African Trypanosomiasis

The haemoflagellates are parasites of major medical and economic importance. They include Trypanosoma and Leishmania. They dwell in the blood tissues of man and animals either as extracellular or intracellular parasites and are transmitted by insects. Their contribution to human suffering in terms of morbidity and mortality is immense.

Trypanosomes are protozoan haemoflagellates that affect a variety of domestic and wild animals, as well as humans. Some types of trypanosomes cause a debilitating disease called human sleeping sickness. If not treated, human sleeping sickness is invariably fatal.

The geographical distribution of trypanosomiasis is limited by the distribution of the vectorGlossina or tsetse fly. African trypanosomiasis is confined to the continent of Africa south of the Sahara, which corresponds to the distribution of the tsetse flies that serve as its vectors.

The major haemoflagellates transmitted by tsetse flies include Trypanosoma bruceirhodesiense and Trypanosoma brucei gambiense, the two species that cause human sleeping sickness, and Trypanosoma brucei, a parasite of livestock and wild game known as nagana that is morphologically identical to the human parasites. Other important trypanosome diseases transmitted by tsetse flies, are Trypanosoma congolense andTrypanosoma vivax, which are important animal parasites, responsible for serious losses in cattle, sheep and goats. Trypanosoma evansi is a parasite of camels in Africa and Asia that is transmitted mechanically by biting flies. T. vivax is a parasite of domestic animals inAfrica, the West Indies, Central and South America. In Africa, it is transmitted by tsetse flies, whereas outside Africa where there are no tsetse flies, it is mechanically transmitted by horse flies, indicating that it was probably introduced in those areas from Africa.

                       Structure of a trypanosome

The flagellum is a thin whip-like structure that originates from a basal body that is not visible but is located close to the kinetoplast. It extends toward the anterior end of the trypanosome, hanging freely in most species. It is used for locomotion. The undulating membrane is a fold of the cell wall that extends from the body of the trypanosome to which the flagellum is attached. In addition to these major features, the trypanosomes may contain various cytoplasmic inclusions and vacuoles. These appear as small granules throughout the surface.

African Trypanosomiasis

Trypanosoma brucei is a common haemoflagellate of mammals in Africa. In domestic animals, it is usually quite virulent, causing high mortality. This parasite is probably a parent form from which both Trypanosoma gambiense and Trypanosoma rhodesiense were derived. The two human trypanosomes have separate but not distinct distribution. The distribution ofT. gambiense extends from Senegal in West Africa all the way down to Gabon, Central African Republic, Congo and the Democratic Republic of Congo. There is a small focus in theWest Nile region of Uganda, which is probably an extension from the Democratic Republic of Congo. T. rhodesiense is endemic in East Africa, Malawi, Zimbabwe, Zambia andMozambique.

Many species of tsetse flies serve as vectors of trypanosomes but only six are important as vectors of sleeping sickness. These are G. palpalis, G. tachinoides, G. pallidipes, G. fuscipes, G. morsitans and G. swynnertoni. Tsetse flies prefer shade, humidity and temperatures that range from 20 ^oC to 30 ^oC. Each species, however, has slightly different requirements. G. palpalis, G. tachinoides and T. fuscipes are most often found in forest areas, which are shady and have a higher humidity. G. morsitans lives in savannah woodlands and G. pallidipes characteristically is associated with denser thickets in East Africa.

A typical Glossina habitat consists of water holes surrounded by bushes. Glossina rests in the bushes and bites both humans and livestock using the water. The flies are most active during the cool hours before noon and after three in the afternoon.

          A woman draws water in a tsetse fly infested pond

Tsetse flies live for a few months under wet conditions and for 3 to 4 weeks under dry conditions. Once a fly is infected, it remains infective throughout its life.

Life cycle

Development in the tsetse fly

Trypanosomes are grouped into Salivaria and Stercoraria depending on where they undergo development within the vector’s tissues. In the Salivaria, the trypanosomes develop in the midgut and salivary glands and enter the host via the saliva. Both T. gambiense and T. rhodesiense are transmitted via the saliva.

                         Trypanosomes develop in the salivary glands of tsetse

In the Stercoraria, they trypanosomes are taken up in the blood stream, grow, and divide in the hindgut of the insect vector. Infection of the vertebrate host is by contamination. When the insect feeds, it defecates and the trypanosomes gain entry through the feeding site or by skin being scratched. The most important stercorarian trypanosome is T. cruzi, the causative agent of chagas disease.

The life cycles of T. rhodesiense and T. gambiense are indistinguishable. The trypomastigotes are ingested by a feeding tsetse fly. Both male and female tsetse flies are capable of transmitting infection. The parasites multiply in the fly’s midgut for 10 to 15 days during which they become greatly elongated. They then change into epimastigotes and migrate forwards to the proventriculus, where they spend several days undergoing further multiplication.

Life cycle of Trypanosoma rhodesiense. Animals, such as the bushbuck may be involved in the transmission. 

 The epimastigotes leave the proventriculus and proceed to the salivary glands, where they attach to the walls and continue to multiply.  About 20 to 40 days post-infection, the so-called metacyclic trypanosomes or trypomastigote forms appear in the lumen of the salivary glands. The development within the fly takes at least 3 weeks.

Development in the vertebrate

The metacyclic trypomastigotes present in the fly’s salivary glands are transferred to the host’s skin when the fly takes a blood meal. They undergo multiplication within the vicinity of the inoculation site before appearing later in the vertebrate blood one to two weeks after infection. Soon after appearing in the blood stream, the trypanosomes begin to multiply by binary fission and invade all the tissues of the body via the blood and lymphatic systems.

Trypomastigotes found in the blood show morphological polymorphism characterised by long ‘slender’ and short ‘stumpy’ forms. The slender forms have a free flagellum while the stumpy forms are without a free flagellum. The proportions of stumpy and slender forms change as the infection progresses. The slender forms are usually present in large numbers in an active acute infection, whereas the stumpy forms seem to predominate in a chronic infection.

Pathogenesis

The infection occurs in two phases: the early phase and the late phase.

The early phase

A painful local swelling that resembles a boil follows the bite by a tsetse fly. The swelling is known as a chancre. Examination of the chancre shows the presence of trypomastigotes that are dividing. About 2 to 3 weeks later the chancre subsides. The lymph nodes closest to the bite site are swollen while others remain normal at this period.

The incubation period is marked by early clinical symptoms that are extremely variable, depending on the virulence of the trypanosome itself, the resistance of the individual and the presence of other infections. The symptoms may last from a few days to a few weeks, even years. The symptoms are characterized by an intermittent fever which may even disappear later but which is accompanied by headaches, loss of appetite, weakness, joint pains, pruritus (itching) and loss of weight.

Other symptoms include anaemia, cardiovascular and endocrine disorders, and enlargement of the spleen, liver and inflammation of the lymph glands. The cervical, subclavicular and inguinal lymph nodes are particularly palpable. The symptoms are easy to confuse with those of early attacks of malaria infection, or a common cold.

One of the effects of the early infection is the presence of oedema, especially of the ankles, which is due to the leakage of the small blood vessels. The involvement of the lungs at this stage is particularly important because it predisposes to secondary infections, and pneumonia, the latter being a frequent cause of death.

The late phase

As the infection progresses, the parasites cross the blood brain barrier and enter the central nervous system, heralding the second phase of the infection. The involvement of the central nervous system is confirmed by an examination of the cerebrospinal fluid (CSF). It is important to note that the second stage cases may occasionally be asymptomatic. This is a latent stage of infection when only CSF analysis will show the involvement of the central nervous system.

In the late advanced stage of infection, when the parasites are in the central nervous system, the disease takes a dramatic turn. The patient is unable to concentrate and may show moods of irritation, aggressiveness and lethargy.

An advanced case of trypanosomiasis

The patient is overcome by extreme tiredness, apathy and sleep-like unconsciousness as the infection progresses. Because he is unable to eat food, he becomes wasted and eventually falls into a deep coma and dies.

Epidemiology

Trypanosomiasis is endemic in Africa between 20^o N and 20^o S of the equator. It is widely spread throughout the equatorial belt of the continent of Africa with distinct foci where the infection persists and flares up from time to time.

Trypanosomes have rendered huge areas of the most fertile parts of the African continent unsuitable for human settlement and animal rearing. More than one fourth of the arable land inAfrica is unavailable for agriculture and livestock keeping because of the high mortalities caused by human trypanosomiasis and nagana. With the exception of probably malaria, both human and animal trypanosomiasis has contributed greatly to the socioeconomic stagnation of tropical Africa.

Complex epidemiology of trypanosomiasis, involving humans, domestic and wild animals. 

Reservoir hosts are a source infection to humans. Many animals act as reservoir hosts for trypanosomiasis. Trypanosomiasis is, therefore, a zoonosis. Among the reservoirs are cattle, sheep, dogs, goats, bushbuck, giraffe, warthog, hyena, lion, and hartebeest. These animals play a significant role in the maintenance and as a source of infection to man and compound efforts to control the disease.

T. brucei brucei in game is probably the same parasite that infects man as T. gambienseor T. rhodesiense. There are important differences in the behaviour of T. gambiense and T. rhodesiense. T. rhodesiense infections typically appear in thinly populated areas where game animals are common, such as the savannas of east and southern Africa. T. gambienseoccurs in the more densely populated areas, especially riverine-forested areas of West andCentral Africa. T. gambiense produces a slowly developing chronic disease that may go on for several years before actual sleeping sickness symptoms appear. On the other hand, T. rhodesiense is much more acute, taking five to seven days for the symptoms to appear and if not treated, the patient dies in a few weeks to a year.

Because of its acute nature, T. rhodesiense is easier to diagnose, making it possible to deal with outbreaks early enough before they spread. Because of its chronicity, T. gambienseis usually mistaken for malaria or other human diseases that present with fever, and may not be diagnosed until it has spread widely and a major outbreak has occurred.

Diagnosis

For a quick demonstration of the trypanosomes, an examination of a drop of blood under the microscope will show actively moving organisms. However, trypanosomes can easily be demonstrated in thick or thin blood smears stained with ordinary laboratory stains.

                     Trypanosomes stained with Giemsa Chronic low infections are detected by inoculating laboratory animals with blood from suspected human cases. The laboratory animals, usually rats or mice, are monitored for two to three weeks.

Swollen glands are characteristic of an early infection. One of the neck glands is palpated and then squeezed between the fingers and punctured with a hypodermic needle. Juice is aspirated and examined for the presence of parasites.

To demonstrate whether there is neurological involvement, a hypodermic needle is inserted into the spinal cord through the lumbar region. The cerebral spinal fluid (CSF) is withdrawn and examined. Trypanosomes may be present but if not present, an elevated protein content and increased white blood cell count may be indicative of a current or previous infection. Various serological techniques for detection of trypanosomiasis exist but they are not used routinely. For example, in endemic areas serological findings in animals and humans that indicate high Igm titres have been associated with trypanosomiasis.

Vector Control

The use of insecticides is an integral part of tsetse control. Ground spraying is used along infested streams and rivers, including coastal areas. Aerial spraying is used for large-scale operations. Insecticides are, unfortunately, environmentally unfriendly, as they not only kill the tsetse flies but also other non-target insects, including amphibians and even small mammals. They must therefore be used with care.

Bush clearing has been undertaken to clear large areas of tsetse flies. However, the tsetse flies re-establish unless the cleared areas are used for resettlement and crop production. Traps impregnated with deltamethrin, permethrin and other suitable insecticides are very effective in reducing tsetse fly numbers. For example, a 99 .9 % reduction in tsetse fly numbers was achieved in some Ivory Coast villages using insecticide impregnated traps and screens. Similar control methods have been carried out in Uganda with equally good results.

               A mass of tsetse flies captured by traps

Better catches can be achieved by incorporating fly attractants into the traps. Studies inZimbabwe showed that the flies were attracted to natural odours of calves and oxen in large numbers. Further studies identified specific attractants as carbon dioxide, acetone and octenol.

Fly trapping is an inexpensive method of control that can easily be undertaken by the affected community and should always be encouraged.

biological control methods have been attempted. one of these is the sterile male release technique. this is usually used where spraying has already reduced the population of the flies. under this method, tsetse flies are mass reared and then subjected to gamma ray radiation that sterilizes the males but does not affect their ability to mate. on being released, the mating of the sterilized males with normal females in the wild does not lead to the production of viable eggs and since the female tsetse flies mate only once, these mated females become effectively sterile. with further releases of sterile males, the fly population continues to decline, with a corresponding decrease in the transmission of infection.

Treatment

Drugs are effective against trypanosomiasis. Their main drawback is the fact that they show nasty side effects. Suramin is used to treat the early phase of T. rhodesiense while pentamidine is used to treat T. gambiense. These two drugs do not enter the brain. Another drug, melarsoprol or Mel B, can cross the blood barrier and attack the parasites in the central nervous system. It is therefore used to treat the late stages of the infection. A relatively new drug, eflornithine, is effective against late stage T. gambiense but not against T. rhodesiense and has less side effects than Mel B. Experimental studies with mice show that eflornithine with either suramin or melarsoprol was