Discussion
Chagas disease is endemic in Latin America, where it is a common cause of cardiac death due to ventricular arrhythmias, heart failure and/or thromboembolic events (3, 5). The vector-borne disease is caused by the protozoan Trypanosoma cruzi, which is most commonly transmitted by blood-sucking triatomine bugs (6). Transmission can also occur from mother to child, and via contaminated food, blood and organ transplantation.
The infection is typically asymptomatic to start with, but a few patients develop acute myocarditis or meningoencephalitis a few weeks after being infected. Patients' infections remain chronic, and 30–40 % develop clinical disease after 10–30 years, most commonly in the form of cardiomyopathy. Heart transplantation is a life-saving treatment for severe Chagas cardiomyopathy, but there is a high risk of parasite dissemination to the transplanted heart and reactivation of the disease when the patient is immunosuppressed (7).
Our patient was followed up as recommended after heart transplantation, with PCR monitoring of Trypanosoma cruzi. One year after the transplant, she had reactivation of Chagas myocarditis, with arrhythmias and positive PCR findings in myocardial biopsy and blood. An implantable cardioverter defibrillator was fitted, and she was treated with benznidazole for 90 days.
Chagas encephalitis is a rare but serious condition. Mortality in immunocompromised patients is reported to be 85 % (1, 8). However, our patient's history shows that even with a coma and severe neurological findings, treatment can lead to a life with normal cognitive function and no apparent sequelae.
Chronic Chagas disease is a common condition, with a risk of cardiomyopathy and gastrointestinal disease. The disease is endemic in Latin America but has spread to other continents through migration. The prevalence among Latin American immigrants to Europe is estimated at 4 % (9). The majority of people with asymptomatic chronic Trypanosoma cruzi infection are likely undiagnosed, as healthcare personnel in non-endemic areas often have little knowledge of the disease.
Our patient had been admitted with arrhythmia and heart failure in Norway, but the diagnosis of Chagas cardiomyopathy was only made when she was subsequently hospitalised with ventricular tachycardia during a stay in Latin America. Heart transplantation is not an uncommon treatment for Chagas disease. In Brazil, Chagas cardiomyopathy is the third most common indication for heart transplantation (10). In a report from the United States, the risk of reactivation with myocarditis in the graft was as high as 61 % (7). This is the background for the recommendation of post-transplant follow-up with PCR testing from blood and the myocardium, and treatment upon reactivation, which our patient received with subsequent disease control for many years before experiencing encephalitis reactivation. Regular monitoring for reactivation is recommended during the first year after transplantation, one month after any steroid treatment for rejection, and if fever occurs or signs of myocarditis develop (11).
In chronic asymptomatic Trypanosoma cruzi infection, serology with antibody detection is the most sensitive diagnostic method. In acute infection or reactivation, the parasites can often be detected in blood or cerebrospinal fluid by microscopy or PCR. Microscopy of cerebrospinal fluid in suspected encephalitis is a relatively simple method that requires few resources, and in this case, it contributed to rapid clarification (video). Routine microscopy of a Gram stain from cerebrospinal fluid will not detect the infection, as special Giemsa staining is required to see the parasites (Figure 1). Bacterial culture and standard PCR with a central nervous system panel will be negative.
Benznidazole and nifurtimox have shown clinical efficacy against Trypanosoma cruzi in randomised controlled trials (2). Fexinidazole, which is used to treat African trypanosomiasis caused by Trypanosoma brucei gambiense, has recently been shown to be effective against Chagas disease in a randomised controlled trial but is not currently in use due to adverse effects in the form of neutropenia (12). Benznidazole is the most extensively tested treatment and is particularly effective in acute and early chronic infection. Clinical efficacy trials are based on seroconversion or PCR negativity after treatment. The largest randomised controlled trial of benznidazole in patients with chronic Chagas disease and cardiomyopathy showed that significantly more patients were PCR-negative after treatment, but over five years of follow-up, no effect was observed on the risk of worsening cardiomyopathy (13).
Treatment of asymptomatic seropositive patients has not been studied in large-scale randomised controlled trials, but non-randomised controlled trials have shown a reduced risk of cardiomyopathy and reduced mortality (14, 15). Treatment of asymptomatic patients is therefore common practice in most countries (16). Treatment is recommended as early in the course of the disease as possible, while in older patients with chronic Chagas disease and organ involvement, the risk of adverse effects is weighed against the benefits (5). There are no clinical trials of encephalitis in immunosuppressed patients, but both benznidazole and nifurtimox have good penetration into the central nervous system, and we chose combination therapy for our patient when her condition became critical after starting benznidazole.
Chagas disease is normally a chronic condition for which treatment with medication is not urgent. However, in cases of acute infection or reactivation, prompt treatment is important.
Contact details for ordering benznidazole and nifurtimox and for advice on Chagas disease can be found at the WHO's website (17).
In Europe, Chagas disease is not vector-borne, but it can be transmitted from mother to child, or via blood or organ transplantation. In Norway, control measures have been introduced to prevent transmission during blood transfusion (18). Vertical transmission from seropositive mothers occurs in around 5 % of births and in up to 30 % if the mother is PCR-positive (3). More than 90 % of infants born with the infection are cured if treated in the first year of life (2). Benznidazole and nifurtimox are contraindicated during pregnancy, but treating fertile women can prevent transmission in subsequent pregnancies (19).
The Trypanosoma cruzi antibody test is performed at the National Reference Function for Serological Parasite Diagnostics at the University Hospital of Northern Norway. All patients of Latin American origin with arrhythmia, cardiomyopathy, or enlarged viscera should be tested for Chagas disease. Screening and treatment of Chagas disease in asymptomatic Latin American immigrants in Europe are cost-effective (16). Antibody testing in risk groups and treatment of seropositives should also be recommended in Norway to prevent transmission during pregnancy and prevent organ complications of Chagas disease.