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 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. The 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. 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. unusual in the former and common in the latter. Still, if there is any doubt, scientific I 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 deciding point. the malarial parasites is, however, the 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. Grave and fatal cases of urethra should always be examined in 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, brownIn ish, more vigorously dancing, etc. The 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. 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. 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 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 petechiæ 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. If The drop of blood taken should be very It is small, unless the patient is anemic. 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. 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 Aquæ dest. . . . q.s. drs. ijss Sig. Sixteen drops to the injection. 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: acute pain. A small nucleus of induration forms at the level of the puncture. Most generally that nucleus vanishes and becomes absorbed, but sometimes an abscess or dry eschar about the size of a dime or even as large as a quarter dollar may form and afterward slowly separate. Sometimes larger eschars or even diffuse inflammation has been observed; but these are quite exceptional, and not the injection but the way of making it is to blame. The hypodermic method allows quinin to be introduced into the general circulation pretty nearly as quickly as the intravenous injection. The latter is only allowable in the most grave pernicious attacks when it might be feared that the hypodermic method would not allow the quinin to be introduced quickly enough into the blood. It has often been considered sufficient to cut short the fever with two or three doses of quinin, waiting for a return of the fever to recommence the treatment. In the opinion of leading physicians the endeavor should be to prevent relapse by the help of repeated treatment. Unless this is done, only a few attacks are suppressed, as the parasites, stopped for a time in their development, very soon increase and all has to be gone over again. Practice shows that two or three doses are often enough to arrest an ordinary intermittent fever, but that it often reappears at the end of seven or eight days. After the fever is arrested the first time, treatment should be recommenced six or eight days after the time of the beginning of the former attack. Quinin might with out doubt be administered for a fortnight or three weeks, but that would present enormous inconveniences on account of its producing ringing in the ears, deafness, etc. It has not been demonstrated that continued treatment has any advantage over interrupted treatment. Better results are obtained by giving a few fairly strong doses than in prescribing the drug for a lengthened time but in small doses daily. It is evident that if 15 grains of the hydrochlorate of quinin is prescribed in a single dose that the blood at a given time is found much more charged with quinin and as a consequence is much more fatal to hematozoa than if five grains were prescribed for four days. The type of fever does not require material modification of treatment. After having been assured (notably by examina. tion of the blood) that the fever is really due to paludism, the following would be correct treatment for an adult man, according to the principles advanced by Lav eran : First, second and third days, eighttenths to one gram of the hydrochlorate of quinin. (It will be remembered that one gram equals 15 grains.) Fourth, fifth, sixth, seventh days, no quinin. Eighth, ninth, tenth days, six-tenths to eight-tenths gram of quinin hydrochlorate. Eleventh, twelfth, thirteenth, fourteenth days, no quinin. Fifteenth and sixteenth days, resume quinin as above. Seventeenth, twentieth, no quinin. eighteenth, nineteenth, Twenty-first and twenty-second, quinin as before. If fever reappears in the course of the treatment, it is necessary to prolong it. Quinin is better tolerated during the period of apyrexia than during an attack of fever. It excites vomiting less often and the absorption of the drug is probably more complete. On the other hand, it cannot be expected to control or cut short the evolution of an attack of fever of normal duration when that attack has already begun. Let it be ever kept in mind that in the grave or continued fevers the intermissions or even the remissions need not be waited for before administering the quinin. In serious cases, hypodermic injections of 1 to 2 grams daily should be made, without regard to temperature. As soon as the fever has yielded, the treatment for simple fever, as outlined above, should be followed. Hydrochlorate of quinin should be prescribed internally in solutions or in tabloids, preferably the former. In the grave palustral fevers, accompanied by pernicious symptoms, the first thing to attend to and by far the most important thing of all is to get the quinin taken, but in addition to this there is often occasion to prescribe some further aids to the special treatment. For the patients attacked with the algid form of the fever, friction, either dry or with the evaporating camphor liniment, should be used. stimulating drinks, alcohol in tea, for example, diffusible stimulants, ether, acetate of ammonia in the form of a draught, or better still, hypodermic injections of ether, may be given. Two to four grams of sulfuric ether must be prescribed. Hot The hypodermic injections of ether also |