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The Gorgas Courses in Clinical Tropical Medicine are given at the Tropical Medicine Institute at Cayetano Heredia University in Lima, Peru.  Each August we run one of our 2-week refresher courses for those with previous training in tropical medicine; currently running is the Gorgas Expert Course.   For the past 6 years, we have been pleased to share interesting cases seen by the participants during the weeks of the year that our courses are in session.  Each case includes a brief history and digital images pertinent to the case.  A link to the actual diagnosis and a brief discussion follow.

The patient was seen as a consultation in the Outpatient Department of the 36-bed tropical disease unit of the Cayetano Heredia National Hospital.   The patient is being cared for by Drs. Eddie Doroteo and Francisco Campos from Hospital San Bartolomé whom we thank for referring the patient.  We thank Sr. Augusto Marimon for laboratory assistance in making the diagnosis.

History: 6 year old female with 20 days of fever, fatigue, irritability, loss of appetite, sore throat and mild cough.  No pain, gastrointestinal problems, or musculoskeletal symptoms.  No rash.  She was seen in several hospitals and medical settings and treated at different times with co-trimoxazole and gentamicin for a presumed urinary tract infection (pysuria with no culture performed) without effect one week earlier.  Vaccines including yellow fever and hepatitis B are up to date.

Epidemiology: Lifelong resident of the Amazon basin.   No ill contacts or known TB exposure.  Lives in small tourist hotel run by the family with modern construction and amenities.  One visit to the Andean highlands for a few days in the past year.

Physical Examination: Heart rate 112, respiratory rate 36, T° 38.8, blood pressure 100/60.  Alert and cooperative.  Non toxic.  No pallor or icterus.  No skin lesions.  Chest was clear, cardiac examination without gallops, rubs or murmurs.  Abdominal examination: not distended, no tenderness, liver at 4 cm below costal border [Image A].  No spleen palpable but dullness over Traube’s space.  No obvious ascites.

Laboratory Examination: Hematocrit 37%, white blood cell count 15,100 with 38 neutrophils, 3 segs, 3 monocytes, and 56 lymphocytes.  Liver function: INR 1.7. ALT 183, AST 100, bilirubin 0.6.  Salmonella and brucella agglutination negative.  Stool exam negative.  Urine positive for urobilinogen, otherwise normal.  Chest x-ray is shown [Image B].  EKG showed sinus tachycardia with inverted T-waves in leads V1-V4.  Ultrasound showed hepatosplenomegaly without ascites.  A diagnostic test was performed.

Discussion: A peripheral blood film demonstrated large numbers of extracellular trypomastigotes of T. cruzi [Image C].  These forms are easily missed by examiners in non-endemic areas not familiar with Chagas’ disease.

T. cruzi is a single-celled protozoan found in two forms in infected humans.  The infective trypomastigotes are found in the acute phase of disease circulating in the bloodstream.  After they infect muscle, nerve and other cells, they transform into small 3 micron intracellular amastigotes as the infection enters the chronic phase.  Amastigotes replicate slowly by binary fission and are released after host cell rupture to infect other host cells.  Initial human infection occurs when the vector, large triatomine bugs (5-45 mm in length), take a blood meal at the end of which they defecate on the victim.  The victim then self-inoculates with trypomastigotes present in the feces by rubbing on the irritated spot and the parasites enter by any small break in skin integrity or often through intact mucosal tissues such as the conjunctivae.

In the acute stage of infection, such as in our case, the clinical manifestations can vary widely.   Most infections are asymptomatic, up to 20% have a mild undifferentiated febrile syndrome, and less than 5% have a severe or fatal illness that is usually associated with myocarditis, heart failure or meningoencephalitis.   The incubation period is 1-2 weeks, hepatosplenomegaly is common and acute disease lasts 1-3 months.  An inoculation chancre or chagoma is seen in about half of cases and when the entry is via the conjunctiva, unilateral bipalpebral orbital edema (Romana’s sign) is seen.  Non-specific EKG changes are common, with evidence of myocarditis is more severe cases.  The severe conduction abnormalities seen in chronic disease are uncommon in acute disease.

Patients in the chronic phase of disease, have progressive infection of myocardial and automonic nervous tissue and present with cardiomyopathy, cardiac conduction abnormalities, and gastrointestinal disease including megaesophagus and mega-colon.  The alarmingly poor survival curves in individuals who manifest clinical cardiac cardiac disease have now been clearly elucidated [see article published this week in NEJM].  Unlike the acute phase where parasites are present in circulating blood, diagnosis of chronic cases can be difficult and usually depends on serology, or, optimally where available, PCR of blood.

Human Chagas’ disease is found in all countries of the Americas from the southern USA to Argentina and Chile.  The majority of the 10 million infected individuals are found in Brazil, though Bolivia has the highest seroprevalence rates.  There are more than a hundred species of triatomine bugs in the Americas but most human disease is due to Triatoma infestans, Rhodnius prolixus, and Panstrongylus species.  The vectors generally live in thatched roofs and cracks in the walls of poorly constructed homes in impoverished rural areas.  More than 100 mammal species can act as reservoirs including dogs, cats and guinea pigs.

In Peru, limited foci of Chagas’ disease have been described with highest risk in Southern Peru near Arequipa.  Posuzo, where this child lives, is not a previously known endemic area.  Extensive search of her house by an entomology team failed to find any triatomine vectors, but several uninfected Panstrongylus geniculatus [Image D] were found in palm trees adjacent to the house and are the presumed local vector.

While the benefit of treating chronic cases is controversial with existing drugs, consensus is that specific treatment is beneficial in acute cases.  Nevertheless complete parasitologic cure likely occurs in only about 50% of acute cases.  The patient was begun on a 60-day course of benznidazole, which she is tolerating well.  One month after initiation of therapy she is markedly improved but still with some low grade fever.  Repeat echocardiography shows cardiac function and size within normal limits.