Targeted Active Case Detection Among High Risk Populations in Southern Lao Peoples Democratic Republic
- Conditions
- Plasmodium Falciparum Malaria
- Interventions
- Registration Number
- NCT03783299
- Lead Sponsor
- University of California, San Francisco
- Brief Summary
This study assesses the effectiveness of targeted active case detection among high-risk populations in Southern Lao Peoples Democratic Republic (PDR). The investigators hypothesize that active case detection using the next generation of HRP-2 rapid diagnostic tests (RDTs) can help bridge gaps in identification of high-risk asymptomatic individuals with low density parasitemia, allowing for targeting of this reservoir and thereby reducing transmission. The investigators hypothesize that active case detection (testing and treating positive cases) with these RDTs will lead to a reduction in P. falciparum transmission.
- Detailed Description
This study is the second phase of work in Champasak Province, Southern Lao PDR, building off a formative phase of work that characterized the demographics, occupations, migratory patterns, health-seeking behaviors, and social networks of mobile and migrant populations (MMPs) in four target districts. This phase of the study now aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of proactive targeted test-and-treat activities using high-sensitivity malaria rapid diagnostic tests (HS-RDTs) for reducing Plasmodium falciparum malaria transmission in Champasak Province among (1) village residents and (2) mobile and migrant populations (MMPs) and other high-risk populations (HRPs).
The study will specifically assess the role of HS-RDTs, a diagnostic test that offers potentially \~10-fold greater sensitivity than standard RDTs, in active case detection at both the village-level and in forest-going HRPs for decreasing prevalence and incidence of P. falciparum in target areas. The effectiveness of these interventions will be compared independently and in combination against areas with no study interventions (standard of care) over the course of implementation (planned for October 2017 - November 2018).
The two main study interventions are mass test and treat (MTAT) using HS-RDTs in village-based populations, and peer navigator (PN) led focal test and treat (FTAT) using HS-RDTs in forest based HRPs. Primary outcomes will include PCR-based P. falciparum prevalence at endline. Following a baseline cross-sectional survey in November-December 2017, the interventions will consist of 3 rounds of MTAT spaced throughout the year, with potential to reduce to 2 based upon initial prevalence estimates, and ongoing FTAT by PNs among forest and forest-fringe HRPs, with the primary evaluation to be conducted through an end-line cross-sectional survey in November 2018.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39968
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Village-based MTAT Primaquine Phosphate Intervention: For all households in intervention villages, after obtaining informed consent, MTAT will be conducted with all household members aged 18 months and older. The MTAT team will test each individual using both a standard RDT and HS-RDTs. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ) Peer navigator-led FTAT Primaquine Phosphate Intervention: Peer navigators will actively seek non-village based HRPs in forested areas, rice fields and plantations, and any other non-permanent settlements within target health center catchment areas, and conduct FTAT among all consenting individuals. The Peer Navigators will test each individual using both a standard RDT and HS-RDT. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ) Village-based MTAT Artemether-lumefantrine Intervention: For all households in intervention villages, after obtaining informed consent, MTAT will be conducted with all household members aged 18 months and older. The MTAT team will test each individual using both a standard RDT and HS-RDTs. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ) Peer navigator-led FTAT Standard RDT and HS-RDT Intervention: Peer navigators will actively seek non-village based HRPs in forested areas, rice fields and plantations, and any other non-permanent settlements within target health center catchment areas, and conduct FTAT among all consenting individuals. The Peer Navigators will test each individual using both a standard RDT and HS-RDT. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ) Village-based MTAT Standard RDT and HS-RDT Intervention: For all households in intervention villages, after obtaining informed consent, MTAT will be conducted with all household members aged 18 months and older. The MTAT team will test each individual using both a standard RDT and HS-RDTs. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ) Peer navigator-led FTAT Artemether-lumefantrine Intervention: Peer navigators will actively seek non-village based HRPs in forested areas, rice fields and plantations, and any other non-permanent settlements within target health center catchment areas, and conduct FTAT among all consenting individuals. The Peer Navigators will test each individual using both a standard RDT and HS-RDT. Positive cases will be treated with age-appropriate doses of Artemether-lumefantrine (AL) and Primaquine Phosphate (SLD-PQ)
- Primary Outcome Measures
Name Time Method Community-level PCR-based P. falciparum prevalence in sampled villages 4 months This is defined as the proportion of individuals \>18 months old with P. falciparum infection (detected by PCR) out of all individuals \>18 months tested within the 2017 and 2018 surveys.The effectiveness of the interventions will be assessed as P. falciparum prevalence via PCR at end-line (post only) using generalized linear mixed effects models with separate random intercepts to allow for clustering within villages and health center catchments. The binomial distribution will be used to analyze prevalence outcomes (logistic regression)
Community-level confirmed P. falciparum malaria parasite incidence 1 year This is defined as the number of total and confirmed outpatient (OPD) malaria confirmed and suspected cases per person per year for each village, as ascertained from the health facility registers, utilizing village population size estimates for the exposure denominator. Data pertaining to this outcome will be analyzed on an intention-to-treat basis. Monthly counts of confirmed malaria cases from the health facility registers will be linked to villages and analyzed in a time series Poisson or negative binomial model with random intercepts at the health center catchment and village levels.
HS-RDT-based test positivity rate in village-based and forest-based samples 6 months This is defined as the proportion of all individuals tested by HS-RDT at each round of the MTAT interventions or during routine FTAT, with a positive HS-RDT, among the population older than 18 months.The HS-RDT and RDT test positivity rates will be estimated for the MTAT villages during each intervention round. This will be done as soon as data on RDT and HS-RDT results are available, which would be expected to be one month following each round. Differences in prevalence measures at each round will be assessed using a χ2 test, as well as logistic regression models to account for potential confounding factors.
Village-based population coverage of test and treat interventions 3 months This indicator will be measured in two ways for each round of village MTAT. Operational program coverage is defined as the proportion of individuals ≥18 months old and households visited and offered the MTAT interventions within the target areas. Effective program coverage is defined as the proportion of individuals (≥18 months old) that agreed to participate in the MTAT intervention among all individuals ≥18 months old eligible to participate in the intervention in the target population
- Secondary Outcome Measures
Name Time Method Cost and cost effectiveness 12 months For the costing portion of the study, the cost per case investigation conducted, cost per additional positive case identified using FTAT in village- and forest-based HRPs, and the cost per case actively detected per person screened during screen and treat. The cost-effectiveness of screen and treat will also be compared between village-based activities and peer-navigator led testing.
Serology 2 months Seropositivity to a panel of standard malaria parasite antigens for P. falciparum and P. vivax (including merozoite surface protein-1 (MSP-1) and apical membrane antigen-1 (AMA-1), will be used to examine both recent and medium-term exposures. These data will also be mapped used captured global positioning system (GPS) coordinates to examine serological hotspots. Finally, novel antigens will also be used to further explore any differences in parasite exposure between study arms. Vector exposure may also be explored using antigens to anopheline salivary proteins.
Sensitivity and specificity of HS-RDTs 6 months The P. falciparum prevalence from all individuals tested with HS-RDTs will be compared with parallel results from standard RDTs (all field testing activities) and to subsequent PCR-based testing (cross-sectional survey, FTAT and MTAT subset). In the latter case, the PCR-based result will serve as the gold standard for all comparisons. Sensitivity and specificity and receiver operating curve (ROC) analyses will be conducted to assess the performance of the HS-RDTs in field situations, and in the presence of mixed-species infections. DBS will be collected for cross-sectional survey, FTAT and MTAT.
Trial Locations
- Locations (1)
Centre for Marialogy, Parasitology, and Entomology
🇱🇦Vientiane, Lao People's Democratic Republic