Topic Editor: Becky Box, MBBS
Review Date: 10/7/2012
Definition 
- Chagas disease, also known as American trypanosomiasis, is a systemic zoonotic infection that occurs in humans by the infestation of the protozoan parasite Trypanosoma cruzi
- This disease manifests as an acute infection followed by either an indeterminate state or a determinate/chronic disease state
- Chronic disease results in cardiac and/or gastrointestinal motility disorders that have significant morbidity and mortality associated with them
- The most common mode of transmission is via the triatome bug (commonly known as kissing, assassin or conenose bug), which releases the protozoa when it defecates
Description
- Chagas disease was first discovered by Brazilian physician Dr. Carlos Chagas in 1909
- The primary causative organism responsible for Chagas disease is the protozoan parasite T. cruzi
- The majority of cases involve transmission through triatomine bugs, also known as reduviid, kissing, conenose, or assassin bugs. The triatomine bugs acquire infection by sucking blood from animals or humans with parasites circulating in their blood
- Other less common modes of transmission include blood transfusion or organ transplantation from an infected donor, congenital transmission, and oral transmission. These are far less common with the implementation of large scale vector control programs and screening of blood donors
- Endemic Chagas disease has grown to epidemic proportions in Latin America, and in recent times has been compared to the HIV/AIDS pandemic
- The progression of Chagas disease can be categorized into three phases
- Acute phase: Many people are asymptomatic, or simply have a non-specific febrile illness as the only acute manifestation. The acute phase usually lasts for 2-4 weeks and may be characterized by an inflammatory nodule (i.e. a chagoma) at the site of parasite entry. In this situation, there may be an associated inflammatory infiltrate with trypomastigotes (circulating form of parasite) found in the cells of subcutaneous tissues. A reactive hyperplasia of adjacent lymph nodes and interstitial edema can be found clinically, along with hepatomegaly, and splenomegaly. If the inoculation site was conjunctival, there may be unilateral periorbital swelling (Romaña's sign ). Nonspecific symptoms may include fever, headache, and malaise
- Intermediate phase: The acute phase is followed by a prolonged latent phase of up to 10–20 years in some cases. Although patients may be asymptomatic during this phase, parasites continue to reproduce in the host
- Chronic phase: A significant percentage (30-40%) of patients will progress from intermediate to chronic phase, which is characterized by severe cardiac and/or GI manifestations with extensive organ damage
Epidemiology
Incidence/prevalence
- Chagas disease is endemic to Mexico, Central America, and South America, particularly in rural and underdeveloped areas. Together these regions account for approximately 8-11 million cases currently
- This disease has also spread to elsewhere, particularly Spain, Japan and Australia, due to a large population of immigrants from Latin American countries
- The Center for Disease Control (CDC) estimates that 300,000 individuals in the U.S. are chronically infected. Acute Chagas disease is rare in the US, but chronic T. cruzi infection has substantially increased over the past 20 years, mostly as a result of immigration. It is important to note that triatomine bugs have been reported living from the mid U.S. southward
- Due to the implementation of screening for blood donors and large scale vector control programs throughout endemic regions, the incidence of Chagas disease has significantly decreased. In 1990, an incidence of 700,000 cases/year was reported. In 2006, this figure reduced to 41,2001
- Approximately 30-40% of infected patients develop chronic Chagas disease with symptoms such as cardiomyopathy and/or gastrointestinal disease
- Current mortality rate due to Chagas disease is reported as 10-14,000 deaths per year
Age
- Children residing in rural endemic areas are more likely to acquire new infections
- Children have a higher incidence of morbidity associated with complications of the acute phase of the disease
- Cardiac and gastrointestinal (GI) abnormalities associated with the chronic phase of the disease occurs predominantly in adults
Gender
- Genders are equally affected
Race
- No racial predilection is known to exist
Risk factors
- Triatomine bug infestation
- Residing in an endemic area
- Poor housing conditions, particularly dwellings made of wood, stone or thatched roofing
- Travel to an endemic area
- Transfusion of blood or blood-derived products from infected donors. Risk of transmission after receiving one unit from an affected donor is around 10-20%. The risk is higher with platelet transfusion
- Transplant recipients receiving organs from infected donors
- Immunosupression associated with HIV, chemotherapy, or organ graft
- Accidental laboratory exposure
- Perinatal transmission - transmission rate ~ 5-6% in chronically infected mothers
- Contaminated food or drink (rare)
Etiology
- The primary causative organism responsible for Chagas disease is a protozoan parasite, T. Cruzi
- Vector-borne transmission
- Transmission of T.cruzi among humans and other mammalian hosts occurs through blood sucking reduviid bugs belonging to the subfamily Triatominae
- There are more than 130 species, the four most common species implicated in transmission are Triatoma infestans; Rhodnius prolixus; Panstrongylus megistus and Triatoma dimidiata
- Infection is transmitted to a second vertebrate host when abraded skin, mucous membranes, or conjunctivae become contaminated with feces or urine dropped by the bug following feeding
- Other methods of transmission include
- Receiving a blood transfusion or blood derived products obtained from an infected donor
- Transplantation of solid organ or bone marrow harvested from a chronically infected donor
- Rarely through consumption of food or liquid contaminated with T. cruzi. Regional outbreaks resulting from oral transmission have been reported in areas without the presence of insect vectors
- Transplacental transmission from an infected mother to the fetus
- Accidental infection during handling T. cruzi in laboratories
[Outline]
History
- Acute infection
- Acute Chagas disease may manifest immediately following infection, with a duration ranging from a few weeks to months
- The usual incubation period for vector-borne infection is 1-2 weeks, but may be longer (20-40 days) for transfusion-acquired infection
- Most patients show mild symptoms or remain asymptomatic
- Induration, swelling and erythema may be observed at the site of inoculation
- Nonspecific symptoms seen during the acute phase of infection include:
- Generalized - fever/ malaise/ headache/ myalgia
- GI - anorexia/ diarrhea/ vomiting
- Skin - lymphadenopathy/ rash/ edema
- Intermediate phase
- The acute phase is followed by a prolonged latent period during which patients are usually asymptomatic
- Chronic phase
- Presence of dyspnea, reduced exercise tolerance, fatigue and edema in lower extremities may be indicative of cardiomyopathy
- Palpitations, syncope and dizziness may be associated with conduction abnormalities
- Patients with megaesophagus may complain of dysphagia, odynophagia, and epigastric discomfort
- Chronic constipation and persistent abdominal pain may be present in patients with megacolon
Physical findings on examination
- Acute phase
- Specific findings observed during the acute phase of infection include:
- Chagoma: Inflammatory nodule at the portal of entry of T. cruzi through skin
- Romaña's sign: A characteristic sign of Chagas disease which is unilateral periorbital swelling around the eyelid in cases involving transmission through the conjunctiva
- Schizotrypanides: A non-pruritic morbilliform rash
- Hepatomegaly and splenomegaly, particularly in children
- Hypotonicity and anemia in congenitally infected infants
- Serious manifestations such as meningoencephalitis and myocarditis
- Intermediate phase
- Although patients remain asymptomatic during the intermediate phase, serological testing will be positive
- Chronic phase
- The chronic phase occurs in 30-40% of infected patients
- The digestive or cardiodigestive forms usually occur late, typically 10-30 years after the acute phase
- It is characterized by cardiac and/or gastrointestinal (GI) abnormalities
- Cardiac abnormalities are the most serious and frequent manifestation of chronic infection – 20-30% of patients develop cardiac disease
- The Digestive form occurs in approximately 10-15% of affected patients and is seen almost exclusively south of the Amazon Basin (Argentina, Brazil, Chile, Bolivia). This is thought to be due to the predominance of a certain parasitic strain
- Cardiac abnormalities:
- Cardiac abnormalities include: apical aneurysms: Brady and tachyarrhythmias (brady-tachy syndrome);Conduction abnormalities: Right bundle branch block and premature ventricular beats; Dilated cardiomyopathy; Heart failure (biventricular with right-sided predominance); Thromboembolism: Mural thrombi formed inside cardiac chambers
- Sudden cardiac death accounts for 2/3 of Chagasic cardiac deaths
- The mortality rate of patients with CHF due to Chagas disease is higher than CHF due to other causes
- GI abnormalities:
- These are characterized by abnormalities in secretive, motor and absorptive functions of both the esophagus & colon
- The damage from parasitic infiltration predominantly results in denervation of the myoenteric plexus of Auerbach. Most damage occurs during acute infection, with a slower process of denervation occurring during the chronic phase.
- Findings in patients with chagasic megaesophagus include: Aspiration pneumonitis; epigastric pain; dysphagia; odynophagia; ptyalism (hypersalivation); malnourishment and weight loss; regurgitation
- Findings in patients with Chagastic megacolon include: abdominal distension; abdominal pain; altered peristalsis; fecal impaction; fecaloma; persistent constipation; obstruction; volvulus
[Outline]
Blood test findings
- Complete blood count (CBC)
- Leukocytosis and lymphocytosis may be evident during the acute phase of infection
- Parasitology
- Microscopy
- Direct microscopic visualization of mobile trypomastigotes in blood is the preferred diagnostic method for detection of acute infection involving a high load of circulating parasites in blood
- Cord blood or peripheral blood may be examined for detection of neonatal infection, especially during the first month of life
- The parasite may be undetectable in peripheral blood within 90 days of disease onset & is not detectable in the chronic phase of infection
- Blood smear
- Alternatively, morphological characteristics of trypomastigotes may also be visualized using a stained blood smear (thick or thin). This technique offers lower sensitivity than microscopic detection
- Microhematocrit
- A parasitic concentration technique is useful for detection of congenital infection due to its superior sensitivity and need for only a small blood sample
- Indirect parasitological techniques include xenodiagnosis and hemoculture, though sensitivity largely depends on the level of circulating parasites in blood
- Testing of infants with high risk (seropositive mothers) requires both microscopic and PCR based testing within the first few months of life. If negative, repeat testing at 9-12 months is recommended at which time the level of maternal antibodies are expected to have decreased
- Serology
- Low levels of parasitemia during the chronic phase necessitates detection of IgG antibodies against T. cruzi using serological techniques
- Conventional serology tests
- The most widely used conventional serology tests include enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence (IIF), and indirect hemagglutination (IHA). These tests have a much higher sensitivity compared to microscopy, and each has its own advantages and shortcomings
- WHO recommends at least 2 subsequent assays using different methods to improve the accuracy of results
- The IIF test is extremely sensitive (99%), yet requires skilled personnel, specialized equipment and involves multiple steps
- The ELISA test offers good sensitivity and specificity; yet requires skilled personnel and a longer time to produce results
- The IHA test provides prompt results (within 2 hours), but has a sensitivity lower than that of IIF and ELISA (96% to 98%)
- Serological tests sometimes produce false-positive results in patients with other infectious and parasitic conditions, i.e. Leishmania sp.
- Non-conventional serology tests
- Immunoblot assay (IBA)
- IBA effectively detects antibodies against T.cruzi using recombinant proteins as target antigens. IBA can serve as a valuable supplemental test for confirming results derived from conventional serology tests, and identifying false-positive results
- Emerging tests
- Polymerase chain reaction (PCR)
- PCR based assays have been widely investigated for detection of T. cruzi, and have demonstrated excellent sensitivity
- Use of PCR in routine diagnostic practices has been limited by the need for specialized laboratory facilities, lack of standardization, and commercial availability
- PCR should be utilized to confirm a diagnosis of T. cruzi in cases involving uncertain serology results
- Radio-immunoprecipitation assay (RIPA) and Ortho® T. cruzi ELISA Test System
- Used in the U.S. to screen blood donors for T. cruzi
Radiographic findings
- Echocardiography and Doppler
- 2D echocardiography and Doppler studies are useful in assessment of early myocardial damage and the extent of cardiomegaly. These serve as an important prognostic tool for evaluation of mortality risk in patients with chronic Chagas-related heart disease
- Echocardiography may help rule out other causes of cardiac failure such as cardiac tamponade or significant pericardial effusion
- Echocardiography can effectively detect the presence of mural thrombi and apical aneurysms
- Doppler may show evidence of prolongation of isovolumic contraction and relaxation times
- Chest x-ray
- May be useful in detection of cardiomegaly and left ventricular failure
Other diagnostic test findings
- Electrocardiography (ECG)
- 12- lead ECG monitoring is essential during both acute and chronic phases of infection for detection of conduction abnormalities, often indicative of life-threatening arrhythmias
- ECG findings during the acute phase include
- First-degree atrioventricular block
- Low QRS voltage
- Primary T-wave changes
- Sinus tachycardia
- ECG findings during the chronic phase include
- Abnormal Q-wave
- Left anterior fascicular block
- Low QRS voltage
- Premature ventricular contractions
- Right bundle branch block
- ST-T changes
[Outline]
- Leishmaniasis
- Malaria
- Bacterial or mycobacterial infection
- Clostridium difficile colitis
- Constipation
- Congenital Syphilis
- Hypertensive encephalopathy
- Infectious mononucleosis
- Meningitis
Chronic Chagas disease - digestive form
- Achalasia
- Carcinoma of esophagus
- Colon obstruction
- Esophageal motility disorders
- Esophageal rupture
- Esophageal spasm
- Gastroesophageal reflux disease
- Hirschsprung disease
- Inflammatory bowel disease
- Megacolon (acute, chronic or toxic)
Chronic Chagas disease - cardiac form
- Atrioventricular block (first, second or third degree)
- Atrioventricular dissociation
- Atrioventricular nodal reentry tachycardia (AVNRT)
- Cardiogenic pulmonary edema
- Cardiomyopathy (non-chagastic causes)
- Coronary artery atherosclerosis or vasospasm
- Myocardial ischemia or infarction
- Myocardial rupture
- Myocarditis (non-chagastic)
- Pulmonary embolism
- Pulmonic regurgitation
- Right ventricular infarction
- Sinus node dysfunction
- Sudden cardiac death
- Ventricular tachycardia or fibrillation
General treatment items
- Antitrypanosomal therapy is the mainstay of Chagas disease management. It is directed towards reducing parasitic load and alleviating signs and symptoms of the disease
- All patients with acute, congenital and reactivated infections, including immunosuppressed individuals and children, should receive antitrypanosomal drugs
- Seventy percent of cases that are treated during the acute period of Chagas disease are cured. Even better results are seen, with close to 100% cure rate in newborns and nursing children treated for congenital Chagas disease
- Antitrypanosomal therapy is strongly indicated (but not yet proven) for patients aged 19-50 years with chronic Chagas disease, without evidence of advanced cardiomyopathy. Treatment beyond 50 years of age remains controversial as a benefit in this age group has not been established
- The only two drugs with proven antitrypanosomal activity are benznidazole and nifurtimox. These drugs are not approved by the U.S. Food and Drug Administration (FDA), but can be obtained from the CDC
- Both agents have comparable efficacy; however, benznidazole is recommended as first line as the side effect profile is more favorable
- Both drugs have been associated with dose-dependent adverse effects such as hypersensitivity reactions (rash, fever, edema, lymphadenopathy, arthralgia, and myalgia), bone marrow depression (neutropenia, thrombocytopenic purpura) and peripheral polyneuropathy
- Use of these drugs is contraindicated in patients with severe renal or hepatic impairment, pregnant women, and nursing mothers
- The benefit of treatment with benznidazole in patients with chronic chagasic cardiomyopathy is being assessed in a multinational survey, called the Benefit project, with results expected at the end of 2013
- A recent study, using Itraconazole, only showed a 20% cure rate in a subgroup of chronic cases; however there was an improvement in cardiomyopathy in 50% of these cases
Treatment of cardiac abnormalities
- Cardiac arrhythmias should be treated with appropriate antiarrhythmic agents. Amiodarone is the drug of choice for sustained and non-sustained ventricular tachycardia. Other alternatives such as radiofrequency catheter ablation or implantable defibrillator may also be considered
- Patients with severe bradyarrhythmias may benefit from a pacemaker
- Patients with a high risk of thromboembolism, particularly those with atrial fibrillation or apical aneurysms, should receive anticoagulant therapy
- Patients with heart failure may be treated for this using standard treatments
- In some patients with end-stage heart failure, cardiac transplantation can be considered. Some studies suggest an improved mortality rate for survivors of cardiac transplant performed for Chagas heart disease versus transplant for alternative causes of cardiomyopathy
Treatment of GI dysfunction
- Patients with severe megaesophagus may require dilation of the esophogastric junction using a pneumatic balloon
- Temporary relaxation of the esophogastric sphincter to aid the transit of food and liquids may be achieved using sublingual nitrates or injecting botulinum toxin into the esophagus
- Management of megacolon requires adequate intake of fluids and dietary fiber, along with the use of laxatives or enemas
- Patients refractory to conservative management of megacolon may require surgical resection
- Fragmentation may aid removal of fecalomas
Medications indicated with specific doses
Antiparasitic agents
Antiarrhythmic agents- Amiodarone [Injectable]
- Amiodarone [Oral]
Dietary or Activity restrictions
- Patients with colonic abnormalities should be advised to follow a fiber-rich diet along with adequate fluid intake, to avoid the risk of fecal impaction
- Severe acute infection may require bed rest or decrease in normal activities until resolution
[Outline]
Prevention
- The lack of an effective vaccine necessitates greater emphasis on vector control and prevention of transmission from non-vector sources
- Improved habitation, use of residual insecticides, and educational interventions can significantly reduce infestation of triatomine bugs, and subsequently the spread of Chagas disease
- Individuals traveling to endemic regions should be advised to avoid residing in dilapidated housing
- Use of mosquito nets and insect repellents is recommended in endemic areas
- Disease propagation in non-endemic regions may be prevented through screening of travelers returning from endemic areas
- Mandatory screening of blood donors has significantly reduced the incidence transfusion-acquired infection
- Screening of blood-products may be considered, however, there is no FDA-approved assay procedure
- Laboratory personnel handling T. cruzi and infected vectors should be provided adequate protective measures such as gloves and goggles
Prognosis
- The majority of patients with acute disease show spontaneous resolution of symptoms. Acute disease has an extremely low mortality rate
- It is estimated that 30% of patients develop chronic disease consisting of cardiac or GI complications
- The risk of progression to heart disease is the most significant prognostic indicator of Chagas disease
- The strongest predictors of mortality associated with Chagas heart disease include
- New York Heart Association functional class III or IV cardiomegaly
- Impaired left ventricular systolic function
- Non-sustained ventricular tachycardia
- Cardiac causes of mortality include sudden cardiac death, heart failure and stroke
- In infants with Chagas disease, meningoencephalitis and/or myocarditis indicate a poor prognosis
- Immunosuppressed individuals have a higher risk of reactivated infection
Pregnancy/Pediatric affects on condition
- Perinatal transmission of T. cruzi occurs in 5-6% of women with chronic Chagas disease
- The risk of transmission depends on factors such as maternal age, timing of infection, form of disease and obstetric history
- The majority of neonates with congenital infection remain asymptomatic or demonstrate non-specific findings such as prematurity, low birth weight, and low Agpar scores
- Specific findings include positive serology, hepatosplenomegaly, anemia, and thrombocytopenia
- Neonatal mortality rate is low, however, complications such as myocarditis or meningoencephalitis are associated with a high risk of mortality
- Use of benznidazole and nifurtimox is contraindicated during pregnancy and breastfeeding
Synonyms
ICD-9-CM
- 086.0 Chagas' disease with heart involvement
- 086.1 Chagas' disease with other organ involvement
- 086.2 Chagas' disease without mention of organ involvement
ICD-10-CM
- B57.0 Acute Chagas' disease with heart involvement
- B57.1 Acute Chagas' disease without heart involvement
- B57.2 Chagas' disease (chronic) with heart involvement
- B57.3 Chagas' disease (chronic) with digestive system involvement
- B57.4 Chagas' disease (chronic) with nervous system involvement
- B57.5 Chagas' disease (chronic) with other organ involvement
[Outline]
