Clinical trial NCT04535505: Pathogenic Bordetella Rapid Detection
Official title: Establishment a Nucleic Acid Rapid Detection Technology Platform for Detecting Pathogenic Bordetella and Its Drug Resistance Genes
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Pertussis
Keywords: Pertussis；Children；Diagnostic test；CPA; CRISPR
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2020-09-02
Enrollment: 0
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 600 cases of suspected pertussis clinically diagnosed in the outpatient clinic and ward of Children's Hospital of Fudan University would be enrolled. The enrollment would start in October 2021 and end in June 2022. Patients who are admitted to the Children's Hospital of Fudan University during the enrollment period and are clinically suspected of pertussis would be the research objects. There are no special requirements for gender of the enrolled patients.

Brief summary: A CPA platform based on the CRISPR technology is going to established to achieve the goal of detecting pathogenic bordetella and drug resistance genes in one step. The accuracy of this platform will be checked through prospective diagnostic test evaluation methods. Bordetella pertussis isolation culture and identification would be set as a gold standard method.

Detailed description: Pertussis is an acute respiratory infectious disease caused by bordetella pertussis. Although it is a vaccine-preventable disease, outbreaks and epidemic cases of whooping cough worldwide have been reported from time to time. Bordella parapertussis, Bodella bronchiseptica, and bordetella hosei can cause pertussis-like diseases with symptoms similar to those of whooping cough. The clinical manifestations are difficult to distinguish, and they are easily reported as cases of whooping cough through the infectious disease network.

The diagnosis of the infectious diseases caused by the four pathogenic bodella mainly relies on laboratory pathogenic testing. At present, the laboratory tests of bordetella that can be carried out in the clinical microbiology laboratory include culture, bordetella pertussis specific antibody (PT-IgG) serological detection, and bordetella pertussis nucleic acid PCR detection. However, none of them meet the requirements of early diagnosis.

Cross primer constant temperature amplification (CPA) is nucleic acid constant temperature amplification technology with independent property rights. The fully automated nucleic acid detection platform equipped with CPA technology would make the detection of four pathogenic bordetella easy, quick and safe and accurate.

As pathogenic bodella is difficult to cultivate and there is no standard for drug susceptibility test. Studies have shown that 57.4% of the isolated clinical isolates of bordetella pertussis have MIC value for erthomycin ≥256 μg/mL , and 23s rRNA 2047 site adenine (A) were mutated to guanine (G).CRISPR/Cas is an immune system in bacteria that can specifically recognize invading nucleic acids and shear them. The CRISPR technology developed based on the CRISPR/Cas principle can detect single point mutations in genes.

The hypothesis that 4 pathogenic bordetella and their erythromycin resistance would be detected in one testing platform simultaneously. The accuracy, reliability, predictive value of this platform would be checked through prospective diagnostic test evaluation methods. Bordetella pertussis isolation culture and identification would be as the gold standard method.

Eligibility criteria: Inclusion Criteria:

* Patients with continuous cough (paroxysmal cough) for more than 1 week, peripheral white blood cell 18×109/L (infants and young children), or\> 15×109/L (children), ineffective use of cephalosporin antibacterial drugs，and these patients whose nasopharyngeal swabs are collected for routine bordetella culture identification and drug susceptibility testing would be included as research object.

Exclusion Criteria:

* Patients with pertussis are suspected clinically but no nasopharyngeal swab specimens are collected or patients with pertussis are clinically excluded.

Primary outcomes:
measure: Accuracy of the new CPA platform based on CRISPR technology, including sensitivity and specificity
timeFrame: At enrollment
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Chuanqing Wang, Phd
role: STUDY_DIRECTOR
References: