Chagas in Brazil

Clinical care guide based on current protocols for the diagnosis, treatment and follow-up of Chagas disease.

Active protocolBrazilian Ministry of Health (CONITEC)
Review2018 (PCDT, Portaria SCTIE/MS nº 57/2018)

Diagnosis

Summary

Who to test

  • People who have lived or live in an area with triatomines or infected reservoirs, especially in mud, thatch, wattle-and-daub or wooden housing: test.
  • People who received blood or blood-component transfusion before 1992: test.
  • Relatives or household members of a person diagnosed with Chagas disease, especially children of an infected mother: test.
  • Pregnant women with a risk factor: test during antenatal care, ideally alongside HIV, syphilis and hepatitis B.
  • People without risk factors: do not screen — prevalence is low and the number of tests needed to detect one case is high.

Acute phase

  • Direct parasitological examination (reference standard): fresh smear and a concentration method (Strout, microhaematocrit or buffy coat), performed simultaneously.
  • First sample negative with persistent suspicion: repeat after 12–24 hours.
  • Blood culture and xenodiagnosis: they do not confirm the acute phase.
  • Notification: compulsory within 24 hours (SINAN).

Chronic phase

  • Serological diagnosis: two tests based on different principles or antigen preparations (ELISA, IFA, IHA, WB or CLIA), on the same sample.
  • Both reactive: chronic infection confirmed.
  • Discordant: third test on a new sample; if discordance persists, refer to a reference centre.
  • Both non-reactive: infection ruled out.
  • PCR: do not use in the chronic phase, because of low sensitivity.
  • Rapid test: a non-reactive result rules out infection when used as a single test; a reactive result requires serological confirmation.

Newborn

  • Newborn of an infected mother: direct parasitological examination in the first days of life, with more than one sample.
  • Negative examination: serology after 9 months; before that, maternal antibodies may give a reactive result.
  • Two reactive tests: congenital transmission confirmed.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Diagnostic algorithm

Step 1 — When to suspect

Epidemiological history (area with triatomines or infected reservoirs; housing made of mud, thatch, wattle-and-daub or wood; blood transfusion before 1992; household or family member with Chagas disease; child of an infected mother) or compatible clinical picture.

Determine the likely phase — it defines which test to request:

Acute phase
High parasitaemia
Pregnant woman / newborn
Risk of vertical transmission
Chronic phase
Undetectable parasitaemia
Step 2A — Acute phase: direct parasitological examination

Reference standard. Perform fresh smear and a concentration method simultaneously:

Fresh smear → Strout → Microhaematocrit → Buffy coat

POSITIVE → acute phase confirmed: treat immediately + notify within 24 h (SINAN)
NEGATIVE with persistent suspicion → repeat sampling in 12–24 h; repeat until confirmed, until symptoms resolve, or until another diagnosis is confirmed
Suspected myopericarditis → echocardiogram · suspected meningoencephalitis → CSF
Blood culture and xenodiagnosis do not confirm the acute phase (they may be positive in chronic infection). Orally transmitted cases tend to be more severe: rash, gastrointestinal bleeding, jaundice, raised transaminases.
Step 2B — Chronic phase: serology

Two serological tests based on different principles or with different antigen preparations, on the same sample:

ELISA IFA IHA WB CLIA

Two ELISA assays are acceptable provided they use different antigen preparations.

Both reactive → Chronic infection confirmed → assess clinical form and treatment indication
Discordant → third test on a new sample (ELISA, IFA, IHA, WB or CLIA)
Both non-reactive → infection ruled out
PCR must not be used in the chronic phase (low diagnostic sensitivity). Rapid test: non-reactive rules out infection when used as a single test; reactive requires serological confirmation (many false positives).
Step 3 — Clinical assessment and form classification

History + physical examination + ECG in every case. Echocardiogram if the ECG is abnormal or there are cardiac symptoms.

Asymptomatic with no abnormalities → Indeterminate chronic form
ECG abnormality, palpitations, syncope, dyspnoea → echocardiogram, Holter, exercise test → Chagasic cardiopathy (early or advanced)
Dysphagia, regurgitation, constipation → contrast radiography or endoscopy (rule out malignancy) → Digestive form

The clinical form defines management: treat, shared decision, or do not treat (see Treatment).

Acute phase: tests and management

In the acute phase parasitaemia is high and direct examination identifies the parasite in peripheral blood.

  • Fresh smear: quick and more sensitive than a blood film; collect within 30 days of symptom onset.
  • Concentration methods (Strout, microhaematocrit or buffy coat): perform simultaneously with the fresh smear, even when it is negative.
  • Suspected myopericarditis: echocardiogram. Suspected meningoencephalitis: cerebrospinal fluid examination.

Orally transmitted cases are more severe: rash, gastrointestinal bleeding, jaundice and heart failure. In an outbreak, investigate household contacts.

Chronic phase: test interpretation

  • Two ELISA assays may be used, provided they use different antigen preparations.
  • WB and CLIA are not required when two other tests are available.

Treatment

Summary

Drugs

Benznidazole is first-line in all phases and clinical forms. Nifurtimox is second-line, reserved for intolerance to or unavailability of benznidazole, and is not used in adults routinely.

Who to treat

  • Children and adolescents with indeterminate or digestive form: treat.
  • Adults under 50, indeterminate or digestive form: treat.
  • Adults aged 50 or over: do not treat routinely.
  • In that age group, consider shared decision-making, especially for people infected in adulthood, without comorbidities and with longer life expectancy.
  • Early cardiopathy (ECG abnormality, ejection fraction > 40 %, no heart failure and no severe arrhythmias): treating or not treating, through shared decision-making.
  • Advanced cardiopathy: do not treat.
  • Digestive form: antiparasitic treatment does not change the course; apply the recommendations for the indeterminate form and manage megaoesophagus and megacolon with their own measures.

When treatment is always indicated

  • Acute phase, in all age groups: treat immediately; in persistent suspicion with an asymptomatic case, consider empirical treatment.
  • Congenital infection, and children and adolescents with chronic infection: treat.
  • Immunosuppressed patients (HIV without reactivation, transplant recipients): treat, preferably with benznidazole.
  • Women of childbearing age: treat outside pregnancy, with contraception during treatment, to reduce vertical transmission.

Regimens and doses

  • Benznidazole (adult): 5 mg/kg/day, in 1 to 3 doses, for 60 days.
  • Alternative for people over 60 kg: 300 mg/day for a number of days equal to body weight, maximum 80 days.
  • Nifurtimox (adult): 10 mg/kg/day, in 3 doses, for 60 days.
  • Children and adolescents: see the Paediatrics section.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Benznidazole: formulations and precautions

First-line in all phases. Tablets of 12.5 mg (paediatric) and 100 mg (adult).

  • Adult: 5 mg/kg/day, in 1 to 3 doses, for 60 days.
  • Alternative for people over 60 kg: 300 mg/day, in 2 to 3 doses.
  • In this regimen, one treatment day per kilogram of body weight, maximum 80 days (70 kg → 70 days).
  • Paediatric: 5 to 10 mg/kg/day, in 2 doses, for 60 days.

The 12.5 mg formulation is soluble in water, orange juice or milk. Request a full blood count three weeks after starting, because of the risk of neutropenia.

Nifurtimox: restricted use

Second-line, in tablets of 120 mg.

  • Adult: 10 mg/kg/day, in 3 doses, for 60 days.
  • Paediatric: 15 mg/kg/day, in 3 doses, for 60 days.

Not routinely recommended in adults: lower availability in the country and more adverse events. Reserve for children, adolescents and young adults with recent infection and intolerance to benznidazole. Dispensed only at reference centres, on demand.

Megaoesophagus and megacolon

Antiparasitic treatment does not change the course of the digestive forms; management is symptomatic and broadly follows that of non-chagasic forms.

Megaoesophagus: small volumes, soft foods, avoid irritants and do not eat before lying down. Relax the lower oesophageal sphincter with nifedipine 10 mg sublingually 30 minutes before meals or isosorbide dinitrate 2.5 to 5 mg sublingually 15 minutes before. The effect is symptomatic; stop if adverse events occur. Nifedipine is contraindicated in severe cardiopathy, because of the risk of hypotension and fluid retention. Refractory cases: botulinum toxin, balloon dilatation or surgery.

Megacolon: high-fibre diet, plenty of fluids, avoid constipating foods and drugs, use emollient or osmotic laxatives and glycerol suppositories; surgery in indicated cases.

Always exclude malignancy and non-chagasic causes: idiopathic achalasia, amyloidosis, sarcoidosis, reflux and tumours; investigate with contrast radiography and endoscopy.

Chagasic cardiopathy: heart failure and arrhythmias

ECG abnormalities are the first indication of cardiac involvement and allow the deterioration of cardiac function to be tracked.

Heart failure: treat as in other causes — ACE inhibitor or ARB, diuretic and spironolactone; beta-blockers with caution, because they may worsen bradycardia or conduction blocks. Start in a compensated patient, at a low dose, and titrate to the maximum tolerated dose, usually lower than in other cardiomyopathies.

Arrhythmias: the leading cause of death; sudden death accounts for 55 to 65 % of deaths. Amiodarone 200 mg/day is the drug of choice, with attention to thyroid dysfunction, QT prolongation, torsades de pointes and pulmonary fibrosis.

Assess referral for pacemaker, implantable cardioverter-defibrillator or heart transplantation, in a specialist service.

Follow-up

Summary

Where to follow up

  • Primary care: non-severe acute phase, indeterminate chronic form, stable cardiac, digestive or cardiodigestive forms and pregnant woman without comorbidities.
  • Specialist service: severe or unstable cases, pregnant woman with cardiopathy or in the acute phase, HIV, transplant recipients and candidates for nifurtimox.

Monitoring during treatment

  • Regular clinical assessment, with particular attention to adverse events.
  • Benznidazole: full blood count three weeks after starting, because of the risk of neutropenia.
  • Nifurtimox: must be managed in a specialist service, with regular assessment.
  • Severe adverse events or disease progression: refer to a specialist service.

After treatment

  • There is no routine serological monitoring or retreatment after a completed course.
  • Maintain longitudinal follow-up with periodic ECG, even without aetiological treatment; serological negativisation is slow and is not a cure criterion.
  • On amiodarone: appointments every 3 months in the first year and every 6 months thereafter.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Criteria for referral to a specialist service

  • Severe acute phase: suspected encephalitis or myocarditis.
  • Pregnant woman with the acute phase or with cardiopathy.
  • Cardiopathy with severe arrhythmias, heart failure, candidacy for pacemaker or implantable cardioverter-defibrillator, or thromboembolic risk.
  • Digestive involvement eligible for a specialist procedure: botulinum toxin, dilatation or surgery.
  • HIV co-infection, transplant recipients and candidates for nifurtimox.

Pregnancy and Congenital Chagas

Summary

Pregnant woman with chronic Chagas disease

  • Do not treat during pregnancy: the risk of congenital transmission is low and there is no demonstrated benefit of antiparasitic treatment at this time.
  • Without cardiopathy or comorbidities: follow up in primary care.

Pregnant woman in the acute phase

  • Severe acute disease (myocarditis or meningoencephalitis): treat regardless of gestational age; preferably from the second trimester, when the risk of malformations is lower.
  • Non-severe acute disease in the first trimester: wait until the second trimester, with informed shared decision-making.
  • Drug of choice: benznidazole.
  • Pregnant woman in the acute phase: follow-up in a specialist service.

Preventing vertical transmission

  • Women of childbearing age: treat outside pregnancy, with contraception during treatment, to reduce congenital transmission.

Newborn

  • Direct parasitological examination in the first days of life, with more than one sample.
  • Negative examination: serology after 9 months. Two reactive tests confirm congenital transmission and early treatment has a high cure rate.
  • Notify mother-to-child transmission identified up to 2 years of age.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Flow for the pregnant woman and the newborn

Pregnant woman

Screen during antenatal care according to clinical and epidemiological risk (ideally alongside HIV, syphilis and hepatitis B). Routine screening is not recommended for low-risk pregnant women.

Non-reactive → rules out infection (rapid tests are highly sensitive)
Reactive → confirm with two serological tests using different methods
Confirmed and without cardiopathy or comorbidities → chronic form: do NOT treat during pregnancy · follow up in primary care
With cardiopathy → refer to a specialist service
Trypanocidal treatment for the chronic form is given outside pregnancy: it reduces vertical transmission. Advise contraception during treatment.
Exception: acute phase during pregnancy
Severe acute disease (myocarditis or meningoencephalitis) → treat regardless of gestational age · preferably from the second trimester
Non-severe acute disease in the first trimester → wait until the second trimester; not treating is justifiable, with informed shared decision-making
Benznidazole is the drug of choice. Acute-phase pregnancy → follow-up in a specialist service.
Newborn of an infected mother

Direct parasitological examination in the first days of life — collect more than one sample (false negatives occur).

Positive → congenital infection confirmed → treat
Negative → serology after 9 months of age
Two reactive tests → congenital transmission confirmed → treat
Non-reactive → not infected: discharge from follow-up
Before 9 months serology is not valid: maternal antibodies may give a reactive result. If follow-up cannot be guaranteed, testing between 6 and 9 months is an option, accepting more false positives. PCR and SAPA are not routine methods.

Notify mother-to-child transmission identified up to 2 years of age.

Congenital transmission: why test after 9 months

Maternal antibodies may give false-positive results in the neonatal period; serology is therefore only interpretable after 9 months. A high titre that persists is a strong indication of congenital transmission.

  • Children not tested at 9 months: test after that period — serological negativisation exceeds 95 %.
  • When follow-up is difficult, testing may be brought forward to between 6 and 9 months, accepting more false positives.
  • PCR and SAPA are not routine methods for the congenital diagnosis.

Pediatrics

Summary

Indication

Treat all children and adolescents with indeterminate or digestive chronic infection: serological negativisation is more likely, adverse events are less frequent and severe, and early treatment reduces future congenital transmission.

Regimens and doses

  • Benznidazole: 5 to 10 mg/kg/day, in 2 doses, for 60 days.
  • Formulation: 12.5 mg tablets, soluble in water, orange juice or milk.
  • 2.5 to 5 kg: 1 tablet (12.5 mg) twice daily.
  • 5 to 10 kg: 2 tablets (25 mg) twice daily.
  • 10 to 15 kg: 3 tablets (37.5 mg) three times daily.

Congenital infection

  • Treat as soon as it is confirmed: serological negativisation exceeds 95 % and early treatment is well tolerated.
  • Children not tested at 9 months: test after that period.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Paediatric benznidazole: safety

More than 50 % of patients experience adverse events, but children tolerate them better than adults and discontinuation due to adverse events is uncommon.

The dose is calculated per kilogram: weight-band regimens are practical guidance and do not replace calculating the dose.

Adverse Reactions

Summary

Adverse events are common and are the main reason for discontinuing treatment; counselling before starting and symptomatic management prevent many discontinuations.

Benznidazole

Around 53 % of patients experience an adverse event.

  • Dermatitis and rash in 30 to 44 %, usually without the need to stop treatment.
  • Alopecia in 0.9 %.
  • Gastrointestinal intolerance in 13.3 %.
  • Paraesthesias in 10.3 %, with possible functional impact and persistence for months.
  • Arthralgia in 8.1 %.
  • Neutropenia: request a full blood count three weeks after starting.

Nifurtimox

Around 85 % of patients experience adverse events.

  • Gastrointestinal intolerance in 61 %.
  • Arthralgia in 33 %.
  • Dermatological involvement in 15 %.

Management

  • Mild or moderate events: symptomatic treatment without stopping the antiparasitic drug.
  • Severe events or paraesthesias with functional impact: stop and reassess reintroduction or switching.
  • Nifurtimox: management in a specialist service.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Management of severe adverse events

Paraesthesias may correspond to peripheral polyneuropathy, with functional impact and persistence for months after discontinuation; in those cases, stop the antiparasitic drug and reassess.

Neutropenia: request a full blood count three weeks after starting; in the presence of leucopenia or neutropenia, stop and reassess.

Severe cutaneous hypersensitivity, such as Stevens-Johnson syndrome, is rare but requires immediate discontinuation and specialist assessment.

Nifurtimox: watch for neuropsychiatric events — irritability, insomnia and mood changes.

Surveillance

Summary

Notification

  • Suspected acute cases: compulsory notification within 24 hours (Portaria SVS/MS No. 204 of 17 February 2016).
  • Mother-to-child transmission: notify cases identified up to 2 years of age.
  • Chronic cases: strongly consider notification, to gauge the burden of disease.

Control measures at the probable site of infection

  • Vector transmission: environmental surveillance, entomological and reservoir investigation, serology for residents and health education.
  • Oral transmission: sanitary inspection to identify the contaminated food.
  • Vertical transmission: when the child is the first case, investigate the mother and family members.

Screening

  • Screen people with clinical and epidemiological risk factors (see detail); do not screen without risk factors.
  • Pregnant women: screen those at high risk; routine screening is not recommended for low-risk women.
  • Risk of reactivation due to immunosuppression: screen at any age.
Source: Clinical Protocol and Therapeutic Guidelines for Chagas Disease. Brazilian Ministry of Health, 2018 (Portaria SCTIE/MS No. 57/2018)

Risk factors for screening

Screening identifies asymptomatic people, or people with non-specific symptoms, exposed to T. cruzi.

  • Having lived in childhood, or living, in an area with the transmitting vector or animal reservoirs (sylvatic or domestic) infected with T. cruzi.
  • Having lived or living in mud, thatch, wattle-and-daub or wooden housing, with possible contact with the vector.
  • Living in, or coming from, an area with active transmission or an epidemiological history suggestive of past transmission.
  • Having received blood or blood-component transfusion before 1992, when screening tests were introduced into blood services.
  • Having relatives or household members diagnosed with Chagas disease — especially being the son or daughter of a mother with confirmed infection.

Pregnant women with no previous serology and with risk factors should be screened; women of childbearing age with a previous negative serology do not need repeat testing, unless there is strong suspicion of infection since the last test.

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