temperature falls rapidly and the pulse becomes slow and full. During this stage the patient, exhausted, falls into sleep. Within a relatively short time, rarely over four hours, often only two, the temperature reaches the normal. It does not, however, remain at this point, but becomes subnormal, and lasts so during the greater part of the intermission, or until after the beginning of another chill. The length of the entire paroxysm, from the time the temperature passes 99° until it again reaches that point on the downward course, averages eleven hours. These paroxysms are more frequent during the day than in the night, and the onset is usually during the morning hours, tho paroxysms during the afternoon and night are not unknown. After the immediate exhausting effects of the paroxysm have passed away, the patient very commonly feels perfectly well, so much so that he may leave his bed and go about his business. Indeed, many patients feel so well between paroxysms that they allow several to pass before seeking treatment, believing after each paroxysm that the fever is at an end. However, almost exactly 48 hours after the onset of the first paroxysm, a second similar attack follows, the febrile periods and intermissions continuing thus with great regu larity. Malarial Manifestations in Children. In children the clinical manifestations may be very different from those observed in adults. Frequently both the chill and the sweating stage may be quite absent or only abortive; under these circumstances the first stage is generally represented by a slight restlessness, the face looks pinched, the eyes sunken, the finger tips and toes become cyanotic and cold, while the child yawns and stretches itself. These may be the only manifestations of the first stage. Nausea and vomiting and diarrhea are very common. These symptoms are often followed by grave nervous phenomena. The chill in malaria, as in other acute diseases, is frequently in a young child represented by general convulsions. These may begin with a slight spasmodic twitching of the eyelids and extremities, the 'spasm soon becoming general. The febrile stage and the whole paroxysm are often shorter than in the adult, while the sweating stage may be entirely absent. Following the sweating stage the patient passes thru an afebrile stage, lasting usually 37 hours. Often during the greater part of this time the temperature is sub-normal. It is almost invariably so during the hours following the paroxysm. General History and Different Types of Malaria. Beyond the presence of parasites the blood shows usually little that is remarkable. If the infection has lasted for any great length of time, the evidences of acute anemia become apparent, such as pallor of the red corpuscles, marked difference in the size of the individual elements, and perhaps a little poikilocytosis. The most striking fact is that the number of the leucocytes is always sub-normal, while the large mono-nuclear forms are relatively increased at the expense of the polymorphonuclear varieties. The double tertian or quotidian types of intermittent fever are double infections, the parasites reaching maturity on alternate days and therefore giving rise to daily paroxysms. These differ in no wise from those of the single tertian type already described, unless they be a trifle shorter, lasting on an average only about 10 hours, consisting of the regular stages of chill, fever and sweating. The regularity in the recurrence of these paroxysms is not quite so great as in quartan infections. The chills on alternate days often come at hours surprisingly similar, the cause of this being hard to understand. Irregular or continued malarial fever is due probably to infection with multiple groups of parasites or to the lack of arrangement of the parasites in well-defined groups. This condition is rare in adults, being more often seen in children, where the malarial infections pursue a much less regular course. Single quartan fever. depends upon infec tion with the quartan parasite, whose cycle of existence is about 72 hours. This parasite also possesses the remarkable characteristic of appearing in the blood in large groups, all the members of which are approximately at the same stage of development. This form is not common in the United States, only occasional cases being met with. The paroxysms are quite similar to those of tertian fever, their duration being about the same, while the defervescence is also followed by a period of subnormal temperature which may last until the onset of the succeeding attack. Estivo autumnal fevers (summer-autumnal, or the so-called typho-malarial fevers) appear the latter part of July, in August, and especially in September and October. They are especially notable for a marked irregularity in their clinical manifestations, depending upon a third variety of parasite not fully studied as yet. It is observed clinically in many forms, the chief of them being probably the quotidian estivo-autumnal, with a materially longer paroxysm than in tertian, averaging nearly 20 hours, instead of 10 or 12. While the onset in the tertian quotidian is very sharp, the chill coming on very shortly after the initial rise, in estivo-autumnal fever of the quotidian type the rise is often more or less gradual, the paroxysm beginning with headache and general pains, while the actual chill, if at all observed, may not occur until some time after the temperature has become already elevated. Here the fall in the temperature is also much more gradual, and the regularity of the paroxysms is also much less. Estival tertian fever has intervals of approximately 48 hours between paroxysms. The longer the interval, usually the longer the paroxysm; these differing very markedly from those of regularly intermittent fevers. Their onset, tho sometimes quite rapid, is often very gradual. The chill is not infrequently wanting, and when present, comes on sometimes relatively late in the course. The general picture is so similar to typhoid that, without examination of the blood, confusion is sometimes inevitable. Altho the onset of the estivo type is not generally so alarming as the ordinary malarial types, it needs to be closely watched, because of its tendency to develop so-called pernicious symptoms. Pernicious or malignant forms of malarial fever are almost invariably from the estivoautumnal types of malarial fever. In a general way, the pernicious symptoms may be said to be due (a) to abundance of parasites present and their capacity for rapid multiplication; (b) to special involvement of certain vital organs; (c) to special malignancy of the parasite. The comatose type of malarial infection often begins with a period of excitement, perhaps delirium, frequently nausea and vomiting, rapidly followed by drowsiness, somnolence and coma. The pulse, at first slow and full, becomes rapid and feeble, the skin hot and dry, the tongue dry and coated. There is commonly slight jaundice of the skin and conjunctivæ, an important symptom. Examination of the lungs will generally be negative, tho the sonorous rales may be present. The cardiac sounds are generally clear. The abdomen is negative save for the palpable spleen. In a small proportion of the cases of this type, the spleen cannot be felt, and this may cause confusion with sunstroke, which this type of malaria closely resembles in its clinical manifestations. In fatal cases coma continues, the pulse is rapid, feeble and irregular, becoming quite impalpable before the death of the patient. In favorable instances the temperature, after remaining elevated for a certain length of time, begins to fall more or less rapidly, sometimes in association with sweating, while the patient gradually returns to consciousness." The algid type of malarial fever has often been confused with Asiatic cholera, presenting symptoms not unlike the algid stage of the latter disorder. The patient goes into profound collapse, the eyes being sunken, the features drawn, the skin cold and blue, while the body is bathed in a profuse sweat. The tongue is dry and tremulous, and is protruded with difficulty. The prostration is great, the patient being unable to raise his hand to do himself the slightest service. The pulse is sometimes not palpable at the wrist, while on auscultation the heart sounds are very rapid and feeble, the second sound perhaps being entirely absent. The temperature is very little if any elevated, the mind is usually clear to the last, tho the expression of the face is anxious and the voice husky. During the earlier stages, owing to the quiet listless condition of the patient, the severity of the case may fail to be appreciated, sometimes the first real alarm being awakened by the discovery that the patient is practically pulseless. Diagnosis. The matter of diagnosis is one of the first importance, since upon it depends treatment, etc. Hence the points of differentiation should be carefully observed. In tertian or quartan intermittent fever the regularity of the manifestations and the occurrence usually of the paroxysm with its three characteristic stages, the chill, fever, the sweating, are apt to render clear the diagnosis in typical cases. The presence of herpes on the lips and the nose is often of important assistance in forming the diagnosis. The presence of a wellmarked anemia may also be a distinct help, chiefly in distinguishing malarial infections from tuberculosis where the mucous membranes are usually of fairly good color tho the face may be pale. spleen is almost invariably demonstrably enlarged, and at times a slight enlargement of the liver exists. An important point is the peculiar grayish-yellow color of the skin, which is more or less characteristic. The In a number of other conditions somewhat resembling malaria in clinical manifestations, more especially those of a septic nature, paroxysms simulating those of malaria may occur, but the periods are distinctly shorter, even to being only six hours in duration. There is also not the same regular periodicity in diseases simulating malaria. There is most danger of confusion with tubercular disease of the lungs. It is safe to say that the majority of cases of pulmonary tuberculosis occurring in malarious districts in the country are, at some time in their course, mistaken for malarial fever. This confusion occurs at the stage usually present at some time in the course of phthisis where intermittent fever, often associated with chills, is present. In tuberculosis, apart from the pulmonary lesions, there is an absence of the sallow, yellowish-gray color so common in malaria. The mucous membranes are usually of a good color, while in malaria there is pallor. It is seldom that the spleen is demonstrable in tuberculosis, but it is almost invariably palpable in malaria. Herpes is unusual in the former and common in the latter. Still, if there is any doubt, scientific examination of the blood and sputa will settle the question. The blood in tuberculosis with intermittent fever shows generally a marked leucocytosis which is absent in malarial fever. The discovery of the malarial parasites is, however, the deciding point. Chills occurring during the course of gonorrhea or following catheterization or the passing of a sound are not infrequently confused with malarial paroxysms. The doubtful cases. urethra should always be examined in Grave and fatal cases of septicemia may, however, follow gonorrhea while there is little or no evidence of acute urethritis. The examination of the blood here, as in tuberculosis, will settle the culosis there is distinct leucocytosis, while question. In both gonorrhea and tuberin malaria there are only a normal or a reduced number of leucocytes, and the presence of the parasites. The examination of the blood is the one certain method of diagnosis,-the only manner in which a positive diagnosis of malaria is to be made. In rare cases tertian infections may show for a time continuous fever which may be confounded with typhoid. Yet, in almost all conditions which simulate malarial fever there is a well-marked leucocytosis, while in malarial fever the absence of leucocytosis, indeed even a reduction in the number of the leucocytes is the rule. The presence of an appreciable leucocytosis is strong evidence against the existence of uncomplicated malarial fever. At times, when there are very few parasites present, pigment-bearing leucocytes may be an important aid to diagnosis. The skilled observer can usually distinguish malarial pigment from extraneous particles. The differential diagnosis between tertian and quartan intermittent fever is usually readily made in the fresh specimen. The tertian organisms are larger, paler and more active, the pigment finer, brownish, more vigorously dancing, etc. therapeutic test of the rapid disappearance of the paroxysms under treatment by quinin is probably the best indication upon which to rely where the microscopic test is not available. The The estivo-autumnal fever more closely resembles typhoid, and for a differential diagnosis from clinical symptoms it is well to note the anemia in malaria, the sallow ness, the presence of herpes, etc. In addition there is the presence of the rose-colored petechiae in typhoid fever and of urticaria in malaria. Diagnosis of Malaria by Examination of the Blood. The importance of the demonstration of the malarial parasite has so often been pointed out, that it is well to give a description of the best methods for obtaining a specimen and conducting the examination. The following is the procedure at Johns Hopkins University: To examine the blood, use a 1-12 oil-immersion lens. Wash cover glases and slides carefully in alcohol and ether immediately before use, in order to remove all fatty substances. They should also be vigorously rubbed with a clean linen cloth, in order to facilitate the spreading of the blood, and thus conduce to easier and more accurate examination. The blood may be taken from any convenient part, but the place usually selected is the lobe of the ear, as it is less sensitive and more easily approached than the finger-tip, while a smaller puncture will draw more blood. It is often important that patients, especially nervous people or children, should not witness the process. The ear should first be thoroly cleaned. The lobe is then punctured with a small knife or lancet. A needle or pin may be used, but they cause more pain and are less satisfactory. If one desires to be especially careful, the ear may first be washed with soap and water and afterward with alcohol and ether, but in many instances it is advisable to make the preparation as short as may be, and in such cases, unless the ear or finger be extremely dirty, it is well to proceed at once. Pigment or epithelial scales coming from the surface are readily recognizable by the skilled eye. An instrument with a sharp cutting edge is taken in the right hand while the lobe of the ear is held firmly in 'the fingers of the left in such a way that the skin is held tense. If one proceed in this manner a very slight pressure will cause an incision deep enough for all purposes, while the process is almost painless. Let the first few drops be wiped away while a freshly cleaned cover glass held in a pair of forceps is allowed to touch the tip of the minute drop which next appears. This is placed immediately upon a perfectly clean slide. If the slide and cover are perfectly clean the drop of blood will immediately spead between them, so that, unless the amount be too great, the corpuscles may be seen lying side by side quite unaltered in their main characteristics. The drop of blood taken should be very small, unless the patient is anemic. It is inportant that the cover should touch only the tip of the drop of blood. If it be applied rudely, and perhaps pressed against the ear, the blood is so spread out that drying may begin at the edge of the drop before the glass is laid on the slide. If this be the case, the immediate spreading out of the blood between the slide and the cover does not occur. It is an error to exert any pressure whatever upon the top of the cover, neither should the cover be pushed or allowed to slide, all of these proceedings damaging the specimen. Another convenient and satisfactory way is to take the drop of blood from the ear upon a slide which is immediately inverted, and gently lowered until the tip of the pendent drop touches a clean cover glass lying on the table or bed. It is then lifted, the cover of course adhering to it. The blood usually spreads evenly between the two glasses. Such specimens will remain in good condition an hour or more, especially if vaselin or paraffin be placed about the edges. The parasites may thus be examined while yet alive and in active motion. Degenerative and regenerative processes may be followed out, and the most interesting examples of phagocytosis may be observed. For Staining Specimens of Blood. To prepare glasses for staining various methods may be used. They may be heated on a copper bar or in a thermostat at from 100° to 120° for two hours, or they may be placed in absolute alcohol and ether, equal quantities, for from to 8 hours, according to the stain used. The malarial parasite is well stained by most of the basic nuclear dyes. With Loeffler's methylene blue the red corpuscles remain unstained, while the nuclei of the leucocytes and the parasites are of a clear blue color. A good contrast stain may be obtained by first fixing the cover glass specimen in absolute alcohol and ether for from 4 to 24 hours. Then place it for from 30 seconds to five minutes in a five-tenths per cent. solution of eosin in 60 per cent. alcohol. Wash in water, dry between filter paper, and place from one-half to two minutes in a concentrated aqueous solution of methylene blue or in Loeffler's methylene blue. Then wash again in water, dry between filter paper, and mount in Canada balsam. The red corpuscles and the eosinophilic granules are stained a clear pink, while the leucocytes and parasites take on a blue color. To bring out most clearly the small hyaline bodies of estivo-autumnal fever, gentian violet may be used. Treatment of the Malarial Fevers. Malaria is one of the few diseases for which there exists a specific, and so long as quinin holds the position it does in the pharmacopeia there seems to be little use of seeking for another remedy. Laveran, Baker, Thayer and other authorities agree in the statement that so assured is the position of the drug as a specific for the malarial infection, that the fact of any given disease not yielding to its administration is the prima facie evidence that it is not a case of malaria. It cures the fever by killing the hematozoa, and its action can be watched under the microscope if desired, by allowing a weak solution of quinin to flow beneath a cover glass where there are some live specimens of the parasite. In the ordinary cases of simple intermittent fever quinin should be prescribed internally by the mouth, so high a dosage as 15 to 20 grains per day being often used. It is better borne when administered during the period of apyrexia. Quinin is most effective in solution; but, as it is difficult to administer in solution on account of the intense bitter taste, it would be well to give the drug in the form of tablets and follow these by an acid drink which will quickly dissolve the quinin in the stomach and aid in developing its therapeutic effects. In the grave forms requiring rapid intervention recourse should be had to the hypodermic method of administration. This mode must also be adopted when patients who are suffering from simple fevers do not easily stand quinin when administered by the mouth, also when vomiting occurs. Some writers advocate the use of enemata in such cases, but in prescribing enemata one can never be sure that the dose will not be rejected before absorption of the medicine has begun. It is also always impossible to gauge exactly how much has been absorbed. In prescribing quinin, whenever possible. preference should be given the hydrochlorates over the sulfate, as it contains 81 per cent. of pure quinin, and the sulfate only contains 53 per cent. It is more stable. more soluble, and more easily obtained pure than the sulfate. Quinin should be classified first from its proportion of alkaloid, and second from its solubility. The hydrochlorate is more expensive, but is prescribed in smaller doses. Because of its solubility it is the best salt for hypodermic use. When hypodermic use of quinin is indicated, the following may be used: B Quinin bihydrochlor.. grs. lxxv The solution is very acid to turmeric paper, but is not caustic. There is sometimes acute pain from its injection but this can be obviated by adding a little carbolic acid. Use the ordinary Pravaz syringe, making a separate puncture for every two injections, the absorption being easy and rapid under such conditions. If the bihydrochlorate or hydrochlorate is not obtainable in a case where hypodermic medication is desirable, use the following prescription: |