(1/1819) Candidate parasitic diseases.
This paper discusses five parasitic diseases: American trypanosomiasis (Chagas disease), dracunculiasis, lymphatic filariasis, onchocerciasis and schistosomiasis. The available technology and health infrastructures in developing countries permit the eradication of dracunculiasis and the elimination of lymphatic filariasis due to Wuchereria bancrofti. Blindness due to onchocerciasis and transmission of this disease will be prevented in eleven West African countries; transmission of Chagas disease will be interrupted. A well-coordinated international effort is required to ensure that scarce resources are not wasted, efforts are not duplicated, and planned national programmes are well supported. (+info)
(2/1819) Induction of CD8+ T cell-mediated protective immunity against Trypanosoma cruzi.
Trypanosoma cruzi was transformed with the Plasmodium yoelii gene encoding the circum-sporozoite (CS) protein, which contains the well-characterized CD8+ T cell epitope, SYVPSAEQI. In vivo and in vitro assays indicated that cells infected with the transformed T. cruzi could process and present this malaria parasite-derived class I MHC-restricted epitope. Immunization of mice with recombinant influenza and vaccinia viruses expressing the SYVPSAEQI epitope induced a large number of specific CD8+ T cells that strongly suppressed parasitemia and conferred complete protection against the acute T. cruzi lethal infection. CD8+ T cells mediated this immunity as indicated by the unrelenting parasitemia and high mortality observed in immunized mice treated with anti-CD8 antibody. This study demonstrated, for the first time, that vaccination of mice with vectors designed to induce CD8+ T cells is effective against T. cruzi infection. (+info)
(3/1819) Chagas' disease diagnosis: comparative analysis of parasitologic, molecular, and serologic methods.
During the course of chronic chagasic infection, low parasitemia levels prevent parasite detection by current techniques such as hemoculture and xenodiagnosis. Since serologic tests have sensitivity but lack specificity, molecular assays based on the polymerase chain reaction (PCR) have been proposed as alternative tools for parasite detection in individuals with chronic Chagas' disease. A variable degree of PCR efficiency has been reported in the literature and illustrates the need for further evaluation of large numbers of chagasic patients. In this study, we compared an optimized PCR technique with hemoculture and complement-mediated lysis (CoML) in 113 individuals from or living in endemic areas of Brazil who had conventional serologic results that were either positive, negative, or inconclusive. The PCR amplification yielded positive results in 83.5% (66 of 79) of individuals with positive serology, 47.6% (10 of 21) with negative serology, and 46.2% (6 of 13) with inconclusive serology. Of 10 patients with negative serology and positive PCR result, eight (80%) had positive CoML, indicating that they could have been chagasic but were not mounting immune responses. The PCR results were also positive for all individuals who had positive hemoculture, for 37 individuals with negative hemoculture and positive serology, and for two of six individuals with inconclusive serology and negative hemoculture. Thirteen individuals living in nonendemic areas who had negative serology were used as a negative control group: 100% had negative PCR results. Our results show that the optimized PCR protocol used here was very sensitive in detecting the presence of Trypanosoma cruzi in chronic chagasic patients. The PCR and CoML results were well correlated in all of the groups studied, which suggests that our PCR protocol may be effective in the evaluation of cure in patients who receive anti-parasite treatment. (+info)
(4/1819) Enzyme-linked immunosorbent assay for IgA antibodies to Trypanosoma cruzi in congenital infection.
With the aim of achieving earlier diagnosis of congenital Trypanosoma cruzi infection, we assessed the usefulness of detecting specific IgA antibody by an ELISA. We evaluated 12 pregnant women chronically infected with T. cruzi, their newborn infants, and three additional neonates with parasitemia at birth. The IgA-specific antibody was detected by adapting the procedure for use of a commercial IgG ELISA, the Hemagen Chagas' Kit (Hemagen Diagnostics, Inc., Waltham, MA). Trypanosoma cruzi-specific IgA was detected in 10 (83%) of 12 mothers at delivery, in one of three parasitemic infants, and one of 12 newborns of the chronically infected women. Testing of 13 infants at six months of age revealed IgA in seven infants (54%), of whom four also had persistent T. cruzi-specific IgG. Detection of T. cruzi-specific IgA could provide a criterion for diagnosis of congenital infection in the absence of detectable parasitemia. (+info)
(5/1819) Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and epidemiologic study.
A clinical, parasitologic, and serologic study carried out between 1988 and 1996 on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is endemic showed 19 symptomatic patterns or groups of symptoms appearing in combination with different frequencies. The symptomatic pattern with the highest frequency was that showing simultaneously fever, myalgia, headache, and Romana's sign, which was detected in 20% of the acute-phase patients. Asymptomatic individuals and patients with fever as the only sign of the disease made up 15% and 11.9% of the total acute cases, respectively. Statistical correlation analysis revealed that xenodiagnosis and hemoculture were the most reliable and concordant of the five parasitologic methods used; these two methods also showed the highest proportions in detecting any clinical symptomatic pattern in acute-phase patients. A similar high reliability and concordance was obtained with a direct agglutination test, an indirect immunofluorescent antibody test, and an ELISA as serologic tests, which also showed a higher proportion of positive detection of clinical patterns than parasitologic methods (P < 0.001). It is recommended that individuals coming from endemic areas showing mild and/or severe clinical manifestations should be suspected of being in contact or having been in contact with Trypanosoma cruzi, be referred for parasitologic and serologic evaluations to confirm the presumptive clinical diagnosis of acute Chagas' disease, and start specific treatment. The epidemiologic implications of the present findings are discussed and the use of similar methodology to evaluate other areas where Chagas' disease is endemic is suggested. (+info)
(6/1819) CD40 ligation prevents Trypanosoma cruzi infection through interleukin-12 upregulation.
Because of the critical role of the CD40-CD40 ligand (CD40L) pathway in the induction and effector phases of immune responses, we investigated the effects of CD40 ligation on the control of Trypanosoma cruzi infection. First, we observed that supernatants of murine spleen cells stimulated by CD40L-transfected 3T3 fibroblasts (3T3-CD40L transfectants) prevent the infection of mouse peritoneal macrophages (MPM) by T. cruzi. This phenomenon depends on de novo production of nitric oxide (NO) as it is prevented by the addition of N-nitro-L-arginine methyl ester, a NO synthase inhibitor. NO production requires interleukin (IL)-12-mediated gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) synthesis as demonstrated by inhibition experiments using neutralizing anti-IL-12, anti-IFN-gamma, and anti-TNF-alpha monoclonal antibodies (MAb). We found that an activating anti-CD40 MAb also directly stimulates IFN-gamma-activated MPM to produce NO and thereby to control T. cruzi infection. To determine the in vivo relevance of these in vitro findings, mice were injected with 3T3-CD40L transfectants or 3T3 control fibroblasts at the time of T. cruzi inoculation. We observed that in vivo CD40 ligation dramatically reduced both parasitemia and the mortality rate of T. cruzi-infected mice. A reduced parasitemia was still observed when the injection of 3T3-CD40L transfectants was delayed 8 days postinfection. It was abolished by injection of anti-IL-12 MAb. Taken together, these data establish that CD40 ligation facilitates the control of T. cruzi infection through a cascade involving IL-12, IFN-gamma, and NO. (+info)
(7/1819) A multi-epitope synthetic peptide and recombinant protein for the detection of antibodies to Trypanosoma cruzi in radioimmunoprecipitation-confirmed and consensus-positive sera.
Peptide epitopes of Trypanosoma cruzi have been identified through expression cloning. A tripeptide (2/D/E) containing three epitopes (TcD, TcE, PEP-2) was used in ELISA to detect antibodies to T. cruzi in 239 of 240 consensus-positive sera and 41 of 42 sera confirmed positive by radioimmunoprecipitation assay. The 1 discrepant consensus-positive serum was used to expression-clone a novel gene that contained a repeat sequence. A peptide corresponding to this sequence, TcLo1.2, was specific for T. cruzi. This antigen detected the discrepant consensus-positive serum and enhanced reactivity of low-positive sera in the tripeptide assay. A branched synthetic peptide, 2/D/E/Lo1.2, or a linear recombinant, r2/D/E/Lo1.2, realized all of the diagnostic features of the four epitopes, including the ability to boost reactivity of low-reactive sera. These studies show that peptides and recombinants containing multiple repeat epitopes are powerful tools for developing assays for T. cruzi antibody detection and have direct application in blood screening. (+info)
(8/1819) Chagas' disease and the autoimmunity hypothesis.
The notion that the pathology of Chagas' disease has an autoimmune component was initially based on the finding of circulating antibodies binding heart tissue antigens in patients and mice chronically infected with Trypanosoma cruzi. Later, T lymphocytes reactive with heart or nerve tissue antigens were found in chagasic mice and patients, extending the concept to include cell-mediated immunity. However, there is disagreement about whether the observed immunologic autoreactivities are triggered by T. cruzi epitopes and then affect host tissue antigens by virtue of molecular mimicry or are elicited by host antigens exposed to lymphocytes after tissue damage caused by the parasite. There is also disagreement about the relevance of immunologic autoreactivities to the pathogenesis of Chagas' disease because of the lack of reproducibility of some key reports supporting the autoimmunity hypothesis, conflicting data from independent laboratories, conclusions invalidated by advances in our understanding of the immunologic mechanisms underlying cell lysis, and, last but not least, a lack of direct, incontrovertible evidence that cross-reacting antibodies or autoreactive cells mediate the typical pathologic changes associated with human Chagas' disease. The data and views backing and questioning the autoimmunity hypothesis for Chagas' disease are summarized in this review. (+info)