African Animal Trypanosomiasis: Part I. Disease and Chemotherapy
African Animal Trypanosomiasis: Part I. Disease and Chemotherapy
African Animal Trypanosomiasis: Part I. Disease and Chemotherapy
Trypanosomes
African animal trypanosomiasis can be caused by several species of trypanosomes:
Trypanosoma congolense is found in most domestic mammals: cattle, sheep, goats, horses, pigs, camels and dogs;
and also in many wild animals (Figure 1).
T. vivax is a parasite of domestic and wild ruminants and of horses.
T. simiae is found mainly in domestic and wild pigs.
T. brucei is a parasite very close to T. gambiense and T. rhodesiense, which are the causes of human sleeping
sickness. It can be found in practically all domestic and wild animals.
T. evansi is found in Africa only in the Saharan and Sahelian regions where it is primarily a camel parasite, but it
may be a parasite of horses, cattle and dogs as well. It also occurs in Asia — where it commonly causes disease in
camels and horses, and less commonly in cattle, water buffaloes, elephants and dogs — and in Central and South
America. Thus it has a very wide distribution.
1
Figure 1. Photomicrograph of a film of blood showing three specimens of Trypanosoma congolense.
T. equiperdum is the causal agent of dourine, a contagious equine disease transmitted by coitus, which in Africa
occurs only in the north African region and in South Africa. As control of dourine is an entirely different problem
from that presented by other forms of trypanosomiasis, it will not be discussed in the present review, which deals
only with the African trypanosomiasis transmitted by insects.
Transmission of trypanosomes
Transmission of trypanosomes by insects may be effected by widely different means.
Cyclical transmission, during which the trypanosomes actively multiply in the vectors, occurs through the
intermediary of Glossina or tsetse flies (Figures 3 and 4). This form of transmission occurs with T congo-lense, T.
vivax, T. simiae, T. brucei, and the trypanosomes responsible for human sleeping sickness, T. gam-biense and T.
rhodesiense. Glossina spp. are strictly blood feeders living exclusively in tropical Africa. There are about thirty
species or subspecies, classified in three groups: palpalis, morsitans and fusca. Each species has distinct biological
characteristics, but in general it may be said that the palpalis group consists basically of the species living in forest
galleries or in the marginal areas of forests; the fusca group consists of large-sized species whose habitat is
generally associated with equatorial forests; and the morsitans group consists mainly of species living in wooded
savanna.
Mechanical transmission is effected by various blood-sucking insects such as flies of the family Tabanidae (horse
flies) and Stomoxys spp. In the course of a blood meal begun on an infected animal and ended on a healthy one,
these insects may carry trypanosomes provided that the interval between the two meals is short. This form of
transmission is the rule for T. evansi, but may also occur with trypanosomes habitually transmitted cyclically by
Glossina, particularly T. vivax which may therefore be found in regions far from the Glossina distribution area
(such as Latin America).
2
Figure 2. Demonstration of chemotherapeutic treatment against trypanosomiasis by inoculation with a trypanocidal
drug in the dewlap.
Trypanosomiasis
Trypanosomiasis is generally a chronic evolving disease which is usually fatal if appropriate treatment is not
established. It leads to considerable loss of weight and anaemia. Various symptoms are exhibited, including fever,
oedema, adenitis, dermatitis and nervous disorders. Because of its protean symptomatology the disease cannot be
diagnosed with certainty except through detection of parasites by microscopic examination of blood or by various
serological reactions.
The evolution of trypanosomiasis varies widely according to the try-panosome involved and the animal species or
breed affected. Trypanosomiasis caused by T. simiae in pigs usually assumes a highly acute form leading to rapid
death, at least in improved pig strains. T. brucei is highly pathogenic for horses and dogs, but in cattle this
trypanosome usually causes asymptomatic infection. Zebu cattle are extremely susceptible to infections caused by
T. congolense and T. vivax, but the humpless cattle of west Africa and the Guinean strain of goats show
remarkable resistance, enabling these animals to live in areas where other breeds cannot exist.
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Biologically-based control of animal trypanosomiasis
In the control of animal trypanosomiasis action is possible on various aspects of the epizootiological cycle of the
infection: parasites, host animals and vectors.
ACTION ON PARASITES
This consists of the use of trypano-dal drugs on infected animals. The method aims first at limiting losses caused
by the disease, and second at eliminating trypanosome reservoirs. Thus, detection and treatment of infected
animals can be considered to be both a curative and a prophylactic procedure.
ACTION ON VECTORS
This method applies primarily to Glossina. Attempts may be made to (a) destroy the insects, particularly through
the use of insecticides; (6) make the environment unsuitable as a habitat, either by altering the vegetation or by
eliminating the animal species which constitute the preferred hosts of these insects; (c) reduce their reproductive
capacity by the release of sterile males; {d) limit their number by using biological control methods. The two latter
techniques are still only in the research stage and have not been used so far as a practical control method for
Glossina.
The various methods will now be considered which can be used in the control of African animal trypanosomiasis,
excluding dourine; and the account will be confined to measures for the treatment and protection of cattle, small
ruminants, pigs, horses and camels. The measures reviewed include (a) chemotherapy, (b) chem-oprophylaxis, (c)
breeding of try-panosome-tolerant animals and {d) vector control.
Chemotherapy
Since 1938, the date of the discovery of the trypanocidal properties of the phenanthridines, the chemotherapy of
animal trypanosomiasis has made great progress and there are several highly active drugs now available which are
easy to use. The use of trypanocides has consequently become widespread, and the number of trypanocidal
treatments carried out every year in Africa can be estimated at over 6 million, the great majority of them for
combating bovine trypanosomiasis.
The trypanocides currently employed are: homidium salts (Ethi-dium-Novidium); quinapyramine sul-fate
(Antrycide); diminazene acetu-rate (Berenil); isometamidium (Samo-rin-Trypamidium) and suramin sodium.
Table 1, which gives the data concerning the use of these products, shows that the action of the different
trypanocides varies according to the animal species infected and the try-panosomes involved.
4
Figure 4. Different stages of evolution of the tsetse fly: larva, pupa and adult fly.
CATTLE TRYPANOSOMIASIS
T. congolense and T. vivax
Cattle infections caused by T. congolense and T. vivax are by far the most serious, both for frequency and for
economic influence. The first really effective trypanocides were the dimidium salts which were widely used during
the 1950s. However, their toxic effects, the difficulties involved in their adoption and the frequent appearance of
drug-resistant trypanosomes have made the use of more recent trypanocides preferable. Homidium salts have been
and are widely used, but a considerable number of cases of drug resistance to homidium have been reported and in
many countries it has been necessary to suspend their use. Drug resistance has also been a serious handicap in the
employment of quinapyramine sulfate (Antrycide) which is no longer extensively used in cattle for the treatment
of either T. congolense or T. vivax trypanosomiasis.
Diminazene aceturate (Berenil) offers numerous advantages: its high activity against T. congolense and T. vivax,
particularly on those strains resistant to other trypanocides, its very low toxic effects in cattle and its easy
utilization make it a practical and safe trypanocide, at least for cattle. Although some cases of resistance were
observed early in the use of the trypanocide, it was the accepted view at the time that this was the result of cross-
resistance with quinapyramine, and that diminazene did not directly cause resistance because of its rapid
elimination through the kidneys, which prevents accumulation of residual subcurative doses. Since 1967, however,
strains of trypanosomes directly resistant to diminazene have been found in var-ious countries, notably in the
Central African Republic, Chad, Kenya, Nigeria and Uganda, primarily with regard to T. vivax but also to T.
congolense. These strains are fortunately still vulnerable to the phen-anthridine group of trypanocides, particularly
isometamidium, leading to the conclusion that in case of failure of a diminazene treatment it is preferable to use
another trypano-cide such as isometamidium rather than give further treatment with an increased dose of
diminazene.
5
Method of treatment Indications Toxic effects
Cattle
T.congolense
Antrycide5 10 cold Sheep
Quinapyra- 5 SC T. vivax Horses Isometami-
(sulfate) water Goats
mine sulfate T. brucei dium
Camels
T. evansi
Cattle
Samorin,3 1 or 2 IM
0.25 to Sheep
lsometami- Trypami- cold T. vivax Cattle
1 T.brucei Goats Diminazene
dium chloride dium6 water (deep) T.congolense
Horses
10 cold Camels
Suramin 10 IM T. evansi Quinapyra-
water Horses
sodium T. brucei mine
1 im = intramuscular injection: sc = subcutaneous injection.
2 Boots Pure Drug Co. Ltd.
3 May & Baker Ltd.
4 Farbwerke Hoechst A.G.
5 Imperial Chemical (Pharmaceutical) Ltd.
6 Specia.
Isometamidium (Samorin, Trypa-midium) is the most recent of the commonly employed trypanocides. Its main
advantage is its effectiveness on trypanosomes resistant to other drugs. At the same time it has the disadvantage of
easily creating drug-resistant strains itself; however, these trypanosomes show no cross-resistance with
diminazene, which therefore retains its effectiveness on such strains. The isometamidium deposit at the injection
site can cause a persistent local reaction which may be invisible from outside if deep in-tramuscular injection has
been given, as is recommended. This reaction makes the surrounding flesh unfit for consumption and partial
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confiscation of the carcass is necessary. It is therefore advisable to choose an inoculation site on a part of the body
where the meat is inexpensive; the neck muscles are usually recommended.
The two foregoing drugs, diminazene and isometamidium, are currently the preferred treatments for T. congolense
and T. vivax trypano-somiasis in cattle.
T. brucei and T. evansi
Trypanosomiasis in cattle caused by T. brucei is of secondary importance as this trypanosome is only slightly
pathogenic for cattle. The most active trypanocide against it is quina-pyramine.
T. evansi trypanosomiasis is extremely rare in cattle in Africa, where the disease occurs mainly in camels. It is
encountered more frequently, however, both in cattle and in water buffaloes in southeast Asia. The best treatment
is quinapyramine.
TRYPANOSOMIASIS IN PIGS
T. simiae, which is found mainly in domestic and wild pigs, presents a special problem because of its low
vulnerability to the various trypano-cides, requiring the application of considerably higher doses than those used
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against other trypanosomes. Two treatments appear to be effective: an extremely high dosage of isometamidium
(12.5 to 35 mg/kg); or a combination of quinapyramine sulfate (7.5 mg/kg) with diminazene (5 mg/kg).
However, the rapid course of this form of trypanosomiasis usually makes any therapeutic action impossible, so that
it is necessary to rely on preventive rather than curative treatment.
EQUINE TRYPANOSOMIASIS
T. congolense and T. vivax
Diminazene is not as well tolerated by horses as by cattle. Local reaction and fatal poisoning, with kidney or brain
lesions, have been reported. Homidium and isometamidium can be used on horses, although both drugs often
cause local reactions; doses should therefore be divided so as to inject no more than 10 milli-litres per injection
site.
T. brucei and T. evansi
Quinapyramine sulfate is the most effective trypanocide against these two trypanosomes, but this drug is often
poorly tolerated and is likely to cause serious local reactions and general disorders. It is therefore advisable to
administer the dose in two or three parts at six-hour intervals.
CAMEL TRYPANOSOMIASIS
Quinapyramine sulfate is the preferred treatment for T. evansi trypanosomiasis in camels, but suramin sodium is
still used in many countries although its cost is markedly higher and cases of drug resistance have been observed.
Suramin-resis-tant strains of T. evansi remain sensitive to quinapyramine.
Conclusions
Several drugs are now available which are highly effective (except in the case of T. simiae) and easy to use; but for
each of these products there are specific instructions which must be observed. Care and expert advice must always
be taken before any large-scale treatment is started.
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The first article in this series exam-ined the possibilities afforded by direct action on the parasites responsible for
animal trypanosomiasis by the use of trypanocidal drugs on diseased animals. This second paper reviews two
other methods of control: protecting susceptible animals by the use of preventive drugs, and making use of the
natural resistance of certain breeds of cattle to trypanosomiasis.
Chemoprophylaxis
There are three trypanoprophylactic drugs which can be used: quinapyra-mine prophylactic (Antrycide Prosalt),
pyrithidium (Prothidium), and isome-P. Finelle is Animal Health Officer, Animal Production and Health Division,
fao, Rome. tamidium (Samorin-Trypamidium). Quinapyramine can also be used in complex forms with suramin,
but as this formula is not on the market it must be prepared by the user as follows:
Quinapyramine sulfate 10 g
CATTLE TRYPANOSOMIASIS
T. congolense, T. vivax, T. brucei
Quinapyramine (Antrycide Prosalt) was the first trypanoprophylactic drug that was sufficiently active for use in
common practice. However, it has fallen into disuse because of the frequent appearance of drug-resistant
trypanosome strains. Moreover, its prophylactic action, extending over two to three months, is considerably less
than that of more recent products. Isometamidium and pyrithidium afford protection ranging from three to six
months, depending on the risk. In principle it would be advisable to make a preliminary trial in each case in order
to determine the treatment rate. In practice, a four-month cycle may generally be adopted — three injections per
year. Isometamidium is most frequently used, particularly because of its lower cost. As in curative treatment, and
especially since higher doses are administered for prevention, it is advisable to give the injection in a muscle where
the local reaction is not likely to affect the price of the carcass substantially For large animals it is also advisable to
divide the dose so as not to inject more than 15 ml per injection site. If trypanosomes reappear before another
preventive injection has been given, a curative treatment with diminazene should be administered so as to
eliminate theisometamidium-resistant trypanosomes.
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Table 1. Use of trypanoprophylactic drugs
Method of treatment Indications Toxic effects Treatment
of relapses
Trypanocide-
Trade name Possible
laclics Injection Length of Good
Solution Dosage Trypanosomes local
1 protection tolerance
reactions
1 to 2 Cattle
Samorin 2 T. vivax
parts per IM Sheep
Isometamidium Trypami- Mg/kg 0.5-1 T.congolense 3-6 Cattle
100 cold (deep) Goats Diminazene
chloride dium3 T. brucei months
water Horses
2 parts
Diminazene
Prothidium per 100 IM Cattle
Pyrithidium 2 T. vivax 3-6 Cattle Isometamidi
4 boiling (deep) Sheep
bromide T.congolense months um
water Goats
3.5 g per
Horses
Quinapyramine Antrycide 15 ml
7.4 SC T. brucei 2-3 Camels Horses
chloride and Prosalt 5 cold Suramin
T.evansi months Cattle
sulfate water
5 parts young 3
40 (of
Quinapyramine- per 100 months; Isometamidi
quinapyramine SC Pigs
suramin cold T. simiae adults 6 um 12.5-35
)
complex water months mg/kg
10
resistance is lowered by travel stress. It is therefore necessary that trypano-prophylactic treatment be administered
before livestock intended for slaughter enter tsetse-infested areas. Because (a) a large number of animals are to be
treated at low cost, (b) a comparatively short period of protection is required (about one month), and (c) drug
resistance is unlikely since the animals are to be slaughtered, the following drugs may be used:
homidium salts, which in regions where drug resistance to this product has not yet appeared give
—
protection for about one month; or
isometamidium, which in doses of 0.25 or 0.5 mg/kg makes it possible to obtain protection lasting up to
—
two months.
Figure 1. Herd of N'dama trypanotolerant cattle in Ivory Coast. These cattle are humpies s, and their coats are
light fawn in colour.
TRYPANOSOMIASIS IN PIGS
For the prevention of T. simiae infection in pigs, the following can be used:
quinapyramine-suramin complex in a dose of 40 mg/kg (quinapyramine sulfate), or 4 ml of suspension
— for 5 kg liveweight. This product affords protection lasting about three months for piglets and six months
for adult pigs;
isometamidium through deep intramuscular injection into the neck muscles, in doses between 12.5 and
—
35 mg/kg. This treatment provides protection for about four months.
EQUINE TRYPANOSOMIASIS
T. congolense, T. vivax, T. brucei
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Isometamidium and pyrithidium can be used for horses and donkeys under the same conditions as for cattle,
although such treatments may cause temporary lameness. It is advisable to administer deep intramuscular
injections and to divide the dose if a large amount is to be injected.
T. evansi
Quinapyramine (Antrycide Prosalt) is the most effective, but this product causes serious local reactions in horses.
The protection period is from three to four months.
TRYPANOSOMIASIS IN CAMELS
Quinapyramine can also be used to prevent T evansi trypanosomiasis in camels.
Drug resistance
The discovery of trypanocidal drugs with preventive action raised high hopes that their use would make it possible
to turn subtropical Africa into a flourishing livestock production area. It must be admitted that most of these hopes
have not been realized. Although these drugs do provide protection, which in some conditions may last up to six
months, all of them frequently give rise to the formation of drug-resistant try-panosome strains. This drug
resistance occurs when the'trypanosomes are in contact with a trypanocide administered in a subcurative dose
insufficient to ensure the destruction of the parasites. This situation may be due to one or more of the following
factors:
a. the application of insufficient doses, due in particular to underestimating the weight of animals;
b. the formation of abscesses followed by partial rejection of the drug;
c. a cyst-forming reaction which prevents the diffusion of the product;
d. preventive treatments at too long or irregular intervals;
e. halting the application of try-panoprophylactics while the animals are still exposed to the risk of infection ;
f. the occasional use of preventive drugs in curative treatments.
Trypanoprophylactic drugs should therefore be used with considerable caution, especially since there is a cross
drug resistance between various trypanocides and drug-resistant try-panosome strains which may persist for a long
time even after passage through tsetse. In fact, these drugs can be used without danger only on controlled
livestock, where it can be certain that the treatment rate and application requirements will be fully observed. These
prerequisites sharply limit the possibilities of applying chemoprophylaxis under traditional African livestock
production conditions.
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Figure 2. Herd of small short-horned humpless cattle in Dahomey. This breed is the second of the trypanotolerant
breeds in west Africa, where it is known by different names.
HEREDITARY CHARACTERISTICS
Trypanotolerance is a feature of the small, humpless cattle of west Africa. By studying the behaviour of zebu
cios=breds it has been shown that the ujscfjtibility of these animals to trypanosomiasis is intermediate between that
of pure humpless and zebu breeds and is approximately proportional to the degree of zebu blood.
ACQUIRED CHARACTERISTICS
Humpless cattle raised in tsetse-free areas have no resistance to trypanosomiasis and behave like those of other
breeds; their serum does not contain antibodies and when they become infected the course of the disease is acute
and results in death. Trypanotolerance is therefore in part an acquired immunological phenomenon. It is also
relative and may break down in certain conditions, particularly in the case of too frequent infections which may
succeed in overcoming the animal's immuno-logical defences. Moreover, all the causes capable of affecting the
production of antibodies can also reduce it or cause it to disappear. These include malnutrition, overwork,
intestinal parasitism and infectious diseases.
The mechanism of trypanotolerance may therefore be explained as follows: the trypanotolerant breeds have a
hereditary capacity to produce try-panosome antibodies; but the production of antibodies is set off by infections
contracted while the young animal is still protected by the mother's antibodies. Subsequent production of
antibodies is maintained and strengthened by subsequent infections, but it can be reduced and even eliminated by
all the factors which exert an unfavourable action on the immunological defences.
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Two systems for the introduction of trypanotolerant animals can be adopted. In the first, imported breeding stock
is assembled on ranches, and the increase in the herd, the offspring, is distributed to the farmers. This permits an
effective control of the herd and is perfectly suited to N'dama cattle, which respond well to ranching. The short-
horned cattle however, appear to settle better in small herds. In the second system, the breeding stock is distributed
directly to the farmers, which has the advantage of immediately involving the village people in the operation. A
farmer is given several females and a bull, which are to be repaid in cattle later as the increase in his herd makes
this possible. These will be used to start new herds. Whichever system is applied, the operation is faced with
technical and human problems.
Figure 3. Crossbreeding between N'dama and west African short-horned cattle is frequent. This crossbred
Dahomian heifer with short horns and a fawn coat is a good example.
TECHNICAL PROBLEMS
These are primarily the problems connected with any importation of animals, in particular the danger of
introducing contagious diseases: rinderpest and contagious bovine pleuro-pneumonia. Since trypanotolerance is
related to local strains of trypano-somes, the transferred animals may be susceptible to other strains. It is therefore
advisable to ensure strict sanitary inspection during the first few months after importation. If necessary,
trypanocidal treatments should be given to help the animals overcome trypanosome infections and enable them to
adapt their production of antibodies to new strains against which they have no immunity.
HUMAN PROBLEMS
Trypanotolerant livestock are usually distributed in areas where cattle husbandry is a completely new activity. The
operation therefore requires considerable organization and resources, at least for the first few years, its success
depends on the training of the new stock-raisers. Under prose i': conditions, the introduction of" y anotolerant
cattle is one of the most Hxtive methods for developing livestock production in countries where tr/panosomiasis is
prevalent. It is costly, requiring considerable personnel, and is slow to start, but these drawbacks are more than
offset by the results, which are permanent, whereas the methods considered previously, chemotherapy and
chemoprophylaxis, must be repeated constantly.
A fourth method, vector control, can also be employed, and will be the subject of the third article in this series on
African animal trypano-somiasis.
14
PART III. CONTROL OF VECTORS
P. FlNELLE
INDIRECT METHODS
Deforestation
The microclimate that is established by plant cover provides the most suitable combination of temperature and
humidity for the tsetse fly because it limits variations in climate to a minimum. The fly concentrates in certain
types of vegetation, which vary for the different tsetse species. When this vegetation is cleared, changes occur in
the microclimate that may cause the species concerned to disappear. Use of this selective deforestation method
therefore requires a very precise knowledge of the biology of the species concerned in the prevailing conditions.
Destruction of the vegetation can be done manually, by felling the trees, or by ringbarking in the case of plant
species for which this technique is effective. Mechanical means can be employed with quicker results, but these
can only be used in flat country. The use of arboricides has not proved very practical as they are expensive and
slow-acting products that do not work well with all plant species.
Regardless of the technique used, the selective destruction of vegetation presents two major drawbacks: it is
generally a very expensive operation and it increases soil erosion, which is liable to cause sterility in the cleared
land. This method is now seldom employed, except to establish deforested barriers to prevent areas cleared by
insecticide spraying from being reinvaded.
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eliminating the preferred hosts. This method has been employed to a considerable extent in some countries of east
and southern Africa with noteworthy results, but at the cost of the massive destruction of big game.
However, the elimination of wild animals, even if restricted only to host species, is not easy to accomplish,
especially when it involves destroying small animals like the warthog, the bush pig and the small antelope which
are the favourite hosts of many testse species. It has also been observed that the tsetse is not rigidly dependent on
specific animal species, and that when the preferred hosts disappear it can feed on other species.
Because of these difficulties, and the increasing concern for wildlife protection, the control of tsetse fly by the
selective elimination of wild animals is not to be recommended at present.
DIRECT METHODS
Insecticides
The treatment of tsetse-infested zones with insecticides is currently the most common method of eradication.
Insecticides may be applied from the ground or from the air.
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Ground spraying with portable prepressurized sprayers.
The preferred resting sites of the tsetse fly vary with the different species, the season and local ecological
conditions. It is therefore essential to have accurate knowledge of the biology of the species in the region to
determine the types of vegetation to be treated. In Nigeria, for example, in the Sudanian regions infested by
Glossina morsitans submorsitans and G. tachinoides, a 2 percent DDT solution is applied exclusively on the
supports where the tsetse flies rest during the hottest hours at the end of the dry season. In the case of G.
morsitans, these supports are shady tree trunks with a diameter of over 20 centimetres from ground level to a
height of about 1.5 metres. For G. tachinoides it is necessary to treat all tree trunks, visible roots overhanging the
banks of streams and woody vegetation near water, all up to a height of about 1 metre. When forest galleries are
relatively narrow and well separated from both banks of streams, only 5-metre strips are treated along each bank in
the case of G. tachinoides and 10-metre strips for G. morsitans. If the forest is broader and the banks are not clear,
treatment is effected in strips, about 20 metres wide, along the outside edge of the forest and inside the forest
galleries in the direction of the stream, at intervals of about 100 metres. In flood plains, where the forest is divided
into thickets, only the edges of the thickets and narrow parallel strips inside them, about 20 metres apart, are
sprayed. Operations of this kind in northern Nigeria have given highly satisfactory results, and the zones where
tsetse flies have reappeared and require further treatment do not exceed 1 percent of the total area treated.
The technique of selective spraying with persistent insecticides using ground equipment has been and continues to
be widely and successfully employed in several countries against various species of tsetse fly. It has been most
extensively applied in northern Nigeria, where it has led to the clearing of some 125 000 square kilometres, and
where the programme is continuing at the rate of about 12 500 square kilometres a year. It is an attractive method
because of its effectiveness, its relatively low cost, and because it results in reduced environmental contamination.
It should be stressed, however, that it requires thorough prior studies of tsetse fly ecology to determine the
conditions for using insecticide, and large, well-equipped and well-trained spraying teams, as well as a dense
network of roads and tracks. The method is of real value only in regions where the habitat of the tsetse fly is
relatively restricted, at least for part of the year. These various conditions, which cannot often be met, have led to
the adoption of aerial spraying, which gives quick results and requires limited personnel.
AERIAL SPRAYING
The first attempts to control tsetse fly by the aerial spraying of insecticide were made in 1948 in Tanzania, and the
first large-scale operation was carried out shortly afterwards in South Africa, leading to the elimination, although
at a very high cost, of G. pallidipes in the Zululand region. Research, particularly in Tanzania, has led to
improvements in this technique and to appreciable reductions in its cost. The .insecticide can be applied either as
an aerosol without residual action, distributed over the whole infested zone, or as a deposit, with a persistent effect,
on the preferred resting sites only.
17
Ground spraying with portable motorized sprayers.
Aerial spraying.
Aerosol
The aerosol method has been used in various countries, including Rwanda, Kenya and Tanzania, but has been
applied most widely in Zambia.
The insecticide is sprayed in the form of fine droplets with a diameter between 10 and 60 \im, which because of
their lightness remain suspended in the air and can penetrate through the vegetation and reach the adult tsetse flies.
However, the insecticide is not deposited on the vegetation and has no persistent action, so the treatment must be
repeated to reach the tsetse flies which had been in the pupal stage at the time of the first operation.
DDT, BHC, dieldrin, endosulfan, iso-benzan, fenthion and pyrethrum have been used. Light single-engined
aircraft are generally employed for these operations, fitted either with heat generators working off the engine
exhaus| pipe or with rotary sprayers. In Zambia, heavier two-engined aircraft, which allow more rapid operation,
are used successfully. Recent advances in aerial spraying techniques have enabled considerable reductions to be
made in rates of application, with highly concentrated insecticides; in Zambia, endosulfan is sprayed at the rate of
30 grams per hectare. Operations are carried out during the dry season, at a time when many trees lose their leaves,
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and at hours when the meteorological conditions are favourable, at dawn and just before sunset. The aircraft are
guided either by ground teams using radio or markers, or by the aircraft's own navigating equipment.
Aerial sprayings are repeated four or five times, at three-week intervals. The conclusion to be drawn from the
various, operations for controlling tsetse flies by the aerial spraying of nonpersistent insecticides is that total
elimination is possible provided the treated area is suitably isplated from other contaminated regions. In Zambia
aerial spraying has led to the eradication of G. morsitans from nearly 15 000 square kilometres at a lower cost than
spraying with ground equipment. However, the method suffers from several disadvantages: it requires total
coverage of the tsetse-infested zone and all that this implies from the point of view of environmental pollution; it
requires several applications staggered over about 100 days; the insecticide, which is dispersed in the form of fine
droplets, is often carried away by the wind to areas outside those to be treated. Because of these disadvantages the
application of long-lasting insecticides is sometimes preferred.
Persistent insecticides
Various tests involving the aerial spraying of persistent insecticides have been made, using an inverted-emulsion
insecticide or by selective spraying from helicopters.
Inverted emulsions. In these tests, performed in Kenya under a who/ fao project, dieldrin was used as a water-in-oil
emulsion instead of the normal oil-in-water formula. With these inverted emulsions, in which the oil phase is the
continuous one, evaporation is limited and the droplets are coarser and less sensitive to atmospheric conditions, so
that they reach the target zone with greater accuracy. The vegetation of the region chosen was composed of very
dense thicket infested by G. pallidipes. Applications were made from aircraft and helicopters, but the latter proved
to be more expensive. The results of these preliminary tests proved that the technique was effective in the
conditions prevailing in the region, and that its cost was competitive with that of the other methods. The tests
should be continued and extended to other species and other types of vegetation.
Selective spraying. The principle underlying the selective spraying of persistent insecticides by helicopter is
similar to that of selective spraying using ground equipment: the aim is to treat only the vegetation used as a refuge
by the tsetse fly, when weather conditions for the insect are most severe. This method has been successfully
employed in northern Nigeria in regions infested by G. morsitans submorsitans. A helicopter flying at a low speed
(about 40 kilometres an hour) 1 or 2 metres above the treetops sprays (in the dry season) 10 percent dieldrin in the
form of droplets with a diameter varying between 90 and 200 (xm, over a width of about 20 metres, at the rate of
1.5 kg of active product per hectare. This technique has turned out to be effective, but expensive if the price is
related to the area treated. However, if account is taken of the fact that only 10 percent of the total area is
effectively treated, the cost of this method calculated in terms of the cleared area is comparable to that of
unselective spraying by aircraft.
19
Chemical control of the tsetse fly certainly raises the pollution level of the area concerned. The insecticides used,
usually chlorinated hydrocarbons, are toxic to other insects, including useful species such as bees or predatory
insects. They are also very toxic to fish. Their toxicity as far as birds and mammals are concerned is still not very
clear, but it is known that they can accumulate in fats.
It must be noted, however, that the levels and quantities of insecticides used for tsetse fly control are much lower
than those for controlling crop parasites, and hence account for only a very small part of the general pollution
caused by pesticides. Nevertheless, it is highly desirable that new insecticides should be tested with the aim of
finding a product with a more selective action and with fewer effects on the environment than the
organochlorinated compounds currently used. Biological control methods may also provide a solution to this
problem.
PATHOGENIC ORGANISMS
Little is known about the pathology of tsetse flies. While there is information concerning insect parasites which
prey on tsetse pupae and which in nature certainly play a part in limiting the number of flies, so far there has been
no success in breeding these parasites in the laboratory.
Likewise, no work has been done on organisms that are pathogenic to tsetse flies, an approach which has been so
promising in the control of other insect species. These matters should receive the very close attention of research
laboratories.
GENETIC CONTROL
Research on the genetic control of the tsetse fly has made great strides since it became possible to breed these
insects in the laboratory on a large scale. It is now possible to consider methods involving induced sterilization or
the transmission of lethal genes. The underlying principle is that as the female tsetse fly generally copulates only
once at the beginning of its life, it will produce no progeny when inseminated by a male whose spermatozoids
have undergone chromosomal modifications that render them incapable of fertilizing the egg. By releasing a
sufficient number of sterile males in a region so that they have a greater chance of mating with the females than the
existing normal males, a reduction and eventually an extinction of the population through reduced numbers of
progeny can be achieved.
Contact with various chemical products can cause sterility in males, and the gamma irradiation of adult males has
the same effect. Laboratory studies have shown that although the longevity of the males is reduced, they live long
enough to copulate several times and retain their ability to mate. The advantages of this system are obvious. The
species is used to destroy itself, without disturbing the natural biological equilibrium. The males seek out the
females and can track them down in places inaccessible to man.
The application of this method requires a large number of males, which is now possible through recent
improvements in laboratory breeding techniques. One important problem which remains to be solved concerns the
behaviour of the artificially bred insects when they are released in a natural environment. First experiments suggest
that after some days of adaptation the sterilized males tend to behave like normal insects, although their longevity
is significantly curtailed. However, the practical and economic feasibility of this method can be fully established
only after pilot tests have been carried out on the most important tsetse fly species.
20
The main factor governing feasibility is the size of the natural tsetse fly population. It will certainly be effective to
release sterile males after the population has been reduced by treatment with a nonpersistent insecticide. From this
point of view, the release of sterile males may be regarded as a supplement to chemical control, opening the way to
the complete elimination of the tsetse fly after a brief and nonpolluting insecticide treatment.
Conclusions
The methods of controlling animal trypanosomiasis are numerous and varied; each possesses advantages and
disadvantages and these must be assessed in the light of local data and the end results that are sought.
In the fourth and final article in this series, the economic problems raised by animal trypanosomiasis and its
control will be considered, in order to assess the relative costs and benefits of the various methods.
Socioeconomic consequences
It may therefore be useful to assess the socioeconomic consequences of African animal trypanosomiasis, and the
cost of the different control methods.
21
— areas where there is virtually no livestock raising;
areas where only certain livestock breeds, possessing a natural resistance to trypanosomiasis (try-
—
panotolerant breeds), can live;
areas where, despite the presence of tsetse fly, livestock susceptible to trypanosomiasis can be raised
— either because of particular local conditions (tsetse flies are limited in number or confined to certain plant
types) or because curative or preventive treatment is regularly practised.
In every case, however, trypanosomiasis leads to considerable under-exploitation of natural resources, and to a
lower level of animal production than could be achieved if the disease were eliminated.
The influence of the tsetse fly on animal production is nowhere more clearly illustrated than in Tanzania, where
the geographical pattern of cattle distribution is almost exactly the opposite of that of tsetse distribution.
22
ANALYSIS OF SOCIOECONOMIC CONSEQUENCES
The socioeconomic importance of African animal trypanosomiasis is extremely difficult to assess, as the data
available are fragmentary and frequently very approximate. In the Present state of knowledge it is possible only to
enumerate the various consequences of trypanosomiasis, in the hope that this list can serve as a base for
assessments at the local level. Two sets of consequences, direct and indirect, can be identified:
1. The direct consequences, represented by the economic losses due to the disease and to the various expenditures
incurred in controlling it.
They comprise:
a. mortality;
b. disease, which manifests itself in emaciation, retarded growth, abortion, temporary sterility and various
organic lesions;
c. the cost of detection and treatment of infected animals (veterinary service personnel, trypanocidal drugs,
equipment, operating expenses);
d. the cost of preventive operations (chemoprophylaxis, tsetse fly control, development of trypanotolerant
livestock);
e. the cost of research on animal trypanosomiasis control.
2. The indirect consequences of animal trypanosomiasis affect:
a. human health, as the shortage of meat and milk causes protein deficiencies which are particularly harmful
to children;
b. agriculture, because the lack of draught animals and manure reduces agricultural output;
c. livestock production: (i) trypanosomiasis limits the possibilities of introducing improved breeds, which are
highly sensitive to this disease, thus preventing the upgrading of local livestock by crossing with imported
sires; (ii) the presence of trypanosomiasis causes livestock to be concentrated in limited grazing areas,
which results in their overuse and deterioration; (Hi) seasonal variations in the incidence of
trypanosomiasis prevent some pastures from being grazed throughout the year and compel herdsmen to
practise transhu-mance, which holds them back from integration in the national community;
d. the economy: the deficit in animal production compels countries where trypanosomiasis is rife to resort to
imports of meat and dairy products, a practice harmful to their balance of trade.
23
— possibility of increasing the cattle population: 120 million head;
— value of additional meat production (on the basis of 50 cents per kg): US$750 million.
Although very approximate, this estimate shows how animal trypanosomiasis control could contribute to the
development of animal production at a time when demand for animal protein, especially beef, is constantly
growing and when projections indicate a serious shortfall in the years to come.
CHEMOTHERAPY
Approximate cost of a curative dose for a 300-kg bovine animal:
Diminazene (3.5 mg/kg) 15 cents Isometamidium (0.5 mg/kg) 19 cents
The cost of application is difficult to calculate, as it must include a proportion of the costs of the veterinary service
and of its budget (peisonnel, equipment and operation) devoted to trypanosomiasis detection and treatment.
However, this can be estimated to be around 50 cents. It may therefore be assumed that the cost of curative
treatment for a 300-kg bovine animal varies between 65 and 70 cents.
CHEMOPROPHYLAXIS
Approximate cost of a preventive dose for a 300-kg bovine animal:
Isometamidium (1 mg/kg) 38 cents Cost of the opetation 50 cents
As preventive treatments must be repeated on average every four months, the annual cost of chemo-prevention for
a 300-kg bovine animal would be about US$2.65.
Transport 35.3
24
Salaries of purchasing mission personnel 25.3
Miscellaneous 22.4
The average purchase price of an animal was US$40, and its total average imported cost was US$247 (1966).
25
Table 2. Cost of air spraying
Average cost per square
Method Country Tsetse fly kilometre, 1971 Remarks
Treated Cleared
... U.S. dollars ...
Conclusions
This attempt to analyse the economic problems raised by African animal trypanosomiasis shows that accurate data
are so limited that it is almost impossible at present to draw up even an approximate report.
Aware of these significant limitations, fao plans to undertake a two-year study which will include a number of
local surveys in carefully selected regions. The study will furnish the basic data for an assessment of the
socioeconomic importance of trypanosomiasis and the costs of the various methods used to control it, and should
draw the attention of interested governments and assistance organizations to the necessity for a very substantial
increase in funds for field operations if the disease is to be controlled to an extent that would allow a significant
expansion in animal production.
References
FAO. 1969. African trypanosomiasis: report of a joint FAO/WHO Expert Committee. Rome, fao Agricultural
Study No. 81.
International Scientific Council for Trypano Research and Control. 1971. Thirteenth meeting. Lagos, OAU/SCTR.
Publication No. 105.
Mulligan, H.W. 1970. The African Trypanosomiases. London, George Allen and Unwin Ltd.
Park, P.O., Gledhill, J.A., Alsop, N. & Lee, C.W. 1972. A large-scale scheme for the eradication of Glossina
morsi-tans morsitans Westw. in the Western Province of Zambia, by aerial ultra-low volume application of
endosulfan. Bull. ent. Res,, 61: 373-384.
* Animal Health Officer, Animal Production and Health Division, fao, Rome.
P. Finelle Animal Health Officer, Animal Production and Health Division, fao, Rome.
P. Finelle is Animal Health Officer, Animal Production and Health Division, fao, Rome.
26
P. Finelle is Animal Health Officer, Animal Production and Health Division, fao, Rome.
1 Lacrouts, M., Sarniguet, J. & Tyc, J. Le cheptel bovin en République centrafri-caine. Paris, Secretariat d'Etat aux
affaires étrangères, 1966.
27
Variable antigen types (VATs).
Antigenic variation, the major obstacle to developing a trypanosome vaccine, is the process whereby trypanosomes
sequentially express a series of surface antigens; it is these antigens that are capable of inducing protective
immunity. The immune response against each variant, although rapid and highly effective in destroying any
trypanosomes that possess that particular antigen, is invariably too late to affect that proportion of the population
that has altered its antigenic identity. Thus, parasitaemia rises and falls in waves with each parasite population
carrying different surface antigens (reviewed by Cross, 1978; Vickerman, 1978). This picture of successive waves
of a specific antibody chasing variant trypanosomes has been likened by Goodwin (1970) to a "Tom and Jerry
cartoon with a monstrously inept cat pulling the place down in its efforts to pulverize a diminutive and highly
resourceful mouse".
What would appear to be required is as complete as possible an understanding of antigenic variation in order that,
eventually, it might be possible to produce an effective vaccine by the strategic use of certain trypanosomes or
their components. At the population level, the authors' knowledge has been increasing over the past few years,
thanks mainly to the concept of multiple cloning in which bloodstream populations are divided into their
component parts, namely single trypanosomes, each of which gives rise, in a fresh host, to a defined population
that can be frozen as reference material. It is essential that as large a number of clones as possible be isolated, since
only then will it be possible to detect some of the subtle immunological and biological differences within and
between populations.
This approach has begun to reveal what occurs within a parasitaemic peak, to the level of the individual parasite. It
appears that a peak is usually a mixture of vats (Van Meirvenne, Janssens and Magnus, 1975a) with the switch to
expression of another type, probably occurring before the appearance of antibody, which is thought to act merely
as a selective agent (Van Meirvenne, Janssens and Magnus, 1975a; Le Ray et al., 1977). Examination of sequence
of appearance of vats arising within cloned infections has confirmed and extended the observation of Gray, 1965)
that there is a tendency for certain types to occur preferentially in the early parasitaemic peaks. Thus, it would
appear that vats can be divided into these early "predominant" types and other groups of vats that occur later (Van
Meirvenne, Janssens and Magnus, 1975a; Capbern et al. 1977).
28
Figure 1 Parasitaemia profile in an individual four-year-old N'Dama (•) and a four-year-old zebu (o) inoculated
with Trypanosoma congolense. Note that the level of parasitaemia is lower in the N'Dama as is the duration of
parasitaemia. Both animals were negative for detectable parasites for several months prior to the termination of
the experiment and both made a clinical recovery.
29
Figure 2 Parasitaemia profile in an individual C57BI/6J mouse (•) and A/J mouse (o) inoculated with
Trypanosoma congolense. The CS7BI/6J was able to control and reduce parasitaemia levels to a significantly
greater extent than the A/J and as a result was able to survive for over 100 days. Irrespective of breed or strain,
cattle were able to control and reduce parasitaemia to a much greater extent than mice. Following infection in
mice, death was inevitable, whereas in cattle recovery may occur, particularly in N'Dama animals.
The total number of vats that a trypanosome can express is known as its "vat repertoire," the full extent of which is
as yet unknown although Capbern et al. (1977) have been able to isolate 101 vats from one clone of Trypanosoma
equiperdum. Comparison of vat repertoires from different clones has been initiated (Van Meirvenne et al., 1975b;
Van Meirvenne, Magnus and Vervoort, 1977) and has revealed a surprisingly high degree of similarity; in fact,
some vats have been found in every repertoire examined. In addition, there is now indirect evidence from
serological studies that during an infection certain vats may recur, in some cases within a few weeks of one
another. This has been described in cattle infected with Trypanosoma congolense (Wilson and Cunningham, 1971)
and with T. brucei (Nantulya, Musoke, Barbet and Roelants — unpublished results).
As regards vaccination, a rational approach may be successful. Immunization against individual vats is highly
effective using such regimes as infection and treatment; irradiated organisms; killed organisms; crude emulsions
containing released soluble antigens; formalized whole infected blood or plasma and purified variable antigen
glycoprotein (reviewed by Murray and Urquhart, 1977). As little as 3 µg of variable antigen can give protection in
mice (Baltz et al, 1977). A cocktail vaccine based on predominant vats is likely to be effective against with that
repertoire. Investigation of the feasibility or such an approach requires complete analyses of the number of vats,
both predominant and otherwise, within a repertoire, of the extent of crossreaction between repertoires and,
eventually, of the number of vats that exist within and without given geographical areas.
30
A word of warning regarding studies on antigenic variation: it is necessary to define not only the parasite but also
the host. The parasitaemic patterns produced by a trypanosome will vary with species of host, breed or strain, age,
sex, etc. (Figures 1 and 2). In this regard, there is little doubt that exploitation of the in vitro culture system, which
supports the growth of animalinfective forms of trypanosomes (Hirumi, Doyle and Hirumi, 1977) by eliminating
the variable effects of the host, must yield new information on the basis and mechanisms of antigenic variation.
Since much of the above work has been carried out with T. brucei the authors believe that it is essential that similar
efforts be made with T. congolense and T. vivax, which are regarded as the major pathogens of bovine African
trypanosomiasis.
Metacyclic antigens.
Following ingestion by the tsetse fly, T. brucei loses its surface coat, which contains the variable antigen. It
eventually regains the coat in the fly's salivary gland in becoming the mammalianinfective metacyclic stage
(Vickerman, 1969). It has been suggested that all trypanosomes of a particular clone revert to a common "basic"
antigen type in the salivary gland (Jenni, 1977, for T. brucei; Nantulya, Doyle and Jenni, 1979, for T. congolense)
akin to the "basic" type arising in the bloodstream after cyclical transmission (Gray, 1965). Vaccination against
such types would obviously be of importance. However, there is now evidence to suggest that this is not the case
and that T. brucei metacyclics arising from the passage of a clone through the tsetse are antigenically
heterogeneous (Figure. 3) (Le Ray, Barry and Vickerman, 1978; Barry and Hajduk, 1979; Barry et al, 1979b),
although it is still the case that there may be only a limited number. A drawback to the potential use of metacyclic
populations for vaccination is that they are antigenically unstable (Le Ray et al, 1977; Le Ray, Barry and
Vickerman, 1978), preventing mass production of antigen and mRNA (see later, molecular and genetic
engineering) for potential vaccine preparation. However, these dfficulties may be overcome by a recently devised
protocol (Barry et al, 1979b) whereby antigenically more stable mammalian bloodstream forms with the same vat
as metacyclics can be identified and cloned giving rise to populations suitable for bulk preparative procedures.
This approach could be pursued to define the vat complement of metacyclic populations with a view to vaccination
against trypanosomes of that vat repertoire. Furthermore, it is essential to determine the degree of crossreaction
between metacyclics of different repertoires.
31
Figure 3 Antigenic heterogeneity among mammalianinfective metacyclic forms in the saliva of a tsetse fly. The fly
was allowed to salivate onto a heated glass slide, to which immunofluorescence was applied using specific
antiserum against a characterized bloodstream form trypanosome vat. Metacyclics with trypanosome vat fluoresce
strongly, while those of other vat display the weak fluorescence of the counterstrain.
The in vitro culture system would also appear to have potential in this area. It has now been shown that
"bloodstream forms" of T. brucei in culture ( Figure 4) can be induced to undergo morphological changes similar
to those that occur in the fly, including the eventual production of metacyclic types, by appropriate manipulation
of the culture conditions (Hirumi, Hirumi and Doyle, 1978a). As it has now become possible to clone parasites in
culture (Hirumi, Hirumi and Doyle, 1978b) this approach might offer a source of metacyclic types of defined
antigenic identity.
32
Figure 4 Bloodstream forms of Trypanosoma brucei (ILR-TbC-221) grown in vitro for over 31 months. Giemsa's
stain.
In vivo and in vitro attenuation. Another facet of the problem is that, despite the authors' steadily increasing
knowledge of antigenic variation, very little is known of how it is linked to the biology of the trypanosome and the
hostparasite interaction, apart from the fact that it allows the trypanosome to evade the host's immune response and
thus survive. For example, an association between vat and virulence has been proposed (McNeillage and Herbert,
1968; Van Meirvenne, Janssens and Magnus, 1975a) although it is essential that the precise circumstances of such
a link are fully investigated (Barry, Le Ray and Herbert, 1979a). It is a common mistake to equate the vat of a
clone with all the characteristics displayed by that clone; the vat is just one phenotypic marker. Confirmation of a
link between vat and virulence, and the observation that trypanosomes of different vat may interfere with the
expression of each other at the population level (Herbert, 1975) conceivably could be exploited to decrease the
number of variable antigens required in a vaccine. At a later stage of infection, after expression of predominant
vats, it appears that trypanosomes are in some way biologically altered as evidenced by their decreased infectivity
and virulence in fresh hosts. The basis of this and whether it is linked to vat or some other characteristic of the
parasite remains to be investigated.
Can these changes in behaviour be induced artificially and incorporated into a vaccination protocol ? The
possibility now exists of attenuating trypanosomes by continuous passage in culture. In preliminary studies, it has
been found that mice infected with parasites maintained in vitro by serial subcultivation over 12 months have
shown alteration in pathogenicity when compared with noncultured organisms or organisms that have been
33
maintained in vitro for less than three months (Hirumij unpublished data). The potential protective effect of
attenuated protozoa has already been demonstrated in the control of babesiosis in cattle in Australia (Callow,
1977).
34
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Experimental Parasitology, 32: 165-173.
Part II
M Murray, J.D. Berry, W.I. Morrison, R.O. Williams, H. Hirumi and L. Rovis
In Part I of this review of the prospects of vaccination against African trypanosomiasis, contained in the previous
issue of World Animal Review, the constraints in developing a vaccine were discussed and current knowledge on
the molecular biology of the trypanosome and on antigenic variation with respect to possible future vaccines was
evaluated. In this part other possible regimes for immunological intervention, including the immunogenicity and
cross reactivity of trypanosome subcellular fractions, reduction of host susceptibility to African trypanosomes by
the nonspecific use of immunostimulants or chemotherapy and also the role of trypanotolerant livestock in such
approaches, are discussed.
37
although with the membrane and kinetoplast preparations there was significant prolongation of survival
accompanied by an alteration in the parasitaemic profile. This was possibly a result of a nonspecific stimulant
effect of these fractions (see below, the section on "Induction of increased resistance by immunostimulants").
Using a subcellular fraction of T. brucei or T. rhodesiense that probably contained a mixture of variable antigen,
mitochondrion and kinetoplast to immunize mice, Powell (1976; 1978) found increased survival times and reduced
parasitaemias in mice challenged with T. brucei. Using T. brucei in C57BI/6J mice and a similar fraction for
immunization, the authors were able to stimulate protection only if trypanosomes of the same vat were used for
challenge (Table 1). When another vat was used for challenge protection was not achieved although there was a
significant increase in survival time. Of considerable interest is the report of Powell (personal communication) that
the use of the above fraction in aluminium hydroxide protected across trypanosome species. Three sheep were
immunized in the "feet" with three doses of 1-mg protein fraction of T. rhodesiense in aluminium hydroxide. On
subsequent challenge with T. vivax each of the three sheep developed a transient parasitaemia and then made a
complete recovery. All three challenge control sheep became infected and died. These observations now await
confirmation.
TABLE 1. Immunization with various subcellular fractions of Trypanosoma brucei
Challenge
Fraction Same VAT Different VAT
38
Luckins, 1972), a large proportion of which would appear not to be specific for the trypanosome (Freeman et al.,
1970; Corsini et al., 1977). It is possible that the capacity of the trypanosome to survive may be related to the
immunologically compromised state of the host. Thus, a complete understanding of the basis of
immunosuppression and the relevant immunological effector mechanisms that kill the trypanosomes might allow
some form of intervention so that effector mechanisms are stimulated and the host is able to control or eliminate
the parasite.
TABLE 2. Effect of Bordetella pertussis on survival of A/J and C57BI/6J mice challenged with
Trypanosoma congolense
Percentage survival
A/J 1 C57BI/6J 1
Days after challenge. Control
Control B. pertussis B.pertussis
10 68 96 100 100
15 0 43 88 100
20 43 88 96
30 43 88 96
40 39 80 96
50 35 80 91
100 8 26 64
150 0 0 24
Average time to 11.2+1 26.4+24.6 2 75.4+35.4 113.3+47.8 2
death, in days
1 25 mice per group.
2 Significant to controls (arithmetic mean + one standard deviation).
In this regard, the authors attempted to improve the host's immune response, and thus host resistance, by using the
immunostimulants Bordetella pertussis, Corynebacterium parvum and Bacillus Calmette-Guérin (BCG) prior to or
at the time of challenge (Murray and Morrison, 1979). So far this strategy has been successful, at least in mice. It
was possible to increase survival times in both susceptible (A /J) and more resistant (C57BI/6J) strains of mice
(Table 2). Thus, following challenge with T. congolense, the treated A/J strain behaved in a manner much more
akin to the more resistant C57BI/6J. It should be emphasized, however, that complete protection was never
induced by this method. The reduced susceptibility appeared to be ? related to the ability of these
immunostimulants, particularly B. pertussis and C. parvum, to delay the onset of parasitaemia or to reduce the
level of parasitaemia (Figures 1 and 2). The best results were achieved when both of these parameters were
affected. The possibility that these immunostimulants acted by improving the immune response is being
investigated at present.
The strategy of increasing host resistance by nonspecifically acting immunostimulants offers an attractive
alternative or additional approach to the complex undertaking of a breeding programme for trypanotolerant
livestock. However, whether immunostimulants can be employed effectively in this way in domestic livestock
remains to be determined.
39
Trypanotolerance.
As trypanotolerance was the subject of an earlier review in this journal (Murray et al., 1979), the authors will limit
their remarks.
There is now a substantial body of evidence to indicate that certain breeds of cattle, sheep and goats are able to
survive and be productive without the aid of treatment in areas of tsetsefly challenge, where other breeds cannot.
This attribute is known as trypanotolerance although, as this state is not absolute, it would be better termed as
reduced susceptibility. These trypanotolerant breeds are of considerable interest and importance. Not only is there
evidence that they are economically exploitable in their own right but they also provide an excellent experimental
system for evaluating the important factors that influence host susceptibility to trypanosomiasis. If it is confirmed,
as the results of Desowitz (1959) strongly indicate, that the basis of trypanotolerance is the ability to mount a more
effective immune response to the trypanosome, it might well be that any immunotherapeutic strategy that may be
developed would be more effectively employed if used in trypanotolerant breeds of animals.
40
In contrast, a second group of steers, all of which were treated with Berenil whenever blood infection rather than
clinical signs was detected, showed no evidence of developing immunity and they required treatment every 26
days throughout the course of the experiment. When treatment was withdrawn from some of the steers six months
before termination of the experiment, their mean weight gains were 58 kg less than those steers in which treatment
continued and, in addition, one animal died.
With a third group of steers, Samorin (isometamidium) was used in the same way as Berenil in Group 2, and there
was some evidence of the development of immunity. While the need for therapy did not decrease throughout the
experiment, pvc values and growth rates were maintained in the animals in which drug treatment was withdrawn
six months prior to termination of the experiment, despite the more frequent presence of parasites in this group.
In terms of weight gain there was no doubt that the use of drugs prophylactically on a group basis, particularly
Samorin, gave by far the best results. Nevertheless, as Wilson et d. (1976) pointed out, the particular advantage in
encouraging the development of nonsterile immunity by infection and treatment might lie in the development of
lesssusceptible breeding herds over periods of several years, particularly in areas of low to medium trypanosome
challenge. This procedure might be even more successful if used with trypanotolerant breeds of livestock. It should
be emphasized that drug resistance was not experienced in these studies.
The basis of this form of tolerance or "nonsterile" immunity to the trypanosome awaits investigation. It may be
that the host has built up a whole battery of immune responses to the range of metacyclic antigens and vat
repertoires that occur in that particular location, or alternatively there might exist a common priming antigen that
allows the host to make a series of secondary responses to each vat, thus controlling the infection in the manner of
the carrierhapten effect proposed for malaria by Brown (1971). However, it might be related to some nonspecific
effect such as expansion and activation of the mononuclear phagocytic system.
41
Figure 1.The parasitaemia profile of a Bordetella pertussisfreated C57BI/J61 mouse (•) and a control C57BI/6J
mouse (o) challenged with Trypanosoma congolense. The broken line just below 2 logio trypanosomes per \il
indicates the level of sensitivity for detection of trypanosomes with the haemocytometer technique.
42
Figure 2.The parasitaemia profile of a Bordetella pertussistreated A/J mouse (•) and a control A\J mouse (o)
challenged with Trypanosoma congolense. The broken line just below 2 logio trypanosomes per (i/ indicates the
level of sensitivity for detection of trypanosomes with the haemocytometer technique.
Conclusions.
While a vaccine against trypanosomiasis is not an immediate prospect, what the two parts of this article have
attempted to show is that there are several promising avenues for immunological exploration, namely vat cocktails,
trypanosomes attenuated in in vitro culture systems, genetic engineering, crossreacting subcellular fractions,
intervention against the tsetse, nonspecific induction of increased resistance by immunostimulants, and infection
and treatment regimes. It is likely, if any one of these areas is rewarding, that the resulting vaccine will be more
successfully exploited, at least initially, in trypanotolerant animals.
The authors would like to emphasize that any immunotherapeutic solution for trypanosomiasis control can come
only through a thorough knowledge of the lifecycle of the trypanosome and its basic biology coupled with a
comprehensive understanding of the immune response of the finite host. ■
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The authors are with the International Laboratory for Research on Animal Diseases (ILRAD), PO Box 30709,
Nairobi, Kenya.
The authors are with the International Laboratory for Research on Animal Diseases (ILRAD), PO Box 30709,
Nairobi, Kenya.
45