Approaches to Bovine Tuberculosis Control in India

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Approaches to Bovine Tuberculosis Control in India P. Dandapat Principal Scientist Indian Veterinary Research Institute Eastern Regional Station, Kolkata West Bengal, India Indian Council of Agricultural Research

Outline Brief background Bovine TB: Indian scenario Evidences and initiatives on control of btb Human TB vs Animal TB: Indian context Challenges on control of btb in India Alternate control strategy Provisions in Law Conclusion

Milk Production (in million Tonnes) Growth Rate (%) of Milk Production Milk production in India and corresponding growth rate (%) from 1985-86 to 2015-16 India continues to be the largest milk producer in world (155 MT) with about 300 million bovines. 180 160 140 120 100 80 60 40 20 0 44 7.85 4.5 4.56 80.64.35 66.2 53.9 97.1 4.09 121.8 5.09 127.9 132.4 5.01 3.52 137.7 3.97 146.3 155.5 9 8 7 6.24 6.28 6 1985-86 1990-91 1995-96 2000-01 2005-06 2010-11 2011-12 2012-13 2013-14 2014-15 2015-16 Milk Production (in million tonnes) Years Growth Rate of Milk Production (%) per year Species wise milk contribution 3% 1% Exotic Cows 13% 26% Crossbred Cows Indigenous Cows 36% 12% Non- Descript Cows 9% Indigenous Buffalo Non- Descript Buffalo Goat 5 4 3 2 1 0

Species-wise share of Meat Production Poultry, 46% Cattle, 5% Goat, 13% Buffalo, 23% Sheep, 7% Pig, 5.50% Economic loss due to Bovine TB in animal productivity Milk productivity: Up to 22% Reproductive efficiency: Up to 6.5 % Loss of meat production: Up to 7 % Weight loss: Up to 11% M. bovis infection in humans living and working in close contact with animals not addressed sufficiently in India

History of btb in India Mention of TB by name of Yakshma in Rigveda and Atharva Veda (3500-1800 B.C.) & Samhyta of Charaka and Susruta (1000 and 600 B.C. approx.) Atharvans (1800-1000 BC) treated skeletal TB cases with Sipudru, a herbal preparation and sunshine After examining thousands of carcasses in abattoirs, Dr. Nield Cook (1902) concluded that tuberculosis in animals is a rare disease in India. In 1923, Dr. M.B. Soparkar started working on animal TB in IVRI. Sheather (1920-21) reported low degree of virulence of organisms isolated locally.

History of btb research at IVRI During 1925-1967, researchers revealed that Indian indigenous cattle showed localized and less progressive form of TB although virulent organisms were also isolated. Team at IVRI started research on (i) Susceptibility of Indian indigenous cattle, (ii) Diagnostic reliability of tuberculin test, (iii) Types of tubercle bacilli infecting man and animals Scheme for investigation on TB and JD was sponsored by ICAR at IVRI from 1942 to 1955 Thereafter, research on animal TB was taken as routine programme by IVRI.

History of btb research at IVRI 3 hypothetical reasons for lower incidences of bovine tuberculosis in India as explained by Dhanda and Lall (1959): Natural resistance among indigenous cattle Prevalence of low virulent tubercle bacilli in indigenous cattle compared to strains prevalent in European countries Rearing of cattle in open-air condition

Current status of btb in India Incidences of btb largely based on tuberculin testing of herds and slaughter house surveillance (i) Slaughter House Surveillance: First systematic study over 6,000 slaughtered cattle conducted by Taylor (1918) at Ferozpur abattoir reporting 3.5% TB affected animals. Animal TB confirmed through inspection of PM samples in states of India (Punjab, Haryana, West Bengal, Tamil Nadu, Uttar Pradesh, Maharashtra, Assam, Meghalaya etc) and positivity reported from 0.2 to over 30%.

Surveillance of btb in slaughtered animals State/ Area Species screened Animals tested % (+)ve to btb Year of report Punjab Cattle 416 17.5 1917 Maharashtra (Bombay) Bovine 1586 4.8 1927 Punjab & Uttar Pradesh Cattle 614 16.0 1927 Lahore (Undivided India) Bovine 1116 22.8 1931 Uttar Pradesh Buffalo 250 2.4 1932 Maharashtra (Bombay) Buffalo 120 13.3 1944 West Bengal (Calcutta) Buffalo 130 2.3 1944 Uttar Pradesh Buffalo 754 1.5 1966 Uttar Pradesh Cattle 1268 13.3 1985 Punjab Buffalo 4010 0.2 1957 Haryana Buffalo 603 1.0 1987 Assam Buffalo 2028 0.8 1988 Uttar Pradesh Cattle 141 59.6 1998 West Bengal (Kolkata) Cattle 1050 7.1 2001 West Bengal (Kolkata) Cattle 3600 0.9 2002 Meghalaya Cattle 120 28 2016 Assam Cattle 924 2.1 2017

M. bovis infected deer lung Surveillance in slaughtered and dead animals at IVRI, Kolkata No. of carcass screened: 1235 Carcass with tuberculous nodule(s): 54 PM samples screened: 23 (Cattle: 2, Deer: 5, Monkey: 1, Mithun: 1, Nilgai:1, Bison: 2, Sloth beer: 11) M. bovis isolates: 29 (Cattle: 23, Deer: 5, Bison: 1) M. tuberculosis isolates: 11 Tuberculous lesions in bovine lung

(i) Tuberculin testing Current status of btb in India Bovines screened in almost every parts of India viz., Andhra Pradesh, Bihar, Gujarat, Jammu and Kashmir, Karnataka, Kerala, Madhya Pradesh, Maharashtra, Puducherry, Punjab, Rajasthan, Tamil Nadu, Uttar Pradesh, West Bengal and percent positivity varies significantly, e.g. Northern India: 15.7%, Western India: 0.6 1.8% (Mukherjee, 2006) Southern India: 30 35% (Dhinakaran et al., 1991) Overall prevalence in H.P.: 14.3% and farm prevalence:16.6% (Thakur et al., 2010)

State-wise status of btb in cattle State Year Test conducted Prevalence (%) Ref. Gujarat 1947-48 - 12.1 (Cattle) & 17.4 (Buff) Dhanda & Lall, 1959 2014 Cultural Isolation 14.5 Parmar et al., 2014 Haryana 1970-79 SIT 1.9 (Cattle) & 3.8 (Buff) Kulshrehtha et al., 1980 H.P. 2010 SIT 14.3-34.4 Thakur et al., 2010 Karnataka 1973 SIT 31.4 Nagaraja et al. 1973 1973-74 SIT 13.6 Zaki, 1975 1995 SIT 14.8 Prakash, 1995 2008 SIT 9.0 Isloor et al. 2008 2010 SIT 0.0 22.0 Phaniraja et al., 2010 Maharashtra 1914-7.6 Joshi et al., 1914 1969 SIT 1.9 (Cattle) & 6.4 (Buff) Lall et al., 1969 Tamil nadu 1991-34.9 Dhinakaran et al., 1991 Punjab 1955 CTT 3.0 45.0 Taneja et al., 1955 1976 SIT 4.4 Joshi et al., 1976 1986-09 SIT 1.5 13.9 Sharma et al., 2013 Uttar Pradesh 2004-06 SIT 0.6-2.4 Trangadia et al., 2013 Northern & Western India 2006 CTT 0.7-15.8 Mukherjee et al., 2010

Current status of btb in India In Gangetic delta, our group recorded higher incidences in organized farms (25.4%) than unorganized sectors (3.2%). In positive organized farms, animal positivity varied from 35 to 73% with higher prevalence in exotic crossbred animals (34.6%) compared to indigenous cattle (10.5%). TB in other domestic and wild animals in India In India, TB is also reported in sheep, goat, horse, camel, dog and pig. No systematic study has been conducted to find out the incidence rate and typing of tubercle bacilli.

Evidences and initiatives on control of btb Plan for eradication of animal TB proposed long back aimed at building up a clean herd and later cleaner areas following a test-and-segregation with slaughter in clinical cases (Dhanda and Lall, 1959). Evidence of control of TB only by segregation of reactors in a dairy herd of 150 cows: Reduction of 20% prevalence to nil in a period of 2.5 years (Krishnaswami and Mani, 1983) Several reports indicate that indigenous breeds do not develop a rapidly progressive form of tuberculosis.

Evidences and initiatives on control of btb All India Project for control of btb was prepared by ICAR in 1962 and approved by Planning Commission. Proposed to undertake a three-phased programme: Phase I: Systematic control of TB in organized farm Phase II: Extension of the control programme in whole country covering all the animals Phase III: Final eradication programme of bovine TB Proposed test and slaughter policy at last phase with payment of compensation to farmers.

Control of TB in India: Human vs Animal Initiatives towards prevention and control of human TB in India started almost in the same period (opening of first open air sanatorium in Rajasthan in 1906 and Almora in 1908) First TB dispensary was established in Bombay in 1917 followed by another in Madras Tackling of human TB in an organized way started in 1930 Dr Frimodt Moller introduced BCG vaccination first time in India in 1948 BCG vaccine production centre established in Madras and in 1951, mass BCG campaign on large scale took place

Control of TB in India: Human vs Animal Nationwide TB control programme implemented with Formulation of National Tuberculosis Control Programme (NTCP) in 1962 Initially through conventional chemotherapy (1961-1986) By short course chemotherapy (1986-1993) Finally, GoI implemented Revised National Tuberculosis Control Programme (RNTCP) with DOTS strategy in 1997. To prevent spread of TB in human, pace of decision making was rapid which translated into action with setting of tight schedules.

Challenges in control of btb in India 1. Unknown magnitude of infection btb is endemic in India, but paucity of data on actual prevalence in different animal groups Scale of infection is biggest challenge Probably cattle movement linked with sporadic cases in backyard sector Need for systematic prevalence study employing a common protocol 2. Awareness on btb among animal owners Farmers unwilling to screen their animals One recent encouraging example: farmers in Gujarat are willing to have their animals screened against BT

Challenges in control of btb in India 3. Availability of diagnostics Single tuberculin test is main diagnostic test used in India using bovine PPD produced by IVRI. Confirmatory test is still a challenge, as no single test can diagnose btb in all species of animals and at all stages of infection. In our study, positivity of cattle to btb using different screening tests (SIT, CTT and γ-ifn assay) ranged from 23.7 62.4%. New tools for diagnosis and new biomarkers need to be evaluated. Although reports on new candidate biomarkers are numerous, validation and independent confirmation are rare.

Screening of cattle using biomarkers Parameters ESAT6 (Test 1) CFP10 (Test 2) ESAT6-CFP10 fusion protein (Test 3) MPB70 (Test 4) MPB 83 (Test 5) Cut off value 0.148 0.1245 0.134 0.048 0.084 Sensitivity (%) 81.82 93.94 96.7 78.79 51.52 Specificity (%) 100 98.18 100 94.55 90.91 PPV (%) 100 96.88 100.0 89.66 77.27 NPV (%) 90.16 96.43 98.21 88.14 75.76 k-score 0.849 0.927 0.976 0.752 0.455 Relative PA (%) 93.18 98.86 98.86 95.45 87.5 120 100 80 60 40 20 0 ESAT6 CFP10 ESAT6-CFP10 fusion protein MPB70 MPB 83 Sensitivity (%) Specificity (%) PPV (%) NPV (%)

Challenges in control of btb in India 4. Role of wildlife TB confirmed in number of wild animal species in India. Considering wide diversity in Indian wildlife, risk assessment to domestic livestock as well as human being from TB infected wild animals has not yet been initiated. 5. Test and slaughter policy In India, very difficult to follow due to various social and economic constraints and existence of wide spread wild reservoirs. Transmission among susceptible hosts and especially between wildlife and domestic animals to be prevented.

Challenges in control of btb in India 6. Zoonoses and reverse zoonoses Due to lack of surveillance, real time data on human tuberculosis due to M. bovis is lacking Epidemiology of M. bovis in humans is insufficiently explored in India Most laboratories not equipped to differentiate M. bovis and M. tuberculosis Zoonotic TB in humans is often extra-pulmonary and therefore, often misdiagnosed M. bovis is naturally resistant to pyrazinamide: Chances of inadequate treatment

Challenges in control of btb in India M. tuberculosis in animals Period/ Year M. tuberculosis isolates Animals positive Reported by 1942 to 25 16 from pigs, 6 dogs, IVRI 1967 2 monkeys and 1 chimpanzee 1982 2 2 of 16 isolates from 60 Krishnaswami tuberculin reactor cattle in and Mani, 1982 West Bengal 1987 to 8 7 from bovine and 1 from IVRI (Verma and 1999 black buck Srivastava, 2001) 2005 9 (16 confirmed by N-PCR) Cattle Prasad et al., 2005 2013 to 2017 8 8 from sloth bear ERS, IVRI, Kolkata

Alternate control strategies 1. Segregation and quarantine of infected animals Domestic animals positive for btb may be separated immediately after testing and help both to protect herd and give animal a proper facility for recuperation. Isolation is a feasible option in organized farms but difficult in unorganized sector.

2. Vaccination Alternate control strategies BCG vaccination in animals is being explored in some countries as adjunct to test and slaughter control programs which if implemented in India, May reduce onward transmission of btb, accelerating control of btb in endemic regions However, before its introduction, DIVA tests need to be developed.

Alternate control strategies 3. Treatment of affected animals (i) Emergence of drug resistance In a drug resistance study carried at ERS, IVRI Kolkata; out of 21 M. bovis isolates, 30% found resistant to each of Rifampicin and Isoniazid and 90% isolates were resistant to Streptomycin. Need for continuous surveying of drug resistance by a network of investigators in different regions of the country.

Alternate control strategies (ii) Bottlenecks in animal treatment Cost effectiveness M. bovis is naturally resistant to pyrazinamide Drug delivery mechanism (iv) Exploration of alternate medicine Homeopathic remedies used in treating human TB Effectiveness of medicinal plants Not much progress in this area, may be due to implementation of test and slaughter policy in most countries.

Alternate control strategies Lessons from a organized farm Cattle population: 350 Positive to btb: 95 Positive with symptoms: 30 Treated by Tuberculinum and Arsenicum lodatum since January, 2017 First 3 months: No visible improvement After 6 months: Some animals gained weight, healthier, symptomless Few representative cattle tested negative by γ-ifn assay Following Homeoprophylaxis at 1 month of age by Tuberculinum

Provisions in Law Prevention and Control of Infectious and Contagious Diseases inanimals Act, 2009 To provide for prevention, control and eradication of infectious and contagious animal diseases For prevention of outbreak or its spreading To meet international obligations for facilitating import and export of animals and animal products Duty to segregate infected animals Prohibition of movement of animals from controlled area Prohibition of markets, fairs, exhibition, etc., in the controlled areas Check posts and quarantine camps

Conclusion Holistic approach towards Systematic study to assess extent of btb infection in all sectors including domestic, wild life and public health Research on epidemiology of btb in Indian diversity Need of diagnostics, vaccines/ other prophylactics Awareness among farmers/ farm owners Coordination among stakeholders through one health approach Planning of national level control strategy Regional and international collaborations

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