ZoonoticTuberculosis in India

p`aNaIjanya xayaroaga

Dr. Ashok Kale

M.D.(Community Medicine )

Mob : 9406109410

ashokpkale2003@yahoo.com
ashok.kale995@gmail.com

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Yearwise Tuberculosis mortality and different
interventions

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 Times of India ,Nov 8, 1996.
Dr. Ashok Kale & Dr. S. V. Gore wrote:
1.Tuberculin Test + vity has a special relevance in
animals.
2. In tub. animals majority (80 %) have lung tub.
3.Only 1% of tub. Animals have lesions in milking part
mastitis (udder)
4.Animals shed tubercle bacilli through exhaled air and
faeces (gober).
5. In Indian rural household animals and human stay
under one roof.
6. South African study – INH cures Tub. Of Animals.
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 National Medicos Organisation’s
resolution , Jan 1997- Tiru.
• Zoonotic aspect of pulmonary tuberculosis
needs to be attended by controlling
tuberculosis in animals, especially cattle to
protect the rural people staying with animals
under one roof.
• District Tuberculous Centres should
coordinate with the Veterinary department.
• GOI should initiate necessary action in this
regard.

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TAI’s Nagpal’s letter 1997

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 Views of Vice-chairman of TAI(1997)
1.Report of RTC, TT testing etc is now history
2.Invariable boiling of milk practice can not
cause Zoonotic Tub, even if there are
tub.cows
3. Cross reaction due to non-tub mycobacteria
4.Culture of samples did not yield M.bovis.
I(Nagpal) know all this does not mean we
should ignore this (ZTB) issue.
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 Dr. Kale Ashok*, Dr. Deshpande Shailesh, Dr. Gore

• Medico Friends Circle Bulletin – Jan-Feb 2000

Can Human Tuberculosis be Controlled in India

Without Control of TB in Domestic Animals ?

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 Understanding tubercle bacillus,
some queries to the audience.
1. Why bovine bacillus was taken by Dr. Albert
Calmette for human vaccine (BCG)
development?
2. Why we cannot differentiate by observing
Tuberculin reaction the type of causative
organism ,i.e. human or animal (bovis) ?
3. Why there is cross immunity?
4. If M. bovis & M.tuber. are 2 species , how can
they have cross immunity ?
5. Are they different species or variants of same
species?
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Tubercle Bacillus Infection & Tuber . In
Man & Animals- Dr.Calmette , 1923

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Tuberculosis in Animals and Man-
Francis, 1957

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Bovine Tub control in Man & Animals-
Dr. Steele & Myers, 1971 , USA

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 Steele and Myers from USA
• Tuberculin and it’s use :
• Dr. Robert Koch– 1890
• Russia – Guttman, Denmark- Bang
• On postmortem they found– reacting animals
had TB in one or more organs.

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 Tuberculin Test studies
• Pearson’s study in 1891 (USA)
• Tested 80 cattle – reacted 30 – PM showed TB
lesions
• Russel, Europe, 1892-- 30 tested--26 +ve

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 Tuberculin Test in Human
• Ghon- 1908-12- PM of 183 children who
during lifetime had no evidence of
Tuberculosis except TT positivity.
• Children had died of Nontuberculous
conditions.
• Except one ,all had tuberculous lesions.
• He had done the study to test the specificity
of Pirquet’s belief.

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 Francis– What happens in cattle after
infection of tub bacillus?
• Unlike human ,Primary tuberculous infection in
cattle –
*Lesions do not heal, progressive TB.

* In man – large population reacts to the

tuberculin test but does not spread infection.

*But in cattle – All T.T. positive are INFECTIOUS,

verified by Bang, Pearson and other
veterinarians.

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 Veterinary pathology
• Lesions in the dog –
Three- quarters of natural cases of infection-
Caused by human type of bacillus.
• The disease runs a progressive course in the
dog.
• One rarely encounters healed TB in PM
examinations.

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 True meaning of the term-- Bovine Tuberculosis

• Strictly ,this term should only be used to refer

to tuberculosis in cattle , but is often used to
denominate tuberculosis caused by bovine
strains irrespective of the host.
• --- Bovine tubercle bacilli and
disease in animals and man, Epidem Inf
(1987), 92, 221-234. Grange & Collins.

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 Grange J.M. and Collins, Epidem Inf. (1987), 92, 221-- 234 ,
Bovine tubercle bacilli and disease in animals and man

• As in man, in animals ,the lung is the usual

site of disease, and spread of infection occurs
by the respiratory route. Although milk is the
principal vector for transmission of infection
to man, disease of the udder relatively
uncommon, effecting only about 1% of
tuberculous cows.

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 (BMJ,Oct.24,1908).
Why TT +ve cattle are called infectious?

• Dr. E. C. Schroeder, of the Department of

Agriculture, Washington, read a paper on his
investigations,( International Congress on
Tuberculosis held in Washington, September,
1908 )
• About 40 per cent of cattle apparently healthy,
and known to be tuberculous only because they
had reacted with tuberculin, intermittently
passed tubercle bacilli with their faeces.

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 When a number of such cattle were kept
under continued observation, the
percentage that expelled tubercle bacilli
per rectum was found to double in about
eighteen months; and both the frequency
with which bacilli occurred and the
number found in individual animals also
showed an increase. Among twelve cows,
bacilli in the faeces were at first found in
five, but before the end of two years the
number had risen to ten.
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 Tople wilson Bacteriology
• Response of Bacteria to the Environment
(Section B) :
Bacteria flourish in physical environments that
differ widely.
Bacteria prove to be the most ADAPTABLE of
the living organisms in their modes of
obtaining energy for growth.

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 Tople wilson Bacteriology
• May alter their phenotype in response to
environment change while the genotype remains
unchanged.
• Mutant cell with a temporary selective advantage
can over grow a population of unaltered cells
within a few hours.
• If cells are examined on times scales that permit
many generations, what is in reality genotype
variation may appear to be phenotypic variation.
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 The Bacteriology of Tuberculosis,
Ergons Darzins,
Univ. of Minnesota, 1958, Chapter XXI, 273 – 286.

• Pathogenicity is the disease-producing

property of microorganisms.
• Virulence expresses the degree of
pathogenicity of bacilli.

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Do Fixed Types of Tubercle
Bacilli Exist?
Chapter XXI ,

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Price’s (1932), study of the incidence of bovine
tub infection in same region of Canada
Number Percentage Bovine
infection
Children 286 14.1
Adult 168 3.5

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 Rich,1951-
“very curious phenomenon”
Number Percentage bovine
Children 877 22.2
Adult 1330 2.2

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 Explanation of supporters of the
theory of stable types of bacilli
• Generally children are more frequently
exposed to bovine infection than adults,
because milk is the chief food of children,
• That the resistance of adults to tuberculous
infection is greater than that of children

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 But
• These hypotheses are insufficient to explain
why the bacillus of bovine type disappears
from the human body and why the bacillus of
human type takes its place when the infected
child develops into a tuberculous adult.

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 Another explanation?
• The theory of the superinfection with bacilli of
human type cannot explain this phenomenon;
*Consequently, it is necessary to seek a
different answer to the problem.

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 Jensen and Frimodt-Moller (1936)-
Change of types
• Described seven strains of tubercle bacilli, all
of low virulence for rabbits, as bacilli of human
type.
• In all seven cases the authors
• were able to cultivate bacilli of the bovine
type from rabbits inoculated with these strains.

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 Interesting history of strain 1832
Jensen and Frimodt-Moller (1936b).
This strain of human type was cultured from urine
and grew dysgonic, being virulent for guinea pigs
and only slightly virulent for rabbits and calves.
The passage of this strain through a
rabbit produced a typical bovine
type bacilli. This transformation of the
original human type into a bovine type of bacilli
was performed seven times.

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 Conclusion of
Jensen and Frimodt-Moller
The appearance of bovine type of bacilli was the

result of the transformation of the original

human type of bacilli into the bovine
type within the rabbit organism.

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 Pinner (1935)
• by means of passages through guinea pigs
succeeded in transforming two strains of
nonpathogenic acid-fast bacilli, isolated from
tuberculous patients, into bacilli producing
typical tuberculosis in guinea pigs

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 Smithburn (1939)
• restored the virulence of attenuated bovine
and human types of bacilli by serial transfer of
these strains to rabbits and by serial brain-to-
brain passages through guinea pigs.

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 RTC-(Griffith )
• tubercle bacilli derived from cases of human
pulmonary tuberculosis, discovered cultures
consisting of a mixture of both the human and
bovine types of bacilli.
• out of 1,068 cases studied, 5 were mixtures of
bovine and human types of bacilli.

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 Griffith gives two reasons
1. Transformation, within the human body, of
one type of bacilli into another

OR

2. Later association of another type of bacilli

with the already existing infection

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 British Medical Journal, March3,
1934,371, Walker
• Discussion :-
• It has been suggested that mutation of type
occurs in the human body, so that an
• infecting bovine organism after
many years in human tissues
acquires the characteristics
associated with human type
bacilli, and becomes manifest as such in
chronic pulmonary tuberculosis in adults.

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 British Medical Journal, Aug 15,
1936,pg 324-325.John Blacklock ,
Tuberculosis in Infancy and Childhood.

• The immunity from childhood infection –

It seems certain, from my figures that tub
infection in the child under 3 years is serious,
and should , if possible, be prevented.

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 British Medical Journal, Aug 15,
1936,pg 324-325.
John Blacklock

• Tuberculin-positive children more frequently

develop fatal phthisis in later life than those
who react negatively

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 British Medical Journal, Aug 15, 1936,pg 324-325.
John Blacklock

• After many years' sojourn in the tissues it may

mutate to a more pathogenic form or even to
a human type. Calmette himself thought it
possible that in naturally occurring bovine
infections in man, mutation to the human
type after a time was possible, and might be
the cause of pulmonary tuberculosis.

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Bovine and Human Tuberculosis– Prof.Orth,
BMJ ,1913

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Rabinowitsh, The transmission of Tuberculosis
through Domestic animals, Amer Rev
Tuber,1927,v.15,419-428

Author believes that it is not

impossible for the biological
properties of the various types of
bacilli to alter while in the human
body- the bovine becoming
converted into the human.

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Book. --Tubercle Bacillus Infection AND Tuberculosis in
Man & Animals, Dr. Albert Calmette , 1923, page 294.
• We are not justified in inferring the duality of
human and bovine tuberculous bacillus.
• These types differ one from another only because
they have more or less adapted themselves,
through a series of successive cultural generations
to a human or bovine environment.
• And it cannot be conceived to constitute special
types.
• In all of these we have to do with the same
bacillus.
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 Book. --Tubercle Bacillus Infection AND Tuberculosis in
Man & Animals, Dr. Albert Calmette , 1923, page 294.

• Many efforts have been made in a variety of

ways to convert what by agreement is called
the human type into the bovine type, for
example by inoculating successively the same
virus from man to cattle, then from cattle to
cattle or through an intermediate stage in the
goat. It would seem that in a few cases partial
success has been attained.

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Zoonoses

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 Dung of Tuberculous animal
Milk Borne diseases, Douglas,
BMJ, July 30 ,1932 , 198 – 200.
• Frequently such animals excrete large number of
tubercle bacilli in the faeces.
• virulent bovine tubercle have been recovered
from cow manure after one year, from a lump of
cow dung for upwards of two years, and even
from the effluent of a drainage system of the
septic tank type

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 Mode of Infection from Cattle to
Human
• Magnussen emphasizes the danger children run
when they play in infected cowsheds.

• Infection between cattle generally occurs by the

airborne route. The most infectious particle is a
recently exhaled moist droplet containing a few
bacilli. Tubercle bacilli are not only excreted by
bovines with open pulmonary lesions but also by
those in the initial period .
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Tuberculous Mastitis

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U.S.A. agri 1957 book- Tuberculosis and its eradication

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 US agriculture yearbook 1957
*When they swallow the tub sputum, the
tubercle bacilli in it are passed unchanged
through the intestines, and their dung is
extremely infectious.
*In animals, the organs most commonly
affected are lungs.

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 US agriculture yearbook 1957
The death rate from tuberculosis was 150
per 100,000 population in 1918. The rate
came down to 15 per 100,000 in 1952.The
eradication of bovine tuberculosis must be
recognised as a factor in this improved
condition.

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 Exploring PCR technology
veterinarian , June 1997,

Striking homologies at genomic level

between M.tuberculosis and M. bovis
made it very difficult to differntiate
between the two by PCR based
methods.

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Tuberculosis,
(2001),81,71-77, J.M.Grange
• Strictly speaking, all strains within this
(M.tuberculosis complex) complex should be
regarded as belonging to a single species but ,
for convenience, the separate specific names
M.tuberculosis M.bovis were proposed in
1970.

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 Veterinarians established facts
• 1. T.T. stands alone in the determination of TB in
animal’s body.
• 2. Herditary predisposition of a animal breed has
no significance.
• 3. Tubercle bacilli are not ubiquitous. They are
present only in places where tuberculous animals
(or human beings) live.
• 4.Digestive tract is the most common portal of
entry .
• 5.The ratio between the tuberculous mortality for
the TT reactors :non-reactors was 38:1 (children)
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 Dr. Robert Koch , died in 1910

• Koch’s convictions that bovine tuberculosis is

different from human tuberculosis, and that it
“does not seem advisable to take any
measures against bovine tuberculosis,” were
most striking, because they were diametrically
opposed to the opinions which he had held
before.

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 Koch
*Koch defended his new views with extreme
tenacity.
* At a special meeting of the International
Tuberculosis Congress at Washington in
1908, he rejected the evidence of the British
Tuberculosis Commission on the existence of
types of intermediate and unstable
pathogenicity as well as the arguments of
Calmette, Fibiger, Ravenel, Dorset, and
others who defended the possibility of the
evolution of types.
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 Unequal Vertical split,(274)
• The Washington International Tuberculosis Congress
split the tuberculosis workers into two unequal groups:
• The great majority followed Koch and accepted the
existence of different constant types of tubercle bacilli,
responsible for tuberculosis in humans, bovines, and
birds. This was the beginning of the reign of the dogma
of types in tuberculosis bacteriology.
• The scientists of the opposite camp, who regarded the
types, varieties, and intermediate forms as links
between the evolving forms, remained a small
minority.

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Thank you.

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 Studied Answers
1. M. bovis and M. tuberculosis( human )are not two
species . They are one. (conclusion of Royal Tub
Com. in 1911)
2. They are antigenically 99.95 % similar.
3. There is difference in virulence.
4. Many scientists ,including Calmette , Jenson (L-J
media), Dorset (culture media)believed that Bovis
gets transformed (converted) into M. tuberculosis
after a prolong stay in human body.
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 Trends after Th.smith

274- To designate differences in

origin and virulence of tubercle
bacilli, Koch accepted the term
“type” proposed by Kossel but
emphasized that to him this term is
no better than the word “variant” or
any other name.

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 Conclusions.

Final years’ work toward the typing

of tubercle bacilli has shown the
inconstancy of the types, and in a
great many cases impossibility of
differentiating them.

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 Conclusions

Facts are not compatible with the

opinion of Th. Smith and the final
views of Koch on the constancy of
the types of tubercle bacilli.
A return to the early unitary concept
is necessary.

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 Conclusions
The bacilli of “bovine type” are those
with high virulence to experimental
animals and more frequent in
bovines than in humans; the bacilli of
the “human type” are bacilli less
virulent to experimental animals than
the bovine ones and more common
in humans than in bovines.

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 Real Situation in India as stated by one French doctor 94 years
back.

• “The authority of Koch, which proclaims the

nontransmission of bovine tuberculosis to human
beings, has for too long proved a fatal illusion to
consumers, has excused administrative
indifference, and has encouraged frauds in every
country.”
• Source - JULY II, 1914, BMJ, 75, DR.
LASSANLIIRE,
Chef do Laboratoire A la Facul$t de ihidecine de Paris., April
29th.

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2001 understanding

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 saMixaPt mao vaO&ainak sa%ya
1. baaovaIsa AaOr Tyaubar@yaulaaosaIsa
xayaijavaaNaU ko dao $p hO.
2. xayaraogaI gaaovaMSa gaaobar AaOr saaMsa sao
xayaijavaaNa U]%saija-t krta hO.
3. Tyaubar@yaulaIna TosT sakara%mak Aanao ka
Aqa- hO pSaU saaMsaiga-k hO.
4.baaovaa[-na TIbaI ka Aqa- pSauxaya hO naa kI
baaovaIsa xayaijavaaNaU ko karNa huvaa xayaraoga.
5.gaaovaMSa mao xayaraoga p`gatISaIla haota hO.
6. xayainayaM~aNa ko ivanaa gaaovaMSa SauwIkrNa
AsaMBava hO.
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