Malaria drug as effective in low doses

Date: Nov-15-2013A new study finds that lower doses of the drug primaquine are as effective at preventing

transmission of malaria as standard doses.

Primaquine targets the transmission stages of the malaria parasite, the gametocytes, and is

considered an important tool for malaria elimination.

The new study, led by researchers from the London School of Hygiene & Tropical Medicine (LSHTM)

in the UK, is published in the latest online issue of The Lancet Infectious Diseases.

The findings are good news because there are not many drugs that target this stage of the

disease, and unfortunately, at standard doses primaquine can reduce blood count in people with a red

blood cell disorder caused by a deficiency in an enzyme called G6PD.

Half a standard dose of primaquine is just as effective in reducing the transmission potential of malaria.

The inherited blood disorder is common in places where malaria is endemic and so has limited the

use of primaquine in those areas.

Because of this side effect, the World Health Organization (WHO) advised that dosage of primaquine be

reduced from 0.75 mg/kg to 0.25 mg/kg. However, until now, nobody had formally evaluated the

effectiveness of the drug at lower doses.

Lead author Dr. Alice Chi Eziefula, Wellcome Trust clinical research fellow at LSHTM, says:

"Until now, the use of primaquine was limited because of safety concerns, but lower doses had

never been tested formally."

Half of standard dose just as effective

The study took place in Jinja, Uganda, where children without the red blood cell disorder were

treated with a malaria drug either on its own or with one of three different doses of

primaquine.

The children were then monitored for 2 weeks to test their malaria gametocytes, and they were kept under

observation for another 2 weeks.

The resuls showed that a dose of 0.4 mg/kg of primaquine, or about half of the previously

recommended (standard) dose, was as effective at reducing the transmission potential of individuals

with malaria.

Dr. Chi Eziefula says:

"More questions remain to be answered regarding the best operational strategy for the

deployment of primaquine to block malaria transmission."

The next step is to evaluate the effectiveness of the current WHO-recommended 0.25 mg/kg dose of

primaquine in people without the red blood cell disorder, and then to test the safety of such a

dose in people with the blood disorder.

Co-author Moses Kamya, a professor with the Infectious Disease Research Collaboration in Kampala,

Uganda, says:

"This study provides important contemporary information that allows malaria control programmes

in endemic countries in Africa to consider the use of primaquine as part of their efforts to deal

with this killer disease."

Richard W. Steketee, of the Malaria Control Program, PATH, in Seattle, WA, and

Feiko ter Kuile, of the Liverpool School of Tropical Medicine in the UK, note in a linked comment

published in the same issue of the journal:

"Mass malaria treatment campaigns must focus on ensuring that full dosing of artemisinin

combination therapy is achieved. To this end, we will all welcome a safe and highly effective

single-dose treatment that can be combined with one dose of primaquine and can be given as directly

observed treatment for malaria."

Funds from the Wellcome Trust and the Bill & Melinda Gates Foundation helped to finance the

study.

In another recently published study, researchers from the US and Italy described how they found

a molecular switch in female

malaria-carrying mosquitoes that prompts her to produce eggs. The switch is triggered by a

male's hormone during sex, and the team suggests blocking the trigger will prevent the mosquitoes

reproducing, thereby preventing the spread of the disease.

Written by Catharine Paddock PhD

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