I have found that in treating the ordinary agues of Great Britain, there is a decided advantage in employing large doses given only in the intermission. In the case of an ague of moderate severity, and which has not yet lasted very long, a tertian for instance of not more than two or three weeks' standing, the best plan is to order one twenty-grain dose to be taken on the day on which the fit is expected, and about an hour before the time at which it habitually occurs. In quotidian ague, especially when it has lasted for some time, or has become quotidian from being previously tertian or quartan, at least twenty grains should be given every day, also about an hour before the expected attack is due. In quartan ague it is not always sufficient to give one large dose on the day when the fit is due; for some unknown reason the quartan type is frequently more obstinate than would have been supposed from the rarity of the fits; and I have usually found it best in these cases to give one ten- or fifteen-grain dose every day, some time before the hour when the fit occurs.

1 See especially Appendix E to the "Beginnings of Life," vol. ii. Macmillan, 1872.

In the severe forms of intermittent fever which are met with in tropical countries, it is probably always well to employ large doses; and it is not unfrequently necessary to give the medicine during the paroxysm, as well as in the periods of intermission. The pernicious remittents still more often require the use of large and continuous doses of quinine; thirty to fifty or sixty grains1 may be given in very severe cases several times a day, and without any special regard to the presence or absence of exacerbation. At the present day we have no reason to dread giving quinine during a paroxysmal period; on the contrary, we reckon quinine among our most active reducers of febrile temperature, and there can be no possible reason for withholding it when other considerations point to the advisability of speedily impregnating the system with it. Whether the fungoid theory of malaria be true or not, it is certain that something like the saturation which is necessary to produce an effect upon low organisms is by far the most effective way of dealing with any malarial fever which is heavily oppressing the system. It will be best at once to go on to the production of decided though not severe cinchonism. As soon as the ringing noise in the ears is fairly set up, we shall in almost every case observe a marked abatement in the fever; and a gentle perspiration is often the immediate forerunner of entire or partial convalescence.

It is not only in cutting short the typical symptoms of malarial fever that quinine is valuable; the majority of the complications of these diseases, of whatever kind they may be, yield better to the treatment by quinine than to any measures addressed immediately to the organ that appears to be suffering. Among these complications of ague, one of the most remarkable is the tumefaction of the spleen which forms the so-called "ague-cake;" and in a less degree the liver is liable to a similar change. I have rarely seen the slightest good effected by measures locally or specially addressed to these organs when so affected; nor indeed will quinine always produce an impression; but, at least in the majority of such cases, the action of quinine in reducing enlarged spleen is not less decided than its influence in cutting short the course of the general feverish symptoms. It is so likewise with the intense gastric irritability, causing incessant vomiting, which is almost universal in bad remittents; nothing quiets the stomach half so effectually as the production of full cinchonism. And the distressing pain and heat of the head, which drives such patients almost frantic, is also far better treated by the influence of quinine than by any local or other remedies for the mere symptoms. In regard to all these matters the profession owes much to Dr. Maclean and other recent Indian writers for the decisive courage with which they have put aside all temporizing measures, and have both practised and taught the radical treatment by quinine in sufficient doses to affect the system fully.

1 It is right to say that so experienced an authority as Dr. Maclean deprecates the use of larger doses than fifteen or at most twenty grains. But the limit is too strict to suit all cases.

Although we may have full trust and confidence in the benefits conferred by a bold and unshrinking use of quinine in the acute stages of fever, there is no reason, however, why we should be reckless in the doses we employ, and more especially in the continuance of large doses beyond the necessary period. This remark gives me the opportunity to notice what I believe is the sole fact which keeps up the belief in the truth of Hahnemann's assertion that bark can produce intermittent fever. A great many, perhaps the majority of those persons who have ever been seriously affected with malarial fever, and have experienced the marvellous benefits of quinine, get into the habit of taking it upon the smallest indication of illness, and in quantities which are often extravagant. This cannot be done with impunity; it throws the nervous system at least into a state of great commotion. And we know very well that great nervous disturbance, from whatever cause arising, is a powerful influence to bring back the phenomena of ague in a person who has once suffered from them; for there are great numbers of persons who live quite comfortably on condition that they pass tranquil and carefully guarded lives, but who immediately suffer from a relapse of aguish symptoms when they happen to be exposed to harassing emotions, or anything else which much distresses the nervous system. And thus it may be said with truth that though quinine is quite unable to produce intermittent fever in a healthy person, its untimely and improper use by a person formerly aguish may very easily reproduce the paroxysm with greater or less severity. I have witnessed many examples of this occurrence, more especially in Americans and Indians who come from districts where malaria appears to be a more serious matter than in England.1