General Characteristics and Epidemiology

Basic features of Trypanosoma cruzi

• Parasitic protozoan
• Taxonomy:
  • Family: Trypanosomatidae
  • Genus: Trypanosoma
• General characteristics:
  • Thin, irregularly shaped
  • Single, polar flagellum
  • Undulating membrane
• Morphologic forms:
  • Epimastigote (extracellular, noninfectious form)
  • Trypomastigote (infectious form)
  • Amastigote (intracellular form that replicates)

Associated disease

American trypanosomiasis is called Chagas disease.

Epidemiology

• Geographic distribution:
  • South America
  • Central America
• Prevalence: Approximately 8 million people are infected.
  • Previously, more prevalent in rural communities
  • Infections are becoming more widespread because of migration.
• Morbidity is higher in children.

Pathogenesis

Reservoir

• Humans
• Domesticated and wild mammals

Transmission

• Primarily vector-borne: triatomine bugs (reduviid bug or “kissing bug”)
• Less common:
  • Blood transfusion
  • Organ transplantation Organ Transplantation Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Organ Transplantation
  • Ingestion of contaminated food or drink
  • Vertical
  • Laboratory exposure

Host risk factors

• Living in an endemic region
• Poor housing conditions
• Prolonged exposure to vectors

Life cycle and pathophysiology

• Reduviid bug feeds on an infected human or mammal host → bug becomes infected with trypomastigotes
• Transform into epimastigotes in the midgut → replicate 
• Differentiate into trypomastigotes in the hindgut
• During a blood meal on a human host, bug defecates
• Trypomastigote entry into the host occurs through contact of infected feces with:
  • Bug bite wound
  • Conjunctiva
  • Mucous membranes
• Invasion of cells at the site of inoculation → become intracellular amastigotes → asexual replication (binary fission)
• Differentiation into trypomastigotes → disseminate through the bloodstream to other organs
• Immune reaction → tissue damage
• Chronic dissemination of T. cruzi is associated with:
  • Fibrosis of cardiac tissue → cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Overview of Cardiomyopathies
  • Fibrosis involving cardiac conduction pathways → arrhythmias
  • Invasion of nerve plexuses (often GI tract) → megaesophagus and megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon

Clinical Presentation

Acute infection

The incubation period is approximately 1–2 weeks, and the infection lasts 8–12 weeks.

• Many patients are asymptomatic.
• Inflammation and pruritus may occur at the site of inoculation
  • Chagoma: 
    • Subcutaneous inflammatory nodule
    • Typically on the face or extremities
  • Romaña’s sign: 
    • Unilateral swelling of the eyelid secondary to chagoma
    • Occurs when the conjunctiva is the site of inoculation
• Nonspecific signs and symptoms:
  • Fever
  • Malaise
  • Anorexia
  • Lymphadenopathy
• Severe disease (↑ risk of mortality):
  • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
  • Pericardial effusion Pericardial effusion Pericardial effusion is the accumulation of excess fluid in the pericardial space around the heart. The pericardium does not easily expand; thus, rapid fluid accumulation leads to increased pressure around the heart. The increase in pressure restricts cardiac filling, resulting in decreased cardiac output and cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
  • Meningoencephalitis

Chronic infection

A minority of patients develop chronic infection, which presents 10–20 years after the initial inoculation period. 

• Chronic Chagas cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Overview of Cardiomyopathies (primary cause of mortality)
  • Enlargement of all chambers → biventricular heart failure
  • Apical aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Extremity and Visceral Aneurysms → thromboembolism
  • Conduction abnormalities
    • Left anterior fascicular block
    • Right bundle branch block
    • Atrioventricular block Atrioventricular block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular Block
    • Ventricular arrhythmias
• Megaesophagus 
  • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
  • Regurgitation
  • Recurrent aspiration → aspiration pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
• Megacolon
  • Obstipation
  • Bloating
  • Volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus → bowel ischemia
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries

Congenital disease

Congenital disease occurs in a minority of infants born to infected mothers.

• Low birth weight
• Fever
• Hepatosplenomegaly
• Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview

Differential Diagnosis

• African trypanosomiasis African trypanosomiasis African trypanosomiasis, or African sleeping sickness, is a parasitic infection caused by the protozoa Trypanosoma brucei. Initial infections present with localized inflammation (chancre), cervical lymphadenopathy, intermittent fevers, and other nonspecific findings. If untreated, CNS involvement occurs, which is characterized by sleep disturbances, behavioral changes, coma, and death. Trypanosoma brucei/African trypanosomiasis: infection caused by Trypanosoma brucei Trypanosoma brucei African trypanosomiasis, or African sleeping sickness, is a parasitic infection caused by the protozoa Trypanosoma brucei. There are 2 notable subtypes, T. brucei gambiense and T. brucei rhodesiense. Transmission is primarily vector borne through the tsetse fly. Trypanosoma brucei/African trypanosomiasis and transmitted by the tsetse fly. Signs and symptoms include a trypanosomal chancre, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, facial swelling, and erythematous rash. CNS involvement is associated with “sleeping sickness” syndrome. The diagnosis is confirmed with identification of organisms in a fluid sample (e.g., blood, CSF). Management depends on the stage of disease and can include pentamidine, suramin, eflornithine, or melarsoprol.
• Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia: primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia with solids and liquids along with regurgitation. Diagnosis is established by high-resolution manometry. Management options include pneumatic balloon dilation, surgical myotomy, and botulinum toxin injection. 
• Large bowel obstruction Large Bowel Obstruction Large bowel obstruction is an interruption in the normal flow of intestinal contents through the colon and rectum. This obstruction may be mechanical (due to the actual physical occlusion of the lumen) or functional (due to a loss of normal peristalsis, also known as pseudo-obstruction). Malignancy and volvulus are the most common causes of mechanical large bowel obstruction. Large Bowel Obstruction: interruption in the normal flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of intestinal contents through the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix and rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal. This obstruction may be mechanical (due to actual physical occlusion of the lumen) or functional (due to a loss of normal peristalsis, also known as pseudo-obstruction). Typical symptoms include intermittent lower abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, abdominal distention, and obstipation. Diagnosis is established with imaging. Mechanical large bowel obstruction requires surgery in most cases.
• Toxic megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon: complication of severe colitis, frequently associated with Clostridium difficile, inflammatory bowel disease, or ischemic colitis. Patients with toxic megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon present with severe abdominal distention and pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain with associated systemic toxicity ( fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachycardia, and altered mental status). The diagnosis is established with the history, physical findings, and imaging. Treatment depends on the cause, but can include supportive care and surgery.
• Leishmaniasis Leishmaniasis Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Leishmania/Leishmaniasis: infection caused by Leishmania Leishmania Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The disease is endemic to Asia, the Middle East, Africa, the Mediterranean, and South and Central America. Clinical presentation varies, dependent on the pathogenicity of the species and the host's immune response. Leishmania/Leishmaniasis species, which are obligate intracellular parasites transmitted by the sandfly. The mildest form is cutaneous leishmaniasis, characterized by painless skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin ulcers. The mucocutaneous type involves more tissue destruction and deformities. Visceral leishmaniasis (VL) presents with hepatosplenomegaly, anemia, thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Management is based on clinical severity. Systemic treatment (amphotericin B) is needed for VL.
• Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria: mosquito-borne infectious disease caused by Plasmodium species. Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria often presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, rigors, diaphoresis, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia, hepatosplenomegaly, and renal impairment. A blood smear shows a single pleomorphic ring. Rapid testing for Plasmodium antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs Antimalarial drugs Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person's bloodstream. Sporozoites then infect the hepatocytes and differentiate into schizonts, which subsequently rupture, and merozoites invade red blood cells. Antimalarial Drugs.