The parasites are thus present in the blood in great groups, all the individuals of which reach maturity and segment at approximately the same time. This explains the regular recurrence of the paroxysms at intervals corresponding to the time occupied by the asexual cycle of the parasite. Not infrequently there is multiple infection, one group reaching maturity while the others are still young; but the presence of two groups which segment upon the same day is extremely rare. Fevers of longer intervals—six, eight, ten days—are probably due to the ability of the body, sometimes of itself, sometimes by aid of quinin, to resist the parasites so that a number sufficient to cause a paroxysm do not accumulate in the blood until after several repetitions of the asexual cycle. In estivo-autumnal fever the regular grouping, while usually present at first, is soon lost, thus causing "irregular malaria."

(b) Sexual Cycle.—Besides the ameboid individuals which pass through the asexual cycle, there are present with them in the blood many individuals with sexual properties. These are called gametes. They do not undergo segmentation. Many of them are apparently extracellular, but stained preparations usually show them to be surrounded by the remains of a corpuscle. In tertian and quartan malaria they cannot easily be distinguished from the asexual individuals until a variable time after the blood leaves the body, when the male gamete sends out one or more flagella. In estivo-autumnal malaria the gametes take distinctive ovoid and crescentic forms, and are not difficult to recognize. They are very resistent to quinin and often persist in the blood long after the ameboid forms have been destroyed, but are probably incapable of continuing the disease until they have passed through the cycle in the mosquito.

When a malarious person is bitten by a mosquito, the gametes are taken with the blood into its stomach. Here a flagellum from the male unites with the female, which soon thereafter becomes encysted in the wall of the intestine. After a time it ruptures, liberating many minute rods, or sporozoites, which have formed within it. These migrate to the salivary glands, and are carried into the blood of the person whom the mosquito bites. Here they enter red corpuscles as young malarial parasites, and the majority pass through the asexual cycle just described.

FIG. 79.—Mosquitos—Culex (1) and anopheles (2) (Bergey).
FIG. 80.—Showing, on the left, anopheles in resting position, its dappled wing, and the position of its larvæ in water; on the right, culex in resting position, its plain wing, and the position of its larvæ in water. The arrows indicate the directions taken by the larvæ when the water is disturbed (Abbott).

The sexual cycle can take place only within the body of one genus of mosquito, anopheles. Absence of this mosquito from certain districts explains the absence of malaria. It is distinguished from our common house-mosquito, culex, by the relative lengths of proboscis and palpi (Fig. 79), which can be seen with a hand-lens, by its attitude when resting, and by its dappled wing (Fig. 80). Anopheles is strictly nocturnal in its habits; it usually flies low, and rarely travels more than a few hundred yards from its breeding-place, although it may be carried by winds. These facts explain certain peculiarities in malarial infection; thus, infection occurs practically only at night; it is most common near stagnant water, especially upon the side toward which the prevailing winds blow; and the danger is greater when persons sleep upon or near the ground than in upper stories of buildings. The insects frequently hibernate in warmed houses, and may bite during the winter. A mosquito becomes dangerous in eight to fourteen days after it bites a malarious person, and remains so throughout its life.

(2) Detection.—Search for the malarial parasite may be made in either fresh blood or stained films. If possible, the blood should be obtained a few hours before the chill—never during it nor within a few hours afterward, since at that time (in single infections) only the very young, unpigmented forms are present, and these are the most difficult to find and recognize. Sometimes many parasites are found in a microscopic field; sometimes, especially in estivo-autumnal infection, owing to accumulation in internal organs, careful search is required to find any, despite very severe symptoms. Quinin causes them rapidly to disappear from the peripheral blood, and few or none may be found after its administration. In the absence of organisms, the presence of pigment granules within leukocytes—polymorphonuclears and large mononuclears—may be taken as presumptive evidence of malaria. Pigmented leukocytes ([Plate VI]) are most numerous after a paroxysm.

(a) In Fresh Unstained Blood (Plate VII).—Obtain a small drop of blood from the finger or lobe of the ear. Touch the center of a cover-glass to the top of the drop and quickly place it, blood side down, upon a slide. If the slide and cover be perfectly clean and the drop not too large, the blood will spread out so as to present only one layer of corpuscles. Search with a one-twelfth-inch objective, using very subdued light.

The young organisms appear as small, round, ring-like or irregular, colorless bodies within red corpuscles. The light spots caused by crenation and other changes in the corpuscles are frequently mistaken for them, but are generally more refractive or have more sharply defined edges. The older forms are larger colorless bodies containing granules of brown pigment. In the case of the tertian parasite, these granules have active vibratory motion, which renders them conspicuous; and as the parasite itself is very pale, one may see only a large pale corpuscle in which fine pigment-granules are dancing. Segmenting organisms, when typical, appear as rosets, often compared to daisies, the petals of which represent the segments, while the central brown portion represents the pigment. Tertian segmenting forms are less frequently typical than quartan. Flagellated forms are not seen until ten to twenty minutes after the blood has left the vessels. As Cabot suggests, one should, while searching, keep a sharp lookout for unusually large or pale corpuscles, and for anything which is brown or black, or in motion.