« AGD/TAC:IAR/81/9 r Restricted » THE CONSULTATIVE GROUP ON INTERNATIONAL AGRICULTURAL RESEARCH * TECHNICAL ADVISORY COMMITTEE Twenty-Fifth Meeting, Addis Ababa (Ethiopia), 24 February - 3 March 1981 DRAFT REPORT OF THE TAC QUINQUENNIAL REVIEW OF THE INTERNATIONAL LABORATORY FOR RESEARCH ON ANIMAL. DISEASES (ILRAD) NOTE BY THE SECRETARIAT r (Agenda Item 12) Proposed objectives of the discussion i) Is the TAC satis fried with the way the Quinquennial Review Panel has dealt with its terms of reference and the special list of questions prepared for the Quinquennial Review of ! ILRAD activities? ■ ii) Does TAC agree with the observations and recommendations made by the Panel? Does it wish to clarify some points with the Panel Chairman and/or the ILRAD representatives who will be present during the relevant discussions at the 25th TAC Meeting? Hi) Uhat would be the provisional comments to be made on the draft report which will be presented in its final form to TAC at its 26th meeting? N. B. The comments made by the Executive Committee on the draft report of the Panel are attached herewith (see letter from Sir A. Robertson to Mr. S.A. Risopoulos. This letter was considered by the Editorial Committee of the Panel which met in Paris on 16-17 December 1980 to edit the draft report). TAC SECRETARIAT FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS January 1981 4 ; INTERNATIONAL LABORATORY ILRAD FOR RESEARCH ON ANIMAL DISEASES P. O. Box 30709, Nairobi, Kenya Cable: Ilead/Naibobi/Kenya Telephone: Naieobi Telex: 22040 592311 Mr 3.A. Bisopoulos, Deputy Executive Secretary, TAC/CGIAB, i FAQ, Via delle Terme di Caracalla, 00100 Borne, ! Italy jar Mr Bisopoulos, I enclose some brief comments by HEAD'S Executive Committee on the draft Quinquenni al Bevi e v Beport. I trust this will be in time to be considered by the Bevi e v Panel. i Yours sincerely, ' (2. Chairman ': ; : t COMMENTS BY THE EXECUTIVE COMMITTEE OF ILRAD ON THE DRAFT REPORT OF THE TAC QUINQUENNIAL REVIEW OF ILRAD As you know the Executive Committee of ILRAD gained the impression from the oral presentation by the Chairman of the Review Panel on 17th October that the draft Report was an excellent document whose findings would be largely acceptable to the Board. A perusal of the text confirms that reaction and we are particularly impressed by the excellent work done by the Panel in a relatively short time and under conditions which were by no means ideal for their task. Th^re are, however, some aspects on which we feel we should comment. We were rather surprised to read on page 7 para 6 iJ of the Introduction that the Panel had extensive discussions with the Executive Committee. Apart from the final meeting, the only occasion I can recall on which formal discussion took place was during a brief meeting with some members of the Panel; and we would certainly have welcomed an opportunity for extensive discussion, particularly of management problems but realised that the pressure on the Panel was such as to render that impossible. Ch. IV Research Management While we agree that a clear delineation between policy setting by the Board and management by the Director is essential, we feel we must emphasise the Board’s right and indeed duty to take action should it consider that management is jeopardising the work of the institute, the harmony of the staff or relations with the host country. Ch. IV Administration and Structure It is true that some of ILRAD's troubles stem from a lack of mutual confidence, communication and trust between the Board and the Director; for although his appointment was greeted with real enthusiasm and support by the staff and the Board, within little more than a year of his appointment he had effectively isolated himself from a large section of the Board as well as from a considerable proportion of the senior staff. The implication throughout much of this section of the Report is that the Board failed to give the Director full authority and support for the management and conduct of the institute's affairs. It is unfortunate, therefore, that the Executive Committee was not given an opportunity to comment on the information on which this was based. 1/ Now para 26, page 12; the comment of the Executive Committee was taken into account in the present version (note from TAC Secretariat). 2 : The other item on which we would wish to comment is in ■ Chapter IV, para 45 JV recommending a system of research management by : projects. Some of us are not convinced that this is necessarily as effective as the Panel appears to suggest. Project financing has two main disadvantages viz. that it can only be successful if backed by a highly trained accounting staff; and, since only those activities which are part of ah existing programme can be readily financed, it makes it difficult to achieve the flexibility which is essential for scientific innovation. / r 1/ Now para 85 et sqq, page 27 (note from TAC Secretariat). <■ !1 !: ; . i DRAFT REPORT OF THE TAC QUINQUENNIAL REVIEW OF THE INTERNATIONAL LABORATORY FOR RESEARCH ON ANIMAL DISEASES (ILRAD) \ DRAFT Dear Dr. Cummings, • • • I have pleasure in sending you herewith the report of the Quinquennial Review Panel of the International Laboratory for Research on Animal Diseases (ILRAD). ILRAD is an unusual Centre in the CGIAR system in that it is entirely devoted to basic mission-oriented research. It is appropriate to state here first that the Panel is convinced that this approach continues to be fully justified for the solution of two of the most difficult problems which veterinary sciences have to face; the Panel is unanimously satisfied with the very rapid progress achieved by ILRAD in building up a first class research tool, with the remarkable advances made in the scientific knowledge of trypanosomiasis and theileriasis and with the high quality of the scientific leadership. To answer the first group of questions addressed to the Panel by TAC, the Panel is of the opinion that the mandate of ILRAD should remain as it is, basically focussed on trypanosomiasis and East Coast Fever until significant success has been achieved in at least one of the two mandated diseases. The Panel, in the last chapter of the report, indicates some well defined avenues which ILRAD could use to enlarge somewhat its investigations in the framework of the above diseases. • As regards the implementation of the mandate and programmes, the Panel is well satisfied with the high scientific standard of ILRAD's work: it would recommend increased horizontal integration of the different laboratories by the use of research management by projects, a method which would assist also in reappraising regularly internal priorities and resources allocation, In addition to the ongoing pro- gramme which the Panel generally supports, the Panel would strongly, recommend the inclusion in ILRAD's operations of a well defined project on trypanotolerance with outposted staff in West or Central Africa. The collaborative links with ILCA, already good and functional as regards administration and communication, would here be extended to cover scientific investigations in a field, trypanotolerance, which development assistance and recipient countries agree to consider of high priority for the future of livestock production in the humid and sub- humid areas of Africa. Some advice on staffing has been expressed on this and other matters by the Panel at the end of Chapter VII. The training and technology transfer role of ILRAD has taken second place so far, major attention being devoted first by the Centre Dr. R.W. Cummings Chairman Technical Advisory Committee 2 to the formidable task of establishing the physical facilities and the major research thrusts; however, training has made a good start which the Panel would strongly recommend ILRAD to continue and develop at all levels; in doing so, African universities and institutions should be closely associated in the selection of trainees, The limited involvement of ILRAD in the field in Kenya would assist the Centre in putting to test several hypotheses regarding the identification of the strains of the parasites under study and vaccination strategies; the Panel would wish to endorse the collaborative links which ILRAD has established with Kenyan veterinary research institutions, ILCA and ICIPE and which will be further integrated in a particular study area of Kenya. ILRAD's administration has had some problems, and in spite of which the high quality of scientific activities has been preserved. The Panel has been satisfied by its visit to the proposed site of ILRAD's cattle production ranch and by the criteria which have been used for its selection. Good and significant contributions have been made by the Director and staff of ILRAD to the understanding of the two mandated diseases: the control of these diseases presents unusually difficult problems which require for their solution a highly qualified and integrated team. It is with satisfaction that the Panel has ascertained that ILRAD has the competence, enthusiasm and wherewithal to fulfill its mandate; this will require time, but the pay-off will likely have an application far beyond the two diseases under study, and benefit man as well as his animals. I would conclude by reiterating my thanks to my colleagues of the Panel tfio have spared no efforts to produce a report which I hope will be useful to ILRAD, TAC and the CGIAR. Yours sincerely, Guy Camus Chairman ILRAD Quinquennial Review Panel TABLE OF CONTENTS Page .-■4r" I. SUMMARY OF CONCLUSIONS AND RECOMMENDATIONS 1 (a) Past Achievements and Guidelines for the Future 1 (b) Research Management 3 (c) Research Priorities 5 (d) Administration and Structure 6 • (e) Training, Communication and Technology Transfer 7 II. INTRODUCTION 8 ' III. REVIEW OF HISTORICAL BACKGROUND AND MANDATE 13 IV. ADMINISTRATION AND STRUCTURE 19 (a) Administrative Organization 20 (b) Research Management 22 (c) Facilities for Recombinant DNA Research 29 (d) Support Units 29 (e) Supply of Animals for Research 30 V. RESEARCH PROBLEMS AND ACHIEVEMENTS 36 (a) General Introduction 36 (b) Trypanosomiasis 37 (c) Theileriasis 46 VI. TRAINING, COMMUNICATION & TECHNOLOGY TRANSFER 52 (a) Training 52 (b) Documentation 56 (c) Communications and Information 56 (d) Recommendations 57 VII. FUTURE PLANS AND RECOMMENDATIONS FOR RESEARCH 58 (a) Trypano s omia sis 59 (b) East Coast Fever 60 (c) New Ventures and the Mandate 62 (d) Recommendations regarding Staffing 64 VIII. ACKNOWLEDGEMENTS 65 ANNEX I. A. PROGRAMME OF THE REVIEW PANEL B. LIST OF DOCUMENTS MADE AVAILABLE TO PANEL ANNEX II. GLOSSARY DRAFT REPORT OF THE TAC QUINQUENNIAL REVIEW OF ILRAD 5-18 October 1980 1. SUMMARY OF CONCLUSIONS AND RECOMMENDATIONS (a) Past Achievements and Guidelines for the Future 1. Although ILRAD was established in 1974 with the mandate of "controlling the disease of trypanosomiasis and East Coast Fever by immunological or related means" it is only within the past two years that facilities became available for work with domesticated animals and the vectors of these two diseases. Progress has been hampered by changes in the Directorship and by the inevitable difficulties attendant on the installation, maintenance and repair of sophisticated scientific equipment on a new site in a developing country. 2. Despite all these difficulties, ILRAD is now an outstanding laboratory complex of considerable architectural beauty and with facilities, possibly unique in Africa, for the study of almost every aspect of the two diseases selected for attention. The scientific staff, currently comprising approximately 50 scientists have, in this short time, established an impressive range of technology embracing parasitology, pathology, immunology, biochemistry and molecular and cell biology. 3. The immunology of trypanosomiasis and East Coast Fever is very complex, possibly more so than other parasitic diseases and, despite the best efforts of scientists in the past, has so far defied practical solution. The eventual success of the studies currently under way at LLRAD hopefully will provide an immunological solution to one, or both, of these diseases. In the case of East Coast Fever there is a possibility that within the next five years it will be possible to combat the disease by an immunological method and the Panel approves the increased • - - emphasis that has been given during the last two years by ILRAD to the study of this disease. 4. With trypanosomiasis the outlook is less certain because of the great complexity of the phenomenon of antigenic variation which enables the parasite to evade the immune response of the host. However, there are some promising leads. There is evidence that the repertoire of antigens expressed by the infective form of the trypanosome may be quite limited and that only a small number of these antigens may be necessary for an effective vaccine. In this connection, the previously insoluble problem of producing massive quantities of antigen for vaccine preparation has been solved in principle by the potential of the recombinant DNA technique. Furthermore the staff has already made significant contributions to our understanding of such important problems as 2 the mechanism of antigenic variation in trypanosomiasis and the defence mechanisms of hosts infected with either disease. For instance new knowledge on the metabolism of trypanosomes is being produced by bio­ chemical research which may lead to important possibilities for both the immunological and the chemotherapeutic approaches. These and other achievements open new prospects and possibilities which are very encouraging. 5. The Panel, comprising a range of disciplines from veterinary medicine to molecular biology, was unanimously impressed with the quality of the research at ILRAD, with the general orientation of the work and the progress made in the brief period during which the full facilities have been available. It must be stressed again that an immunological solution to these two diseases has no easy answers and demands a wide ranging approach, at least in the early stages of looking for profitable leads. 6. However, even before ILRAD succeeds in developing control methods for one or both diseases it may be that with hindsight, the most important role of ILRAD will have been to act as a catalyst for the development of veterinary science in Africa and beyond. Collaborative projects with the veterinary institutes in Kenya are being started to the mutual benefit of both. On a wider front, joint experiments and investigations are planned, or are already in progress, with organizations such as ICIPE, ILCA, FAO and Universities in Europe and America. An ambitious training, programme is in progress. This includes technician training, predoctoral studies, short-term courses on the transfer of technology and a programme of seminars, conferences and scientific meetings. For this to develop it is imperative that ILRAD continue to function as an international laboratory. 7. The agreed involvement of ILRAD on a limited scale, in the field, in Kenya in association with the national veterinary institutions should not only be of practical assistance to the latter but should provide a fertile feedback of new ideas and information for ILRAD staff. Furthermore, a prior understanding of epidemiology and experience of natural disease is essential for a realistic approach to control techniques. 8. One particular aspect which must be considered is the development of a further programme on the value of trypanotolerant cattle and on the mechanisms underlying their apparently unique resistence to trypanosomes. ILRAD was associated with trypanotolerance in its early days, a consequence of its take-over of the Gambian project sponsored by the Rockefeller Foundation. Although trypanotolerance was already known in West and Central Africa for a long time, and its practical implications understood, its scientific mechanisms had been insufficiently studied in cattle and small ruminants. The systematic approach by a highly-qualified scientific team to this patho-physiological problem was able to confirm the existence of trypanotolerance and to highlight several previously unknown biological features. The emphasis put into this exercise by ILRAD and the results 3 achieved have encouraged interested scientists, experts in veterinary science and animal husbandry, particularly in West and Central African countries, and national and international donor agencies to regard a better understanding of trypanotolerance and the development of such livestock as a high priority. These results, if fully published, disseminated and followed up, would give new hope to immense parts of Afric-a, particularly to those situated in the humid savannah areas of West Africa, that livestock productivity and human welfare may both be improved. 9. A final and important point is that FAO has been involved in many parts of Africa in the research and control of trypanosomiasis and tick- borne disease for many years. The Panel unanimously recommends, now that ILRAD is functional, that the Board of Trustees should invite, as it is already the case with other IARCs, an FAO observer to attend its deliberations. 10. Part of this report is devoted to various types of management questions both in the administrative and the research areas. The Panel recommends a strengthening of the administration and that the introduction of research management by projects be studied. In this latter case it would be a departure from the classic laboratory structure but this approach to the organization of research would provide the flexibility required to make the best use of human and financial resources in rapidly developing fields of science. These proposals aim at still further increasing the efficiency of the Institute without in anyway being critical of what has been achieved. On the contrary, the Panel reiterates its commendation of the excellence of the research programme and achievements. 11. As far as the future of the Institute is concerned, at least for the next quinquennium, the work at ILRAD should continue to be concentrated on trypanosomiasis of animals and theileriasis, in the latter case, specifically East Coast Fever. The Panel feels therefore, that whatever strong case might be made, the present activities conducted under the mandate should not be extended or modified until significant success has been achieved concerning at least one of the two mandated sieases. (b) Research Management 12. As mentioned above, the Panel is impressed by the high quality of the scientific work at ILRAD. It believes that through increased co­ ordination and continued reassessment of priorities this high standard can be further enhanced. The Panel therefore recommends: 4 i) that a clear definition of responsibilities for the Board of Trustees, the Programme Committee, the Scientific Advisory Committee and the Director is agreed, understood and implemented based on the Board's primary identification with general policy and the Director's identification with manag ement; ii) that the Director be given by the Board of Trustees authority and full support for the management and the conducting of the approved research programmes; iii) that the next Director be an internationally recognized scientist with proven research leadership and ability; iv) that the scientific staff be brought up as far as possible to its full complement based on the availability of funds, as soon as the new Director has had the opportunity to review the programmes and the achievements; v) that the present two-year contracts procedure be reviewed by the Board to determine whether contracts of a longer period could be initiated after the first two years, so as to give more security and permanence to the staff; Vi) that the stimulus provided by the policy of encouraging outside scientists to join ILRAD group be continued but with the*funding of the visiting scientists coming under a separate budget heading when they do not have their own financial support; vii) that the system of research management by project be studied for its possible introduction; this would give a clear delegation of responsibility for research and financial control to a selected leader of a group of scientists collaborating on a project basis; viii ) that more elaborate procedures be established for the selection of priorities accompanied by the appropriate allocation of resources; that priorities be reviewed at regular intervals concurrently with research progress and in relation to the preparation of each biennial budget. 13. Supply of animals for research. The prerequisite for research on animal diseases is the availability of a supply of suitable animals, In view of the increasing cattle needs of ILRAD for its research programmes and the escalating cost of specific disease-free cattle, the Panel recommends : i) that the negotiations for the purchase of the leasehold and the fixed and movable assets of the Rapiti Plains Estate be completed as soon as possible; 5 ii) that the Board of Trustees take note that this large investment with such a potentially favourable cost/ benefit ratio could prove to be a financial embarassment unless the very highest standards of estate management and animal production precepts are observed. (c) Research Priorities 14. The projects on trypanosomiasis and East Coast Fever which the Panel considers should have a high priority for the future are listed in more detail in Chapter 6. The priority of individual projects should be re-evaluated annually. 15. Trypanosomiasis, The Panel recommends five priority projects on trypanosomiasis, which are: i) the proposed immuno—epidemiological project at Kilifi which is necessary for a pilot study of the potential number of antigenic strains of tsetse-transmitted trypanosomes (metacyclic trypanosomes), This information is essential for an appraisal of the feasibility of vaccination using such antigens; ii) that in view of recent studies at ILRAD which indicate that recombinant DNA technology may provide a fast and accurate method of typing the basic antigenicity of trypanosomes (serodemes), the use of this technique be . accelerated and its potential compared with traditional ' immunological techniques; { iii) that in view of preliminary indication that the metacyclic forms of one trypanosome (T. vivax) may not possess a protective coat, that attempts be made at vaccination against this species, using membrane antigens of vivax; iv) that the ongoing immunological and biochemical studies on trypanosomes be continued since these may uncover pathways peculiar to the parasite which can be used to interfer with its survival; v) that a large-scale project on trypanotolerance in West and Central Africa be launched in collaboration with other interested organizations, in view of its potential importance to livestock production and human welfare in that area; two ILRAD scientists should be assigned to this project and extra core funds sought to support the proj ect. 6 16. East Coast Fever. The Panel recommends five projects on this disease, which are: i) the determination of the number of antigenic types of Theileria parva prevalent in one area such as the Kilifi district; immunization trials with these strains should then be undertaken in the same area and results extended to other parts of Kenya and countries in which theileriasis ‘is prevalent; in this context, the continuation of a recently developed i^i vitro technique for antigenic typing should be given high priority as this could lead to the replacement of the expensive and time consuming method of eross-immunization using large numbers of cattle; ii) the continuation of the studies on the comparable immunogenicity of live, attenuated or killed antigens from sporozoites or macroschizonts; iii) the examination of the strains of parva lawrencei for the possible production of monoclonal antibodies and the study of antigenic variation within the sub-species of T. parva; iv) the use of genetically related cattle in the study of cell mediated immunity; V) the continuation of the electron microscope studies on the interaction of Theileria and Trypanosoma with their mammalian and arthropod hosts. 17. Staffing. The Panel recommends that eight present vacant positions should be used to: i) add one Research Associate or Scientist each to the tsetse and tick units; ii) supervise the field activities at Kilifi, to reinforce the Molecular Biology, Biochemistry and Immunology Laboratories, and to start the new trypanotolerance programme. (d) Administration and Structure 18. In view of the present administrative difficulties at ILRAD, the Panel strongly recommends: i) that steps be urgently taken to ensure that the highest level of competence is available at Associate Director of Administration level; 7 ii) that the presently vacant positions of Financial Controller and Chief of Personnel be filled immediately, even through temporary recruitment procedures, by highly experienced and qualified specialists in order to strengthen the present administrative set-up; iii) that in view of the highly specialized equipment required for the research programme, competent staff be appointed to provide regular maintenance ..and repair of the equipment; iv) that vehicle and farm equipment be regularly and adequately maintained. (e) Training, Communication and Technology Transfer' 19. The Panel notes that training is an important component of ILRAD's mandate in view of the need to strengthen African institutions and facilitate technology transfer. 20. The Panel recommends: i) that the Technicians Training Programme be extended to include, wherever possible, technicians from outside the East African sub-region; .ii) that ILRAD's training programme receive high priority in resource allocation in order that the institute can better fulfill its Africa-wide mandate of technology transfer; iii) that collaborative arrangements in training both at the technician and postgraduates levels, being negotiated by ILRAD with Universities, national and international organizations and institutions, be continued with increased vigour; iv) that African Universities and institutions be closely involved in the selection of suitable postgraduate students; V) that selected postgraduate students be sent to co-operating Universities to undertake relevant course work before returning to ILRAD to pursue their research thesis; Vi) that ILRAD continue to organize either jointly with other organizations or singly, workshops, seminars and conferences as a means of training, informing scientists of the work of ILRAD and of facilitating beneficial interaction of research workers; vii) that short-term courses, either on individual basis for the acquisition of specialized techniques or on group 8 basis as a means of additional training and contribution to technology transfer, be introduced; viii) that ILRAD strengthen its communication and information section, produce non-technical Newsletter or Research Highlights in English and in French, that will be widely distributed and ensure that its annual reports reach as many institutes and individuals as possible especially within Afiica to avoid the criticisms of many African countries of their ignorance of ILRAD's excellent work. 1 II. INTRODUCTION 21. The Consultative Group on International Agricultural Research (CGIAR) is an international consortium composed of 35 members. On 1 September 1980 these were made out of nineteen governments, eleven international funding organizations and five foundations. The three co-sponsors of the system are the Food and Agriculture Organization of the U.N. (FAO), the United Nations Development Programme (UNDP}and the World Bank. The CGIAR has an independent, Technical Advisory Committee (TAC) to which is entrusted, inter alia, the periodical assessment of the achievements made by the thirteen international agricultural centres and programmes on which the system rests, and to make recommendations for their future. This assessment is carried out by TAC at intervals of no less than five years. 22. ILRAD having been created in 1974, the preparation for its quinquennial review started in early 1979 and, after consultation between the Board of Trustees and Director of the Centre and TAC it was agreed that TAC would field a Review Panel in October 1980. The same consultation took place for the establishment of the Panel; the Panel was chaired by Prof. G. Camus, Director General of the Office de la Recherche Scientifique et Technique Outre-Mer (Paris, France). The members were: Prof. J. David, Harvard Medical School (Boston, U.S.A.), Prof. K.T. Friedhoff, School of Veterinary Medicine, Department of Parasitology (Hannover, F.R.G.), Sir William Henderson, former Secretary to the Agricultural Research Council (London, U.K.), Dr. A.A. Ilemobade, Ahmadu Bello University (Zaria, Nigeria), Prof. J. Mortelmans, Institut de Medecine Tropicale (Anvers, Belgium), Prof. G. McDonald Urquhart, Department of Parasitology, University of Glasgow (U.K.). Mr. S. Risopoulos, TAC Deputy Executive Secretary, acted as Secretary to the Panel and Dr. D. Plucknett (CGIAR Scientific Advisor) was observer on behalf of the CGIAR Secretariat. 9 23. Terms of reference. The terms of reference of the Panel follow: "On behalf of the Consultative Group, to assess the content, quality, impact and value of the overall programme of ILRAD and to examine whether the operations being funded are being carried out in line with declared policies and to acceptable standards of excellence. It is hoped that the review will inter alia assist ILRAD itself in planning its programmes and ensuring the validity of the research priorities recognized by the Board of the Centre. In pursuance of the main objectives, defined above, the Mission is requested to give particular attention to the following aspects: i) The mandate of the Centre, its appropriateness and the interpretation thereof with respect to: I (a) the immediate and long-term needs for improved food supply and human welfare in developing countries; (b) present and possible future areas of work. ii) The relevance, scope and objectives of the present programme of work and budget of the Centre and of its forward plans for the next five years in relation to: (a) its mandate and the criteria for the allocation of resources as defined by TAC; lb) the ongoing activities of other international institutes and organizations, and of relevant national institutes in co­ operating countries and in others where the work of the institutes has bearing; (c) the policy, strategy and procedures adopted by the Centre in carrying out its mandate, and the mechanisms for their formulation; (d) the Centre's rationale for its present allocation of resources, its present and future overall size, and the composition and balance of the programme in the fields of research, training, documentation, information exchange and related cooperative activities. Hi) The content and quality of the scientific and related work of the Centre with particular reference to: (a) the results of past research; (b) the current and planned research and the role of the scientific disciplines therein; 10 (c) the information exchange and training programmes, their methodologies and the participation of the research staff therein; (d) the adequacy of the research support and other facilities ; (e) the management of the scientific and financial resources of the Centre and the coordination of its activities. iv) The impact and usefulness of the Centre's activities in relation to: (a) the present and potential impact of the research conducted by the Centre; (b) its information exchange and training programmes; (c) cooperation with national research and development pro­ grammes; (d) cooperation with other international institutes and organizations. v) Constraints on the Centre 's activities which may be hindering the achievement of its objectives and the implementation of its programmes, and possible means of reducing or eliminating such constraints. vi) Any specific questions which concerned members of the CGIAR, co­ operating institutions, the Centre 's Director or its Board of Trustees, may request TAC to examine. On the basis of its review, the Mission will report to the Chairman of TAC its views on the need for any changes in the basic objectives or orientation of the Centre 's programme elements, and on means of improving the efficiency of operations3 and will make proposals for overcoming any constraints identified under item (v). While the Mission should feel free to make any observations or recommendations it wishes3 it must be clearly understood that the Mission cannot commit the sponsoring organization3 viz. the CGIAR/TAC. " 24. To these terms of reference, TAC after consultation with CGIAR members and the Board of Trustees of ILRAD added the following questions: i) Mandate, long-term plans and priorities ILRAD has been established initially to concentrate research on the immunological and related aspects of controlling trypanosomiasis and theileriasis. The original mandate left open the eventual 11 extension of its research, to "other serious animal disease problems for which its facilities and expertise are appropriate3 provided such extension is approved by its governing body and the Government of Kenya does not object from a disease safety standpoint During the first quinquennium3 ILRAD limited its activities to the initial part of its mandate3 i.e. the immunological aspects of theileriasis and trypanosomiasis, (a) What will be the principal features of the Centre 's forward plans for the next five years? (b) What could be the possible alternatives: status quo (with the same two mandate diseases) 3 restriction (limitation of resources to one disease)3 expansion which could concern: - other major diseases hampering animal production in Africa; other aspects than the immunological one3 sdy the improvement of chemotherapy or the identification of field diagnosis techniques which would be suitable for training and transfer to African countries ; activities in support to medical research. (c) What would be the implications of the breadth of the mandate in terms of resource allocation? (see also question(xiv) regarding the number of small and large animals). ii) Programme implementation (a) Is trypanotolerance the object of a continuing study, apart from the study made in Gambia during the early stage of ILRAD? (b) Considering the restriction to the importation of trypano- tolerant West African breeds by Kenya3 would it be advisable that part of the trypanosomiasis programme go to the strengthening of some suitable animal health laboratories in West Africa? (c) What are the present plans to test or replicate in the field and in other countries than Kenya3 the present results or assumptions already made by ILRAD; what should be the guidelines for the choice of small and large-scale field tests? (d) Which parts of the programme are or could be implemented through cooperative agreements with other research institutions; what are the policies and criteria used by ILRAD in this respect? 12 Hi) Role of ILRAD in Africa and technology transfer (a) To what extent is the present programme of ILRAD responsive to the needs of African Governments? (b) From the onset ILRAD was supposed to have a catalytic role: how best has it been fulfilled; what are the relationships with existing African laboratories; similar laboratories in other parts of the world? (c) How is technology transfer supposed to be effected; what is the relationship with ICTPE, with ILCA, with FAO; are precise collaborative programmes in existence, being planned? What would be the relationship with the FAO-supported African trypanosomiasis programme ? (d) What has been done so far in training and information exchange; what are the gaps and possible plans for the future? How is it possible to respond to the needs of African countries3 English y French and Portuguese speaking? (e) Would it be possible for ILRAD to participate in {joint activities such as the FAO/WHO/OAU Tsetse and Trypanosomiasis Information and News Servicey as well as FAO/WHO/OAU training activities? iv) Management (a) What are the adequacy and present use of existing facilities and equipment; what are the maintenance problems; what are the future capital requirements and their rationale in terms of cost effectiveness? (b) What are the present personnel policies and future requirements; which use is made of visiting scientists and postdoctorals? (c) What are the present and future requirements of ILRAD for small and large animals; what are the alternatives for orderly and cost effective supply? 25. Operations of the Panel. The Panel was provided with extensive documentation by ILRAD and the TAC Secretariat before starting its business and was able to consult additional internal papers prepared by ILRAD's Director and staff as well as relevant FAO documents during its stay in Kenya. 26. The Panel assembled in Nairobi on 5 October 1980 and departed 18 October 1980. During its stay in Kenya, the Panel was received by H.E. the Minister of Livestock Development, Mr. J.N. Osogo; it also visited the prospective cattle production farm of ILRAD at Kapiti Plains, and had extensive discussions with the ILRAD Director and staff; opportunity was taken of a meeting of the ILRAD Executive Committee informally to exchange views on various matters with the Chairman of the Board and some of its members. 13 On 17 October the Panel, through its Chairman, presented its collective findings and recommendations to the Director and the Executive Committee of the Board of Trustees of ILRAD. Details on the Panel programme and documentation perused are mentioned in Annex I of the present report and a glossary of some technical terms figures in Annex II. III. REVIEW OF HISTORICAL BACKGROUND AND MANDATE 27. The establishment of a specialized centre to conduct research on tropical animal diseases was considered at the end of the sixties by the Rockefeller Foundation, in the wake of the establishment of the Rice Research Institute in the Philippines (IRRI), of the International Maize and Wheat Improvement Centre (CIMMYT) in Mexico, of the International Institute of Tropical Agriculture (IITA) in Nigeria, of the International Centre for Tropical Agriculture (CIAT) in Colombia. In October 1969 the Rockefeller Foundation called a meeting of scientists and administrators at Bellagio (Italy) to discuss the need of such a laboratory and the means by which it could be established. The following year (April 1970), a donor agencies meeting, again at Bellagio, supported the idea and recommended to the Rockefeller Foundation to proceed with a draft proposal; at that time the need for such a laboratory and the suitability of Kenya ‘ as a potential site were recognized by the group assembled at Bellagio. 28. Drs. J. McKelvey Jr. and J. Pino, both from the Rockefeller ! Foundation, recommended the establishment of an international laboratory for animal diseases research in Africa and their report recommended that a block of 400 acres of land be made available to a laboratory in Kenya. It also proposed a budget for capital investment and operations, made recommendations on financing, legal status, management, relationship with Kenyan and other institutions conducting research on animal diseases and universities, etc. 29. When the Consultative Group on International Agricultural Research (CGIAR) was created, its Technical Advisory Committee (TAC) discussed, at its first meeting (July 1971) the above proposal of the Rockefeller Foundation. TAC was on the whole sympathetic to the priorities identified by the report, although doubts were expressed whether one centre, however well equipped, could cater adequately to all major animal health problems of Africa. At the end TAC endorsed the establishment of the Task Force 1/ "An International Laboratory for Animal Disease Research in Africa", by J. McKelvey, Jr. and J.A. Pino, November 1970. 14 commissioned by the Rockefeller Foundation to survey the animal industry in Africa and to outline general and specific objectives of a proposed Animal Production Research and Training Centre for Africa. Although open to the views expressed by the McKelvey and Pino report, TAC debated the concept of a single centre versus support to existing institutions with a coordinating mechanism: it stressed the need to consider the relationship of the health problem to the overall problem of livestock improvement and to make an assessment of all existing facilities. 30. At its second meeting (October 1971) TAC examined the report of the above Task Force and recognized as separate the two issues dealt with by the report, i.e. a laboratory for animal diseases and a centre for animal production in Africa; the report had proposed the establishment of the laboratory at Nairobi, to deal primarily with immunological studies on East Coast Fever and Trypanosomiasis while a small team of specialists would deal with livestock production. The Task Force had also recognized three major ecological zones for the whole of tropical Africa for which an international research structure was needed to improve livestock production. TAC found that the proposal related to the animal disease laboratory was advanced enough to allow for a firm recommendation for acceptance to be made to the CGIAR; in the case of animal production TAC required further information, whilst agreeing on the real need for inter­ national research on the subject; by this course of action, the way was paved for two international agricultural research centres (ILRAD and what was to become ILCA) V to be added to the CGIAR system. 31. At its second meeting (December 1971), the CGIAR: i "... endorsed -in principle the recommendation for establishment of an animal disease laboratory, but concluded that it should he viewed as an aspect of the overall improvement of African livestock systems. It was agreed that the Chairman should appoint a subcommittee of the Consultative Group3 composed of members intending to provide major financial support for livestock improvement in Africa or having large current investments in African livestock research. It would be the responsibility of the subcommittee to arrange for negotiations looking toward establishment of an animal disease laboratory which might ultimately be integrated into an African livestock centre. The subcommittee would also select a task force to undertake the studies recommended by the TAC3 including a review of past and current research3 with a view to determining the feasibility of establishing an African livestock centre; proposed terms of reference for the task force would be formulated by the Chairman of the TAC in consultation with the TAC. • • • >t 2/ 1/ International Livestock Centre for Africa. 21 Summary of proceedings CGIAR Second Meeting, December 1971, p.4. 15 32. At its third meeting (July/August 1972), the CGIAR noted the conclusions reached by the executive team, nominated by the CGIAR African livestock subcommittee to respond to the comments made by the CGIAR at its second meeting and review the present research status of Trypanosomiasis and Theileriasis; the executive team was led by Dr. W. Pritchard (USA) and composed, besides the leader, of Sir Alexander Robertson (UK) and Dr. Rildiger Sacks of Germany; the executive team report underlined that "there was a need to augment the research that had been carried out in the past on the two diseases ; the team confirmed the earlier recommendation that ILRAD be established and focus on the control of both trypanosomiasis and theileriasis as their main research effort, not only because of the importance of the diseases but also because research on these two diseases is highly related ...". The team " • • • recommended also that the major emphasis of the research be on highly fundamental immunological studies that are vitally needed and that are not presently being done. ..." 1/ 33. At its following meeting in November 1972, the CGIAR endorsed the recommendation made by the African Livestock Subcommittee that the Government of Kenya should be approached to establish ILRAD in this country, as the idea to have the Centre sited at the East African Community Research Centre at Muguga, Kenya, was not possible, The Group reaffirmed its position that the centre should be considered as a potential subunit of an integrated African Livestock Research Organization, if and when established. 34. At its fifth meeting (January/February 1973) TAC discussed mostly the establishment of ILCA; it was mentioned i.a. that "... regarding liaison with ILRADTAC noted that these two centres have very different objectives and suggested that, at least initially3 they should be developed separately, The TAC did not however discount the possibility of a later fusion into a single body3 although of the opinion that if this were done from the outset it might unnecessarily complicate the development of investment work." 2J 35. The Memorandum of Agreement for the establishment of ILRAD as an autonomous, non-profit organization, international in character, was signed between the Government of Kenya and the Rockefeller Foundation, acting as executive agent of the CGIAR, on 13 September 1973. The document states as purpose of the laboratory: 1/ Informal summary of proceedings, CGIAR Meeting, July-August 1972, presentation of Dr. W. Pritchard. 2/ Report of the 5th TAC Meeting, Jan.-Feb. 1973, Annex V, p.3. 16 "The purpose of the Laboratory wilt he to serve as a world centre for research on ways and means of conquering3 as quickly as possible3 major animal diseases which seriously limit livestock industries in Africa and in many other parts of the world. The Laboratory will concentrate initially on intensive research concerning the immunological and related aspects of controlling Trypanosomiasis and Theileriasis (mainly East Coast Fever). It may3 however3 eventually extend its research to other seri.cn.4g animat disenee problems for which its facilities and expertise are appropriate3 provided such extension is approved by its Board of Trustees and the Government of Kenya does not object from a disease safety standpoint. In carrying forward its programme3 the Laboratory will develop close linkages with governmental and regional organizations undertaking research on the same or related disease problems." 1/ 36. The activities foreseen for the Centre were as follows: "The Laboratory will engage in the following types of activities: 1. Basic research3 applied research3 experimentation and field testing of results. These activities may be undertaken by the Laboratory on its own premises or in association with appropriate national or regional organizations3 but field testing shall in all cases be carried out in accordance with appropriate disease safety regulations of the'Government in whose territory it is conducted; 2. Publication and dissemination of research results; _ i 3. Strengthening and creating appropriate links with national and regional institutions dealing with the control of animal diseases and related problems of animal production3 particularly in Africa; 4. Organization of discussion groups3 seminars3 workshops and conferences on topics related to the work of the Laboratory ; 5. In cooperation with universities and other research institutes3 provision of opportunities for advanced professional training and experience in animal disease research within the scope of the Laboratory ; 6. Training of scientists who will be involved in research, education and action programmes in cooperating countries in which the Laboratory's programme wilt be applicable; 7. Assistance to cooperating countries in using and applying the research results of the Laboratory; and 8. Such other activities as may be found necessary or desirable to further the objectives of the Laboratory. " 2J 1/ Memorandum of Agreement, pp. 3-4. 2/ Ibid, pp. 4-5. 17 37. A special paragraph of the Memorandum of Agreement deals with the cooperation with ILCA and states that: "In realizing its purpose and carrying out its activities, the Laboratory shall closely cooperate with ILCA. If and when the CGIAR determines that it would be appropriate to modify the cooperation between the Laboratory and ILCA under a formal relationship3 the CGIAR will determine the terms and conditions under which that relationship shall be entered into'. The Board of Trustees of the Laboratory shall take all such action as shall be necessary to conclude, and realize the purpose of, such formal relationship in accordance with the directives of the CGIAR." 1/ 38. Several privileges are nominally granted to ILRAD in the Memorandum and as regards land, the memorandum specifies: "The Government of Kenya will make available to the Laboratory on a long-term (example -SO years) lease at a nominal rental a tract of land of approximately 100 acres act or near Kabete which is suitable for the purposes of the Laboratory, including land for office and service buildings and for other appropriate facilities. The Government of Kenya will also make available, without cost, from time to time and for such periods as may be necessary, such additional land as the Laboratory may need for its field tests." 2/ 39. At its 6th meeting (July-August 1973), a proposal from the French Government was submitted to TAC: it concerned research to be carried out in Upper Volta by the Institut d'Elevage et de Medecine Veterinaire [ Tropicale (IEMVT) on the vector of trypanosomiasis (tsetse fly), through the sterile male technique, pupal parasites and eventual chemical eradication; besides, studies on trypanotolerance of native breeds would be conducted; whilst welcoming the initiative taken by the Government of Upper Volta and IEMVT, TAC felt that further exploration of the effectiveness of the research lines proposed was required; it recommended therefore the proposal for support by individual donors rather than by the CGIAR, and recognized that it would complement research on immunization against trypanosomiasis conducted by ILRAD. 40. During the year 1974, ILRAD was formally established; unfortunately the first director designated, Dr. E.H. Sadun passed away before taking up his functions. He was succeeded by Dr. J. Henson. 41. At the 10th Meeting of TAC (July 1975), the new Director made a full presentation of the progress made by the Centre; TAC discussed the possible use of existing facilities at ICIPE (insect rearing, electron 1/ Memorandum of Agreement, p. 9. 2/ - Ibid - pp. 11-12. 18 microscope); it noted that ILRAD and ICIPE "had research problems which overlap, and the Corrmittee hoped that their association would continue to the benefit of both"; V TAC recorded its satisfaction in the progress made by the Centre. 42. At its 13th meeting (May 1976) TAC noted the growing amount of cooperation between ILRAD and other institutions and strongly supported the immediate establishment at ILRAD of tsetse and tick breeding facilities as these insects could not be obtained in sufficient numbers and of the right type and quality elsewhere. 43. At its 16th meeting (June 1977) TAC noted its satisfaction at the early scientific advances made by the Centre (in vitro culture of TL brucei) and at its 19th meeting (June 1978) TAC "recognized the difficulties faced by ILRAD in obtaining adequate animals for its research and approved the interim measures proposed by the Board for 1979 in this respect. However the Committee would wish ILRAD to develop a long term strategy for covering their livestock needs, including the balance to be kept between different categories of animals and the way to meet their forage requirements. TAC also requested that the possibility of importing trypanotolerant livestock from West Africa be further considerea. 2/ 44. At its 22nd meeting (July 1979) TAC met the new ILRAD Director, Dr.' Allison. TAC "recognized the need for ILRAD to have an adequate number of disease-free .large animals for. its experimentation but drew the attention of the Board to the large number being requested by the manage- ment. The Committee recommended that all alternatives leading to the use of a farm by ILRAD be explored and that separate accounts be kept of future farm operations." 3/ At its 24th meeting (June/July 1980), TAC reiterated its previous recommendations that the expenditures related to farm operations be accounted separately and monitored carefully. 45. Implementation of the mandate. Over the years the Board did not attempt any modification of the mandate and seemed to have been satisfied with it. At its 1977 Meeting, the Board instructed the management to increase efforts on theileriasis and to reflect this in the Programme and Budget document, despite the fact that some members of the Board underlined the importance of'trypanosomiasis in Central and West Africa. 46. At its meeting in 1978, the Board suggested that more scientists from the Prench speaking African countries should be engaged by ILRAD and that field work on epidemiology should be increased; it was remarked that 1/ Report of the 10th TAC Meeting, Washington, July 1975, p. 102. 2/ Report of the 19th TAC Meeting, Nairobi, June 1978, p. 60. 3/ Report of the 22nd TAC Meeting, Hyderabad, July 1979, p. 66. 19 there had been little response from West African countries when positions had been advertised. 47. At a joint meeting of the Programme and Scientific Advisory Committee in February 1979 the possibility for ILRAD to initiate a pro­ gramme on African Swine Fever was considered with interest but it was stressed that it should be separately funded so as not to interfere with the two mandated diseases; the subsequent Meeting of the Board of Trustees decided however that ILRAD should not engage into any new research venture. 48. Observations. It can be said that since the very beginning, when the idea of a laboratory for research on livestock diseases in Africa was first mooted, the concept and subsequent mandate of ILCA have remained very stable and have not undergone any significant changes; the siting, the research approach, the scope of the mandate, have remained the same; the simplicity of the mandate and objectives has made possible an unusual,- concentration of efforts. As said below in Chapter VII (page 62, para 233) the Panel feels that ILRAD should continue to concentrate its efforts on trypanosomiasis and East Coast Fever. i t IV. ADMINISTRATION AND STRUCTURE 49. ILRAD has been initially set up, like most IARCs, with a governance represented by a Board of Trustees made up in this case of no more than twelve members; two members are designated by the Government of Kenya, three by CGIAR and they are complemented by six members at large out of which three are intended to represent African countries. The Director of ILRAD is an ex-officio member of the Board. 50. Over the years the Board has established several committees to help itself in its task - namely the Executive Committee, and the Programme, Finance, Training and Nominating Committees. Only Board members fill these committees and no scientific personalities from outside are members of the Programme Committee, as is sometimes the case in other IARCs: however, in view of the highly specialized nature of ILRAD*s research there is a Scientific Advisory Committee whose members are chosen on an ad hoc basis according to the problem upon which the Scientific Advisory Committee has Ì to give advice. 20 51. Besides the Board Committee's ILRAD has tried to meet the challenge of its unusual nature and mandate by developing a series of administrative mechanisms, some of which are particular to ILRAD. The present chapter, therefore, is divided between Administrative Organization and Research Management; some paragraphs will also be devoted to the facilities for recombinant DNA research, the support units and the supply of farm animals to research units. (a) Administrative Organization 52. ILRAD is administered and managed by a Director appointed by the Board of Trustees. There is no Associate Director for Research although the matter was mooted some years ago, and the second in command is an Associate Director for Administration, who deputizes for the Director during his absences. His responsibilities are extensive and encompass the following services: finance and accounting, personnel, library, supplies and stores, graphic arts, food and housing, general services, animal production and maintenance, engineering and transport. Non-scientific personnel are responsible to him. 53. The management of ILRAD, i.e. the reconciliation of the scientific objectives and requirements and administrative practices have necessitated a growing number'of internal committees, the premier of which is the Director's Advisory Committee (DAC). It was composed in the past by three scientists who have acted in lieu of an Assistant Director for Research and as such, cooperated with the Assistant Director for Administration in running the Centre in the interim period between the departure of Dr. Henson and the arrival of Dr. Allison. 54. The present Director felt, after taking over, that internal policy decisions should be best ensured by an enlarged DAC and that each laboratory should be represented by a coordinator; the present membership of DAC is thus made of six laboratory coordinators, the Chiefs of the four special units (Tsetse Unit, Tick Unit, Clinical Medicine/Animal Production and Electron Microscope), the Assistant Director for Administration and the Chief Engineer; The DAC meets about once a month and covers a wide range of scientific and administrative subjects. The other internal committees (animal, library, publications, technical staff, equipment, general staff, safety, research associates and training) meet less frequently, sometimes once a year at the time of budget preparation. 55. In general it can be said that administration at ILRAD has had more that its share of problems, due primarily to lack of precision regarding the respective areas of responsibilities of the governance and top level of management aggravated by a lack of competent and responsible administrative personnel. Much of ILRAD's trouble lies in lack of mutual confidence, communication and trust between the Board and the Director. As a 21 consequence of the above ILRAD's governance is now looking for a new incumbent to the post of Director, The Panel feels that these problems must be clarified and settled before the appointment of a successor to the present Director. 56. Personnel. Since August 1978, there is no Personnel Officer at ILRAD and some dissatisfaction has been voiced in several quarters regarding terms- and timing of contracts, terms of employment, etc. and it has had considerable bearing on the concern of some categories of support staff. This unsatisfactory situation may spread since ILRAD has nearly 400 staff members and the wide range of grades and categories of staff requires a full time professional officer. 57. Finane e. There have been difficulties in the issuance of monthly reports of expenditures which has meant that laboratory coordinators have not been made aware for some time of the financial situation of their respective units. This has caused discontent. A new finance comptroller is to be hired to replace the present one, whose contract has recently been terminated by the Board; this is an urgent matter which has to be dealt with in order to implement the finance and purchasing guidelines established by the present Director to overcome long lasting deficiencies; besides, the financial situation of the Institute has to be constantly monitored. Finally, it should be noted that the 1980-81 budget has been established on a very sound basis by the present Director and it is strongly felt by the Panel that any delay in hiring the necessary competent personnel might have a negative effect on the preparation of the next budget. i 58. Maintenance, Housing and Catering. After several unfortunate experiences ILRAD has now a new chief engineer; maintenance of vehicles is the first area for improvement and a chief mechanic is to be recruited; for many laboratory items there is no servicing organization in Kenya and laboratories have tried to overcome the problem by redundancy of certain items but this approach is expensive, One or more electrical engineers are needed, who are trained to maintain specific items of the sophisticated scientific apparatus of ILRAD. 59. With hindsight it could be regretted that ILRAD was not allowed to build more houses during its formative years — the shortage of housing in Nairobi, the escalating costs of rents in town as well as security problems make it necessary for ILRAD to build more housing on site, which, however, has now to meet increased building prices; recently it has been decided that personnel residing on site would pay a rent, as well as paying for the use of water and electricity. 60. The Food and Housing Service has been functioning excellently from the start and this is an attractive facet of the Hostel, which can accommodate twenty short-term residents. 22 61. Recommendations. The Panel recommends: i) a clear delineation between policy setting by the Board and the management of the Institute for which the Director should be fully responsible; ii) in view of the current administrative difficulties, that steps be urgently taken to ensure that the highest level •of competence is available at Associate Director of Administration level; iii) the immediate filling of Financial Comptroller and Chief of Personnel positions, even through temporary secondment procedures, by highly experienced and qualified specialists in order to strengthen the present administrative set up; iv) that competent staff be approached to provide regular maintenance of the highly specialized equipment required for the research programme, combined with the capability for repair; regular vehicle and farm equipment maintenance is also a requirement which should be adequately met. i 62. The Panel commends the administrative support so far provided by ILRAD to CIP, CIMMYT and ILCA and supports its continuation. (b) Research Management 63. General. The mandate of ILRAD has been established by TAC, the CGIAR and the ILRAD Board of Trustees. It is to develop effective control methods for trypanosomiasis and theileriasis, two diseases that are important in an estimated 50 developing countries. The responsibility for the specific research carried out at ILRAD is that of the Director, within the limits decided by the Board of Trustees at its annual meeting in March. To aid it in its decision, the Board has a Programme Committee which meets in January and again in March with the whole Board. A Scièntific Advisory Committee usually consisting of four persons with expertise in parasitology, immunology and animal diseases, selected by the Director, meets at the same time as the Programme Committee in January. The membership may change from year to year depending on the scientific problems at the time. It goes over the work of each laboratory and scientific support facilities and its report goes both to the Director and to the Programme Committee. 64. The research facilities under the Director include six laboratories in parasitology, biochemistry and molecular biology, cellular biology, immunobiology, immunology, pathology and four support units, including a tsetse unit, a tick unit, an electron microscopy facility and the ILRAD farm including its clinical diagnostic section for serology and microbiology. ) : 23 65. Each of the six laboratories has a coordinator who is responsible for its programme and budget, As said above, the coordinators are members of the Directors Advisory Committee (DAC) which meets approximately once a month, at which overall policies of ILRAD are discussed. The two pro­ grammes, that on trypanosomiasis and that on theileriasis, have each a moderator. In addition to the DAC there are an additional nine committees of which the committee for animals, library, publication, equipment, and safety are relevant to the subject of scientific management. The library and animal committees are dealt with elsewhere. The equipment committee meets once a year to determine the equipment needed for the programmes and a publication committee reviews all manuscripts before they are sent out for publication. 66. Staffing pattern. The ILRAD staff is represented by approximately 20 nationalities and consists of different categories of senior staff involved in the execution of the two programmes at ILRAD. These researchers include core scientists, visiting scientists, post-doctorals, research associates and postgraduate students. The distribution of the staff according to the existing laboratory structure is given below (Table 1). Table 1 Staff Disposition by Categories (excluding support units) Lab 1 Lab 2 Lab 3 Lab 4 Lab 5 Lab 6 Total tryps ECF Core Scientists 2 1 2 1 3 2 3 14 Visiting Scientists 1 3 3 2 9 Post-doctorals 1 3 1 4 2 13 Research Associates 1 3 2 2 3 11 3 6 8 7 9 4 8 47 67. Apart from postgraduate students, all senior staff are on a two- year contract renewable by mutual agreement for periods of two years. Only 70% of the approved staff positions have been filled, but this has been compensated for by non-ILRAD supported staff. 68. The core scientists are recruited specifically for their expertise and for their ability to provide leadership in research and training. Several distinguished scientists visit ILRAD yearly and carry out useful collaborative projects with ILRAD staff, generally for short periods of time (approximately three months) or carry out specific assignments. 24 Some of them are also involved in training and providing useful contacts for the scientists. Visiting scientists are supported by non-ILRAD funds but make use of ILRAD's facilities. 69. A total of 13 postdoctorals are presently working in ILRAD, six of whom are supported from outside sources. Postdoctorals are selected on the basis of calibre of training and ability to carry out independent research; they are expected to assist in training programmes. Over the years, several postgraduates have, based on their performance been appointed Scientists. It is fair to say that recruitment into the postdoctoral cadre has helped in the selection of suitable candidates to fill posts of scientists on ILRAD staff. 70. The Research Associates are highly-trained technicians who provide technical support for the different projects being carried out. This cadre of workers is attached to the different laboratories in which their speciality is required. The post graduate group is considered under the chapter on training and technology transfer. 71. Selection of priorities. During the preceding Directorship there were relatively few senior members of the staff and the policy was to permit a wide degree of freedom to the individual scientist in the pursuit of his interests. During this period, there was also generous funding of the research programme, Under these circumstances the selection of . priorities is not related to the pressure of the allocation of financial resources. In these earlier'years certain limitations, especially of certain equipment and of animals and vectors for experiment, restricted the possibilities for the expansion of programmes in a number of directions. 72. Under the present Directorship there was a larger staff and there had to be a greater sharing of resources. As described above, a moderator was appointed for each of the two programmes, i.e. trypanosomiasis and theileriasis. Twice a year each Moderator convenes a meeting of all staff involved in any way with the programme in question, These meetings are chaired by the Director. By a process of discussion a consensus is reached on the priorities for each programme, This exercise, however, is not taken far enough to be meaningful as the agreed priorities are not, apparently, related to any identifiable cost. The basis for this statement is that each laboratory is allocated an annual financial provision for consumables which does not include one of the most expensive items, namely cattle. 73. Directing of research. The directing of research refers to the taking of decisions for the continuing functioning of the programme, especially the choice of options when resources are limiting, There are various levels at which these decisions must be taken with the Director acting as the final arbitrator, The Panel noted a number of examples where this responsibility was not exercised but it was not always able to determine the reasons. One possibility in such situations is that the information about the problem may not be sufficiently well communicated. Another possibility is that measures for effective action may not exist. : 25 74. _O__b_s_e_r_v_a__ti_o_n_s. The top structure consisting of the Board of Trustees, the Programme Committee, the Scientific Advisory Committee and the Director is orthodox and, with the correct observation of respective responsibilities, need not be changed, It would appear, however, as pointed out earlier, that a clearer definition or a better recognition of responsibilities is required. 75. The membership of the Programme Committee of the Board requires careful selection. The Panel is pleased to note the relevance of a recent appointment; a further move in this direction could be the appointment of an appropriate biochemist. 76. The Scientific Advisory Committee can play a very useful and stimulating role but sufficient time should be allocated to permit them not only to hear formal presentations by the staff but to discuss, and comment upon, the work with the scientists before advising the Director. The efficiency of the Committee would also be improved if its composition was broadened to ensure that it comprises all the necessary competence. 77. The Director has the responsibility for the conducting of the research programmes, It must be ensured that, in performing this task, he is given the authority and the full support of the Board of Trustees. In view of the administrative problems that have beset ILRAD in recent years it might be considered'that the Director could, more appropriately, be an administrator than a scientist. The Panel is unanimous in stating that the Director must be knowledgeable in today’s science derived from recent active participation, and with an established reputation for research leadership, With this background, he can attract the best scientists to work at ILRAD; he will receive invitations to participate in scientific meetings internationally and thus spread knowledge about ILRAD’s achievements and add to its prestige. Another advantage of these activities is that from the relatively isolated location of ILRAD contact with the scientific community would yet be strengthened. 78. The Director’s Advisory Committee has fulfilled a very necessary function by providing an opportunity for participation of staff in manage- ment. Although the agenda of the meetings include many diverse subjects, this is merely a reflection of the complexity of the operation of an international institute. 79. The Panel considers that the choice of business for the Director's Advisory Committee is that of the Director, combined with the opportunity of the members of the Committee to propose items of concern to them. It is important that a regular schedule of meetings is adhered to. 80. The present system of the supervision and management of the research programmes at ILRAD lacks an adequate procedure for the selection of priorities and the subsequent allocation of resources. The selected 26 priorities must be reviewed based on the results of the evaluation of the research progress. In this exercise it is suggested that the Scientific Advisory Committee plays a key role in support of the discussions of the Programme Committee. 81. The staffing rate is only about 70% and in 1980 the unexpected salary balance was used for unanticipated increased building costs; this is an instantaneous situation and vacant posts should be filled in 1981 as soon as the next Director has an opportunity to assess the situation. 82. The Panel noted a certain unbalance in the staffing pattern in that the number of core scientists is unusually low. The current distribution of staff based on the six laboratories with this minority of core staff suggests that a certain fragility might exist. On the other hand, an analysis indicates that, based on scientific disciplines, the total staffing situation at ILRAD is reasonably balanced as illustrated by the following table. . Table 2 Staff Disposition by Scientific Disciplines* Scientific Discipline No. of staff Parasitology 7* Cell Biology 6 Immunology 9 Molecular Biology 2 Biochemistry 7 Pathology 7 * Research associates not included The Panel is not against retaining a certain degree of flexibility, but is of the opinion that a more solid basis of core staff must be provided. 83. As an aid to recruitment of core staff, consideration should be given to providing further security by modifying the contracts of employment, For example, there could be an initial contract for two years which is a period of probation, In the case of renewal the next period could be extended to say, three or four years. 84. The present system based on six laboratories, each with a coordinator, and a moderator for each of the two programmes, is an attempt to introduce a framework within which there could be adequate collaboration and mter- action. The disadvantage is that it is bereft of authority in that no identification of responsibilities exists. 27 84. It has been frequently stated to the Panel that the design of the research accommodation into adjoining laboratory spurs hampers free communication. This might be for some staff members an excuse to avoid close collaboration. Anyone accustomed to be a member of an institute or a University scattered over a very much larger area or housed in multistorey buildings might comment favourably on the design of this laboratory complex. 85. The Panel urges that the new Director with the help of the Board and the staff gives serious consideration to a system of research manage- ment by projects under project leaders, which has proved to be a most effective form of research management in rapidly developing fields of science. 86. A project is built up of the relevant components within a scientific community which in this case is ILRAD. At a later date, however, an ILRAD system could well incorporate a component from a neighbouring organization such as the Kenyan Institutes at Kabete and Muguga or with ICIPE, which would enhance the already existing collaboration. 87. For this system to be viable, a Project Leader has to be designated with delegation of authority over all the included staff, Each project must have its budget to cover all its activities, The Project Leader should be one of the scientists most actively involved in the project and his rank or grade need not be taken into account. The selection of the Project Leader should be on the criteria of involvement, potential leadership, and scientific competence, It is usual, under such a system, that each senior scientist might be a member of two or, perhaps, three projects. In one, he might be the Leader and in another, play a relatively minor role because of his contribution being relatively small or of a service nature. 88. The organization of such projects in ILRAD should be horizontal across the laboratories, The research progress of each project must be frequently assessed so that flexibility can be exercised to take advantage of advances in one that might influence the planning and resource allocation in another, The Panel in studying the requirements for the management of research at ILRAD was very conscious of the complexity of the programmes. There is a difference in pattern, for example between the characteristic long-term programmes of, say plant breeding. There i are short-term and long-term components within each of the programmes at ILRAD. Also the research progress provides the expectation of increased field activities, which are in the long-term category as opposed to short­ term fundamental research in, say, molecular biology. There must be an acceptance of the necessity to create new projects and to terminate existing projects. Changes of this nature can conveniently be related to biennial budgeting which indicates the frequency of major review that is appropriate. : ■ ? I 28 89. Recommendations. The Review Panel recommends : i) that a clear definition of responsibilities for the Board of Trustees, the Programme Committee, the Scientific Advisory Committee and the Director is agreed, understood and implemented based on the Board's primary identification with general policy and the Director's identification with management; ii) that the Director be given by the Board of Trustees the authority and full support for the management and the conducting of the approved research programme; iii) that the next Director be an internationally recognized scientist. Proven research leadership and administrative ability are required; iv) that the scientific staff be brought up as far as possible . to its full complement within the availability of funds as soon as the next Director has had the opportunity to review the programmes and the achievements; v) that the present system of two year contracts for scientific staff be reviewed by the Board to determine whether a system which allows contracts of a longer period could be initiated after the first two year period, so as to give more security to the staff and more permanence to the scientific group; Vi) that the stimulus that can be provided by the policy of encouraging outside scientists to join ILRAD group should be continued but with these scientists coming with their own financial support, or, if not, under a budget heading separate from core staff; vii) that the system of research management be studied for its possible introduction by which there is a clear delegation of responsibility for research and financial control given to a selected leader of a group of scientists collaborating on a project basis; viii) that procedures be established for the selection of priorities accompanied by the appropriate allocation of resources; that these priorities be reviewed at regular intervals with a frequency appropriate to research progress and certainly in relation to the preparation of each biennial budget. The review of priorities must be made and discussed at several levels starting with the project leaders and progressing through discussion involving the Director, the Scientific Advisory Committee and the Programme Committee to the Board of Trustees for final endorsement. 29 (c) Facilities for Recombinant DNA Research 90. Work is in progress on the isolation of the genetic material (DNA) responsible for the antigen determinants of Trypanosoma brucei. Since 1974 the United States of America and the United Kingdom have seen fit to impose controls on the use of this new technology to alter the nucleic acid structure of the lower organisms such as bacteria by introducing into them genetic material from the higher organisms, such as animals and plants. Such guidelines have been followed in several industrialized countries. The visiting Panel was pleased to find that ILRAD had informed the Recombinant Advisory Committee of the National Institutes of Health of the USA that it proposed to conduct these experiments with brucei and that according to the NIH guidelines, had installed a laboratory of the then recommended standard of safety. 91. Sir William Henderson, a member of the visiting Panel, is currently the Chairman of the Genetic Manipulation Advisory Group of the United Kingdom. This is the controlling authority in the UK for this type of work. He and Professor John David visited the designated laboratory for this work and found it to be more than adequate for the containment of the potential hazards for the project in question. 92. The Laboratory has been installed to conform to the US "P3" category of containment which, today, is regarded as being unnecessarily restrictive. The category of containment recommended since 1979 for the work in question is "PI". Professor David and Sir William Henderson affirm that the present programme presents no hazard by using the selected biological system in the accommodation provided. 93. The Review Panel is pleased to note that an ILRAD Biohazards Safety Committee ensures that the correct procedures are followed and that two representatives from appropriate Kenyan Government Departments have been invited to join this Committee. (d) Support Units —1/ 94. Electron Microscopy Unit. The unit planned and equipped during 1978-79 was activated in January 1980, and is since then directed by a senior scientist who is supported by a research associate. The unit has 1/ The four main support units are the tick unit, the tsetse unit, electron microscopy and clinical medicine/diagnostic laboratory/ farm unit; the first two have been treated under their relevant general programme (trypanosomiasis and theileriasis) in Chapter •V; due to budgetary implications for the present and future, the questions of the supply of animals for research and their health conditions have received a fuller treatment in the following paragraph. The support units paragraphs deal therefore with electron microscopy and the work of the central core unit. 30 a dual mission: i) To provide ultrastructural information relevant to problems under investigation by scientists in other laboratories, and ii) To conduct independent research on the ultrastructure of Theileria and Trypanosoma, their location in the -tissues of their arthropod vectors, and their inter­ actions with the cells of the mammalian hosts. 95. The unit is well equipped with a "Zeiss" transmission Electron Microscope and is highly efficient. It provides excellent service to ILRAD scientists. 96. Central Core. This unit has the responsibility for glassware washing and sterilization and media preparation for all of the laboratories and research units. The standard required is much higher than in a routine bacteriology or microbiology laboratory, and the unit is organized accordingly. It has its own budget. (e) Supply of Animals for Research 97. Introduction. A prerequisite for research on animal disease is the availability of a supply of suitable animals for experiment. Such animals of whatever species, must be of one breed per usage, healthy, in a state of good nutrition, susceptible to the disease which is the object of the experiment, uniform in size and age and there may be specific requirements of sex and genetic background, A further requirement in countries in which the diseases being studied are endemic is that previous exposure to infection must be avoided. A well organized and efficiently run system is required to meet these criteria. There must also be a support service for the screening of the animals for specific pathogens and for the determination of serum antibody levels. This is part of the procedure for the selection of suitable animals and for the monitoring of their health status during the period prior to their use in an experiment. 98. Animal disease research has a significant advantage over human disease research in that the scientists can conduct experiments using the species of animal which suffers from the disease in question, Much initial work and many basic studies can be done using laboratory animals or cultures of certain cells. Sooner or later, however, most research of this type has to be conducted in farm livestock. In the case of the ILRAD mandate this necessity applies both to the trypanosomiasis and to the East Coast Fever programmes and both demand the use of cattle. 99. The high cost of cattle makes it necessary to plan experiments with care to ensure that the results obtained are to be of significance. 31 Unfortunately, the statistical requirement of experimentation makes it necessary for certain work to use cattle in groups of at least eight animals. For the above reasons the ILRAD research requirement is for some hundreds of cattle, The numbers of all animals used in 1979 is shown in Table 3. It must be expected and indeed, hoped that the demand for cattle will be increased. This will be a consequence of successful progress. For this reason the present level of about five hundred animals has been increased to some six hundred in preparing proposals for supply from an ILRAD ranch and the investment analysis for this proposal has been based on an increase to eight hundred head per annum. 100. The visiting Panel is in full agreement for the justification of the current use of cattle and for anticipating subsequent increases. Apart from the success factor which has been mentioned it must be noted that the full staff complement has not been achieved. A very important item on the immediate forward planning of the ILRAD facilities is that of accommodation for animals under experiment. Unless this is considerably increased, the present bottleneck in the provision of cattle for experiment will be exacerbated to an unacceptable extent. Table 3 Animals Used for Research in 1979 Cattle 452* Sheep and Goats 404 Rats 12,000 Mice 20,000 Rabbits 400 * 117 of these cattle were used for more than one purpose, thus the total number of cattle units in 1979 was 569. 101. Clinical- medicine/diagnostic laboratory and farm. The rapid expansion of ILRAD's requirements for farm animals has made the services of a diagnostic laboratory particularly needed and important, especially as animals are maintained on ILRAD premises under intensive management conditions for a period of time. The diagnostic laboratory was established to develop serological screening tests for adult field cattle; to provide on site serological screening for monitoring experimental animals; to provide a diagnostic capability in microbiology, hematology and helminthology; and to provide assistance to other laboratories for their current activities. The unit has thus the responsibility to ensure that animals purchased by ILRAD are in good health and stay in good health; all ILRAD-reared cattle are serologically screened every eight weeks; in addition for each group of bought-in calves, one animal is splenectomized and blood slides are examined twice a week; all non-research animals are screened every twelve 32 weeks. The unit is composed of a core scientist, an associate expert, a postgraduate fellow and a research associate and has also the responsibility for the ILRAD farm. 102. The Farm Animal Production Unit comprises 92 acres of land on the Institute site. It consists primarily of open experimental pens, enclosed buildings for housing animals under experiment and calf rearing facilities, both enclosed and open. There are a number of paddocks but, in general, the topography of the site on the sloping side of a valley hinders maximum utilization of the limited acreage. 103. Two systems are used for cattle production: (1) the rearing of calves purchased when three days old and (2) the purchase of weaned cattle about six months old. Prior to initiating both systems, several thousand sera from adult cattle from six large, well managed ranches in Kenya's non-tsetse fly areas were screened for evidence of previous infection with: Theileria parva (East Coast Fever); Trypanosoma congolense, T. vivax; T. brucei (Trypanosomiasis); Anaplasma marginale (Anaplasmosis); and Babesia bigemina (Babesiosis). 104. Calf rearing. Contracts for calf rearing are made one year in advance with ranchers selected according to the acceptability of the animals from the result of serological testing. The newborn calves are collected in groups (25 to 35) following further on-ranch testing and brought to the ILRAD calf-rearing unit. They are fed with milk from nipple-bottles and weaned on to a concentrate feed at about 10 to 12 weeks of age. At that time they are moved to roofed pens where they can remain until ready for use in experiment. Depending upon the manner of costing, the financial expenditure to produce one calf by this method is not less than $700 nor more than $1,000. The present facilities permit the rearing of 270 to 290 calves per year. 105. The success of this system can be judged by, at least, three criteria: calf mortality in 1979 was 0.9%; condition of the animals: without exception, the members of the Panel were very impressed with the excellent condition of the animals; acceptance by users: the scientists using cattle were unanimous in the appreciation of their quality although not necessarily so receptive of the results of allocation decisions. 106. Careful consideration must be necessary to increase the calf­ rearing facilities. The possibility is that the increased use of cattle described earlier may not require many more of these specially reared animals. If expansion does become necessary, it may be tempting to provide the accommodation at Kapiti Plains (see paras 110 to 117) because of the restricted nature of the ILRAD site. The Review Panel is of the opinion that this should not be contemplated nor should any facility be provided on the ranch for laboratory work. One minor exception is that a small room may be required for the work of the Clinical Medicine/ Diagnostic Laboratory Unit which will, no doubt, require to collect blood samples from the ranch cattle from time to time. 33 107. _W_e_a_n_e_d_ __c_a__tt_le. These animals are purchased around six months of age and are used in experiments with less exacting requirements than are met by the animals reared at ILRAD from birth, The same difficulties arise over their allocation as with reared calves, The numbers required at the current rate of usage are about 250 to 300 per year. 108. Allocation of cattle. The allocation of cattle is primarily the responsibility of the ILRAD Animal Committee. The implementation of the Committee's decisions is the responsibility of the officer-in-charge of the ILRAD Farm Animal Production Unit. Because of limited accommodation for rearing, and holding, any delay during any phase of this sequence decreases the throughput, Consequently, delays may occur in the scientist receiving the animals which it had been decided he or she should have. This would appear to be a serious cause of frustration but projects are in hand to increase the holding and experimental accommodation. 109. Other laboratory animals. Sheep and goats are purchased as required. The small animal unit produces large numbers of rats and mice which satisfy 80% of the demand for rats and 100% of the demand for mice with the exception of small numbers of strains of a specific genetic specification; accommodation for the supply of rabbits seems to be limited. 110. An ILRAD cattle production ranch. The original system of purchasing cattle for experiment had difficulties from the beginning. The problem was to identify large enough farms possessing good records and with a good health history, It was anticipated that the number of such farms would tend to decrease. The alternative of ILRAD having its own farm or ranch for animal production began to be considered some two years ago and financial provision was requested in the budget submission for 1980. This proposal received the approval of TAC and a total sum of US$1.2 million was allocated for the purchase of land and livestock. 111. A search for a suitable property was commenced in mid-1979. Two farms were selected for further study: 1) Marula Estates Limited, Naivasha, and 2) Rapiti Plains Estates Limited, Ronza. These two farms were examples of what might be possible within the financial limit, namely, a relatively small farm on good land (Marula) or a large ranch in an arid area (Rapiti Plains). A firm of agricultural consultants (Capricorn Consultants Limited, Rilifi) was engaged to conduct a study of both properties. As a result of this study it was decided that Rapiti Plains Estate provided the better option. The visiting Panel visited Rapiti Plains Estated on the 12th of October 1980 and met the owner, Mr. F. Howden, who had established the ranch some 40 years ago, and Mr. J. Howard, the Estate Manager. The following is a summary of the salient points. 34 112. The area of the estate is 13,000 hectares at an altitude of around 1,800 m. The region is arid with an average rainfall of about 500 mm per annum. Communications by tarmac road and by rail are good, the distance from ILRAD being about 60 km. Although the N.E. boundary is formed by the main Mombasa/Nairobi road there is no public road or track crossing the estate. The sole entrance is from the main road and the internal roads are well constructed and well maintained giving access to all parts of the estate in all weather. A minor road to Konza runs parallel to the S.E. boundary. The Mombasa/Nairobi railway runs parallel to the S.W. boundary at a distance of 2.5 to 3 km with the intervening ground in Government ownership but undeveloped. The boundary fencing and the internal fencing which divides the property into one mile squares is well constructed and maintained. The boundary fence on the S.W. boundary is .incomplete but an inner perimeter fence is provided by the line of the first of the one mile square fences within the boundary. The herd has been built up and maintained on a policy of maximum self-containment. All these factors account for its excellent health status and its high calving rate. 113. The aridness of the ranch has been overcome by a system of widely spread boreholes and dams supported by a pipe distribution system and catchment furrows providing an adequate water supply. The railway line, because of transport of cattle from the coast, presents a slight risk of the introduction of infected tsetse flies being brought from the fly belts in the coastal area. The undeveloped Government land between the railway and the S.W. boundary of the ranch provides a most effective barrier which must be preserved. Measures should be taken to ensure that if any development of this land is ever contemplated, its use be restricted to the growing of crops. 114. The conclusion of the consultants was "It is an outstandingly well run going concern which any purchaser could take over with minimal problems". The Panel was impressed with the excellent condition of the cattle, the meticulous way in which the owner had developed an adequate supply of water in this arid zone. The owner is sympathetic towards game, large numbers of which were seen (hartebeeste, Impala, Thomson's Gazelle and Grant's Gazelle) and which might have to be discouraged or other steps taken to limit the problem of contact with the cattle. 115. The principal assets possessed by the property from the point of view of the ILRAD requirements is its isolation and very limited access yet being within easy distance; the self-contained animal population which is not exposed in any way to other domesticated stock; the excellent condition and health status of the stock; and the stock-carrying capacity of the estate which would be sufficient for ILRAD's requirements except, perhaps, if there were more than two consecutive years of drought, The rearing of three day old calves at ILRAD would still continue on about the same scale as at present but with the calves being supplied from the ! 35 ranch. This procedure is required for the supply of as "clean cattle as possible for specific experiments for which such a specification for the animals is critical. The Panel believes that special measures will have to be taken on the Kapiti Plains Estates in view of the large numbers of game and in view of the extensive nature of the ranching. 116. An appropriate system would be to erect a game fence around one portion of the estate within which a herd was maintained for the production of the calves for rearing at ILRAD. Special efforts within this enclosed area would be taken to keep the tick population to a minimum, In addition I the possibility of introducing game control measures as an exceptional procedure should be discussed with the Kenyan authorities, The management of the estate for many years has been solely for beef production from Boran cattle by first-calving heifers calving at about three years of age and the produce as steers or surplus heifers, being sold at three years of age on a twice yearly basis when their condition was optimum after each of the two seasons of rains. Culled cows are of course, another product. 117. The ILRAD use of the ranch would make some fundamental changes. For example, some 250 head previously kept for three years or longer would be removed at three days. Some 400 head previously kept for three years or longer would be removed at six to nine months. This would have a potential advantage in that the carrying capacity for breeding females could be increased. This would provide a considerable potential for increasing the numbers of animals which could be used for experiment. The production of a surplus is no problem as they can readily be sold. Once the ILRAD operation becomes established at Kapiti Plains, consideration should be given to the.possibility of using land below a suitable dam for the growing of grasses or lucerne for the making of hay. This, of course, would require irrigation and a careful assessment would have to be made for the consequences of using the scarce resource of water for a product which can be purchased from areas of the country with a higher rainfall. This suggestion would probably not have been made by the Panel had it not noted that the purchase of hay in the past had engendered problems of various kinds. 118. There are several points which could not be readily assessed by the Panel especially the arrangements and their cost that would be necessary during the intermediary period of change from the current system to the new system. The principal point to be made is that it should not be assumed that the ILRAD programme can immediately be substituted for the ranch's present programme without the risk of unanticipated problems. The solving of such problems would undoubtedly incur additional financial expenditure. The Panel therefore strongly endorsed the ILRAD proposal to employ the present owner as a consultant and to continue to employ the present manager as an insurance against any precipitate changes in management jeopardising the success of the venture by which the savings on calf and cattle purchase would cover the running costs of the Kapiti Plains Estate.. 36 119. Recommendations. The Review Panel recommends: i) That the negotiations for the purchase of the leasehold and the fixed and movable assets of the Rapiti Plains Estate be completed as soon as possible; ii) That the self-contained characteristics of the herd be rigidly maintained; iii) 'That particular consideration be given to ensuring that the calves for rearing at ILRAD are from dams kept as free as possible from ticks; iv) That in view of the much more frequent traffic that will be produced by the ILRAD use of the ranch, strict discipline be maintained with regard to disinfection of cattle trucks and restriction of visitors to those with legitimate business; v) That the Board of Trustees take note that this large investment with such a potentially favourable cost/benefit ratio could prove to be a financial embarassment unless the very highest standards of estate management and animal production precepts are observed; Vi) That the ranch accounts be kept separately and be very carefully 'monitored ; vii) That every effort be made to ensure the preservation of the tsetse fly barrier between the railway and the ranch; viii ) That the possibility of obtaining authorization for control of game be discussed with the Kenyan authorities; ix) That the facilities for housing additional experimental animals on ILRAD premises be completed as quickly as possible. V. RESEARCH PROBLEMS AND ACHIEVEMENTS (a) General Introduction 120. The historical background of ILRAD outlined in Chapter III indicates why trypanosomiasis and East Coast Fever were initially selected for study but it is appropriate here to give more information on the selection of an immunological approach to their control. 121. In the case of East Coast Fever, there would be general agreement among interested scientists that this approach was justified. At that time no drugs were available to treat the disease, once clinically diagnosed and infected animals almost inevitably died. Even today there are no drugs as yet on the market although several promising leads have 37 been established. Even if available the problems of diagnosis and the economics of nursing convalescent animals for weeks remain serious drawbacks to a chemotherapeutic approach. Finally, (see Introduction to East Coast Fever) there was clear evidence that artificial immunization, with some important reservations, could be used successfully. 122. The situation was perhaps rather different with trypanosomiasis. The problems associated with antigenic variation in three species of parasite seemed to many observers probably insurmountable, On the other hand, there was no hard data on the actual number of metacyclic antigens (i.e. from the tsetse fly) and the possibility of "common" antigens was unexplored (see Introduction to Trypanosomiasis). There was also clear evidence that some West African breeds of cattle are naturally resistant to the disease and that East African cattle, with the aid of judicious chemotherapy, could develop immunity. If the mechanisms underlying these phenomena .could be understood the possibility of vaccination might be realized. 123. As far as ILRAD is concerned, it should be pointed out that research on large animals only became possible with the establishment of cattle—rearing facilities two years ago. Prior to that, work was confined to trypanosomiasis in small laboratory animals. Only since then have the contemporaneous creation of a Tick Unit and a Tsetse Unit made possible studies on East Coast Fever (a disease confined to cattle) and metacyclic trypanosomes. In spite of these limitations the achievements are considerable. 124. These are still early days, and the "spin off" in terms of antigenic variation, biochemistry, pathogenesis and immunology in these, perhaps the remaining outstanding veterinary problems in the world, is of great interest and real value to many aspects of basic and applied science which support veterinary and medical research. 125. In this difficult task ILRAD is not isolated. Already a network of collaboration has been established with centres of excellence in many countries. Relevant work is in progress in a number of institutes in both developing and developed countries. At the local level this includes the Kenyan Agricultural Research Institute, Muguga, the Kenyan Veterinary Research Institute, Kabete and the International Centre of Insect Physiology and Ecology. The Panel is hopeful that collaboration between ILRAD and the scientists at these laboratories will become more intensive. The signing of a recent agreement between ICIPE and ILRAD is a constructive move in this direction which the Panel commends. (b) Trypanosomiasis 126. _In__t_r_o_d_u__c_t_i_o_n. Trypanosomiasis is a disease complex which affects both man and his livestock in Africa, Asia and South America. Especially 38 in Africa it is one of the major constraints of rural development and is a serious disease of man. The disease in cattle is caused by three species of trypanosomes: Trypanosoma brucei, Trypanosoma vivax and Trypanosoma Congolense. The transmission of these three trypanosomes is mainly done by the tsetse flies. Trypanosoma evansi may be important in camels; the transmission of this species is mainly achieved by bites of bloodsucking flies other than tsetse flies. T. gambiense (West Africa) and T. rhodesiense (East Africa) are well known human pathogens, transmitted by tsetse as well. 127. Most of the countries south of the Sahara are affected and large areas potentially capable of raising large and small domestic ruminants are not used or only sparingly used for animal production. It is known that Africa harbours about 160 million head of cattle and even more sheep and goats; specialists estimate that these figures, especially those concerning cattle may be doubled and in some cases even tripled providing trypanosomiasis can' be kept under permanent control or eradicated. 128. Cattle, sheep and goats as well as other domesticated and wild animals may be infected by one, two or three trypanosome species. The animals develop an acute or chronic disease showing anemia and weakness and death occurs very frequently. In any case productivity is seriously affected and the economic losses are very heavy. This correspondingly influences human welfare and health. 129. •Some effective methods for control of both animal and human trypanosomiasis and their vectors are available and it is known that in some areas chemotherapy and insecticides have been successfully implemented. Nevertheless except in rare areas where success has been obtained after great and expensive efforts, trypanosomiasis still constitutes a major hazard for man and his livestock; neither chemotherapy nor prophylaxis, nor the use of short-acting or residual insecticides can be considered as yet economic and effective methods against the disease or its vector. The use of sterile male technique with tsetse flies is still uncertain and costly. 130. For some years both national and international authorities have become conscious of the potential importance of the phenomenon of trypano- tolerance which is known to be prevalent in some breeds of cattle and small ruminants and in many species of wild herbivores as well. Moreover, some trypanosolerant animals and maybe man, are capable of self-curing a trypanosome infection. 131. Despite the fact that trypanotolerance has been known for nearly 80 years, very little is known of its mechanism; only recently have modern techniques provided some hope for the study of this phenomenon. Its understanding could provide an opportunity for the development of many areas of Africa. This is quite apart from the opportunity to expand the indigenous trypanotolerant breeds of cattle, sheep and goats which survive at a very low cost under unfavourable conditions and tsetse pressure. Also East Africa may hopefully look to taking advantage of the potential of its trypanotolerant wildlife. 39 132. A practical vaccine for animal trypanosomiasis would be of inmense value. However, until now, the major constraints which have prevented the development of a suitable vaccine are: i) the trypanosomes may escape the host defense mechanism through their ability to undergo antigenic variation; ii) there are many different species of trypanosomes and in the same species one may have different serodemes . capable of producing different repertoires of variable antigens ; iii) trypanosomes may induce immunosuppression in their hosts up to a certain degree depending on the mammalian species. Recently, however, new knowledge has been acquired in the fields of biochemistry genetic engineering and immunology which allows better understanding of the intimate physiopathological mechanisms in both mammalian hosts and flies. 133. Obj ectives. The primary objective is to develop a vaccine for trypano somia sis. The major obstacles in achieving this is the ability of trypanosomes to vary their antigen, the presence of different strains of T. brucei, T. congolense and T. vivax, (the exact number being unknown) and the difficulty in culturing and maintaining in small animals the last two parasite species, For these reasons efforts are directed at determining the number of different strains, detecting and enumerating the different variant antigens, determining if there is a smaller number of metacyclic antigens and searching for common antigens which might produce immunity, perhaps combined with inmune manipulation. 134. It is also important to study the mechanism of antigenic variation at the gene and cell level in order to develop tools which might interfere with this process. Methods are being pursued to culture the trypanosomes in vitro and to produce relevant antigens by recombinant DNA as the latter method allows the production of large amounts of antigen not possible by isolating these directly from organisms especially T^_ congolense and T. vivax. 135. Studies on the immune response of the bovine to the various stages of trypanosomes are important in order to discover mechanisms which may be enhanced to produce a vaccine, In addition, the mechanism of killing of trypanosomes in vitro by different means is being analysed. 136._S_i_n_m_n_a_r_y_ _o_f_ _m__a_j_o_r_ _a_c_h_i_e_v__ements. Some major achievements have been made at ILRAD on the study of African trypanosomiasis. These include: i) The culture of T. brucei in vitro for the first time. ii) The discovery of a universally cross-reacting antigen consisting of carbohydrate-polypeptide. iii) The demonstration of the rearrangement of gene coding for the variant antigen in T_^ brucei and the expression of variant antigen in bacteria using recombinant DNA technology. 40 iv) The discovery of a unique pathway of glycosylation of the carbohydrate base in trypanosomes, not sensitive to tunicamycin and which could be the basis for new chemo­ therapy. V) The definitive demonstration of a restricted number of T. gambiense metacyclic antigens using monoclonal anti­ bodies. Vi) The study of the significance of immunosuppression by ‘trypanosomes in bovines. vii) Studies suggesting that stimuli which increase the transformation of slender to stumpy forms of 1\_ brucei may lead to organisms which can be better handled by the host. viii) Basic studies on antigen variation demonstrating that new variants arise as early as six days before the antibody response to the initial antigen is present. ix) The demonstration that the metacylic form of T\_ vivax has no coat; in this connection T. vivax membrane antigens might be effective in producing immunity to this species. x) A study of the chancre in cattle and wildlife which may be a valuable marker to detect different trypanosome strains (serodemes). xi) Basic studies of the pathology of trypanosomiasis. xii) The development of a multidisciplinary group! of experts with special facilities unique for the study of trypanosomiasis and ideal for the transfer of basic knowledge to field conditions. Comments on major achievements i) Biology 137. The ability to culture Trypanosoma brucei in vitro, at ILRAD, was a major advance in trypanosomiasis research. This has greatly advanced the ability to understand the biology and immunology of the parasite. Since the initial studies which achieved international recognition, the complete life cycle of T. brucei has been reproduced in culture. Tissue culture techniques have been improved using bovine epithelial cells which allow increase in recovery of the parasite. There still remains a problem in obtaining a large number of metacyclic forms. In addition, 42 clones of T. brucei have been cloned in vitro. These cloned organisms however, have not yet been able to be cultured throughout their cycle. 138. More recently attention has been directed to T. congolense. Tissue culture would be especially .useful since much smaller numbers of these organisms can be recovered from experimental animals for study compared to T^ brucei. By the use of endothelial cells as a feeder layer, it has been possible to grow T. congolense blood stream forms for about 35 days. 41 Further improved methods for isolating these trypanosomes using Percol gradients have been achieved. In contrast to the difficulties in growing blood stream forms of T. congolense, the developing forms found in the insect and which have no coat grow very well. 139. The ability to grow trypanosomes vitro has made possible some important studies. It has been possible to show that antigenic variation will occur in vitro in the complete absence of antibody demonstrating that antibody plays a selective role rather than an inductive role in antigenic variation. This had been suggested before by other experiments using x-irradiated animals, The in vitro culture system has been used successfully to screen trypanocidal drugs and may prove useful in studying the pharmacodynamics of these drugs. 140. Interesting studies on immune evasion have been carried out. Trypanosomes without their antigenic coat are able to activate the alternative complement pathway and are lysed whereas blood stream forms with their antigenic coat are not; those studies further suggest that the coat may have evolved to protect to protozoa from this powerful primitive blood lytic system. It further suggests that, were it possible to prevent coat formation, the resulting organisms would be rapidly lysed in the host. 141. Recent interest has centred on the killing of parasites by toxic products which result from the oxidation of polyamines by polyamine oxidases. African trypanosomes are known to contain the polyamine spermidine. It is of interest that six ruminant sera containing polyamine oxidase killed the trypanosomes in the presence of spermidine; six non-ruminant sera lacking this enzyme did not. Studies in the future will be directed to see if this killing mechanism can be exploited in host resistance to trypanosomes. ii) Immunology 142. Studies have been carried out which carefully analyse the phenomenon of antigenic variation. Using cloned ^ brucei organisms it was confirmed that the progression of antigens A—>B---->C—>D was not invariable - i.e. that A could progress to a number of other antigens, but B was the most common. Of interest was the finding, using the fluorescent activation cell sorter, that new variants occurred as early as six days after the injection of a clone: long before antibody was induced to diminish the number of the earlier variant. 143. Basic studies on the host response to T. brucei may have uncovered a most interesting finding, namely that slender forms of T^ brucei are not recognized by the host at all: and antibodies are only produced when the slender trypanosomes change into pleomorphic stumpy forms. Other 42 strains of mice in which the change from slender to stumpy forms is faster resist the infection better. When a slender form is injected into the bovine it becomes pleomorphic and evokes an antibody response, The proteins of slender and stumpy forms are being analyzed by two dimensional gels a most sensitive assay to determine the specific proteins involved in this transformation, Once detected, the techniques of monoclonal antibodies, recombinant DNA, and biochemistry will be applied to determine how this switch-can be facilitated. 144. Studies on the metacyclic form of cloned T. brucei show that the number of metacyclic antigens may be limited, Using monoclonal antibodies, four antigens have been identified, of which two make up over 90% of the organisms. When all four monoclonals are used, all the metacyclics are stained using immunofluorescence, Monoclonals to one strain however do not stain metacyclics of another strain. Studies on T. congolense are planned. 145. Of special interest is the finding that the metacyclic form of T. vivax may have no coat but only a membrane, A common membrane antigen has been identified and is being characterized, It is possible that membrane antigens of these organisms might produce immunity, and this deserves further investigation as a possible vaccine. 146'. Studies in the bovine have shown that much of the antibodies IgM •and IgG in the serum is directed against the trypanosome, This is different from studies in the mouse which showed that trypanosomes induced a lot of IgM and IgG which was not specific for the trypanosome, a phenomenon known as polyclonal activation. iii) Biochemistry and Molecular Biology 147. A universally cross—reacting antigen present in all variant antigens so far studied (greater than 20) consists of a protein carbohydrate complex. This complex may play a role in building up the variant antigen on the surface of the blood stream form of the trypanosome. Of interest is the finding that the build up of carbohydrate on this common antigen, a process known as glycosylation, is by a unique metabolic pathway not known to exist in mammals, and not inhibited by tunicamycin, an inhibitor of glycosylation in mammalian systems, Isolation of this enzyme and the delineation of its mode of action could lead to the search for specific inhibitors which might lead to a new chemotherapeutic approach to the treatment of trypanosomiasis. 148. Studies of synthesis of variant antigen have shown that a protein without sugars can be translated by messenger RNA (m RNA) iai vitro. Sugars are then added inside the trypanosome, in the Golgi endothermic reticular system of the cell by glycosylation enzymes, These are inhibited by tunicamycin. On the other hand the carbohydrate formation of another chain, which appears to be important for stacking the variant antigen on 43 the surface, is not inhibited by tunicamycin. A number of membrane- bound enzymes which glycosylate the variant antigen have been identified. 149. Recent studies using a new drug, Sinefungin, which inhibits methylation show much promise, This drug will inhibit new mRNA synthesis: it might thus inhibit the appearance of new variant antigens. 150. The first cloning of a parasite gene and the expression of V» parasite antigen by recombinant DNA technology was carried out at ILRAD. Further studies are contributing to the understanding of the mechanism of antigenic variation at the gene level. Recombinant DNA technology is a powerful tool which has the possibility for example, of producing large quantities of T. vivax and T^_ congolense metacyclic or other antigens. iv) Pathology 151. The ongoing studies in this field are: the susceptibility of the host to infection and the factors involved; the kinetics of the parasite populations in the hosts; the pathogenesis; the mechanism of the immune reaction in the host at the time of infection and through its course; the methods to detect the parasite and the host reactions particularly the immune response. 152. The appearance of a swelling, the so-called chancre, in human beings after the bite of an infected tsetse fly is a phenomenon known for a long time. It is the place of the first contact between the parasite and the host; it is important to have valuable and exact information about the immune reaction which takes place on this site. 153. Studies have been carried out with T. congolense, T. brucei and T. vivax in cattle and goats. Microscopical changes could be found at the bite site; the trypanosomes seem to multiply in the skin itself and this is associated with a marked lymphoid cellular reaction. Another interesting immune phenomenon was the different reaction against homologous and heterolous challenges which reflected the difference in serodemes and could be used as a biological marker; this could be a first step in the study of a feasible metacyclic vaccine, provided the number of serodemes is low. Further experience in this field is urgently needed. 154- In view of the practical application of immunization procedures, studies have been carried out to assess the use of adjuvants in potentiating different types of immune responses in cattle; the antigen used was variant specific surface antigen, biochemically well characterized; marked differences were observed depending on the kind of adjuvants used and some promising protective reactions were observed. 44 155. As the phenomenon of immunosuppression in laboratory animals has been known for a few years, it was interesting to study the reaction in cattle as well, in order to determine the susceptibility to infection with trypanosomes and other pathogenic agents, Preliminary studies in cattle have already given evidence that there are different reactions in mice and in cattle; in the latter species there seems to be no significant degree of depression. 156. The reason why animals die from trypanosomiasis is mainly anaemia; studies in this field will be continued since many pathogenic mechanisms remain obscure, It should be noted that the laboratory of pathology plays a service role for the other laboratories of ILRAD. 157. Trypanotolerance. It is recognized that the exploitation of trypanotolerant breeds of cattle offers one of the most important additional methods for the control of animal African trypanosomiasis, particularly in the humid savanna areas of West Africa. 158. Recent scientific advances at ILRAD in the understanding of the immune response to trypanosomes in cattle, have provided the ILRAD scientists with the opportunity to investigate the basic mechanisms of trypanotolerance. At the same time important field studies have been carried out in the Gambia; the objectives were to study the mechanism of the trypanotolerant phenomenon in N'Dama cattle in its natural environ­ ment and to compare it with the reactions of trypano-sensitive zebu cattle. 159. For the first time a large-scale comparative study of zebu and N'Dama cattle has unequivocally demonstrated the advantage of the N'Dama cattle in terms of parasitaemia, morbidity, mortality and self cure. Several papers on this study were issued and the Panel expects that a comprehensive report for wider circulation be published, possibly as a joint venture between ILRAD, FAO and ILCA. 160. More information is required about several aspects of trypanotolerance which include: i) the mechanism underlying trypanotolerance and the environmental factors which might affect trypano­ tolerance; ii) the genetics of trypanotolerance; this information is essential for future breeding programmes; iii) the identification of a genetic marker for trypano­ tolerance; iv) the evaluation of the productivity of trypanotolerant breeds living under different levels of challenge and kept under different management systems. 45 161. This work should be linked to the FAO African Trypanosomiasis Control-Programme and the ILCA network in West Africa established to evaluate the productivity of trypanotolerant livestock (point (iv) above). Potential sites include the Gambia, Ivory Coast, Upper Volta, Togo and Zaire. This ambitious but highly valuable five year project will need on ILRAD's side the participation of two scientists; the related costs are likely to be obtained through special funding in view of the interest of recipient and donor' countries in this area. 162. The Tsetse Unit. Soon after starting studies in trypanosomiasis it became evident to ILRAD scientists that the establishment of a tsetse fly breeding unit on the premises itself was needed, An isolated 1 independent building was built providing room for breeding different species of Glossina under natural and artificial feeding procedures as well. The following tsetse flies are already reared or will be in the near future: Glossina morsitans morsitans, £.m. centralis, £. pallidipes, G. fuscipes fuscipes, £. austeni and £. brevipalpis. The Glossina morsitans morsitans breeding unit is the most important one, harbouring about 9,000 breeding females; the other species will be maintained at 1,200 breeding females each. Natural bloodsucking feeding is carried out on rabbits. Besides this classical system an _in vitro system utilizing silicone membranes has been developed successfully. 163. The main function of the tsetse unit is to provide the different ILRAD scientists with both infected and non-infected flies. £. congolensq, T. vivax and £. brucei are used to infect the tsetse-. In the tsetse unit 1 itself or in collaboration with other ILRAD scientists the following research projects are undertaken or will start in the near future: i) Comparative studies on the vectorial capacity of G.m. morsitans and G.m. centralis for £. brucei, T. congolense and vivax; ii) Studies to discover if the establishment of trypanosomes is genetically determined; iii) The development of the trypanosomes in tsetse flies in terms of transmission to hosts. This will include studies on the infection rate and transmission index; iv) Feeding behaviour in relation to epidemiology; v) Artificial membrane feeding on wildlife blood in terms of epidemiology; vi) The "chancre" in different host species including wildlife. 46 ; 164. The well equipped and maintained fly-rooms allow a meticulous monitoring of the colonies, which is the first step to a comprehensive genetic approach. Emphasis is put on two main points: epidemiology and the preliminary phase of the immune process in the host, These studies are conducted with high accuracy and deserve great interest and support. (c) Theileriasis 165. Introduction. East Coast Fever (ECF) caused by Theileria parva is the most important tick-borne disease of cattle in East and parts of Central Africa. Annual mortality has been estimated in the region of half a million cattle each year, This loss represents an enormous drain on the agricultural resources of the countries affected, where cattle play an important role in the economy of rural communities as well as the countries as a whole, In addition, the improvement of breeds by using exotic stock is prevented, because of the complete susceptibility of exotic breeds to ECF. Advances have been made in the understanding of ECF during the last decade, particularly at the former East African Veterinary Research Organization (EAVRO) now KARI (Kenyan Agricultural Research Institute) at Muguga in Kenya. Immunization of cattle was achieved by concurrent injection of a normally lethal dose of sporozoites with tetracycline drugs. However, immunity was confined to homologous challenge and immunized animals were not necessarily protected against challenge with heterologous strains of T^ parva and T^_ mutans. This problem was partly overcome by using a "cocktail" consisting of sporozoites of several T. parva strains, but it has been more difficult to protect cattle against the various strains of T^_ parva lawrencei carried by the African buffalo which serves as a reservoir host of this T. parva sub-species. 166. Another immunization method has been developed against T. annulata by the Kmron Veterinary Institute in Beit Dagan, Israel, T. annulata causes a disease in cattle similar to that caused by T. parva. This disease is of great importance for a large number of countries; virtually all countries between 10° and 40°N from Morocco to Bangladesh are affected. Lymphoblastoid cell-lines infected with macroschizonts of T^ annulata were passaged 100 to 300 times until attenuation of the parasites was achieved. Attenuation does not impair immunogenicity of live schizonts. Cattle are vaccinated with such schizonts. Recently the inoculum has been made available in the frozen state and more than 10,000 animals have been vaccinated up to now. The vaccine does not produce carriers since the attenuated macroschizonts have lost their ability to transform into microschizonts. Hence parasitaemia is not induced by vaccination and the vaccine strain cannot be transmitted by ticks. The protection induced by attenuated macroschizonts is usually sufficient except in pregnant cows or after very severe exposure to infected ticks. Although 47 killed antigen from macroschizonts induces immunity against the macroschizonts it does not protect against sporozoite challenge. 167. Thus it has been shown in principle that cattle can successfully be immuni zed against both 1\_ parva and T^_ annulata; these results suggest that it may well be possible to develop a practical immunization method against parva and that other stages than the sporozoite stage may be potent immunogens. It would be desirable to develop a vaccine containing only killed antigen, or, at least, stages which will not develop further to the tick-infective forms in the red blood cells. 168. Objectives. The primary objective is the development of a vaccine against ECF; the major problem encountered in the field is the existence of antigenically different strains that do not induce cross-protection. Such strains, especially those showing major antigenic differences, should •I be identified. 169. Successful research on 1\_ parva can be carried out on a large scale only if a steady supply of sporozoites, macroschizont-infected cells and other material is available. To this end it should be possible to select highly susceptible tick strains which will produce large numbers of sporozoites. In addition, _in vitro techniques for the production of sporozoites or sporozoite antigens should be developed if possible. 170. Macroschizont production in lymphoblastoid cell cultures should be improved since large scale production would probably be necessary. Besides sporozoites and macroschizonts, the culture of other stages (sexual stages, kinetes, erythrocytic stages) would be extremely helpful for further research, e.g. cloning of parasite strains and isolation of stage-specific antigens. A major objective is the cloning and purification of developmental stages of parva, especially of sporozoites and macroschizonts. 171. The development of T. parva in its bovine and its tick host is insufficiently known and requires further research. The target cells of the sporozoites in the bovine host should be identified, as well as possible secondary host cells of macroschizonts. It would also be desirable to identify the haploid and diploid stages in the tick vector. 172. Another objective of the programme would be the appreciation of the mechanisms underlying acquired immunity to theilerial parasites i using the bovid/T. parva model. In theory these could depend on a humoral response against the sporozoites inoculated by the tick or on a cell- mediated reaction against the schizont-infected cells. Generally speaking most workers have favoured the latter explanation since protective anti­ body has never been adequately demonstrated in the past and since immuni zed cattle usually show only a mild schizont reaction after challenge. ! 48 173. Before the inception of ILRAD information on these mechanisms was limited ; this was due partly to the difficulties associated with working with the disease outside East Africa; also within East Africa the previous remit was to develop practical techniques of immunization. 174. The pathology of East Coast Fever has not been extensively st^’d ied. It is. important to know how the parasite becomes established and operates in the host and the mechanisms by which clinical disease is produced. In particular it is important to study quantified infections since the hope of a successful vaccine may depend on the events subsequent to minimal infective doses and whether or not these can induce a protective response. 175. A study of adjuvants to potentiate the immune response is desired since little is known about this in the bovid; since adjuvants may be necessary in both candidate trypanosomiasis and theilerial vaccines, a study of these in relation to humoral and cell-mediated responses is a sensible objective. 176. Summary of major achievements. These include: i) An isolated area for epidemiological studies and vaccination trials has been selected and evaluated; ii) Sufficient supply with infected ticks has been achieved by establishing a tick unit; iii) Three T.£. parva and one T._p. lawrencei strains have been cloned in lymphoblastoid cell lines (total: 32 clones); iv) A start has been made to analyse DNA in Theileria parasites. Recombinant DNA technology could conceivably be used for antigen production; v) Analysis structures and functions of the salivary glands of the tick vector are making excellent progress; vi) The development of vitro techniques which indicate that cell-mediated immune responses ; are highly relevant in the acquisition of resistance in designing vaccination methods and in typing Theileria strains; vii) A preliminary study has been made which indicates that anti-sporozoite antibody may also be highly important in the immune response; 49 vii i ) A study of the sequential pathogenesis of the disease and the kinetics of the infection in the lymphoid system is largely completed. Comments on major achievements i) Epidemiology 177. The area chosen for epidemiological study is the Coast Province of Kenya where ECF is endemic but limited in distribution by ecological boundaries which determine the survival of the vector. This study will be conducted in the Kilifi District in close collaboration with the Kenyan Veterinary Services. One strain Thjp. parva (Kilifi) has already been investigated and typed. It appeared to be identical with another strain of T. parva (Muguga) on both _in vivo cross immunity trials and ju vitro monoclonal and cell cytotoxicity tests. The fact that these two strains from distant areas are antigenically identical gives hope that the number of different strains is limited in the study area. ii) Parasitology 178. The supply of the research units of ILRAD with infected ticks or with sporozoites and their stabilates has been much improved during the last two years by the tick unit, A significant increase in infection rates of ticks was achieved by selection of certain tick strains. 179. Cell lines (lymphoblastoid cells infected with macroschizonts) from four isolates of T\_ parva (T\_p. Muguga, lh£. Kiambu 5, ^T._p. lawrencei Serengeti, l\_p. Kilifi) have been cloned. The clones were partly identified on the basis of host cell karyotypes and iso-enzyme patterns. 180. Recombinant DNA technology has been introduced and the first results have been obtained with variant-antigen genes of trypanosomes. Since this new technology is available important studies can be carried out with Theileria genes. 181. The structure and function of the acini and cell types of salivary glands of unfed and fed adults of Rhipicephalus appendiculatus have been described. The cell types-in which Theileria sporozoites develop can now be identified with certainty. Preliminary results were achieved on the structure of T. parva sporozoites and on the transformation of their host cell. iii) Immunology 182. Detailed studies on the immune reaction against the schizont have utilized the fact that schizonts may be grown _iu vitro in cultures of lymphoid cells which become "transformed" after infection with sporozoites. It has been shown that the transformed cell bears the phenotype of a 50 mature T-cell. Current research is attempting to show whether this implies that only T-cells or perhaps only sub-sets of T-cells are infected by sporozoites or whether other cell types may become infected and after transformation express a T-cell phenotype. 183. It has also been shown that the lymphocytes of donor calves mount in vitro responses against their own transformed cell lines: a mixed lymphocyte reaction (MLR), an index of cell mediated immunity is mounted by the cells of donor calves against their own transformed cell line. This was first demonstrated in collaborative work with the Kenya: Agriculture Research Institute (KARI). One interesting observation is that while lymphocytes from cattle undergoing infection or immunization provoke KLR reactions, those from •immune cattle which resist challenge, as demonstrated by the absence of schizonts, do not. This perhaps suggests that" in these cattle a very early immune response is elicited. 184. A highly significant advance in this area of immunology has been the demonstration that lymphoid cells from immune animals show cytotoxic reactions against Theileria-transformed cell lines (cell-mediated lympholysis- CML). Further, the reaction is MHC restricted (i.e. the cells of immune animals are only effective against their own infected cells and not those from other bovines). 185. This observation is important in three ways: it demonstrates a mechanism of resistance; it shows that immune T lymphocytes must recognize both parasite antigens and MHC antigens on the surface of the infected cell. This is of great relevance in vaccination techniques; it hopefully provides a simple, cheap and rapid technique for typing Theileria strains from any area without the need to undertake long, cumbersome and expensive cross immunization experiments. 186. Other aspects currently under study include a categorization of the cell types involved in cell mediated reactions in the bovine, a rather neglected subject, using the MLR and CML reactions. 187. An interesting observation has been that sporozoites incubated with antibody raised in rabbits and subsequently inoculated into cattle failed to produce infection. This suggests that a sporozoite antibody may also be useful for strain typing and is possibly encouraging for vaccine develop­ ment, perhaps ultimately with recombinant DNA technique. iv) Pathology 188. In the field of pathogenesis one of the main accomplishments has been a study of the interaction of sporozoites with host cells; it has confirmed that the addition of infective tick salivary gland material to bovine lymphocytes _in vitro and the subsequent inoculation of the washed cells into syngeneic or allogeneic cattle will establish infection in the 51 former (as few as 103 cells) but not in the latter (up to 106 cells); an important point as regards a potential live sporozoite vaccine is that there seems to be a narrow margin between the establishment of a lethal infection and failure to establish any infection; this work is continuing. 189. The study of the establishment of infection with schizont- infected cell lines has highlighted that the situation is rather similar in that infection may be induced with 103 infected cells in syngeneic hosts whereas more than 106 cells are required in allogeneic cattle. However, in contrast to sporozoites, there seems to be a wider dose- range within which animals recover from the infection. The pathogenesis of East Coast Fever has been examined with particular emphasis on the kinetics of the infection in the lymphoid system, This may be of great importance in the designing of a live vaccine, The results showed that the increase in parasite numbers does not follow a simple exponential pattern but that 8-10 days after infection the level of parasitism was still less £han 1%. 190. A long overdue study in the history of ECF, now largely completed, has dealt with the dissemination of the disease in the host and the resultant lesions. It describes the sequential pathogenesis of the disease from the initial germinal centre response to the parasite in the drainage lymph node to the final lesions associated with lymphocytolysis. 191. As regards adjuvants, this work on cattle is quite recently established. 192. _T_h_e_ _T__ick Unit. The tick unit was established in June 1978, and is managed by one scientist who is supported by a technician, Colonies of Rhipicephalus appendiculatus; R. evertsi; Amblyomma variegatum and Boophilus decoloratus were obtained from various sources. Sporozoite- stabilates were or will be made of: Theileria parva parva (Muguga) ; parva (Kiambu 5); T. mutans and T. velifera. 193. The main function of the tick unit is the supply to ILRAD scientists of sporozoite stabilates, infected and non-infected ticks and with material from infected and non-infected cattle. The tick unit itself and in collaboration with other institutions has undertaken to initiate the following projects: studies on sporozoites of parva ; in vitro culture of various stages of T.j). parva ; tick cell culture; preparation of transformed and autologous lymphoblastoid cell lines; development of more efficient techniques of infecting ticks with Theileria; cloning of T. parva kinetes (Babesia bigemina is used as a model); _in vitro production of ecdysteroids by tick tissues; production of large numbers of ticks for infestation of experimental paddocks. 194. The well managed unit is fulfilling a key service function for ILRAD and cooperating institutions. Further expansion of the unit is necessary. 52 VI. TRAINING, COMMUNICATION & TECHNOLOGY TRANSFER (a) Training 195. The mandate of ILRAD provides, among others, for the training of different levels of man-power in furtherance of its objectives; according to the Memorandum of Agreement it was envisaged that training could take different forms among which are; organization of discussion groups, seminars, workshops and conferences on topics related to the work of the Laboratory; provision of opportunities for advanced professional training and experience in animal disease research within the scope of the Laboratory in cooperation with Universities and other research institutes; training of scientists who will be involved in research, education and action programmes in cooperating countries in which the Laboratory's programme will be applicable; and assistance to cooperating countries in using and applying i tbe research results of the Laboratory. : 196. _O_r_g_a__n_iz__a_t_io__n. The programme is under the direction of a Training and Outreach Officer who has the responsibility for expanding an existing on-the-job technician's training programme, the coordination of training ; for higher degrees and the organization of conferences, This officer was , annointed in August 1979 and is supported in the technician s training programme by two other experienced senior officers (one a Research Associate and the other the ILRAD Services Officer), The policy of the training programme is formulated by the ILRAD s Training Committee which is responsible to the Board of Trustees through the Board s Training Committee. 197. _T_e__c_h_n_icians' training. Trainee technicians are given on-the-job training in their respective laboratories and formal training on a day- release basis at the Kenya Polytechnic, Nairobi, Different courses are offered and of different duration, varying from three months (pre-technician's course) to three years (Ordinary Diploma in Laboratory Technology). A total of 19 trainees are presently enrolled in different courses at the Polytechnic. In vie-w of shortage of trained manpower, ILRAD has taken steps to strengthen the Kenya Polytechnic in order to ensure that technicians needed for its work can be adequately trained and also to contribute to trained manpower supply in the area, In this respect, some of ILRAD's staff are already involved in the teaching of certain courses at the Polytechnic which are relevant to its needs and also participate in joint training efforts with ICIPE, Kenya Veterinary Research Institute, Muguga, Kenya Trypanosomiasis Research Institute, Kabete and the Veterinary t 53 Faculty of the University of Nairobi, Also because no suitable course exists in the Polytechnic for animal attendants, ILRAD is planning to mount a suitable course for its staff on the production of laboratory animals and laboratory animal medicine so that a diploma to be awarded will be recognized throughout Kenya. 198. Undergraduate training. During 1980, four undergraduates from the University of Nairobi were employed .at ILRAD during the summer vacation and were exposed to the activities of the different laboratories as part of training, for future participation in the centre's programme. The Panel does not feel able to justify this programme because it is not particularly relevant, has limited productivity, and imposes additional burden on the Centre that may affect more relevant training programmes. 199._P_o__s_tg__ra__d_u_a_t_e_ __tr_a__ining. A significant part of ILRAD's training programme is postgraduate training. Arrangements are being negotiated with the Universities of Guelph and Nairobi and with the New York and Washington States Veterinary Colleges for suitable candidates to be registered at the Universities and carry out in ILRAD, research relevant to its programme. Such students will be supervised by ILRAD's scientists with support from postdoctoral fellows. At present, ILRAD has eight postgraduate students who are doing research leading to a Ph.D. degree. Three of the students are sponsored by ILRAD, two by the Kenya Government, two by the Government of the Sudan and one by WHO/Kenya Government. These graduates come from different countries including Uganda, Kenya, Australia, and Rwanda. It is projected that the number of postgraduate students registered at any (one time may reach as many as twenty, dependent on the number of core scientists. 200. There are at present no clearly defined procedures on how post- graduates are selected, it would therefore be desirable for ILRAD to establish contacts with African institutions and universities in the above fields and systematically identify promising individuals who could be incorporated into the training programme of ILRAD, and particularly :: into the postgraduate component, For Ph.D students in particular, it would seem best to have arrangements whereby one to two years would be | spent at a university doing course work and the rest at ILRAD. The research projects, once defined by the ILRAD training committee, should be advertised and the best candidates sought. ILRAD should closely collaborate in this 1 respect with IBAR/OAU, FAO and Association of African Universities. A meeting of interested African institutions and universities would also help ILRAD in this endeavour. 201. Postdoctoral training. Originally, postdoctorals were conceived primarily within the training structure of ILRAD. The oustanding calibre of those recruited over the years has, in fact, shown that this group should i not come primarily under training but be included within the scientist ; staffing structure, a trend which ILRAD has followed. At present, 13 .- ■ ! ,: 54 postdoctorals, six of whom are supported from outside sources, are in post, most of them are from the more developed countries of the world. There are still eight ILRAD budgeted positions to be filled. The Panel is of the strona opinion that postdoctorals should not be part of the training component of the institute but should be part of the staffing pattern. 202. International Training Courses i) African Trypanosomiasis, ILRAD was involved in the leadership training course on African trypanosomiasis jointly organized in 1977 with OAU/FAO/WHO at ILRAD's facilities. Seventy-one participants from 31 African countries participated in the training which aimed at equipping individuals capable of training others with necessary technical skill so as to strengthen national institutions and form a basis upon which future work of the cooperating bodies can be applied to field problems. ii) UNESCO/ICRO*/ILRAD/DSE**/WHO Course. This course titled: "Advanced Techniques in Immunological and Biochemical Approaches to Haemoparasitic Research" was held at ILRAD in September 1980 and provided participants opportunity to study modern parasitological, biochemical and immunological techniques used in the study of blood—borne parasites. Sixteen participants most of whom were from African countries took part in the course. 203. Miscellaneous Training i) Cooperative programme with GTZ. Under this programme, research workers from Germany can come to ILRAD for research experience and training, Two German research workers have benefitted under this scheme. ii) Participation of staff in other training programmes. ILRAD's staff have participated in the training courses organized by the International Atomic Energy Agency on the application of nuclear techniques in animal parasitology and the FA0/WH0/0AU training seminar on trypanosomiasis held at Bobo—Dioulasso, Upper Volta. ! Conferenc f 204.___________ e_s_ _and Workshops. Dissemination of information and communication are also ensured by conferences and workshops, One conference held in 1979 on the "Beneficial Application of in vitro techniques to Health and Economy of Developing Nations" was jointly sponsored with the United States Agency for International Development, FAO, the Rockefeller Foundation, WHO and the Wellcome Trust. * ICRO = International Cell Research Organization. ** DSE = Deutsche Stiftung ftir Entwicklungshilfe. 55 205. Two training conferences were also held in 1979, one on "Recent Developments in Research on Ticks and Tick-borne Diseases in Kenya , and the other one "Immune System and Parasites". Also in 1979, a workshop was held at ILRAD, in collaboration with WHO on the "In vitro Cultivation of Major Tropical Disease Pathogens". In 1980 a conference on "The Impact of Research and Animal Disease Control on Livestock Production", was held with the collaboration of IBAR (OAU), ILCA and the Association of Institutes for Tropical Veterinary Medicine. 206. _O__b_s_e_r_v_a__ti_o_n_s. Training represented in 1980 about 2.7% of the operational budget of ILRAD and for 1981 it is envisaged that it would represent about 4.8% of the above total, the calculations having taken into account in addition to stipends and cost of reagents, the cost of animals used by the laboratories where the postgraduates have been training. The amount of resources devoted to training is somewhat misleading as the indirect costs, related to laboratory work, are particularly high, due for instance to the rather generous use of equipment and supplies. This does not imply, however, that an increase in postgraduates will necessarily be accompanied by a comparable increase in the demand for large animals and thus increased cost. 207. Training and technology transfer have not, as yet, found their proper niche in the planning and strategy of ILRAD. The major cause of this situation has been the full concentration of ILRAD staff attention and efforts in the formulation and implementation of their respective research programmes. ILRAD has, therefore, selected institutes of advanced learning in Kenya for collaborative efforts in training (Kenya I ; Polytechnic and Nairobi University) and has established with institutions \: existing in Kenya joint research programmes (with the Kenya Veterinary Research Organization, Muguga, the Veterinary Laboratories, Kabete, and the International Centre for Insect Physiology and Ecology, Nairobi). 208. While the efforts of ILRAD in training courses must be commended in view of the short period of its existence, the above situation must be improved because ILRAD is an international institution and should devote the same attention and energy to fulfilling its Africa-wide mandate as other Africa-based IARCs, i.e. WARDA, IITA and ILCA. 209. This would evidently entail the reappraisal of the resources to be devoted to training and of the budgetary allocations, It should also make imperative a better definition of training priorities and policies and the establishment of a functional training unit. Irrespective of ILRAD's achievements in attaining one or both of its major objectives, the scientific work at ILRAD is of such a high standard that its training component could well be one of the major assets of the Centre. 210. Apart from these practical and essential considerations it is also mandatory for the Centre to contribute significantly to the improve- 56 ment of the research capabilities of African states in the fields of parasitology, biology, pathology, immunology and biochemistry. A planned process of technology transfer should be instituted with less ad hoc arrangements in the choice of collaborative projects and more attention paid to linking training to subsequent transfer of ILRAD's technology and results. In other words ILRAD has so far confined itself to narrow territorial limits as regards technology transfer in the belief that the vaccines, once discovered, would then easily be transferred to interested countries. The first years' of ILRAD's activities have demonstrated that the work is even more complex than anticipated and it is therefore recommended that technology generation and transfer include a wider and more active participation of scientists and institutions in African and possibly other countries. (b) Documentation 211. Library. The Panel is satisfied with the services provided by the library to ILRAD's scientific staff and trainees. During the last two years, it has increased its journal holdings from 62 to 233 titles which cater to most of the needs of the different research disciplines. The library also carries a substantial number (about 2,000) of relevant books and some documents. Journals or books not available in its holdings are usually obtained through the inter-library loan, a system which has worked satisfactorily. Back copies of journals are held as'microfiches or microforms. Photocopies of original documents are made .available to staff requiring them. The possibilities for ILRAD to be linked with a computerized retrieval .system should be explored. 212. Organization and future plans. The library has a professional librarian who is in charge and is assisted by two graduate assistant librarians and a library assistant. The library committee of the institute is responsible for overseeing the library activities and decides, based on consultation with scientific staff which journals should be added, which should be continued and which should be discontinued. Although there was no indication of future plans, it is clear that with the develop­ i ment at ILRAD, the library will be involved in the extraction of abstracts ■ of work relevant to ILRAD's activities for circulation amongst the scientific staff and also in preparing bibliography for the two major diseases of its concern, trypanosomiasis and theileriasis. (c) Communications and Information 213. The communication and information section of ILRAD is more or less in its embryonic stage and would need to develop fast in order to cope with anticipated activities of ILRAD. It is expected that this section will be responsible for collating materials for the annual reports, for the translation of printed materials and the distribution of information 57 on ILRAD to interested organizations and individuals, So far the annual research and training report of ILRAD is the only communication which aims at giving an overview of ILRAD's progress; it is highly technical in nature and represents an assembly of scientific papers written by groups of scientists; it is suggested that a newsletter, or a "research highlights", type of report be published so as to make ILRAD better known in the world at large, and particularly in Africa. ILRAD could also profitably participate in the FAO/WHO/OAU Tsetse and Trypanosomiasis Information and News Service. 214. At the present time, communication from ILRAD is unilingual; efforts must be made to reach those Francophone and possibly Portuguese speaking areas of Africa that will make use of developments at ILRAD. The question of language is so important to the communitation process in Africa that ILRAD cannot afford to be unconcerned. Among the four Africa-based IARCs, ILRAD is the only one which is strictly unilingual; this is largely due to the absence of a well structured training policy and of any outreach programme; however as suggested in other parts of the report the situation is bound to change rapidly and ILRAD would need to devote resources to the translation of the proposed research Newsletter/ Highlights and to the language training of ILRAD staff and prospective postgraduates. With the modern audiovisual methods now available, the solution of this problem is no longer lengthy nor difficult. (d) Recommendations 215. In general, the Panel is favourably impressed with the efforts : made by ILRAD since its inception to develop its training programme in order to meet the challenge of strengthening its African input, and lay good basis for technology transfer. In particular, the Panel strongly commends ILRAD's efforts in the Technicians' training programme, endorses the collaborative arrangements in training both at the technician and postgraduate levels being negotiated with Universities, national and international organizations; and endorses the organization by ILRAD either jointly with other organizations or singly, of workshops, seminars and conferences as a means of training, informing scientists of the work of ILRAD and of facilitating beneficial interaction of research workers. 216. The Panel recommends: i) that Technicians' training be extended to include whenever possible, technicians from countries other than the East African subregion; ii) that ILRAD's training programme receive high priority in resource allocation in order that the institute can better fulfill its mandate for technology transfer. In this respect, the Panel recommends that 58 ILRAD should not wait for a scientific breakthrough before a substantial training of African scientists is undertaken; iii) that a better arrangement for identification and selection of potential postgraduate students and delineation of their research areas, than presently operates, be worked out. The Panel recommends that African Universities and institutions be closely involved in the selection of Suitable postgraduate students; iv) that selected postgraduate students be sent to cooperating Universities to undertake relevant course work before returning to ILRAD to pursue their research thesis. This necessarily reduces the amount of workload imposed on scientific staff in terms of instruction and offers better chances that the target number of postgraduates can be attained; v) that postdoctoral fellow’s should be part of the staffing pattern and not of the training programme; Vi) the introduction of short-term courses, either on individual basis for the acquisition of specialized techniques or on group basis as a means of additional training and contribution to technology transfer; vii) that ILRAD strengthens its communication and information section, produces a Newsletter or Research Highlights in English and French that will be widely distributed and ensure its annual reports reach as many institutes and individuals as possible especially within Africa to avoid the criticisms of many African countries of their ignorance of ILRAD's excellent work. VII. FUTURE PLANS AND RECOMMENDATIONS FOR RESEARCH 217. Starting from an assessment of the ongoing research on trypanosomiasis and theileriasis the Panel has examined the future plans and activities of the Institute as published in a document submitted to the Panel by the Director and entitled "The Next Five Years at ILRAD", dated February 1980. The document, which has not been examined in detail by the Board of Trustees pending the reaction of the Quinquennial Review Panel, describes proposals for further study on trypanosomiasis and East Coast Fever. It also makes suggestions for new ventures. 218. The Panel considers that some of the proposals are especially productive and these are described below in two sections, one on trypanosomiasis and one on East Coast Fever. The exact sequential priority of these projects and thus the specific allocation of personnel and other • .. * 59 funds should be determined by discussion between the Director, the co­ ordinators, with concrete inputs of the Scientific Advisory and Programme Committees. 219. By their nature, some of the projects are short-term, of two or three years duration, whereas others - such as field work studies - are long-term. Nevertheless the Panel recommends that each project be assessed annually and their internal priorities reappraised every two years in preparation of the biennial budget. The Panel's comments oc the proposals for new ventures follow under section (c). (a) Trypanosomiasis 220. Immuno-epidemiology 1 studies, including isolation of type serodemes from the Kilifi area and the determination of the frequency of infection by trypanosomes. This is a prerequisite for estimating the heterogeneity of the metacyclic challenge necessary to appraise the feasibility of a vaccination programme. It is important to develop methods to culture T. congolense and T. vivax in vitro and to facilitate their propagation in small animals. It is crucial to be able to handle these strains in order to evaluate and study the different strains (serodemes) in the field. Various methods should be applied to identify the serodemes and delineate immune mechanismsi to produce monoclonal antibodies to variant and common antigens, bovine immunoglobulin classes, specific bovine lymphocyte markers and methods to detect cellular immunity _in vitro and jLn vivo to trypanosomes including the use of the chancre. Current studies on the "interference phenomenon" observed when trypanosomes infection of one species is superimposed on another species, should be continued. 221. Project on the characteristics and number of metacyclic antigens of T. brucei, T. congolense and T. vivax. It appears that there are less variants of metacyclic antigens than variants of blood stream form antigens. Further, there are studies that suggest that animals immunized with metacyclic antigen by tsetse of one strain are immune to that strain, but not to others. It is thus necessary to pursue these findings by determining the number of metacyclic antigens present and whether they can induce immunity. These antigens may also be useful in developing reagents for research use in the field. An alternative approach to typing serodemes utilizing recombinant DNA technology should be explored. 222, T. vivax project. It is.important to confirm the preliminary electron microscopy findings that the metacyclic form of T. vivax is coatless. This would suggest that it shouldbe possible to immunize cattle against the membrane antigens and the organism would be killed before it had time to develop a coat. The lack of natural immunity could be 60 explained by the small amount of membrane antigen encountered from the tsetse bite. This project would also involve production of T\ vivax by culture and production of antigen by recombinant DNA. 223. Project directed at preventing antigenic variation includes: i) Studies on the isolation and mechanisms of the trypanosomal enzyme which glycosylates the universal protein-carbo- .hydrate antigen, and characterization of this antigen. This enzyme which is tunicamycin-resistant involves a metabolic pathway not found so far in mammals, The basic carbohydrate glycosylated by this enzyme may play a major part in placing the variant antigen on the outside of the membrane. Inhibitors of this enzyme - which because it is unique should not effect the host - could then prevent the expression of the variant antigen. It is a major finding which needs to be pursued actively. ii) Studies on the role and mechanism of polyamine oxydase in killing trypanosomes. The finding that polyamine oxydase in the presence of polyamines (which trypanosomes contain) produces products which are toxic to trypanosomes, should be pursued, It could be one basis for trypano- tolerance. Further it allows the delineation in detail of how trypanosomes cap be killed. iii) Studies on the role of Sinefungin in preventing variant antigen synthesis. This drug which inhibits methylation appears to prevent variant antigen synthesis, It may thus prove useful either in chemotherapy alone or in developing a vaccine. iv) Studies on the mechanism of transition of slender to stumpy forms, Present studies suggest that the latter form is better handled by the host. If ways were found to accelerate this process, it might be possible to develop a more effective attack on trypanosomes. 224. A collaborative study with West African institutions on the mechanism of trypanotolerance is encouraged, This is discussed in detail in an earlier section. Further studies on the mechanism and practical value of trypano­ tolerance of sheep, goats, wildlife and perhaps cattle in East Africa should be encouraged. (b) East Coast Fever 225. Immuno-epidemiological project. More strains of T. parva should be isolated from the Kilifi coastal area and typed. Cattle should be immunized against these local strains using various methods (see oelow) and exposed to field 61 challenge at a number of preselected geographic sites, Subject to successful results,the immunization programme should be extended and intensified with the ultimate aim of eliminating ECF in the study area. This is a long-term project. 226. The relationship between resistance to infection and the specificity of the cell mediated cytotoxic reaction (CML) response should be given a high priority because of its potential in the typing of strains and in the elucidation of the mechanism of immunity. 227. Project on antigen immunogenicity. Of interest are the studies on the immunogenicity of various antigens of macroschizonts killed or attenuated in culture, the use of attenuated sporozoites; and the vise of infection and treatment method. ! 228. Sporozoite research project. The production of sporozoites by infected ticks should be improved and the sporozoites concentrated, purified, quantitated and if possible also cloned. It is strongly recommended that sporozoites of 1\£. lawrencei should be obtained from KARI, Muguga, for preliminary parasitological studies. Immunological techniques and recombinant DNA technology should be applied to identify, purify, and produce sporozoite antigens. Irradiation or other means of attenuation of sporozoites should not be started before sporozoites can be quantitated. 229. In vitro culture project. Macroschizonts should be isolated from cloned cell lines and characterized. At the same time cloned cell lines should be characterized and large-scale production of such cells should be initiated. It is strongly recommended that stages other than the macroschizonts are also propagated _in vitro, particularly sporozoites. To this end tick cell cultures should be established. The in vitro cultivation of T. mutans and other Theileria species should be attempted. 230. Immunology project. Detailed analysis of the mixed lymphocyte reaction and cell-mediated cytotoxicity responses should be continued. As regards the cloning of _T. parva lawrencei, the production of monoclonal anti­ bodies to its sporozoites requires particular attention. A study on the efficacy of adjuvants in cattle should be continued. The use of genetically closely related cattle should be encouraged. This may be achieved by line­ breeding from the same sire or more closely by superovulation and ovum transfer. 231. Electron microscopy. The interaction between various parasite stages (kinetes, multiple fission bodies) and the salivary glands should be studied further. Other stages of the parasite and their host cells should be investigated subsequently. 62 (c) New Ventures and the Mandate 232. The mandate for the operation of ILRAD left open the question of a possible extension of its research programmes to "other serious animal diseases problems, for which its facilities ana expertise are appropriate, provided such extension is approved by its governing body and the Govern­ ment of Kenya does not object from a disease safety standpoint." The research programmes at ILRAD on trypanosomiasis and theileriasis have necessitated bringing together a group of scientists of many different disciplines. Their work has had to be supported by much sophisticated equipment in specially designed laboratories, The success of this has been described elsewhere in this report and the critical mass of intellectual force available at ILRAD could obviously be turned on to solving other intractable problems that still exist in medicine, both veterinary and medical. In animals, for example, with the virus disease, African Swine Fever, there are mysterious features about the response of the domesticated pig and its failure to develop an adequate defensive response. There are other "new" virus diseases of animals and man that have not yet been adequately studied. In the field of. parasitology, however, and especially in trypanosomiasis the infections of man present the same problems as do the infections of animals. Furthermore there are a number of other parasitic diseases of animals and man such as schistosomiasis, or those caused b}1 the Fasciola, the Anaplasmodia and the Babesia. The ILRAD group could make a significant attack on these problems. 233. The Review Panel has given careful consideration to the proposals for additional research presented to them in the ILRAD presentation. The Panel feels strongly that in spite of the case that can be made for extending the activities currently conducted within the mandate, the work at ILRAD should continue to be concentrated on the trypanosomiasis of animals and theileriasis - in the latter case specifically East Coast Fever. However, because of the incidence of a number of species of Theileria in Kenya, the work on East Coast Fever must include studies of these other organisms, namely T. parva lawrencei, T. mutans and T. taurotragi. An example of the necessity of this is that the African buffalo is the host of Theileria parva lawrencei from which theileriasis may be transmitted to cattle. 234. A summary.of the specific proposals of ILRAD and the comments of the Panel are given below. The comments of the Panel are given about each. i) Parasitic diseases of man 235. The Board of Trustees has accepted the principle that research at ILRAD can be undertaken on parasitic diseases of humans, provided that the projects are separately funded and that the techniques used and results obtained are. relevant to the main programme of ILRAD. 63 236. The Panel believes that to establish specific projects on human parasitology is to go too far beyond the mandate. On the other hand, it cannot accept that special knowledge available at ILRAD should be denied for the progress of science in general. It is proposed, therefore, that scientists in the field of human parasitology should be permitted to work at ILRAD to acquire a technique or to discuss subjects of comparative interest. This can be arranged on a limited ad hoc basis with complete support being provided by external funding. ii) Other Theileriasis 237. It is proposed that in addition to work in the context of East Coast Fever on the species of Theileria present in Kenya, there might also be work on T\_ annulata and 1\_ sergenti which occur.in Africa, North of the Sahara, and in Asia and Europe. 238. The Panel reiterates that work on the Theileria present in Kenya is appropriate and necessary but solely within the context of the research programme on East Coast Fever. It strongly opposes work on T. annulata and T\_ sergenti. Application of results obtained at ILRAD relevant to the two species could only be considered as cooperative programmes. iii) Heartwater 239. The Panel is against ILRAD embarking on a comprehensive programme on laboratory research, field studies and epidemiology of heartwater until more progress has been made in the trypanosomiasis and theileriasis programmes. It accepts, however, that occasions will arise when field 1 work is begun, when differential diagnosis will be required. iv) African Swine Fever 240. Despite the interest evidenced by some countries actually affected by African Swine Fever, the Panel considers that work on this disease cannot be justified at ILRAD because of the studies already in progress in the United States of America and Europe. It also notes that scientists in other disciplines would be required, Besides the Government of Kenya is presently against work with this virus. v) Tick-borne viruses 241. It is proposed to work also on the Nairobi Sheep Disease and the Congo Crimean Haemorrhagic Fever group of viruses. The Panel does again not recommend a diversion from the two ILRAD programmes. Work on these viruses is proceeding in a number of other places and presently they are not of great economic importance. 64 (d) Recommendations regarding New Ventures 242. The Panel _re_c_ommends that of the additional research topics proposed by ILRAD only the following should be endorsed by the Board: i) Limited visits by parasitologists working on human disease to acquire techniques or exchange information on an ad hoc basis with complete external funding; ii) Research in the context of East Coast Fever on species of Theileria present in Kenya; iii) Differential diagnosis of heartwater as part of field work on theileriasis and trypanosomiasis. 243. It may appear that the Panel is being unduly restrictive in its limited recommendations for new ventures but it believes that there should be no diversion from the two ILRAD programmes on trypanosomiasis and East Coast Fever. It does, however, envisage a continuing progress towards success in conquering these diseases which would, consequently, permit undertaking research on new topics. Diversification could not be immediate as such success would require a change in emphasis towards training and co­ operative programmes for the dissemination of the new knowledge and \ technologies, changes which would be likely to absorb the available resources. The time for these developments must anyway be measured in quinquennia at which point a new assessment would have to be made of the priorities for research on animal disease. One reason for having to make new assessments would result from the greatly increased utilization of land for animal production by the conquering of either trypanosomiasis or East Coast Fever. i (e) Recommendations regarding Staffing 244. The Panel recommends:.. i) That the Tsetse Unit should have one additional scientist or research associate since the whole supply of tsetse and metacyclic trypanosomes depends on a single individual at present; ii) That the Tick Unit be expanded to allow concurrent infestation of at least six further calves. One additional research associate should be recruited to help manage the unit for the same reasons as (i) above; iii) That as soon as possible four scientists be recruited on the core budget on an initial two year contract. One of these should be a field immunologist based in Kilifi to co­ ordinate the ILRAD/Kenya Government project. A further two should be concerned with biochemistry/immunology and with molecular biology respectively for Theileria research; the last one should be affected to cell sorting in the Immunology Laboratory; 65 iv) that a programme of trypanotolerance in West Africa be instituted as soon as possible and linked to the ILCA network*, two ILRAD senior core scientists should : be associated with the project and ILRAD should attempt : to obtain extra core funds to support it. VIII. ACKNOWLEDGEMENTS 245. The Panel wishes to thank ILRAD's Director, Dr. Allison, for the careful preparations made for the Review, for making available his wide knowledge of. the research programmes of the Centre, for the excellent organization of the Panel timetable and for the hospitality which the Panel enjoyed during its stay in Kenya. The Panel is also grateful to the Board Chairman and Executive Committee of ILRAD for having shared the final stage of the Review; to the scientific staff of ILRAD, with which the Panel had numerous informative and interesting discussions. Finally the Panel expresses its deep gratitude to Mrs H. Drummond and secretarial staff and to Mrs Susan McRae without whom the draft report would not have been finished on time. t 1■: I ■■ t « ANNEX I A. PROGRAMME OF THE REVIEW PANEL Sunday 5 October Assembly of the Panel Monday 6 cL • in • Meeting of Panel with Dr. Allison and senior staff (laboratory coordinators and heads of support units); exposi of Director about ILRAD programme: questions and answers. p .m> Ministry of Livestock Development: meeting of Panel with H.E. Mr. J.N. Osogo, Minister for Livestock Development and Dr. I.E. Muriithi, Director, Livestock Development Department. Tuesday 7 & ILRAD: Visit to the tsetse vector unit. Visits to Wednesday 8 laboratories and support units. Discussions and interviews regarding administrative and scientific management. Thursday 9 à • IQ • Kabete: Visit to the Veterinary Research Laboratory (Dr. S. Chema, Chief, Veterinary Research Officer, Drs. E. Fink, D. Rtìttcher, M. Heising, GTZ, L. Roberts, Walter Reed Hospital) . P-m- Muguga: Visit to the Kenyan Agricultural Research Institute (Dr. W. Masiga, Director Veterinary Laboratories, KARI and Dr. A. Young and his ODA team) Friday 10 sl .m. Chiromo: Visit to ICIPE laboratories (part of the Panel) ILRAD: Visit to clinical medicine and farm unit; visit to tick unit (part of the Panel) P • IQ • ILRAD: Visit tó laboratories by individual Panel members. Saturday 11 ILRAD 10:00-11:00 Meeting with internal Training Committee and discussions on training policies 11:00-15:30 Individual interviews of Panel with laboratory coordinators and chiefs of support units 15:30-18:00 Discussions with Director and above staff regarding ILRAD's future plans Sunday 12 a .m. Visit to prospective cattle production farm, F. Howden's ranch at Rapiti Plains (F. Howden, J. Howard, G. Davies) p • IQ • ILRAD: preparation of draft report Annex I - page 2 Monday 13 & ILRAD: Individual discussions of Panel members with Tuesday 14 senior staff; Panel meetings for preparation of draft r report Wednesday 15 & Thursday 16 ILRAD: Drafting/typing of draft report Friday 17 ILRAD: Finalization of draft report. Expose by Panel Chairman of Review findings and recommendations to Director, Executive Committee (Sir Alexander Robertson, Board Chairman, Dr. K.F. Wells, Dr. D. Zwart, Dr. I.E. t Muriithi) and senior staff. B. ' LIST OF DOCUMENTS MADE AVAILABLE TO PANEL 1. Originated by ILRAD Report on Research and Training Activities, 1979 Summary Report of the Scientific Advisory Committee Report of the Meeting of the Programme Committee List of Publications Five-Year Plan 1980-81 Programme and Budget with Mid-term Revision Research' Summaries - several notes on individual laboratories and units I 2. Originated by TAC Secretariat Terms of Reference Revised List of Questions Notes on the Meeting between the Quinquennial Review Panel Chairman and ILRAD Board Comments on the List of Questions by: USAID, UNDP, Australia, WorId Bank Tentative Programme for Panel Tentative Outline of Final Report » Annex I - page 3 Note on the Meeting between FAO Animal Production and Health Division (AGA) and Quinquennial Review Panel Chairman and Secretary Review of Historical Background and Mandate i Tentative Observations on the above CGIAR/TAC Guidelines for Quinquennial Reviews TAG Report on ICIPE Application to become Membèr of the CGIAR System with Report of TAC Mission to ICIPE (September 1980) Excerpts of TAC Meetings Reports related to ILRAD 3. Originated by FAO Report of the Expert Consultation on Research on Trypanosomiasis (October 1979) Report of the Second Consultation of the Programme for the Control of African Animal Trypanosomiasis (December 1978) The African Trypanosomiasis (November 1976) FAO Programme for the Control of African Animal Trypanosomiasis and Related Development (November 1979) Trypanosomiasis Risk or Challenge (December 1979) Second FAO Expert Consultation on Research on Tick-borne Diseases and their Vectors (December 1977) Review of Recent Progress in the Control of Ticks and Tick-borne Diseases in East Africa (August 1976) East Coast Fever Immunization in Malawi Report of the Informal Discussion on Research Needs to Produce an African Swine Fever Vaccine 4. Miscellaneous Informal Summary of Proceedings - CGIAR Meeting (Oct./Nov. 1979) Brochures on the CGIAR System An International Laboratory for Animal Disease Research in Africa (by J.J. McKelvey Jr. and J. Pino - November 1970) Memorandum of Agreement between the Government of Kenya and the Rockefeller Foundation (September 1973) » ANNEX II * - » SHORT GLOSSARY 1 In view of the technical nature of the report it has been found useful to list hereunder the definitions of some of the terms used, kindly provided by ILRAD and completed by FAO. 1. Acini - Group of cells in tick salivary glands which can be infected by theilerial parasites. 2. Allogeneic - Genetically different animals of the same species. 3. Ecdysteroid - Hormone controlling moulting. 4. Glycosylation - Process by which sugars are specifically attached by the action of enzymes (glycosyl transferases) to protein molecules so converting them to glyco­ proteins . 5. IgG - An antibody class arising later in infections, of single unit structure which has high specificity. Various classes of IgG have different biological functions, e.g. transfer of immunity from mother to newly born offspring, parasite killing, etc. ? 6. IgM - An antibody class arising early in infection which because of its structure (equivalent to five IgG molecules) is very efficient at initiating such biological processes as parasite killing, etc. 7. Kinete - Motile developmental stage of Theileria which develops in tick gut cells and invades tick salivary gland cells. 8. Macroschizont - The stage of Theileria developing in the bovine lymphoid cells, which is largely responsible for the pathogenesis of theileriasis by destroying host lymphoid cells. 9. Metacylic - The stage of development of the parasite in the trypanosomes tsetse fly which is able to infect new mammalian hosts. They usually occur in the salivary glands and/or mouth parts. ; .. I • Annex II - page 2 10. Methylation - Addition of methyl groups to newly formed nucleic acids. ht 11. MHC - Major histocompatibility complex - a complex of genes responsible for recognition of nonself substances and the process which removes them from the body. 12. Percol - A medium by which cells can be separated according to their density. 13. Pleomorphism - The differentiation of Trypanosoma brucei bloodstream forms into stages, which are capable of infecting the tsetse fly. 14. Seroderne - The range of different surface variable antigens r expressed by the descendants of a single trypanosome. 15. Sporozoite - The infective form of Theileria transmitted from the tick to the mammalian host. 16. Stabilate - The form in which a live organism is stored at low temperature for use at a later stage. 17. Syngeneic - Genetically identical individuals (i.e. identical twins or cells). ■I 18. T. Cell - A lymphocyte (white cell) which has passed through the thymus and is fundamental to the activation of F defence mechanisms. 19. Tunicamycin - An antibiotic which specifically inhibits the first lipid intermediate step of glycosylation. 1