled and randomised trials confirm that patients with nonHodgkin's lymphoma or acute lymphocytic leukaemia who receive rGM-CSF 250 µg/m 2 by daily 2-hour infusion for 21 days or more post transplantation, have significant reductions in duration of infectious episodes, antibiotic administration and hospitalisation. More limited data support a similar acceleration of neutrophil recovery in allogeneic bone marrow transplant recipients treated with rGM-CSF, with no apparent effect on the incidence or severity of graft-versus-host disease. rGM-CSF is less effective in patients in whom progenitor cell numbers are reduced by chemical purging of the marrow whether administered immediately after marrow infusion or when used as salvage therapy in patients with graft failure. A substantial proportion of patients with failure of autologous or allogeneic bone marrow grafts respond to prompt administration of rGM-CSF after diagnosis of graft failure, with an increase in absolute neutrophil count and bone marrow cellularity. In 1 study of 37 such patients, overall survival was significantly improved compared with historical controls. rGM-CSF increases the number of progenitor cells in peripheral circulation and, either alone or in combination with cyclophosphamide, facilitates the harvest of stem cells by apheresis for subsequent transplantation. Similar to the effect seen after myeloablative therapy and marrow transplantation, rGM-CSF accelerates neutrophil recovery following cytoreductive chemotherapy in patients with nonhaematological malignancies. Less frequent and less severe mucositis was also observed in rGM-CSF-treated versus control patients in several studies. Importantly, adjunctive use of rGM-CSF facilitated delivery of planned cycles of high or escalated doses of antineoplastic drugs although the value of such chemotherapy regimens remains to be proven. There has been no evidence to date that rGM-CSF increases the rate of relapse of patients with haematological malignancies when administered after myeloablative therapy and bone marrow transplantation or, in patients with acute myelogenous leukaemia, after induction therapy. Use of rGM-CSF to recruit quiescent leukaemic blast cells into S phase prior to chemotherapy is under investigation. rGM-CSF has been investigated in various disorders of haematopoiesis. A substantial number of adults and children with refractory aplastic anaemia respond to treatment with increases in bone marrow cellularity and peripheral blood granulocyte count; however, the response is generally not sustained after withdrawal of rGM-CSF. Elevation of neutrophil counts may not occur in patients with long-standing and severe aplasia; however, beneficial stimulation of macrophage function may still occur. Generally, rGM-CSF induces eosinophilia without correcting the neutropenia in patients with congenital neutropenic conditions. In myelodysplasia, rGM-CSF is capable of increasing the neutrophil count in a proportion of patients for the duration of administration. Caution is appropriate in administering this drug to patients with high (> 14% blasts) initial leukaemic burdens or with chronic myelomonocytic leukaemia in view of the potential for rGM-CSF to stimulate the leukaemic clone and precipitate acute leukaemia. Despite this concern, encouraging preliminary results from a trial with rGM-CSF (3 µg/kg/day by subcutaneous injection) and observation-only treatment groups suggest that, after > 6 months, the rate of transformation to acute leukaemia is similar in both groups but that rGM-CSF recipients have a sustained increase in neutrophil counts and an associated reduction in infection rate. rGM-CSF 1 to 5 µg/kg/day by subcutaneous injection ameliorates leucopenia associated with HIV infection and corrects zidovudine (azidothymidine)-induced neutropenia without affecting the disease course as determined by p24 antigen levels, CD4: CD8 ratios and recovery of HIV from mononuclear cells. Similar dosages ameliorate myelosuppression induced by ganciclovir in the treatment of AIDS-associated cytomegalovirus retinitis and by the combination of zidovudine and interferon-α in treating Kaposi's sarcoma. A trilineage response to rGM-CSF has been seen occasionally (e.g. some children with aplastic anaemia and some patients with myelodysplasia). Disease-or drug-induced anaemia or thrombocytopenia is generally not improved; however, both significant increases and decreases in platelet count have been reported, and the effect of rGM-CSF on megakaryocytosis and splenic phagocyte function require clarification. The combination of rGM-CSF with other recombinant colony-stimulating factors to expand the lineages stimulated is an exciting future possibility. At clinically useful dosages rGM-CSF is generally well tolerated. Limited comparison with placebo suggests that the type and incidence of adverse reactions reported are generally similar in both groups with the possible exception of slightly higher incidences of diarrhoea, asthenia, rash and malaise. However, reports from noncomparative and open-label trials indicate that mild to moderate flu-like symptoms (myalgias, bone pain, fatigue and headache) are common with rGM-CSF. Management of patients in whom this agent is indicated may be complicated by rGM-CSF-induced fever and, rarely, by a capillary leak syndrome causing fluid retention and potentially peripheral oedema, pericardial or pleural effusions which necessitate drug withdrawal. Also reported are rash (particularly at sites of subcutaneous injection), and occasional incidents of central venous catheter thrombosis. The occasional report of respiratory distress has led to the recommendation that respiratory symptoms be monitored and caution exercised in patients with preexisting lung disease. The approved (USA) dosage of yeast-derived rGM-CSF (sargramostim) for myeloid reconstitution after autologous bone marrow transplantation is 250 µg/m 2 by daily 2-hour intravenous infusions, beginning 2 to 4 hours after marrow infusion and continued for 21 days. For management of bone marrow transplantation failure or delayed engraftment, the approved (USA) dosage of yeast-derived rGM-CSF is 250 µg/m 2 /day by 2-hour intravenous infusion. Treatment should be continued for 14 days and, if clinically indicated, may be repeated after 7 days off therapy. A third 14-day course of rGM-CSF at the increased dosage of 500 µg/m 2 /day by 2-hour infusion may be administered after a further 7 days off therapy. Further dose escalation in non-responding patients is unlikely to be of benefit. rGM-CSF has also been successfully administered by continuous intravenous infusion and by subcutaneous injection, including self-administration of long term therapy by the subcutaneous route. The optimal route for administration, dose and duration of therapy for indications other than autologous bone marrow transplantation and failure or delay of engraftment have not been established.

Cerebrospinal fluid white cell count: discriminatory or otherwise for enteroviral meningitis in infants and young children?

PubMed

Tan, Natalie Woon Hui; Lee, Elis Yuexian; Khoo, Gloria Mei Chin; Tee, Nancy Wen Sim; Krishnamoorthy, Subramania; Choong, Chew Thye

2016-04-01

Non-polio enteroviruses (EV) are the most common viruses causing aseptic meningitis in children. We aim to evaluate the cerebrospinal fluid (CSF) characteristics of neonates and children with EV meningitis with a view to determine whether it could be discriminatory or otherwise in making a positive diagnosis. We performed a 3-year (July 2008-July 2011) retrospective study of children ≤16 years, treated at a tertiary children's hospital, with positive CSF EV polymerase chain reaction (PCR) and negative blood and CSF bacterial cultures. A total of 206 children were studied. The median CSF white cell count was 79 cells/mm(3) (range 0-4608 cells/mm(3)). CSF pleocytosis was observed in 99/150 (66%) aged ≤90 days, 3/4 (75%) aged 90 days-1 year, and 49/52 (94%) children ≥3 years. There was a huge variability in CSF pleocytosis in infants ≤90 days, where 34% of them had no pleocytosis, while in 66%, a wide range of pleocytosis that might even suggest bacterial meningitis was noted. CSF red cells were low, and protein or sugar values were not discriminatory. CSF pleocytosis in relation to increasing age was found to be statistically significant (p < 0.001). Early lumbar puncture within 48 h of symptoms and absence of CSF pleocytosis was also statistically significant (p = 0.039). CSF pleocytosis in EV meningitis is commoner in older children. As there was a huge variability in CSF pleocytosis in infants ≤90 days particularly, CSF analysis including EV PCR could avoid unnecessary antibiotic therapy.

Q fever as a cause of fever of unknown origin and thrombocytosis: first molecular evidence of Coxiella burnetii in Brazil.

PubMed

Lemos, Elba R S; Rozental, Tatiana; Mares-Guia, Maria Angélica M; Almeida, Daniele N P; Moreira, Namir; Silva, Raphael G; Barreira, Jairo D; Lamas, Cristiane C; Favacho, Alexsandra R; Damasco, Paulo V

2011-01-01

We report a case of Q fever in a man who presented with fever of 40 days duration associated with thrombocytosis. Serological and molecular analysis (polymerase chain reaction) confirmed infection with Coxiella burnetii. A field study was conducted by collecting blood samples from the patient's family and from the animals in the patient's house. The patient's wife and 2 of 13 dogs showed seroreactivity. Our data indicate that C. burnetii may be an underrecognized cause of fever in Brazil and emphasize the need for clinicians to consider Q fever in patients with a febrile illness, particularly those with a history of animal contact.

Mathematical Modelling of CSF Pulsatile Flow in Aqueduct Cerebri.

PubMed

Czosnyka, Zofia; Kim, Dong-Joo; Balédent, Olivier; Schmidt, Eric A; Smielewski, Peter; Czosnyka, Marek

2018-01-01

The phase-contrast MRI technique permits the non-invasive assessment of CSF movements in cerebrospinal fluid cavities of the central nervous system. Of particular interest is pulsatile cerebrospinal fluid (CSF) flow through the aqueduct cerebri. It is allegedly increased in hydrocephalus, having potential diagnostic value, although not all scientific reports contain unequivocally positive conclusions. For the mathematical simulation of CSF flow, we used a computational model of cerebrospinal blood/fluid circulation designed by a former student as his PhD project. With this model, cerebral blood flow and CSF may be simulated in various vessels using a system of non-linear differential equations as time-varying signals. The amplitude of CSF flow seems to be positively related to the amplitude of pulse waveforms of intracranial pressure (ICP) in situations where mean ICP increases, such as during simulated infusion tests and following step increases of resistance to CSF outflow. An additional positive association between the pulse amplitude of ICP and CSF flow can be seen during simulated increases in the amplitude of arterial pulses (without changes in mean arterial pressure, MAP). The opposite effect can be observed during step increases in the resistance of the aqueduct cerebri and with decreasing elasticity of the system, where the CSF flow amplitude and the ICP pulse amplitude are related inversely. Vasodilatation caused by both gradual decreases in MAP and by increases in PaCO2 provokes an elevation in the observed amplitude of pulsatile CSF flow. Preliminary results indicate that the pulsations of CSF flow may carry information about both CSF-circulatory and cerebral vasogenic components. In most cases, the pulsations of CSF flow are positively related to the pulse amplitudes of both arterial pressure and ICP and to a degree of cerebrovascular dilatation.

Fever in the Neutropenic Patient

PubMed Central

Atkinson, K.; Kay, H. E. M.; McElwain, T. J.

1974-01-01

A total of 100 consecutive episodes of fever of 101° F (38·3°C) or above in 56 neutropenic patients have been investigated. All the patients had either acute leukaemia or aplastic anaemia. A cause for the fever was found in 68 of these episodes, in 87% of which it was due to infection. The commonest single finding was septicaemia (30 episodes). Only two episodes of fever could be ascribed solely to the underlying malignant disease. Infection should be assumed to be present and the cause of fever in neutropenic patients until proved otherwise. PMID:4843653

Biggest Threats

MedlinePlus

... Resistant Salmonella Serotype Typhi Salmonella serotype Typhi causes typhoid fever, a potentially life-threatening disease. People with typhoid fever usually have a high fever, abdominal pain, and ...

An unusual cause of acute abdominal pain in dengue fever.

PubMed

Waseem, Tariq; Latif, Hina; Shabbir, Bilquis

2014-07-01

Dengue fever is an acute febrile viral disease caused by the bite of Aedes aegypti mosquito. It is a major health problem especially in tropical and subtropical areas including South East Asia and Pakistan. In the past few years, dengue fever has been endemic in Northern Punjab. Physicians managing dengue fever come across varied and uncommon complications of dengue fever. We report a case of dengue fever that developed severe right upper quadrant abdominal pain and induration after extreme retching and vomiting for 2 days. A rectus sheath hematoma was confirmed on noncontrast computed tomography (CT). Rectus sheath hematoma as a complication of dengue fever has rarely been reported before and never from this part of the world. Rectus sheath hematoma is an uncommon and often clinically misdiagnosed cause of abdominal pain. It is the result of bleeding into the rectus sheath from damage to the superior or inferior epigastric artery or their branches or from a direct tear of the rectus muscle. It can mimic almost any abdominal condition (See Fig.) (See Table).

[Fever in pediatric office practice].

PubMed

Murahovschi, Jayme

2003-05-01

To determine how to select a child who requires in depth laboratory investigation, defining the most appropriate laboratory screening tests, and to detect the individual who requires immediate therapy, when fever is the main symptom presented by the child seen in an outpatient clinic, or at the physician's office. Additionally, this review aims at providing suggestions on how to deal with fever, and with the anxiety it causes. Bibliographic review using Medline database and previously selected manuscripts. Fever may cause both negative and positive outcomes, none of major consequence. Age group, fever magnitude and duration, shivering, appetite decrease or behavioral changes (toxemia), and other localizing symptoms should be investigated through the patient's medical history. Laboratory screening tests should include complete blood count, erythrocyte sedimentation rate, C-reactive protein, urinalysis (white cells count and gram stain of the sediment), and in some cases, lumbar puncture and blood culture. The treatment should include antipyretic medications and, occasionally, physical methods (cool baths, sponging) in order to reduce discomfort caused by the fever. Children with fever request both scientific expertise, as well as empathy from the pediatrician, so that they can receive individualized therapy.

Herpes simplex virus 2 meningitis: a retrospective cohort study.

PubMed

Miller, Stephanie; Mateen, Farrah J; Aksamit, Allen J

2013-04-01

Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration of valacyclovir treatment following the first episode was 10 days (range 3 to 14 days, n = 13). The median duration of valacyclovir treatment following a subsequent meningitic episode was 9 days (range 7 days to indefinite period, n = 9). No patient was reported to have seizures, neurological disability, or death in extended follow-up (mean follow-up 3.4 years). Recurrence of meningitic symptoms was not universal.

Infectious causes of fever of unknown origin.

PubMed

McGregor, Alastair C; Moore, David A

2015-06-01

The causes of fever of unknown origin (FUO) are changing because advances in clinical practice and diagnostics have facilitated the identification of some infections. A variety of bacterial infections can cause FUO, and these can be divided into those that are easy to identify using culture and those that require serological or molecular tests for identification. A number of viral, parasitic and fungal infections can also cause prolonged fever. This article summarises the clinical features and diagnostic strategy of these infections. © Royal College of Physicians 2015. All rights reserved.

Malignant Mediterranean spotted fever

PubMed Central

Lunge, Snehal Balvant; Patil, Vaibhav; Ambar, Sameer; Naik, Vishwas

2015-01-01

Fever with rash is one of the most common causes of referral to a dermatologist. A plethora of conditions need to be considered in the differential diagnosis. They may be broadly classified into infectious causes, drug reactions, and autoimmune disorders. Here we present a rare case of rickettsial fever with cardiac involvement in an elderly male patient with no comorbidities. PMID:26904440

Typhoid fever: case report and literature review.

PubMed

Sanhueza Palma, Natalia Carolina; Farías Molina, Solange; Calzadilla Riveras, Jeannette; Hermoso, Amalia

2016-06-21

Typhoid fever remains a major health problem worldwide, in contrast to Chile, where this disease is an isolated finding. Clinical presentation is varied, mainly presenting with fever, malaise, abdominal discomfort, and nonspecific symptoms often confused with other causes of febrile syndrome. We report a six-year-old, male patient presenting with fever of two weeks associated with gastrointestinal symptoms, malaise, hepatomegaly and elevated liver enzymes. Differential diagnoses were considered and a Widal reaction and two blood cultures were requested; both came back positive, confirming the diagnosis of typhoid fever caused by Salmonella typhi. Prior to diagnosis confirmation, empirical treatment was initiated with ceftriaxone and metronidazole, with partial response; then drug therapy was adjusted according to ciprofloxacin susceptibility testing with a favorable clinical response. We discuss diagnostic methods and treatment of enteric fever with special emphasis on typhoid fever.

[Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice].

PubMed

Kabaya, K; Watanabe, M; Kusaka, M; Seki, M; Fushiki, M

1994-08-25

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 micrograms/body/day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also revealed an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation.

Donor-Derived West Nile Virus Infection in Solid Organ Transplant Recipients: Report of Four Additional Cases and Review of Clinical, Diagnostic, and Therapeutic Features

PubMed Central

Winston, Drew J.; Vikram, Holenarasipur R.; Rabe, Ingrid B.; Dhillon, Gundeep; Mulligan, David; Hong, Johnny C.; Busuttil, Ronald W.; Nowicki, Marek J.; Mone, Thomas; Civen, Rachel; Tecle, Selam A.; Trivedi, Kavita K.; Hocevar, Susan N.

2017-01-01

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived. Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5–37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity. PMID:24827763

Donor-derived West Nile virus infection in solid organ transplant recipients: report of four additional cases and review of clinical, diagnostic, and therapeutic features.

PubMed

Winston, Drew J; Vikram, Holenarasipur R; Rabe, Ingrid B; Dhillon, Gundeep; Mulligan, David; Hong, Johnny C; Busuttil, Ronald W; Nowicki, Marek J; Mone, Thomas; Civen, Rachel; Tecle, Selam A; Trivedi, Kavita K; Hocevar, Susan N

2014-05-15

We describe four solid-organ transplant recipients with donor-derived West Nile virus (WNV) infection (encephalitis 3, asymptomatic 1) from a common donor residing in a region of increased WNV activity. All four transplant recipients had molecular evidence of WNV infection in their serum and/or cerebrospinal fluid (CSF) by reverse transcription polymerase chain reaction (RT-PCR) testing. Serum from the organ donor was positive for WNV IgM but negative for WNV RNA, whereas his lymph node and spleen tissues tested positive for WNV by RT-PCR. Combination therapy included intravenous immunoglobulin (4 cases), interferon (3 cases), fresh frozen plasma with WNV IgG (2 cases), and ribavirin (1 case). Two of the four transplant recipients survived.Review of the 20 published cases of organ-derived WNV infection found that this infection is associated with a high incidence of neuroinvasive disease (70%) and severe morbidity and mortality (30%). Median time to onset of symptomatic WNV infection was 13 days after transplantation (range 5-37 days). Initial unexplained fever unresponsive to antibiotic therapy followed by rapid onset of neurologic deficits was the most common clinical presentation. Confirmation of infection was made by testing serum and CSF for both WNV RNA by RT-PCR and WNV IgM by serological assays. Treatment usually included supportive care, reduction of immunosuppression, and frequent intravenous immunoglobulin. The often negative results for WNV by current RT-PCR and serological assays and the absence of clinical signs of acute infection in donors contribute to the sporadic occurrence of donor-derived WNV infection. Potential organ donors should be assessed for unexplained fever and neurological symptoms, particularly if they reside in areas of increased WNV activity.

An approach to model monitoring and surveillance data of wildlife diseases-exemplified by Classical Swine Fever in wild boar.

PubMed

Stahnke, N; Liebscher, V; Staubach, C; Ziller, M

2013-11-01

The analysis of epidemiological field data from monitoring and surveillance systems (MOSSs) in wild animals is of great importance in order to evaluate the performance of such systems. By parameter estimation from MOSS data, conclusions about disease dynamics in the observed population can be drawn. To strengthen the analysis, the implementation of a maximum likelihood estimation is the main aim of our work. The new approach presented here is based on an underlying simple SIR (susceptible-infected-recovered) model for a disease scenario in a wildlife population. The three corresponding classes are assumed to govern the intensities (number of animals in the classes) of non-homogeneous Poisson processes. A sampling rate was defined which describes the process of data collection (for MOSSs). Further, the performance of the diagnostics was implemented in the model by a diagnostic matrix containing misclassification rates. Both descriptions of these MOSS parts were included in the Poisson process approach. For simulation studies, the combined model demonstrates its ability to validly estimate epidemiological parameters, such as the basic reproduction rate R0. These parameters will help the evaluation of existing disease control systems. They will also enable comparison with other simulation models. The model has been tested with data from a Classical Swine Fever (CSF) outbreak in wild boars (Sus scrofa scrofa L.) from a region of Germany (1999-2002). The results show that the hunting strategy as a sole control tool is insufficient to decrease the threshold for susceptible animals to eradicate the disease, since the estimated R0 confirms an ongoing epidemic of CSF. Copyright © 2013 Elsevier B.V. All rights reserved.

Molecular tracing of classical swine fever viruses isolated from wild boars and pigs in France from 2002 to 2011.

PubMed

Simon, Gaëlle; Le Dimna, Mireille; Le Potier, Marie-Frédérique; Pol, Françoise

2013-10-25

There were three outbreaks of classical swine fever (CSF) in north-eastern France between 2002 and 2011. The first two occurred in April 2002 in the Moselle department, in a wild boar and pig herd, respectively, while the third occurred in April 2003, in the Bas-Rhin department, in a wild boar. A survey was subsequently implemented in wild boar and domestic pig populations, during which 43 CSF viruses (CSFVs) were genetically characterized to provide information on virus sources, trace virus evolution and help in the monitoring of effective control measures. Phylogenetic analyses, based on fragments of the 5'NTR, E2 and NS5B genes, showed that all French CSFVs could be assigned to genotype 2, subgenotype 2.3. CSFVs isolated in Moselle were classified in the "Rostock" lineage, a strain first described in 2001 in wild boar populations in the Eifel region of north-western Rhineland-Palatinate in Germany, and in Luxemburg. In contrast, the CSFVs isolated in Bas-Rhin were homologous to strains from the "Uelzen" lineage, a strain previously isolated from wild boars in south-eastern Rhineland-Palatinate, Germany, as well as in Vosges du Nord, France, during a previous outbreak that had occurred in wild boars between 1992 and 2001. The outbreak in Moselle domestic pigs was quickly resolved as it concerned only one herd. The infection in wild boars from Moselle was extinguished after a few months whereas wild boars from Bas-Rhin remained infected until 2007. Molecular tracing showed that the Bas-Rhin index virus strain evolved slightly during the period but that no strain from a novel lineage was introduced until this outbreak ended after application of a vaccination scheme for six years. Copyright © 2013 Elsevier B.V. All rights reserved.

Classical swine fever vaccines-State-of-the-art.

PubMed

Blome, Sandra; Moß, Claudia; Reimann, Ilona; König, Patricia; Beer, Martin

2017-07-01

Due to its impact on animal health and pig industry, classical swine fever (CSF) is still one of the most important viral diseases of pigs. To control the disease, safe and highly efficacious live attenuated vaccines exist for decades. These vaccines have usually outstanding efficacy and safety but lack differentiability of infected from vaccinated animals (DIVA or marker strategy). In contrast, the first generation of E2 subunit marker vaccines shows constraints in efficacy, application, and production. To overcome these limitations, new generations of marker vaccines are developed. A wide range of approaches have been tried including recombinant vaccines, recombinant inactivated vaccines or subunit vaccines, vector vaccines, and DNA/RNA vaccines. During the last years, especially attenuated deletion vaccines or chimeric constructs have shown potential. At present, especially two new constructs have been intensively tested, the adenovirus-delivered, Semliki Forest virus replicon-vectored marker vaccine candidate "rAdV-SFV-E2" and the pestivirus chimera "CP7_E2alf". The later was recently licensed by the European Medicines Agency. Under field conditions, all marker vaccines have to be accompanied by a potent test system. Particularly this point shows still weaknesses and it is important to embed vaccination in a well-established vaccination strategy and a suitable diagnostic workflow. In summary, conventional vaccines are a standard in terms of efficacy. However, only vaccines with DIVA will allow improved eradication strategies e.g. also under emergency vaccination conditions in free regions. To answer this demand, new generations of marker vaccines have been developed and add now to the tool box of CSF control. Copyright © 2017 Elsevier B.V. All rights reserved.

CSF-1–dependant donor-derived macrophages mediate chronic graft-versus-host disease

PubMed Central

Alexander, Kylie A.; Flynn, Ryan; Lineburg, Katie E.; Kuns, Rachel D.; Teal, Bianca E.; Olver, Stuart D.; Lor, Mary; Raffelt, Neil C.; Koyama, Motoko; Leveque, Lucie; Le Texier, Laetitia; Melino, Michelle; Markey, Kate A.; Varelias, Antiopi; Engwerda, Christian; Serody, Jonathan S.; Janela, Baptiste; Ginhoux, Florent; Clouston, Andrew D.; Blazar, Bruce R.; Hill, Geoffrey R.; MacDonald, Kelli P.A.

2014-01-01

Chronic GVHD (cGVHD) is the major cause of late, nonrelapse death following stem cell transplantation and characteristically develops in organs such as skin and lung. Here, we used multiple murine models of cGVHD to investigate the contribution of macrophage populations in the development of cGVHD. Using an established IL-17–dependent sclerodermatous cGVHD model, we confirmed that macrophages infiltrating the skin are derived from donor bone marrow (F4/80+CSF-1R+CD206+iNOS–). Cutaneous cGVHD developed in a CSF-1/CSF-1R–dependent manner, as treatment of recipients after transplantation with CSF-1 exacerbated macrophage infiltration and cutaneous pathology. Additionally, recipients of grafts from Csf1r–/– mice had substantially less macrophage infiltration and cutaneous pathology as compared with those receiving wild-type grafts. Neither CCL2/CCR2 nor GM-CSF/GM-CSFR signaling pathways were required for macrophage infiltration or development of cGVHD. In a different cGVHD model, in which bronchiolitis obliterans is a prominent manifestation, F4/80+ macrophage infiltration was similarly noted in the lungs of recipients after transplantation, and lung cGVHD was also IL-17 and CSF-1/CSF-1R dependent. Importantly, depletion of macrophages using an anti–CSF-1R mAb markedly reduced cutaneous and pulmonary cGVHD. Taken together, these data indicate that donor macrophages mediate the development of cGVHD and suggest that targeting CSF-1 signaling after transplantation may prevent and treat cGVHD. PMID:25157821

False localizing sign of cervico-thoracic CSF leak in spontaneous intracranial hypotension.

PubMed

Schievink, Wouter I; Maya, M Marcel; Chu, Ray M; Moser, Franklin G

2015-06-16

Spontaneous spinal CSF leaks are an important cause of new-onset headaches. Such leaks are reported to be particularly common at the cervico-thoracic junction. The authors undertook a study to determine the significance of these cervico-thoracic CSF leaks. The patient population consisted of a consecutive group of 13 patients who underwent surgery for CSF leak repair based on CT myelography showing CSF extravasation at the cervico-thoracic junction but without any evidence of an underlying structural lesion. The mean age of the 9 women and 4 men was 41.2 years. Extensive extrathecal longitudinal CSF collections were demonstrated in 11 patients. At surgery, small leaking arachnoid cysts were found in 2 patients. In the remaining 11 patients, no clear source of CSF leakage could be identified at surgery. Resolution of symptoms was achieved in both patients with leaking arachnoid cysts, but in only 3 of the 11 patients with negative intraoperative findings. Postoperative spinal imaging was performed in 9 of the 11 patients with negative intraoperative findings and showed persistence of the longitudinal intraspinal extradural CSF. Further imaging revealed the site of the CSF leak to be ventral to the thoracic spinal cord. Five of these patients underwent microsurgical repair of the ventral CSF leak with resolution of symptoms in all 5 patients. Cervico-thoracic extravasation of dye on myelography does not necessarily indicate the site of the CSF leak. Treatment directed at this site should not be expected to have a high probability of sustained improvement of symptoms. © 2015 American Academy of Neurology.

IFNγ inhibits G-CSF induced neutrophil expansion and invasion of the CNS to prevent viral encephalitis.

PubMed

Ramakrishna, Chandran; Cantin, Edouard M

2018-01-01

Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17. This resulted in uncontrolled expansion and infiltration of apoptosis-resistant, degranulating neutrophils into the brainstem, causing fatal HSE in GKO but not WT mice. Excessive G-CSF in GKO mice also induced granulocyte derived suppressor cells, which inhibited T-cell proliferation and function, including production of the anti-inflammatory cytokine IL-10. Unexpectedly, we found that IFNγ suppressed G-CSF signaling by increasing SOCS3 expression in neutrophils, resulting in apoptosis. Depletion of G-CSF, but not GM-CSF, in GKO mice induced neutrophil apoptosis and reinstated IL-10 secretion by T cells, which restored their ability to limit innate inflammatory responses resulting in protection from HSE. Our studies reveals a novel, complex interplay among IFNγ, G-CSF and IL-10, which highlights the opposing roles of G-CSF and IFNγ in regulation of innate inflammatory responses in a murine viral encephalitis model and reveals G-CSF as a potential therapeutic target. Thus, the antagonistic G-CSF-IFNγ interactions emerge as a key regulatory node in control of CNS inflammatory responses to virus infection.

Csf2 null mutation alters placental gene expression and trophoblast glycogen cell and giant cell abundance in mice.

PubMed

Sferruzzi-Perri, Amanda N; Macpherson, Anne M; Roberts, Claire T; Robertson, Sarah A

2009-07-01

Genetic deficiency in granulocyte-macrophage colony-stimulating factor (CSF2, GM-CSF) results in altered placental structure in mice. To investigate the mechanism of action of CSF2 in placental morphogenesis, the placental gene expression and cell composition were examined in Csf2 null mutant and wild-type mice. Microarray and quantitative RT-PCR analyses on Embryonic Day (E) 13 placentae revealed that the Csf2 null mutation caused altered expression of 17 genes not previously known to be associated with placental development, including Mid1, Cd24a, Tnfrsf11b, and Wdfy1. Genes controlling trophoblast differentiation (Ascl2, Tcfeb, Itgav, and Socs3) were also differentially expressed. The CSF2 ligand and the CSF2 receptor alpha subunit were predominantly synthesized in the placental junctional zone. Altered placental structure in Csf2 null mice at E15 was characterized by an expanded junctional zone and by increased Cx31(+) glycogen cells and cyclin-dependent kinase inhibitor 1C (CDKN1C(+), P57(Kip2+)) giant cells, accompanied by elevated junctional zone transcription of genes controlling spongiotrophoblast and giant cell differentiation and secretory function (Ascl2, Hand1, Prl3d1, and Prl2c2). Granzyme genes implicated in tissue remodeling and potentially in trophoblast invasion (Gzmc, Gzme, and Gzmf) were downregulated in the junctional zone of Csf2 null mutant placentae. These data demonstrate aberrant placental gene expression in Csf2 null mutant mice that is associated with altered differentiation and/or functional maturation of junctional zone trophoblast lineages, glycogen cells, and giant cells. We conclude that CSF2 is a regulator of trophoblast differentiation and placental development, which potentially influences the functional capacity of the placenta to support optimal fetal growth in pregnancy.

CSF neurofilament concentration reflects disease severity in frontotemporal degeneration

PubMed Central

Scherling, Carole S.; Hall, Tracey; Berisha, Flora; Klepac, Kristen; Karydas, Anna; Coppola, Giovanni; Kramer, Joel H.; Rabinovici, Gil; Ahlijanian, Michael; Miller, Bruce L.; Seeley, William; Grinberg, Lea T.; Rosen, Howard; Meredith, Jere; Boxer, Adam L.

2014-01-01

Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid-β42 (Aβ42), tau and phosphorylated tau (ptau) concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer’s disease, 6 Parkinson’s disease and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural MR images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, and not in other diagnostic groups. Analyses in two independent FTD cohorts and a group of autopsy verified or biomarker enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. PMID:24242746

Adrenaline administration promotes the efficiency of granulocyte colony stimulating factor-mediated hematopoietic stem and progenitor cell mobilization in mice.

PubMed

Chen, Chong; Cao, Jiang; Song, Xuguang; Zeng, Lingyu; Li, Zhenyu; Li, Yong; Xu, Kailin

2013-01-01

A high dose of granulocyte colony stimulating factor (G-CSF) is widely used to mobilize hematopoietic stem and progenitor cells (HSPC), but G-CSF is relatively inefficient and may cause adverse effects. Recently, adrenaline has been found to play important roles in HSPC mobilization. In this study, we explored whether adrenaline combined with G-CSF could induce HSPC mobilization in a mouse model. Mice were treated with adrenaline and either a high or low dose of G-CSF alone or in combination. Peripheral blood HSPC counts were evaluated by flow cytometry. Levels of bone marrow SDF-1 were measured by ELISA, the transcription of CXCR4 and SDF-1 was measured by real-time RT-PCR, and CXCR4 protein was detected by Western blot. Our results showed that adrenaline alone fails to mobilize HSPCs into the peripheral blood; however, when G-CSF and adrenaline are combined, the WBC counts and percentages of HSPCs are significantly higher compared to those in mice that received G-CSF alone. The combined use of adrenaline and G-CSF not only accelerated HSPC mobilization, but also enabled the efficient mobilization of HSPCs into the peripheral blood at lower doses of G-CSF. Adrenaline/G-CSF treatment also extensively downregulated levels of SDF-1 and CXCR4 in mouse bone marrow. These results demonstrated that adrenaline combined with G-CSF can induce HSPC mobilization by down-regulating the CXCR4/SDF-1 axis, indicating that the use of adrenaline may enable the use of reduced dosages or durations of G-CSF treatment, minimizing G-CSF-associated complications.

Case Series of Naegleria fowleri Primary Ameobic Meningoencephalitis from Karachi, Pakistan.

PubMed

Ghanchi, Najia K; Jamil, Bushra; Khan, Erum; Ansar, Zeeshan; Samreen, Azra; Zafar, Afia; Hasan, Zahra

2017-11-01

Naegleria fowleri causes primary amoebic meningoencephalitis (PAM) which is almost always fatal. Naegleria fowleri is waterborne, and its infections are usually associated with aquatic activities but it can also be transmitted via the domestic water supply. An increasing number of N. fowleri cases have been reported from Pakistan. Improved methods for diagnosis are required. We report the utility of polymerase chain reaction (PCR) for the diagnosis of N. fowleri in patients suspected of PAM. One hundred and sixteen cases suspected of having PAM were examined. Cerebrospinal fluid (CSF) specimens were tested at the Aga Khan University Hospital, Karachi. Nineteen CSF specimens were positive for N. fowleri using PCR. Naegleria fowleri positive patients had a median age of 28 years and were 84% male and 16% female. Overall, CSF wet preparation microscopy was performed in 85 (73%) cases and identified that seven specimens were positive for motile trophozoites. The CSF wet preparation results were available for 15 of the 19 N. fowleri PCR positive CSF samples; seven (40%) wet preparations were positive. Our data highlight the threat of N. fowleri infection as a cause of PAM. It also emphasizes the utility of the PCR-based diagnosis of the amoeba for early diagnosis and management of the disease.

Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects

PubMed Central

Mathur, Deepali; María-Lafuente, Eva; Ureña-Peralta, Juan R.; Sorribes, Lucas; Hernández, Alberto; Casanova, Bonaventura; López-Rodas, Gerardo; Coret-Ferrer, Francisco; Burgal-Marti, Maria

2017-01-01

Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity. PMID:29267205

Tick-borne infectious diseases in Australia.

PubMed

Graves, Stephen R; Stenos, John

2017-04-17

Tick bites in Australia can lead to a variety of illnesses in patients. These include infection, allergies, paralysis, autoimmune disease, post-infection fatigue and Australian multisystem disorder. Rickettsial (Rickettsia spp.) infections (Queensland tick typhus, Flinders Island spotted fever and Australian spotted fever) and Q fever (Coxiella burnetii) are the only systemic bacterial infections that are known to be transmitted by tick bites in Australia. Three species of local ticks transmit bacterial infection following a tick bite: the paralysis tick (Ixodes holocyclus) is endemic on the east coast of Australia and causes Queensland tick typhus due to R. australis and Q fever due to C. burnetii; the ornate kangaroo tick (Amblyomma triguttatum) occurs throughout much of northern, central and western Australia and causes Q fever; and the southern reptile tick (Bothriocroton hydrosauri) is found mainly in south-eastern Australia and causes Flinders Island spotted fever due to R. honei. Much about Australian ticks and the medical outcomes following tick bites remains unknown. Further research is required to increase understanding of these areas.

Typhoid fever & vaccine development: a partially answered question.

PubMed

Marathe, Sandhya A; Lahiri, Amit; Negi, Vidya Devi; Chakravortty, Dipshikha

2012-01-01

Typhoid fever is a systemic disease caused by the human specific Gram-negative pathogen Salmonella enterica serovar Typhi (S. Typhi). The extra-intestinal infections caused by Salmonella are very fatal. The incidence of typhoid fever remains very high in impoverished areas and the emergence of multidrug resistance has made the situation worse. To combat and to reduce the morbidity and mortality caused by typhoid fever, many preventive measures and strategies have been employed, the most important being vaccination. In recent years, many Salmonella vaccines have been developed including live attenuated as well as DNA vaccines and their clinical trials have shown encouraging results. But with the increasing antibiotic resistance, the development of potent vaccine candidate for typhoid fever is a need of the hour. This review discusses the latest trends in the typhoid vaccine development and the clinical trials which are underway.

Fever in immunocompromised hosts.

PubMed

Patel, Devang M; Riedel, David J

2013-11-01

Fever is one of the most common reasons for the emergency department presentation of immunocompromised patients. Their differential diagnosis can be broad and includes rare or unexpected pathogens. Certain infectious causes of fever portend true emergencies; if they are not managed appropriately, rapid progression and death may ensue. This article reviews the diagnosis and management of fevers in patients immunocompromised by human immunodeficiency virus/AIDS, solid-organ and hematopoietic transplants, chemotherapy-induced neutropenia, and tumor necrosis factor-α inhibitors. Prompt recognition of the type of immunosuppression and delineation of possible causes of fever are critical for management of these complex patients. Copyright © 2013 Elsevier Inc. All rights reserved.

[Complications and cause of death in mexican children with rocky mountain spotted fever].

PubMed

Martínez-Medina, Miguel Ángel; Rascón-Alcantar, Adela

Rocky Mountain spotted fever is a life threatening disease caused by Rickettsia rickettsia, characterized by multisystem involvement. We studied 19 dead children with Rocky Mountain spotted fever. All children who were suspected of having rickettsial infections were defined as having Rocky Mountain spotted fever by serology test and clinical features. Through the analysis of each case, we identified the clinical profile and complications associated to the death of a patient. In nine (69.2%) of 13 cases that died in the first three days of admission, the associated condition was septic shock. Others complications included respiratory distress causes by non-cardiogenic pulmonary edema, renal impairment, and multiple organ damage. The main cause of death in this study was septic shock. The fatality rate from Rocky Mountain spotted fever can be related to the severity of the infection, delay in diagnosis, and delay in initiation of antibiotic therapy. Pulmonary edema and cerebral edema can be usually precipitated by administration of excess intravenous fluids.

The latex agglutination test versus counterimmunoelectrophoresis for rapid diagnosis of bacterial meningitis

PubMed Central

Bortolussi, Robert; Wort, Arthur J.; Casey, Stephanie

1982-01-01

A modified latex agglutination (LA) test was compared with Gram-staining and counterimmunoelectrophoresis (CIE) for the rapid detection in the cerebrospinal fluid (CSF) of antigen to Haemophilus influenzae type b, Neisseria meningitidis groups A, B and C, Escherichia coli K1, Streptococcus pneumoniae and group B streptococci, seven frequent causes of bacterial meningitis in children. Of 50 CSF samples from patients with culture-proven bacterial meningitis 90% were correctly shown by the LA test to contain antigen of the responsible organism. Gram-staining revealed organisms in 80% of 45 of these samples. In 75% of the 40 samples that were of sufficient volume for CIE, positive results for the appropriate antigen were obtained. The concentration of antigen detected in the CSF by the LA test varied from undetectable to 800 000 ng/ml. Patients with a high concentration (more than 2000 ng/ml or a positive result at dilutions of CSF over 1/8) were significantly more likely to have a poor response to therapy (two died and two had persistent pleocytosis or bacteria in the CSF) than patients with a lower concentration (4/16 v. 0/18, P < 0.05). After appropriate therapy was begun the concentration of antigen fell dramatically, but measurable amounts of antigen persisted in the CSF for up to 6 days. The LA test detected bacterial antigen at concentrations 2 to 70 times below the lower limit detected by CIE. In seven additional patients who had received antibiotics before lumbar puncture was performed the LA test detected antigen from meningitis-causing bacteria even though cultures of the CSF were sterile. In another 145 patients who did not have meningitis the results of the LA test were negative. The LA test, done as described in this article, is easier to perform than CIE and should be a useful addition to the diagnostic tests carried out on the CSF of any patient suspected of having meningitis. PMID:6749272

Fever and Taking Your Child's Temperature

MedlinePlus

... after the fever comes down. How Can I Help My Child Feel Better? Again, not all fevers need to ... cause the temperature to rise. Make sure your child's bedroom is a ... fever, this method only helps temporarily, if at all. In fact, sponge baths ...

Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.

PubMed

Roos, Per M; Vesterberg, Olof; Syversen, Tore; Flaten, Trond Peder; Nordberg, Monica

2013-02-01

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS.

Direct observation of cerebrospinal fluid bulk flow in the brain

NASA Astrophysics Data System (ADS)

Mestre, Humberto; Tithof, Jeffrey; Thomas, John; Kelley, Douglas; Nedergaard, Maiken

2017-11-01

Cerebrospinal fluid (CSF) serves a vital role in normal brain function. Its adequate flow and exchange with interstitial fluid through perivascular spaces (PVS) has been shown to be important in the clearance of toxic metabolites like amyloid- β, and its disturbance can cause severe neurological diseases. It has long been suspected that bulk flow may transport CSF, but limitations in imaging techniques have prevented direct observation of such flows in the PVS. In this talk, we describe a novel approach using high speed two photon laser scanning microscopy which has allowed for the first ever direct observation of CSF flow in the PVS of a mouse brain. By performing particle tracking velocimetry, we quantify the CSF bulk flow speeds and PVS geometry. This technique enables future studies of CSF flow disturbances on a new scale and will pave the way for evaluating the role of these fluxes in neurodegenerative disease. R01NS100366 (to M.N.).

False-positive cerebrospinal fluid cryptococcus antigen in Libman-Sacks endocarditis.

PubMed

Isseh, Iyad N; Bourgi, Kassem; Nakhle, Asaad; Ali, Mahmoud; Zervos, Marcus J

2016-12-01

Cryptococcus meningoencephalitis is a serious opportunistic infection associated with high morbidity and mortality in immunocompromised hosts, particularly patients with advanced AIDS disease. The diagnosis is established through cerebrospinal fluid (CSF) cryptococcus antigen detection and cultures. Cryptococcus antigen testing is usually the initial test of choice due its high sensitivity and specificity along with the quick availability of the results. We hereby report a case of a false-positive CSF cryptococcus antigen assay in a patient with systemic lupus erythematosus presenting with acute confusion. While initial CSF evaluation revealed a positive cryptococcus antigen assay, the patient's symptoms were inconsistent with cryptococcus meningoencephalitis. A repeat CSF evaluation, done 3 days later, revealed a negative CSF cryptococcus antigen assay. Given the patient's active lupus disease and the elevated antinuclear antibody titers, we believe that the initial positive result was a false positive caused by interference from autoantibodies.

Confirmed viral meningitis with normal CSF findings.

PubMed

Dawood, Naghum; Desjobert, Edouard; Lumley, Janine; Webster, Daniel; Jacobs, Michael

2014-07-17

An 18-year-old woman presented with a progressively worsening headache, photophobia feverishness and vomiting. Three weeks previously she had returned to the UK from a trip to Peru. At presentation, she had clinical signs of meningism. On admission, blood tests showed a mild lymphopenia, with a normal C reactive protein and white cell count. Chest X-ray and CT of the head were normal. Cerebrospinal fluid (CSF) microscopy was normal. CSF protein and glucose were in the normal range. MRI of the head and cerebral angiography were also normal. Subsequent molecular testing of CSF detected enterovirus RNA by reverse transcriptase PCR. The patient's clinical syndrome correlated with her virological diagnosis and no other cause of her symptoms was found. Her symptoms were self-limiting and improved with supportive management. This case illustrates an important example of viral central nervous system infection presenting clinically as meningitis but with normal CSF microscopy. 2014 BMJ Publishing Group Ltd.

Hyperthermia and Pregnancy

MedlinePlus

... illness causing your fever needs to be treated. Acetaminophen is usually recommended to reduce fever during pregnancy. Tylenol® is one brand of acetaminophen. I had a fever in the second trimester. ...

Studies on Typhus and Spotted Fever.

DTIC Science & Technology

1981-02-01

Rocky Mountain spotted fever , DNA, homology, genome, lymphocytes, immunity...spotted fever group. Certain studies have suggested that R. canada may be able to cause a severe illness in man clinically similar to Rocky Mountain spotted fever (Z...the Conference and are also in press. 10. Paul Fiset, Charles L. Wisseman, Jr., A. Farhang-Azad, Harvey Fischman. Rocky Mountain Spotted Fever

Lesson of the month 1: Subacute thyroiditis: a rare cause of fever of unknown origin.

PubMed

Bahowairath, Fatima Amar; Woodhouse, Nicholas; Hussain, Samir; Busaidi, Mujahid Al

2017-02-01

Fever of unknown origin (FUO) is sometimes a diagnostic dilemma for clinicians. Endocrine causes reported in the literature include subacute thyroiditis, thyrotoxicosis, adrenal insufficiency and pheochromocytoma. Among these, subacute thyroiditis is often overlooked as it can occasionally lack typical symptoms. This case illustrates the fact that subacute thyroiditis should be considered as a possible cause of fever even if signs and symptoms of hyperthyroidism and thyroid tenderness are absent. © Royal College of Physicians 2017. All rights reserved.

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

PubMed

Hammadur Rahaman, S K; Khandelwal, Deepak; Khadgawat, Rajesh; Kandasamy, Devasenathipathy; Bakhshi, Sameer

2018-03-15

Pineal gland lesions usually present with central precocious puberty. A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. He received chemotherapy followed by radiotherapy and responded well. CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

PubMed

Morita, Y; Osaki, Y; Doi, Y; Forghani, B; Gilden, D H

2003-08-15

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

[A Case of Clinically Mild Encephalitis/encephalopathy with a Reversible Splenial Lesion due to Dengue Fever].

PubMed

Saito, Nobuo; Kitashouji, Emi; Kojiro, Maiko; Furumoto, Akitugu; Morimoto, Konosuke; Morita, Kouichi; Ariyoshi, Koya

2015-07-01

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has been recently proposed as a clinical-radiological syndrome. Several causes of MERS have been reported including infectious diseases. We present herein on a case of MERS induced by dengue fever in a Japanese traveler. A 48-year-old male returning from Thailand and Cambodia was admitted for an unknown fever. Following admission, the dengue virus was diagnosed with a positive RT-PCR result. On day 5 of the illness, regardless of reduced fever, weakness suddenly developed in both upper limbs. A cerebral MRI showed hyperintensities in the splenium of the corpus callosum on T2-weighted and diffusion-weighted images. The symptoms resolved completely within two days of onset. The patient was diagnosed as having MERS due to the MRI features and the mild clinical course. Although only a few cases of MERS caused by dengue fever have been reported, the condition is possibly underdiagnosed. It is hypothesized that dengue fever can induce MERS as dengue fever can cause increased endothelium permeability and hypo-sodium which have been proposed in the pathogenesis of MERS. However, there is currently limited evidence for this. Further research is recommended to demonstrate a causal association between dengue fever and MERS.

Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

PubMed

Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

2017-06-01

Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

Chronic Q Fever Diagnosis—Consensus Guideline versus Expert Opinion

PubMed Central

Wegdam-Blans, Marjolijn C.A.; Wever, Peter C.; Renders, Nicole H.M.; Delsing, Corine E.; Sprong, Tom; van Kasteren, Marjo E.E.; Bijlmer, Henk; Notermans, Daan; Oosterheert, Jan Jelrik; Stals, Frans S.; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

2015-01-01

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%) would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice. PMID:26277798

Ebola Virus Disease

MedlinePlus

... EVD from other infectious diseases such as malaria, typhoid fever and meningitis. Confirmation that symptoms are caused by ... EVD from other infectious diseases such as malaria, typhoid fever and meningitis. Confirmation that symptoms are caused by ...

Fever of unknown origin as the first manifestation of colonic pathology.

PubMed

Belhassen-García, Moncef; Velasco-Tirado, Virginia; López-Bernus, Amparo; Alonso-Sardón, Montserrat; Carpio-Pérez, Adela; Fuentes-Pardo, Lucía; Pardo-Lledías, Javier; Alvela-Suárez, Lucia; Romero-Alegría, Angela; Iglesias-Gomez, Alicia; Sánchez, Miguel Cordero

2013-04-01

Fever of unknown origin (FUO) is an entity caused by more than 200 diseases. Haematologic neoplasms are the most common malignant cause of FUO. Fever as a first symptom of colonic tumour pathology, both benign and malignant, is a rare form of presentation. Our work is a descriptive study of a series of 23 patients with colonic tumoral pathology who presented with fever of unknown origin. The mean age was 67.6 years; 56.5% of patients were men and 43.5% were women. Primary malignant neoplasia was the most common diagnosis. Blood cultures were positive in 45% of the samples. Coagulase-negative staphylococci were the most common cause of bacteraemia. Nine of 10 faecal occult blood tests performed were positive. Fever secondary to colon neoplasms, both benign and malignant, usually presents with a bacteraemic pattern, with positive results for blood-culture tests in a high percentage of cases.

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

PubMed Central

Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

2008-01-01

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion PMID:18479516

Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: Parasite load, viability, co-infections and histological alterations.

PubMed

Oliveira, Valéria da Costa; Boechat, Viviane Cardoso; Mendes Junior, Artur Augusto Velho; Madeira, Maria de Fátima; Ferreira, Luiz Claudio; Figueiredo, Fabiano Borges; Campos, Monique Paiva; de Carvalho Rodrigues, Francisco das Chagas; Carvalhaes de Oliveira, Raquel de Vasconcellos; Amendoeira, Maria Regina Reis; Menezes, Rodrigo Caldas

2017-01-01

Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined. Cerebrospinal fluid (CSF) samples were analyzed by parasitological culture, quantitative real-time PCR (qPCR) and the rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and spleen samples were submitted to parasitological culture, qPCR, and histological techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis antibodies in serum and distemper virus antigens in CSF were investigated. None of the dogs showed neurological signs. All dogs tested positive for L. infantum in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61% of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31% of the animals; of these, 66% were seropositive for E. canis and/or T. gondii. Amastigote forms were associated with granulomatous non-suppurative encephalomyelitis in a dog without evidence of co-infections. The highest frequency of L. infantum DNA was observed in the brain (98%), followed by the spinal cord (96%), spleen (95%), and CSF (50%). The highest L. infantum load in CNS was found in the spinal cord. These results demonstrate that L. infantum can cross the blood-brain barrier, spread through CSF, and cause active infection in the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the CNS that can lead to neurological signs with progression of the disease.

Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: Parasite load, viability, co-infections and histological alterations

PubMed Central

Oliveira, Valéria da Costa; Boechat, Viviane Cardoso; Mendes Junior, Artur Augusto Velho; Madeira, Maria de Fátima; Ferreira, Luiz Claudio; Figueiredo, Fabiano Borges; Campos, Monique Paiva; de Carvalho Rodrigues, Francisco das Chagas; Carvalhaes de Oliveira, Raquel de Vasconcellos; Amendoeira, Maria Regina Reis

2017-01-01

Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined. Cerebrospinal fluid (CSF) samples were analyzed by parasitological culture, quantitative real-time PCR (qPCR) and the rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and spleen samples were submitted to parasitological culture, qPCR, and histological techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis antibodies in serum and distemper virus antigens in CSF were investigated. None of the dogs showed neurological signs. All dogs tested positive for L. infantum in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61% of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31% of the animals; of these, 66% were seropositive for E. canis and/or T. gondii. Amastigote forms were associated with granulomatous non-suppurative encephalomyelitis in a dog without evidence of co-infections. The highest frequency of L. infantum DNA was observed in the brain (98%), followed by the spinal cord (96%), spleen (95%), and CSF (50%). The highest L. infantum load in CNS was found in the spinal cord. These results demonstrate that L. infantum can cross the blood-brain barrier, spread through CSF, and cause active infection in the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the CNS that can lead to neurological signs with progression of the disease. PMID:28419136

Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation

PubMed Central

Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W.

2015-01-01

Objective and design Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. Methods CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. Results CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P <0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P =0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4+ cell count or CNS penetration-efficacy score. Conclusion Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury. PMID:25022595

Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation.

PubMed

Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W

2014-09-24

Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score. Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.

What is the role of biosimilar G-CSF agents in hematopoietic stem cell mobilization at present?

PubMed

Korkmaz, Serdal; Altuntas, Fevzi

2017-12-01

Mobilization of hematopoietic stem cells, which has largely replaced bone marrow harvesting as a source of hematopoietic stem cells, using recombinant agents such as filgrastim or lenograstim has become a standard procedure in both patients and healthy donors prior to peripheral blood stem cell collection for autologous and allogeneic stem cell transplantation. Published literature data suggest that mobilization with recombinant granulocyte-colony stimulating factor (G-CSF) is safe and mobilization outcomes are satisfactory. In recent years, besides G-CSF originators, biosimilar G-CSF agents have been approved by the regulatory agencies for the same indications. Current data showed that by using the biosimilar G-CSF, similar results regarding safety and efficacy of hematopoietic stem cell mobilization may be achieved compared to the originator G-CSF. Although the issues such as the similarity to a licenced biological medicine, differences in manufacturing processes, the potential to cause immunogenicity, extrapolation and interchangeability of these biosimilar products are still being discussed by the scientific area, however, more experience with these agents now exists in approved endications and there seems to be no reason to expect significant differences between biosimilar G-CSF and originator G-CSF regarding their efficacy and safety in both patients and healthy donors. Also, the significant cost savings of biosimilars in real life setting may enhance the use of these agents in the future. Nonetheless, the collection of long-term follow-up data is mandatory for both patients and healthy donors, and multicentre randomized clinical trials that directly compare biosimilar G-CSF with the originator G-CSF are needed in order to allow the transplant community to make informed decisions regarding the choice of G-CSF. Copyright © 2017 Elsevier Ltd. All rights reserved.

CSF-1R as an inhibitor of apoptosis and promoter of proliferation, migration and invasion of canine mammary cancer cells

PubMed Central

2013-01-01

Background Tumor-associated macrophages (TAMs) have high impact on the cancer development because they can facilitate matrix invasion, angiogenesis, and tumor cell motility. It gives cancer cells the capacity to invade normal tissues and metastasize. The signaling of colony-stimulating factor-1 receptor (CSF-1R) which is an important regulator of proliferation and differentiation of monocytes and macrophages regulates most of the tissue macrophages. However, CSF-1R is expressed also in breast epithelial tissue during some physiological stages i.g.: pregnancy and lactation. Its expression has been also detected in various cancers. Our previous study has showed the expression of CSF-1R in all examined canine mammary tumors. Moreover, it strongly correlated with grade of malignancy and ability to metastasis. This study was therefore designed to characterize the role of CSF-1R in canine mammary cancer cells proliferation, apoptosis, migration, and invasion. As far as we know, the study presented hereby is a pioneering experiment in this field of veterinary medicine. Results We showed that csf-1r silencing significantly increased apoptosis (Annexin V test), decreased proliferation (measured as Ki67 expression) and decreased migration (“wound healing” assay) of canine mammary cancer cells. Treatment of these cells with CSF-1 caused opposite effect. Moreover, csf-1r knock-down changed growth characteristics of highly invasive cell lines on Matrigel matrix, and significantly decreased the ability of these cells to invade matrix. CSF-1 treatment increased invasion of cancer cells. Conclusion The evidence of the expression and functional role of the CSF-1R in canine mammary cancer cells indicate that CSF-1R targeting may be a good therapeutic approach. PMID:23561040

IFNγ inhibits G-CSF induced neutrophil expansion and invasion of the CNS to prevent viral encephalitis

PubMed Central

Ramakrishna, Chandran

2018-01-01

Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune cells in response to infections by pathogens, a process that must be carefully regulated to prevent potentially life threatening inflammatory responses. Here, we describe a novel regulatory role for the cytokine IFNγ that is critical for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE) is triggered by the invasion of the brainstem by inflammatory monocytes and neutrophils. In mice lacking IFNγ (GKO), we observed unrestrained increases in G-CSF levels but not in GM-CSF or IL-17. This resulted in uncontrolled expansion and infiltration of apoptosis-resistant, degranulating neutrophils into the brainstem, causing fatal HSE in GKO but not WT mice. Excessive G-CSF in GKO mice also induced granulocyte derived suppressor cells, which inhibited T-cell proliferation and function, including production of the anti-inflammatory cytokine IL-10. Unexpectedly, we found that IFNγ suppressed G-CSF signaling by increasing SOCS3 expression in neutrophils, resulting in apoptosis. Depletion of G-CSF, but not GM-CSF, in GKO mice induced neutrophil apoptosis and reinstated IL-10 secretion by T cells, which restored their ability to limit innate inflammatory responses resulting in protection from HSE. Our studies reveals a novel, complex interplay among IFNγ, G-CSF and IL-10, which highlights the opposing roles of G-CSF and IFNγ in regulation of innate inflammatory responses in a murine viral encephalitis model and reveals G-CSF as a potential therapeutic target. Thus, the antagonistic G-CSF-IFNγ interactions emerge as a key regulatory node in control of CNS inflammatory responses to virus infection. PMID:29352287

Measurement of peak CSF flow velocity at cerebral aqueduct, before and after lumbar CSF drainage, by use of phase-contrast MRI: utility in the management of idiopathic normal pressure hydrocephalus.

PubMed

Sharma, Ashwani Kumar; Gaikwad, Shailesh; Gupta, Vipul; Garg, Ajay; Mishra, Nalini K

2008-04-01

Since it was first described, normal pressure hydrocephalus (NPH) and its treatment by means of cerebrospinal fluid (CSF) shunting have been the focus of much investigation. Whatever be the cause of NPH, it has been hypothesized that in this disease there occurs decreased arterial expansion and an increased brain expansion leading to increased transmantle pressure. We cannot measure the latter, but fortunately the effect of these changes (increased peak flow velocity through the aqueduct) can be quantified with cine phase-contrast magnetic resonance imaging (MRI). This investigation was thus undertaken to characterize and measure CSF peak flow velocity at the level of the aqueduct, before and after lumbar CSF drainage, by means of a phase-contrast cine MRI and determine its role in selecting cases for shunt surgery. 37 patients with clinically suspected NPH were included in the study. Changes in the hyperdynamic peak CSF flow velocity with 50 ml lumbar CSF drainage (mimicking shunt) were evaluated in them for considering shunt surgery. 14 out of 15 patients who were recommended for shunt surgery, based on changes peak flow velocity after lumbar CSF drainage, improved after shunt surgery. None of the cases which were not recommended for shunt surgery, based on changes in CSF peak flow velocity after lumbar CSF drainage, improved after shunt surgery (2 out of 22 cases). The study concluded that the phase-contrast MR imaging, done before and after CSF drainage, is a sensitive method to support the clinical diagnosis of normal pressure hydrocephalus, selecting patients of NPH who are likely to benefit from shunt surgery, and to select patients of NPH who are not likely to benefit from shunt surgery.

Comparison of epidemiology and clinical characteristics of infections by human parechovirus vs. those by enterovirus during the first month of life.

PubMed

Cabrerizo, María; Trallero, Gloria; Pena, María José; Cilla, Amaia; Megias, Gregoria; Muñoz-Almagro, Carmen; Del Amo, Eva; Roda, Diana; Mensalvas, Ana Isabel; Moreno-Docón, Antonio; García-Costa, Juan; Rabella, Nuria; Omeñaca, Manuel; Romero, María Pilar; Sanbonmatsu-Gámez, Sara; Pérez-Ruiz, Mercedes; Santos-Muñoz, María José; Calvo, Cristina

2015-11-01

Human parechoviruses (HPeV) have been recently recognized as important viral agents in paediatric infections. The aims of this study were to investigate the HPeV infection prevalence in infants <1 month in Spain and, secondly, to analyse the clinical and epidemiological characteristics of the infected patients compared with those infected by enterovirus (EV). Infants <1 month with neurological or systemic symptoms were included in a multicentre prospective study. EV and HPeV detection by RT-PCR and genotyping were performed in cerebrospinal fluids (CSF), sera or throat swabs. Out of the total of 84 infants studied during 2013, 32 were EV positive (38 %) and 9 HPeV positive (11 %). HPeV-3 was identified in eight cases and HPeV-5 in one. Mean age of HPeV-positive patients was 18 days. Diagnoses were fever without source (FWS) (67 %), clinical sepsis (22 %) and encephalitis (11 %). Leukocytes in blood and CSF were normal. Pleocytosis (p = 0.03) and meningitis (p = 0.001) were significantly more frequent in patients with EV infections than with HPeV. Although HPeV-3 infections were detected less frequently than EV, they still account for approximately 10 % of the cases analysed in infants younger than 1 month. HPeV-3 was mainly associated with FWS and without leukocytosis and pleocytosis in CSF. In these cases, HPeV screening is desirable to identify the aetiologic agent and prevent unnecessary treatment and prolonged hospitalization.

Encephalitis

MedlinePlus

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A sensitive WST-8-based bioassay for PEGylated granulocyte colony stimulating factor using the NFS-60 cell line.

PubMed

Tiwari, Krishna; Wavdhane, Madan; Haque, Shafiul; Govender, Thavendran; Kruger, Hendrik G; Mishra, Maheshwari K; Chandra, Ramesh; Tiwari, Dileep

2015-06-01

Granulocyte colony stimulating factor (G-CSF) has been commonly used to treat neutropenia caused by chemotherapy, radiotherapy, and organ transplants. Improved in vitro efficacy of G-CSF has already been observed by conjugating it to polyethylene glycol (PEG). The in vivo bioassay using tetrazolium dye with the NFS-60 cell line has been recommended for G-CSF but no such monographs are available for PEGylated G-CSF in pharmacopeias. In the present study, the assay recommended for G-CSF was evaluated for its suitability to PEGylated G-CSF. The generally used MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]-based assay was compared with a bioassay employing a water-soluble tetrazolium dye, WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium], using NFS-60 cells at a concentration of 7 × 10(5) cells/ml against 800 IU/ml of PEGylated G-CSF at 24, 48, 72, and 72 h time points to determine the efficacy of PEGylated G-CSF. Further, the optimized WST-8 dye-based assay was used to test the potency of various commercially available PEGylated G-CSF preparations. The results demonstrated enhanced sensitivity of the WST-8-based assay over the conventional MTS-based assay for determining the potency of PEGylated G-CSF using the NFS-60 cell line. Our study demonstrates the potential application of WST-8-based bioassays for other biotherapeutic proteins of human and veterinary interest.

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

PubMed

Germovsek, Eva; Lutsar, Irja; Kipper, Karin; Karlsson, Mats O; Planche, Tim; Chazallon, Corine; Meyer, Laurence; Trafojer, Ursula M T; Metsvaht, Tuuli; Fournier, Isabelle; Sharland, Mike; Heath, Paul; Standing, Joseph F

2018-04-19

Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed. A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered.

CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

PubMed

Bradley, W G

2015-05-01

CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood. © 2015 by American Journal of Neuroradiology.

Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study

PubMed Central

Mallewa, Macpherson; Vallely, Pam; Faragher, Brian; Banda, Dan; Klapper, Paul; Mukaka, Mavuto; Khofi, Harriet; Pensulo, Paul; Taylor, Terrie; Molyneux, Malcolm; Solomon, Tom

2013-01-01

Summary Background Fever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an important cause of CNS infection in such patients, and examined the relative contribution of viral pathogens and malaria parasitaemia. Methods We did a prospective cohort study in Blantyre, Malawi. From March 1, 2002, to Aug 31, 2004, we enrolled children aged between 2 months and 15 years who were admitted to hospital with suspected non-bacterial CNS infections. Children with a cerebrospinal fluid (CSF) white cell count of less than 1000 cells per μL and negative bacterial microscopy and culture were deemed to have suspected viral CNS infection. Blood was examined for asexual forms of P falciparum. PCR was done on CSF or on post-mortem brain biopsy specimens to detect 15 viruses known to cause CNS infection. Findings Full outcome data were available for 513 children with suspected viral CNS infection, of whom 94 (18%) died. 163 children (32%) had P falciparum parasitaemia, of whom 34 (21%) died. At least one virus was detected in the CNS in 133 children (26%), of whom 43 (33%) died. 12 different viruses were detected; adenovirus was the most common, affecting 42 children; mumps, human herpes virus 6, rabies, cytomegalovirus, herpes simplex virus 1, and enterovirus were also important. 45 (9%) of the 513 children had both parasitaemia and viral infection, including 27 (35%) of 78 diagnosed clinically with cerebral malaria. Children with dual infection were more likely to have seizures than were those with parasitaemia alone, viral infection only, or neither (p<0·0001). 17 (38%) of the 45 children with dual infection died, compared with 26 (30%) of 88 with viral infection only, 17 (14%) of 118 with parasitaemia only, and 34 (13%) of 262 with neither (p<0·0001). Logistic regression showed children with a viral CNS infection had a significantly higher mortality than did those who did not have a viral CNS infection (p=0·001). Interpretation Viral CNS infections are an important cause of hospital admission and death in children in Malawi, including in children whose coma might be attributed solely to cerebral malaria. Interaction between viral infection and parasitaemia could increase disease severity. Funding Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. PMID:24748325

Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study.

PubMed

Mallewa, Macpherson; Vallely, Pam; Faragher, Brian; Banda, Dan; Klapper, Paul; Mukaka, Mavuto; Khofi, Harriet; Pensulo, Paul; Taylor, Terrie; Molyneux, Malcolm; Solomon, Tom

2013-09-01

Fever with reduced consciousness is an important cause of hospital admission of children in sub-Saharan Africa, with high mortality. Cerebral malaria, diagnosed when acute Plasmodium falciparum infection and coma are recorded with no other apparent reason, is one important cause. We investigated whether viruses could also be an important cause of CNS infection in such patients, and examined the relative contribution of viral pathogens and malaria parasitaemia. We did a prospective cohort study in Blantyre, Malawi. From March 1, 2002, to Aug 31, 2004, we enrolled children aged between 2 months and 15 years who were admitted to hospital with suspected non-bacterial CNS infections. Children with a cerebrospinal fluid (CSF) white cell count of less than 1000 cells per μL and negative bacterial microscopy and culture were deemed to have suspected viral CNS infection. Blood was examined for asexual forms of P falciparum. PCR was done on CSF or on post-mortem brain biopsy specimens to detect 15 viruses known to cause CNS infection. Full outcome data were available for 513 children with suspected viral CNS infection, of whom 94 (18%) died. 163 children (32%) had P falciparum parasitaemia, of whom 34 (21%) died. At least one virus was detected in the CNS in 133 children (26%), of whom 43 (33%) died. 12 different viruses were detected; adenovirus was the most common, affecting 42 children; mumps, human herpes virus 6, rabies, cytomegalovirus, herpes simplex virus 1, and enterovirus were also important. 45 (9%) of the 513 children had both parasitaemia and viral infection, including 27 (35%) of 78 diagnosed clinically with cerebral malaria. Children with dual infection were more likely to have seizures than were those with parasitaemia alone, viral infection only, or neither (p<0·0001). 17 (38%) of the 45 children with dual infection died, compared with 26 (30%) of 88 with viral infection only, 17 (14%) of 118 with parasitaemia only, and 34 (13%) of 262 with neither (p<0·0001). Logistic regression showed children with a viral CNS infection had a significantly higher mortality than did those who did not have a viral CNS infection (p=0·001). Viral CNS infections are an important cause of hospital admission and death in children in Malawi, including in children whose coma might be attributed solely to cerebral malaria. Interaction between viral infection and parasitaemia could increase disease severity. Wellcome Trust, US National Institutes of Health, and UK Medical Research Council.

Alternative sampling strategies for passive classical and African swine fever surveillance in wild boar.

PubMed

Petrov, Anja; Schotte, Ulrich; Pietschmann, Jana; Dräger, Carolin; Beer, Martin; Anheyer-Behmenburg, Helena; Goller, Katja V; Blome, Sandra

2014-10-10

In view of the fact that African swine fever (ASF) was recently introduced into the wild boar population of the European Union and that classical swine fever (CSF) keeps reoccurring, targeted surveillance is of utmost importance for early detection. Introduction of both diseases is usually accompanied by an increased occurrence of animals found dead. Thus, fallen wild boar are the main target for passive surveillance. However, encouraging reporting by hunters and sampling of these animals is difficult. Partly, these problems could be solved by providing a pragmatic sampling approach. For this reason, we assessed the applicability of three different dry/semi-dry blood swabs, namely a cotton swab, a flocked swab, and a forensic livestock swab, for molecular swine fever diagnosis. After nucleic acid extraction using manual and automated systems, routine quantitative real-time polymerase chain reactions (qPCR) were carried out. Results obtained from swabs or their fragments were compared to results generated from EDTA blood. It was shown that reliable detection of both pathogens was possible by qPCR. Shifts in genome copy numbers were observed, but they did not change the qualitative results. In general, all swabs were suitable, but the forensic swab showed slight advantages, especially in terms of cutting and further storage. Robustness of the method was confirmed by the fact that different extraction methods and protocols as well as storage at room temperature did not have an influence on the final outcome. Taken together, swab samples could be recommended as a pragmatic approach to sample fallen wild boar. Copyright © 2014 Elsevier B.V. All rights reserved.

Soluble sortilin is present in excess and positively correlates with progranulin in CSF of aging individuals.

PubMed

Molgaard, Simon; Demontis, Ditte; Nicholson, Alexandra M; Finch, Nicole A; Petersen, Ronald C; Petersen, Claus M; Rademakers, Rosa; Nykjaer, Anders; Glerup, Simon

2016-11-01

Mutations in progranulin are a major cause of frontotemporal lobe degeneration (FTLD). Hence, plasma progranulin is an attractive biomarker in FTLD but poorly reflects levels in cerebrospinal fluid (CSF), suggesting tissue-specific regulation of progranulin levels. Sortilin was recently identified as a progranulin scavenger receptor that destines it for lysosomal degradation. Proteolysis or alternative splicing generates soluble sortilin variants that retain progranulin binding and potentially functions as a decoy receptor. In the present study, we analyzed soluble sortilin and progranulin in plasma and CSF in 341 aging individuals. We found that soluble sortilin exists in CSF in ten-fold molar excess compared to progranulin and observed a highly significant positive correlation between soluble sortilin and progranulin levels in CSF but not in plasma. However, carriers of the minor allele of SNP rs646776 in SORT1 encoding sortilin displayed significantly increased soluble sortilin and reduced progranulin specifically in plasma but not in CSF. Taken together, our findings suggest that soluble sortilin may affect progranulin levels in both a tissue-specific and genotype-dependent manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

NASA Astrophysics Data System (ADS)

Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

2012-06-01

Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

Rotavirus infection as a frequent cause of neonatal fever.

PubMed

Kang, Ha-Na; Park, Hyun Kyung; Lee, Hyun-Ju; Moon, Jin-Hwa; Oh, Jae Won; Kim, Chang-Ryul

2018-04-01

Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns. © 2017 Japan Pediatric Society.

Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury

PubMed Central

Kuo, Jon-Son; Wang, Jia-Yi

2015-01-01

Granulocyte-colony stimulating factor (G-CSF) protects brain from ischemic/reperfusion (I/R) injury, and inhibition of nitric oxide (NO) synthases partially reduces G-CSF protection. We thus further investigated the effects of G-CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF) and neurological deficit. Endothelin-1 (ET-1) microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia) which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion) within the striatal region. Regional NO concentration increased rapidly (NO surge) during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-NG-Nitroarginine Methyl Ester (L-NAME) significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury. PMID:26146654

Analysis of clinical outcomes in pediatric bacterial meningitis focusing on patients without cerebrospinal fluid pleocytosis.

PubMed

Lin, Wen-Li; Chi, Hsin; Huang, Fu-Yuan; Huang, Daniel Tsung-Ning; Chiu, Nan-Chang

2016-10-01

Cerebrospinal fluid (CSF) cell count and biochemical examinations and cultures form the basis for the diagnosis of bacterial meningitis. However, some patients do not have typical findings and are at a higher risk of being missed or having delayed treatment. To better understand the correlation between CSF results and outcomes, we evaluated CSF data focusing on the patients with atypical findings. This study enrolled CSF culture-proven bacterial meningitis patients aged from 1 month to 18 years in a medical center. The patients were divided into "normal" and "abnormal" groups for each laboratory result and in combination. The correlations between the laboratory results and the outcomes were analyzed. A total of 175 children with confirmed bacterial meningitis were enrolled. In CSF examinations, 16.2% of patients had normal white blood cell counts, 29.5% had normal glucose levels, 24.5% had normal protein levels, 10.2% had normal results in two items, and 8.6% had normal results in all three items. In logistic regression analysis, a normal CSF leukocyte count and increased CSF protein level were related to poor outcomes. Patients with meningitis caused by Streptococcus pneumoniae and hyponatremia were at a higher risk of mortality and the development of sequelae. In children with bacterial meningitis, nontypical CSF findings and, in particular, normal CSF leukocyte count and increased protein level may indicate a worse prognosis. Copyright © 2014. Published by Elsevier B.V.

The role of macrophages in the regulation of erythroid colony growth in vitro.

PubMed

Wang, C Q; Udupa, K B; Lipschitz, D A

1992-10-01

Depletion of macrophages from murine marrow by the use of a monoclonal anti-macrophage antibody resulted in a significant increase in the number of erythroid burst forming units (BFU-E). This increase could be neutralized by the addition back to culture of macrophages or macrophage conditioned medium indicating that the suppression was mediated by soluble factors. To further characterize this effect, the addition to culture, either alone or in combination, of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage-containing and macrophage-depleted cultures. The addition of IL-1 alpha to culture stimulated the release of both TNF alpha and GM-CSF and acted synergistically with both cytokines, resulting in a dose-dependent suppression of BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by monoclonal antibodies the addition of IL-1 alpha resulted in a significant increase in BFU-E growth. The addition of GM-CSF to culture caused a dose-dependent suppression of BFU-E that was mediated by TNF alpha, as colony number was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were simultaneously added to culture. TNF alpha-induced suppression of BFU-E only occurred in the presence of macrophages. In macrophage-depleted cultures, a dose-dependent suppression of BFU-E could be induced if subinhibitory concentrations of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly synergistic so that the doses required to induce suppression when added simultaneously was only 10% of that required when either were added to culture alone. Suppression of BFU-E by GM-CSF or the combined addition of GM-CSF and TNF alpha did not require IL-1 alpha because inhibition was not neutralized by the addition of anti-IL-1 alpha antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Population Explosions of Tiger Moth Lead to Lepidopterism Mimicking Infectious Fever Outbreaks

PubMed Central

Wills, Pallara Janardhanan; Anjana, Mohan; Nitin, Mohan; Varun, Raghuveeran; Sachidanandan, Parayil; Jacob, Tharaniyil Mani; Lilly, Madhavan; Thampan, Raghava Varman; Karthikeya Varma, Koyikkal

2016-01-01

Lepidopterism is a disease caused by the urticating scales and toxic fluids of adult moths, butterflies or its caterpillars. The resulting cutaneous eruptions and systemic problems progress to clinical complications sometimes leading to death. High incidence of fever epidemics were associated with massive outbreaks of tiger moth Asota caricae adult populations during monsoon in Kerala, India. A significant number of monsoon related fever characteristic to lepidopterism was erroneously treated as infectious fevers due to lookalike symptoms. To diagnose tiger moth lepidopterism, we conducted immunoblots for tiger moth specific IgE in fever patients’ sera. We selected a cohort of patients (n = 155) with hallmark symptoms of infectious fevers but were tested negative to infectious fevers. In these cases, the total IgE was elevated and was detected positive (78.6%) for tiger moth specific IgE allergens. Chemical characterization of caterpillar and adult moth fluids was performed by HPLC and GC-MS analysis and structural identification of moth scales was performed by SEM analysis. The body fluids and chitinous scales were found to be highly toxic and inflammatory in nature. To replicate the disease in experimental model, wistar rats were exposed to live tiger moths in a dose dependant manner and observed similar clinico-pathological complications reported during the fever epidemics. Further, to link larval abundance and fever epidemics we conducted cointegration test for the period 2009 to 2012 and physical presence of the tiger moths were found to be cointegrated with fever epidemics. In conclusion, our experiments demonstrate that inhalation of aerosols containing tiger moth fluids, scales and hairs cause systemic reactions that can be fatal to human. All these evidences points to the possible involvement of tiger moth disease as a major cause to the massive and fatal fever epidemics observed in Kerala. PMID:27073878

Acute lumbosacral polyradiculopathy due to cytomegalovirus in advanced HIV disease: CSF findings in 17 patients.

PubMed Central

Miller, R F; Fox, J D; Thomas, P; Waite, J C; Sharvell, Y; Gazzard, B G; Harrison, M J; Brink, N S

1996-01-01

OBJECTIVES: To describe the abnormalities in CSF from HIV infected patients with acute lumbosacral polyradiculopathy (ALP) caused by cytomegalovirus (CMV) infection. METHODS: Retrospective case notes and laboratory records were reviewed for 17 consecutive patients with CMV associated ALP admitted to specialist HIV/AIDS units at UCL Hospitals and Chelsea and Westminster Hospital. RESULTS: Infection with CMV was confirmed by detection of CMV DNA by polymerase chain reaction amplification in 15 patients (all of whom were negative by culture), by culture in one patient, and by objective clinical response to anti-CMV treatment in one patient. Only nine patients had a CSF pleocytosis 28-1142 (median 150) cells/mm3; in seven there was a polymorphonuclear (PMN) leucocyte preponderance. Protein concentrations in CSF were moderately or considerably raised in 13 patients; CSF: plasma glucose ratios were < or = 50% in five patients. Two patients had no pleocytosis, normal CSF: plasma glucose, and normal or near normal protein values. CONCLUSIONS: Abnormalities in CSF in CMV associated ALP are varied: only 50% of patients have a "typical" PMN preponderant pleocytosis. The diagnosis of this condition should not rely on demonstration of a PMN preponderant pleocytosis, but on identification of CMV DNA in CSF and the exclusion of other opportunistic infections and lymphoma in order that specific anti-CMV treatment may be instituted. PMID:8937337

Zika Virus, a Cause of Fever in Central Java, Indonesia

DTIC Science & Technology

1981-01-01

ZIKA VIRUS , A CAUSE OF FEVER IN CENTRAL JAVA, INDONESIA J.G. Olson, T.G. Ksiazek, Suhandiman and Triwibowo REPORT NO. TR-879 NAMRU- DT1 &, AUG 0 9...75, No. 3, 1981 Zika virus , a cause of fever in Central Java, Indonesia J. G. OLSON’, T. G. KSIAZEK’, SUHANDIMAN 2 AND TRIwIBOWO 2 ’U.S. Naval...more days on admission. A physician member of the team recorded the Introduction patient’s age, sex and date of onset of symptoms and Zika virus ( ZIKA

Careful: Acetaminophen in Pain Relief Medicines Can Cause Liver Damage

MedlinePlus

... and Fever Reducers Careful: Acetaminophen in pain relief medicines can cause liver damage Share Tweet Linkedin Pin ... ingredient in many over-the-counter and prescription medicines that help relieve pain and reduce fever. More ...

Management of post-neurosurgical meningitis: narrative review.

PubMed

Hussein, K; Bitterman, R; Shofty, B; Paul, M; Neuberger, A

2017-09-01

Infections complicating neurosurgery pose unacceptable mortality and morbidity. To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria. However, knowledge of the local epidemiology is necessary to treat PNM. The diagnosis of PNM is difficult because, unlike community-acquired meningitis, symptoms are less specific; patients are ill at baseline and many neurosurgical conditions mimic meningitis and cause cerebrospinal fluid (CSF) abnormalities. Pivotal CSF findings for diagnosis of PNM are the CSF glucose, CSF lactate and Gram stain. CSF leucocyte counts are not specific in PNM. Current diagnostic capabilities leave a non-negligible category of patients with microbiologically negative, uncertain diagnosis of PNM. There is no high-quality evidence on several cardinal issues in PNM management, including the effectiveness of intraventricular or intrathecal (IV/IT) antibiotics, effectiveness of dual antibiotic therapy for multidrug-resistant Gram-negative bacteria; clinical benefit of routine therapeutic drug monitoring; and safest timing of shunt replacement. Some data point to a potential benefit of IV/IT antibiotic treatment, mainly for PNM caused by carbapenem-resistant Gram-negative bacteria. Carbapenem-colistin combination therapy is suggested for PNM caused by carbapenem-resistant Gram-negative bacteria with a carbapenem MIC ≤8 mg/L. Guiding the optimal management of PNM will necessitate collaborative multicentre efforts and unique study designs. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Syringomyelia caused by an arachnoid web in a patient with shunted Dandy-Walker malformation.

PubMed

Lee, Hee Chang; Choi, Jung Won; Lee, Ji Yeoun; Phi, Ji Hoon; Kim, Seung-Ki; Cho, Byung-Kyu; Wang, Kyu-Chang

2017-04-01

Dandy-Walker malformation (DWM) is a congenital brain anomaly characterized by dysgenesis of the cerebellar vermis and the presence of a posterior fossa cyst. The association of syringomyelia with DWM is extremely rare. A 10-year-old patient who was diagnosed with DWM in infancy presented with progressive scoliosis and fecal incontinence. He had been treated with cystoventriculoperitoneal shunting with a Y-connection during infancy, which was followed by a revision 6 years later. During the revision surgery, intraventricular bleeding occurred and was managed conservatively. Imaging studies for the current visit revealed syringomyelia along the cervicothoracic spinal cord and a membranous structure around the cervicomedullary junction. Phase-contrast cine magnetic resonance imaging (MRI) revealed disturbed cerebrospinal fluid (CSF) flow across the membrane. We excised the arachnoid web that was tethering the brainstem and blocking CSF flow. Postoperatively, the patient experienced symptom relief, and the follow-up imaging study demonstrated a dramatic decrease in the size of the syringomyelia. We suggest that syrinx formation in this patient was possibly caused by disturbed CSF flow and tethering of the brainstem. We experienced an unusual case of DWM with syringomyelia which was caused by an arachnoid web blocking CSF flow and tethering the brainstem. The arachnoid web seems to be formed by previous bleeding which occurred at the time of shunt revision. After excision of the arachnoid web, the patient showed good outcome.

Lumbar puncture requirement in acute hemiparesis: diagnosis of tuberculous meningitis after hemiparesis in a child.

PubMed

Sahin, Sevim; Cansu, Ali; Kamaşak, Tülay; Eyüboğlu, İlker; Esenülkü, Gülnur; Ökten, Ayşenur

2014-12-01

Infections are an important acquired cause of cerebral arteriopathy. Tuberculous (TB) meningitis leading to infectious cerebral vasculopathy is a rare cause of acute hemiparesis. A 14-year-old male patient was examined after acute hemiparesis developing within 1 day. Neurological examination revealed total hemiplegia on the left side. Brain MRI findings showed bilateral focal T2-weighted signal hyperintensity in the subcortical and deep white matter regions. There were also areas of restricted diffusion in the right basal ganglia. Although the father had a history of pulmonary TB, the patient had not been given TB prophylaxis because of PPD negativity. At lumbar puncture, opening cerebrospinal fluid (CSF) pressure was 50 cm/H20, CSF protein 66.9 mg/dL, and glucose 54 mg/dL (concurrent blood glucose 93 mg/dL); 170 polymorphonuclear leukocytes per cubic millimeter were present in CSF. Following tests for TB, treatment was started immediately with four anti-TB drugs. TB PCR of CSF and acid-fast bacteria (AFB) staining in gastric aspirate were positive. At clinical follow-up, the patient was able to walk with support at the end of the first month. Various infectious agents have been reported as causes of cerebral vasculopathy. TB, which affects a significant number of patients worldwide, should be kept in mind in terms of cerebral vascular complications. Lumbar puncture is essential in order to diagnose TB meningitis.

Soluble CD14 in cerebrospinal fluid is associated with markers of inflammation and axonal damage in untreated HIV-infected patients: a retrospective cross-sectional study.

PubMed

Jespersen, Sofie; Pedersen, Karin Kæreby; Anesten, Birgitta; Zetterberg, Henrik; Fuchs, Dietmar; Gisslén, Magnus; Hagberg, Lars; Trøseid, Marius; Nielsen, Susanne Dam

2016-04-21

HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver of systemic and CNS inflammation. However, LPS was not detectable in the CSF, and since sCD14 is a marker of monocyte activation sCD14 may be increased due to other causes than microbial translocation. Further studies regarding cognitive impairment and biomarkers are warranted to fully understand causality.

Central effect of taurine and its analogues on fever caused by intravenous leukocytic pyrogen in the rabbit.

PubMed Central

Lipton, J M; Ticknor, C B

1979-01-01

1. Taurine infused I.C.V. after I.V. injection of leukocytic pyrogen (LP) inhibited the initial rise in body temperature and prolonged fever when infusion was stopped. 2. Similar infusion of taurine also inhibited the hypertermic effect of I.C.V. PGE2 (0.5 microgram) but did not cause prolonged hyperthermia. 3. I.C.V. administration of the taurine analogues hypotaurine and beta-alanine, compounds which have been shown previously to compete with taurine for facilitated transport in C.N.S. tissue, also inhibited the initial increase in body temperature and prolonged LP fever. 4. These results suggest that taurine prolongs LP fever by preferentially occupying a carrier system normally required for termination of the effects of endogenous pyrogens or related central mediators of fever. There was no evidence that taurine prolongs fever by blocking inactivation of central PGE2, a substance proposed previously to be a central mediator of fever. PMID:107309

Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

PubMed

Thomas, G R; Thibodeaux, H; Margolius, H S; Webb, J G; Privitera, P J

1987-07-01

The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

What is the risk of infecting a cerebrospinal fluid-diverting shunt with percutaneous tapping?

PubMed

Spiegelman, Lindsey; Asija, Richa; Da Silva, Stephanie L; Krieger, Mark D; McComb, J Gordon

2014-10-01

Most CSF-diverting shunt systems have an access port that can be percutaneously tapped. Tapping the shunt can yield valuable information as to its function and whether an infection is present. The fear of causing a shunt infection by tapping may limit the physician's willingness to do so. The authors of this study investigate the risk of infecting a shunt secondary to percutaneous tapping. Following institutional review board approval, CSF specimens obtained from tapping an indwelling CSF-diverting shunt during the 2011 and 2012 calendar years were identified and matched with clinical information. A culture-positive CSF sample was defined as an infection. If results were equivocal, such as a broth-only-positive culture, a repeat CSF specimen was examined. The CSF was obtained by tapping the shunt access port with a 25-gauge butterfly needle after prepping the unshaven skin with chlorhexidine. During the study period, 266 children underwent 542 shunt taps. With 541 taps, no clinical evidence of a subsequent shunt infection was found. One child's CSF went from sterile to infected 11 days later; however, this patient had redness along the shunt tract at the time of the initial sterile tap. The risk of infection from tapping a shunt is remote if the procedure is done correctly.

Cerebrospinal fluid findings after epileptic seizures.

PubMed

Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

2015-12-01

We aimed to evaluate ictally-induced CSF parameter changes after seizures in adult patients without acute inflammatory diseases or infectious diseases associated with the central nervous system. In total, 151 patients were included in the study. All patients were admitted to our department of neurology following acute seizures and received an extensive work-up including EEG, cerebral imaging, and CSF examinations. CSF protein elevation was found in most patients (92; 60.9%) and was significantly associated with older age, male sex, and generalized seizures. Abnormal CSF-to-serum glucose ratio was found in only nine patients (5.9%) and did not show any significant associations. CSF lactate was elevated in 34 patients (22.5%) and showed a significant association with focal seizures with impaired consciousness, status epilepticus, the presence of EEG abnormalities in general and epileptiform potentials in particular, as well as epileptogenic lesions on cerebral imaging. Our results indicate that non-inflammatory CSF elevation of protein and lactate after epileptic seizures is relatively common, in contrast to changes in CSF-to-serum glucose ratio, and further suggest that these changes are caused by ictal activity and are related to seizure type and intensity. We found no indication that these changes may have further-reaching pathological implications besides their postictal character.

Refining the Association of Fever with Functional Outcome in Aneurysmal Subarachnoid Hemorrhage.

PubMed

Kramer, Christopher L; Pegoli, Marianna; Mandrekar, Jay; Lanzino, Giuseppe; Rabinstein, Alejandro A

2017-02-01

We analyzed the impact of cause, severity, and duration of fever on functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Fever characteristics were analyzed in 584 consecutive patients with aSAH. Fever was defined as core body temperature ≥38.3 °C on ≥2 consecutive days. Subfebrile measurements were those between 37 and 38.2 °C. Febrile and subfebrile loads were the number of hours with fever or subfebrile measurements, respectively. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration. Febrile measurements were observed in 281/584 (48.1 %) patients, recurring over a mean duration of 2.1 ± 3.0 days. Early fever within 24 and 72 h was encountered in 69 (11.9 %) and 110 (18.9 %) of patients, respectively. An infectious source was discovered in 126 (44.8 %) febrile patients. On univariate analysis, days of fever, febrile load, and fever onset within 24 and 72 h were associated with poor outcome (all p < 0.001); but subfebrile load was not (p = 0.56). On multivariate model constructed with all variables associated with outcome on univariate analyses, days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95 % CI 1.06-1.22; p = 0.0006) displacing all other fever measures from the final model. Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, subfebrile load does not influence clinical outcome. These data suggest prolonged fever should be avoided, but subfebrile temperatures may not justify intervention.

Tick Bites (For Parents)

MedlinePlus

... can carry harmful germs that cause diseases like Rocky Mountain spotted fever and Lyme disease . The deer tick is tiny, ... disease) red dots on the ankles and wrists (Rocky Mountain spotted fever) flu -like symptoms such as fever , headache , fatigue, ...

Fever with Rashes.

PubMed

Soman, Letha

2018-07-01

Fever with rashes is one of the commonest clinical problems a general practitioner or pediatrician has to face in day-to-day clinical practice. It can be a mild viral illness or a life-threatening illness like meningococcemia or Dengue hemorrhagic fever or it can be one with a lifelong consequence like Kawasaki disease. It is very important to arrive at a clinical diagnosis as early as possible with the minimum investigational facilities. The common causes associated with fever and rashes are infections, viral followed by other infections. There can be so many non-infectious causes also for fever and rashes like auto immune diseases, drug allergies etc. The type of rashes, their appearance in relation to the fever and pattern of spread to different parts of body and the disappearance, all will help in making a diagnosis. Often the diagnosis is clinical. In certain situations laboratory work up becomes essential.

Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis

PubMed Central

Qvarnstrom, Yvonne; Xayavong, Maniphet; da Silva, Ana Cristina Aramburu; Park, Sarah Y.; Whelen, A. Christian; Calimlim, Precilia S.; Sciulli, Rebecca H.; Honda, Stacey A. A.; Higa, Karen; Kitsutani, Paul; Chea, Nora; Heng, Seng; Johnson, Stuart; Graeff-Teixeira, Carlos; Fox, LeAnne M.; da Silva, Alexandre J.

2016-01-01

Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis. PMID:26526920

Treatment of cerebrospinal fluid leak after spine surgery.

PubMed

Fang, Zhao; Tian, Rong; Jia, Yu-Tao; Xu, Tian-Tong; Liu, Yang

2017-04-01

Owing to the complexity of spinal surgery, there is a great prevalence of dural tear causing cerebrospinal fluid (CSF) leakage. Many studies focused on suture repair for dural tear to stop CSF leak. Now some new treatment strategies have shown a promising effect that is listed as follows: 1) creating watertight dural closure to stop CSF leak with the help of dural substitute material; and 2) retarding CSF leak by changing pressure difference, including reducing the subarachnoid fluid pressure, increasing the epidural space pressure and both. In fact several methods mentioned above are usually combined to treat CSF leak. However, no update review summarized the relevant studies implemented in recent years. In this review, the authors would compare the effects of different dural closure techniques, and introduce the latest treatment methods and mechanisms. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Intrasphenoidal encephalocele and spontaneous CSF rhinorrhoea.

PubMed

Daniilidis, J; Vlachtsis, K; Ferekidis, E; Dimitriadis, A

1999-12-01

Intrasphenoidal encephalocele is a rare clinical entity. In the international literature only 16 cases have been reported up today, with female predominance. Clinically they manifest at middle and advanced ages (40-67 years), when spontaneous CSF rhinorrhoea or recurrent meningitis occurs. We present our case, a 46 years old female, who had CSF rhinorrhoea from the right vestibule for 10 months. The diagnosis was based on the history and the high-resolution brain and skull base CT-scanning in conjunction with opaque fluid injection in the subarachnoidal space through a lumbar puncture. She was successfully treated with an operation, through an endonasal trans-ethmoid microendoscopic approach, using the Draf and Stammberger technique. We discuss the pathogenesis of the intrasphenoidal encephalocele, the existence of small occult defects in the skull base, which cause, at the middle and advanced ages, CSF fistula with spontaneous CSF rhinorrhoea and/or recurrent meningitis. Finally we emphasize the advantages of the endonasal surgical approach for the treatment of this condition.

Hospital-acquired fever in oriental medical hospitals.

PubMed

Moon, Soo-Youn; Park, Ki-Ho; Lee, Mi Suk; Son, Jun Seong

2018-02-07

Traditional Oriental medicine is used in many Asian countries and involves herbal medicines, acupuncture, moxibustion, and cupping. We investigated the incidence and causes of hospital-acquired fever (HAF) and the characteristics of febrile inpatients in Oriental medical hospitals (OMHs). Patients hospitalized in two OMHs of a university medical institute in Seoul, Korea, were retrospectively reviewed from 2006 to 2013. Adult patients with HAF were enrolled. There were 560 cases of HAF (5.0%). Infection, non-infection, and unknown cause were noted in 331 cases (59.1%), 109 cases (19.5%), and 120 cases (21.4%) of HAF, respectively. Respiratory tract infection was the most common cause (51.2%) of infectious fever, followed by urinary tract infection. Drug fever due to herbal medicine was the most common cause of non-infectious fever (53.1%), followed by procedure-related fever caused by oriental medical procedures. The infection group had higher white blood cell count (WBC) (10,400/mm 3 vs. 7000/mm 3 , p < 0.001) and more frequent history of antibiotic therapy (29.6% vs. 15.1%, p < 0.001). Multivariate analysis showed that older age (odds ratio (OR) 1.67, 95% confidence interval (C.I.) 1.08-2.56, p = 0.020), history of antibiotic therapy (OR 3.17, C.I. 1.85-5.41, p < 0.001), and WBC > 10,000/mm 3 (OR 2.22, C.I. 1.85-3.32, p < 0.001) were associated with infection. Compared to previous studies on HAF in Western medicine, the incidence of HAF in OMHs was not high. However, Oriental medical treatment does play some role in HAF. Fever in patients with history of antibiotic therapy, or high WBC was more likely of infectious origin.

Sarcocystis neurona-specific immunoglobulin G in the serum and cerebrospinal fluid of horses administered S neurona vaccine.

PubMed

Witonsky, Sharon; Morrow, Jennifer K; Leger, Clare; Dascanio, John; Buechner-Maxwell, Virginia; Palmer, Wally; Kline, Kristen; Cook, Anne

2004-01-01

A vaccine against Sarcocystis neurona, which induces equine protozoal myeloencephalitis (EPM), has received conditional licensure in the United States. A major concern is whether the immunoglobulin G (IgG) response elicited by the vaccine will compromise the use of Western blotting (WB) as a diagnostic tool in vaccinated horses with neurologic disease. Our goals were to determine if vaccination (1) causes seroconversion: (2) causes at least a transient increase in S neurona-specific IgG in the cerebrospinal fluid (CSF); and (3) induces an IgG response that can be differentiated from that induced by natural exposure. Horses included in the study (n = 29) were older than 6 months with no evidence of neurologic disease. The presence or absence of anti-S neurona antibodies in the serum of each horse was determined by WB analysis. Seropositive horses had CSF collected and submitted for cytology, CSF index, and WB analysis. The vaccine was administered to all the horses and boostered 3-4 weeks later. On day 14 after the 2nd administration, serum and CSF were collected and analyzed. Eighty-nine percent (8 of 9) of the initial seronegative horses seroconverted after vaccination, of which 57% (4 of 7) had anti-S neurona IgG in their CSE Eighty percent (16 of 20) of the seropositive horses had an increase in serum S neurona IgG after vaccination. Of the 6 of 20 horses that were initially seropositive/CSF negative, 2 were borderline positive for anti-S neurona IgG in the CSF, 2 tested positive, and 2 were excluded because the CSF sample had been contaminated by blood. There were no WB banding patterns that distinguished samples from horses that seroconverted due to vaccination versus natural exposure. Caution must be used in interpreting WB analysis from neurologic horses that have been recently vaccinated for EPM.

A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia

PubMed Central

Russell, A; Emmerson, A; Wilkinson, N; Chant, T; Sweet, D; Halliday, H; Holland, B; Davies, E

2001-01-01

OBJECTIVES—The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.
DESIGN—Neonates (⩽ 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of ⩽ 5 × 109/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 µg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.
RESULTS—Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p ⩽ 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).
CONCLUSIONS—In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.
 PMID:11320043

Ventriculosubgaleal shunts for posthemorrhagic hydrocephalus in premature infants.

PubMed

Willis, Brian K; Kumar, Cherukuri Ravi; Wylen, Esther L; Nanda, Anil

2005-01-01

The early management of posthemorrhagic hydrocephalus in premature infants is challenging and controversial. These infants need a temporary cerebrospinal fluid (CSF) diversion procedure until they gain adequate weight, and the blood and protein levels in CSF are reasonably low before permanent shunt can be placed. Various options are available with their associated advantages and disadvantages. Ventriculosubgaleal shunts have been recommended as a more physiologic and less invasive means of achieving this goal. We have performed this procedure in 6 premature infants to evaluate their effectiveness and complications. Six consecutive premature infants with posthemorrhagic hydrocephalus underwent placement of ventriculosubgaleal shunts over a 1-year period of time. We reviewed their clinical and imaging progress to assess the ability of the shunt to control hydrocephalus and the complication rates. In all 6 patients, the ventriculosubgaleal shunt controlled the progression of hydrocephalus as assessed by clinical and imaging parameters. A permanent shunt was avoided in 1 patient (16.6%). However, 4 patients developed shunt infections, 1 involving the ventriculosubgaleal shunt itself, and 3 immediately after conversion to ventriculoperitoneal shunt. The total infection rate of the series was 66.6%. All infections were caused by staphylococcus species. There was only a 1% shunt infection rate in our institution for all nonventriculosubgaleal shunts during the same period of time. Placement of ventriculosubgaleal shunts for interim CSF diversion in neonates with posthemorrhagic hydrocephalus is effective as a temporary method of CSF diversion. However, our experience has shown that it is associated with a unacceptably high CSF infection rate. A potential cause for infection is CSF stasis just beneath the extremely thin skin of the premature infants, promoting colonization by skin flora. CSF sampling before conversion to a permanent shunt and replacement of the proximal hardware, which has been in situ for a prolonged period, may decrease the infection rates. At present, the procedure is no longer performed at our institution.

Detection of cerebrospinal fluid leakage: initial experience with three-dimensional fast spin-echo magnetic resonance myelography.

PubMed

Tomoda, Y; Korogi, Y; Aoki, T; Morioka, T; Takahashi, H; Ohno, M; Takeshita, I

2008-03-01

The pathogenesis of cerebrospinal fluid (CSF) hypovolemia is supposed to be caused by CSF leakage through small dural defects. To compare source three-dimensional (3D) fast spin-echo (FSE) images of magnetic resonance (MR) myelography with radionuclide cisternography findings, and to evaluate the feasibility of MR myelography in the detection of CSF leakage. A total of 67 patients who were clinically suspected of CSF hypovolemia underwent indium-111 radionuclide cisternography, and 27 of those who had direct findings of CSF leakage were selected for evaluation. MR myelography with 3D FSE sequences (TR/TE 6000/203 ms) was performed at the lumbar spine for all patients. We evaluated source images and maximum intensity projection (MIP) images of MR myelography, and the findings were correlated with radionuclide cisternography findings. MR myelography of five healthy volunteers was used as a reference. The MR visibility of the CSF leakage was graded as definite (leakage clearly visible), possible (leakage poorly seen), or absent (not shown). CSF leakage was identified with source 3D FSE images in 22 (81.5%) of 27 patients. Of the 22 patients, 16 were graded as definite and six were graded as possible. For the definite cases, 3D FSE images clearly showed the extent of the leaked CSF in the paraspinal structures. In the remaining five patients with absent findings, radionuclide cisternography showed only slight radionuclide activity out of the arachnoid space. Source 3D FSE images of MR myelography seem useful in the detection of CSF leakage. Invasive radionuclide cisternography may be reserved for equivocal cases only.

Serious adverse events associated with yellow fever vaccine.

PubMed

de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira

2015-01-01

Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.

[A case of central nervous system infection due to west nile virus lineage-1 in ankara province, Turkey].

PubMed

Ocal, Murat; Onder, Halil; Arsava, Ethem M; Alp, Sehnaz; Ozkul, Aykut; Ergünay, Koray

2013-01-01

West Nile virus (WNV) is a mosquito-borne Flavivirus (family Flaviviridae), maintained in an enzootic cycle between birds as amplifying hosts and mosquito vectors. While WNV exposure in humans frequently remain subclinical, a febrile illness called West Nile fever occurs in about 20% and neuroinvasive disease in less than 1% of the affected individuals. For the last two decades, WNV has caused outbreaks of severe neuroinvasive disease in humans and horses in Europe, the Mediterranean Basin and emerged in the American continent. Although, previous serosurveillance reports have revealed human WNV exposure in various regions in Turkey; well-characterized clinical cases have only been reported after 2009-2010. In this report, a case of WNV encephalitis caused by a Lineage 1 virus strain and identified in Ankara province, Central Anatolia, Turkey, was presented. An 87 year-old woman with a history of hypertension and a recent febrile episode was admitted to Hacettepe University Hospital in late May 2012, with altered consciousness, myoclonic jerks in facial muscles and left extremity. Hyponatremia and increased alanine and aspartate aminotransferase levels were noted in blood analyses. Initial electroencephalogram (EEG) demonstrated diffuse slow waves. Areas of restricted diffusion in right dorsal thalamus was observed in cranial magnetic resonance imaging (MRI). Despite supportive therapy, the patient's neurological condition worsened. Follow-up EEG displayed paroxysmal lateralizing epileptiform discharges (PLEDs) in the right hemisphere and T2-hyperintense lesions in the right temporoparietal cortex, insula and thalamus with components of cytotoxic and vasogenic edema were observed in MRI. A cerebrospinal fluid (CSF)-serum pair was evaluated to identify potential causes of encephalitis. CSF biochemical and microscopic findings were within normal limits except for decreased glucose levels. Bacterial, mycobacterial and fungal cultures, antigen assays and polymerase chain reaction (PCR) employed for Herpes simplex virus types 1 and 2 were negative. Commercial and in house assays for WNV, tick-borne encephalitis virus, Toscana virus (TOSV) antibodies revealed TOSV IgG in serum. Previously described nested PCRs targeting WNV envelope glycoprotein and phlebovirus consensus sequences demonstrated WNV positive results in serum and CSF, which were further characterized via cycle sequencing of amplicons as WNV Lineage 1 Clade 1a. Four serum samples obtained within 23 days after the diagnosis were negative for viral RNA and specific antibodies via commercial assays and WNV plaque reduction neutralization assay. During follow-up with supportive therapy and anti-epileptics, the patient's general and neurological condition improved mildly and control EEG and MRI demonstrated regression of previous lesions. However, the patient passed away on the 10th week of hospital admission due to nosocomial infections. These findings confirmed the inital data which indicated the circulation of WNV Lineage 1 strains in Central Anatolia, Turkey. WNV seroconversion may be delayed or absent in elderly individuals without overt diseases associated with immunosuppression. Thus investigation of WNV RNA together with the specific serological tests may help the accurate diagnosis of suspected cases.

Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice.

PubMed

Horiguchi, Hyogo; Oguma, Etsuko

2016-12-01

Acute exposure to cadmium (Cd), a toxic heavy metal, causes systemic inflammation characterized by neutrophilia. To elucidate the mechanism of neutrophilia induced by Cd, we investigated the induction of granulocyte colony-stimulating factor (G-CSF), which regulates neutrophil production, in mice with acute Cd toxicity, and compared it with mice injected with lipopolysaccharide (LPS) as an inducer of general inflammatory responses. We injected BALB/c mice with Cd at 2.5 mg/kg i.p. or LPS at 0.5 mg/kg i.p. and sampled the peripheral blood and organs at time points up to 24 h. In Cd-treated mice, the peripheral neutrophil count increased steadily up to 24 h, whereas LPS-treated mice showed a more rapid increase with a peak at 12 h. The serum G-CSF level increased gradually to reach a plateau at 12-18 h in Cd-treated mice, but LPS-treated mice showed a marked increase, reaching a peak at 2-3 h. A gradual elevation of G-CSF mRNA expression up to 24 h was detected by real-time PCR in the livers of Cd-treated mice, but in LPS-treated mice its highest expression was observed in the liver with a rapid increase at 2 h. By in situ hybridization using G-CSF RNA probes, hepatic Kupffer cells were identified as G-CSF-producing cells in the liver. These results indicated that Cd has a characteristic effect of delayed induction of G-CSF in the liver, causing systemic inflammation accompanied by prolonged neutrophilia.

Periodic and chaotic host-parasite interactions in human malaria.

PubMed Central

Kwiatkowski, D; Nowak, M

1991-01-01

It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite. PMID:2052590

Cerebrospinal fluid hypersecretion in pediatric hydrocephalus.

PubMed

Karimy, Jason K; Duran, Daniel; Hu, Jamie K; Gavankar, Charuta; Gaillard, Jonathan R; Bayri, Yasar; Rice, Hunter; DiLuna, Michael L; Gerzanich, Volodymyr; Marc Simard, J; Kahle, Kristopher T

2016-11-01

Hydrocephalus, despite its heterogeneous causes, is ultimately a disease of disordered CSF homeostasis that results in pathological expansion of the cerebral ventricles. Our current understanding of the pathophysiology of hydrocephalus is inadequate but evolving. Over this past century, the majority of hydrocephalus cases has been explained by functional or anatomical obstructions to bulk CSF flow. More recently, hydrodynamic models of hydrocephalus have emphasized the role of abnormal intracranial pulsations in disease pathogenesis. Here, the authors review the molecular mechanisms of CSF secretion by the choroid plexus epithelium, the most efficient and actively secreting epithelium in the human body, and provide experimental and clinical evidence for the role of increased CSF production in hydrocephalus. Although the choroid plexus epithelium might have only an indirect influence on the pathogenesis of many types of pediatric hydrocephalus, the ability to modify CSF secretion with drugs newer than acetazolamide or furosemide would be an invaluable component of future therapies to alleviate permanent shunt dependence. Investigation into the human genetics of developmental hydrocephalus and choroid plexus hyperplasia, and the molecular physiology of the ion channels and transporters responsible for CSF secretion, might yield novel targets that could be exploited for pharmacotherapeutic intervention.

[Neopterin in serum and cerebrospinal fluid in Lyme disease].

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Garlicki, Aleksander; Mach, Tomasz

2009-01-01

Lyme disease is a multiorgan disease, caused by spirochetes of Borrelia species. Clinical picture is diverse, borreliosis can affect skin, nervous system, musculoskeletal system and heart. Neopterin is a marker of cytotoxic lymphocytes T activities, it is produced by monocytes/macrophages stimulated with IFNgamma. The aim of our study was to evaluate the level of neopterin in serum and cerebrospinal fluid in borreliosis and correlate it with the symptoms, markers of inflammation in cerebrospinal fluid (CSF), and serological tests against Borrelia burgdorferi. We have enrolled in the study 39 patients treated for Lyme borreliosis. The level of neopterin in serum was assessed in all patients, among patient with suspicion of neuroborreliosis (n = 33) we assessed the level of neopterin, protein, glucose and chlorium in CSF. The level of neopterin in CSF was lower among patients who were treated due to presence of erithema migrans in their past regarding patients who had never had erithema migrans (p = 0.008). The level of neopterin in CSF was higher (6.6 nmol/l) in patients with the presence of inflammation in CSF versus patients with no changes in CSF (3.8 mmol/l; p = 0.019). There was no correlation between neopterin in serum or CSF and Westernblot test. Patients with neuroborreliosis who had lymphocytic meningitis had higher level of neopterin in CSF. We suggest the role of neopterin in pathogenesis on neuroborreliosis. Neopterin as a marker of cytotoxic lymphocytes T activities can be useful in borreliosis diagnosis but more studies regarding this problem should be done.

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis.

PubMed

England, Timothy J; Sprigg, Nikola; Alasheev, Andrey M; Belkin, Andrey A; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M

2016-11-15

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.

Cerebrospinal fluid enhancement on fluid attenuated inversion recovery images after carotid artery stenting with neuroprotective balloon occlusions: hemodynamic instability and blood-brain barrier disruption.

PubMed

Ogami, Ryo; Nakahara, Toshinori; Hamasaki, Osamu; Araki, Hayato; Kurisu, Kaoru

2011-10-01

A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

[Factitious fevers as a cause of prolonged fevers. Apropos of 5 clinical cases].

PubMed

Potin, M; Regamey, C; Glauser, M P

1983-10-22

Among the numerous causes of prolonged fever of unknown origin, the factitious fevers are frequently considered last after much diagnostic and therapeutic effort. Five observations of factitious fever are presented including 2 cases of thermometer manipulation in men aged 45 and 80. The latter patient is the oldest in whom such a case has been reported. In the first case the prolonged fever led to exploratory laparotomy with splenectomy followed by antilymphoma chemotherapy before the thermometer manipulation was discovered. This patient had previously been treated successfully for stage Ib Hodgkin lymphoma. In the other case hospitalization had lasted several weeks, and much antibiotic and steroid treatment had been administered, before the manipulation was suspected. A third case of thermometer manipulation was observed in a 57-year-old woman who had been presenting with factitious symptoms for over 10 years. Two other cases of factitious fever due to self-induced infections have been observed in two young women aged 23 and 27, both in paramedical professions. These self-induced infections led to polymicrobial bacteremia, exploratory laparotomy and hemicolectomy in one case, and to probable bacterial meningitis in the other. Certain aspects of these cases agree well with the diagnostic criteria of factitious fever described in the literature. We feel it is important to recognize this cause of febrile states, even if there is an apparent etiology, in order to avoid much vain investigation and prolonged hospitalization.

CRISPRs: Molecular Markers for Tracking Antibiotic Resistant Strains of Salmonella Enterica

DTIC Science & Technology

2014-01-01

S.Paratyphi A, B and C) are confined to human hosts and cause typhoid and paratyphoid (enteric) fevers . These are spread from human to human—often shed by...poisoning) with symptoms of diarrhea, fever , and abdominal cramps that run 5-7 days. In contrast, non- typhoidal salmonellosis in sub-Saharan Africa... typhoid fever , due to Salmonella Typhi, is an important cause of illness and death. Most serotype Typhi infections in the United States are acquired

Treating Meningitis

MedlinePlus

... other instances, the CSF undergoes a series of tests, all designed to find the cause of the meningitis. DIAGNOSIS AND TREATMENT Understanding the cause is critical to starting the best treatment. Anti- biotics are ...

Classical Swine Fever—An Updated Review

PubMed Central

Blome, Sandra; Staubach, Christoph; Henke, Julia; Carlson, Jolene; Beer, Martin

2017-01-01

Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries are mainly based on classical intervention measures; i.e., quarantine and strict culling of affected herds. In these countries, vaccination is only an emergency option. However, live vaccines are used for controlling the disease in endemically infected regions in Asia, Eastern Europe, the Americas, and some African countries. Here, we will provide a concise, updated review on virus properties, clinical signs and pathology, epidemiology, pathogenesis and immune responses, diagnosis and vaccination possibilities. PMID:28430168

Diagnostic approaches for Rift Valley Fever

USDA-ARS?s Scientific Manuscript database

Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus (RVFV) is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in Sub-Saha...

Fever

MedlinePlus

... causes of fevers include Medicines, including some antibiotics, blood pressure medicines, and anti-seizure medicines Heat illness Cancers Autoimmune diseases Some childhood immunizations Treatment ...

[Evaluation of the increasing serum lactate dehydrogenase caused by recombinant human granulocyte-colony stimulating factor].

PubMed

Sawa, Toshiyuki; Yoshida, Tsutomu; Ikoma, Tetsuroh; Toyoda, Miki; Ohno, Yasushi; Fujiwara, Hisayoshi

2003-01-01

Increasing serum lactate dehydrogenase (LDH) is often caused by granulocyte-colony stimulating factor (G-CSF) for leukopenia following chemotherapy in patients with lung cancer. To evaluate the increase in LDH, we investigated the significance of its elevation and LDH isozyme during chemotherapy supported by recombinant human G-CSF (rhG-CSF). To exclude effects of liver diseases and chemotherapy-induced liver dysfunction, only patients in whom laboratory findings concerning liver function were within normal range were entered in this study. If leukocyte or neutrophil counts were less than grade 3, subcutaneous injection of 50 micrograms/m2 of filgrastim was given daily until leukocyte counts increased to more than 10,000/mm3. Sixty patients with unresectable lung cancer were enrolled in this study and the LDH isozyme was evaluable in 54 patients. Increasing LDH was observed in 38 patients(70.4%), and LDH isozyme was measured in these 38 patients. Increases in granulocytes and LDH isozymes were found to have a positive correlation. LDH2, LDH3, LDH4 and LDH5 increased significantly after rhG-CSF administration, although LDH 1 did not increase. It was found that a rapid increase in leukocytes by rhG-CSF induced an increase in LDH, especially LDH 3.4. Considering the results of principal component analysis and the distribution ratio of LDH isozymes in neutrophils, it is thought that elevation of LDH is reflected in the rapid production and consumption of neutrophils.

Rural-Urban Differences in Maternal Responses to Childhood Fever in South East Nigeria

PubMed Central

Uzochukwu, Benjamin S. C.; Onwujekwe, Emmanuel O.; Onoka, Chima A.; Ughasoro, Maduka D.

2008-01-01

Background Childhood fevers due to malaria remain a major cause of morbidity and mortality among under-five children in Nigeria. The degree of vulnerability perceived by mothers will affect their perception of the severity and threat of their child's fever and the patterns of health care use. This study was undertaken to compare maternal responses to childhood fever in urban and rural areas of Enugu, south east Nigeria. Methodology/Principal Findings Data was collected with pre-tested interviewer-administered questionnaires from 276 and 124 urban and rural households respectively. In each household, only one woman aged 15–49 years who had lived in each of the urban and rural communities for at least one year and had at least one child less than 5 years old was interviewed. Malaria was mentioned as the commonest cause of childhood fevers. Rural mothers were more likely to recognize danger signs and symptoms than urban mothers. Rural mothers use more of informal than formal health services, and there is more home management of the fever with urban than rural mothers. Chloroquine, ACT, SP and Paracetamol are the main drugs given at home for childhood fevers, but the rural mothers were more likely to use leftover drugs from previous treatment to treat the fevers than urban mothers. The urban respondents were also more likely to use a preventive measure. Urban mothers sought actions faster than rural mothers and the total cost of treatment was also higher in urban areas. Conclusions/Significance Both urban and rural mothers are aware that malaria is the major cause of childhood fevers. Although rural mothers recognize childhood fever and danger signs better than urban mothers, the urban mothers' responses to fever seem to be better than that for rural mothers. These responses and differences may be important for geographical targeting by policy makers for malaria interventions. PMID:18335058

Acute Arthritis in Crimean-Congo Hemorrhagic Fever

PubMed Central

Ahmeti, Salih; Ajazaj-Berisha, Lindita; Halili, Bahrije; Shala, Anita

2014-01-01

Crimean-Congo hemorrhagic fever is a severe viral disease caused by a Nairovirus. An atypical manifestation in the form of acute arthritis was found in a confirmed Crimean-Congo hemorrhagic fever virus Kosova-Hoti strain positive patient. Acute arthritis in Crimean-Congo hemorrhagic fever (CCHF) may be as a result of immune mechanisms or the bleeding disorder underlying CCHF. PMID:24926169

High seroprevalence of antibodies against spotted fever and scrub typhus bacteria in patients with febrile Illness, Kenya.

PubMed

Thiga, Jacqueline W; Mutai, Beth K; Eyako, Wurapa K; Ng'ang'a, Zipporah; Jiang, Ju; Richards, Allen L; Waitumbi, John N

2015-04-01

Serum samples from patients in Kenya with febrile illnesses were screened for antibodies against bacteria that cause spotted fever, typhus, and scrub typhus. Seroprevalence was 10% for spotted fever group, <1% for typhus group, and 5% for scrub typhus group. Results should help clinicians expand their list of differential diagnoses for undifferentiated fevers.

The role of movement restrictions and pre-emptive destruction in the emergency control strategy against CSF outbreaks in domestic pigs.

PubMed

Thulke, Hans-Hermann; Eisinger, Dirk; Beer, Martin

2011-04-01

Classical swine fever (CSF) outbreaks in domestic pig herds lead to the implementation of standard control measures according to legislative regulations. Ideal outbreak control entails the swift and efficient culling of all pigs on premises detected positive for CSF virus. Often all pig holdings around the detected cases are pre-emptively destroyed to exclude transmission into the neighbourhood. In addition to these measures, zones are defined in which surveillance and protection measures are intensified to prevent further distant disease spread. In particular, all movements are prohibited within standstill areas. Standstill also excludes the transport of fattened pigs to slaughter. Historical outbreaks provide evidence of the success of this control strategy. However, the extent to which the individual strategy elements contribute to this success is unknown. Therefore, we applied a spatially and temporally explicit epidemic model to the problem. Its rule-based formulation is tailored to a one-by-one model implementation of existing control concepts. Using a comparative model analysis the individual contributions of single measures to overall control success were revealed. From the results of the model we concluded that movement restrictions had the dominant impact on strategy performance suggesting a reversal of the current conceptual thinking. Additional measures such as pre-emptive culling only became relevant under imperfect compliance with movement restrictions. The importance of movement restrictions for the overall control success illustrates the need for explicit consideration of this measure when contingency strategies are being amended (e.g. emergency vaccination) and associated risks assessed. Copyright © 2011 Elsevier B.V. All rights reserved.

Community-Acquired Meningitis in Older Adults: Clinical Features, Etiology, and Prognostic Factors

PubMed Central

Wang, Amy Y.; Machicado, Jorge D.; Khoury, Nabil T.; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2014-01-01

Background Bacterial meningitis in older adults is a well-studied and serious disease, but few studies have investigated the epidemiology and outcomes of community-acquired meningitis in older adults. Methods We conducted a retrospective study of 619 adults in Houston, Texas, with community-acquired meningitis hospitalized between January 1, 2005, and January 1, 2010. Patients were categorized as older if age ≥65 (N=54) and younger if age 18–64 (N=565). An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Older patients consisted of 8.7% (54/619) of the total cohort and had higher rates of comorbidities, abnormal neurological and laboratory findings, abnormalities on computed tomography and magnetic resonance imaging of the head and adverse clinical outcomes (ACO) (p<0.05). The majority of patients (65.8%) had meningitis of unknown etiology. Bacterial meningitis was an infrequent cause (7.4%). Of the known causes, bacterial meningitis and West Nile virus were more common in older patients. In contrast, younger patients more frequently had cryptococcal and viral meningitis. On logistic regression, female gender was predictive of a poor outcome in the older patients, whereas abnormal neurologic exam, fever, and CSF glucose <45mg/dLwere significant poor prognostic factors in younger patients (p<0.05). Conclusion Most cases of community-acquired meningitis are of unknown origin. Older patients are more likely to have bacterial meningitis and West Nile virus infection when a cause can be identified. They also have more neurologic abnormalities, laboratory and imaging abnormalities, as well as adverse clinical outcomes. PMID:25370434

Towards a better understanding of Rift Valley fever epidemiology in the south-west of the Indian Ocean

PubMed Central

2013-01-01

Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in East Africa. Infection causes severe and often fatal illness in young sheep, goats and cattle. Domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. Rift Valley fever virus was historically restricted to sub-Saharan countries. The probability of Rift Valley fever emerging in virgin areas is likely to be increasing. Its geographical range has extended over the past years. As a recent example, autochthonous cases of Rift Valley fever were recorded in 2007–2008 in Mayotte in the Indian Ocean. It has been proposed that a single infected animal that enters a naive country is sufficient to initiate a major outbreak before Rift Valley fever virus would ever be detected. Unless vaccines are available and widely used to limit its expansion, Rift Valley fever will continue to be a critical issue for human and animal health in the region of the Indian Ocean. PMID:24016237

Towards a better understanding of Rift Valley fever epidemiology in the south-west of the Indian Ocean.

PubMed

Balenghien, Thomas; Cardinale, Eric; Chevalier, Véronique; Elissa, Nohal; Failloux, Anna-Bella; Jean Jose Nipomichene, Thiery Nirina; Nicolas, Gaelle; Rakotoharinome, Vincent Michel; Roger, Matthieu; Zumbo, Betty

2013-09-09

Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in East Africa. Infection causes severe and often fatal illness in young sheep, goats and cattle. Domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. Rift Valley fever virus was historically restricted to sub-Saharan countries. The probability of Rift Valley fever emerging in virgin areas is likely to be increasing. Its geographical range has extended over the past years. As a recent example, autochthonous cases of Rift Valley fever were recorded in 2007-2008 in Mayotte in the Indian Ocean. It has been proposed that a single infected animal that enters a naive country is sufficient to initiate a major outbreak before Rift Valley fever virus would ever be detected. Unless vaccines are available and widely used to limit its expansion, Rift Valley fever will continue to be a critical issue for human and animal health in the region of the Indian Ocean.

CSF and plasma testosterone in attempted suicide.

PubMed

Stefansson, Jon; Chatzittofis, Andreas; Nordström, Peter; Arver, Stefan; Åsberg, Marie; Jokinen, Jussi

2016-12-01

Very few studies have assessed testosterone levels in the cerebrospinal fluid in suicide attempters. Aggressiveness and impulsivity are common behavioural traits in suicide attempters. Dual-hormone serotonergic theory on human impulsive aggression implies high testosterone/cortisol ratio acting on the amygdala and low serotonin in the prefrontal cortex. Our aim was to examine the CSF and plasma testosterone levels in suicide attempters and in healthy volunteers. We also assessed the relationship between the testosterone/cortisol ratio, aggressiveness and impulsivity in suicide attempters. 28 medication-free suicide attempters and 19 healthy volunteers participated in the study. CSF and plasma testosterone sulfate and cortisol levels were assessed with specific radio-immunoassays. The Karolinska Scales of Personality was used to assess impulsivity and aggressiveness. All patients were followed up for cause of death. The mean follow-up period was 21 years. Male suicide attempters had higher CSF and plasma testosterone levels than age- matched male healthy volunteers. There were no significant differences in CSF testosterone levels in female suicide attempters and healthy female volunteers. Testosterone levels did not differ significantly in suicide victims compared to survivors. In male suicide attempters, the CSF testosterone/cortisol ratio showed a significant positive correlation with both impulsivity and aggressiveness. Higher CSF testosterone levels may be associated with attempted suicide in young men through association with both aggressiveness and impulsivity, a key endophenotype in young male suicide attempters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Encephalitis in a traveller with typhoid fever: efficacy of corticosteroids.

PubMed

Mellon, Guillaume; Eme, Anne-Line; Rohaut, Benjamin; Brossier, Florence; Epelboin, Loïc; Caumes, Eric

2017-09-01

Typhoid fever is a bacterial infection caused by Salmonella typhi or S. paratyphi, recognized as a classical cause of fever in returning travellers. However, neuropsychiatric presentations are rarely reported in travellers diagnosed in western countries, whereas they are more commonly described in patients treated in endemic areas. We describe such a case and discuss the pathophysiologic mechanisms of this complication. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Parental and medical knowledge and management of fever in Italian pre-school children.

PubMed

Chiappini, Elena; Parretti, Alessandra; Becherucci, Paolo; Pierattelli, Monica; Bonsignori, Francesca; Galli, Luisa; de Martino, Maurizio

2012-07-13

Guidelines for the management of fever in children have been recently published, however "fever phobia" is still spreading. To provide information which may sustain educational interventions tailored to our population we investigated the parental and medical knowledge and management of fever in preschool children. A questionnaire was administered to a convenient sample of Italian parents and paediatricians. The questionnaire elicited information about definition and cause of fever, concerns about fever, method of temperature measurement, and treatment modalities. Overall, 388 parents and 480 paediatricians were interviewed. All the parents believed that fever could cause at least one harmful effect and 89.9% (n = 349) believed that, if left untreated, it can cause brain damage or seizures. Parents used multiple resources to obtain information about fever but 67.8% (n = 264) considered paediatricians as their primary resource. Several wrong behaviours were found in the same proportions among parents and paediatricians: 78.5% of paediatricians (n = 377) and 77.8% of parents (n = 302) used physical method to reduce fever (P = 0.867); 27.0% of paediatricians (n = 103) and 21.4% (n = 83) of parents declared to alternate ibuprofen and acetaminophen (P = 0.953). Differently, 73.1% (n = 351) of paediatricians preferred oral to rectal administration of antipyretics compared to 48.7% (n = 190) of parents (P < 0.0001). Worrisomely, 1.4% of paediatricians and 1.2% of parents declared to use acetylsalicylic acid or steroids as second-choice antipyretics (P = 0.937) and 6.7% (n = 26) of parents declared to use table- or teaspoons for determining the dose of drug. Paediatricians' attitudes greatly influence the parental behaviours and beliefs. Implementation of educational programs regarding the management of the febrile child are needed in our setting.

Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings.

PubMed

Daly, R C; Su, T P; Schmidt, P J; Pickar, D; Murphy, D L; Rubinow, D R

2001-02-01

Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.

CSF 5-HIAA and DST non-suppression--orthogonal biologic risk factors for suicide in male mood disorder inpatients.

PubMed

Jokinen, Jussi; Nordström, Anna-Lena; Nordström, Peter

2009-01-30

Two biomarkers of suicide risk; non-suppression in the dexamethasone suppression test (DST) and low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been reported to be predictors of suicide in mood disorders. The interrelation of the two systems seems to be different in suicide attempters compared with depressed inpatients who have not made a suicide attempt, indicating that the two biomarkers may be seen as independent. This investigation examined the interrelation of low CSF 5-HIAA and DST non-suppression in suicide victims with mood disorder. Fifty-eight mood disorder inpatients not receiving any treatment with antidepressants underwent lumbar puncture and the DST. Plasma cortisol levels at 8:00 a.m., 4:00 p.m. and 11:00 p.m. were analysed in relation to CSF 5-HIAA. All patients were followed up for causes of death and suicides were verified with death certificates. During follow-up (mean 21 years), 11 (19%) patients had committed suicide. In male suicide victims (n=6), the serum cortisol level at 4:00 p.m. showed a significant positive correlation with CSF 5-HIAA. Low CSF 5-HIAA predicted all early suicides (within 1 year), whereas all males who committed suicide after 1 year were DST non-suppressors. In female suicide victims (n=5), the post-DST serum cortisol did not correlate with CSF 5-HIAA. Low CSF 5-HIAA and DST non-suppression are orthogonal biologic risk factors for suicide in male mood disorder inpatients. CSF 5-HIAA is associated with short-term suicide risk; dysregulation of the hypothalamic-pituitary-adrenal axis seems to be a long-term suicide predictor.

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

PubMed

Rozen, Todd; Swidan, Sahar Z

2007-01-01

To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

Massive Lower Gastrointestinal Bleed caused by Typhoid Ulcer: Conservative Management.

PubMed

Goel, Apoorv; Bansal, Roli

2017-01-01

Typhoid fever is caused by gram-negative organism Salmonella typhi. The usual presentation is high-grade fever, but complications like gastrointestinal (GI) hemorrhage and perforation are also seen frequently. With the advent of antibiotics, these complications are rarely seen now. We present a case of a young female who was admitted with a diagnosis of typhoid fever presented with a massive GI bleed from ulcers in the terminal ileum and was managed conservatively without endotherapy and surgery. How to cite this article: Goel A, Bansal R. Massive Lower Gastrointestinal Bleed caused by Typhoid Ulcer: Conservative Management. Euroasian J Hepato-Gastroenterol 2017;7(2):176-177.

The Pathogenesis of Rift Valley Fever

PubMed Central

Ikegami, Tetsuro; Makino, Shinji

2011-01-01

Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. PMID:21666766

Pathology Review of Two New Rift Valley Fever Virus Ruminant Models

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neona...

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

PubMed Central

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

2015-01-01

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

Corticosteroid Treatment for Prolonged Fever in Hepatosplenic Cat-Scratch Disease: A Case Study.

PubMed

Phan, Amanda; Castagnini, Luis A

2017-12-01

Hepatosplenic cat-scratch disease (CSD) may cause prolonged fever. We present the case of a 4-year-old boy with confirmed hepatosplenic CSD with fever lasting 3 months despite use of multiple different antimicrobial agents. The patient became afebrile soon after corticosteroid therapy was started. Our case indicates corticosteroids may be useful in patients with hepatosplenic CSD and prolonged fever.

Penetration of amoxicillin and potassium clavulanate into the cerebrospinal fluid of patients with inflamed meninges.

PubMed Central

Bakken, J S; Bruun, J N; Gaustad, P; Tasker, T C

1986-01-01

A single intravenous dose of 2.0 g of amoxicillin and 0.2 g of potassium clavulanate was given to patients with bacterial meningitis, and the pharmacokinetics of both drugs in the cerebrospinal fluid (CSF) and plasma were evaluated. Twenty-one patients aged 14 to 76 years were studied. Both amoxicillin and potassium clavulanate were detectable in the CSF as early as 1 h and reached peak concentrations by approximately 2 h. The highest mean CSF concentrations were 2.25 micrograms/ml for amoxicillin and 0.25 micrograms/ml for potassium clavulanate and were found in patients with moderately or severely inflamed meninges. The CSF penetration relative to plasma for amoxicillin and potassium clavulanate was 5.8 and 8.4%, respectively. These levels suggest that the amoxicillin-potassium clavulanate combination may be effective for the treatment of bacterial meningitis caused by beta-lactamase-producing pathogens. PMID:3777911

Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia.

PubMed

Gómez Raposo, César; Pinto Marín, Alvaro; González Barón, Manuel

2006-10-01

The hematopoietic growth factors (HGFs) are a family of glycoproteins which plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, and in the functions of some mature cells. More than 20 different molecules of HGF have been identified. Among them, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been demostrated to be effective in reducing the incidence of febrile neutropenia when administered inmediately after chemotherapy and as supportive therapy in patients undergoing bone marrow transplantation. Chemotherapy used for treatment of cancer often causes neutropenia, which may be profound, requiring hospitalization, and leading to potentially fatal infection. The uses of the recombinant human hematopoietic colony-stimulating factors G-CSF and GM-CSF for treatment and prophylaxis of chemotherapy-induced febrile neutropenia will be reviewed here.

Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis.

PubMed

Qvarnstrom, Yvonne; Xayavong, Maniphet; da Silva, Ana Cristina Aramburu; Park, Sarah Y; Whelen, A Christian; Calimlim, Precilia S; Sciulli, Rebecca H; Honda, Stacey A A; Higa, Karen; Kitsutani, Paul; Chea, Nora; Heng, Seng; Johnson, Stuart; Graeff-Teixeira, Carlos; Fox, LeAnne M; da Silva, Alexandre J

2016-01-01

Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis. © The American Society of Tropical Medicine and Hygiene.

[Bath Plug Closure Method for Cerebrospinal Fluid Leakage by Endoscopic Endonasal Approach:Cooperative Treatment by Neurosurgeons and Otolaryngologists].

PubMed

Kawaguchi, Tomohiro; Arakawa, Kazuya; Nomura, Kazuhiro; Ogawa, Yoshikazu; Katori, Yukio; Tominaga, Teiji

2017-12-01

Endoscopic endonasal surgery, an innovative surgical technique, is used to approach sinus lesions, lesions of the skull base, and intradural tumors. The cooperation of experienced otolaryngologists and neurosurgeons is important to achieve safe and reliable surgical results. The bath plug closure method is a treatment option for patients with cerebrospinal fluid(CSF)leakage. Although it includes dural and/or intradural procedures, surgery tends to be performed by otolaryngologists because its indications, detailed maneuvers, and pitfalls are not well recognized by neurosurgeons. We reviewed the cases of patients with CSF leakage treated by using the bath plug closure method with an endoscopic endonasal approach at our institution. Three patients were treated using the bath plug closure method. CSF leakage was caused by a meningocele in two cases and trauma in one case. No postoperative intracranial complications or recurrence of CSF leakage were observed. The bath plug closure method is an effective treatment strategy and allows neurosurgeons to gain in-depth knowledge of the treatment options for CSF leakage by using an endoscopic endonasal approach.

Long-term Response of Cerebrospinal Fluid Pressure in Patients with Idiopathic Intracranial Hypertension - A Prospective Observational Study.

PubMed

Gafoor, V Abdul; Smita, B; Jose, James

2017-01-01

Idiopathic intracranial hypertension (IIH) is increased intracranial pressure (ICP) with normal cerebrospinal fluid (CSF) contents, in the absence of an intracranial mass, hydrocephalus, or other identifiable causes. The current knowledge of the treatment outcome of IIH is limited, and the data on the natural history of this entity are scant. The objective of the study is to study the treatment response of IIH by serially measuring the CSF opening pressure and to delineate the factors influencing the same. A prospective observational study in a cohort of fifty patients with IIH in whom CSF opening pressure was serially measured at pre-specified intervals. The mean CSF opening pressure at baseline was 302.4 ± 51.69 mm of H 2 O (range: 220-410). Even though a higher body mass index (BMI) showed a trend toward a higher CSF opening pressure, the association was not significant ( P = 0.168). However, the age of the patient had a significant negative correlation with the CSF pressure ( P = 0.006). The maximum reduction in CSF pressure occurred in the first 3 months of treatment, and thereafter it plateaued. Remission was attained in 12 (24%) patients. BMI had the strongest association with remission ( P = 0.001). In patients with IIH, treatment response is strongly related to BMI. However, patients with normal BMI are also shown to relapse and hence should have continuous, long-term follow-up. The reduction in CSF pressure attained in the first 3 months could reflect the long-term response to treatment.

Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

PubMed

Hozumi, Isao; Kurita, Hisaka; Ozawa, Kazuhiro; Furuta, Nobuyuki; Inden, Masatoshi; Sekine, Shin-Ichiro; Yamada, Megumi; Hayashi, Yuichi; Kimura, Akio; Inuzuka, Takashi; Seishima, Mitsuru

2018-05-15

Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1. Copyright © 2018 Elsevier B.V. All rights reserved.

Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood-Brain Barrier Disruption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogami, Ryo, E-mail: ogami.r@mazda.co.jp; Nakahara, Toshinori; Hamasaki, Osamu

2011-10-15

Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors weremore » examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.« less

Suppressive Effects on the Immune Response and Protective Immunity to a JEV DNA Vaccine by Co-administration of a GM-CSF-Expressing Plasmid in Mice

PubMed Central

Chen, Hui; Gao, Na; Fan, Dongying; Wu, Jiangman; Zhu, Junping; Li, Jieqiong; Wang, Juan; Chen, Yanlei; An, Jing

2012-01-01

As a potential cytokine adjuvant of DNA vaccines, granulocyte-macrophage colony–stimulating factor (GM-CSF) has received considerable attention due to its essential role in the recruitment of antigen-presenting cells, differentiation and maturation of dendritic cells. However, in our recent study of a Japanese encephalitis virus (JEV) DNA vaccine, co-inoculation of a GM-CSF plasmid dramatically suppressed the specific IgG response and resulted in decreased protection against JEV challenge. It is known that GM-CSF has been used in clinic to treat neutropenia for repopulating myeloid cells, and as an adjuvant in vaccine studies; it has shown various effects on the immune response. Therefore, in this study, we characterized the suppressive effects on the immune response to a JEV DNA vaccine by the co-administration of the GM-CSF-expressing plasmid and clarified the underlying mechanisms of the suppression in mice. Our results demonstrated that co-immunization with GM-CSF caused a substantial dampening of the vaccine-induced antibody responses. The suppressive effect was dose- and timing-dependent and likely related to the immunogenicity of the antigen. The suppression was associated with the induction of immature dendritic cells and the expansion of regulatory T cells but not myeloid-derived suppressor cells. Collectively, our findings not only provide valuable information for the application of GM-CSF in clinic and using as a vaccine adjuvant but also offer further insight into the understanding of the complex roles of GM-CSF. PMID:22493704

Analytical variables affecting analysis of F2-isoprostanes and F4-neuroprostanes in human cerebrospinal fluid by gas chromatography/mass spectrometry.

PubMed

Yen, Hsiu-Chuan; Wei, Hsing-Ju; Chen, Ting-Wei

2013-01-01

F2-isoprostanes (F2-IsoPs) are a gold marker of lipid peroxidation in vivo, whereas F4-neuroprostanes (F4-NPs) measured in cerebrospinal fluid (CSF) or brain tissue selectively indicate neuronal oxidative damage. Gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is the most sensitive and robust method for quantifying these compounds, which is essential for CSF samples because abundance of these compounds in CSF is very low. The present study revealed potential interferences on the analysis of F2-IsoPs and F4-NPs in CSF by GC/NICI-MS due to the use of improper analytical methods that have been employed in the literature. First, simultaneous quantification of F2-IsoPs and F4-NPs in CSF samples processed for F4-NPs analysis could cause poor chromatographic separation and falsely higher F2-IsoPs values for CSF samples with high levels of F2-IsoPs and F4-NPs. Second, retention of unknown substances in GC columns from CSF samples during F4-NPs analysis and from plasma samples during F2-IsoPs analysis might interfere with F4-NPs analysis of subsequent runs, which could be solved by holding columns at a high temperature for a period of time after data acquisition. Therefore, these special issues should be taken into consideration when performing analysis of F2-IsoPs and F4-NPs in CSF to avoid misleading results.

Analytical Variables Affecting Analysis of F2-Isoprostanes and F4-Neuroprostanes in Human Cerebrospinal Fluid by Gas Chromatography/Mass Spectrometry

PubMed Central

Yen, Hsiu-Chuan; Wei, Hsing-Ju; Chen, Ting-Wei

2013-01-01

F2-isoprostanes (F2-IsoPs) are a gold marker of lipid peroxidation in vivo, whereas F4-neuroprostanes (F4-NPs) measured in cerebrospinal fluid (CSF) or brain tissue selectively indicate neuronal oxidative damage. Gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is the most sensitive and robust method for quantifying these compounds, which is essential for CSF samples because abundance of these compounds in CSF is very low. The present study revealed potential interferences on the analysis of F2-IsoPs and F4-NPs in CSF by GC/NICI-MS due to the use of improper analytical methods that have been employed in the literature. First, simultaneous quantification of F2-IsoPs and F4-NPs in CSF samples processed for F4-NPs analysis could cause poor chromatographic separation and falsely higher F2-IsoPs values for CSF samples with high levels of F2-IsoPs and F4-NPs. Second, retention of unknown substances in GC columns from CSF samples during F4-NPs analysis and from plasma samples during F2-IsoPs analysis might interfere with F4-NPs analysis of subsequent runs, which could be solved by holding columns at a high temperature for a period of time after data acquisition. Therefore, these special issues should be taken into consideration when performing analysis of F2-IsoPs and F4-NPs in CSF to avoid misleading results. PMID:23957004

Malaria

MedlinePlus

Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium ... Malaria is caused by a parasite that is passed to humans by the bite of infected anopheles ...

Hemorrhagic

MedlinePlus

... Hemorrhagic diseases are caused by bleeding, or they result in bleeding (hemorrhaging). Related topics include: Primary thrombocythemia (hemorrhagic thrombocythemia) Stroke Yellow fever Bleeding disorders Ebola fever Dengue hemorrhagic ...

Neutropenic Fever.

PubMed

White, Lindsey; Ybarra, Michael

2017-12-01

Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients. Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of post-stroke fever and infections: a systematic review and meta-analysis.

PubMed

Wästfelt, Maja; Cao, Yang; Ström, Jakob O

2018-04-23

Fever after stroke is common, and often caused by infections. In the current study, we aimed to test the hypothesis that pneumonia, urinary tract infection and all-cause fever (thought to include at least some proportion of endogenous fever) have different predicting factors, since they differ regarding etiology. PubMed was searched systematically for articles describing predictors for post-stroke pneumonia, urinary tract infection and all-cause fever. A total of 5294 articles were manually assessed; first by title, then by abstract and finally by full text. Data was extracted from each study, and for variables reported in 3 or more articles, a meta-analysis was performed using a random effects model. Fifty-nine articles met the inclusion criteria. It was found that post-stroke pneumonia is predicted by age OR 1.07 (1.04-1.11), male sex OR 1.42 (1.17-1.74), National Institutes of Health Stroke Scale (NIHSS) OR 1.07 (1.05-1.09), dysphagia OR 3.53 (2.69-4.64), nasogastric tube OR 5.29 (3.01-9.32), diabetes OR 1.15 (1.08-1.23), mechanical ventilation OR 4.65 (2.50-8.65), smoking OR 1.16 (1.08-1.26), Chronic Obstructive Pulmonary Disease (COPD) OR 4.48 (1.82-11.00) and atrial fibrillation OR 1.37 (1.22-1.55). An opposite relation to sex may exist for UTI, which seems to be more common in women. The lack of studies simultaneously studying a wide range of predictors for UTI or all-cause fever calls for future research in this area. The importance of new research would be to improve our understanding of fever complications to facilitate greater vigilance, monitoring, prevention, diagnosis and treatment.

Current status of rift valley fever vaccine development

USDA-ARS?s Scientific Manuscript database

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease that presents substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Pheuniviridae within the order Bunyavirales. The wide distribution of ...

Recurrent Fever in Children

PubMed Central

Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

2016-01-01

Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time. PMID:27023528

Recurrent Fever in Children.

PubMed

Torreggiani, Sofia; Filocamo, Giovanni; Esposito, Susanna

2016-03-25

Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.

[Fever profile of febrile neutropenia in patients treated with cancer chemotherapy for hematological malignancies].

PubMed

Tamai, Yotaro; Imataki, Osamu; Kawakami, Kimihiro

2010-05-01

It is important to diagnose infectious events in cancer patients during chemotherapy. Since many of them have complications of febrile neutropenia (FN), determining its cause is critical for their treatment course. We analyzed all febrile events (>38.0 degrees C, single axillary temperature) in hospitalized cancer patients treated at Shizuoka Cancer Center over a period of 8 months. Based on the clinical presentation at the onset, we estimated the cause of fever and classified it as infection, tumor fever, immunologic reaction or unknown. Clinical presentations found at the onset of FN were categorized into 4 groups: (1) oral mucositis, and (2) respiratory, (3) gastrointestinal and (4) cutaneous findings. We detected 85 febrile episodes (median age 58, range 26 approximately 86; 37 males and 48 females). Neutropenia was observed (500/mL) in 52. 9% (45/85) of the patients and clinical symptoms were detected in 74.1% (63/85). In eleven of 18 infection-proven cases, we successfully predicted the infection focus at the onset of fever. Multivariate analysis revealed that initial high fever, antimicrobial prophylaxis, cutaneous findings and severe neutropenia were important influencing factors in predicting infectious disease during FN. Physical examination can support the diagnosis of the cause of fever in FN patients.

The use of dried cerebrospinal fluid filter paper spots as a substrate for PCR diagnosis of the aetiology of bacterial meningitis in the Lao PDR

PubMed Central

Elliott, I; Dittrich, S; Paris, D; Sengduanphachanh, A; Phoumin, P; Newton, P N

2013-01-01

We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/μL (interquartile range 5.5 GE/μL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 104 GE/μL (1.2 × 105; 1 to 6.1 × 106 DNA GE/μL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies. PMID:23738720

Acute radiation syndrome (ARS) - treatment of the reduced host defense.

PubMed

Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

2012-01-01

The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. Review of the current literature. The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage's important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250-400 μg GM-CSF/m(2) or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14-21 days. The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction.

GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

PubMed

Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

2017-11-01

Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 during wound healing. © 2018 by the Wound Healing Society.

East coast fever caused by Theileria parva is characterized by macrophage activation associated with vasculitis and respiratory failure

USDA-ARS?s Scientific Manuscript database

Respiratory failure and death in East Coast Fever (ECF), a clinical syndrome of African cattle caused by the apicomplexan parasite Theileria parva, has historically been attributed to pulmonary infiltration by infected lymphocytes. However, immunohistochemical staining of tissue from T. parva infect...

Viral hemorrhagic fevers of animals caused by DNA viruses

USDA-ARS?s Scientific Manuscript database

Here we outline serious diseases of food and fiber animals that cause damaging economic effect on products all over the world. The only vector-borne DNA virus is included here, such as African swine fever virus, and the herpes viruses discussed have a complex epidemiology characterized by outbreak...

Utility of Antibody Avidity for Rift Valley Fever Virus Vaccine Potency and Immunogenicity Studies

USDA-ARS?s Scientific Manuscript database

Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in sub-Saharan Afr...

Potential for North American Mosquitoes to Transmit Rift Valley Fever Virus

USDA-ARS?s Scientific Manuscript database

The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, including North Ameri...

Potential for North American mosquitoes to transmit Rift Valley fever virus

USDA-ARS?s Scientific Manuscript database

The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, possibly even North A...

Viral hemorrhagic fevers of animals caused by DNA viruses

USDA-ARS?s Scientific Manuscript database

Here we outline serious diseases of food and fiber animals that cause damaging economic effects on producers all over the world. The only vector-borne DNA virus is included here (i.e., African swine fever virus), and the herpesviruses discussed have a complex epidemiology characterized by outbreaks ...

Community Knowledge and Attitudes and Health Workers' Practices regarding Non-malaria Febrile Illnesses in Eastern Tanzania

PubMed Central

Chipwaza, Beatrice; Mugasa, Joseph P.; Mayumana, Iddy; Amuri, Mbaraka; Makungu, Christina; Gwakisa, Paul S.

2014-01-01

Introduction Although malaria has been the leading cause of fever for many years, with improved control regimes malaria transmission, morbidity and mortality have decreased. Recent studies have increasingly demonstrated the importance of non-malaria fevers, which have significantly improved our understanding of etiologies of febrile illnesses. A number of non-malaria febrile illnesses including Rift Valley Fever, dengue fever, Chikungunya virus infection, leptospirosis, tick-borne relapsing fever and Q-fever have been reported in Tanzania. This study aimed at assessing the awareness of communities and practices of health workers on non-malaria febrile illnesses. Methods Twelve focus group discussions with members of communities and 14 in-depth interviews with health workers were conducted in Kilosa district, Tanzania. Transcripts were coded into different groups using MaxQDA software and analyzed through thematic content analysis. Results The study revealed that the awareness of the study participants on non-malaria febrile illnesses was low and many community members believed that most instances of fever are due to malaria. In addition, the majority had inappropriate beliefs about the possible causes of fever. In most cases, non-malaria febrile illnesses were considered following a negative Malaria Rapid Diagnostic Test (mRDT) result or persistent fevers after completion of anti-malaria dosage. Therefore, in the absence of mRDTs, there is over diagnosis of malaria and under diagnosis of non-malaria illnesses. Shortages of diagnostic facilities for febrile illnesses including mRDTs were repeatedly reported as a major barrier to proper diagnosis and treatment of febrile patients. Conclusion Our results emphasize the need for creating community awareness on other causes of fever apart from malaria. Based on our study, appropriate treatment of febrile patients will require inputs geared towards strengthening of diagnostic facilities, drugs availability and optimal staffing of health facilities. PMID:24852787

Data-Driven Risk Assessment from Small Scale Epidemics: Estimation and Model Choice for Spatio-Temporal Data with Application to a Classical Swine Fever Outbreak

PubMed Central

Gamado, Kokouvi; Marion, Glenn; Porphyre, Thibaud

2017-01-01

Livestock epidemics have the potential to give rise to significant economic, welfare, and social costs. Incursions of emerging and re-emerging pathogens may lead to small and repeated outbreaks. Analysis of the resulting data is statistically challenging but can inform disease preparedness reducing potential future losses. We present a framework for spatial risk assessment of disease incursions based on data from small localized historic outbreaks. We focus on between-farm spread of livestock pathogens and illustrate our methods by application to data on the small outbreak of Classical Swine Fever (CSF) that occurred in 2000 in East Anglia, UK. We apply models based on continuous time semi-Markov processes, using data-augmentation Markov Chain Monte Carlo techniques within a Bayesian framework to infer disease dynamics and detection from incompletely observed outbreaks. The spatial transmission kernel describing pathogen spread between farms, and the distribution of times between infection and detection, is estimated alongside unobserved exposure times. Our results demonstrate inference is reliable even for relatively small outbreaks when the data-generating model is known. However, associated risk assessments depend strongly on the form of the fitted transmission kernel. Therefore, for real applications, methods are needed to select the most appropriate model in light of the data. We assess standard Deviance Information Criteria (DIC) model selection tools and recently introduced latent residual methods of model assessment, in selecting the functional form of the spatial transmission kernel. These methods are applied to the CSF data, and tested in simulated scenarios which represent field data, but assume the data generation mechanism is known. Analysis of simulated scenarios shows that latent residual methods enable reliable selection of the transmission kernel even for small outbreaks whereas the DIC is less reliable. Moreover, compared with DIC, model choice based on latent residual assessment correlated better with predicted risk. PMID:28293559

Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

NASA Technical Reports Server (NTRS)

Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

1998-01-01

The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

Involvement of suppressor of cytokine signaling-1 in globular adiponectin-induced granulocyte colony-stimulating factor in RAW 264 cell.

PubMed

Fujimoto, Akie; Akifusa, Sumio; Hirofuji, Takao; Yamashita, Yoshihisa

2011-09-01

We previously demonstrated that treatment with a globular type of adiponectin (gAd) induced expression of granulocyte colony-stimulating factor (G-CSF) via the MEK/ERK signaling pathway in a murine macrophage cell line, RAW 264. In the present study, we investigated whether suppressor of cytokine signaling-1 (SOCS1) has roles in the regulation of gAd-induced G-CSF generation. Intracellular G-CSF generation induced by gAd treatment peaked after 10h and then attenuated. SOCS1 mRNA and protein were expressed at 1h and 4h after gAd treatment, respectively. Overexpression of SOCS1 reduced G-CSF generation and phosphorylation of ERK, JNK, and p38 MAPK in gAd-treated cells. While gAd treatment induced the translocation of STAT3 to the nucleus under control conditions, STAT3 stayed in the cytosol when SOCS1 was overexpressed. Additionally, knockdown of SOCS1 by interfering RNA caused levels of G-CSF to continue to rise beyond 10h after gAd treatment. These results suggest that SOCS1 is involved in providing negative feedback for gAd-induced production of G-CSF. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detection by PCR of Enteroviruses in Cerebrospinal Fluid during a Summer Outbreak of Aseptic Meningitis in Switzerland

PubMed Central

Gorgievski-Hrisoho, Meri; Schumacher, Jean-Daniel; Vilimonovic, Nevenka; Germann, Daniel; Matter, Lukas

1998-01-01

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. PMID:9705364

Prolonged fever and involuntary weight loss as manifestations of bacterial endocarditis: A case report

NASA Astrophysics Data System (ADS)

Sukmawati, N. M. D. D.; Merati, T. P.; Somia, A.; Utama, S.; Gayatri, Y.

2018-03-01

We reported an unusual presentation of prolonged fever and involuntary weight loss in older adult as a manifestation of infective bacterial endocarditis. The patient had pre-existing compensated asymptomatic valvular heart disease without treatment. A positive fecal occult blood test is prompting an investigation of malignancy of gastrointestinal as one of other possible cause of prolonged fever with wasting, evaluation of HIV serostatus shows seronegative. The case fulfilled criteria for definitive infective endocarditis: one major criterion of positive blood culture for Streptococcus mitis, which was one of viridans group streptococci and three minor criteria of fever at least 38°Celsius, immunologic phenomena in the form of glomerulonephritis, and a predisposing heart condition. One course of third-generation cephalosporin successfully cleared the Streptococcus mitis infection proven by culture. Infective endocarditis should be considered as one of the causes of prolonged fever with wasting, especially in cases with the previous history of heart disease.

Determination and Validation of a Lower Cut Off Value of Cerebrospinal Fluid Adenosine Deaminase (CSF-ADA) Activity in Diagnosis of Tuberculous Meningitis.

PubMed

Raviraj; Henry, Renoy A; Rao, G Ganapathi

2017-04-01

Tuberculous meningitis is an infection of the meninges caused by Mycobacterium tuberculosis . It is one of the most common infectious diseases of the Central Nervous System (CNS) and a major health problem in developing countries like India. If there is delay in diagnosis and initiation of specific treatment, it causes significant morbidity and mortality. CSF-ADA 10 U/l is the standard cut off value that is used for differentiation between Tuberculous (TBM) and Non-Tuberculous Meningitis (non-TBM). To determine and validate a lower cut off value for CSF-ADA for diagnosing TBM in an Indian setting. This was a prospective study involving 85 cases of meningitis whose CSF were analysed and ADA estimated using an enzymatic deamination assay kit. Diagnosis of various types of meningitis was made based on specified diagnostic criteria. The comparison of mean value of CSF- ADA activity of the two types of meningitis was done using two Sample t-test. A p-value of <0.05 was considered as significant. Cut off value to differentiate between TBM and non-TBM meningitis was determined using ROC curve analysis. The CSF-ADA activity of TBM and non-TBM cases was compared. The mean CSF-ADA activity was found to be significantly higher in TBM patients (10.97±4.43; Mean±SD) than in non-TBM patients (5.09±1.53) which was statistically significant with a p-value of <0.001. A cut off value of 6.65 was calculated using ROC curve for the diagnosis of TBM which gave a sensitivity of 85.3% and a specificity of 84.3% for differentiating TBM from non-TBM. The positive predictive value was 78.3% and negative predictive value of 89.5% using the above cut off. The positive likelihood ratio was 5.44 and negative likelihood ratio of 0.17 when this lower cut off value was applied. This study has demonstrated that CSF-ADA can be used as an important diagnostic tool in early diagnosis of TBM using a cut off value of 6.65. This cut off value gave a good sensitivity and specificity in differentiating it from non-TBM.

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

DTIC Science & Technology

2003-12-01

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques Evidence that Dendritic Cells Are Early and Sustained Targets of Infection Thomas W...is known about the development of EBOV hemorrhagic fever . In the present study, 21 cynomol- gus monkeys were experimentally infected with EBOV and...Am J Pathol 2003, 163:2347–2370) Among viruses causing hemorrhagic fever (HF), and among emerging infectious diseases with global impact in general

Diagnosis and Differential Diagnosis of Hydrocephalus in Adults.

PubMed

Langner, Sönke; Fleck, Steffen; Baldauf, Jörg; Mensel, Birger; Kühn, Jens Peter; Kirsch, Michael

2017-08-01

Purpose  Hydrocephalus is caused by an imbalance of production and absorption of cerebrospinal fluid (CSF) or obstruction of its pathways, resulting in ventricular dilatation and increased intracranial pressure. Imaging plays a crucial role in the diagnosis, differential diagnosis and planning of treatment. Methods  This review article presents the different types of hydrocephalus und their typical imaging appearance, describes imaging techniques, and discusses differential diagnoses of the different forms of hydrocephalus. Results and Conclusion  Imaging plays a central role in the diagnosis of hydrocephalus. While magnetic resonance (MR) imaging is the first-line imaging modality, computed tomography (CT) is often the first-line imaging test in emergency patients. Key points   · Occlusive hydrocephalus is caused by obstruction of CSF pathways.. · Malabsorptive hydrocephalus is caused by impaired CSF absorption.. · The MR imaging protocol should always include sagittal high-resolution T2-weighted images.. · When an inflammatory etiology is suspected, imaging with contrast agent administration is necessary.. Citation Format · Langner S, Fleck S, Baldauf J et al. Diagnosis and Differential Diagnosis of Hydrocephalus in Adults. Fortschr Röntgenstr 2017; 189: 728 - 739. © Georg Thieme Verlag KG Stuttgart · New York.

Molecular Detection of Rickettsia amblyommii in Amblyomma americanum Parasitizing Humans

DTIC Science & Technology

2010-01-01

Rocky Mountain spotted fever [RMSF...diseases in North Carolina: is "Rickettsia amblyommii" a possible cause of rickettsiosis reported as Rocky Mountain spotted fever ? Vector Borne Zoonot...HN, et al. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever . Clin Infect Dis 2008; 47:1188-

The maxillary palp of aedes aegypti, a model of multisensory integration

USDA-ARS?s Scientific Manuscript database

Female yellow-fever mosquitoes, Aedes aegypti, are obligate blood-feeders and vectors of the pathogens that cause dengue fever, yellow fever and Chikungunya. This feeding behavior concludes a series of multisensory events guiding the mosquito to its host from a distance. The antennae and maxillary...

[Simultaneous meningitis caused by Candida and tuberculosis as manifestation of AIDS].

PubMed

Arias Gómez, M; Requena Caballero, I; Lema Devesa, C; Suárez Dono, J; Llovo Martínez, J; Martino, V

2001-09-01

Opportunistic germs meningoencephalitis plays an important role within neurologic pathology in aids. Treponema pallidum and Mycobacterium tuberculosis among bacteries, Cryptococcus neoformans in fungus group, Toxoplasma gondii in protozoos group and Papovavirus JC in virus one are the most frequently implicated germs. Sometimes infections are mixed. We present a simultaneous meningitis case produced by Candida albicans and Mycobacterium tuberculosis that coursed with neutrophilic pleocytosis in CSF and normal glucose CSF levels, consisting the clinical debut of aids. Repeated CSF examinations are the diagnostic clue owing, as in our case, instauration of early treatment. Present case of simultaneous tuberculous and candidiasic meningitis is the first one described in a HIV positive patient.

Climate controls on valley fever incidence in Kern County, California

NASA Astrophysics Data System (ADS)

Zender, Charles S.; Talamantes, Jorge

2006-01-01

Coccidiodomycosis (valley fever) is a systemic infection caused by inhalation of airborne spores from Coccidioides immitis, a soil-dwelling fungus found in the southwestern United States, parts of Mexico, and Central and South America. Dust storms help disperse C. immitis so risk factors for valley fever include conditions favorable for fungal growth (moist, warm soil) and for aeolian soil erosion (dry soil and strong winds). Here, we analyze and inter-compare the seasonal and inter-annual behavior of valley fever incidence and climate risk factors for the period 1980-2002 in Kern County, California, the US county with highest reported incidence. We find weak but statistically significant links between disease incidence and antecedent climate conditions. Precipitation anomalies 8 and 20 months antecedent explain only up to 4% of monthly variability in subsequent valley fever incidence during the 23 year period tested. This is consistent with previous studies suggesting that C. immitis tolerates hot, dry periods better than competing soil organisms and, as a result, thrives during wet periods following droughts. Furthermore, the relatively small correlation with climate suggests that the causes of valley fever in Kern County could be largely anthropogenic. Seasonal climate predictors of valley fever in Kern County are similar to, but much weaker than, those in Arizona, where previous studies find precipitation explains up to 75% of incidence. Causes for this discrepancy are not yet understood. Higher resolution temporal and spatial monitoring of soil conditions could improve our understanding of climatic antecedents of severe epidemics.

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience.

PubMed

García-Recio, Marta; Cladera, Antonia; Bento, Leyre; Dominguez, Julia; Ruiz de Gracia, Silvia; Sartori, Francesca; Del Campo, Raquel; García, Lucia; Ballester, Carmen; Gines, Jordi; Bargay, Joan; Sampol, Antonia; Gutiérrez, Antonio

2017-01-01

Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20-30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity. Other options are the administration of intrathecal (IT) MTX, cytarabine or liposomal cytarabine (ITLC). Our aim is to analyze the experience of the centers of the Balearic Lymphoma Group (BLG) about the toxicity and efficacy of ITLC in the prophylaxis and therapy of CNS lymphomatosis. We retrospectively reviewed cases from 2005 to 2015 (n = 58) treated with ITLC. Our toxicity results were: 33% headache, 20% neurological deficits, 11% nausea, 9% dizziness, 4% vomiting, 4% fever, 2% transient blindness and 2% photophobia. In the prophylactic cohort (n = 26) with a median follow-up of 55 months (17-81) only 3 CNS relapses (11%) were observed (testicular DLBCL, Burkitt and plasmablastic lymphoma, with a cumulative incidence of 8%, 14% and 20% respectively). In the treatment cohort (n = 32), CSF complete clearance was obtained in 77% cases. Median OS was 6 months (0-16). Death causes were lymphoma progression (19 patients, 79%), treatment toxicity (2 patients) and non-related (3 patients, 12%). Toxicity profile was good especially when concomitant dexamethasone was administered. In the prophylactic cohort the incidence of CNS relapse in DLBCL group was similar to previously reported for HDMTX and much better than IT MTX. A high number of ITLC injections was associated with better rates of CSF clearance, clinical responses, PFS and lower relapses. Survival is still poor in CNS lymphomatosis and new therapeutic approaches are still needed.

Regulatory T Cells in Peripheral Blood and Cerebrospinal Fluid of Syphilis Patients with and without Neurological Involvement

PubMed Central

Li, Kang; Wang, Cuini; Lu, Haikong; Gu, Xin; Guan, Zhifang; Zhou, Pingyu

2013-01-01

Background Syphilis, a sexually transmitted disease caused by spirochetal bacterium Treponema pallidum, can progress to affect the central nervous system, causing neurosyphilis. Accumulating evidence suggest that regulatory T cells (Tregs) may play an important role in the pathogenesis of syphilis. However, little is known about Treg response in neurosyphilis. Methodology/Principal Findings We analyzed Treg frequencies and Transforming Growth Factor-β (TGF-β) levels in the blood and CSF of 431 syphilis patients without neurological involvement, 100 neurosyphilis patients and 100 healthy donors. Suppressive function of Tregs in peripheral blood was also assessed. Among syphilis patients without neurological involvement, we found that secondary and serofast patients had increased Treg percentages, suppressive function and TGF-β levels in peripheral blood compared to healthy donors. Serum Rapid Plasma Reagin (RPR) titers were positively correlated with Treg numbers in these patients. Compared to these syphilis patients without neurological involvement, neurosyphilis patients had higher Treg frequency in peripheral blood. In the central nervous system, neurosyphilis patients had higher numbers of leukocytes in CSF compared to syphilis patients without neurological involvement. CD4+ T cells were the predominant cell type in the inflammatory infiltrates in CSF of neurosyphilis patients. Interestingly, among these neurosyphilis patients, a significant decrease in CSF CD4+ CD25high Treg percentage and number was observed in symptomatic neurosyphilis patients compared to those of asymptomatic neurosyphilis patients, which may be associated with low CSF TGF-β levels. Conclusions Our findings suggest that Tregs might play an important role in both bacterial persistence and neurologic compromise in the pathogenesis of syphilis. PMID:24244772

CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.

PubMed

Fardo, David W; Katsumata, Yuriko; Kauwe, John S K; Deming, Yuetiva; Harari, Oscar; Cruchaga, Carlos; Nelson, Peter T

2017-04-01

Hippocampal sclerosis of aging (HS-Aging) is a common cause of dementia in older adults. We tested the variability in cerebrospinal fluid (CSF) proteins associated with previously identified HS-Aging risk single nucleotide polymorphisms (SNPs). Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454). For controls, non-HS-Aging SNPs in APOE (rs429358/rs7412) and MAPT (rs8070723) were also analyzed against Aβ1-42 and total tau CSF analytes. The GRN risk SNP (rs5848) status correlated with variation in CSF proteins, with the risk allele (T) associated with increased levels of AXL Receptor Tyrosine Kinase (AXL), TNF-Related Apoptosis-Inducing Ligand Receptor 3 (TRAIL-R3), Vascular Cell Adhesion Molecule-1 (VCAM-1) and clusterin (CLU) (all p<0.05 after Bonferroni correction). The TRAIL-R3 correlation was significant in meta-analysis with an additional dataset (p=5.05×10 -5 ). Further, the rs5848 SNP status was associated with increased CSF tau protein - a marker of neurodegeneration (p=0.015). These data are remarkable since this GRN SNP has been found to be a risk factor for multiple types of dementia-related brain pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular determinants of Pichinde virus infection of guinea pigs--a small animal model system for arenaviral hemorrhagic fevers.

PubMed

Liang, Yuying; Lan, Shuiyun; Ly, Hinh

2009-09-01

Arenaviruses are enveloped single-strand RNA viruses that mostly have natural hosts in rodents. Upon infection of humans, several arenaviruses can cause severe hemorrhagic fever diseases, including Lassa fever that is endemic in West Africa. The virulence mechanism of these deadly arenaviruses can be studied in a safe and economical small animal model-guinea pigs infected by a nonpathogenic arenavirus Pichinde virus (PICV), a virulent strain of which can cause similar disease syndromes in guinea pigs as arenaviral hemorrhagic fevers in humans. We have recently developed molecular clones for both the virulent and avirulent strains of PICV. Using the available reverse genetics tools, we are characterizing the molecular determinants of virulent arenavirus infections in vivo.

Rickettsial Infections and Fever, Vientiane, Laos

PubMed Central

Phongmany, Simaly; Rolain, Jean-Marc; Phetsouvanh, Rattanaphone; Blacksell, Stuart D.; Soukkhaseum, Vimone; Rasachack, Bouachanh; Phiasakha, Khamphong; Soukkhaseum, Surn; Frichithavong, Khamthavi; Chu, Vang; Keolouangkhot, Valy; Martinez-Aussel, Bertrand; Chang, Ko; Darasavath, Chirapha; Rattanavong, Oudayvone; Sisouphone, Siho; Mayxay, Mayfong; Vidamaly, Sisouphane; Parola, Philippe; Thammavong, Chanpheng; Heuangvongsy, Mayboun; Syhavong, Bounkong; Raoult, Didier; White, Nicholas J.

2006-01-01

Rickettsial diseases have not been described previously from Laos, but in a prospective study, acute rickettsial infection was identified as the cause of fever in 115 (27%) of 427 adults with negative blood cultures admitted to Mahosot Hospital in Vientiane, Laos. The organisms identified by serologic analysis were Orientia tsutsugamushi (14.8%), Rickettsia typhi (9.6%), and spotted fever group rickettsia (2.6% [8 R. helvetica, 1 R. felis, 1 R. conorii subsp. indica, and 1 Rickettsia "AT1"]). Patients with murine typhus had a lower frequency of peripheral lymphadenopathy than those with scrub typhus (3% vs. 46%, p<0.001). Rickettsioses are an underrecognized cause of undifferentiated febrile illnesses among adults in Laos. This finding has implications for the local empiric treatment of fever. PMID:16494751

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

PubMed

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

Rift Valley Fever Virus Growth Curve Kinetics in Cattle and Sheep Peripheral Blood Monocyte Derived Macrophages

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neona...

Immunohistochemical Detection of Rift Valley Fever Virus with Non-Infectious, Recombinant Viral Protein Antibodies

USDA-ARS?s Scientific Manuscript database

Rift Valley fever virus (RVFV) causes re-emerging disease outbreaks and abortion storms in mature cattle, sheep, and goats, and can cause 100% mortality in young animals. The spread of this exotic, insect transmitted virus is of particular concern because of its widely recognized potential for being...

Factors Affecting the Ability of American Mosquitoes to Transmit Rift Valley Fever Virus

USDA-ARS?s Scientific Manuscript database

The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, including North Ameri...

Goats are a potential reservoir for the herpesvirus (MCFV-WTD),causing malignant catarrhal fever in deer

USDA-ARS?s Scientific Manuscript database

In the recent investigation of malignant catarrhal fever (MCF) in a red brocket deer (Mazama americana) from a Texas zoo, the MCF viral DNA from the newly recognized herpesvirus causing disease in white-tailed deer (Odocoileus virginianus) (termed MCFV-WTD) was detected. The epidemiology information...

Sleep and rhythm consequences of a genetically induced loss of serotonin.

PubMed

Leu-Semenescu, Smaranda; Arnulf, Isabelle; Decaix, Caroline; Moussa, Fathi; Clot, Fabienne; Boniol, Camille; Touitou, Yvan; Levy, Richard; Vidailhet, Marie; Roze, Emmanuel

2010-03-01

A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

[Haemorrhagic septicaemia in a pig caused by extraintestinal pathogenic Escherichia coli (ExPEC) as a differential diagnosis in classical swine fever--case report and review of the literature].

PubMed

Reiner, Gerald; von Berg, Stephan; Hillen, Sonja; Clemens, Nina; Huisinger, Maike; Burkhardt, Eberhard; Weiss, Reinhardt; Reinacher, Manfred

2010-01-01

Domestic pig herds in some regions of Germany are permanently threatened by Classical Swine Fever. In the case of suspicion, a series of infectious and non infectious causes has to be excluded. The present paper describes a case of Escherichia coli septicaemia, with clinical and pathological symptoms that could not be differentiated from European or African Swine Fever. The E. coli strain could not be classified by standard serotyping. Virulence factors common for ETEC (enterotoxic E. coli) or EDEC (edema-disease E. coli) were not detected. Instead, we found P-fimbriae and aerobactin, thus characterising this strain as an extraintestinal pathogenic strain. Such strains have sporadicly been reported as the cause of septicaemia in piglets or weaners, but the present case is the first report of an E. coli-associated septicaemia in an adult pig. This case shows that extraintestinal pathogenic E. coli can be the cause of severe septicaemia and haemorrhagia. They thus have to be considered as a further differential diagnosis in swine fever.

Clinical features and treatment of drug fever caused by anti-tuberculosis drugs.

PubMed

Fang, Yong; Xiao, Heping; Tang, Shenjie; Liang, Li; Sha, Wei; Fang, Yuanyuan

2016-07-01

Tuberculosis is a major global health problem. However, anti-tuberculosis drug treatment has many adverse effects, such as drug-caused fever. The aim of this study was to investigate the clinical features and treatments of anti-tuberculosis drugs-induced fever. A total of 78 inpatients and outpatients with pulmonary tuberculosis accompanied by drug fever during the anti-tuberculosis treatment were analysed retrospectively from April 2006 to March 2013. Among the anti-tuberculosis drugs that caused the drug fever, rifampicin was the most common one, followed by para-aminosalicylic and pyrazinamide. The symptoms occurred within 2 months after treatment, mainly in the 1-3 weeks, and the main symptom was high fever with body temperature above 39°C. The accompanying symptoms include rash, chills, headache, stuffy nose, runny nose, nausea, vomiting and joint pain. Routine blood examination found that eosinophilia increased in 15 cases and decreased in another 15. Among 63 patients who underwent liver function tests, there were 10 cases of abnormal function and 4 cases of liver damage. When the drug fever was suspected, the measure of withdrawal was taken first. All the suspected drugs were withdrawn in 59 cases, while gradual withdrawal was conducted in 19 cases. Patients with complications were first treated in accordance with the principles of complications treatment and then were gradually given some drugs after recovery. The patients without complications were gradually given some drugs after the body temperature was back to normal. Drug fever is an allergic reaction, the resolution of which depends on whether it was accompanied by liver damage and/or rash or not. © 2014 John Wiley & Sons Ltd.

Dengue hemorrhagic fever and acute hepatitis: a case report.

PubMed

Mourão, Maria Paula Gomes; Lacerda, Marcus Vinícius Guimarães de; Bastos, Michele de Souza; Albuquerque, Bernardino Cláudio de; Alecrim, Wilson Duarte

2004-12-01

Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

Yellow fever in China is still an imported disease.

PubMed

Chen, Jun; Lu, Hongzhou

2016-05-23

Yellow fever is a vector-borne disease endemic to tropical regions of Africa and South America. A recent outbreak in Angola caused hundreds of deaths. Six cases of yellow fever imported from Angola were reported recently in China. This raised the question of whether it will spread in China and how it can be prevented. This article discusses the possibility of yellow fever transmission in China and the strategies to counter it.

5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis

PubMed Central

Grace, Marcy B.; Singh, Vijay K.; Rhee, Juong G.; Jackson, William E.; Kao, Tzu-Cheg; Whitnall, Mark H.

2012-01-01

The steroid androst-5-ene-3ß,17ß-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-κB (NFκB)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not well understood. The aim of this study was to investigate the mechanisms of action of 5-AED administered subcutaneously (s.c.) to mice 24 h before total body γ- or X-irradiation (TBI). We used neutralizing antibodies, flow cytometric functional assays of circulating innate immune cells, analysis of expression of genes related to cell cycle progression, DNA repair and apoptosis, and assessment of DNA strand breaks with halo-comet assays. Neutralization experiments indicated endogenous G-CSF but not IL-6 was involved in survival enhancement by 5-AED. In keeping with known effects of G-CSF on the innate immune system, s.c. 5-AED stimulated phagocytosis in circulating granulocytes and oxidative burst in monocytes. 5-AED induced expression of both bax and bcl-2 in irradiated animals. Cdkn1a and ddb1, but not gadd45a expression, were upregulated by 5-AED in irradiated mice. S.c. 5-AED administration caused decreased DNA strand breaks in splenocytes from irradiated mice. Our results suggest 5-AED survival enhancement is G-CSF-dependent, and that it stimulates innate immune cell function and reduces radiation-induced DNA damage via induction of genes that modulate cell cycle progression and apoptosis. PMID:22843381

5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis.

PubMed

Grace, Marcy B; Singh, Vijay K; Rhee, Juong G; Jackson, William E; Kao, Tzu-Cheg; Whitnall, Mark H

2012-11-01

The steroid androst-5-ene-3ß,17ß-diol (5-androstenediol, 5-AED) elevates circulating granulocytes and platelets in animals and humans, and enhances survival during the acute radiation syndrome (ARS) in mice and non-human primates. 5-AED promotes survival of irradiated human hematopoietic progenitors in vitro through induction of Nuclear Factor-κB (NFκB)-dependent Granulocyte Colony-Stimulating Factor (G-CSF) expression, and causes elevations of circulating G-CSF and interleukin-6 (IL-6). However, the in vivo cellular and molecular effects of 5-AED are not well understood. The aim of this study was to investigate the mechanisms of action of 5-AED administered subcutaneously (s.c.) to mice 24 h before total body γ- or X-irradiation (TBI). We used neutralizing antibodies, flow cytometric functional assays of circulating innate immune cells, analysis of expression of genes related to cell cycle progression, DNA repair and apoptosis, and assessment of DNA strand breaks with halo-comet assays. Neutralization experiments indicated endogenous G-CSF but not IL-6 was involved in survival enhancement by 5-AED. In keeping with known effects of G-CSF on the innate immune system, s.c. 5-AED stimulated phagocytosis in circulating granulocytes and oxidative burst in monocytes. 5-AED induced expression of both bax and bcl-2 in irradiated animals. Cdkn1a and ddb1, but not gadd45a expression, were upregulated by 5-AED in irradiated mice. S.c. 5-AED administration caused decreased DNA strand breaks in splenocytes from irradiated mice. Our results suggest 5-AED survival enhancement is G-CSF-dependent, and that it stimulates innate immune cell function and reduces radiation-induced DNA damage via induction of genes that modulate cell cycle progression and apoptosis.

Differential Effects of CSF-1R D802V and KIT D816V Homologous Mutations on Receptor Tertiary Structure and Allosteric Communication

PubMed Central

Da Silva Figueiredo Celestino Gomes, Priscila; Panel, Nicolas; Laine, Elodie; Pascutti, Pedro Geraldo; Solary, Eric; Tchertanov, Luba

2014-01-01

The colony stimulating factor-1 receptor (CSF-1R) and the stem cell factor receptor KIT, type III receptor tyrosine kinases (RTKs), are important mediators of signal transduction. The normal functions of these receptors can be compromised by gain-of-function mutations associated with different physiopatological impacts. Whereas KIT D816V/H mutation is a well-characterized oncogenic event and principal cause of systemic mastocytosis, the homologous CSF-1R D802V has not been identified in human cancers. The KIT D816V oncogenic mutation triggers resistance to the RTK inhibitor Imatinib used as first line treatment against chronic myeloid leukemia and gastrointestinal tumors. CSF-1R is also sensitive to Imatinib and this sensitivity is altered by mutation D802V. Previous in silico characterization of the D816V mutation in KIT evidenced that the mutation caused a structure reorganization of the juxtamembrane region (JMR) and facilitated its departure from the kinase domain (KD). In this study, we showed that the equivalent CSF-1R D802V mutation does not promote such structural effects on the JMR despite of a reduction on some key H-bonds interactions controlling the JMR binding to the KD. In addition, this mutation disrupts the allosteric communication between two essential regulatory fragments of the receptors, the JMR and the A-loop. Nevertheless, the mutation-induced shift towards an active conformation observed in KIT D816V is not observed in CSF-1R D802V. The distinct impact of equivalent mutation in two homologous RTKs could be associated with the sequence difference between both receptors in the native form, particularly in the JMR region. A local mutation-induced perturbation on the A-loop structure observed in both receptors indicates the stabilization of an inactive non-inhibited form, which Imatinib cannot bind. PMID:24828813

Negative-pressure and low-pressure hydrocephalus: the role of cerebrospinal fluid leaks resulting from surgical approaches to the cranial base.

PubMed

Filippidis, Aristotelis S; Kalani, M Yashar S; Nakaji, Peter; Rekate, Harold L

2011-11-01

Negative-pressure and low-pressure hydrocephalus are rare clinical entities that are frequently misdiagnosed. They are characterized by recurrent episodes of shunt failure because the intracranial pressure is lower than the opening pressure of the valve. In this report the authors discuss iatrogenic CSF leaks as a cause of low- or negative-pressure hydrocephalus after approaches to the cranial base. The authors retrospectively reviewed cases of low-pressure or negative-pressure hydrocephalus presenting after cranial approaches complicated with a CSF leak at their institution. Three patients were identified. Symptoms of high intracranial pressure and ventriculomegaly were present, although the measured pressures were low or negative. A blocked communication between the ventricles and the subarachnoid space was documented in 2 of the cases and presumed in the third. Shunt revisions failed repeatedly. In all cases, temporary clinical and radiographic improvement resulted from external ventricular drainage at subatmospheric pressures. The CSF leaks were sealed and CSF communication was reestablished operatively. In 1 case, neck wrapping was used with temporary success. Negative-pressure or low-pressure hydrocephalus associated with CSF leaks, especially after cranial base approaches, is difficult to treat. The solution often requires the utilization of subatmospheric external ventricular drains to establish a lower ventricular drainage pressure than the drainage pressure created in the subarachnoid space, where the pressure is artificially lowered by the CSF leak. Treatment involves correction of the CSF leak, neck wrapping to increase brain turgor and allow the pressure in the ventricles to rise to the level of the opening pressure of the valve, and reestablishing the CSF route.

GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

PubMed

Halstead, E Scott; Umstead, Todd M; Davies, Michael L; Kawasawa, Yuka Imamura; Silveyra, Patricia; Howyrlak, Judie; Yang, Linlin; Guo, Weichao; Hu, Sanmei; Hewage, Eranda Kurundu; Chroneos, Zissis C

2018-01-05

Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi. Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ). Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

Outbreak of Rocky Mountain spotted fever in Córdoba, Colombia.

PubMed

Hidalgo, Marylin; Miranda, Jorge; Heredia, Damaris; Zambrano, Pilar; Vesga, Juan Fernando; Lizarazo, Diana; Mattar, Salim; Valbuena, Gustavo

2011-02-01

Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the obligate intracellular bacterium Rickettsia rickettsii. Although RMSF was first reported in Colombia in 1937, it remains a neglected disease. Herein, we describe the investigation of a large cluster of cases of spotted fever rickettsiosis in a new area of Colombia.

The effects and safety of dexibuprofen compared with ibuprofen in febrile children caused by upper respiratory tract infection

PubMed Central

Yoon, Jong Seo; Jeong, Dae-Chul; Oh, Jae-Won; Lee, Keun Young; Lee, Hyun Seung; Koh, Young Yull; Kim, Jin Tack; Kang, Jin Han; Lee, Joon Sung

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTThe analgesic and anti-inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain. WHAT THIS STUDY ADDSDexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children. AIM To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI). METHODS The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer-based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group. RESULTS In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups (P > 0.05). There also was no significant difference in adverse drug reaction (P > 0.05). CONCLUSIONS Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children. PMID:19032727

[Dengue fever--not just a tropical infectious disease].

PubMed

Stock, Ingo

2016-03-01

Dengue fever is a viral disease that is transmitted primarily by Aedes mosquitoes, i. e., A. aegypti and A. albopictus. Other species are rarely involved. The disease is caused by dengue virus, an enveloped RNA virus which belongs to the family of flaviviridae. Although most infections are asymptomatic, in 20 to 30 percentages all cases infections are accompanied with high fever and other influenza-like signs of illness. Serious medical conditions with lethal complications also occur. During the last decades, the incidence of dengue fever rose sharply in many tropical and subtropical countries. In some of these regions, dengue is one of the leading causes of death in children. In Europe, since a few years a strong clustering of dengue fever cases has been registered in travelers returning from certain tropical or subtropical regions. Recently, autochthonous outbreaks have been observed on the Atlantic island of Madeira and in a few other regions of South Europe. Treatment of dengue fever is supportive and symptomatic, a specific therapy does not exist. For prevention of disease, vector control is of crucial importance.

Simulated effect of pig-population density on epidemic size and choice of control strategy for classical swine fever epidemics in The Netherlands.

PubMed

Mangen, M-J J; Nielen, M; Burrell, A M

2002-12-18

We examined the importance of pig-population density in the area of an outbreak of classical swine fever (CSF) for the spread of the infection and the choice of control measures. A spatial, stochastic, dynamic epidemiological simulation model linked to a sector-level market-and-trade model for The Netherlands were used. Outbreaks in sparsely and densely populated areas were compared under four different control strategies and with two alternative trade assumptions. The obligatory control strategy required by current EU legislation was predicted to be enough to eradicate an epidemic starting in an area with sparse pig population. By contrast, additional control measures would be necessary if the outbreak began in an area with high pig density. The economic consequences of using preventive slaughter rather than emergency vaccination as an additional control measure depended strongly on the reactions of trading partners. Reducing the number of animal movements significantly reduced the size and length of epidemics in areas with high pig density. The phenomenon of carrier piglets was included in the model with realistic probabilities of infection by this route, but it made a negligible contribution to the spread of the infection.

Early onset primary pulmonary cryptococcosis in a renal transplant patient.

PubMed

Tarai, B; Kher, V; Kotru, P; Sabhikhi, A; Barman, P; Rattan, A

2010-01-01

We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

Atelectasis as a cause of postoperative fever: where is the clinical evidence?

PubMed

Mavros, Michael N; Velmahos, George C; Falagas, Matthew E

2011-08-01

Atelectasis is considered to be the most common cause of early postoperative fever (EPF) but the existing evidence is contradictory. We sought to determine if atelectasis is associated with EPF by analyzing the relevant published evidence. We performed a systematic search in PubMed and Scopus databases to identify studies examining the association between atelectasis and EPF. A total of eight studies, including 998 cardiac, abdominal, and maxillofacial surgery patients, were eligible for analysis. Only two studies specifically examined our question, and six additional articles reported sufficient data to be included. Only one study reported a significant association between postoperative atelectasis and fever, whereas the remaining studies indicated no such association. The performance of EPF as a diagnostic test for atelectasis was also assessed, and EPF performed poorly (pooled diagnostic OR, 1.40; 95% CI, 0.92-2.12). The significant heterogeneity among the studies precluded a formal metaanalysis. The available evidence regarding the association of atelectasis and fever is scarce. We found no clinical evidence supporting the concept that atelectasis is associated with EPF. More so, there is no clear evidence that atelectasis causes fever at all. Large studies are needed to precisely evaluate the contribution of atelectasis in EPF.

Parental and medical knowledge and management of fever in Italian pre-school children

PubMed Central

2012-01-01

Background Guidelines for the management of fever in children have been recently published, however “fever phobia” is still spreading. To provide information which may sustain educational interventions tailored to our population we investigated the parental and medical knowledge and management of fever in preschool children. Methods A questionnaire was administered to a convenient sample of Italian parents and paediatricians. The questionnaire elicited information about definition and cause of fever, concerns about fever, method of temperature measurement, and treatment modalities. Results Overall, 388 parents and 480 paediatricians were interviewed. All the parents believed that fever could cause at least one harmful effect and 89.9% (n = 349) believed that, if left untreated, it can cause brain damage or seizures. Parents used multiple resources to obtain information about fever but 67.8% (n = 264) considered paediatricians as their primary resource. Several wrong behaviours were found in the same proportions among parents and paediatricians: 78.5% of paediatricians (n = 377) and 77.8% of parents (n = 302) used physical method to reduce fever (P = 0.867); 27.0% of paediatricians (n = 103) and 21.4% (n = 83) of parents declared to alternate ibuprofen and acetaminophen (P = 0.953). Differently, 73.1% (n = 351) of paediatricians preferred oral to rectal administration of antipyretics compared to 48.7% (n = 190) of parents (P < 0.0001). Worrisomely, 1.4% of paediatricians and 1.2% of parents declared to use acetylsalicylic acid or steroids as second-choice antipyretics (P = 0.937) and 6.7% (n = 26) of parents declared to use table- or teaspoons for determining the dose of drug. Conclusions Paediatricians’ attitudes greatly influence the parental behaviours and beliefs. Implementation of educational programs regarding the management of the febrile child are needed in our setting. PMID:22794080

Does natalizumab treatment increase the risk of herpes simplex encephalitis in multiple sclerosis? Case and discussion.

PubMed

Sharma, Kanchan; Ballham, Samantha A; Inglis, Kirsty E A; Renowden, Shelley; Cottrell, David A

2013-10-01

This report presents the 4th documented case worldwide of herpes simplex encephalitis in multiple sclerosis (MS) patients treated with natalizumab and the first case in the UK. Natalizumab is licensed for relapsing remitting multiple sclerosis in patients with high disease activity despite treatment with interferon-beta and patients with rapidly evolving severe, multiple sclerosis. Natalizumab is a monoclonal antibody targeted against alpha-4 integrin. Its proposed mechanism is attenuation of the migration of immune cells into the central nervous system. Reactivation of the JC virus causing progressive multifocal leucoencephalopathy (PML) and its association with natalizumab is well documented. This case adds support to the suggestion that natalizumab also increases the reactivation risk of CNS herpes simplex infection. A 34 year old woman was admitted with a generalized tonic-clonic seizure, fever and confusion following her 40th infusion of natalizumab. MRI demonstrated increased signal in the medial temporal lobes and EEG showed focal sharp waves over the temporal lobe. CSF PCR later confirmed herpes simplex virus. The patient made an eventual excellent recovery following 21 days of intravenous acyclovir therapy followed by 14 days of oral treatment. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis.

PubMed

Lind, Liza; Studahl, Marie; Persson Berg, Linn; Eriksson, Kristina

2017-07-10

The closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation. Secretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum. Most measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate. We show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.

Optimizing Preventive Strategies and Malaria Diagnostics to Reduce the Impact of Malaria on US Military Forces

DTIC Science & Technology

2012-05-01

but not limited to dengue fever , early shigellosis, typhoid fever , rickettsiosis, leptospirosis or acute retroviral syndrome). (strong recommendation...provided support for a Multiplex RDT to identify fever causing pathogens in the blood, but the performance of this assay was deemed inadequate and...index.jsp 7 Yeboah-Antwi K, Pilingana P, Macleod WB, et al. Community case management of fever due to malaria and pneumonia in children under five in

Genome-Wide Profiling of Humoral Immune Response to Coxiella burnetii Infection by Protein Microarray

DTIC Science & Technology

2010-01-01

mortality rate for Chronic Q fever to less than 1% [1, 4, 5]. Chronic infections may cause life-threatening endocarditis but may not show apparent...Houpikian, P., Tissot Dupont, H., Riss, J. M. et a/., Treatment of a fever endocarditis : comparison of 2 regimens containing doxycycline and ofloxacin...fever endocarditis . J. Infect. Dis. 1998, 178, 278-281. [7) Yu, X., Raoult, D., Serotyping Coxiella burnetii isolates from acute and chronic a fever

Fever: Its History, Cause, and Function

PubMed Central

Atkins, Elisha

1982-01-01

Concepts of fever from Hippocrates to the present are briefly outlined and compared with current ideas of the pathogenesis of fever. Evidence is presented that endogenous pyrogen, the hormone that elevates body temperature, is identical with lymphocyte-activating factor, a monokine that stimulates lymphocyte proliferation and function. It now appears that inflammation and fever are closely interrelated phenomena that are modulated by a single hormone and that have been selected by evolution to protect the host against infection. PMID:6758374

Salmonella Infections

MedlinePlus

... reptiles like snakes, turtles, and lizards. Symptoms include Fever Diarrhea Abdominal cramps Headache Possible nausea, vomiting, and ... be serious. The usual treatment is antibiotics. Typhoid fever, a more serious disease caused by Salmonella, is ...

A Type II Arabinogalactan from Anoectochilus formosanus for G-CSF Production in Macrophages and Leukopenia Improvement in CT26-Bearing Mice Treated with 5-Fluorouracil.

PubMed

Yang, Li-Chan; Lu, Ting-Jang; Lin, Wen-Chuan

2013-01-01

Anoectochilus formosanus is an herb well known in Asian countries. The polysaccharide isolated from A. formosanus consists of type II arabinogalactan (AGAF), with branched 3,6-Gal as the major moiety. In this study, AGAF was examined for the granulocyte colony-stimulating factor (G-CSF) production and related protein expression in RAW 264.7 murine macrophages. The signaling pathway of G-CSF production involves AGAF and mitogen-activated protein kinases (MAPKs) inhibitors and pattern-recognition receptor antibodies. AGAF was evaluated to ease the leukopenia in CT26-colon-cancer-bearing mice treated with 5-fluorouracil (5-FU). The results of this study showed that AGAF was a stimulant for Toll-like receptor 2 and Dectin-1 and that it induced G-CSF production, through p38 and ERK MAPK, and NF- κ B pathways. In vivo examination showed that the oral administration of AGAF mitigated the side effects of leukopenia caused by 5-FU in colon-cancer-bearing mice. In conclusion, the botanic type II AGAF in this study was a potent G-CSF inducer in vivo and in vitro.

Antioxidant capacity and protein oxidation in cerebrospinal fluid of amyotrophic lateral sclerosis.

PubMed

Siciliano, G; Piazza, S; Carlesi, C; Del Corona, A; Franzini, M; Pompella, A; Malvaldi, G; Mancuso, M; Paolicchi, A; Murri, L

2007-05-01

The causes of Amyotrophic Lateral Sclerosis (ALS) are unknown. A bulk of evidence supports the hypothesis that oxidative stress and mitochondrial dysfunction can be implicated in ALS pathogenesis. METHODS =: We assessed, in cerebrospinal fluid (CSF) and in plasma of 49 ALS patients and 8 controls, the amount of oxidized proteins (AOPP, advanced oxidation protein products), the total antioxidant capacity (FRA, the ferric reducing ability), and, in CSF, two oxidation products, the 4-hydroxynonenal and the sum of nitrites plus nitrates. The FRA was decreased (p = 0.003) in CSF, and AOPP were increased in both CSF (p = 0.0039) and plasma (p = 0.001) of ALS patients. The content of AOPP was differently represented in CSF of ALS clinical subsets, resulting in increase in the common and pseudopolyneuropathic forms (p < 0.001) and nearly undetectable in the bulbar form, as in controls. The sum of nitrites plus nitrates and 4-hydroxynonenal were unchanged in ALS patients compared with controls. Our results, while confirming the occurrence of oxidative stress in ALS, indicate how its effects can be stratified and therefore implicated differently in the pathogenesis of different clinical forms of ALS.

Far East Scarlet-Like Fever Caused by a Few Related Genotypes of Yersinia pseudotuberculosis, Russia.

PubMed

Timchenko, Nelly F; Adgamov, Ruslan R; Popov, Alexander F; Psareva, Ekaterina K; Sobyanin, Konstantin A; Gintsburg, Alexander L; Ermolaeva, Svetlana A

2016-03-01

We used multivirulence locus sequence typing to analyze 68 Yersinia pseudotuberculosis isolates from patients in Russia during 1973-2014, including 41 isolates from patients with Far East scarlet-like fever. Four genotypes were found responsible, with 1 being especially prevalent. Evolutionary analysis suggests that epidemiologic advantages could cause this genotype's dominance.

Chikungunya: a bending reality.

PubMed

Her, Zhisheng; Kam, Yiu-Wing; Lin, Raymond T P; Ng, Lisa F P

2009-12-01

Chikungunya fever is an acute illness caused by the arbovirus Chikungunya virus. The virus is transmitted primarily in a sylvatic cycle involving the Aedes mosquitoes. Since 2005, a Chikungunya fever outbreak of unprecedented magnitude occurred on several Indian Ocean islands. Since then, the disease has spread to many parts of the world due to imported cases among travellers returning from epidemic areas. Chikungunya virus causes a wide spectrum of illness including fever, a characteristic rash, disabling joint symptoms which can sometimes become severe that lasts months. This review summarises on this history of Chikungunya fever, host specificity, the characteristics of Chikungunya virus, clinical features of disease and current control measures. It focuses on how the re-emergence of an old changed the outlook of managing arboviral diseases in the present social and public health context.

Myocardial involvement in rocky mountain spotted fever: a case report and review.

PubMed

Doyle, Amy; Bhalla, Karan S; Jones, James M; Ennis, David M

2006-10-01

Rocky Mountain Spotted Fever (RMSF), caused by Rickettia rickettsii, is a serious tickborne illness that is endemic in the southeastern United States. Although it is most commonly known as a cause of fever and rash, it can have systemic manifestations. The myocardium may rarely be involved, with symptoms that can mimic those of acute coronary syndromes. This report describes a case of serologically proven RMSF causing symptomatic myocarditis, manifested by chest pain, elevated cardiac enzyme levels, and decrease myocardial function. After treatment with antibiotics, the myocarditis resolved. Thus, although unusual, the clinician should be aware of myocardial disease in patients with appropriate exposure histories or other clinical signs of RMSF. Close monitoring and an aggressive approach are essential to reduce mortality rates.

Serum and cerebrospinal fluid cytokine profile of patients with 2009 pandemic H1N1 influenza virus-associated encephalopathy.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Shirabe, Komei; Fukano, Reiji; Ichiyama, Takashi

2011-05-01

Since April 2009, the number of patients with 2009 pandemic H1N1 influenza virus infection has been increasing in Japan just as in the rest of the world. Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have also been reported. The common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously reported the possible association between seasonal influenza-associated encephalopathy (sIE) and proinflammatory cytokines. However, the pathogenesis of pIE remains to be elucidated. In pIE patients with a poor outcome, the serum levels of interleukin (IL)-6, IL-10, and soluble tumor necrosis factor (TNF) receptor (sTNFR1) were significantly higher than those in pIE patients without neurological sequelae. Similarly, the cerebrospinal fluid (CSF) IL-6 levels in pIE patients with a poor outcome were significantly higher than those in pIE patients without neurological sequelae. Our results suggest that IL-6, TNF-α, and IL-10 play important roles in pIE, and that the serum levels of IL-6, IL-10, and sTNFR1 and the CSF levels of IL-6 are related to neurological complications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Severe invasive listeriosis--case report.

PubMed

Teodor, Andra; Teodor, D; Miftode, Egidia; Prisăcaru, D; Leca, Daniela; Petrovici, Cristina; Dorneanu, Olivia; Dorobăt, Carmen-Mihaela

2012-01-01

Listeriosis is a rare food borne infection which, in the invasive form, presents as bloodstream infection, central nervous system infection, materno-fetal infection, or focal infection. Certain immunosuppressive conditions have been identified as risk factors for severe invasive disease. The invasive forms of listeriosis are associated with a high case fatality rate. We present the case of a 62-year-old male with an unremarkable medical history admitted to the Iasi Infectious Diseases Hospital for fever. headache, ataxia, and diplopia. Physical examination revealed high temperature, confusion, relative bradycardia, and signs of meningeal irritation. Laboratory test showed leukocyt osis with neutrophilia. pathological CSF findings (high WBC count with predominance of neutrophils, low glucose and high protein levels), increased liver enzymes (ALAT, ASAT, AP, gammaGT), and important renal impairment (normal levels at presentation). No abnormalities at chest x-ray, cranial CT and abdominal ultrasound. CSF and blood cultures were positive for Listeria monocytogenes. Under antibiotics (ampicillin and ciprofloxacin), the course was marked by respiratory failure requiring mechanical ventilation, coma, hypotension, tachycardia. and death 12 days after admission. The particularity of this case consists in the association of the two classical forms of invasive listeriosis, meningitis and bacteriemia, with a focal infection. acute hepatitis, and a course marked by multiple organ dysfunction syndromes and exitus in a previously apparently healthy individual.

Supportive therapy in medical therapy of head and neck tumors

PubMed Central

Link, Hartmut

2012-01-01

Fever during neutropenia may be a symptom of severe life threatening infection, which must be treated immediately with antibiotics. If signs of infection persist, therapy must be modified. Diagnostic measures should not delay treatment. If the risk of febrile neutropenia after chemotherapy is ≥20%, then prophylactic therapy with G-CSF is standard of care. After protocols with a risk of febrile neutropenia of 10–20%, G-CSF is necessary, in patients older than 65 years or with severe comorbidity, open wounds, reduced general condition. Anemia in cancer patients must be diagnosed carefully, even preoperatively. Transfusions of red blood cells are indicated in Hb levels below 7–8 g/dl. Erythropoiesis stimulating agents (ESA) are recommended after chemotherapy only when hemoglobin levels are below 11 g/dl. The Hb-level must not be increased above 12 g/dl. Anemia with functional iron deficiency (transferrin saturation <20%) should be treated with intravenous iron, as oral iron is ineffective being not absorbed. Nausea or emesis following chemotherapy can be classified as minimal, low, moderate and high. The antiemetic prophylaxis should be escalated accordingly. In chemotherapy with low emetogenic potential steroids are sufficient, in the moderate level 5-HT3 receptor antagonists (setrons) are added, and in the highest level Aprepitant as third drug. PMID:23320053

Herpes Simplex Virus Encephalitis: Atypical Presentation as a Right Middle Cerebral Artery Stroke.

PubMed

Shoaib, Maria; Kraus, Jacqueline J; Khan, Muhammad T

2018-01-15

Herpes simplex virus encephalitis (HSVE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis. We report a case of HSVE presenting as a stroke mimic in a 76-year-old female with a history of atrial fibrillation on warfarin. She was admitted to our medical intensive care unit with intermittent fever, lethargy, and new onset left-sided hemiparesis. A computed tomography (CT) of the head showed a right middle cerebral artery (MCA) acute ischemic stroke with midline shift and a dense right MCA sign. Brain magnetic resonance imaging (MRI) showed evidence of acute stroke with consideration of herpes encephalitis. CSF analysis was positive for herpes simplex virus (HSV) type one. She recovered with high-dose intravenous acyclovir therapy. Our patient was a diagnostic dilemma, initially being diagnosed with an acute ischemic stroke and yet found to have HSVE, which mimicked an acute ischemic stroke. Delay in treatment may result in devastating clinical outcomes that may include severe cognitive, focal neurological deficits, persistent seizures, and even death. This case highlights the importance of a multidisciplinary approach and the need for increased awareness of an atypical presentation of HSVE among emergency physicians, neurologist, intensivists, and radiologists.