2.5 Sleeping sickness and glossinids

Human sleeping sickness is a trypanosomiasis, the transmission of which is linked to Glossinids (Tsetse). It is present only in Africa; Madagascar is not affected.

The West African nosodema is an anthroponosis, the clinical course is chronic and sleeping symptoms can appear many years after the initial infection. The East African nosodema is a zoonosis based on antilopes as a natural reservoir of the pathogen. In man it occurs acutely and death is sudden, e.g. by heart insuffiency. Typical sleeping symptoms are absent.

The pathogenesis involves two stages:
Stage I: the haemo-lymphatic phase. After an incubation period without symptoms, a primary lesion appears at the original entry point, i.e. the location of the infective tsetse bite. This lesion represents a hypersensitivity reaction against trypanosomes in the skin. The regional lymph nodes may swell and trypanosomes appear in the circulating blood indicating the onset of the tranferent phase.
Stage II: the meningo-encephalitic phase. The trypanosomes appear in the cerebrospinal fluid (CFS) and cause sleeping symptoms, which can be considered as an intoxication of the central nervous system (CNS).

The clinical course in detail:
West African nosodema, pathogen Trypanosoma brucei gambiense. Incubation lasts more than two weeks, the primary lesion is weak (local oedema), the onset of patency occurs 2 to 4 weeks post infection (p.i.), with swelling of lymph nodes (fig. 2.37, page 79) not being noticeable before 6 months p.i. and the puncture site is trypanosoma-positive. Central nervous system symptoms rarely appear before 6 months p.i. and are manifested as somnolence, anorexia and marasm and lead to death in 2 to 6 years by kachexia (fig. 2.38, page 80).
East African nosodema, pathogen T. brucei rhodesiense. Incubation lasts a few days and the dramatic primary lesion ulcerates within 1 to 2 weeks p.i. Invasion into the cerebrospinal fluid occurs rapidly within a few weeks p.i., central nervous system symptoms appear 3 to 5 months p.i. and patients survive rarely longer than 9 to 12 months.

Protective immunity is absent in all cases. Without treatment, exitus is unavoidable. For diagnosis, trypanosomes have to be seen microscopically or by other means, either in lymph nodes (West African nosodema) or in the circulating blood or cerebrospinal fluid. Chemotherapy has to be carried out immediately under strict medical observation. In stage I treatment by Suramin (Bayer 205), Pentamidine or Berenil can be carried out. At stage II, treatment by Melarsoprol or Eflornithin is indicated. Advanced cases are difficult to cure.

Trypanosomiasis of livestock and domestic animals, called Nagana, is attributable on one hand to T. brucei brucei parasitizing horse, donkey, mule, dog, cat and mice, but not cattle and on the other hand to T. vivax and T. congolense attacking cattle, giraffe and antilopes and T. congolense attacking zebra, warthog and elefant. Development in the vectors is cyclical only for T. brucei brucei; the others are transmitted contaminatively by Glossinids, Tabanids and Stomoxys spec. Nagana threatens the supply of protein for humans and requires permanent control by sophisticated measures (see below).

The trypanosomes producing human sleeping sickness undergo a change of shape in the vertebrate host and in the vector. All morphs are flagellate and live exclusively in body fluids. The promastigotes in the intestine of the tsetse migrate, after many binary divisions, to the salivary gland of the tsetse and change to epimastigotes, which adhere with their flagellopodium and propagate to produce premetacyclic and later free metacyclic trypomastigotes. On transmission to the vertebrate host, they divide by binary division and some of the originally slender forms become stumpy. The latter are able to develop further when taken up once again by a tsetse fly (fig. 2.40, page 82).

The surface coat of the trypomastigotes consists of glycoproteins. Their first type of specifity, which is exhibited in the warmblooded host, has been developed in the glossinid vector. During patency of the vertebrate host, the antigenic specifity of the surface coat of the circulating trypomastigotes changes repeatedly. This antigenic variance creates a sequence of populations exhibiting changing antigenic specifities, viz. variable antigenic types (VATs) and surface proteins (VSGs), respectively. The corresponding immune responses are permanently neutralised by these VATs and parasitaemia is continuously restored during the latency necessary to elaborate a new specifity. The sequence of VATs is determined in some strains, wheras in others it occurs by pure chance.

Tsetse harbour three species of symbiontic bacteria that are generatively transmitted. Wigglesworthia spec. lives in epithelial cells (bacterioma) of the anterior midgut (fig. 2.39, page 81). Sodalis spec. is an endosymbiont of the cells of the midgut, but also of the muscles, fat body, haemolymph cells and salivary and milk glands. Both are transmitted contaminatively. Wolbachia spec. is located in a bacterioma of the ovaries and is transmitted transovarially.

Glossinids are viviparous delivering mobile prepupae developing alternatively one by one from two ovaries with two ovarioles each. The remaining body enables a distict age grading of the parous flies. The embryo changes into a first instar larva, which is nourished by a milk gland and which moults inside the uterus until it is laid. The prepupa borrows into the leaf-mould below trees and bushes where its tegument hardens immediately (fig. 2.42, page 86).

Both sexes suck blood, the male considerably less than the female. Copulation is carried out only once but lasts for hours. The piercing apparatus corresponds morphologically to the haustellum of cyclorrhaphic flies (fig. 2.41, page 85). The penetration organ consists of the labium, which acts by rasping, reaching a maximal depth of 200 micrometers (fig. 2.43, page 87 and 2.44, page 88). The main glossinid genera are determined by the male and female genitalia (fig. 2.46, page 89).

The biotop of glossinids is usually covered loosely with bushes. In the open grass savannah, tsetse are unable to survive in the dry season because of high midday temperatures and low air humidity. Tsetse find their blood hosts predominantly by optic stimuli. They recognice colours and mobile objects up to 100 meters away in open areas.

The geographical distribution of Gambian and Rhodesian sleeping sickness (fig. 2.49, page 92) and the relationships between many zymodemes isolated from men, domestic and wild animals indicate that the origin of sleeping sickness lies around Lake Victoria (fig. 2.48, page 91).

The control of tsetse is directed against imaginal flies. They can be caught en masse by movable traps made of blue and black cloth. The use of 1 to 2 traps per square kilometer can reduce a tsetse population to 10 to 0.1 % of a comparable non-controlled population. New infections of nagana (cattle) can practically be prevented by such traps.

Insecticides spread by helicopters applying ultra low volume (ULV) techniques can hit tsetse in their resting places on the underside of leaves. The spraying of the bark of trees until to 2 meters from the ground with long-acting substances destroys a tsetse population effectively because the flies escape the local lethal midday temperatures by creeping into cracks in tree bark. No biological control has been established to date, in spite of the low fecundity of glossinids. Mass rearing in the laboratory is possible but is made difficult as sterile cauteles have to be set up for blood feeding because of the presence of bacterial symbionts. The sterile male technique has been succesful only in narrow restricted areas of distribution with natural limits for the flies.

Human sleeping sickness could be controlled effectively by strict supervision combined with chemotherapy of all cases, which have to be actively detected. During politically stable times, incidence remains at about 10 000 new cases per year. The control of the various forms of nagana takes priority because the provision of protein to the human population is threatened.

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