Chagas disease in the Amazon region

The risk that Chagas disease becomes established as a major endemic threat in Amazonia (the world's largest tropical biome, today inhabited by over 30 million people) relates to a complex set of interacting biological and social determinants. These include intense immigration from endemic areas (possibly introducing parasites and vectors), extensive landscape transformation with uncontrolled deforestation, and the great diversity of wild Trypanosoma cruzi reservoir hosts and vectors (25 species in nine genera), which maintain intense sylvatic transmission cycles. Invasion of houses by adventitious vectors (with infection rates > 60%) is common, and focal adaptation of native triatomines to artificial structures has been reported. Both acute (approximately 500) and chronic cases of autochthonous human Chagas disease have been documented beyond doubt in the region. Continuous, low-intensity transmission seems to occur throughout the Amazon, and generates a hypoendemic pattern with seropositivity rates of approximately 1-3%. Discrete foci also exist in which transmission is more intense (e.g., in localized outbreaks probably linked to oral transmission) and prevalence rates higher. Early detection-treatment of acute cases is crucial for avoiding further dispersion of endemic transmission of Chagas disease in Amazonia, and will require the involvement of malaria control and primary health care systems. Comprehensive eco-epidemiological research, including prevalence surveys or the characterization of transmission dynamics in different ecological settings, is still needed. The International Initiative for Chagas Disease Surveillance and Prevention in the Amazon provides the framework for building up the political and scientific cooperation networks required to confront the challenge of preventing Chagas disease in Amazonia.     

Immunopathology of Chagas disease

The main clinical forms of Chagas disease (acute, indeterminate and chronic cardiac) present strong evidences for the participation of the immune system on pathogenesis. Although parasite multiplication is evident during acute infection, the intense acute myocarditis of this phase exhibits clear ultrastructural signs of cell-mediated immune damage, inflicted to parasitized and non-parasitized myocardiocytes and to the endothelium of myocardial capillaries (microangiopathy). Inflammation subsides almost completely when immunity decreases parasite load and suppressor factors modulate host reaction, but inflammation does not disappear when the disease enters the indeterminate phase. Inflammation becomes mild and focal and undergoes cyclic changes leading to complete resolution. However, the process is maintained because the disappearance of old focal lesions is balanced by the upsurge of new ones. This equilibrium allows for prolonged host survival in the absence of symptoms or signs of disease. The chronic cardiac form is represented by a delayed-type, cell-mediated diffuse myocarditis, that probably ensues when the suppressive mechanisms, operative during the indeterminate phase, become defaulted. The mechanism responsible for the transition from the indeterminate to the cardiac form, is poorly understood.     

Chagas disease in Andean countries

The Andean Countries' Initiative (ACI) for controlling Chagas disease was officially created in 1997 within the framework of the Hipolito Unanue Agreement (UNANUE) between the Ministries of Health of Colombia, Ecuador, Peru, and Venezuela. Its objective was to interrupt transmission via vector and transfusion in the region, taking into account that there are 12.5 million people at risk in the four Andean countries forming the initiative in the area and around 3 million people are infected by Trypanosoma cruzi. The progress of control activities for the vector species present in the Andean sub-region, for different reasons, has been slow and control interventions have still not been installed in all geographical areas occupied by the target species. This has been partly due to lack of knowledge about these vector populations' biological characteristics, and consequent uncertainty about which are the appropriate control measures and strategies to be implemented in the region. The main vector species present important similarities in Venezuela and Colombia and in Ecuador and Northern Peru and they can be approached in a similar way throughout the whole regions, basing approaches on and adapting them to the current strategies being developed in Venezuela during the 1960s which have been progressively adopted in the Southern Cone and Central-American region. Additional measures are needed for keeping endemic areas free from Rhodnius prolixus silvatic populations, widely spread in the Orinoco region in Colombia and Venezuela. Regarding aetiological treatment, it is worth mentioning that (with the exception of Colombia) none of the other countries forming the ACI have registered medicaments available for treating infected young people. There are no suitable follow-up programmes in the sub-region or for treating cases of congenital Chagas disease. An integral and integrated programme encompassing all the aspects including transmission by transfusion which seems to have achieved extremely encouraging results in all countries, are urgently needed.     

Autoimmunity in Chagas heart disease

The possibility that cardiac autoimmunity contributes to the pathogenesis of Chagas heart disease is controversial. In this paper, we address the following questions regarding the genesis of autoimmunity in Chagas heart disease: (i) What mechanism(s) are potentially responsible for the generation of self-directed antibodies and lymphocytes? (ii) What is the evidence that any of these mechanisms actually can occur? (iii) What are the implications of the presence of autoimmunity for other mechanisms of cardiac inflammation?     

Immunopathology of cardiomyopathy in the experimental Chagas disease

The mechanisms by which Trypanosoma cruzi causes cardiomyopathy and induces neuronal destruction are discussed in this paper. The results suggest that autoimmunity in the chronic phase is the main cause of the progressive cardiac destruction, and that autoreactivity is restricted to the CD4+ T cell compartment. During the acute phase, the neuronal and cardiac fiber destruction occurs when ruptured parasite nests release T. cruzi antigens that bind to the cell surface in the vicinity which become targets for the cellular and humoral immune response against T. cruzi. The various factors involved in the genesis of autoimmunity in chronic T. cruzi infection include molecular mimicry, presentation of self-antigens and imbalance of immune regulation.     

Natural Chagas disease in four baboons

Background  Chagas disease is common in Central and South America and the southern United States. The causative agent is Trypanosoma cruzi (order Kinetoplastida, family Trypanosomatidae), a kinetoplastid protozoan parasite of humans and other vertebrates. It is a serious public health issue and the leading cause of heart disease and cardiovascular death in Central and South America. In 1984, a colony baboon was discovered to be infected with T. cruzi .
Methods  As the initial diagnosis was made by microscopic observation of the amastigote forms of T. cruzi in myocardial fibers, T. cruzi amastigotes have been identified in three additional baboons.
Results  The primary findings were similar in all four baboons and were congestive heart failure with edema of dependent areas, hydrothorax, hydropericardium, and multifocal to diffuse lymphoplasmacytic myocarditis.
Conclusions  A baboon animal model of Chagas disease could contribute significantly to the development of therapies for the disease in humans.     

Environmental distribution and persistence of Quahog Parasite Unknown (QPX)

Quahog Parasite Unknown (QPX) is the cause of mass mortality events of hard clams Mercenaria mercenaria from Virginia, USA, to New Brunswick, Canada. Aquaculture areas in Massachusetts, USA, have been particularly hard hit. The parasite has been shown to be a directly infective organism, but it is unclear whether it could exist or persist outside of its clam host. We used molecular methods to examine water, sediment, seaweeds, seagrass and various invertebrates for the presence of QPX. Sites in Virginia and Massachusetts were selected based upon the incidence of QPX-induced clam die-offs, and they were monitored seasonally. QPX was detectable in almost all of our different sample types from Massachusetts, indicating that the parasite was widely distributed in the environment. Significantly more samples from Massachusetts were positive than from Virginia, and there was a seasonal pattern to the types of samples positive from Massachusetts. The data suggest that, although it may be difficult to completely eradicate QPX from the environment, it may be possible to keep the incidence of disease under control through good plot husbandry and the removal of infected and dying clams.     

Immunoglobulins in the chronic phase of Chagas disease]

Since divergent results were obtained by different authors about immunoglobulins concentration in sera from acute and chronic cases of Chagas disease, the problem was submitted to statistical approach in field conditions in the endemic zone of Bambui, state of Minas Gerais, Brazil. Positives cases were considered in all individuals presenting evidences in parasitological, immunological or electrocardiographical examination living exactly in the same conditions, but without any evidence of infection under the same criteria. The sample consisted of 32 chronic cases and no significant difference in the immunoglobulins levels were detected in chronic cases of Chagas disease as compared with the control group. Heterophili antibodies are being determined in chronic cases and apparently there is no relationship between its concentration and pathogenic effects.