Part 1 — CHAPTER I MALARIA (continued 2)

The use of a small square of wire gauze on a handle (fly swatter) to kill mosquitoes as they rest on a wall is of great value in keeping them down in a screened house.

2. Protection of the Individual.

The house should be thoroughly screened with copper-wire screens which should have 18 meshes to the inch. Mosquitoes can pass through a 15 mesh screen. Screen doors should always open outward and close automatically with spring hinges.

It is almost impossible to screen a ship’s hatches effectually. Then too the screening of fan intakes and ports interferes with free circulation of air, thus adding to the discomfort of the heat of the tropics.

As malarial mosquitoes bite chiefly toward evening one should not expose himself after sunset.

Houses should be far removed from native habitations.

Mosquitoes prefer the lower floors of a house so that the upper stories are preferable for sleeping.

Mosquito nets at night, with protection by veils for the face or coverings for the hands and ankles, when going out of the house, are well-known measures.

It is stated that Emin Pascha always carried a mosquito net and never suffered from malaria. He thought that the cause of malaria was too large to go through the net.

Even when mosquito nets are intact and well tucked in there is the weak point that a person sleeping on a narrow cot is apt to put his arm or leg against the net, in which case the mosquitoes readily bite the skin presenting at the open spaces.

Oil of citronella is often used to keep away mosquitoes.

Brooks recommends Neal’s method. In this daub a solution of 1 ounce Epsom salts in 10 ounces of water on the exposed parts and allow to dry.

Application of certain pine products used as mange cures will keep away mosquitoes.

3. Quinine Prophylaxis.

The ease of application of quinine prophylaxis, as compared with the more permanent methods of mosquito destruction and screening, appeals to the sanitarian, especially in the tropics.

It is just as easy to give quinine to a man in the tropics as it is in temperate climates, but when one considers the propositions of draining tropical swamps and shutting off circulation of air on a torrid night with fine wire gauze in the windows and closely woven mosquito nets around the bed, the question is decidedly different. In consequence, the tendency is for the average man to despair of accomplishing anything in the way of mosquito destruction and screening and to seize eagerly on the inferior alternative, that of quinine prophylaxis.

Ronald Ross presents this matter concisely and to the point when he states that it is not a good policy to substitute a measure which does not exclude infection, but is merely extirpative in some cases, for positive prevention. From this it will be seen that unless it is clearly recognized that quinine prophylaxis may in some cases extirpate, but does not prevent, there might be a tendency to adopt this measure and neglect the two proper ones.

As regards the relative merits of quinine prophylaxis and protection from mosquitoes Celli gives the following figures:

Treatment Infected

Mosquito protection plus quinine prophylaxis 1.76 %

Mosquito protection alone 2.5 %

Quinine prophylaxis alone 20.0 %

No protection at all 33.0 %

With quinine prophylaxis, there is the possibility of producing an immunity to quinine on the part of the parasites which have been introduced by infected mosquitoes and held in check by the prophylactic but not curative dose of quinine. Later on when the quinine prophylaxis is discontinued the parasites begin to multiply vigorously and seem to possess an immunity to quinine.

As an instance of this, 398 marines served in 1906 for about one month on the Isthmus of Panama during which time they were given 9 grains of quinine daily as a prophylactic.

During this month there was only an occasional case of malaria among the men. At the end of the month 298 of the original 398 returned aboard ship and sailed for the North. Two days later 20 cases of malaria developed, followed the next day by 53 and the day following that by 45. The medical officer then resumed 10-grain prophylactic doses for those not down with malaria but notwithstanding this there were 215 acute malarial paroxysms, some of them of pernicious type, among the 298 men.

It was noted that these men did not respond satisfactorily to quinine treatment even when the drug was administered intramuscularly.

Of the greatest value have been the observations of Stott. Using native Indian troops he gave one group (3931) prophylactic quinine while the other (3906) did not take quinine prophylactically. He continued this experiment one year giving 15 grains 3 times weekly for five months, and 10 grains 3 times weekly for the remaining seven months. Those taking quinine gave 170 primary admissions while those not taking it gave 179 (43.2 per thousand strength for the former as against 45.8 per thousand for those not taking quinine prophylaxis). Further observations were that those taking quinine prophylaxis showed a greater tendency to relapse, had somewhat longer fever, and required more quinine for treatment.

Linnell states that he used quinine prophylaxis among 2000 coolies for a year, giving 5 grains or more daily with most discouraging results. It seemed to act as a slow poison and did not protect.

Quinine Immunity.—Bignami thinks that malarial relapses may be connected with insufficient initial treatment so that quinine-resisting forms survive and later, when some factor lowers the patient’s resistance, active multiplication of parasites, which are not readily destroyed by quinine, follows.

While quinine prophylaxis may not be desirable on board ship, where one is in a position to readily recognize and treat the onset of malaria and to more or less efficiently carry out mosquito protection methods, or in a wealthy seaport, where sufficient interest in and funds for draining and screening exist, yet on military expeditions or exploring trips in tropical or subtropical countries it is the only practical method of keeping a force efficient.

Of course, one should also utilize mosquito nets as assisting in protection from malaria, and as effective for yellow fever, dengue and filariasis.

Methods of Prophylaxis.—There are innumerable methods of carrying out quinine prophylaxis among which may be noted.

(a) Celli’s method. In this there is given 3 grains of quinine each morning and 3 grains each night. Taken in this way Celli thinks that harmful effects from quinine are avoided, that quinine immunity does not occur and that there is no danger from quinine haemoglobinuria. For children he recommends the tannate in chocolate tablets.

(b) In 1909 Bertrand and other members of a French Commission recommended two consecutive doses of 5 to 10 grains every seventh and eighth day for benign infections and two consecutive prophylactic doses of 10 to 15 grains every third and fourth days where malignant tertian was prevalent.

(c) Ziemann gives 15 grains every fourth day with the idea that the quinine is entirely eliminated in four days. Nocht gives about 12 grains on two succeeding days of each week in divided doses of 2 or 3 grains instead of the entire amount in one dose.

Koch gave 15 grains on tenth and eleventh days.

(d) Castellani’s method of 5 grains daily and a double dose once a week is the one I recommend.

Sterilization of Carriers.—In addition to quinine prophylaxis for those not infected we also have quinine disinfection for native or other carriers of malaria. For these infected persons Koch recommends 15 grains on two to three successive days of each week, the course to be continued for three months. This plan of extirpation of the parasites of malarial carriers is of great practical application. Gill uses 10 grains of quinine daily for six months after discharge from hospital. The effect of tartar emetic on malarial gametes may prove of value.

Treatment.—Cinchona bark was first introduced into Europe in 1640 and has its name from Countess Chinchon, wife of the Peruvian Viceroy, who was cured of a fever by this bark in 1638.

Much of our knowledge of the therapeutics of cinchona bark is due to Torti. In giving the drug he used a large dose the first day and the same for the subsequent two days. After that he administered smaller doses for a week and then still smaller doses for two or three weeks. Quinine was not introduced until 1820.

At present quinine or some salt of the alkaloid is used in malaria instead of preparations of cinchona bark.

Toxic Effects of Quinine.—The most important untoward manifestations of cinchonism are the very common scarlatiniform, eczematous or urticarial rashes, gastric disturbances and vertigo. Impairment of vision may be brought about by quinine and quinine haemoglobinuria is a recognized possibility. In quinine amblyopia the pupils do not react to light and the optic disc is very pale, thus distinguishing the impairment of vision due to the plugging of the retinal vessels by the malarial parasite, in which condition the pupils do react to light and the disc is a grayish red.

Quinine Idiosyncrasy.—Fortunately the taking of quinine is well borne by the great majority of persons but in exceptional cases we may have developing, even after doses as small as one grain, of (a) severe nausea vomiting or diarrhoea, (b) various skin eruptions, usually of a scarlatiniform or urticarial type, (c) marked ringing in the ears, dizziness or deafness, (d) impairment of vision, (e) dyspnoea and (f) malarial haemoglobinuria. To determine an idiosyncrasy make a scratch on the flexor surface of the forearm and apply a drop of a 1 to 10 solution of quinine. Oedema with a wide zone of erythema in about 5 minutes shows idiosyncrasy. A control with normal saline should be made. It is well to make this skin test before giving quinine intravenously. For desensitization we give 1/10 grain of quinine combined with 5 grains of bicarbonate of soda and in about 1½ hours we give 1 grain with 5 grains of bicarbonate of soda.

The cheapest and most generally obtainable salt is the sulphate. It is soluble in 720 parts of water and contains 74% of alkaloid. The opinion now prevails that this is one of the less desirable of forms for the administration of quinine. It is frequently obtained in pill or tablet form and it must not be forgotten that such preparations may be almost stone-like and pass through the alimentary tract without absorption. If used it is best to give it in acid solution made by dissolving 5 grains of quinine sulphate in one teaspoonful (1 dram) of water with one drop of concentrated hydrochloric acid.

Dosage of Quinine.—The ordinary full dose of quinine for an adult is 10 grains repeated three times in a day or 30 grains daily. Some authorities recommend 15 grains three times daily (45 grains) at the commencement of treatment and such dosage seems to be just as efficient as the larger dose of 60 grains in a day. In cinchonism we have ringing in the ears, fullness in the head, deafness and dizziness. For children Bass recommends 1/20 of the adult dose for each year of age so that a child of 5 years age would receive ¼ of the adult dose. Beyond 15 years of age the dose is that of an adult.

There now seems to be a tendency to use the alkaloid itself instead of its salts, it having been found that the alkaloid and its very insoluble tannate are absorbed from the digestive tract equally as well as the soluble salts. Quinine is almost insoluble in water (1-1560) and hence has less bitter taste than the soluble salts. It is also less haemolytic so that it may be used with greater safety where blackwater fever is feared.

Euquinine or ethylcarbonate of quinine contains 81% quinine, and is only soluble in 1-12,000 parts of water, hence its comparative tastelessness. It is expensive.

Quinine tannate contains only about 30% of quinine and is practically insoluble in water. It is often given to children in chocolate tablet form. It can often be taken by those who suffer disagreeable effects from other salts. The dose should be 2½ times that of quinine sulphate.

Until recently the bimuriate (72% of alkaloid and soluble in 1 part of water) or the chlorhydrosulphate (74% of alkaloid and soluble in 2 parts of water) have been considered the most desirable salts for hypodermic injections or oral administration. At present, owing to its extensive use in local anaesthesia and incident availability, bimuriate of quinine and urea is to be recommended for intramuscular use. It contains 60% of quinine and is soluble in an equal amount of water.

It has been found to have a slightly greater tendency to produce amblyopia than other quinine salts and should not be used intravenously.

In a very important series of experiments on prisoners, MacGilchrist found that hydroquinine (a synthetic product of quinine) was about 20% more efficient than quinine. Cinchonine was about the same as quinine while quinidine was about one-half as potent as quinine.

Acton has praised the value of cinchona febrifuge (the combined alkaloids of cinchona) given in daily doses of 21 grains for ten days.

Methods of Administration

By Mouth.—This is the usual method and is the one to be preferred in all cases where other methods of administration are not necessitated.

Golgi believes that quinine is most effective at the time of liberation of merozoites from the bursting merocytes, hence he administered quinine four hours before the attack with a view to having it in its greatest concentration in the blood at such times. When given intravenously the full concentration is obtained in a very few minutes but with other methods this is a matter of great variation.

It is usual to give the quinine in capsules or cachets, the pills and tablets being often so hard that they do not dissolve in the alimentary tract.

The method usually in vogue in military services is to give quinine sulphate in acid solution. This method is trying to the stomach.

By Subcutaneous Injections.—This method is liable to be followed by necrosis and abscess formation or fibrous indurations. Quinine and urea hydrochloride is preferable either for subcutaneous or intramuscular injection.

Cohen holds that quinine and urea hydrochloride controls malarial infection more rapidly and efficaciously than any other salt of quinine when given intramuscularly. In order to prevent tetanus or other infections he is very careful about asepsis. He recommends that a 10 to 15-grain dose be injected every day for a week, then once a week for a month, then once every two weeks for another month. He considers a 33% solution as best, thus one could give 10 grains in the contents of an all-glass 2 cc. syringe.

James has recommended very dilute solutions for subcutaneous injections (1-150). There are practical objections to this method. It is usual to give about 1 gram (15 grains) of a soluble salt in 10 cc. of water. The present view is that subcutaneous injections deserve condemnation.

Intramuscular Injections.—It is now recognized that when quinine is not well borne when given by mouth the two modes of administration to be followed are either by intramuscular injection or introduction of the drug into a vein. For intramuscular use we dissolve a soluble salt of quinine, as the bimuriate or chlorhydrosulphate, in distilled water or sterile saline. A 50% solution is commonly used and from 6 to 10 grains of quinine is injected into the gluteal muscles of one side about 3 inches below the iliac crest. Repeat the injection on the other side. Repeat this daily dose of 12 to 20 grains for 3 or 4 days; then give quinine by mouth.

The solution should be autoclaved before use and the skin at the site of injection painted with iodine. Dudgeon has called attention to the constant production of oedema and necrosis in the area of the injection. This tissue necrosis occurs immediately and persists for a long time. If the injection is made in the neighborhood of an important nerve, neuritis may ensue. Repeated injections should not be given in the same area.

Of course in the use of quinine salts through the medium of the hypodermic needle everything must be sterile.

Intravenous Injections.—Bass and many others think that when quinine cannot be administered by mouth it should be given intravenously. Not only is there the objection of inflammatory reactions or necrosis when the drug is given subcutaneously or intramuscularly but the absorption of the drug is so slow that the patient may die before we obtain the desired effect. Ross condemns the subcutaneous method and recognizes the advantages of the intravenous method over the intramuscular one when rapidity of action is desirable.

In giving quinine intravenously Bass thinks that 10 grains at one time is sufficient and that a 20-grain dose is not without danger.

He does not think it necessary to give more than 30 grains daily in this way. Intravenous quinine seems to be entirely eliminated within twenty-four hours and most of it within twelve hours.

When used in cerebral malaria he repeats the 10 grains intravenously in eight hours if the drug cannot then be given by mouth. Bass thinks that theoretically amyl nitrite might relax the cerebral capillaries which are obstructed by parasite-infected red cells and thus enable the quinine in the circulation to reach such cells.

The best known method of administering quinine intravenously is that of Bacelli. In this method 1 gram (15 grains) of a soluble salt of quinine is given in 10 cc. of water.

MacGilchrist has shown experimentally that such a strength of quinine (1-10) will coagulate blood serum.

In my opinion this is a dangerous method if the injection is made rapidly. There is no doubt as to the necessity for using the intravenous channel in cerebral or algid types of perniciousness when intramuscular injections do not give results. The generally accepted method is to use a salvarsan technique with a dilute solution of quinine, giving 1 gram (15 grains) of some soluble salt of quinine in 250 cc. salt solution. Such injections should be given cautiously. Quinine hydrochloride, which is soluble in 40 parts of water, is the salt usually recommended. MacGilchrist considers the very soluble acid salts as haemolytic and prefers to give quinine base—3 pints of a solution of the alkaloid, containing about 12 grains.

McLean has used concentrated solutions of quinine intravenously several hundred times in cases of malaria (6 being blackwater fever ones) without any untoward results. He autoclaves his 10-grain solution of hydrochlor-sulphate in 10 cc. of sterile water for twenty minutes at 15 pounds, and injects it slowly into an arm vein, allowing about two minutes for the injection. The patients complain of a slight cough and hot feeling in the lungs with a succeeding dizziness which rapidly disappears. He is opposed to intramuscular injections and found intravenous ones diluted 1 to 250 often to cause shock and collapse.

Rectal Administration.—Some authorities recommend the administration per rectum of a soluble salt of quinine in about 3 times the usual dose by mouth or hypodermically. It is considered applicable in cases where there is marked vomiting. It certainly is the least satisfactory way of giving quinine.

Dosage and Length of Treatment.—In Panama the standard preliminary treatment is to give from 3 to 5 grains of calomel followed by 1 or 2 ounces of 50% magnesium sulphate.

Fayrer holds that a torpid liver interferes with the efficient action of quinine, hence the value of calomel and salts. I prefer to give 2 or 3 grains of calomel, in divided doses, followed by sodium phosphate, 2 drams, every two hours, for three or four doses.

Standard Method.—The National Malaria Committee of the United States recommends the following treatment: Give 30 grains of quinine daily in three 10-grain doses. Keep this up for 4 days and follow by 10 grains every night for 8 weeks. Where the infection does not present acute symptoms give the 10 grains daily for 8 weeks.

Canal Zone Treatment.—So soon as the diagnosis is made give 15 grains of quinine 3 times daily (45 grains in twenty-four hours) and continue such treatment for a week or until the temperature has been normal for five or six days. Then give 10 grains 3 times daily for ten or twelve days.

It is considered that by employing such thorough treatment from the beginning the tendency to latency or relapse is prevented—in other words the disease is really cured. It is interesting to note that Torti recommended large single doses at the commencement of treatment.

Espach has noted that he had frequent relapses in many cases treated by this method. In my opinion the Canal Zone treatment should be followed by 10 grain doses daily for 8 weeks.

Tonics of iron, arsenic and strychnine are valuable in treating the anaemia, but it is not advisable to add small doses of quinine to such tonic mixture.

Repeated Small Doses.—In Nocht’s method we give the quinine in small doses repeated several times in the day, as 3 or 4 grains given 5 or 6 times daily. Such treatment is thought advisable when there is a tendency to haemoglobinuria or when giving quinine to pregnant women.

In giving the small doses one should see that they are given during the night as well as the day.

Quinine and Pregnancy.—There is frequently hesitancy in giving quinine to a pregnant woman but unless the malaria is controlled the patient will be apt to abort. Potassium bromide is thought to control the ecbolic influences of quinine.

Clark states that the experience at Ancon Hospital would indicate that quinine can be given with impunity to pregnant women. In malarial subjects quinine after parturition is of value not only in controlling a fever due to malaria but it also favors involution and aids in the healing of perineal tears. The quinine also is beneficial in improving the quality of the mother’s milk and does no harm to the child.

Manson’s Method.—In a benign malarial infection Manson prefers to wait until the hot stage has been passed and the patient is beginning to perspire, this idea being that the headache and other symptoms are aggravated and that very little advantage is gained by treatment during the early part of the paroxysm. He gives 10 grains at the onset of the sweating stage and afterward 5 grains, 3 or 4 times daily, for the following week. He then gives a daily tonic containing arsenic and iron, with a quinine treatment every seventh day for about two months.

For regularity he advises the quinine treatment on Sunday giving a dose of salts in the morning followed by three 5-grain doses during the day.

Manson notes the danger of large doses of quinine as producing not only serious disturbances of sight and hearing but pronounced cardiac depression as well.

There are many who speak highly of Warburg’s tincture in treatment. It is both laxative and sudorific. The dose is ½ ounce (15 cc.) which contains about 5 grains of quinine sulphate and 4 grains of extract of aloes. As a rule it is better to give the quinine and the laxative separately.

More recently the tendency has been to give large doses of quinine, not only for its greater curative value but, as well, for the prevention of relapses. Craig, however, states that in his experience with aestivo-autumnal infections he has yet to see a single case, in which treatment was promptly instituted, that did not recover with a daily treatment of 30 grains.

Koch’s Method.—Koch recommended 15 grains each day for a week, then three days without quinine. Then three days with 15-grain doses each day. Then one week without quinine, followed by three days of treatment. This plan of a weekly interval followed by three days of treatment is continued until not fewer than 30 15-grain doses are given over nine or ten weeks.

Drugs Other than Quinine.—Salvarsan and neosalvarsan have been extensively used and with some success in benign infections but without material effect in malignant tertian ones.

Intermittent Treatment.—There are those who consider a treatment in which days of quinine administration are followed by days without quinine as equally efficient and less trying on the patient. Some of the experiences of Stephens and his colleagues indicated that 45 grains on two consecutive days of each week and continued for 8 weeks gave better results than 30 grains daily over such a period. In their experiments a dosage above 45 grains in a day did not seem any more efficient than 45 grains, so that this may well be considered as a maximum dose. On the whole however there seems to be a greater tendency to relapse following an intermittent treatment and Acton, as a result of his comparison of intermittent and continuous methods, deprecates the intermittent one.

Some have thought that salvarsan aided the specific action of quinine.

Many physicians recommend arsenic in the form of Fowler’s solution or as sodium cacodylate. It is most useful in chronic cases. Some preparation of iron is, of course, indicated in malarial anaemias.

It has been claimed that radium and X-ray treatment, when directed to the spleen, assist the action of quinine.

Methylene blue, next to quinine, has been considered as the most valuable drug. It is given in 2-grain doses every four hours. It is also given intravenously.

The form of methylene blue to use is that labelled “Medicinal.”

It is often stated that the opium fiends of the tropics are immune to malaria and some physicians have claimed antiperiodic properties for the drug. Dover’s powder is lauded by some as of value in symptomatic treatment.

Surveyor has recommended picric acid in the treatment of malaria in doses of 2 grains two or three times daily.

Recently hectine, a remedy somewhat similar to the cacodylates, has been strongly recommended by the French. It is given intramuscularly in 2-grain doses. It is said to be valuable when there is a leucopenia as it has a tonic action. It has been recommended to combine this treatment with quinine.

It is said to be a good substitute for quinine in blackwater fever.

Rogers has recently noted the value of tartar emetic injections in eradicating the sexual parasites of carriers.

After rather extended trial of this drug for the above purpose and as a method of treating ordinary infections the general opinion is against its value.

General and Symptomatic Treatment.—During the course of the fever the patient should remain in bed and given only broths. In the intermissions of the benign forms one may allow a more generous diet. It is important that the patient be not allowed to become constipated and as a laxative one grain of calomel in divided doses followed by effervescing phosphate of soda is very satisfactory.

For the nausea sips of an ice-cold alkaline mineral water or cracked ice will generally prove effective. In more refractory cases spirits of chloroform or even a hypodermic of morphine may be necessary. Counterirritation to the epigastrium is often a help. Phenacetine may be given for the headache although ice water compresses are generally sufficient. In algid states hot water bottles should be applied to the body. During convalescence excesses in food or drink should be avoided as well as fatigue or exposure to wet or cold.