Transcript Tuberculosis

Tuberculosis
Pearly disease
• Definition: Tuberculosis (TB) is an infectious,
granulomatous disease of mammals including
human, caused by acid-fast bacilli of the
genus Mycobacterium, characterized clinically by
progressive development of primary nodular
granulomas known as tubercles (caseous nodules) in
lungs and pulmonary lymph nodes and disseminated
caseous nodules in internal organs.
• Any body tissue can be affected but lesions are
frequently observed in lymph nodes (particularly of
head and thorax), lungs, intestine, liver, spleen, and
pleura. Clinical signs depend on the involved organs
Etiology
• Three main types of tubercle bacilli are recognized:
human, bovine, and avian,
respectively, M. tuberculosis , M. bovis ,
and M. avium complex ( M. avium-intracellularescrofulaceum ). The 3 types differ in cultural
characteristics and pathogenicity.
• M. bovis can cause progressive disease in most
warm-blooded vertebrates, including humans.
• Skin tuberculosis of cattle is caused by M. fortuitum
but skin tuberculosis of sheep and goats is due to the
infection with M. bovis. There is a cross antigenic
reaction among the members of this group also with
other organisms such as Corybacterium, Nocardia
and Rhodococci
• Morphology and staining:
▫ Mycobacteria are Gram positive, acid
fast, no motile and non spore forming
small rods. They can be stained by
acid-fast stain or Ziehl-Neelsen stain
(appear red color).
• Growth requirements and
characteristics:
▫ Mycobacteria grow well but slowly on
Lowenstein-Jensen slants and egg yolk
agar with incubation under aerobic
conditions at 33-39 °C for up to 8
weeks. Colonies are dry, delicate,
dome-shaped (avian type) and crumbly
(mammalian type).
Epidemiology:
1. Distribution: The disease is worldwide
distributed and endemic in Egypt.
2. Animal susceptible:
▫ The disease affects all species of vertebrates.
Cattle, buffaloes, pigs and humans are highly
susceptible. Sheep, goats, camels and equines are
sporadically affected.
• Factors effect on susceptibility:
▫ The disease is more common in dairy cattle than
in fattening cattle due to the long life span of dairy
cattle. Also, the incidence of the disease is high in
old animals.
▫ It is of low prevalence in cattle kept on pasture.
The indoor housed animals are at high risk of the
infection due to aerosol transmission.
▫ Stress factors as repeated pregnancy, lactation,
debilitating factors (poor feeding, chronic
disease), close housing and poor ventilation.
3. Transmission:
• Source of infection:
▫ Infected cattle are the main source of infection for other
cattle. Organisms are excreted in the exhaled air, in
sputum, feces, milk, urine, vaginal and uterine
discharges, and discharges from open peripheral lymph
nodes.
• Mode of transmission:
▫ Commonly entry is affected by inhalation or ingestion.
▫ Inhalation is the almost invariable portal of entry in
housed cattle
▫ by ingestion is possible at pasture when feces
contaminate the feed and communal drinking water
▫ The drinking of infected milk by young animals
▫ Other uncommon routes of infection include
intrauterine infection at coitus, by the use of infected
semen
▫ intramammary infection by the use of contaminated teat
siphons
Pathogenesis
• Tuberculosis spreads in the body by two stages, the primary complex and
postprimary dissemination.
• The primary complex consists of the lesion at the point of entry and in the
local lymph node, especially when infection is by inhalation.
• More commonly the only observable lesion is in the pharyngeal or
mesenteric lymph nodes. A visible primary focus develops within 8 days of
entry being affected by the bacteria. Calcification of the lesions commences
about 2 weeks later. The developing necrotic focus is soon surrounded by
granulation tissue, monocytes, and plasma cells and the pathognomonic
'tubercle' is established.
• Bacteria pass from this primary focus, which is in the respiratory tract 9095% of cases, to a regional lymph node and cause the development of a
similar lesion
Pathogenesis
• Post-primary dissemination from the primary
complex may take the form of acute military
tuberculosis, discrete nodular lesions in various
organs, or chronic organ tuberculosis caused by
endogenous or exogenous reinfection of tissues
rendered allergic to tuberculoprotein.
• In the latter case there may be no involvement of the
local lymph node.
• Depending upon the sites of localization of infection,
clinical signs vary, because the disease is always
progressive, there is the constant underlying
toxemia which causes weakness, debility, and the
eventual death of the animal.
Clinical signs
• The incubation period is long and varied from 2
months to several years. Morbidity and mortality
rates are generally low (5-20%) and depend on
the rearing system.
• General signs:
▫ Most cases progressive emaciation unassociated
with other signs occurs, and should arouse
suspicion of tuberculosis. A capricious appetite
and fluctuating temperature are also commonly
associated with the disease. Affected animals tend
to become more docile and sluggish. These general
signs often become more pronounced after
calving.
• Specific signs:
• Pulmonary involvement:
▫ Pulmonary involvement is characterized by a chronic
cough due to bronchopneumonia. The cough is never loud
occurring only once or twice at a time. It is easily
stimulated by squeezing the pharynx or by exercise and is
most common in the morning or in cold weather.
▫ In the advanced stages when much lung has been
destroyed, dyspnea with increased rate and depth of
respiration becomes apparent. At this stage,
abnormalities may be detected by auscultation and
percussion of the chest. Areas with no breath sounds and
dullness on percussion are accompanied by areas in which
squeaky crackles are audible.
▫ Involvement of the bronchial lymph nodes may cause
dyspnea because of constriction of air passages, and
enlargement of the mediastinal lymph node is commonly
associated with recurrent and then persistent ruminal
tympany.
• Alimentary tract involvement:
▫ Rarely tuberculous ulcers of the small intestine cause
diarrhea. Retropharyngeal lymph node enlargement
causes dysphagia and noisy breathing due to pharyngeal
obstruction. Pharyngeal palpation, or endoscopy, reveals
a large, firm, rounded swelling in the dorsum of the
pharynx. Chronic, painless swelling of the submaxillary,
prescapular, precrural, and supramammary lymph nodes
is relatively rare.
• Genital system:
▫ There is tuberculous metritis, there may be infertility, or
conception may be followed by recurrent abortion late in
pregnancy, or a live calf is produced which in most cases
dies quickly of generalized tuberculosis.
▫ . Rare cases of tuberculous orchitis are characterized by
the development of large, indurated, painless testicles.
• Udder involvement (tuberculous mastitis):
▫ it has characteristic feature is a marked induration
and hypertrophy which usually develops first in the
upper part of the udder, particularly in rear quarter.
In the early stages, the milk is not macroscopically
abnormal but very fine floccules appear later and
settle after the milk stands, leaving a clear, amber
fluid. Later still the secretion may be an amber fluid
only.
• Lymphatic involvement:
▫ There is chronic painless swelling in the affected
lymphnodes as submaxillary, prescapular, prefemoral
and supramammary. These lesions may be unilateral
or bilateral. The affected lymph node may be
containing fistula or discharging duct.
• Brain involvement:
▫ In young calve; tuberculosis meningitis with
nervous manifestation may develop.
• Skin involvement:
▫ Skin lesions appear as nodules similar to small
hard cauliflower on skin of the neck, shoulder and
upper forelegs. These lesions may involve the
lymphatics.
Postmortem lesions:
• Carcass is emaciated. Tuberculous nodules may be
found in many organs and lymph nodes especially
bronchial and mediastinal lymph nodes.
• In lungs, there is bronchopneumonia and military
abscesses.
• Pus is creamy to orange in color and varies in
consistency from thick cream to crumbly cheese.
• Small nodules may be found on pleura and
peritoneum.
• Closed lesions are characteristically discrete
nodules containing thick yellow to orange caseous
materials. They are often calcified and surrounded
by thick capsules.
Diagnosis
• Field diagnosis: It is depend on history of area
where TB is endemic or not, clinical signs such
as progressive emaciation and chronic cough,
postmortem lesions and zoonotic implications.
In living animal TB can be diagnosed by allergic
field tuberculin test.
Tuberculin test
• The standard method for detection of bovine
tuberculosis is the tuberculin test, which
involves the intradermal injection of bovine
tuberculin purified protein derivative (PPD) and
the subsequent detection of swelling (delayed
hypersensitivity) at the site of injection 72 hours
later
Types of tuberculin test
1. Single intradermal test (SID):
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it can be applied on calves more than 6
months of age. This test can be
detecting more than 90% of infected
animals.
Indication: It can be used as an initial
test in unknown herds, in case of the
suspected reactors and in the
introduction of animals from free herds.
Procedure:
Dose: 0.1 ml in unknown status herd
and 0.2 ml for infected one
Site: ID middle part of the neck or
mucocuataneous J as anal or caudal
fold of base of the tail (england)
• Result: read result after 48 (for max. sens.)-96 h
(for max. specf.)
▫ Increase thickness of skin more than 4mm, +ve
▫ Increase thickness 3-4 mm, doubtful
▫ Increase thickness 1-2 mm, -ve
Disadvantage:
 Lack of specificity, can not differentiate between
pathogenic and non pathogenic TB
 Non of non visible lesion reactors exceed 10%
 False (-ve) with min. sensitized animals;
 Early stage of infection
 Late stage of infection
 Old animal
 Recent parturition
• False positive result with;
▫ Non pathogenic mycobacterium (Avium,
paratuberculosis, Neocadia)
▫ Animal vaccinated with BCG vaccine within 8-60
d post vaccination
▫ Recent born calve suckling milk of infected dam
during first 3 w after parturition
Single intradermal comparative (SIDC) test:
• The test used to differentiate between infection due to
pathogenic TB and non pathogenic mycobacterium
(avian, paratuberulosis)
• Procedure; Avian and bovine tuberculin are injected
simultaneously into two separate sites on the same
side of the neck, 12 cm apart and one above the other,
and the test is read 72 hours later
• Result;
▫ increase thickness of skin more than 3 mm indicate
positive for homologous organism which responsible for
reaction
Short Thermal Test
• It has a high efficiency in the detection of spreaders that give
negative result with SID
• Dose,
▫ 4 ml S/C, The body temp. of examined animal must be normal
during and 2 h after injection.
• Result;
▫ read the result after 4, 6 and 8 h
Increase body temp 1 C , indicate +ve
Normal body temp, indicate –ve
• Advantage
▫ It can be detect min sensitized animals.
• Disadvantage:
▫ Anaphylactic shock due to large dose of PPD
Stormont test
• This test has a highly efficiency in the detection and
selection of the poorly sensitized animals especially
cows that have calved recently.
• Dose; 0.1 ml I/D in middle part of cervical region and
repeat after 7 days in the same site
• Result, read after 24 h fro 2nd injection, increase of
thickness more than 4mm indicate +ve result
• Disadventages;
▫ It causes long period of desensitization, laborious and
needs three visits to the farm, need special PPD with
specified potency.
• Post-parturient desensitization:
▫ It occurs immediately before and after parturition,
the loss of sensitivity may be due to removal of the
fixed cells antibodies from skin to general
circulation then to colostrums. On the other
hands, colostral antibodies cause false positive
result in calve for up to 3 weeks.
• Anergic animals:
• Those animals are with visible lesion of TB but
not react with the cutaneous test. Those anergic
animals can be reduced by the inoculation of
sufficient amount of PPD and read the results at
48-72 hours.
Laboratory Diagnosis:
• Samples: nasal discharges, sputum, trachobronchial
and gastric lavage, discharges of the reproductive tract,
lymph nodes, thoracic and abdominal fluid, milk, urine,
feces and samples from organs (liver, kidney, lung and
reproductive organs), blood, serum.
• Procedures:
1.
2.
Direct microscopic examination for tissue and organ
smear after staining with Ziehl Neelsen acid fast stain.
Isolation and identification of the organism: the organism
grows on Lowenstein media at 37°C for 6 w.
Identification of the colonies can be done on the basis of
culture characteristics, morphology, staining and
biochemical reaction. It is important to know that
detection of the organism is not sufficient by culture.
Also, negative culture results do not mean that the animal
is free of infection.
3. Serological examination:
Various serological examinations can be applied such
as ELISA (gives some false positive results but it
picks up some carriers that missed by SID),
FAT (of great value in detection of some cases that gave
false negative results with tuberculin but it failed to
detect high number of tuberculous cattle),
the gamma interferon test (it detects specific
lymphokines produced by lymphocytes due to the
response to the organism and can be used with SID).
4. Lung radiograph: it can be used to detect the lung
nodules.
5. PCR: It is rapid and sensitive. It can detect even one
tubercle bacillus in the suspected material.
Treatment
• Because of the progress being made in the
treatment of human tuberculosis with such
drugs as combinations of streptomycin and para
aminosalicylic, and other acids
Control
• The control depends on the identification of the
infected animals by tuberculin test and
elimination of the positive cases by slaughter
I. Control on herd basis:
▫ Control in a herd depends on:
1. removal of the infected animals,
2. prevention of spread of infection, and
3. avoidance of further introduction of the disease.
1. Detection and removal of infected animals:
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control is applied by careful and regular clinical examination
and tuberculin testing of all animals above 3-6 months every
6 months and then immediate culling (slaughter) of the
reactors.
Doubtful cases should be isolated and retested after 2 months.
SIDC test should be used if there is high incidence of infection
with human or avian types
If there is a high incidence of reactors at first step of
examination or if open lesions were observed in culled animals
at PM examination, the test should be repeated at short
intervals (2-3 months) till negative results are obtained and
then another confirmatory test should be applied after 6
months.
If last test gives negative results, herd is considered free from
TB and should be tested annually.
2. Prevent spread of infection and avoidance of
further introduction of disease:
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Hygienic measures to prevent the spread of infection should
be instituted as soon as the first group of reactors is removed.
Feed troughs should be cleaned and thoroughly disinfected
with 5% phenol . Water troughs and drinking cups should be
emptied and similarly disinfected.
Separation of infected and susceptible animals by a double
fence provides practical protection against spread of the
disease.
It is important that calves being reared as herd replacements
be fed on tuberculosis-free milk
After Culling of the reactors, the replacement animals should
be from free herd
II. Control on an area basis:
▫ The incidence and distribution of the disease should
be defined by tuberculin testing of samples of cattle
along with the good meat inspection in abattoirs to
detect the free areas, low incidence and high
incidence areas.
▫ In the low incidence areas, disease should be
eradicated by test and slaughter policy.
▫ In the high incidence areas, it is impossible to apply
the routine test and slaughter policy. These areas
should be divided into infected and non-infected
herds on basis of clinical examination and
tuberculin test and so on to reduce the infected area
III. During outbreaks of TB:
▫ The clinically infected herds should be isolated.
Infected animals should be slaughtered and
subjected to pathological examination. The herd
should be monitored with elimination of the
reactors every 3 months and then every 6 months
for several years. Farms should be carefully
cleaned and disinfected. The source of the
infection should be investigated.