Glanders

Paul L. Nicoletti, in Equine Infectious Diseases, 2007

ETIOLOGY
Burkholderia mallei (formerly Pseudomonas, Bacillus, Pfeiferella,
Loefflerella, Malleomyces, Actinobacillus, Corynebacterium,
and Mycobacterium) is a short, rod-shaped, gram-negative, aerobic,
facultative intracellular, nonmotile and non–spore-forming
bacterium. The organisms survive outside the host for varying times
depending on many factors. Relatively little is known about
virulence factors of B. mallei. Capsular polysaccharide is essential
for virulence in hamsters and mice.6 An acapsular mutant of B.
mallei failed to induce disease in experimentally infected
horses.7 Disease caused by B. mallei must be reported to the World
Organization for Animal Health.
Infectious diseases
Ann A. Cullinane, ... J.F. Timoney, in The Equine Manual (Second
Edition), 2006
Etiology
B. mallei has few bacteriologic features in common with other
members of the genus and its taxonomic position has always been
problematic.
Epidemiology and pathogenesis
B. mallei is an obligate parasite that does not survive for more than
about 6 wk outside its hosts. It is very sensitive to sunlight and
drying even when partly protected by the purulent exudate it
produces in its host. Horses usually acquire the infection
by ingestion or inhalation.
After penetrating the mucosae passively, the organism, like the
tubercle bacillus, has a marked propensity to travel and deposit
itself in lymphatic tissues. It also infects pulmonary tissue where
it is associated at first with microscopic inflammatory foci. These
foci enlarge to form macroscopic nodules and ultimately
larger, chronic granulomas. A diffuse interstitial pneumonia can
accompany this process. At any point during these events exudates
containing the bacilli from the nodules can be discharged into the
airways and so reach the upper respiratory tract where they
produce nodules in the nasal cavity similar to those in the lungs.
These nodules eventually rupture to produce the
characteristic punched-out ulcers along the nasal septum. The
ulcers discharge a gluey, purulent exudate. They can be seen in the
congested and even hemorrhagic mucous membrane of the nasal
cavity simply by everting the alar cartilage.
The bacilli may also infect the lymphatic tissues of the limbs where
they give rise to farcy. Farcy comprises a chronic lymphangitis (the
“farcy cords”) and lymphadenitis (the “farcy buds”). As in the nasal
cavity, these lesions rupture to discharge purulent exudate. The
exudate contaminates stables, tack, harness and utensils with B.
mallei and is thus a major source of infection for other animals and
humans. The clinical and pathologic events that follow inhalation (or
cutaneous inoculation) of B. mallei are similar to those that occur
after its ingestion.
Although horses that have apparently recovered from the disease
are resistant to further infection, they may suffer the occult form of
the disease. In occult (latent) glanders, the pulmonary lesions are
quiescent but can be provoked by stress into renewed
development, leading to dissemination of the agent in the body and
its release to the exterior. The reactivation of these quiescent
lesions in the infected horse explains why in the past the severe
strain of military operations was often associated with major
outbreaks of the disease in the cavalry.
Although humans are much more resistant to B. mallei than
Equidae, the organism can produce disease that chronically affects
the skin and subcutaneous tissues and can generalize with fatal
consequences.
Diagnosis
Clinical glanders is distinctive once the nasal and cutaneous
lesions have formed and B. mallei is easily recognized in smears
from such lesions. It is a Gram-negative, beaded rod approximately
1–5 μm long by 0.5 μm wide. B. mallei is easy to grow in the
laboratory, but growth is slow even with media such as those
containing glycerol which favor it and on which its colonies
resemble drops of honey that gradually become brown. Affected
horses can also be detected by serologic methods and
the complement fixation test is generally regarded as the most
reliable. However, counterimmunoelectrophoresis with
appropriate antigen is fast and simple and is said to be as reliable
as the technically more complicated CFT.
The mallein test can also be employed to detect infected horses.
Mallein is a protein produced by B. mallei during growth. When it is
inoculated intradermally into the eyelid or instilled into the
conjunctival sac, it gives rise to swelling of the eyelid and the
formation of a purulent exudate in the eye of a glanderous animal
within 24 h. This test, like the CFT, is a prescribed test for
international trade and is indispensable in the control of glanders.
Treatment and control
The horse is essential to the persistence of B. mallei.
Consequently no convincing case can be made for treating a
horse with the confirmed disease or infection. The destruction of
infected animals has eliminated the disease from the horse
populations of many areas of the world.
Behavioral
B.E. Turvey, in Encyclopedia of Forensic Sciences (Second Edition), 2013
The Malleus Maleficarum
One of the first published texts that offered explicit instruction on the subject and practice of
profiling criminal behavior is the Malleus Maleficarum (The Witches' Hammer). Two
Dominican monks, Henry Kramer and James Sprenger, professors of theology from the Order
of Friars Preachers, originally published this work around 1486. It was intended to provide
rationales and guidelines for those involved with the Medieval Inquisition (namely the
authors) to assist in the identification, prosecution, and punishment of witches.
According to the Malleus Maleficarum, witches and other criminals may be identified by
specific circumstances, abilities, and characteristics as defined by the experiences of both its
authors in concert with their interpretation of the Bible. Witches were described primarily as
women who:
•
have a spot, scar, or birthmark, sometimes on the genitals and sometimes invisible to
the Inquisitor's eye;
•
live alone;
•
keep pets (a demon in animal form known as a familiar)
•
suffer the symptoms of mental illness (auditory or visual hallucinations, etc.);
•
cultivate medicinal herbs;
•
have no children.
The Malleus Maleficarum also explains that dead bodies will flow blood from their wounds
when their murderer is near.
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Types of Hearing Loss
Jos J. Eggermont, in Hearing Loss, 2017
5.2.2 Loss of Tympanometry, Malleus, and Incus
When the TM, malleus, and incus are missing, the resulting air–bone gap may be explained in
terms of remaining acoustic coupling (Peake et al., 1992). With the TM and ossicles missing,
ossicular coupling is abolished and acoustic coupling is approximately 10–20 dB larger than
in the normal ear. Therefore, the air–bone gap for these conditions is 40–50 dB. Similar gaps
should also occur when there is a large perforation of the TM in conjunction with ossicular
disruption (Merchant et al., 1997).
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Bradley L. Njaa, in Pathologic Basis of Veterinary Disease (Sixth
Edition), 2017
Malleus.
The largest of the ossicles is the malleus. The manubrium of the malleus is embedded in the
tympanic membrane (see Fig. 20-5). The most ventromedial convexity of the malleus is the
“umbo” (see Figs. 20-6, F, and 20-12). The muscular process of the manubrium near the neck
of the malleus is the attachment site of a thin tendinous portion of the tensor tympani muscle.
Various ligaments stabilize the malleus in the epitympanic cavity by anchoring the long, thin
rostral process, the neck, and the head of the malleus. The head of the malleus articulates
with the articular surface of the body of the incus, forming the incudomallearis joint
(see Figs. 20-9, 20-12, and 20-13). In the horse and cow and in aged dogs and cats, the
incudomallearis joint capsule is a narrow but thick ligament that
makes disarticulation difficult and gives the external appearance of a falsely fused joint. In
younger dogs and cats the incudomallearis ligament is not nearly as tenacious, and
disarticulation is much less difficult.
The Skull
Craig Cunningham, ... Sue Black, in Developmental Juvenile
Osteology (Second Edition), 2016
Sideing the Auditory Ossicles
Malleus (Fig. 5- Place with the head pointing superiorly and the manubrium
28A) inferiorly. Turn so that the slender anterior process is pointing
downwards and the articular surface for the incus is visible on the
head. The short lateral process points to the side from which the
bone comes.
Incus (Fig. 5- Place with the short crus pointing horizontal and the long crus
28B) pointing inferiorly. Turn so that the lenticular process is pointing
upwards and the superior half of the articular surface for the malleus
is visible. The short crus points to the side from which the bone
comes.
Stapes (Figs. 5- Place with the head pointing superiorly and the footplate pointing
28C and 5-28D) inferiorly. Turn so that the footplate has its flat surface below and its
rounded surface uppermost. The more curved and slightly more
robust posterior crus is on the side from which the bone comes. It is
sometimes difficult to side a stapes, as many of the features are not
at all well defined.
Burkholderia mallei and Burkholderia pseudomallei
Mitali Sarkar-Tyson, Richard W. Titball, in Vaccines for Biodefense and Emerging and
Neglected Diseases, 2009
Classification
B. mallei and B. pseudomallei have previously been assigned to the
genus Bacillus, Acinetobacter, Loefferella, Actinobacillus,
Malleomyces, or Pfeifferella (NCBI Taxonomy). Most recently, based on their 16S
ribosomal nucleic acid sequences, DNA homology, cellular lipid and fatty acid composition,
and phenotypic characteristics, they were known as Pseudomonas mallei and Pseudomonas
pseudomallei (Leelarasamee and Bovornkitti, 1989). Currently, these species are classified in
the genus Burkholderia, which is named after U.S. microbiologist Walter Burkholder, who
first described Burkholderia cepecia, formerly known as Pseudomonas cepecia (Yabuuchi et
al., 1992).
The genome sequence of B. pseudomallei strain K96243 reveals that it is one of the
largest prokaryotic genomes comprising two chromosomes of 4.07 and 3.17 Mb (Holden et
al., 2004). The larger chromosome carries genes associated with housekeeping functions
involved in processes such as cell growth and metabolism, and the smaller chromosome is
thought to encode genes required for adaptation and survival in different environments. This
proposal is also supported by the finding that genes important during the early phase growth
of B. pseudomallei in vitro are preferentially located on chromosome 1, whereas genes
involved in stationary-phase growth are biased toward chromosome 2 (Rodrigues et al.,
2006). There is significant intraspecies diversity that is attributed to either DNA acquisition
or loss (Ou et al., 2005). An unusual feature of the B. pseudomallei genome is the presence of
16 genomic islands, which make up 6.1% of the entire genome, and is thought to be acquired
by horizontal gene transfer. These genome islands are absent in the B. mallei genome, which
is smaller than that of B. pseudomallei, consisting to two chromosomes of 3.51 and 2.32 Mb
(Nierman et al., 2004). The presence of a number of insertion sequence elements is thought to
have mediated the extensive deletions and rearrangements of the genome relative to that of B.
pseudomallei (Nierman et al., 2004). The genome downsizing supports previous Multi-Locus
Sequence Typing (MLST)-derived conclusions that B. mallei has evolved from B.
pseudomallei (Godoy et al., 2003). Subtractive hybridization between B. mallei and B.
pseudomallei has identified several DNA fragments specific to the latter, which may provide
functional detection tools (Monastyrskaya et al., 2004).
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Audition
S. Puria, C.R. Steele, in The Senses: A Comprehensive Reference,
2008
3.10.4.8 Middle-Ear Muscles
The malleus and stapes each have a tendon attached to a tiny
muscle, the tensor tympani muscle and the stapedius muscle,
respectively. The muscles contract when exposed to high-level
sounds, and are part of the middle-ear reflex arc involving the spiral
ganglion neurons, the auditory nerve, cochlear nucleus, the
superior olive, the facial nerve nucleus, the facial nerve, and the
two middle-ear muscles (Margolis, R. H., 1993). This reflex arc can
reduce sound transmission through the middle ear at high levels,
and may serve to control the dynamic range of the auditory system
and to protect the cochlea at high sound levels. The reflex is slow,
and thus does not provide protection to the cochlea against sudden
impulsive sounds. The time for the stapedius reflex may be on the
order of about 20 ms, while the tensor tympani arc is more than ten
times slower (Teig, E., 1972).
Two additional functions are attributed to the middle-ear muscle
reflex. Low-frequency sounds, particularly when they are high in
level, normally tend to mask mid- and high-frequency sounds due to
their upward excitation patterns on the BM. One role of the middle-
ear muscles is to reduce the level of low-frequency inputs so they
do not mask the higher frequency sounds on the BM (Pang, X. D.
and Guinan, J. J., Jr., 1997). A second role of the middle-ear reflex
is in the reduction of the audibility of self-generated sounds during
speech, mastication, yawning, and sneezing (Simmons, F. B. and
Beatty, D. L., 1962; Margolis, R. H. and Popelka, G. R., 1975).
Because the reflex arc involves so many mechanisms, its
measurement is used clinically to diagnose central and peripheral
pathologies.
Recently it has been discovered that there are smooth muscle
arrays within the peripheral edge of the tympanic membrane, the
annulus fibrosus, in all four of the mammalian (bats, rodents,
insectivores, and humans) species studied (Henson, O. W., Jr. and
Henson, M. M., 2000; Henson, M. M. et al., 2005). The role of this
rim of contractile muscle cells in the par tensa region is not clear,
but two suggested possibilities are to maintain tension of the
tympanic membrane and to control blood flow to the membrane
(Henson, M. M. et al., 2005). Measurements indicate that these
smooth muscles can exert control over the input to the cochlea as
measured by cochlear microphonics (Yang, X. and Henson, O. W.,
Jr., 2002).
Neuro-Otology
R.A. Davies, in Handbook of Clinical Neurology, 2016
Abnormalities of the tympanic membrane and middle ear
Congenital abnormalities
•
Fused malleus and incus
•
Incus fixed to posterior bony annulus
•
Congenital stapes fixation and grossly deformed stapes
•
Absent stapedius tendon
 •
Uncovered seventh nerve
•
Partial bony plate formation.
Acquired abnormalities
Acute otitis media
Acute otitis media is frequently associated with upper respiratory
tract infections. Common causative organisms
include pneumococcus, Haemophilus influenzae, and Moraxella
catarrhalis. There is an exudative phase associated with
a conductive hearing loss and a negative MEP and a recovery
phase when the middle ear becomes well ventilated again.
Chronic otitis media
Chronic otitis media may develop from acute otitis media and be
associated with TM perforation, incus necrosis,
myringostapediopexy, malleus head fixation, cholesteatoma, and
tubotympanic disease. The size and location of a perforation
determine the degree of hearing loss – a large perforation in
general is associated with a greater degree of hearing loss. The
location of the perforation generally distinguishes “safe” from
“unsafe” perforations, the marginal perforation being the “unsafe”
perforation and likely to be associated with cholesteatoma.
Cholesteatoma
Cholesteatoma is a cyst lined with squamous epithelium that can
arise in an ear undergoing long periods of negative MEP. Cysts are
likely to begin in the attic of the ear and extend into the
mastoid antrum. They are associated with “unsafe,” marginal
perforations when the cyst penetrates the TM. They can penetrate
the bone with which they come into contact, and lead to intracranial
complications by eroding through the dura of the middle or posterior
fossa, or into the lateral sinus or the horizontal semicircular canal.
The facial nerve may be eroded in the middle ear or mastoid.
Tubotympanic disease
Tubotympanic disease is characterized by recurrent
infections rather than persistent infections and by odorless
discharge. A central TM perforation and a break in the ossicular
chain or malleus fixation are regarded as “safe” and unlikely to be
associated with cholesteatoma.
Otitis media with effusion
Otitis media with effusion (OME) is recognized by the presence of
an air–fluid level in the middle ear and a bluish discoloration of the
TM. In adults the presence of bilateral OME should trigger
investigation for neoplastic obstruction in the nasopharyngeal end
of the eustachian tube. In children OME is more commonly known
as “glue ear.” Hemotympanum may be seen after a head
injury associated with a temporal bone fracture, or
with barotrauma associated with scuba diving.
Otosclerosis
Otosclerosis is an autosomal-dominant condition associated with
gene TGBF1 that can be identified during the osteoblastic phase
by hyperemia of the middle-ear promontory, visible through the TM
as a rosy glow, known as Schwartze's sign. It is associated with a
conductive hearing loss due to fixation of the stapes footplate (but,
characteristically with no air–bone gap at 2 kHz, known as a
Carhart notch). Absent stapedius reflexes are a feature early in the
progression of the disease and the TM compliance peak is low.
Head trauma
Head trauma can lead to a variety of outer, middle-, and inner-ear
abnormalities depending on the presence of a fracture of the
petrous temporal bone. If there is bloody otorrhea, audiometry is
mandatory and may show a conductive hearing loss, but also a
sensorineural hearing loss associated with labyrinthine concussion.
Glomus tympanicum tumor
Glomus tympanicum tumor is identified as a vascular mass behind
the TM and the patient may describe pulsatile tinnitus. In such
cases audiometry may show a conductive hearing loss and the
tympanogram may be pulsatile.
Tuning fork tests
Traditionally tuning fork tests have been used in the clinic to
distinguish conductive from sensorineural loss. However, with the
widespread availability of pure-tone audiometry, these tests are less
used clinically. The most commonly used tuning forks are those
tuned to 256 and 512 Hz. Lower frequencies produce a vibrotactile
stimulus that leads to misleading hearing thresholds.
Two general principles apply:
1.
The inner ear is more sensitive to sound conducted by air than
by bone.
 2.
In pure conductive hearing loss, the affected ear is less
subject to environmental noise and is more sensitive to bone-
conducted (BC) sound.
Rinne
The 512-Hz tuning fork should be struck two-thirds of the way along
its tines (to minimize distortion products) against a hard but elastic
mass, e.g., a rubber pad (otherwise overtones may be produced).
The fork is then held perpendicular to the long axis of the EAM with
its closest tine within 1 cm of the entrance to the meatus. The
patient is asked to report if s/he can hear the sound. The fork is
then immediately transferred behind the ear, with the base soundly
pressed to the bone overlying the mastoid. The patient is asked
which sound is louder, that “in front of the ear” or that “behind the
ear.”
Positive Rinne (AC > BC)
The Rinne is described as positive if the sound in front of the ear
(air-conducted (AC) sound) is reported as louder than that behind
the ear (BC sound). In an ear with a normal conductive mechanism,
AC sound will be perceived as louder than BC sound. A positive
test is found in a normally hearing ear or with a sensorineural
hearing loss.
Negative test (AC < BC)
The Rinne is described as negative if the sound in front of the ear is
reported as quieter. If it is negative, this indicates a significant
conductive component (> 15 dB hearing level (HL)). A false-
negative Rinne can occur if there is a severe sensorineural hearing
loss in the tested ear. In this situation, the BC stimulus is heard in
the nontested ear because of intracranial transmission, and BC
sounds will be greater than AC sound. Masking of the nonaffected
ear is then performed using a Bárány box, delivering white noise
and raising the threshold of hearing, so that BC sound cannot be
heard. The Rinne is best used as a test for conductive hearing loss,
but has a high specificity and a low sensitivity.
Weber
The Weber test is used in conjunction with the Rinne test and is
most useful in patients with unilateral hearing loss. The aim is to
identify the better-hearing cochlea. The 512-Hz tuning fork is struck
and placed in the midline on either the forehead or the vertex. The
patient is asked if the sound is heard louder in one ear or equally in
both ears. In a normally hearing patient, the tone is heard centrally.
Otherwise, the sound is heard on the side of the better cochlea
unless there is a conductive hearing loss, in which case the tone
may be heard in the poorer-hearing ear.