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.