Infection-enhancing anti-SARS-CoV-2

antibodies recognize both the original

Wuhan/D614G strain and Delta variants.
A potential risk for mass vaccination?
Nouara Yahi & Henri Chahinian &
Jacques Fantini
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JID: YJINF
ARTICLE IN PRESS [m5G;August 16, 2021;16:58]
Journal of Infection xxx (xxxx) xxx

Contents lists available at ScienceDirect

Journal of Infection
journal homepage: www.elsevier.com/locate/jinf

Letter to the Editor

Infection-enhancing anti-SARS-CoV-2 antibodies recognize both

the original Wuhan/D614G strain and Delta variants. A
potential risk for mass vaccination?

The aim of the present study was to evaluate the recognition

of SARS-CoV-2 Delta variants by infection enhancing antibodies di-
rected against the NTD. The antibody studied is 1052 (pdb file
#7LAB) which has been isolated from a symptomatic Covid-19 pa-
tient1 . Molecular modeling simulations were performed as previ-
ously described2 . Two currently circulating Delta variants were in-
vestigated, with the following mutational patterns in the NTD :

- G142D/E154K (B.1.617.1)
- T19R/E156G/del157/del158/A222V (B.1.617.2)

Each mutational pattern was introduced in the original

Wuhan/D614G strain, submitted to energy minimization, and then
tested for antibody binding. The energy of interaction (G) of the
reference pdb file #7LAB (Wuhan/D614G strain) in the NTD region Fig. 1. Infection enhancing antibodies recognize the NTD of Delta variants. A.
was estimated to −229 kJ/mol−1 . In the case of Delta variants, the Molecular model of the Delta B.1.617.1 spike trimer as viewed from the host cell
energy of interaction was raised to −272 kJ.mol−1 (B.1.617.1) and surface (chains A, B and C in cyan, yellow and purple, respectively), with the NTD
and RBD of each chain indicated. The 1052 antibody is in green. B. Spike trimer
−246 kJ.mol−1 (B.1.617.2). Thus, these infection enhancing antibod-
with the B subunit bound to a lipid raft (with 6 ganglioside GM1 molecules). C.
ies not only still recognize Delta variants but even display a higher Trimolecular [spike-antibody-raft] complex. D. Focus on the NTD-antibody complex
affinity for those variants than for the original SARS-CoV-2 strain. bound to the lipid raft. E. Secondary structures of the NTD (yellow) and the anti-
The global structure of the trimeric spike of the B.1.617.1 vari- body (green) bound to lipid raft gangliosides. F. The 1052 antibody clamps the NTD
and the edge of the lipid raft.
ant in the cell-facing view is shown in Fig. 1A. As expected, the
facilitating antibody bound to the NTD (in green) is located behind
the contact surface so that it does not interfere with virus-cell at-
tachment. Indeed, a preformed antibody-NTD complex could per-
fectly bind to the host cell membrane. The interaction between the
NTD and a lipid raft is shown in Fig. 1B, and a whole raft-spike-
antibody complex in Fig. 1C. Interestingly, a small part of the anti-
body was found to interact with the lipid raft, as further illustrated
in Figs. 1D-E. More precisely, two distinct loops of the heavy chain
of the antibody encompassing amino acid residues 28–31 and 72–
74, stabilize the complex through a direct interaction with the edge
of the raft (Fig. 1F). Overall, the energy of interaction of the NTD-
raft complex was raised from −399 kJ.mol−1 in absence of the an-
tibody to −457 kJ.mol−1 with the antibody. By clamping the NTD
and the lipid raft, the antibody reinforces the attachment of the Fig. 2. Neutralization vs ADE balance according to SARS-CoV-2 strains.
spike protein to the cell surface and thus facilitates the conforma-
tional change of the RBD which is the next step of the virus infec-
tion process2 . Neutralizing antibodies directed against the NTD have also been
This notion of a dual NTD-raft recognition by an infection en- detected in Covid-19 patients4-5 . The 4A8 antibody is a major rep-
hancing antibody may represent a new type of ADE that could resentant of such antibodies5 . The epitope recognized by this an-
be operative with other viruses. Incidentally, our data provide a tibody on the flat NTD surface is dramatically affected in the NTD
mechanistic explanation of the FcR-independent enhancement of of Delta variants2 , suggesting a significant loss of activity in vacci-
infection induced by anti-NTD antibodies1 . The model we propose, nated people exposed to Delta variants. More generally, it can be
which links for the first time lipid rafts to ADE of SARS-CoV-2, is in reasonably assumed that the balance between neutralizing and fa-
line with previous data showing that intact lipid rafts are required cilitating antibodies may greatly differ according to the virus strain
for ADE of dengue virus infection3 . (Fig. 2).

https://doi.org/10.1016/j.jinf.2021.08.010
0163-4453/© 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
JID: YJINF
ARTICLE IN PRESS
N. Yahi, H. Chahinian and J. Fantini
Current Covid-19 vaccines (either mRNA or viral vectors) are
based on the original Wuhan spike sequence. Inasmuch as neu-
tralizing antibodies overwhelm facilitating antibodies, ADE is not a
concern. However, the emergence of SARS-CoV-2 variants may tip
the scales in favor of infection enhancement. Our structural and
modeling data suggest that it might be indeed the case for Delta
variants.
In conclusion, ADE may occur in people receiving vaccines
based on the original Wuhan strain spike sequence (either mRNA
or viral vectors) and then exposed to a Delta variant. Although
this potential risk has been cleverly anticipated before the mas-
sive use of Covid-19 vaccines6 , the ability of SARS-CoV-2 antibodies
to mediate infection enhancement in vivo has never been formally
demonstrated. However, although the results obtained so far have
been rather reassuring1 , to the best of our knowledge ADE of Delta
variants has not been specifically assessed. Since our data indicate
that Delta variants are especially well recognized by infection en-
hancing antibodies targeting the NTD, the possibility of ADE should
be further investigated as it may represent a potential risk for mass
vaccination during the current Delta variant pandemic. In this re-
spect, second generation vaccines7 with spike protein formulations
lacking structurally-conserved ADE-related epitopes should be con-
sidered.
2
[m5G;August 16, 2021;16:58]
Journal of Infection xxx (xxxx) xxx
References
1. Li D, et al. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and
neutralizing antibodies. Cell 2021;184:4203–19.
2. Fantini J, Yahi N, Azzaz F, Chahinian H. Structural dynamics of SARS-CoV-2 vari-
ants: a health monitoring strategy for anticipating Covid-19 outbreaks. J Infect
2021;83:197–206.
3. Puerta-Guardo H, Mosso C, Medina F, Liprandi F, Ludert JE, del Angel RM. An-
tibody-dependent enhancement of dengue virus infection in U937 cells requires
cholesterol-rich membrane microdomains. J Gen Virol 2010;91:394–403.
4. Chi X, et al. A neutralizing human antibody binds to the N-terminal domain of
the Spike protein of SARS-CoV-2. Science 2020;369:650–5.
5. Liu L, et al. Potent neutralizing antibodies against multiple epitopes on SARS–
CoV-2 spike. Nature 2020;584:450–6.
6. Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in
COVID-19. Nat Rev Immunol 2020;20:339–41.
7. Fantini J, Chahinian H, Yahi N. Leveraging coronavirus binding to gangliosides for
innovative vaccine and therapeutic strategies against COVID-19. Biochem Biophys
Res Commun 2021;538:132–6.
Nouara Yahi
Henri Chahinian
Jacques Fantini
INSERM UMR_S 1072, Aix-Marseille Université, 13015 Marseille,
France
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 INSOLATION.
Insolation is an exceptional accident in animals of the bovine,
ovine, or porcine species. If at liberty these animals move about, and
always seek shelter when the sun is fierce. If, on the contrary, they
are harnessed and kept standing for long, exposed to the full midday
sun during June, July or August, they may suffer from insolation.
During the International Cattle Show attached to the Exhibition of
1900 in Paris, a considerable number of cases of insolation occurred
in animals of one class, exposed to the full midday sun, in an ill-
ventilated spot. The other classes only received sunlight from the
sides, and in them not a single case occurred.
Death may follow in a few hours; it is difficult to say precisely how
it is brought about, but it is always accompanied by congestion of the
cerebro-spinal centres and general blood stasis.
The symptoms of the development of insolation occur very
rapidly. In animals of the bovine species there is accelerated
respiration, which soon amounts to dyspnœa. The mucous
membranes then become cyanotic. The animals attacked seem
anxious, although not agitated, and soon afterwards the eyes water,
the mucous membrane and the lips of the vulva display œdematus
infiltration and congestion, and areas of cutaneous congestion,
closely resembling mud fever in the horse, appear over the mammæ.
At this stage the animals move with difficulty, and show all the
symptoms seen at the outset of gangrenous coryza.
All these symptoms develop in one, two, or three hours, and death
may follow if nothing is done. They disappear, however, as rapidly as
they appear. In an hour or less we have seen in some cases a
complete return to the normal condition. Given the facts, the
diagnosis is extremely easy.
Treatment. Treatment should be commenced by immediately
removing the animal to a cool, airy, shady place. It may then be bled,
and the head and neck should be freely drenched with cold water.
The symptoms generally disappear as though by magic.
 POST-PARTUM PARALYSIS—MILK FEVER—
MAMMARY TOXÆMIA—PARTURIENT APOPLEXY
—DROPPING AFTER CALVING.
For a great part of the following short account we are indebted to
an excellent report by J. J. Repp, V.M.D., in the Journal of Comp.
Medicine and Veterinary Archives, September, 1901:—
The word “fever” in connection with the terminology of this
disease is not very appropriate, because in the majority of cases fever
is not present, but the animal has a subnormal temperature. The
term milk fever is very misleading and indefinite, as it is also used by
the laity to designate other diseases, such as parturient septicæmia
and the various forms of mammitis. Parturient paralysis must be
clearly differentiated from parturient septicæmia, which is a disease
of an entirely different character and which may occur in any of the
domestic species, whereas parturient paralysis occurs only in the
cow.
Distribution. Parturient paralysis occurs wherever milch cows
are kept. It is more prevalent in dairy districts, because it is the heavy
milking strains of cows that are most subject to the disease.
Cause. No definite cause can be assigned for this disease.
Schmidt’s theory is that parturient paralysis is caused by the
evolution in the mammary gland of a poisonous substance through
the over-activity of the epithelial cells of this gland excited by the
determination to the udder after birth of large quantities of blood
which was supplied to the uterus and the fœtus before birth, but
which now goes to the udder because of the natural demand for milk
secretion. This poisonous substance being carried in the circulation
to various parts of the body, brings on the symptoms which
characterise the disease. It is well recognised that living cells may,
under certain circumstances, produce poisonous substances.
Schmidt’s theory, therefore, is in accord with an established
principle.
 Pathogenesis, or generation, of the disease. Parturient
paralysis, as a rule, occurs in cows which give a heavy flow of milk
and which are in a high state of nutrition. It may develop at any age,
but is extremely rare in cows before they have reached adult age and
have given birth to several calves. It is also rare in old cows. It occurs,
then, in cows which are of middle age and in the full height of their
activity as milk producers. The disease attacks the cow after she has
given birth to a calf, usually within twenty-four hours thereafter, but
in some cases not until a week or even a month after parturition. In a
few cases the disease has its inception a short time before
parturition. Cows which are stabled and deprived of exercise are said
to be more prone to the disease than those which are permitted to
exercise at will. There are many exceptions to this statement,
although it is the usual teaching. Further observation may show that
it is not correct. In Iowa more cows take this disease while at pasture
than in any other circumstance. This doubtless arises from the fact
that in Iowa cows are given more freedom than is customary in older
dairy States. The disease may arise at any time in the year, but, on
account of the fact that spring-time is pre-eminently the calving
season, most cases originate at this season.
Morbid anatomy. The morbid alterations are limited and
variable, and offer nothing characteristic. The blood is irregularly
distributed, a condition which probably indicates marked vaso-
motor disturbance resulting from the profound interference with the
nervous functions which accompanies the disease. The abdominal
organs are usually filled with blood. The brain may be anæmic,
œdematous, easily torn, and yellowish in colour. In other cases it
shows hyperæmia of the meninges and of the brain substance.
Symptoms. The disease usually appears within twenty-four to
forty-eight hours after parturition. In extreme cases it may not occur
until two months or even six months after parturition. It may rarely
occur before birth. It usually follows an easy birth. At the onset of the
disease the cow manifests some uneasiness; it moves about in a
restless manner, stamps, strikes the abdomen with its hind legs,
perhaps bellows, grinds the teeth, and may have spasms of groups of
muscles or even a general convulsion. After this period, which may
be unnoticed, the symptoms of paralysis come on. The cow shows
weakness, staggers, and at last falls. As the paralysis advances it
stretches on the ground, lying on its side usually with the neck bent
to one side so as to bring the nose into the flank or the costal region.
This is the characteristic position in parturient paralysis. If the head
is brought into the normal position, it at once returns to the
unnatural position in which it was found. The animal is in a state of
partial or complete unconsciousness, does not respond to blows or
calls, and takes no note of its surroundings. The eye is dull and not
sensitive to the finger touch, sunken, pupil dilated, and the upper lid
is drooping; the tongue is paralysed, saliva runs from the mouth, the
pharynx and œsophagus have lost the power of motion, so that the
animal is unable to swallow; the peristalsis of the stomachs and
intestines is in abeyance, and as a result digestion is arrested,
fermentation sets in, and the animal becomes tympanitic; the
contents of the rectum and colon are hard and dry, and may be
covered with mucus or blood, urination is suspended; the os uteri is
almost invariably dilated if the disease occurs within a day of
parturition; pulse small, often imperceptible, 60 to 120 per minute;
temperature, usually normal or below normal, may be as low as 95°
Fahr., in some cases may be as high as 105° Fahr. Such a high
temperature probably does not occur in a case of pure parturient
paralysis, but only when there is a complication of parturient
septicæmia. The extremities are cold. The after-birth is sometimes
retained. There may be accompanying prolapse of the uterus.
Course. Without treatment, and, indeed, with most kinds of
treatment which have been applied in the past, the disease usually
runs rapidly to a fatal issue. It lasts two to three days, and in some
cases longer, the condition gradually becoming more and more
aggravated. Death results from sudden failure of the heart or brain,
and is often preceded by profuse diarrhœa. In milder cases the cow
may linger as long as two to four weeks and then die of pneumonia,
which results from the inhalation, or introduction through attempts
at medication, of foreign substances into the lungs during the period
of paralysis of the pharynx and œsophagus. If recovery occurs, the
animal is entirely well in two to five days. In rare cases paralysis of
the hind parts may persist for a long while.
Diagnosis. This is made by a study of the history and symptoms.
It is comparatively easy.
 Differential diagnosis. It must be distinguished from ante-
partum paralysis, broken-back, parturient septicæmia; but one
familiar with the character of these diseases will find no difficulty in
making this differentiation.
Treatment. This may be considered under two distinct
subdivisions, viz., preventive treatment and curative treatment.
(a) Preventive treatment.—By considering what has been said
under the head of “generation of the disease,” one can easily infer
what measures should be adopted to prevent the disease. Cows in the
later stage of gestation should be fed moderately, grain especially
being given sparingly or entirely withheld; the animals should be
given an opportunity to take plenty of exercise; the bowels should be
kept in good condition by the administration of such salines as
magnesium sulphate, sodium chloride, and sodium bicarbonate. The
after-birth should be removed soon after parturition and several
uterine douches administered.
(b) Curative treatment.—The older methods of treatment
comprised: warmth and friction to the mammary gland; the
administration of sedatives, such as opium, chloral and bromide of
potassium; stimulants, including ammonia, ether, turpentine and
alcohol; washing out the uterus with water or disinfectant solutions;
the relief of tympany by the use of the trocar and canula (by which
instrument medicines may also be injected directly into the rumen);
the removal of fæces from the rectum; warm clothing of the body and
general attention to the animal’s comfort, and to the teachings of
hygiene. For all these widely diversified methods good results have
been claimed, and, we may add, bad ones at times recorded. F. T.
Harvey (Cornwall) estimates the average mortality at from 40 to 66
per cent., though he claims for his more recent practice a lessened
mortality of only 20 per cent.
Schmidt does not claim that his method of treatment disposes
bodily of the morbid condition, but that it does measurably assist
Nature in her efforts to restore the animal to the normal
physiological state. It is well known that after the beginning of the
attack the animal, if left to itself, rapidly grows worse until the crisis
of the disease is reached, at which time death occurs or
convalescence begins, usually the former. It has been observed,
however, that if the treatment is applied within a few hours after the
inception of the disease its progress is modified in such a way that
convalescence at once begins, as a rule, and the animal hastily
recovers its health, usually within twelve hours, although in extreme
cases it may be as late as forty-eight hours. The following is an
outline of the plan of treatment of parturient paralysis suggested by
Schmidt. The operator should disinfect his hands and the udder and
teats of the cow by washing with a 5 per cent. solution of carbolic
acid or creolin, or a 1½ per cent. solution of lysol or trikresol. The
apparatus needed for the treatment consists of a small glass funnel, a
rubber hose three feet long and one-eighth inch in calibre into which
the funnel fits, and an ordinary milking tube over which the rubber
hose fits. This apparatus should be sterilised immediately before it is
used by boiling or soaking in such a solution as recommended for
washing the udder. Dissolve from 2 to 2½ drachms of potassium
iodide—the size of the dose depending upon the size of the cow and
the character of the attack—in about one quart of clean water
previously boiled to sterilise it, and allow the solution to cool to a
little above body temperature, or 40° C. or 104° Fahr. The
temperature may be determined with the clinical thermometer.
Withdraw all the colostrum or milk from the udder. Then insert the
milking tube, with hose and funnel attached, into one of the teats,
elevate the funnel about two feet above the teat and slowly pour in
one-fourth of the solution, allowing the funnel and hose to become
empty several times during the process in order to permit the
entrance of a liberal quantity of air. Repeat this infusion with the
other three quarters of the udder. After all is introduced, knead the
udder carefully so as to cause the solution to permeate the ducts and
acini as much as possible.
As the condition of the cow is usually such as to call for additional
treatment, the veterinarian should not be content with injecting the
potassium iodide solution, but should resort to any and all other
measures which promise assistance.
As the cow is usually unable to urinate, the bladder will be found
filled with urine. This should be removed with the catheter, and its
removal accomplished at intervals until the recovery of the cow
renders this procedure no longer needful.
It may be advisable that catharsis be brought about. As the cow is
usually unable to swallow, it is dangerous to attempt to give
medicines by the mouth. This may be done if assurance that the cow
can swallow is obtained. Some have given medicines successfully
through a probang inserted into the stomach. The plan is feasible.
Schmidt says that he usually resorted to an aloe powder. If this is
done 1 ounce to 1½ ounces of aloes may be given. It would seem
preferable to give the aloes in a bolus, capsule, or drench. Some have
given linseed oil or Epsom salts. If the animal cannot swallow and a
probang is not at hand, one may administer 1½ to 2 grains of
physostigmine salicylate subcutaneously, repeating the dose in about
three hours if purgation is not produced. Rectal injections should be
given at short intervals in order to get rid of the accumulation of
hard, dry fæces in the rectum. These injections may be of linseed oil,
cotton-seed oil, or warm soap solution. Schmidt recommends, also,
enemata of sodium chloride solution. Meanwhile the cow should be
kept propped up on the sternum by means of bags of straw or pieces
of wood. If the temperature is below normal, as it usually is, the cow
should be thickly clothed with blankets and straw heaped up about it.
Schmidt used powdered digitalis given by the mouth when the heart
was rapid and weak. It would seem much better in every way to give
the tincture of digitalis subcutaneously. He has also resorted to
subcutaneous injections of camphor and caffeine. This is good
treatment. If the cow does not show marked improvement within
eight hours the potassium iodide infusion may be repeated. Schmidt
has found that as much as 6 drachms may be injected into the udder
without harm to the cow. Schmidt, in his first report, made in 1898,
recorded 50 cases treated for parturient paralysis by this method
with but two deaths from the disease. There were, however, only 46
recoveries, as two cows were slaughtered for beef during the first day
of convalescence. A short time later a report was made by Jensen
showing that in Denmark up to that time sixty-five veterinarians of
that country had treated 412 cases by the Schmidt method, 90 per
cent. of which recovered. Such results seem to indicate this as the
treatment par excellence for parturient paralysis. It still remained to
secure the introduction of this treatment into the United States and
to determine what results could be obtained. In all 166 cases were
reported; of these 166, 119 resulted in recovery, while 47 were fatal.
Of the fatal cases, in eight of the cows death may be traced to some
complication, such as prolapse of the uterus, foreign-body
pneumonia, etc. In these cases the Schmidt treatment cannot be said
to have failed, for it is not in any way intended that it shall be able to
overcome such accidental conditions. If the cow has recovered from
its condition of paralysis as a result of the Schmidt treatment far
enough to be out of danger from that source and to promise recovery,
but later falls a victim to some complication that is in no measure a
part of parturient paralysis, but only a result of that disease, it may
with justice be said that the Schmidt treatment was a success so far
as the malady against which it was directed is concerned. Looking at
the reports from this generous point of view, in 127 cases out of 166,
or 76·5 per cent., the Schmidt treatment was successful so far as the
parturient paralysis was concerned.
In a paper published in the Berliner Thierärztliche Wochenschrift
in August, 1902, Schmidt reviews the results of his treatment as
evinced by 914 patients treated by thirty-one different practitioners:
884, or 96·7 per cent., recovered, twelve died and six were
slaughtered during the course of the disease. Twelve others were
slaughtered at a later period in consequence of complications.
Jensen reported the results of 1,744 cases.
Schmidt also found that the simple injection of air was in many
cases sufficient to produce recovery, and subsequent observation
tends to show that the fluid injected is of less importance than was
first anticipated. A large number of unirritating solutions may be
employed. Schmidt, however, still counsels the use of a quart of 1 per
cent. solution of iodide of potassium, in which can be dissolved 5
grammes of caffein sodio-salicylate if the heart’s action is weak.
About 10 ounces of this solution are injected into each quarter, and
are followed by a liberal injection of air. The parts should afterwards
be freely massaged.
 CŒNUROSIS (GID, STURDY, TURN-SICK).
Cœnurosis is a disease due to invasion of the animal body by
embryos of larvæ of the Tænia cœnurus of dogs and wolves. These
embryos only develop freely in the brain substance (Cœnurus
cerebralis) and medulla oblongata. The hosts of the larvæ include
the calf, sheep, goat, roedeer, reindeer and horse.
The disease was formerly erroneously called “turn-sick,” for the
turning is only a manifestation, and even a tardy manifestation, of
the disease, while in addition it is not invariably present.
Cœnurosis principally attacks lambs of from three to six months,
although it occurs up to eighteen months, and sometimes even two
years. It is exceptional, however, in adults. Similarly in the bovine
species it usually affects young animals up to the fourth or fifth year.
Cœnurosis with diffuse parasitic encephalitis often remains
unrecognised, the animals being regarded as affected with epizootic
meningitis of unknown cause or septic intoxication, and when they
die the owners are ignorant as to the cause of death. The stage
corresponding to turn-sick, which is an advanced phase of the
disease, is only seen in animals which have been infested to a slight
extent, and in which three or four parasites only, sometimes only
one, have attained the brain and developed there. Such cases exhibit
all the classic symptoms of turn-sick, viz., turning movements,
heaviness, vertigo, etc.
Causation. Cœnurosis is due solely to one cause, viz., the
ingestion of eggs or embryos in feeding or drinking.
The Tænia cœnurus lives in the dog, and fertilised segments are
passed with the fæces in yards, pastures and fields, and on the
margins of roads, ditches and ponds. Amongst damp grass or in
water the eggs, which contain more or less well-developed embryos,
may retain their vitality for several weeks, and when swallowed the
embryos are set at liberty in the intestine.
The six-hooked embryos perforate the walls of the intestine, pass
into the blood stream or chyle ducts, and from these points are
carried in all directions. Those which gain the nervous centres, the
brain or spinal cord, continue to develop; the others, dispersed
through different tissues, degenerate and disappear.
 Experimental infection with these parasites shows that the brain is
invaded after about a week’s time. From the twentieth day the
presence of embryos can easily be detected in the superficial layers of
the convolutions. They make their way through the grey substance,
leaving behind them greenish-yellow sinuous tracts with caseous
contents.
The cyst or finn undergoing development can be found at the end
of one of these tracts in the form of a little transparent bladder, of a
size varying between that of a pin’s head and that of a lentil or a
small hazel-nut.
Later the tracts, with their caseous contents, disappear, and the
development of many of the vesicles proves abortive. At the end of a
month the vesicles, continuing to develop regularly, attain to about
the size of a pea. Between the fiftieth and sixtieth days heads or
scolices appear in the interior of the vesicle, which then reaches the
dimensions of a hazel-nut. From this time the vesicles continue to
increase in size until the death of the patient. Usually they become as
large as a walnut, or even larger, and the interior contains hundreds
of scolices, each showing a head.
 Fig. 214.—Brain of sheep. Cœnurosis of the left
hemisphere. Œstrus larvæ exposed by trepanation.

The cystic phase only develops completely in animals whose brains

contain a limited number of cysts, and in such the signs of turn-sick
are well developed. In others, where the numbers are large (ten to
fifteen embryos or more), death occurs during the primary stage,
usually towards the end of the first month, in consequence of acute
encephalitis and without any of the symptoms of turn-sick.
 Fig. 215.—Skull of a sheep showing the
brain infested with a gid bladder-worm
(Cœnurus cerebralis). Two-thirds natural
size.

The number of animals attacked is sometimes enormous. Moussu

has recorded cases where fifty, one hundred, and even four hundred
lambs of one flock were affected. The enormous mortality in such
cases is very apt to cause errors in diagnosis. Cœnurosis occurs most
frequently during rainy seasons, moisture favouring the preservation
of the eggs. Young animals become infected, particularly during the
spring and autumn, more rarely in the summer, as prolonged
desiccation, say for a period of twelve to fifteen days, destroys the
vitality of the eggs, but animals may become infested at any time
through drinking contaminated water. Moussu has seen cœnurosis
(acute encephalitis) from the last-named cause in the middle of
January.
 Symptoms. First phase.—Disseminated encephalitis.—The
symptoms vary with the phases of evolution of the parasite and of the
disease which it causes. After the six-hooked embryos have
penetrated to the brain, the animals affected lose appetite and show
a certain degree of dulness, which is all the more marked inasmuch
as the animals usually affected are young, and therefore should
appear bright and alert. Then follow wasting and depression; the
animals remain stationary for whole hours together, the head being
carried low or inclined to one side. At this stage disturbance in vision
and irregularities in movement may appear.
The eyesight is almost always
affected, but the symptoms may vary
widely. In some cases the patients seem
to be absolutely blind, and strike
against any obstacle in their way; in
others the power of vision seems to be
lost only on one side. All that can be
discerned objectively is an inequality in
the pupils, together with retraction or
dilatation, convergent or divergent
strabismus, nystagmus, etc. The
humours of the eye appear infected, but
examination with the ophthalmoscope
reveals lesions of more or less extensive
neuro-retinitis.
The visual disturbance is of central
origin. The powers of movement may
be affected in numerous ways, which at
times are extremely difficult to estimate
with accuracy. Sometimes the gait is
uncertain, inco-ordinated, and
hesitant; at others the animal shows
Fig. 216.—An adult gid lameness or loss of control over a front
tapeworm (Tænia or hind limb, or over two limbs
cœnurus). Natural size. simultaneously (either the two front or
(After Railliet.) hind limbs or the diagonal limbs), or it
may be absolutely unable to stand.
 It walks obliquely, or
the front or hind limbs
collapse; or again, it
may persistently lie
down, a fact which
makes the shepherd
think it is suffering
from paralysis. On
examination, however,
no true indications of
paralysis can be found;
sensation and motor
power are both
preserved in a modified
form.
Death is very
frequent at this stage of
the disease; the animals
eat little or nothing,
refuse drink, and die of
exhaustion.
All this general Fig. 217.—Sexually mature segment of the
disturbance is of gid tapeworm (Tænia cœnurus). cp, Cirrus
central origin, and is pouch; gp, genital pore; n, nerve; ov,
due to disseminated ovary; sg, shell gland; t, testicles; tc,
parasitic encephalitis, transverse canal; ut, uterus; v, vagina; vc,
but up to this point the ventral canal; vd, vas deferens; vg,
seat of the disease is vitellogene gland. × 20. (After Deffke.)
not yet clearly
apparent.
Second phase.—Turn-sick.—The central symptoms are slow of
development, and are due to the progressive growth of one or two,
more rarely three or four, fertile vesicles. These are the true
symptoms of turn-sick, and it is only after this phase of the disease
has developed that the term becomes appropriate.
Left at liberty, the patient usually walks in a circle towards the
right or left in an impulsive and irresponsible fashion. Sometimes it
describes a circle, always of the same size. In other cases, on the
 Fig. 218.—Brain of a lamb infested with young gid bladderworms
(Cœnurus cerebralis). Natural size. (After Leuckart.)

contrary, it travels along a spiral track, getting further from or nearer

to the centre as the case may be. The turning movement may become
so accentuated that the animal appears to revolve as on a pivot, and
if it is confined in a field or straw-yard its legs become caught in the
litter and it falls to the ground.
Attempts have been made under these circumstances to discover
the exact point of compression, i.e., the point at which the cyst exists,
by noting the direction of the turning movement. The diagnosis,
however arrived at in this way is frequently illusory, because it is not
uncommon to find two or three vesicles, and in any case the most
important information in regard to diagnosis is to be derived from
the ocular symptoms.
When only one vesicle exists, the turning movement usually occurs
towards the side on which it is situated, and the eye of the opposite
side is affected with amaurosis.
 Fig. 219.—Sheep’s skull, the hind portion thin and
perforated, due to the presence of gid bladderworms
(Cœnurus cerebralis). (After Dewitz.)

If the cyst is situated near the olfactory lobes, the animal marches
with a high-stepping movement and the head drawn back towards
the body. If the cyst is in the cerebellum the animal is incapable of
moving, because it can no longer co-ordinate its movements. Finally,
if the cyst develops in the occipital region, animals turn towards the
wind, with the neck raised and the head extended.
At the moment when they fall to the ground they sometimes have
epileptiform convulsions, grind their teeth, and salivate profusely. In
a severe attack even death may supervene at this point.
Cœnurosis of the Medulla. The embryos may develop in the
medulla oblongata as well as on the brain itself. Compression and
atrophy of the medulla then give rise to true paralysis.
 The animals exhibit paralysis of the hind quarters, unilateral
paralysis only, or still less marked signs. Everything depends on the
degree of development of the cysts.
Bovine Animals. Cœnurosis in oxen is less important than in
sheep. Moreover, it very rarely affects a large number of young
animals belonging to one farm. Loss of appetite, dulness and
depression are the earliest indications, as in sheep. The gaze seems
fixed, the neck is held stiffly and almost rigidly, the animal shows a
tendency to vertigo, pushes its head against a wall, or leans the head
or neck on the manger or trough.
Inequal
ity in the
size of the
pupils,
amaurosi
s,
hesitating
and inco-
ordinated
movemen
ts may
also be
seen
developed
in
different
degrees.
The
animals
have the
appearan
ce of
horses Fig. 220.—An isolated gid bladder-worm (Cœnurus
suffering cerebralis), showing the heads. (After Railliet.)
from
“immobili
té”—that is, the very peculiar general condition produced by dropsy
of the brain ventricles, or from encephalitis. They forget to eat or do
not attempt to chew unless handfuls of food are thrust between the
molars; they plunge the muzzle into a bucketful of water and do not
drink, etc. They take little notice of what passes around them,
although they may become greatly excited if an attempt is made to
move them, to give them medicine from a bottle, or to set them at
liberty, etc. Such attacks of excitement often end in vertigo and in the
animals falling to the ground and showing epileptiform movements.
All these symptoms may occur with extraordinary variations, due in
reality to the peculiar position which the cœnurus occupies.
Second phase. If set at liberty during the first phase of the
disease, the animal’s gait appears only slightly disordered, but when
a single vesicle has become well developed in one of the hemispheres
(and this is usually the case with oxen), the symptoms of turn-sick
appear as in sheep, and are equally varied. The patients seem
impelled to move in a given direction, whatever obstacles may be in
their way. It is not at all uncommon to see them thrusting their heads
against walls or trees, falling into ponds or ditches, or attempting to
force their way through blind alleys between hay or straw stacks.
After the cyst develops in the cerebellum, the animals are soon
unable to move. They may be able to stand in one position, but on
any attempt to move they fall.
Lesions. The lesions develop successively from the moment the
embryos arrive in the mass of the brain. At first the six-hooked
embryos only excite a slight disseminated encephalitis. Their course
through the brain is marked by short, greyish-green caseous tracts,
the thickness of a needle, which are readily discoverable in the
superficial layers. Later these caseous deposits become absorbed, the
lesions of disseminated encephalitis diminish and disappear, while a
certain number of vesicles after partial development undergo
atrophy and disappear. Before long nothing remains but local
atrophic encephalitis caused by the development of the vesicles, and
from this time the central symptoms begin to appear.
Diagnosis. When the turning movement has developed the
diagnosis is generally easy, but it is more difficult during the first
period, when encephalitis alone exists; or at least, it is very difficult
at this period to discover whether the symptoms are attributable to
encephalitis, meningoencephalitis, cœnurosis, tuberculosis, or to
some injury.
 Fig. 221.—Diagrammatic section of a gid bladder-worm (Cœnurus cerebralis).
a, Normal disposition of scolex; b, c, d, e, diagrammatic drawing to show the
homology between cysticercus and cœnurus. (After Railliet.)

Prognosis. The prognosis is grave, and very few animals recover.

Zürn estimated the cases of recovery in flocks at 2 per cent. In these
cases the cysts degenerate and disappear.
Treatment. At the present moment there is no really practical
curative treatment.
The best plan appears to be to trephine the skull and remove the
cyst, provided its exact position can previously be determined. That,
however, is the great difficulty. Its solution presupposes a perfect
knowledge of the central nervous system and of the real purport of
any apparent symptoms.
On the other hand, in sheep at least, the position of the cyst must
always remain somewhat uncertain, because there are generally
several, and the symptoms are of a mixed character.
 The only treatment, therefore, which would be likely to succeed is
difficult to carry out, and more difficult in the ox than in the sheep
because of the great development of the frontal sinuses.
It has been mentioned that under exceptional circumstances the
cœnurus, if very superficially placed, may cause atrophy of the
cranial wall in the sheep by the outward pressure it exerts, and that
the points of least resistance may be detected by the touch. In such
cases intervention is necessary and is greatly facilitated; but they
must be extremely rare, and Moussu declares he has never seen one.
Hartenstein has suggested continuous cooling of the cranium by
irrigation or by applications of ice, the local lowering of temperature
serving to impede the development of the cœnurus. This method
should be tried in animals of high value, and, if the symptoms have
not yet become too alarming, recovery is possible. On the other hand,
when the symptoms indicate the presence of an old-standing cyst,
there is little chance of success. Moreover, the treatment could not be
applied where a large number of animals are affected.
It is much better to send the animals to the butcher if they are in
good condition. In Scotland, however—particularly in Caithness—
operation is said to be frequently practised with success.
Prophylaxis. In well-managed establishments it is easy to avoid
the appearance of cœnurosis.
The development of this condition being due to the Tænia
cœnurus of the dog, which passes ripe segments containing eggs with
its fæces in the pastures, the first indication is to prevent the
development of this tænia in sheep dogs, sporting dogs and house
dogs, and the sole precaution required is to avoid giving them as food
sheeps’ heads containing the bladder-worms. But, as despite these
precautions they may accidentally contract infection with Tænia
cœnurus by eating the offal of slaughtered animals, it is a wise
precaution to administer to all farm dogs, twice a year at least, a dose
of some tænicide.
They should be starved and kept in for twenty-four hours, and
should then receive a full dose of some energetic vermifuge, such as
areca nut, kamala, kousso, powdered pomegranate root, extract of
male fern, etc., followed by a purgative. The material passed and the
fæces should be burned or mixed with quick-lime. By these simple