Rectal artesunate (RAS)

Severe malaria, a life-threatening condition, may ensue rapidly if a bout of uncomplicated malaria is not promptly treated. For severe malaria patients under 6 years of age who are unable to immediately access WHO-recommended parenteral treatment (preferably injectable artesunate), pre-referral intervention with rectal artesunate (RAS) at the community level has been shown to save lives; in particular for critically ill young children unable to access parenteral treatment within 6 hours. Once admitted to a referral centre, patients should receive parenteral artesunate, followed by a full treatment with an ACT, as per WHO guidelines.

Although the WHO Guidelines for the Treatment of Malaria have included recommendations for the use of RAS for over 10 years, the lack of quality-assured RAS 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 standards.

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

In June 2017, after review of an application submitted by Cipla, the 100mg presentation of RAS was added to the World Health Organization’s Model List of Essential Medicines (EML) and Model List of Essential Medicines for Children (EMLc). WHO’s Model EML identifies medicines that “satisfy the priority health care needs of the population.”  

In 2018, both the Cipla and Strides Pharma RAS products secured WHO prequalification. It is estimated that over 80% of procured product is now WHO prequalified. In 2018,1.5 million orders of 100mg  suppositories were placed by international donors to be delivered to malaria-endemic countries. Currently the product is registered in 16 countries. 

As a pre-referral intervention, RAS is not intended to substitute for WHO-recommended parenteral treatments, preferably injectable artesunate. In addition, RAS is not intended as a substitute for the treatment of uncomplicated malaria, for which WHO recommends the use of artemisinin-combination therapies (ACTs).

  • Access in Action 

    • To secure WHO prequalification for RAS, MMV supported both Cipla and Strides Pharma by providing technical guidance and know-how, supplying reference materials, co-funding development activities including bioequivalence studies, and helping prepare dossiers for submission. These activities were carried out with funding from Unitaid, and with the support of TDR.

    • MMV has conducted an initial forecast to estimate the need for RAS in countries coping with high burdens of severe malaria; this forecast has been instrumental in helping manufacturers understand the potential demand they will encounter for their products.

    • To understand current policies and identify barriers to the introduction of RAS, MMV has carried out country assessments, which include reviewing the training, relating to the management of severe malaria, of healthcare workers in a pre-referral setting.

    • MMV and partners convened a RAS stakeholders meeting in Nairobi in February 2016 to discuss experiences, challenges, and options for overcoming obstacles confronting RAS rollout. The meeting report documented key issues relating to the adoption and implementation of RAS in malaria-affected regions and outlined recommended actions to speed up access to this life-saving medicine. The guidance from this workshop was disseminated in a Stakeholders' Meeting Report.

    • In July 2017, MMV initiated a new collaboration with Transaid to implement innovative approaches to increase rural access to commodities for the case management of severe malaria in Zambia. Transaid was selected following an “Access Challenge” competition that considered six applications from various implementing partners across Africa. 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 from 8% to 0.25% and only three deaths were recorded during the study period – 94 fewer than would previously have been expected in the timeframe.

    • Given the importance of providing correct information in easy-to-understand materials, MMV has worked closely with partners to develop clear product information for RAS. In October 2017 this training material was included into the “WHO information note on rectal artesunate for pre-referral treatment of severe malaria”.

    • In October 2017 MMV was awarded its first Unitaid Supply Grant to strengthen the global supply chain and to support rational use of quality medicines needed to prevent malaria in children and pregnant women, and to improve survival of children with severe malaria. As a result, MMV is working closely with the Clinton Health Access Initiative (CHAI) to support the responsible introduction of quality-assured RAS in select areas as part of a continuum of care for severe malaria patients. As part of this project MMV will also work closely with partners including the WHO Global Malaria Programme to support the dissemination of RAS project experiences and findings.

     


    Past and current partners:

    Clinton Health Access Initiative (CHAI), Cipla, health-E-net, Malaria Consortium, Strides Pharma, Transaid, WHO-TDR

     

    Updated January 2019