Synonym: T. pecaudi.
Disease: Trypanosomosis, nagana.
Hosts: Horse, mule, donkey, ox, zebu, sheep, goat, camel, pig, dog, and many wild game animals. Antelopes are the natural hosts of T. brucei and serve as reservoirs of infection for domestic animals. Experimental attempts to infect man have failed (Ashcroft, 1959a).
Location: Blood stream, lymph, cerebrospinal fluid.
Geographic Distribution: Widely distributed in tropical Africa between 15° N and 25° S latitude, coinciding with the distribution of its vector, the tsetse fly.
Prevalence: T. brucei is one of the commonest and most important parasites of domestic animals in Africa. It has prevented the raising of livestock in vast areas.
Morphology: Polymorphic, with slender, intermediate and stumpy forms. Undulating membrane conspicuous. Kinetoplast small, subterminal. Slender forms average 29 u, in length but range up to 42 u; posterior end usually drawn out, tapering almost to a point, with kinetoplast up to 4 u from posterior end, with a long, free flagellum. Stumpy forms stout, averaging 18 u in length with a range of 12 to 26 u; posterior end broad, obtusely rounded, with kinetoplast almost terminal; free flagellum typically absent. Intermediate forms average 23 u in length; body of medium thickness, with blunt posterior end; moderately long free flagellum always present. A fourth form with a posterior nucleus often appears in laboratory animals.
Life Cycle: When it is first introduced into the body, T. brucei multiplies in the blood and lymph by longitudinal binary fission in the trypanosome stage, being particularly common in the lymph glands. Later the trypanosomes pass into the cerebrospinal fluid and multiply here and between the cells of the brain. Leishmanial forms have also been reported from the heart muscle of infected monkeys (Noble, 1955).
The vector is a tsetse fly of the genus Glossina. T. brucei is generally transmitted by members of the morsitans group of this genus, i.e., G. morsitans, G. swynnertoni and G. pallidipes. Both males and females feed on blood and act as vectors. Only a small percentage of the tsetse flies which feed on an infected animal become infected, most being apparently resistant. In experimental studies, 10% or less become infected, while less than 1% of wild flies caught in endemic areas are infected.
When ingested by a tsetse fly, T. brucei localizes in the posterior part of the midgut and multiplies in the trypanosome form for about 10 days. At first the trypanosomes are relatively broad, up to 35 u long, with a kinetoplast about halfway between the posterior end of the body and the nucleus, with a less pronounced undulating membrane than the blood form, and with a free flagellum. On the 10th to 12th day, slender forms appear and migrate slowly toward the proventriculus, where they are found on the 12th to 20th days. They then migrate forward into the esophagus and pharynx, thence into the hypopharynx and finally into the salivary glands. Here they attach themselves to the walls by their flagella or lie free in the lumen, and turn into the crithidial form. These multiply further and then transform into the metacyclic trypanosome form, which is small, stumpy, and may or may not have a short free flagellum.
The metacyclic trypanosomes are the infective forms. They are injected into the blood with the saliva when the fly bites; up to several thousand may be introduced by the bite. The whole life cycle in the tsetse fly takes 15 to 35 days, and the flies are not infective until the metacyclic trypanosomes have appeared in the salivary glands.
This type of development, in which the trypanosomes are found in the anterior part of the vector and are introduced by its bite, is known as development in the anterior station to contrast it with development in the posterior station or hindgut. In the latter, exemplified by the lewisi group, infection is by contamination with feces.
In addition to the cyclical transmission described above, T. brucei may occasionally be transmitted mechanically by tsetse flies or other biting flies. In this case, the trypanosomes remain alive in the proboscis for a short time and are transferred to a new host if the fly bites it soon enough after having bitten an infected one.
Pathogenesis: The signs and pathogenesis of the trypanosomoses of domestic animals are more or less similar. Different hosts are affected to different degrees. Horses, mules and donkeys are very susceptible to T. brucei. Affected animals have a remittent fever, edematous swellings of the lower abdomen, genitalia and legs, a watery discharge from the eyes and nose, and anemia. The animals become emaciated altho their appetite is good. Muscular atrophy sets in, and eventually incoordination and lumbar paralysis develop, followed by death. The course of the disease is 15 days to 4 months, and untreated animals rarely recover.
The disease in sheep, goats, camels and dogs is also severe. The signs are much the same as in horses. In the dog, fever may appear as shortly as five days after infection, and the parasites often cause conjunctivitis, keratitis and blindness.
The disease is usually more chronic in cattle. There is remittent fever with swelling of the brisket, anemia, gradual emaciation, and discharge from the eyes and nose. The animals may survive for several months. Swine are more resistant than cattle and usually recover.
Following infection, the trypanosomes appear first in the blood and lymph, causing fever, edema, anemia, etc. and only later on are they able to invade the central nervous system, causing incoordination, paralysis and meningoencephalitis.
The exact way in which they act to kill their victims is unknown, altho several theories have been advanced. It is known that they have a high glucose metabolism, and one theory was that they rob the body of glucose so that death is due to hypoglycemia. In experimental animals, life can be prolonged by feeding glucose and shortened by injecting insulin. This theory, however, has been discredited.
It is known that the serum potassium level increases in trypanosomosis, and another theory was that the effects are due to the high potassium level. However, the latter is a result of the disease and not a cause. It is due to the destruction of red cells with consequent release of potassium into the plasma, and the observed levels are not too harmful.
Epidemiology: The epidemiology of the diseases caused by T. brucei and other tsetse-borne trypanosomes depends upon the bionomics and distribution of their vectors. This is such a vast subject that no attempt will be made to cover it here. In general, tsetse flies occupy almost 4 million square miles of Africa. They occur in woodlands, bush or forested areas where there is ample rainfall and where the mean annual temperature is above about 70° F. Not all species are good vectors, and trypanosomosis does not occur every place that tsetse flies do. For further information on tsetse flies and the epidemiology of trypanosomosis, see Buxton (1948, 1955, 1955a), Hornby (1949, 1952), Davey (1958) and Ashcroft (1959).
Diagnosis: In the acute or early stage of the disease, trypanosomes can be found in the peripheral blood. Thick blood smears are preferable to thin ones. The protozoa are found even more often in the lymph glands. They can be detected in fresh or stained smears of fluid obtained by puncture of the glands. In the later stages of the disease, trypanosomes can be found in the cerebrospinal fluid. Laboratory animals such as the rat can also be inoculated. The complement fixation test can also be used; it is not specific for T. brucei infections, but also reacts in a number of other trypanosomoses.
Cultivation: Trypanosomes can be successfully cultivated in a number of media. A common one is NNN medium, which is essentially a 25% blood agar slant. Another medium is that of Weinman (1946), which contains beef extract, peptone, washed erythrocytes and plasma. Still another is that of Tobie, von Brand and Mehlman (1950). A discussion of problems of cultivation and diagnosis is given by Weinman (1953). Trypanosomes can also be cultivated in developing chick embryos or in tissue culture. See Pipkin (1960) for a review of this subject.
Treatment: Many different drugs have been used in the treatment of trypanosomosis. Indeed, the first synthetic organic compound of known composition ever used to cure an experimental disease was trypan red, which was developed by Ehrlich and Shiga (1904). Since that time thousands of drugs have been found to show some activity, but the number of satisfactory ones is very small. The chemotherapy of trypanosomiasis has been reviewed by Findlay (1950), Ing (1953), Browning (1954), Goodwin and Rollo (1955), Davey (1957), and others.
Altho much of the earlier work on chemotherapy was done on members of the brucei subgroup, most of that since World War II on trypanosomosis of livestock has dealt with the vivax and congolense groups.
Antrycide methyl sulfate is perhaps the drug of choice for T. brucei in horses. It is injected subcutaneously at the rate of 5 mg/kg body weight; two treatments may be given 4 days apart. Antrycide is also effective against T. brucei in dogs, cattle and other animals.
Suramin (Germanin, Naganol, Antrypol, Moranyl, Bayer 205, Fourneau 309, etc.) has been used for many years. A single dose of 4 g per 1000 lb body weight is given intravenously to horses, but it may be toxic in some animals. In dogs, 4 mg/kg is given intravenously.
The diamidines, pentamidine and stilbamidine, have been used extensively against T. gambiense and T. rhodesiense in man, but have been used very little in veterinary medicine. Another diamidine, Berenil, appears promising against T. brucei, but needs more study.
Control: Preventive measures against trypanosomosis include measures directed against the parasite, measures directed against the intermediate hosts, livestock management, elimination of reservoir hosts, and avoidance of accidental, mechanical contamination. Measures directed against the parasite include continuous survey and treatment or slaughter of all affected animals and periodic mass prophylactic treatment of all animals. The latter is discussed in the section on treatment of T. congolense.
Fly traps and fly repellents have been used without much success in attempting to control tsetse flies. Elimination of breeding places has been practiced on a wide scale in many areas. Since the tsetse flies breed under brush along streams or in other localities, such measures consist essentially of brush removal. Two methods are used:
Eradicative clearing aims at eradication of tsetse flies thruout an area. All the species of trees and shrubs under which the flies survive thru the dry season are removed. When this is done thoroughly over a large area, the flies disappear completely.
Protective clearing is more limited. It is designed to break the contacts between tsetse flies and domestic animals and man at the places where transmission is taking place. Fly-free belts wide enough so that the flies cannot cross them are established. In addition, inspection stations known as deflying houses may be set up on traffic routes to remove flies which may be carried across on vehicles or animals.
Bush clearing can be quite successful. The incidence of trypanosomosis was reduced by 92% between 1938 and 1944 in the Kamba area of Africa by this means (Morris, 1946). However, it is expensive, requires a large amount of labor, and the initial clearing must be followed up faithfully as new growth occurs.
A potentially much more satisfactory control measure is the spraying of insecticides on fly breeding places by means of aircraft. DDT and benzene hexachloride are highly effective for this purpose. Glossina pallidipes was eradicated from Zululand by airplane spraying with these insecticides at a total cost of 2. 5 million pounds, or slightly less than 2 shillings per acre (DuToit, 1959).
Since tsetse flies bite only in the daytime, night grazing has been practiced by African natives to avoid their bites. The animals are held in a protected corral during the day.
Cattle can be sprayed with DDT or another insecticide in order to kill any tsetse flies which light on them.
The elimination of reservoir hosts, e.g., wild game in Africa, has been advocated and practiced in some regions despite the protests of many people interested in game preservation. The Trypanosomiasis Committee of Southern Rhodesia (1946) has described and defended the practice. It claims that if a zone 10 miles wide with its ends in fly-free country is fenced off and all the game within it is killed, Glossina morsitans will disappear in less than 10 years. The fences can then be removed and the game allowed to return into the area.
Since trypanosomes can be transmitted mechanically by inoculation of infected blood or lymph, there is danger of its transmission by the use of contaminated instruments in bleeding, castrating, etc.
A great deal has been written on trypanosomosis control. For further information, see Hornby (1949, 1952), Morris (1946), Buxton (1948, 1955) and the proceedings of the meetings of the International Scientific Committee for Trypanosomiasis, which held its sixth meeting in 1956.