Introduction
Chagas disease (CD) is a zoonosis caused by infection withTrypanosoma cruzi , a protozoan parasite. Humans can acquire this infection by contact with insect vectors (hematophagous triatomine or Reduviidae bugs), by ingestion of contaminated food1, congenital transmission, blood transfusions or organ or tissue transplants from infected donors. In the past, CD was believed to exclusively affect rural populations in Latin America, but movement of people from rural to urban areas (as well as expanding screening strategies to urban dwellers), has revealed the infection as a worldwide problem2,3. Congenital transmission in particular has become an important route of infection and the main reason for acute CD in non-endemic countries, such as North America and Europe.
The World Health Organization (WHO) estimates that over 8 million people worldwide are infected with T cruzi , and that an excess of 10,000 deaths occur every year due to CD 2. Under-diagnosis of CD cases is suspected to be as high as 90%, and even higher in cases of congenital CD which is alarming considering that estimated T. cruzi prevalence among pregnant women ranges from 2% to 40% depending on geographical area 4,5.
CD has a clinical course characterized by an acute phase, commonly asymptomatic, that resolves spontaneously in most cases but which can sometimes (i.e. less than 5% of cases) be severe, leading to serious sequelae and even death. Following the acute phase, a chronic stage ensues, with patients usually remaining asymptomatic for many decades. However, approximately 30% of infected patients eventually develop progressive and irreversible target organ damage, mainly in the heart and/or esophagus and colon. The ‘silent’ asymptomatic phase between acute and chronic phases is referred to as ‘indeterminate stage’ by some authors.6,7
The decision to implement CD treatment was historically based on age, due to limited evidence of efficacy, and an increasing frequency and severity of side effects in relation to patient age. 8Currently there is agreement in international clinical guidelines that anti-parasitic treatment is effective and therefore should be offered at least to 1) patients with acute CD, 2) all children with congenital or acquired acute CD 3) immunosuppressed hosts with acute or reactivation of chronic disease 4) women of childbearing age in order to prevent congenital transmissions 9–12.
Treatment effectiveness in chronic CD continues to be highly debated13–15; for adults over 50 years old, trypanocidal therapy is still considered optional due to an unclear risk-benefit balance. On the one hand there is a general agreement that parasitic persistence increases the risk for development or progression of cardiac lesions in chronically infected patients and therefore parasite eradication may be necessary in the early stages of the disease16,17. On the other hand, advanced CD seems to involve irreversible cardiac damage, and therefore parasiticidal treatment of affected older patients may be futile13. However, the evidence for either position is still limited18.
Unfortunately, anti-parasitic therapy has not been widely implemented, even for those age groups that can clearly benefit from it (e.g. pediatric patients, early chronic infections, etc.) in spite of existing national and international guidelines that support treatment. This failure to treat may possibly be explained by many obstacles, including health care providers’ low awareness of CD and its treatment options, overblown concerns about side effects, low access to healthcare for many patients with CD, lack of an optimal straightforward test of CD cure, widespread drug shortages and irregular supplies, and regulatory barriers19. Even though WHO 2020 Goals for CD included access to treatment and/or care of all infected/ill patients, and The London Declaration on Neglected Tropical Diseases 20 announced plans for the elimination or control of Chagas disease by 2020, current estimates indicate that less than 1% of CD infected patients are treated and those lofty aims are far away from becoming a reality.21 Sub-optimal CD treatment implementation continues in many countries in spite the fact that failing to treat a CD patient could be considered medical negligence in many jurisdictions22.
In South America, CD causes the loss of over 750,000 working days because of premature deaths and $1.2 billion in productivity loss every year 23. The calculated annual global burden of disease is over $600 million dollars per year in health-care costs and 10% of this burden affects non-endemic countries24. According to a study conducted in Mexico that evaluated the impact and economic outcomes (costs, cost-effectiveness, cost-benefit) of identifying and treating different percentages of CD patients in the acute and indeterminate phases, identifying and treating CD cases earlier was always economically dominant compared to no treatment21. Authorities in charge of health policies should acknowledge that this would result not only in reduced transmission rates and better health outcomes but also in huge cost-savings, besides being a medical duty, and human rights issue.
Despite the fact that CD was first described over a century ago25, only two drugs are currently available for treatment, benznidazole (BZN) and nifurtimox (NF), which were developed over 40 years ago. Both drugs require prolonged treatments (30 to 60 days) and are associated with adverse events that increase in severity and prevalence with age. Prompt diagnosis and treatment, especially in pediatric patients, are vital for an effective use of these medications.