Background

Artesunate Rectal Capsules is a pre-referral intervention for children under six 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 or 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. Work by Medicines for Malaria Venture (MMV) funded by Unitaid has enabled two artesunate rectal capsules products to obtain WHO prequalification.

Grant Overview

Unitaid has approved several grants across various domains to help prevent malaria deaths among pregnant women and children under five 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 artesunate rectal capsules (ARC) as a pre-referral intervention for suspected cases of severe malaria in children under five.

The three-year CARAMAL project, implemented by the Clinton Health Access Initiative (CHAI), UNICEF, and the Swiss Tropical and Public Health Institute (Swiss TPH) provided artesunate rectal capsules as a pre-referral intervention for severe malaria patients. The CARAMAL project, focused on three highly malarious countries: DRC, Nigeria and Uganda. It built upon in-country integrated community case management (iCCM) programmes and generated evidence to support improved ARC introduction and scale up in other countries. It is estimated that appropriate roll out of ARC could benefit up to a million children and save up to 20,000 lives per year.

Supply Grant

This project was supported by Medicines for Malaria Venture (MMV) through a Unitaid supply grant that increased the registration and availability of ARC and evaluated the effectiveness of training material for community health care workers and the community.

Enabler Agreement

WHO supported 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 ensured 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 ARC.

Intervention

The project generated evidence on the feasibility of achieving mortality reductions by delivering quality-assured ARC through established iCCM platforms, using only minimal additional supportive interventions to the health system. The research investigated 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 Artesunate Rectal Capsules 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 quality-assured Artesunate Rectal Capsules on suspected severe malaria case fatality rate;
• Identify the minimal requirements of a community case management system to ensure that Artesunate Rectal Capsules is an effective part of a continuum of care from community to a referral facility;
• Identify interventions to avoid the inappropriate use of Artesunate Rectal Capsules as a monotherapy intervention against uncomplicated falciparum malaria;
• 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.