THE INFECTION IN THE INTERMEDIATE HOST: 
SYMPTOMATOLOGY, GENERAL 
CONSIDERATIONS 
By MARK F. BOYD 
INTEBNATIONAL HEALTH DIVISION, BOCKEFELLEB FOUNDATION, TALLAHASSEE, FLA. 
Since the introduction of cinchona, com¬ 
paratively few physicians have had the op¬ 
portunity to observe the natural evolution 
of malarial infections to a spontaneous ter¬ 
mination. This is in striking contrast to 
typhoid, for example, for which the lack to 
date of any specific bactericidal agent pre¬ 
vents a physician- from brusquely inter¬ 
rupting the evolution of the disease. Hence 
in the period from the beginning of specific 
medication until the introduction of natu¬ 
rally induced malaria as a therapeutic 
agent in the treatment of neurosyphilis, 
the personal acquaintance of medical men 
with the natural history of these diseases 
greatly deteriorated. 
Malarial infections are either naturally 
or artificially acquired. Naturally acquired 
infections, excluding instances of congeni¬ 
tal malaria, result from the parenteral in¬ 
oculation of sporozoites by an infected 
mosquito. Depending upon whether the 
inoculation was effected by the chance bites 
of wild mosquitoes in a free condition, or by 
the deliberate application of experimentally 
infected insects, we may distinguish au¬ 
tochthonous from induced infections. To 
the latter class belong the few reported 
instances where inoculation has been 
effected with suspensions of sporozoites 
prepared from the glands of infected 
anophelines (James, Nicoll and Shute 
1927). Artificially acquired infections fol¬ 
low the parenteral inoculation of trophozo¬ 
ites in infected blood. Probably the only 
autochthonous infections of this class are 
the instances of congenital malaria. A 
further exception to the foregoing state¬ 
ment is afforded by the recent report by 
Shortt and Menon (1940) of their success 
in infecting 6 of 7 rhesus monkeys with P. 
knowlesi, and 7 of 17 chickens with P. 
gallinaceum by dropping defibrinated in¬ 
fected blood into their open mouths. Most 
are induced either deliberately in malaria 
therapy, or accidentally as a consequence of 
transfusion (Hutton and Shute 1939), or 
intravenous medication (Black 1940), or 
the communal apparatus for the prepara¬ 
tion of * ‘ shots ’ ’ by gregarious narcotic 
addicts (Biggam 1929; Himmelsbach 1933; 
Faget 1933; Helpern 1934; Most 1940b). 
The minimal number of sporozoites 
which can initiate infection in a susceptible 
intermediate host is not known. The cir¬ 
cumstance that the mere insertion of the 
proboscis of a single infected anopheline 
can introduce an infecting dose does not 
answer the question, as the density of infec¬ 
tion in different insects varies widely, so 
that some specimens might only introduce 
a few, others many hundreds or even thou¬ 
sands. Sporozoites removed from infected 
glands may be suspended in Locke’s solu¬ 
tion and injected by a syringe (James, 
Nicoll and Shute 1927). Using such a 
method, Shute (1937) reports having 
effected inoculations with as few as fifty. 
De Sanctis Monaldi (1935) reports takes 
after incubation periods of from 15 to 17 
days in 3 of 7 patients intravenously inocu¬ 
lated with from 2,500 to 100,000 suspended 
sporozoites. The length of these incuba¬ 
tion periods he regarded as normal for the 
strain. 
While it is probable that most of the 
sporozoites introduced by an anopheline 
are discharged into the blood stream, since 
immediate excision of the tissues about the 
site of the insertion of the proboscis will 
not forestall an infection, the slender fusi¬ 
form shape of the sporozoite suggests an 
