INFECTION OF THE INTERMEDIATE HOST 
179 
case of 6 of the 11 patients who experi¬ 
enced renewed activity in from 8 to 24 
weeks. The effect attributed to our use of 
quinine in the patients simultaneously in¬ 
oculated with two species of parasites may 
be recalled. This suggests that recurrences 
after the longest intervals may be related 
to the prematurely early administration of 
a drug. 
It is thus seen that in vivax malaria 
there is a striking parallelism, as pointed 
out by James (1931), in the length of the 
interval between inoculation and onset in 
those patients who experience protracted 
incubation periods and the length of the 
interval between the termination of the 
primary attack and the beginning of a 
recurrence. In this connection we may re¬ 
iterate that: long-term recurrences are only 
observed in naturally infections; the clini¬ 
cal activity which marks the termination of 
the period of quiescence is most commonly 
observed in the spring; and they are fre¬ 
quently observed in patients who were 
receiving a plasmodicidal drug at the time 
of inoculation or shortly after the clinical 
onset. 
In this connection we may also reiterate 
the following significant facts previously 
brought out: the failure to observe the 
penetration of erythrocytes by sporozoites; 
the non-infectiousness of the blood for sev¬ 
eral days following natural inoculation; 
the inability to shorten the duration of the 
intrinsic incubation period by the employ¬ 
ment of massive doses of sporozoites; 
and the complete elimination of an incu¬ 
bation period following massive doses of 
trophozoites. 
These facts are not inconsistent with the 
hypothesis of the existence of a stage of 
the parasite living in fixed tissue cells 
which intervenes between the sporozoite 
and the trophozoite, the development of 
which may either be retarded, or inhibited 
or narcotized by a drug. 
Added interest and significance is af¬ 
forded this view by the recent discoveries 
of an exo-erythrocytic schizogony in several 
species of avian malaria parasites. In P. 
gallinaceum, in which this stage has been 
most extensively studied, the exo-erythro¬ 
cytic phases are passed in endothelial cells. 
According to James (1939) they are ob¬ 
served subsequent to either natural or 
artificial inoculation. However, subsequent 
to the former inoculations they are observed 
at the onset; in the latter, only at a late 
stage of the disease. He consequently con¬ 
cludes that in this parasite the stages of 
schizogony can alternate between erythro¬ 
cytes and fixed tissue cells. It seems very 
probable that something similar occurs with 
the human parasite subsequent to natural 
inoculation. Since chronic infections do 
not follow artificial inoculations with the 
human parasite, while they do with certain 
species at least of the avian parasites, it 
is suggested that in the human infection 
this stage only follows the sporozoite. 
Diagnosis 
Although many cases of malarial infec¬ 
tion presenting the characteristic symptoms 
of intermittent febrile paroxysms regu¬ 
larly recurring at quotidian, tertian or 
quartan intervals can be diagnosed with 
reasonable certainty from the symptoma¬ 
tology, the diagnoses for those patients in 
whom the fever is remittent or the parox¬ 
ysms irregular, in whom the onset is 
accompanied by alarming symptoms of a 
dangerous portent, or in whom the infec¬ 
tion has become latent must be based on 
the demonstration of the parasites in blood 
smears. Additional clinical signs observ¬ 
able as the infection progresses are an 
enlargement of the spleen and a progressive 
anemia. 
The practitioner or clinician is most often 
concerned with the diagnosis of clinically 
active infections in individual patients; 
the epidemiologist or malariologist, with 
the recognition of latent infections among 
a population group. 
Objective criteria of varying value for 
the diagnosis of malarial infections are 
afforded by: (a) The detection of parasites 
in the blood; (b) the detection of spleno¬ 
megaly; (c) changes in the normal hema¬ 
tological picture; (d) serological tests; and 
(e) biochemical tests. 
