TSETSE-FLY DISEASE (morbus dormitivus; synonym African trypanosomiasis) — protozooz, caused by trypanosomes and characterized by irregular attacks of fever, an enanthesis, increase in lymphatic glands, the increasing drowsiness. There are Gambian (West African) and Rhodesian (East African) forms of a disease differing in epidemiology and a clinical picture.
About S.'s epidemics. it is mentioned in the Arab manuscripts of 14 century. J. Atkins in 1734 gave the first description of its clinic. Trypanosomes in blood of the healthy person Ford for the first time found (R. M of Ford) in 1901 in Gambia, and in 1902 Dutton (J. E. Dutton) described them under the name Trypanosoma gambiense. In 1909 Stefens and Fantem (J. WT. W. Stephens, H. Century of Fantham) found in the Rhodesian with acute fever of trypanosomes, to-rykh described in 1910 and called T. rhodesiense. D. Bruce and D. Nabarro in 1903 and Kingkhorn and York (A. Kinghorn, W. Yor-ke) in 1912 established that carriers of T. gambiense and T. rhodesiense are tsetse flies (see), according to Glos-sina paipalis and Glossina morsitans. In 1909 Dr. Klein and in 1913 Robertson (M. of Robertson) studied a life cycle of trypanosomes in an organism of carriers. The first tripanotsidny to lay down. drug — atoksit synthesized in 1905 P. Ehrlich and S. Hata.
C. is defined by an area of tsetse flies. These thermophilic and hygrophilous insects of the African continent live in a zone with the annual sum of rainfall more than 500 mm. The Gambian form meets in many countries of the Western and Central Africa, Rhodesian — hl. obr. in Uganda, Tanzania, Zambia. In the western Africa in the 70th 20 century annually were registered on average apprx. 8,5 thousand cases of a Gambian form C. Number of registered S.'s cases. the Rhodesian form averages 1,5 thousand a year. Tsetse flies are registered in 36 countries of Africa, and to risk of infection, according to WHO data, are exposed apprx. 35 million inhabitants.
Activators of the Gambian — T. gambiense (Dutton 1902) and Rhodesian — T. rhodesiense (Stephens Fantham 1910) of a form C. treat the salivaria group (salivar-ny trypanosomes) and are transferred to the person or an animal at a sting by a carrier with saliva. Morphologically they are indistinguishable from each other. The development cycle of trypanosomes passes with change of owners — in an organism of vertebrate animals or the person and in an organism of insects carriers (tsetse flies). In an organism of vertebrate animals salivarny trypanosomes get into stages of metatrypanosomes — thin short aflagellar forms of 2,5X X15 of micron in size. In hypodermic cellulose of a metatrypanosome turn into so-called blood forms of trypanosomes. The expressed polymorphism and antigenic variability are characteristic of trypanosomes. At the beginning of an invasion in blood and an intercellular lymph thin long forms — 20 — 40 microns with a plait (fig.) prevail; in process of development of immunity — short aflagellar forms — of 15 — 25 microns. By serological researches it is established that at development of an invasion the antigenic structure of the activator changes. Trypanosomes longitudinal division breed. Having got with blood of the person or an animal to an average gut of a tsetse fly, long forms die off, short breed, migrate in sialadens where turn in metatrypanosomes. Tsetse flies catch trypanosomes at a krovoso-saniye in the first two days after breeding from a doll. Development of a parasite in a carrier in 20 — 25 days comes to an end. The infected flies are capable to keep the activator in sialadens and to transfer him to the person or an animal until the end of the life, i.e. before half a year.
Main source of T. gambiense is the person (the patient or a parazitonositel), however the parasite was found also at pigs, cows, sheep. Carriers of T. gambiense are tsetse flies of the paipalis group (Glossina paipalis, G. tachinoides, G. fuscipes, etc.), to-rye eat in public, and also on domestic animals. On the basis of it it is assumed that the livestock can be an additional source of an invasion. Flies of the palpalis group live in the territories of the Central and Western Africa differing in the increased humidity, hl. obr. in the woods and in heavy beds on valleys of the rivers. Flies attack in the afternoon, infectiousness their trypanosomes is usually small (apprx. 1%). The contact of flies with people and a livestock sharply increases during droughty seasons when the number and the area of reservoirs decreases, people and animals concentrate about the remained reservoirs. During such periods intensity of transfer of activators increases in the centers, epidemic flashes are possible. Villagers are ill preferential. A part of the infested persons remains parazitonositel (see the Carriage of contagiums). Territories, endemic on Gambian trypanosomiasis, tend to decrease under the influence of activity of the person, however all areas occupied by tsetse flies shall be considered as potentially epidemic dangerous.
Source of an invasion of T. rhodesien-se — antelopes, perhaps, other wildings and the person. Carriers of the activator are tsetse flies of the morsitans group (G. morsi-tans, G. pallidipes, G. swynnertoni, etc.). Their biotopes are shrubby thickets of the East African savannas and a thicket on coast of lakes, main «prokormitel» — wildings (antelopes, wild boars, etc.). The Rhodesian trypanosomiasis — a natural and focal invasion. People are attacked by tsetse flies and T catch. rho-desiense at visit of the natural center for the purpose of hunting, fishing. In settlements S.'s centers. arise with a big number of flies of G. morsitans. Transfer of activators in these cases happens on a chain the sick person — a fly — the person.
Pathogeny and pathological anatomy
Pathogeny and pathological anatomy of both forms C. are similar. The trypanosomes which were implemented into hypodermic cellulose of the person breed on site a sting, causing formation of a trypanosomic chancre by 5th day. Dissimination of parasites on limf. to vessels is followed by a lymphadenopathy, and in 5 days (at a Gambian form C.) and in 12 days (at the Rhodesian form) from the moment of formation of a chancre of a trypanosome appear in blood, and soon and in cerebrospinal liquid; at the same time the quantity of parasites in blood changes — the periods of big number of parasites (2 — 3 days) are replaced by the periods of low number of parasites (2 — 10 days). At Gambian S. the parasitemia is rather scanty, at the Rhodesian form level reaches it 105 parasites in 1 ml of blood. Level of conglutinin increases (see Conglutination), the complement (see) is besieged in fabrics, the gipokomplementemiya and a hypergammaglobulinemia of hl develops. obr. at the expense of IgM, the kinin system becomes more active. Along with specific antibodies (see) heterophyllous antibodies, substances like a rhematoid factor are produced (see), antinuclear antibodies, are found the cell-bound immune complexes circulating and connected with fabrics that corresponds to decrease in a host defense of an organism of the patient.
In various bodies, including a brain, the numerous centers of perivascular infiltration by plasmocytes, dot hemorrhages, necroses are found. Inflammatory changes in a brain extend to a cerebral cortex, take basal kernels, average and a diencephalon. Process of the demyelination caused by autoimmune reaction begins.
the Person has natural immunity (see) to many types of the African trypanosomes striking animals it is also susceptible only to T. gambiense and T. rhodesiense. The postponed disease does not leave behind durable immunity.
One of the factors breaking development of specific immunity at S., antigenic variability of trypanosomes on the course of an invasion is. The formed antibodies specific in relation to this antigenic option of a parasite, suppress its number, but do not affect new option. At an experimental trypanosomiasis on the course of an invasion it was possible to reveal up to thirty three antigenic options of trypanosomes. Thereof the invasion continuously progresses without tendency to self-healing. For the reasons of antigenic variability of activators it was not succeeded to develop a method of specific immunoprevention of S. yet.
The clinical picture
the Gambian form of a trypanosomiasis differs long hron. current. Allocate two periods of a disease: early (gematolimfatichesky) and late (meningoentsefaliticheskrsh). The Gemato-limfatichesky period proceeds from several months to 5 years, on average — year. On skin in the place of a sting of a tsetse fly in 5 days there is primary affect — a trypanosomic chancre, or a tripanom — a dense painful blister to dia. 1 — 2 cm surrounded with a whitish wax-like zone, sometimes ulcerating. Usually it spontaneously disappears in several days.
At a puncture in contents of a blister find numerous parasites. At an exit of trypanosomes in limf, system and blood process generalizutsya; a characteristic symptom of this period of a disease is the fever of the wrong type, the Feverish periods lasting for weeks, are replaced by remissions from several days to several months. On skin there can be erythematic rashes (tripani-da), shaped full or incomplete rings. Their preferential localization — a breast, a back, is more rare the person and other parts of a body. Constant headaches, sleeplessness, tachycardia are characteristic. Early and frequent manifestation of this period of a disease is the lymphadenopathy. Increase mesenteric and peripheral limf, nodes, increase occipital limf, nodes (Uinter-bottom's symptom) is especially characteristic. They are mobile, usually painless, in the first 6 months soft, fibrozirutsya later. Usually the spleen increases, it is frequent also a liver. There are peripheral hypostases, including on a face. In the absence of treatment patients quite often perish during the first period of a disease, but in considerable number of cases the disease passes into the meningo-encephalitic period or actually tsetse-fly disease. During this period there is a drowsiness (and it is observed in the afternoon, and the concern is characteristic at night). At patients the tremor of hands, legs, language, fibrillar twitchings of muscles, a hyperesthesia develop. Patients painfully react to usual noise, napr, to a zakhlopyvaniye of doors (Kerandel's symptom); visual disturbances, scanning speech, spasms of extremities which are replaced by paralyzes, disturbance of mentality up to marasmus (see), a look indifferent are observed. Duration of this period is 4 — 8 months. The general exhaustion, changes in c progress. N of page; usually patients perish in coma. At a part of patients the disease proceeds in the erased form or is limited to a parasitosis.
The clinical picture of the Rhodesian form of a trypanosomiasis is characterized by more acute and short current. The periods of fever are longer, the periods of decrease in temperature are shorter, limf, nodes often do not increase, weakness, exhaustion in connection with the expressed intoxication increases quicker. Usually patients suddenly perish even before development of the expressed phenomena of an encephalomeningitis.
For both forms C. frequent accession of the intercurrent diseases proceeding hard owing to weakening of protective functions of an organism is characteristic. Page. at children proceeds more sharply and it is characterized by early involvement in patol. process of c. N of page
the Diagnosis establish on the basis a wedge, the symptoms given to Epi-demiol. anamnesis and laboratory researches. In the presence of fever, persistent headaches, sleeplessness, a lose of weight, a lymphadenopathy, increase in a spleen and liver at the persons who visited an endemic zone a month before development of a disease it is necessary to suspect S. The diagnosis is considered final at detection of trypanosomes in blood, cerebrospinal liquid or in punctate increased limf. Node.
In the early period of a gambiiskoa of a form C. parasites the easiest are found in native or painted across Romanovsky — to Gimza punctate limf, a node (in firm sclerosed limf, the nodes characteristic of the late period of a disease, trypanosomes usually are absent); at this time pressure of cerebrospinal liquid (see) at the patient increases, in it the cytosis with dominance of lymphocytes is noted, find cells — Mott's morulas producing IgM, sometimes trypanosomes. At the Rhodesian form C. trypanosomes are always found in blood smears. In some cases S.'s diagnosis. establish at detection of trypanosomes in blood of laboratory animals (rats or Guinea pigs), the Crimea enter intraperitoneally blood or cerebrospinal liquid of the patient. From immunol. reactions most often apply reaction of an immunofluorescence (see), reaction of en-winters-marked antibodies (see. Enzyme-immunological method).
Differential diagnosis of a Gambian form C. carry out with malaria (see), lymphadenopathies of other etiology, in particular with a lymphogranulomatosis (see), tuberculosis (see), a toxoplasmosis (see), heart failure (see) and a glomerulonephritis (see), mental disorders, meningitis (see), encephalitis (see). Rhodesian form C. it is necessary to distinguish from a typhoid (see), a septicaemia (see Sepsis), tropical malaria (see).
If necessary to differentiate various forms C. consider epidemiol. anamnesis (stay of the diseased in an area of this or that form C. in Africa), the increased level in blood serum of sick heterophyllous antibodies at the Rhodesian form.
Treatment is most effective in the early period of a disease. The analysis a wedge, yielded and results of a research of cerebrospinal liquid allows to define whether it is involved in patol. process of c. as N of page and depending on it to choose tactics of chemotherapy. In the early period of a disease, if c. by N of page it is not struck, apply suramin or pentamidine. Suramin is shown for treatment of both forms C. It is entered intravenously, preparing 10% ex tempore solution in a dose to 20 mg! kg, but no more than 1,0 g. The discontinuous scheme of introduction is recommended: in the beginning — every second, and further — every fifth or every seventh day, only 5 injections on a course. At diseases of kidneys suramin do not appoint. Treatment by him is carried out under control of function of kidneys: emergence of the riya moderated to a leukocyte (see), to a protein of a riya (see) naturally. The high proteinuria, a cylindruria, emergence of erythrocytes in urine demonstrate development of toxic nephrite (see) also serve as the indication for interruption of a course of chemotherapy.
Pentamidine is effective only at a Gambian form C. It is applied intramusculary in a daily dose of 3 — 4 mg! kg within 7 — 10 days in a row or every other day, on a course 8 — 10 injections. Suramin and pentamidine it is possible to apply combined.
In the late period of a disease apply melarsoprol (arsobat) or other arsenous drugs which are well getting through a blood-brain barrier into tissue of a brain. Drug differs in high performance, but it is necessary to apply it carefully since it can cause reactive encephalopathy with a lethal outcome. Appoint in a dose 1,8 — 3,6 mg/kg intravenously during 3 days. After a week break conduct the second same year and if necessary — the third. The drug is administered strictly in a vein a dry needle since at hit even of its drop in skin there is a strong irritation and long hypostasis. Purpose of the disintoxication, hyposensibilizing, symptomatic means is necessary.
Without S.'s treatment. comes to an end letalno. At the Rhodesian form the lethal outcome is possible in the next few days, at Gambian — in the next weeks after the beginning of a disease. Early the begun treatment leads to an absolute recovery. Treatment in a late stage is much less effective.
In fight against Gambian S. the important place is taken by early detection and treatment of patients. This event is held by specialized mobile groups, to-rye inspect annually in the Western and Central Africa several million inhabitants. In a number of the countries hold broad events for destruction of tsetse flies of the palpalis group by means of insecticides (see), and in districts of distribution of tsetse flies of the morsitans group — by clearing of the area from shrubby thickets for the purpose of reduction of number of biotopes of tsetse flies near settlements. In the years of epidemic raising of Gambian S. among locals carry out mass chemoprophylaxis by pentamidine (3 — 4 mg/kg intramusculary once in 6 months). Chemoprophylaxis by the visitor in Gambian S.'s centers. carry out by pentamidine or suraminy. The visitor in a zone, endemic according to the Rhodesian S., chemoprophylaxis is not recommended to be carried out because of short duration of effect of pentamidine and danger of development of defeats of c. N of page of nonspecific character.
Bibliography: Baroyan O. V. and Bradley D. Modern views on tropical pathology, page 123, M., 1979; Kassirsky I. A., etc. Guide to tropical diseases, M., 1974; The African trypanosomiases, Techn. rep. ser., No. 635, Geneva, WHO., 1979; Raadt P. a. Seed J. R. Trypano-somes causing disease in man in Africa, in book: Parasitic protozoa, ed. by J. P. Krei-er, v. 1, N. Y. — L., 1977.
A. Ya. Lysenko.