Life cycle, pathogenesis, clinical presentation and management of chagas 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.