Severe malaria, a life-threatening condition, may ensue rapidly if a bout of acute uncomplicated malaria is not promptly treated. Artesunate rectal capsules (ARC) administered at the community level have been shown to save lives, in particular those of critically ill young children unable to access parenteral treatment within 6 hours.
Getting WHO prequalification
MMV supported both Cipla and Strides Pharma in their efforts to secure WHO prequalification for ARC. These activities were carried out with funding from Unitaid, and with the support of the Special Programme for Research and Training in Tropical Diseases (TDR).
Introducing ARC to the market in malaria-endemic countries
MMV conducted an initial forecast 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 their products.
To understand current policies and identify barriers to the introduction of ARC, MMV carried out country assessments, which included evaluations of countries readiness to implement ARC. One of the considered aspects was the level of training of healthcare workers to recognize signs of severe febrile illness at the community level.
MMV and partners convened an ARC stakeholders meeting in Nairobi in February 2016 to discuss experiences, challenges and options for overcoming obstacles confronting ARC rollout. They identified the key issues relating to the adoption and implementation of ARC in malaria-impacted regions and recommended actions to speed-up access to this life-saving medicine.
MMV worked closely with partners to develop clear product information for ARC. In October 2017, the resulting training material was included in the WHO 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.
Successfully introducing ARC in Zambia
In July 2017, MMV initiated a new collaboration with Transaid to increase access to commodities for the case management of severe malaria in Zambia. The year-long project was launched in August 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. The project has been scaled up to five districts and the Ministry of Health is in the process of identifying another five districts to make this intervention available.
Generating evidence to support countries with ARC implementation
MMV has worked with partners in Malawi to assess the role that targeted Information, Education, and Communication (IEC) tools play in health seeking and the delivery of care. The study concludes that an IEC toolkit for the Health Surveillance Assistants used in conjunction with written referral slips helps improve the continuum of care between community and facility settings. In Madagascar, MMV has supported the NMCP with the training of health workers at regional, district and community levels. Currently, MMV is supporting the country with an independent process evaluation.
Strengthening the global supply chain of ARC
In October 2017, MMV was awarded its first Unitaid Supply Grant to strengthen the global supply chain of ARC and to support rational use of quality medicines to prevent and cure malaria. As a result, MMV is working closely with the Clinton Health Access Initiative (CHAI) to support the introduction of ARC in select areas, in the context of the Unitaid Grant for the CARAMAL study, led by CHAI, and supported by Swiss TPH, Unicef and WHO.
Evaluating the real-world stability of ARC
The data indicate that ARC is a reasonably robust product, but do not support 24-month shelf life under Zone IVb (30°C/75%RH) conditions. WHO prequalification recommends a cautious approach in case temperatures regularly exceed 30°C, whereby stocks of ARC should remain in the field from 4 to 6 months maximum. The need to frequently discard and resupply ARC has proven to be logistically difficult. There is a risk of stockout at the community health worker level, which may undermine confidence in the product.
Encouraged by the data from the controlled storage studies, MMV has worked with CHAI to retrieve and test ARC that has been in totally un-controlled field storage for 12 months. The data from the testing of these real-world samples will complement the existing data from the controlled storage studies and allow end-users and regulatory agencies to make better informed decisions regarding the intervals required for product replacement in the field.
Collaborating with all stakeholders to reduce mortality from severe malaria
In October 2019, MMV and CHAI convened a global stakeholder meeting on severe malaria case management. The key objective was to share experiences of severe malaria care, from the community to referral facility levels, incorporating ARC and injectable artesunate. The meeting was characterized by a very high level of engagement and motivation from both countries and partners. As a next step, countries were encouraged to develop concrete action plans for the next 12 months for the successful implementation of ARC and Inj AS. The meeting report is available on MMV’s Severe Malaria Observatory. In 2021, a similar meeting is under consideration with the aim to share final CARAMAL study results and to discuss progress made in other countries.
Supporting countries with the roll-out of artesunate rectal capsules and injectable artesunate
MMV works with countries to conduct rapid assessment of severe malaria case-management 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.