All of the currently available fixed-dose artemisinin combination treatments (ACTs) for falciparum malaria are highly effective in Myanmar (Burma), providing rapid parasite clearance and cure rates greater than 95%, with the exception of artesunate-amodiaquine, which should not be used as a first-line treatment in Myanmar. Moreover, the addition of a single dose of primaquine to ACT regimens was well tolerated and would substantially reduce transmission potential. These results are published in an Article Online First and in the November edition of The Lancet Infectious Diseases.
Renewed efforts to eradicate malaria will require effective and safe medicines that reduce transmission. ACTs lower gametocyte* carriage rates, but fail to kill gametocytes at all developmental stages. Thus, the gametocytocidal drug primaquine might be useful in combination with ACTs and reduce the potential of the parasite to spread.
In this study, an international team led by Frank Smithuis of Médecins Sans Frontières in Holland and Nicholas White from Mahidol University in Bangkok, Thailand, recruited 808 adults and children with uncomplicated falciparum malaria from three clinics in Myanmar. Patients were randomly allocated to receive one of four fixed-dose ACTs; artesunate-amodiaquine (155), artemether-lumefantrine (162), artesunate-mefloquine (169), loose artesunate-mefloquine (161), or dihydroartemisinin-piperaquine (161). All patients were also randomised to receive either a single dose of primaquine or not. Patients were followed up for 63 days, and time to recurrence of malaria after treatment was recorded.
The artesunate-amodiaquine regimen had the lowest cure rate and the highest rate of reinfection and was not effective enough to be recommended as a first-line treatment. All the other drug combinations were substantially more effective with cure rates greater than 95%. The regimens were all well tolerated, and most side-effects were mild and did not substantially affect adherence to treatment.
Overall, the artesunate-mefloquine fixed-dose regimen had fewer recurrences of falciparum malaria, the highest cure rates, and lowest rates of gametocyte carriage.
Without primaquine the ACT regimens had wide variations in gametocytocidal activity. The addition of a single dose of primaquine almost completely eliminated the risk of gametocyte carriage for all the ACT regimens, removing any differences in the transmission-blocking action.
The authors conclude: "The addition of a single gametocytocidal dose of primaquine was well tolerated and highly effective and did not cause any serious adverse effects…[and] could have a major effect on malaria transmission from treated patients and could have a crucial role in elimination programmes."
In a Comment, Ric Price, from the Menzies School of Health Research in Australia, and Nicholas Douglas, from the University of Oxford in the UK, discuss the difficulties policy makers face in deciding between one highly efficacious drug regimen and another. They point out that using empirical assessment to gauge a regimen's ability to limit the emergence and spread of resistance and decrease transmission is not easy.
Professor Nicholas White, Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand. T) +44 186 485 7433 (secretary in the UK) E) nickw@tropmedres.ac
Professor Ric Price, Menzies School of Health Research, Darwin, Australia. T) +61 434 365 897 mobile (in the UK and Geneva week beginning Monday 6 Sept)
Or via Zoe Malone, Press Office, Menzies School of Health Research. T) +61 447 275 415 E) zoe.malone@menzies.edu.au
Notes to Editors: * The gametocyte is the developmental stage of the parasite that can be transmitted by the mosquito. There are five distinct morphological stages of gametocyte development.
For full Article and Comment see: http://press.thelancet.com/tlidmaldrugs.pdf
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Journal
The Lancet Infectious Diseases