166 
MALARIA 
circulating blood of the recipient, while 
furthermore with such large doses, the 
recipient may clinically experience passive 
paroxysms, attributable to the division of 
the original parasites received from the 
donor (Boyd and Kitchen 1936c). 
Depending on the species of parasite, the 
intrinsic incubation may vary inversely 
with the dosage of sporozoite inoculum, as 
roughly measured by the number of in¬ 
fected mosquitoes applied (Boyd 1940e; 
Boyd and Kitchen 1937c; and Boyd and 
Kitchen 1937e). This is shown by the 
summary presented in Table III. 
It will be noted from Table III that even 
by the crude method of appraising the rela¬ 
tive sporozoite dosage, an inverse relation 
between the dosage and the time elapsing 
to the first detection of trophozoites is evi¬ 
dent with the vivax inoculations but is not 
apparent with the falciparum inoculations. 
This suggests that the latter parasite may 
have a very low minimal infecting dose, 
which conversely is likely much higher for 
P. vivax. But more significant still, it will 
be noted that even with the maximum 
inoculum, the intrinsic incubation period 
not only has not been suppressed, but has 
not been reduced below a characteristic 
minimal interval for each species. 
Furthermore, natural inoculation even 
by massive doses of sporozoites, is followed 
by a period in which the blood is free from 
trophozoites, in marked distinction to arti¬ 
ficial inoculation. This has been demon¬ 
strated for P. vivax by Boyd and Stratman- 
Thomas (1934c), for P. falciparum by Ciuca 
et al. (1937a) as well as by Boyd and Mat¬ 
thews (1939), while Warren and Cogges- 
hall (1937) have shown that this character¬ 
istic is also exhibited by the P. cathemerium 
of birds. Using massive inoculations of 
250 cc of blood, Raffaele (1937a) found the 
blood of a naturally inoculated vivax 
patient infectious as early as the fifth day 
after inoculation. These observations in¬ 
dicate that it is unlikely that any trophozo¬ 
ites of P. vivax or P. falciparum are in the 
blood stream earlier than the 5th day subse¬ 
quent to natural inoculation. This is 
strong evidence against the view that sporo¬ 
zoites directly initiate schizogony, and 
perhaps explains the general failure of all 
efforts to confirm the claim of Schaudinn 
(1902-03) to have observed the penetration 
of erythrocytes by sporozoites in vitro. 
The facts just related give support to 
James’ (1931) hypothesis of the existence 
of a hitherto unrecognized fixed tissue cell 
stage intervening between the sporozoite 
and the trophozoite, which was suggested 
in an endeavor to explain why quinine is 
not effective as a causal prophylactic. 
The criteria by which the termination of 
the incubation period is recognized do not 
usually coincide, although as seen from 
Table IV, they usually vary directly with 
each other. The extent to which they do 
TABLE III 
Showing the Relation Between the Length op the Incubation Period and the Number op 
Infected Mosquitoes Applied (Sporozoite Dosage) in Naturally Induced Malaria 
Parasite 
Number of 
infected 
mosquitoes 
Days from inoculation to first detection of parasites 
0 1 1 2 3 8 13 18 23 
7 12 17 22 27 
Total 
P. vivax 
1-5 
. 38 74 9 
121 
6-10 
. ... 33 7 . 
40 
11 + 
. 3 1 . 
4 
Total 
0 0 0 0 74 82 9 
165 
P. falciparum 
1-5 
. 2 18 11 . 
31 
6-10 
. 37 9 . 
46 
11 + 
. 15 4 . 
19 
Total 
0 0 0 2 70 24 . 
96 
