<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/NCT03304704</url>
  </required_header>
  <id_info>
    <org_study_id>999917180</org_study_id>
    <secondary_id>17-I-N180</secondary_id>
    <nct_id>NCT03304704</nct_id>
  </id_info>
  <brief_title>Community Dynamics of Malaria Transmission and Mosquito Feeding in Bancoumana, Mali</brief_title>
  <official_title>Community Dynamics of Malaria Transmission and Mosquito Feeding in Bancoumana and Doneguebougou, Mali</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Half of the world's population is at risk of malaria. Malaria is a disease that affects many&#xD;
      people in Mali and other parts of Africa. It is caused by germs spread by mosquito bites.&#xD;
      Malaria may be mild. But it can also be serious or can lead to death if it is not diagnosed&#xD;
      and treated promptly. Researchers want to learn more about the disease so they can develop&#xD;
      new approaches to malaria control.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To collect data on how mosquitoes spread malaria and how many people get malaria in the&#xD;
      community by comparing different areas, seasons, and years.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Residents of a certain area of Mali who are of any age&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with a physical exam and medical history.&#xD;
&#xD;
      All participants will have at least 1 visit. They will answer questions about their health&#xD;
      and malaria. They may have a physical exam. They will have blood collected.&#xD;
&#xD;
      Some participants will have 1 visit every month for 3 years. They will repeat the procedures&#xD;
      above.&#xD;
&#xD;
      These participants will have mosquitoes collected in their home monthly. They may be able to&#xD;
      catch some of the mosquitoes alive or may need to use a spray to kill the mosquitoes.&#xD;
      Participants in this part of the study can be up to 65 years old.&#xD;
&#xD;
      Some participants will also have about 60 mosquitoes directly feed on their arm or leg for&#xD;
      15-20 minutes each month. These participants must be 5-65 years old.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A vaccine that interrupts malaria transmission is critical to eradicate the disease, but&#xD;
      improved assays are needed to measure the efficacy of vaccines. Transmission-blocking&#xD;
      vaccines (TBVs) work by inducing antibodies in vaccinees that inhibit parasite development in&#xD;
      the mosquito interrupting transmission. Efficacy of vaccines may be estimated by in vitro&#xD;
      membrane feeding assays using immune sera and laboratory mosquitoes, but qualified assays&#xD;
      that measure transmission in the field are needed to assess transmission-blocking&#xD;
      interventions in natura. Clinical trials of TBV have started in Bancoumana and Doneguebougou,&#xD;
      and we expect to expand TBV studies here and in adjacent areas in the future. This protocol&#xD;
      will use a longitudinal cohort to gather information on mosquito feeding and infection&#xD;
      patterns in Bancoumana, Doneguebougou and surrounding villages in Mali. Individuals actively&#xD;
      participating in LMIV vaccine trials will be approached first for participation, including&#xD;
      permission to contact their household and neighbors of their compound for participation.&#xD;
      Households will be identified using census data and individuals will be consented for&#xD;
      participation. Malaria smears will be obtained at monthly visits, in conjunction with&#xD;
      mosquito collections in/around village residences and with direct skin feeds (DSFs) using&#xD;
      insectary-raised mosquitoes. Parasite transmission to mosquitoes will be assessed&#xD;
      longitudinally for differences by season and year, and compared between wild-caught and&#xD;
      laboratory-raised mosquitoes. Data will also be obtained on gametocyte and parasite carriage&#xD;
      rates by season and year. Genotyping of individual subjects will be performed to pair with&#xD;
      the bloodmeals of wild-caught mosquitoes.&#xD;
&#xD;
      A total of 3,200 volunteers from Bancoumana, Doneguebougou and surrounding areas will be&#xD;
      enrolled into three distinct cohorts. The Genotype Only Cohort (n=1000), which will include&#xD;
      the vaccine trial participants, will complete a single visit to obtain a blood sample for&#xD;
      genotyping with no additional follow up. The DSF Cohort (n=1200) will enroll subjects aged 5&#xD;
      to 65 years for monthly blood sampling, DSF, and mosquito collection at their household. The&#xD;
      Parasite Surveillance Cohort (n=1000) will enroll subjects under the age of 5 years (as young&#xD;
      as 6 months) and subjects of any age who are unwilling to participate in DSF; they will have&#xD;
      monthly blood sampling and mosquito collection at their household. Enrollment into the&#xD;
      Genotype and Parasite Surveillance Cohorts will be linked to full enrollment of the DSF&#xD;
      Cohort. Participants in the Parasite Surveillance and DSF cohorts, will be followed for up to&#xD;
      3 years, to collect data that will guide the design of future community-based trials of TBV.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2018</start_date>
  <completion_date type="Actual">July 12, 2020</completion_date>
  <primary_completion_date type="Actual">July 12, 2020</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>Measurement of estimated rates of Infection rate in mosquitoes by DSF measured as the rate (per blood-fed mosquito) of malaria transmission (human to mosquito)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Infection rate in mosquitoes by DSF measured as the rate (per blood-fed mosquito) of malaria transmission (human to mosquito; and Infection rate in live wild-caught mosquitoes measured as the rate (per blood-fed mosquito) of malaria transmission (human to mosquito)</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">1928</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>DSF Cohort</arm_group_label>
    <description>Accrual/Screening up to 1800 will include volunteers between the ages of 5 and 17 years and will be enrolled for genotyping and monthly blood sampling</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Genotype Cohort</arm_group_label>
    <description>Accrual/Screening up to 1500 will complete a single visit with blood draw for genotyping for future fidelity assessments with blood-fed, spray wild-caught mosquitoes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parasite Surveillance Cohort</arm_group_label>
    <description>Accrual/Screening up to 1500 will be enrolled for genotyping and a minimum of six monthly blood sampling and mosquito wild catches wild-caught mosquitoes within their compound</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Known resident of Bancoumana, Doneguebougou or the surrounding villages; and Willingness to&#xD;
        allow stored laboratory specimens to be used for future research@@@@@@&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  GENOTYPE ONLY COHORT&#xD;
&#xD;
               -  Any age&#xD;
&#xD;
               -  Known resident of Bancoumana or the surrounding villages&#xD;
&#xD;
               -  Acceptance and signature of the written informed consent and the assent for&#xD;
                  children aged 12-17 years&#xD;
&#xD;
               -  Willingness to allow stored laboratory specimens to be used for future research&#xD;
&#xD;
          -  PARASITE SURVEILLANCE COHORT&#xD;
&#xD;
               -  6 months to 65 years of age&#xD;
&#xD;
               -  Known resident of Bancoumana or the surrounding villages&#xD;
&#xD;
               -  Willingness to allow stored laboratory specimens to be used for future research&#xD;
&#xD;
               -  Acceptance and signature of the written informed consent and the assent for&#xD;
                  children aged 12-17 years&#xD;
&#xD;
          -  DSF COHORT&#xD;
&#xD;
               -  Aged between 5 and 65 years, inclusive&#xD;
&#xD;
               -  Good general health as determined by review of medical history and/or clinical&#xD;
                  testing at the time of screening&#xD;
&#xD;
               -  Known resident of Bancoumana or the surrounding villages&#xD;
&#xD;
               -  Willingness to allow stored laboratory specimens to be used for future research&#xD;
&#xD;
               -  Willingness to undergo DSF&#xD;
&#xD;
               -  Acceptance and signature of the written informed consent and the assent for&#xD;
                  children aged 12-17 years&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  GENOTYPE ONLY COHORT&#xD;
&#xD;
               -  Behavioral, cognitive, or psychiatric disease that in the opinion of the&#xD;
                  investigator affects the ability of the subject to understand and cooperate with&#xD;
                  the study protocol&#xD;
&#xD;
               -  Other condition that, in the opinion of the investigator, would jeopardize the&#xD;
                  safety or rights of a volunteer participating in the trial or would render the&#xD;
                  subject unable to comply with the protocol&#xD;
&#xD;
          -  PARASITE SURVEILLANCE CHORT&#xD;
&#xD;
               -  Behavioral, cognitive, or psychiatric disease that in the opinion of the&#xD;
                  investigator affects the ability of the subject to understand and cooperate with&#xD;
                  the study protocol&#xD;
&#xD;
               -  Other condition that, in the opinion of the investigator, would jeopardize the&#xD;
                  safety or rights of a volunteer participating in the trial or would render the&#xD;
                  subject unable to comply with the protocol&#xD;
&#xD;
               -  Currently enrolled participant in protocol 17-I-N006 or another active LMIV/MRTC&#xD;
                  vaccine clinical trial&#xD;
&#xD;
          -  DSF COHORT&#xD;
&#xD;
               -  Behavioral, cognitive, or psychiatric disease that in the opinion of the&#xD;
                  investigator affects the ability of the subject to understand and cooperate with&#xD;
                  the study protocol&#xD;
&#xD;
               -  Other condition that, in the opinion of the investigator, would jeopardize the&#xD;
                  safety or rights of a volunteer participating in the trial or would render the&#xD;
                  subject unable to comply with the protocol&#xD;
&#xD;
               -  Currently enrolled participant in protocol 17-I-N006 or another LMIV/MRTC vaccine&#xD;
                  clinical trial&#xD;
&#xD;
               -  History of severe reaction to mosquito bites&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer C Hume</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Univ of Sciences, Techniques and Technology</name>
      <address>
        <city>Bamako</city>
        <country>Mali</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mali</country>
  </location_countries>
  <reference>
    <citation>Toure YT, Doumbo O, Toure A, Bagayoko M, Diallo M, Dolo A, Vernick KD, Keister DB, Muratova O, Kaslow DC. Gametocyte infectivity by direct mosquito feeds in an area of seasonal malaria transmission: implications for Bancoumana, Mali as a transmission-blocking vaccine site. Am J Trop Med Hyg. 1998 Sep;59(3):481-6. doi: 10.4269/ajtmh.1998.59.481.</citation>
    <PMID>9749648</PMID>
  </reference>
  <reference>
    <citation>Diallo M, Toure AM, Traore SF, Niare O, Kassambara L, Konare A, Coulibaly M, Bagayogo M, Beier JC, Sakai RK, Toure YT, Doumbo OK. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar J. 2008 Dec 2;7:248. doi: 10.1186/1475-2875-7-248.</citation>
    <PMID>19055715</PMID>
  </reference>
  <reference>
    <citation>Drakeley C, Sutherland C, Bousema JT, Sauerwein RW, Targett GA. The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol. 2006 Sep;22(9):424-30. doi: 10.1016/j.pt.2006.07.001. Epub 2006 Jul 17.</citation>
    <PMID>16846756</PMID>
  </reference>
  <verification_date>April 26, 2023</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 9, 2017</study_first_posted>
  <last_update_submitted>September 9, 2023</last_update_submitted>
  <last_update_submitted_qc>September 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Assays</keyword>
  <keyword>Direct Skin Feeds</keyword>
  <keyword>Infection</keyword>
  <keyword>Parasite</keyword>
  <keyword>Gametocyte</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <!-- 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/NCT03304704
org study id: 999917180
secondary id: 17-I-N180
nct id: NCT03304704
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Half of the world's population is at risk of malaria. Malaria is a disease that affects many
      people in Mali and other parts of Africa. It is caused by germs spread by mosquito bites.
      Malaria may be mild. But it can also be serious or can lead to death if it is not diagnosed
      and treated promptly. Researchers want to learn more about the disease so they can develop
      new approaches to malaria control.

      Objective:

      To collect data on how mosquitoes spread malaria and how many people get malaria in the
      community by comparing different areas, seasons, and years.

      Eligibility:

      Residents of a certain area of Mali who are of any age

      Design:

      Participants will be screened with a physical exam and medical history.

      All participants will have at least 1 visit. They will answer questions about their health
      and malaria. They may have a physical exam. They will have blood collected.

      Some participants will have 1 visit every month for 3 years. They will repeat the procedures
      above.

      These participants will have mosquitoes collected in their home monthly. They may be able to
      catch some of the mosquitoes alive or may need to use a spray to kill the mosquitoes.
      Participants in this part of the study can be up to 65 years old.

      Some participants will also have about 60 mosquitoes directly feed on their arm or leg for
      15-20 minutes each month. These participants must be 5-65 years old.
A vaccine that interrupts malaria transmission is critical to eradicate the disease, but
      improved assays are needed to measure the efficacy of vaccines. Transmission-blocking
      vaccines (TBVs) work by inducing antibodies in vaccinees that inhibit parasite development in
      the mosquito interrupting transmission. Efficacy of vaccines may be estimated by in vitro
      membrane feeding assays using immune sera and laboratory mosquitoes, but qualified assays
      that measure transmission in the field are needed to assess transmission-blocking
      interventions in natura. Clinical trials of TBV have started in Bancoumana and Doneguebougou,
      and we expect to expand TBV studies here and in adjacent areas in the future. This protocol
      will use a longitudinal cohort to gather information on mosquito feeding and infection
      patterns in Bancoumana, Doneguebougou and surrounding villages in Mali. Individuals actively
      participating in LMIV vaccine trials will be approached first for participation, including
      permission to contact their household and neighbors of their compound for participation.
      Households will be identified using census data and individuals will be consented for
      participation. Malaria smears will be obtained at monthly visits, in conjunction with
      mosquito collections in/around village residences and with direct skin feeds (DSFs) using
      insectary-raised mosquitoes. Parasite transmission to mosquitoes will be assessed
      longitudinally for differences by season and year, and compared between wild-caught and
      laboratory-raised mosquitoes. Data will also be obtained on gametocyte and parasite carriage
      rates by season and year. Genotyping of individual subjects will be performed to pair with
      the bloodmeals of wild-caught mosquitoes.

      A total of 3,200 volunteers from Bancoumana, Doneguebougou and surrounding areas will be
      enrolled into three distinct cohorts. The Genotype Only Cohort (n=1000), which will include
      the vaccine trial participants, will complete a single visit to obtain a blood sample for
      genotyping with no additional follow up. The DSF Cohort (n=1200) will enroll subjects aged 5
      to 65 years for monthly blood sampling, DSF, and mosquito collection at their household. The
      Parasite Surveillance Cohort (n=1000) will enroll subjects under the age of 5 years (as young
      as 6 months) and subjects of any age who are unwilling to participate in DSF; they will have
      monthly blood sampling and mosquito collection at their household. Enrollment into the
      Genotype and Parasite Surveillance Cohorts will be linked to full enrollment of the DSF
      Cohort. Participants in the Parasite Surveillance and DSF cohorts, will be followed for up to
      3 years, to collect data that will guide the design of future community-based trials of TBV.
observational model: Cohort
time perspective: Prospective
measure: Measurement of estimated rates of Infection rate in mosquitoes by DSF measured as the rate (per blood-fed mosquito) of malaria transmission (human to mosquito)
time frame: Up to 3 years
description: Infection rate in mosquitoes by DSF measured as the rate (per blood-fed mosquito) of malaria transmission (human to mosquito; and Infection rate in live wild-caught mosquitoes measured as the rate (per blood-fed mosquito) of malaria transmission (human to mosquito)
arm group label: DSF Cohort
description: Accrual/Screening up to 1800 will include volunteers between the ages of 5 and 17 years and will be enrolled for genotyping and monthly blood sampling
arm group label: Genotype Cohort
description: Accrual/Screening up to 1500 will complete a single visit with blood draw for genotyping for future fidelity assessments with blood-fed, spray wild-caught mosquitoes.
arm group label: Parasite Surveillance Cohort
description: Accrual/Screening up to 1500 will be enrolled for genotyping and a minimum of six monthly blood sampling and mosquito wild catches wild-caught mosquitoes within their compound
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Months
maximum age: 65 Years
healthy volunteers: No
last name: Jennifer C Hume
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
facility: 
country: Mali
citation: Toure YT, Doumbo O, Toure A, Bagayoko M, Diallo M, Dolo A, Vernick KD, Keister DB, Muratova O, Kaslow DC. Gametocyte infectivity by direct mosquito feeds in an area of seasonal malaria transmission: implications for Bancoumana, Mali as a transmission-blocking vaccine site. Am J Trop Med Hyg. 1998 Sep;59(3):481-6. doi: 10.4269/ajtmh.1998.59.481.
PMID: 9749648
citation: Diallo M, Toure AM, Traore SF, Niare O, Kassambara L, Konare A, Coulibaly M, Bagayogo M, Beier JC, Sakai RK, Toure YT, Doumbo OK. Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity. Malar J. 2008 Dec 2;7:248. doi: 10.1186/1475-2875-7-248.
PMID: 19055715
citation: Drakeley C, Sutherland C, Bousema JT, Sauerwein RW, Targett GA. The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol. 2006 Sep;22(9):424-30. doi: 10.1016/j.pt.2006.07.001. Epub 2006 Jul 17.
PMID: 16846756
responsible party type: Sponsor
mesh term: Malaria