Droplet Digital PCR and PCR-free BIOSensors for the Detection of Resistance-associated SNPs in Pneumocystis Jirovecii

NCT06431958 | Active Not Recruiting

• 1 other identifier: 29BRC24.0085 - DDBIOS
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the proposed research is to identify Pneumocystis jirovecii mutant strains on 4 genes encoding therapeutic targets such as dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), cytochrome b (CYB), inosine-5'-monophosphate dehydrogenase (IMPDH) and therefore to assess the prevalence of potentially resistant strains in patients infected with P. jirovecii.

Conditions

Pneumocystis Pneumonia

Keywords

Pneumocystis jirovecii; mutant; anti-microbial resistance; DHPS; DHFR; Cytochrome b; IMPDH

Outcome Measures

Primary Outcomes (1)

• Presence of specific strains of Pneumocystis jirovecii potentially resistant to treatments in patients infected with this fungus

  Four genes encoding therapeutic targets such as dihydropteroate synthase (DHPS), dihydrofolate reductase (DHFR), cytochrome b (CYB), inosine-5'-monophosphate dehydrogenase (IMPDH) will be amplified and sequenced to detect single nucleotide polymorphisms (Single Nucleotide Polymorphism, SNP), in particular those potentially linked to resistance to anti-Pneumocystis treatments.

  at inclusion

Secondary Outcomes (1)

• to determine the factors associated (e.g. exposure to treatments) with P. jirovecii mutant strains

  at inclusion

Other Outcomes (2)

• to determine the impact of mutations on the effectiveness of anti-Pneumocystis treatment (e.g. favorable vs. unfavorable evolution of the infection)

  1 month and 3 month

• to evaluate two methods - digital droplet PCR and biosensors without PCR - for the detection and characterization of mutations associated with resistance in Pneumocystis jirovecii

  at inclusion

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients in whom P. jirovecii was detected in a pulmonary sample (bronchoalveolar lavage, sputum, bronchial aspiration, oropharyngeal rinse, nasopharyngeal sample) can be included in the study

You may qualify if:

• Patients in whom P. jirovecii was detected in a pulmonary sample (bronchoalveolar lavage, sputum, bronchial aspiration, oropharyngeal rinse, nasopharyngeal sample)
• No opposition
• Patient affiliated to a social security system

You may not qualify if:

• Patients under legal protection (guardianship, curatorship)
• Refusal to participate

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

Chu Brest

Brest, 29609, France

Location

Related Publications (7)

• Hoffmann CV, Nevez G, Moal MC, Quinio D, Le Nan N, Papon N, Bouchara JP, Le Meur Y, Le Gal S. Selection of Pneumocystis jirovecii Inosine 5'-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid. J Fungi (Basel). 2021 Oct 10;7(10):849. doi: 10.3390/jof7100849.

  PMID: 34682270 RESULT

• Argy N, Le Gal S, Coppee R, Song Z, Vindrios W, Massias L, Kao WC, Hunte C, Yazdanpanah Y, Lucet JC, Houze S, Clain J, Nevez G. Pneumocystis Cytochrome b Mutants Associated With Atovaquone Prophylaxis Failure as the Cause of Pneumocystis Infection Outbreak Among Heart Transplant Recipients. Clin Infect Dis. 2018 Aug 31;67(6):913-919. doi: 10.1093/cid/ciy154.

  PMID: 29514207 RESULT

• Bonnet PL, Hoffmann CV, Le Nan N, Bellamy L, Hoarau G, Flori P, Demar M, Argy N, Morio F, Le Gal S, Nevez G. Atovaquone exposure and Pneumocystis jirovecii cytochrome b mutations: French data and review of the literature. Med Mycol. 2023 Sep 4;61(9):myad095. doi: 10.1093/mmy/myad095.

  PMID: 37656874 RESULT

• de la Horra C, Friaza V, Morilla R, Delgado J, Medrano FJ, Miller RF, de Armas Y, Calderon EJ. Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii. J Fungi (Basel). 2021 Oct 13;7(10):856. doi: 10.3390/jof7100856.

  PMID: 34682277 RESULT

• Nahimana A, Rabodonirina M, Bille J, Francioli P, Hauser PM. Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis. Antimicrob Agents Chemother. 2004 Nov;48(11):4301-5. doi: 10.1128/AAC.48.11.4301-4305.2004.

  PMID: 15504856 RESULT

• Kojabad AA, Farzanehpour M, Galeh HEG, Dorostkar R, Jafarpour A, Bolandian M, Nodooshan MM. Droplet digital PCR of viral DNA/RNA, current progress, challenges, and future perspectives. J Med Virol. 2021 Jul;93(7):4182-4197. doi: 10.1002/jmv.26846. Epub 2021 Mar 11.

  PMID: 33538349 RESULT

• Pla L, Avino A, Eritja R, Ruiz-Gaitan A, Peman J, Friaza V, Calderon EJ, Aznar E, Martinez-Manez R, Santiago-Felipe S. Triplex Hybridization-Based Nanosystem for the Rapid Screening of Pneumocystis Pneumonia in Clinical Samples. J Fungi (Basel). 2020 Nov 17;6(4):292. doi: 10.3390/jof6040292.

  PMID: 33213011 RESULT

MeSH Terms

Conditions

Pneumonia, Pneumocystis

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Infections; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: May 29, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
• Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement

Locations

FR (1)