scholarly journals 672. Diagnosis of Rocky Mountain Spotted Fever Using Plasma Metagenomic Next-Generation Sequencing

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S438-S438
Author(s):  
Leslie Chiang ◽  
Nanda Ramchandar ◽  
Nicole Coufal ◽  
Lauge Farnaes ◽  
Jennifer Foley
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Care ◽  
Spotted Fever ◽  
Panel Member ◽  
Rocky Mountain ◽  
Next Generation ◽  
Rocky Mountain Spotted Fever ◽  
Rickettsia Rickettsii ◽  
Serologic Testing ◽  
Generation Sequencing

Abstract Background Rocky mountain spotted fever (RMSF), caused by Rickettsia rickettsii, incurs significant morbidity and mortality, especially in children. Early in the course of illness, standard diagnostic tests are of limited sensitivity, and diagnosis is often based on clinical symptoms and local epidemiology. The diagnosis can be missed in areas where RMSF is not endemic, and a delay in initiation of therapy may lead to poor clinical outcomes. Plasma metagenomic next-generation sequencing (mNGS), with turnaround times approaching 48 hours, may be a useful adjunctive tool in the diagnosis of RMSF. Methods We describe four children hospitalized with RMSF between January 1, 2017 to May 15, 2021 at a tertiary children’s hospital in southern California. All had plasma mNGS and rickettsial serologic testing as part of clinical care. Results mNGS detected Rickettsia rickettsii in all 4 patients. Only 2 subjects had positive serologic testing initially and required repeat testing in the convalescent stage to confirm RMSF. The mean turnaround time for mNGS was 2.75 days, which was comparable to serologic testing. Antibiotic therapy was changed in three subjects as a result of the plasma mNGS result. Conclusion Plasma mNGS may be a useful diagnostic modality early in the disease course of RMSF. Disclosures Lauge Farnaes, MD, PhD, Cardea Bio (Advisor or Review Panel member)IDbyDNA (Employee)

Mitbringsel aus den Ferien

Praxis ◽  
2005 ◽  
Vol 94 (47) ◽  
pp. 1869-1870
Author(s):  
Balestra ◽  
Nüesch
Keyword(s):  
Rocky Mountains ◽  
Spotted Fever ◽  
Rocky Mountain ◽  
Rickettsia Conorii ◽  
Rocky Mountain Spotted Fever ◽  
Klinische Diagnose ◽  
Rickettsia Rickettsii

Eine 37-jährige Patientin stellt sich nach der Rückkehr von einer Rundreise durch Nordamerika mit einem Status febrilis seit zehn Tagen und einem makulösem extremitätenbetontem Exanthem seit einem Tag vor. Bei suggestiver Klinik und Besuch der Rocky Mountains wird ein Rocky Mountain spotted fever diagnostiziert. Die Serologie für Rickettsia conorii, die mit Rickettsia rickettsii kreuzreagiert, war positiv und bestätigte die klinische Diagnose. Allerdings konnte der beweisende vierfache Titeranstieg, möglicherweise wegen spät abgenommener ersten Serologie, nicht nachgewiesen werden. Nach zweiwöchiger antibiotischer Therapie mit Doxycycline waren Status febrilis und Exanthem regredient.

Assessing the Value of Next-Generation Sequencing Tests in a Dynamic Environment

2018 ◽  
pp. 139-146 ◽  
Author(s):  
Howard A. Burris ◽  
Leonard B. Saltz ◽  
Peter P. Yu
Keyword(s):  
Next Generation Sequencing ◽  
Cancer Biology ◽  
Health Care Policy ◽  
Clinical Care ◽  
Dynamic Environment ◽  
Investigational Drug ◽  
Next Generation ◽  
Genomic Alterations ◽  
Clinical Annotation ◽  
Generation Sequencing

Next-generation sequencing (NGS)–based technology has lowered the cost of cancer testing for genomic alterations and is now commercially available from a growing number of diagnostic laboratories. However, laboratories vary in the methodologies underlying their tests, the types and numbers of genomic alterations covered by the test, and the clinical annotation of the sequencing findings. Determining the value of NGS tests is dependent on whether it is used to support clinical trials or as a part of routine clinical care at a time when both the investigational drug pipeline and the list of U.S. Food and Drug Administration–approved or Compendium-listed therapeutics is in a high state of flux. Reimbursement policy for NGS testing by the Centers for Medicare & Medicaid is evolving as the value of NGS testing becomes more clearly defined for specific clinical situations. Patient care and clinical decisions-making are dependent on the oncologist’s knowledge of when NGS testing has value. Here, we review principles and practice for NGS testing in this dynamic confluence of technology, cancer biology, and health care policy.

Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 584-584
Author(s):  
Kristin Lynn Koenig ◽  
Jarred Burkart ◽  
Sameh Mikhail ◽  
Christina Sing-Ying Wu ◽  
Anne M. Noonan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Clinical Care ◽  
Comprehensive Cancer Center ◽  
Genomic Profiling ◽  
Next Generation ◽  
Wild Type ◽  
Genomic Alterations ◽  
Generation Sequencing

584 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 265 pts with GI malignancies underwent successful genomic profiling. 1205 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through next generation sequencing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.

scholarly journals Solution structure of the cold-shock-like protein fromRickettsia rickettsii

2012 ◽  
Vol 68 (11) ◽  
pp. 1284-1288 ◽  
Author(s):  
Kyle P. Gerarden ◽  
Andrew M. Fuchs ◽  
Jonathan M. Koch ◽  
Melissa M. Mueller ◽  
David R. Graupner ◽  
...  
Keyword(s):  
Solution Structure ◽  
Cold Shock ◽  
Spotted Fever ◽  
Rocky Mountain ◽  
Rocky Mountain Spotted Fever ◽  
Cold Shock Proteins ◽  
Rickettsia Rickettsii ◽  
The Family ◽  
Α Helix ◽  
Shock Proteins

Rocky Mountain spotted fever is caused byRickettsia rickettsiiinfection.R. rickettsiican be transmitted to mammals, including humans, through the bite of an infected hard-bodied tick of the family Ixodidae. Since theR. rickettsiigenome contains only one cold-shock-like protein and given the essential nature of cold-shock proteins in other bacteria, the structure of the cold-shock-like protein fromR. rickettsiiwas investigated. With the exception of a short α-helix found between β-strands 3 and 4, the solution structure of theR. rickettsiicold-shock-like protein has the typical Greek-key five-stranded β-barrel structure found in most cold-shock domains. Additionally, theR. rickettsiicold-shock-like protein, with a ΔGof unfolding of 18.4 kJ mol−1, has a similar stability when compared with other bacterial cold-shock proteins.

scholarly journals Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs.

1997 ◽  
Vol 41 (1) ◽  
pp. 141-147 ◽  
Author(s):  
E B Breitschwerdt ◽  
M G Davidson ◽  
B C Hegarty ◽  
M G Papich ◽  
C B Grindem
Keyword(s):  
Spotted Fever ◽  
Rocky Mountain ◽  
Rocky Mountain Spotted Fever ◽  
Serum Samples ◽  
Concurrent Administration ◽  
Rickettsia Rickettsii ◽  
Beneficial Effects ◽  
Concurrent Use ◽  
Antibody Titers ◽  
Anti Inflammatory

Dogs were experimentally inoculated with Rickettsia rickettsii to determine if anti-inflammatory or immunosuppressive dosages of prednisolone, when administered in conjunction with an antirickettsial antibiotic (doxycycline), induced therapeutically relevant pathophysiological consequences that ultimately influence disease outcome. Although the duration of rickettsemia was prolonged in dogs receiving immunosuppressive, but not anti-inflammatory, corticosteroids, concurrent administration of doxycycline and corticosteroids conferred no other detected detrimental effects. Treatment with doxycycline or doxycycline in conjunction with prednisolone resulted in decreased R. rickettsii-specific antibody titers; however, examination of appropriately timed acute- and convalescent-phase serum samples would have facilitated an accurate diagnosis of Rocky Mountain spotted fever (RMSF) in all 16 dogs. We conclude that the concurrent use of anti-inflammatory or immunosuppressive doses of prednisolone in conjunction with doxycycline, early in the course of experimental RMSF, confers no clinically relevant detrimental effects and that additional studies might be indicated to detect possible beneficial effects in cases of severe or potentially fulminant RMSF. However, because the illness induced in these dogs was of mild to moderate severity, the results of this study should definitely not be construed as supporting the safety or efficacy of prednisolone for treatment of severe canine or human RMSF.

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