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

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT04416945

Collaborator

Center for Malariology, Parasitology, and Entomology (Other), Tulane University School of Public Health and Tropical Medicine (Other), University of Massachusetts, Amherst (Other), Centers for Disease Control and Prevention (U.S. Fed)

31,443

Enrollment

Location

Arms

13.4

Anticipated Duration (Months)

2351.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum Malaria Plasmodium Vivax Malaria	Other: Household Reactive Case Detection Other: RACD of cases' co-workers/co-travelers Other: Case Management and Follow-up	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

31443 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Screening

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

Actual Study Start Date :

Sep 20, 2020

Anticipated Primary Completion Date :

Sep 30, 2021

Anticipated Study Completion Date :

Nov 1, 2021

Arms and Interventions

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	Other: Household Reactive Case Detection 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. Other: RACD of cases' co-workers/co-travelers 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. Other: Case Management and Follow-up 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	Other: Case Management and Follow-up 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

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

Other: Household Reactive Case Detection

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.

Other: RACD of cases' co-workers/co-travelers

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.

Other: Case Management and Follow-up

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

Other: Case Management and Follow-up

Outcome Measures

Primary Outcome Measures

Confirmed P. falciparum and P. vivax malaria parasite incidence [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.
PCR-based P. falciparum and P. vivax parasite prevalence in sampled HCCAs [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).
HS-RDT/RDT-based test positivity rate in village and forest-based reactive case detection [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Malariology, Parasitology, Entomology, Laos Ministry of Health	Vientiane		Lao People's Democratic Republic

Sponsors and Collaborators

University of California, San Francisco
Center for Malariology, Parasitology, and Entomology
Tulane University School of Public Health and Tropical Medicine
University of Massachusetts, Amherst
Centers for Disease Control and Prevention

Investigators

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

Study Documents (Full-Text)

Study Protocol - Jul 12, 2019

More Information

Publications

Responsible Party:

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT04416945

Other Study ID Numbers:

19-27966

First Posted:

Jun 4, 2020

Last Update Posted:

Sep 16, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Malaria

Malaria, Falciparum

Malaria, Vivax

Study Results

No Results Posted as of Sep 16, 2021