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
