<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02983487</url>
  </required_header>
  <id_info>
    <org_study_id>2015-055</org_study_id>
    <nct_id>NCT02983487</nct_id>
  </id_info>
  <brief_title>Pertussis Immunization Programs in Low Income Countries</brief_title>
  <acronym>PERILIC</acronym>
  <official_title>Pertussis Immunization Programs in Low Income Countries</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut Pasteur</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut Pasteur, Cambodia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Pasteur de Madagascar</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Agence de Médecine Préventive, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut Pasteur</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Due to waning of infectious as well as vaccine immunity and lack of vaccination boosters, a&#xD;
      large number of adolescents and adults are no longer immunized against Bordetella pertussis,&#xD;
      the agent of whooping cough and consequently may contract whooping cough. Furthermore, these&#xD;
      populations represent a reservoir of the infectious agent from which the dissemination to&#xD;
      non-immune infants is possible, causing severe illness, or even death, in this age group.&#xD;
&#xD;
      Few studies have been carried out on whooping cough in developing countries (incidence,&#xD;
      contaminator's age, etc.) and, specifically, none have assessed the duration of protection&#xD;
      induced by the whole cell pertussis (wP) vaccine mainly presently used in these countries.&#xD;
&#xD;
      However, data on the duration of vaccine induced protection are essential to determine i) the&#xD;
      usefulness of vaccine boosters and ii) the target age group for these boosters.&#xD;
&#xD;
      The aims of the present study are:&#xD;
&#xD;
        -  To evaluate the proportion of confirmed pertussis cases in infants presenting whooping&#xD;
           cough syndrome (WP1a)&#xD;
&#xD;
        -  To evaluate the proportion of confirmed pertussis cases or healthy carriers among&#xD;
           contact cases&#xD;
&#xD;
        -  To determine origin of the infant's contamination (WP1b)&#xD;
&#xD;
        -  To determine the duration of protection induced by the wP vaccines used in contact cases&#xD;
           and the child population aged 3 to 15 yo (WP1b and WP2)&#xD;
&#xD;
        -  To bring new scientific evidences documenting the potential need for initiating boosters&#xD;
           (WP1b and WP2)&#xD;
&#xD;
        -  To allow a comparison of the results with those obtained using the same methodology for&#xD;
           the acellular pertussis vaccine and/or in other contexts. Potential implications for the&#xD;
           use of pertussis vaccines in low and moderate income countries.&#xD;
&#xD;
        -  To increase local capabilities by the transfer of materials and expertise that will make&#xD;
           the diagnosis of pertussis possible in the centres of reference and strengthen a&#xD;
           pertussis monitoring network in the implicated countries.&#xD;
&#xD;
        -  To improve children's health through a better match of the vaccination schedule&#xD;
           according to the reality of the situation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Vaccination of infants and young children with a whole-cell pertussis (wP) vaccine&#xD;
      dramatically decreased the mortality and morbidity due to B. pertussis. However, twenty-five&#xD;
      years of &quot;honeymoon&quot; period, after the introduction of high vaccination coverage,&#xD;
      reappearance of whooping cough cases in industrialized countries was observed in infants&#xD;
      contaminated by adolescents and adults. This modification in transmission of the disease&#xD;
      after the introduction of the wP vaccine indicated that the immunity provided by the vaccine&#xD;
      is not lifelong, just like that provided by natural infection, and that it decreases7-9 years&#xD;
      after the first vaccination and the first booster. Due to secondary effects, wP vaccines&#xD;
      cannot be used for boosters. Moreover, the wP vaccines have been shown to be different in&#xD;
      terms of efficacy (varying from 30 to 95%). Acellular pertussis (aP) vaccines consisting of&#xD;
      purified and inactivated bacterial proteins, have therefore been developed and&#xD;
      commercialized. These vaccines induce much fewer side effects and may therefore be used for&#xD;
      primary-vaccination as well as for vaccine boosters. They are expensive but have more&#xD;
      reproducible manufacturing. The humoral and long-term cell-mediated immunities granted by the&#xD;
      aP vaccines have been shown to be comparable to the immunity granted by the wP vaccines,&#xD;
      effective for 6-7 years after the booster vaccine in the second year of life, also inducing&#xD;
      different cell immunity. Since 2007, the proportion of B. pertussis and B. parapertussis&#xD;
      isolates no longer producing vaccine antigen(s) has increased in the industrialized countries&#xD;
      that use aP vaccines. These isolates may decrease the efficacy of the aP vaccines. Does this&#xD;
      type of isolates circulate in the Low income countries still using wP vaccines ? Does it&#xD;
      reduce the efficacy of the wP vaccines? Moreover, the wP vaccines used in the Southern&#xD;
      countries have not been assessed like the ones used in the Northern countries. In particular,&#xD;
      the duration of protection after the primary-vaccination and a vaccine booster is not known.&#xD;
&#xD;
      Rational:&#xD;
&#xD;
      For various reasons, a large difference exits between the monitoring systems across the&#xD;
      world: awareness of the disease is variable depending on the population; differences in the&#xD;
      immunization coverage and strategies; diverse compositions of the vaccines used; but overall&#xD;
      the large differences between the vaccines in terms of immunity against the disease,&#xD;
      protection against infection and/or decrease in the transmission of the pathogen. The&#xD;
      underestimation of pertussis is recognized by the World Health Organisation (WHO) and the&#xD;
      (Global Pertussis Initiative) who highlight the problem of the reliability of the declared&#xD;
      data.&#xD;
&#xD;
      This situation is the result of i) limited use of biological diagnostics (problems in&#xD;
      isolating the bacteria in the laboratories); ii) diagnostic errors due to the fact that&#xD;
      diagnosis is mainly clinical ; iii) inadequate monitoring of the illness ; iv) a lack of&#xD;
      awareness among physicians. Pertussis is not considered when it is comes to identifying the&#xD;
      respiratory pathogen: most clinicians continue to consider it as only a child illness and&#xD;
      ignore adult infections. The absence of an available tool allowing a reliable diagnostic to&#xD;
      be made makes difficult to assess the real impact of this pathogen in child respiratory&#xD;
      syndromes.&#xD;
&#xD;
      Several studies have been performed on the duration of protection induced by the wP and aP&#xD;
      vaccines in Australia, the USA and in Europe. However, few studies have been performed on the&#xD;
      wP vaccines used in middle and low income countries and none in Cambodia, Madagascar and&#xD;
      Togo. This is one of the objectives of our study. This will allow the vaccination strategy of&#xD;
      each region concerned to be adapted when needed, as recommended by the WHO.&#xD;
&#xD;
      Expected Outcomes:&#xD;
&#xD;
      Impact on vaccination strategy:This study, as well as the analysis of data from other&#xD;
      national programs for the surveillance of Pertussis, may raise public health authorities'&#xD;
      awareness and help them adapting their assessment method for national vaccination programs by&#xD;
      including the duration of protection induced by their national wP vaccine and their data on&#xD;
      vaccine coverage, on the basis of the information in vaccination booklets, as recommended by&#xD;
      WHO.&#xD;
&#xD;
      Impact on the improvement the children's health: The results of our study should raise the&#xD;
      public health authorities' awareness on vaccine-preventable diseases, especially whooping&#xD;
      cough. This raising of awareness will focus on the surveillance/monitoring and diagnosis of&#xD;
      this disease. Moreover, the development of reliable biological diagnostic tools for pertussis&#xD;
      will help the clinicians to confirm pertussis diagnosis and to adapt the therapeutic approach&#xD;
      accordingly, thus improving the care of the infected person and to stop transmission of the&#xD;
      disease which is very contagious.&#xD;
&#xD;
      Impact on the surveillance of the disease by developing an hospital-based&#xD;
      surveillance,Training, technology transfer and strengthening of the surveillance network: For&#xD;
      the first time, the detection and identification techniques for the other species of&#xD;
      Bordetella genus (i.e. B. parapertussis and B. holmesii) will be transferred to laboratories&#xD;
      in low income countries. The diagnosis of the different Bordetella species by real time&#xD;
      polymerase chain reaction (RT-PCR) and the measure of anti-pertussis toxin Immunoglobulin G&#xD;
      (IgG) level by serological tests will be set up in the laboratories participating in this&#xD;
      study. These laboratories could further be used by the national surveillance network and thus&#xD;
      improve the quality of the data available for the local health authorities and for WHO. Thus,&#xD;
      this study will allow the establishment of an effective monitoring of pertussis in the&#xD;
      countries participating in the study through the raising of the population's awareness, the&#xD;
      training of local doctors on the clinical screening of this disease, and finally via the&#xD;
      transfer of diagnostic techniques within the laboratories.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2017</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">July 25, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of biologically confirmed cases of pertussis in patients under 6 months old admitted into hospital with clinical signs corresponding to whooping cough syndrome.</measure>
    <time_frame>November 2018</time_frame>
    <description>Primary Outcome of WP1a (Cohort 1)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of cases tested positive for B.Pertussis given by the presence of B. pertussis DNA in the nasopharyngeal sample or by the presence of an anti-pertussis toxin IgG level &gt;100 IU/mL in the serum.</measure>
    <time_frame>November 2018</time_frame>
    <description>Primary Outcome of WP1b (Cohort 2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of cases tested positive given by the presence of an anti-pertussis toxin IgG level &gt;100 IU/mL in the serum.</measure>
    <time_frame>November 2018</time_frame>
    <description>Primary Outcome of WP2 (Cohort 3)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Estimation of the relative risk of the disease occurring in the contact patients based on their immunization status and age groups</measure>
    <time_frame>April 2019</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">3587</enrollment>
  <condition>Bordetella Pertussis, Whooping Cough</condition>
  <arm_group>
    <arm_group_label>Index case (WP1a)</arm_group_label>
    <description>Infant under 6 months old with clinical signs of whooping cough syndrome.&#xD;
Nasopharyngeal sampling:&#xD;
A nasopharyngeal sample collected from each nostril by aspiration or swabbing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control case (WP1b)</arm_group_label>
    <description>Contact cases of infant with a positive diagnosis for whooping cough.&#xD;
Nasopharyngeal sampling:&#xD;
A nasopharyngeal sample collected from each nostril by aspiration or swabbing&#xD;
Blood sampling:&#xD;
A blood sample collected by fingerprick</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Seroepidemiological cohort (WP2)</arm_group_label>
    <description>Children between 3 and 15 years old with complete primo-vaccination against B.Pertussis&#xD;
Blood sampling:&#xD;
A blood sample collected by fingerprick</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nasopharyngeal sampling</intervention_name>
    <description>Nasopharyngeal sample by aspiration or swabbing</description>
    <arm_group_label>Control case (WP1b)</arm_group_label>
    <arm_group_label>Index case (WP1a)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood Sampling</intervention_name>
    <description>Blood sample by the tip of a finger (fingerprick)</description>
    <arm_group_label>Control case (WP1b)</arm_group_label>
    <arm_group_label>Seroepidemiological cohort (WP2)</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Nasopharyngeal sample; Blood sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Cohort 1 (WP1a): Infants under 6 months old coming to hospital with clinical signs of&#xD;
        whooping cough syndrome.&#xD;
&#xD;
        Cohort 2 (WP1b): Contact cases of confirmed infants included in the WP1a module&#xD;
&#xD;
        Cohort 3 (WP2): Children from 3 to 15 years old included, without underlying illness, with&#xD;
        complete pertussis primo-vaccination&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Cohort 1 (WP1a)&#xD;
&#xD;
          -  Infants under 6 months old&#xD;
&#xD;
          -  Presenting clinical signs of a whooping cough syndrome&#xD;
&#xD;
          -  Written consent obtained from a parent/guardian of the child&#xD;
&#xD;
        Cohort 2 (WP1b)&#xD;
&#xD;
          -  People in regular and prolonged contact (&gt;1h per day) with the index case for at least&#xD;
             5 days before the signs of whooping cough occurred in the infected child, living (or&#xD;
             not) in the same household.&#xD;
&#xD;
          -  For the adults, written consent obtained.&#xD;
&#xD;
          -  For minors under 7 yo: written consent obtained from a parent/guardian.&#xD;
&#xD;
          -  For minors over 7 yo: written consent obtained from parent/guardian and oral assent&#xD;
             obtained from the child.&#xD;
&#xD;
        Cohort 3 (WP2)&#xD;
&#xD;
          -  Child aged between 3 and 15 yo&#xD;
&#xD;
          -  Up to date first pertussis vaccination (vaccination booklet or official register)&#xD;
&#xD;
          -  Last pertussis vaccination done more than one year before inclusion&#xD;
&#xD;
          -  For minors under 7 yo: written consent obtained from parent/guardian.&#xD;
&#xD;
          -  For minors over 7 yo: written consent obtained from parent/guardian and oral assent&#xD;
             obtained from the child.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Cohort 3 (WP2)&#xD;
&#xD;
        - Pertussis vaccination done more than one year before inclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fabien TAIEB, MD, MSc, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institut Pasteur</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nicole GUISO, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Institut Pasteur</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut Pasteur of Cambodia</name>
      <address>
        <city>Phnom Penh</city>
        <country>Cambodia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Pasteur de Madagascar</name>
      <address>
        <city>Antananarivo</city>
        <country>Madagascar</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Agence de Médecine Préventive</name>
      <address>
        <city>Dapaong</city>
        <country>Togo</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Cambodia</country>
    <country>Madagascar</country>
    <country>Togo</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>27224518</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25955837</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25020131</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>27257822</PMID>
  </reference>
  <reference>
    <citation>Guiso N, Taieb F. Pertussis in Low and Medium Income Countries: A Pragmatic Approach. Adv Exp Med Biol. 2019;1183:137-149. doi: 10.1007/5584_2019_409.</citation>
    <PMID>31342458</PMID>
  </reference>
  <reference>
    <citation>Noel G, Badmasti F, Nikbin VS, Zahraei SM, Madec Y, Tavel D, Ait-Ahmed M, Guiso N, Shahcheraghi F, Taieb F. Transversal sero-epidemiological study of Bordetella pertussis in Tehran, Iran. PLoS One. 2020 Sep 1;15(9):e0238398. doi: 10.1371/journal.pone.0238398. eCollection 2020.</citation>
    <PMID>32870922</PMID>
  </reference>
  <reference>
    <citation>Noel G, Lotfi MN, Mirshahvalad S, Mahdi S, Tavel D, Zahraei SM, Ghanaie RM, Heidary T, Goudarzi A, Kazemi A, Karimi A, Nateghian A, Ait-Ahmed M, Guiso N, Shahcheraghi F, Taieb F. Hospital-based prospective study of pertussis in infants and close contacts in Tehran, Iran. BMC Infect Dis. 2021 Jun 18;21(1):586. doi: 10.1186/s12879-021-06266-6.</citation>
    <PMID>34144678</PMID>
  </reference>
  <results_reference>
    <citation>Noel G, Borand L, Leng C, Keang C, Botr C, Dim B, Kerleguer A, Peng YS, Sreng N, Ork V, Ait-Ahmed M, Guiso N, Taieb F. Circulation of Bordetella pertussis in vaccinated Cambodian children: A transversal serological study. Int J Infect Dis. 2021 May;106:134-139. doi: 10.1016/j.ijid.2021.03.054. Epub 2021 Mar 22.</citation>
    <PMID>33766688</PMID>
  </results_reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>March 21, 2022</last_update_submitted>
  <last_update_submitted_qc>March 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bordetella Pertussis</keyword>
  <keyword>Whooping Cough</keyword>
  <keyword>vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Whooping Cough</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02983487
org study id: 2015-055
nct id: NCT02983487
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
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.
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) 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 Cambodia, Madagascar and
      Togo. This is one of the objectives of our study. This 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 low income countries. The diagnosis of the different Bordetella species by real time
      polymerase chain reaction (RT-PCR) and the measure of anti-pertussis toxin Immunoglobulin G
      (IgG) level by 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 the
      countries participating in the study 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.
observational model: Cohort
time perspective: Prospective
measure: Proportion of biologically confirmed cases of pertussis in patients under 6 months old admitted into hospital with clinical signs corresponding to whooping cough syndrome.
time frame: November 2018
description: Primary Outcome of WP1a (Cohort 1)
measure: Proportion of cases tested positive for B.Pertussis given by the presence of B. pertussis DNA in the nasopharyngeal sample or by the presence of an anti-pertussis toxin IgG level >100 IU/mL in the serum.
time frame: November 2018
description: Primary Outcome of WP1b (Cohort 2)
measure: Proportion of cases tested positive given by the presence of an anti-pertussis toxin IgG level >100 IU/mL in the serum.
time frame: November 2018
description: Primary Outcome of WP2 (Cohort 3)
measure: Estimation of the relative risk of the disease occurring in the contact patients based on their immunization status and age groups
time frame: April 2019
arm group label: Index case (WP1a)
description: Infant under 6 months old with clinical signs of whooping cough syndrome.
Nasopharyngeal sampling:
A nasopharyngeal sample collected from each nostril by aspiration or swabbing
arm group label: Control case (WP1b)
description: Contact cases of infant with a positive diagnosis for whooping cough.
Nasopharyngeal sampling:
A nasopharyngeal sample collected from each nostril by aspiration or swabbing
Blood sampling:
A blood sample collected by fingerprick
arm group label: Seroepidemiological cohort (WP2)
description: Children between 3 and 15 years old with complete primo-vaccination against B.Pertussis
Blood sampling:
A blood sample collected by fingerprick
intervention type: Procedure
intervention name: Nasopharyngeal sampling
description: Nasopharyngeal sample by aspiration or swabbing
arm group label: Control case (WP1b)
arm group label: Index case (WP1a)
intervention type: Procedure
intervention name: Blood Sampling
description: Blood sample by the tip of a finger (fingerprick)
arm group label: Control case (WP1b)
arm group label: Seroepidemiological cohort (WP2)
Nasopharyngeal sample; Blood sample
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Fabien TAIEB, MD, MSc, MPH
role: Principal Investigator
affiliation: Institut Pasteur
last name: Nicole GUISO, PhD
role: Study Chair
affiliation: Institut Pasteur
facility: 
facility: 
facility: 
country: Cambodia
country: Madagascar
country: Togo
citation: 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.
PMID: 27224518
citation: 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.
PMID: 25955837
citation: 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.
PMID: 25020131
citation: 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.
PMID: 27257822
citation: Guiso N, Taieb F. Pertussis in Low and Medium Income Countries: A Pragmatic Approach. Adv Exp Med Biol. 2019;1183:137-149. doi: 10.1007/5584_2019_409.
PMID: 31342458
citation: Noel G, Badmasti F, Nikbin VS, Zahraei SM, Madec Y, Tavel D, Ait-Ahmed M, Guiso N, Shahcheraghi F, Taieb F. Transversal sero-epidemiological study of Bordetella pertussis in Tehran, Iran. PLoS One. 2020 Sep 1;15(9):e0238398. doi: 10.1371/journal.pone.0238398. eCollection 2020.
PMID: 32870922
citation: Noel G, Lotfi MN, Mirshahvalad S, Mahdi S, Tavel D, Zahraei SM, Ghanaie RM, Heidary T, Goudarzi A, Kazemi A, Karimi A, Nateghian A, Ait-Ahmed M, Guiso N, Shahcheraghi F, Taieb F. Hospital-based prospective study of pertussis in infants and close contacts in Tehran, Iran. BMC Infect Dis. 2021 Jun 18;21(1):586. doi: 10.1186/s12879-021-06266-6.
PMID: 34144678
citation: Noel G, Borand L, Leng C, Keang C, Botr C, Dim B, Kerleguer A, Peng YS, Sreng N, Ork V, Ait-Ahmed M, Guiso N, Taieb F. Circulation of Bordetella pertussis in vaccinated Cambodian children: A transversal serological study. Int J Infect Dis. 2021 May;106:134-139. doi: 10.1016/j.ijid.2021.03.054. Epub 2021 Mar 22.
PMID: 33766688
responsible party type: Sponsor
mesh term: Whooping Cough
sharing ipd: No