Health system readiness and the implementation of rectal artesunate for severe malaria in sub-Saharan Africa: an analysis of real-world costs and constraints

Lambiris, Mark; Venga, Guy Ndongala; Ssempala, Richard; Balogun, Victor; Galactionova, Katya; Musiitwa, Michael; Kagwire, Fred; Olosunde, Oluseyi Oluseyi; Emedo, Emmanel; Luketa, Sylvie; Sangare, Moulaye; Buj, Valentina; Delvento, Giulia; Tshefu, Antoinette; Okitawutshu, Jean; Omoluabi, Elizabeth; Awor, Phyllis; Signorell, Aita; Hetzel, Manuel W; Lee, Tristan; Brunner, Nina C.; Cereghetti, Nadja; Visser, Theodoor; Napier, Harriet G.; Burri, Christian; Lengeler, Christian

doi:10.1016/s2214-109x(22)00507-1

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…The relatively high rate of treatment compliance observed in DRC during the post-implementation period may be a result of a number of supportive interventions implemented to facilitate the roll-out and uptake of RAS [ 14 , 18 ]. In particular, this included distributing injectable artesunate to RHFs to limit use of the inferior quinine [ 29 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…The Community Access to Rectal Artesunate for Malaria (CARAMAL) project was designed as a large-scale operational study to address these questions [ 14 ]. The study aimed to assess healthcare seeking patterns [ 15 ], RAS use and acceptance [ 16 ], antimalarial treatment received at the various points of contact with the health system, health outcome at day 28 [ 17 ], as well as health system costs associated with the roll-out of pre-referral RAS [ 18 ]. Contrary to expectations, we found that RAS did not have a beneficial effect on child survival: In the Democratic Republic of the Congo (DRC) and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (adjusted odds ratio (aOR) = 3.06, 95% CI 1.35 to 6.92 and aOR = 2.16, 95% CI 1.11 to 4.21, respectively).…”

Section: Introductionmentioning

confidence: 99%

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Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study

et al. 2023

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Background For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years. Methods and findings This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study. Conclusions Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality. Trial registration ClinicalTrials.gov (NCT03568344).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study

et al. 2023

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“…The cost of goods for any new treatments for severe malaria will need to be consistent with a purchase price that is not greater than currently available treatments. However, drug purchase price represents a small cost relative to the overall implementation costs of the severe malaria continuum of care, particularly when patients are hospitalized or when treatment fails [ 68 ]. Thus, a more costly drug, which decreases the duration of hospitalization or prevents recrudescence without the need for follow-up oral therapy could be more cost-effective than one which must be implemented within the current continuum of care paradigm.…”

Section: Updating the Tpp For New Severe Malaria Therapeuticsmentioning

confidence: 99%

Defining the next generation of severe malaria treatment: a target product profile

Achan,

Barry,

Leroy

et al. 2024

Malar J

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Background Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.

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Rectal artesunate as pre-referral treatment for severe malaria in sub-Saharan Africa: still a long way to go

Cook¹

2023

The Lancet Global Health

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Health system readiness and the implementation of rectal artesunate for severe malaria in sub-Saharan Africa: an analysis of real-world costs and constraints

Cited by 5 publications

References 26 publications

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study

Defining the next generation of severe malaria treatment: a target product profile

Rectal artesunate as pre-referral treatment for severe malaria in sub-Saharan Africa: still a long way to go

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