The WHO Guidelines

for the treatment of malaria...

...provide comprehensible, global and

evidence-based guidelines for the formulation of
policies and protocols for the treatment of malaria

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Striking Back at Malaria, Dakar, Senegal 13 September 2006

The WHO Guidelines

for the treatment of malaria...
:provide recommendations for the treatment of...
uncomplicated malaria

severe malaria

in special groups (young children, pregnant women, HIV /AIDS)

in travellers (from non-malaria endemic regions)
in epidemics and complex emergency situations
Not a clinical management manual for the treatment of malaria
Do not deal with preventive uses of antimalarials, such as intermittent preventive
treatment or chemoprophylaxis

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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Malaria diagnosis

"...Prompt and accurate diagnosis

of malaria is the key
to effective disease management
and to the reduction of
unnecessary use
of antimalarial medicines."
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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Malaria diagnosis
Parasitological confirmation (microscopy or RDT) before
treatment

Exceptions:
children under 5 years of age, from areas of high
transmission where treatment is based on clinical
diagnosis
suspected severe malaria where parasitological
confirmation is not immediately possible
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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Treatment
of uncomplicated falciparum malaria
Artemisinin-based combination therapies (ACT) are the treatments
recommended for all cases of uncomplicated falciparum malaria
including:
in infants,
in people living with HIV/AIDS
for home-based management of malaria
pregnant women in the 2nd and 3rd trimesters

Exception:
1st trimester of pregnancy*
*only use when there are no alternative effective antimalarials
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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Treatment
of uncomplicated falciparum malaria
The following ACTs are presently recommended:
artemether-lumefantrine
artesunate + amodiaquine
artesunate + mefloquine
artesunate + sulfadoxine-pyrimethamine
efficacy of ACTs depend on the efficacy of the partner medicine

The artemisinin derivatives (oral, rectal, or parenteral

formulations) and partner medicines of ACTs are not
recommended as monotherapy for uncomplicated malaria.

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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Dihydroartemisinin and Piperaquine

Phosphate is a later addition

Changing antimalarial treatment policy

Treatment failure of >10% (as assessed through monitoring
of therapeutic efficacy at 28 days)
New treatment an average cure rate of > 95% as
assessed in clinical trials

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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Treatment
of severe falciparum malaria
Any of the following antimalarial medicines are recommended

Artesunate* (i.v. or i.m)

artemether (i.m.)
artemotil** (i.m)
quinine (i.v. or i.m).

* 1st choice areas of low transmission

** use when other alternatives not
available

When patient can tolerate oral treatment, give a full

course of ACT or quinine + (clindamycin or
doxycycline)
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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Treatment
of severe falciparum malaria
Pre-referral treatment
Single dose treatment
Artesunate or artemisinin by rectal
administration
Artesunate or artemether (i.m)
Quinine (i.m)

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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Treatment of vivax malaria

Chloroquine + primaquine
Where ACT has been adopted for P.falciparum malaria, it may
also be used for P.vivax malaria in combination with
primaquine

Exception:
artesunate + sulfadoxine-pyrimethamine should not be
used

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Striking Back at Malaria, Dakar, Senegal 13 September 2006

Antimalarial drug combinations

before ACT

Combinations of chemotherapeutic agents can

accelerate therapeutic response, improve cure rates and
protect the component drugs against resistance

There are several examples of the successful use of

antimalarial combinations before the development of
ACT, specifically quininetetracycline (or quinine
doxycycline), sulfadoxinepyrimethamine and, most
recently, atovaquoneproguanil

Why these Combinations were Unfavorable

With each of these combinations, issues have hampered

continued application
Quininetetracycline is associated with frequent side
effects
including

the nausea, dysphoria, tinnitus and deafness of

cinchonism

has to be given over a long period (710 days) which can

affect compliance
efficacy is failing in some tropical countries

For sulfadoxinepyrimethamine, high-grade

resistance is increasingly encountered
Atovaquoneproguanil is given as a short-course
(3-dose) regimen and is one of the most expensive
antimalarial therapies
Despite its relatively recent introduction and limited
availability, highly resistant cases have already been
reported

Candidate partner drugs in ACT

In the case of ACT, the artemisinin component provides

a well-tolerated drug with a unique mode of action that
clears asexual forms quickly and has gametocidal
activity
The partner drug should be one that is also well
tolerated and non-toxic
Must be present in the blood at therapeutic
concentrations for at least several times the duration of
the parasite lifecycle (48 hours in the case of P.
falciparum)

THE IDEAL ACT

Components have different modes of action

No interactions
Short-course regimens (3 days at most)
At least one drug which clears asexual forms rapidly
At least one drug with long half-life (> 4 days)
Well tolerated, low toxicity
Broad spectrum of action (including against
gametocytes)
Coformulation possible
Inexpensive

Exclusion of partners in ACT

but ACT effectiveness is compromised by using

failing drugs as partners
Despite this situation, WHO has prioritised
artesunate plus amo-diaquine (a chloroquinelike drug) and artesunate plus sulfadoxine
pyrimethamine as the second-line and third-line
ACT combinations, respectively