14 May 2006
New highly active anti-malarial Artemisinin-based
Combination Therapy (ACT) protected by phase-out of
marketing single-drug artemisinin malaria pills
On May 11 the World Health Organization (WHO) announced that
their recommendation to stop marketing single-drug artemisinin malaria pills
has been agreed to by 13 pharmaceutical companies. This phase-out of
single-drug artemisinin monotherapy for the oral treatment of malaria is a
major advance in maximizing the probability that Artemisinin-based Combination
Therapies (ACTs) currently recommended as the drugs of choice by WHO for
uncomplicated falciparum malaria will remain highly active and effective.
Earlier in 2006 the WHO posted online new
"Guidelines for the Treatment of Malaria". This 240-page document
contained clear advice on the diagnosis and treatment of all four types of
malaria: Plasmodium falciparum ("uncomplicated" and
"severe"), Plasmodium vivax, Plasmodium ovale, and Plasmodium
malariae.
WHO listed alphabetically the following specific
Artemisinin-based Combination therapies (ACTs) (page 21):
A. Artemether-lumefantrine (already available as
co-formulated tablets containing 20 mg of artmether plus 120 mg of
lumefantrine. The total recommended therapy course is a 6-dose regimen with one
tablet being taken orally twice a day for three (3) days.
b. Artesunate plus amodiaquine
c. Artesunate plus mefloquine
d. Artesunate plus sulfadoxine-pyrimethamine
The choice of ACT for uncomplicated falciparum malaria
depends on the level of resistance of the partner medicine in the combination.
For example, in Africa (page 23) WHO recommends artemether-lumefantrine, OR
artesunate plus amodiaquine, OR artesunate plus sulfadoxine-pyrimethamine. In
areas of multidrug resistance malaria, such as SE Asia, WHO recommends
artemether-lumefantrine OR artesunate and mefloquine.
In Africa WHO notes (page 22) concerns about
"insufficient safety and tolerability data on artesunate and
mefloquine at the recommended dose of 25mg/kg in African children to support
its recommendation there. Trials with mefloquine monotherapy (25mg/kg) have
raised concerns of tolerability in African children. Countries may therefore
opt instead to use artesunate plus amodiaquine, OR artesunate plus
sulfadoxine-pyrimethamine which may have lower cure rates because of
resistance".
Monotherapy with amodiaquine, or montherapy with
sulfadoxipine-pyrimethamine are widely available and provide continued
selection pressure for the P. falciparum malaria parasite to develop resistance.
Lumefantrine has never been available as a
monotherapy. Instead, it is only available as a co-formulated tablet with
artemether and thus resistance is less likely.
Remarkably, "artemisinin and its derivatives
(artesunate, artemether, artemotil, dihydroartemisinin) produce rapid clearance
of parasitemia and rapid resolution of symptoms. They reduce parasite numbers
by a factor of approximately 10,000 in each asexual cycle, which is more than
other current antimalarials (which reduce parasites numbers 100-1,000-fold per
cycle)" (page 17).
Artemisinin drugs are eliminated rapidly from the body.
Thus, when given in combination with other rapidly eliminated
antimalarial compounds (tetracyclines or clindamycin) seven (7) days of
the artemisinin medication are required. When given in combination with slowly
eliminated antimalarial medications, however, shorter courses of only three (3)
days of the artemisinin compounds are required (page 17, WHO 2006).
This important step announced May 11 by the WHO of the
phase-out of marketing single-drug artemisinin malaria pills should help
preserve Artemisinin-based Combination Therapies (ACTs) as highly
effective treatment for uncomplicated falciparum malaria. Combination therapy
with several effective medications against the malaria parasite is analogous to
combination therapy with highly active antiretroviral drugs for the human
immunodeficiency virus, and combination therapy with multiple antibiotics
against tuberculosis. In parts of the world where all three infections
(malaria, HIV. and TB) can occur in the same patient such combination therapies
can increase the probability of successful treatment.
Daniel R. Lucey, MD, MPH
Adjunct Professor of Microbiology and Immunology
Georgetown University Medical Center
Director, Center for Biodefense and Emerging Infectious
Diseases
EROne Institutes, Washington Hospital Center
Washington, DC
e-mail:Daniel.R.Lucey@Medstar.net website: www.BePast.org