INFECTION OF THE INTERMEDIATE HOST 
181 
ceeded, while in falciparum malaria no 
limit is apparent. In the latter infections 
counts of 500,000 per cmm are a bad prog¬ 
nostic sign. 
One possible factor, at least in determin¬ 
ing the potential density, would appear to 
be the available numbers of erythrocytes of 
different ages for which different species 
of parasites appear to show a specific pre¬ 
dilection. Thus the studies of Kitchen 
(1939b) indicate that P. malariae prefers 
mature or perhaps even aged erythrocytes, 
P. falciparum is indifferent to the age of 
the erythrocytes it attacks, while P. vivax 
prefers reticulocytes. As might be ex¬ 
pected, therefore, the rate of blood destruc¬ 
tion is most rapid in falciparum infections 
and slowest in quartan. In the former, 
rapid blood destruction may conceivably be 
a factor in producing a fatal outcome, as 
a consequence of an anoxemia. On the 
other hand, clinical activity in vivax infec¬ 
tions frequently comes to a spontaneous 
cessation when the erythrocyte density is 
lowered to the neighborhood of 1,750,000, 
with 5 grams of hemoglobin. In the attacks 
of longest duration restoration of erythro¬ 
cyte density and hemoglobin is evident 
before the termination of the attack. Resto¬ 
ration of the former proceeds more rapidly 
than that of the latter. 
The anemia does not present distinctive 
characteristics. A moderate degree of ani- 
socytosis will be observed, while the color 
index is variable. Evidence of regenera¬ 
tion of erythrocytes, afforded by the pres¬ 
ence of reticulocytes and normoblasts, is 
quite constant in acute infections. Since 
the iron from the destroyed cells is retained 
in the body, the anemia is not hypochromic. 
Individuals who experience a protracted 
chronic relapsing infection may develop an 
intense anemia, probably of an aplastic 
character. 
Less striking but nevertheless noteworthy 
changes occur among the leucocytes. In 
general, particularly in the apyrexial inter¬ 
missions, these infections are characterized 
by a leucopenia, although at the time of 
a paroxysm a slight leucocytosis is evident. 
Furthermore, in the intervals between 
paroxysms there is noted a marked increase 
in the proportion of cells of the mononu¬ 
clear varieties, so that they fluctuate in¬ 
versely with the temperature. During these 
intervals the polymorphonuclear leucocytes 
decline from 70 to 50 per cent of the total 
leucocytes, while the mononuclear leuco¬ 
cytes rise from 25 to 45 per cent or even 
higher. The increase is most evident in 
the monocytes. As a paroxysm declines 
much phagocytosis of pigment by poly¬ 
morphonuclear leucocytes may be observed. 
(d) Serological methods. Serological 
methods of diagnosis are still in the experi¬ 
mental stage. One of these, based on the 
fixation of complement, appears to be of 
promise and will be discussed in the section 
on humoral immunity ( q.v .). 
(e) Biochemical methods. In 1927 
Henry, assuming that the “melanotic” and 
“yellow ferruginous” pigments formed in 
the tissues of malaria patients might either 
give rise to the formation of specific anti¬ 
bodies, or disturb the colloidal state of the 
serum so as to impart to it certain flocculat¬ 
ing properties, reported on certain tests 
designed to reveal such changes. These 
were designated as the melano-reaction and 
the ferro-flocculation tests, respectively, in 
which, owing to the difficulty of securing 
true malaria pigments, choroidal melanine 
and certain organic iron compounds were 
employed as “antigens.” The latter test 
soon fell into disuse but reports on the 
former indicate that it merited some con¬ 
sideration. It has, however, attracted but 
little attention in this country. 
As originally devised, choroidal melanin 
secured from ox-eyes was used as antigen, 
but difficulties in securing a uniform sus¬ 
pension led Greig, van Rooyen and Hendry 
(1934) to modify the test so as to employ 
melanin pigment extracted from human 
hair. 
The demonstration that melanin and or¬ 
ganic iron compound were antigenically 
inert, with the observation that positive 
melano-reactions were secured from the 
serum of patients ill with other diseases in 
which neither of these pigments were pro¬ 
duced, plus the further circumstance that 
