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Puumala Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Must Be Considered across the Borders of Nephrology to Avoid Unnecessary Diagnostic Procedures.

ABSTRACT: Nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, is caused by Puumala virus and is characterized by acute kidney injury and thrombocytopenia.A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed.Of the 456 investigated patients, 335 had received inpatient treatment. At time of admission to hospital, 72% of the patients had still an AKI and thrombocytopenia was present in 64% of the patients. The 335 patients were treated in 29 different hospitals and 6 of which had nephrology departments. 10 out of 335 patients received treatment in university hospitals and 63% of patients admitted themselves to hospital. Initially, the patients were admitted to 12 different clinical departments (29% of the patients were referred to a nephrology department) and during the course of the disease, 8% of the patients were transferred to another department in the same hospital and 3% were transferred to a nephrology department at another hospital. Regarding diagnostic procedures, in 28% of the inpatients computed tomography to exclude pulmonary embolism or due to severe gastrointestinal symptoms, lumbar puncture to exclude meningitis, magnetic resonance tomography of the brain owing to suspected stroke because of visual disorders, gastroscopy, or colonoscopy due to gastrointestinal symptoms was performed at time of admission to hospital.NE must be considered by physicians across the borders of nephrology to avoid unnecessary diagnostic procedures especially in areas where NE is endemic.

SUBMITTER: Kitterer D

PROVIDER: S-EPMC4674130 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:CRISPR (clustered regularly interspaced short palindromic repeats), an ancient defense mechanism used by prokaryotes to cleave nucleic acids from invading viruses and plasmids, is currently being harnessed by researchers worldwide to develop new point-of-need diagnostics. In CRISPR diagnostics, a CRISPR RNA (crRNA) containing a "spacer" sequence that specifically complements with the target nucleic acid sequence guides the activation of a CRISPR effector protein (Cas13a, Cas12a or Cas12b), leading to collateral cleavage of RNA or DNA reporters and enormous signal amplification. CRISPR function can be disrupted by some types of sequence mismatches between the spacer and target, according to previous studies. This poses a potential challenge in the detection of variable targets such as RNA viruses with a high degree of sequence diversity, since mismatches can result from target variations. To cover viral diversity, we propose in this study that during crRNA synthesis mixed nucleotide types (degenerate sequences) can be introduced into the spacer sequence positions corresponding to viral sequence variations. We test this crRNA design strategy in the context of the Cas13a-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) technology for detection of Crimean-Congo hemorrhagic fever virus (CCHFV), a biosafety level 4 pathogen with wide geographic distribution and broad sequence variability. The degenerate-sequence CRISPR diagnostic proves functional, sensitive, specific and rapid. It detects within 30-40 minutes 1 copy/μl of viral RNA from CCHFV strains representing all clades, and from more recently identified strains with new mutations in the CRISPR target region. Also importantly, it shows no cross-reactivity with a variety of CCHFV-related viruses. This proof-of-concept study demonstrates that the degenerate sequence-based CRISPR diagnostic is a promising tool of choice for effective detection of highly variable viral pathogens.

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Puumala Hantavirus-Induced Hemorrhagic Fever with Renal Syndrome Must Be Considered across the Borders of Nephrology to Avoid Unnecessary Diagnostic Procedures.

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