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

University of California San Francisco (UCSF)

Status: Unknown

Conditions: Plasmodium Vivax Malaria; Plasmodium Falciparum Malaria

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

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04416945

19-27966

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31,443 estimated patients

Sex: All

Ages: 18+ months old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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31,443 participants in 2 patient groups

RACD

Experimental group

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

Treatment:

Other: Case Management and Follow-up

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

Other: Household Reactive Case Detection

Control

Active Comparator group

Description:

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

Treatment:

Other: Case Management and Follow-up