Chagas Disease

Chagas disease is a parasitic infection caused by Trypanosoma cruzi, endemic across much of Latin America. It is transmitted predominantly through contamination of a bite wound or mucous membrane with the infected faeces of triatomine ("kissing") bugs.

Additional recognised transmission routes include congenital (vertical) transmission, blood transfusion, organ transplantation, and, rarely, oral transmission through contaminated food.

The disease is characterised by an acute phase (frequently asymptomatic or mild) followed by a prolonged, often lifelong indeterminate (latent) phase. A proportion of infected individuals eventually develop chronic, potentially severe cardiac or gastrointestinal complications.

This makes it a globally relevant disease given substantial migration from endemic regions.

Pathophysiology and natural history

• Following inoculation, the parasite disseminates and invades host cells, particularly cardiac and smooth muscle. The acute phase reflects direct parasitic tissue invasion and the associated inflammatory response.
• Chronic phase pathology develops over years to decades in the affected minority. It is now understood to reflect an immune mediated, ongoing inflammatory and fibrotic process rather than simply persistent direct parasitic tissue damage alone.
• Approximately thirty percent of chronically infected individuals eventually develop clinically significant chronic disease. It is predominantly cardiac or gastrointestinal.
• Cardiac disease is Chagas cardiomyopathy, the leading cause of non ischaemic cardiomyopathy in endemic regions of Latin America. Gastrointestinal disease is megaoesophagus and megacolon, reflecting destruction of the myenteric plexus.
• The remaining majority of chronically infected individuals remain in the indeterminate phase without ever developing clinically apparent organ specific disease.

• Acute infection is frequently asymptomatic or produces only mild, non specific febrile illness.
• Characteristic though uncommon local signs are Romaña sign (unilateral painless periorbital oedema, reflecting inoculation at the conjunctiva) and chagoma (a localised inflammatory nodule at the site of skin inoculation). They are useful though inconsistently present clinical clues in the small proportion of patients where the acute phase is symptomatic and recognised.
• The indeterminate (latent) chronic phase is entirely asymptomatic, with normal cardiac and gastrointestinal function on standard clinical assessment, though serology remains positive. Ongoing surveillance for eventual development of organ specific disease is therefore appropriate in this population.
• Chagas cardiomyopathy presents with progressive dilated cardiomyopathy and heart failure. It has a characteristic propensity for significant conduction system disease and life threatening ventricular arrhythmia.
• Right bundle branch block combined with left anterior fascicular block is a classically described and relatively specific electrocardiographic pattern. Sudden cardiac death is a significant cause of mortality in this population.
• Gastrointestinal Chagas disease presents with megaoesophagus (progressive dysphagia, regurgitation, aspiration risk) and megacolon (chronic constipation, abdominal distension, and risk of volvulus). It reflects progressive destruction of the enteric neural plexus controlling normal gastrointestinal motility.
• Reactivation of chronic, previously indeterminate infection can occur in the context of significant immunosuppression (advanced HIV infection, immunosuppressive therapy following transplantation). It presents with severe, sometimes fulminant disease including myocarditis or meningoencephalitis.
• Reactivation is an important consideration in any chronically infected patient undergoing significant immunosuppression.

• Acute infection is diagnosed through direct parasitological methods. These include examination of blood for motile trypomastigotes on fresh blood film (given typically high parasitaemia during this phase) or polymerase chain reaction testing. Both offer good sensitivity during this early, high parasite burden phase of illness.
• Chronic infection (indeterminate phase or established organ specific disease) is diagnosed serologically, given the typically very low or undetectable parasitaemia at this stage. A positive result on at least two different serological assay methods is generally required for confident diagnosis, given imperfect specificity of any single assay in isolation.
• Screening for and staging of chronic cardiac and gastrointestinal involvement in confirmed chronically infected individuals guides both prognostic assessment and specific management planning.
• Cardiac screening includes baseline and periodic electrocardiography and echocardiography. Gastrointestinal screening, where relevant symptoms are present, includes barium swallow or oesophageal manometry and barium enema or other relevant gastrointestinal assessment.
• Screening of blood donors is an important public health measure. So is screening of organ donors in endemic regions, or for donors with relevant risk factors from non endemic regions.
• Antenatal screening of pregnant women in or from endemic regions, with subsequent testing of the newborn, is likewise important. These measures reflect the recognised transfusion, transplantation and congenital transmission routes.

• Antitrypanosomal treatment is benznidazole 5 to 7 mg per kg per day in two divided doses for sixty days, or nifurtimox as an alternative.
• It is indicated for acute infection (where treatment achieves high cure rates), congenital infection in the newborn, reactivation in the immunosuppressed, and, increasingly, for chronic infection in children and younger adults.
• For chronic infection, treatment is generally given up to age fifty, given a more favourable benefit to toxicity balance in this population. In older adults with established, generally irreversible chronic organ damage, treatment benefit is less well established.
• Treatment in the chronic indeterminate phase in older adults remains a subject of ongoing clinical trial evidence and specialist guidance. The decision is individualised, given the more modest and less certain benefit of antiparasitic treatment in preventing progression once significant time has elapsed since initial infection.
• This is balanced against the significant adverse effect burden of the available antiparasitic agents (including hypersensitivity reactions, peripheral neuropathy and bone marrow suppression). It warrants specialist tropical medicine or infectious disease input for this specific treatment decision.
• Established chronic Chagas cardiomyopathy is managed according to standard heart failure principles. Pay specific attention to arrhythmia management and conduction disease.
• Arrhythmia management may require implantable cardioverter defibrillator consideration given the significant sudden cardiac death risk in this population. Conduction disease may require permanent pacing.
• Antitrypanosomal treatment is not indicated at this established, chronic organ damage stage, given the absence of demonstrated benefit for reversing already established structural cardiac disease.
• Megaoesophagus and megacolon are managed symptomatically and, for more advanced disease, surgically. Surgery is oesophageal myotomy or resection for severe megaoesophagus, and colonic resection for complicated megacolon. This follows general principles applicable to severe gastrointestinal motility disorders from other causes.
• Prevention in endemic regions centres on vector control (improved housing construction to eliminate triatomine bug habitat, residual insecticide spraying), together with screening of blood and organ donors and antenatal screening programmes, given the absence of a currently available vaccine.