Trypanosomiasis, African (T b gambiense)

Essentials of Diagnosis

• Exposure to tsetse flies; chancre at bite site uncommon

• Hemolymphatic disease: Irregular fever, headache, joint pain, rash, edema, lymphadenopathy

• Meningoencephalitic disease: somnolence, severe headache, progressing to coma

• Trypanosomes in blood or lymph node aspirates; positive serologic tests

• Trypanosomes and increased white cells and protein in cerebrospinal fluid (CSF)

General Considerations

• African trypanosomiasis is caused by the hemoflagellates Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense

• T b gambiense causes West African trypanosomiasis and is transmitted in the moist sub-Saharan savannas and forests of west and central Africa

• Organisms are transmitted by bites of tsetse flies (Glossina species), which inhabit shaded areas along rivers

• Humans are the principal mammalian host, but domestic animals can be infected

• Trypanosomes ingested in a blood meal undergo a developmental period of 18–35 days in the fly

• When the fly feeds again on a new mammalian host, the infective stage is injected

Demographics

• The number of reported cases increased from the 1960s to1990s, and has since decreased greatly, although cases are reported from over 20 countries

• Total incidence has been estimated at about < 5000 cases per year, the large majority due to T b gambiense, with the largest number in the Democratic Republic of the Congo

• Infections are rare among travelers

Symptoms and Signs

• Chancres at the site of the bite are uncommon

• Patient may be asymptomatic for months before hemolymphatic disease develops

• Hemolymphatic disease progresses to meningoencephalitic disease, which leads to coma and death

Hemolymphatic disease

• Fever, headache, myalgias, arthralgias, weight loss, and lymphadenopathy

• Discrete, nontender, rubbery nodes, referred to as Winterbottom sign when in a posterior cervical distribution

• Mild splenomegaly

• Transient edema

• Pruritic erythematous rash

• Febrile episodes may be broken by afebrile periods of up to several weeks

Meningoencephalitic disease

• Somnolence, irritability, personality changes

• Severe headache

• Parkinsonian symptoms

Differential Diagnosis

• T b rhodesiense infection

• Malaria

• Influenza and pneumonia

• Tuberculosis

• Infectious mononucleosis

• Leukemia or lymphoma

• HIV

• Arbovirus encephalitis

• Wilson disease

• Psychosis due to other causes, eg, neurosyphilis

Laboratory Tests

• During the hemolymphatic stage, detection of parasites in Giemsa-stained blood smears is difficult

• Serial specimens should be examined, since parasitemias vary greatly over time

• Meningoencephalitic (or second stage) disease is defined by the World Health Organization as CSF showing at least 5 mononuclear cells per mcL, elevated protein, or trypanosomes

• Concentration techniques can aid identification of parasites in blood or CSF

• Serologic tests are positive

• The simple card agglutination test for trypanosomes (CATT)

  • Has excellent sensitivity and specificity

  • Can be performed in the field

  • However, the diagnosis should be confirmed by identification of the parasites

• Field-applicable immunochromatographic lateral flow rapid diagnostic tests that are lower cost and simpler to produce than CATT are available; combining tests improves sensitivity and specificity

• Molecular diagnostic tests, including PCR and field-friendly loop-mediated isothermal amplification (LAMP) are available but not yet standardized or routinely available

Medications

• Pentamidine

  • 4 mg/kg intramuscularly or intravenously every day or every other day for 7 days

  • Used to treat infection that does not involve the CNS

  • Side effects include immediate hypotension; tachycardia; gastrointestinal symptoms during administration; sterile abscesses; and pancreatic (hypoglycemia), liver, and kidney abnormalities

• Eflornithine

  • Alternative to pentamidine

  • 100 mg/kg/day intravenously every 6 hours for 14 days

• Combination of intravenous eflornithine (400 mg/kg/day in two doses for 7 days) and oral nifurtimox (15 mg/kg/day in three doses for 10 days)

  • Treatment of choice for CNS infection; advanced infection defined as CNS leukocytes > 100/mcL)

  • Has improved efficacy and less toxicity than older regimens

• Eflornithine, though less toxic than older trypanocidal drugs, can cause gastrointestinal symptoms, bone marrow suppression, seizures, and alopecia

• Melarsoprol is alternative agent

• Fexinidazole

  • Recommended for patients 6 years of age and older, with body weight at least 20 kg, and a CSF leukocyte count < 100/mcL

  • As efficacious and safe as eflornithine plus nifurtimox when administered orally over 10 days

  • Approved by the WHO for both early and CNS infection and will likely replace other therapies for all but advanced CNS disease

  • Adverse events include

    • Headache

    • Nausea

    • Vomiting

    • Insomnia

    • Anxiety

    • Weakness

    • Tremor

    • Decreased appetite

Prevention

• Individual prevention should include

  • Wearing neutral-colored clothes with long sleeves and pants

  • Insect repellents

  • Using mosquito nets while sleeping

• Control programs focusing on vector elimination and treatment of infected persons and animals have shown good success but suffer from limited resources