Intermittent Fever—Simple Forms

The clinical phenomena of intermittent fevers afford strong support to the opinion that this type of malarial attacks illustrates more strongly than any other the primary influence of the poison upon the human system. Fits of ague often occur very shortly after exposure in infected localities, and the persons thus suddenly attacked may present little or no evidence of cachexia before or after the paroxysm. Indeed, they frequently resume their ordinary avocations after the paroxysms, apparently as well as if they had not occurred.

It is therefore my opinion that the pathology of an intermittent fever does not necessarily involve an hypothesis that the attacks are the results of certain changes which the poison undergoes after its inception, nor, on the other hand, that certain perversions of systemic chemistry are required to inaugurate the paroxysms.

In accordance with these conclusions, it seems likely that the phenomena of intermittent malarial fever result from the primary effects of its specific poison exerted directly upon the fluids and solids of the system, and disturbing their functions, and especially the nerve-function.

Those malarial attacks which ensue almost immediately after exposure are principally manifested in persons exposed at points of unusually abundant evolution. The rule of malarial attacks in temperate latitudes is, that they require repeated exposure to infection for their production. The long residence of the poison in the system may render additional doses possible, until a point of saturation is reached which occasions paroxysmal explosions. In these cases the period of incubation is reckoned from the first date of exposure, thus forming the most striking contrast with the incubative periods of the cases occurring almost immediately after exposure.

Whether the quiescent period after exposure to malaria be long or short, attacks are seldom abrupt in their announcement. The symptoms which usually precede pronounced attacks consist, for the most part, in some derangement of the functions presided over by the organic nervous system. Derangement of digestion, vitiated taste, coating of the tongue, loaded urine, and sallow skin are ordinarily found among the prodromic symptoms. Next in succession come feelings of malaise, hot and cold flushes, and those neuralgias which precede and attend malarial paroxysms.

The symptoms of an ordinary or typical malarial paroxysm are so characteristic, as to be generally readily interpreted. Creeping, chilly, sensations over the surface, especially along the spine, yawning, livid coloration beneath the finger-nails, retreat of blood from superficial capillaries, and that consequent papillary elevation which is commonly called goose-skin, comprise the earliest symptoms. Then decided shiverings with chattering of the teeth come on, and the patient asks for blankets to be heaped upon him and hot applications to be made, even though the atmospheric temperature may be decidedly elevated.

Nausea and vomiting are frequent symptoms, no doubt due to the fact that the portal system of blood-vessels is so often the seat of congestion during a chill. No intelligent practitioner can watch a patient during the cold stage of a malarial paroxysm without realizing how important the attendant congestion is as a pathological state. It should first be considered that every chill necessarily implies a condition of congestion in some part of the system. The blood driven from the surface and extremities must be accounted for elsewhere; and the amount of blood which is lost from one part of the circulatory tree must correspond with that accumulated elsewhere. But in treating of the pernicious forms of malarial fevers this question will again receive notice.

In our present state of knowledge we are no more able to explain those perversions of the normal action of the physical forces of the system which occasion the phenomena of a chill than we are to explain how the altered circulation in the first steps of an inflammation is brought about. The theory which Cullen adopted is quite as explanatory and consistent as any which has been promulgated since his time. According to this, a state of spasm of the arterioles and capillaries causes the chill, while the fever is merely the rebound of functions held in abeyance during the chill.

After a variable length of time there occurs a change in these symptoms: the patient begins to remove the blankets which covered him; the face shows signs of returning circulation; the veins of the whole surface gradually fill again, apparently beyond their normal state. But the reaction goes far beyond any normal physiological state. The face becomes flushed and the eyes injected, and the patient complains of headache, thirst, dryness and heat of the surface; he will not permit any covering, and constantly shifts his place in the bed in the hope that some new position may afford him more comfort. Nausea and vomiting are commonly present. If the fever runs high, delirium is apt to occur. The thermometer seldom shows a temperature above 105°, but I have seen 106.5° recorded in the axilla in the hot stage of a paroxysm of simple intermittent fever.

The duration of the hot stage is different in different cases. According to Aitken, the mean duration is three to eight hours.

There is a very old and quite well-supported opinion, that the cold stage is shorter in the quotidian than in the tertian type, and also that the hot stage is longer in the former than in the latter. It may certainly be affirmed that in individual cases of either type there is no fixed relation between the duration of the chill and that of the hot stage.

The decline of the hot stage begins by the appearance of a gentle perspiration, limited at first to the forehead, face, and neck. This gradually extends itself over the surface and increases in quantity until the whole body is bathed in a profuse sweat. During this period the patient's symptoms, both subjective and objective, undergo wonderful mitigation, and, although this stage is usually short, it often happens that by the time it is concluded a restoration to ordinary health seems to have occurred.

The sweating stage terminates a malarial paroxysm. The intermission now begins, and lasts until the inauguration of another paroxysm. The intermission is longer or shorter accordingly, first, as the paroxysm occupies less or more time; and, second, as the interval may affect it. The interval is that period of time which reaches from the beginning of one paroxysm to the beginning of another. It therefore furnishes the basis of classification of simple intermittents into the following forms: quotidian, tertian, and quartan.

Statistics gathered from a great many sources and relating to many countries and climates indicate that quotidian intermittents are more common than tertian. It may then be assumed that the natural type of intermittents is that form characterized by diurnal paroxysms. It must be remarked, however, that if any natural law does exist establishing the quotidian as the typical form of intermittent fevers, it is very often set aside by unknown influences. In certain epidemics the tertian cases preponderate, and under all circumstances convertibility may be witnessed between the various forms.

It is probable that the statistics gathered by the medical staff of the United States Army during the late Civil War afford the most valuable data which we possess touching these points, in so far as they relate to this country. During three years of the war 724,284 cases of intermittent fever were recorded, tabulated as follows:

Quotidian, 370,401 cases, 388 deaths—equivalent to 1047 + deaths per 1,000,000 cases.

Tertian, 318,704 cases, 324 deaths—equivalent to 1007 + deaths per 1,000,000 cases.

Quartan, 35,179 cases, 79 deaths—equivalent to 2245 + deaths per 1,000,000 cases.

It has been remarked by several writers that quartan attacks have a smaller ratio in the Southern States than in other parts of the Union. My observations on this point have not been sufficiently well recorded to make them especially authoritative, but they support such a conclusion.

The morbid anatomy of malarial fevers is more properly discussed in treating of the graver forms, since the paroxysms of simple intermittent do not often occasion death.

TREATMENT.—This must necessarily vary with the stage of the paroxysm and condition of the patient at the time of the first visit.

Let us suppose this to be the incipiency of the paroxysm, or the early part of the cold stage. However little the danger to life from the paroxysm of a simple intermittent attack, the practitioner should not forget that whatever danger does exist is to be ascribed to damages suffered during or in consequence of the chill. There are few exceptions to this rule, and those will be noticed presently. With this fact in view the practitioner's duties are much simplified. He should first endeavor to remove any complications present which tend to aggravate the cold stage. If the chill has come on after a full meal or after eating indigestible food, the stomach should be promptly emptied; otherwise the cold stage will be prolonged and rendered more violent. Large draughts of warm water will frequently produce sufficient emesis. If this should fail, ipecacuanha may be added. The warm infusion of eupatorium perfoliatum answers well as an emetic, producing also a laxative effect. But it is disgusting to the palate, and sometimes prolongs its action beyond desired results. The effect of an emetic in abridging a chill by revulsive action are uncertain, and I avoid resorting to them for this purpose alone in simple intermittents.

The patient's subjective complaints of suffering should receive a due degree of attention. Additional blankets and warm applications should be allowed when solicited. I always discourage hot or heating drinks, except for the purpose just mentioned. I especially oppose alcoholic stimulants, because they seldom do any good in mitigating the chill, oftener aggravating the patient's symptoms during the hot stage, particularly the headache and vomiting, and sometimes directly occasioning perplexing perturbations. For example, I have seen convulsions speedily follow a strong brandy toddy given to shorten a chill.

While the removal of complications is imperatively indicated, it is also important to use promptly those means which are designed to modify and shorten the chill. It is a remarkable fact that all the agents found to be useful for this purpose are such as directly influence nervous function. Opium in some form enters into all prescriptions which I have found efficient in modifying a chill. It is quite efficacious when given alone, but I think its therapeutic energy and certainty are increased by the addition of other agents of the same class. I have often exhibited twenty to thirty drops of chloroform with an equal quantity of laudanum with excellent results. The tincture of opium may be combined with aromatic spirit of ammonia, or with bromide of potassium, or with chloral hydrate. In combination with either of the latter medicines it may be given by rectal injection. If the stomach is intolerant, or by preference because of facility of dosage and quickness of effect, the opiate may be given hypodermically. For this purpose one-sixth to one-quarter of a grain of morphia may be given, together with one-sixtieth to one-fortieth of a grain of atropia. It is rarely necessary to repeat the dose whichever form may be adopted.

After much experience in these methods of mitigating and abridging the chills of intermittent fever, I feel entitled to say that, whether the objects be achieved or not, no injurious consequences ensue.

The conditions of the circulatory and digestive organs are not favorable for the introduction of quinia or of any preliminary purgative which may be supposed to be necessary, and I therefore delay their exhibition. It may be excepted, however, that sometimes a very obstinately irritable stomach or exceedingly vitiated state of the fluids can be appropriately met by gr. x to xx of calomel.

The hot stage of a simple intermittent seldom calls for medical interference on account of excessive temperature. If the headache is very violent or the vomiting troublesome, a subcutaneous dose of morphia will bring speedy relief. The existence of high temperature does not contra-indicate its use.

I am in the habit of giving opium in the following combinations:

Rx. Morphiæ Acet. gr. ss;

Liq. Ammon. Acet. fl. oz. iv. M.

S. Two tablespoonfuls every second hour.

Or, occasionally, the following:

Rx. Sodii Bicarb. gr. xx.

Morphiæ Sulph. gr. i;

Aquæ Lauro-Cerasi,

Aquæ Menth. Pip. aa. fl. drachm iv. M.

S. Teaspoonful pro re nata.

I do not limit the use of opiates in the hot stage to old and infirm subjects, as Dickson suggests, but give them in all cases where vomiting, headache, or other neuralgias are excessive, or where unusual restlessness and jactitation are present.

The propriety of giving purgatives as a preliminary measure of treatment during the hot stage must be determined by symptoms connected with individual cases. In the majority of cases falling under my care purgatives are avoided. When regarded necessary, gentle purgation is solicited by administering bitartrate of potassium in lemonade or by combining mild mercurial doses with antiperiodics when these latter are resorted to during the fever. In some cases a very furred tongue, sallow skin, and costive bowels indicate more active purgatives, which may be exhibited during the febrile stage.

The most important question which relates to medication during the hot stage is in respect to the administration of antiperiodics. It may be safely stated that practitioners of this country were the first to adopt this method of procedure in malarial fevers. Here it has been well demonstrated that a competent dose of quinia, given during any part of the hot stage, is so often followed by the defervescence of the fever that it would be illogical to attribute the change to any other cause. Sometimes the remedy fails in producing this result; then excessive physiological disturbances may follow, and perhaps some general aggravation of the patient's symptoms.

There are four different circumstances, each of which, in my opinion, calls for the exhibition of quinia during the hot stage, whether the fever has reached its maximum point or not:

First. If the period which has elapsed since the beginning of the paroxysm is so considerable that further delay might prevent sufficient cinchonism to intercept the next accession.

Second. When the fever is so excessive that quinia should be given as an antipyretic.

Third. When apprehensions exist that the fever will occasion some complication or accident.

Fourth. When the tongue is clean and the state of the system is favorable to absorption.

The hot stage is not usually favorable to absorption, and consequently the economical use of quinia must not be attempted. It should be given in doses varying from ten to twenty grains, preferably in solution. I may remark that I have seldom failed in getting good results from the powder or pills if lemonade or some fluid facile of absorption be given at the same time. The mixtures previously formulated answer this purpose very well, and at the same time mitigate the disagreeable physiological effects of the quinia.

Allusion has been made to certain symptoms occasionally connected with the hot stage which involve danger. Convulsions are among the most important of these. They occur most often among children, but occasionally with adults. They should be met by chloroform, cold to the head, hypodermic injection of morphia, and cupping or leeching if the face is flushed, the eyes injected, and the carotids pulsating forcibly.

The sweating stage may be classed with the intermission in respect to medication. No time should be lost in securing cinchonism. From the moment the sweating stage announces itself the fluids of the system begin to resume their normal physiological functions. Absorption from the intestinal surfaces is again restored, and remedies may be administered with confidence in their effects.

The question is now no longer whether antiperiodics should be administered, but how they shall be given. Many practitioners prefer exhibiting them in one large dose; others think it better to give them in repeated small doses. I have usually adopted the latter method. Beginning with the sweating stage, I give three grains of quinia every hour or two hours, until eighteen grains have been taken. This would occupy periods of five to ten hours to complete the doses, ordinarily quite a sufficient length of time to obtain cinchonism before the advent of another paroxysm. If the physician elects to give his antiperiodic in one or two large doses, he should not trust to so small an amount as eighteen grains. Allowance must be made for the loss incident to the probable over-taxation of the power to dissolve and receive a large amount into the circulation.

Purgation should not be induced to a sufficient degree to hurry the quinia off before absorption takes place. Some practitioners favor the employment of adjuvants to the quinia. Very few of these have appeared to me to be of service except opium. A very convenient formula is a solution of quinia in peppermint-water by addition of dilute sulphuric acid, in such proportions that fl. drachm j of the solution shall represent five grains of quinia and seven and a half drops of laudanum.

But, however we may boast of the efficacy of cinchona as the anceps remedium for malarial diseases, we are forced to admit that it is not certainly an immediate cure, and very commonly fails in producing a permanent curative effect. If we could in all cases discern and remove the impediments to its immediate or temporarily curative action, its claims to be regarded as a practical specific would be undeniable. It is probable that these impediments generally rest upon the fact that either the remedy does not gain admission to the circulation or that some complication exists not within the range of its therapeutic action.

The failure of cinchona to cure a malarial attack in such a permanent manner that it shall not be liable to return is probably owing to the incompetent action of the drug because of its transitory stay in the system as compared with that of the malarial poison. Some objections apply to this theory, because when the succession of intermittent attacks is broken by quinia and it is continuously administered afterward, the paroxysms occasionally recur in spite of its presence in the system. These objections may be answered by pleading that under these circumstances secondary blood-poisons precipitate the attacks, and cinchona should not be expected to cure these conditions.

The best methods of practice I know of to prevent a recurrence of intermittent fever after having interrupted the succession of attacks are, first, to continue the cinchona for at least forty-eight hours, giving at least three three-grain doses a day. After this no medicine need be given except such as may be required to correct chronic toxæmic states of the system or to act as blood-restoratives until such time as prodromes of another paroxysm may exhibit themselves. At the instant when these manifest themselves ten to fifteen grains of quinia in solution should be taken. In order that no loss of time should occur in applying this method, I always advise patients to keep a solution of quinia within immediate reach. The following prescription has sometimes appeared to effect a permanent exemption from recurrence of paroxysms:

Rx. Ferri Redacti gr. xl;

Acid. Arseniosi gr. j;

Quiniæ Sulph. gr. xl;

Ol. Pip. Nigr. gtt. x. M.

Ft. pil. No. xx.

S. One pill three times daily.

It seems sometimes to occur that intermittent attacks so impress the nervous system that they become, like epilepsy, more liable to recur because of an established habit. I have known chills to occur when the ears were ringing with quinia. Strychnia fails to arrest them; arsenic has more value, but frequently fails. Pure nitric acid, properly diluted, in doses of six to ten drops, given every four to six hours without regard to the stage of the paroxysm, succeeds more often than any medication I have ever resorted to.

Before dismissing the subject of the treatment of simple intermittent fever it may be proper to mention that I have made trials of cure by carbolic acid, administered by mouth and subcutaneously, and also of the sulphites, with no results worthy of recommendation.