Safe Rollout of Primaquine for Malaria Elimination in Swaziland

The Kingdom of Swaziland’s National Malaria Control Program (NMCP) is pursuing the ambitious goal of malaria elimination, which is defined as zero local malaria cases (originating within Swaziland’s borders). If realized, Swaziland would be the first country in sub-Saharan Africa to achieve this public health milestone. Swaziland is close: during the July 2014-June 2015 malaria season, there were just 273 reported local malaria cases. Since 2008, CHAI has been working closely with the NMCP, supporting its technical staff to implement aggressive strategies to move toward this goal of local malaria elimination.

To achieve elimination every malaria case must be detected and reported. So in Swaziland, when a healthcare provider suspects a patient has malaria, national guidelines state the case must be confirmed parasitologically using either a rapid diagnostic test (RDT) or microscopy and correctly treated using Artemisinin Combination-Based Therapy (ACT) drugs. ACTs are remarkably effective at curing patients with malaria; however, they are not able to clear mature malaria parasites, known as gametocytes, from the blood stream. So while patients are cured of malaria and are free of its symptoms, they can still transmit the malaria parasite to mosquitos, potentially contributing to onward transmission to another person. To address this challenge, in 2012, the World Health Organization (WHO) recommended that in areas threatened by artemisinin resistance or countries targeting malaria elimination, a single, low dose of primaquine, a drug capable of destroying mature gametocytes, should be administered to patients with confirmed Plasmodium falciparum (P. falciparum) malaria in conjunction with ACTs.

However, it is still a common concern that primaquine, even at low doses, may result in severe hemolysis in individuals with G6PD enzyme deficiency. Hemolysis, which affects the red blood cells and destroys them before their typical life span has been reached, is dangerous because it limits the amount of oxygen circulated throughout the body. Before adopting the WHO’s recommendation, Swaziland wanted to better understand this safety concern in its local context. To do this, the NMCP partnered with CHAI and the University of California, San Francisco (UCSF) to pilot the Primaquine Rollout Monitoring Pharmacovigilance Tool (PROMPT) to rapidly generate primaquine safety data. Prior to the pilot, CHAI supported the NMCP to assess the feasibility of PROMPT, select sentinel sites, identify study staff, and develop a process to integrate PROMPT into the existing clinical workflows of both sites. The pilot took place at two of Swaziland’s referral hospitals between March 2014 and April 2015, where 102 patients with confirmed uncomplicated P. falciparum malaria were enrolled into the pilot and received single low-dose primaquine. Prior to enrollment and administration of primaquine, patients were screened for G6PD deficiency and hemoglobin concentration estimations to determine eligibility. Throughout the pilot, CHAI provided regular implementation support to the study team to ensure effective implementation of the study protocol and comprehensive capture of safety data.

At the conclusion of the PROMPT pilot, the collected safety data indicated that routine treatment of uncomplicated P. falciparum malaria with ACTs and single low-dose primaquine could be well tolerated in non-anemic, G6PD normal individuals and that primaquine could safely be used as an effective transmission-blocking tool to support malaria elimination in Swaziland. Using funds from The Global Fund to Fight AIDS, Tuberculosis and Malaria, the NMCP has now procured primaquine and is working to ensure that all health facilities are stocked with the drug. In conjunction with this work, CHAI has partnered with the NMCP to train healthcare workers on safe primaquine administration and to develop a risk management manual to support patient safety and high quality clinical care when using primaquine.

With primaquine available in all health facilities, Swaziland aims to ensure that all cases are treated with the combination of ACT and single low-dose primaquine as per national guidelines to clear gametocytes and ensure no onward transmission in communities. Using this coupled with other strategies in surveillance, vector control, and information education and communication, the NMCP hope to accelerate towards becoming the first country in sub-Saharan Africa to achieve malaria elimination. The learnings from Swaziland in rolling out single low-dose primaquine will serve as a resource for neighboring countries trying to implement a similar strategy as the region works together to eliminate malaria.