PROPHYLAXIS OF MALARIA. 
83 
quinine. In stained preparations the morphological changes are 
much more apparent, consisting in poor staining reactions of the 
cytoplasm, while the chromatin of the nucleus stains darker and is 
stainable long after the cytoplasm has ceased to stain; the preven¬ 
tion of normal increase in the amount of chromatin, as shown by the 
plasmodia containing much less of this material at certain stages of 
growth than normal; the prevention of normal division, as shown by 
plasmodia in which only a portion has divided, thus producing 
atypical sporulating forms; and sporulating forms in which many 
of the spores or merozoites are devoid of chromatin. Many of the 
organisms show undoubted evidences of fragmentation in the stained 
preparations. The changes observed are present at every stage in 
the development of the organism except when quinine has been given 
just before sporulation and in the fully-developed gametes. 
Plasmodium malariae (quartan plasmodium ).—The changes pro¬ 
duced by quinine, as shown in fresh and stained preparations of 
blood containing Plasmodium malariae , are essentially the same as 
those produced in Plasmodium vivax , and while there is some 
evidence that this species is slightly more resistant that the tertian 
plasmodium my observations showed that even the older parasites 
were affected, just as in the case of the tertian species. 
The estivo-autumnal plasmodia. —In both species of estivo- 
autumnal plasmodia quinine produces practically the same changes 
as in the tertian and quartan species, except that fragmentation is 
not so frequently observed. The crescentic gametes of the estivo- 
autumnal plasmodia appeared unaffected by quinine so far as any 
morphological changes are concerned. 
My observations proved that the old theory that only the young 
spores are affected by quinine and that the drug must be in the 
blood at the time of sporulation is untenable, for while the merozoites 
are undoubtedly more easily affected by the drug than the older 
forms, the changes in morphology of the schizonts almost up to the 
time of sporulation demonstrate conclusively that quinine causes 
degeneration in even the older plasmodia. Recent observers have 
confirmed my observations regarding the action of quinine upon the 
later stages in the development of the plasmodia and upon the mor¬ 
phological changes that are produced in these organisms by the drug. 
Rieux 41 studied the action of the drug upon the tertian plasmodium 
and found that not only were the young schizonts affected, but that 
if the drug was commenced 24 hours after the paroxysm when the 
schizonts were half grown many of them Avere arrested in develop- 
ment and fragmentation occurred in a considerable percentage. He 
found that the sporulating bodies were not affected, but that the con¬ 
tinued use of quinine caused degeneration of the gametes and eventu¬ 
ally a disappearance of these forms from the peripheral blood. Bil- 
