114 TRANSACTIONSOF THE ROYAL SOCIETY OF’TROPICAL MEDICINE AND HYGIENE, VOL. 70. No. 2, 1976.
Sixteenth Seminar on Trypanosomiasis Organized by the Trypanosomiasis Advisory Panel of the Ministry of Overseas Development, held at the Zoological Society of London, Regents Park, London, on 9th and 10th October, 1975 DR. L. G. GOODWIN, F.R.c.P., in the Chair The seminar had as its theme “Trypanosomiasis Today”, the first day dealing with African trypanosomiasis and the second day with South American trypanosomiasis, and took the form of nine invited papers followed by discussion, the invited speaker acting as the sectional chairman. The following papers are shortened versions of the invited papers.
African sleeping sickness today P. DE RAADT Division of Malaria
and other Parasitic Diseases, World Health Organization,
In addition to the recorded occurrence and geographical distribution of sleeping sickness there is an inestimable proportion which remains undetected. Present diagnostic methods, of limited reliability, require facilities and skills, often beyond the capacity of rural health services. The Figure and Table illustrating recorded new cases of sleeping sickness over the last five years must therefore be regarded with caution. Since 1950 the diseasehas been in a “state of controlled endemicity”. From the work of ASHCROFT(1959), NASH (1969), DUGGAN (1970), JANSSENS(1971) and BAKER (1974), four main phases of development may be distinguished, starting with the obscure phase, when there was evidence that sleeping sickness existed but when no epidemiological information was available. Before the 20th century, when African populations were concentrated in towns and villages, with little intercommunication, it is likely that trypanosomiasis occurred as separate foci, each running independent endemic and epidemic courses. The scale of transmission widened with the establishment, at the turn of the century, of colonial administrations, and the development of internal communications. Absence of medical surveillance resulted in the large classical epidemics characteristic of the second phase (along the Congo River between 1896 and 1906, and north of Lake Victoria from 1902 to 1906). The urgent need for control was recognized and remarkable progress was made in the 10 years following the first notification of trypanosomes in human blood by DIJTTON (1902): trypanosome species were identified, life cycles and principal vectors were discovered, the first chemotherapeutic remedy, Atoxyl, was developed, and even detailed experimental studies on antigenic variation were carried out. The next phase was initiated with large scale control operations, through bush clearing, and surveillance and treatment of the population by mobile teams. Eradication was never achieved but no further major epidemics occurred. Prior to this a series of epidemics occurred in Central and West Africa during the 1920s and 193Os,and at the same time Trypanosoma rhodesiense started its spread northwards. By the early 1950s a spectacular decline in most of the African foci was brought about, bringing us to the fourth and present stage, of “controlled endemicity”. The situation is vulnerable owing to the permanent menace of activation or re-activation of tsetse infected areas up to epidemic levels. This can occur for unpredictable reasons, such as:
Switzerland
1. Individual travel, from one tsetse area to another The concept of SCOTT(1965) that particular strains may have epidemic properties by being more virulent to man and easier in establishing infection in flies, may be valid and deserves further investigation. Local travel in Africa has often been underestimated in range and frequency (MANSELL PROTHTXRO, 1963). ~A striking example is the Koudougou focus in Upper Volta, where recently an outbreak of sleeping sickness occurred. Circumstantial evidence has been obtained that the increase in trypanosomiasis was due to the frequent visits of relatives backwards and forwards over a distance of 800 kilometres (MASSACRIERand DWALLET, personal communication). 2. Population movements. Settlement in previous trypanosomiasis foci as occasioned by development schemes, man-made lake projects, or political disturbances, may occur before development of the necessary social infrastructure, and public health services are often inadequate to handle sleeping sickness. 3. Increased man-fly contact. Increased transmission can be occasioned by environmental changes forcing the vector to concentrate on man as a source of food. 4. Chance occurrence, as suggested by ONYANGO et al (1971). 5. Re-infestation of previously cleared tsetse areas. Inadequate maintenance of population surveillance, or follow-up of previous control operations, during long periods of low endemicity, or because of lack of facilities, are important causes of resurgence of infections. Turning to the situation in Africa today, the geographic distribution appears as follows: West Africa In the seven countries collaborating in OCCGE* (Dahomey, Ivory Coast, Mali, Niger, Senegal, Togo and Upper Volta), the incidence is as low as 10 new infections yearly out of 100,000 people examined by mobile teams. Although surveillance teams make over five million examinations yearly, total coverage is not obtained and breakthrough epidemics were reported in Mali around Bamako (which are now under control) in north-east Dahomey and 40 kilometres north of Abidjan. The latter was discovered by an incidental observation and apparently a severe but localized outbreak is developing. The turning point in the OCCGE countries was probably the application of pentamidine prophylaxis in 1949, and this is still practised to a limited extent, routinely in isolated foci, and elsewhere if emergencies occur. Nigeria has its excellent tsetse control scheme, which has been well maintained up to the present day, and for several years
115
P.DERAADT
Table - Number of recorded new cases of human trypanosomiasis, Africa, 1968-74 Number of new cases Total population (in miilions)
Country Western Africa 3 Dahomey 10 Ghana 3.7 Guinea 0.5 Guinea Bissau 5 Ivory Coast 5.5 Mali 4.4 Niger 79 Nigeria 4.2 Senegal 2.1 Togo Upper Volta 5.8 Central Africa 6.2 Cameroon 1.7 C.A.R. 4 Chad 1 Congo 1 Gabon 25 Zaire Eastern and Southern Africa 0.7 Botswana 4 Burundi 26 Ethiopia 13 Kenya 5 Malawi 4 Rwanda 15 Sudan 15 Tanzania 11 Uganda 4.5 Zambia TOTAL
Fig. Known foci of sleeping sickness, 1975.
1968
1969
1970
1971
17 181 379
18 160 351
11 166
135
357
425
38
376 356
176 221
9 944
0 599
393
190 0 529
144 193 1 498
43 36 164
16 84 262
16 14 145
57 114
219 19
217
229
125
103
22
63 47
112 17
:i
59
175 IS 172 38 5,124
61 134 86 3,357
4,9:;
6,l:;
36 65 28 43
37 12 173 20
I
0
21
20
403
530 56
90 SO 7,148
148 231 4
69 8,172
59 78
44 16
0 69 8 564
81 127 9,140
1972
22
272 75 12 26 2 35 2
569 184 200
8,501
17 23
69
49 413 4,126
1973 2157 156 55 46 136 388
0 331 10 25 75
297 91 15 42 32
1974 410
>69 31
11 87
188 0 >132 2 21 78 476
79 54
91 47
114
1 7
13
0 13 22 612
160 394 7,126
125 477 37
391 2,899
287 488 2,551
116
SEMINAR
ON
TRYPANOSOMIASIS
sleeping sickness has only been reported from Gboko area.
-
the
Central Africa Zaire has been the typical example of how interruption of medical surveillance, as occurred between 1960 and 1966, can disturb controlled low endemic situations. The prevalence, which had been kept under 0.02% for several years, had risen to well over 10 ‘A before systematic surveillance was restored. Mobile teams are now operational again, although full coverage has not yet been obtained. Zaire remains the country with the highest number of sleeping sickness patients in Africa. Of the countries collaborating under the aegis of OCEAC** (Chad, Central African Republic, Cameroon and Congo), in Chad and CAR mobile teams succeeded in covering the total population at risk. In Cameroon the Fontem focus was re-activated recently, and several hundred patients were reported. These were diagnosed by passive detection, and there is an urgent need for systematic examination of the population. With regard to Angola, the prospects give cause for concern as several cases have been reported in recent years across the Za’ire border and the present unstable situation in the country is likely to favour conditions for a new outbreak. East and South Africa The foci in Southern Sudan are at the moment the most important in Africa, with 287 new patients discovered last year by passive detection in only a small area, where the public health services cannot possibly cope with the problems involved. There is no information on the development of the T. rhodesiense focus in Ethiopia and the adjacent sleeping sickness area in the Sudan. The main T. rhodesiense areas are in Tanzania and in Zambia; apparently low virulent strains appear in the Luangwa Valley and the occurrence of healthy carriers may indicate a change of surveillance strategy as the situation becomes more similar to that of T. gumbiense. In conclusion, in spite of the cumbersome nature of medical surveillance and vector control, substantial efforts are continued in Africa. The coverage is far from complete and where breakdown of surveillance occurs, classical epidemic outbreaks can result. The answer is to develop a system of monitoring which must be adapted to suit the local services. This may mean that compromises have to be made in terms of sensitivity and even safety, if it is the price to be paid to obtain a guarantee for the continuity of efforts. Different levels of sophistication of control efforts can be defined. The first consists of the application ofsimple means of case detection in the field, for instance by using convenient serological tests, plus a standardized generally apphcable treatment scheme. At the next level, a more refined method of diagnosis could be applied in nearby specialized laboratories, and special treatment centres could be established in each area. An effort can also be made to reduce man/fly contact by simple vector control operations such as regular spraying of frequented sites near bridges and water collecting points. Where facilities permit, the maximum level of control methods can be exploited. For T. gambiense this means mobile teams with microscopists, and for T. rhodesiensethe establishment of equipment and trained microscopists in the rural dispensaries and hospitals, including facilities for animal **Organisation de Co-ordination pour la Lutte contre les Endemies en Afrique Centrale.
AFRICAN
SLEEPING
SICKNESS
TODAY
inoculation. Entomological analysis should be carried out and appropriate measures taken to maintain the lowest possible man/fly contact. As the latter level of efforts can only be attained in a few areas, the W H O programme for trypanosomiasis aims to assist research on improving diagnosis, particularly those techniques which require relatively little skill and materials. In the W H O programme, relevant fundamental research is supported in the field of chemotherapy and to stimulate co-ordinated efforts on research on chemotherapy and immunology, a special programme has been initiated to support joint research programmes among African centres and academic centres outside Africa. As far as the optimai application of current control tools is concerned, W H O is establishing a team in West Africa which will study the vector control methods of the moist Savannah and will evaluate and develop new serological tests, such as the Enzyme Linked Immunosorbent Assay (ELISA) and the indirect haemagglutination test in capillary tubes (BON& 1976). With these two components, it is hoped to establish an all-round application of trypanosomiasis control methods in Africa by distributing technical manuals and making appropriate equipment in the form of test kits available all over Africa. References Ashcroft, M. T. (1959). A critical review of the epidemiology of human trypanosomiasis in Africa. Tropical Diseases Bulletin, 56,1073-1093. Baker, J. R. (1974). Epidemiology of African sleeping sickness. In Trypanosomiasis and Leishmaniasis - with special reference to Chagas’ disease, pp. 29-50. Ciba Foundation Symposium 20 (new series). Bone, G. (1976). In Annales de la Societe’ Beige de Midecine tropicale (in press). Duggan, A. J. (1970). An historical perspective. In The African Trypanosomiases, ed. Mulligan, H. W. & Potts, W. H., pp. 41-88. London: Allen & Unwin. Dutton, J. E. (1902). Preliminary note on a trypanosome occurring in the blood of man. Thomas Yates Laboratory Reports, 4,455. Janssens, P. G. (1971). Review of the sleeping sickness situation. Zeitschrift fiir Tropenmedizin und Parasitologic, 22, 213-225. Manse11 Prothero, R. (1963). Population mobility and trypanosomiasis in Africa. Bulletin of the World Health Organization, 28,615-626. Nash, T. A. M. (1969). Africa’s Bane: The Tsetse Fly. London: Collins. Onyango, R. J., Geigy, R., Mwambu, P. M. & Moloo, S. K. (1971). Sleeping sickness survey in Musuma District, Tanzania. V. The endemicity of Rhodesian sleeping sickness in Ikoma Serengeti area-final discussion. Acta tropica, 28,221-225. Scott, D. (1965). Epidemic Disease in Ghana. London: Oxford University Press. As a footnote to this paper Scheiber, Braun-Munzinger and Southgate* reported detection of ultra-low density parasitaemias in large volumes of haemolysed human blood from two well-known residual foci of T. gambiense in Togo. Densities of l-3 trypanosomes per ml of blood from four out of 75 healthy people receiving routine pentamidine prophylaxis were reported. The possibility that such individuals might occasionally infect tsetse flies was suggested. *National Institute of Hygiene, Lome, Togo and Ross Institute of Hygiene, London.
Sixteenth Seminar on Trypanosomiasis Organized by the Trypanosomiasis Advisory Panel of the Ministry of Overseas Development, held at the Zoological Society of London, Regents Park, London, on 9th and 10th October, 1975 DR. L. G. GOODWIN, F.R.c.P., in the Chair The seminar had as its theme “Trypanosomiasis Today”, the first day dealing with African trypanosomiasis and the second day with South American trypanosomiasis, and took the form of nine invited papers followed by discussion, the invited speaker acting as the sectional chairman. The following papers are shortened versions of the invited papers.
African sleeping sickness today P. DE RAADT Division of Malaria
and other Parasitic Diseases, World Health Organization,
In addition to the recorded occurrence and geographical distribution of sleeping sickness there is an inestimable proportion which remains undetected. Present diagnostic methods, of limited reliability, require facilities and skills, often beyond the capacity of rural health services. The Figure and Table illustrating recorded new cases of sleeping sickness over the last five years must therefore be regarded with caution. Since 1950 the diseasehas been in a “state of controlled endemicity”. From the work of ASHCROFT(1959), NASH (1969), DUGGAN (1970), JANSSENS(1971) and BAKER (1974), four main phases of development may be distinguished, starting with the obscure phase, when there was evidence that sleeping sickness existed but when no epidemiological information was available. Before the 20th century, when African populations were concentrated in towns and villages, with little intercommunication, it is likely that trypanosomiasis occurred as separate foci, each running independent endemic and epidemic courses. The scale of transmission widened with the establishment, at the turn of the century, of colonial administrations, and the development of internal communications. Absence of medical surveillance resulted in the large classical epidemics characteristic of the second phase (along the Congo River between 1896 and 1906, and north of Lake Victoria from 1902 to 1906). The urgent need for control was recognized and remarkable progress was made in the 10 years following the first notification of trypanosomes in human blood by DIJTTON (1902): trypanosome species were identified, life cycles and principal vectors were discovered, the first chemotherapeutic remedy, Atoxyl, was developed, and even detailed experimental studies on antigenic variation were carried out. The next phase was initiated with large scale control operations, through bush clearing, and surveillance and treatment of the population by mobile teams. Eradication was never achieved but no further major epidemics occurred. Prior to this a series of epidemics occurred in Central and West Africa during the 1920s and 193Os,and at the same time Trypanosoma rhodesiense started its spread northwards. By the early 1950s a spectacular decline in most of the African foci was brought about, bringing us to the fourth and present stage, of “controlled endemicity”. The situation is vulnerable owing to the permanent menace of activation or re-activation of tsetse infected areas up to epidemic levels. This can occur for unpredictable reasons, such as:
Switzerland
1. Individual travel, from one tsetse area to another The concept of SCOTT(1965) that particular strains may have epidemic properties by being more virulent to man and easier in establishing infection in flies, may be valid and deserves further investigation. Local travel in Africa has often been underestimated in range and frequency (MANSELL PROTHTXRO, 1963). ~A striking example is the Koudougou focus in Upper Volta, where recently an outbreak of sleeping sickness occurred. Circumstantial evidence has been obtained that the increase in trypanosomiasis was due to the frequent visits of relatives backwards and forwards over a distance of 800 kilometres (MASSACRIERand DWALLET, personal communication). 2. Population movements. Settlement in previous trypanosomiasis foci as occasioned by development schemes, man-made lake projects, or political disturbances, may occur before development of the necessary social infrastructure, and public health services are often inadequate to handle sleeping sickness. 3. Increased man-fly contact. Increased transmission can be occasioned by environmental changes forcing the vector to concentrate on man as a source of food. 4. Chance occurrence, as suggested by ONYANGO et al (1971). 5. Re-infestation of previously cleared tsetse areas. Inadequate maintenance of population surveillance, or follow-up of previous control operations, during long periods of low endemicity, or because of lack of facilities, are important causes of resurgence of infections. Turning to the situation in Africa today, the geographic distribution appears as follows: West Africa In the seven countries collaborating in OCCGE* (Dahomey, Ivory Coast, Mali, Niger, Senegal, Togo and Upper Volta), the incidence is as low as 10 new infections yearly out of 100,000 people examined by mobile teams. Although surveillance teams make over five million examinations yearly, total coverage is not obtained and breakthrough epidemics were reported in Mali around Bamako (which are now under control) in north-east Dahomey and 40 kilometres north of Abidjan. The latter was discovered by an incidental observation and apparently a severe but localized outbreak is developing. The turning point in the OCCGE countries was probably the application of pentamidine prophylaxis in 1949, and this is still practised to a limited extent, routinely in isolated foci, and elsewhere if emergencies occur. Nigeria has its excellent tsetse control scheme, which has been well maintained up to the present day, and for several years
115
P.DERAADT
Table - Number of recorded new cases of human trypanosomiasis, Africa, 1968-74 Number of new cases Total population (in miilions)
Country Western Africa 3 Dahomey 10 Ghana 3.7 Guinea 0.5 Guinea Bissau 5 Ivory Coast 5.5 Mali 4.4 Niger 79 Nigeria 4.2 Senegal 2.1 Togo Upper Volta 5.8 Central Africa 6.2 Cameroon 1.7 C.A.R. 4 Chad 1 Congo 1 Gabon 25 Zaire Eastern and Southern Africa 0.7 Botswana 4 Burundi 26 Ethiopia 13 Kenya 5 Malawi 4 Rwanda 15 Sudan 15 Tanzania 11 Uganda 4.5 Zambia TOTAL
Fig. Known foci of sleeping sickness, 1975.
1968
1969
1970
1971
17 181 379
18 160 351
11 166
135
357
425
38
376 356
176 221
9 944
0 599
393
190 0 529
144 193 1 498
43 36 164
16 84 262
16 14 145
57 114
219 19
217
229
125
103
22
63 47
112 17
:i
59
175 IS 172 38 5,124
61 134 86 3,357
4,9:;
6,l:;
36 65 28 43
37 12 173 20
I
0
21
20
403
530 56
90 SO 7,148
148 231 4
69 8,172
59 78
44 16
0 69 8 564
81 127 9,140
1972
22
272 75 12 26 2 35 2
569 184 200
8,501
17 23
69
49 413 4,126
1973 2157 156 55 46 136 388
0 331 10 25 75
297 91 15 42 32
1974 410
>69 31
11 87
188 0 >132 2 21 78 476
79 54
91 47
114
1 7
13
0 13 22 612
160 394 7,126
125 477 37
391 2,899
287 488 2,551
116
SEMINAR
ON
TRYPANOSOMIASIS
sleeping sickness has only been reported from Gboko area.
-
the
Central Africa Zaire has been the typical example of how interruption of medical surveillance, as occurred between 1960 and 1966, can disturb controlled low endemic situations. The prevalence, which had been kept under 0.02% for several years, had risen to well over 10 ‘A before systematic surveillance was restored. Mobile teams are now operational again, although full coverage has not yet been obtained. Zaire remains the country with the highest number of sleeping sickness patients in Africa. Of the countries collaborating under the aegis of OCEAC** (Chad, Central African Republic, Cameroon and Congo), in Chad and CAR mobile teams succeeded in covering the total population at risk. In Cameroon the Fontem focus was re-activated recently, and several hundred patients were reported. These were diagnosed by passive detection, and there is an urgent need for systematic examination of the population. With regard to Angola, the prospects give cause for concern as several cases have been reported in recent years across the Za’ire border and the present unstable situation in the country is likely to favour conditions for a new outbreak. East and South Africa The foci in Southern Sudan are at the moment the most important in Africa, with 287 new patients discovered last year by passive detection in only a small area, where the public health services cannot possibly cope with the problems involved. There is no information on the development of the T. rhodesiense focus in Ethiopia and the adjacent sleeping sickness area in the Sudan. The main T. rhodesiense areas are in Tanzania and in Zambia; apparently low virulent strains appear in the Luangwa Valley and the occurrence of healthy carriers may indicate a change of surveillance strategy as the situation becomes more similar to that of T. gumbiense. In conclusion, in spite of the cumbersome nature of medical surveillance and vector control, substantial efforts are continued in Africa. The coverage is far from complete and where breakdown of surveillance occurs, classical epidemic outbreaks can result. The answer is to develop a system of monitoring which must be adapted to suit the local services. This may mean that compromises have to be made in terms of sensitivity and even safety, if it is the price to be paid to obtain a guarantee for the continuity of efforts. Different levels of sophistication of control efforts can be defined. The first consists of the application ofsimple means of case detection in the field, for instance by using convenient serological tests, plus a standardized generally apphcable treatment scheme. At the next level, a more refined method of diagnosis could be applied in nearby specialized laboratories, and special treatment centres could be established in each area. An effort can also be made to reduce man/fly contact by simple vector control operations such as regular spraying of frequented sites near bridges and water collecting points. Where facilities permit, the maximum level of control methods can be exploited. For T. gambiense this means mobile teams with microscopists, and for T. rhodesiensethe establishment of equipment and trained microscopists in the rural dispensaries and hospitals, including facilities for animal **Organisation de Co-ordination pour la Lutte contre les Endemies en Afrique Centrale.
AFRICAN
SLEEPING
SICKNESS
TODAY
inoculation. Entomological analysis should be carried out and appropriate measures taken to maintain the lowest possible man/fly contact. As the latter level of efforts can only be attained in a few areas, the W H O programme for trypanosomiasis aims to assist research on improving diagnosis, particularly those techniques which require relatively little skill and materials. In the W H O programme, relevant fundamental research is supported in the field of chemotherapy and to stimulate co-ordinated efforts on research on chemotherapy and immunology, a special programme has been initiated to support joint research programmes among African centres and academic centres outside Africa. As far as the optimai application of current control tools is concerned, W H O is establishing a team in West Africa which will study the vector control methods of the moist Savannah and will evaluate and develop new serological tests, such as the Enzyme Linked Immunosorbent Assay (ELISA) and the indirect haemagglutination test in capillary tubes (BON& 1976). With these two components, it is hoped to establish an all-round application of trypanosomiasis control methods in Africa by distributing technical manuals and making appropriate equipment in the form of test kits available all over Africa. References Ashcroft, M. T. (1959). A critical review of the epidemiology of human trypanosomiasis in Africa. Tropical Diseases Bulletin, 56,1073-1093. Baker, J. R. (1974). Epidemiology of African sleeping sickness. In Trypanosomiasis and Leishmaniasis - with special reference to Chagas’ disease, pp. 29-50. Ciba Foundation Symposium 20 (new series). Bone, G. (1976). In Annales de la Societe’ Beige de Midecine tropicale (in press). Duggan, A. J. (1970). An historical perspective. In The African Trypanosomiases, ed. Mulligan, H. W. & Potts, W. H., pp. 41-88. London: Allen & Unwin. Dutton, J. E. (1902). Preliminary note on a trypanosome occurring in the blood of man. Thomas Yates Laboratory Reports, 4,455. Janssens, P. G. (1971). Review of the sleeping sickness situation. Zeitschrift fiir Tropenmedizin und Parasitologic, 22, 213-225. Manse11 Prothero, R. (1963). Population mobility and trypanosomiasis in Africa. Bulletin of the World Health Organization, 28,615-626. Nash, T. A. M. (1969). Africa’s Bane: The Tsetse Fly. London: Collins. Onyango, R. J., Geigy, R., Mwambu, P. M. & Moloo, S. K. (1971). Sleeping sickness survey in Musuma District, Tanzania. V. The endemicity of Rhodesian sleeping sickness in Ikoma Serengeti area-final discussion. Acta tropica, 28,221-225. Scott, D. (1965). Epidemic Disease in Ghana. London: Oxford University Press. As a footnote to this paper Scheiber, Braun-Munzinger and Southgate* reported detection of ultra-low density parasitaemias in large volumes of haemolysed human blood from two well-known residual foci of T. gambiense in Togo. Densities of l-3 trypanosomes per ml of blood from four out of 75 healthy people receiving routine pentamidine prophylaxis were reported. The possibility that such individuals might occasionally infect tsetse flies was suggested. *National Institute of Hygiene, Lome, Togo and Ross Institute of Hygiene, London.
