Forty dogs from the periphery of the city of Rio de Janeiro were studied. All dogs where diagnosed as positive for leishmaniasis either parasitologically and/or serologically. Among them, 19 came from areas where only Visceral Leishmaniasis (VL) occurs (Realengo, Bangu, Senador Camará). Clinical signs of the disease were seen in 36.8% of the cases, including emaciation - 100%, lymphadenopathy and depilation - 85.7%. The other 21 dogs came from an area (Campo Grande) where both diseases (VL, and American Cutaneous Leishmaniasis - ACL) occur. Clinical signs of the disease, mainly cutaneous or mucocutaneous ulcers were seen in 76.2% of the cases. Leishmania parasites were found in 39 cases: 22% in viscera, 42.5% in viscera and normal skin and 35% in cutaneous or mucocutaneous ulcers. All the Leishmania stocks isolated from dogs which came from Realengo, Bangu, Senador Camará (VL area), and from Campo Grande (VL + ACL area) were characterized as L. donovani (except in one case) according to their schizodeme, zymodeme and serodeme. The only stock characterized as L. b. braziliensis, was isolated from the lymph node of a dog from Campo Grande with visceral disease and without skin lesions. Antimony therapy attempted in eight Leishmania donovani positive dogs was unsuccessful.
INTRODUÇÃOA leishmaniose visceral (LV) canina, no Brasil, coexiste com a doença humana em todos os focos conhecidos sendo, porém, mais prevalente e, regra geral, precedendo à ocorrên-cia de doença humana 3 . Os cães infectados pela Leishmania donovani chagasi, à semelhança do calazar canino do Mediterrâneo, apresentam um bem conhecido espectro de características clínicas que podem variar de aparente estado sadio ao severo estágio final. Classicamente, na LV canina, tanto natural como experimentalmente induzida, se admite um período de incubação e prepatente de 3 a 6 meses até vários anos. Esta, invariavelmente, evolui para os estados latente ou patente que, por sua vez, em períodos variáveis de semanas, meses ou anos, podem evoluir para a forma aguda, subaguda, crô-nica ou regressiva 3,9,21 . De modo geral, o quadro clínico se assemelha à doença humana, com febre irregular de longo curso, palidez de mucosas e um emagrecimento progressivo, até o estado de caquexia intensa, na fase terminal. A hiperRecebido para publicação em 29/07/85
Foi realizado um inquérito entomológico no período de agosto a dezembor de 1977 na área de procedência de caso autóctone de leishmaniose visceral, encosta do Rio da Prata, bairro de Bangu, Rio de Janeiro. Utilizando-se capturadores manuais foram investigados os peri-domicílios de 13 das 27 habitações da área, tendo-se selecionado quatro locais de capturas que haviam demonstrado serem de maior produtividade. Em 22 capturas (73,3 horas - capturador), coletou-se 1.585 flebotomíneos, sendo 828 (52,2%) Lutzomyia intermediata, 684 (43,1%) Lutzomyia longipalpis, 57 (3,6%) Lutzomyia migonei, 5 (0,3%) Lutzomya cortelezzii e Lutzomyia fischeri, 3 (0,2%) Lutzomyia micropyga, 1(0,1%) LUtzomyia firmatoi e 2 (0,2%) Brumptomyia sp. L. longipalpis predominou nos locais de captura acima de 100 metros de altitude, tanto em abrigos de animais do tipo galinheiro como chiqueiro. A maioria deles foi capturada no horário entre 18 e 21 horas mas eventualmente foram também capturados entre 15 e 17 horas. L. intermedia predominou abaixo de 100 metros e em chiqueiro, sendo encontrados em galinheiro menos freqüentemente que L. longipalpis. Os autores ressaltam a necessidade de adoção de medidas de controle na localidade, dado o risco potencial de transmissão de leishmaniose visceral em área próxima a grande concentração urbana.
In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones.
In this study, we have the objective of evaluating the lymphoproliferative response and determining interferon (IFN)‐γ and interleukin (IL)‐10 cytokine production in the peripheral blood mononuclear cells (PBMC) of patients with American tegumentary leishmaniasis prior and post 12 months of chemotherapy treatment with meglumine antimoniate compared with the PBMC of noninfected donors. Lymphoproliferation, such as cytokine production, was evaluated through in vitro stimulus with the soluble antigenic fraction from Leishmania (Viannia) braziliensis promastigotes (1.25 µg/ml) and Concanavalin A (2.5 µg/ml). Patients showed a significant lymphoproliferative response prior and post treatment compared with the control group. Similar result, prior to chemotherapy treatment, was observed in IFN‐γ and IL‐10 production when patients were compared with the control group. After chemotherapy treatment, PBMC lymphoproliferative response of the patients revealed an increase, whereas patients have shown a decrease in IFN‐γ levels and an increase in IL‐10, although without statistical difference. These results may indicate that the patients produced a specific cellular response to the soluble antigenic fraction suggesting that besides Th1 and Th2 dichotomy, immunological regulation mechanisms with the participation of memory T cells and regulatory T cells could be present in the clinical evolution of these patients. This understanding will allow the study and identification of new L. (V.) braziliensis molecules potentially candidates to vaccines. J. Clin. Lab. Anal. 23:63–69, 2009. © 2009 Wiley‐Liss, Inc.
The influence of immune response on the treatment of American tegumentary leishmaniasis is pointed by several authors, and the existence of protective immunity in self‐healed patients (SH) is also suggested. Thus, interferon‐gamma (IFN‐γ), tumour necrosis factor‐alpha (TNF‐α), interleukin (IL‐) 10, IL‐17, IL‐22 and nitric oxide (NO) production was determined in PBMC culture supernatants from patients with active disease (AD) and after therapy, SH patients and healthy subjects, in response to the soluble antigen of Leishmania (Viannia) braziliensis. It was demonstrated that, during the active disease, there is a predominance of IFN‐γ and TNF‐α, indicating a proinflammatory phase of the response; IL‐17 is also highlighted at this clinical state. Also, TNF‐α was slightly increased in patients after therapy. NO secretion was noticed in SH individuals, while IL‐17 appeared in low levels in these patients and seems to be regulated by NO. The presence of IL‐10 was observed in all groups of patients. From this study, we can suggest that in the active disease and after clinical cure, with or without chemotherapy, specific cellular immunity takes part against Leishmania, but with some similarities between the clinical states. Thus, it indicates that the mediators herein described are necessary for the cure to occur.
For better efficiency in the establishment of American tegumentary leishmaniasis clinical cure, the World Health Organization suggests that the clinical criteria are supported by serologic data. The present study aims to investigate the dynamics of IgG subclass production in clinical evolution post-treatment of cutaneous leishmaniasis (CL). Paired sera from 23 subjects with CL resulting from Leishmania braziliensis infection were studied during the active lesion phase (aCL) and after clinical cure post-therapy (hCL), which included an alternative protocol with a low dose of antimony. Anti-Leishmania IgG and its subclasses were measured using ELISA, and the immunoglobulin levels were correlated with patients' clinical data. All of the subjects were clinically healed and did not present relapse during follow-up. Serum levels of anti-Leishmania IgG (r = -0·79; P < 0·0001), IgG1 (r = -0·64, P < 0·001) and IgG3 (r = -0·42, P < 0·045) in hCL were negatively correlated with the duration of clinical cure. After 24 months of clinical cure, 73% of samples were negative for IgG1 and 78% were negative for IgG3. In conclusion, the detection of serum anti-Leishmania IgG1 and IgG3 is an improved laboratory strategy to aid in the decision of interruption of the ambulatory follow-up of CL patients.
Em 1974 foram diagnosticados vários casos de leishmaniose tegumentar americana, no Município do Rio de Janeiro, RJ (Brasil). Naquela ocasião, foram usadas como medidas profiláticas o tratamento dos doentes e a dedetização dos domicílios e anexos, resultando na interrupção da transmissão. Com o aparecimento de novos casos, a partir de 1979, foram reestudadas algumas características de uma das localidades (Camorim) do mesmo município. De junho de 1979 a agosto de 1981, foram comprovados nessa localidade 19 casos novos de leishmaniose tegumentar americana (18 humanos e um em cão). Coletaram-se 1.149 flebótomos (11,4% fêmeas e 88,6% machos) com predomínio de Lutzomyia intermedia (95%). De acordo com o estudo dos casos, pressupõe-se que a transmissão tenha ocorrido no domicílio ou peridomicílio. Acredita-se, pois, que na área estudada, as medidas de controle, adotadas em 1974, foram eficientes por um período de aproximadamente quatro anos.
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