African trypanosomiasis

African Trypanosomiasis, also known as “sleeping sickness”, is caused by microscopic parasites of the species Trypanosoma brucei. It is transmitted by the tsetse fly (Glossina species), which is found only in sub-Saharan Africa. Control efforts have reduced the number of annual cases and for the first time in 50 years, the number of reported cases fell under 10,000 in 2009. In 2017–2018, fewer than 2000 cases were reported to WHO . Sleeping sickness is curable with medication but is fatal if left untreated.

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Types

Two morphologically indistinguishable subspecies of the parasite cause distinct disease patterns in humans: T. b. gambiense causes a slowly progressing African trypanosomiasis in western and central Africa and T. b. rhodesiense causes a more acute African trypanosomiasis in eastern and southern Africa.

Cause

Two subspecies of the parasite Trypanosoma brucei, T. b. gambiense and T. b. rhodesiense, cause disease in humans, with clinical features of the infection dependent on the subspecies involved.

Epidemiology & Risk Factors

T. b. gambiense is endemic in western and central Africa, while T. b. rhodesiense is restricted to eastern and southern Africa. Their ranges do not overlap except in Uganda where both subspecies are co-endemic, with T. b. gambiense in the northwest corner of the country along the borders with South Sudan and the Democratic Republic of the Congo, and T. b. rhodesiense mostly clustered in the center of the country.

T. b. rhodesiense (East African sleeping sickness) is found in focal areas of eastern and southeastern Africa. Since 2015, less than 100 cases have been reported annually to WHO. Domestic and wild animals are the main reservoir of infection. Cattle have been implicated in the spread of the disease to new areas and in local outbreaks. Both forms of sleeping sickness are transmitted by the bite of the tsetse fly (Glossina species). Tsetse flies inhabit rural areas, living in the woodlands and thickets that dot the East African savannah. Tsetse flies bite during daylight hours. Both male and female flies can transmit the infection, but even in areas where the disease is endemic only a very small percentage of flies are infected. Although the majority of infections are transmitted by the tsetse fly, other modes of transmission are possible. Occasionally, a pregnant woman can pass the infection to her unborn baby (T. b. gambiense). In theory, the infection can also be transmitted by blood transfusion, sexual contact, organ transplantation and accidental laboratory exposure, but such cases are rare and poorly documented.

Biology

During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream image . Inside the host, they transform into bloodstream trypomastigotes image , are carried to other sites throughout the body, reach other body fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission image . The entire life cycle of African trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host image , image . In the fly’s midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission image , leave the midgut, and transform into epimastigotes image . The epimastigotes reach the fly’s salivary glands and continue multiplication by binary fission image . The cycle in the fly takes approximately 3 weeks. Rarely, T. b. gambiense may be acquired congenitally if the mother is infected during pregnancy.

Stages

Infection occurs in two stages, an initial haemolymphatic stage followed by a meningoencephalitic stage after the trypanosomes invade the central nervous system (CNS).

Signs and symptoms

First-stage symptoms for both types of sleeping sickness include headache, malaise, weakness, fatigue, pruritis, and arthralgia. First-stage signs can include hepato-splenomegaly, weight loss and intermittent fevers lasting one day to one week. The intervals between fevers can last days or months. Lymphadenopathy, mainly posterior cervical but in some cases axillary, inguinal or epitrochlear, may also occur. Posterior triangle cervical lymphadenopathy, or “Winterbottom’s sign” is commonly seen in T. b. gambiense infections. T. b. gambiense infection progresses to the second stage after an average of 300–500 days, whereas T. b. rhodesiense infection progresses to the second stage after an estimated 21–60 days.

For both types of disease, the stage is determined by examining cerebrospinal fluid (CSF) and observing trypomastigotes. In second-stage disease, invasion of the central nervous system causes a variety of neuropsychiatric manifestations to appear in addition to the first-stage signs and symptoms, with fever occurring less frequently over time. The sleep/wake cycle becomes reversed, hence the common name “African sleeping sickness”, with daytime somnolence, nocturnal insomnia, and sudden urges to sleep. The patient also experiences mental (hallucinations, delirium, anxiety, emotional lability, attention deficit, apathy, aggression, mania, confusion), motor (motor weakness, abnormal tone, gait disturbance, ataxia, tremor, speech disturbances), sensory (paraesthesia, hyperaesthesia, anaesthesia, pruritis, visual problems), and neurologic (abnormal reflexes, seizures, coma) signs and symptoms. Compared to T. b. gambiense, T. b. rhodesiense is more likely to result in endocrine abnormalities such as adrenal insufficiency, thyroid dysfunction and hypogonadism; and cardiac involvement, such as myocarditis, is more severe.

Diagnosis

Early diagnosis is difficult because signs and symptoms in the first stage are non-specific and because diagnostic measures are insensitive. The classic approach for diagnosing T. b. gambiense infection is by light-microscopic detection of the parasite in a lymph node aspirate (usually, from a posterior cervical node). Concentration techniques and serial examinations can be used for blood (centrifugation followed by buffy coat examination, mini-anion exchange centrifugation technique, or microhematocrit centrifugation technique). With T. b. rhodesiense, parasitemia is usually higher than with T. b. gambiense and symptomatic patients typically have detectable parasites in the blood. The parasite also may be found in chancre fluid, or bone marrow aspirates.

Reliable serologic testing for T. b. rhodesiense is not available and microscopic detection of the parasite is definitive diagnosis.

Serologic testing for T. b. gambiense is used for screening purposes only and the definitive diagnosis rests on microscopic observation of the parasite.

Staging for both T. b. gambiense and T. b. rhodesiense (i.e., assessment of neurological infection) is performed by microscopic examination of CSF collected by lumbar puncture on a wet preparation looking for motile trypomastigotes and white blood cells (WBC). Patients with five or fewer WBC per microliter and no trypomastigotes are considered to be in the first stage, and those with more than five WBCs per microliter or trypomastigotes are considered to be in the second stage. CSF testing is done after a parasitologic diagnosis has been made by microscopic examination of blood, lymph node aspirates, chancre fluid, or bone marrow or when indications of infection are present that justify a lumbar puncture (e.g., clinical signs and symptoms of sleeping sickness or strong serologic suspicion).

Treatment

Anyone diagnosed with African Trypanosomiasis should be treated, with specific drug and treatment course depending on type of infection (T. b. gambiense or T. b. rhodesiense) and disease stage (i.e., presence or absence of central nervous system involvement). Pentamidine, the recommended drug for first stage T. b. gambiense infection, is available in the United States. The other drugs (suramin, melarsoprol, eflornithine, and nifurtimox when used in combination with eflornithine) used to treat African trypanosomiasis are not commercially available in the United States but can be obtained from CDC. Physicians can consult with CDC staff to obtain these otherwise unavailable treatment drugs.

There is no test of cure for African trypanosomiasis. After treatment, patients should be closely followed for 24 months and monitored for relapse. Recurrence of symptoms will require examination of body fluids, including CSF, to detect the presence of trypanosomes.

Prevention & Control

There is no vaccine or drug for prophylaxis against African trypanosomiasis. Preventive measures are aimed at minimizing contact with tsetse flies. Local residents in endemic countries are usually aware of the areas that are heavily infested and may be able to provide advice about places to avoid. Other helpful measures include:

Wear long-sleeved shirts and pants of medium-weight material in neutral colors that blend with the background environment. Tsetse flies are attracted to bright or dark colors, and they can bite through lightweight clothing. Inspect vehicles before entering. The flies are attracted to the motion and dust from moving vehicles. Avoid bushes. The tsetse fly is less active during the hottest part of the day but will bite if disturbed. Use insect repellent. Permethrin-impregnated clothing and insect repellent have not been proved to be particularly effective against tsetse flies, but they will prevent other insect bites that can cause illness.

NIH genetic and rare disease info

• NIH info on African trypanosomiasis

African trypanosomiasis is a rare disease.

African trypanosomiasis Resources
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