Lessons learnt from mass vaccination campaigns
The experience gained in the execution of a massive national vaccination campaign is indeed a rewarding experience for all those involved in this ambitious programme of rinderpest eradication from India. The federal nature of the governments and the total financial support from the central government to the states played a pivotal central role in the active implementation and sustenance of the prolonged campaigns and also timely switch over from GTV to TCRV. It was rightly a national veterinary effort that paid rich dividends and paved way to the present status of ‘declaration of freedom from rinderpest disease’ through the OIE pathway.

However, the Indian campaigns did not address the field based operational problems of cold chain, mobility, quality of vaccines, extension education, post vaccinal sero-monitoring, diagnostic laboratory infrastructure and beyond all, lacked a time frame for final eradication. Perhaps, some of these could be attributed to the technological and financial limitations existed at those times. Yet it would be prudent to be aware of those epidemiological, technical and operational deficiencies or shortcomings that needed attention of veterinarians, vaccine manufacturers, diagnosticians, epidemiologists, administrators and policy makers for the success of the future vaccination campaign. The following is a long list. 

1. Apathy of the farmers to report disease outbreaks was an indication of their unawareness and inadequacy of the mass communication system built into the eradication campaign.

2. A notable deficiency in the implementation of the mass vaccination campaign was the inability of state authorities to enforce compulsory vaccination and administrative measures to prevent unauthorised movement of unvaccinated stock despite the existence of nation-wide rinderpest check posts.

3. Vaccine quality assurance was perhaps the most obvious by looking back at the sero-conversion levels reached at the end of decades of vaccination. It was just 50 per cent in two states and appallingly low in most of the other states. However, the quality of vaccine alone cannot be blamed for low sero- conversion, which could as well be due to poor cold chain maintenance and faulty vaccination.

4. Disquieting disease trends developed in the select geographic locations and the resurgence of the disease in the southern states from 1964, which later continued to be a highly endemic zone in the country till September 1995 was an intrigue. The epidemiological factors that contributed to this situation were not explored. The cumulative mass vaccination coverage vis-à-vis reported disease outbreaks in the mid-eighties clearly confirmed the need for much higher vaccination coverage to reduce the number of outbreaks and the inescapable conclusion that the incidence of rinderpest had reached irreducible limits.

5. Retrospectively, the rinderpest outbreaks, reported in sheep and goats in the southern peninsular India, unlike in the African continent added yet another new dimension to the hitherto totally neglected possible epidemiological role of these species under Indian scenario (2). Interestingly then, there existed a school of ‘learned people’ who vehemently believed that rinderpest did not exist in small ruminants in India. Perhaps this was one of the serious lapses of the then rinderpest control / eradication programme that did not accept the ground realities of disease in these animals and they were indeed the ‘alternate sustenance hosts’ for rinderpest virus under vaccinal pressure among bovine population (3).

6. The incidence of rinderpest in sheep and goats steadily escalated from 1972 onwards in the southern states and the virus recovered from sheep and pigs (thought to be derived from infected sheep) was pathogenic to cattle, buffaloes, sheep and goats (4). The disease was most often mild and often inapparent in small ruminants and sporadic bovine outbreaks invariably occurred when sheep or goats brought for slaughter were temporarily mixed with bovines. In an experimental study, sheep spleen tissue from an outbreak failed to produce clinical disease in 20 odd sheep, which promptly killed 5 crossbred calves, confirmed the inapparent nature of infection in the former species (Personal communication, M. Rajasekhar and M.S. Shaila). Perhaps this was one of the major epidemiological factors as to how rinderpest established such a stronghold in the southern states. Epidemiologicaly, the virus was at large and remained at its best in establishing endemicity through a variety of susceptible hosts. A high-density ratio of small to large ruminants and the presence of highly susceptible exotic and crossbred populations might have been contributory factors.

7. The mass vaccination campaign was not supported by adequate post vaccination seromonitoring programme and the herd immunity levels were never ascertained in a national perspective. Perhaps, then the laborious serum neutralisation test was the only tool available to assess sero-conversion as the ELISA techniques came in later.

8. The media and press were not effectively utilised.

The final thrust - Launch of European Union supported National Project on Rinderpest Eradication (NPRE) 

a. Phase-I : Strengthening of veterinary infrastructure, vaccination, seromonitoring programmes and declaration of substantial freedom from rinderpest disease to OIE.

This phase of final thrust of rinderpest eradication has to be viewed from the perspective that India has the largest and diverse rinderpest susceptible livestock population in the world, that are maintained under very different husbandry, uncontrolled migratory, poor zoo-sanitary and health coverage conditions. 

By late 1990’s, it was a foregone epidemiological conclusion that rinderpest outbreaks had bottomed out to an irreducible level and it was logical to give a final thrust for its total eradication. Also, it was then generally agreed that the four decades of eternal mass vaccinations, if continued, would be a drain on the country’s resources and veterinary manpower.

With this reasonably very low and stable rinderpest situation in the country, the Government of India, in early 1991, launched the present National Project on Rinderpest Eradication (NPRE) with an outlay of Rs. 405 crores of which Rs. 341 crores were provided by Government of India and the remaining Rs. 64 crores by the European union as component of a broad based project namely - “Strengthening of veterinary services in India for disease control” 

NPRE was conceived as a timely, multiple approach and result oriented national programme. It has several components including mass immunisation, strengthening of tissue culture vaccine production and diagnostic facilities, vaccine quality control, seromonitoring, serosurveillance, mass communication and holding of training workshops. In addition, supportive research programmes on vaccine improvement and quality control, epidemiology of rinderpest in small ruminants and development of diagnostic kits for differential diagnosis, seromonitoring and serosurveillance of rinderpest and peste des petits ruminants (PPRV).

The concept of landscape epidemiological approach to eradicate rinderpest with appropriate vaccination strategy as per the OIE pathway was the keystone for the successful implementation of NPRE programme. This demarcated the country into four specific zones (A, B, C and D) strictly on the basis of retrospective epidemiological history of rinderpest and perhaps, this is the best thing to happen as it took the advantage and also cashed on the gains of the forty and odd years of mass vaccination campaign (1). 

The successful implementation of NPRE jointly by the EU and Government of India is a classical case study of a massive field programme of sorts and has set a good example for a co-ordinated effort for the rinderpest eradication from south-Asia. It had imbibed all the aspects of OIE perceptions of rinderpest eradication, focused and committed approaches by the central and state agencies, co-ordination and monitoring of field operations, vaccine quality control, cold chain establishment, mobility of field staff and beyond all, the political and administrative support.

The NPRE programme was implemented in its entirety and the natural outcome is the absence of rinderpest outbreaks since September 1995. India has declared “Provisional freedom from rinderpest disease” to OIE authorities and has now successfully embarked on the serosurveillance programme for the declaration of ‘freedom from rinderpest infection’. 

Impressive achievements of NPRE include

• Ably administered the OIE pathway through effective state-centre coordination.

• Interactive regional meetings organised

• Strengthened TCRV production, cold chain and transport facilities

• Established a central vaccine quality control facility

• Established national network of 32 state level ELISA labs

• Established national facility for ELISA training at Project Directorate on Animal Disease Monitoring And Surveillance (PD_ADMAS)

• Established national morbillivirus laboratory at IVRI, Mukteswar

• Established national serum bank facility at PD_ADMAS

• Provided the national random sampling frame for sero-monitoring

• Carried out post vaccinal sero-monitoring of random samples

• Stopped TCR vaccine production and sale in the country

• Created national emergency vaccine banks

• Print and electronic media propaganda carried out

• HRD through training of more than 250 state level lab. scientists

• Indigenous development of C-ELISA kit for serosurveillance

• Indigenous development of first recombinant C-ELISA kit

• Declared ‘substantial freedom’ from rinderpest disease to OIE

• Preparedness for declaration of ‘freedom from infection’ to OIE

b. Phase-II : Sustenance of rinderpest-free status and preparedness for surveillance programme for declaration of “freedom from rinderpest infection”.

India has remained free from rinderpest for the past five years as evidenced by the absence of clinical disease and serological evidence of rinderpest virus activity in the unvaccinated susceptible population. Culmination of decades of vaccination has revealed that the peak levels of herd immunity of 50 per cent was achieved in the states of Maharashtra and Gujarat, around 20-30 percent in most of the states and dismal in few states. With this sero-epidemiological scenario, it is difficult to ascertain and explain the factors that have contributed to the absence of disease in the past five years in the country. After the isolation of PPRV for the first time in India (6), the unforeseen upsurge of PPR throughout the country during this contemporary period appears to be the most important critical factor for sustained absence of rinderpest. This assumption finds support by the fact that PD_ADMAS studies have confirmed the presence of PPR specific antibodies in 20 per cent of randomly selected rinderpest antibody negative bovine serum samples across the country. 

This level of natural cross protection against rinderpest is quite significant compared to the poor sero-conversion levels recorded in several states at the end of the vaccination campaign. Epidemiologically, widely rampant PPR in sheep and goats during the 90’s appears to have effectively ‘blocked’ rinderpest virus from taking ‘shelter’ in these species. At this point, it must be remembered that India has a huge sheep and goat population and intermixing of small and large ruminants is by far the most common in the agrarian milieu of the country. 

With this highly favourable situation, the country has recently declared ‘substantial freedom from clinical rinderpest’ to the OIE authorities. Now the onus lies on the country to take rinderpest eradication to its logical final phase of ‘declaration of freedom from infection’. 

This crucial concluding phase of OIE pathway is being implemented through the experience gained in the past years. It is a matter of great satisfaction that the preparedness for the process of ‘rinderpest serosurveillance’ to detect the subtle or inapparent virus activity in the population is already operational at field level. 

The three major areas that are conceived in this phase are a. Clinical surveillance, b. Serological surveillance and c. International border surveillance.

a. Clinical surveillance: 
Each state veterinary regulatory authority has a state level rinderpest officer totally responsible for all the rinderpest related activities. This is a grass root based activity aimed at searching for all the indications of disease entities that resemble rinderpest. This is mandatory for all the veterinary institutions in the country to participate in the NPRE activity and submit regular reports to the state rinderpest officer who liaises between the state veterinary regulatory authority and the NPRE hqs. at New Delhi. This activity is already institutionalised with appropriate proforma and the schedule of reporting operational NPRE hqs. is keeping a very close watch on this crucial programme. There is a great deal of commitment for this activity at all levels. It has three components:

i. Village searches: A village with several herds/flocks of susceptible livestock population is the basic epidemiological unit for rinderpest surveillance activity. There are 634,000 villages in the country with an average of 750 heads of livestock population. As a specific rinderpest surveillance activity, the trained paraveterinary staffs enquire farmers on the occurrence of any disease resembling rinderpest during their regular village visits within the administrative jurisdiction of the rural veterinary hospital. The paravet records details of his visits endorsed by the signatures of the prominent persons of the village as proof of this surveillance activity. He submits combined report to the scrutiny of higher officials. 

ii. Institutional searches: India has a well spreadout network of rural veterinary institutions within a radius of about 5-10 km. The trained paraveterinary and professional veterinarians provide the basic livestock healthcare through first aid centres, hospitals and polyclinics. They have been under strict instructions to look for animals with high fever, ocular/nasal discharges and diarrhoea to rule out rinderpest. They have facilities for collection and dispatch of clinical specimens for laboratory confirmation. The visiting senior officers verify the hospital records. 

iii. Stock route searches: Livestock movement for trade and migration in search of grazing are a part of the husbandry activity. In certain areas of the country, these activities are intense and result in the free mixing of infected and healthy animals. The veterinary institutions located along the trade/migration routes conduct regular searches for any rinderpest-like disease along these routes. The details are routinely sent to higher authorities.
Also there are designated ‘Check Posts’ exclusively established for rinderpest surveillance activity along inter-state borders and the animals entering/leaving the state are examined and quarantined if necessary. 

b. Sero-surveillance: 
This is the backbone of rinderpest surveillance aimed to detect any subtle virus activity in the population. It is specially designed to provide almost fool proof evidence for the presence or absence of the virus activity in the selected population that is free from rinderpest antibodies. For this purpose, the NPRE has established its exclusive rinderpest ELISA Training and Data Management Centre (ETDMC) and national serum bank facility for rinderpest serosurveillance programmes in PD_ADMAS, Bangalore. It is one of the best laboratory facilities in the country and derives its strength from the ICAR Project Directorate on Animal Disease Monitoring And Surveillance (PD_ADMAS), which has the expertise in conducting population surveys, production of software based ELISA diagnostics, national livestock and disease related databases for developing disease forecasting models and ELISA training facilities.
The ETDMC provides training in the use of ELISA kits for rinderpest seromonitoring and serosurveillance and manages the national network of 32 state level rinderpest ELISA laboratories for NPRE. So far, it has trained more than 250 state level veterinary scientists in the use of rinderpest C-ELISA kits. 

Development of recombinant RP C-ELISA kit for RP serosurveillance: 
There was a need to develop a C-ELISA kit exclusively for RP serosurveillance, as the presently marketed commercial kit is primarily intended for post vaccinal seromonitoring. To quote “There is no escaping the fact that no single assay currently available (and validated) is capable of achieving the required sensitivity and specificity for the detection of recent rinderpest virus infections caused by all lineages of rinderpest virus” - Source: Empres Transboundary Animal Diseases Bulletin No.13 - Rinderpest (1999), Global Rinderpest Eradication Programme (GREP) meeting on rinderpest surveillance.

A baculovirus expressed recombinant hemagglutinin protein of RPV has earlier been used as a vaccine candidate in cattle which generated very good humoral and cell mediated immune responses (7, 8) using the expertise available at PD_ADMAS and Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, it was possible to develop a C-ELISA kit using baculo virus recombinant RPV-H secretory (Sec H) protein. A secretory form of H protein expressed by a recombinant baculovirus (7) was used to develop the C-ELISA kit and also a unique mAb which recognises only RPV H protein.

The newly developed rec.H C-ELISA kit is highly specific, sensitive, robust, cost effective and is superior compared to existing commercial kit.

Comparative results of serum samples screened by ADMAS-IISc C-ELISA and commercial ELISA kits

Tests	Number tested	Number Positive	Number Negative
Rec.H C-ELISA kit	1,819	543 (29.8%)	1276 (70.2%)
Commercial kit	1,819	483 (26.6%)	1336 (73.4%)

The ability of the rec.H C-ELISA kit to detect more number of positives over the conventional commercial kit is explained below. 

1. This could be due to the superior inherent capacity of the recombinant antigen when used even at 1 in 100 dilution.

2. The additional positives may represent hitherto unrecognized lineage of RPV circulating in India. A similar situation exists where the commercial kit has failed to detect antibodies to African lineage 2 and 3 within 30 days post infection (GREP Bulletin). A large number of serum samples during serosurveillance programme may answer this possibility. It is important to have an open mind on this important issue.

c. International border surveillance:
Rinderpest may still be endemic in Pakistan and Afghanistan. The contiguity of the landmass and uninterrupted livestock movement make other countries vulnerable for cross border infection. It is gratifying that India and Bangladesh took a common stand some years ago not to vaccinate livestock on either side of the international borders and this has helped both countries to remain free from this disease. Nepal and Bhutan have been free.
The long and porous international border stretching over a few thousand miles between Pakistan and India is a major concern as on two occasions in the recent past a few hundred cattle strayed into India. The Indian border security forces impounded these and their sera were rushed to ETDMC, Bangalore, to rule out rinderpest. 

A special surveillance programme needs to be developed for the bordering Indian states to keep vigilance on cross border reintroduction of rinderpest. International disease obligation has to be given due importance by all the SAARC and APHCA countries in their larger regional interests. 

Conclusion
India has come a long and arduous way in its efforts to eradicate rinderpest. The achievements made so far mark a high degree of commitment by the veterinary profession, inter-institutional, centre-state co-ordination, administrative and international support which have been appreciated as a role model for RP eradication. The sustenance of RP absence status over the past five years confirms the operational success of the ongoing NPRE programme. The eradication of RP in India is imminent.

References

1. Khera, S.S. (1980). Proc. 2nd International Symposium on Veterinary Epidemiology and Economics. p. 581. Canberra, Australia.

2. Ramani, K. et al. (1974). Indian vet. J., 51: 36.

3. Ramesh Babu, N.G. and Rajasekhar, M. (1988). Vet. Rec., 123: 595.

4. Ananth, M. (1980). Proc. State level seminar on rinderpest, Tirupati.

5. Anonymous. Annual Reports (1994 to 1998). ELISA Training and Data Management Centre, PD_ADMAS, Hebbal, Bangalore.

6. Shaila, M.S. et al. (1989). Vet. Rec., 125: 602. 

7. Naik, S. et al. (1997). Vaccine, 15: 603.

8. Sinnathamby, G. et al. (2001). Vaccine, 19: 3870.