American Trypanosomiasis (Chaga’s Disease)

Class IC2 Course Tropical Medicine Code TM Title Dr Lecturer Ciaran Bannan Date 18th September 2015

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Objectives

Understand the life cycle of T cruzi

Pathogenesis, clinical presentation, complications, differential diagnosis, investigations and management of T cruzi

Strategies for clinical surveillance and control

Overview

1907-1909: Carlos Chagas accidentally discovers the trypanosome

Named after his mentor Oswaldo Cruz

It is endemic in 21 countries

100 million people at risk

10 - 12 million persons infected

15,000 deaths per annum

Economic loss: $400 million in South America

Large medical costs of treatment

Estimated Prevalences of Trypanosoma cruzi Infection.

Bern C. N Engl J Med 2015;373:456-466

300,000 Latin immigrants living with T Cruzi in USA

Trypanosoma cruzi

Hemoflagellate Protozoa

Replication is intra-cellular (compared with African Trypanosomiasis)

Transmission

Reduviid Bug (Kissing Bug)

Inoculation through direct bite or through mucosal surface

Falling feces from roofs

Blood Transfusions

– 5% of S American donors seropositive

Bone Marrow Transplant

Organ Transplant

Transplacental

Laboratory Exposure

Reduviid Bug

• Order Hemiptera

• Nine Genera

• 1-3 cm in length

• Nocturnal

• Feed on human or animal blood

• Painless bite

• Mud adobe houses

• Thatched roofs

Oral Transmission

March 2005 in Brazil

31 confirmed cases

5 deaths

64 suspected

Sugar cane juice: garapa

Insects may have been inside when crushed

High doses of trypanosomes

Associated with more severe acute infection

Reservoir Hosts

Many mammals are reservoir hosts

rats dogs sloths bats cats opossums armadillos

Over 100 mammal species

Life Cycle

Trypomastigote is the active infective agent

Amastigotes reside in cells

Reticuloendothelial

Myenteric Plexus

Cardiac Muscle

Central Nervous System

Phases of Trypanosoma cruzi Infection

Bern C. N Engl J Med 2015;373:456-466

Acute Infection – local multiplication

Incubation Period 1-2 weeks

Symptoms usually mild and non-specific

May be asymptomatic – infrequently recognised

Rarely a chagoma (skin nodule) may develop at site of introduction 2-4 days afterwards

Erythematous,painful, brawny, & firm

Neuropathy may be present at site, that resolves

Last 2 weeks and then area is depigmented

Chagoma of the eye = Romana’s sign

Acute Infection - dissemination

Fever

Lymphadenopathy

Hepatomegaly

Splenomegaly

Myocarditis

CHF tachycardia

cardiomegaly arrhythmias

Acute Infection - dissemination

Meningoencephalitis / Myocarditis

Responsible for mortality (rare)

Orchitis

Thyroiditis

5-10% fatality rate

Resolves 4-12 weeks

Patients enter latent phase

Pathogenesis of Myocarditis

Parasites in the cardiac fibers cause a marked cellular infiltrate, particularly around cardiac cells that have ruptured and released the parasites.

Involvement may extend into the endocardium, resulting in thrombus formation

Involvement of the epicardium may result in pericardial effusions

Immune lysis by antibody and cell-mediated immunity directed against antigens released from T. cruzi-infected cells, which become adsorbed onto the surface of infected and noninfected host cells.

Progression to Chronic Infection

20-30% of infected individuals

Reasons:

Parasite persistence

Inflammatory host immune response is the most determinant of progression

Parasite factors e.g. strain may be important

Ongoing superinfection

Chronic Infection

Presents many years later Following latent period from acute disease (10 – 30 years) Cardiac

Cardiomyopathy Cardiac Conduction – earliest signs seen

RBBB Left Anterior Hemiblock Sick Sinus Syndrome Complete heart block Sudden death Congestive Heart Failure Thromboembolic episodes

Sudden Death

Chronic Infection: Megaesophagus

Less than 5% of cases Cat face (Salivary gland hypertrophy) Dysphagia Regurgitation Aspiration risk/Pneumonitis related to regurgitation (particularly during

sleep) Irritative esophagitis Weight loss and cachexia (in severe cases) Signs of rupture of esophagus Increased incidence of cancer of the esophagus

Chronic Infection:Megacolon

Rarer

Destruction of autonomic nervous system

Like Hirschsprung’s Disease

Asymmetric distended abdomen

Constipation

Sigmoid volvulus

Chronic Infection:Rare

Megaureters

Megabladder

Mega gallbladder

Bronchiectasis

Diagnosis

Peripheral blood - Trypomastigotes in blood film (acute)

Xenodiagnosis – used historically

Amastigotes in biopsy specimens

Culture in NNN medium & mouse subinoculation

Immunoflouresence antibody assay (IFA)

PCR – being used increasingly commonly

Serology EIA / ELISA – Antibody positive for life after 30 days

Echocardiogram

Dilated cardiomyopathy with increased end-diastolic and end-systolic volumes and reduced ejection fraction, often with enlargement of the left atrium and right ventricle.

Diastolic filling of the left ventricle is frequently abnormal

Advanced cases often show the left ventricular posterior wall hypokinesis and relatively preserved interventricular septal motion

An apical aneurysm is often seen

Imaging

Perfusion scanning with thallium-201 may show fixed defects (corresponding to areas of fibrosis) as well as evidence of reversible ischemia.

MRI with gadolinium

Left ventricular cineangiography in advanced cases shows a dilated, hypokinetic left ventricle with one large or several apical aneurysms containing intracavitary thrombus, often with evidence of mitral regurgitation.

Coronary angiography is usually normal, although abnormalities of the coronary microcirculation have been suggested as a cause of the clinical manifestations of Chagas disease.

Treatment indications

Acute phase

Pre-transplant

Reactivation in immunocompromised

e.g. HIV, Chemotherapy

Accidental exposure

Latent phase – No end organ damage

Risk / Benefit ?

Recent evidence supports treating majority of patients with chronic infection

Treatment

Benznidazole – first line treatment 5-10mg/kg QD for 1-2 months Side Effects:

Dermatological / Photosensitivity Neuropathy Bone marrow depression

Nifurtimox 10mg/kg divided TID for 1-3 months Side Effects: Anorexia Weight loss Hemolytic anemia Neuropathy Psychosis

Challenge of availability

Chronic Disease

Treatment recommended except in severe cases

May be asymptomatic for 20-30 years

Chronic Cardiomyopathy Digitalis

Diuretics

Pacemaker/AICD

Antiarrythmics

Partial left ventriculectomy

Anticoagulation

Transplant – excellent outcomes reported

Aneurysm repair

Amiodarone: Sudden Death in Chagas' Disease, Anis Rassi Jr., MD; Anis Rassi, MD;

Sérgio Gabriel Rassi, MD; Alexandre Gabriel Rassi, MD Hospital São Salvador, Goiânia (GO), Brazil

Pacemaker

Gastrointestinal Chronic Disease

• Megaesophagus

– Dilation of lower esophagus

– Surgical repair

• Megacolon

– Cholinergic Drugs

– Laxatives

– Fibre

– Recto-sigmoidectomy

• Treatment felt to be unlikely to stop progression of GI disease

Bern C. N Engl J Med

2015;373:456-466

Prevention

• Insecticides – resistance reported

• Mosquito Nets

• Changing structure of homes

• Screening blood donors and individuals from at risk countries

• No vaccine available to date

Take home messages

• Disease of poverty – ‘Kissing bug’

• Acute, latent and chronic phase

• Treatment lengthy and potentially toxic but effective if given early

• Late disease involves management of complications

• Control measures