an acute or chronic nephritis. The peritonaeum and the gastro-intestinal
mucous membrane may be slate color due to the deposition of pigment.
Symptoms. The symptoms of the paroxysms of quotidian, tertian or quar-
tan malaria are practically identical in their clinical manifestation; they occur,
however, at difierent intervals depending upon the time of sporulation of the
causative organism. In tertian infection the chill occurs every other day,
in quotidian, daily and in quartan, every 72 hours.
The incubation period of malaria is variable; it may be as short as 24 hours
or as long as several months; the average being from one to two weeks, prob-
ably depending upon the amount of infectious matter in the system.
48
THE INPECTIOUS DISEASES.
The paroxysm may be preceded by prodromal symptoms such as indefinite
malaise, yawning, headache or nausea. Prodromata may be wholly absent.
The paroxysm consists of three stages, the chill, the fever and the sweat. The
chill lasts from i- to 2 hours; it usually manifests itself late in the morn-
ing and almost never at night. Its onset is usually gradual beginning with
chilly feelings of increasing intensity until the body shivers with intense
cold and the teeth chatter. Even hot water bottles and numerous blankets
will not keep the patient comfortable; the face is pinched and pale; the lips
are blue, and the patient is apparently very cold yet at the same time the body
temperature is elevated even to 105° or 106° F. (4o.5°-4i.i.°C.). There is
severe frontal headache and nausea and vomiting may be present. The pulse
is rapid, tense and small. The urine is pale, increased in amount and of low
specific gravity but before this stage it may have been dark colored and
DAY OF
DISEASE
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Fig. 5. — Clinical chart of tertian malarial fever.
heavy. At the end of the stage of chill the febrile stage begins. This is char-
acterized by flushing of the face, a hot and dry skin, coated tongue, great
thirst, severe headache and pain in the back and limbs; the pulse is full,
bounding and rapid and active delirium may be present. The temperatvire
may be but little higher than during the cold stage and at times the
maximum may be reached at the termination of the chill. The stage
of fever lasts from 30 minutes to four or five hours, and is at the end of this
time followed by the stage of sweating. All the symptoms subside and there
is profuse perspiration beginning on the face and gradually involving the
skin of the whole body and the patient falls asleep to awake later feeling
MALARIAL FEVERS. 49
perfectly well. This stage lasts ^ to 2 or 3 hours. The sweating may at
times be very slight.
The duration of the whole paroxysm is from 8 to 12 hours, but may be
shorter. Splenic enlargement may appear and disappear synchronously
with the paroxysm but in long continued infections this organ usually becomes
permanently increased in size.
The intervals between the paroxysms differ with the type of the infection.
Thus in simple tertian fever (infection with one set of tertian organisms) the
chill recurs at 48 hour intervals. If two sets of this organism, sporulating on
alternate days, are present the paroxysm appears every 24 hours. When
a simple set of quartan organisms is present the seizure takes place every
72 hoiurs, if two groups, maturing on different days, are present, the patient
will have two paroxysms on successive days, then a day free from chill occurs
and the round is then successively repeated. If three sets of quartan parasites
are present a chill will occur on every day. The chills may appear at nearly
the same hour upon different days or they may anticipate — that is each will
occur an hour or so earlier than its predecessor; again the seizures may be
retarded, appearing successively at a later hour.
Without treatment the paroxysms may cease after several have occurred
or they may disappear after two or three weeks. In these events they are,
however, very likely to recur. If the disease continues the chronic form of
malaria, followed by cachexia (q.v.) supervenes.
^stivo -autumnal malaria, after a period of incubation similar to that
of the preceding types, usually begins with a chill which is more frequently
preceded by prodromata than is that of the intermittent types of the disease.
There are malaise, general pains and nausea often with vomiting of bile.
The chill may not be well marked and is followed by a regularly intermittent
fever; the intermissions are longer than those of the tertian type, or the par-
oxysms may be anticipated or retarded, rendering the fever continuous with
exacerbations. This form of remittent fever markedly resembles enteric
fever, the patient appears prostrated, the pulse is rapid and full and the
temperature rises, with daily remissions, to 102° to 104° F. (38.9°-4o° C);
initial bronchitis may be present, jaundice may be observed and there is acute
splenic enlargement. Nervous symptoms may be noted. The infection
varies in severity; it may ameh orate after from 7 to 10 days, there may be
irregular remissions and exacerbations. In the severe forms the infection
may become of the pernicious type. Here the resemblance to enteric fever
is especially marked. The tongue is thickly coated, the facies closely resembles
that of enteric fever, and the fact that the two affections frequently occur in
the autumn renders the differential diagnosis particularly difficult. Blood
examination and the test of quinine treatment are aids in the distinction
between the two infections.
50 THE INFECTIOUS DISEASES.
Pernicious malarial fever is a result of infection with the haematozoon
of sestivo-autumnal malaria and occurs in three forms.
a. The comatose form may or may not begin with a chill but in its severest
type this manifestation is usually well-marked (the congestive chill) and
accompanpng it delirium, or more often, coma, is rapidly developed. The
skin is hat and dry and the temperature ranges from 104° to 106° F. (40° to
41.1° C). The course lasts from 12 to 24 hours and may be followed by a
second attack. The coma is a result of the accumulation of the parasites
in the vessels of the brain and may prove fatal.
h. The algid or asthenic form is characterized at its onset by marked
prostration and vomiting; collapse may follow and though the patient may
complain of chilly sensations no real chill may be present. The surface
is cold and the temperature normal or subnormal. The pulse is small, rapid
and feeble and the respiration shallow. Marked choleraic diarrhoea and
urine diminished, sometimes to suppression, may be noted.
These symptoms may continue, slight rises of temperature occurring from
time to time, for a few days, at the end of which time death may occur from
prostration and the severity of the infection.
c. The hcemorrhagic form. This type includes black-water fever and
malarial haemoglobinuria. This is the result of the malarial toxin although
it has been attributed to the use of large doses of quinine; the administration
of this drug may however aggravate the haemoglobinuria. Black- water fever
occurs in the Southern states, in Central America, in Italy and in Africa.
The condition is met most frequently in patients who have had frequent
attacks of malaria and whose condition approaches that of the cachectic
form of the disease. The haemoglobinuria is usually not accompanied by
active malarial symptoms although preceding its appearance a febrile move-
ment may have been present for a few days. The cause of the haemoglo-
binuria is certainly malaria but whether this manifestation is the result of
infection by a distinct type of parasite is unknown. The exciting cause of the
paroxysm has also never been ascertained.
Malarial cachexia may result from long-continued exposure to and repeated
attacks of any of the types of this disease. Its most prominent symptoms
are anaemia and splenic enlargement (ague-cake). The anaemia is character-
ized by a sallow skin with sometimes an added subicteroid tinge, coated
tongue, disordered digestion and constipation, palpitation and dyspnoea,
oedema and coldness of the extremities. The temperature may be subnormal
with irregular ascents to 102° to 103° F. (38.9° to 39.5° C). Haemorrhages
into the retina, from the stomach and other structures may be observed.
The examination of the blood reveals the presence of a typical secondary
anaemia and, it may be, the presence of malarial organisms, usually crescentic
in form.
MALARIAL FEVERS. 5 1
The edge of the spleen may extend as low as the crest of the ilium and the
consistence of the organ is hard and firm.
Complications referable to the nervous system, such as paraplegia, resulting
from a peripheral neuritis or deranged circulation in the cord, hemiplegia,
acute ataxia and symptoms suggestive of disseminated sclerosis may occur.
Areas of cutaneous gangrene and testicular inflammation have been noted.
The diagnosis of malarial fever is in most cases easily verified by means of
examination of the blood, although special training is necessary in order to
become expert in the detection of the more unusual forms of the parasite.
Fiu"ther aids in differential diagnosis are absence of Widal reaction and of
leucocytosis and the test of treatment by quinine.
The prognosis in simple intermittent fever is favorable. Under proper
treatment it is easily curable and in certain instances spontaneous recovery
takes place. Continued exposm"e or insufl&cient treatment may result in chronic
malaria. The sestivo-autumnal type can usually be controlled by proper
treatment but may merge into the pernicious or chronic types. Pernicious
malaria may result in death but recovery from malarial cachexia is the
rule.
Treatment. The prevention of this disease consists in the employment
of means to exterminate mosquitoes, of screens to prevent ingress of infective
insects to dwellings and in treatment of patients suffering from the disease
as well as protecting them from possible mosquito bites, lest the infection be
thus transmitted. In malarial regions all exposiire to infection, especially
after nightfall, is to be avoided. Prophylactic doses of quinine — two to
three grains (0.13 to 0.20) — three times a day should be taken by individuals
coming to malarial districts.
During the chill, endeavors should be made by means of blankets and
hot-water bottles and the administration of hot drinks to keep the patient
warm. The headache may be relieved by hot or cold applications. Spong-
ing with cold water may be practised diu-ing the febrile stage and the thirst
may be mitigated by frequent drinks of cold water or lemonade. Dm"ing the
stage of sweating the patient may be made more comfortable by wiping his
skin with hot flannel.
The treatment of intermittent fever consists primarily in the administration
of quinine. This drug being absorbed into the blood exerts there a directly
poisonous influence upon the parasites present in the same medium. The
latter are most susceptible to the effect of the quinine when free in the blood
stream, that is, at the termination of the process of sporulation, consequently
the drug should be so administered that it shall have been absorbed in time
to be present while segmentation is taking place. In order that quinine shall
be quickly and in sufficient quantity absorbed measures should always be
taken to render the gastro-intestinal tract — if the drug is to be given by mouth
52 TELE INFECTIOUS DISEASES.
— as active in performing this function as possible, consequently it is wise
to clear the intestine, before the administration of the quinine, by means of
fractional doses of calomel to be followed by a saline. Then, in order that
the blood shall be impregnated with the drug for an hour or thereabouts
before sporulation takes place, it should, when given by mouth, be admin-
istered lour to six hours before the expected paroxysm. The quantity nec-
essary varies with the severity of the infection and the absorptive power of the
gastro-intestinal tract. In the less severe types of the disease 15 to 20 grains
(i.o to 1.33) are often sufficient while in other instances three or four times
this amount may be necessary. For several days following, the patient should
receive 10 grains (0.66) or more of quinine three times a day, when the dosage
may be reduced to five grains (0.33) three times a day. On the seventh day
following the last paroxysm an amount commensurate to that administered
at the beginning of the treatment should be given and this procediu"e should
be continued every seventh day for about two months. During the first
two or three days of the treatment the action of the quinine will be enhanced
by confinii3g the patient to bed. After this time he may be allowed up.
The drug may be given in solution, in pill form or in capsules. The solution
has the disadvantage of an extremely bitter taste and the advantage of being
most readily absorbed. Freshly-made pills or soft gelatin capsules con-
taining the powdered drug are also to be recommended, particularly if their
administration is followed by five to eight drops (0.33 to 0.5) of dilute hydro-
chloric acid to facilitate dissolution. Compressed tablets and stale pills
of quinine are very likely to pass through the body undissolved. To patients
who cannot take the drug by mouth it may be given hypodermatically in the
form of the dehydrochloride or of quinine and urea hydrochloride. Either
of these may be taken in doses of 10 to 20 grains (0.66 to 1.33) every two or
three hours.
The following formulae are useful: I^. Quininae sulphatis, gr. xv (i.o);
acidi tartarici, gr. vii ss (0.5); aquae destillatae, ni cl (lo.o). I^. Quininae
hydrochloridi, gr. Ixxv (5.0); aquae destillatae, 5ii ss (lo.o). I^. Quininae
hydrobromidi, gr. xxx (2.0); aquae destiUatae, ttl xc (6.0).
Quinine hydrobromate may also be given subcutaneously. The drug
may likewise be administered in enemata or suppositories, the rectal dosage
being at least twice that appropriate by mouth.
Substitutes for quinine spring up from time to time and of these quinidine
sulphate and cinchonine sulphate, especially the latter, may be mentioned.
The doses of each of these are about A greater than that of quinine sulphate.
If in long-continued infections quinine fails to exert its usual influence arsenic
may be substituted. It may be given in the form of the liquor potassii arsenitis
beginning with doses of five drops (0.33) three times a day or as arsenic
trioxide, beginning dose ^V <^^ ^ grain (0.003) three times a day. These
MALARIAL FEVERS. 53
doses should be gradually increased until the physiological effect is evidenced
by oedema under the eyes or gastro-intestinal disturbance.
Methylthionine hydrochloride sometimes succeeds when quinine is not well
borne or is contraindicated, as in pregnancy or hsemoglobinuria. Its action is
supposed to be exerted upon the parasite in the blood, just as is that of the latter
drug. It should be given in capsules containing two to three grains (0.13 to
0.20) each, of which three per day may be taken. The patient should always
be warned that the urine becomes blue while this drug is administered.
Mstivo-autumnal fever should be treated along lines identical with those
described above. The patient is, however, much more ill and needs careful
nursing. In the forms resembling enteric fever he should be kept in bed and
receive fluid diet and stimulants, especially strychnine, as indicated. If
vomiting is a feature of the infection it is Hkely to interfere with the admin-
istration of quinine by mouth, consequently hypodermatic injections as
described above may become necessary. Enemata of quinine dissolved
in starch water are also useful. The vomiting should be treated sympto-
matically, the bowels kept active and the hepatic torpor combated by means
of calomel. Rectal feeding may be necessary.
Pernicious malarial fever demands the most active and energetic treatment.
The patient should be kept in bed and thoroughtly cinchonized as quickly
as possible by means of hypodermatic injections of large doses. An even
more rapid method is that by intravenous injection of the drug.
The following solution may be employed: I^. Quininae hydrochloridi,
gr. XV (i.o); sodii chloridi, gr. i (0.65); aquas destillatae, 5ii ss (10. o).
The cerebral symptoms may be relieved by the bromides or by opium, if
necessary, and stimulation by means of strychnine or alcohol may be indi-
cated. The bowels should be kept open; the chills may be relieved by ex-
ternal warmth and the excessive fever by cool sponging.
In giving hypodermatic injections of quinine a long needle inserted deeply
into the muscular tissues of the back or buttocks, should be used. Abscesses
are very prone to follow and in order that they may be prevented, in so far
as may be possible, the strictest aseptic technique should be employed.
Malarial Cachexia. Here quinine is also indicated although not neces-
sarily in large doses, Warburg's tincture containing 10 grains (0.66) of quinine
to the ounce, often acts well in doses of ^ an ounce (15.0) three times a day.
Cinchonidine sulphate in doses of 10 to 15 grains (0.66 to i.o) three times
a day is also useful. It is in this form of malarial infection that arsenic is
particularly indicated, it may be given alone in the form of liquor potassii
arsenitis or in combination with iron and quinine. The following formulas
are suggested: I^. Quininae sulphatis, 5ii (8.0); ferri et potassii tartratis,
5ss (15.0); arseni trioxidi, gr. i (0.065); ^-quae destillatae q. s. ad §iv (120.0).
Misce et signa, one teaspoonful after each meal. I^. Arseni trioxidi, gr, ^V
54 THE INFECTIOUS DISEASES.
(0.003); massse ferri carbonatis, gr. v (0.33). Misce. Sig. Take one such
pill after each meal.
Arsenic may also be given hypodermatically as follows : I^. Sodii arsen-
atis, gr. xV (0.006); aquas destillatse q. s.; or, I^ sodii arsenatis, gr. xV (0.006);
sodii phosphatis, gr. ^\ (0.003); ^o^i' sulphatis, gr. xV (0.006); aquae destil-
latae q. -e.; or, R ferri et ammonii citratis, gr. i ss (o.i); sodii arsenatis, gr.
To (0.006); strychninae sulphatis, gr, -jV (0.002); aquae destillatae q. s.
Of these one injection may be given daily. Sodium cacodylate J to 2^
grains (0.03 to 0.15) daily may prove useful. In treating this form of malaria
either with or without iron the bowels should be kept regular; a course of
fractional doses of calomel may be indicated from time to time in order to
keep the Hver active and at intervals mild laxative pills may be employed.
The treatment otherwise than that discussed above consists in the employ-
ment of all measures, dietetic, hygienic and hydrotherapeutic, to improve
the patient's general condition, and removal to a different climate, a moun-
tainous district if possible.
The Treatment oj Malarial Hcematuria. Here imless active parasites
are present in the blood it is wise to omit quinine but should they be foimd
this drug is strongly indicated. In the milder forms five grains (0.33) three
times a day will cause this symptom to cease. Even when no plasmodia are
present certain vmters advocate small doses of quinine beginning with one
grain (0.065) ^^^ watching the effect on the hsmoglobiniu-ia. Methylthionine
hydrochloride gr. ii to iii (0.13 to 0.2) three times a day may be given as
also may sodium hyposulphite in doses of 20 grains to i drachm (1.33 to 4.0)
three or four times a day. Otherwise the treatment of haemoglobinuria is