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The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0896-8) contains supplementary material, which is available to authorized users.

Establishing and strengthening pharmacovigilance in resource-limited settings provides a valuable opportunity to identify, quantify and address pertinent safety concerns regarding the use of single low-dose (SLD) primaquine. While it is understood that primaquine causes dose-dependent hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals with P. falciparum and P. vivax malaria, the extent of this risk when using low doses of primaquine remains to be defined. Prospective pharmacovigilance methods are needed to confirm or refute these safety concerns that have likely hindered the uptake of the new WHO policy for SLD primaquine. Pharmacovigilance in resource-limited settings is challenging, especially when attempting to identify unknown or poorly understood adverse drug reactions over weeks of follow-up. In contrast, the objectives of a pharmacovigilance program for SLD primaquine are specific, measurable, and attainable within a short time frame. The nadir of primaquine-induced hemolytic anemia, measurable by hemoglobin concentrations, has been shown to occur on or near day 7. Thus, it is expected that adverse drug reactions related to primaquine can be captured within a week of drug administration by active surveillance methods involving patient follow-up. Furthermore, dark urine is a characteristic sign of acute hemolytic anemia, an easily identifiable and documentable symptom of hemolysis. Numerous pharmacovigilance efforts are ongoing, supporting individual countries in the collection of standardized SLD primaquine safety data. These efforts seek to establish the expected fall in hemoglobin from baseline levels before treatment to levels seven days post-treatment and include G6PD testing and recording of adverse events using standard data collection instruments. Each participating in-country program or study site aims to collect data on 100-400 subjects depending on malaria endemicity and expected G6PD prevalence. We plan to collate data across these countries in a global database of individual patient data, contributing to the evidence-base for benefit-risk assessments of SLD primaquine. As other 8-aminoquinoline drugs such as tafenoquine come to market, we will be faced with related safety concerns of dose-dependent hemolysis in G6PD-deficient individuals. Active pharmacovigilance and the establishment of a standardized database for SLD primaquine not only provide opportunities to harmonize efforts, address unanswered questions regarding the safe use of SLD primaquine, and assist programs planning widespread roll-out of SLD primaquine in routine malaria case management they can also serve as a common platform for other current and future pharmacovigilance needs. The methods used in these efforts and the composition of this database will be described.

As the only marketed drug that is capable of clearing mature P. falciparum gametocytes, primaquine offers a unique ability to stop malaria transmission from humans to mosquitoes. Despite its potential role in malaria control and elimination, the widespread adoption of primaquine has been slow due to its ability to induce hemolysis in G6PD-deficient individuals. While hemolysis is understood to be dose dependent, there are limited data to support the safety and efficacy of current WHO recommendation to give, in conjunction with an artemisinin-based combination therapy, single low-dose primaquine (0.25 mg/kg) to all parasitologically-confirmed P. falciparum cases in areas threatened by artemisinin resistance or in settings approaching elimination. In March 2012, a group of experts from academia, industry, non-governmental organizations, malaria programs, and funders convened to discuss existing data on the use of primaquine as a malaria transmission blocker. The meeting served to identify roadblocks and to propose a roadmap to establish whether low-dose primaquine can be safely and effectively deployed to block P. falciparum malaria transmission in sub-Saharan Africa [1]. Since then, much knowledge has been gained on the pharmacokinetics, safety and efficacy of low-dose primaquine. Regulatory barriers to the supply and manufacture of low-dose primaquine in Africa have also been investigated. In March 2014, the group of experts reconvened to discuss roadmap progress and update potential knowledge gaps that need to be addressed in order to determine if and how low-dose primaquine can be implemented as a malaria transmission blocker. We will provide roadmap updates based on the latest meeting and will highlight gaps to welcome discussion and advice from the malaria research community.