Serum cytokines in chronic Chagas' disease

We studied the serum levels of IL-2, IFN-g and TNF in different clinical forms of Chagas' disease and in patients clinically compensated and decompensated. Cytokines measured in 91 patients with the chronic form of the disease did not differ from those of 13 normal individuals, suggesting the absence of activation of the TH1 pattern of lymphocyte response. There were no statistical differences among the 17 patients in the indeterminate form of the disease, the patients presenting either early (n = 4) or well-developed signs of cardiomyopathy (n = 62), the digestive (n = 4) or the mixed (n = 4) forms of the disease. Serum TNF was undetectable and IFN-g levels did not differ between clinical forms and severities of Chagas' disease. However, we found IL-2 higher levels in the 25 non-controlled patients than in the 66 controlled individuals (p < 0,001). We suggest that IL-2 dosage may be useful as an indicator of the need for more aggressive procedures.

Confocal fluorescence microscopy: a powerful tool in the study of Chagas' disease

Confocal scanning fluorescence microscopy has become widely used in cell biology and pathology. In conjunction with monoclonal antibodies it may turn out to be a powerful diagnostic tool that also enables detailed studies of tissue forms of Trypanosoma cruzi.

Immunodiagnosis of chronic Chagas' disease using the Tc 46 and Tc 58 antigens

The polypeptides of 46 and 58kDa were recognized in different T. cruzi strains (Y, WSL and Colombiana) by serum of all chagasic patients studied. These polypeptides were isolated from T. cruzi Y strain and used in ELISA. The sensitivity and specificity were 97.6% [CI 95%: 86-100%] and 100% [CI 95%: 89.3-100%], respectively when Tc 46 was used. When Tc 58 was used the sensitivity and specificity were 100% [CI 95%: 89.6-100%] and 90.2% [CI 95%: 75.9-96.8%], respectively.

Aminoquinolone WR6026 as a feasible substitute for gentian violet in Chagas' disease prophylaxis in preserved blood for transfusional purposes

The search for a colorless, nontoxic and efficient drug to prevent transfusion-associated Chagas' disease (TACD) has been underway unsuccessfully since 1953 when gentian violet was preconized and to date is still being used as the only in vitro trypanocidal agent. The recent findings of aminoquinolone "WR6026" as a trypanocidal agent, led the authors to study the metabolism of red cells stored with this compound, the main objective of which was to define its applicability in TACD control. Ten units of human whole blood collected in CPDA-1 were divided into two equal satellite bags. One had "WR6026" (final concentration 62.5µg/mL) added and the other was used as a control, both were stored at 4ºC. At baseline, day 7, 14, 21 and 28, samples were taken for the following measurements: adenosine triphosphate (ATP), hemoglobin, electrolytes (sodium and potassium), gases (pO2 and pCO2) and osmotic fragility. The results of tests and control were analyzed through parametric t-student test. The results were similar in both groups throughout the experiment except for the level of ATP on day 14, which presented significantly higher values in the tests when compared with the controls (p = 0.012). It was concluded that WR6026 does not interfere in the preservation and probably the viability of the erythrocytes also until day 28 of storage. Consequently the authors suggest that WR6026 could emerge as a colorless substitute for gentian violet in the control of TACD in endemic areas.

New evidence of spontaneous cure in human Chagas' disease

A new case of spontaneous cure of human Chagas' disease is described in Uruguay. An 87-year-old man who had a typical acute phase of Trypanosoma cruzi infection in 1947 and never received specific treatment against the disease, when examined in 1998 revealed several completely negative parasitological and serological tests, including traditional serology, PCR and flow cytometry. As a whole, such findings fulfill the current criteria to define the cure of Chagas' disease. Clinical data suggest the possibility of a benign evolution of Chagas' disease in this case, but the basic findings (slight cardiac and esophageal impairment) could also be due to the advanced age of the patient.

Autochthonous Chagas' disease in Santa Catarina State, Brazil: report of the first case of digestive tract involvement

We report the first case of digestive tract pathology (megaesophagus) determined by Trypanosoma cruzi infection in Santa Catarina State, southern Brazil. A 63-year- old female had presumptive clinical diagnosis of Chagas' disease, which was confirmed by imaging (endoscopy and esophagogram) and immunological methods. Further molecular diagnosis was carried out with esophagus and blood samples collected during corrective surgery. Polymerase chain reaction tested positive for Trypanosoma cruzi in both esophagus and buffy coat samples.

Chagas' disease: study of congenital transmission in cases of acute maternal infection

We studied three pregnant women with acute chagasic infection. Two patients, infected in the third trimester of pregnancy, had uninfected children. The third patient, infected earlier, had an infected newborn. These results encourage research on risk factors of transmission and on medical decisions concerning pregnant women with acute Chagas' disease.

Assessment of chemiluminescence and PCR effectiveness in relation to conventional serological tests for the diagnosis of Chagas' disease

While testing 414 sera for the diagnosis of Chagas' disease, the conventional reactions of indirect hemagglutination, indirect immunofluorescence and the immunosorbent assay showed a sensitivity of 95.7%, 100% and 98.2% and a specificity of 98%, 98% and 96.4%, respectively, and an excellent association using Fisher's exact test. Chemiluminescence presented 100% sensitivity and 89.6% specificity, while PCR showed 100% specificity and 1.2% sensitivity. It is believed that the three conventional serological reactions are still adequate for diagnosing Chagas' disease.

Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution

The efficacy of treatment with nifurtimox and/or benznidazole among adults with chronic Chagas disease with no previous electrocardiographic disturbances was evaluated over a mean follow-up of 21 years, by means of conventional serology, xenodiagnosis, clinical examination, electrocardiograms and chest X-ray. One hundred and eleven patients, between 17 and 46 years old, were studied: 54 underwent treatment (nifurtimox 27, benznidazole 27) and 57 remained untreated (control group). Xenodiagnosis was performed on 65% of them: 36/38 of the treated and 9/34 of the untreated patients had previous positive xenodiagnosis. Post-treatment, 133 xenodiagnoses were performed on 41 patients, all resulting negative. In the control group, 29 xenodiagnoses were performed on 14 patients; 2 resulted positive. Sera stored during the follow-up were simultaneously analyzed through conventional serology tests (IHA; DA-2ME; IIF). The serological evolution in the treated group was: a) 37% underwent negative seroconversion (nifurtimox 11, benznidazole 9); b) 27.8% decreased titers (nifurtimox 9, benznidazole 6), 9 showed inconclusive final serology (nifurtimox 7, benznidazole 2); c) 35.2% remained positive with constant titers (nifurtimox 7; benznidazole 12). The control group conserved the initial antibody levels during the follow-up. In the clinical evolution, 2/54 (3.7%) of the treated and 9/57 (15.8%) of the untreated patients showed electrocardiographic disturbances attributable to Chagas myocardiopathy, with a statistically relevant difference (p<0.05). Treatment caused deparasitation in at least 37% of the chronically infected adults and a protective effect on their clinical evolution.

Gallbladder neuron count in cholelithiasis patients with and without Chagas disease

Various investigators agree that the incidence of cholelithiasis is greater in patients with Chagas disease. The most plausible explanation for this is based on the parasympathetic denervation that occurs over the whole digestive tract due to Chagas disease. In order to analyze the occurrence of this alteration, gallbladder neuron counts were performed on cholelithiasis patients with and without Chagas disease who were being treated at the Department of Digestive Surgery, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil. In the present study, a notable reduction in the number of neurons in the gallbladder wall was observed in Chagas patients, in comparison with non-Chagas subjects.

Problems and perspectives for Chagas disease control: in search of a realistic analysis

Chagas disease was an important medical and social problem in almost all of Latin America throughout the twentieth century. It has been combated over a broad swath of this continent over recent decades, with very satisfactory results in terms of vector and transfusional transmission. Today, a surveillance stage still remains to be consolidated, in parallel with appropriate care required for some millions of infected individuals who are today living in endemic and non-endemic areas. Contradictorily, the good results attained have generated excessive optimism and even disregard among health authorities, in relation to this disease and its control. The loss of visibility and priority may be a logical consequence, particularly in Latin American healthcare systems that are still disorganized and overburdened due to insufficiencies of financial and human resources. Consolidation of the victories against Chagas disease is attainable but depends on political will and continual attention from the most consequential protagonists in this struggle, especially the Latin American scientific community.

Chagas disease as a mechanistic model for testing a novel hypothesis

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.

International meeting: new diagnostic tests are urgently needed to treat patients with Chagas disease

Trypanosoma cruzi infection is often not detected early on or actively diagnosed, partly because most infected individuals are either asymptomatic or oligosymptomatic. Moreover, in most places, neither blood banks nor healthcare units offer diagnostic confirmation or treatment access. By the time patients present clinical manifestations of advanced chronic Chagas disease, specific treatment with current drugs usually has limited effectiveness. Better-quality serological assays are urgently needed, especially rapid diagnostic tests for diagnosis patients in both acute and chronic phases, as well as for confirming that a parasitological cure has been achieved. Some new antigen combinations look promising and it is important to assess which ones are potentially the best, together with their requirements in terms of investigation and development. In August 2007, a group of specialized researchers and healthcare professionals met to discuss the state of Chagas infection diagnosis and to build a consensus for a plan of action to develop efficient, affordable, accessible and easy-to-use diagnostic tests for Chagas disease. This technical report presents the conclusions from that meeting.

Further evidence of spontaneous cure in human Chagas disease

An acute case of Chagas disease was studied in 1944, with clinical and laboratory follow-up until 2007, in Bambuí, Minas Gerais, Brazil. A five-year-old girl living in a rural hut that was highly infested with Triatoma infestans presented a febrile clinical condition compatible with the acute form of trypanosomiasis. She presented a positive thick blood smear, but never again showed serological and/or parasitological evidence of Trypanosoma cruzi infection, on several occasions. This patient never received any specific treatment and, to this day, she remains completely asymptomatic, with normal findings from clinical, electrocardiographic, X-ray and echocardiographic examinations.