African trypanosomiasis infectious diseases msd manual profi edition

African sleeping sickness is an infectious disease caused by infection with protozoa of the species Trypanosoma brucei and is transmitted by the bite of the tsetse fly. Symptoms occur such as z. B. characteristic skin lesions, intermittent fever, headache, rigor, transient edema, generalized lymphadenopathy, and often fatal meningoencephalitis. Diagnosis is made by detection of the causative agent in blood, lymph node aspirate, or cerebrospinal fluid, and sometimes by serologic testing. Therapy is with suramin , pentamidine, melarsoprol, or eflornithine, depending on the infecting subspecies and clinical stage.

African trypanosomiasis is transmitted in West and Central Africa by Trypanosoma brucei gambiense and in East Africa by T. brucei rhodesiense Causes transmitted by tsetse flies. African trypanosomiasis has been targeted for eradication by the World Health Organization, and as a result of control efforts, there has been a dramatic decline worldwide over the past 20 years (> 95%) of the reported cases. On average, 1 case is diagnosed each year in the U.S. The pathogens are transmitted by tsetse flies. Can be transmitted prenatally from a mother to her child. In rare cases, infection is transmitted through blood transfusion; theoretically, it can be transmitted through organ transplantation.

Another trypanosomal species, Trypanosoma cruzi, is endemic to South and Central America and causes Chagas disease Chagas disease Chagas disease is an infection with Trypanosoma cruzi, transmitted by Triatominae bug bites or, less commonly, by ingestion of sugarcane juice or with infected Triatominae bugs. Learn more (American trypanosomiasis).

Pathophysiology

Metacyclic trypomastigotes inoculated by tsetse flies transform into blood trypomastigotes that multiply by binary division and spread through the lymphatics and bloodstream after inoculation. Blood trypomastigotes multiply until the number of parasites is drastically reduced by specific antibodies produced by the host organism. However, some of the parasites escape destruction by the immune system through a change in the variable surface glycoprotein and begin a new reproductive cycle. The multiplication-. Lytic cycle repeats.

Later in the course of African trypanosomiasis, trypanosomes appear in the interstitial fluid of many organs, including myocardium and ultimately in the central nervous system. The cycle continues when a tsetse fly bites an infected human or animal.

Humans are the most important reservoir of T. b. gambiense, but this type can also occur in other animals. Wild animals are the main reservoir of T. b. rhodesiense.

Symptoms and complaints

African trypanosomiasis has three stages:

Cutaneous

A papule may develop at the site of the tsetse fly bite within a few days to 2 weeks. It further develops into a dark red, painful indurated nodule that may ulcerate (trypanosome chancre). A chancre is present in about half of Caucasians with T.b. rhodesiense present, but is less common in Africans with T. b. rhodesiense and rarely occurs together with T.b. gambiense on.

Hemolymphatic

Develops over several months in a T. b. gambiense-infection, but over a period of several weeks in TT. b. rhodesiense, intermittent fever, headache, chills, muscle and joint pain, and transient facial swelling. A fading, annular, erythematous exanthema may also develop, which is most visible in fair-skinned patients. Often results in a generalized lymphadenopathy.

In the case of an infection caused by T. b. gambiense caused sleeping sickness, the characteristic Winterbottom sign may appear, d. h. An enlargement of lymph nodes of the posterior triangle of the neck.

Central Nervous System (CNS)

In the Gambia type, CNS involvement occurs for months to years after the onset of acute disease. In the rhodesia form, the disease is more fulminant, and CNS invasion often occurs within a few weeks.

CNS involvement causes persistent headache, inability to concentrate, personality changes (z. B. progressive fatigue and dullness), daytime drowsiness, tremor, ataxia, and terminal coma.

If not treated, infection with T. b. rhodesiense within months after the onset of the disease, in infection with T. b. gambiense. within the 2. or 3. year of death a. Untreated patients die in coma due to malnutrition or secondary infections.

Diagnosis

Light microscopy of blood (thin or thick streaks) or other liquid samples

Diagnosis of trypanosomiasis is made by identifying trypanosomes in fluid from a chancre, lymph node aspirates, blood, bone marrow aspirates, or, during the late stages of infection, from cerebrospinal fluid. Preferred sources are blood smears of T. b. rhodesiense and aspirated fluid from an enlarged lymph node at T. b. gambiense. Native, fresh specimens should be examined for motile trypanosomes, and smears should be fixed, stained with Giemsa (or Field), and examined. The concentration of trypanosomes in the blood is often low, and concentration techniques (z. B. Centrifugation, miniature anion exchange centrifugation, quantitative buffy coat technique) improve sensitivity.

Assays to detect antibodies are not clinically very useful because seroconversion occurs after the onset of symptoms. However, a CATT (card agglutination test for T. b. gambiense) useful in mass screening programs to identify candidates for microscopic examination. A Lumbar Puncture Lumbar puncture (CSF puncture) A lumbar puncture is used for the following: Evaluate intracranial prere. CSF composition from (see table CSF abnormalities in various diseases) therapeutic reduction of the. Learn more should be performed in all patients with African trypanosomiasis. When CSF is involved, opening prere may be increased, and CSF has increased levels of lymphocytes ( ≥ 6 cells/mcL), total protein, and nonspecific IgM. In addition to trypanosomes, characteristic Mott cells (morula-like plasma cells filled with immunoglobulin ["Russell corpuscles"]) may be present.

Other nonspecific laboratory findings include anemia, monocytosis, and markedly elevated serum levels of polyclonal IgM.

Therapy

Treatment of African trypanosomiasis varies by species and stage of disease.

Without CNS involvement, pentamidine for T. b. gambiense; suramin in T. b. rhodesiense

With CNS involvement, eflornithine or melarsoprol for T. b. gambiense; melarsoprol for T. b. rhodesiense

Without CNS involvement

Pentamidine and suramin are effective against the blood stages of both T. brucei-Subspecies effective, but does not cross the blood-brain barrier and is not appropriate in CNS infection. Pentamidine is used for T. b. gambiense used, and suramin is the only drug that is effective in the hemolymphatic stage at T. b. rhodesiense is effective. The dosage of pentamidine is 4 mg/kg i.m. or i.v. 1 time daily for 7 to 10 days. Adults, suramin (available through CDC) is initially administered as a test dose of 100 mg i.v. (to rule out hypersensitivity) is given, then followed by 20 mg/kg (up to 1 g) i.v. on days 1, 3, 7, 14 and 21. Suramin is not indicated for the treatment of T. b. gambiense used. It is potentially effective but has been associated with adverse effects such as nausea, vomiting, photophobia, hyperesthesia, peripheral neuropathy, nephrotoxicity, urticaria, and pruritus. Severe hypersensitivity reactions may also occur in patients treated with Onchocerca volvulus coinfected, which is common in many areas of West Africa where T. b. gambiense Occurs, is endemic.

With CNS involvement

If available, eflornithine 100 mg/kg i should be used.v. 4 times per day for 14 days in the presence of CNS disease due to T. b. gambiense should be used (eflornithine is ineffective against T. b. rhodesiense). The World Health Organization recommends eflornithine 3 times daily in combination with nifurtimox 5 mg/kg for 10 days (1 Treatment information African sleeping sickness is an infectious disease caused by infection with protozoa of the species Trypanosoma brucei caused and transmitted by the bite of the tsetse fly&#252. Learn More ). Adverse effects of eflornithine include gastrointestinal symptoms, bone marrow suppression, and seizures. Common side effects of nifurtimox include anorexia, nausea, vomiting, weight loss, polyneuropathy, headache, drowsiness, and dizziness.

In the U.S., eflornithine, nifurtimox, and melarsoprol can be obtained from the Centers for Disease Control and Prevention (CDC).

Melarsoprol, an organic arsenic compound, is commonly used in African countries because of the limited availability of eflornithine, although its side effects can be severe and life-threatening. Melarsoprol dosage is as follows:

At T. b. gambiense: 2.2 mg/kg i.v. 1 time daily for 10 days.

At T. b. rhodesiense 2 to 3.6 mg/kg i.v. once per day for 3 days; after 7 days, 3.6 mg/kg once per day for 3 days, followed by another 3-day course at this dose

For debilitated patients with severe CNS involvement, alternative regimens have been proposed. Serial follow-up, including CSF analysis, is recommended every 6 months (sooner if symptoms return) for 2 years.

Serious side effects of melarsoprol include encephalopathic reactions, exfoliative dermatitis cardiovascular toxicity (hypertension, arrhythmia, heart failure), and gastrointestinal and renal toxicity from arsenic compounds.

Corticosteroids have been used to reduce the risk of encephalopathic reactions.

Treatment notes

1. Buscher P, Cecchi G, Jamonneau V, et al: Human African trypanosomiasis. Lancet, 390(10110):2397-2409m 2017. doi: 10.1016/S0140-6736(17)31510-6.

Prevention

Prevention of African trypanosomiasis includes avoidance of endemic areas and protection from tsetse flies. Wildlife park visitors should wear adequate clothing that covers wrists and ankles (tsetse flies can bite through thin clothing) and neutral colors that blend into the background, and use insect repellents, although their repellent effectiveness against tsetse flies may be limited.

Pentamidine can help a T. b. gambiensePrevent infection, but damage can occur to pancreatic beta cells, leading to insulin -release and hypoglycemia, followed later by diabetes. Thus, it is rarely used for prophylaxis.

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