typhoid organism.
It was also shown that yellow fever blood, which was negative
for _B. icteroides_, could produce yellow fever when injected
subcutaneously. In 11 autopsies made shortly after death cultures
from various viscera were negative for _B. icteroides_. It was
then decided to abandon, as fruitless, further investigations as
to Sanarelli’s organism, and to take up the mosquito transmission
theory.
=Mosquito Transmission.=—In 1848, Doctor Nott, of Mobile,
strongly advocated the insect transmission of yellow fever but not
specifically incriminating the mosquito.
Riley from a study of Nott’s original paper, thinks that the author
had in mind invisible forms of insect life, which could act as
disease producers, and simply cited the mosquito to illustrate his
views. In 1853, Dr. Beauperthuis, in Guadeloupe, noted that malaria
and yellow fever ceased to exist in regions which from their
altitude fail to nourish “insectes tipulaires.”
He also thought that the virus of these diseases was introduced by
the channel of insect inoculation. Furthermore he stated that the
variety, zancudo bobo (_Stegomyia_), had white stripes on the legs
and was in a way the domestic species. However, there is a question
whether his zancudo bobo was _Stegomyia_ and furthermore if we
translate the expression _inoffensif_ as without result it would
negate the connection between this mosquito and disease production.
From 1881 Doctor Carlos Finlay had been advocating the transmission
of yellow fever by _Culex fasciatus_ (Synonym for _Stegomyia
calopus_).
In 100 experiments made by Finlay 13 cases of yellow fever
developed.
In no instance had these experimental mosquitoes fed on a yellow
fever patient more than six days previous to their biting and,
knowing that a period of at least twelve days must elapse, the
infections in the 13 cases could not have been brought about by
these experimental mosquitoes.
=Extrinsic Incubation.=—An observation by Carter influenced the
Commission in their investigations. Carter, in 1898, noted that a
period of about two weeks generally elapsed between the appearance
of the first case and the group of cases resulting from this first
case. He termed this period the “extrinsic incubation” and we now
know this as synonymous with the twelve-day period of incubation in
the mosquitoes infected by the first case plus the two to five days
of the period of incubation in man.
The American Commission obtained ova from Doctor Finlay and from
these ova mosquitoes were hatched for the experimental work. Of 11
susceptible persons, bitten by contaminated mosquitoes, the first 9
remained uninfected while the two volunteers, bitten subsequently
(Aug. 27 and 31), developed the disease. One of these cases was
that of Doctor Carroll, whose infection was brought about by one
of these laboratory reared mosquitoes which had fed on 4 cases
of yellow fever, two of which were severe cases and two mild.
This mosquito had fed on one of the severe cases just twelve days
previously. The other case was bitten by 4 contaminated mosquitoes,
one of which was the one that had infected Doctor Carroll.
Of the 9 negative cases 6 were bitten by mosquitoes which had fed
on yellow fever patients from the fifth to the seventh day of
the disease and the remaining 3 failures were where the interval
between contamination and biting the volunteer was from two to six
days only.
At this time the medical mind was obsessed with the idea that
yellow fever was transmitted by fomites.
It had been forgotten that Cathrall, in 1800, had failed to infect
himself with black vomit and that Ffirth, in 1804, in order to
obtain material for a graduation thesis, swallowed black vomit
and smeared it, as well as blood, upon wounds he had made on
his skin with negative result. (It will be remembered that the
fourth proposition of the French Commission was that application
of infectious serum to the abraded skin would not produce the
disease—the hypodermic injection being required.)
=Fomites.=—To settle the question of the relative importance of
fomites and infected mosquitoes the Commission caused two houses,
14 × 20 feet, to be erected, one well ventilated for the infected
mosquitoes and the other poorly lighted and ill ventilated for the
black vomit contaminated clothes, sheets and blankets (fomites).
A medical officer and two privates of the Hospital Corps slept in
this room for twenty days in most intimate contact with the infected
material. No infections resulted.
There were other experiments with similar results.
One of the occupants of the fomites building was afterward
inoculated subcutaneously with 2 cc. of blood taken from a patient
in the first day of the disease and developed yellow fever after
four days of incubation. This proved that he was susceptible to
yellow fever.
Blood from this patient, taken in the first three days of his
attack, was injected into a third man who also developed yellow
fever. This experiment was to prove that the production of the
disease was due to a virus capable of multiplying rather than to a
toxin. Of course, it would be impossible to conceive of a toxin so
potent that it could produce symptoms in a third man when diluted
in the circulation of the second man.
In the other building there was a screen partition dividing the
space into two compartments, one containing 15 contaminated
mosquitoes, the other with the same air but without mosquitoes.
Controls occupying the mosquito free section remained free
from yellow fever, while those exposing themselves in the
mosquito-containing compartment developed yellow fever. One of
these cases was bitten by mosquitoes contaminated thirty-nine days
previously, a second one with fifty-one day insects and a third,
who developed a severe case, was bitten by mosquitoes contaminated
fifty-seven days previously.
As above stated the Commission inoculated men subcutaneously with
blood, taken from yellow fever patients in the first three days of
the disease, with positive results. It was also found that if the
blood was heated to 55°C., for ten minutes the virus was destroyed
and, finally, it was found that the filtrate from a Berkefeld
filter was infectious, thus showing that the virus was so minute
as to pass through the pores of a filter which would hold back the
smallest known bacterium (_filterable virus_).
_Experiments of Guiteras._—During the summer of 1901 Doctor
Guiteras, with a view to immunity production, repeated the
experiments of the Army Commission and infected 8 persons, 3 of
whom died. Gorgas thinks the greater severity of these infections
may be explained by greater virulence of the virus developing
in the mosquito during the hot season. It is known that the
development of this virus requires fifteen to twenty days in winter
as against the twelve days for summer.
_Note._—Doctor Lazear, who had charge of the mosquito work of the
Commission, tried to infect himself with experimental insects prior
to his applying a twelve-day mosquito to Doctor Carroll. About
three weeks later he was bitten by a mosquito which he did not at
the time consider a _Stegomyia_. The attack of yellow fever which
resulted from this bite ended fatally.
_To summarize, the American Commission found:_
1. That _B. icteroides_ had nothing to do with yellow fever.
2. That fomites was a negligible factor.
3. That _Stegomyia calopus_, when fed on the blood of a yellow fever
patient, in the first three days of the disease, became contaminated
and, after a period of twelve days, but not before, was capable of
transmitting the disease to a susceptible person. Once infectious the
mosquito so remained for the rest of life.
[Illustration: FIG. 43.—_Aedes calopus_ (_Stegomyia calopus_),
female. From P. H. Reports.
FIG. 44.—_Aedes calopus_ (_Stegomyia calopus_), male.
From P. H. Reports.]
4. The blood of a yellow fever patient in the first three days, which
was sterile for _B. icteroides_, was capable of producing the disease
when injected subcutaneously. If heated to 55°C. for ten minutes
the virus was destroyed however. Furthermore, infectious blood when
passed through a Berkefeld filter remained infectious, thus showing
that the virus is a filterable virus.
The French Commission verified these findings and in addition
brought out the following points.
1. Cutaneous vaccination with infective serum is without result.
2. Infectious serum loses its yellow fever-producing power in
forty-eight hours unless preserved under liquid petrolatum when it
remains virulent for five days.
3. Infectious serum if heated for five minutes at 55°C. loses its
virulence but has prophylactic and curative power.
4. Besides the method of hypodermic inoculation yellow fever can
only be transmitted by the bite of a mosquito in which the virus
has remained for at least twelve days.
5. In one instance it was thought that the progeny of infected
mosquitoes transmitted the disease. Rosenau and Goldberger, in 38
experiments, failed to obtain such result.
_Paraplasma flavigenum._—In 1909, Seidelin reported certain minute
protozoa as existing in the red cells of yellow fever patients.
He considered them as related to the piroplasms and gave the name
_Paraplasma flavigenum_. It is stated that the parasite has been
found as late as the fourteenth day from the onset of the attack.
The idea is advanced that there may be carriers of yellow fever.
These claims are generally denied.
=Epidemiology.=—There are numerous records which attest the almost
universal susceptibility to yellow fever. In the Orwood epidemic,
Carter has reported that of 46 persons entering an infected house,
“Gray Mansion,” 45 contracted yellow fever.
On the “Lombardia,” with a complement of 249, there were 242 cases
and 134 deaths. The 7, who escaped, were immunes.
The idea that the colored race possesses immunity is now thought
to be connected with the contraction of the disease in infancy
or childhood, attacks at this period of life being very mild and
difficult of diagnosis.
_Immunity._—As proof that such immunity is not racial we may note
that in Ecuador the natives of the endemic area about Guayaquil
possess an immunity due to mild attacks in childhood, but the natives
of Quito, 300 miles distant, where there is no yellow fever, do not
possess it, and many residents of Quito have contracted the disease
when passing through Guayaquil to take steamer to Europe.
There has been some inclination to question the immunity conferred
by an attack of yellow fever but Carter has shown that in
quarantine practice we can admit such immunes with perfect safety.
Thirty thousand such immunes were allowed to enter Key West and
Tampa from Havana between 1888 and 1898 and no case of yellow fever
developed from them. During the same period 450 non-immunes from
Havana gave 13 cases in the quarantine stations.
_The Yellow Fever Mosquito._—A knowledge of the life history of
_Stegomyia calopus_ explains the epidemiology of yellow fever.
This culicine species is widely distributed in the tropical
and subtropical world, extending from 38° north to 38° south
latitude. It is rarely found at a greater altitude than 3000 feet.
Petropolis, a railway-connected suburb of Rio, has an altitude of
2300 feet, with cool nights, at times about 9°C, and a freedom
from _Stegomyia_. Persons having occupation in Rio during the day
but returning to Petropolis in the afternoon escape yellow fever.
In this connection it is generally accepted that the female
_Stegomyia_ only bites between 5 o’clock P.M. and midnight. While
the first feeding may occur earlier in the day, all subsequent
feedings, which alone could be infectious, occur late in the
afternoon or at night. (Recent observations show _Stegomyia_ to
bite in daytime,—not at night.)
These views, which were advanced by Marchoux, would explain the
apparent freedom from infection of those leaving infected areas
by the early afternoon. Seidelin, however, claims that these
mosquitoes will continue to bite in the day after numerous feedings
of blood.
It is recognized that railways are unimportant factors in
transporting these mosquitoes, differing in this respect from ships
which offer better conditions.
The _Stegomyia_ is preëminently a house mosquito and a town mosquito.
It is the domesticated one, while the malaria-transmitting ones are
rural and feed in natural plant-containing bodies of water instead of
the water in old tin cans, roof gutters, cisterns or other utensils
surrounding the house which are preferred by the yellow fever
mosquitoes.
_Stegomyia_ seem to prefer water for breeding that is slightly
tainted with sewage, although developing equally well in fresh
water. They will also develop in brackish water.
When once this mosquito takes up its residence in a certain room
of a house it rarely leaves it and thus is explained the danger of
occupying a room which has been occupied by a yellow fever patient.
Then too, the warning sound, so characteristic of the approach of
most mosquitoes, is not given by _Stegomyia_.
The female lays about 70 eggs in small groups and not in a compact
egg raft as with _Culex_. The eggs are therefore difficult of
detection. The eggs do not suffer after rather prolonged drying.
Even temperatures approximately 0°C. do not seem to destroy the
viability. It would seem probable that it is this stage in the
metamorphosis of _Stegomyia_ which is responsible for the survival
of the species under unfavorable conditions.
The eggs the American Commission received from Finley had been
deposited thirty days previously on the edge of some water in a
basin. The water had meanwhile evaporated and the eggs were dry.
Notwithstanding this the eggs promptly hatched out when water was
poured in the basin.
The most favorable temperatures for these mosquitoes range from 29°
to 31°C. Under 20°C. the eggs do not hatch out.
The larvae, which hatch out in about two days, develop into pupae
in approximately one week. In about two days the fully developed
insect breaks out of the pupal case. It will thus be seen that
a period of ten to fourteen days suffices for a generation. The
insect is almost black and has a silvery lyre or Jew’s harp pattern
marking on the thorax. The legs and abdomen also have silvery
bands. The female lays several batches of eggs and has been
observed in one instance to live 154 days. The French Commission
kept a female alive 106 days. They consider that life under normal
conditions is much shorter in duration than in captivity. If
deprived of water the adult insect only lives about five days. In a
refrigerator, Guiteras was able to keep mosquitoes alive, without
food or water, for eighty-seven days.
On fruit and sugar vessels the conditions for the development of
_Stegomyia_ are exceptionally favorable.
These mosquitoes are prone to remain in the same house where they
have been feeding. Carter has pointed out that yellow fever rarely
spreads more than 75 yards from an infected house so that it is
improbable that infected mosquitoes fly, or are carried by the
wind, any great distance.
The same authority has also noted that ships in Havana harbor lying
about 400 yards from shore never become infected when the crew have
not been ashore or where infected ships have not been anchored near
by.
It is probable that they are carried aboard ships in connection
with coaling or provisioning rather than blown aboard by prevailing
winds.
[Illustration: FIG. 45.—Temperature chart of Yellow Fever. A,
Mild case with recovery. B, Severe case showing the saddle-back
temperature curve similar to that of dengue. C, Chart of fatal case
of yellow fever.]
PATHOLOGY AND MORBID ANATOMY
The toxic effects are chiefly borne by the liver and endothelial
linings of the capillaries. The cloudy swelling of the liver cells
obstructs the bile canaliculi, causing jaundice, and the more
advanced fatty degeneration of these cells brings about disturbances
caused by interference with the important liver functions. The
degenerative changes in the endothelial cells lining the capillaries
bring about the haemorrhages so much a feature of yellow fever.
The icterus is apt to be more marked after death, and is especially
prominent about the neck and eyelids. Dutroulau considers the
absence of icterus in a cadaver as negativing yellow fever.
The liver is of a boxwood or chamois skin color and on section is
very oily. Haemorrhagic patches may be seen dotting the yellow cut
surface.
A midzonal fatty degeneration of the liver cells may be noted in
cases dying by the 4th and 5th day but later there is degeneration of
the entire lobule.
The stomach and intestines contain disintegrated blood. Petechiae
and erosions are common in the cardiac end of the stomach. The
upper part of the duodenum shows changes similar to those seen
in the stomach but the other portions of the intestines are
essentially negative.
The spleen does not show any particular change. The kidneys are
enlarged, congested and on microscopical examination show fatty
degeneration of the renal epithelium.
The adrenals often show fatty degeneration, especially of the
cortex.
Haemorrhagic infiltrations are marked features in skin and mucous
and serous membranes.
SYMPTOMATOLOGY
=A Typical Case.= _Sthenic Stage._—With very slight or absent
prodromata, often during the night, the disease sets in rather
abruptly with chilly sensations and the temperature rapidly rises
to about 104°F. The face is flushed, dusky and swollen, the eyes
injected. Very severe frontal and orbital headaches with marked
rachialgia of the lumbo-dorsal region are peculiarly characteristic.
The pulse is of high tension and the rate from 90 to 110. The
systolic pressure is increased—at times as high as 175. These are
the early manifestations of the _first or sthenic period_ of the
disease.
Vomiting, first of mucus and bile, comes on very early. About the
second day albumin appears in the urine and by the 3d or 4th day
this is present in large amount and is associated with the presence
of hyaline and granular casts. The temperature remains fairly
high for three or four days, with morning remissions and evening
exacerbations. Of great diagnostic value is _Faget’s law_ as to
lack of correlation of temperature and pulse, in that by the 2d
day, notwithstanding the high temperature, the pulse rate becomes
less and by the 3d or 4th day it has probably decreased 20 to 40
beats from its initial rate.
_Stage of Remission._—About the close of the 3rd day or upon the
4th day there may occur a fall in the temperature and a decided
amelioration of the symptoms. This however is frequently not
noted and even when present may last only for a few hours. It
is often called the _stage of remission or calm_. By the 3d day
the congestion of the facies and other sthenic manifestations
have disappeared and, possibly preceded by the short period of
remission, there is ushered in the _second or asthenic stage_.
_Asthenic Stage._—It is at this time that we have the appearance
of the most characteristic features of yellow fever—the jaundice
and the haemorrhages. The jaundice is first noted in the sclerotics
and rapidly spreads over the body as a lemon to orange yellow
tinging. Swelling and bleeding of the gums are the earliest signs
of the damage to the capillaries. This may go on to bleeding from
the nasal mucosa, the intestines and, best known and most dreaded,
the coffee ground vomiting or black vomit of gastric haemorrhage.
Epigastric tenderness is often marked. In very severe cases
haemorrhagic extravasation into the skin may appear. The mind
is peculiarly clear, the patient alert and suspicious. At times
patients may be delirious even to the extent of wild struggling to
throw themselves out of bed.
In favorable cases the temperature rapidly falls to normal,
associated with an unusually slow pulse rate, even below 45.
In the first few days there is a normal white count, with an increase
in the percentage of the polymorphonuclears and later on an increase
in the large mononuclears.
[Illustration: FIG. 46.—Temperature chart from one of the
experimental yellow fever cases reported by the U. S. Army Yellow
Fever Commission. A severe case with recovery.]
Besides the typical course we may have cases so mild that the
albuminuria is insignificant and the jaundice and haemorrhages
entirely absent. On the other hand we may have fulminating cases
with jaundice and black vomit setting in by the end of the 3rd day
and rapidly going on to a fatal termination.
=Symptoms in Detail=
_The Temperature._—This rises abruptly, reaching its maximum by
the 1st day. Very high temperatures are not a feature of yellow
fever. There is nothing characteristic in the further course of
the fever chart and it should be borne in mind that the so-called
intermission is transient and deceitful.
_General Appearance._—On the 1st day the face is swollen and
congested. This florid congestion, which may extend down the neck
to the upper part of the chest, is more marked in yellow fever
than in any other disease. The eyes are shining, the conjunctivae
injected and there is photophobia.
About the end of the 2d day the facial congestion disappears to
be succeeded by an earthy tinging and subicteroid tinting of the
conjunctivae. The jaundice does not appear until about the fourth
day. This may be noted somewhat earlier if one blanches the skin by
pressure with a glass slide. Petechial eruptions may be prominent
in the later stages. The jaundice is best seen at a distance of 5
to 6 feet.
_The Circulatory System._—Of peculiar value in diagnosis is
_Faget’s law_—a falling pulse rate with constant temperature or a
constant pulse rate with a rising temperature.
A markedly slow pulse, between 40 and 50, is often recorded about
the time of the period of remission.
It is interesting to note that the pulse of yellow fever made
a great impression upon Benjamin Rush, who called it the
indescribable or sulky pulse. The systolic blood pressure is high
at first, but by the 2d day begins to fall, becoming quite low in
the asthenic stage (even below 70 mm.) due probably to supra-renal
involvement rather than to cardiac weakness.
Haemorrhages, especially from gums, nose and intestines, are
common. Black vomit is the best known of these haemorrhages.
_Blood Examination._—This has generally been considered as varying
but slightly from normal findings.
Noc states that in the first stages of the disease there is
an increase of the polymorphonuclear percentage with a marked
diminution or disappearance of eosinophiles while later on,
from the 3d to the 6th day, there is an increase in the large
mononuclears.
_The Alimentary Tract._—The tongue may be coated in the
center. Vomiting often appears early and consists of whitish or
bile-stained mucus. It must be remembered that if black vomit
should appear it almost never comes on before the 4th day. There is
usually marked epigastric tenderness. Bleeding from the gums and
intestinal canal are not rare.
_The Nervous System._—The mind is unusually clear, the patient
often mentally alert and suspicious. There is often insomnia. The
severe cephalalgia, often frontal or supraorbital, as well as the
severe loin pains (_coup de barre_) are striking features. There
may be a marked hyperaesthesia. A delirious state may be present.
_The Liver and Spleen._—There is no special alteration in the
size of either liver or spleen. There may be tenderness about the
liver region. The jaundice of the asthenic stage is incident to
the pressure of the swollen degenerating liver cells on the bile
capillaries while the fatal issue is connected with the loss of the
urea formation function. It has been claimed that an acidosis may
occur. The spleen is not affected.
_The Genito-urinary System._—Albuminuria begins to appear about
the second day and tends steadily to increase in amount. Various
types of tube casts, often bile-stained, are abundant. The urine
shows neither bile nor blood cells except in the later stages
of the disease. The reaction is very acid. It is of the utmost
importance to note the quantity of urine voided, as scanty
secretion, leading to anuria, makes for a very grave prognosis.
DIAGNOSIS
The main points to consider in the diagnosis are: (1) the facies, (2)
the severe cephalalgia and rachialgia, (3) the early albuminuria, (4)
the epigastric tenderness, (5) Faget’s law of lack of correlation
between pulse and temperature, (6) the absence of clouding of the
consciousness, and finally the late appearance of the jaundice and
haemorrhages.
Of the greatest importance is the history of the case as to recent
whereabouts and associates. Also careful questioning as to prior
attacks of jaundice or albuminuria related to hepatic or renal
diseases. Influenza in its sudden onset and fever and pains has much
in common with yellow fever. Weil’s disease is much like yellow fever.
The diseases with which yellow fever is most apt to be confused are:
_Aestivo-autumnal Malaria._—In ordinary aestivo-autumnal malarial
paroxysms the search for the malarial parasite is of great
importance, although the finding of a malarial infection does not
exclude yellow fever. Albuminuria is not a feature of tropical
malaria.
In that type of tropical malaria known as bilious remittent fever
the clinical picture is rather asthenic and bile pigment in the
urine is an early feature. Again jaundice comes on fairly early and
the slow pulse is absent. The spleen is enlarged and tender.
_Blackwater Fever._—This is an asthenic disease with marked
and very early jaundice. The haemoglobinuria (Blackwater) is
pathognomonic. Splenic tenderness is marked.
_Smallpox._—The early headache, backache and vomiting of smallpox
may well confuse one before the eruption of variola appears.
_Dengue._—This is probably the most difficult disease to diagnose
from yellow fever. The facies, orbital pains and backache of yellow
fever and dengue are similar. Dengue also shows a slowing of the
pulse. The high blood pressure of the onset is not present in
dengue. There is no albuminuria in dengue and there is a marked
and early leukopenia with reduction of the polymorphonuclear
percentage, which does not exist in yellow fever. The jaundice of
yellow fever and the eruption of dengue do not show themselves
until after the first three days.
Relapsing fever, typhus fever and plague have been considered by
some authorities as possible of confusion with yellow fever.
_Bilious Typhoid of Egypt._—In 1851 Griesinger described a
disease he called bilious typhoid of Egypt in which there was a
sudden onset with marked chill and rise of temperature in four or
five hours to 103° or 104°F. Rachialgia and bilious vomiting were
marked. There was splenic enlargement. The temperature fell on
the fourth or fifth day with at about this time the appearance of
icterus. Relapses were the rule and the mortality was very high.
Bone pains, especially about the knee, were common and severe. This
disease is now considered a relapsing fever. It is this disease
which affected the troops of Napoleon in Egypt and which was
thought by some authorities to have been yellow fever. Others think
it may have been epidemic jaundice.
PROGNOSIS
This is bad with advancing years and possible lesions of liver or
kidneys. It is difficult to make a statement as to the average
mortality. Thus, in the epidemic of 1853, one of the most virulent
that ever visited New Orleans, the mortality was estimated at 85%,
while that of 1897, one of the mildest epidemics on record, only gave
a mortality of ½%.
As a general rule the earlier in the year an epidemic starts the
more virulent the disease; thus the 1853 epidemic, just referred
to, started in May.
High temperatures and excessive albuminuria, as well as early
appearance of jaundice, are bad signs. The mortality may be
considered as averaging about 20%.
PROPHYLAXIS AND TREATMENT
=Prophylaxis.=—By screening a patient during the first three days of
the disease we prevent the infection of _Stegomyia_ (_Aedes_).
It must be remembered that this mosquito not only breeds near human
habitations but that it tends to remain in the same room where it
has been feeding. Consequently we should use sulphur fumigations or
Giemsa’s spray or killing by hand to destroy insects. The larvae
breed by preference in old tin cans near the house door. To kill
these one should empty every old receptacle of water, and oil or
cover other collections of water.
All receptacles used for collecting and storing water draining from
roofs should be carefully screened with fine copper wire gauze. Of
particular importance is it to treat every suspicious case as it if
were one of yellow fever and screen the patient as well as destroy
any mosquitoes in the room or house occupied by such patient.
Noguchi reports success in prophylaxis by the injection of 2 cc.
of a killed culture of _Leptospira icteroides_. Immunity is not
conferred until after the tenth day. He notes that among 3607
persons vaccinated in Salvador there were no cases of yellow fever
while among the unvaccinated 181 cases occurred. Killed cultures of
_Leptospira icteroides_ were first used for protective inoculation
in 1918 when 427 vaccinations were carried out.
=Treatment.=—At the onset one should give calomel in small doses,
repeated every twenty minutes, until about 2 grains are taken, as
8 doses of ¼ grain calomel with soda. Magnesium citrate or sodium
phosphate should follow the calomel. Some prefer castor oil in large
doses (2 ounces). This treatment should not be repeated, it is only
indicated at the onset of the disease, so that if the case is not
seen until after the second day the laxative or purgative measures
should be withheld.
During the first three days of the disease no nourishment whatever
should be given. The patient should be allowed an abundance of
fluid, of which the best is Vichy, of which may be given a couple
of ounces every twenty minutes or so, iced or just cool, as the
patient prefers. Water, to which 30 grains of bicarbonate of soda
to the pint has been added, makes a good substitute. It is of vital
importance to put the patient to bed and keep him quiet. When
vomiting is severe cracked ice or iced champagne may be of value.
Alkaline enemata are indicated when the patient cannot retain the
Vichy. There would seem to be an acidosis in yellow fever.
A mustard foot bath is best given in bed, the feet and legs of the
prone patient being immersed in a foot tub half full of warm water
into which a pound of freshly ground mustard has been stirred.
Every few minutes there should be added a quart of very hot water
so that the bath may be very hot—just short of burning the feet.
The blankets are kept over the patient and the foot tub, so that we
also give a vapor bath which causes free sweating. This treatment
relieves the headache and backache. This foot bath can be repeated
2 or 3 times in the first twenty-four hours. After the bath, the
sweating patient must be thoroughly dried. Cold spongings are
important means of keeping down fever. For anuria use dry cups
to the loins or hot fomentations. Strychnine may be indicated in
the asthenic stage and camphor in oil hypodermically for extreme
cardiac weakness. The Sternberg treatment is 150 grains of sodium
bicarbonate and ⅓ grain of bichloride of mercury in a quart of
water. The dose is 1½ ounces every hour.
Any exertion causing a rise in blood pressure may be fatal. It
is possible that the stimulation of the circulation incident to
the taking of food may explain the dangers of allowing food to a
patient. As before stated no food should be given for the first two
or three days. Then commence with albumin water and thin barley
gruel. Later on wine jelly and easily digestible broths. Even when
convalescence sets in we should be very careful as to diet.
Noguchi has produced an immune serum to his spirochaete by
injecting horses. He has records of 170 cases of yellow fever
treated with this serum with a mortality of 13.6%, while untreated
cases gave a death rate of 52%. He notes that the serum must be
given before the third day of the disease to be of any value—best
results in the first day. He believes also that though salvarsan
and neosalvarsan have some leptospiricidal action they are both too
damaging to the kidney to supplant serum in treatment.
CHAPTER VI
INFECTIOUS JAUNDICE
DEFINITION AND SYNONYMS
=Definition.=—Infectious jaundice is a spirochaete infection, caused
by _Leptospira icterohaemorrhagiae_. This spirochaete is a common
parasite of rats in various parts of the world and man possibly
receives his infection from this source. There is a sudden onset
with rather high fever, headache and vomiting. The jaundice appears
about the third or fourth day when the urine shows albumin and bile.
Haemorrhages, especially epistaxis, are common and the liver rather
than the spleen shows enlargement. A polymorphonuclear increase is a
feature.
=Synonyms.=—Epidemic jaundice. Spirochaetosis icterohaemorrhagica.
Typhus bilieux. Weil’s disease.
HISTORY AND GEOGRAPHICAL DISTRIBUTION
[Illustration: FIG. 47. FIG. 48.
FIG. 47.—Showing _Leptospira_. (After Noguchi in Journal of
Experimental Medicine.)
FIG. 48.—A group of _Leptospira icterohaemorrhagiae_ from a culture.
(After Noguchi in Journal of Experimental Medicine.)]
=History.=—This disease was probably the form of jaundice noted in
the forces of Napoleon during the Egyptian campaign. It was first
recognized as a distinct disease by Weil, in 1886, who described
it as a peculiar form of acute infectious disease characterized by
jaundice, swelling of spleen and nephritis. Inada and his Japanese
colleagues discovered the causative spirochaete in 1915 and noted
the frequency of this parasite in rats. Infectious jaundice was an
important disease of the soldiers of the recent war.
=Geographical Distribution.=—Japan and Egypt may be considered as
the parts of the world in which the disease is most common. It is
endemic in West Africa and cases have frequently been reported from
the shores of the Mediterranean.
During the Russo-Turkish war (1877) cases of jaundice seen in
the Balkans by Sandwith were probably infectious jaundice as the
disease was frequently noted in that region during the recent war.
Cases were noted in Flanders during the war. A few cases have been
reported from the United States.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—The spirochaete causing infectious jaundice, _Leptospira
icterohaemorrhagiae_, is the type species of a genus described by
Noguchi as having minute elementary spirals running throughout the
body and failing to show either flagella or undulating membrane. The
caudal portion of the spirochaete is remarkably flexible and when
in motion the whole body seems drawn into a straight line except
for the hook formation of one or both terminal portions. Propulsion
seems to occur by the rotary motion of the hook and progresses in the
direction of the straight end. If both ends become curved progression
ceases.
[Illustration: FIG. 49.—Four specimens of _Leptospira icterohaemorrhagiae_. (After
Noguchi in Journal of Experimental Medicine.)]
[Illustration: FIG. 50.—A leptospira viewed under the dark-field microscope. (After
Noguchi in Journal of Experimental Medicine.)]
It is insoluble in 10% saponin thus differing from the other
blood spirochaetes. The constituent spirals are closely placed
and the total length may reach 15 to 20 microns. The dark-field
illumination is preferable for its demonstration although it shows
up well by various staining methods. To culture use a medium of
one part of rabbit’s serum with three parts of Ringer’s solution
inoculating with citrated plasma. The organism is found in the
blood during the first three or four days of the disease. It is
also present in the urine. Young guinea pigs are particularly
susceptible and in them we have, following injection of the blood
of a case, jaundice, albuminuria and haemorrhages. At autopsy the
spirochaetes are best demonstrated in a liver emulsion. Infection
with this spirochaete is common among rats in various parts of the
world so that it may be considered a natural infection of rats, but
they do not seem to suffer from it.
=Epidemiology.=—It is considered that the infection is transmitted
through the urine of infected rats or men. The spirochaetes may
gain entrance through the skin or by mouth. The fact that the
spirochaetes seem to die in urine within 24 hours makes infection
by the contaminated urine questionable but experiments with various
arthropods have failed to indicate their connection with the
transmission of the disease.
In Japan it has been noted that the disease is most common in wet
mines, disappearing when the mines are pumped dry. Before we knew
the cause of the disease attention was directed to the connection
between the infection and working about defective sewers. Trench
warfare, with the accompanying rats and wet conditions, seemed to
favor infection.
PATHOLOGY
The liver shows enlargement and fatty degeneration, but less marked
than in yellow fever. The organisms are found in the liver and also
in the kidneys, which latter show an intertubular congestion together
with haemorrhages in this region. Haemorrhagic areas may be present
in various portions of the alimentary tract and elsewhere.
SYMPTOMATOLOGY
After an incubation period of from 5 to 7 days the disease sets in
abruptly with rigors, headache, muscular pains and vomiting. The
patient is prostrated and has the appearance of extreme illness;
the face flushed and the conjunctivae injected. There is fever of
an irregular type usually running between 102° to 104°F. for the
first three or four days, when it begins to fall by lysis although
occasionally by crisis about the fifth day. Following a few days
of moderate fever or normal temperature there is a tendency for a
second rise toward the end of the second week, which continues for
approximately another week when a slow convalescence sets in in
favorable cases. The secondary fever shows rather marked oscillations.
Jaundice appears about the third or fourth day with marked
tenderness of the liver and slight or moderate enlargement of the
spleen. The urine is scanty and high colored showing albumin and
bile pigments. Early in the second week urine of a low specific
gravity is excreted in large amounts. The pulse is rapid at first
to become slow with the appearance of the jaundice. There is a
tendency to sleeplessness and nocturnal delirium and in unfavorable
cases the “typhoid state” comes on. Pains in the nape of the neck
and calf muscles are common features.
Haemorrhages, starting as epistaxis, are commonly observed.
Next to epistaxis intestinal haemorrhage is the most frequent.
Haematuria is rarely observed. The red cells and the haemoglobin
fall in percentage with an increase in the polymorphonuclears. The
leucocytosis runs about 15,000.
The spirochaetes may be found with the dark-field illumination
early in the disease in a blood examination and later on in the
urine.
DIAGNOSIS
It must be remembered that the causative spirochaete is very scarce
in the blood of this disease which is usually not the case with
relapsing fever showing jaundice. It is best to inject 2 to 4 cc.
of blood into young guinea pigs intraperitoneally and after the
development of the infection in the animal we find the spirochaetes
rather abundantly in preparations made from liver emulsions and
examined with dark-field illumination. Noguchi cultured the organism
from the blood early in the disease but found it difficult. Wataguchi
states that when the blood is simply diluted with water and kept at a
temperature of about 25°C. growth may be obtained by the fourth day,
reaching a maximum by the second week.
Agglutinins appear in the blood about the end of the first week and
cultures may be agglutinated by such serum diluted as high as 1 to
500.
Bilious remittent fever shows earlier jaundice, a more rapid pulse
rate and malarial parasites.
In yellow fever there is more marked rachialgia and earlier and
more marked albuminuria. The marked leucocytosis of Weil’s disease
should be of differentiating value.
The early jaundice and haemoglobinuria of blackwater fever should
distinguish this disease.
Prophylaxis and Treatment
=Prophylaxis.=—As the infection appears to be transmitted through
the medium of the urine and faeces, sterilization of these discharges
from those sick with the disease should be practised. Extermination
of the rat, the host of the parasite, is the important method of
eradication of the disease.
=Treatment.=—This would appear to be solely symptomatic.
Arsphenamine has no effect on the infection. Hexamethylenamine has
been recommended. A serum against the organism has been prepared and
seems to show protective value.
CHAPTER VII
RAT BITE FEVER
DEFINITION
Rat bite fever is a relapsing type of fever following the bite of
rats infected with _Leptospira morsus-muris_, which brings about
the infection of man with this spirochaete. Following the healing
of the wound we have developing in the cicatrix inflammatory signs
with lymphangitis and swelling of the tributary lymphatic glands. The
onset is sudden with rigors and fever, which latter continues for
several days to then fall to normal and after an apyrexial period to
be followed by relapse. Numerous relapses follow during the following
weeks, months or even years of the disease. In Japan the disease is
known by the name of Sodoku.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—In a study of this disease Futaki and others discovered
a spirochaete in the tissues of the bite area and the adjacent
lymphatic glands (1915). These spirochaetes were about 10 microns
long. In the blood of man and infected animals shorter and thicker
spirochaetes are found (3 to 6 microns). When cultivated in the media
used for other _Leptospira_ we have longer forms up to about 20
microns. The shorter forms are considered as young organisms.
_Leptospira morsus-muris_ is found in the blood of infected
mice, rats or guinea pigs during the first two weeks and then
becomes distributed in the connective tissues especially that
of the lips, bridge of nose and tongue. They are not secreted
in the saliva but the transfer seems to occur by a break in the
spirochaete-containing tissues and thus inoculated into the bite
wound. The organism may possibly be excreted in the urine.
=Epidemiology.=—It has been found that about 3% of house-rats in
Japan are carriers of the disease. It is less frequent in other
countries although reported from various European countries, America
and especially China. The disease has also been reported from
Australia. It seems probable that the construction of the Japanese
houses gives greater opportunity for the occurrence of bites of rats
than elsewhere.
[Illustration: FIG. 51.—_Spirochaeta (morsus) muris_ in lung of
mouse inoculated with blood from human rat bite fever. Silver
impregnation. × 1500. (From MacNeal. After Futaki, Takaki, Taniguchi
and Osumi.)]
[Illustration: FIG. 52.—_Spirochaeta (morsus) muris_ in blood of
guinea pig with experimental-rat-bite fever. Giemsa’s stain. × 1250.
(From MacNeal. After Futaki and associates.)]
PATHOLOGY
In infected guinea pigs there is swelling of the lymphatic glands
and the spleen with the presence of spirochaetes. The liver is
congested and may show a few spirochaetes. In human autopsies there
are degenerative changes in the liver and kidneys. The infection is
rarely fatal in experimental animals although it causes about a 10%
mortality in man.
SYMPTOMATOLOGY
Following a rather long incubation period of from six to eight weeks,
although cases have been reported where not more than two weeks had
elapsed from the time of injury, during which time the wound of
the rat bite heals, we have a rather sudden onset with headache,
nausea and marked weakness. The cicatrix now becomes inflamed and
the surrounding tissues show oedema and at times vesicle formation.
Leading from the inflamed areas is a line of tender lymphatics which
extend to a group of swollen lymphatic glands.
The onset is often characterized by chills and malaise. A rapid
pulse and prostration are present during the pyrexial period.
The fever rises rapidly to 101°F. or 102°F. and within two or three
days has reached about 104°F. and remains high for two or three more
days. About this time it falls rapidly to normal, attended with
profuse sweating. The temperature remains normal for a few days,
during which time the local swelling and inflammation subside. An
eruption of purplish spots may accompany the fever, appearing chiefly
on chest and arms. There may be urticarial lesions. Joint pains,
together with motor and sensory disturbances, may be noted.
Symptoms of nephritis may appear.
After the critical fall of temperature there is usually an
apyrexial period of several days during which time the local
manifestations about wound and glands subside. The fever again
comes on, to later disappear and reappear.
The successive paroxysms are usually of less severity.
The fever is suggestive of the relapsing fevers. The pulse is
rapid and weak. There may be as many as twelve of these febrile
accessions and the course of the disease may extend over several
months. There is an eosinophilia and during the febrile paroxysm
a leucocytosis of about 15,000. The spirochaetes should be looked
for in the blood during the early febrile periods. The dark-field
illumination is the best method for their demonstration.
TREATMENT
Treatment is entirely symptomatic. Some success seems to have
followed the administration of salvarsan.
Strychnine for the heart weakness and tonics during convalescence
are recommended.
Aspirin is often necessary to relieve the headache and joint pains.
As prophylactic measures the same precaution should be taken as to
cauterization of the wound as one would observe in rabies.
CHAPTER VIII
THE LEISHMANIASES
DEFINITION AND SYNONYMS
=Definition.=—Under this designation we group three diseases, two
of which are general infections and one a cutaneous affection. It
is now thought that the visceral leishmaniasis of adults or Indian
kala-azar and that of young children or infantile kala-azar are one
and the same disease. The cutaneous leishmaniasis of the Near East
or oriental sore and the various leishmania ulcerations of tropical
America are grouped with the others solely by reason of their cause,
this being a protozoon of the same genus, _Leishmania tropica_ for
the skin leishmaniases, and _L. donovani_ for the visceral ones. Most
authorities assign to infantile kala-azar a distinct species, _L.
infantum_.
The visceral leishmaniases are characterized by a chronic course,
marked splenic enlargement, progressive anaemia and emaciation
together with leucopenia. The cutaneous leishmaniases can only
surely be differentiated from other tropical sores by the finding
of the leishman bodies from smears made from the granulomatous
tissue of the sore.
=Synonyms.=—Dum-Dum Fever, Tropical Splenomegaly (for Indian
Kala-azar), Splenic Anaemia of Infants, Ponos (for infantile
kala-azar), Oriental Sore, Biskra Button, Bagdad Boil, Bouton
d’Orient, Aleppo Boil, Granuloma Endemicum (for the Eastern cutaneous
leishmaniasis), Espundia, Bubas Braziliana, Uta, Forest Yaws (for the
American cutaneous leishmaniasis).
GENERAL CONSIDERATIONS OF HISTORY, ETIOLOGY AND RELATIONSHIP
=History.=—In 1869 the English medical authorities in India
became familiar with a very fatal disease among the natives of
Assam but regarded it as a very malignant form of malaria. The
native designation for the disease was kala-azar. In 1889 Giles
investigated this disease and finding hookworm ova in almost all of
the cases he came to the conclusion that it was ancylostomiasis.
Rogers (1896) and Ross (1898) after studying the disease were of
the opinion that it had to do with malaria, the former regarding it
as a malignant form of malaria and the latter that it was malaria
plus some secondary infection.
Owing to the very similar temperature charts and misled by
agglutination tests of the serum of kala-azar patients, which he
regarded as showing agglutinins for the _Micrococcus melitensis_,
Bently, in 1902, claimed that kala-azar was a malignant form of
Malta fever.
In 1903 Manson suggested that the disease might be caused by a
trypanosome, the absence of malarial parasites and non-response to
quinine being against the then usually accepted malarial etiology.
A few months later in the same year, May, 1903, Leishman reported
findings which he considered as degenerated trypanosomes in the
spleen pulp of a soldier who died in 1900 at Netley Hospital
of dum-dum fever. Although first noting the peculiar bodies
in 1900, at the time of making the autopsy, he was at a loss
to explain their significance but in 1903, while examining a
trypanosome-infected rat, he came to the conclusion that there was
a similarity in the parasites of the two infections and published
his paper entitled “On the possibility of the occurrence of
trypanosomiasis in India.”
[Illustration: FIG. 53.—_Leishmania donovani._ Smear from juice
after puncture of spleen of case of Indian Kala-azar. (MacNeal from
Doflein after Donovan.)]
In July, 1903, Donovan reported the finding of similar parasites in
material from splenic puncture of cases of dum-dum fever and taken
during life.
There was much discussion as to the true nature of these leishman,
or leishman-donovan bodies, Laveran regarding them as piroplasms
while others thought them to be trypanosomes.
In 1904 Rogers succeeded in cultivating these parasites in citrated
salt solution and noted that the cultural forms were those of
flagellates. In 1903, Wright, of Boston, found similar parasites
in the granulation tissue of a tropical ulcer in a little Armenian
girl.
In 1905, Pianese found leishman bodies in smears from liver and
spleen of children dying with infantile splenic anaemia in Italy.
About the same time Laveran in examining spleen smears made by
Cathoire from an infant dying of an undetermined disease in Tunis
found these bodies. Later investigations have shown this infantile
leishmaniasis to be rather prevalent in the Northern part of Africa
and Southern part of Europe.
Quite recently it has been determined that not only is the classical
oriental sore a form of leishmaniasis but, as well, certain skin
ulcerations found in South and Central America, such as espundia and
uta in Peru, bubas in Brazil and forest yaws in the Guianas.
=Etiology.=—The parasites which cause a general infection in
kala-azar and leishmania infantile splenic anaemia but a local one in
oriental sore are usually separated as distinct species, _Leishmania
donovani_ for kala-azar, _L. infantum_ for infantile splenic anaemia
and _L. tropica_ for oriental sore.
These parasites are grouped with the haemoflagellates and
occur in their vertebrate hosts exclusively as small, oval,
cockle-shell-shaped bodies, measuring 2.5 × 3.0 microns. The
protoplasm stains a faint blue and contains a rather large
trophonucleus which is peripherally placed and gives the appearance
of the hinge of the cockle shell. Besides this macronucleus we have
a second chromatin-staining body which is often rod-shaped and set
at a tangent to the larger nuclear structure. It is called the
blepharoplast or micronucleus and stains a more intense reddish
than the rather fainter stained pinkish macronucleus. One or more
vacuoles are common in the cytoplasm.
Some consider these nonflagellated bodies, which are usually found
packed in endothelial cells of spleen, liver, lymphatic glands and
bone marrow, as resting stages, the flagellate existence occurring
in some other host than its vertebrate one. Patton has carried on
an immense amount of experimental work with the bedbug and has
noted the development of flagellate forms from the 5th to the 8th
days in bugs which fed on kala-azar patients showing leishman
bodies in their peripheral circulation. If the bugs are allowed
a second feeding after the infecting blood meal the flagellates
disappear within twelve hours, so that for full development in the
bedbug a single feeding is requisite. He states that the flagellate
forms change to post-flagellate ones by the twelfth day. At the
same time, although much evidence exists in favor of the bedbug as
host for the flagellate forms, it has not been shown experimentally
that the bedbug is definitely connected with the transmission of
the disease.
Donovan is disposed to incriminate _Conorhinus rubrifasciatus_ as
the transmitting agent and furthermore he feels that there has not
been sufficient investigation of mosquitoes along this line.
_Canine Leishmaniasis._—In the regions where leishmaniasis of
infants occurs there is also found a similar disease of dogs and
Basile has claimed that the disease is transmitted from dog to dog by
the dog flea. As the dog has been regarded by some as the reservoir
of the virus, so naturally the transmission of the disease from dog
to child through the flea has been considered.
Wenyon, however, tried to infect two young dogs with great number
of fleas which had previously fed on dogs infected with canine
leishmaniasis and at autopsy, five or six weeks later, was unable
to find parasites in smears from spleen, liver or bone marrow and
did not succeed in obtaining cultures from this material inoculated
into tubes of N. N. N. medium.
Basile states that a temperature of 22°C. is necessary for
the development of the parasite in the flea and that negative
experiments have been due to their not having been conducted in
the winter. Patton has had fleas feed on a heavily infected dog,
whose peripheral blood showed hundreds of parasites per film. These
experiments were made in the winter and although examining 200 of
these fleas he failed to find any evidence of the flagellates after
eight hours.
Views have been entertained that the canine infection is one with
a flea herpetomonad distinct from _Leishmania_, but as dogs can be
infected with _L. infantum_ and then show manifestations similar to
canine leishmaniasis the parasites are probably the same.
Patton fed great numbers of fleas on a dog experimentally infected
with _L. donovani_ and found that the flagellates had entirely
disappeared from the alimentary tract of fleas dissected after
eight hours, although fleas dissected within four to six hours
showed degenerating _Leishmania_.
As regards oriental sore Wenyon has found that bedbugs and
_Stegomyia_ will feed from the sores and take up parasites which
develop into flagellate forms in the gut of the insects.
Proof of transmission by these agents however is lacking and others
are inclined to suspect the house fly or some species of moth midge.
In Brazil there exists some evidence that the cutaneous
leishmaniasis found there may be transmitted by species of the
tabanid family.
It must be understood that there is always a suspicion that the
flagellate forms noted in arthropod experiments may be those of
nonpathogenic herpetomonad or crithidial species as such forms are
common in arthropods and are difficult to distinguish from the
flagellate stage of leishman bodies.
_Cultural Forms._—Very definite is our knowledge of the cultural
forms of _Leishmania_. Rogers first cultured material from splenic
juice of kala-azar patients in 10% sodium citrate solution at a
temperature of 17° to 24°C. The medium was slightly acidulated
with citric acid. There was no satisfactory development at blood
temperature. In forty-eight hours the oval parasites have developed
into herpetomonad flagellates, from 20 to 22 microns long by 3½
microns broad, with a 20-micron flagellum which takes origin from
the blunt anterior end of the body near the blepharoplast. The
peripheral blepharoplast and centrally placed macronucleus are at
a distance from one another as opposed to the approximation of the
crithidial blepharoplast to the centrally placed nucleus in a body
with pointed anterior end.
Formerly it was thought that there were differences in the three
species of _Leishmania_ from the standpoint of growth on various
culture media, _L. donovani_ not growing on N. N. N. medium while _L.
infantum_ grew well on N. N. N. medium but not in citrated blood. It
is now known that both species will grow on these two media.
It is absolutely essential in culturing _L. donovani_ or _L.
infantum_ that the blood agar or citrated blood be sterile, as
any bacterial contamination prevents growth. With the parasite
_L. tropica_, however, bacterial contamination does not inhibit
development and statements have even been made that growth is
favored by a staphylococcal symbiosis. _L. tropica_, it would seem,
will develop into flagellated forms in cultures at 28°C. while it
will be remembered that Rogers in his original experiments failed
to obtain other than commencing signs of division at 27°C., 22°C.
being the temperature necessary for the development of flagellate
forms.
_L. tropica_ from South American cutaneous leishmaniases seems to
grow more luxuriantly on N. N. N. medium than does that of oriental
sore of Asia and Africa.
Giugni tried N. N. N. media made with human, rabbit and dog blood,
respectively. The parasites grew well on dog and rabbit blood media
but not on that made with human blood. He found growth best when
he added salt in quantity from 5 to 9 grams per liter. When red
corpuscles are laked in a medium the growth is less favorable.
While differences in development on different culture media may
obtain not only with different species but with different strains
of the same species, it would appear that such variations cannot be
utilized as a means of separating the three species.
_Animal Inoculation._—With animal inoculations we formerly thought
that the parasite of kala-azar could be differentiated from that of
infantile leishmaniasis by the fact that dogs could not be infected
with _L. donovani_, while they were susceptible to infections
with _L. infantum_. Recently Donovan and Patton have successfully
inoculated dogs with kala-azar splenic material. Patton found the
parasites in the liver, spleen and lymphatic glands as well as bone
marrow of the inoculated dogs. Consequently we cannot separate the
two visceral leishmaniases from a standpoint of susceptibility
of the dog. Monkeys are susceptible to both diseases. It is
important to recognize the fact that animal inoculations, even with
spleen-juice, rarely give rise to infection.
As regards separating oriental sore from the visceral leishmaniases
Gonder has shown that white mice may be infected with both
kala-azar and oriental sore, there being produced in each case a
general infection with the presence of parasites in spleen and
liver. A point of difference, however, is that the oriental-sore
mice develop lesions on feet, tail and head which was not observed
with the kala-azar mice. There are some reasons for thinking that
in human cutaneous leishmaniasis a generalized infection may
precede the local manifestations.
Dogs and monkeys can be infected with _L. tropica_ as well as mice,
but in them we have only cutaneous lesions produced. Inoculation
should be made intraperitoneally.
A very interesting point is that the dogs in India never show a
natural infection with _L. donovani_, while in the regions where _L.
infantum_ is responsible for human infections the natural infection
of dogs is not uncommon, indeed many think the dog the reservoir of
virus for both _L. infantum_ and _L. tropica_. It has been suggested
that the dogs of India, where kala-azar prevails, may be immune.
_Morphology._—As regards morphology it is usually stated that the
parasites of the three species of _Leishmania_ are practically
identical. In cultures it has been noted that the flagella of _L.
tropica_ are longer and more twisted than those of _L. infantum_.
Again it has been observed that the parasites of the Oriental
and South American skin lesions may at times show a flattened or
band-like trophonucleus instead of the constant round or oval one
of the visceral leishmaniases.
Escomel has reported the finding of flagellated _Leishmania_ in the
South American sores.
_Relationship._—Within the past year the view has been generally
accepted that Indian kala-azar and infantile kala-azar are one and
the same disease, the points of difference between _L. donovani_
and _L. infantum_ which had been advanced from cultural and animal
inoculation standpoints having been disproved.
It has been suggested that the Mediterranean basin may have been
the original focus of visceral kala-azar and that it spread thence
to India by way of Greece and the Russian Caucasus, cases having
been reported from districts which would join the two foci.
Just as children bear the brunt of malaria in old malarious
districts and adults suffer in places in which the disease has been
more recently imported, so by analogy we may consider the disease
as of more recent introduction in India. We now know that visceral
leishmaniasis is widely distributed in China, north of Yangtse, as
well as in the Sudan, and quite recently a case of kala-azar has
been reported from South America, in an Italian, who had lived in
Brazil from 1897 to 1910.
In the Mediterranean basin there is a natural canine leishmaniasis
and some think the human form may be contracted from the dog
through the medium of the flea. This dog kala-azar exists in two
types, one acute and the other chronic.
Some entertain the view that the virus of oriental sore is that of
a modified visceral leishmaniasis and there has been experimental
work along the line of determining whether the cutaneous infection
immunized against the visceral or vice versa as with vaccinia and
small pox.
Manson has suggested that as oriental sore is common in camel-using
countries it might be that a passage through the camel lowered
the virulence of the parasite as passage through the bovines does
variola, so that such an infection was of a mild type.
More recently there has been some evidence to indicate that
oriental sore may simply be a manifestation of a visceral infection
as shown in Gonder’s work with mice and from the fact of the long
period of incubation in oriental sore with the appearance in some
cases of general symptoms as well as the cutaneous ones.
The South American leishmaniases differ clinically from oriental
sore in that, following the primary lesions, ulcerating
granulomatous processes of nasal and buccal cavities frequently set
in subsequently, at times even after the primary manifestations
have healed.
VISCERAL LEISHMANIASIS
=General Considerations.=—There are two types of kala-azar, as
the visceral leishmaniasis is termed, one the Indian kala-azar,
which prevails in Assam, Madras, Indo-China, China and the Sudan
and characterized by a subacute or chronic febrile course and
splenomegaly in older children or adults and the other, the infantile
type, which in over 90% of cases occurs in children under four years
of age.
In 195 cases reported from Assam, by Mackie, 100 were in children
between six and ten years of age so that it is hardly true to call
Indian kala-azar a disease of adults.
The infantile type, which occurs chiefly in the countries bordering
the Mediterranean, is usually stated to be caused by _Leishmania
infantum_ while the adult type is said to be caused by _L. donovani_.
If, as is now thought, the two parasites are identical it will be
necessary to drop the name _L. infantum_.
=Epidemiology.=—Whether Indian kala-azar is transmitted by the
bedbug or infantile kala-azar by the flea are points which have not
been experimentally proven. It must be admitted that epidemiological
evidence supports the bedbug transmission view for the former.
On the other hand, Mackie dissected 322 bedbugs which he had fed on
kala-azar cases with practically negative results. He also injected
material from 588 bugs into two monkeys with negative results.
Mackie was likewise unsuccessful with lice, mosquitoes and sand
flies.
Rogers, investigating the disease in Assam, found that the usual
history in the villages was that someone with the disease came to
a village and subsequently other cases appeared. It was shown that
where a village escaped while others near at hand suffered there
was a history of nonintercourse with the infected villages. The
natives took extreme steps to eradicate the infection, it having been
reported that the Garos even burned the patients as well as their
huts. All evidence shows that the infection is contracted by sleeping
in an infected house. House epidemics and family epidemics are often
noted.
At the same time various observers have frequently noted instances
where an advanced case may associate intimately with his relatives
for months or years and yet none of these develop the disease.
There is little to support the view that it is a contact infection,
as such does not occur in hospitals where verminous insects are
absent. By isolating the sick and moving the uninfected to new
houses, only a short distance away, there is no spread of the
disease. The disease practically appears only in those Europeans
who live with or among natives.
In view of the fact that _Leishmania_ may be found in the
intestinal ulcerations or in the kidneys there have been
suggestions that the disease may be spread through the medium of
faeces or urine. There is not the slightest evidence that the
parasites could live in water which they might contaminate and the
view that some sort of transmitting host might take up parasites
from the faeces or urine is improbable, as the parasites have never
been found in faeces or urine.
The fact that a distance of 300 yards seems to suffice for
permanent protection of the uninfected excludes from consideration
such transmitting agents as the mosquito or house fly.
The tendency of some to incriminate soil factors can be explained
by the well-known fact that bedbugs can live for months without
food, being ready to bite those entering an infected house even
after long disuse as a habitation of man.
Infantile kala-azar may possibly be connected with the disease in
dogs and may be transmitted by the agency of the flea but there is
nothing like the evidence for this view that obtains for the bedbug
theory in Indian kala-azar.
=Pathology.=—At autopsy there is noted marked emaciation with
greatly enlarged spleen and liver, dropsical effusions and ulceration
of the large intestine. The spleen is often enormously enlarged,
rather firm but quite friable. The liver may at times show cirrhosis
but the usual change is a distention of the endothelial cells of the
intralobular capillaries with great numbers of parasites, as many as
100 or more parasites being at times found in a single cell. Not only
do the endothelial cells of the liver contain parasites but those of
the spleen, particularly the cells lining the venous sinuses as well
as those of the pulp cords, the lymphatic glands and bone marrow.
The parasites are present in the intestinal ulcerations of the
terminal stages. Less frequently they are found in kidneys, adrenals,
testicles, pancreas and lungs. Rarely, parasites may not be found
at the autopsy of advanced cases. It is possible that the finding
of coccus-like bodies in the cells of such cases may represent
degenerated leishman bodies. The mesenteric and prevertebral lymph
glands are swollen. The bone marrow is red.
When the phagocytic endothelial cells rupture the parasites
are taken up by other cells and if by large mononuclear or
polymorphonuclear cells may appear in the peripheral circulation.
In possibly 80% of cases the parasites may be found after prolonged
search in smears of peripheral blood. The leucopenia and large
mononuclear increase are the blood features.
SYMPTOMATOLOGY
_Indian kala-azar._—As with all diseases tending to a chronic course
it is difficult to be sure of the length of the period of incubation
of kala-azar and various authorities have given it as from two to
three weeks to several months. Manson states that one of his cases
developed the initial fever of the disease ten days after arriving in
the endemic area. As a rule the period of onset is rather indefinite.
There may be a history of daily rigors, so that malaria is suspected,
but it is found that the fever does not respond to quinine. The fever
is usually of a low remittent type, rarely a low continued fever, in
which the temperature does not exceed 101°F. At times however in the
early stage the remittent fever is of a high type, the temperature
reaching 104°F.
[Illustration: FIG. 54.—Fever chart of a case of kala-azar reported
by Bassett-Smith. This chart shows how easily one might confuse the
temperature curve of this disease with that of Malta fever.]
Rogers attaches particular importance to the fact that four-hour
charts will show a double or even triple rise of fever in the
twenty-four hours instead of the single one in typhoid fever.
The patients also show a striking absence of typhoid malaise and
apathy often stating that they feel well when the temperature may
approximate 104°F.
The febrile accessions last from two to six weeks to be followed by
periods of apyrexia and apparent improvement. Then follow further
waves of fever and apyrexia so that the fever chart may resemble that
of Malta fever.
In the early stages of the disease the loss of weight is apt to be
marked. Later on, owing to improvement in appetite and increase in
spleen, this is not so manifest.
The spleen begins to enlarge early in the disease and has usually
reached the level of the umbilicus by the third month. In some
cases there is little if any enlargement of the spleen even in
the chronic stages. At times we note only an irregular fever with
weakness, anaemia and emaciation. The liver does not usually become
distinctly enlarged until about the sixth month.
The course of the disease in India is chronic often covering a
period of one or two years. In the Sudan, however, Bousfield noted
that the symptoms ran an acute course, the average duration being
only about 5 months. Rarely he encountered chronic cases with
greatly enlarged spleen.
As the disease progresses anaemia and emaciation become marked so
that the bulging spleen and liver in a dusky or earthy colored,
skeleton-like native (black fever) make a striking picture. The
lymphatic glands of cases in North China show enlargement.
Symptoms referable to intestinal ulcerations, such as diarrhoea or
dysentery, are often noted at the end. Bleeding from the gums and
nose is not infrequently noted.
The marked leucopenia, with accompanying decrease in the
polymorphonuclears (the bacterial phagocytes), makes septic
infections and pneumonia especially common in the course of kala-azar.
These complications frequently bring about a fatal termination so
that we do not get the typical terminal cachexia with emaciation,
exhaustion, dry brittle hair, petechiae, oedema and ascites. On
the other hand the tendency of a bacterial infection to cause a
leucocytosis may bring about a cure.
_Infantile kala-azar._—The symptoms on the whole are similar to
those of the adult type of kala-azar and differ only to the extent
that might be expected in a disease occurring in very young children
instead of in those older.
The onset is insidious with some fever and gastro-intestinal upset.
The spleen enlarges, the child becomes apathetic, anaemic and
emaciated. Irregular attacks of fever occur and the child often
suffers from epistaxis, bleeding from the gums or haemorrhages into
the skin. According to Nicolle a peculiar pallor of the skin is
characteristic. Ulcerations of the intestines and noma may bring
about a fatal termination. The liver does not enlarge to the extent
that the spleen does. The finding of the parasites is necessary for
the distinction of this infantile splenomegaly from those of other
origin. The lymphatic glands are not usually enlarged.
Symptoms in Detail
_Onset and Fever Chart._—The disease commences in a rather
indefinite manner, often with gastro-intestinal symptoms or
possibly daily rigors. The fever chart is that of a remittent
fever with rather marked oscillations and in particular a double
rise in the 24 hours, which Rogers regards as characteristic. The
absence of a high continued fever and this double daily rise assist
in differentiating typhoid. Waves of fever separated by apyrexial
periods often simulate the fever chart of Malta fever.
_The Spleen, Liver and Lymphatic Glands._—The splenic enlargement,
which may reach the umbilicus by the third month, is the most
characteristic clinical sign of kala-azar. The diagnosis was
formerly made by spleen puncture but owing to many fatalities
the liver puncture is to be preferred, although the results of
such exploratory examinations are often negative, the liver being
involved to a less extent than the spleen and rarely showing
appreciable enlargement before the third month. It is during the
pyrexial periods that the spleen and liver enlarge.
Cochran has brought forward the importance of examining smears from
excised lymph glands for the parasites and others have shown that
gland puncture is of value. The glands in the infantile type of the
disease often do not show enlargement.
_The Blood._—Marked anaemia is only found in the later stages and
the color index is about normal. The number of red cells rarely
falls below 2,000,000.
Leucopenia is characteristically marked, this having been below
2000 in 62% of Rogers’ cases. This authority considers the finding
of 1 white to 1000 red cells, in a case of fever, very significant
of kala-azar.
There is also an increase in the large mononuclear percentage which
would aid in differentiating typhoid.
The coagulability of the blood is decreased and this may be a
factor in the fatal results which at times follow spleen puncture.
Parasites are found in the peripheral circulation in about 80% of
cases, after prolonged search, and may be phagocytized by either
large mononuclears or polymorphonuclears.
Patton found parasites in the peripheral blood in the examination
of a single slide in 42 out of 84 cases and with three slides in 25
of those not showing parasites with the first slide. By repeated
examinations up to the seventeenth slide, he got positive results
in all 84 cases.
The Sudan commission found that the alkalinity of the serum of
their patients was diminished.
Rogers has noted an acidosis in unfavorable cases of kala-azar
while those showing improvement only showed slight or no acidosis.
_Respiratory and Circulatory Systems._—There is very little that
is constant, the lungs being quite normal in 90% of Rogers’ cases.
The pulse rate is rather variable, although usually accelerated.
Diagnosis
_Clinical Diagnosis._—Cases of kala-azar are usually diagnosed as
malaria and it is in the lack of response to quinine that we have our
best point of differentiation.
In children showing splenomegaly the probability of the case being
kala-azar rather than malaria is indicated if the case has shown
progressive deterioration of health.
Malta fever shows a rather similar succession of febrile and
afebrile periods but the spleen of the former rarely shows marked
enlargement and the bronchial catarrh, sweatings, transient joint
swellings and neuralgic manifestations are characteristic of Malta
fever. Kala-azar may show muscular pains and slight sweatings and
the differentiation has at times only been made by the laboratory
diagnosis.
Typhoid and the paratyphoids are best differentiated clinically by
the presence of a continued fever, the absence of a double daily
rise and the existence of a more marked apathy.
The recent statements that hookworm disease may show enlargement of
the spleen would make this a condition to differentiate. Hookworm
ova and an eosinophilia indicate ancylostomiasis but there is
always the question here as with malaria as to the existence of
kala-azar and some other affection.
_Laboratory Diagnosis._—The leukemias can be easily differentiated
by the blood picture, an important matter because the spleen of
spleno-myelogenous leukemia is very friable and the danger from
splenic puncture is far greater in this condition than in kala-azar.
Banti’s disease with its leucopenia shows a rather similar blood
picture and can only be surely differentiated by the finding of
leishman bodies in kala-azar.
While malaria may at times show a leucopenia below 4000, a
polynuclear percentage below 50 and a large mononuclear one of 20
or more, yet the simultaneous appearance of all three is rare in
malaria while common in kala-azar.
Malta fever, typhoid and the paratyphoids are best differentiated
by blood cultures or agglutination tests.
Until recently it was recommended that for diagnosis our best
procedure was to make a splenic puncture. Manson and others have
pointed out the dangers from splenic puncture in kala-azar and have
rather preferred puncture of the liver, although recognizing that
the chances of obtaining parasites from a liver puncture, are less
than from a splenic one.
Statistics have been given where a mortality approximating 1% has
followed spleen puncture. Bousfield, however, using an all-glass
syringe with a 1½ inch needle did not have a fatality in 120 spleen
punctures.
For diagnosis the spleen or liver juice, rather than pure blood, is
smeared on a slide and stained by some Romanowsky method, preferably
that of Giemsa.
Cultures on N. N. N. medium can also be made.
Human blood seems to inhibit growth so that N. N. N. medium for
cultivating _Leishmania_ should be made from rabbit blood.
The culture should be kept at a temperature of about 22°C.
One should always first examine a smear of the peripheral blood for
parasites in polymorphonuclear or large mononuclear leucocytes. The
Sudan Commission found leishman bodies in the peripheral blood of
13 out of 15 cases so examined, but rarely did they find more than
one parasite-containing leucocyte to a slide.
It is well to select a time when some pyogenic infection causes a
leucocytosis.
Quite recently Wenyon and others have noted the desirability of
culturing the peripheral blood in N. N. N. medium. Diagnosis may be
made in this way, provided one wait from two to three weeks before
reporting negatively as to the presence of flagellated _Leishmania_
in the cultures. As before stated, strict asepsis and a room
temperature are requisite for flagellate development.
It has been noted that artificial pustulation might assist in
diagnosis by giving a multitude of polymorphonuclear leucocytes for
examination for phagocytized _Leishmania_.
Cochran has recently noted the advisability of excising a lymphatic
gland and making gland smears to examine for _Leishmania_. Others
have reported success with gland puncture as utilized in the gland
of trypanosomiasis.
Animal inoculation has no place in diagnosis as such a procedure is
but rarely successful. Ray has recently proposed a turbidity test
in which about 2 drops of blood are added to 20 drops of distilled
water. Instead of giving a clear solution of haemoglobin we have a
turbidity followed later by a white flocculent precipitate. It is
now thought that this turbidity is due to excess of serum globulin
in the blood of this disease and the test can be carried out with
serum instead of whole blood.
=Prognosis.=—Kala-azar is a chronic disease in the great majority
of cases although both the adult and infantile types may show cases
rapidly running to a fatal termination. Marked intestinal disturbance
makes for a bad prognosis as does also a low large mononuclear
percentage. A marked leucopenia is a bad sign particularly when
associated with such low polymorphonuclear percentages as ten to
twenty. Rogers notes that in children the polymorphonuclears several
times did not give more than 5% of the total leucocyte percentage.
The mortality is usually given as about 95% although Rogers states
that he has reduced this to 75% by large doses of quinine. The
action of antimony is that of a specific. Patients often succumb to
complicating septic conditions or pneumonia.
Prophylaxis and Treatment
_Prophylaxis._—The best results in India have been obtained by
abandoning infected houses and establishing new ones for the
non-infected villagers, which need not be more than 300 yards from
the old ones, thus showing that mosquitoes and flies are probably
not concerned in transmission. Measures directed against the bedbug
seem to offer the best chance of success. Often, however, the bugs
are so deeply located in cracks of thick-walled houses that they may
not be reached by sulphur fumigation. Flaming of such crevices with a
plumber’s lamp has been recommended.
_Treatment._—Rogers has recommended quinine in doses of 60 to 70
grains daily, claiming thereby to have reduced the mortality of the
disease to 75%.
Castellani recommends a combination of quinine and atoxyl, while
Manson has reported success with atoxyl in 2 cases, giving 3 grains
intramuscularly every other day.
Salvarsan has been tried, but without much success, as is also true
of X-rays.
Some have tried cinnamate of soda with the idea of increasing the
leucocytes.
With the purpose of increasing leucocytes Rogers has tried
hypodermic injections of sodium nucleate and killed staphylococcus
vaccines as well as splenic substance tablets. The sodium nucleate
injections were most painful and did not increase the leucocytes.
He had some success with tabloids of spleen substance.
If the blood serum shows a lessened alkalinity the intravenous
injection of solutions of bicarbonate of soda should be tried.
Rogers reports very favorable results from the administration of
alkalies by mouth.
Recently hectine has been recommended in infantile kala-azar.
Following the successful employment of intravenous injections of
antimony tartrate in American leishmaniasis it has been used in
Indian and infantile kala-azar.
Rogers has used the same treatment in Indian kala-azar with a
considerable degree of success. He has also used a 5% ointment of
finely divided antimony. The treatment should be continued until
the temperature has been normal several weeks and the leucocyte
count approach the normal.
Antimony may now be considered as a specific in the treatment of the
leishmaniases.
Knowles, at Shillong, has had long experience and striking success
with the intravenous administration of tartar emetic in kala-azar.
The heavy powder alone should be used—not the light powder. A 1%
solution is prepared in normal saline and the solution autoclaved
for 10 minutes at 110°C. If there is any opalescence or deposit
discard the solution. Knowles begins with the intravenous injection
of 3 to 4 cc. for an adult and gives the injections on alternate
days, increasing the dose until we are giving from 10 to 12 cc.,
the maximum dose. It will be noted that the dosage ranges from 3
to 10 centigrams (½ to 1½ grains). The amount of drug given for a
complete course of treatment is 200 cg. (33 grains). In the latter
part of the course of treatment the effects on the patient are more
marked so that caution must be observed, and it may be necessary
to lengthen the interval or reduce the dose. The injections
should not be given within two hours of a meal. Organic disease
of the heart or kidneys contraindicates the antimony treatment.
Coughing, a metallic taste in the mouth and constriction of the
chest are frequently noted following the injection. Nausea, colic
and diarrhoea show that the limit of the drug has been reached
and albuminuria and jaundice are signs of warning to decrease the
dose or stop the treatment. Christopherson considers that 5 to 8
grains will cure oriental sore, but for kala-azar 60 grains may be
necessary. This authority considers 3 grains of tartar emetic as
the maximum dose intravenously. For children under 1 year of age
the intravenous dose of the 1% solution is ¼ to 1 cc., from 1 to 5
years old 1 to 3 cc. and from 5 to 10 years of age 1 to 5 cc.
Manson-Bahr has reported the successful use of an
organic preparation of antimony, the sodium salt of
p-acetylaminophenylstibinic acid. It is a powder, readily soluble
in water and has the trade name of “stibenyl.” It can be injected
intravenously up to 0.8 gram. The drug contains 36% of antimony.
Knowles advises the use of tonics and, when indicated, of
anthelminthics. He also recommends cod liver oil to increase the
weight.
CUTANEOUS LEISHMANIASIS
=General Considerations.=—There is good reason to believe that much
that was written about oriental sore prior to our knowledge of its
etiology referred to tuberculous, syphilitic and other ulcerative
skin lesions. As regards the work done in the investigations as to
etiology Cunningham, in 1885, described deeply staining bodies in
cells which were larger than lymphocytes. Later, in 1901, Firth
confirmed the findings of Cunningham, but considered the bodies as
degenerative changes in the cells rather than entertaining the view
of Cunningham that they were parasitic protozoa. The name _Sporozoa
furunculosa_ was given these parasites. As previously stated, Wright,
in 1903, using his modification of the Romanowsky stain, found round
or oval bodies, from 2 to 4µ in diameter, packed in the cytoplasm of
endothelial cells, in smears from an oriental sore in a child from
Armenia. He called the parasites _Helcosoma tropicum_.
[Illustration: FIG. 55.—_Leishmania tropica._ Smear from granulation
tissue of Delhi boil or oriental sore. (MacNeal from Doflein after J.
H. Wright.)]
As the result of our knowledge that such lesions are caused by
leishman bodies, _Leishmania tropica_, we have been forced to
include among such sores clinical types entirely different from the
classical oriental sore of Fayrer or Tilbury Fox. Even a keloid
type of lesion described by the workers in the Sudan is known now
to be caused by leishman bodies. In 1909 leishman bodies were
demonstrated in ulcerative processes from Brazil and since that
time we have divided cutaneous leishmaniasis into two groups,
according to geographical distribution, that of the East, or
oriental sore, and that of the West, or American leishmaniasis.
Oriental sore is found chiefly in North Africa, Asia Minor, Syria,
Persia and India, and more recently cases have been reported from
Italy and Greece and New Caledonia. American leishmaniasis is found
chiefly in Central America, Brazil, Peru and the Guianas.
=Epidemiology.=—There is nothing definite known as to the
epidemiology of cutaneous leishmaniasis. The fact that oriental sore
almost always occurs on the uncovered parts of the body would suggest
transmission by some insect as the house fly or mosquito rather than
by the body louse, flea or bedbug, these latter showing no special
preference for the uncovered skin.
There has been a great deal written about the origin of the disease
in drinking water, various inorganic constituents having been
incriminated as factors. In certain places, as Delhi, oriental sore
has decreased among the British troops with the discontinuance of
the use of water from certain city wells. We know that oriental
sore is rather easily inoculable, it having been stated that
certain people of Bagdad inoculated their children in order to
insure against the possible appearance of the sore on the face with
the resulting scar disfiguration. Wenyon found that the virus would
not pass through the unabraded skin.
The disease is most prevalent about the end of summer and in the
autumn. It is a disease of towns. Some have thought that it might
be transmitted through the medium of the laundry. Not only can man
be infected by inoculation but this is also possible with monkeys
and dogs when a scarified area about nose or over eyebrows is
inoculated with virus from a sore.
The lesions are similar to those in man but last a shorter time.
It has been suggested that the dog may be the reservoir of this
virus as well as for that of infantile kala-azar. There is some
experimental evidence to show that an animal which has recovered
from a visceral leishmaniasis is immune to a cutaneous one.
There has been an idea that lizards or snakes might serve as
the reservoir of virus for oriental sore and that species of
_Phlebotomus_ feeding on these reptiles might take in the
flagellates and subsequently transmit them to man. Laveran,
however, has been unable to infect lizards with _L. tropica_.
Patton’s observations point to infection from the crushing of
infected sandflies when biting the exposed surfaces of the skin.
The natural infection of man with oriental sore produces a rather
lasting immunity.
As regards the American sores there is a great deal of difference
of statement as to the probable transmitting agent. These sores
seem to occur in forest regions where clearing of the trees is
going on. Infections occur in late summer or autumn. Marshy
districts appear to favour infection. Brumpt thinks the fact that
dogs, which are susceptible as well as monkeys to inoculation with
the American leishmaniasis, are often bitten by ticks without
the production of the sore, is against the view that ticks act as
transmitting agents. He rather favors a tabanid fly and in a case
reported by Darling the patient incriminated a tabanid fly.
Five cases are reported by Cerqueira as following the bite of
_Phlebotomus lutzi_.
The disease seems to occur naturally in the dog in the infected
regions.
=Pathology.=—In oriental sore there is an infiltration of the corium
and its papillae with plasma and lymphoid cells as well as with large
phagocytic cells packed with leishman bodies which cells Wright
regards as endothelial cells. There is atrophy of the epidermis.
In the keloid type of leishmaniasis noted by the Sudan Commission
epithelial cell nests were characteristic although there was no
other evidence of epithelioma.
In the American leishmaniasis there is rather constant involvement
of the lymphatic glands and often lymphangitis. Histologically the
appearance is rather that of granulation tissue with occasionally
giant cells.
SYMPTOMATOLOGY
_Oriental Sore._—Wenyon inoculated a scarified area on his arm which
became infected with pyogenic organisms but eventually healed. It was
thought that this inflammation would destroy any _Leishmania_ which
might have been present. About six months later he became ill and
had fever up to 103°F. for a week with malaise and gastro-intestinal
upset. At this time a small red papule was noted upon the site of the
original scarification which subsequently enlarged and was found to
contain leishman bodies.
The period of incubation is usually given as about two months,
although in some instances it may be as short as a week. Usually
the earliest appearance of the sore is similar to that of a
mosquito bite. The papule continues to enlarge, becoming purplish
in color with a glazed surface. It somewhat resembles an inflamed
acne lesion. Growing larger, the surface of the blind boil-like
lesions now becomes covered with brownish scales and, either from
scratching of the rather pruriginous spot or from the development
of vesicles, it becomes covered with a yellowish crust, beneath
which is an ulcer with raised edges and discharging a thin
offensive pus.
The ulceration does not generally occur before the third or
fourth month. The ulcer is painless and may be an inch or more
in diameter. Healing comes on in about seven to ten months, the
yellowish unhealthy granulations giving place to healthy pink ones.
The sore tends to run a course of about one year, hence the French
designation _bouton d’un an_.
According to Weber’s statistics about 85% of the sores were located
on the upper or lower extremities and about 10% on the face, while
the trunk served as the location for only about 5% of the sores.
There are generally 2 or 3 sores.
According to Déperet and Boinet the number of sores to a case was
one sore in 30%, 2 to 4 sores in 50% and from 4 to 20 in about 20%
of cases.
[Illustration: FIG. 56.—Oriental sore. (Ruge and zur Verth after
Cardamatis.)]
_American Leishmaniasis._—Under a number of names such as
_espundia_, _uta_, _bubas_ and _forest yaws_ there has been found in
many parts of Central and South America an ulcerating sore, more or
less resembling oriental sore, but often associated with ulcerating
granulomatous lesions of nasal and buccal mucosae. Da Silveira
states that in Brazil about 20% of cases develop the mucous membrane
lesions. He notes an incubation period of two to three months. In
Venezuela the mucous membrane lesions are more rare.
The lymphatic glands and lymphatics are commonly affected.
Just as with oriental sore one or more pruriginous papular lesions
appear on the uncovered parts of the body. In a few days it
develops a pustular summit. This undergoes ulceration and after
several months or even after the primary lesions have healed
nodules may make their appearance in nose and mouth.
These ulcerate and form fungoid granulations. Even the larynx may
be involved. The nasal septum and other cartilaginous portions
of the nose are often destroyed and the overlying tissues
become swollen and often eroded by ulceration, so that the
patients present the appearance of similar cases where syphilis,
tuberculosis or leprosy may be the cause.
A point of distinction between syphilitic and leishmaniasis lesions
of the nasal mucosa is that the latter do not involve the bony
structures.
Rabello noted that a positive Wassermann may be present in
cutaneous leishmaniasis which is in agreement with Sutherland’s
findings of 27% positives in cases of kala-azar.
The patients suffer from fever, joint pains, bronchitis and general
symptoms. After a long period of ten to twenty years, during which
they often die of some intercurrent affection, there may be a
terminal cachexia.
[Illustration: FIG. 57.—A case of _Leishmaniasis_ from Brazil
showing lesions in the mouth. (After Carini; from Mense.)]
=Diagnosis.=—The diagnosis in either oriental sore or in
American leishmaniasis can only be made surely by the finding of
_Leishmania_, either by scrapings from the edges of the ulcer or by
culturing in N. N. N. medium the blood from the immediate site of the
sore. Cultures were once obtained from the blood of a finger where
the sore was located on the arm of the same side but usually the
parasites are absent from the peripheral circulation. Gland puncture
in American leishmaniasis may give positive findings of parasites.
=Prophylaxis and Treatment.=—Knowing that the application of
material from a sore to a scarified surface will bring about
infection, it would seem advisable to cover any abrasions or open
wounds with flexible collodion or other protectives so as to prevent
flies, which may have fed on oriental sores, from having access to
the wound.
It has been recommended to paint the spot of insect bites with
tincture of iodine.
Atoxyl and salvarsan have been tried in oriental sore and American
leishmaniasis without any particularly striking curative results.
Attempts have been made to excise the early lesions but unless one
goes well beyond the infected area, severe recurrences may result.
Bier’s passive congestion method has been tried without success.
An expectant treatment is usually resorted to, the crusts being
softened and removed with antiseptic fomentations with subsequent
disinfection of the ulcer with bichloride or potassium permanganate
solution and the application of some antiseptic ointment or powder.
Thorough cauterization with pure carbolic acid followed by rapid
neutralization with alcohol can be tried. The injection of killed
cultures of _Leishmania_ does not seem to have been effective.
Wenyon has had good results from an ointment of equal parts of
methylene blue, lanoline and vaseline in an American sore.
Carbon dioxide snow has been shown by Mitchell to be an efficient
local application for oriental sore.
The remarkable effect of antimony on the parasites of leishmaniasis
was first noted in the treatment of the cutaneous types. The
treatment is similar to that described under kala-azar. The effect of
the drug is less pronounced on the lesions of the mucous membranes.
CHAPTER IX
DYSENTERY
DEFINITION AND SYNONYMS
=Definition.=—The designation dysentery refers to a symptom-complex
of (1) small, frequently passed mucous or muco-sanguinolent stools
and (2) pains connected with spasm of the sphincter ani (tenesmus) or
intestinal gripings (tormina).
The condition may be set up by numerous causes but of these two so
outweigh the others that it is usual to have in mind either bacillary
or amoebic dysentery when the term is employed.
=Synonyms.=—The Bloody Flux. French: Dysenterie. German: Ruhr.
GENERAL CONSIDERATIONS
As will be noted in the sections dealing with amoebic and bacillary
dysentery our present knowledge of these conditions is of recent
date. There was so much that was etiologically, epidemiologically
and clinically contradictory that the subject was impossible of
elucidation until the existence of a group of dysentery bacilli was
generally accepted, following the reporting, in 1898, by Shiga, of
his bacillus of dysentery.
Although Hippocrates was the first accurately to describe the
disease we now know as dysentery yet there is good ground for
believing that the disease existed in Egypt and India for centuries
before Christ.
Many of the older writers failed to differentiate conditions which
showed admixtures of mucus and blood in the stools from those with
blood alone.
Commencing with the last century, authorities have considered
the association of mucus with the blood as essential in clinical
diagnosis.
It is interesting that with a better knowledge of etiology we are
now recognizing as of dysenteric nature diarrhoeal conditions in
which there is an absence of the typical stool of dysentery.
Our views as to the etiology and epidemiology of bacillary
dysentery have been fairly definite for at least twenty years,
while those relating to amoebic dysentery, notwithstanding the
important researches of Kartulis, Councilman and Lafleur, Schaudinn
and others have remained rather chaotic until quite recently.
_The Term Dysentery._—By the term dysentery we understand a
symptom-complex of more or less characteristic stools and more or
less characteristic pains.
As a rule the stool is composed of one or more teaspoonfuls of
greenish yellow or dirty brown mucus, the altered blood being
intimately admixed with the mucus, or we may have a whitish to
grayish muco-purulent mass with streaks or flecks of blood on the
outside. These mucoid masses may be found suspended in serous,
sanguineous or more or less feculent discharges which are usually
small in amount and passed with much frequency.
The terms tormina and tenesmus are the ones used to designate the
characteristics of the pains of dysentery, tormina for the griping
colicky pains, which center about the umbilicus or run in the
direction of the large intestine, and tenesmus for the painful
spasmodic contractions of the sphincter ani to which is due the
sensation of lack of ability to complete the act of defecation
leading to straining and justifying Manson’s description “glued to
the commode.”
It is usually stated that the nearer the dysenteric process is to
the rectum, the greater the tenesmus and the nearer to the caecum,
the greater the tormina.
THE MODERN CLASSIFICATION OF DYSENTERIES IS BASED ON ETIOLOGY RATHER
THAN UPON CLINICAL MANIFESTATIONS
Owing to the great importance of the two main kinds of dysentery,
amoebic, or that caused by _Entamoeba histolytica_, and bacillary,
or that caused by some strain of _Bacillus dysenteriae_, we shall
consider them separately from the other causes of the dysenteric
symptom-complex.
=A. Dysenteries caused by animal parasites.=
_Protozoal dysenteries._
1. Amoebic dysentery (_Entamoeba histolytica_).
2. Flagellate dysenteries (_Lamblia intestinalis_, _Trichomonas
intestinalis_ and _Chilomastix mesnili_).
While in adults these intestinal flagellates usually cause only
a diarrhoea, with at times marked nervousness, they may produce
dysenteric symptoms in young children. The onset in children under
three years of age may be insidious and attended with fever. The
stool contains much mucus with only a little blood.
In cases of amoebic dysentery, the diarrhoeal attacks, which at
times occur, are often associated with an abundance of flagellates,
which may well be the cause of the complication. Cases of dysenteric
diarrhoea have been reported from Gallipoli in which _Lamblia
(Giardia)_ were apparently the only parasites involved. Such stools
are often of a yellow ochre color. Relapses are common features
of _Lamblia_ infections. _Lamblia_ is an inhabitant of the upper
intestine while _Trichomonas_ and _Chilomastix_ belong to the
large intestine, especially in the region of the caecum. While
these last named flagellates are often found in the stools of those
convalescent from dysentery there is a general opinion that they
are nonpathogenic. These organisms may be present in diarrhoeal
conditions in which case it is common to designate such diarrhoeas as
flagellate diarrhoeas. Fantham and Porter have reported 187 cases of
pure lambliasis.
In diagnosis it is important to recognize the encysted _Lamblia_.
These are oval cysts, about 10 × 7µ and show a curved central line,
with two lateral dots. When stained these dots show as chromatin
areas. These cysts may be found in the faeces in great numbers. The
vegetative _Lamblia_ has 4 pairs of flagella, is about 15µ long and
has a tumbling motion. Calomel alone or calomel and ipecac give
good results at times. Enemata of organic silver salts may be of
benefit.
Porter recommends bismuth salicylate. Low has noted the tendency of
lambliasis to recur and thinks many of the reported cases of cures
are only temporary. His experience with bismuth, salol, thymol and
cyllin has not been encouraging.
It is well known that lambliasis is of rather frequent occurrence
in mice and rats so that these rodents may be factors in spreading
the infection through the agency of their faeces deposited about
human food.
Of other drugs recommended in treatment Dobell and Low have had no
success with methylene blue, turpentine or beta-naphthol. These
authors failed to find any increase in either large mononuclears or
eosinophiles in a case of the infection.
Since Lamblia inhabit the upper parts of the small intestine, it
may be that the administration of drugs by the duodenal tube will
prove an effective method of treatment. Owens reports successful
results in the treatment of amoebic dysentery from ipecac so
administered. Stiles has recommended sulphur in lambliasis.
3. Ciliate dysenteries (_Balantidium coli_).
While various ciliates may cause a severe type of dysentery it is
very exceptional that others than _Balantidium coli_ do so. This oval
ciliate is from 60 to 100 microns long by about 50 to 70 microns
broad. It is a commensal of hogs and the disease in man is usually
found in those having the care of hogs. Infections have been reported
from various parts of the world, temperate as well as tropical
regions. These ciliates may be found in the faeces of persons
apparently well but in such cases symptoms may eventually appear. The
parasites multiply in the submucosa and the pathologic process is
similar to that observed in the large intestine in amoebic dysentery.
The parasite is so large and has such an active motility that
it would be impossible to fail to detect it in a microscopic
examination of the faeces. Encysted parasites are round. The
onset is rather insidious with diarrhoea which may be followed by
dysentery. A severe form of anemia may be noted.
Ipecac, emetine, arsenic and quinine appear to be of little
value in the treatment, but Walker considers the organic silver
compounds, as protargol, etc., of value. Methylene blue enemata
(1-3000) and 2-grain pills by mouth have been recommended.
[Illustration: FIG. 58.—Important pathogenic Protozoa of the
intestinal tract. (1a) Motile _E. coli_. Note large amount of
peripheral arrangement of chromatin in nucleus. (1b) Encysted _E.
coli_. Note larger size than _E. histolytica_ cyst, 8 ring form
nuclei and absence of chromidial bodies. (2) Motile _E. histolytica_
from acute dysenteric stool. Note histolytica nucleus with scanty
chromatin. (3) Tetragena type of _E. histolytica_ from case of
chronic dysentery. Note greater amount of chromatin and central
karyosome with centriole. (4a) Preëncysted _E. histolytica_ from
carrier. Note small size and heavy peripheral ring of chromatin in
nucleus making this feature of chromatin in nucleus similar to the
larger _E. coli_. (4b) Encysted _E. histolytica_ from dysentery
convalescent. Note small size, 4 ring nuclei and a dark chromatin
staining mass, “chromidial body.” (5a and 5b) Motile and encysted
cultural amoebae from Manila water supply. (6a and 6b) Oocyst and
sporozoite production in 4 spores of _Eimeria stiedae_. (7a and
7b) Oocyst with 2 sporoblasts and oocyst with 2 spores containing
4 sporozoites of _Isospora bigemina_. (8a and 8b) Vegetative
and encysted _Trichomonas intestinalis_. (9a and 9b) Vegetative
and encysted _Lamblia intestinalis_. (10) _Balantidium coli._
Illustrations of amoebae from Walker—others from Doflein.]
4. There are also dysenteric manifestations noted in the terminal
stages of kala-azar (_Leishmania donovani_) and in algid pernicious
malaria (_Plasmodium falciparum_). These conditions are taken up
under the diseases kala-azar and malaria.
Wenyon noted a case of coccidial infection (_Isospora hominis_)
in which there was a dysenteric syndrome. There have been about
seventy cases of infection with this parasite reported, chiefly
from soldiers serving in Gallipoli. The usual opinion is that they
are nonpathogenic parasites. The oocysts are ovoid, with one end
narrowed, and measure 28 × 14 microns. There are two sporocysts,
each of which contains four sporozoites. The cyst when first passed
is unsegmented.
_Helminthic dysenteries._—1. In addition to the protozoal causes
above noted we may have dysenteric symptoms following infections with
trematodes, especially _Schistosoma mansoni_ and _S. japonicum_. In
these cases we have mucus coating the stool with more or less clotted
blood in which mucus we may find the diagnostic ova. A rather high
eosinophilia is present.
2. Infections with _Gastrodiscus hominis_ also give rise to
dysenteric manifestations.
3. A very small cestode, _Heterophyes heterophyes_, has been noted
to cause a condition suggestive of dysentery.
4. In 1902, Brumpt noted the finding of a nematode,
_Oesophagostomum brumpti_, in the large intestine of an African
native, which caused dysenteric symptoms and, more recently,
another species, _O. stephanostomum_, has been reported as causing
a fatal dysentery in a Brazilian at Manaos.
5. There have also been reported cases with dysenteric
manifestations which were apparently connected with intestinal
myiasis.
=B. Dysenteries caused by bacteria.=
1. Those caused by either the more toxic, nonacid mannite strain of
Shiga, or the less toxic, acid mannite strains of the Flexner group.
2. Morgan has reported as the cause of certain bacillary dysenteries
a bacillus known as B. Morgan No. 1. It is motile, produces indol,
and in glucose bouillon gives a very slight amount of gas. It does
not change mannite and does not produce a primary acidity in litmus
milk. This organism is a frequent cause of summer diarrhoea of
children. Flies from houses with such cases often show Morgan’s
bacillus.
Paratyphoid infections may give the clinical picture of a colitis
and such cases at times show a large amount of blood in the
dysenteric stools. Usually the symptoms are rather those of an
entero-colitis or a gastro-enteritis.
3. In Japan, dysentery-like epidemics of a very fatal disease, termed
_ekiri_, occur among young children. The organism is very motile,
producing gas and acid in glucose, but not in lactose media. It is
reported at times to show indol production. Apparently a member of
the Gärtner group.
4. Spirillar dysentery. LeDantec has reported a type of dysentery
which shows the presence of great numbers of spiral forms. These
are Gram negative and noncultivable. It is in question whether they
belong to the bacteria. There is no fever in this type of dysentery.
5. Other bacterial causes. Cases of dysentery have been reported
as caused by _B. pyocyaneus_, streptococci, atypical _B. coli_ and
organisms of the Gärtner group.
In a _Pyocyaneus_ infection the color of the stools would be
suggestive. This cause should be borne in mind in the dysenteric
infections of debilitated children in the tropics. Some of the
cases of so-called ptomaine poisoning due to members of the Gärtner
group have clinical similarities to dysentery especially at the
commencement of the attack.
=C. Dysenteries resulting from mechanical irritants or poisonous
substances.=
A very interesting form of poisoning which gives rise to serious
illness or death and is attended with marked abdominal pain and
manifestations of dysentery is that reported from North China
through the use of short lengths of bristles which are given mixed
with the food.
Various irritant metallic poisons as arsenic, antimony and mercury
may give rise to dysenteric symptoms. In cancer and syphilis of the
rectum there may be a suspicion that the process is an ordinary
dysenteric one.
Intussusception shows marked tenesmus with bloody rather than
muco-sanguineous stools.
While dysenteric symptoms may be present in the terminal stages
of various chronic diseases, especially tuberculosis and cardiac
affections, yet it is in chronic nephritis, leading to uremia, that
we may see symptoms of a marked catarrhal or even diphtheritic
colitis.
CHAPTER X
AMOEBIC DYSENTERY
HISTORY AND GEOGRAPHICAL DISTRIBUTION
=History.=—Lambl, in 1859, was the first one to note the presence of
amoebae in man, these being found in the stools of a child affected
with diarrhoea. It was Lösch, however, who, in 1875, first accurately
described the parasite which he found in the intestinal ulcerations
as well as in the stool of a patient with chronic dysentery and was
able to produce dysenteric ulcerations in the dog, by injecting
amoebae-containing faeces into the dog’s rectum.
In 1879 Grassi noted the encysted forms of amoebae, but as he
found them in well people, he denied their pathogenic importance.
Cunningham found amoebae in the stools of cholera patients and
Perroncito in those of typhoid cases, both of these authorities,
however, viewing the question of their pathogenicity as did Grassi.
This was the general attitude of the medical mind until Koch, in
1883, while investigating cholera in Egypt, was impressed with the
striking penetration of amoebae in the walls of intestinal ulcers
and considered that this fact favored the view that amoebae were
pathogenic.
Kartulis continued the work of Koch and in 1886 published his
findings in 150 cases of dysentery, noting the presence of amoebae
in the stools of all these cases. In 1887 he noted the presence
of amoebae in liver abscess. In 1891, Lutz noted that amoebae in
dysentery contained red cells. In the same year Councilman and
Lafleur came to the conclusion that there were two species of
amoebae in man, one harmless and the other, which was found in
the submucosa of intestinal ulcers, pathogenic, Casagrandi and
others put forward the view that amoebae only acted as carriers for
bacteria, but in 1893 Kruse and Pasquale injected all the bacterial
species isolated from a dysenteric stool into a cat’s rectum with
negative result. Hlava and Kartulis first produced dysenteric
lesions in cats by injecting per rectum, amoebic stools. Kruse
and Pasquale produced dysentery in cats by injecting per rectum
bacteria-free pus from a liver abscess which however contained
amoebae.
A stumbling block as to the connection between amoebae and
dysentery was the fact that many cases of typical dysentery failed
to show amoebae. In 1898 Shiga settled this matter by reporting
a group of bacilli which were concerned in the production of
dysentery. His findings were confirmed all over the world and the
distinction gradually obtained of cases of dysentery from bacillary
as well as from amoebic infections.
In 1903 Schaudinn reported the existence of two species of amoebae,
one harmless and named _Entamoeba coli_, the other pathogenic and
named _E. histolytica_. In 1907 Viereck described a pathogenic
amoeba which, by reason of its four nuclei in the encysted stage,
he called _E. tetragena_.
As the result of the work of Hartmann, Whitmore, Darling, Wenyon and
the recent conclusive findings of Walker we now hold the view that
Schaudinn was working with _E. tetragena_ and not with a separate
species, so that by the law of priority we must drop the name _E.
tetragena_ and accept _E. histolytica_.
=Geographical Distribution.=—Amoebic dysentery seems to be
especially prevalent in Indo-China, China and the Philippines, as
well as in parts of India. It is also very common in Egypt and
Northern Africa. In South America, especially Brazil, it is common,
as is also true of the West Indies and Central America. It is an
important disease in the Southern States of the United States, as
well as in Italy and other parts of Southern Europe. On the whole
it is probable that it exists in greater or less degree in most of
the tropical and subtropical parts of the world.
ETIOLOGY AND EPIDEMIOLOGY
=Etiology.=—For a long time the authorities in Manila held that
it was impracticable to differentiate between a pathogenic and
nonpathogenic species, taking the view that the principal factor
in the production of dysentery was that of symbiosis between
amoebae and suitable bacteria, it having been thought that they
observed in cultures of amoebae evidences of both symbiosis and
antagonism on the part of amoebae to certain species of bacteria.
They furthermore were convinced that pathogenic amoebae could be
cultured on a medium of about 1/10th the strength of ordinary
nutrient bouillon or agar and that dysentery could be produced
by such cultural amoebae. Such views had an important bearing on
epidemiology as it was thought that where amoebae could be cultured
from green vegetables, fruit, or water supply there was positive
evidence of the possibility of infection with amoebic dysentery
from such a source.
The above views are no longer entertained and, due to Walker, working
in Manila with experiments on man, we now know that cultural amoebae
are without effect in the production of dysentery and that there are
certainly two well known species of amoebae having man for a host,
the one pathogenic, _Entamoeba histolytica_, and the other a harmless
commensal, _Entamoeba coli_. Two other species, _Endolimax nana_ and
_Iodamoeba bütschlii_, have recently been described but are generally
considered nonpathogenic.
Some authorities prefer the generic names _Löschia_ and _Endamoeba_
to _Entamoeba_.
Schaudinn, in 1903, described the pathogenic amoeba, which he named
_E. histolytica_, as follows: 1. Distinct, highly refractile and
tenacious ectoplasm. He considered this tough external portion of
the cytoplasm as the explanation of the ability of the pathogenic
amoeba to bore its way into the intestinal submucosa. 2. Eccentric
nucleus which was indistinct by reason of little chromatin. 3.
Reproduction by peripheral budding in which small aggregations of
chromatin reached the periphery of the cytoplasm and, enclosed in a
resistant capsule, broke off from the parent amoeba and constituted
the infecting stage.
[Illustration: FIG. 59.—_Entamoeba histolytica_. The same living
individual drawn at brief intervals while moving. (From Doflein after
Hartmann.)]
For the nonpathogenic _E. coli_ he noted: (1) No distinction
between a granular endoplasm and refractile ectoplasm; (2)
centrally placed and sharply outlined nucleus, rich in chromatin;
and (3) encystment with the formation of eight nuclei, which cysts
with their nuclei or amoebulae form the infecting stage.
The pseudopodia of _E. histolytica_ are actively projected as long
finger-like processes which show the ectoplasm quite distinctly,
while the pseudopodia of _E. coli_ are lobose and sluggishly
projected and show a uniformly opaque grayish color. In dysenteric
stools _E. histolytica_ tends to show contained red cells. _E.
coli_ never contains them but instead shows bacteria and food
particles.
In 1907 Viereck and later Hartmann recognized a pathogenic amoeba
with four nuclei in its encysted form, to which was given the name
_E. tetragena_.
All authorities now consider that Schaudinn made an error in
observation as to the existence of peripheral budding for _E.
histolytica_, so that we recognize but two types of encystment, one
with a larger cyst and thicker cyst wall, with eight nuclei and an
absence of chromidial bodies—_E. coli_—the other, smaller, with
a thin cyst wall one to four nuclei and chromidial bodies in the
encysted stage, the pathogenic amoeba, _E. histolytica_. Synonym,
_E. tetragena_.