RESUMO
The presence of memory T cell specific for Trypanosoma cruzi in subjects with discordant serology for Chagas disease supports a cleared infection in these subjects. Using high-dimensional flow cytometry, ELISPOT assays and quantitative PCR, antibody-secreting cells and memory B cells specific for T. cruzi, total B-cell phenotypes, innate immune responses and parasite DNA were evaluated in serodiscordant, seropositive and seronegative subjects for T. cruzi infection. T. cruzi-specific memory B cells but no antibody-secreting cells specific for T. cruzi, increased proportion of nonclassical monocytes and increased levels of polyfunctional NK cells were found in serodiscordant compared with seropositive subjects. None of the serodiscordant subjects evaluated showed detectable parasite DNA, most of them did not show cardiac abnormalities and a group of them had had confirmed positive serology for Chagas disease. The unique immune profiles in serodiscordant subjects support that T. cruzi infection was cleared or profoundly controlled in these subjects.
Assuntos
Doença de Chagas , Células Matadoras Naturais , Células B de Memória , Trypanosoma cruzi , Humanos , Doença de Chagas/imunologia , Doença de Chagas/sangue , Trypanosoma cruzi/imunologia , Células Matadoras Naturais/imunologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Células B de Memória/imunologia , Anticorpos Antiprotozoários/imunologia , Anticorpos Antiprotozoários/sangueRESUMO
Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events (n = 22) and compared with those without adverse events (n = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4+ and CD8+ T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4+ and CD8+ T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.
Assuntos
Doença de Chagas , Dermatite , Nitroimidazóis , Trypanosoma cruzi , Linfócitos T CD8-Positivos , Doença de Chagas/induzido quimicamente , Doença de Chagas/tratamento farmacológico , Dermatite/tratamento farmacológico , Humanos , Nitroimidazóis/efeitos adversosRESUMO
BACKGROUND: Migration is a growing phenomenon with a well-known impact in infectious diseases epidemiology. Currently, immigrants represent almost 10% of the Spanish population. The majority come from countries where the prevalence of chronic viral illnesses is higher than in Spain. METHODS: To describe clinicoepidemiological features of human immunodeficiency virus (HIV)-infected immigrants attending our Unit and to compare differential characteristics depending on geographical origin, information from all new immigrants from January 1997 to December 2006 was collected. STUDY DESIGN: noninterventional retrospective chart review. RESULTS: We screened 1,609 patients of whom 77 (4.8%) were HIV antibody (Ab) positive. Of these, 80% were sub-Saharan Africans (SSAFR) and 20% were South-Central Americans (SCA). HIV prevalence was higher in SSAFR (5.6% vs 3.2%; p= 0.04). Overall, of those who were HIV Ab positive, 70% were male (median age 30 years), 59% heterosexuals, 9% hepatitis C virus coinfected, 8.6% hepatitis B virus coinfected, and 34% showed a positive tuberculin skin test. Median CD4 cell count was 263 cells/microL, median HIV-ribonucleic acid viral load 4.6 Log/mL, and 48% had a late diagnosis [acquired immunodeficiency syndrome (AIDS)-defining illness or <200 CD4 microL at the time of diagnosis]. Only 68% of patients for whom antiretroviral therapy was indicated actually started therapy and 22% were lost to follow-up just after diagnosis. SCA had lower CD4 cell counts (26 vs 168 cells/microL; p= 0.016), higher viral loads (5.3 vs 4.8 Log; p= 0.001), and were more likely to have an AIDS-defining illness (53% vs 21%; p= 0.04) compared to SSAFR. Tuberculin skin test reactivity was more common among SSAFR versus SCA [adjusted by CD4 count, odds ratio (OR) 6.3 and 95% confidence interval (CI): 0.65-60.5]. The main risk factor for late diagnosis was geographical origin: OR 4.6 (95% CI: 1.11-19.3) (SCA vs SSAFR; adjusted by the interval between the date of arrival in Spain and the date of HIV diagnosis). CONCLUSIONS: Almost half the HIV-infected immigrants were diagnosed in late stages. Patients were frequently lost to follow-up, and a significant minority did not start highly active antiretroviral therapy when indicated. SCA seem to have more severe immunosuppression at the time of diagnosis than SSAFR. Early voluntary routine HIV screening should be promoted.