Definition
African animal trypanosomiasis (AAT) is a disease complex caused
by tsetse-fly-transmitted Trypanosoma congolense, T. vivax, or T. brucei
brucei, or simultaneous infection with one or more of these trypanosomes. African
animal trypanosomiasis is most important in cattle but can cause serious losses in pigs,
camels, goats, and sheep. Infection of cattle by one or more of the three African animal
trypanosomes results in subacute, acute, or chronic disease characterized by intermittent
fever, anemia, occasional diarrhea, and rapid loss of condition and often terminates in
death. In southern Africa the disease is widely known as nagana, which is derived from a
Zulu term meaning "to be in low or depressed spirits"— a very apt
description of the disease.
Etiology
African animal trypanosomiasis is caused by protozoa in the family
Trypanosomatidae genus Trypanosoma. T. congolense resides in the subgenus Nannomonas,
a group of small trypanosomes with medium-sized marginal kinetoplasts, no free flagella,
and poorly developed undulating membranes. In east Africa, T. congolense is
considered to be the single most important cause of AAT. This trypanosome is also a major
cause of the disease in cattle in west Africa. Sheep, goats, horses, and pigs may also be
seriously affected. In domestic dogs, chronic infection often results in a carrier state.
T. vivax is a member of the subgenus Duttonella, a
group of trypanosomes with large terminal kinetoplasts, distinct free flagella, and
inconspicuous undulating membranes. T. vivax is a large (18-26 µm long)
monomorphic organism that is very active in wet-mount blood smears. Cattle, sheep, and
goats are primarily affected. Although this organism is considered to be less pathogenic
for cattle than T. congolense, it is nevertheless the most important cause of AAT
in west African cattle. This trypanosome readily persists in areas free of tsetse flies
(for example, in Central and South America and in the Caribbean), where it is transmitted
mechanically by biting flies or contaminated needles, syringes, and surgical instruments.
T. brucei brucei resides in the subgenus Trypanozoon.
T. b. brucei is an extremely polymorphic typanosome occurring as short, stumpy
organisms without flagella, long slender organisms with distinct flagella, and
intermediate forms that are usually flagellated. Horses, dogs, cats, camels and pigs are
very susceptible to T. b. brucei infection. Infection of cattle, sheep, goats and
sometimes pigs results in mild or chronic infection. This last observation, although
widely accepted, has been called into question by Moulton and Sollod (13), who cite
evidence that this organism is widespread in east and west Africa and that it can cause
serious disease and high mortality in cattle, sheep, and goats.
Host Range
Cattle, sheep, goats, pigs, horses, camels, dogs, cats, and
monkeys are susceptible to AAT and may suffer syndromes ranging from subclinical mild or
chronic infection to acute fatal disease. Rats, mice, guinea pigs, and rabbits are useful
laboratory species.
More than 30 species of wild animals can be infected with
pathogenic trypanosomes, and many of these remain carriers of the organisms. Ruminants are
widely known to be active reservoirs of the trypanosomes. Wild Equidae, lions, leopards,
and wild pigs are all susceptible and can also serve as carriers of trypanosomes.
Geographic Distribution
The tsetse-fly-infested area of Africa extends from the southern
edge of the Sahara desert (lat. 15° N.) to Angola, Zimbabwe, and Mozambique
(lat. 20° S.). Of the three African animal trypanosomes, only T. vivax occurs in the Western Hemisphere in at least 10 countries in the Caribbean and South and
Central America
Transmission
In Africa, the primary vector for T. congolense, T.
vivax, and T. b. brucei is the tsetse fly. These trypanosomes replicate in the
tsetse fly and are transmitted through tsetse fly saliva when the fly feeds on an animal.
The three main species of tsetse flies for transmission of trypanosomes are Glossina
morsitans, which favors the open woodland of the savanna; G. palpalis, which
prefers the shaded habitat immediately adjacent to rivers and lakes; and G. fusca,
which favors the high, dense forest areas. Trypanosomiasis is also mechanically
transmitted by tsetse and other biting flies through the transfer of blood from one animal
to another. The most important mechanical vectors are flies of the genus Tabanus,
but Haematopota, Liperosia, Stomoxys, and Chrysops flies have also been
implicated. In Africa, both T. vivax and T. b. brucei have spread beyond the
"tsetse fly belts" (20), where transmission is principally by tabanid and
hippoboscid flies.
The vector for T. vivax in the Western Hemisphere remains
unknown, but several species of hematophagous (especially tabanid and hippoboscid) flies
are believed to serve as mechanical vectors.
Incubation Period
The incubation period for T. congolense varies from 4 to 24
days; for T. vivax, from 4 to 40 days; and for T. b. brucei, from 5 to 10
days.
Pathogenesis
Initial replication of trypanosomes is at the site of inoculation
in the skin; this causes a swelling and a sore (chancre). Trypanosomes then spread to the
lymph nodes and blood and continue to replicate. T. congolense localizes in the
endothelial cells of small blood vessels and capillaries. T. b. brucei and T.
vivax localize in tissue. Antibody developed to the glycoprotein coat of the
trypanosome kills the trypanosome and results in the development of immune complexes.
Antibody, however, does not clear the infection, for the trypanosome has genes that can
code for many different surface-coat glycoproteins and change its surface glycoprotein to
evade the antibody. Thus, there is a persistent infection that results in a continuing
cycle of trypanosome replication, antibody production, immune complex development, and
changing surface-coat glycoproteins.
Immunologic lesions are significant in trypanosomiasis, and it has
been suggested that many of the lesions (e.g., anemia and glomerulonephritis) in these
diseases may be the result of the deposition of immune complexes that interfere with, or
prevent, normal organ function. The most significant and complicating factor in the
pathogenesis of trypanosomiasis is the profound immunosuppression that occurs following
infection by these parasites. This marked immunosuppression lowers the host's resistance
to other infections and thus results in secondary disease, which greatly complicates both
the clinical and pathological features of trypanosomiasis.
Clinical Signs
Because simultaneous infections with more than one trypanosome
species are very common (18), and simultaneous infection with trypanosomes and other
hemoparasites (Babesia spp., Theileria spp., Anaplasma spp., and Ehrlichia spp.) frequently occurs, it is difficult to conclude which clinical signs are attributable
to a given parasite. Few adequately controlled studies have been made, and thus a
"typical" clinical response to each trypanosome is difficult to reconstruct.
What follows is a summation of the syndromes observed in field and experimental cases of
trypanosomiasis caused by each of the three African animal trypanosomes.
The cardinal clinical sign observed in AAT is anemia. Within a
week of infection with the hematic trypanosomes (T. congolense and T. vivax)
there is usually a pronounced decrease in packed cell volume, hemoglobin, red blood cell,
and white blood cell levels, and within 2 months these may drop to below 50 percent of
their preinfection values. Also invariably present are intermittent fever, edema and loss
of condition (Fig. 2). Abortion may be
seen, and infertility of males and females may be a sequel. The severity of the clinical
response is dependent on the species and the breed of affected animal and the dose and
virulence of the infecting trypanosome. Stress, such as poor nutrition or concurrent
disease, plays a prominent role in the disease process, and under experimental conditions,
where stress may be markedly reduced, it is difficult to elicit clinical disease.
T. congolense is a hematic trypanosome found only
in the blood vessels of the animals it infects. It does not localize and multiply outside
blood vessels. Infection with T. congolense may result in peracute, acute, or
chronic disease in cattle, sheep, goats, horses, and camels. Pigs often develop a milder
disease; chronic disease is common in dogs. The incubation period is followed by
intermittent febrile episodes, depression, lethargy, weakness, loss of condition, anemia,
salivation, lacrimation, and nasal discharge. As the disease progresses, loss of
condition and hair color changes from black to metallic brown are seen. The back is often
arched and the abdomen "tucked up." Accelerated pulse and jugular pulsation
occur and breathing is difficult. Anemia is a prominent sign. Early in the infection, the
organisms are readily demonstrable in blood smears, but, as the disease progresses to its
acute and chronic forms, organisms are most readily demonstrated in lymph node smears.
T. vivax has a variable incubation period, and, although it
is considered to be less virulent for cattle than T. congolense, mortality rates of
over 50 percent can occur. There seems to be a marked variation in the virulence of
different strains of T. vivax, but it remains the most important cause of
trypanosomiasis of cattle, sheep, and goats in west Africa. It causes mild disease in
horses and chronic disease in dogs. T. vivax is often difficult to find in blood
smears and can also be demonstrated in lymph node smears.
T. brucei brucei has a relatively short
incubation period and causes severe to fatal infection in horses, camels, dogs, and cats.
It usually causes mild, chronic, or subclinical disease in cattle, sheep, goats, and pigs.
A febrile response occurs in the horse 4-14 days after infection. This is followed by
recurrent febrile reactions. The heartbeat and respiration may be accelerated, and loss of
condition and weakness are seen, whereas the appetite remains good. Progressive anemia and
icterus, and edema of the ventral regions, especially the male genitalia, are
characteristic. The organisms are not always easily perceived in blood smears and are best
demonstrated in tissue smears or sections, (e.g., lymph nodes). Infected animals die in a
few weeks or several months, depending on the virulence of the strain of T. b. brucei.
The marked immunosuppression resulting from trypanosome infection
lowers the host's resistance to other infections and causes in secondary disease, which
greatly complicates both the clinical and pathological features of trypanosomiasis.
Gross Lesions
No pathognomonic change is seen in AAT. Anemia, edema, and serous
atrophy of fat are commonly observed. Subcutaneous edema is particularly prominent and is
usually accompanied by ascites, hydropericardium, and hydrothorax. The liver may be
enlarged, and edema of lymph nodes is often seen in the acute disease, but they may be
reduced in size in the chronic disease. The spleen and lymph nodes may be swollen, normal,
or atrophic. Necrosis of the kidneys and heart muscle and subserous petechial hemorrhages
commonly occur. Gastroenteritis is common, and focal polioencephalomalacia may be seen. A
localized lesion (chancre) may be noted at the site of fly bite, especially in goats. The
anemic blood changes are anisocytosis, poikilocytosis, polychromasia, and punctate
basophilia. All, some, or none of the above may be seen.
The lesions caused by the trypanosomes in susceptible host species
vary considerably, depending on the species and strain of trypanosome and the species and
breed of host animal affected. The hematic trypanosomes (T. congolense and T.
vivax) cause injury to the host mainly by the production of severe anemia, which is
accompanied in the early stages of the disease by leukopenia and thrombocytopenia. In the
terminal stages of the disease caused by the hematic trypanosomes, focal
polioencephalomalacia probably results from ischemia due to massive accumulation of the
parasites in the terminal capillaries of the brain.
The lesions resulting from T. b. brucei (a tissue parasite)
are remarkably different from those seen with the hematic trypanosomes. Anemia is an
important lesion, but much more dramatic are the inflammation, degeneration, and necrosis
resulting from cellular invasion of various organs. Marked proliferative changes
reflecting immunologic response are observed in most body tissues.
Diagnosis
Field Diagnosis
Trypanosomiasis should be suspected when an animal in an endemic
area is anemic and in poor condition. Confirmation depends on the demonstration of the
organism in blood or lymph node smears.
In the early phases of infection, especially with T. vivax and T. congolense, the parasite can readily be observed by microscopic examination
of a wet-mount of blood slides. Thick blood films and stained with Giemsa are also a good
technique (Fig. 1), but in thin fixed
blood films, which are favored for species identification, the parasites may be hard to
demonstrate. When parasitemia is low, smears of buffy coat (obtained by microhematocrit
centrifugation) can be useful for demonstration of the parasites. Because T. congolense tends to associate with the erythrocytes, it is essential that buffy coat and adjacent
erythrocytes be included in the smear to ensure demonstration of the parasite.
Stained lymph node smears are a very good method for diagnosis,
especially for T. vivax and T. b. brucei. In chronic T. congolense infection, the parasites localize in the microcirculation of the lymph nodes and in other
capillary beds, allowing diagnosis by examination of lymph node smears or smears made with
blood collected from the ear. Early in infection, blood smears are optimal for the
demonstration of T. congolense.
These conventional techniques of microscopic examination for the
presence of trypanosomes are still widely used, but newer and far more sensitive methods
are beginning to supplant them. The antigen-detecting enzyme-linked immunosorbent assay is
extremely sensitive for the detection of trypanosomiasis in cattle and goats (12, 25), and
species-specific DNA probes have been shown to detect simultaneous infection of cattle
with T. vivax, T. b. brucei, and T. congolense when conventional
methods revealed only single infections (18).
Specimens for the Laboratory
To perform the preceding and more sensitive procedures, the
following specimens should be submitted to the laboratory from several animals: serum,
blood with the anticoagulant EDTA, dried thin and thick blood smears, and smears of needle
lymph node biopsies.
Control and Eradication
Vector Control
Fly eradication and drug prophylaxis are the only effective
trypanosomiasis control methods now available. Several approaches to fly control have been
used with varying degrees of success.
Discriminative bush clearing, extensively used in early tsetse fly
eradication campaigns, has been locally useful because it eliminates the breeding places
of the tsetse. But, to be completely effective, bush clearing requires ecologically
unacceptable destruction of vast areas of brush and forest. It is still a useful procedure
when used locally in conjunction with other control methods.
Game elimination, and thus elimination of the main source of
bloodmeals for the tsetse, was used in early eradication campaigns.
This was an ineffective and wasteful procedure.
Application of the sterile male technique (as used in screwworm
eradication in the United States) received considerable attention in the 1980's. Early
problems with breeding of the male flies have been overcome, and field trials have been
done in both east and west Africa to determine the effectiveness of this approach in
vector control. In limited trials, this procedure has reduced fly populations.
Ground and aerial spraying with insecticides and the use of
synthetic pyrethroids on cattle have lowered fly densities in some areas, but widespread
use would require considerable international cooperation and expense. Widespread
application of insecticide has the tremendous disadvantage of also eradicating many other
arthropods, several of which are desirable. The recent introduction of odor-baited targets
impregnated with insecticides is proving promising as a means of reducing the tsetse fly.
Chemotherapy and Chemoprophylaxis
The use of drugs for the prevention and treatment of
trypanosomiasis has been important for many decades, but the rapidity with which the
trypanosomes have developed resistance to each drug introduced has tremendously
complicated this approach to controlling the disease. In spite of this, some of the older
chemoprophylactic drugs such as the quinapyramine derivatives Antrycide and Antrycide
Prosalt are still used and give effective protection against T. b. brucei infection
in horses, camels, and cattle for up to 3 months. The drug pyrithidium bromide (Prothidium
and AD2801) is useful in the prophylaxis of T. vivax and T. congolense infections in cattle, sheep, and goats and can give protection for up to 6 months. The
most widely used of the newer chemoprophylactic drugs (and also the least expensive) is
isometamidium chloride (26). This drug, in use for over 20 years and sold under the trade
names Samorin, Trypamidium, and M&B 4180A, is excellent for the prophylaxis of all
three African animal trypanosomes, and gives protection for 3-6 months. The development of
resistance to this drug has been reported in both east and west Africa. Homidium bromide
has also been found to be an effective chemophrophylactic drug in Kenya, and the newly
introduced arsenical Cymelarsan is effective in treatment of T. b. brucei infection.
A very widely used chemotherapeutic drug is diminazine aceturate
(Berenil), which is effective against all three African animal trypanosomes. The
isometamidium drugs are also excellent chemotherapeutic agents as are the quaternary
ammonium trypanocides Antrycide, Ethidium and Prothidium.
Although extensively used in trypanosomiasis control,
chemoprophylaxis is an expensive, time-consuming, and thus unsatisfactory long-term
solution to the problem of African animal trypanosomiasis.
Immunization
No vaccine is currently available for African animal
trypanosomiasis.
Trypanotolerance
It has long been recognized that certain breeds of African cattle
are considerably more resistant to African trypanosomiasis that others. This is especially
true of the west African short-horned cattle (Muturu, Baoule, Laguna, Samba, and Dahomey)
and the N'Dama, which is also of west Africa. These cattle have existed in the region for
over 5,000 years. Susceptibility studies have shown the N'Dama to be the most resistant
breed followed by the smaller west African short-horned cattle, but the large and more
recently introduced Zebu is the most susceptible (15). The mechanisms of trypanotolerance
have been extensively studied, and it is now well established that trypanotolerance has a
genetic basis (13, 17). Trypanotolerance in sheep and goats has also been described, but
the mechanisms of the tolerance phenomenon have not been defined.
Public Health
The three AAT trypanosomes are considered to be nonpathogenic for
humans. T. b. brucei, although not causing human disease, is closely related to T.
b. gambiense and T. b. rhodesiense. The latter is the cause of human sleeping
sickness, a very debilitating and often fatal disease considered to be of major public
health significance in 36 sub-Saharan countries of west, central, and east Africa with 50
million people at risk (18). In west and central Africa, a chronic form of human sleeping
sickness is caused by T. b. gambiense, which uses humans as its major host but also
infects pigs. In east and southern Africa, T. b. rhodensiense is the cause of a
much more acute form of human sleeping sickness. This trypanosome also infects cattle,
bushbuck (Tragelaphus scriptus), and probably many other wild animals that may
serve as reservoirs of the parasite.
GUIDE TO THE LITERATURE
1. ANOSA, V.O., LOGAN-HENFREY, L.L., and SHAW, M.K. 1992. A
light and electron microscopic study of changes in blood and bone marrow in acute
hemorrhagic Trypanosoma vivax infection in calves. Vet. Pathol., 29:33-45
2. ASHCROFT, M.D., BURTT, E., and FAIRBAIRN, H.
1959. The experimental infection of some African wild animals with Trypanosoma
rhodesiense, T. brucei, and T. congolense. Ann. Trop. Med. Parasitol.,
53:147-161
3. DOLAN, R. B. 1987. Genetics and trypanotolerance. Parasit.
Today 3:137-143.
4. EPSTEIN, H. 1971. The Origin of the Domestic Animals of
Africa, Vols. 1 and 2. New York: Africana.
5. FINELLE, P. 1973. African animal trypanosomiasis. World Animal
Review, 7:1-6 and 8:24-27.
6. GOODING, R.H. 1992. Genetic variation in tsetse flies and
implications for trypanosomiasis. Parasit. Today 8:92-95.
7. KOBAYASHI, A., TIZARD, I.R., and WOO, P.T.K. 1976. Studies on
the anaemia in experimental African trypanosomiasis. II. The pathogenesis of the anemia in
calves infected with Trypanosoma congolense. Am. J. Trop. Med. Hyg., 25:401-406.
8. KUZOE, F.A.S. 1991. Perspectives in research and control of
African trypanosomiasis. Ann. Trop. Med. Parasit., 85:33-41.
9. LOGAN-HENFREY, L.L., GARDINER, P.R., and MAHMOUD, M.M. 1992.
"Animal Trypanosomiasis in Subsaharan Africa." In Parasitic Protozoa,
Vol. 2, J. Krier and J. Baker, Eds., Academic Press, pp. 157-276.
10. LOSOS, G.J., and CHOUINARD, A. 1979. Pathogenicity of
Trypanosomes. Ottawa: IDRC Press..
11. LOSOS, G.J., and IKEDE, B.O. 1972. Review of the pathology of
disease in domestic and laboratory animals caused by Trypanosoma congolense, T.
vivax, T. brucei, T. rhodesiense, and T. gambiense. Vet. Pathol.
9 (Suppl):1-71.
12. MASAKE, R.A., and NANTULYA, V.M. 1991. Sensitivity of an
antigen-detecting enzyme immunoassay for diagnosis of Tyrypanosoma congolense infections in goats and cattle. J. Parasitol. 77:231-236.
13. MOULTON, J.E.. and SOLLOD, A.E. 1976. Clinical, serological
and pathological changes in calves with experimentally induced Typanosoma brucei infection. Am. J. Vet. Res., 37:791.
14. MULLA, A.F., and PICKMAN, L.R. 1988. How do African game
animals control trypanosome infections ? Parasit. Today 4:352-354.
15. MURRAY, M., BARRY, J.D., MORRISSON, W.I., WILLIAMS, R.O.,
HIRUMI, H., and ROVIS, L. 1979. A review of the prospects for vaccination in African
trypanosomiasis. World Animal Review, 32:913.
16. MURRAY, M., MORRISON, W.I., MURRAY, P.K., CLIFFORD, D.J., and
TRAIL, J.C.M. 1979. Trypanotolerance — A review. World Animal Review, 31:2-12.
17. MURRAY, M., TRAIL, J.C.M., DAVIS, C.E., and BLACK, S.J. 1984.
Genetic resistance to African trypanosomiasis. J. Inf. Dis. 149:311-319.
18. NYEKO, J.H.P., OLE-MOIYOI, O.K., MAJIWA, P.A.O., OTIENO, L.H.,
and OCIBA, P.M. 1990. Characterization of trypanosome isolates from cattle in Uganda using
species-specific DNA probes reveals predominance of mixed infections. Insect Sci. Applic.
11:271-280.
19. ONAH, D.N. 1991. Porcine trypanosomiasis in Nigeria. Trop.
Anim. Hlth. Prod. 23:141-146.
20. RODER, P.L., SCOTT, J.M., and PEGRAM, R.G. 1984. Acute Trypanosoma
vivax infection of Ethiopian cattle in the apparent absence of tsetse. Trop. Anim.
Hlth. Prod. 16:141-147.
21. ROGERS, D.J., and RANDOLPH, S.E. 1991. Mortality rates and
population density of tsetse flies correlated with satellite imagery. Nature 351:739-741.
22. SPRIGGS, D.R. 1985. Antigenic variation in trypanosomes:
Genomes in flux. J. Inf. Dis. 152:855-856.
23. TIZARD, I.R., HOLMES, W.L., YORK, D.A., and MELLORS, A. 1977.
The generation and identification of the hemolysin of Trypanosoma congolense.
Experientia (Switzerland), 33:901-902.
24. TIZARD, I., NIELSEN, K.H., SEED J.R., and HALL., J.E. 1978.
Biologically active products from African trypanosomes. Microb. Rev., 42:661-681.
25. TRAIL, J.C.M., DIETEREN, G.D.M., MAILLE, J.C., YANGARI, G.,
and NANTULYA, V.M. 1991. Use of antigen-detection enzyme immunoassays in assessment of
trypanotolerance in N'Dama cattle. Acta Tropica 50:11-18.
26. OGUNYEMI, O., and ILEMOBADE, A.A. 1989. Prophylaxis of African
trypanosmiasis; A review of some factors that may influence the duration of isometamidium
chloride prophylaxis. Vet. Bul. 59:1-4.
27. SULIMAN, H.B., and FELDMAN, B.F.1989. Pathogenesis and
aetiology of anaemia in trypanosomiasis with special reference to T. brucei and T.
evansi. Vet. Bull. 59:99-107.
28. WELLS, E.A., RAMIREZ, L.E., and BETANCOURT, A. 1982.
Trypanosoma vivax in Colombia: Interpretation of field results. Trop. Anim. Hlth. Prod.,
14:141-150.
29. WILLIAMS, D.J.L, NAESSENS, J., SCOTT, J.R., and McODIMBA, F.A.
1991. Analysis of peripheral leucocyte populations in N'Dama and Boran cattle following a
rechallenge infection with Trypanosoma cogolense. Parasite Immunol. 13;171-185.
C. J. Maré, B.V.Sc.. Ph.D., Veterinary Science/Microbiology,
University of Arizona, Tuson, Az
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