Chapter III: The Trypanosomiases

DEFINITION AND SYNONYMS

=Definition.=—African trypanosomiasis is an important protozoal disease of Central and West Africa, due to a flagellate, _Trypanosoma gambiense_, and transmitted by a tsetse fly, _Glossina palpalis_. The trypanosome undergoes a developmental cycle in the fly which does not become infective until after about twenty days. The period of incubation is about two or three weeks, after which an irregular fever with approximately normal morning temperature and high evening rise appears, attended with a rapid pulse rate at all times. This is called the stage of trypanosome fever and may show trypanosomes in the peripheral blood. Later on the glands enlarge and gland juice shows trypanosomes. With the appearance of a fine tremor of the tongue, a state of apathy or lethargy, known as sleeping sickness, sets in, attended with trypanosomes in the cerebro-spinal fluid. Gradually increasing mental deterioration marks the almost invariable course to death. A more virulent type of trypanosomiasis is found in Rhodesia.

In Brazil there is a disease caused by a flagellate,
_Schizotrypanum cruzi_, which resembles a trypanosome and is
transmitted by a bug, _Lamus megistus_. The disease runs an acute
course with a high fever and great mortality in infants showing
chiefly manifestations of involvement of brain or thyroid gland. In
adults it runs a chronic course showing neurological manifestations
or signs of myxoedema or even of Addison’s disease.

=Synonyms.=—Sleeping sickness; Negro lethargy. French: Maladie du sommeil. German: Schlafkrankheit. For the Brazilian trypanosomiasis, Schizotrypanosomiasis; Chagas’ disease.

HISTORY AND GEOGRAPHICAL DISTRIBUTION

=History.=—In describing sleeping sickness, in 1803, Winterbottom
brought out the importance of enlargements of the posterior
cervical glands (Winterbottom’s sign).

In 1880 Evans had found a trypanosome in the blood of horses
affected with surra and several years afterward Bruce discovered
that nagana, a fatal disease of cattle, was due to a trypanosome,
_T. brucei_. In 1890 Nepveu found a trypanosome in the blood of a
man in Algeria but owing to vagueness of description the discovery
did not attract attention.

In 1901, Forde found a parasite in the blood of a patient in the
River Gambia Colony who had a fever and in 1902 Dutton recognized
the parasite as a trypanosome and gave it the name _T. gambiense_.
In 1902, Castellani, finding a trypanosome in the cerebro-spinal
fluid of a patient with sleeping sickness, brought about the
establishment of the connection between the trypanosome in the
blood (trypanosome fever) and the trypanosome in the cerebro-spinal
fluid (sleeping sickness). In 1903, Bruce and Nabarro reported that
this disease was spread by a tsetse fly, _Glossina palpalis_.

In 1910 Stephens and Fantham brought forward the existence of a
more virulent trypanosome, _T. rhodesiense_.

=Geographical Distribution.=—The disease exists on the West Coast
of Africa, from Senegal to Mossamedes. It is also present in the
Congo basin and particularly in Uganda. The more virulent form is
found in Rhodesia.

ETIOLOGY AND EPIDEMIOLOGY

=Etiology.=—The African trypanosomiases follow infection with two species of trypanosomes; the more virulent type of the disease, occurring in South Central Africa, being due to _Trypanosoma rhodesiense_, transmitted by _Glossina morsitans_ and that of less severe type, but of more general distribution, being due to _T. gambiense_ and transmitted by _Glossina palpalis_. The very important _Trypanosoma brucei_, which is the devastating agent in the African horse, dog and cattle disease, nagana, is also transmitted by _Glossina morsitans_ and there exists the opinion that this trypanosome is identical with _T. rhodesiense_.

Macfie has reported a new trypanosome, _T. nigeriense_, from young persons in Nigeria. It is said to be less virulent than _T. gambiense_, and to be transmitted by _Glossina tachinoides_.

Bruce considers _T. nigeriense_ as being _T. gambiense_. Macfie
noted many short stumpy forms in animals inoculated with _T.
nigeriense_.

These trypanosomes are blood flagellates and are typical of the
Binucleata in possessing two chromatin-staining areas, the larger
and more centrally situated mass being the tropho or macronucleus
and the smaller, but more deeply staining one, the kineto or
micronucleus (Blepharoplast). Trypanosomes have a fusiform or
fish-shaped body which stains blue. Near the less pointed,
nonflagellated end, usually called the posterior end, is the deeply
stained blepharoplast. Adjoining this is a vacuole and, taking
origin from this part of the trypanosome, is the flagellum. This
borders an undulating membrane attached to the body and then,
carried along to the other extremity, projects free as a long,
whip-like flagellum.

In fresh preparations the body of the trypanosome progresses in the
direction of its flagellated end, although occasionally it will be
observed to move in the opposite direction.

Some trypanosomes show granules at certain stages and it has been observed that the extrusion of these granules precedes disintegration of the trypanosome. It has been suggested that such granules might be infective, explaining the infectivity of blood from which trypanosomes were absent. In the separation of trypanosomes into groups and species Bruce relies upon morphology, action on animals, and manner of development in the tsetse fly. He does not consider serum diagnosis and cross inoculation methods as reliable for differentiation. The human trypanosomes are polymorphic.

_T. gambiense_ varies much in length and breadth. The normal
type, as found in the blood, varies from 14 to 20 microns, while
longer forms, 20 to 24 microns, are growth ones and, in the
longest ones (23 to 33 microns), we have those preparing to divide
longitudinally. The normal short forms are the ones from which
the development takes place in the tsetse fly. In width these
flagellates are from 1.5 to 2 microns. The blepharoplast is oval
and the nucleus situated about the center.

With _T. rhodesiense_ the nucleus is typically located almost adjacent to the blepharoplast. As a matter of fact it may require the passage of this trypanosome through rats to bring out these “posterior nuclear forms,” the nuclear location being at times almost entirely that of _T. gambiense_. In addition to the characteristic of nucleus being near the blepharoplast, this trypanosome is more virulent for laboratory animals than _T. gambiense_, agreeing in this respect with the more severe clinical course in man.

When the tsetse fly, _Glossina palpalis_, feeds on a man in whose
peripheral circulation there are normal type trypanosomes we
have an accumulation of such forms in the middle and posterior
portions of the gut. From the eighth to the eighteenth day long,
slender forms develop and pass forward into the proventriculus.
None of the intestinal forms can cause infection when injected
into animals. These proventricular types work their way into the
salivary ducts and thence into the salivary glands, where further
development takes place. Here we have shorter forms developing,
which are similar in morphology to the normal blood type. It is at
this stage that the fly becomes infective by the passing of these
trypanosomes down the salivary ducts and through the channel in the
hypopharynx to the subcutaneous tissues of the person bitten. High
temperatures, 75 to 85°F., are favorable to development, while low
temperatures, 60 to 70°F., are inimical to development, but do not
kill the ingested trypanosomes. This explains the long period which
at times elapses before a fly becomes infective. Under favorable
conditions a fly becomes infective in twenty to thirty-four days
and remains infective the rest of its life, up to 185 days. The
infection is not transmitted to the pupa. This is an inoculative,
cyclical or indirect type of infection. It is usually considered
that a tsetse fly whose proboscis has just been contaminated with
trypanosome blood is capable of transferring the infection for a
few hours. This would be a mechanical or direct method of infection
and such power for infection only lasts for a few hours.

There are other groups of trypanosomes, not important for man,
in which the cyclical development does not include the salivary
glands. In the _T. pecorum_ group of small monomorphic trypanosomes
development takes place only in intestines and proboscis, while in
the _T. vivax_ group this occurs in the proboscis alone.

When tsetse flies feed on animals infected with trypanosomes only from 2 to 6% become infective. Again, it has been shown that where the wild animals on which tsetse flies feed may show an infection of from 16 to 50% yet not more than 2 out of every 1000 tsetse flies, caught and tried out on susceptible animals, show themselves infective.

Both of the human trypanosomes of Africa have been cultured by
using the N.N.N. medium in which rat’s blood was substituted for
that of the rabbit. Human blood will also serve as a substitute.
Growth however is not constant.

=Epidemiology.=—Practically the only method of transmission of the disease is by the bite of infected tsetse flies. The female gives birth to a single, yellowish brown, motile larva, which is almost as large as the mother and which, upon reaching the ground, bores its way into a coarse, sandy soil for a depth of about two inches and then becomes a pupa. The larval stage in the mother lasts about two weeks and the pupal stage about a month.

The tsetse fly is much like _Stomoxys_, but has a branching of
the feathering of the arista, long palps, a bulb to the proboscis
and a characteristic upbending of the fourth longitudinal vein
to meet the mid-cross vein. The female deposits her larva near a
shady place upon loose, dry, sandy soil. Moisture and sunlight are
not favorable for pupal development, the sun being particularly
injurious, so that pupae, buried only an inch deep and away from
shade, are killed. This fact has been utilized in prophylaxis by
cutting down the trees. The trouble is that the bush growth which
soon follows is favorable as providing shade for the pupae.

Male and female flies bite and transmit the disease. They bite in
the daytime, usually from 9 A.M., to 4 P.M., and will bite in the
sunlight.

It has been stated that tsetse flies are attracted by persons
wearing khaki clothing.

With a view to eradication of the disease certain areas have been depopulated, but upon examining the flies caught in the district a year or more later, infected flies have been obtained. This would indicate some other reservoir than man. It is now generally conceded that the trypanosome strain in the antelope is the same as _T. rhodesiense_, both being transmitted by _G. morsitans_.

Taute, however, believes them different as he not only injected
blood containing such trypanosomes into himself, with negative
result, but also allowed flies which had fed on antelopes, which
were infective for laboratory animals, to feed on himself, likewise
with negative result. It is a well-known fact that men in good
condition are refractory to trypanosome infection so that this
courageous experiment does not prove the antelope strain to be
different from the human one.

One measure that has been proposed is to kill off the big game from
a certain area with a view to depriving the flies of their main
source of infection.

The probabilities of an animal reservoir for _T. gambiense_ however
is not so well settled. Many think that we may have trypanosome
carriers and that such persons in the enjoyment of health may act
as reservoirs of the virus. Koch suggested that crocodiles were
important factors in the life of the tsetse flies and recommended
the destruction of the crocodile eggs.

Koch noted the infection of 15 women in a fly-free district and considered their infection as coming from sexual intercourse with their husbands, who had returned home from fly districts where they had contracted trypanosomiasis.

This same method of infection of prostitutes has quite recently
been brought to notice by Bernard.

It will be remembered that dourine, a trypanosome disease of
horses, caused by _T. equiperdum_, is transmitted by the sexual act.

All observations however indicate that the spread of the disease is
almost exclusively through the medium of the tsetse fly. Professor
Lanfranchini was infected in his laboratory by a strain which was
supposed to be _Trypanosoma brucei_.

PATHOLOGY

The chief pathological findings are the enlargements of the lymphatic glands. The dura mater may be adherent in places and the pia mater may show areas of thickening. The cerebro-spinal fluid is increased in amount. The pathological process is a chronic polyadenitis which is followed by a chronic inflammation of lymphatics of brain and spinal cord.

We have a meningo-encephalitis in which the most characteristic
feature microscopically is a widespread perivascular infiltration
of small round cells surrounding the vessels of the pia-arachnoid
of both brain and cord. The process is most marked about vessels
of pons and medulla. The nerve cells are but little affected other
than those of the bulbar nuclei.

SYMPTOMATOLOGY

_The Period of Invasion._—After an incubation period which may be as short as ten or twelve days, following the bite of an infective tsetse fly, the trypanosomes may be found in the blood or in gland juice. One case has been reported where an official of the Belgian Congo showed trypanosomes less than four weeks after his arrival in the colony. His first symptoms were noted about ten days after his arrival.

In natives, trypanosomes may be present in the blood for long
periods of time during which they may do heavy work; thus 7 of
Koch’s 52 native porters showed trypanosomes. In Europeans however
the course of the disease is rarely so insidious but rapidly enters
upon the stage of trypanosome fever.

_The Stage of Trypanosome Fever._—Although fever may be absent in natives until the onset of the period of sleeping sickness, yet in Europeans there are usually noted febrile paroxysms, lasting for a few days, and followed, by afebrile periods varying from a few days to two or three weeks.

The temperature curve is of a markedly remittent type, approaching
normal in the morning and going up to 103°F. or higher in the
evening—a wide daily range. Very characteristic is a low-tension
rapid pulse which often is as rapid when the temperature
approximates the normal as when it is higher. Early in the disease
there are evidences of involvement of the nervous system, as shown
by headache insomnia, difficulty of concentration for mental work
and cardiac instability.

_Winterbottom Sign._—Very important are the glandular enlargements, particularly of the glands of the posterior cervical triangle (Winterbottom’s sign), which upon puncture may show trypanosomes when the blood examination fails to reveal them. The glands are discrete, soft, usually painless and may show but very slight enlargement. Oedematous swellings, especially about the eyes or joints or in localized areas upon the trunk, may be rather prominent in some cases. In Europeans pinkish erythematous rings appearing early in the infection may make one think of syphilis. These erythematous patches are not visible on the skin of natives. A dryness of the skin is rather constant and, especially in natives, papules which itch greatly may be present. Rarely such manifestations as orchitis or choroiditis may be observed.

_Kérandel Sign._—Recently great prominence has been given to a
deep hyperaesthesia, which shows itself as a lively pain, often
retarded, after some slight blow upon a bony projection of the
body. Kérandel, who suffered from trypanosomiasis, noted that
the fear of striking against objects became with him an absolute
obsession. It is called the Kérandel sign. It is during this first
stage, when the trypanosomes are to be found only in the blood or
gland juice that the disease would appear to be curable. Upon the
appearance of the trypanosomes in the cerebro-spinal fluid (second
stage) we have practically a hopeless prognosis.

There may be a latent period of several months in which health
seems normal, to be followed by the sleeping-sickness stage. It has
also been noted that untreated cases, as well as those receiving
more or less treatment, may remain in good health for periods up to
several years. There is therefore reason to believe that certain
cases may not enter upon the sleeping sickness stage.

_The Stage of Sleeping Sickness._—In this stage the mentality becomes more weakened. The native from being happy and willing to work becomes morose and apathetic. This change of disposition is frequently the first thing to be noted in a patient by his family. There is a tendency to gaze into the distance. The speech is rather low and tremulous like that of a tired, sleepy child. The tongue especially shows a decided tremor which may also be present in the lips and hands.

The gait is one of weakness and apathy—a shuffling gait. The
reflexes may be exaggerated. Romberg’s sign may be present but
the Argyll-Robertson pupil has not been noted. There may be an
alternation of periods of crying and laughing which with the
occasional exhibition of intention tremor and rarely nystagmus may
make one think of multiple sclerosis. The patient tends to sleep
even when lying in a bright sunlight. Again he may go to sleep
with a morsel of food in his mouth. Notwithstanding the apparent
stupid state of the patient, he will, when aroused, answer fairly
intelligently but with apathy and retardation. The hebephrenic and
catatonic manifestations of dementia praecox may be exhibited in
some cases.

Finally the patient becomes weaker and more emaciated. The pulse
becomes rapid and feeble, the blood pressure being extremely low.
The mouth becomes dry, the teeth covered with sordes and bed sores
develop. There may be convulsions. The coma and general weakness
become more marked and the patient dies. Frequently terminal
pneumonias or dysenteries bring about the end.

The sleeping sickness stage rarely lasts longer than a year and
even with treatment not more than two years.

The Symptoms in Detail

_The Nervous System._—Headache and lack of mental concentration
may be early features of the disease. Deep hyperaesthesia, or
Kérandel’s sign, often present. Patients tend to be morose and
apathetic. Tremor of tongue and lips are rather constant signs
about the commencement of the stage of sleeping sickness. Early
insomnia gives way to the drowsiness that characterizes the second
stage. There is very little disturbance of sensory or motor
functions until near the end. Epileptiform convulsions may be late
manifestations. Coma deepens as the end approaches.

_The Temperature Curve._—The febrile paroxysms, which may not be
present in natives until the sleeping-sickness stage, show great
irregularity of course and a marked remission in the morning. The
fever may be absent for several weeks to return later. Trypanosomes
are more apt to be present in the peripheral circulation during the
fever than when the temperature is normal.

_The Circulatory System._—The pulse tends to run from 90 to 120
beats per minute and is fast even without fever. The tension is
low and the systolic pressure tends to be extremely low during the
later stages of the disease.

_The Lymphatic System._—Most important in diagnosis is the
enlargement of the lymphatic glands, especially those of the
posterior cervical triangle (Winterbottom’s sign). Other enlarged
glands may be the supraclavicular, epitrochlear and axillary
glands. The inguinal glands suffer enlargements so frequently
as the results of wounds and infections of the foot that their
enlargement is of less diagnostic value. The natives of certain
parts of Africa not only attach great diagnostic importance to
gland enlargement but they imagine they cure the disease by
removing the glands with various primitive cutting tools. The
glands are not painful, do not become matted together and rarely
suppurate. Our best means of diagnosing trypanosomiasis is by
withdrawing gland juice with a syringe and examining the smears.

_The Skin._—Erythematous areas may be present in Europeans.
Localized oedemas are rather marked features. The skin may be very
dry and itch markedly.

_Other Manifestations._—The spleen may be enlarged, the
respirations may be more rapid than normal and the blood show a
secondary anaemia. In a blood examination the large mononuclears
show an increase with a normal white count.

The eye may show keratitis or irido-cyclitis in trypanosomiasis.

Trypanosomiasis seems to favor abortion and still-births, in this
respect resembling syphilis.

DIAGNOSIS

In making a survey of a native population Schwetz considers gland palpation as almost as reliable as gland puncture and of course more expeditious. The typical gland should be large and soft or elastic although he admits trypanosomes may be found in small hard glands.

When the glandular enlargement is distinct, with the erythema and headache, there is much that suggests syphilis. Another point of confusion is that positive Wassermann tests are often obtained in sleeping sickness.

The increase in large mononuclears goes with malaria, kala-azar and
syphilis as well as with trypanosomiasis so that such findings are
of little assistance in differential diagnosis.

An early history of attacks of fever, with marked fluctuation of
temperature, associated with rapid pulse, even with the apyrexial
morning fall, is suggestive. Then with the glandular enlargements
we think immediately of laboratory examinations. As with pellagra
the history is very important in the diagnosis of trypanosomiasis.

_For the laboratory diagnosis_ we may use peripheral blood with some thick film method. The examination of preparations from the peripheral blood is usually very discouraging. Very much better results (in fact some prefer this method to any other) can be obtained by taking 10 to 20 cc. of blood in about 25 cc. of citrated salt solution, centrifuging 2 or 3 times and examining the sediment of the third centrifugalization. Dutton and Todd prefer to centrifuge citrated blood and to collect the leucocyte layer for examination as is done in opsonic work.

_Gland Puncture._—The English workers usually prefer the gland
puncture method, using a sterile but dry hypodermic needle. Water
in the needle distorts both leishman bodies and trypanosomes.

In the sleeping-sickness stage trypanosomes can almost constantly
be found in the cerebro-spinal fluid.

In a diagnostic study of 336 cases Broden obtained 87% of positives
from gland puncture, 80% from centrifugalizing the supernatant
fluid left from the second centrifugalization of the blood and 4.5%
from spinal fluid examinations.

Some prefer to inoculate susceptible animals, particularly the
guinea pig or monkey, with blood or gland juice from the suspected
case. A very satisfactory material is an emulsion from an excised
gland which may be inoculated intraperitoneally into white rats.
The further course, after animal inoculation, is the examination of
the blood of these animals for trypanosomes. Usually at the time
the guinea pigs die we find numerous trypanosomes.

Other tests are: (1) Trypanolysis, when unheated suspected serum
and trypanosomes are incubated together for one hour. Normal serum
may occasionally cause disintegration and treated cases give it in
only about 45% of cases. Unfavorable untreated cases give it in
about 80% of cases.

(2) The so-called auto-agglutination test is not of much value.
In this the red cells of the blood of a trypanosomiasis case come
together in clumps when one makes a wet preparation. It is not
a rouleaux formation. (3) The attachment test is made by making
a mixture of inactivated serum, leucocytes and trypanosomes and
allowing them to be in contact for 20 minutes. A positive test
shows attachment of the trypanosomes to the leucocytes.

PROGNOSIS

If the patient cannot be removed from the infected district or cannot receive the atoxyl or atoxyl-tartar-emetic treatment the prognosis is almost surely that of a prolonged but fatal end.

There is very little hope of cure if the disease has gone on to the
sleeping-sickness stage.

PROPHYLAXIS AND TREATMENT

=Prophylaxis.=—The question of depopulation of districts and destruction of the big game therein, when the area is infected with _Glossina palpalis_, has been fully considered under epidemiology.

Isolation, in the fly-free districts, of infected natives has
not proven a very practical measure but that of rendering their
peripheral blood free of trypanosomes by atoxyl injections would
seem more desirable. In this we aim to cure the patient as well as
render him safe to others.

The most practical measure is that employed in Uganda of clearing
the plant and tree growth for at least fifteen feet from the
streams of water, it having been noted that the tsetse flies
confine themselves to a narrow strip not more than fifteen feet
from the water’s edge. The tsetse fly requires considerable
moisture for its existence.

The catching of flies in traps or with a sticky lime does not offer
much encouragement.

As regards personal prophylaxis, white clothes are to be worn as the tsetse fly, along with mosquitoes, prefers dark-colored garments. The legs should be protected by leggings and possibly one could consider the wearing of gloves or veils. As a matter of fact, however, the heat of the tropics precludes these latter measures. As the fly only bites in the daytime one should choose the night for going about, if practicable.

=Treatment.=—The general opinion is that trypanosomiasis is only curable at a time prior to the appearance of trypanosomes in the cerebro-spinal fluid. Consequently, the stage of sleeping sickness offers little chance of cure by treatment.

Such cases have been treated with injections of 10 cc. of 1 to 1000
solution of neosalvarsan into the spinal canal, after withdrawing
about 15 cc. of spinal fluid, but without appreciable curative
effect. On the assumption that trypanosomes invading the central
nervous system are protected from drug action, Marshall proposed
the injection of salvarsanized serum intrathecally. Three hours
after the administration of 0.6 gm. of salvarsan enough blood is
withdrawn from a vein to give about 20 cc. of serum. Following
the withdrawal of a slightly greater amount of cerebro-spinal
fluid from 5 to 20 cc. of the serum is injected in its place.
Yorke in a critical article on the claims for this treatment is
of the opinion that there is no satisfactory evidence that such
a method sterilizes the infected cerebro-spinal fluid. He cites
cases where the trypanosomes disappeared from the spinal fluid
after ordinary treatment and where cases lived for extended periods
after trypanosomes were found in their spinal fluid. Corbus
and associates have described a new method of obtaining a high
medicinal content in the cerebro-spinal fluids. Their work was done
with neo-arsphenamine, but there seems to be no reason why other
drugs may not be similarly administered.

The basis of the method is the observation that hypertonic salt
solution, injected intravenously, will dehydrate the central
nervous system, and that restoration of fluid begins at about
the sixth hour. If a drug is injected into the circulation just
at the time when the restorative formation of spinal fluid is
taking place, it appears that a large quantity is carried into the
subarachnoid spaces with the fluid, as on a flood tide.

Method:

1. 8 A.M. Patient is put to bed.

2. 10 A.M. Intravenous injection of 100 cc. of 15% saline, warmed
and administered slowly by gravity. The symptoms produced by this
injection are mild and transitory.

3. No food is permitted at midday.

4. 4 P.M. Neo-arsphenamine is injected with the usual technic.

5. 8 P.M. Light nourishment is allowed. Patient is kept under
observation, preferably in bed, for the ensuing thirty-six hours.

_Atoxyl._—The first drug to offer hope of cure was sodium
arsanilate, atoxyl, which contains about 26% of As. This is best
given in doses of about 0.5 gram (7½ gr.) in about 15 cc. of
sterile distilled water intramuscularly. Several cases of optic
neuritis were reported but the drug is still a standard treatment.
We give the atoxyl at intervals of five days, Manson gives 3 grains
every third day.

Probably the best treatment is one in which three doses of atoxyl are followed by from 10 to 15 daily or every other day injections of 0.1 gram (1½ gr.) of tartar emetic. The course is repeated after an interval of three weeks. It is advisable to give a hypodermic of caffein a few minutes before the tartar emetic to lessen depression. Kérandel received the atoxyl-tartar-emetic double treatment and ascribed his cure to the tartar emetic. Tartar emetic is also given intravenously, 0.1 gram in 150 cc. water.

Intravenous injection of arsenophenylglycin, in doses of about
1.0 gram. (15 gr.) intravenously has been highly recommended.
Recent reports from German East Africa state that of 35 treated
with this drug six died of the effects of the drug. Salvarsan and
neosalvarsan have been used but apparently without particular
success.

A combination of treatments in which salvarsan, sodium salicylate
and ethyl-hydrocuprein (a quinine derivative) have been used has
been favorably reported by Morganroth where the action of a single
drug was of little value.

Very remarkable claims in experimental animals have been made for
“trixidin,” a preparation of antimony trioxide which is given
intramuscularly. Even inunctions with this preparation have been
quite successful in curing infected mice. In larger animals abscess
formation is an objection.

Daniels has reported good results from the injection of oxide of
antimony. The preparation used is Martindale’s injectio antimonii
oxidi given subcutaneously in 30 minim doses (1/20 grain of the
oxide). Masters gives this preparation intramuscularly and notes
its greater efficiency than any other drug or combination of drugs.
He gives 3/100 grain every other day until 40/100 grain has been
given. If trypanosomes continue present he gives a .77 gram dose
of soamin. Soamin is a drug similar to atoxyl but said to be less
toxic.

In the treatment of 18 cases of _T. rhodesiense_ infections Newham
notes that tartar emetic alone was as effective as the combined
treatment with atoxyl. He gave the tartar emetic injections twice
weekly intravenously commencing with 1 grain and going up to 3
grains. An organic antimony preparation, “Stibenyl,” has been
recommended. See kala-azar.

Very favorable reports have been made from the use of galyl and
ludyl, arsenical compounds.

A drug which is reported to have exceptional trypanocidal effect
on animals infected with both human trypanosomes is “Bayer 205.”
Dogs infected with the dourine parasite and showing oedema
and eye symptoms have been cured by the injection of the drug
intravenously. A dose of 0.5 mg. causes disappearance of parasites
in mice. It is stated that the drug produces a protection against
reinfection which lasts for months.

BRAZILIAN TRYPANOSOMIASIS

=General Considerations.=—In 1909, Chagas reported the finding of a flagellate in the intestines of _Conorhinus megistus_ or, more properly, _Lamus megistus_. He was also able to transmit the flagellate to laboratory animals and could culture it on blood agar.

In investigating the matter of the importance of this flagellate, _Schizotrypanum cruzi_, in Minas Geraes, Brazil, where the above-named bug was present in great numbers in the cracks of the houses of the poor he associated this flagellate infection, which he at first considered trypanosomal, with a disease of the children of that section.

The bug is a vicious feeder and, from its biting chiefly about the
face, has been called barbeiro or barber by the natives. Both the
male and female of _Lamus_ bite and can transmit the disease and
although the parasite is not transmitted hereditarily the nymph is
capable of sucking blood and becoming infected.

It requires several months for the insect to go through the egg,
larval and pupal stage to maturity. Some consider this bug to
belong to the genus _Triatoma_. The insects may live for more than
a year and tend to remain in the same house where they may have
become infected but leave such house if it be abandoned by man.
Brumpt thinks that the bedbug may also transmit the disease. A
large proportion of armadillos in the endemic areas are infected
with _S. cruzi_ but do not seem to be affected thereby. It has been
suggested that this animal may be a reservoir of virus.

_S. cruzi_ is found in the blood of children during the acute febrile stage but at other times in children, and as a rule in adults, it is rarely present in the peripheral blood. The early blood forms are narrow and very motile. They increase in size and slacken in motility when they become about 20 microns long. _S. cruzi_ is characterized by a very large blepharoplast. Dividing forms are never seen in the blood. The common site of multiplication is in the cells of the voluntary muscles and heart and also in the cells of the central nervous system, adrenals, and bone marrow. In these tissues the flagellate takes on a rounded form and undergoes binary division. Continued division converts the infected cell into a cyst. It is this process going on in various important structures that accounts for the extreme variation in symptomatology and pathology.

Chagas thinks that the gametes for the cycle in _Lamus_ arise
from parasites developing in the lungs of the vertebrate host.
Flagellated parasites enter the lungs, lose the flagellum and
become oval in shape, later on dividing into 8 parts. These assume
an elongated form and enter the red cells of the host. Against this
is the statement of various observers that the flagellates are only
to be found free in the plasma, never within red cells. The forms
taken up by _Lamus_ multiply in the intestine and then pass to the
salivary glands after about 8 days. The bug is then infectious when
it bites. Brumpt notes that infection may occur from inoculation of
the faeces passed by the bug, especially through the conjunctiva.

=Symptomatology.= _Acute types._—This form of the disease usually occurs in children under one year of age. The period of incubation is about ten days. It is attended by a high continued fever which may show a slight morning drop. There is marked puffiness of the face and enlargement of the thyroid. The lymphatic glands and spleen are also enlarged. The case may give the picture of a meningitis in which form the disease is exceedingly fatal. During the febrile period parasites are to be found in the blood but in the afebrile intervals which alternate with the febrile ones parasites are not present.

_Chronic Types._—The type of the disease as seen in adults is mainly chronic. They often show enlargement of the thyroid and manifestations of myxoedema. The lymphatic glands are enlarged. Where the adrenal is attacked we have the syndrome of Addison’s disease.

In the cardiac types there are present various forms of cardiac irregularities.

In the cerebral types various neurological manifestations may be noted.

An irregular fever may accompany the signs of involvement of the
various important organs.

The disease is attended by a marked anaemia.

=Diagnosis.=—In the laboratory diagnosis of those cases not showing the flagellates in the blood the usual method is to inoculate a guinea pig with the blood and in about two weeks _S. cruzi_ may be found in the blood of the animal. The parasites may not appear, however, in the blood, when one should resort to culturing the guinea pig’s blood or more surely examine sections of muscle of the animal for the forms in the muscle cells undergoing binary division.

Brumpt has recently advocated the xenodiagnostic method. Thus, in a
number of guinea pigs infected with _S. cruzi_, parasites could not
be found, but by having third stage larvae of _Conorhinus_ feed on
these animals the parasites developed in the bugs. He regards the
alimentary tract of these bugs as a most favorable culture medium.

=Prophylaxis and Treatment.=—Other than destroying the bugs by sulphur fumigation or whitewashing there is little to note. The bugs show a liking for leather articles, as old harness.

The same plan of treatment as for African trypanosomiasis may be
tried but such treatment is not effective with infected animals.

In the myxoedema types thyroid extract is indicated.

NOTE: Escomel has reported the finding of a trypanosome 20 to 40
microns by 3 to 4 microns which had a flagellum as long as the
body and with a very small but distinct blepharoplast (unlike _S.
cruzi_) in the blood of a native of Peru. The patient at the time
of the blood examination was afebrile and showed a generalized firm
oedema. There was noted anaemia, prostration and somnolence. This
may be a new species.

TRYPANOSOMIASES OF ANIMALS

=Trypanosoma brucei.=—This trypanosome causes a surely fatal
disease in horses and one from which few cattle recover. It is
called “nagana” or the fly disease, from being transmitted by
the tsetse fly, _Glossina morsitans_. All animals except man and
possibly the goat seem susceptible. The disease is characterized
by fever, oedematous areas about neck, abdomen and extremities,
progressive anaemia and emaciation. It is an important disease of
domesticated animals of many parts of Africa.

=Trypanosoma evansi.=—This is the cause of a very fatal disease
of horses in India and the Orient and known as “surra.” It also
affects camels and even cattle. It is thought to be transmitted
by biting flies (_Stomoxys_). The symptoms are fever, emaciation,
oedematous areas and great muscular weakness.

=Trypanosoma equinum.=—This trypanosome causes a fatal disease in
horses in South America. There is paralysis of the hind quarters of
the horse which gives the disease the name “mal de caderas.”

=Trypanosoma equiperdum.=—This trypanosome causes a disease of
horses in many parts of the world. It is known as “dourine” and is
transmitted by coitus. The genital organs show marked oedema which
is followed by anaemia and paralysis.

=Trypanosoma dimorphon.=—This trypanosome causes a disease of
horses in Gambia. It is also found in horses and cattle in other
parts of Africa. The parasite shows marked variation in morphology.

=Trypanosoma lewisi.=—Rats in many parts of the world show this
infection which is rarely fatal to them. It is transmitted by the
rat flea by a process of regurgitation. It can also be transmitted
by the rat louse.