Targeting High Risk Populations With Enhanced Reactive Case Detection in Southern Lao Peoples Democratic Republic (COMBAT)

September 8, 2021 updated by: University of California, San Francisco

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

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.

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

31443

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Vientiane, Lao People's Democratic Republic
        • Recruiting
        • Center for Malariology, Parasitology, Entomology, Laos Ministry of Health
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

RACD:

- Inclusion Criteria

  • Inclusion Criteria for index cases: Presented as a confirmed malaria case to an intervention health facility or village malaria worker, and lives in a village within a selected intervention health facility catchment area, or worked or spent at least one night at a forest or forest-fringe site in the past 30 days located within an intervention health facility catchment area
  • Inclusion criteria for village residents: Lives in a village within a selected intervention health facility catchment area and in one of the five households closest to the residence of an index case of malaria
  • Inclusion criteria for co-worker/traveler referral: Worked or traveled and spent at least one night in forest in past 30 days in same location within an intervention health facility catchment area as an index case of malaria
  • Inclusion criteria for all participants: Willing and available to participate in the study

Informed consent for participant under the age of 18 will be provided by the parent or guardian.

- Exclusion Criteria:

  • Previous participation in the study as a result of any RACD event in the past 30 days.
  • Individuals with suspected severe malaria or other severe illness (including those with symptoms of severe anemia, prostration, impaired consciousness, respiratory distress, convulsions, circulatory collapse, abnormal bleeding, jaundice or passing dark urine) will be excluded from the treatment component and referred to the nearest health facility for clinical assessment and treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RACD
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
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.

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:

  1. 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.
  2. 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.

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.
Active Comparator: Control
Standard of care including case management through health facilities and malaria posts/VMWs; village-based RACD conducted by district staff in some areas

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed P. falciparum and P. vivax malaria parasite incidence
Time Frame: 4 months
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.
4 months
PCR-based P. falciparum and P. vivax parasite prevalence in sampled HCCAs
Time Frame: 4 months
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).
4 months
HS-RDT/RDT-based test positivity rate in village and forest-based reactive case detection
Time Frame: 4 months
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.
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Adam Bennett, MA, PhD, University of California, San Francisco
  • Principal Investigator: Viengxay Vanisaveth, MD, Center of Malariology, Parasitology, Entomology in Laos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2020

Primary Completion (Anticipated)

September 30, 2021

Study Completion (Anticipated)

November 1, 2021

Study Registration Dates

First Submitted

June 1, 2020

First Submitted That Met QC Criteria

June 1, 2020

First Posted (Actual)

June 4, 2020

Study Record Updates

Last Update Posted (Actual)

September 16, 2021

Last Update Submitted That Met QC Criteria

September 8, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared with any parties outside of the study team.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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