Chagas disease – causes, symptoms, diagnosis, treatment, pathology

Chagas Disease, also called American trypanosomiasis,
is a parasitic disease common in Central and South America, caused by a protozoan called
Trypanosoma cruzi or T. cruzi for short. T. cruzi is transmitted through the feces
of the insect triatominae. Triatominae is a type of reduviid bug also
called the kissing bug because it typically bites people on the face as they sleep at
night – one heck of a good night kiss, huh? The disease gets its name from Carlos Chagas,
the physician who first described it. The life cycle of T. cruzi starts with the
epimastigote T. cruzi which sits in the lumen of the Reduviid bug’s midgut. –Mastigote refers to the whip-like structure
called a flagellum which protrudes from the center of the T. cruzi and helps it move around. While in the midgut, the epimastigote multiplies
through binary fission. Over time, the epimastigote transforms into
a trypomastigote and at that point it loses its ability to divide, but the trade-off is
that it gains the ability to invade human cells. In fact “trypo” means to bore or punch
into. Reduviid bugs feed off the blood of humans,
and they prefer biting a person’s face, which is why they’re also called kissing
bugs. But unlike a normal kiss, the reduviid bug
then defecates at the bite site, and if the reduviid bug is infected with T. cruzi, the
feces can contain trypomastigotes. These trypomastigotes can then infect human
skin cells at the bite location; or at mucous membranes, particularly the conjunctiva of
the eyes. That can happen if a person unknowingly transfers
the trypomastigotes by rubbing the bite site on their face and then touching their eyes. Once the trypomastigote invades a human cell,
it transforms into an amastigote meaning that it loses its flagellum. The amastigotes multiply intracellularly,
again through binary fission, and then transform into blood trypomastigotes which can move
through the blood and lymph to other tissues. The blood trypomastigotes then invade more
cells, and then again turn into amastigotes to multiply intracellularly again – and that’s
how the cycle goes. Now, a person infected by a T. cruzi infected
reduviid bug, can then get bitten by a brand new reduviid bug. In that case, that reduviid bug might get
infected by the trypomastigotes, and those trypomastigotes would make their way into
the reduviid bug’s midgut and then differentiate into epimastigotes – completing the life cycle. Transmission from the reduviid bug to a person
can also happen through infected organ and blood donations, which is why blood screening
is super important, and it can also spread from mother to child during a pregnancy. Now when a person is infected with Chagas
disease, there’s initially an incubation period of up to two weeks. During that incubation period, T. cruzi trypomastigotes
invade host cells, amastigotes multiply, and blood trypomastigote levels begin to increase
in the blood. Usually there’s local inflammation as immune
cells move towards the area of tissue damage. When this happens at the bite site it’s
called a chagoma, and if it happens around the eye, it can cause eyelid swelling which
is called a Romaña’s sign. Further inflammation can also lead to meningoencephalitis,
which is inflammation of the membranes covering the brain and brain tissue, and hepatosplenomegaly,
which is when the liver and spleen become enlarged. Trypomastigotes have a tendency to target
certain tissues and cells – like smooth muscle, cardiac muscle, and skeletal muscle, as well
as neurons. When those cells are damaged it can lead to
problems like a pericardial effusion where fluid collects around the heart which disrupts
its function, or issues with the electrical signals in the heart leading to heart block. Generalized tissue damage can also lead to
symptoms like fevers and fatigue. The acute phase resolves when T. cruzi trypomastigotes
are cleared from the blood, and over time, antibodies against T. cruzi gradually decrease,
indicating that the infection has been cleared. However, in some individuals, that doesn’t
happen, and they go on to the chronic phase of the infection. In the chronic phase amastigotes linger in
infected cells, and there are elevated levels of T. cruzi antibodies even though trypomastigotes
aren’t usually in the blood. The chronic phase can be asymptomatic, but
some individuals develop progressive symptoms from nerve and muscle damage. The most notable symptom is cardiomyopathy,
where the heart gets really large, which in turn can cause arrhythmias like ventricular
fibrillation and heart failure. There can also be nerve damage; and gastrointestinal
tract symptoms, like enlargement of the esophagus and colon – called megaesophagus and megacolon. The most definitive diagnosis for the acute
phase is made by microscopic detection of blood trypomastigotes in a blood smear or
buffy coat preparation. Polymerase chain reaction to detect T. cruzi
DNA is also possible for certain sub-species, even at very low levels in the blood. But there’s no “gold-standard” for diagnosing
the chronic phase of the infection. Some helpful tools are serology which identifies
antibodies or molecular tests that look for the presence of T. cruzi antibodies or antigens. There’s also xenodiagnosis which is when
a reduviid bug’s midgut is tested for T. cruzi. Finally, imaging like a chest X-ray to look
at the size of the heart or a barium swallow study to look for swelling of the colon can
be helpful. Finally, in the advanced stages, an electrocardiogram
can be done to identify arrhythmias. Treatment depends on the phase of the diseases. The most effective way to resolve the acute
phase beginning anti-parasitic medication, like benznidazole or nifurtimox, early after
infection and continuing for 2 to 4 months. The chronic phase is mostly about managing
the symptoms of cardiomyopathy, like with pacemakers or anticoagulation medications,
and treated cases of reactivation with anti-parasitic medication. A heart transplant may become necessary in
advanced stages. Alright, as a quick recap: Chagas disease
is caused by an infectious parasite, Trypanosoma cruzi that is most commonly transmitted through
the feces of a reduviid bug after a bite. In the acute phase, symptoms include inflammation
and fever; and in the chronic phase there’s gastrointestinal disease and cardiomyopathy.