<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/NCT04416945</url>
  </required_header>
  <id_info>
    <org_study_id>19-27966</org_study_id>
    <nct_id>NCT04416945</nct_id>
  </id_info>
  <brief_title>Targeting High Risk Populations With Enhanced Reactive Case Detection in Southern Lao Peoples Democratic Republic</brief_title>
  <acronym>COMBAT</acronym>
  <official_title>Targeting High-risk Populations With Enhanced Reactive Case Detection: a Study to Assess the Effectiveness and Feasibility for Reducing Plasmodium Falciparum and P. Vivax Malaria in Southern Lao Peoples Democratic Republic</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Center for Malariology, Parasitology, and Entomology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tulane University School of Public Health and Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Massachusetts, Amherst</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study assesses the effectiveness and feasibility of enhanced reactive case detection&#xD;
      (RACD) targeting high-risk villages and forest workers for reducing Plasmodium falciparum and&#xD;
      Plasmodium vivax transmission in southern Lao Peoples Democratic Republic. The authors&#xD;
      hypothesize that enhanced community-based RACD will be more effective than standard of care&#xD;
      case management and RACD at reducing P. falciparum and P. vivax confirmed case incidence and&#xD;
      parasite prevalence over an 18-month period in Lao Peoples Democratic Republic.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the Greater Mekong Subregion (GMS), the risk of malaria infection is often due not to&#xD;
      village-based transmission but rather to occupational and behavioral risk factors leading to&#xD;
      exposure in forest settings. Additionally, a substantial portion of infections are&#xD;
      asymptomatic and/or submicroscopic, limiting the scope of current diagnostics and&#xD;
      surveillance approaches. The proposed research will evaluate the effectiveness of reactive&#xD;
      case detection (RACD) using highly-sensitive rapid diagnostic tests (HS-RDTs), targeting both&#xD;
      village and forest working populations, compared to control for reducing the health center&#xD;
      catchment-level incidence and prevalence of P. falciparum and P. vivax within two provinces&#xD;
      in Lao People's Democratic Republic.&#xD;
&#xD;
      To test this hypothesis, this study will employ a cluster randomized controlled trial design&#xD;
      with two comparison arms: (1) Control: standard of care - passive case management provided&#xD;
      through community-based Village Malaria Workers (VMWs) and existing health facilities;&#xD;
      includes village-based RACD with conventional rapid diagnostic tests (RDTs) conducted by&#xD;
      district surveillance teams and (2) enhanced community-based RACD: RACD conducted by&#xD;
      community-based VMWs using both HS-RDTs and conventional RDTs within villages and among&#xD;
      forest workers.&#xD;
&#xD;
      The primary outcome measures to assess effectiveness include P. falciparum and P. vivax&#xD;
      confirmed case incidence over the study period; PCR-based P. falciparum and P. vivax&#xD;
      prevalence at end line; and HS-RDT test positivity rate in village and forest worker RACD.&#xD;
      Secondary outcomes measures will examine the operational feasibility, safety, and&#xD;
      acceptability of VMW-led reactive approaches and glucose-6-phosphate dehydrogenase (G6PD)&#xD;
      testing, referral to district or provincial-level facilities, safety and treatment adherence&#xD;
      for P. vivax cases.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 20, 2020</start_date>
  <completion_date type="Anticipated">November 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Confirmed P. falciparum and P. vivax malaria parasite incidence</measure>
    <time_frame>4 months</time_frame>
    <description>This is defined as the number of outpatient (OPD) malaria confirmed and suspected cases per person per year for each Health Center Catchment Area (HCCA), as ascertained from the health facility registers, utilizing administrative catchment population size estimates for the exposure denominator.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PCR-based P. falciparum and P. vivax parasite prevalence in sampled HCCAs</measure>
    <time_frame>4 months</time_frame>
    <description>This is defined as the proportion of individuals ≥18 months old with P. falciparum or P. vivax infection (detected by PCR) out of all individuals ≥18 months tested within the end line survey (2020).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HS-RDT/RDT-based test positivity rate in village and forest-based reactive case detection</measure>
    <time_frame>4 months</time_frame>
    <description>This is defined as the proportion of all individuals tested by HS-RDT/RDT in response to an index cases, with a positive HS-RDT/RDT, among the population older than 18 months.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">31443</enrollment>
  <condition>Plasmodium Falciparum Malaria</condition>
  <condition>Plasmodium Vivax Malaria</condition>
  <arm_group>
    <arm_group_label>RACD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Reactive case detection led by VMWs in response to cases in study area HCCA, with follow up testing with HS-RDTs/RDTs in both villages and forest workers; referrals for qualitative G6PD testing for P. vivax cases and 14-day PQ for G6PD non-deficient</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Standard of care including case management through health facilities and malaria posts/VMWs; village-based RACD conducted by district staff in some areas</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Household Reactive Case Detection</intervention_name>
    <description>Within 7 days of the index case notification, all members of the index case's household and everyone in the neighboring five households will then be invited to participate in the study. After consenting, a finger stick blood sample will be collected for each consenting individual for testing with the HS-RDT for P. falciparum, a standard combination RDT, and four blood spots on filter paper.</description>
    <arm_group_label>RACD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>RACD of cases' co-workers/co-travelers</intervention_name>
    <description>Index cases will be screened by the VMW at their households at the time of case investigation to determine if they have traveled or worked in a forest or forest-fringe area within the past 30 days. If eligible, the case will trigger two reactive recruitment strategies to screen and treat others who recently traveled or worked with the case in a forest or forest-fringe location:&#xD;
Peer-referral RACD (PR-RACD): In this strategy, the case will identify specific co-travelers or co-workers resident in their village who had spent the night with the case at a forest or forest-fringe area and spent the night there in the past 30 days.&#xD;
Venue-based RACD (VB-RACD): In this strategy, co-workers will be recruited directly from (accessible) forest or forest-fringe work sites where the index case worked and spent at least one night in the past 30 days.</description>
    <arm_group_label>RACD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Case Management and Follow-up</intervention_name>
    <description>All individuals who test positive by either HS-RDT or Standard RDT will be told of their results and treated on site per national guidelines:&#xD;
Individuals with P. falciparum infection will be treated with an age-appropriate course of artemether-lumefantrine (AL) and a single low dose of primaquine (SLD-PQ). Weight-based dosing is described in Tables 2 and 3 below.&#xD;
At all study sites in Lao Peoples Democratic Republic, patients with a P. vivax infection identified by RDT (both febrile and asymptomatic) will be given a unique coded and signed informational letter directing them to the nearest district hospital (or other testing facility) for G6PD deficiency testing and possible radical cure administration depending on results. At the health facility, G6PD normal individuals will be treated with AL and a 14-day course of PQ, whereas G6PD deficient individuals will receive AL alone as per the national guidelines and referred to a hospital for further primaquine management decisions.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>RACD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        RACD:&#xD;
&#xD;
        - Inclusion Criteria&#xD;
&#xD;
          -  Inclusion Criteria for index cases: Presented as a confirmed malaria case to an&#xD;
             intervention health facility or village malaria worker, and lives in a village within&#xD;
             a selected intervention health facility catchment area, or worked or spent at least&#xD;
             one night at a forest or forest-fringe site in the past 30 days located within an&#xD;
             intervention health facility catchment area&#xD;
&#xD;
          -  Inclusion criteria for village residents: Lives in a village within a selected&#xD;
             intervention health facility catchment area and in one of the five households closest&#xD;
             to the residence of an index case of malaria&#xD;
&#xD;
          -  Inclusion criteria for co-worker/traveler referral: Worked or traveled and spent at&#xD;
             least one night in forest in past 30 days in same location within an intervention&#xD;
             health facility catchment area as an index case of malaria&#xD;
&#xD;
          -  Inclusion criteria for all participants: Willing and available to participate in the&#xD;
             study&#xD;
&#xD;
        Informed consent for participant under the age of 18 will be provided by the parent or&#xD;
        guardian.&#xD;
&#xD;
        - Exclusion Criteria:&#xD;
&#xD;
          -  Previous participation in the study as a result of any RACD event in the past 30 days.&#xD;
&#xD;
          -  Individuals with suspected severe malaria or other severe illness (including those&#xD;
             with symptoms of severe anemia, prostration, impaired consciousness, respiratory&#xD;
             distress, convulsions, circulatory collapse, abnormal bleeding, jaundice or passing&#xD;
             dark urine) will be excluded from the treatment component and referred to the nearest&#xD;
             health facility for clinical assessment and treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adam Bennett, MA, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Viengxay Vanisaveth, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center of Malariology, Parasitology, Entomology in Laos</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Adam Bennett, MA, PhD</last_name>
    <phone>1-415-476-5590</phone>
    <email>adam.bennett@ucsf.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Center for Malariology, Parasitology, Entomology, Laos Ministry of Health</name>
      <address>
        <city>Vientiane</city>
        <country>Lao People's Democratic Republic</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Keobuphaphone Chindavongsa, MD</last_name>
      <phone>+8562055617339</phone>
      <email>chinda07@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Lao People's Democratic Republic</country>
  </location_countries>
  <reference>
    <citation>Bousema T, Griffin JT, Sauerwein RW, Smith DL, Churcher TS, Takken W, Ghani A, Drakeley C, Gosling R. Hitting hotspots: spatial targeting of malaria for control and elimination. PLoS Med. 2012 Jan;9(1):e1001165. doi: 10.1371/journal.pmed.1001165. Epub 2012 Jan 31.</citation>
    <PMID>22303287</PMID>
  </reference>
  <reference>
    <citation>Cotter C, Sturrock HJ, Hsiang MS, Liu J, Phillips AA, Hwang J, Gueye CS, Fullman N, Gosling RD, Feachem RG. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013 Sep 7;382(9895):900-11. doi: 10.1016/S0140-6736(13)60310-4. Epub 2013 Apr 15. Erratum In: Lancet. 2013 Sep 7;382(9895):858.</citation>
    <PMID>23594387</PMID>
  </reference>
  <reference>
    <citation>Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, Abeyasinghe RR, Rodriguez MH, Maharaj R, Tanner M, Targett G. Operational strategies to achieve and maintain malaria elimination. Lancet. 2010 Nov 6;376(9752):1592-603. doi: 10.1016/S0140-6736(10)61269-X. Epub 2010 Oct 28.</citation>
    <PMID>21035841</PMID>
  </reference>
  <reference>
    <citation>Hustedt J, Canavati SE, Rang C, Ashton RA, Khim N, Berne L, Kim S, Sovannaroth S, Ly P, Menard D, Cox J, Meek S, Roca-Feltrer A. Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting. Malar J. 2016 Mar 1;15:132. doi: 10.1186/s12936-016-1191-z.</citation>
    <PMID>26931488</PMID>
  </reference>
  <reference>
    <citation>Rossi G, Van den Bergh R, Nguon C, Debackere M, Vernaeve L, Khim N, Kim S, Menard D, De Smet M, Kindermans JM. Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia. Clin Infect Dis. 2018 Jan 6;66(2):296-298. doi: 10.1093/cid/cix781.</citation>
    <PMID>29020325</PMID>
  </reference>
  <reference>
    <citation>Das S, Peck RB, Barney R, Jang IK, Kahn M, Zhu M, Domingo GJ. Correction to: Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples. Malar J. 2019 Feb 4;18(1):33. doi: 10.1186/s12936-019-2669-2.</citation>
    <PMID>30717748</PMID>
  </reference>
  <reference>
    <citation>Landier J, Parker DM, Thu AM, Lwin KM, Delmas G, Nosten FH; Malaria Elimination Task Force Group. Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme. Lancet. 2018 May 12;391(10133):1916-1926. doi: 10.1016/S0140-6736(18)30792-X. Epub 2018 Apr 24.</citation>
    <PMID>29703425</PMID>
  </reference>
  <reference>
    <citation>Howes RE, Dewi M, Piel FB, Monteiro WM, Battle KE, Messina JP, Sakuntabhai A, Satyagraha AW, Williams TN, Baird JK, Hay SI. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J. 2013 Nov 15;12:418. doi: 10.1186/1475-2875-12-418.</citation>
    <PMID>24228846</PMID>
  </reference>
  <reference>
    <citation>White MT, Karl S, Battle KE, Hay SI, Mueller I, Ghani AC. Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission. Elife. 2014 Nov 18;3:e04692. doi: 10.7554/eLife.04692.</citation>
    <PMID>25406065</PMID>
  </reference>
  <reference>
    <citation>Douglas NM, Poespoprodjo JR, Patriani D, Malloy MJ, Kenangalem E, Sugiarto P, Simpson JA, Soenarto Y, Anstey NM, Price RN. Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study. PLoS Med. 2017 Aug 29;14(8):e1002379. doi: 10.1371/journal.pmed.1002379. eCollection 2017 Aug.</citation>
    <PMID>28850568</PMID>
  </reference>
  <reference>
    <citation>Ministry of Health Lao PDR. The Evaluation of G6PD Rapid Tests and the Use of Primaquine for the Treatment of Plasmodium Vivax Infections in Luangprabang, Savannakhet and Champasak Provinces (Apr-Nov 2015). (2015).</citation>
  </reference>
  <reference>
    <citation>Center for Malariology Parasitology and Entomology Lao PDR. Lao PDR Malaria National Strategic Plan 2016-2020. (2015).</citation>
  </reference>
  <reference>
    <citation>WHO. Updated WHO policy recommendation: Single dose primaquine as a gametocytocide in Plasmodium falciparum malaria. World Health Organisation (2012).</citation>
  </reference>
  <reference>
    <citation>Baum E, Sattabongkot J, Sirichaisinthop J, Kiattibutr K, Davies DH, Jain A, Lo E, Lee MC, Randall AZ, Molina DM, Liang X, Cui L, Felgner PL, Yan G. Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax infections are common in western Thailand - molecular and serological evidence. Malar J. 2015 Feb 25;14:95. doi: 10.1186/s12936-015-0611-9.</citation>
    <PMID>25849211</PMID>
  </reference>
  <reference>
    <citation>Corran P, Coleman P, Riley E, Drakeley C. Serology: a robust indicator of malaria transmission intensity? Trends Parasitol. 2007 Dec;23(12):575-82. doi: 10.1016/j.pt.2007.08.023. Epub 2007 Nov 7.</citation>
    <PMID>17988945</PMID>
  </reference>
  <reference>
    <citation>Chan CW, Sakihama N, Tachibana S, Idris ZM, Lum JK, Tanabe K, Kaneko A. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies. PLoS One. 2015 Mar 20;10(3):e0119475. doi: 10.1371/journal.pone.0119475. eCollection 2015.</citation>
    <PMID>25793260</PMID>
  </reference>
  <reference>
    <citation>Beutler E, Duparc S; G6PD Deficiency Working Group. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg. 2007 Oct;77(4):779-89.</citation>
    <PMID>17978087</PMID>
  </reference>
  <reference>
    <citation>Campbell MK, Piaggio G, Elbourne DR, Altman DG; CONSORT Group. Consort 2010 statement: extension to cluster randomised trials. BMJ. 2012 Sep 4;345:e5661. doi: 10.1136/bmj.e5661. No abstract available.</citation>
    <PMID>22951546</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>September 8, 2021</last_update_submitted>
  <last_update_submitted_qc>September 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
    <mesh_term>Malaria, Falciparum</mesh_term>
    <mesh_term>Malaria, Vivax</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will not be shared with any parties outside of the study team.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT04416945/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04416945
org study id: 19-27966
nct id: NCT04416945
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study assesses the effectiveness and feasibility of enhanced reactive case detection
      (RACD) targeting high-risk villages and forest workers for reducing Plasmodium falciparum and
      Plasmodium vivax transmission in southern Lao Peoples Democratic Republic. The authors
      hypothesize that enhanced community-based RACD will be more effective than standard of care
      case management and RACD at reducing P. falciparum and P. vivax confirmed case incidence and
      parasite prevalence over an 18-month period in Lao Peoples Democratic Republic.
In the Greater Mekong Subregion (GMS), the risk of malaria infection is often due not to
      village-based transmission but rather to occupational and behavioral risk factors leading to
      exposure in forest settings. Additionally, a substantial portion of infections are
      asymptomatic and/or submicroscopic, limiting the scope of current diagnostics and
      surveillance approaches. The proposed research will evaluate the effectiveness of reactive
      case detection (RACD) using highly-sensitive rapid diagnostic tests (HS-RDTs), targeting both
      village and forest working populations, compared to control for reducing the health center
      catchment-level incidence and prevalence of P. falciparum and P. vivax within two provinces
      in Lao People's Democratic Republic.

      To test this hypothesis, this study will employ a cluster randomized controlled trial design
      with two comparison arms: (1) Control: standard of care - passive case management provided
      through community-based Village Malaria Workers (VMWs) and existing health facilities;
      includes village-based RACD with conventional rapid diagnostic tests (RDTs) conducted by
      district surveillance teams and (2) enhanced community-based RACD: RACD conducted by
      community-based VMWs using both HS-RDTs and conventional RDTs within villages and among
      forest workers.

      The primary outcome measures to assess effectiveness include P. falciparum and P. vivax
      confirmed case incidence over the study period; PCR-based P. falciparum and P. vivax
      prevalence at end line; and HS-RDT test positivity rate in village and forest worker RACD.
      Secondary outcomes measures will examine the operational feasibility, safety, and
      acceptability of VMW-led reactive approaches and glucose-6-phosphate dehydrogenase (G6PD)
      testing, referral to district or provincial-level facilities, safety and treatment adherence
      for P. vivax cases.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Confirmed P. falciparum and P. vivax malaria parasite incidence
time frame: 4 months
description: This is defined as the number of outpatient (OPD) malaria confirmed and suspected cases per person per year for each Health Center Catchment Area (HCCA), as ascertained from the health facility registers, utilizing administrative catchment population size estimates for the exposure denominator.
measure: PCR-based P. falciparum and P. vivax parasite prevalence in sampled HCCAs
time frame: 4 months
description: This is defined as the proportion of individuals ≥18 months old with P. falciparum or P. vivax infection (detected by PCR) out of all individuals ≥18 months tested within the end line survey (2020).
measure: HS-RDT/RDT-based test positivity rate in village and forest-based reactive case detection
time frame: 4 months
description: This is defined as the proportion of all individuals tested by HS-RDT/RDT in response to an index cases, with a positive HS-RDT/RDT, among the population older than 18 months.
arm group label: RACD
arm group type: Experimental
description: Reactive case detection led by VMWs in response to cases in study area HCCA, with follow up testing with HS-RDTs/RDTs in both villages and forest workers; referrals for qualitative G6PD testing for P. vivax cases and 14-day PQ for G6PD non-deficient
arm group label: Control
arm group type: Active Comparator
description: Standard of care including case management through health facilities and malaria posts/VMWs; village-based RACD conducted by district staff in some areas
intervention type: Other
intervention name: Household Reactive Case Detection
description: Within 7 days of the index case notification, all members of the index case's household and everyone in the neighboring five households will then be invited to participate in the study. After consenting, a finger stick blood sample will be collected for each consenting individual for testing with the HS-RDT for P. falciparum, a standard combination RDT, and four blood spots on filter paper.
arm group label: RACD
intervention type: Other
intervention name: RACD of cases' co-workers/co-travelers
description: Index cases will be screened by the VMW at their households at the time of case investigation to determine if they have traveled or worked in a forest or forest-fringe area within the past 30 days. If eligible, the case will trigger two reactive recruitment strategies to screen and treat others who recently traveled or worked with the case in a forest or forest-fringe location:
Peer-referral RACD (PR-RACD): In this strategy, the case will identify specific co-travelers or co-workers resident in their village who had spent the night with the case at a forest or forest-fringe area and spent the night there in the past 30 days.
Venue-based RACD (VB-RACD): In this strategy, co-workers will be recruited directly from (accessible) forest or forest-fringe work sites where the index case worked and spent at least one night in the past 30 days.
arm group label: RACD
intervention type: Other
intervention name: Case Management and Follow-up
description: All individuals who test positive by either HS-RDT or Standard RDT will be told of their results and treated on site per national guidelines:
Individuals with P. falciparum infection will be treated with an age-appropriate course of artemether-lumefantrine (AL) and a single low dose of primaquine (SLD-PQ). Weight-based dosing is described in Tables 2 and 3 below.
At all study sites in Lao Peoples Democratic Republic, patients with a P. vivax infection identified by RDT (both febrile and asymptomatic) will be given a unique coded and signed informational letter directing them to the nearest district hospital (or other testing facility) for G6PD deficiency testing and possible radical cure administration depending on results. At the health facility, G6PD normal individuals will be treated with AL and a 14-day course of PQ, whereas G6PD deficient individuals will receive AL alone as per the national guidelines and referred to a hospital for further primaquine management decisions.
arm group label: Control
arm group label: RACD
criteria: 
gender: All
minimum age: 18 Months
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Adam Bennett, MA, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Viengxay Vanisaveth, MD
role: Principal Investigator
affiliation: Center of Malariology, Parasitology, Entomology in Laos
last name: Adam Bennett, MA, PhD
phone: 1-415-476-5590
email: adam.bennett@ucsf.edu
facility: 
status: Recruiting
contact: 
country: Lao People's Democratic Republic
citation: Bousema T, Griffin JT, Sauerwein RW, Smith DL, Churcher TS, Takken W, Ghani A, Drakeley C, Gosling R. Hitting hotspots: spatial targeting of malaria for control and elimination. PLoS Med. 2012 Jan;9(1):e1001165. doi: 10.1371/journal.pmed.1001165. Epub 2012 Jan 31.
PMID: 22303287
citation: Cotter C, Sturrock HJ, Hsiang MS, Liu J, Phillips AA, Hwang J, Gueye CS, Fullman N, Gosling RD, Feachem RG. The changing epidemiology of malaria elimination: new strategies for new challenges. Lancet. 2013 Sep 7;382(9895):900-11. doi: 10.1016/S0140-6736(13)60310-4. Epub 2013 Apr 15. Erratum In: Lancet. 2013 Sep 7;382(9895):858.
PMID: 23594387
citation: Moonen B, Cohen JM, Snow RW, Slutsker L, Drakeley C, Smith DL, Abeyasinghe RR, Rodriguez MH, Maharaj R, Tanner M, Targett G. Operational strategies to achieve and maintain malaria elimination. Lancet. 2010 Nov 6;376(9752):1592-603. doi: 10.1016/S0140-6736(10)61269-X. Epub 2010 Oct 28.
PMID: 21035841
citation: Hustedt J, Canavati SE, Rang C, Ashton RA, Khim N, Berne L, Kim S, Sovannaroth S, Ly P, Menard D, Cox J, Meek S, Roca-Feltrer A. Reactive case-detection of malaria in Pailin Province, Western Cambodia: lessons from a year-long evaluation in a pre-elimination setting. Malar J. 2016 Mar 1;15:132. doi: 10.1186/s12936-016-1191-z.
PMID: 26931488
citation: Rossi G, Van den Bergh R, Nguon C, Debackere M, Vernaeve L, Khim N, Kim S, Menard D, De Smet M, Kindermans JM. Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia. Clin Infect Dis. 2018 Jan 6;66(2):296-298. doi: 10.1093/cid/cix781.
PMID: 29020325
citation: Das S, Peck RB, Barney R, Jang IK, Kahn M, Zhu M, Domingo GJ. Correction to: Performance of an ultra-sensitive Plasmodium falciparum HRP2-based rapid diagnostic test with recombinant HRP2, culture parasites, and archived whole blood samples. Malar J. 2019 Feb 4;18(1):33. doi: 10.1186/s12936-019-2669-2.
PMID: 30717748
citation: Landier J, Parker DM, Thu AM, Lwin KM, Delmas G, Nosten FH; Malaria Elimination Task Force Group. Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme. Lancet. 2018 May 12;391(10133):1916-1926. doi: 10.1016/S0140-6736(18)30792-X. Epub 2018 Apr 24.
PMID: 29703425
citation: Howes RE, Dewi M, Piel FB, Monteiro WM, Battle KE, Messina JP, Sakuntabhai A, Satyagraha AW, Williams TN, Baird JK, Hay SI. Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malar J. 2013 Nov 15;12:418. doi: 10.1186/1475-2875-12-418.
PMID: 24228846
citation: White MT, Karl S, Battle KE, Hay SI, Mueller I, Ghani AC. Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission. Elife. 2014 Nov 18;3:e04692. doi: 10.7554/eLife.04692.
PMID: 25406065
citation: Douglas NM, Poespoprodjo JR, Patriani D, Malloy MJ, Kenangalem E, Sugiarto P, Simpson JA, Soenarto Y, Anstey NM, Price RN. Unsupervised primaquine for the treatment of Plasmodium vivax malaria relapses in southern Papua: A hospital-based cohort study. PLoS Med. 2017 Aug 29;14(8):e1002379. doi: 10.1371/journal.pmed.1002379. eCollection 2017 Aug.
PMID: 28850568
citation: Ministry of Health Lao PDR. The Evaluation of G6PD Rapid Tests and the Use of Primaquine for the Treatment of Plasmodium Vivax Infections in Luangprabang, Savannakhet and Champasak Provinces (Apr-Nov 2015). (2015).
citation: Center for Malariology Parasitology and Entomology Lao PDR. Lao PDR Malaria National Strategic Plan 2016-2020. (2015).
citation: WHO. Updated WHO policy recommendation: Single dose primaquine as a gametocytocide in Plasmodium falciparum malaria. World Health Organisation (2012).
citation: Baum E, Sattabongkot J, Sirichaisinthop J, Kiattibutr K, Davies DH, Jain A, Lo E, Lee MC, Randall AZ, Molina DM, Liang X, Cui L, Felgner PL, Yan G. Submicroscopic and asymptomatic Plasmodium falciparum and Plasmodium vivax infections are common in western Thailand - molecular and serological evidence. Malar J. 2015 Feb 25;14:95. doi: 10.1186/s12936-015-0611-9.
PMID: 25849211
citation: Corran P, Coleman P, Riley E, Drakeley C. Serology: a robust indicator of malaria transmission intensity? Trends Parasitol. 2007 Dec;23(12):575-82. doi: 10.1016/j.pt.2007.08.023. Epub 2007 Nov 7.
PMID: 17988945
citation: Chan CW, Sakihama N, Tachibana S, Idris ZM, Lum JK, Tanabe K, Kaneko A. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies. PLoS One. 2015 Mar 20;10(3):e0119475. doi: 10.1371/journal.pone.0119475. eCollection 2015.
PMID: 25793260
citation: Beutler E, Duparc S; G6PD Deficiency Working Group. Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg. 2007 Oct;77(4):779-89.
PMID: 17978087
citation: Campbell MK, Piaggio G, Elbourne DR, Altman DG; CONSORT Group. Consort 2010 statement: extension to cluster randomised trials. BMJ. 2012 Sep 4;345:e5661. doi: 10.1136/bmj.e5661. No abstract available.
PMID: 22951546
responsible party type: Sponsor
mesh term: Malaria
mesh term: Malaria, Falciparum
mesh term: Malaria, Vivax
sharing ipd: No
ipd description: Individual participant data will not be shared with any parties outside of the study team.
provided document: 