RSUSSH 2020
Overcoming the challenges to vivax elimination
Dr. Walter RJ Taylor
Mahidol Oxford University Wellcome Trust Tropical Medicine Research Unit (MORU)
Keynote G2-1
QUESTIONS & ANSWERS
Thank you very much for your presentation, we are grateful for the time and effort you to share your experience on "overcoming the challenges to vivax elimination". I would like to get some more details that are there different adverse effects of primaquine/tafenoquine, regarding hemolysis, in G6PDd patients with Pv infection and mixed infection? and what is the optimal treatment regimen for Pv infected-G6PDd patients? Thank you again in advance.
@30 Apr 20, 11:44 AM Thank you for the great presentation. I would like to know more details about guidelines of WHO and MOPH. Thank you very much.
@30 Apr 20, 02:35 PM Can Primaquine and Tatenoquineí be used for other plasmodium spp.? If not, please explain for the reason.
Do both drugs have any other side effect?
How much it might cost for the G6PD test?
@30 Apr 20, 03:31 PM Thank you very much for your valued presentation! You have put a lot of effort in to this work. Are there any consideration G6pD def when treating vivax malaria in Thailand?
@30 Apr 20, 07:17 PM Dear all, thank you for your excellent questions. I will answer them in sequence.
Dr. Preeyaporn, the difference between primaquine and tafenoquine is that tafenoquine has a long half-life (mean 16 days) so, in theory, the haemolysis it causes in G6PD deficient males and homozygous females could be more severe because of its longer half-life. This also supposes that primaquine is stopped early in a G6PD deficient patient who is on daily primaquine.
There are some data in a small number of heterozygous female healthy volunteers showing that 300 mg of tafenoquine produced essentially the same haemolysis as 15 mg of daily primaquine; the haemolysis was well tolerated (Rueangweerayut et al. Am J Trop Med Hyg. 2017 Sep;97(3):702-711).
I do not know of any papers that detail haemolysis in patients with pure P. vivax vs. mixed infections who received daily primaquine. I suspect there would not be so much difference unless the falciparum parasitaemia were very high. Don't forget that in pure infections diagnosed by microscopy, up to about 25% can be mixed infections by PCR.
The optimal dose of primaquine in G6PD deficiency is not yet known and we need to do more research. The main problem is the G6PD variant and the degree of deficiency. In SE Asia, we have moderately severe variants but in some parts of the world like Pakistan and the Middle East, there is the Mediterranean form which is severe so the dose of primaquine should be less than that in areas where there are moderately severe and mild forms of G6PD deficiency. For now, we only have the recommended weekly dose – 0.75mg/kg/w x 8 doses. These patients should be monitored closely, especially in the first week.
Dr. Apichai, the WHO recommends two doses of daily primaquine – 0.5 mg/kg/d x14d in SE Asia and Oceania and 0.25 mg/kg/d x 14d for other countries. The reason why there is this difference is because in our region and Oceania, the relapse rate (that is the number of infections over time derived from hypnozoites) is higher than other regions and the hypnozoites need a higher primaquine dose to reduce relapses.
Because countries do not yet test for G6PD deficiency, they use the 0.25 mg/kg dose because they are worried about haemolysis with the 0.5 mg/kg dose in G6PD deficient males and homozygous females. Thailand, to the best of my knowledge, recommends currently 0.25 mg/kg as do Cambodia and Laos.
Dr. Tirasak, the other plasmodium species that causes relapse is P. ovale, which is far less common than P. vivax. There are limited published data of primaquine as antirelapse treatment in P. ovale and some report success with the 0.25 and 0.5 mg/kg/d x 14d doses whilst others report relapses with the 0.25 mg/kg dose. There is no reason to suggest that tafenoquine cannot be used in P. ovale but there are no published data on its efficacy. Nevertheless, it is recommended as anti-relapse treatment.
The other reason to use primaquine is to kill gametocytes in the blood so that when mosquitoes bite humans and take up these gametocytes, the gametocytes cannot fuse and complete the life cycle in the mosquito. This is called transmission blocking and is recommended by the WHO in regions like ours where there is low transmission of artemisinin resistance. Tafenoquine may have a similar effect but this has yet to be proven.
The other main side effects of primaquine and tafenoquine are abdominal pain (reduced by food) and methaemoglobinaemia; both are dose dependent.
The G6PD rapid test cost will vary depending on bulk buying. In my research studies, one test costs about 2 USD. The Biosensor is quite expensive about 350 USD for the Biosensor then about 3-4 USD per cuvette. These prices will come down with competition in the market.
Dr. Sirima, Thailand has done very well with eliminating malaria but the troublesome areas are the forested borders where movement of people and economic activity make malaria elimination more challenging. I do not know if the government of Thailand is distributing rapid tests to clinics and hospitals. Ideally, the 0.5 mg/kg/d dose should be used but if the diagnosis of G6PD can only be done in the larger hospitals, then this dose will not be used.
I am aware that there is an initiative to introduce Biosensors and tafenoquine into Thailand and this is being funded by the Medicines for Malaria Venture.
@1 May 20, 12:32 AM Thanks a lot for the reply Dr. Taylor. Could you explain more concerning the mechanism of the drug? I just wonder, why it is more specific to P. vivax and P. ovale?
@1 May 20, 11:52 AM