CINCHONA AND ITS ALKALOIDS IN MALARIA 
257 
Commission of the Health Organization of 
the League of Nations has set up standards 
for a preparation of the “total alkaloids” 
under the name “Totaquina” which has 
been widely used throughout the world 
(Pampana and Fletcher 1934). This 
preparation was adopted into the British 
Pharmacopoeia in 1933, and its adoption 
for the U. S. P. XII has been urged on the 
ground that this would establish standards 
for the preparation used in the Philippines. 
It can be produced in the Philippines and 
quite possibly in Central America. Any 
dislocation of commerce with the East 
Indies that cut off supplies of alkaloids 
would in all probability at the same time 
disturb traffic with the Philippines. The 
flow of supplies from Central America, 
however, should be free from interruption. 
The most important alkaloid in cinchona 
is quinine. The most extensive experience 
in this hemisphere in the treatment of ma¬ 
laria is that making use of quinine or of 
its salts. The emphasis in the rest of this 
paper will therefore be placed on a discus¬ 
sion of this substance. The pharmacology 
of quinine and its relatives will be discussed 
only in so far as this may relate to their 
use in malaria. 
Fundamentally, it may be said that the 
action of quinine, in adequate dosage, is to 
destroy all forms of P. vivax and P. 
malariae in the peripheral blood of the 
human host, and the trophozoites but not 
the gametocytes of P. falciparum (Craig 
1939). Treatment with quinine in the 
usual dosage does not affect the patient’s 
general condition adversely, and generally 
has no depressive or toxic effect, if the 
period of administration is limited to the 
strictly necessary number of days. This 
summary statement should of course be 
amplified. It is well recognized that there 
are differences in the action of quinine on 
the different species of plasmodium causing 
malaria, and possibly also on different 
strains within the same species. Further, 
as already indicated, different stages in the 
life cycle of the plasmodium react differ¬ 
ently. It is generally held that quinine is 
parasiticidal, in the sense of causing their 
disappearance, to both trophozoites and to 
the fully developed gametocytes of P. vivax 
and P. malariae in the circulating blood. 
On the fully developed gametocytes of P. 
falciparum, quinine has only a slight 
action, if any. It is believed by some (Par¬ 
rot, Catanei and Ambialet 1937) that 
quinine, if not toxic to fully formed gameto¬ 
cytes, does in fact retard their formation. 
These workers insist that any “drug with 
schizonticidal properties ipso facto pos¬ 
sesses gametocidal properties in regard to 
sexual forms in progress of development.” 
The correctness of this view has not been 
established and further evidence is needed. 
The point is of considerable importance in 
relation to the control of malaria. So far 
as treatment of the individual is concerned, 
it makes no difference whether he carries 
sexual forms in his blood or not. 
The relief of clinical symptoms and the 
disappearance of the parasites from the 
blood stream are more or less parallel. In 
the benign tertian infection the trophozoites 
disappear about the third day, and the 
clinical symptoms are relieved at the same 
time. For quartan fevers clinical improve¬ 
ment comes on in about the same time. 
With malignant tertian the trophozoites 
persist a day or more longer, and similarly 
there may be three or four paroxysms after 
treatment is started. In no case, however, 
can the relief of symptoms be taken to 
indicate that the body has been freed of 
the invading organisms. Cessation of treat¬ 
ment is followed by relapse in a consider¬ 
able number of cases. In primary infec¬ 
tions treated by the ordinary doses of 
quinine as high as 50 per cent may relapse. 
This tendency to relapse has resulted in 
the development of two quite different 
practices in the treatment of malaria. The 
National Malaria Committee recommended 
as a plan of treatment quinine sulfate, 0.6 
gm 3 times per day for 8 days, followed by 
0.6 gm daily for 8 weeks. Craig (1939) 
using this treatment finds not over 5 per 
cent of relapses. The League of Nations 
Malaria Commission on the other hand 
recommends 1.0 to 1.2 grams daily for 5 to 
7 days, with treatment of relapses only 
