Sleeping sickness is a protozoic, the causative agent of which is the simplest genus Trypanosoma, and the carriers are blood–sucking tsetse flies. The symptoms are characterized by the formation of primary affect at the site of the bite (trypanosomal chancre), wave-like fever, lymphadenitis, skin rashes, local edema, increasing drowsiness, paralysis, mental disorders, coma. Diagnosis is based on the detection of trypanosomes in biological material (chancre punctate, lymph nodes, blood, cerebrospinal fluid). Therapy is carried out with drugs pentamidine, suramin, melarsoprol, eflornitin.
Sleeping sickness (African trypanosomiasis) is a disease from the group of transmissible trypanosomiasis that occurs with fever, damage to the lymphatic and central nervous system. There are 2 forms of sleeping sickness: Gambian (West African) and Rhodesian (East African) trypanosomiasis caused by various types of pathogens. Sleeping sickness is endemic to 36 countries of tropical Africa, where there are carriers of the disease – tsetse flies. The largest epidemics of sleeping sickness were recorded in 1896-1906, 1920 and 1970. Every year, 7-10 thousand people are registered on the African continent. new cases of sleeping sickness. The disease is most common among rural residents engaged in agriculture, animal husbandry, fishing or hunting. In addition to African trypanosomiasis, American trypanosomiasis (Chagas disease) is a danger to humans.
Two morphologically identical species of the causative agent of human sleeping sickness are known: Trypanosoma brucei gambiense, which causes the Gambian form, and Trypanosoma brucei rhodesiense, which causes the Rhodesian form of African trypanosomiasis. Parasites have an oblong-fusiform, flat shape, a length of 12-35 microns and a width of 1.5-3.5 microns. Both types of trypanosomes are transmitted through saliva during the bite of the tsetse fly (Glossina palpalis), which serves as a carrier of the disease and after infection is able to transmit trypanosomes throughout life. To infect a person with sleeping sickness, one bite of an invaded fly is enough, which secretes about 400 thousand parasites with saliva, while the minimum invasive dose is 300-400 trypanosomes.
During blood sucking of invaded vertebrates or humans, blood trypomastigotes enter the insect’s body, which multiply by binary division in the intestinal lumen of the tsetse fly. By day 3-4, the trypomastigous forms penetrate into the salivary glands, where they transform into epimastigotes. In the salivary glands, epimastigous forms undergo multiple division and complex morphological changes, as a result of which they turn into metacyclic trypomastigotes, representing the invasive stage of trypanosomes. With a repeated bite, together with saliva, the tsetse fly introduces metacyclic trypomastigotes under the human skin, which after a few days penetrate into the blood and lymph, spread throughout the body, turning into blood trypomastigotes.
After the bite of an infected fly at the entrance gate, a local inflammatory reaction develops in the form of painful itchy chancre and regional lymphadenitis. After 1-3 weeks, after the penetration of trypanosomes into the blood and lymphatic system, the hemolymphatic stage of sleeping sickness develops. The late (meningoencephalitic) stage of African trypanosomiasis is caused by the penetration of the parasite into the central nervous system. In response to the invasion, the immune system reacts by producing specific IgM class antibodies, which allow to restrain parasitemia for a while. However, the high antigenic variability of trypanosomes disrupts the formation of specific immunity, causing the continuous progression and recurrent nature of sleeping sickness.
The early (hematolymphatic) stage of sleeping sickness lasts about 1 year (sometimes from several months to 5 years). About a week after the tsetse fly bite, a primary affect forms on the skin – a trypanoma, or trypanosomal chancre, which is a painful erythematous nodule 1-2 cm in diameter, resembling a boil. This element is most often localized on the head or limbs, often ulcerates, but after 2-3 weeks it usually spontaneously heals, leaving behind a pigmented scar. Simultaneously with the formation of trypanosomal chancre, pink or purple spots with a diameter of 5-7 cm (trypanids) appear on the trunk and limbs, as well as swelling of the face, hands, feet.
The further development of sleeping sickness is associated with the release of parasites into the blood, which is accompanied by the appearance of fever of the wrong type. Feverish periods with temperature peaks up to 38.5-40°With alternate with apirexic periods. A characteristic sign of sleeping sickness is an increase in regional lymph nodes, especially posterior ones (Winterbottom’s symptom), which become dense and can reach the size of a pigeon egg. The course of the hemolymphatic stage of sleeping sickness is characterized by increasing weakness and apathy, tachycardia, arthralgia, weight loss, enlargement of the liver and spleen. In 30% of patients, urticary rashes appear on the skin, swelling of the eyelids develops. Possible damage to the organ of vision in the form of keratitis, iridocyclitis, hemorrhage in the iris, clouding or scarring of the cornea.
The duration of the hemolymphatic stage of sleeping sickness can be several months or years, after which the disease passes into a late (meningoencephalitic, or terminal) stage. During this period, the symptoms of meningoencephalitis and leptomeningitis, caused by the penetration of trypanosomes through the blood-brain barrier and brain damage, come to the fore in the clinical course. The most typical manifestation of African trypanosomiasis is increasing daytime drowsiness, which leads to the fact that the patient can fall asleep, for example, while eating.
The progression of sleeping sickness is accompanied by the development of ataxic gait, slurred speech (dysarthria), salivation, tremor of the tongue and limbs. The patient becomes indifferent to what is happening, is inhibited, complains of a headache. There is a violation of the mental status in the form of depressive or manic states. In the late period of sleeping sickness, convulsions, paralysis, epileptic status join, coma develops.
The Rhodesian form of sleeping sickness has a more severe and transient development. Fever and intoxication are more pronounced, exhaustion occurs faster, heart damage often occurs (arrhythmia, myocarditis). The death of the patient may occur already during the first year of the disease even before the transition of trypanosomiasis to the meningoencephalitic stage. The cause of death of patients is most often intercurrent infections: malaria, dysentery, pneumonia, etc.
Diagnosis and treatment
Preliminary diagnosis of sleeping sickness is carried out on the basis of clinical and epidemiological data, the most important of which are staying in endemic areas of Africa, the presence of prolonged, recurrent fever, primary affect, cervical lymphadenitis, edema, drowsiness, etc. An irrefutable proof of infection with African trypanosomiasis is the detection of trypanosomes in laboratory studies of native and Romanovsky-Giemse-stained biological material. In order to detect the parasite, a punctate of trypanosomal chancre, altered lymph nodes, blood, cerebrospinal fluid can be analyzed.
In some cases, a biological test with intraperitoneal injection of blood or cerebrospinal fluid of the patient to guinea pigs is carried out to recognize sleeping sickness. From immunological reactions, RIF and ELISA are used. The Gambian form of sleeping sickness should be differentiated with malaria, toxoplasmosis, lymphogranulomatosis, tuberculosis, meningitis, encephalitis, etc.; the Rhodesian form, in addition, with typhoid fever, septicemia.
Specific therapy of sleeping sickness is most effective in the early stage, before the development of cerebral symptoms. In the Gambian form of sleeping sickness, suramin, pentamidine or eflornitine is prescribed at the hemolymphatic stage; only eflornitine is effective at the meningoencephalitic stage. In the early period of the Rhodesian form of sleeping sickness, suramin is used; in the late period, melarsoprol. Additionally, detoxification, hyposensitizing, symptomatic therapy is carried out.
Prognosis and prevention
Without treatment, the mortality rate from sleeping sickness is close to 100%. In case of initiation of specific therapy in the early stage of African trypanosomiasis, complete recovery is possible; with late treatment, the prognosis is much worse. In addition to the timing of the start of treatment, the outcome is affected by the form of sleeping sickness: with the Rhodesian variant of trypanosomiasis, the prognosis is always more serious.
In the prevention of sleeping sickness, the main role is played by the extermination of tsetse flies with the help of insecticidal preparations, the cutting down of shrubby thickets near settlements, the use of personal protective equipment against bites of blood-sucking insects in endemic areas of Africa. During periods of epidemic outbreaks of sleeping sickness, mass chemoprophylaxis with pentamidine is carried out among local residents and visitors. Immunoprophylaxis of African trypanosomiasis has not been developed.