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

African trypanosomiasis (sleeping sickness) is an obligate vector-borne infection characterized by fever, skin rashes, enlarged lymph nodes, local edema, and damage to the central nervous system, leading to lethargy, cachexia, and death.

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

African trypanosomiasis (sleeping sickness) is common in the savannah zone. Its noso-area is limited by the range of the carrier - the tsetse fly. Sleeping sickness is endemic in 36 countries of tropical Africa. Up to 40 thousand new cases are registered annually. 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.

There are two known forms of African trypanosomiasis: Gambian, or West African, and Rhodesian, or East African. The first is caused by Tr. gambiense, the second by Tr. rhoresiense.

Both causative agents 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 an anthroponosis, although farm animals also play a part in the transmission of its causative agent.

The symptoms of African trypanosomiasis were first described in 1734 by the English doctor Atkins among residents of the coast of the Gulf of Guinea (West Africa). In 1902, Forde and Dutton found T. gabiense in human blood. Bruce and Nabarro established that the fly Glossina palpalis (tsetse) is the carrier of the pathogen.

[ 1 ], [ 2 ]

Development cycle in a vertebrate host

The method of infection with African trypanosomiasis allows us to classify the pathogens as Salivaria, and the disease as a salivary (salivar) trypanosomiasis. After penetrating the skin, trypanosomes remain in the subcutaneous tissue for several days, and then penetrate the bloodstream, lymph, and cerebrospinal fluid, where they divide by simple binary fission. Sometimes it is found in the vascular plexus of the brain in the amastigote stage. In this case, different forms of trypanosomes are distinguished: thin and long, short and wide, as well as intermediate trypomastigote forms. The incubation period of sleeping sickness lasts from several days to several weeks.

What causes African trypanosomiasis (sleeping sickness)?

African trypanosomiasis (sleeping sickness) is caused by Trypanosoma gambiense. Polymorphic stages of trypanosomes, trypomastigotes and epimastigotes, develop in the blood of vertebrate hosts. Among them, thin trypomastigote forms are found, 14-39 (27 on average) μm long, with a well-defined undulating membrane and a long free part of the flagellum. Their posterior end is pointed, the kinetoplast is located at a distance of about 4 μm from the posterior end of the body. There are also short forms of trypomastigotes, 11-27 μm long (18 μm on average), with a rounded posterior end and a very short free part of the flagellum. There are also various transitional forms between them. When stained according to Romanovsky-Giemsa, the nucleus, flagellum and kinetoplast are stained pink, and the protoplasm is stained blue. Morphological differences between various causative agents of trypanosomiasis are insignificant.

Biology of African trypanosomiasis (sleeping sickness)

The main host is a human, the additional host is a pig. The carrier is a blood-sucking fly of the genus Glossina, mainly G. palpalis. A distinctive feature of the tsetse fly 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 human clothing will protect against the tsetse fly. The second feature of the fly is the excellent elasticity of the intestinal walls, which allows it to absorb blood that is tens of times greater than the weight of a hungry fly. These features ensure the reliability of the transmission of the pathogen from the donor to the recipient. Tsetse flies attack during daylight hours, mainly in the open air, some anthropophilic species can fly into villages. Both males and females drink blood. The invasive stage for the carrier is the trypomastigote form. Trypanosomes enter the carrier's body when feeding on the blood of an infested vertebrate animal or a person. About 90% of trypanosomes ingested by the tsetse fly die. The rest multiply in the lumen of its midgut and hindgut.

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

When entering the stomach of a tsetse fly after bloodsucking, trypanosomes change and transform into epimastigote forms by the 3rd-4th day, becoming narrower and more elongated and dividing intensively. 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 further into the proboscis, and from there, by the 20th day, into the salivary glands of the fly. Trypanosomes can also penetrate the salivary glands through the hemocoel. In the salivary glands, trypanosomes undergo a number of morphological changes, divide repeatedly and turn into an invasive stage for humans and vertebrates - trypomastigote. The development of trypanosomes in the carrier continues on average 15-35 days depending on the ambient temperature. Effective infection of flies occurs at temperatures between 24 and 37 °C. Once infected, the tsetse fly is capable of transmitting trypanosomes throughout its 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 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 long course. 1-3 weeks (or several months) after invasion, a primary lesion (primary affect) sometimes develops at the site of the tsetse fly bite, 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 a trypanosomal chancre. Within 2-3 weeks, the primary local lesion spontaneously disappears, leaving a pigmented scar in its place. Trypanosomal chancre occurs mainly in non-native Africans.

Simultaneously with the appearance of the primary affect on the skin of the trunk and extremities, so-called tripanids may appear, which look like pink or purple spots of various shapes with a diameter of 5-7 cm. In Africans, against the background of dark skin, tripanids are less noticeable than in Europeans. Edema is noticeable on the face, hands, feet and in places of erythematous rashes, and skin pain is noted when it is squeezed.

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

A few days after the onset of fever in patients with Gambian trypanosomiasis, peripheral and mesenteric lymph nodes, primarily the posterior cervical ones, enlarge and can reach the size of a pigeon's egg. At first, the nodes have a soft consistency, later they become dense.

Hemolymphatic stage

Symptoms of African trypanosomiasis (sleeping sickness) in the hemolymphatic stage include weakness, weight loss, tachycardia, joint pain, and hepatosplenomegaly. A third of patients develop urticarial rashes on the skin of the eyelids and their edema. The edema is usually so severe that the edematous tissue sometimes hangs over the cheek. There is an increase in the parotid salivary gland on the corresponding side. Later, unilateral or bilateral keratitis, iridocyclitis, hemorrhage into the iris, and characteristic diffuse vascular opacity of the cornea with damage to all its layers develop. In severe cases, persistent, intense scarring of the cornea occurs. Weakness and apathy increase, which are early signs of CNS damage.

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 several months or years, the vast majority of patients develop African trypanosomiasis (sleeping sickness) into the second phase, which is characterized by damage to the central nervous system. Trypanosomes overcome the blood-brain barrier and penetrate the central nervous system, concentrating in the frontal lobes of the cerebral hemispheres, the pons and the medulla oblongata, which is accompanied by enlargement of the cerebral ventricles, swelling of the brain tissue, thickening of the convolutions and the development of clinical symptoms of meningoencephalitis and leptomeningitis. Perivascular infiltration around the blood vessels, swelling and degeneration of their walls are observed.

The most characteristic symptoms of African trypanosomiasis (sleeping sickness) in the second stage of the disease are: 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. Neuropsychiatric disorders gradually increase and progress. When walking, the patient drags his feet, his facial expression is sullen, the lower lip hangs down, drooling comes from the mouth. The patient loses all interest in the surroundings, answers questions slowly and reluctantly, complains of headache. Impaired mental status is accompanied by the development of manic or depressive states. Tremor of the tongue, arms, legs, fibrillary twitching of the muscles of the face, fingers, slurred speech, ataxic gait appear. Pressure on the palms causes acute pain soon after it stops (Kerandel's symptom). Later, convulsions occur, followed by paralysis.

Rhodesian form of African trypanosomiasis

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

Causes and biology

The causative agent is T. rhodesiense, which is morphologically similar to T. Gambiense. The main hosts of T. rhodesiense are various species of antelope, as well as cattle, goats, sheep, and, less commonly, humans.

The main carriers of the Rhodesian form are tsetse flies of the "morsitans" group (C. morsitans, G. Pallides, etc.). They live in savannas and savannah forests, are more photophilous and less moisture-loving than the "palpalis" species, are more zoophilic and more willing to attack large ungulates and small warthogs than people.

Epidemiology

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

The zoonotic form of sleeping sickness is common in the plain savanna, unlike the anthroponotic form, which tends to river valleys. In natural savanna conditions, T. rhodesiense circulates in the chain: antelope - tsetse fly - antelope, without human participation. Humans become infected episodically when visiting enzootic foci. The relative rarity of human infection in the wild is also facilitated by the pronounced zoophilia of the carrier, as a result of which tsetse flies of these species are reluctant to attack humans. In these conditions, representatives of certain professions become ill - hunters, fishermen, travelers, military personnel. Men become ill much more often than women and children.

With agricultural development of the territory and the appearance of a permanent population, sleeping sickness becomes endemic and humans are included in the cycle. In this case, the circulation of T. rhodesiense can be carried out according to the following chain: antelope - tsetse fly - human - tsetse fly - human.

It has been shown that in some cases the transmission of sleeping sickness can be carried out mechanically by tsetse flies, without going through 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 over and bites a healthy person or animal.

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

Symptoms

Symptoms of the Rhodesian type of sleeping sickness are more acute and severe. The incubation period is shorter than that of the Gambian form, and is 1-2 weeks.

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

Diagnostics

Diagnosis is the same as for the Gambian form.

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

Treatment

Treatment is carried out with suramin and melarsoprol.

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

Diagnosis of African trypanosomiasis (sleeping sickness)

Clinical symptoms of African trypanosomiasis (sleeping sickness) are the basis for a preliminary diagnosis of "sleeping sickness", however, irrefutable confirmation of the diagnosis of sleeping sickness is the detection of T. gambiense in laboratory parasitological studies.

To detect trypanosomes, studies are conducted on chancre punctures and enlarged lymph nodes (before fibrous changes develop in them), blood, and cerebrospinal fluid. Native preparations and preparations stained according to Romanovsky-Giemsa are prepared from the obtained substrate.

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

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 of using pentamidine (pentamidine isothionate) - an 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.

Often, a combination treatment of African trypanosomiasis (sleeping sickness) is used with pentamidine (4 mg/kg intramuscularly for 2 days) or suramin (2-3 days in increasing doses of 5-10-20 mg/kg) followed by the administration of melarsoprol (1.2-3.6 mg/kg per day intravenously by drip) - 3 three-day cycles with weekly breaks.

There is evidence of the circulation of melarsoprol-resistant strains of T. gambiense in Uganda.

Eflornithine is effective for the treatment of all stages of Gambian trypanosomiasis. The drug is administered intravenously by drip, slowly, every 6 hours for 14 days. A single dose for adults is 100 mg / kg. When treating with eflornithine, anemia, leukopenia, thrombocytopenia, seizures, facial edema, anorexia may develop.

The Gambian form of trypanosomiasis is predominantly an anthroponosis. The main source of invasion is humans, and an additional source is pigs. These species of flies are shade-loving and active during daylight hours. They live in thickets of vegetation along the banks of rivers and streams in a number of regions of West and Central Africa. Tsetse flies are viviparous, the female lays a single larva directly on the surface of the soil, in crevices, under the roots of trees. The larva immediately burrows into the soil and turns into a pupa after 5 hours. The imago emerges 3-4 weeks after pupation. An adult female lives 3-6 months; during her entire life, she lays 6-12 larvae.

The epidemic significance of a particular tsetse fly species is determined primarily by the degree of their contact with humans. The most anthropophilic species is G. palpalis. It often concentrates near villages and flies into them, attacking humans outdoors. However, tsetse flies of this and other species most often attack in natural landscapes, so hunters, fishermen, road builders, lumberjacks, etc. are most at risk of infection with these pathogens.

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

Theoretically, mechanical introduction of trypanosomes into human blood by blood-sucking arthropods is possible during additional repeated blood-sucking of a sick person, since pathogens remain viable for several hours on the proboscis of flies, horseflies, mosquitoes, bedbugs and other arthropods. Infection can also occur during blood transfusions or with insufficient sterilization of syringes during injections. The Gambian form of trypanosomiasis occurs in foci in West and Central Africa between 150 N and 180 S.

The mortality rate from trypanosomiasis in Congo in the middle of the last century was about 24%, and in Gabon - 27.7%, so trypanosomiasis represents a serious economic and social problem for the countries of tropical Africa.

The incidence is seasonal. The peak occurs during the dry season of the year, when tsetse flies concentrate near the remaining water bodies that have not dried up and are intensively used by the population for economic needs.

How is sleeping sickness, or African trypanosomiasis, prevented?

The complex of measures for improving the health of foci of sleeping sickness includes the detection and treatment of African trypanosomiasis (sleeping sickness), public and individual prevention of the population, and the fight against carriers. Serological examination is important, especially for people belonging to the risk group (hunters, loggers, road builders, etc.). The examination should be carried out at least twice a year (before and after the season of greatest risk of infection).