EUpertstrain 4 Study of Bordetella Pertussis Isolates

Bordetella Pertussis, Whooping Cough Clinical Trial

Official title:

EUpertstrain 4 Study of Bordetella Pertussis Isolates

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03197597
• Other study ID #: EUpert IV
• Status: Completed
• Phase: N/A
• First received: June 13, 2017
• Last updated: June 22, 2017
• Start date: October 12, 2015
• Est. completion date: December 31, 2016

Study information

• Verified date: June 2017
• Source: University of Turku
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study focus on the genetic changes of B. pertussis clinical isolates. For this panels of B. pertussis isolates has been collected during four periods in different European countries.

Description:

B. pertussis is considered as a monomorphic pathogen. However, genetic changes have been observed in several antigens (pertussis toxin, pertactin, filamentous haemagglutinin and fimbriae) included in the current acellular pertussis vaccines between vaccine strains and circulating isolates.

To study genetic changes in the B. pertussis populations in Europe, four distinct panels have been collected: EUpert I in 1999-2001 including 102 isolates, EUpert II in 2004-2005 including 154 isolates, EUpert III in 2007-2009 including 140 isolates and EUpert IV in 2012-2015 including 265 isolates. Selection criteria have remained unchanged for all four collections, which enables the opportunity to study changes in B. pertussis populations during the last 15 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 265
• Est. completion date: December 31, 2016
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• B. pertussis clinical isolates should be collected from subjects from different regions and be epidemiologically unrelated.

• An equal number of isolates from vaccinated and unvaccinated subjects should be collected. Optimally, the isolates are preferred to be selected from individuals less than 5 years of age.

• For countries with large numbers of isolates in their collections, isolates should be randomly selected according to criteria above.

Exclusion Criteria:

• There is no strict exclusion criteria for this study

Related Conditions & MeSH terms

• Bordetella Pertussis, Whooping Cough
• Whooping Cough

Intervention

Other:
• Strain isolation from the nasopharynx
B. pertussis strains has been collected from the nasopharynx of the patients during the clinical visit

Locations

Country	Name	City	State
Finland	University of Turku	Turku

Sponsors (3)

Lead Sponsor	Collaborator
University of Turku	GlaxoSmithKline, Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

Finland, 

References & Publications (8)

Advani A, Hallander HO, Dalby T, Krogfelt KA, Guiso N, Njamkepo E, von Könnig CH, Riffelmann M, Mooi FR, Sandven P, Lutynska A, Fry NK, Mertsola J, He Q. Pulsed-field gel electrophoresis analysis of Bordetella pertussis isolates circulating in Europe from 1998 to 2009. J Clin Microbiol. 2013 Feb;51(2):422-8. doi: 10.1128/JCM.02036-12. Epub 2012 Nov 21. — View Citation

Barkoff AM, Guiso N, Guillot S, Xing D, Markey K, Berbers G, Mertsola J, He Q. A rapid ELISA-based method for screening Bordetella pertussis strain production of antigens included in current acellular pertussis vaccines. J Immunol Methods. 2014 Jun;408:142-8. doi: 10.1016/j.jim.2014.06.001. Epub 2014 Jun 10. — View Citation

Barkoff AM, Mertsola J, Guillot S, Guiso N, Berbers G, He Q. Appearance of Bordetella pertussis strains not expressing the vaccine antigen pertactin in Finland. Clin Vaccine Immunol. 2012 Oct;19(10):1703-4. Epub 2012 Aug 22. — View Citation

Bouchez V, Brun D, Cantinelli T, Dore G, Njamkepo E, Guiso N. First report and detailed characterization of B. pertussis isolates not expressing Pertussis Toxin or Pertactin. Vaccine. 2009 Oct 9;27(43):6034-41. doi: 10.1016/j.vaccine.2009.07.074. Epub 2009 Aug 8. — View Citation

Caro V, Njamkepo E, Van Amersfoorth SC, Mooi FR, Advani A, Hallander HO, He Q, Mertsola J, Riffelmann M, Vahrenholz C, Von König CH, Guiso N. Pulsed-field gel electrophoresis analysis of Bordetella pertussis populations in various European countries with different vaccine policies. Microbes Infect. 2005 Jun;7(7-8):976-82. — View Citation

Heikkinen E, Xing DK, Olander RM, Hytönen J, Viljanen MK, Mertsola J, He Q. Bordetella pertussis isolates in Finland: serotype and fimbrial expression. BMC Microbiol. 2008 Sep 25;8:162. doi: 10.1186/1471-2180-8-162. — View Citation

Mooi FR, van Loo IH, van Gent M, He Q, Bart MJ, Heuvelman KJ, de Greeff SC, Diavatopoulos D, Teunis P, Nagelkerke N, Mertsola J. Bordetella pertussis strains with increased toxin production associated with pertussis resurgence. Emerg Infect Dis. 2009 Aug;15(8):1206-13. doi: 10.3201/eid1508.081511. — View Citation

van Amersfoorth SC, Schouls LM, van der Heide HG, Advani A, Hallander HO, Bondeson K, von König CH, Riffelmann M, Vahrenholz C, Guiso N, Caro V, Njamkepo E, He Q, Mertsola J, Mooi FR. Analysis of Bordetella pertussis populations in European countries with different vaccination policies. J Clin Microbiol. 2005 Jun;43(6):2837-43. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vaccine antigen deficient (VAD) B. pertussis clinical isolates	We screened a panel of 265 B. pertussis clinical isolates collected from 9 European countries. We used previously developed ELISA to measure the antigen expression of pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and fimbriae 2&3 (Fim2&3). In addition, we used sequencing to further characterize the pertactin gene of the bacteria.	24 months
Primary	Study of genetic changes in the B. pertussis genomic content measured by specific molecular methods	We studied genetic changes in the main virulence genes of B. pertussis. We genotyped pertussis toxin promoter (ptxP), pertactin (PRN), fimbriae3 (Fim3) and pertussis toxin subunit A (ptxA). Serotyping of Fimbriae (Fim), Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable number tandem repeat Analysis (MLVA) were used for further genomic analysis.	24 months
Primary	Association between vaccine antigen deficient (VAD) B. pertussis clinical isolates and their association to the introduction of acellular pertussis vaccination (ACV)	We studied the association between the frequency of VAD B. pertussis clinical isolates and their association to the introduction of ACV. Data of vaccination schedules by country and number of VAD isolates were collected and compared.	24 months