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CompletedNCT03388034PERILIC-ICUpdated Apr 1, 2022

Pertussis Immunization Programs in Low Income Countries - Ivory Coast

An observational study in Bordetella Pertussis, Whooping Cough, sponsored by Institut Pasteur. Completed at 5 sites in Côte D'Ivoire. Per ClinicalTrials.gov, last updated 2022-04-01.

Sponsored by Institut Pasteur · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
789
Sex
All
01

Study summary

Due to waning of infectious as well as vaccine immunity and lack of vaccination boosters, a large number of adolescents and adults are no longer immunized against Bordetella pertussis, the agent of whooping cough and consequently may contract whooping cough. Furthermore, these populations represent a reservoir of the infectious agent from which the dissemination to non-immune infants is possible, causing severe illness, or even death, in this age group.

Few studies have been carried out on whooping cough in developing countries (incidence, contaminator's age, etc.) and, specifically, none have assessed the duration of protection induced by the whole cell pertussis (wP) vaccine mainly presently used in these countries.

However, data on the duration of vaccine induced protection are essential to determine i) the usefulness of vaccine boosters and ii) the target age group for these boosters.

The aims of the present study are:

  • To evaluate the proportion of confirmed pertussis cases in infants presenting whooping cough syndrome (WP1a)
  • To evaluate the proportion of confirmed pertussis cases or healthy carriers among contact cases
  • To determine origin of the infant's contamination (WP1b)
  • To determine the duration of protection induced by the wP vaccines used in contact cases and the child population aged 3 to 15 yo (WP1b and WP2)
  • To bring new scientific evidences documenting the potential need for initiating boosters (WP1b and WP2)
  • To allow a comparison of the results with those obtained using the same methodology for the acellular pertussis vaccine and/or in other contexts. Potential implications for the use of pertussis vaccines in low and moderate income countries.
  • To increase local capabilities by the transfer of materials and expertise that will make the diagnosis of pertussis possible in the centres of reference and strengthen a pertussis monitoring network in the implicated countries.
  • To improve children's health through a better match of the vaccination schedule according to the reality of the situation.
Read the detailed description

Background:

Vaccination of infants and young children with a whole-cell pertussis (wP) vaccine dramatically decreased the mortality and morbidity due to B. pertussis. However, twenty-five years of "honeymoon" period, after the introduction of high vaccination coverage, reappearance of whooping cough cases in industrialized countries was observed in infants contaminated by adolescents and adults. This modification in transmission of the disease after the introduction of the wP vaccine indicated that the immunity provided by the vaccine is not lifelong, just like that provided by natural infection, and that it decreases7-9 years after the first vaccination and the first booster. Due to secondary effects, wP vaccines cannot be used for boosters. Moreover, the wP vaccines have been shown to be different in terms of efficacy (varying from 30 to 95%). Acellular pertussis (aP) vaccines consisting of purified and inactivated bacterial proteins, have therefore been developed and commercialized. These vaccines induce much fewer side effects and may therefore be used for primary-vaccination as well as for vaccine boosters. They are expensive but have more reproducible manufacturing. The humoral and long-term cell-mediated immunities granted by the aP vaccines have been shown to be comparable to the immunity granted by the wP vaccines, effective for 6-7 years after the booster vaccine in the second year of life, also inducing different cell immunity. Since 2007, the proportion of B. pertussis and B. parapertussis isolates no longer producing vaccine antigen(s) has increased in the industrialized countries that use aP vaccines. These isolates may decrease the efficacy of the aP vaccines. Does this type of isolates circulate in the Low income countries still using wP vaccines ? Does it reduce the efficacy of the wP vaccines? Moreover, the wP vaccines used in the Southern countries have not been assessed like the ones used in the Northern countries. In particular, the duration of protection after the primary-vaccination and a vaccine booster is not known.

Rational:

For various reasons, a large difference exits between the monitoring systems across the world: awareness of the disease is variable depending on the population; differences in the immunization coverage and strategies; diverse compositions of the vaccines used; but overall the large differences between the vaccines in terms of immunity against the disease, protection against infection and/or decrease in the transmission of the pathogen. The underestimation of pertussis is recognized by the World Health Organisation (WHO) and the Global Pertussis Initiative (GPI) who highlight the problem of the reliability of the declared data.

This situation is the result of i) limited use of biological diagnostics (problems in isolating the bacteria in the laboratories); ii) diagnostic errors due to the fact that diagnosis is mainly clinical ; iii) inadequate monitoring of the illness ; iv) a lack of awareness among physicians. Pertussis is not considered when it is comes to identifying the respiratory pathogen: most clinicians continue to consider it as only a child illness and ignore adult infections. The absence of an available tool allowing a reliable diagnostic to be made makes difficult to assess the real impact of this pathogen in child respiratory syndromes.

Several studies have been performed on the duration of protection induced by the wP and aP vaccines in Australia, the USA and in Europe. However, few studies have been performed on the wP vaccines used in middle and low income countries and none in Ivory Coast.

This study is part of a program entitled PERILIC which is currently conducted in Cambodia, Madagascar and Togo (NCT02983487). This research program will allow the vaccination strategy of each region concerned to be adapted when needed, as recommended by the WHO.

Expected Outcomes:

Impact on vaccination strategy:This study, as well as the analysis of data from other national programs for the surveillance of Pertussis, may raise public health authorities' awareness and help them adapting their assessment method for national vaccination programs by including the duration of protection induced by their national wP vaccine and their data on vaccine coverage, on the basis of the information in vaccination booklets, as recommended by WHO.

Impact on the improvement the children's health: The results of our study should raise the public health authorities' awareness on vaccine-preventable diseases, especially whooping cough. This raising of awareness will focus on the surveillance/monitoring and diagnosis of this disease. Moreover, the development of reliable biological diagnostic tools for pertussis will help the clinicians to confirm pertussis diagnosis and to adapt the therapeutic approach accordingly, thus improving the care of the infected person and to stop transmission of the disease which is very contagious.

Impact on the surveillance of the disease by developing an hospital-based surveillance Training, technology transfer and strengthening of the surveillance network: For the first time, the detection and identification techniques for the other species of Bordetella genus (i.e. B. parapertussis and B. holmesii) will be transferred to laboratories in Ivory Coast. The diagnosis of the different Bordetella species by real time PCR and the serological tests will be set up in the laboratories participating in this study. These laboratories could further be used by the national surveillance network and thus improve the quality of the data available for the local health authorities and for WHO. Thus, this study will allow the establishment of an effective monitoring of pertussis in Ivory Coast through the raising of the population's awareness, the training of local doctors on the clinical screening of this disease, and finally via the transfer of diagnostic techniques within the laboratories.

02

Conditions studied

  • Bordetella Pertussis, Whooping Cough

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03

In context

Whooping Cough

290 studies on the registry are indexed under Whooping Cough; 23 are open to participants now.

This study's enrollment of 789 is above the median of 510 across 60 observational studies indexed under Whooping Cough.

Browse Whooping Cough studies →

Lead sponsor

Institut Pasteur is the lead sponsor of 99 studies on the registry; 41 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

Cohort 1 (WP1a): Infants under 6 months old coming to hospital with clinical signs of whooping cough syndrome.

Cohort 2 (WP1b): Contact cases of confirmed infants included in the WP1a module Cohort 3 (WP2): Children from 3 to 15 years old included, without underlying illness, with complete pertussis primo-vaccination

Eligibility criteria

Inclusion Criteria (Cohort 1):

  • Infants under 6 months old
  • Presenting clinical signs of a whooping cough syndrome
  • Written consent obtained from a parent/guardian of the child

Inclusion Criteria (Cohort 2):

  • People in regular and prolonged contact (>3h per day) with the index case for at least 15 days before the signs of whooping cough occurred in the infected child, living (or not) in the same household.
  • For the adults, written consent obtained.
  • For minors under 7 yo: written consent obtained from a parent/guardian.
  • For minors over 7 yo: written consent obtained from parent/guardian and oral assent obtained from the child.

Inclusion Criteria (Cohort 3):

  • Child aged between 3 and 15 yo
  • Up to date first pertussis vaccination (vaccination booklet or official register)
  • Last pertussis vaccination done more than one year before inclusion
  • For minors under 7 yo: written consent obtained from parent/guardian.
  • For minors over 7 yo: written consent obtained from parent/guardian and oral assent obtained from the child.

Exclusion Criteria (Cohort 3):

  • Pertussis vaccination done more than one year before inclusion
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Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
789 participants (actual)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • Index case (WP1a)

    Infant under 6 months old with clinical signs of whooping cough syndrome. Nasopharyngeal sampling: A nasopharyngeal sample collected from each nostril by swabbing

    Procedure: Nasopharyngeal sampling

  • Control case (WP1b)

    Contact cases of infant with a positive diagnosis for whooping cough. Nasopharyngeal sampling: A nasopharyngeal sample collected from each nostril by swabbing Blood sampling: A blood sample collected by fingerprick

    Procedure: Nasopharyngeal sampling · Procedure: Blood Sampling

  • Seroepidemiological cohort (WP2)

    Children between 3 and 15 years old with complete primo-vaccination against B.Pertussis Blood sampling: A blood sample collected by fingerprick

    Procedure: Blood Sampling

Interventions

  • ProcedureNasopharyngeal sampling

    A nasopharyngeal sample collected from each nostril by swabbing

  • ProcedureBlood Sampling

    Blood sample by the tip of a finger (fingerprick)

06

What researchers measure

Primary outcomes

  1. Proportion of biologically confirmed cases of pertussis in patients under 6 months old admitted into hospital with clinical signs corresponding to whooping cough syndrome.

    Primary Outcome of Cohort 1 (WP1a)

    Time frame: December 2019

  2. Identification of the contaminator of the index case

    Primary Outcome of Cohort 2 (WP1b)

    Time frame: December 2019

  3. Estimation of the protection period induced by the primo-vaccination in children between 3 and 15 yo

    Primary Outcome of Cohort 3 (WP2)

    Time frame: December 2019

Secondary outcomes

  1. Estimation of the relative risk of the disease occurring in the contact patients based on their immunization status and age groups

    Time frame: June 2020

07

Study locations

5 sites
  • Centre de Santé Urbain à base Communautaire (CSU-Com) d'Angré
    Abidjan, Côte D'Ivoire
  • CHU d'Angré
    Abidjan, Côte D'Ivoire
  • Hôpital Général de Port-Bouët
    Abidjan, Côte D'Ivoire
  • Hôpital Général de Yopougon Attié
    Abidjan, Côte D'Ivoire
  • Institut Pasteur de Côte d'Ivoire
    Abidjan, Côte D'Ivoire
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References and documents

Publications

  • Guiso N, Wirsing von Konig CH. Surveillance of pertussis: methods and implementation. Expert Rev Anti Infect Ther. 2016 Jul;14(7):657-67. doi: 10.1080/14787210.2016.1190272. Epub 2016 May 31. PubMed 27224518 ↗
  • Tubiana S, Belchior E, Guillot S, Guiso N, Levy-Bruhl D; Renacoq Participants. Monitoring the Impact of Vaccination on Pertussis in Infants Using an Active Hospital-based Pediatric Surveillance Network: Results from 17 Years' Experience, 1996-2012, France. Pediatr Infect Dis J. 2015 Aug;34(8):814-20. doi: 10.1097/INF.0000000000000739. PubMed 25955837 ↗
  • Guiso N. Pertussis vaccination and whooping cough: and now what? Expert Rev Vaccines. 2014 Oct;13(10):1163-5. doi: 10.1586/14760584.2014.941816. Epub 2014 Jul 14. PubMed 25020131 ↗
  • Heininger U, Andre P, Chlibek R, Kristufkova Z, Kutsar K, Mangarov A, Meszner Z, Nitsch-Osuch A, Petrovic V, Prymula R, Usonis V, Zavadska D. Comparative Epidemiologic Characteristics of Pertussis in 10 Central and Eastern European Countries, 2000-2013. PLoS One. 2016 Jun 3;11(6):e0155949. doi: 10.1371/journal.pone.0155949. eCollection 2016. PubMed 27257822 ↗
  • Guiso N, Levy C, Romain O, Guillot S, Werner A, Rondeau MC, Bechet S, Cohen R. Whooping cough surveillance in France in pediatric private practice in 2006-2015. Vaccine. 2017 Oct 27;35(45):6083-6088. doi: 10.1016/j.vaccine.2017.09.072. Epub 2017 Sep 30. PubMed 28974408 ↗
  • von Koenig CHW, Guiso N. Global burden of pertussis: signs of hope but need for accurate data. Lancet Infect Dis. 2017 Sep;17(9):889-890. doi: 10.1016/S1473-3099(17)30357-2. Epub 2017 Jun 13. No abstract available. PubMed 28623145 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Apr 2019 to primary completion in Jul 2021, 27 months.

Of 22 observational studies under Whooping Cough, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 61. This study's 27 months is close to that.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 22, 2017
First posted
Jan 2, 2018
StartActual
Apr 11, 2019
Primary completionActual
Jul 21, 2021
CompletionActual
Jul 21, 2021
Last update
Apr 1, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 1, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03388034
Lead sponsor
Institut Pasteur
Collaborators
Institut Pasteur of Cote d'Ivoire, Sanofi Pasteur, a Sanofi Company
Responsible party
Sponsor
First posted
Jan 2, 2018
Start date
Apr 11, 2019
Primary completion
Jul 21, 2021
Completion
Jul 21, 2021
Last update
Apr 1, 2022

Study contacts

Fabien TAIEB, MD, MSc, MPH
principal investigator · Institut Pasteur
Man-Koumba SOUMAHORO, PhD
principal investigator · Institut Pasteur of Cote d'Ivoire
Nicole GUISO, PhD
study chair · Institut Pasteur

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.

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