Artesunate rectal capsules: a pre-referral intervention for severe malaria

Severe malaria, a life-threatening condition, may ensue rapidly if a bout of acute uncomplicated malaria is not promptly treated. The manifestations of severe malariainclude severe anaemia, respiratory distress and end-organ damage.1 2

Artesunate rectal capsules (ARC) administered at the community or primary health facility level have been shown to save lives, in particular those of critically ill young children unable to access parenteral treatment within 6 hours. This emergency intervention halts the progression of the disease, reducing parasite levels in the blood while the patient is transported to a referral health facility. Once admitted to a referral centre, patients should receive treatment for severe malaria as per WHO guidelines.  

Developing quality ARC for malaria-endemic countries 

The WHO Guidelines for the treatment of malaria have recommended ARC for over 10 years, but the lack of a quality-assured ARC product on the market hampered its widespread availability and use, forcing malaria-endemic countries to choose from sources of drug supply that did not meet international quality standards. 

MMV collaborated with two pharmaceutical partners (Strides Pharma and Cipla) to develop and secure WHO prequalification of ARC as part of the Unitaid-funded project ‘Improving Severe Malaria Outcomes’ (ISMO). This work also supported the correct rollout and use of ARC as a pre-referral intervention. 

An initial forecast was conducted to estimate the need for ARC in countries with a high burden of severe malaria; this forecast was instrumental in helping manufacturers understand the potential demand they would encounter for the products they were developing. 

Increasing supply and supporting uptake

MMV has worked with partners to increase access to ARC, generate evidence to support countries with implementation and strengthen the global supply chain.

Since 2017, 3.8 million ARC have been supplied to malaria-endemic countries with the support of international donor funding. Currently the product is registered in 20 countries

Currently, a collaboration initiated in 2017 to increase access to commodities for the case management of severe malaria in one Zambian district is being implemented in five additional districts, and the Zambian Minsitry of Health is in the process of identifying five more. The initial, year-long project was launched in the district of Serenje in Central Province, Zambia. The impact was notable. Death rates in children with severe malaria fell by 96% (from 8% to 0.25%) with 94 children’s lives saved as compared to what would previously have been predicted in the timeframe. 

MMV is working to strengthen the global supply chain of ARC and to support its rational use. This is thanks to the work initiated under a supply grant awarded to MMV by Unitaid in 2017. Currently MMV is working with the Clinton Health Access Initiative (CHAI) to support the introduction of ARC in select areas. This is in the context of the Unitaid grant for the CARAMAL study, led by CHAI, and supported by Swiss TPH, Unicef and WHO. 

Supporting countries with roll-out and ensuring appropriate use

MMV has worked closely with partners to develop clear product information for ARC. The resulting training material was included in theWHO information note on rectal artesunate for pre-referral management of severe malaria. The aim of the note is to prepare countries for large-scale deployment of artesunate rectal capsules (ARC) for pre-referral management of severe malaria in children, while reinforcing the importance of using ARC and other artemisinin-containing medicines appropriately. While appropriate use could save the lives and reduce disability in children with severe malaria, incorrect use of medicines like ARC could increase the risk of artemisinin-resistant malaria in Africa. 

MMV has supported NMCPs with the training of health workers at regional, district and community levels. A recent example is Madagascar where MMV supported the implementation of ARC in eight regions.

Rapid assessments of severe malaria case-management are also conducted with the aim to identify best practices and areas for improvement. Recommendations are shared with the NMCP and partners to strengthen care delivery. In 2019, an assessment was done in Liberia and in 2020, in Angola and in Mali. These assessments help identify barriers to the introduction of ARC as well as evaluate country-readiness to implement the intervention.

In April of 2021 and thanks to a real-world ARB stability testing programme, wording in the WHO-Public Assessment Reports (Strides and Cipla) was changed from “… product should be distributed as short-term stock not exceeding 4-6 months…” to a recommendation of 6 months storage, in order to remove any doubt that the 4-6 month bracket may cause. This clarification makes a huge difference to the use of ARC in the field where frequent resupply of the product to remote regions is a constant challenge. The initiation of the programme was the result of a meeting convened by the Clinton Health Access Initiative (CHAI), MMV and other partners, and hosted by the Nigerian Ministry of Health in Abuja.

→Learn more about severe malaria from the Severe Malaria Observatory.

→Take a look at the interactive map to see the countries where ARC is registered.