MALARIA PROPHYLAXIS FOR
PATIENTS WITH PORPHYRIA TRAVELLING IN
Malaria is the disease
which results from infection by the malaria
parasite called Plasmodium, which is spread
by a particular type of mosquito, with
infection resulting from a mosquito bite.
There are four species of Plasmodium.
In southern Africa, by far the most common
species is Plasmodium falciparum. This
is somewhat unfortunate since it not only
causes the most severe disease, but has
a strong tendency to become resistant
to the drugs used for prevention and treatment.
In particular, chloroquine, a drug which
was widely used until fairly recently
in southern Africa, is now useless because
of widespread chloroquine resistance in
Plasmodium falciparum. The other three
species of parasite, P. vivax, P. malariae
and P. ovale are uncommonly encountered
in southern Africa. Though they are mostly
chloroquine-sensitive, the treatment is
more complicated in that they require
treatment with a second drug, primaquine,
since these parasites have the ability
to shelter in the liver as well as the
bloodstream, unlike Plasmodium falciparum
which confines itself to the bloodstream.
PREVENTION OF MALARIA
In order to reduce the
risk of developing malaria, sensible precautions
must be taken. Simple steps to lessen
the risk of being bitten by mosquitoes
in the first place will substantially
reduce the risk of malaria. Wear adequate
clothing, use insect-repellent sprays
and employ impregnated sleeping nets.
Avoid being out of doors at dusk when
mosquitoes are most active. The frequency
of malaria in southern Africa is also
highly seasonal, and cases of malaria
are very much less likely during the dry
season than in the rainy season.
All travelers must understand
the necessity of recognising possible
malaria, and should seek urgent medical
assistance in the event that any suspicious
symptoms occur. Should you travel in a
country with unreliable medical services,
it is wise to carry a course of quinine
tablets so that you can begin treatment
yourself in the event that you develop
symptoms of malaria. You should, however,
return urgently to a country such as South
Africa with appropriate medical services,
since self treatment is not a substitute
for prompt consultation with a doctor
with the knowledge and resources to undertake
diagnosis and treatment.
In addition to the sensible
precautions, appropriate prophylactic
use of antimalarial drugs is important.
DRUGS USED FOR THE PREVENTION
The following recommendations
are intended for patients with acute intermittent
porphyria (AIP), variegate porphyria (VP)
and hereditary coproporphyria (HCP). Patients
with porphyria cutanea tarda (PCT) and
erythropoietic protoporphyria (EPP) are
not drug-sensitive, and may use antimalarial
Note that the safety of
the drugs recommended here cannot be guaranteed.
These are newer drugs and there is still
little actual clinical experience of their
use in porphyria. However, on current
information, they would not be expected
to result in an exacerbation of porphyria.
Drugs recommended for use
The following are the
drugs recommended for use in porphyria.
Atovaquone plus proguanil
These drugs are combined
in a single tablet as Malanil in South
Africa and Malarone elsewhere. The combination
is effective in preventing malaria in
southern Africa. Proguanil is known to
be safe in porphyria. Atovaquone appears
on consideration to be safe since it is
not significantly metabolised. Common
side effects reported with this combination
include abdominal pain, nausea, vomiting,
skin rashes and headache. The drug is
contraindicated in children weighing less
than 11 kg, in pregnant or breast-feeding
women and in patients with severe renal
There is some clinical
experience with mefloquine in patients
with porphyria and the drug appears to
be well tolerated in these patients. Common
side effects include headache, nausea,
dizziness, poor sleeping, anxiety and
dreaming. More serious side effects include
depression, psychosis and seizures. The
drug is contraindicated in people with
a history of depression, psychosis or
other major psychiatric problems, seizures
and disturbances of heart rhythm.
Drugs which should not
Dapsone is known to be
dangerous in porphyria, and as a combination
is any event no longer useful for prevention
of malaria because of widespread resistance.
Chloroquine is safe in
porphyria, however, all falciparum malaria
is chloroquine-resistant in southern Africa
and chloroquine therefore has no place
in the prevention of porphyria.
) and proguanil/chloroquine combination
Both agents are safe for
use in porphyria but are considerably
less effective in preventing malaria than
mefloquine and atovaquone/proguanil and
are therefore not recommended for use
in southern Africa.
Drugs which should be
used with extreme caution only
Though previously reported
as unsafe in porphyria, more recent work
has suggested that doxycycline may be
safer than was previously thought since
it undergoes little hepatic metabolism.
However, since its safety is contentious
we do not recommend it unless there are
strong contraindications to the use of
the drugs recommended above, mefloquine
or atovaquone/proguanil. Where doxycycline
is used, you must remain extremely cautious.
Any symptoms suggestive of an incipient
acute attack, particularly abdominal pain,
indicating urgent need to stop the drug
and to seek the assistance of a doctor
experienced in the management of porphyria
consulted; this will almost certainly
mean an urgent interruption of your travels.
There is no information
on the safety of halofantrine in porphyria.
However the use of halofantrine is generally
discouraged because of the risk of cardiovascular
This is a potentially
useful drug combination in the management
of malaria. Unfortunately the safety of
either component in porphyria is not yet
established. Both are metabolized by the
cytochrome P450 system which implies that
porphyria induction is a possibility.
It should therefore be used with extreme
caution only, and any experience with
its use in porphyria should be reported
TREATMENT OF MALARIA
Drugs recommended for use
Quinine sulphate as a
single agent is highly effective in the
treatment of porphyria and should be given
for a fall 10-day course. This is the
recommended treatment in porphyria.
This is used in higher
doses for treatment than for prophylaxis
and therefore has a higher incidence of
side-effects. Though not entirely proven
to be safe in porphyria, it would appear
to be an acceptable alternative to quinine.
Drugs to be avoided
All falciparum malaria
is chloroquine-resistant in southern Africa,
and chloroquine therefore has no place
in the treatment of malaria.
Most guidelines for the
management of malaria suggest that doxycycline,
tetracycline or clindamycin be given in
addition to quinine in order to shorten
the length of the course of treatment.
This is however unnecessary provided that
a full 10 day course of quinine is given.
Since these three agents may potentially
be hazardous in porphyria, their use is
and pyrimethamine combination)
Sulfadoxine is absolutely
contraindicated in porphyria as it may
induce acute attacks.
The Plasmodium parasites
responsible for the vivax, malariae and
ovale forms of malaria are typically still
sensitive to chloroquine. Therefore chloroquine
therapy remains appropriate treatment
for these infections provided that the
possibility of coexistent falciparum malaria
has been excluded. Since these forms of
malaria also have a hepatic phase as well
as a blood phase (as described in introduction),
chloroquine must be followed by additional
primaquine therapy to eradicate parasites
within the liver. Primaquine is safe in
For comprehensive information
on malaria in southern Africa, consult
pages of the US Centers for Disease
TRAVELLING TO AREAS OTHER
THAN SOUTHERN AFRICA
These notes are
intended for people traveling in southern
Africa. Recommendations for other areas
of the world in which malaria may be encountered
will differ since different types of malaria,
with varying degrees of drug-resistance
are encountered. If you are traveling
to another area, we suggest that you consult
the appropriate authorities or else the
for Disease Control web site to determine
which prophylactic regimens are recommended.
this information, you should check their
safety of the recommended drugs against
the information contained in this document
or approach us for advice on prophylaxis
in your with your specific circumstances.
can also contact the Medicines Safety
Centre (Dept of Pharmacology, University
of Cape Town, Tel. +27 (0) 21-4066427)
for updated information on risk profiles
for particular destinations.
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