Malaria High-Risk Populations in Namibia

NCT04094727 | Completed Phase 4

• 1 other identifier: Malaria HRP in Namibia
• Study Type: interventional
• Target: 3,302
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

malaria; Namibia

Outcome Measures

Primary Outcomes (4)

• Effective coverage of AL (presumptive treatment)

  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.

  6 months, measured post-intervention only

• Effective coverage of IRS

  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.

  6 months, measured pre-and post-intervention

• Effective coverage of LLIN

  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.

  6 months, measured pre-and post-intervention

• Prevalence of infection measured by polymerase chain reaction (PCR)

  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.

  6 months

Secondary Outcomes (12)

• Odds of symptomatic malaria associated with receiving each intervention

  6 months

• Total confirmed outpatient (OPD) malaria case incidence by health facility, stratified by HRP status

  6 months

• Malaria seroprevalence in HRPs

  6 months

• Test positivity rates from RACD

  6 months

• Entomological Indicators

  6 months

Study Arms (2)

Presumptive treatment and enhanced vector control

EXPERIMENTAL

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.

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

Standard of care

NO INTERVENTION

The control arm will receive the standard of care in Namibia: passive case detection through health facilities and health extension workers, routine indoor residual spraying (IRS), and reactive case detection (RACD) accompanied by reactive IRS.

Interventions

Presumptive treatment with Artemether-lumefantrine (AL) DRUG

All eligible HRPs will be presumptively treated with artemether-lumefantrine (AL) at two timepoints, separated by at least one month. All individuals who have provided informed consent, meet eligibility criteria, are not pregnant or breastfeeding, and who do not have symptoms associated with severe malaria or another severe illness, will be offered an age-appropriate course of AL (age-specific blister packages). AL is currently the first line drug used for uncomplicated malaria in Namibia, and has been used previously in northern Namibia for focal mass drug administration and has no severe adverse effects and is well-tolerated, with high adherence and acceptability in this context. AL requires two daily doses for three consecutive days, for a total of six doses. The first antimalarial dose will be delivered by directly observed therapy (DOT) and subsequent doses will be left with the subject, with instructions to self-administer them.

Also known as: Coartem

Presumptive treatment and enhanced vector control

Enhanced vector control OTHER

The mop up indoor residual spraying (IRS) campaign will be targeted to farms and cattle posts/kraals in intervention areas in December 2019 to fill gaps from the routine spray campaign (September to November 2019) and utilize the same insecticides and protocols as the national campaign. The team will spray each unsprayed structure with the recommended solution of dichloro-diphenyl-trichloroethane (DDT) for traditional structures and/or Actellic for modern structures, tarps and tents. Alternative vector control interventions, including LLINs (long-lasting insecticide treated bed nets), sprayed tents/tarps and topical repellents will be distributed to eligible HRPs between November and January 2020 during one round.

Also known as: Indoor residual spraying (IRS), Long-lasting insecticide treated bed nets, Topical repellents

Presumptive treatment and enhanced vector control

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Namibia: collaborator
• Ministry of Health and Social Services, Namibia: collaborator
• University of Texas Southwestern Medical Center: collaborator
• University of Notre Dame: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

University of Namibia, Multidisciplinary Research Centre

Windhoek, Namibia

Location

Related Publications (12)

• Jacobson JO, Cueto C, Smith JL, Hwang J, Gosling R, Bennett A. Surveillance and response for high-risk populations: what can malaria elimination programmes learn from the experience of HIV? Malar J. 2017 Jan 18;16(1):33. doi: 10.1186/s12936-017-1679-1.

  PMID: 28100237 BACKGROUND

• Smith JL, Ghimire P, Rijal KR, Maglior A, Hollis S, Andrade-Pacheco R, Das Thakur G, Adhikari N, Thapa Shrestha U, Banjara MR, Lal BK, Jacobson JO, Bennett A. Designing malaria surveillance strategies for mobile and migrant populations in Nepal: a mixed-methods study. Malar J. 2019 May 3;18(1):158. doi: 10.1186/s12936-019-2791-1.

  PMID: 31053075 BACKGROUND

• Smith JL, Auala J, Haindongo E, Uusiku P, Gosling R, Kleinschmidt I, Mumbengegwi D, Sturrock HJ. Malaria risk in young male travellers but local transmission persists: a case-control study in low transmission Namibia. Malar J. 2017 Feb 10;16(1):70. doi: 10.1186/s12936-017-1719-x.

  PMID: 28187770 BACKGROUND

• Wu L, van den Hoogen LL, Slater H, Walker PG, Ghani AC, Drakeley CJ, Okell LC. Comparison of diagnostics for the detection of asymptomatic Plasmodium falciparum infections to inform control and elimination strategies. Nature. 2015 Dec 3;528(7580):S86-93. doi: 10.1038/nature16039.

  PMID: 26633770 BACKGROUND

• Kern SE, Tiono AB, Makanga M, Gbadoe AD, Premji Z, Gaye O, Sagara I, Ubben D, Cousin M, Oladiran F, Sander O, Ogutu B. Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis. Malar J. 2011 Jul 29;10:210. doi: 10.1186/1475-2875-10-210.

  PMID: 21801345 BACKGROUND

• Hsiang M, Ntuku H, Roberts K, Dufour M-s, Whittemore B, Tambo M, et al. The effectiveness of malaria reactive focal mass drug administration (rfMDA) and reactive vector control (RAVC), a cluster-randomised controlled two-by-two factorial design trial from the low-endemic setting of Namibi. 2019. Unpublished.

  BACKGROUND

• Initiative ME. Planning for targeted malaria interventions in high-risk populations (HRPs) in Northern Namibia: Findings from a rapid formative assessment in Zambezi Region. University of California, San Francisco, 2019.

  BACKGROUND

• The Global Health Group. Screen and treat strategies for malaria elimination: a review of evidence. 2018.

  BACKGROUND

• Malaria Elimination Initiative. Planning for targeted malaria interventions in high-risk populations (HRPs) in Northern Namibia: Findings from a rapid formative assessment in Ohangwena Region. University of California, San Francisco, 2019.

  BACKGROUND

• Naing C, Whittaker MA, Tanner M. Inter-sectoral approaches for the prevention and control of malaria among the mobile and migrant populations: a scoping review. Malar J. 2018 Nov 16;17(1):430. doi: 10.1186/s12936-018-2562-4.

  PMID: 30445959 BACKGROUND

• IOM (International Organization for Migration). A global report on population mobility and malaria: moving towards elimination with migration in mind. 2013.

  BACKGROUND

• Smith JL, Ntuku H, Rerolle F, Burke AM, Mwema T, Turcios K, Uusiku P, Haikali JK, Lifasi M, Smith-Gueye C, Vajda E, Jacobson JO, Greenhouse B, Gosling R, Bennett A, Mumbengegwi DR. Targeting malaria in high-risk populations in low endemic regions in northern Namibia: a quasi-experimental controlled trial to reduce malaria in seasonal agricultural workers and cattle herders. BMJ Glob Health. 2025 Feb 17;10(2):e015565. doi: 10.1136/bmjgh-2024-015565.

  PMID: 39961693 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Jennifer Smith, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2019
• First Posted: September 19, 2019
• Study Start: October 31, 2019
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: November 3, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

NA (1)