scholarly journals The Natural History of Aerosolized Francisella tularensis Infection in Cynomolgus Macaques

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 597
Author(s):  
Ondraya Frick ◽  
Virginia Livingston ◽  
Chris Whitehouse ◽  
Sarah Norris ◽  
Derron Alves ◽  
...  
Keyword(s):  
Natural History ◽  
Francisella Tularensis ◽  
Cynomolgus Macaque ◽  
Primate Model ◽  
Cell Counts ◽  
Cynomolgus Macaques ◽  
Similar Disease ◽  
History Of ◽  
White Blood Cell Counts ◽  
Schu S4

Tularemia is a severe, zoonotic infection caused by the Gram-negative bacterium Francisella tularensis. Inhalation results in a rapid, severe bacterial pneumonia and sepsis, which can be lethal. Because the cynomolgus macaque is the accepted nonhuman primate model for tularemia, we conducted a natural history study of pneumonic tularemia by exposing macaques to target inhaled doses of 50, 500, or 5000 colony forming units (CFU) of F. tularensis subsp. tularensis SCHU S4. Two animals within the 50 CFU group (calculated doses of 10 and 11 CFU) survived the challenge, while the remainder succumbed to infection. Exposure of cynomolgus macaques to aerosolized SCHU S4 resulted in fever, anorexia, increased white blood cell counts, lymphopenia, thrombocytopenia, increased liver enzymes, alterations in electrocardiogram (ECG), and pathological changes typical of infection with F. tularensis, regardless of the challenge dose. Blood pressure dropped during the febrile phase, particularly as temperature began to drop and macaques succumbed to the disease. ECG analysis indicated that in 33% of the macaques, heart rate was not elevated during the febrile phase (Faget’s sign; pulse-temperature disassociation), which has been reported in a similar percentage of human cases. These results indicated that infection of cynomolgus macaques with aerosolized F. tularensis results in similar disease progression and outcome as seen in humans, and that cynomolgus macaques are a reliable animal model to test medical countermeasures against aerosolized F. tularensis.

scholarly journals The Fluorocycline TP-271 Is Efficacious in Models of Aerosolized Francisella tularensis SCHU S4 Infection in BALB/c Mice and Cynomolgus Macaques

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Trudy H. Grossman ◽  
Michael S. Anderson ◽  
David Christ ◽  
Melanie Gooldy ◽  
Lisa N. Henning ◽  
...  
Keyword(s):  
Francisella Tularensis ◽  
Respiratory Infections ◽  
Vehicle Control ◽  
Primate Model ◽  
Once Daily ◽  
Content Type ◽  
Aerosol Exposure ◽  
Cynomolgus Macaques ◽  
Schu S4

ABSTRACT TP-271 is a novel, fully synthetic fluorocycline in development for complicated bacterial respiratory infections. TP-271 was active in vitro against a panel of 29 Francisella tularensis isolates, showing MICs against 50% and 90% of isolates of 0.25 and 0.5 μg/ml, respectively. In a mouse model of inhalational tularemia, animals were exposed by aerosol to 91 to 283 50% lethal doses (LD50)/mouse of F. tularensis SCHU S4. Following 21 days of once-daily intraperitoneal dosing with TP-271 at 3, 6, 12, and 18 mg/kg of body weight/day, initiating at 24 h postchallenge, survival was 80%, 100%, 100%, and 100%, respectively. When treatment was initiated at 72 h postchallenge, survival was 89%, 100%, 100%, and 100% in the 3-, 6-, 12-, and 18-mg/kg/day TP-271 groups, respectively. No mice treated with the vehicle control survived. Surviving mice treated with TP-271 showed little to no relapse during 14 days posttreatment. In a nonhuman primate model of inhalational tularemia, cynomolgus macaques received an average aerosol exposure of 1,144 CFU of F. tularensis SCHU S4. Once-daily intravenous infusion with 1 or 3 mg/kg TP-271, or vehicle control, for 21 days was initiated within 6 h of confirmed fever. All animals treated with TP-271 survived to the end of the study, with no relapse during 14 days after the last treatment, whereas no vehicle control-treated animals survived. The protection and low relapse afforded by TP-271 treatment in these studies support continued investigation of TP-271 for use in the event of aerosolized exposure to F. tularensis.

scholarly journals Clinical Analysis of 9 Cases of Neonatal Influenza A

2021 ◽  
Author(s):  
Yanlan Zhang ◽  
Lin Xu ◽  
Caiying Wang ◽  
Lin Pang
Keyword(s):  
Influenza A ◽  
Nasal Congestion ◽  
Antiviral Treatment ◽  
Clinical Analysis ◽  
Runny Nose ◽  
Reactive Protein ◽  
Cell Counts ◽  
History Of ◽  
White Blood Cell Counts ◽  
Medical University

Abstract Background: The population is generally susceptible to influenza A, while neonatal cases are relatively rare. The study aims to explore the clinical characteristics, diagnosis, treatment, and prognosis of neonates with influenza A.Methods: The clinical data from neonates with influenza A who were treated in the neonatal department of Beijing Ditan Hospital affiliated with Capital Medical University from November 2017 to January 2019 were retrospectively analyzed.Results: A total of 9 neonates with influenza A were admitted and treated, with a distribution of 7 males and 2 females. The onset was 1.44 ± 1.46 days (mean ± SD), and age at diagnosis was 21.44 ±6. 53 days. All cases had a history of exposure to febrile patients, The main symptoms are fever, nasal congestion, runny nose, sneezing, coughing, other respiratory symptoms and digestive symptoms such as vomiting milk, choking milk, less milk, diarrhea. Laboratory tests showed 7 cases of decreased white blood cell counts, 3 cases of increased plasma C-reactive protein concentrations. All cases were administered antiviral therapy on the day of admission. Eight neonates reverted to a normal temperature within 48 hours after hospitalization, one neonate’s temperature returned to normal after 48 hours of hospitalization, and all cases' symptoms gradually improved.Conclusion: The symptoms of influenza A in neonates are atypical, once a diagnosis is confirmed, the prognosis is likely to be favorable as long as antiviral treatment with antiviral is initiated as soon as possible.

scholarly journals Nasal upregulation of CST1 in dog-sensitised children with severe allergic airway disease

2021 ◽  
Vol 7 (2) ◽  
pp. 00917-2020
Author(s):  
Ulrika Käck ◽  
Elisabet Einarsdottir ◽  
Marianne van Hage ◽  
Anna Asarnoj ◽  
Anna James ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical History ◽  
Airway Disease ◽  
Forced Expiratory Volume ◽  
Allergic Airway Disease ◽  
Healthy Controls ◽  
Cell Counts ◽  
History Of ◽  
White Blood Cell Counts ◽  
Methacholine Provocation

BackgroundThe clinical presentation of children sensitised to dog dander varies from asymptomatic to severe allergic airway disease, but the genetic mechanisms underlying these differences are not clear. The objective of the present study was to investigate nasal transcriptomic profiles associated with dog dander sensitisation in school children and to reveal clinical symptoms related with these profiles.MethodsRNA was extracted from nasal epithelial cell brushings of children sensitised to dog dander and healthy controls. Blood sample analyses included IgE against dog dander, dog allergen molecules, other airborne and food allergens, basophil activation and white blood cell counts. Clinical history of asthma and rhinitis was recorded, and lung function was assessed (spirometry, methacholine provocation and exhaled nitric oxide fraction).ResultsThe most overexpressed gene in children sensitised to dog dander compared to healthy controls was CST1, coding for Cystatin 1. A cluster of these children with enhanced CST1 expression showed lower forced expiratory volume in 1 s, increased bronchial hyperreactivity, pronounced eosinophilia and higher basophil allergen threshold sensitivity compared with other children sensitised to dog dander. In addition, multi-sensitisation to lipocalins was more common in this group.ConclusionsOverexpression of CST1 is associated with more severe allergic airway disease in children sensitised to dog dander. CST1 is thus a possible biomarker of the severity of allergic airway disease and a possible therapeutic target for the future treatment of airborne allergy.

scholarly journals Meningococcal Pneumonia in a Young Healthy Male

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Abdullah M. Al Alawi
Keyword(s):  
Emergency Department ◽  
Lower Lobe ◽  
Community Acquired Pneumonia ◽  
Cell Counts ◽  
History Of ◽  
Chest X Ray ◽  
White Blood Cell Counts ◽  
The Right ◽  
Local Guideline

A 23-year-old male presented to the emergency department with one-day history of right-sided pleuritic chest pain, haemoptysis, and fever. In the emergency department, the blood pressure was 140/60 mmHg, heart rate 89/min, body temperature 40°C, respiratory rates 20 breaths/min, and oxygen saturation 98% in room air. Physical examination revealed rales and bronchial breathing in the right infrascapular region. Laboratory analysis showed raised white blood cell counts and elevated inflammation markers. Chest X-ray showed right lower lobe consolidation. Intravenous(IV) ceftriaxone and doxycycline were started for the management of community-acquired pneumonia as per the local guideline. Later, on admission, blood culture was positive for Neisseria meningitidis (N. meningitidis). Ceftriaxone was continued for 4 days, and the patient was discharged while being on oral amoxicillin (1 gm TDS) for another 3 days. He remained well during the outpatient follow-up.

scholarly journals Characterization of lethal inhalational infection with Francisella tularensis in the common marmoset (Callithrix jacchus)

2010 ◽  
Vol 59 (9) ◽  
pp. 1107-1113 ◽  
Author(s):  
Michelle Nelson ◽  
Mark S. Lever ◽  
Rachel E. Dean ◽  
Victoria L. Savage ◽  
F. Javier Salguero ◽  
...  
Keyword(s):  
Francisella Tularensis ◽  
Immunological Response ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Post Challenge ◽  
Primate Model ◽  
Immunological Parameters ◽  
Suitable Animal Model ◽  
The Common ◽  
Schu S4

The intracellular Gram-negative pathogen Francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. To determine whether the common marmoset (Callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. Ten animals were challenged with ∼102 c.f.u. F. tularensis strain SCHU S4 (F. tularensis subsp. tularensis). To look for trends in the infection, pairs of animals were sacrificed at 24 h intervals between 0 and 96 h post-challenge and blood and organs were assessed for bacteriology, pathology and haematological and immunological parameters. The first indication of infection was a raised core temperature at 3 days post-challenge. This coincided with a number of other factors: a rapid increase in the number of bacteria isolated from all organs, more pronounced gross pathology and histopathology, and an increase in the immunological response. As the disease progressed, higher bacterial and cytokine levels were detected. More extensive pathology was observed, with multifocal lesions seen in the lungs, liver and spleen. Disease progression in the common marmoset appears to be consistent with human clinical and pathological features of tularaemia, indicating that this may be a suitable animal model for the investigation of novel medical interventions such as vaccines or therapeutics.

Intrathecal Colistin and Sterilization of Resistant Pseudomonas Aeruginosa Shunt Infection

2005 ◽  
Vol 39 (5) ◽  
pp. 949-952 ◽  
Author(s):  
Andrea L Quinn ◽  
Jorge P Parada ◽  
Jaime Belmares ◽  
J Paul O'Keefe
Keyword(s):  
Central Nervous System ◽  
Pseudomonas Aeruginosa ◽  
Nervous System ◽  
Renal Function ◽  
Central Nervous System Infections ◽  
Gram Negative ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
History Of ◽  
White Blood Cell Counts

OBJECTIVE: To report 2 cases of multidrug-resistant (MDR) Pseudomonas aeruginosa meningitis and ventriculo-peritoneal shunt (VPS) infection successfully sterilized with intrathecal colistin 10 mg/day after development of nephrotoxicity associated with intravenous administration. CASE SUMMARIES: Case 1. A 69-year-old African American woman with a history of subarachnoid hemorrhage and hydrocephalus requiring VPS placement was admitted with VPS infection and meningitis. Cerebrospinal fluid (CSF) cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but rapidly discontinued due to development of renal dysfunction. Intravenous colistin was the probable cause of the adverse effect. Intrathecal colistin was initiated via an externalized VPS, with subsequent improvement in white blood cell counts in the CSF. Follow-up CSF cultures remained sterile and renal function returned to baseline. Case 2. A 69-year-old white woman with a history of subarachnoid hemorrhage, hydrocephalus, and VPS was transferred from an extended-care facility for management of a VPS infection. CSF cultures revealed MDR P. aeruginosa susceptible only to colistin. Intravenous colistin was initiated but subsequently discontinued due to worsening renal function that, as with the first case, probably correlated with colistin administration and persisted despite dose adjustment. Therapy was changed to intrathecal administration, with subsequent normalization of her CSF white blood cell counts and sterilization of cultures. DISCUSSION: The limited availability of antibiotics for treatment of highly resistant or MDR gram-negative organisms has prompted clinicians to reconsider the use of older drugs. Prior reports have suggested that intravenous colistin is a potential alternative for treating highly resistant gram-negative central nervous system infections, specifically Acinetobacter, but its use is limited by nephrotoxicity. Our experience suggests that intrathecal colistin is a potentially curative intervention for the treatment of severe MDR P. aeruginosa meningitis and VPS infections in patients in whom intravenous colistin is not an option. CONCLUSIONS: Intrathecal use of colistin is a potentially safe, effective, and viable treatment option for MDR P. aeruginosa central nervous system infections when intravenous administration is not feasible.

scholarly journals Brief Report: Natural History of Individuals With Clinically Recognized Monoclonal B-Cell Lymphocytosis Compared With Patients With Rai 0 Chronic Lymphocytic Leukemia

2009 ◽  
Vol 27 (24) ◽  
pp. 3959-3963 ◽  
Author(s):  
Tait D. Shanafelt ◽  
Neil E. Kay ◽  
Kari G. Rabe ◽  
Timothy G. Call ◽  
Clive S. Zent ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Natural History ◽  
B Cell ◽  
Cell Count ◽  
Medical Records ◽  
Absolute Lymphocyte Count ◽  
Continuous Variable ◽  
Lymphocytic Leukemia ◽  
Cell Counts ◽  
History Of

Purpose The diagnosis of monoclonal B-cell lymphocytosis (MBL) is used to characterize patients with a circulating population of clonal B cells, a total B-cell count of less than 5 × 109/L, and no other features of a B-cell lymphoproliferative disorder including lymphadenopathy/organomegaly. The natural history of clinically identified MBL is unclear. The goal of this study was to explore the outcome of patients with MBL relative to that of individuals with Rai stage 0 chronic lymphocytic leukemia (CLL). Patients and Methods We used hematopathology records to identify a cohort of 631 patients with newly diagnosed MBL or Rai stage 0 CLL. Within this cohort, 302 patients had MBL (B-cell counts of 0.02 to 4.99 × 109/L); 94 patients had Rai stage 0 CLL with an absolute lymphocyte count (ALC) ≤ 10 × 109/L; and 219 patients had Rai stage 0 CLL with an ALC more than 10 × 109/L. Data on clinical outcome were abstracted from medical records. Results The percentage of MBL patients free of treatment at 1, 2, and 5 years was 99%, 98%, and 93%, respectively. B-cell count as a continuous variable (hazard ratio [HR] = 2.9, P = .04) and CD38 status (HR = 10.8, P = .006) predicted time to treatment (TTT) among MBL patients. The likelihood of treatment for MBL patients was lower (HR = 0.32, P = .04) than that of both Rai stage 0 CLL patients with an ALC less than 10 × 109/L (n = 94) and Rai stage 0 CLL patients with an ALC more than 10 × 109/L (n = 219; P = .0003). Conclusion Individuals with MBL identified in clinical practice have a low risk for progression at 5 years. Because B-cell count seems to relate to TTT as a continuous variable, additional studies are needed to determine what B-cell count should be used to distinguish between MBL and CLL.

scholarly journals Etiology associated with developing posthemispherectomy hydrocephalus after resection-disconnection procedures

2013 ◽  
Vol 12 (5) ◽  
pp. 469-475 ◽  
Author(s):  
Jennifer Phung ◽  
Paul Krogstad ◽  
Gary W. Mathern
Keyword(s):  
Blood Cell ◽  
Univariate Analysis ◽  
Cns Infection ◽  
Csf Shunts ◽  
Maximum Daily Temperature ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
History Of ◽  
White Blood Cell Counts ◽  
First Time

Object The authors sought to determine if clinical epilepsy variables, maximum daily temperature (Tmax), and blood and CSF findings were associated with the risk of developing hydrocephalus after first-time resection-disconnection hemispherectomy. Methods Patients who underwent cerebral hemispherectomy in whom a standardized perioperative protocol was used, including the use of ventriculostomies (n = 79), were classified into those who developed and those who did not develop hydrocephalus requiring CSF shunts. The authors compared these 2 groups for clinical variables, Tmax, and blood and CSF studies through postoperative Day 12. Results In this cohort, 30% of the patients required CSF shunts, of which 8% developed late hydrocephalus up to 3 years posthemispherectomy. Multivariate analysis found that etiology was associated with developing posthemispherectomy hydrocephalus. Higher shunt rates were observed for patients with hemimegalencephaly (40%; n = 15) and a history of CNS infection (100%; n = 4) compared with cortical dysplasia (17%; n = 23) and Rasmussen encephalitis (17%; n = 12). In univariate analysis, other factors associated with developing hydrocephalus were elevated maximum daily temperatures, elevated white blood cell counts, decreased CSF protein, and increased CSF red blood cell counts. Conclusions The findings of the study indicate that etiology was the factor most strongly associated with developing posthemispherectomy hydrocephalus. These findings suggest that there are variable mechanisms for developing hydrocephalus after cerebral hemispherectomy depending on the procedure, and in resection-disconnection operations the mechanism may involve changes in CSF bulk flow that varies by histopathology.

Sign in / Sign up

Export Citation Format

Share Document