Chapter XIV: Tularaemia

DEFINITION AND SYNONYMS

=Definition.=—This is a plague-like disease of various rodents, transmissible to man, caused by an organism _Bacterium tularense_, which is not closely allied to any other species. A number of human cases have been reported from Utah, where the disease is prevalent among the jack rabbits, and the transmission to man is through the bite of a horsefly, _Chrysops discalis_, which has previously sucked the blood of infected jack rabbits.

The site of the bite in man is usually marked by a punched-out
ulcer, which is associated with swelling and suppuration of the
glands draining the area. The general symptoms are sudden onset,
with rigors, followed by an irregular fever of three or four weeks’
duration and by a prolonged convalescence. Several cases have been
reported in the middle west due to handling infected rabbits. There
have been a number of infections in laboratory workers where the
local signs have been absent. In man death rarely results from the
disease.

=Synonyms.=—Deer-fly fever (in man). Plague-like disease (in rodents).

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—In 1911 McCoy and Chapin discovered the _B. tularense_
in a plague-like disease, first described by McCoy in the
California ground squirrel. They described the organism, succeeded
in cultivating it on special media, transmitted the infection to
various rodents by feeding, nasal inoculation and injection of
infected blood, and demonstrated the probable natural mode of
transmission by the squirrel flea.

In recent publications, Francis, Lake and Mayne, and Wayson have
recorded the transmission of the disease experimentally by the
house fly (_Musca domestica_), the horsefly (_Chrysops discalis_),
the stable fly (_Stomoxys calcitrans_), the rabbit louse, the mouse
louse and the bedbug, and have shown that the freshly recovered
organism can be grown on other than the special media previously
recommended.

=Geographical Distribution.=—The first case of infection occurring
in man was reported from Ohio by Wherry and Lamb in 1914. Since
then a number of cases have been reported by Francis among rural
residents of Utah and by Francis and Lake among laboratory workers
handling animals infected with _B. tularense_.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—_Bacterium tularense_ is a small nonmotile Gram-negative cocco-bacillus, from 0.3 to 0.7µ long and gives the appearance in stained preparations of being surrounded by capsular material. It is very difficult to cultivate and until recently it has been grown only on coagulated egg yolk as used by McCoy and Chapin.

Recently Francis has shown that the organism will grow scantily on
serum or blood agar. However, by adding a piece of fresh sterile
spleen to such media he has obtained a more satisfactory culture
medium, although for routine work the egg yolk medium is preferred.
The organism refuses to grow on ordinary media such as nutrient
broth or agar. Material from a culture, or pus from bubo, or an
emulsion of the spleen of an infected guinea pig, when rubbed into
the abraded skin of an experimental animal brings about infection,
in this respect showing a similarity to plague infection. Upon
autopsy of such an experimentally infected guinea pig we find
haemorrhagic oedema at the site of inoculation with caseation of
lymph glands and small necrotic foci in spleen and liver. Smears
from the spleen show the organism in varying numbers. In infected
rodents the organism is often found abundantly in the blood and in
man a bacteriaemia may occur.

=Epidemiology.=—The infection of ground squirrels with this organism was noted by McCoy in his plague work in California. Francis in studying the disease in man in Utah found infection of the jack rabbits and ground squirrels of the region and showed that the transmission of the disease could be carried out by a biting fly (_Chrysops discalis_) and reported this fly as the common transmitting agent of the human infection. He regarded the sick and dying jack rabbits as the reservoir of virus. Tularaemia is chiefly a disease of the rural population attacking those at work in the fields.

As a result of accidental laboratory infections it would seem that
almost 100% of those carrying on extensive animal experimentation
with this organism become infected.

The louse infesting jack rabbits _Haemodipsus ventricosus_, can
transmit the infection from rabbit to rabbit so that the infection
in the jack rabbits is probably kept up by this agency. Recent
experiments have shown that the infection in white mice can be
transferred by the bites of the mouse louse and also by bedbugs.
Again if the mice are fed on infected bedbugs transmission is found
to take place by such feeding experiments. The faeces of such
bedbugs prove infectious. Guinea pigs injected subcutaneously with
the urine of white mice suffering from the disease die acutely with
typical lesions of tularaemia.

Mice fed on the liver of a rabbit dying of the disease succumbed to
the infection within five days.

As noted under etiology the most important method of spread of the disease to man is by the bite of an infected horsefly (_Chrysops discalis_). From experimental studies it would seem that any biting arthropod might prove a transmitting agent. In view of the fact that the infected deer fly tends to lose its infectivity after about five days Francis is of the opinion that the fly is only a mechanical transmitter of the organism.

Wherry reported the infection as manifested by conjunctivitis with
glandular involvement and due to handling infected wild rabbits.

Lake and Francis have reported that of six investigators from
the Hygienic Laboratory working with this infection all have
contracted the disease. There were fortunately no fatalities. Such
an experience demonstrates the great infectivity of this virus and
must lead to the conclusion that the few cases so far reported of
the disease do not represent the importance of tularaemia in man.
With a knowledge of the existence of such an infection and with
satisfactory methods of laboratory diagnosis we shall probably
have other reports of the infection. We now know that the ground
squirrels of California and Utah, the jack rabbits of Utah and the
wild rabbits of the middle west furnish important reservoirs of
virus.

PATHOLOGY

In experimental animals we have lesions which cannot well be differentiated from those of plague. There is not sufficient data for a statement as to the pathology in man.

In experimental animals we have a definite bacteriaemia but in man
the organism has only in rare instances been obtained from the
blood.

SYMPTOMATOLOGY

It has been difficult to determine the period of incubation but in one laboratory infection the disease set in seven days after the patient began tularaemia work. There do not seem to be any prodromata.

In Utah most of the cases showed local lesions at the site of the fly-bite and subsequent swelling and suppuration of adjoining lymph glands. The local lesions were generally observed about the head or on parts of the body not covered by the clothing. There is a rather sudden onset with chilliness or rigors, generally associated with dizziness, prostration and malaise. Headache is usually present and there may be complaints of pains in the back and limbs. The temperature rises rapidly and when first taken during the rigors may reach 103° or 104°F. An irregular fever course follows for two or three weeks. There is practically no apathy, thus differentiating the mental state of typhoid fever or the marked clouding of the consciousness of plague. At times we may have rhinitis and epistaxis.

Physical examination is almost invariably negative. The spleen is
not palpable. The pulse is rather rapid and the blood pressure
uninfluenced.

The white and differential counts vary but little from normal.

The main feature of the disease, aside from local lesions when
these are present, is prostration and this continues marked during
the several weeks or months of convalescence.

It is a disabling illness rather than a dangerous one though a fatal case is recorded.

In the six laboratory infections above referred to, there were no
local lesions except in the case of one man who had had previously
an attack of the disease. In the second attack, two years after the
first one, there was noted a papule on one finger with subsequent
involvement of the epitrochlear and axillary glands. A guinea pig
inoculated with blood taken from the papule became infected and
showed the typical lesions of tularaemia.

There was no fever or malaise in this second attack, thus showing
a degree of immunity. In cases showing conjunctival ulcerations
with glandular involvement Wherry and Lamb obtained cultures of _B.
tularense_ from inoculated animals.

DIAGNOSIS

There is very little in the clinical picture, other than the local lesions, to indicate a diagnosis.

Material from ulcers or glands should be inoculated into guinea
pigs or white mice. The organism is almost invariably absent
from the blood of human cases so that blood cultures or animal
inoculation from such blood are almost always negative.

Complement fixation and agglutination tests are the methods of
diagnosis to be relied on. In the Hygienic Laboratory an antigen
is prepared by washing off the 72 hour growth from egg yolk
medium with small amounts of saline. The suspension is heated for
30 minutes at 56°C. and then preserved by the addition of O.3%
tricresol. Such an antigen is used for each type of test.

PROGNOSIS

This disease is but rarely followed by death. It is however a most incapacitating disease by reason of the three or four months of convalescence during which time the strength and energy of the patient are markedly affected.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—In view of the very great liability to infection of those carrying on autopsies of animals experimentally infected with the disease it would seem advisable to wear rubber gloves when doing such work. It would appear that house flies, stable flies and horseflies may transmit the disease in nature and we know that bedbugs and lice can transmit the disease among experimental animals. When we consider the natural infection of ground squirrels and jack rabbits in California and Utah and wild rabbits in the middle west, the problem of prophylaxis looms to great proportion.

=Treatment.=—At present treatment is entirely symptomatic. Those who go to bed at once and remain in bed during the stage of fever seem to be less seriously affected.