Disease Watch Focus: Chagas disease
CAUSATIVE AGENT. American trypanosomiasis, or Chagas disease, is a protozoan zoonotic disease caused by the haemoflagellate Trypanosoma cruzi, and is transmitted to humans either by blood-sucking triatomine vectors, blood transfusion or congenital transmission. This parasite infects over 150 species from 24 families of domestic and wild mammals, as well as humans. In the vertebrate host, T. cruzi infects many different cells, but in the human host, the disease is conspicuously limited to the myocardium and to gut nerve fibres.
DISTRIBUTION. Chagas disease is present in 18 countries on the American continent in two different ecological zones: the Southern Cone region, where the main vector lives inside human homes and in peridomiciliary areas; and Central America and Mexico where the main vector species lives both inside dwellings and in uninhabited areas. Country-wide crossectional surveys in the 1980s found an overall prevalence of 17 million cases, with 4.8–5.4 million people exhibiting clinical symptoms, an annual incidence of 700,000-800,000 new cases and 45,000 deaths due to the cardiac form of the disease.
CURRENT GLOBAL STATUS. Large-scale regional initiatives to halt vector-borne transmission and improved screening of blood-donors have been successful. At present, estimates indicate an infection prevalence of 13 million, with 3.0–3.3 million symptomatic cases and an annual incidence of 200,000 cases in 15 countries. The disease remains a priority health problem due to: the need for surveillance and control in areas where sylvatic vectors can invade dwellings; the medical and social costs of care for infected people in the absence of efficient and well-tolerated therapy, especially against the chronic form of the disease; the difficulty in obtaining priority for control activities and vector elimination in areas where vectorial transmission has been interrupted; and the need to continue strengthening mandatory blood-donor screening in endemic areas, as well as in non-endemic areas where increased travel and/or immigration of potentially infected donors might compromise donated blood supplies.
NEW BASIC KNOWLEDGE. The complexity of the pathology of Chagas disease and the diversity of its clinical manifestations have made the understanding of its pathogenesis difficult. The autoimmune hypothesis, once widely accepted, has increasingly been challenged by the parasite persistence hypothesis [1,2]. Arguments for the latter hypothesis come from demonstrations of the presence of parasites in tissues of chronic patients, and the fact that treatments that decrease parasite burden are associated with a decrease in clinical symptoms. The two hypotheses might not be mutually exclusive since anti-immunopathogenic responses in chagasic patients might be driven by the parasite burden. Although further studies are needed, including elucidating the role of the recently described parasitokines , these results indicate an urgent need for the development of new antiparasite drugs , and their evaluation in large-scale randomized clinical trials , as well as for progress in the development of vaccines and immune interventions against pathogenesis [1,6,7].
NEW TOOLS AND INTERVENTION METHODS. New approaches for the characterization of T. cruzi and its vectors have been applied in laboratory , diagnostic [9,10], clinical  and epidemiological studies, as well as in support of disease control .They have shed new light on the biology and genetics of these organisms [13,14], as well as on the genetics of the infected population , and strongly indicate that human infections are due to T. cruzi subgroup II (REF. 16). A possible breakthrough in clinical management of the chronic chagasic cardiomyopathy might involve the autologous transplantation of bone marrow cells into the circulation; patients with severe chagasic cardiomyopathy subjected to this therapy experienced improvement of the cardiac functions of up to 30%, in one case occurring one month after transplantation .
NEW STRATEGIES, POLICIES AND PARTNERSHIPS. A Southern Cone initiative to eliminate the main vector, and interrupt transfusional transmission of T. cruzi was launched by the health ministries in Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay in 1991.More than 2,500,000 houses were sprayed with insecticide between 1992–2001.Uruguay and Chile were declared free of vectorial transmission in 1997 and 1999, respectively, as were 9 of the endemic states of Brazil in 1990, and 4 endemic provinces of Argentina in 1991. Blood donor screening is mandatory in each of these countries. The extension of this model to Mexico, Central America, the Amazon and Andean Regions, however, will require adaptation and testing of vector control strategies to suit local epidemiological conditions [12,18].
CONCLUSIONS AND FUTURE OUTLOOK
The greatest risk to this improved trend in Chagas disease control comes from the success that has already been achieved, as the need for continued surveillance and selective interventions becomes less appreciated at the political level .
As the T. cruzi genome project (see Related Links) nears completion, new approaches will become available for the identification and validation of new drug targets, early diagnostic indicators of infection and vaccine candidates, and for the elucidation of the mechanisms underlying host cell invasion, immune response and pathogenesis. The challenge will be to transform new knowledge into cost-effective, equitably affordable interventions and to guarantee their access to the patients and populations of endemic countries.
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