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Am Fam Physician. 2021;104(2):277-287

Related editorial: Parasitic Infections: Do Not Neglect Strongyloidiasis

Related letter: Treatment of Chagas Disease in Breastfeeding Dyads

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Chagas disease, cysticercosis, and toxoplasmosis affect millions of people in the United States and are considered neglected parasitic diseases. Few resources are devoted to their surveillance, prevention, and treatment. Chagas disease, transmitted by kissing bugs, primarily affects people who have lived in Mexico, Central America, and South America, and it can cause heart disease and death if not treated. Chagas disease is diagnosed by detecting the parasite in blood or by serology, depending on the phase of disease. Antiparasitic treatment is indicated for most patients with acute disease. Treatment for chronic disease is recommended for people younger than 18 years and generally recommended for adults younger than 50 years. Treatment decisions should be individualized for all other patients. Cysticercosis can manifest in muscles, the eyes, and most critically in the brain (neurocysticercosis). Neurocysticercosis accounts for 2.1% of all emergency department visits for seizures in the United States. Diagnosing neurocysticercosis involves serology and neuroimaging. Treatment includes symptom control and antiparasitic therapy. Toxoplasmosis is estimated to affect 11% of people older than six years in the United States. It can be acquired by ingesting food or water that has been contaminated by cat feces; it can also be acquired by eating undercooked, contaminated meat. Toxoplasma infection is usually asymptomatic; however, people who are immunosuppressed can develop more severe neurologic symptoms. Congenital infection can result in miscarriage or adverse fetal effects. Diagnosis is made with serologic testing, polymerase chain reaction testing, or parasite detection in tissue or fluid specimens. Treatment is recommended for people who are immunosuppressed, pregnant patients with recently acquired infection, and people who are immunocompetent with visceral disease or severe symptoms.

Neglected parasitic infections designated by the Centers for Disease Control and Prevention (CDC) include Chagas disease, cysticercosis, toxoplasmosis, toxocariasis, and trichomoniasis.1 These parasitic infections have been prioritized based on the number of people infected, the potential for severe illness, and availability of treatment regimens. This article reviews three infections that are typically not emphasized in medical training—Chagas disease, cysticercosis, and toxoplasmosis. Information on the others (toxocariasis and trichomoniasis) can be found on the CDC website.1 Despite the ability to cause severe illness, limited resources have been devoted to understanding the impact and burden of neglected parasitic infections. Family physicians should understand the basic principles of clinical presentation, diagnosis, and treatment of these diseases. A summary of key points for each disease is presented in Table 1.2

DiseaseEpidemiology and transmissionClinical manifestationsDiagnosisTreatment
Chagas diseaseMore than 300,000 people in the United States are infected; more common in people who have lived in Mexico and Central or South America; locally acquired infection is rare
Transmission is often vectorborne (kissing bugs), less commonly congenital, or via blood transfusion or organ transplant
Blood donations are screened; blood donors who test positive cannot donate again
Acute infection: usually asymptomatic; when symptoms occur, they typically appear four to eight weeks after infection; and include nonspecific febrile illness and swelling around the bite site
Chronic infection: 20% to 30% of people develop symptoms, including cardiac and gastrointestinal manifestations; increased risk of stroke
Congenital infection: usually asymptomatic; anemia, hepatosplenomegaly, low Apgar scores, low birth weight, thrombocytopenia; rarely, meningoencephalitis, myocarditis
Acute and congenital infections: direct microscopy of peripheral or cord blood to detect parasites; polymerase chain reaction testing also available
Chronic infection: no or few parasites in the blood; multiple serologic tests with varying sensitivity and specificity are available; at least two positive results on different serologic tests required for diagnosis
Infection is lifelong without treatment; people with acute or congenital infection and people who are immunocompromised with reactivated infection should be treated; people with severe renal or hepatic insufficiency should not be treated; patients should not be treated during pregnancy but should be evaluated for treatment after delivery; for chronic disease, treatment is strongly recommended in people younger than 18 years and generally recommended in people younger than 50 years who do not have severe cardiomyopathy; all others should be treated on an individual basis
Treatment options include nifurtimox (Lampit) or benznidazole
CysticercosisMore common in immigrants from Central and South America, but can occur in people from other endemic areas and in people born in the United States
Transmission occurs by ingesting eggs excreted in the feces of a tapeworm carrier; transmission does not occur by eating under-cooked infected pork
Neurocysticercosis: may be asymptomatic; seizures are the most common manifestation; chronic meningitis, cranial nerve abnormalities, headache, and intracranial hypertension or hydrocephalus may also occur
Muscular cysticerci are usually asymptomatic
Neurocysticercosis: computed tomography and magnetic resonance imaging are recommended; confirmatory serologic test recommended; number, location, and viability of cysticerci should be determinedNeurocysticercosis: symptom control is the priority; decision to treat with antiparasitic drugs should be individualized; coadministration of corticosteroids may decrease inflammatory response
People with cysticercosis and close contacts should be screened for tapeworm infection
ToxoplasmosisApproximately 11% of people in the United States are infected; symptomatic infection is more common in people who are immunocompromised and in children with congenital infection
Transmission is most often food-borne, zoonotic from cat feces, or congenital
Most people who are immunocompetent are symptomatic; people who are immunosuppressed may develop encephalitis with confusion, fever, headache, poor coordination, or seizures; patients infected during pregnancy may have a miscarriage or a child born with signs of toxoplasmosis; ocular symptoms may include eye pain, blurred vision, or photophobiaToxoplasma antibody test (specialized testing may be required to determine if the infection is acute or chronic); serologic tests may be unreliable in patients who are immunosuppressed; microscopy to detect parasite in blood, cerebrospinal fluid, or tissue; polymerase chain reaction testing also availableSpiramycin should be used before amniocentesis to assess fetal infection in pregnant patients who acquire the infection in the first or early second trimester; can also be used later in pregnancy if it has been demonstrated that the fetus is not infected
Combination therapy with pyrimethamine (Daraprim), sulfadiazine, and leucovorin should be used in infants with congenital infection, in pregnant patients who acquire infection in the late second or third trimester or who acquire the infection earlier and transmit it to the fetus, in patients who are immunosuppressed, and in patients who are immunocompetent with severe symptoms

Chagas Disease

Chagas disease (i.e., American trypanosomiasis) is caused by the parasite Trypanosoma cruzi. Transmission to humans occurs mainly through contact with triatomine insects (kissing bugs), bloodsucking insects that feed on humans and other animals. Infection occurs when an infected triatomine insect defecates after a blood meal, and the feces containing the parasite are rubbed into a bite wound or mucous membranes (Figure 1).3 Transmission can also occur congenitally or by blood transfusion, organ transplant, consumption of food contaminated with triatomine-infected feces, or laboratory exposure.

Chagas disease is endemic in many parts of Mexico and Central and South America, where an estimated 7 million people are infected.4 More than 300,000 people in the United States are thought to be infected, most of whom acquired the disease in Latin America.4 However, infected triatomines have been found in many parts of the southern United States, and domestic transmission via triatomines has occurred.5

In the United States, it is estimated that up to 300 infants are congenitally infected with T. cruzi each year.4 Screening pregnant patients for Chagas disease is not routinely performed, but targeted testing based on their risk history is recommended (Figure 2). Blood donor screening in the United States was implemented in 2007, making the U.S. blood supply safe from the risk of transfusion-transmitted infection.


The acute phase lasts for weeks or months after the initial infection, and the chronic phase is lifelong in the absence of treatment. In the acute phase, clinical manifestations are often mild or absent; however, patients may have swelling around the bite site. If the inoculation site is the conjunctiva, unilateral palpebral edema may occur. In the chronic phase, most patients are asymptomatic, but 20% to 30% develop clinical manifestations that can be life-threatening.6 Cardiac disease, including conduction abnormalities, dilated cardiomyopathy, apical aneurysm, or heart failure, may occur. The risk of stroke is also increased. Gastrointestinal manifestations include megaesophagus or megacolon.

Most congenitally infected infants are asymptomatic; however, some may have low birth weight, low Apgar scores, or develop anemia, thrombocytopenia, or hepatosplenomegaly. Rarely, myocarditis or meningoencephalitis may occur.


Acute or congenital Chagas disease can be diagnosed by detecting parasites via direct microscopy of anticoagulated peripheral or cord blood. Polymerase chain reaction testing for T. cruzi DNA in blood may be used in addition to microscopy.

In the chronic phase, few or no parasites are present on microscopy; therefore, serologic testing for antibodies to T. cruzi is required for diagnosis. Positive results on at least two different tests are required for diagnosis because no single serologic test has sufficient sensitivity and specificity.

Patients who have lived in Mexico, Central America, or South America are at risk of chronic Chagas disease and should be tested. Because of the risk of congenital transmission and potentially shared exposure history, children born to mothers with Chagas disease should also be tested.4,7 Blood donors in the United States who have positive results on screening for T. cruzi infection cannot donate blood and are advised to consult with their physician for diagnostic workup and confirmation of infection.

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