A few large doses at short intervals until the necessary quantity is reached, or a single maximum dose if the stomach is tolerant, should be prescribed, rather than a succession of smaller doses. The rapidity with which elimination takes place is a sufficient reason for adopting the former mode of administration. The effect of quinine is not less happy in the fevers of childhood, and comparatively large doses are well borne at this period, as Jacobi, especially, has shown us. The same rule should be followed as in the case of adults: to give the amount required in several doses within a brief period—an hour, according to Liebermeister—or at one time. The antipyretic use of quinine should not be confounded with its tonic or supporting qualities. In the treatment of fevers, the typhoid state, or the condition of adynamia supervening daring the course of fever, small doses (two, three, or four grains), at short intervals, are employed for the stimulating effects which they have on the organs of circulation, respiration, and digestion. Large doses, as has been set forth, depress these functions.

In cerebrospinal meningitis, doubtless a continued fever with cerebro-spinal lesions, quinine is indicated under the conditions already defined for the treatment of other inflammations, viz., in the beginning of the disease, when the alterations of cutaneous sensibility first occur, and before the febrile movement has developed. If a few large doses—twenty to thirty grains—do not produce a good result, it is useless to repeat them, or to pursue a tentative plan with small doses.

In the treatment of the eruptive fevers, variola, scarlatina, rubeola, quinine has an important place. It is used in small doses, frequently repeated in adynamic states, and in large doses at longer intervals to reduce hyperpyrexia. In scarlet fever, Dr. Hood especially urges the use systematically of quinine from the earliest stage of the disease, preceded by an emetic and purgative, and he states as the result of this practice that since he has adopted it he has not lost a single case of this disease treated by him from the beginning. In measles, large doses of quinine have an unquestionable utility in relieving the catarrhal pneumonia, and in preventing those changes in the exudation products which end in caseation.

The treatment of malarial diseases by quinine is the most successful contribution ever made to practical therapeutics. No adequate explanation of its action had been offered before Binz suggested that its germicide power was the real source of its therapeutical activity. It was not, however, until Laveran discovered the flagellate organism and pigmented bodies which develop in the blood of those infected with malarial poison, that Binz's theory received support of a satisfactory kind. Laveran's discovery, made in 1881 in Algiers, has since been confirmed by Italian, French, and American pathologists, so that the long-sought cause of malarial infection may now be regarded as a known fact. The parasite consists of a pigmented body in the interior of the red blood-corpuscles—pigmented granules of various shapes free, and flagellate organisms, both having amoeboid movements, the filaments of which engage in active vibration.

The alkaloids of cinchona are employed as prophylactics against malarial infection. The experience of the English naval service, of crews engaged on the coast of Africa in the suppression of the slave-trade, of the expeditionary force into Ashantee under Lord Napier, and of our late civil war, has abundantly shown that quinine is in a high degree prophylactic. The first public reference to this property seems to be that of Dr. Bryon in 1854, who called attention to the success which attended its use among the crews of the British vessels serving on the coast of Africa. Since that time, for several years the statistical reports of the British naval medical service have contained conclusive evidence on this point. Dr. Joseph Jones has published since the close of the civil war some valuable statistical data, showing the efficiency of quinine as a prophylactic. The troops who were the subjects of experiment were stationed in a highly malarious locality. Of the number, 230, who took no quinine, 134 had fever. Of those who took quinine irregularly, 246 in number, 96 had fever. Of the 506 who took quinine regularly, 98 had fever. The proportion of cases of fever was, therefore, 1 to 5·66 men. On the coast of Africa, the proportion has varied from 1 in 8 to 1 in 20. Of the unprotected, more than one half —on the coast of Africa, three fourths—were attacked by malarial disease in some form. As the quantity of quinine daily taken has been usually three to five grains, it is probable that the results would be even more favorable if a larger quantity of the prophylactic were given. When the poison is not intense, this amount may be sufficient, but if concentrated and active, and the conditions are otherwise unfavorable, twice as much should be administered daily. An enormous experience has now shown that quinine is entirely free from injurious effects when taken as a prophylactic. It is probable that the influence slowly decreases, and that some addition to the daily quantity may be necessary after a time. The prophylactic dose should be administered on rising in the morning, and may be usefully prescribed in a cup of black coffee, or in pill-form. The practice adopted in the civil war, of giving whisky as the vehicle, is not to be commended. If the quinine administered fail to prevent the disease, those attacked will suffer far less severely than the unprotected. Experience has shown that, to be entirely efficient, the quinine must be administered for some time, at least ten days, after exposure to the causes of fever (Jones).

The mode of using quinine for the cure of intermittents may be formulated as follows :

The antipyretic is nearly equally effective whether administered in the interval or during the seizure.

Tf time is an element of importance, no delay is necessary in order to give the remedy in the stage of apyrexia.

To save the suffering and exhaustion of the febrile movement, the attack should be anticipated, and, if possible, prevented.

As the maximum effect of the quinine is attained in about five hours after being taken, it should be administered this period of time, at least, before the expected paroxysm.

As the elimination of quinine takes place with considerable rapidity, the maximum curative effect is obtained by the administration of the whole amount required in a single dose, rather than by a succession of small doses (Prize Essay).

An intermittent may be successfully treated by giving, during the interval, a number of small doses frequently repeated. The author is convinced by extended observation that a full dose of quinine (ten grains) in the sweating stage, and the same quantity five hours before the time of the next paroxysm, is the more effective method. The anti-periodic property of quinine is increased, and the cerebral effects of large doses diminished, by combination with morphine. It is well known that intermittents, arrested by quinine or other anti-periodics, manifest a tendency to recur about the septenary periods; therefore, ten to fifteen grains of quinine should be administered in anticipation of these recurrent paroxysms, until the third septenary period has passed. Meanwhile, the organs damaged by the malarial infection—intestinal canal, liver, spleen, kidneys, etc.—require appropriate treatment. The action of quinine is much assisted by the continuous administration of arsenic during the intermissions, and until the third septenary period has passed. The unpleasant cerebral effects of quinine are lessened or prevented by the simultaneous administration of diluted hydrobromic acid: Rx Quininae sulph., 3 j ; acid, hydrobromic. dil., 3 ij ; aquae, 3 xiv. M. Sig.: One or two teaspoonfuls at a dose.

In the treatment of remittent fever two modes of using quinine are employed: first, by emetics, purgatives, baths, diaphoretics, etc., to secure a distinct remission when the remedy is administered ; second, to give it in sufficient dose immediately, relying on its apyretic effect. The author is convinced that the latter plan is preferable: from twenty to thirty grains in a single dose once or twice each day until the temperature is reduced to normal. This use of the remedy need not interfere with other appropriate medication.