Chagas Disease (American Trypanosomiasis)

CHAGAS DISEASE - AMERICAN TRYPANOSOMIASIS

GROUP 88

1. ВОНГ Ю СИНГ2. ЧОУ МИЕН ЧИН3. ТАН ЙИ ДЖИНГ4. ЖАЯТЕСВАРАН ВИЖАЯКУМАР5. СВИИ ДЖИАН ЛИК6. КО МИНГ ЯО

• Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite T. cruzi.

• The organism T. cruzi and infection in humans were first described in 1909 by the Brazilian physician Carlos R. J. Chagas.

BACKGROUND & DISCOVERY

WHY DIDN'T HE WIN THE NOBLE PRIZE?It has been accepted that the reason why the prize was not awarded to this brilliant scientist may have been the strong opposition that he faced in Brazil, from some physicians and researchers of that time. They went as far as questioning the existence of Chagas disease, thereby possibly influencing the decision of the Nobel Committee not to award the prize to him. Analysis of the database of the Nobel prize archives, with the revelation of the names of nominators, nominees and prize winners spanning the years 1901-1951, brought information not only about what was considered to be a scientific achievement at that time, but also about who the important scientists were and what the relationships between them were. The connections of the members of the Nobel Committee with the international scientific community, almost exclusively centered in European and North American scientists, also influenced their choices.

STATISTICS ACCORDING TO

WHO(2010)

Table 1. Ranking of countries by the number of people living with Chagas disease and Chagas cardiomyopathy.

STATISTICS ACCORDING TO WHO(2010)

Table 2. Ranking of countries by the prevalence of Chagas disease

STATISTIC ACCORDING TO CDC (2013)

Chagas disease in the United States

The impact of Chagas disease, once thought to be limited to Latin America (where an estimated 8 million people are infected), has moved to the United States, through immigration of persons from Chagas–endemic areas of Mexico, Central America, and South America. The estimated number of infected persons living in the United States is 300,000 or more, based on estimated disease rates by country of origin.

Blood screening for Chagas disease

National screening of the blood supply was instituted in early 2007. More than 500 donors with T. cruzi infection were identified within the first 18 months of testing.

GEOGRAPHIC DISTRIBUTION• T. Cruzi found in the Americas

from the U.S. to Chile and central Argentina.

• In the U.S., this parasite is

thought to be endemic in approximately the southern half of the country, as well as in California. An estimated 8 to 11 million people are infected worldwide.

Transmission

Consumption of food contaminated with T. Cruzi through, for example, contact with infected triatomine bug faeces or urine

Blood transfusion from infected donors Passage from an infected mother to her

newborn during pregnancy or childbirth Organ transplants using organs from infected

donors Laboratory accidents.

VECTOREleven different species of triatomine bugs have been found in the southern United States:Paratriatoma hirsutaTriatoma gerstaeckeriTriatoma incrassataTriatoma indictivaTriatoma lecticulariaTriatoma neotomaeTriatoma protractaTriatoma recurvaTriatoma rubidaTriatoma rubrofasciataTriatoma sanguisuga

CARRIERS (OR RESERVOIRS)

The Chagas Cycle

TRANSMISSIONACUTE PHASE CHRONIC PHASEIndeterminate Phase of

Chronic Chagas Disease

2 Months

Period of 20-30 years without any signs or

symptoms

25-30% of those who are chronically infected develop heart complications

10-30% of those who are chronically infected develop cardiac and gastrointestinal lesions that can lead to serious morbidity or death

60% of those infected by the T. cruzi parasite are asymptomatictheir entire lives

Vector

Transfusions/Transplants

Congenital

Oral

10,000 deaths from Chagas each year

This phase is typically

characterized by subpatent

parasitemia and easily detectable antibodies to T.

cruziSpontaneous Resolution

This phase is typically

characterized by mild febrile

disease

Pathophysiology of Chagas Disease

Acute Infection

Chronic Infection

DisseminationIs characterized by local histologic changes that include the presence of

parasites within leukocytes and cells of subcutaneous tissues and the development

Interstitial edema

Reactive hyperplasia of adjacent

lymph nodes

Lymphocytic

Infiltration

Lymphatics

Bloodstream

Highly Parasitized

See Next Slide

Chronic Infection 1) Chronic Infection of The HeartThe heart is the most commonly affected

organ. In what way? You might ask? It can lead to:

Thinning of the ventricular wallsBiventricular enlargementApical aneurysmMural thrombi

Widespread lymphatic infiltration, diffuse interstitial fibrosis & atrophy of myocardial cells are often apparent, but parasites are difficult to find in myocardial tissue by conventional histological methods

Conduction system abnormalities are also present. They usually affect the:

Right branch &/Left Anterior branch of the bundle of His

2) Chronic Infection of GIT (Megadisease) Esophagus & colon may exhibit varying

degrees of dilation

On microscopic examination: focal inflammation lesions with

lymphocytic infiltration are present

the number of neurons in the myenteric plexus might be markedly reduced as well

Chagas Disease (American Trypanosomiasis)The trypomastigote is the infective flagellated form of the parasite found in the blood of the mammalian hosts (blood trypomastigote) and in the hindgut of vectors (metacyclic trypomastigote).

Trypanosoma cruzi in the heart muscle of a child who died of acute Chagas’ myocarditis.

An infected myocyte containing several dozen T. cruzi amastigotes is in the center of the field (hematoxylin and eosin, 900×).

The characteristic pseudocysts present in sections of infected tissues are intracellular aggregates of multiplying parasites.

The Takeaway

The pathogenesis of cardiac and gastrointestinal lesions of chronic Chagas disease has been a focus of debate for decades. During the last 20 years, however, convincing evidence has shown that the low levels of parasites in chronically affected tissue, detectable with molecular

methods, provokes a chronic inflammatory response - rather than an autoimmune response- as the basis for

the pathology in patients with Chronic T. cruzi infection.

Associated Signs & Symptoms in the Acute Stage of Infection

The first signs of acute Chagas’ disease develop at least 1 week after invasion by the parasites.

When the organisms enter through a break in the skin, an indurated area of erythema and swelling accompanied by local lymphadenopathy, may appear. This is known as the Chagoma.


Romana’s SignIs a classic finding in acute

Chagas’s disease, which consist of unilateral painless edema of the palpebrae and periocular tissue

It can result when the conjunctiva is the portal of entry.


These initial local signs may be followed by:

MalaiseFeverAnorexiaEdema of the face and lower

extremitiesGeneralized lymphadenopathy and

hepatosplenomegaly may develop. Severe myocarditis develops rarely;

most deaths in acute Chagas disease are due to heart failure.

Neurological signs are not common, but meningoencephalitis occurs occasionally, especially in children under 2 years old.

Remember! Usually within 4-8 weeks, acute signs and symptoms resolve spontaneously in virtually all patients, who then enter the asymptomatic or indeterminate phase of chronic T. cruzi infection.

Associated Signs & Symptoms in the Indeterminate Stage of Infection

Asymptomatic

Associated Signs & Symptoms in the Chronic Stage of Infection

Symptomatic chronic Chagas disease becomes apparent years or even decades after the initial infection.

The heart is commonly involved, and the symptoms are caused by:

Rhythm disturbancesSegmental or dilated

cardiomyopathyThromboembolism

Right bundle branch block is a common ECG abnormality, but other types of:

Intraventricular and atrioventricular blocks

Premature ventricular contractions

Tachy- and Brady- arrhythmias occur frequently.


Cardiomyopathy often results in biventricular heart failure with a predominance of right-sided failure at advance stage.

Embolization of mural thrombi to the brain or other areas may take place.

Sudden death is the main cause of death in Chagas heart disease.

Dilated Cardiomyopathy


Patient’s with megaesophagus suffer from:

DysphagiaOdynophagiaChest painRegurgitation

Aspiration can occur (especially during sleep) in patients with severe esophageal dysfunction, and repeated episodes of aspiration pneumonitis are common.

Weight loss, cachexia and pulmonary infection can result in death.

Patients with megacolon are plagued by abdominal pain and chronic constipation, which predisposes them to fecaloma formation.

Advanced megacolon can cause obstruction, volvulus, septicemia and death.


Megaesophagus & Megacolon Fecaloma

DIAGNOSIS Microscopy

Blood, CSF, Tissues Acute Stage

Parasite Isolation Serology

Indirect Immunofluorescence, ELISA

Chronic Stage Molecular Techniques

CONVENTIONAL SEROLOGICAL TESTS

Indirect Hemagglutination (IHA)

Parasite Lysate

ELISA Parasite Lysate Recombinant

Antigens

Conventional Serological TestsPerformance:

Method Sensitivity Specificity

IHA > 97% > 98%

ELISA > 98% > 99%

KITS Chagatest HAI

Chagatest HAI screening A-V

Chagatest ELISA (Lysate)

Chagatest ELISA recombinante v 3.0 (FDA 510k and CE)

New Chagatest ELISA recombinante v.4.0 Chagatest ELISA recombinante v.4.0

Recombinant AntigensSystem with six recombinant Ags

SAPA, Ag1, Ag2, Ag13, Ag30, Ag36

Highly sensitive and specific mixture Proteins present in the trypomastigote stage Proteins preserved in different parasite

strains/linages

Chagatest ELISA recombinante v.4.0 Recombinant Antigens

Ag1, Ag2, Ag30, Ag13, Ag36

Ag2, Ag13, SAPA

Ag13, Ag 36, SAPA

Chronic Congenital

Acute

Xenodiagnoses• In xenodiagnoses, 30-40 laboratory-reared

insects are allowed to feed directly or indirectly on the blood of a person suspected to have Chagas disease. At least one month later, intestinal contents of the insects are extracted and examined microscopically for the presence of parasites.

• Xenodiagnoses is tedious, requires a long time to perform, and yields a sensitivity of only 50% in the best of hands.

• Hemoculture, which involves a specialized liquid culture medium that is not available commercially, takes roughly the same amount of time as xenodiagnoses and has roughly the same level of sensitivity, but it is less tedious.

Prevention

& Control

A vaccine to prevent Chagas doesn’t exist. That’s why it is so important to know the methods of prevention: Vector Control Fumigation of houses where there are vinchuca bugs;Modification and renovation of the house structure;Conditioning and reordering of the house interior

Transfusion ControlRisk prevention measures for blood banks to eliminatethe transmission of infected blood

Mother-child transmission ControlProtocols for screening pregnant women, diagnosis and treatment for children.

Prophylactic Measures (Vector Control)

Synthetic pyrethroid sprays (used in Latin America to remove house infestations)

Consult a licensed pest control operator

Seal cracks and gaps around windows walls, roofs and doors

Remove wood, brush and rock piles near house

Screens on doors and windows and repair holes

Treating Chagas Disease (Acute Phase)

All patients with acute Chagas disease, including those with congenital infection and those with reactivation of chronic infections due to immunosuppression, should be treated with either benznidazole or nifurtimox

Requires early detection and speedy treatment. However, early detection is difficult as the individual may be asymptomatic and parasitological screening tests have a high rate of false negatives with respect to T. cruzi

If disease progresses to a chronic phase: it is no longer curable (will require management of symptoms

Indeterminate Phase Chagas Treatment

All children and adolescents through age 18 years with chronic T cruzi infection should receive either benznidazole or nifurtimox.

The probability of parasitological cure with full courses of either drug in adults with long-standing T. cruzi infection, most of whom were infected while quite young, is less than 10%

Treatment of Chronic Phase

The consensus among experts is that persons who have already developed cardiac or gastrointestinal symptoms should not be given anti-parasitic treatment.

All you can do for the patient is to provide symptom management and relief

Surgical CareCardiopathy

Atrial and ventricular rhythm disturbances may require pacemaker placement. Ablation procedures for tachyarrhythmias, as well as implanted defibrillators, have been used in some patients with Chagas disease

Megaesophagus Wide esophagocardiomyectomy of the anterior gastroesophageal

junction, combined with valvuloplasty to reduce reflux. Laparoscopic myotomy is being used increasingly to manage severe megaesophagus.

Megacolon Duhamel-Haddad operation typically used in the treatment of idiopathic

congenital megacolon.

Potential Applications For Trypanosoma Cruzi?

Possible use for cancer immunotherapy-> triggers a potent CD8+ response needed to kill tumour cells: T. cruzi persists in host tissue and supports a

sustained immune response Parasite presents antigens to induce strong CD8+

response It also produces ligands to activate TLR to reduce

use of adjuvants

Health & Medicine

Chagas Disease (American Trypanosomiasis)