Malaria High-Risk Populations in Namibia

Phase 4

Completed

• Conditions: Malaria
• Interventions: Drug: Presumptive treatment with Artemether-lumefantrine (AL); Other: Enhanced vector control

• Registration Number: NCT04094727
• Lead Sponsor: University of California, San Francisco

Brief Summary

This study aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of targeted delivery of a package of malaria interventions for improving effective coverage and reducing Plasmodium falciparum malaria transmission among malaria high-risk populations in Northern Namibia. Previous research identified cattle herders and agricultural workers as populations at higher risk of infection. The investigators hypothesize that targeted delivery of interventions will lead improve coverage in these groups and lead to a reduction in P. falciparum transmission.

Detailed Description

This study is the second phase of work in Zambezi and Ohangwena Regions, Namibia, building off a formative phase of work that characterized the risk behaviors migratory patterns, health-seeking behaviors, intervention strategies and social networks of agricultural workers and cattle herders, who are previously identified malaria high-risk populations (HRPs). This phase of the study now aims to determine the effectiveness, cost-effectiveness, acceptability, and feasibility of targeted delivery of a package of malaria interventions for improving effective coverage and reducing Plasmodium falciparum malaria transmission in these regions among these populations.

The study will specifically assess the coverage and impact of interventions delivered at worksites to HRPs, including presumptive treatment administered alongside vector control interventions (indoor residual spraying \[IRS\], long-lasting insecticidal nets \[LLINs\], and topical repellents). The effectiveness of these interventions will be compared against areas with no study interventions (standard of care) over the course of implementation (November 2019 - May 2020). Primary outcomes will include the coverage of each intervention at worksites over the study period and PCR-based P. falciparum prevalence measured at endline. Following a baseline cross-sectional survey in November/December 2019, the interventions will consist of 2 rounds of presumptive treatment spaced at least one month apart between January and March, and delivery of vector control interventions at worksites and key access points with support from employers, with the primary evaluation to be conducted through an endline cross-sectional survey in April/May 2020. Secondary outcomes around effectiveness will be assessed through incident case data providing measures of incidence in HRP and non-HRP populations, odds of infection associated with each intervention in cases compared to controls and entomological data collection. In addition, operational and feasibility outcomes will be assessed through qualitative data collection, population size estimation of HRP groups and a global positioning system (GPS) logger study.

Study Timeline

• Study First Submitted: 2019-09-16
• Study First Submitted QC: 2019-09-16
• Study First Posted: 2019-09-19
• Study Start: 2019-10-31
• Primary Completion: 2020-06-30
• Study Completion: 2020-06-30
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-02
• Last Update Posted: 2020-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3302

Inclusion Criteria

HRP study populations (all)

• Study participants include those in the 8 selected health facility catchment areas within Zambezi and Ohangwena Regions.
• Identify primary occupation as a agricultural worker or cattle herder
• Zambezi Region: Have slept or worked outside at a farm or cattle post in the past 7 days or will do over the next 3 weeks (sleeping outside, working outside ploughing or guarding crops/cattle, or sleeping in any type of structure located at a farm or cattle post site)
• Ohangwena Region: Report overnight travel to Angola for grazing cattle during the malaria transmission season (November to May) Be willing and able to provide consent (ie mentally fit)

Inclusion Criteria: Presumptive AL treatment

• In addition to the above, subjects must report travel outside of Namibia within the past 60 days to be eligible to receive AL.

Inclusion Criteria: Enhanced vector control

• In addition to the above, participants must not sleep in a structure sprayed with insecticide to be eligible to receive an LLIN or sprayed tent/tarp.

Inclusion Criteria: Focus group discussions and key informant interviews

• Meet eligibility criteria as a member of an HRP, health facility staff or health extension worker involved in the diagnosis and treatment of HRP populations.
• Individuals must be 18 years and older and willing and able to provide consent to be included in the GPS logger, focus group discussions or key informant interviews

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Exclusion Criteria

• Per national guidelines in Namibia, presumptive treatment with AL will not be given to women who are pregnant in the first trimester, individuals weighing less than 5kg, those with a known AL allergy or suspected severe malaria.
• Individuals under the age of 18 will be excluded from the GPS logger study, focus group discussions and key informant interviews.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Presumptive treatment and enhanced vector control	Presumptive treatment with Artemether-lumefantrine (AL)	For all eligible HRPs in intervention areas, after obtaining informed consent, presumptive treatment for malaria will be carried out using artemether-lumefantrine (AL) at two time points. Enhanced vector control activities will include: (1) a mop up indoor residual spraying (IRS) campaign and (2) distribution of long-lasting insecticide-treated nets (LLINs) and/or vector control packs with topical repellent. The intervention arm will also receive the standard of care in Namibia.
Presumptive treatment and enhanced vector control	Enhanced vector control	For all eligible HRPs in intervention areas, after obtaining informed consent, presumptive treatment for malaria will be carried out using artemether-lumefantrine (AL) at two time points. Enhanced vector control activities will include: (1) a mop up indoor residual spraying (IRS) campaign and (2) distribution of long-lasting insecticide-treated nets (LLINs) and/or vector control packs with topical repellent. The intervention arm will also receive the standard of care in Namibia.

Primary Outcome Measures

Name	Time	Method
Effective coverage of AL (presumptive treatment)	6 months, measured post-intervention only	This is defined as the proportion of eligible HRPs who report receiving a full course of AL (presumptive treatment) at any time over the study period. The difference in intervention coverage between arms at end-line will be assessed using generalized linear models adjusted for potential confounders and a fixed effect to capture clustering at the health facility level.
Effective coverage of IRS	6 months, measured pre-and post-intervention	This is defined as the proportion of eligible HRPs who report sleeping at a worksite in a structure sprayed with insecticide during the past 6 months (IRS), at any time over the study period. The difference in intervention coverage between arms will be assessed using a difference-in-difference approach using generalized linear models adjusted for potential confounders and a fixed effect to capture clustering at the health facility level.
Effective coverage of LLIN	6 months, measured pre-and post-intervention	This is defined as the proportion of eligible HRPs who report sleeping under a bednet (LLIN) the last night staying at a worksite, at any time over the study period. The difference in intervention coverage between arms will be assessed using a difference-in-difference approach using generalized linear models adjusted for potential confounders and a fixed effect to capture clustering at the health facility level.
Prevalence of infection measured by polymerase chain reaction (PCR)	6 months	Species-specific prevalence of malaria infection will be calculated as the proportion of people testing positive for each species malaria by PCR out of all tested HRPs. The reduction in malaria prevalence will be assessed using a difference-in-difference approach, comparing change (pre- versus post-intervention) in all-species infection between intervention and control groups.

Secondary Outcome Measures

Name	Time	Method
Total confirmed outpatient (OPD) malaria case incidence by health facility, stratified by HRP status	6 months	The total confirmed outpatient malaria case incidence will be estimated for each of the study health catchment areas and stratified by HRP status. RDTs used for routine malaria diagnosis will be collected and a short questionnaire affixed to the back to allow collection of key indicators to stratify incidence estimates. Denominators will be based on health catchment populations and population size estimates obtained through this study. A reduction in malaria incidence in HRPs and the overall catchment population will be evaluated using a difference-in-difference approach, comparing change (pre- versus post-intervention) between intervention and control groups.
Cost effectiveness	6 months	The costs and cost-effectiveness of the intervention package will be assessed as an incremental cost effectiveness ratio (ICER), as well as cost per population and case averted as measured through the difference in infections identified subsequent to the intervention. Program data on costs/expenditure for each intervention will be collected and combined with estimates of program effectiveness to estimate these measures.
Self-reported compliance to LLIN and topical repellents.	6 months	Self-reported user compliance to LLINs and topical repellents will be assessed through the quantitative baseline and endline cross-sectional surveys, as well as through a use tracking log tracking compliance over a 30-day period (Appendix 16 and 17) in the cohort included in the pill count. LLIN use and condition will be empirically assessed during the endline cross-sectional survey and at 30 days, as well as repellent containers weighed after 30 in the cohort. Qualitative information on use of these interventions will be collected during key informant interviews and focus group discussions.
HRP movement patterns	6 months	The proportion of individual's time spent in different locations will be measured from aggregating GPS readings (located within pre-defined space-time windows) which are spatially located within a given type of area (farm, cattle post, grazing location, village etc). Where possible, common locations will be tagged and classified by field workers to distinguish individual farms, fields and other points of interests (such as bars, homes, etc). Aggregated GPS readings (located within pre-defined space-time windows) will be plotted to distinguish individual trips and measure specific characteristics of each trip, including distance of travel and frequency of trips.
Test positivity rates from RACD	6 months	Test positivity rates will be calculated as the proportion of individuals screened during routine RACD who test positive for malaria by RDT and PCR. Rates will be stratified by HRP status and location of event (either within villages or at an HRP worksite).Differences in prevalence measures between HRP and non-HRP populations will be assessed using a χ2 test, as well as logistic regression models to account for potential confounding factors.
Odds of symptomatic malaria associated with receiving each intervention	6 months	The odds of clinical malaria associated with receiving each intervention will be measured by comparing the risk of exposure in cases (RDT-positive) to the risk in controls (RDT-negative) in HRPs within study areas.
Malaria seroprevalence in HRPs	6 months	Malaria exposure in HRPs will be measured as the proportion of people with antimalarial antibodies present in their blood serum. ELISA assays will be used to detect biomarkers of Pf exposure, using collected dried blood spots during baseline and endline cross-sectional surveys. The reduction in malaria exposure will be assessed using a difference-in-difference approach, comparing change (pre- versus post-intervention) between intervention and control groups.
Entomological Indicators	6 months	Entomological measurements including descriptions of vector occurrence, estimates of human biting rates, measures of indoor and outdoor densities, and insecticide susceptibility status and frequency. Measures will be compared between intervention and control study areas, for each type of intervention.
Intervention acceptability as evaluated by qualitative assessment	6 months	Qualitative data collection methods such as focus groups and key informant interviews with HRPs, health extension workers, employers and other health sector staff will be implemented to assess intervention acceptability.
Adherence to presumptive treatment intervention as evaluated by pill count	6 months	Participant adherence to presumptive treatment will be assessed within a sub-sample of people distributed the drug and measured as the proportion of people who complete all pills in the pill pack after receiving the first dose of AL by DOT. Changes in proportions over time will be quantified between the two distribution rounds.
HRP population size	6 months	The population size of target HRPs will be estimated in intervention areas using a combination of multiplier and multiple capture-recapture (CR) methods. In Ohangwena Region, the population is assumed fixed, although accessibility of cattle herders in Namibia may vary throughout the year. In Zambezi Region, the population is estimated at two distinct time periods in order to capture turnover between agricultural seasons.
Intervention acceptability as evaluated by participation rate	6 months	The acceptability of a targeted delivery of presumptive treatment and vector control interventions to HRPs will be assessed as the proportion of targeted individuals refusing each intervention, among those eligible for inclusion. Acceptability of IRS will be assessed as the proportion of targeted farms refusing LLIN, among those with at least one sprayable structure missed during the spray campaign.

Trial Locations

Locations (1)

University of Namibia, Multidisciplinary Research Centre; 🇳🇦 Windhoek, Namibia