Tropical Doctor, January I977


Prevention and treatment of malaria L.

J. Bruce-Chwatt, MD, FRCP, MPH


1977, 7, 17-20

Human malaria is caused by four species of malaria parasites: P. falciparum, P. malariae, P. vivax and P. ovale. Vivax and falciparum malaria together represent some 95% of all infections. Once the diagnosis is made the treatment of vivax or quartan malaria is simple, providing that in addition to dealing with the acute attack of the disease some thought is given to general systemic treatment and later to a follow-up treatment to prevent relapses. On the other hand P. falciparum may produce a severe illness which may lead to a medical emergency. Moreover, during the past two decades strains of P. falciparum have appeared which are resistant to common prophylactic or therapeutic drugs. These problems have somewhat complicated the approach to treatment or prevention of malaria and led to some confusion. The present note attempts to outline the general consensus of opinion, while admitting that no standardized procedure can be advocated, since the response of local strains of malaria parasites has rarely been fully investigated by appropriate methods. ACTION OF ANTIMALARIAL DRUGS

Antimalarial drugs have a selective action on the different phases of the life cycle of the parasite. Schizontocidal drugs are those that destroy the plasmodia circulating in the blood. Quinine and the two 4-aminoquinolines (chloroquine and amodiaquine) have this action on all forms of the malaria Table


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parasites with the exception of gametocytes of P. falciparum. The newer antimalarials, such as sulphonamides given together with pyrimethamine, have also a marked schizontocidal action. The gametoeytocidal drugs such as primaquine (an 8-aminoquinoline) destroy the gametocytes of P. falciparum and thus may prevent the spread of the disease by the Anopheles vectors. However, their main practical value is related to the fact that they prevent relapses of attacks due to P. vivax, P. malariae and P. ovale. Thus they belong also to the group of anti-relapse drugs. Causal prophylactic drugs (proguanil and pyrimethamine) are those that act on the early stages of the malaria parasite when it is still confined to the liver tissue, during the incubation period. These sporontocidal drugs have also some action on the parasites developing in the mosquito, when the latter feeds on the blood of a person who takes such drugs. Protection from a malaria infection can be obtained either by the regular administration of causal prophylactic drugs or by the regular use of schizontocidal drugs which keep the numbers of malaria parasites at such low level that no clinical disease will occur. TREATMENT OF SIMPLE ATTACKS OF MALARIA

An acute attack of malaria, irrespective of the parasite species involved, usually responds to administration of quinine or of one of the two available 4-aminoquinolines (chloroquine or amodiaquine). An initial loading dose of the latter drugs is important; in adults of average weight it amounts to 900 mg base of chloroquine or amodiaquine on the first day followed by a 300 mg base daily dosage for the next 2-5 days totalling 1,500-2,100 mg (20-30 mgjkg), As a precautionary measure further once weekly administration of 300 mg base of the drug is advisable over the next month. The usual dosage for treatment of acute malaria in children is shown in the following table although care must be taken to adjust the amount of the drug to the weight and condition of the child.

Dosage of chloroquine (base) in children


Over 16 years Between I I and 16 Between 7 and 10 Between 4 and 6 Between I and 3 Under I year

First intake

600 mg 450 mg 300 mg 225 mg 150 mg 75 mg

(4 tablets) (3 tablets) (2 tablets) (It tablets) (I tablet) (t tablet)

Six hours later

300 mg 225 mg 150 mg 110 mg 75 mg 37 mg

(2 tablets) (I t tablets) (I tablet) C! tablet) Ct tablet) (i- tablet)

Each two consecutive days

300 mg 225 mg 150 mg 1I0mg 75 mg 37 mg



In subjects who have acquired a degree of immunity to malaria and in whom the clinical illness is mild a single dose of chloroquine or amodiaquine (as shown in the third column of the above table) may suffice, though it will not effect a radical cure of the infection. For infections with P. vivax, P. malariae, or P. ovale which may relapse weeks or months later the patient, after the treatment of the acute attack, should be given primaquine at a daily dose of 15 mg for not less than 14 days. This drug may occasionally cause some gastro-intestinal symptoms and a minor degree of haemolytic anaemia in persons with glucose-6phosphate-dehydrogenase (G6PD) deficiency. It is therefore preferable that such patients should be treated under medical supervision. In certain parts of South-East Asia and South and Central America (but not in Africa) strains of P. falciparum resistant to 4-aminoquinolines have appeared and patients infected with such strains may respond more slowly or not at all to the usual or even higher dosage of 4-aminoquinoline drugs. Often the initial good response is followed by a recrudescence of fever and reappearance of parasites in the blood. In such situations, if the condition of the patient is not unduly serious, the best treatment is by oral quinine sulphate, in tablets of 650 mg given three times daily for 10-14 days or (preferably) a 2-3 days quinine treatment followed by one of the modern drug combinations of long-acting sulphonamide with pyrimethamine. One of these combined drugs is now available under the name of Fansidar, each tablet of which contains 25 mg of pyrimethamine and 500 mg of sulphadoxine. Pyrimethamine 50 mg with sulphadoxine 1,000 mg (2 tablets of Fansidar) is the usual dosage for a moderate malaria infection. As an alternative (if Fansidar is not available) a combined treatment with pyrimethamine 50 mg and sulphalene 1,000 mg may be given. Either of the above drug combinations should be given in a single dose or at most in two doses over two days. Higher or multiple dosage of these drugs may cause toxic effects. In parts of the world where resistance to chloroquine is of a low degree or imperfectly known, the above drug combinations may be given together with the usual quinine or chloroquine dosage. TREATMENT OF SEVERE MALARIA

For treatment of severe cases of fa1ciparum malaria with symptoms such as vomiting or diarrhoea that prevent an oral treatment, or in cases with obvious involvement of central nervous system, kidneys, lungs and other organs, specific and rapid parenteral treatment must be given without delay. In parts of the world where resistance of P. falciparum to 4-

Tropical Doctor, January I977

aminoquinolines does not occur (e.g. Africa and Asia, with the exception of South-East Asia) chloroquine is still the most reliable drug. It should be given by intramuscular injection at an adult dose of 200-300 mg base as a 5% solution and repeated after 6-8 hours during the first day. This dose can also be given intravenously, preferably in a slow drip with 500 ml of glucose/saline. Chloroquine by injection may be given to children only when oral administration is really impossible. Small children are particularly sensitive to chloroquine and if given parenterally the drug should be administered at a total dosage not exceeding 20 mg base/kg weight in 2-3 divided fractions of the actual dosage. Wherever chloroquine-resistant strains of P. falciparum may be present, severe infections with this parasite should be treated by intravenous quinine dihydrochloride, administered at the single dosage of 500-600 mg in a slow intravenous drip in glucosesaline or plasma. This dosage should be repeated up to three times during the first 24 hours. Children should be given a proportionately lower dosage. Oral therapy with quinine or other active drugs should replace parenteral treatment as soon as possible. Naturally, the treatment of any severe attack of malaria requires a comprehensive clinical approach to the patient. Dehydration quickly arises from the reduction of fluid intake by comatose or drowsy patients who sweat profusely. Replacement of fluid and salts is necessary. When the central nervous system is involved the administration of dexamethasone (10 mg three times a day) is of value. For convulsions, oral administration of pento-barbitone sodium or similar drugs is advisable; the same may be needed when vomiting is severe. Hyperpyrexia must be dealt with by sponging. Nursing is most important in the management of every case of severe fa1ciparum malaria. Naturally, general systemic treatment of complications of any severe attack of malaria must not be neglected. Convulsions should be controlled by phenobarbitone or other suitable drugs; dialysis may be needed to correct uraemia and electrolyte imbalance; corticosteroids such as dexamethasone (4-6 mg every 4-6 hours) appear to be beneficial; in case of severe haemolytic anaemia (blackwater fever) blood transfusions may be life-saving, provided that blood-group matching is faultless and that no overload of the circulating system occurs. Perfect nursing is of paramount importance. INDIVIDUAL PROPHYLAXIS

The antifolic drugs proguanil, chlorproguanil and pyrimethamine are still relatively the most useful

Tropical Doctor, January I977


prophylactic drugs. Many experienced observers prefer proguanil, which is taken daily (at a dose of 100-200 mg, equivalent to one or two tablets) to pyrimethamine taken once a week (at 25 mg) because the daily regimen offers a better guarantee of a regular intake. However, there are undoubtedly areas of the world where P. falciparum and other plasmodia are resistant to pyrimethamine. Where this occurs a degree of cross-resistance to proguanil is often present. Obviously this limits the prophylactic value of both compounds and chloroquine or amodiaquine are to be preferred as suppressive drugs. In areas of resistance to 4-aminoquinolines the value of the two latter drugs is limited though some degree of protection may still be achieved. The usual dosage of chloroquine is 300 mg base per week (one tablet every three days) (amodiaquine 400 mg base), though in French-speaking parts of Africa a much higher dose of chloroquine (600700 mg) is favoured. Pyrimethamine with chloroquine (Darachlor) are favoured in some parts of the world. Where the resistance to both groups of compounds (antifolates and 4-aminoquinolines) is confirmed an association of pyrimethamine with sulphone (Maloprim) may be considered as an alternative though long-term effects of this regimen are not yet fully



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assessed. Care must be taken not to recommend any prolonged administration of sulphones or sulphonamides to persons with known sensitivity to these compounds. NEW ANTIMALARIAL DRUGS

A number of new antimalarials are now being assessed in the course of field trials. One of them is a quinoline methanol developed by the United States Army Malaria Research programme and released for limited use under the name of Mefloquine. Preliminary results are very promising but this compound is not generally available. The value of co-trimoxazole as an antimalarial is controversial. While the efficacy of the combination of trimethoprim and sulphamethoxazole (Bactrim, Septrin) against a wide range of bacterial infections is beyond any doubt, there is no general consensus of opinion as to the value of these compounds for the treatment of malaria. It appears that they have some schizontocidal action, especially in semi-irnmunes, and could be used in special circumstances if no other antimalarial drug is available or as an additional treatment following a short-term administration of quinine. The usual dosage is one tablet twice daily for 3-5 days. Co-trimoxazole should not be used as a long-term prophylactic drug.

Common drugs for treatment and prevention of malaria

Non-proprietary Name

Proprietary name in UK

Formulation and base content

Adult prophylactic dose

Adult treatment dose




Tabv roo mg

100-200 mg daily

Not advised for treatment

Limited prophylactic effect in areas of resistance to antifolic compounds



Tab. 25 mg

25 mga week As above

As above



Tab.zo mg

zo mg a week As above

As above

Chloroquine sulphate, or phosphate

Avloclor, Nivaquine, Resochin and many other names

Tab.uoo mg, 150mg and 300 mg

300mg a week or 100 mg daily 6-7 days a week

600 mg loading dose, then 300 mg after 6 hours and 300 mg daily for 3-5 days

Limited effect in areas of resistance of P. falciparum to 4-aminoquinolines



Tropical Doetor, January I977


Table 2.-Continued. Non-proprietary name

Proprietary name in UK

Formulation and base content

Adult Prophylactic dose

Adult treatment dose


Chloroquine phosphate for injection

As above

5% solution, 40 mgjml


200-3°0 mg. Intramuscular or intravenous injection. Repeat if necessary

Caution in childreno Less effective in resistant P. falciparum injections. (See text)

Amodiaquine hydrochloride or base

Camoquine (hydrochloride) Basoquine (base)


400mg a week 4°0-600mg a week

As chloroquine

Limited effect in areas of resistance of P. falciparum to 4-aminoquinolines

Quinine sulphate or dihydrochloride


Tabs. 650mg (10 grains) of salt. Solution 60 mgjml

Not used

Injections 300600 mg repeated 2-3 times if necessary (see text)

Preferably in slow intravenous drip. Useful for severe cases of falciparum malaria (especially if resistant to 4aminoquinolines)

Primaquine diphosphate

Primaquine and other names

Tab. 7.5 mg

Not used

15 mg daily for 14 days

Only for prevention of relapsing infections

Pyrimethamine + chloroquine sulphate


Tab. 15 mg and I50mg

1-2 tabs. a week

2 tabs. 3 times daily on day I, 2 tabs. on two following days

Rarely used for treatment

Pyrimethamine+ diaminodiphenyl sulphone (DDS)

Maloprim DDS= dapsone

Tab. 12.5 mg +100 Dig

2 tabs a week before exposure then 1 tab. a week

Not advised

Not used for treatment

Pyrimethamine+ sulphadoxine

Fansidar (sulTab. 25 mg+ phadoxine alone 500 mg is known as Fanasil)

Not used

2 tabs. as a single dose or 1 tab. daily for 2 days

Pyrimethamine -l-sulphalene

Sulphalene alone is known as Kelfizina

Not used

2 tabs. of each compound on day I, repeated if necessary on day 2

Only for treatment of falciparum infections resistant to 4-aminoquinolines. Quinine at 1-2 g daily may be given for the first 5 days. In severe infections parenteral quinine is advocated, to be followed by one of the combined drugs

Tab. 150 mg

No injectable preparation


Tabv yo mg -l-tabs. 1,000 mg

Prevention and treatment of malaria.

Tropical Doctor, January I977 PREVENTION AND TREATMENT OF MALARIA Prevention and treatment of malaria L. J. Bruce-Chwatt, MD, FRCP, MPH TROPICAL D...
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