A Textbook of Clinical Pharmacology and Therapeutics

362 MALARIA AND OTHER PARASITIC INFECTIONS

MALARIA PROPHYLAXIS

Malaria prophylaxis is relative and the agents are chosen
mainly on the basis of the susceptibility patterns of the local
Plasmodiumspecies. The arylaminoalcohols (e.g. mefloquine),
4-aminoquinolines (e.g. chloroquine) and the antifolate
agents (e.g. pyrimethamineandproguanil) are the major
prophylactic drugs. Prophylaxis must start at least one week
(and preferably two weeks) before entering a malaria endemic
region, and must continue for four weeks afterwards.
Chloroquineis only used as a prophylactic in regions where
falciparum malaria is not chloroquineresistant. Drugs for the
prophylaxis of chloroquine-resistant falciparum malaria are
shown below; items 3 and 4 appear to be well tolerated.

1. mefloquine, weekly;
   2.chloroquine, weekly plus proguanildaily;
   3.doxycyclinedaily;
   4.atovaquoneandproguanildaily.

DRUG TREATMENT OF ACUTE MALARIA

THE 4-AMINOQUINOLINES (E.G. CHLOROQUINE)

CHLOROQUINE

Uses

Chloroquineis still one of the most commonly used anti-

malarial drugs world-wide, but increasing resistance (espe-

ciallyP. falciparum) has reduced its efficacy. It is used in:

• acute malaria – chloroquine is effective in terminating an
  acute attack of benign vivax malaria, but is not radically
  curative because it does not eradicate the latent hepatic
  forms of the parasite, and relapses can occur subsequently.
  If given intravenously, chloroquine can cause
  encephalopathy. Following a course of chloroquine,
  primaquinemay be given for 14–21 days to achieve a
  radical cure (i.e. to eliminate hepatic forms and prevent
  relapse). Before starting primaquine, the possibility of
  glucose-6-phosphate dehydrogenase (G6PD) deficiency
  should be considered (Chapter 14).


• malaria prophylaxis (see above);


• rheumatoid arthritis or systemic lupus erythematosis may
  be treated with chloroquineorhydroxychloroquine
  (Chapter 26).

Antimalarial mechanism of action

The erythrocyte stages of Plasmodium are sensitive to

chloroquine. At this stage of its life cycle, the parasite digests

haemoglobin in a food vacuole to provide energy for the par-

asite. The food vacuole is acidic and the weak base chloro-

quineis concentrated within it by diffusion ion-trapping.

Chloroquineand other 4-aminoquinolines are believed to

inhibit the malarial haem polymerase within the food vacuole

of the plasmodial parasite, thereby inhibiting the conversion

of toxic haemin (ferriprotoporphyrin IX) to haemozoin (a pig-

ment which accumulates in infected cells and is not toxic to

the parasite). Ferriprotoporphyrin IX accumulates in the pres-

ence of chloroquineand is toxic to the parasite, which is killed

by the waste product of its own appetite (‘hoist with its own

petard’).

Adverse effects

Short-term therapyThese include the following:

1. mild headache and visual disturbances;
   2.gastro-intestinal upsets;
   3.pruritus.
   Prolonged therapyThese include the following:


2. retinopathy, characterized by loss of central visual acuity,
   macular pigmentation (‘bull’s-eye’ macula) and retinal
   artery constriction. Progressive visual loss is halted by
   stopping the drug, but is not reversible;
   2.lichenoid skin eruption;
   3.bleaching of hair;
   4.weight loss;
   5.ototoxicity (cochleovestibular paresis in fetal life).

Key points

The malaria parasite

• Plasmodium falciparuminfection has the highest
  mortality and causes cerebral malaria.


• P. malariae,P. ovaleandP. vivaxcause more benign
  disease.


• The hepatic forms of P. ovaleandP. vivaxcause
  relapses.


• Antimalarial drugs act at different stages of the malaria
  parasite’s life cycle.


• Resistance, especially of P. falciparum, to chloroquine,
  sulfadoxine–pyrimethamine and mefloquine is an
  increasing problem world-wide.

Key points

Malaria prophylaxis

• All travellers to an endemic area should be made aware
  of the risks.


• Use appropriate measures to avoid mosquito bites (e.g.
  repellents, appropriate cover at night, mosquito nets).


• The choice of chemoprophylaxis regimen is dependent
  on the dominant local parasite species and its drug
  resistance profile.


• Chemoprophylaxis must start before, and continue
  after, travel to and from an endemic area.


• Full compliance with the chemoprophylaxis regimen is
  necessary.


• Drug choice and doses may need to be altered in
  patients with renal or hepatic dysfunction.


• Prophylaxis is not 100% effective.

PREVENTION OF MALARIA IN PREGNANCY

Chloroquineormefloquine(inchloroquine-resistant areas)
are believed to be the most effective and safest antimalarial
drugs for chemoprophylaxis in pregnancy.