Artesun®/Larinate® (injectable artesunate)

Severe malaria, a life threatening condition, may ensue rapidly if a bout of uncomplicated malaria is not promptly treated. Since 2011, based on the results of the landmark studies AQUAMAT and SEAQUAMAT, which demonstrated the superiority of injectable artesunate (Inj AS) over intravenous quinine for the treatment of severe malaria in African and Asian patients respectively, WHO guidelines have recommended Inj AS as the preferred medicine for treating this life-threatening condition. In April 2011 Médecins Sans Frontières (MSF) released a policy paper advocating the immediate switch from using injectable quinine to using Inj As for the treatment of severe malaria, based on the life-saving benefits, safety and convenience.

MMV collaborated with Guilin Pharma, a Fosun Pharma company, to help the manufacturer achieve WHO prequalification for its Inj AS formulation, Artesun®, in November 2010. This approval represented a critical turning point, making it possible for the first time for donor funds to support procurement of Inj AS as WHO’s preferred treatment for severe malaria. In December 2018 a second Inj AS product, Larinate 60, manufactured by Ipca received WHO prequalification. This latest achievement also benefited from a collaboration between MMV and Ipca which helps to ensure a healthier marketplace for this lifesaving drug.

  • Access in Action

    • After WHO’s revision of its guidelines, MMV, WHO Global Malaria Programme and MSF convened a multi-stakeholder consultation in late 2011 to review and address barriers to acceptance of Inj AS. The guidance from this workshop was disseminated in the Stakeholders’ Meeting Report.

    • Given the importance of providing healthcare workers with correct dosing information in easy-to-understand materials, MMV worked closely with partners and a public health consultant to develop clear product dosing information for use in training materials for healthcare workers. This material has now been included into nearly two dozen country national training programs.  

    • During the time period 2012-2013, MMV undertook a program aimed at improving access to Inj AS in two of the highest burden severe malaria countries:

      • Democratic Republic of Congo (DRC): Swiss TPH and MMV carried out the MATIAS study to support policy change and implementation of Inj AS as the preferred treatment for severe malaria. The study demonstrated a ~50% reduction in case fatality rates (3.8% for those treated with intravenous quinine vs 1.7% for those treated with Inj AS).1 This resulted in the Ministry of Health taking the policy decision to make the switch to Inj AS as the preferred treatment for most severe malaria cases, apart from those occurring in pregnant women. 

      • Nigeria: MMV, through its partnership with the Clinton Health Access Initiative (CHAI), accelerated the adoption and uptake of Inj AS in Nigeria via pilot projects in six states and in Abuja, the Federal Capital Territory.

    • The success of both the DRC and Nigeria pilots gave rise to the Improving Severe Malaria Outcomes (ISMO) project, funded by UNITAID and led by MMV. This 3-year project which ended in September 2016 was built around a consortium of implementing and procurement partners, with the participation of CHAI and Malaria Consortium. The beneficiary countries included: Cameroon, Ethiopia (SNNPR and OROMIA), Kenya, Malawi, Nigeria (13 states) and Uganda. Almost 6.0 million vials of treatment were introduced across the multi-country project, sufficient to treat between 1.0 million and 1.5 million children. In addition, more than 18,000 healthcare workers (at over 2,082 healthcare facilities) were trained regarding the correct preparation and administration of Inj AS during the ISMO project. 

    • Globally, since WHO prequalification in 2010, 168 million vials of Inj AS have been delivered to malaria-endemic countries. Given that Inj AS offers a 22%-35% reduction in mortality compared to the alternative, quinine,2,3 an estimated >1 million additional young lives have been saved by this medicine over this time period.

    • MMV is working to encourage additional manufacturers of Inj AS to seek WHO prequalification to create greater stability for the manufacturing supply chain of Inj AS.

    • To help generate more information on Inj AS in real world settings and to create a useful pharmacovigilance blueprint for countries to use, MMV worked with the African Collaborating Centre for Pharmacovigilance, Accra, Ghana. Outcomes of a modified cohort event monitoring study (CEMISA) were gathered from over 1,000 patients in public health facilities in Ghana and Uganda over the course of 2016.

    • In December 2016, MMV signed a collaborative agreement with the National Malaria Control Programme (NMCP) of Kenya and the University of Oxford to collaborate on the implementation of quality-of-care surveys initiated by the NMCP and directed by a senior epidemiologist provided by MMV. The goal of the project is to monitor progress in health-systems' readiness to cope with severe malaria and the quality of inpatient malaria case‐management at county hospitals in Kenya. The project includes 4 rounds of surveys, 6 months apart. 

    • To help share knowledge, experiences and guidance on severe malaria in May 2017, MMV launched the new Severe Malaria Observatory (SMO). The SMO was created to shine a light on severe malaria. It serves as a repository of information about this fatal disease and is consulted by over 8,000 users each month. Partners are encouraged to share this platform widely and motivate members of this community to share their knowledge and experiences with us.

    • To identify and help address the gaps in the management of severe malaria during pregnancy, in 2018, MMV started working with various countries to help support alignment with WHO guidelines for the management of severe malaria during pregnancy. To support this work MMV is helping to map out capacity gaps in the health care system. The assessment findings are used by NMCPs to develop a plan for introducing and improving severe malaria case management. To date, rapid assessments have been conducted in Uganda, DRC and Liberia, in close collaboration with NMCPs and local partners. Angola will soon follow. 

    • In October 2019 MMV and Clinton Health Access Initiative (CHAI) convened a global stakeholder meeting on severe malaria case management, under the auspices of the RBM Case Management Working Group, in collaboration with UNICEF, Swiss Tropical and Public Health Institute (Swiss TPH), Médecins Sans Frontières (MSF), and funded by Unitaid. The key objective is to share experiences from existing efforts to improve the continuum of severe malaria care from community to referral facility levels incorporating rectal artesunate and injectable artesunate. The ultimate goal is to achieve better patient care and reduce mortality from severe malaria. Attendees were from National Malaria Control Programs, Ministry units involved in implementation of community case management, research institutions, donor agencies and implementing partners.

     Past and current partners:

    Centers for Disease Control and Prevention (CDC); CHAI; IPCA Laboratories; École de Santé Publique University of Kinshasa; Guilin Pharma, a Fosun Pharma company; Kenya National Malaria Control Program; Malaria Consortium; Malaria No More; MSF; National Malaria Control Programme Ghana; Nigeria National Malaria Control Programme; Swiss Tropical and Public Health Institute; The Global Fund to Fight AIDS Tuberculosis and Malaria; UNICEF; Unitaid; University of Oxford, WHO GMP. 

    1. Giovanfrancesco Ferrari et al. An operational comparative study of quinine and artesunate for the treatment of severe malaria in hospitals and health centres in the Democratic Republic of Congo: the MATIAS study. Malaria Journal. 2015 14:226.

    2. Dondorp AM et al. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 13;376(9753):1647-57 (2010).

    3. Dondorp A et al. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet.366(9487):717-25 (2005).


    Updated December 2019