Evidence map›Paper›PMID 41664036›Full record

ArticleMalaria journal2026

Severe malaria treatment with rectal artesunate and artemisinin-based combination therapy in remote settings: an effectiveness-implementation hybrid type 3 study protocol (SEMA ReACT).

Sebastian Hachizovu, Christine Manyando, Michael Nambozi, Shepherd Khondowe, Busiku Hamainza, Donald Mukumbuta, Hans Rietveld, Eric Mukomena Sompwe, Ghislain Kikunda, Hypolite Muhindo-Mavoko and 10 more

Abstract read
In one paragraph

Article in Malaria journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Sebastian HachizovuNational Health Research and Training Institute, Lusaka, Zambia. sebastianhachizovu4@gmail.com.
Christine ManyandoNational Health Research and Training Institute, Lusaka, Zambia.
Michael NamboziNational Health Research and Training Institute, Lusaka, Zambia.
Shepherd KhondoweNational Health Research and Training Institute, Lusaka, Zambia.
Busiku HamainzaProgramme Coordination Unit, Ministry of Health, Lusaka, Zambia.
Donald MukumbutaNational Malaria Elimination Centre, Ministry of Health, Lusaka, Zambia.
Hans RietveldMMV Medicines for Malaria Venture, Geneva, Switzerland.
Eric Mukomena SompweNational Malaria Control Programme, Ministry of Health, Kinshasa, Democratic Republic of Congo.
Ghislain KikundaNational Malaria Control Programme, Lubumbashi, Haut-Katanga Province, Democratic Republic of Congo.
Hypolite Muhindo-MavokoUniversity of Kinshasa, Kinshasa, Democratic Republic of Congo.
Flory Luzolo KhoteGlobal Health Institute, University of Antwerp, Antwerp, Belgium.
Deborah KanyamukengeGlobal Health Institute, University of Antwerp, Antwerp, Belgium.
Hilde BastiaensGlobal Health Institute, University of Antwerp, Antwerp, Belgium.
Aimé KakudjiUniversity of Lubumbashi, Lubumbashi, Democratic Republic of Congo.
Tafadzwa MasekoGlobal Health Institute, University of Antwerp, Antwerp, Belgium.
Geofrey MakengaGlobal Health Institute, University of Antwerp, Antwerp, Belgium.
Vito BarakaNational Institute for Medical Research, Tanga, Tanzania.
Augustin MutomboUniversity of Lubumbashi, Lubumbashi, Democratic Republic of Congo.
Stephan DuparcMMV Medicines for Malaria Venture, Geneva, Switzerland.
Jean Pierre Van GeertruydenGlobal Health Institute, University of Antwerp, Antwerp, Belgium.

Funding

European and Developing Countries Clinical Trials Partnerships (EDCTP), under project number 101103191 [HORIZON-JU-GH-EDCTP3-2022-01] with co-funding from the State Secretariat for Education, Research and Innovation (SERI), Switzerland. 101103191 [HORIZON-JU-GH-EDCTP3-2022-01]
6 · The paper itself

Abstract

backgroundAlmost 500,000 children under 5 years die annually from severe malaria in Africa. Prompt access to effective antimalarial treatment is crucial to reduce mortality. Current clinical guidelines recommend pre-referral rectal artesunate (RAS) followed by injectable artesunate and a 3-day course of artemisinin-based combination therapy (ACT). However, adherence to this treatment algorithm is not always feasible due to many reasons. Integrated community case management (iCCM) presents a promising strategy to improve timely access to care through community health workers (CHWs). This study aims to: (i) assess the feasibility of providing rapid treatment of severe malaria with RAS to children aged 6 months-5 years by CHWs or in health facilities (HFs) without injectable artesunate; (ii) evaluate recrudescence rates in children under 5 following RAS by either ACT for whom referral was not feasible or those after referral completion; and (iii) assess the impact of upgrading iCCM services on access to the formal healthcare system, including severe malaria care.

methodsThis is an effectiveness-implementation hybrid Type 3 study. The study is being conducted in Nchelenge, Zambia and Kapolowe, Democratic Republic of Congo using phased rollout of upgraded iCCM according to national guidelines. CHWs will diagnose, treat and monitor study participants, while research assistants will visit each participant on day 14 to complete a questionnaire, conduct in-depth interviews (IDIs) as well as focus group discussions (FGDs) with caregivers of sampled study participants. Primary outcomes include: (i) time from symptom onset to treatment initiation in the participants who seek care via CHWs or HFs; (ii) 28-day PCR-corrected cure rates following RAS + ACT or RAS + injectable artesunate + ACT treatment; and (iii) the proportion of study population utilizing formal healthcare services within the preceding 6 months, including suspected severe malaria cases. DISCUSSION: This study will provide essential evidence on the feasibility and effectiveness of community-based pre-referral treatment for severe malaria in resource-limited settings, address access barriers to injectable artesunate and facility-based care, inform policy and programmatic adaptations and guide scalable strategies to enhance timely treatment, reduce mortality and mitigate drug resistance in high-burden malaria regions.

Indexed as

AntimalarialsArtemisininsArtesunateMalariaAdministration, RectalCase ManagementChild, PreschoolCommunity Health WorkersDrug Therapy, CombinationFemaleHumansInfantAntimalarialsartemisininArtemisininsArtesunateArtemisinin-based combination therapyClinical effectivenessCommunity health workerImpactImplementationImplementation researchInjectable artesunateIntegrated community case managementRectal artesunate

Identifiers

PMID41664036
PMCPMC12954902

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.