Protozoan Parasitic infection with Trypanosoma cruzi.
Infection by the protozoan Trypanosoma cruzi causes Chagas disease, characterized by a reduction in the amount of IL2RA (CD25) expressed on the surface of immune cells.
The reduction in the amount of IL2RA expressed on the surface of immune cells leads to chronic immune suppression, becoming increasingly severe over the course of many years and ultimately resulting in death from Chagas’ disease if left untreated.
Trypanosoma cruzi. carried by triatomine, the reduviid bug, a parasite endemic to Latin American countries that survives in poor rural areas with rudimentary housing.
T cruzi is usually transmitted via inoculation of infected feces of blood feeding triatomine insects through the bite site or intact mucosa.
Infected vectors are found throughout continental Latin America and the southern half of the US.
Transmission can occur from mother to infant in utero or peripartum and through blood transfusions, organ transplant, ingestion of food, or beverages contaminated by vector feces, and accidental laboratory exposure.
Most infected persons are in the US are immigrants from Latin America, but rare infections have been reported in Texas, California, Arizona, and other states.
It is a long-term chronic infection by Trypanosoma cruzi.
Transmitted through the feces of infected blood sucking insects to humans in endemic areas and occasionally by nonvectorial mechanisms such as blood transfusion.
T. Cruzi has two distinct forms in the human host.
The protozoa replicates in the bugs gut and are excreted in its feces.
The protozoa infects humans by way of the reduviid bite wound or by direct entry via mucous membranes.
Human host infection can occur via blood transfusion or organ/tissue transplantation from an infected person and by transmission from mother to fetus during pregnancy.
At risk females of reproductive should be screened before they become pregnant because preconception anti-therapy decreases congenital transmission risk by more than 95%.
The acute infection lasts 2 to 3 months and usually has mild non-specific symptoms, such as fever and fatigue.
The acute symptoms resolve when the immune system controls parasite replication, and the patient enters a lifelong chronic phase, in the absence of treatment.
Most patients are asymptomatic, however 20 to 30% develop cardiac or more rarely G.I. consequences.
Cardiomyopathy begins with conduction system deficits, sinus node dysfunction and/or ventricular arrhythmia.
The initial response to Trypanosoma cruzi infection is inflammation, and cellular damage occurring in heart tissue, followed by fibrosis.
Nearly all cases of chronic Chagas’ disease experience thromboembolic syndrome.
Trypanosoma cruzi occurrence contributes to the death of a patient by four means: arrhythmias, stasis secondary to cardiac dilation, mural endocarditis, and cardiac fibrosis.
These thrombi also affect other organs such as the brain, spleen and kidney.
The first manifestation of cardiomyopathy may be sudden death.
Advanced cardiomyopathy may lead to apical aneurysms, mural thrombi and culminate in refractory CHF or stroke.
Conduction abnormalities are also associated with T. cruzi. due to abnormalities is a depopulation of parasympathetic neuronal endings on the heart.
The loss of parasympathetic innervations can lead to sudden death due to a severe cardiac failure that occurs during the acute stage of infection.
An estimated 57,000 Americans have Chagas cardiomyopathy.
5 to 20% of patients with unexplained bradycardia, bundle branch blocks and or congestive heart failure have Chagas disease.
During the acute phase extracellular motile organisms can be observed in examination of fresh blood, or in cases of meningoencephalitis in the CSF.
T. cruzi is detectable in blood by microscopy and polymerase chain reaction tests.
In the chronic phase of disease. The diagnosis is based on IgG serology.
In the chronic phase IgG is the preferred method for diagnosis.
Spread through contact with contaminated feces or urine of triatomineit bugs.
18,000 million people are chronically infected and 200.000 new cases annually in Latin America.
Children or common targets.
The bug bite transmission is not efficient even in the areas where the disease is common, with an estimated incidence of new infections is less than 1% per year.
In endemic areas, repeat exposure leads to a steadily increased prevalence with time.
Vectorborne transmission is limited to North America, Central America, and South America.
The prevalence among persons who come from areas where T. crizi is endemic and who are currently living in the US is estimated at 1.2%.
Infected triatomine bugs are also present in the US.
Other infection routes include transfusion, organ and marrow transplantation and congenital transmission.
Outbreaks related to contaminated food or drink have been reported involving wild vector populations and mammalian reservoir hosts.
In the absence of effective treatment infection is a lifelong
30-40% of currently infected patients are headed for life threatening heart disease.
Most cases are transmitted by triatomine insect (kissing bug) vectors.
Can be acquired, additionally congenitally, through blood transfusion, organ transplantation, consumption of contaminated food or drink, or laboratory accident.
Infection is often subclinical, and most patients are unaware of their infection.
Can manifest as a non-specific febrile illness.
Clinical infection occurs in two phases:
The acute phase, the first one-two weeks after infection, the parasites invade host cells and replicate.
The host cells subsequently rupture and the parasites undergo hematogenous spread, during which they were visible on microscopic examination.
Despite large number of parasites in the blood, infected individual seldom have severe symptoms: typically mild fever and malaise, but may may have hepatosplenomegaly.
8 to 12 weeks after infection develops patients enter into the chronic phase.
In the chronic phase symptoms improve, parasites are cleared from the blood, but may remain in the muscles of the G.I. tract and the myocardium for years, invoking a chronic immune response associated with death from long-term heart disease in 20-30% of patients or, less often, to chronically impaired G.I. motility.
Myenteric plexi destruction has been found to be secondary to Chagas’ disease, with destruction occurs in the esophagus, intestines, and ureters.
This denervation can lead to secondary achalasia of the lower esophageal sphincter, megacolon, and megaureter.
An intermediate form of Chagas disease is when there is no evidence of disease for many years.
Approximately 30% of affected patients develop cardiac disease manifested by dilated cardiomyopathy, arrhythmias or sudden cardiac death or with gastrointestinal disease or both.
Can be transmitted congenitally and 10-40% of newborns may have low birth weight, low Apgar scores, hepatosplenomegaly, respiratory distress, cardiac failure, anasarca, or meningeal encephalitis.
Congenital transmission occurs in 1-10% of children born to infected mothers.
Effects 8-10,000,000 people worldwide.
Estimated 300,000 individuals are infected in the United States, with 30-45 thousand of these patients having Chagas cardiomyopathy.
Only 23 autochthonous Chagas cases reported in the US, 16 of which found after screening 30 million units of blood (Cantey PT et al).
There are an estimated 300,000 immigrant in the US unknowingly infected with Chagas parasite, with an estimated 30,000-45,000 cases of cardiomyopathy annually.
There are at least 8 species of kissing bugs in the US that carry the Chagas parasite, and they are distributed in the lower 2/3 of the country.
The parasite is found in 24 mammals in the US.
The parasite typically in habits nooks and crannies in walls and roofs of poorly built housing in rural areas and in slums surrounding cities throughout Latin America.
Housing with dirt floors and tile roofs have higher rates of infestation.
Vector control is effective with major reductions in the disease.
Central America has a reservoir with an estimated 2 million infected individuals and 26 million more at risk, with approx 11 percent of infected individuals accounting for the whole continent.
Few cases in the US because kissing bug species display late defecation following a blood meal, and the parasite is transmitted in the feces suggesting inefficient vectorization.
Wide variation in clinical course and prognosis.
Main cause of death is cardiac.
Long term risk of death among patients with chronic disease predicted by the presence of NYHA class III or IV, cardiomegaly on chest x-ray, segmental or global wall motion echocardiography abnormalities, the presence of non sustained ventricular tachycardia, low QRS voltage and male gender creating low, medium and high risk scores based on combinations of the preceding.
Early EKG repolarization abnormalities such as ST segment depression and T-wave inversions are common in Chagas disease.
Common EKG abnormalities include ventricular tachycardia, right bundle branch block, anterior fascicular block, complete heart block, PVCs, and conduction abnormalities.
Arrhythmias in Chagas disease with cardiomyopathy are typically triggered by exercise.
Chagas myocardial damage may lead to ventricular apical aneurysms, heart failure and the predisposition to mural thrombus and subsequent stroke.
Most common cause of death is refractory heart failure followed by unstable electrical arrhythmias and fatal cardioemboliization.
Early detection and treatment are effective.
Untreated, the infection is lifelong.
Majority of patients with chronic infection are asymptomatic, but 20-30% develop disease manifestations and most commonly cardiomyopathy.
Apical aneurysms are suggestive of Chagas cardiomyopathy.
Migration from endemic areas to the US has led to an estimated 300,000 persons suffering with chronic Chagas disease.
Antitrypanosomal drugs Benznidazole and nifurtimox are used to treat Chagas disease.
Benznidazole is considered first line therapy as it is associated with fewer adverse effects and has a more robust evidence of response than nifurtimox.