Chapter XXXIX: Typhus Fever

DEFINITION AND SYNONYMS

=Definition.=—Typhus fever is an acute infectious disease, possibly caused by _Rickettsia prowazeki_. There is a fairly abrupt onset, with a continued fever lasting about two weeks, followed by a critical fall or rather rapid lysis of temperature. About the fifth day a rose spot eruption, similar to that of typhoid, first appears about the loins and abdomen later on extending over the trunk and extremities. The rash tends to become petechial and stands out rather prominently on a general cutaneous mottling. The stuporous state is a marked feature of the disease. It is transmitted by lice.

=Synonyms.=—Jail fever; Ship fever; Putrid fever; Petechial fever; Typhus exanthematicus. Ger. Fleckfieber; Fr. Typhus exanthématique; Sp. El tabardillo; Ital. Typho-esantematico.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—Hirsch notes that the history of typhus fever belongs
to the dark pages of the world’s story, at times when war, famine,
and misery of every kind are present. It is reasonable to suppose,
according to this author, that many of the pestilences of ancient
times and the Middle Ages were typhus fever. This disease was
prevalent among the Spanish soldiers at the time of the conquest of
Grenada and the designation of the disease then used (Tabardillo)
is the one now given typhus fever in Mexico.

The disease was first described with sufficient accuracy by
Frascatorius, in the 16th century, to enable us distinctly to
differentiate it from plague; the stuporous states of the two
diseases having previously caused them to be confounded. In
England, in the 16th century, the disease was very prevalent in
the jails and court officials attending the trials of prisoners
often contracted the disease and died; hence the designation “black
assizes.”

During the Thirty Years War, in the 17th century, typhus fever
spread over central Europe.

Typhus fever was very prevalent at the time of the epidemic of
plague known as the great plague of London and it is a matter of
practical interest that the two diseases were not infrequently
confounded by medical men. There were some very severe epidemics of
the disease in Ireland in the 19th century.

Typhoid fever and typhus fever were only separated as distinct
diseases by Gerhard, 1837. Huxham, however, had previously noted
the marked difference between putrid malignant fever and slow
nervous fever.

Until very recent times it was declared that typhus fever was among
the most contagious diseases of man and innumerable instances were
cited of frequent contagion of those attending or visiting typhus
patients. In 1909, Nicolle, in North Africa, demonstrated that the
disease was transmitted by lice and the recent experiences in the
Balkan war and in the Servian epidemic of 1915 show that in the
absence of such vermin the disease does not appear to be contagious.

=Geographical Distribution.=—The disease has largely been
eradicated from European and other countries where hygienic
measures leading to the destruction of vermin have existed.

During the recent war the disease became one of importance, owing
to the difficulty of preventing the spread of body lice to the
soldiers.

In the tropics the disease, when present, is usually found in
regions of high altitude. In Mexico tabardillo, as typhus is there
designated, is a disease of the elevated regions. This is also true
of India.

Sporadic cases of typhus, known as Brill’s disease, have appeared
from time to time in New York.

During the great war typhus first appeared in Servia, thence
extending to Austria, Germany and Russia. Its nonappearance on the
Western battle line must be attributed to the active measures of
the Germans in attacking the lice problem. It is now widespread in
Russia and Poland.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—Recent work by Anderson and Ricketts has shown that the blood of human cases is infective for monkeys. The virus does not seem to pass through a Berkefeld filter and the epidemiology points to the body louse as the sole transmitting agent. Nicolle reported the filterability of the virus. More recently he has considered this filterability as doubtful.

The guinea pig is susceptible to the virus as well as the monkey
but only shows temperature rise. Nicolle has shown that lice do not
become infective until about the tenth day after feeding on typhus
blood. The virus is found in the blood of man and in the spleen and
blood of monkeys and guinea pigs.

Plotz has isolated a Gram-positive pleomorphic bacillus from
the blood of typhus patients which has been named _B. typhi
exanthematici_. This organism is of historical interest only and
apparently has nothing to do with the causation of typhus fever.

Hort states that only blood recently taken from typhus patients
will cause the disease in monkeys while the same blood which
has been incubated several hours or days fails to produce the
disease. Others, as well as Hort, doubt the etiological relation
of the organism of Plotz to typhus fever or to the mild form of
the disease as seen in New York City and there known as Brill’s
disease. Tabardillo or Mexican typhus is the same as typhus.

Rocha-Lima insists upon the etiological importance of short oval bodies, often showing polar staining with Giemsa preparations, and found in the epithelial cells of the alimentary tract of lice which have fed on the blood of typhus patients.

Ricketts noted similar bodies in such lice. They differ from the
Plotz organism in that they are Gram-negative and apparently cannot
be cultivated. Lice feeding on blood other than that of typhus
patients fail to show these bodies and furthermore the blood of
typhus cases during the period of convalescence fails to infect
lice. When guinea pigs are inoculated with emulsions of lice
containing such bodies they show the temperature reaction of typhus
fever. Plotz states that his organism may be Gram-negative at first
and believes these organisms to be the same. Wolbach and Todd
take the view that the bodies described by Rocha-Lima and called
_Rickettsia prowazeki_ are the cause of typhus fever. Similar
bodies have been found in trench fever and even in certain normal
lice. These bodies, however, are extracellular and are more oval
and stain more intensely than the typhus bodies. These Rocha-Lima
bodies require a Romanowsky stain to bring them out. In man these
bodies are found in the endothelial cells of the small blood
vessels, occurring singly or in clumps. In the louse the epithelial
cells of the intestine may be found distended with masses of these
organisms.

It is not certain whether the virus is transmitted by the bite of
the louse or by inoculation of faeces. Monkeys and guinea pigs can
be infected by injection of emulsions made from infected lice.

Loewe and others have succeeded in cultivating the virus of typhus,
using deep tubes containing 10 cc. of a rich ascitic fluid and a
piece of sterile rabbit kidney. The medium was inoculated with 2
cc. of typhus blood, after which 0.3 cc. of a 20% dextrose solution
was added and the culture sealed with liquid petrolatum. Its
reaction was pH 7 to 7.4. Cultures were incubated at both room and
body temperature.

As proving the culturing of the virus, it was noted that 1 cc. of
a fourth-generation culture would infect a guinea pig. This would
represent 0.00000016 cc. of the original typhus blood. The bodies
cultivated differ in morphology from the bacillus of Plotz in
that they are even more minute, of slight hazy outline and do not
assume polymorphous involution forms. They vary also in cultural
characteristics. Concerning the question as to the identity of the
bodies with _Rickettsia prowazeki_, no definite decision is as yet
permissible, nor were the authors able to decide whether the bodies
are of bacterial or of protozoan nature.

=Epidemiology.=—Until recently authorities stated that typhus fever was the most contagious of all diseases. We now know that in the absence of body or possibly head lice the disease is only slightly, if at all contagious.

At the same time recent experience has shown that it requires
the greatest care on the part of those having charge of louse
destruction to avoid being infected while attending to this duty.
The same is true of those examining patients with the disease prior
to the eradication of the body lice of the sick.

A knowledge of the life history of the body louse is necessary. The body louse, _Pediculus vestimenti_, is slightly larger than the head louse, _P. capitis_, and is the species concerned in the transmission of Indian and North African relapsing fevers as well as typhus fever, although it is probable that the head louse can also transmit these infections.

While the head lice live among the hairs of the head and show
their presence chiefly by the appearance of their pear-shaped
eggs (nits) projecting from the hair shaft, the body lice attach
themselves to the under surface of the garments worn next the skin,
and holding fast to the undershirt, feed about twice daily on the
human host. They are but rarely found on the skin. The female body
louse is about ⅐ inch long and about 1/15 inch broad (3.5 mm. ×
1.5 mm.). The antennae are somewhat longer than those of the head
louse. Warburton found that the egg stage, in experiments, lasted
from eight to forty days, the larval stage about eleven days, and
that the male louse lived three weeks and the female four weeks.
Of course, under natural conditions these periods may not hold.
Development of the eggs takes place best at a temperature of 30°C.

Lice feed at once after being hatched and a young louse will die
unless it feeds within 24 hours.

Lice will leave their host only when he has fever or when he dies
but they may drop off a host or be brushed off. They are not apt to
be found in bedding.

PATHOLOGY

Fraenkel, in 1914, first called attention to proliferative changes in the endothelium of the arterioles and arterial capillaries, followed by necrotic changes. These changes are chiefly manifest in the vessels of the skin, central nervous system and myocardium. In addition to the proliferation of the endothelial cells we have a perivascular infiltration of small round cells. Kurt Nicol notes that there is a combination of proliferative and inflammatory changes. These are microscopical and there is absence of characteristic macroscopic findings.

The petechiae are due to thrombosis of the smaller vessels and subsequent haemorrhagic manifestations. Bronchitis and broncho-pneumonia are extremely frequent and form the most common fatal complication. The brain lesions are most common in the basal ganglia, the cerebral cortex and the medulla.

The blood is dark-colored and the liver and kidneys show cloudy swelling. The spleen is somewhat enlarged during the early stages of the disease but tends to be normal in size later on. It is very soft and may rupture while being handled at autopsy. There are no changes in the Peyer’s patches and the mesenteric glands are not enlarged, thus differentiating from typhoid fever. The heart muscle tends to show degenerative changes.

SYMPTOMATOLOGY

The period of incubation varies from five to fifteen days, usually, however, about twelve days. The period of onset may cover about two days, during which time the patient has headache, giddiness, backache, anorexia, perhaps nausea, and general malaise. There may be rigors or chilly sensations.

About the end of the second day the temperature rises fairly
rapidly to become 103° or 104°F. by the third or fourth day. With
the rise of fever the face becomes flushed, the eyes injected and
the expression apathetic. The headache is usually quite severe and
may be frontal, occipital or generalized. The temperature remains
elevated with slight morning remissions for from twelve to fourteen
days when it may fall by crisis or more gradually by rapid lysis.

Well-marked prostration and cardiac weakness are early noted. There is a tendency to constipation and the mouth becomes foul and the teeth rapidly covered with sordes, unless the greatest precautions in oral cleanliness are observed.

There is a marked tendency to clouding of the consciousness. At
times the disease shows an abrupt onset rather than that described
above.

The eruption first appears about the fifth day and shows as slightly elevated rose spots, which at first disappear on pressure, but quickly tend to become permanent and later purpuric. The eruption first appears in the flanks and then extends to the abdomen, chest and later to the extremities.

The term mulberry rash is sometimes used to describe the rash of
typhus. In addition to the above there is a subcuticular mottling.

Along with the appearance of the rash the symptoms become aggravated, the effect on the heart is more marked and the pulse becomes feeble. The face is often dusky. There may be a bronchial catarrh with an annoying cough.

By the end of the first week the delirious or stuporous condition
becomes more marked with a tendency to muttering delirium, tremors
and subsultus, the coma-vigil of the older writers. Terrifying
hallucinations may cause the patient to jump from the window and
kill himself. There is a tendency to parotitis and otitis media
connected with the mouth condition. On account of the circulatory
weakness there is a tendency to gangrene of the extremities,
especially the toes, rarely the fingers.

In cases which recover there is a critical change in the apparently desperate condition of the patient about the end of the second week, the sudden striking change for the better being more marked in typhus fever than in any other disease. At this time the urine changes from a high-colored, often albuminous one, to an abundant secretion of more or less normal character.

The sporadic mild cases of typhus, which occurred from time to
time over a period of years in New York, were known as _Brill’s
disease_. According to Brill these cases showed intense headache,
apathy and prostration, with a continuous fever, maculo-papular
eruption and a rapid lysis or critical fall of temperature at the
end of about fourteen days. The spots only rarely became purpuric.
There was almost never marked delirium and the mortality was less
than 2%.

Symptoms in Detail

_The Eruption._—This first appears about the fourth day as macules
about loins, then spreading over abdomen, chest and back. It is
often more pronounced on the back than elsewhere. It almost never
appears on the face but may occur on the palms and soles. It has
a resemblance to the rash of measles. At first disappearing on
pressure it soon becomes permanent and then petechial. The livid
color of the rash has brought about the designation “mulberry
rash.” The rash lasts from a few days to two weeks.

_The Fever._—The fever rise following a chill is much more rapid
than in typhoid fever, reaching its fastigium in about three days.
A more or less continuous range of fever (103° to 104°F.) follows
until about the fourteenth day, when there is often a rapid lysis
or possibly crisis, at which time the patient tends to fall into a
refreshing sleep and to show a rather marked diuresis.

_The Alimentary Tract._—Constipation is usually noted. Very marked
is the tendency of the mouth and tongue to become dry and sordes
to collect on the teeth. The dry black tongue has led to the
designation “parrot tongue.” It is difficult to get the patient to
protrude his tongue when told to do so.

_The Circulatory System._—Very outspoken is cardiac weakness due
to myocardial degeneration. The heart sounds are very weak and
the pulse feeble. The blood pressure is very low, especially the
diastolic. Bradycardia may be marked during convalescence.

_The Respiratory System._—Cough may appear in the first days, but
usually is first troublesome about the time of the eruption. By the
end of a week the cough becomes loose and râles of various types
may be noted. Death often occurs from a terminal broncho-pneumonia.

_The Nervous System._—Clouding of the consciousness is as marked
in this disease as in plague. Dull aching frontal headache is
marked and a dull stuporous state soon comes on. Delirium is marked
in some cases. As in plague there are often the facies and mental
state of alcoholic intoxication.

_The Blood._—There does not seem to be anything very
characteristic in the blood examination. Prowazek noted that the
polymorphonuclears showed early fragmentation of the nucleus
and that the cytoplasm stained very red with Giemsa’s stain.
Robinowitsch noted that the leucocyte count fell in the first
day or two, then gradually rose until the crisis and then again
fell. The leucocytosis is only moderate, about 10,000, and the
polymorphonuclears make up about 80 to 85%. Eosinophiles are
decreased. Other observers have noted an increase in the large
mononuclears.

_Complications._—A bronchitis is very common and later on there
may be such a profuse expectoration that the patient cannot get rid
of it and may become cyanotic. Broncho-pneumonia is a very frequent
cause of death. Otitis media and parotitis are not infrequent
complications. Deafness is often marked.

Thrombosis of various vessels may be noted.

Gangrene of the extremities, especially the toes, is frequently
present. Gangrene of areas subjected to pressure, as over the
sacrum, is not infrequent. There does not seem to be the same
tendency to gangrene of the genitalia as in spotted fever of the
Rocky Mountains.

DIAGNOSIS

The more gradual course of the fever and the less marked stuporous condition, together with positive blood cultures, should differentiate typhoid fever.

Plague has the same picture of alcoholic intoxication as typhus,
but is without the rash. Influenza, with its acute onset, is
confusing but does not show any increase in leucocytes.

Other than a moderate leucocytosis and marked acid staining of the polymorphonuclears there is not much that is of help from the laboratory. When guinea pigs are inoculated with typhus virus the period of incubation is from 7 to 10 days.

_Weil-Felix Reaction._—In the diagnosis of typhus fever we attach great importance to an agglutination reaction (Weil-Felix reaction) which the serum of typhus patients has upon certain organisms designated as X_{2} and X_{19}. These correspond in characteristics to certain strains of _Proteus vulgaris_, producing indol in peptone solution, and acid and gas in glucose, maltose and saccharose, but not in lactose or mannite. They digest gelatine and blood serum somewhat more slowly than typical cultures of _Proteus vulgaris_.

Although these organisms have been isolated from the urine of several typhus cases, it seems certain that these X bacilli are neither causative organisms nor secondary invaders. The reaction is therefore heterologous and not specific.

The reaction appears during the first week of the disease but becomes quite marked in the second week and during convalescence. Thus a titre of 1 to 25 on the fifth day usually rises to 1 to 200 or higher by the end of the second week. The test is made either with living or dead cultures and is carried out as for typhoid agglutinations, preferably by the macroscopic method.

PROGNOSIS

Old people are apt to succumb, as do also those who show marked delirium. In childhood it is a very mild disease.

An increase of eosinophiles is favorable while an absence of these
cells makes for a grave prognosis.

The death rate runs from 15 to 60% in many epidemics while Brill’s disease only gives 1 or 2% of deaths.

PROPHYLAXIS AND TREATMENT

PROPHYLAXIS.—This consists almost exclusively in the destruction of body lice, or preventing their access to the person.

Those attending cases should wear gowns, closely fitting at
neck and wrists, and rubber gloves. Better than a gown would be
“unionalls,” with stocking extremities to go over the shoes. The
typhus case should be deloused with the greatest thoroughness, and
his clothing sterilized.

For ridding the body of lice, the following steps are essential:

1. The hair of the body and head should be clipped.

2. The subject should be bathed, there being used freely
kerosene-emulsion soap, prepared by boiling 1 part of soap in
4 parts of water, and then adding 2 parts of kerosene oil. The
resultant jelly, when mixed with 4 parts of water, makes a liquid
soap that is convenient to use and which may be applied effectively.

3. Following the bath, the body may be anointed with kerosene,
special care being devoted to the hairy parts. Skin irritation may,
however, require early removal of the oil.

4. It has been found that lice on clothing removed from the
body may remain alive nine days and their eggs as long as forty
days. The clothing therefore should be disinfected by one of the
following methods:

(_a_) Steam; (_b_) boiling for five minutes; (_c_) 5% compound
cresol solution for 30 minutes; (_d_) chemicals such as cyanide or
chlorpicrin.

5. In the absence of facilities for carrying out the steps
described, or to prevent infestation subsequently, dusting powders
are sometimes used. Of these the N.C.I. powder, containing
commercial naphthalene, 96 Gms., creosote, 2 cc., and iodoform, 2
Gms., is the most widely known; but Moore’s powder—creosote, 1
cc.; sulphur, 0.5 Gm., and talc, 20 Gms.—is less irritating and
is said to be six times as effective. It has also been recommended
to wring out the underclothes in 5% compound cresol solution, then
drying thoroughly, or to impregnate them with substances such as
the halogenated phenols.

TREATMENT.—There is no disease in which careful nursing is so important. This applies especially to the care of the mouth. It is very necessary to maintain the recumbent position.

A mouth wash of equal parts of boric acid solution, glycerine and
lemon juice should be used to swab out the mouth several times
daily. Constipation should be controlled by enemata.

It is best to give the patient abundance of fresh air so that tent
treatment is to be recommended. Cool sponging lessens the nervous
manifestations as well as lowering temperature. Ice bags to the
head relieve the headache. Cardiac stimulants are indicated, as
caffein and camphor. Thyroid extract has been recommended. Lumbar
puncture has given amelioration of symptoms. Abundance of water
should be given and the diet should be milk and broths.

The virus of typhus is present in all the organs of an infected
guinea pig and Nicolle has prepared a serum by injecting horses
with emulsions of spleen and adrenals of such animals. The serum
has apparently given good results in human beings when employed
early in the disease, the temperature falling with each injection.
The dosage was about 20 cc. daily.