Community Access to Rectal Artesunate for MALaria (CARAMAL)

Background

Rectal artesunate is a pre-referral intervention for children under 6 years of age, which when properly administered has the potential to reduce risk of death or permanent disability by up to 50%. In situations where patients with severe malaria do not have immediate access to injectable artesunate/a referral center, the World Health Organization (WHO) recommends giving children in this age group a single rectal dose of artesunate and referring immediately to an appropriate facility where the full management of severe malaria can be provided. Until recently, the lack of a quality-assured product and limited operational guidance meant few countries had successfully introduced this pre-referral intervention in accordance with the WHO recommendation. Recent work by Medicines for Malaria Venture (MMV) that has been funded by Unitaid has enabled two rectal artesunate products to be submitted for WHO prequalification and both of those have received Global Fund ERP approval, paving the way for this project.

Grant Overview

Unitaid has approved several grants across various domains to help to prevent malaria deaths among pregnant women and children under 5 years of age, the groups at highest risk for malaria infection. One grant has been developed into a full project to investigate the necessary conditions required to provide quality-assured rectal artesunate suppositories (RAS) as a pre-referral intervention for suspected cases of severe malaria in children under 5.

The three-year RAS project, implemented by the Clinton Health Access Initiative (CHAI), UNICEF, and the Swiss Tropical and Public Health Institute (Swiss TPH) will provide RAS as a pre-referral intervention for approximately 3,200 cases of severe malaria per year. The project, referred to as Community Access to Rectal Artesunate for Malaria (“CARAMAL”), is focused on three highly malarious countries: DRC, Nigeria and Uganda. It builds upon in-country integrated community case management (iCCM) programs and will also generate evidence to support improved RAS introduction and scale up in other countries. It is estimated that appropriate roll out of RAS could benefit up to a million children and save up to 20,000 lives per year.

Supply Grant

This project is being supported by Medicines for Malaria Venture (MMV) through a Unitaid supply grant that will increase the registration and availability of RAS and evaluate the effectiveness of training material for community health care workers and the community.

Enabler Agreement

WHO will support the work of UNICEF and CHAI by providing technical support and guidance to the project at a global and at a country level through an enabler agreement. Through this work, WHO will ensure relevance and dissemination of findings and, where possible, will engage with other malaria endemic countries that show interest in the introduction or scale-up of RAS.

Intervention

The project aims to generate evidence on the feasibility of achieving mortality reductions by delivering quality-assured RAS through established iCCM platforms, using only minimal additional supportive interventions to the health system. The research will also investigate any unintended consequences of the intervention, such as inappropriate use of an artemisinin monotherapy without appropriate transition to injectable artesunate followed by a full course of an ACT, which could potentially lead to drug resistance. The evidence generated will be used to develop operational guidance for countries looking to scale up this intervention.

The objective of the project is to increase access to quality-assured rectal artesunate as a part of a strengthened severe malaria management system.

The rationale behind the project is to:

  • Generate operational evidence on maximizing operational feasibility of pre-referral QA rectal artesunate on suspected severe malaria case fatality rate;
  • Identify the minimal requirements of a community case management system to ensure that rectal artesunate is an effective part of a continuum of care from community to a referral facility;
  • Identify interventions, if necessary, to avoid the inappropriate use of rectal artesunate as a monotherapy intervention against uncomplicated falciparum malaria; and
  • Understand and mitigate against potential unintended consequences of scaled implementation, such as adverse drug reactions, unforeseen costs, or unforeseen issues in treatment of malaria at all levels of care.