American trypanosomiasis (Chagas disease)

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    Chagas disease is a zoonosis caused by the protozoa Trypanosoma cruzi. It is transmitted to humans by contact of triatomine bug faeces with a break in the skin (often caused by a bite from the triatomine bug), or with mucous membranes. Transmission by contaminated blood transfusion, accidental exposure to blood, mother-to-child (during pregnancy or childbirth) or consumption of contaminated food and water is also possible. 

    Chagas disease has two phases: an acute phase, which lasts approximately 4 to 6 weeks, and a chronic phase, which is lifelong if left untreated.

    The disease is primarily found on the American continent a Citation a. For more information on geographical distribution of cases of T. cruzi infection:
    http://gamapserver.who.int/mapLibrary/Files/Maps/Global_chagas_2009.png
    . It is significantly underdiagnosed. [1] Citation 1. Pan American Health Organization. Guidelines for diagnosis and treatment of Chagas disease. Washington, D.C. 2019.
    http://iris.paho.org/xmlui/bitstream/handle/123456789/49653/9789275120439_eng.pdf?sequence=6&isAllowed=y

    Clinical features

    Acute phase

    • Most cases are asymptomatic.
    • If transmitted through a break in the skin: a red swelling on the skin (chagoma) or unilateral painless purplish periorbital oedema (Romaña's sign) with local lymphadenopathy, headache and fever.
    • Rarely: multiple lymphadenopathies, hepatosplenomegaly, myocarditis (chest pain, dyspnoea), meningoencephalitis (seizures, paralysis).

    Chronic phase

    • Many cases remain asymptomatic (indeterminate phase).
    • Up to 30% of cases develop organ damage: [2] Citation 2. Rassi A, Marin-Neto J. Seminar: Chagas disease. The Lancet, Volume 375, ISSUE 9723, P1388-1402, April 17, 2010.
      • cardiac lesions (conduction disorders, dilated cardiomyopathy): arrhythmia, dyspnoea, chest pain, heart failure;
      • gastrointestinal lesions (dilation of the oesophagus or colon i.e. megaoesophagus, megacolon): difficulty swallowing, severe constipation.
      • Individuals with immunosuppression have a higher risk of developing organ damage than the general population.

    Diagnosis

    Laboratory [1] Citation 1. Pan American Health Organization. Guidelines for diagnosis and treatment of Chagas disease. Washington, D.C. 2019.
    http://iris.paho.org/xmlui/bitstream/handle/123456789/49653/9789275120439_eng.pdf?sequence=6&isAllowed=y

    • Acute phase:
      • Identification of Trypanosoma cruzi by direct microscopy of fresh blood or blood concentrated by microhematocrit method.
      • In case of strong clinical suspicion despite no definitive diagnosis from direct microscopy, perform serologic tests after a delay of approximately 1 month (see "Chronic phase").
    • Chronic phase:
      • Identification of anti-Trypanosoma cruzi antibodies by serologic tests, e.g. enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition assay (HAI), indirect immunofluorescence (IIF) or rapid diagnostic test (RDT).
      • For a definitive diagnosis, two different serological tests should be performed simultaneously; in case of conflicting results, a third test is recommended. b Citation b. If resources are limited, ELISA alone can be performed. If the result is positive, a second serologic test should then be performed to confirm the diagnosis before starting treatment. 

    Other investigations

    • ECG may demonstrate conduction disorders.
    • Chest or abdominal x-ray may demonstrate cardiomegaly, megaoesophagus or megacolon.

    Treatment

    Aetiologic treatment

    • Acute or chronic Chagas disease can be treated with either benznidazole or nifurtimox. However, treatment is not recommended if patient has already developed cardiac or digestive complications.
    • Close clinical monitoring should be provided due to the frequent occurrence of adverse effects. Where available, blood tests (complete blood count, liver and renal function tests) should be performed before, during and after treatment.
    • Protocols vary according to the country, follow national recommendations.

    For information:

      Age Dose and duration

    benznidazole
    PO( (a) Citation a. Benznidazole is contra-indicated in pregnancy, breastfeeding and in patient with severe hepatic/renal impairment.

    2 to 12 years [3] Citation 3. Centers for Disease Control and Prevention. Parasites - American Trypanosomiasis.
    https://www.cdc.gov/parasites/chagas/ [Accessed 17 February 2020]
    5 to 8 mg/kg daily in 2 divided doses for 60 days
    > 12 years and adults [4] Citation 4. World Health Organization. WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition. Geneva. 1995. 
    https://apps.who.int/iris/handle/10665/41765 [Accessed 6 May 2020]
    5 to 7 mg/kg daily in 2 divided doses for 60 days

    nifurtimox
    PO (b) Citation b. Nifurtimox is contra-indicated in pregnancy, breastfeeding, patients with severe hepatic/renal impairment or history of severe mental disorders or seizures. Adverse effects (gastrointestinal disturbances, agitation, sleeping disorders, seizure) are frequent and reversible and should not necessarily result in discontinuation of treatment. Avoid alcohol and fatty meals during treatment. [3] Citation 3. Centers for Disease Control and Prevention. Parasites - American Trypanosomiasis.
    https://www.cdc.gov/parasites/chagas/ [Accessed 17 February 2020]

    ≤ 10 years 15 to 20 mg/kg daily in 3 to 4 divided doses for 90 days
    11 to 16 years 12.5 to 15 mg/kg daily in 3 to 4 divided doses for 90 days
    17 years and adults 8 to 10 mg/kg daily in 3 to 4 divided doses for 90 days

    Symptomatic treatment

    See Seizures (Chapter 1), Pain (Chapter 1) and Heart failure (Chapter 12).

    Prevention

    • Individual protection against bite from triatomine bugs: use of long-lasting insecticidal net.
    • In healthcare settings: standard precautions to avoid contamination with soiled materials or potentially infected body fluids.
    • Blood transfusions: advise patients with Chagas disease not to donate blood. In endemic areas, screen donor blood for Trypanosoma cruzi antibodies. 

     

    Footnotes
    • (a)Benznidazole is contra-indicated in pregnancy, breastfeeding and in patient with severe hepatic/renal impairment.
    • (b)Nifurtimox is contra-indicated in pregnancy, breastfeeding, patients with severe hepatic/renal impairment or history of severe mental disorders or seizures. Adverse effects (gastrointestinal disturbances, agitation, sleeping disorders, seizure) are frequent and reversible and should not necessarily result in discontinuation of treatment. Avoid alcohol and fatty meals during treatment.
    References