INFECTION OF THE INTERMEDIATE HOST 
171 
Fig. 3. Showing clinical attack experienced by Patient 282-1133 inoculated on June 2, 1937, by 6 A. 
quadrimaculatus simultaneously infected with both P. vivax and P. falciparum. The chart covers two 
periods of observation of 68 and 27 days. It will be noted that subsequent to inoculation the two 
species of parasites appeared practically simultaneously. Five-grain doses of quinine -tfere given on the 
15th, 16th, 20th, 22nd, 26th, and 30th days after inoculation. Coincident with the dose given on the 
20th, P. vivax diminished to submicroscopical levels and was not thereafter noted during the first period 
of observation. After the 19th day the clinical attack exhibits the characteristics of falciparum malaria. 
From the 59th to the 66th day intensive quininization by Sinton’s method was effected. After an inter¬ 
val of 227 days, the patient experienced an attack from P. vivax in the following spring. (Am. J. trop. 
Med., 18: 512.) 
than six months after the inoculation. This 
incidence of 42.9 per cent is in marked con¬ 
trast to the 8.05 per cent of renewed activ¬ 
ity after six months following simple vivax 
infection. None of the long term recur¬ 
rences took place in patients who experi¬ 
enced vivax attacks immediately following 
the first period of falciparum activity, 
although all patients had received intensive 
treatment with quinine (Fig. 3) (Boyd and 
Kitchen 1938a). The renewed activity of 
vivax occurred 235, 236 and 282 days, re¬ 
spectively, after the onset of the original 
falciparum dominated attack, or at inter¬ 
vals of 226, 174 and 233 days, respectively, 
after its induced termination. 
The experience of these patients appears 
similar to that observed in the epidemic 
situations cited. 
The Threshold or Pyrogenic Level 
The minimal density which trophozoites 
must attain in the blood before a patient 
presents the first symptoms of illness is 
known as the threshold or pyrogenous level. 
The density prevailing at this time, we 
believe, should be distinguished from that 
which may prevail during the subsequent 
course of the illness and infection. Ross 
(1910), one of the earliest who considered 
this question, estimated that the para¬ 
sites will not generally be numerous enough 
to cause illness unless there is at least 1 
parasite to 100,000 erythrocytes; that is 50 
parasites in 1 cmm of blood, or 150,000,000 
in a man of 142 pounds (64 kg) in weight. 
It would require on the average a 15 minute 
search of a thin smear to detect a parasite 
at this density. 
Assuming that the first elevation of tem¬ 
perature to 100° F or higher marks the 
clinical onset, we (Boyd 1938) have ob¬ 
served the parasite densities at the time of 
onset in induced vivax malaria shown in 
Table IX. 
It is thus seen that P. vivax may induce 
a clinical reaction with densities of 10 or 
fewer trophozoites per cmm of blood re¬ 
gardless of the manner in which the attack 
was induced. It is to be further noted that 
the greater the disparity between the first 
detection of parasites and the first fever, 
the higher will be the pyrogenic level. The 
works of other observers cited by Sinton 
et al. (1931) lead them to suggest that there 
