Chagas Disease and African Trypanosomiasis¶
Chapter 234 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Chagas disease (T. cruzi) and African trypanosomiasis (T. brucei) are neglected tropical diseases affecting low-income populations, with distinct transmission routes and clinical presentations.
- Chagas disease has three phases: acute (asymptomatic or mild), chronic (indeterminate or determinate), and reactivation (in immunocompromised patients).
- African trypanosomiasis (HAT) has two subspecies (T. b. gambiense and T. b. rhodesiense) with differing epidemiology, pathogenesis, and treatment regimens.
- Diagnosis relies on serologic tests (CATT, ELISA), PCR, and microscopic examination of blood/CSF. Treatment includes benznidazole, nifurtimox, fexinidazole, and eflornithine-melarsoprol combinations.
- Prognosis is poor without treatment, with Chagas leading to cardiac/ digestive complications and HAT causing CNS invasion and death.
1. DEFINITION & OVERVIEW¶
Chagas disease (American trypanosomiasis) is caused by T. cruzi, while African trypanosomiasis (sleeping sickness) is caused by T. brucei gambiense and T. brucei rhodesiense. Both are vector-borne neglected tropical diseases affecting socioeconomically disadvantaged populations. Chagas disease has a chronic phase with potential cardiac and digestive complications, while HAT progresses through two stages with CNS invasion.
1.1 Subtopic¶
Chagas disease is a zoonosis with a complex life cycle involving triatomine bugs. HAT is transmitted by tsetse flies and has distinct geographic distribution patterns.
2. EPIDEMIOLOGY¶
6–7 million people are infected with T. cruzi globally, with highest prevalence in Argentina, Brazil, and Mexico. HAT is endemic to sub-Saharan Africa, with T. b. gambiense in western/central Africa and T. b. rhodesiense in eastern/southeastern Africa. Migration and travel have expanded the geographic range of both diseases.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
T. cruzi infects via triatomine bug bites, blood transfusions, congenital transmission, or organ transplantation. T. brucei is transmitted by tsetse flies. Pathogenesis involves immune evasion, persistent parasitemia, and host immune response imbalance leading to chronic inflammation and organ damage.
4. CLINICAL FEATURES¶
Acute Chagas: fever, lymphadenopathy, hepatosplenomegaly. Chronic: cardiac (dilated cardiomyopathy) or digestive (megacolon) complications. HAT: acute (fever, lymphadenopathy) and chronic (CNS involvement, sleep disturbances, psychiatric symptoms).
Table 234-1: Stages of T. cruzi Infection¶
| PHASE OR ONSET OF FIRST | SETTING | CONTEXT | SYMPTOMS | CLINICAL M ANIFESTATI ONS | DURATION | PROGNOSIS |
|---|---|---|---|---|---|---|
| Acute (congenital) | ~5% risk of maternal transmission to newborn | At birth or weeks after delivery | >90% asympt omatic; rare ly mphadenopat hy, hepatospl enomegaly, jaundice, respiratory distress, growth retardation | 2–8 weeks | Favorable when infant is born alive; unknown rate of in utero or neonatal death | |
| Acute (vector-borne) | Vector-borne transmission; oral transmission (ingestion of contaminated food/drinks); blood product transfusion; tissue/organ t ransplantation | 1–2 weeks after vectorial transmission; may be sooner (days) after oral transmission or later (months) after transfusion/tr ansplantation | >90% asymptomatic or mild febrile illness; local swelling at inoculation site (eyelid [Romaña sign] or skin [chagoma]); p olyadenopath y; splenomeg aly; myocarditis, hepatitis, and encephalitis more frequent with oral transmission | 4–8 weeks | Mortality: 0.1–5% with oral transmission or myocarditis /encephalitis | |
| Chronic (indet erminate form) | Balanced immune response after acute phase subsides | No symptoms | Normal clinical examination and ECG result | Lifelong or until determinate phase | No attributable mortality | |
| Chronic (determinate form) | Predominant inflammatory response (in c ardiomyopath y only) | Years to decades after initial infection | Dyspnea, chest pain, palpitation, syncope, sudden death, stroke, dysphagia, regurgitation, constipation, fecaloma, volvulus, peripheral neuropathy | Chronic | 5-year mortality: 2–63%; most important causes of death: cardiac failure and sudden death, followed by stroke |
| PHASE OR ONSET OF FIRST | SETTING | CONTEXT | SYMPTOMS | CLINICAL M ANIFESTATI ONS | DURATION | PROGNOSIS |
|---|---|---|---|---|---|---|
| Acute (reactivation) | Severe immu nosuppressio n | Variable | Myocarditis, erythema nodosum, panniculitis, T oxoplasma-lik e focal brain lesion, menin goencephaliti s | Variable | Mortality depends on rapidity of diagnosis and treatment and on underlying conditions |
Table 234-2: Diagnostic Procedures for T. cruzi Infection¶
| STAGE | TECHNIQUE OF CHOICE | SAMPLE | DIAGNOSTIC CRITERIA |
|---|---|---|---|
| Acute | Microscopy after concentration, PCR | Peripheral blood, cerebrospinal or other body fluids | Positivity in one test |
| Acute (congenital) | Microscopy after concentration, PCR | Cord or peripheral blood | |
| Chronic (indeterminate and determinate forms) | Serology | Peripheral blood | Positivity in two tests with different techniques and antigens |
| Chronic | Microscopy after concentration, PCR | Peripheral blood, cerebrospinal or other body fluids |
5. DIFFERENTIAL DIAGNOSIS¶
Chagas disease may mimic hypothyroidism, adrenal insufficiency, or autoimmune disorders. HAT may resemble malaria, other parasitic infections, or psychiatric conditions. Key differentiators include travel history, serologic testing, and CSF examination for trypanosomes.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic tests include serologic assays (CATT, ELISA), PCR, and microscopic examination of blood/CSF. For HAT, CSF analysis reveals trypanosomes and elevated leukocytes. Congenital transmission is diagnosed via PCR or microscopy of cord blood.
7. MANAGEMENT & TREATMENT¶
Treatment for Chagas: benznidazole (children 2–12 years) and nifurtimox (children 0–17 years). For HAT: fexinidazole (first-line for T. b. gambiense), pentamidine (T. b. gambiense), eflornithine-melarsoprol (T. b. rhodesiense). Treatment is contraindicated in pregnancy and requires close monitoring for adverse effects.
Table 234-3: Chagas Treatment Regimens¶
| DRUG | REGIMEN | DURATION | ADVERSE EVENTS IN ADULTS (FREQUENCY) | PREMATURE DISCONTINUATION (RATE) |
|---|---|---|---|---|
| Benznidazole | Age <12 years: 5–7.5 mg/kg per day in 2 doses; Age >12 years: 5 mg/kg per day in 2 doses | 30–60 days | Allergic dermatitis (29–50%), anorexia and weight loss (5–40%), paresthesia (0–30%), peripheral neuropathy (0–30%), nausea and vomiting (0–5%), leukopenia and thrombocytopenia (<1%) | 7–20% |
| Nifurtimox | Age <10 years: 15–20 mg/kg per day in 3 or 4 doses; Age 11–16 years: 12.5–15 mg/kg per day in 3 or 4 doses; Age >16 years: 8–10 mg/kg per day in 3 or 4 doses | 60–90 days | Anorexia and weight loss (50–81%), nausea and vomiting (15–50%), abdominal discomfort (12–40%), headaches (13–70%), dizziness and vertigo (12–33%), anxiety and depression (10–49%), insomnia (10–54%), myalgia (13–30%), peripheral neuropathy (2–5%), memory loss (6–14%), leukopenia (<1%) |
Table 234-4: HAT Treatment¶
| DISEASE AND STAGE | FIRST-LINE TREATMENT | ALTERNATIVE TREATMENT |
|---|---|---|
| T. b. gambiense HAT First stage | Fexinidazole PO (‡35 kg: 1800 mg for 4 days, followed by 1200 mg for 6 days; 20–34 kg: 1200 mg for 4 days, followed by 600 mg for 6 days) | Pentamidine isethionate IM or IV: 4 mg/kg per day for 7 days |
| T. b. gambiense HAT Nonsevere second stage | Fexinidazole PO (‡35 kg: 1800 mg for 4 days, followed by 1200 mg for 6 days; 20–34 kg: 1200 mg for 4 days, followed by 600 mg for 6 days) | Eflornithine: 200 mg/kg bid for 7 days; Nifurtimox: 5 mg/kg tid for 10 days |
| T. b. gambiense HAT Severe second stage | Eflornithine IV + nifurtimox PO | Fexinidazole (‡35 kg: 1800 mg for 4 days, followed by 1200 mg for 6 days; 20–34 kg: 1200 mg for 4 days, followed by 600 mg for 6 days) |
| T. b. rhodesiense HAT First stage | Suramin IV: 4–5 mg/kg on day 1 followed by 5 weekly injections of 20 mg/kg | Pentamidine isethionate IM or IV: 4 mg/kg per day for 7 days |
| T. b. rhodesiense HAT Second stage | Melarsoprol IV: 2.2 mg/kg per day for 10 days |
8. PROGNOSIS & COMPLICATIONS¶
Chagas disease has a 5-year mortality of 2–63% due to cardiac failure and sudden death. HAT is fatal if untreated, with 5–10% mortality during/after melarsoprol treatment. Complications include cardiomyopathy, digestive tract dysfunction, CNS invasion, and secondary infections.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: treatment contraindicated. Pediatric: dosing adjusted by weight. HIV co-infection does not increase HAT risk. Travelers: HAT risk is low unless in endemic areas. Prevention includes vector control, blood screening, and early diagnosis.
10. KEY POINTS & CLINICAL PEARLS¶
Early diagnosis and treatment are critical for both diseases. Chagas treatment is most effective in acute/early chronic phases. HAT requires CSF examination for staging. Fexinidazole is the first oral treatment for HAT. Monitor for drug toxicity and follow-up for relapse.