Hugh Chisholm.

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less a man. It is not that, it is a mosquito called in Cumana
the ' Zancudo bobo,' the striped or domestic mosquito."
Beauperthuy, recently as he wrote, then stood almost alone
in this opinion. Now we know that yellow fever, in common
with other specific diseases, is caused by the action of an organized
virus. The search for a vegetable parasite, bacillus or micro-
coccus, as above indicated, has been very close and strenuous,
but it may now be held that up to the present no bacillus or
micrococcus, well authenticated as capable of causing yellow
fever, has been discovered. Latterly a search has been made for
protozoal organisms, organisms similar to those present in the
blood of malarious patients and like conditions, or for spiro-
chaetes similar to those associated with relapsing fever, and
Boyce draws attention to the fact that a spirochaete has recently
been identified in the tissues taken from cases of yellow fever.
It has however been demonstrated that the virus, whatever it
may be, is carried by a species of mosquito; this seems to favour
the protozoan hypothesis, especially as it is found that the
Stegomyia fasciata, Fab. (or 5. calopus, Meig.), after taking the
blood from an infected patient is not infective immediately
but only becomes capable of infecting by its bite at the end
of twelve days. It would appear therefore that residence
in this mosquito is necessary for the material to become
fully infective. During this period some special meta-
morphosis may occur, and metamorphosis essential to the
development of the parasite, or, on the other hand, the time
may be required for it to make its way to some position from
which it may emerge from the mosquito when that insect



78o



PARASITIC DISEASES



" strikes." In the interval between the bite of an infected
Stegomyia and the appearance of the disease (5 or 6 days) the
blood of the patient contains a virus which, when taken into the
mosquito, may develop into the infective material; moreover,
this virus persists alive and active for three days after the
disease is fully developed, but at the end of this time it dis-
appears, so far, at any rate, as its infective power is concerned,
from the blood, secretions and tissues of the patient. Further,
there is no evidence that the infective virus is ever transmitted
directly from the patient in secretions or in fact in anything
but blood or blood-serum. The infective material, then, is present
in the human subject for about eight days, during which the
blood and even the blood-serum may serve as a vehicle for
the infective agent. If during this period the patient is bitten
by the Stegomyia the mosquito cannot distribute the infection for
twelve days, but after this the power of transmitting reinfection
persists for weeks and even months during cold weather when
the insect is torpid. As soon, however, as the warm weather
comes round and the mosquito becomes active and again begins
to bite there is evidence that it still maintains its power of
transmitting infection; indeed Boyce states that mosquitos
infected in one year are capable of transmitting infection and
starting a fresh epidemic in the following warm season. When
it is remembered that a mosquito by a single bite is capable of
setting up an attack of the disease, we see how important is
this question.

The Stegomyia, known as the domestic or house mosqmto,
is spoken of as the " Tiger " mosquito, " Scots' Grey," or " Black
and White Mosquito," from the fact that there is " a lyre-
shaped pattern in white on the back of the thorax, transverse
white bands on the abdomen, and white spots on the sides of
the thorax; while the legs have white bands with the last hind
tarsal joint also white " (Boyce). It is also spoken of as the
" cistern mosquito," as it breeds in the cisterns, barrels, water
butts, &c., containing the only water-supply of many houses.
It may pass through its various stages of development in any
small vessels, but the larvae are not usually found in natural
collections of water, such as gutters, pools or wells, if
the ovipositing insect can gain access to cleaner and purer
water.

The egg of the Stegomyia deposited on the water develops in
from 10 to 20 hours into the larval form, the so-called " wiggle-
waggle." It remains in this stage for from i to 8 days, then
becomes a pupa, and within 48 hours becomes a fully developed
mosquito. The larvae can only develop if they are left in
water, though a very small amount of water will serve to keep
them alive. The eggs on the other hand are very resistant,
and even when removed from water may continue viable for
as long a period as three months. The Stegomyia affects clean
water-butts and cisterns by preference. Consequently its
presence is not confined to unhygienic districts; they may,
however, " seek refuge for breeding purposes in the shallow
street drains and wells in the town." The Stegomyia does not
announce its advent and attack by a " ping " such as that made
by the Anopheles, it works perfectly noiselessly and almost
ceaselessly (from 3 p.m. to early morning) so that any human
beings in its neighbourhood are not safe from its attacks either
afternoon or night.

The most important prophylactic measures against the Stego-
myia are ample mosquito nets " with a gauge of eighteen
meshes to the inch " (Boyce), so arranged that the person sleeping
may not come near the net; these nets should be used not only
at night but at the afternoon siesta. Then the living room
should be screened against the entrance of these pests, thorough
ventilation should be secured; and all pools and stagnant waters,
especially in the neighbourhood of houses, should be drained,
water-butts and cisterns should be screened and all stagnant
waters oiled with kerosene or petroleum, where drainage is
impossible. What has been done through the carrying out
of these and similar measures may be gathered from the record
of the Panama Canal. In 1884 the French Panama Canal
Company, employing from 15,000 to 18,000 men, lost by death



60 per 1000 annually (in 1885 over 70 per 1000). In iqo4,
when the Americans had taken over the work of construction.
Col. W. C. Gorgas undertook to clear the country of the Stegomyia,
and within two or three years yellow fever had been eradicated.
The death-rate from malaria was also greatly diminished, and
by the end of 1907 the death-rate per annum amongst 45,000
workers was only 18 per 1000, a lower death-rate than is met with
in many large English towns. Similar examples might be cited
from other places, but the above is sufficiently striking to carry
conviction that the methods employed in carrying on the
warfare against tropical diseases have been attended with
unexampled success. These diseases, at one time so greatly
feared, are now so much under control that some one has said
" ere long we shall be sending our patients to the tropics in search
of a health resort." .,

Weil's disease, a disease which may be considered along with>
acute yellow atrophy and yellow fever, is one in which there is an
acute febrile condition, associated with jaundice, inflammation of
the kidney and enlargement of the spleen. It appears to be a toxic
condition of a less acute character, however, than the other two,
in which the functions and structure of the liver and kidney are
specially interfered with. There is a marked affection of the gastro-
intestinal system, and the nervous system is also in some cases
profoundly involved. Haemorrhage into the mucous and serous
membranes is a marked feature. The liver cells and kidney epithe-
lium undergo fatty changes, though in the earlier stages there is a
cloudy swelling, probably also toxic in origin. Organisms of the
Proteus group, which appear to have the power, in certain circum-
stances, of forming toxic substances in larger quantities than can be
readily destroyed by the liver, and which then make their appear-
ance in the kidney and spleen, are supposed to be the cause of this
condition.

Diphtheria. — In regard to no disease has medical opinion under-
gone greater modification than it has in respect of diphtheria.
Accurately applied, bacteriology has here gained one of its
greatest triumphs. Not only have the aetiology and diagnosis
of this disease been made clear, but knowledge acquired in
connexion with the production of the disease has been apphed
to a most successful method of treatment. In 1875 Klebs
described a small bacillus with rounded ends, and with, here
and there, small clear unstained spaces in its substance. He,
however, also described streptococci as present in certain cases
of diphtheria, and concluded that there must be two kinds of
diphtheria, one associated with each of these organisms. In
1883 he again took up the question; and in the following year
Loeffler gave a systematic description of what is now known
as the Klebs-Loeffler bacillus, which was afterwards proved by
Roux and Yersin and many other observers to be the causa
causans of diphtheria. This bacillus is a slightly-curved rod
with rounded, pointed, or club-shaped end or ends (see Plate
II. fig 9). It is usually from 1-2 to 5/i or more in length and
from 0-3 to 0-5/1 in breadth; rarely it may be considerably
larger in both dimensions. It is non-motile, and may exhibit
great variety of form, according to the age of the culture and the
nature of the medium upon which it is growing. It is stained
by Gram's method if the decolorizing process be not too pro-
longed, and also by Loeffler's methylene-blue method. Except
in the very young forms, it is readily recognizable by a series
of transverse alternate stained and unstained bands. The
bacillus may be wedge-shaped, spindle-shaped, comma-shaped
or ovoid. In the shorter forms the polar staining is usually well
marked; in the longer bacilli, the transverse striation. Very
characteristic club-shaped forms or branching filaments are met
with in old cultures, or where there is a superabundance of nutri-
tive material. In what may be called the handle of the club
the banded appearance is specially well marked. These specific
bacilli are found in large numbers on the surface of the diphther-
itic membrane (Plate II. fig. 10), and may easily be detached
for bacteriological examination. In certain cases they may be
found by direct microscopic examination, especially when they
are stained by Gram's method, but it is far more easy to demon-
strate their presence by the culture method. On Loefiler's
special rpedium the bacilli flourish so weU at body-temperature —
about 37° C. — that, like the cholera bacillus, they outgrow the
other organisms present, and may be obtained in comparatively



PARASITIC DISEASES



781



pure culture. Distinct colonies may often be found as early
as the eighth or twelfth hour of incubation; in from eighteen to
Lvventy-four hours they appear as rounded, elevated, moderately
translucent, greyish white colonies, with a yellow tinge, the
surface moist and the margins slightly irregular or scalloped.
They are thicker and somewhat more opaque in the centre.
When the colonies are few and widely separated, each may grow
to a considerable size, 4 to 5 mm.; but when more numerous and
closer together, they remain small and almost invariably discrete,
with distinct intervals between them. In older growths the
central opacity becomes more marked and the crenalion more
distinct, the moist, shiny appearance being lost. When the
surface of the serum is dry, the growth, as a rule, does not attain
any very large size.

These " pure " colonies, when sown in slightly alkaline broth,
grow with great vigour; and if a small amount of such a 48
hours' culture be injected under the skin of a guinea-pig, the
animal succumbs, with a marked local reaction and distinct symp-
toms of to.xic poisoning very similar to those met with in cases of
diphtheriaof thehumansubject. Roux and Yersin demonstrated
that the poison was not contained in the bodies of the bacilli,
but that it was formed and thrown out by them from and into
the nutrient medium. Moreover, they could produce all the toxic
symptoms, the local reactions, and even the paralysis which
often follows the disease in the human subject, by injecting the
culture from which they had previously removed the whole of
the diphtheria bacilli by filtration. This cultivation, then,
contains a poisonous material, which, incapable of multiplying
in the tissues, may be given in carefully graduated doses. If,
therefore, there is anything in the theory that tissues may be
gradually "acclimatized" to the poisons of these toxic substances,
they saw that it should be possible to prove it in connexion
with this disease. Behring, going still further, found that the
tissues so acclimatized have the power of producing a substance
capable of neutralizing the toxin, a substance which, at first
confined to the cells, when formed in large quantities overflows
into the fluids of the blood, with which it is distributed through-
out the body. The bulk of this toxin-neutralizing substance
remains in the blood-serum after separation of the clot. In
proof of this he showed that (1) if this serum be injected into
an animal before it is inoculated with even more than a lethal
dose of the diphtheria bacillus or its products, the animal
remams perfectly well; (2) a certain quantity of this serum,
mixed with diphtheria toxin and injected into a guinea-pig, gives
rise to no ill effects; and (3) that even when injected some
hours after the bacillus or its toxins, the serum is still capable
of neutralizing the action of these substances. In these experi-
ments we have the germ of the present antitoxic treatment
which has so materially diminished the percentage mortality
in diphtheria. This serum may also be used as a prophylactic
agent.

The antitoxic serum as now used is prepared by injecting into
the subcutaneous tissues of a horse the products of the diphtheria
bacillus. The bacillus, grown in broth containing peptone and
blood-serum or blood-plasma, is filtered and heated to a temperature
of 68° or 70° C. for one hour. It then contains only a small amount
of active toxin, but injected into the horse it renders that animal
highly insusceptible to the action of strong diphtheria toxins, and
even induces the production of a considerable amount of antitoxin.
This production of antito.xin, however, may be accelerated by sub-
sequent repeated injections, with increasing doses of strong
diphtheria toxin, which may be so powerful that | to J of a drop, or
even less, is a fatal dose for a medium-sized guinea-pig. The anti-
toxic serum so prepared may contain 200, 400, 600 or even more
" units " of antitoxin per c.c. — the unit being that quantity of
antitoxin that will so far neutralize 100 lethal doses (a lethal dose is
the smallest quantity that will kill a 250-gramme guinea-pig on the
fifth day) of toxin for a 250-gramme gumea-pig, that the animal
continues alive on the fifth day from the injection. This, however,
is a purely arbitrary standard of neutralizing power, as it is found
that, owing to the complicated structure of the toxin, the neutraliz-
ing and the lethal powers do not always go hand in hand; but as the
toxin used in testing the antitoxin is always compared with the
original standard, accurate results are easily obtained.

Diphtheria, though still prevalent in cities, has now lost many
of its terrors. In the large hospitals under the Metropolitan



Asylums Board the death-rate fell from nearly 40% in 1889
to under 10% in 1003; and if antitoxin be given as soon as the
disease manifests itself, the mortality is brought down to a very
insignificant figure. It has been maintained that as soon as
antitoxin came into use the number of cases of paralysis increased
rather than diminished. This may be readily understood when
it is borne in mind that many patients recover under the use
of antitoxin who would undoubtedly have succumbed in the
pre-antitoxin days; and it cannot be too strongly insisted that
although the antitoxin introduced neutralizes the free toxin
and prevents its further action on the tissues, it cannot entirely
neutralize that which is already acting on the cells, nor can it
make good damage already done before it is injected. Even
allowing that antitoxin is not accountable for the whole of the
improvement in the percentage mortality statistics since 1896, it
has undoubtedly accounted for a very large proportion of
recoveries. Antitoxin often cuts short functional albuminuria,
but it cannot repair damage already done to the renal epithelium
before the antitoxin was given. The clinical evidence of the
value of antitoxin in the relief that it affords to the patient
is even more important than that derived from the consideration
of statistics.

The diphtheria bacillus or its poison acts locally as a caustic and
irritant, and generally or constitutionally as a protoplasmic poison,
the most evident lesions produced by it being degeneration of nerves
and muscles, and, in acute cases, changes in the walls of the blood-
vessels. Other organisms, streptococci or staphylococci, when
present, may undoubtedly increase the mortality by producing
secondary complications, which end in suppuration. Diphtheria
bacilli may also be found in pus, as in the discharges from cases of
otorrhoea.

Tetanus {Lockjaw). — Although tetanus was one of the later
diseases to which a definite micro-organismal origin could be
assigned, it has long been looked upon as a disease typical of
the "septic" group. In 1885 Nicolaier described an organism
multiplying outside the body and capable of setting up tetanus,
but this was only obtained in pure culture by Kitasato, a
Japanese, and by the Italians in 1889. It has a very character-
istic series of appearances at different stages of its development.
First it grows as long, very slender threads, which rapidly break
up into shorter sections from 4 tos^u in length (see Plate II. fig.
11). In these shorter rods spores may appear on the second or up
to the seventh day, according to the temperature at which the
growth occurs. The rods then assume a very characteristic pin or
drumstick form; they are non-motile, are somewhat rounded at
the ends, and at one end the spore, which is of greater diameter
than the rod, causes a very considerable expansion. Before
sporulation the organisms are distinctly motile, occurring in rods
of different lengths, in most cases surrounded by bundles of beau-
tiful flagella, which at a later stage are thrown off, the presence
of flagella corresponding very closely with the " motile " period.
The bacillus grows best at the temperature' of the body; it
becomes inactive at 14° C. at the one extreme, and at from 42°
to 43° C. at the other; in the latter case involution forms, clubs
and branching and degenerated forms, often make their appear-
ance. It is killed by exposure for an hour to a temperature of
from 60° to 65° C; the spores however are very resistant to the
action of heat, as they withstand the temperature of boiling
water for several minutes. The organism has been found in
garden earth, in the excrement of animals — horses — and in
dust taken from the streets or from living-rooms, especially
when it has been allowed to remain at rest for a considerable
period. It has also been demonstrated in, and separated from
the pus of wounds (see Plate II. fig. 12) in patients suffering
from lockjaw, though it is then invariably found associated
with the micro-organisms that give rise to suppuration.

It is important to remember that this bacillus is a strict anaerobe,
and can only grow when free oxygen has been removed from the
cultivation medium. It may be cultivated in gelatine to which has
been added from 2 to 3 % of grape-sugar, when, along the line of the
stab culture, it forms a delicate growth, almost like a fir-tree, the
tip of which never comes quite to the surface of the gelatine. The
most luxuriant growth — evidenced by the longest branches — occurs
in the depth of the gelatine away from free oxygen. After a time the



782



PARASITIC DISEASES



gelatine becomes sticky, and then undergoes slow liquefaction, the
growth sinking and leaving the upper layers comparatively clear.
This organism is not an obligate parasite, but a facultative; it may
grow outside the body and remain alive for long periods.

Lockjaw is most common amongst agricultural labourers,
gardeners, soldiers on campaign, in those who go about with
bare feet, or who, like young children, are liable to get their
knees or hands accidentally wounded by rough contact with
the ground. Anything which devitaUzes the tissues — such as
cold, bruising, malnutrition, the action of other organisms and
their products — may all be predisposing factors, in so far as
they place the tissue at a disadvantage and allow of the multipli-
cation and development of the specific bacillus of tetanus. In
order to produce the disease, it is not sufficient merely to inocu-
late tetanus bacQli, especially where resistant animals are
concerned: they must be injected along with some of their
toxins or with other organisms, the presence of which seems to
increase the power of, or assist, the tetanus organism, by divert-
ing the activity of the cells and so allowing the bacUlus to
develop. The poison formed by this organism resembles the
enzymes and diphtheria poison, in that it is destroyed at a
temperature of 65° C. in about five minutes, and even at the
temperature of the body soon loses its strength, although, when
kept on ice and protected from the action of light, it retains its
specific properties for months. Though slowly formed, it is
tremendously potent, jsuJfisu part of a drop (the five-millionth
part of a c.c.) of the broth in which an active culture has been
allowed to grow for three weeks or a month being sufficient to
kill a mouse in twenty-four hours, ^h of a drop killing a rabbit,
T>'.T a dog, or -^ of a drop a fowl or a pigeon; it is from 100 to 400
times as active as strychnine, and 400 times as poisonous as
atropine. It has been observed that, quite apart from size,
animals exhibit different degrees of susceptibility. Frogs kept
at their ordinary temperature are exceedingly insusceptible,
but when they are kept warm it is possible to tetanize them,
though only after a somewhat prolonged incubation period, such
as is met with in very chronic cases of tetanus in the human
subject. In experimentally-produced tetanus the spasms
usually commence and are most pronounced in the muscles near
the site of inoculation. It was at one time supposed that this
was because the poison acted directly upon the nerve termina-
tions, or possibly upon the muscles; but as it is now known that
it acts directly on the cells of the central nervous system, it
may, as in the case of rabies, find its way along the lymphatic
channels of the nerves to those points of the central nervous
system with which these nerves are directly connected, spasms
occurring in the course of the muscular distribution of the nerves
that receive their impulses from the cells of that area. As the
amount of toxin introduced may be contained in a very small
quantity of fluid and still be very dilute, the local reaction of the
connective-tissue cells may be exceedingly slight; consequently
a very small wound may allow of the introduction of a strong
poisonous dose. Many of the cases of so-called idiopathic
tetanus are only idiopathic because the wound is trifling in
character, and, unless suppuration has taken place, has healed
rapidly after the poison has been introduced. In tetanus, as
in diphtheria, the organisms producing the poison, Lf found in
the body at all, are developed only at the seat of inoculation;
they do not make their way into the surrounding tissues. In
this we have an explanation of the fact that all the earlier
experiments with the blood from tetanus patients gave absolutely
negative results. It is sometimes stated that the production
of tetanus toxin in a wound soon ceases, owing to the arrest of
the development of the bacillus, even in cases that ultimately
succumb to the disease. Roux and Vaillard, however, maintain
that no case of tetanus can be treated with any prospect of success
unless the focus into which the bacilli have been introduced is
freely removed. The antitetanus serum was the first antitoxic
serum produced. It is found, however, that though the anti-
tetanic serum is capable of acting as a prophylactic, and of
preventing the appearance of tetanic symptoms in animals that
are afterwards, or simultaneously, injected with tetanus toxin,



Online LibraryHugh ChisholmThe Encyclopædia britannica; a dictionary of arts, sciences, literature and general information (Volume v. 20) → online text (page 278 of 353)