Trypanosomiasis, American (Chagas Disease)

Essentials of Diagnosis

Acute stage

• Inflammatory lesion at inoculation site

• Fever

• Hepatosplenomegaly

• Lymphadenopathy

• Myocarditis

• Parasites in blood is diagnostic

Chronic stage

• Heart failure, cardiac arrhythmias

• Thromboembolism

• Megaesophagus

• Megacolon

• Serologic tests are usually diagnostic

General Considerations

• Caused by Trypanosoma cruzi, a protozoan parasite

• Parasite infects wild animals and, to a lesser extent, humans from southern South America to southern United States

• T cruzi has a predilection for myocardium, smooth muscle, and CNS glial cells

• In many countries in South America, Chagas disease is the most important cause of heart disease

• Infection occurs when parasite penetrates skin through bite wound, mucous membranes, or conjunctiva

• As disease progresses over decades, multiplication of parasite causes

  • Cellular destruction

  • Inflammation

  • Fibrosis

Demographics

• An estimated 8–10 million people are infected, mostly in rural areas, with the highest national prevalence in Bolivia, Argentina, Paraguay, Ecuador, El Salvador, and Guatemala

• In endemic countries, incidence has decreased to about 40,000 new infections and 12,500 deaths per year

• In the United States, only a few instances of local transmission have been reported

Symptoms and Signs

• Up to 70% of persons remain asymptomatic

Acute stage

• Seen principally in children

• Lasts 1–2 months

• The earliest findings are at the inoculation site

  • In the eye—Romaña sign (unilateral edema, conjunctivitis, lymphadenopathy) or

  • In the skin—a chagoma (swelling with local lymphadenopathy)

• Subsequent findings include

  • Fever

  • Malaise, headache

  • Mild hepatosplenomegaly

  • Generalized lymphadenopathy

• Acute myocarditis and meningoencephalitis are rare but can be fatal

Latent stage (indeterminate phase)

• This asymptomatic stage may last for life, but symptomatic disease develops in 10–30% of infected individuals, commonly many years after infection

Chronic stage

• Generally manifests as abnormalities in cardiac and smooth muscle

• Cardiac disease includes

  • Arrhythmias

  • Heart failure

  • Embolic disease

• Smooth muscle abnormalities lead to megaesophagus and megacolon with

  • Dysphagia

  • Regurgitation

  • Aspiration

  • Constipation

  • Abdominal pain

• These findings can be complicated by superinfections

• Latent Chagas disease may reactivate in immunosuppressed patients; findings include brain abscess and meningoencephalitis

Differential Diagnosis

• Acute stage: malaria, rheumatic fever, African trypanosomiasis

• Myocarditis due to other causes, eg, coxsackievirus, drugs

• Coronary artery disease

• Toxic megacolon due to inflammatory bowel disease or Clostridioides difficile–associated colitis

Laboratory Tests

Acute stage

• Evaluation of fresh blood or buffy coats may show motile trypanosomes

• Fixed preparations may show Giemsa-stained parasites

• Concentration methods increase diagnostic yields

• Trypanosomes may be identified in lymph nodes, bone marrow, or pericardial or spinal fluid

• Molecular tests are highly sensitive, and can be used to detect parasites in organ transplant recipients or after accidental exposure

• When initial tests are unrevealing in a suspicious case, xenodiagnosis, using laboratory vectors, laboratory culture, or animal inoculation may provide a diagnosis, but these methods are expensive and slow

Chronic stage

• Diagnosed serologically

  • Sensitivity and specificity not ideal

  • Confirmatory assays are advised after initial positive test

• Diagnosis of chronic disease with polymerase chain reaction (PCR) remains suboptimal

Medications

• Treatment is inadequate because the two drugs used, benznidazole and nifurtimox, often cause severe side effects, must be used for a long period, and are ineffective in chronic infection

• Nevertheless, all T cruzi-infected patients should be treated regardless of clinical status or time since infection

• In particular, treatment is recommended for acute, congenital, and reactivated infections and for children and young adults with chronic disease

• Benznidazole

  • 5 mg/kg/day orally in divided doses for 60 days

  • Side effects include granulocytopenia, rash, and peripheral neuropathy

• Nifurtimox

  • 8–10 mg/kg orally in four divided doses after meals for 90–120 days

  • Side effects include gastrointestinal (anorexia, vomiting) and neurologic symptoms (headaches, ataxia, insomnia, seizures), which appear to be reversible and to lessen with dosage reduction

• In the United States, nifurtimox is available only from the CDC Drug Service, Centers for Disease Control and Prevention, Atlanta, GA 30333; telephone: 404-639-3670

• Patients with chronic disease may also benefit from

  • Antiarrhythmic therapy

  • Standard therapy for heart failure

  • Conservative and surgical management of megaesophagus and megacolon

Prognosis

• In acute and congenital infections, nifurtimox and benznidazole reduce duration and severity of infection, but cure is achieved in only about 70% of patients

• In the chronic phase, although parasitemia may disappear in up to 70% of patients, treatment does not alter progression of disease

Prevention

• In South America, reductions in new infections has been achieved by initiation of a major eradication program based on

  • Improved housing

  • Use of residual pyrethroid insecticides and pyrethroid-impregnated bed curtains

  • Screening of blood donors

• In endemic areas, blood should not be used for transfusion unless at least two serologic tests are negative