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. 2022 Sep 6;2(9):e0000464.
doi: 10.1371/journal.pgph.0000464. eCollection 2022.

Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda

Christian Lengeler  1   2 , Christian Burri  1   2 , Phyllis Awor  3 , Prosciova Athieno  3 , Joseph Kimera  3 , Gloria Tumukunde  3 , Irene Angiro  3 , Antoinette Tshefu  4 , Jean Okitawutshu  4 , Jean-Claude Kalenga  4 , Elizabeth Omoluabi  5 , Babatunde Akano  5 , Kazeem Ayodeji  5 , Charles Okon  5 , Ocheche Yusuf  5 , Nina C Brunner  1   2 , Giulia Delvento  1   2 , Tristan Lee  1   2 , Mark Lambiris  1   2 , Theodoor Visser  6 , Harriet G Napier  6 , Justin M Cohen  6 , Valentina Buj  7 , Aita Signorell  1   2 , Manuel W Hetzel  1   2 ; CARAMAL Consortium
Affiliations

Community access to rectal artesunate for malaria (CARAMAL): A large-scale observational implementation study in the Democratic Republic of the Congo, Nigeria and Uganda

Christian Lengeler et al. PLOS Glob Public Health. .

Abstract

The key to reducing malaria deaths in highly endemic areas is prompt access to quality case management. Given that many severe cases occur at peripheral level, rectal artesunate (RAS) in the form of suppositories was developed in the 1990s, allowing for rapid initiation of life-saving antimalarial treatment before referral to a health facility with full case management capabilities. One randomized controlled trial published in 2009 showed a protective effect of RAS pre-referral treatment against overall mortality of 26%, but with significant differences according to study sites and length of referral. Two important issues remained unaddressed: (1) whether the mortality impact of RAS observed under controlled trial conditions could be replicated under real-world circumstances; and (2) clear operational guidance for the wide-scale implementation of RAS, including essential health system determinants for optimal impact. From 2018 to 2020, the Community Access to Rectal Artesunate for Malaria (CARAMAL) project was conducted as a large-scale observational implementation study in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda (registered on ClinicalTrials.gov as NCT03568344). CARAMAL aimed to provide high-quality field evidence on the two issues above, in three remote settings with high malaria endemicity. A number of complementary study components were implemented. The core of the CARAMAL study was the Patient Surveillance System (PSS), which allowed tracking of cases of severe febrile illness from first contact at the periphery to a referral health facility, and then on to a Day 28 visit at the home of the patient. Community and provider cross-sectional surveys complemented the PSS. Here we describe in some detail RAS implementation, as well as the key CARAMAL study components and basic implementation experience. This manuscript does not intend to present key study results, but provides an extensive reference document for the companion papers describing the impact, referral process, post-referral treatment and costing of the RAS intervention.

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Conflict of interest statement

Authors EO, BA, KA, CO, and OY are employees of Akena Associates. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the authors have any competing interests in the topic presented in this manuscript.

Figures

Fig 1
Fig 1. Study areas and study populations in the three CARAMAL project countries.
mRDT = malaria Rapid Diagnostic Tests. Map base layers from: https://www.naturalearthdata.com/downloads/50m-physical-vectors/.
Fig 2
Fig 2. Teaching aids developed by Medicines for Malaria Venture (MMV) for the training of health workers in the correct administration of RAS (source: https://www.mmv.org/access/tool-kits/artesunate-rectal-capsules-tool-kit).
Fig 3
Fig 3. Continuum of care for an episode of severe febrile illness (central block) and key themes identified for analysis (numbered with yellow highlights).
1. RAS implementation (coverage), 2. Health impact of introducing pre-referral RAS, 3. Severity of illness, 4. Treatment seeking pathways, 5. Treatment and referral at community-based providers, 6. Case management at referral facilities, 7. Cost and cost-effectiveness of introducing RAS.
Fig 4
Fig 4. Schematic representation of the various CARAMAL survey instruments and the duration of data collection.
Fig 5
Fig 5. Schematic representation of possible points of contact in the Patient Surveillance System.
ID = identification by unique study ID. Green triangles represent points of contact, empty (white) triangles absence of contact. CHW = Community Health Workers. HF = Health facility. No = Number. QA = Quality-assured.
Fig 6
Fig 6. Number of children enrolled in the Patient Surveillance System (grey bars), and percentage of these children being administered rectal artesunate (RAS), by country.
Fig 7
Fig 7. Number of suppositories received by enrolled children, by age group and country.
yr = year. Missing = missing data.
Fig 8
Fig 8. Overall case fatality ratio (CFR) in patients with danger signs and a positive malaria test at enrolment across the entire study period, by enrolment location and country.
Data for Uganda excludes enrolments at PHCs (N = 34).
See this image and copyright information in PMC

References

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