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[08/25/2004]
 Therapeutic choices |
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Therapeutic healthcare at home or in primary healthcare centers
Simple crisis and uncomplicated forms
of malaria disease The good use of antimalarial drugs conforms to certain
principles which take account of the potential toxicity of the
molecules available and their predictable effectiveness against
an a priori Chloroquine-resistant strain. | First principle: Chloroquine should not be used in the treatment
of a non-immune subject suffering fromPlasmodium
falciparum malaria. It retains its place in the other
plasmodial species against which it still remains effective, but
the plasmodium must have been identified beyond any doubt. In case
of doubt, the patient should be considered as being a
priori infected by Plasmodium
falciparum. | | A second principle: the antimalarial drugs used until now for
the treatment of the uncomplicated malaria of the traveler may
induce at times serious toxicity. This is the case of halofantrine,
responsible for potentially fatal cardiac disorders, and
mefloquine, likely to induce frequent neurologic and psychiatric
side efftects and rare encephalopathies. Mefloquine, similar to
halofantrine on the structural level, may, in favorable
circumstances, bring about electrocardiographic modifications
(prolongation of the QT interval, extrasystole, auricular flutter).
The deleterious cardiac effects brought about by halofantrine
involve therapeutic recommendations before the prescription of this
antimalarial drug. These take into account the following
parameters: pathological antecedents, eventual cardiovascular
history, plasmodial species responsible, presence of a sign of
severe malaria, existence of a hydro-ionic imbalance or a
circumstance likely to make it appear. |
An electrocardiogram carried out prior to the prescription of
halofantrine, as currently recommended by the French Health
Ministry comprises a number of limits: availability of an
electrocardiograph, measurement of the QT interval difficult on a
trace carried out by unit (iso-electric line often unstable, trace
sometimes containing interference), end of the T wave difficult to
define for a non-specialist .
All these reasons lead to the non-prescription of amino-alcohols
with a long life cycle (halofantrine, as well as mefloquine) in the
following situations: | pre-existing evidenced cardiopathy even well stabilized by the
treatment | | notion of a cardiovascular anomaly at the anamnesis, even if the
latter has been considered as benign (murmur labeled innocent,
labile arterial hypertension, extrasystole on an apparently healthy
heart..). |
Recent unpublished observations of sudden death after taking
halofantrine in young subjects carriers of a murmur considered in
the past as being inorganic, require extreme care in the issue of
this molecule.
All this data leads to the proposal of the following
recommendations: | Prefer quinine or mefloquine in the initial treatment. The first
does not lead to fatal complications except during prescription
errors (bolus IV, strong doses) intravenously. The cardiac toxicity
of the second is low, but its neurological toxicity is not to be
ignored (1/200 to 1/1 700 curative treatments). | | halofantrine to be used only with extreme care. | | The use of antimalarial drug combinations, atovaquone +
proguanil (Malarone®) or artemether + lumefantrine (Riamet®),
available on the tropical markets, remains to be specified.
Finally, quinine (Quinimax®) administered per os (25 mg/kg for 5
days), which has the advantage of being presented in a
concentration base-equivalent is the safest treatment despite
gastrointestinal minor side-effects. |
Severe Plasmodium falciparum
crisis Defined by the presence of a single clinical or biological sign
of gravity, severe Plasmodium falciparum malaria
always requires the use of parenteral treatment wherever possible.
The prescription of an antimalarial drug orally is to be
excluded.
Quinine is the reference antimalarial drug. It is administered with
a loaded dose (17 mg/kg administered in 4 hours) and strong
follow-up doses (8 mg/kg in 4 hours every 8 hours). Account is
taken of the fact that the commercial formulations of quinine may
not be equivalent: Quinoforme ® contains 83,5 % of quinine base per
ampoule. On the other hand, the new formulations of Quinimax® are
dosed in an equivalent base (the date of the commercial
presentation should be checked for the former presentations contain
60 % quinine base per ampoule). The addition of an antibiotic,
doxycyclin in particular, is pointless when the plasmodial strain
is of African origin. On the other hand, when the patient has been
infected by a South Eastern Asiatic strain or a South American
strain, the combination of doxycyclin (200 mg/j in a drip) is
recommended due to a drop in the sensitivity
of Plasmodium falciparum to quinine in these
regions.
Sufficient stress cannot be given to the need for the perfect
control of saline water intakes in cases of severe malaria, as a
result of the increased risk of a pulmonary edema, as well as the
deleterious effect of certain medicinal agents (corticosteroids,
heparin, aspirin, pentoxyfyllin) which should be counter-indicated
in cases of severe malaria. At the end of a curative treatment, it is pointless to resort to
chemoprophylaxis if malaria has been treated on return from an
endemic zone. On the contrary, if the treatment has been carried
out in a tropical region, the chemoprophylaxis should be followed
according to the recommendations in force. | Therapeutic healthcare within a humanitarian aid program
In malaria endemic areas, there is little difference of clinical
manifestations among the indigenous population who have acquired an
incomplete and fragile immunity after several years of repeated
malarial infections. Tolerance to malaria is often better in these
cases. The symptoms are moderate, the parasitic density is higher,
with patency thresholds higher than 10,000 HPM. It is in this case
difficult to differentiate between a malaria disease and another
infectious illness associated with a malaria infection defined
simply because the subject is an asymptomatic carrier of
hematozoa. Uncomplicated malaria: According to the WHO recommendations, the first line treatment
of the uncomplicated malaria of the semi-immune populations is
based in priority on chloroquine (25 mg/kg, total dose administered
in 3 days). In certain African countries, amodiaquine is also used
in the first instance (35 mg/kg, total dose administered in 3 days)
or the sulfadoxine-pyrimethamine combination (for adults, 2 to 3
pills in a single take, or 2 to 3 ampoules in a single IM
injection; for children, 1/2 pills per 10 kg weight
). Severe malaria: When quinine drips cannot be used, the use of suppositories is
an excellent solution, especially for children. The dosage is 11.8
mg/kg of base quinine every 8 hours, administered in a syringe
containing 5 cc of physiological serum.
The derivatives of artemisinine are another alternative. In this
respect, artemether (Paluther®) is a major aid in the treatment of
severe forms of Plasmodium falciparum malaria.
The recommended protocol is the following:
for adults: 2 x 80 mg ampoules by IM injection the first day, one
80 mg/j ampoule the next 4 days;
for children: 3.2 mg/kg the first day and 1.6 mg/kg the next 4
days.
Different random studies which have compared artemether to quinine
in severe malaria have shown that these two molecules were
equivalent in terms of survival. On the other hand, the parasitic
clearance is more rapid with artemether but the duration of the
coma is longer. |
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