Expression of Interest are invited for Apw for an Independent Assessment of the Approach to 8 Aminoquinoline Antimalarials in the Gms with Recommendations for the Way Forward for the Global Fund Rai3e GrantDeadline 03 Jul 2020 00 00 GMT 7 00 Bangkok Hanoi JakartaThe Regional Artemisinin resistance Initiative RAI was launched in 2013 in response to the emergence of artemisinin resistant malaria in the Greater Mekong Sub region GMS Funded by the Global Fund to Fight AIDS TB and Malaria the Global Fund the first RAI round 2014 2017 was a US 100 million grant covering Cambodia Lao PDR Myanmar Thailand and Vietnam The RAI was then expanded with a follow on investment of US 242 million for 2018 2020 the RAI2 Elimination RAI2E grant An application for a third tranche of funding for 2021 23 RAI3E is currently under review The RAI Regional Steering Committee RSC a multi stakeholder governance body provides strategic guidance and oversees RAI grant implementation tracking progress against programme objectives It also ensures funding is used in accordance with agreed strategic priorities During the RAI2E grant period the RSC decided that the increased volume of funds together with the exceptional nature of malaria elimination required more granular data and attention to sub national implementation challenges to support course correction and problem resolution Routine programme implementation data were clearly vital for RSC oversight but insufficient on their own as they measured outcomes and or coverage of services without the supporting contextual link to implementation quality on the ground The RSC agreed that field level intelligence was therefore required especially to support the tailoring of local implementation to local context For these reasons the RSC with the support of the Global Fund established an Independent Monitoring Panel IMP for the RAI grants The IMP which is now entering its second year of activities informs the RSC whether the RAI implementers are on track to achieve the programme s goals and objectives identifies implementation bottlenecks critical issues and proposes remedial actions to ensure that the RAI grant objectives and targets are achieved and impact is maximized There has been impressive reduction of falciparum malaria in the GMS The decline of vivax malaria has been much slower due to the recurrent character of P vivax infections which form hypnozoites in the liver causing relapses Only a radical cure including 8 aminoquinolines can permanently clear vivax malaria The IMP have identified a need for an independent assessment of the approach to the use of 8 aminoquinoline antimalarials in the five RAI2E supported countries RATIONALEThe 8 aminoquinoline antimalarials which include primaquine and tafenoquine are the only drugs which prevent relapse of vivax and ovale malaria and thereby achieve radical cure in conjunction with antimalarials that target the blood stages of the parasite lifecycle But these drugs can cause dose dependent haemolysis in individuals with glucose 6 phosphate dehydrogenase G6PD 1 deficiency Primaquine has been in widespread use for decades but the long treatment regimens required have resulted in sub optimal compliance with the full course of treatment by patients It was recently shown that in patients with normal G6PD a shorter course of 7 days primaquine at 1 0 mg kg per day was well tolerated and non inferior to a 14 day regimen of 0 5 mg kg per day Whether adherence is improved in the 7 versus 14 day regimen is unknown Tafenoquine solves this potentially important problem by providing a radical cure in a single dose This major operational advantage is also however tafenoquine s weakness Its slow elimination from the body terminal half life of approximately 15 days which allows single dose treatment means that in patients with G6PD deficiency haemolysis of the older erythrocytes continues until all susceptible cells have been destroyed In contrast treatment with primaquine half life of approximately 5 hours can be stopped at the first sign of clinically significant haemolysis usually the development of haemoglobinuria Tafenoquine is thus potentially less safe than primaquine Standard regimens of primaquine and tafenoquine are therefore contraindicated in patients with 30 and 70 of normal G6PD activity respectively both drugs are also currently considered contraindicated in pregnant and lactating women and tafenoquine considered contraindicated in people under the age of 16 Normative guidance is now that all patients should be tested for G6PD deficiency before administering 8 aminoquinoline antimalarials For primaquine this guidance has be qualified by the addition of where feasible since primaquine treatment can be withdrawn if symptoms of haemolysis appear
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