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Trypanosoma cruziComments

Trypanosoma cruzi

Trypanosoma cruzi (aka Schizotrypanum cruzi) is a protozoan parasite and the causative agent of Chagas Disease, aka American trypanosomiasis.

This is in contradistinction to sleeping sickness, which is known as African trypanosomiasis due to its distribution only in Africa. Chagas Disease is prevalent in South and Central America, having infected 15-20 million people and with over 100 million people at risk. Up to 60% of the population is serologically positive for Trypanosoma cruzi in some endemic areas. Once considered an exotic rarity, improved diagnostic methods have revealed Chagas Disease as one of the most widespread Latin America infectious diseases. Over 20% of patients had Chagas Disease in one hospital in Goiania.

Chronic Chagas Disease causes most cases of sudden death in young adults of Latin America due to its weakening of heart muscle.

Chagas Disease is mainly a disease of third world countries where reduviids infest substandard houses with dirt floors, mud walls and thatched roofs.

Chagas Disease is combatted by spraying housing with insecticide and by replacing adobe with modern materials. Hexochlorocyclohexane (BHC) is an ideal insecticide due to its low cost, low non-insect toxicity and high activity in mud walls (which lead to rapid attenuation of most other insecticides). Applications vary in frequency from monthly to twice annually.

Another prevention method is the replacement of adobe with modern materials impervious to reduviid infestation. These two techniques form the core of the Southern CONE Initiative.

Vector

Reduviids (aka kissing bugs) are the Trypanosoma cruzi vector. Several genera of Reduviidae transmit T. cruzi.

VectorOverview
Triatoma infestansFrequently invades homes (mud and stick huts); domestic transmission cycle.
Rhodnius prolixusResides in rural settings or forests; silvatic transmission cycle.
Panstrongylus megistusSame as Rhodnius prolixus
TransmissionReduviids transfer Trypanosoma cruzi when they defecate into a wound while taking a blood meal. Oftentimes the mammal inadvertently rubs the feces into the bite itself due to itch. T. cruzi is thus a dung-type or stercorarian trypanosome. Transmission via blood transfusions have made Chagas Disease not just a rural disease but an urban disease as well. Between 1960 and 1989, infection of blood in South American cities' banks ranged from 1.7% in Sao Paulo, Brazil to 53.0% in Santa Cruz, Bolivia, a percentage far higher than that of hepatitis or HIV infection. Transmission by blood transfusion has spread to Los Angeles due to immigration from Central America. In Los Angeles, 2% of the blood donors in a 1993 study were seropositive. Five cases of Chagas Disease in the US in 1990-1993 came from blood transfusion or organ transplants.

Life Cycle

The protozoan parasite Trypanosoma cruzi is the agent of Chagas Disease. It has an insect cycle and a mammalian cycle. In the mammalian host Trypanosoma cruzi survives inside a host cell (intracellular amastigote) then bursts out (extracellular trypamastigote) then is uptaken into a reduviid consuming a blood meal.

Epimastigote
Metacyclic Trypomastigote
TransmissionAn infected triatomid defecates onto a bite wound or mucosal surface of the vertebrate host. When the host scratches the bite, metacyclic trypomastigotes in the triatomid feces are pushed into the wound.
AttachmentMetacyclic trypomastigotes bind macrophages via receptor-mediated attachment
Lysosome VacuoleWithin the macrophage, the trypomastigote recruits lysosomes. The lysosomes fuse together and encapsulate the trypomastigote in a lysosome-derived vacuole.
Vacuole BurstsThe trypomastigote secrets TcTOX, an antigen similar to the lytic complex C9 that lyses the vacuole. The trypomastigotes enter the cytoplasm.
DifferentiationThe metacyclic trypomastigote differentiates into an amastigote and divides.
Amastigote
ReplicationThe amastigotes go through nine cycles of intracellular replication in 4-5 days.
DifferentiationDifferentiate into trypomastigotes.
Trypomastigotes
RuptureThe host cell ruptures and the parasites are released into the bloodstream, where they are disseminated throughout the body.

Trypanosomiasis

AcuteSymptoms include: RomaƱa's Sign; fever; hepatosplenomegaly; and trypomastigotes in blood. The acute phase lasts 2-8 weeks and has 10% mortality.
IndeterminateNo parasites are evident in blood. Amastigotes nest in muscle tissue, particularly of the heart. A Chagasic Heart has a myriad of amastigote clusters. Anti-Trypanosoma cruzi antibodies are present.
ChronicChronic Chagas Disease symptoms include: nerve degeneration; megaesophagus (25%); megacolon (30%); and cardiomyopathy (80%) including arrhythmia, blocks, cardiomegaly and apical aneurism. Arrhythmia due to Chagas Disease is characterized by a unique and diagnostically useful pattern.

Detection

TechniqueDirect?Overview
XenodiagnosisDirect
PCRDirect
MicroscopyDirectUnfortunately the parasite is not abundant in the blood during indeterminate and chronic infections, leading to diagnosis via microscopy in only 1% of these cases. Also morphological similarities between Trypanosoma rangeli and T. cruzi contribute to misdiagnosis.
IFAIndirect

History

Vinchucas

As early as the Colonial Period, Portugese and Spanish missionaries in Latin America described attacks by vinchucas, biting blood-sucking bugs.

Instead of ordinary bedbugs ... these are bugs bigger and more pernicious to the inhabitants ... they are as big as the tip of a little finger, long brownish and in the shape of beetles. They live in the ceiling of the houses and get out at night guided by the smell of peopleasleep, and getting down on the beds, bite cruelly, making a big wheal and sucking up to a half a thimble full of blood. While they suck blood they do it with such care and sweetness that it cannot be felt; but when they withdraw full they leave an unbearable pain and itching.
Kissing BugsCarlos Chagas was sent by Oswaldo Cruz on an antimalarial campaign in Minas Gerais preceding the construction of a rail line there. After a year in Minas Gerais, Chagas was informed by railroad engineer Cantarino Mota of blood-sucking bugs in local huts called barbeiros (kissing bugs) due to their tendency to bite faces of sleeping people. Curious if these bugs transmitted human or animal disease, Chagas studied Panstrongylus megistus, a blood-sucker of the reduviid subfamily triatominae. Chagas found in its hindgut contents numerous flagellates resembling stages of a trypanosome Chagas had described from a marmoset. Chagas sent infected triatomine bugs to Cruz' medical institute in Rio de Janeiro, where they were allowed to bite monkeys. After 30 days trypanosomes were found in the monkeys' peripheral blood. Other animals (rabbits, pigs, dogs and other monkeys) were subsequently found susceptible to infection.
Human BloodChagas was now convinced that Kissing Bugs were also the vector of a human disease. In 1909, two or three weeks after finding Trypanosoma cruzi in triatomines and a cat, Chagas was called to treat a seriously ill 2 year old named Bernice. She suffered from fever, hepatosplenomegaly and lymphadenopathy; her blood teemed with trypanosomes similar to those Chagas had found in the marmoset. He wrote that,
Examination between cover glass and slide revealed the existence of flagellates in good number and fixing and staining of blood films made it possible to characterize the parasite's morphology and to identify it with Schizotrypanum cruzi.
CorrelationBy 1911, human disease had been correlated to reduviidae. In that year, Chagas identified dividing Trypanosoma cruzi in heart muscle. In 1912, Chagas found that the armadillo was a reservoir host. The parasite was named after Carlos Chagas' mentor and employer Oswaldo Cruz. At 29 years of age, Carlos Chagas had described the agent, vectors and animal and human symptoms and existence of a new disease. Unfortunately, Chagas had enemies including Charles Donovan and German microbiologist Krause. Krause denounced Chagas' findings and his work was forgotten for decades.