Introduction

Chagas disease (CD), also known as American trypanosomiasis, is caused by a protozoan parasite and is an infectious disease. The term ‘protozoa’ refers to single-celled organisms whilst parasites live off another species, known as a ‘host’, and obtain nutrients at this organism’s expense. A protozoan parasite is therefore a protozoan that has the ability to invade and cause disease in another organism.^1,2

Causes and transmission of Chagas disease

Trypanosoma cruzi is the causative agent of CD and can infect many types of cells in the body.

CD is predominantly transmitted through vectors. These are organisms which do not directly cause the disease itself but carry the disease-causing agent from one infected organism to another. In the case of CD, the primary vectors are blood-sucking triatomine bugs, known as ‘kissing bugs’.

Other modes of transmission of CD include:

• Congenital – this occurs when CD is present in a pregnant individual and the infection is passed to the foetus
• Blood-borne – this occurs if you receive a blood transfusion from an individual with the infection
• Organ-derived – this occurs upon receiving an organ transplant from an infected donor
• Oral – this occurs if you ingest food and water contaminated with faeces from triatomine bugs previously infected with T. cruzi
• Accidental – this is occupational exposure owing to inadequate safety measures, for example handling infected animals in a laboratory setting or contamination via infected needles³

Geographic distribution of Chagas disease

For many decades, CD was restricted to areas of poverty in Latin America. The disease typically ranges from southern parts of the USA to the northern regions of Argentina and Chile, encompassing 21 countries. In 2010, over 5 million individuals were infected in this area, with Ecuador posing one of the highest rates of infection risk.  

However, cases of CD have also been detected in other regions which has raised the worldwide public health concern of this disease. Human migration is one of the primary factors influencing the spread and distribution of CD. Non-endemic countries in Europe, Asia and North America are now home to many cases of CD. For example, of the 370,000 Latin American immigrants living in Japan, over 4,000 cases of CD are estimated to be present in this population as of 2007. In 2011, 2% of the immigrants from CD-endemic countries residing in Australia were infected with the disease.¹

Global case numbers of CD have decreased over the years owing to effective vector control programs and more thorough screening of blood and organ donors as well as testing for congenital CD.⁴

Symptoms of Chagas disease

Acute phase

CD is composed of two phases, the first of which is termed the ‘acute’ phase. It typically begins 1 to 2 weeks after initial infection with T. cruzi and its approximate duration is 8 weeks. During this phase, you are likely to be asymptomatic, meaning that you won’t experience any symptoms. However, some cases have reported mild symptoms during the acute phase, such as a fever. Other symptoms include:

• Headache
• Muscle pain
• Swollen lymph glands
• Enlarged liver or spleen
• Pallor
• Difficulty breathing
• Abdominal or chest pain

Romaña’s sign, which is a purplish swelling of the eyelids, is also a key indication of CD whereby the parasite has entered via the conjunctiva, for example through rubbing the eyes. 

Chronic phase

Initial symptoms tend to resolve spontaneously, indicating that the disease has entered the chronic phase. In approximately 60 to 70% of cases, the infection becomes ‘clinically silent’ during this time, in other words, you remain infected with T. cruzi but do not experience any symptoms.

However, 30 to 40% of patients can develop further symptoms over a period of years to decades. The parasite associated with CD mainly resides in the heart and digestive muscles, hence you can experience chronic disease in these areas.

Cardiomyopathy is common as well as heart arrhythmias and blood clots which can often be fatal. Gastrointestinal symptoms are rarer, but can include swallowing difficulties, and the enlargement and eventual failure of body parts like the oesophagus and colon. The nervous system may also be affected, causing symptoms such as seizures, dizziness, and fainting.^1,3,4 

Diagnosis of Chagas disease

Acute phase

During the acute phase, CD is diagnosed by confirming the presence of the parasite T. cruzi. The following methods can be used for this:

• Examination of fresh samples – this involves using a light microscope to look for triatomine bugs in a blood sample
• Blood smear – this involves treating the blood sample with a staining solution before examining it under a light microscope
• Micro-Strout test – this involves centrifuging a blood sample before identifying any triatomine bugs; during centrifugation, the sample is rotated quickly to separate any solids from liquids
• Polymerase chain reaction – abbreviated to PCR, this method involves amplifying the DNA segments from T. cruzi or measuring the amount of circulating parasite in the blood sample

Chronic phase

Diagnosis in the chronic phase of CD focuses on detecting antibodies that have been generated in the immune response against T. cruzi. There are several methods that can be used:

• Enzyme-linked immunosorbent assays (ELISAs) – a colour change will occur if there are T. cruzi antibodies in the blood sample, indicating a positive result
• Immunofluorescence assays (IFAs) – this method follows a similar principle to ELISA
• Haemagglutination – particles in the blood sample will form a clump in the presence of T. cruzi antibodies^3,4

Evaluation of symptoms

In addition to these diagnostic methods, other scans and tests can be used to investigate the heart and digestive symptoms associated with the chronic phase of CD:

• Electrocardiography (ECG) – this is a test that measures your heart’s electrical activity through placement of electrodes on the chest, and can be useful for detecting cardiomyopathies and heart arrhythmias
• Chest radiography and echocardiography – these are imaging-based techniques that evaluate changes in heart structure and function in patients with CD
• Hepatogram – this is another imaging-based technique that uses magnetic resonance imaging to examine the liver for any signs of disease
• Laboratory tests – these involve looking for the presence of biomarkers in a blood sample that may indicate cardiac disease, for example B-type natriuretic peptide (BNP), troponin, and inflammatory biomarkers including tumour necrosis factor (TNF) and interferon-gamma (IFN-γ)^1,2

Treatment of Chagas disease

There are currently two drugs available for the treatment of CD albeit their efficacy at treating the infection in the chronic phase is significantly more limited than that of the acute phase. The purpose of treatment during the acute phase is to lessen the severity of symptoms and reduce the course of the disease.⁴

Benznidazole

This is typically used as a first-line treatment owing to improved tolerance and more thorough evidence on its efficacy. Benznidazole works by causing damage to the DNA of the T. cruzi parasite so that it can no longer survive. The most common adverse effect is dermatitis, although this can usually be managed with antihistamines or topical steroids.^4,5

Nifurtimox

Nifurtimox has a similar mechanism of action to benznidazole; it produces metabolites that disrupt the structure and function of the parasite DNA, thus inhibiting its growth. The side effects of this drug include anorexia and weight loss, which can be experienced by up to 70% of patients. If this is severe, treatment should be discontinued.⁴

Management of chronic symptoms

Cardiac symptoms

For the prevention of blood clots, anti-coagulants can be administered. These are a class of drugs which inhibit coagulation factors so that your blood doesn’t clot too easily.

For patients who develop heart failure, the following classes of drugs can provide symptomatic relief and reduce the risk of sudden death:

• Diuretics – these work by increasing salt and water excretion through the urine to lower the volume of fluid in the body, thus reducing blood pressure
• ꞵ-blockers – these work by blocking the release of stress hormones so that the heart beats less quickly and forcefully
• Angiotensin-converting enzyme (ACE) inhibitors – these work by inhibiting the production of angiotensin II, a hormone that narrows blood vessels and increases blood pressure
• Anti-arrhythmic medications - these can be useful for the treatment of irregular heart rhythms. They ensure the heart beats normally so that the risk of cardiac arrest is reduced.

A heart transplant may be performed in cases that have failed to respond to treatments or those with severe functional impairment of the heart.^2,3

Gastrointestinal symptoms

Oesophageal relaxants and botulinum toxin injections may be recommended to help swallowing difficulties. Laxatives can be helpful for constipation, and a healthy diet should be implemented too.³

Prevention and control of Chagas disease

There are currently no vaccines for the prevention of CD, although there is hope that such a development will be made in the future.³

Existing measures to control CD include:

• Screening programs – this helps to prevent infection with T. cruzi through blood transfusion, organ transplants, and congenital transmission
• Public health education – this includes developing information and communication materials so that individuals are aware of how to reduce their risk of contracting CD
• Personal protective measures – this includes practising good hygiene, using bed nets, wearing clothing that covers your skin, and using insect repellent on exposed skin
• Vector control strategies – this includes spraying of insecticides and carrying out home improvements to prevent vector infestation
• Healthcare access – this ensures a diagnosis can be quickly made so that treatment can be promptly started, thus reducing the risk of complications³

Summary

CD is a protozoal disease and is primarily endemic to Latin America. T. cruzi is the responsible parasite and is transmitted to humans by triatomine bugs. CD consists of an acute and chronic phase, with the former phase typically not causing any symptoms. In the chronic stage of the disease complications involving various body systems can occur. Benznidazole and nifurtimox are used for the treatment of the infection, although a range of other drugs can be used for symptoms of chronic CD, such as heart failure and swallowing difficulties. The spread of CD can be controlled through measures like vector control, screening programs, and personal protection.