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					ZoonoticTuberculosis in India
     p`aNaIjanya xayaroaga


                         Dr. Ashok Kale
                                          M.D.(Community Medicine )

                                   Mob : 9406109410

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

        ABSENCE of Opportunity is CHARACTER                           1
Yearwise Tuberculosis mortality and different
interventions




               ABSENCE of Opportunity is CHARACTER   2
     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.
                   ABSENCE of Opportunity is CHARACTER    3
    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.

                 ABSENCE of Opportunity is CHARACTER   4
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.


                ABSENCE of Opportunity is CHARACTER   6
   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.




                 ABSENCE of Opportunity is CHARACTER   12
        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.

                 ABSENCE of Opportunity is CHARACTER   14
 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.

                  ABSENCE of Opportunity is CHARACTER   15
          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.


                 ABSENCE of Opportunity is CHARACTER   16
       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.


                    ABSENCE of Opportunity is CHARACTER   17
      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.



                      ABSENCE of Opportunity is CHARACTER            18
             (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.

                                                19
 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.
               ABSENCE of Opportunity is CHARACTER   20
      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.


                 ABSENCE of Opportunity is CHARACTER   21
       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.
                 ABSENCE of Opportunity is CHARACTER   22
   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




                 ABSENCE of Opportunity is CHARACTER   27
                           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.




                ABSENCE of Opportunity is CHARACTER   28
         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.




                 ABSENCE of Opportunity is CHARACTER   29
  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.


                 ABSENCE of Opportunity is CHARACTER   30
 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.

                 ABSENCE of Opportunity is CHARACTER   31
             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.



                ABSENCE of Opportunity is CHARACTER   32
               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




                 ABSENCE of Opportunity is CHARACTER   33
            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.




                 ABSENCE of Opportunity is CHARACTER   34
              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.



                ABSENCE of Opportunity is CHARACTER   35
       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


                  ABSENCE of Opportunity is CHARACTER   36
    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.

                ABSENCE of Opportunity is CHARACTER   37
   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.


                  ABSENCE of Opportunity is CHARACTER   38
    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




                 ABSENCE of Opportunity is CHARACTER   39
     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.



                   ABSENCE of Opportunity is CHARACTER   40
Bovine and Human Tuberculosis– Prof.Orth,
BMJ ,1913




             ABSENCE of Opportunity is CHARACTER   41
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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.


               ABSENCE of Opportunity is CHARACTER   43
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.
                   ABSENCE of Opportunity is CHARACTER    44
 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.

                    ABSENCE of Opportunity is CHARACTER    45
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


                                                    47
    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 .
                  ABSENCE of Opportunity is CHARACTER   48
Tuberculous Mastitis




             ABSENCE of Opportunity is CHARACTER   49
U.S.A. agri 1957 book- Tuberculosis and its eradication




               ABSENCE of Opportunity is CHARACTER        50
     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.



                 ABSENCE of Opportunity is CHARACTER   51
   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.




                ABSENCE of Opportunity is CHARACTER   52
    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.



             ABSENCE of Opportunity is CHARACTER   53
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.




                 ABSENCE of Opportunity is CHARACTER   54
   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)
                  ABSENCE of Opportunity is CHARACTER   55
          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.



                ABSENCE of Opportunity is CHARACTER                  56
                        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.
              ABSENCE of Opportunity is CHARACTER   57
       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.

                     ABSENCE of Opportunity is CHARACTER   58
Thank you.




ABSENCE of Opportunity is CHARACTER   59
ABSENCE of Opportunity is CHARACTER   60
             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.
                 ABSENCE of Opportunity is CHARACTER   61
    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.

           ABSENCE of Opportunity is CHARACTER   62
         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.




          ABSENCE of Opportunity is CHARACTER   63
          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.


           ABSENCE of Opportunity is CHARACTER   64
         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.

           ABSENCE of Opportunity is CHARACTER   65
 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.

                      ABSENCE of Opportunity is CHARACTER          66
2001 understanding




    ABSENCE of Opportunity is CHARACTER   67
          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.               ABSENCE of Opportunity is CHARACTER     68

				
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