African trypanosomiasis (sleeping sickness): causes, symptoms, diagnosis, treatment

African trypanosomiasis (sleeping sickness) is an obligate-transmissible invasion characterized by fever, rashes on the skin, enlarged lymph nodes, the appearance of local edema and the defeat of the central nervous system leading to lethargy, cachexia and death.

Trypanosomiasis is a group of vector-borne tropical diseases caused by protozoa of the genus Trypanosoma. Trypanosomes undergo a complex cycle of development with a change of hosts, during which they are in morphologically different stages. Trypanosomes multiply by longitudinal division, feed on dissolved substances.

African trypanosomiasis (sleeping sickness) is common in the savannah zone. Its noso-range is limited by the distribution area of the tsetse fly. Sleeping sickness is endemic in 36 countries of tropical Africa. Annually up to 40 thousand new cases are registered. Probably, the real number of cases is much higher and can be up to 300 thousand. About 50 million people live in conditions of risk of infection.

Two forms of African trypanosomiasis are known: Gambian, or West African, and Rhodesian, or East African. The first is called Tr. Gambiense, the second - Tr. Rhoresiense.

Both pathogens of African trypanosomiasis belong to the Salivaria section, i.e. Are transmitted through saliva. The Gambian form of African trypanosomiasis is an obligate-transmissible disease, in fact anthroponosis, although in the transmission of its pathogen some participation is also taken by agricultural animals.

For the first time, the symptoms of African trypanosomiasis were described in 1734 by the English doctor Atkins from the inhabitants of the coast of the Gulf of Guinea (West Africa). In 1902, Forde and Dutton found in the blood of a human T. Gabiense. Bruce and Nabarro found that the fly Glossina palpalis (tsetse) is the carrier of the pathogen.

[1], [2],

The developmental cycle in the vertebrate host

The method of infection with African trypanosomiasis allows attributing pathogens to the category of Salivaria, and the disease - to salivary (salivary) trypanosomiasis. After penetrating the skin of trypanosome, several days remain in the subcutaneous tissue, and then enter the bloodstream lymph and spinal fluid, where they divide by simple binary division. Sometimes it is found in the cerebral plexus of the brain in the amastigot stage. In this case, different forms of trypanosomes are distinguished: thin and long, short and wide, as well as intermediate tripartomagitic forms. The incubation period of carotid disease lasts from several days to several weeks.

What causes African trypanosomiasis (sleeping sickness)?

African trypanosomiasis (sleeping sickness) is caused by Trypanosoma gambiense. In the blood of vertebrate hosts, polymorphic stages of trypanosome develop - tripomastigoty and epimastigoty. Among them, there are thin tripomastigot forms 14-39 in length (on average 27), with a well-expressed undulating membrane and a long free part of the flagellum. Their posterior end is pointed, the kinetoplast is about 4 μm from the posterior end of the body. There are also short forms of tripomastigot - 11-27 microns in length (on average 18 microns), with a rounded posterior end and a very short free part of the flagellum. There are also various transitional forms between them. When painting according to Romanovsky-Giemsa, the core, flagellum and kinetoplast are colored pink, and protoplasm - in blue. Morphological differences between different pathogens of trypanosomiasis are insignificant.

The biology of African trypanosomiasis (sleeping sickness)

The main owner is a man, additional pigs. The carrier is the blood-sucking flies of the genus Glossina, mainly G. Palpalis. A distinctive feature of the tsetse flies is a strongly chitinized protruding proboscis capable of piercing the skin of even such animals as a rhinoceros and an elephant. In this regard, no clothing a person will not protect against a tsetse fly. The second feature of the fly is the excellent extensibility of the intestinal walls, which allows it to absorb blood that exceeds the weight of a hungry fly by dozens of times. These features ensure the reliability of transmission of the pathogen from the donor to the recipient. Tsetse flies attack during the day, mainly in open nature, some anthropophilous species can fly into villages. Blood is drunk both by males and females. The invasive stage for the carrier is the tripomastigot form. In the body of the transporter, trypanosomes fall into the blood supply of the invaded vertebrate or human. About 90% of trypanosomes, absorbed by the tsetse fly, die. The rest reproduce in the lumen of its middle and posterior intestines.

In the first days after infection, various forms of trypanosomes are found inside the lump of absorbed blood, surrounded by a peritrophic membrane; they differ little from those that are in the human blood, but are somewhat shorter and have a weakly expressed undulating membrane. Then trypanosomes exit into the lumen of the intestine of the insect.

When a tsetse fly hits the stomach after a bloodsucking, trypanosomes change by 3-4 days and are transformed into epimastigotic forms, become narrower and elongated and are intensively divided. By the 10th day a large number of narrow trypanosomes penetrate the peritrophic membrane of the posterior end of the stomach, migrate towards the esophagus, where they again pass through the peritrophic membrane into the lumen of the stomach and then into the proboscis, and from there, by the 20th day, into the salivary glands of the flies . The trypanosomes can penetrate the salivary glands through the hemocoel. In salivary glands, trypanosomes undergo a series of morphological changes, are repeatedly divided and transformed into an invasive stage for human and vertebrate animals - tripomastigot. The development of trypanosomes in the carrier lasts an average of 15-35 days, depending on the temperature of the medium. Effective infection of flies occurs at a temperature of 24 to 37 ° C. After infection, the tsetse fly is able to transmit trypanosomes throughout life.

Symptoms of African trypanosomiasis (sleeping sickness)

African trypanosomiasis (sleeping sickness) is divided into two stages: hemolymphatic and meningoencephalitic, or terminal (sleeping sickness in the narrow sense of the word).

The hemolymphatic stage occurs 1-3 weeks after the invasion and is associated with the spread of trypanosomes in the body (through the lymphatic and circulatory systems) from the site of their primary introduction.

African trypanosomiasis (sleeping sickness) is characterized by a prolonged course. After 1-3 weeks (or several months) after invasion of the tsetse fly bite, a primary lesion (primary affect) is sometimes developed, which is a painful, elastic, red, furuncle-like nodule 1-2 cm in diameter. It contains a large amount of lymph with trypanosomes. Such a nodule is called trypanosomal chancre. Within 2-3 weeks the primary local lesion spontaneously disappears, in its place remains the pigmented scar. Trypanosomal chancre occurs mainly in non-indigenous inhabitants of Africa.

Simultaneously with the appearance of the primary affect on the skin of the trunk and limbs, there may appear the so-called trypanides having the appearance of pink or purple spots of various shapes 5-7 cm in diameter. In Africans, against the background of dark skin, trypanids are noticeably weaker than in Europeans. On the face, hands, feet and on the places of erythematous rashes, swellings are noticeable, the soreness of the skin is noted when it is compressed.

During the development of chancre, or a few days after its disappearance, parasites appear in the blood, and a fever of the wrong type arises with a fever of 38.5 ° C (rarely up to 41 ° C). Feverish periods, alternating with periods of apyrexia, can last for weeks.

A few days after the appearance of fever in patients with Gambian trypanosomiasis, peripheral and mesenteric lymph nodes, mainly the posterior ones, that can reach the size of a pigeon's egg increase. Initially, the nodes have a soft consistency, later they become dense.

Hemolymphatic stage

Symptoms of African trypanosomiasis (sleeping sickness) in the hemolymphatic stage: weakness, weight loss, tachycardia, joint pain, hepatosplenomegaly. A third of patients develop a urticaria rash on the skin of the eyelids and develop their swelling. Edema is usually expressed so strongly that edematous tissue sometimes hangs over the cheek. There is an increase in the parotid salivary gland of the corresponding side. In later terms, unilateral or bilateral keratitis, iridocyclitis, hemorrhage into the iris and characteristic diffuse vascular opacity of the cornea develop with damage to all its layers. In severe cases, persistent intense scarring of the cornea occurs. Growing weakness and apathy, which are early signs of the defeat of the central nervous system.

The severity of the described clinical symptoms and the duration of the first period of the disease in different patients can vary widely, sometimes up to several years.

Meningoencephalitic stage

After a few months or years in the vast majority of patients, the African trypanosomiasis (sleeping sickness) disease passes into the second phase, which is characterized by CNS damage. Trypanosomes cross the blood-brain barrier and penetrate the central nervous system, concentrating in the frontal lobes of the cerebral hemispheres, the variola bridge and the medulla oblongata, which is accompanied by the expansion of the ventricles of the brain, edema of the brain tissue, thickening of the gyri and the development of clinical symptoms of meningoencephalitis and leptomeningitis. There is perivascular infiltration around the blood vessels, swelling and degeneration of their walls.

The most typical symptoms of African trypanosomiasis (sleeping sickness) in the second stage of the disease: increasing drowsiness, which occurs mainly during the day, while night sleep is often intermittent and restless. Drowsiness is so pronounced that the patient can fall asleep even while eating. Gradually grow and progress neuropsychiatric disorders. When walking, the patient drags his legs, his expression sullen, his lower lip hangs, saliva drips from his mouth. The patient loses all interest in the environment, slowly, reluctantly answers questions, complains of a headache. Violation of mental status is accompanied by the development of manic or depressive states. There are tremors of the tongue, hands, feet, fibrillar twitching of the muscles of the face, fingers, indistinct speech, ataxic gait. Pressure on the palm causes the appearance of acute pain shortly after its termination (Kerandel's symptom). Later, convulsions occur, followed by paralysis.

Rhodesian form of African trypanosomiasis

The Rhodesian form is similar in many respects to the Gambian form of African trypanosomiasis, but it is a zoonosis.

Causes and biology

The causative agent is T. Rhodesiense, by morphology it is close to T. Gambiense. The main masters of T. Rhodesiense are various species of antelope, as well as cattle, goats, sheep and less often man.

The main vectors of the Rhodesian form are the tsetse flies of the group "morsitans" (S. Morsitans, G. Pallides, etc.). They live in savannas and savannah forests, are more photophilous and less hygrophilous than species of "palpalis", are more zoophilic and more likely to attack large ungulates and small warthogs than humans.

Epidemiology

The reservoirs of Tryponasoma rhodesiense in nature are various species of antelopes and other ungulates. In some cases, an additional reservoir may be cattle.

The zoonotic form of the sleeping sickness is common in the plain savannah, in contrast to the anthroponous, gravitating to river valleys. In the natural conditions of the savannah, T. Rhodesiense circulates along the chain: the antelope-the tsetse-antelope fly, without human participation. A person becomes infected episodically when visiting enzootic foci. Relative rarity of infection of humans in the wild is also promoted by the pronounced zoophilia of the transporter, as a result of which tsetse flies of these species reluctantly attack humans. In these conditions, representatives of certain professions are caught - hunters, fishermen, travelers, servicemen. Men are ill more often than women and children.

With the agricultural development of the territory and the appearance of a permanent population, the sleeping sickness becomes endemic and the person is included in the cycle. In this case, the circulation of T. Rhodesiense can be carried out already along such a chain: antelope-tsetse fly-man-tsetse fly-man.

It was shown that in a number of cases the transmission of sleeping sickness can be accomplished by tsetse flies mechanically, without passing a multi-day development cycle in the carrier. Such cases are possible during interrupted bloodsucking, when the carrier begins to drink the blood of a sick animal or person, and then flies and bites a healthy person or animal.

[3], [4], [5], [6], [7],

Symptoms

Symptoms of Rhodesian-type sleeping sickness are characterized by a more acute and severe course. The incubation period with it is shorter than with the Gambian form, and is 1-2 weeks.

At the site of the bite, there is a primary affect - "trypanosomal chancre" - in the form of a furuncle, which disappears in a few days, leaving a small scar sometimes. Trypanosomal chancre is not observed in all patients, more often in Europeans than in Africans. During the development of chancre, or a few days after its appearance, the parasite appears in the blood, and this is associated with the onset of the febrile period. The fever is irregular, accompanied by a high temperature rise, a headache. Death of patients in the absence of treatment often occurs in 9-12 months. The hemolymphatic phase of invasion is poorly expressed. In all patients, trypanosomes are found in the blood, in many patients - in the cerebrospinal fluid.

Diagnostics

Diagnosis is carried out in the same way as in the Gambian form.

[8], [9], [10], [11], [12], [13],

Treatment

Treatment is carried out by suramin and melarsoprol.

Prevention and control measures are the same as in the Gambian form.

Diagnosis of African trypanosomiasis (sleeping sickness)

The clinical symptoms of African trypanosomiasis (sleeping sickness) are the basis for a preliminary diagnosis of "sleeping sickness", but an undeniable confirmation of the diagnosis of sleeping sickness is the detection of T. Gambiense in laboratory parasitological studies.

For the detection of trypanosomes, studies of chancre chancre and enlarged lymph nodes (before the development of fibrotic changes in them), blood, cerebrospinal fluid are carried out. From the obtained substrate prepare the native preparations and preparations colored by Romanovsky-Giemsa.

[14], [15], [16], [17], [18]

Treatment of African trypanosomiasis (sleeping sickness)

Treatment of African trypanosomiasis (sleeping sickness) in the first stage of development of the Gambian form of trypanosomiasis consists in the use of pentamidine (pentamidine isothionate) - aromatic diamidine. The drug is administered intramuscularly at a dose of 4 mg / kg / day daily or every other day. The course of treatment is 7-10 days.

It is often used combined treatment of African trypanosomiasis (sleeping sickness) with pentamidine (4 mg / kg intramuscularly 2 days) or suramin (2-3 days in a rising dose of 5-10-20 mg / kg) followed by melarsoprol (1,2-3, 6 mg / kg / day drip) - 3 three-day cycles with weekly interruptions.

There is information about the circulation of melarprofil resistant strains of T. Gambiense in Uganda.

Eflornithine is effective for the treatment of all stages of Gambian trypanosomiasis. The drug is injected / drip, slowly, every 6 hours for 14 days. A single dose for adults is 100 mg / kg In the treatment of eflornithine, the development of anemia, leukopenia, thrombocytopenia, convulsions, edema of the face, anorexia.

The Gambian form of trypanosomiasis is predominantly anthroponose. The main source of infestation is a person, additional - a pig. These species of flies are shade-loving, active during the daytime. They live in thickets of vegetation along the banks of rivers and streams in a number of areas of West and Central Africa. The tsetse fly is viviparous, the female lays the only larva directly to the surface of the soil, into the crevices, under the roots of the trees. The larva immediately gets into the soil and turns into a pupa in 5 hours. The appearance of the adult occurs 3-4 weeks after pupation. The adult female lives 3-6 months; for all her life she lays 6-12 larvae.

The epidemic significance of a particular species of tsetse flies is determined primarily by the degree of their contact with a person. The most anthropophilous species is G. Palpalis. It often concentrates near villages and flies into them, attacking a person outside the premises. However, most often tsetse flies of this and other species attack in natural landscapes, therefore hunters, fishermen, road builders, loggers, etc. Are most at risk of infection by these pathogens.

One bite of an infected fly is enough to make a person fall ill with sleeping sickness, since the minimal invasive dose of trypanosomes is 300-400 parasites, and the fly with saliva for one bite gives them about 400 thousand. The patient becomes a source of infestation from about the 10th day after infection and remains during the entire period of the disease, even during remission and the absence of clinical manifestations.

Theoretically, it is possible to mechanically introduce trypanosomes into the bloodstream of blood-sucking arthropods with additional repeated bloodsucking of the sick person, since on the proboscis of flies, flies, mosquitoes, bedbugs and other arthropods, pathogens remain viable for several hours. Infection can also occur with blood transfusions or with insufficient sterilization of syringes during injections. The Gambian form of trypanosomiasis occurs in the form of foci in West and Central Africa between 150 s. W. And 180 S.

Mortality from trypanosomiasis in Congo in the middle of the last century was about 24%, and in Gabon - 27.7%, so trypanosomiasis for countries of tropical Africa presents serious economic and social problems.

The incidence is seasonal. The peak comes in the dry season of the year, when tsetse flies concentrate around the remaining reservoirs that are not dried up, which are intensively used by the population for household needs.

How is sleeping sickness prevented, or African trypanosomiasis?

The complex of measures for improving the foci of sleeping sickness includes the identification and treatment of African trypanosomiasis (sleeping sickness), public and individual prophylaxis of the population, vector control. Serological examination is of primary importance, especially for people at risk (hunters, loggers, road builders, etc.). The examination should be conducted at least 2 times a year (before the season and after the season of greatest danger of infection).