Chagas disease is caused by the protozoan Trypanosoma cruzi. It is endemic to Latin America and causes two phases of illness - an acute phase with fever and swelling, and a chronic phase that can involve heart or digestive system damage. It is typically transmitted by triatomine bugs but can also be spread through blood transfusions, organ transplants or from mother to child. Treatment involves benznidazole or nifurtimox which are only effective in the early stages of disease.

2. • Chagas disease is an anthropozoonosis caused by the protozoan
Trypanosoma cruzi which is endemic in American continent.
• It is mainly characterised by fever, palpebral edema,
lymphadenopathy, hepatosplenomegaly in its acute form and
cardiomyopathy, arrhythmia, mega viscera, polyneuropathy and
stroke in its chronic form.
• There are mainly two types of trypanosoma infection:
1. Human trypanosomiasis
2. Animal trypanosomiasis
INTRODUCTION

3. 1. HUMAN TRYPANOSOMIASIS :
Human trypanosomiasis are endemic only in 2 continents i.e. America and
Africa. So these are of 2 types ;
a. American trypanosomiasis aka chagas disease caused by T. cruzi
b. African trypanosomiasis aka sleeping sickness caused by T. brucei
• Human trypanosomiasis is not known to exist in india.
2. ANIMAL TRYPANOSOMIASIS :
Animal trypanosomiasis is endemic in india and is caused by either
a. T. evansi in cattle / horses causing a disease called “surra”
b. T. lewisi in rats .
• Only sporadic cases of human infections with animal trypanosomiasis have
been reported from India.
• Eight sporadic cases are reported in India. Three in Maharashtra
in the span of 3 years.

4. LIFE CYCLE
T. cruzi takes two forms in human beings.
Trypomastigote:
Has a flagellum extending along the outer edge of an
undulating membrane,
Does not divide in blood.
Carries the infection throughout the body.
Amastigote:
Which has no flagellum.
Multiplies within various types of cells.

6. MODES OF TRANSMISSION:
 Vectorial spread: Blood sucking triatomine insects ( kissing bugs /
Reduviid bugs ) Triatoma, Panstrongylus, Rhodnius
 Mother to child transmission: 3.9-5.6%
 Blood & blood products: 10-25%
 Solid organ transplantation:
Renal: 0-19%
Liver : 0-29%
Heart: 75-100%
 Oral transmission: consumption of contaminated food & drink.
 Laboratory accidents:

7. PATHOGENESIS:
 In the acute phase of the disease, organ damage is secondary to
. 1. Direct action of the parasite
2. Acute inflammatory response.
 Nests of T .cruzi amastigotes are found in tissues (mainly cardiac,
skeletal, and smooth muscle).
 Intense inflammatory response occur with active antibody
production and activation of the innate immune response (NK cells
and macrophages) by Th1 proinflammatory cytokines such as TNF
α and interferon γ.
 The pathogenesis of chronic chagasic cardiomyopathy is not
completely understood but considered to be autoimmune.
 Although several autoantigens that cross-react with T. cruzi
antigens and autoantibodies have been identified, the role of
autoimmunity in pathogenesis is unknown.
 The balance between persistence of infection and host immune
response is crucial for the establishment and progression of
cardiomyopathy.

8. CLINICAL MANIFESTATION:
 Clinical course has an acute phase and a chronic phase.
ACUTE PHASE:
 Acute infection can occur at any age and is asymptomatic in most
cases.
 Acute phase symptoms include:
Fever
Inflammation at inoculation site- Inoculation chancre
Unilateral palpebral edema- Romana sign
Lymphadenopathy and hepatosplenomegaly

9.  Severe acute disease occurs in less than 1-5% of patients.
 Severe manifestations include
Acute myocarditis
Pericardial effusion
Meningoencephalitis
 Oral transmission through food or drink contaminated with
triatomine faeces seems to cause more severe disease, with
higher mortality than vector-borne disease.
 Acute phase lasts 4 to 8 weeks and usually resolves
spontaneously after which patients remain chronically
infected if untreated.

10. CHRONIC PHASE:
Chronic phase has 2 forms
INDETERMINATE
FORM
CARDIAC & GI
FORM
INDETERMINATE FORM:
 This includes the largest group of patients affected who
never develop symptoms or visceral involvement.
 Good prognosis.
 Characterised by seropositivity for T. cruzi.
 Absence of clinical signs and symptoms of cardiac and
digestive involvement.
 Normal chest radiography and electrocardiography.

11. CHRONIC FORM:
 Roughly 30–40% of chronically infected patients can
develop organ involvement 10–30 years after acute
infection.
 Mainly cardiomyopathy or megaviscera
[megaoesophagus, megacolon, or both].
CHAGAS HEART DISEASE:
 Most frequent and severe type of organ involvement.
 Occurs in 14–45% of chronically infected patients.
 Affects mainly the conduction system and myocardium.

12.  Characterised by:
1. Arrhythmias
2. Progressive dilated cardiomyopathy
with congestive heart failure
3. Apical aneurysms usually of the left ventricle.
4. Emboli due to thrombus formation in the
dilated left ventricle or aneurysm.
 Cause of death in patients with Chagas heart disease:
1. Sudden cardiac death.
2. Refractory heart failure.
3.Thromboembolism.
 Indications of poor prognosis:
1. NYHA class III or IV
2. Cardiomegaly
3. Non-sustained ventricular tachycardia.

13. GASTROINTESTINAL INVOLVEMENT:
 Less common (10-21%).
 Manifestations range from asymptomatic motility disorders to mild
achalasia to severe megaoesophagus.
 Symptoms include:
1.Dysphagia, odynophagia, oesophageal reflux,
2.Weight loss, aspiration, cough, and regurgitation.
 Patients with megaoesophagus may be at increased risk of
oesophageal cancer, and upper GI endoscopy might be indicated,
especially in patients with new or progressive symptoms.
 Megacolon is characterised by persistent constipation and can lead to
faecaloma, volvulus, and bowel ischaemia.
 The sigmoid and rectum are dilated in nearly all cases of megacolon,
whereas dilatation of more proximal colonic segments is rare.

14.  Cardiac and gastrointestinal involvement seldom present
together (5–20% of patients with myocardiopathy)
 Chagas disease is also a major cause of cardioembolic
stroke, which is up to twice as common in Chagas heart
disease as in other forms of cardiomyopathy.
 The incidence of ischaemic stroke has been estimated as
2·7 events per 100 patients per year, and around a third of
patients who experience ischaemic stroke may have
asymptomatic T cruzi infection.
 Neuropathy, in the form of mild sensory polyneuropathy, can
present in up to 10% of patients although may not
necessarily be associated with other visceral involvement.

15. DIAGNOSIS:
PARASITOLOGICAL Dx Dx OF VISCERAL
INVOLVEMENT
In acute &
congenital
disease
In chronic
phase of
disease
Cardiac
Involvement
GI Involvement
Direct
blood
smear
Indirect
PCR
Serology

16.  Diagnosis of acute and congenital disease is made by direct
microscopic visualization of trypomastigotes in blood and,
occasionally, other body fluids such as CSF.
 In congenital infection, diagnosis can also be based on positive
serology results beyond 8 months.
 Parasites can be observed through a simple fresh blood
examination or in Giemsa-stained thin and thick blood smears
(sensitivity 34–85%).
 Indirect parasitological methods include PCR with varying
sensitivities (50%-90%).
 In chronic phase of disease as parasitemia is low & intermittent,
parasitological and PCR-based diagnostic methods are
unreliable.
 Diagnosis of chronic infection, therefore, relies on serological
testing through detection of Ig G antibodies against T cruzi.
PARASITOLOGICAL DIAGNOSIS:

17.  The most common tests are
Indirect fluorescent assay,
Indirect haemagglutination,
ELISA.
 Since no single standard reference test is available, diagnosis should
be based on the presence of at least two serological assays with
different antigens.
 In case of inconclusive results a third assay is then indicated.
 Because of the high sensitivity and specificity of ELISA it is used for
screening,
 PCR may be helpful
1. When serology results are inconclusive
2. For monitoring early detection of treatment failure

18. DIAGNOSIS OF VISCERAL INVOLVEMENT:
CARDIAC
GASTRO INTESTINAL
 ECG
 2D-ECHO
 24 hr holter monitoring
 Ergometry
 Cardiac MRI
 Barium swallow
 Barium enema
 Oesophageal
manometry

20. TREATMENT:
 Treatment with antitrypanosomal drugs is always recommended
for
1. Acute and congenital Chagas disease,
2. Reactivated infections,
3. Chronic disease in children younger than 18 years.
 Only two drugs are licensed:
1. Benznidazole
2. Nifurtimox,
 Both have been the mainstay of parasiticidal treatment for
almost 50 years.
 Their safety and efficacy profile is far from ideal.
 Since the effectiveness of treatment seems to decrease with
time from primary infection, early detection and intervention are
crucial.

21. NIFURTIMOX BENZNIDAZOLE
 Dose:
10-15 mg/kg/day for 60-90 days
 Cure rates:
in the chronic indeterminate
phase range from 86% in children
<14 years to 7–8% in adults.
 Treatment is discontinued due
to adverse effects in
14.5-75.0% of cases.
 Adverse effects:
Anorexia, weight loss
Neurological disorders
Digestive manifestations
5-10 mg/kg/day for 60 days
60–93% in children < 13 years
and 2–40% in adults
9-29% of cases.
Hypersensitivity
Digestive intolerance
General symptoms

22.  Benznidazole is generally preferred over nifurtimox:
1. Better tolerability profile
2. Tissue penetration
3. Efficacy.
Treatment of chagasic cardiomyopathy:
 Medical therapy for heart failure.
 ACEI & beta blocker: target doses can’t be tolerated due to
Low BP
High incidence of bradyarrhythmia.
 Amiodarone: may improve survival in high risk sudden arrhythmia,
 Implantation of pacemaker is recommended for:
Severe bradyarrhythymia
Advanced conduction abnormalities.
Treatment of GI involvement:
 Mild digestive symptoms: no specific management.
 Severe (Megasyndrome): endoscopic & surgical management

23. MEDICAL FOLLOW-UP:
 Typical recommendations include:
1. A clinical interview and physical
. examination at least once a year
2. Annual ECG
3. Echocardiography every 2–3 years
4. Serological testing once year.
5. PCR to monitor treatment failure.