Experimental visceral leishmaniasis in high and low antibody - producer mice (selection IV-A)

A leishmaniose é uma infecção parasitária cuja imunidade protetora envolve a ativação de macrófagos. Neste trabalho avaliamos a susceptibilidade de camundongos H e L (bons e maus produtores de anticorpos, respectivamente) da seleção IV-A, à infecção com o protozoário L. donovani. Camundongos H infectados com 10(7) amastigotas por via intravenosa foram mais suscetíveis, apresentando maior carga parasitária tanto no fígado quanto no baço. Após 60 dias de infecção ambas as linhagens apresentaram um aumento no índice esplênico. Esta esplenomegalia foi conseqüência, pelo menos parcialmente, de um aumento no número de células esplênicas. Os resultados indicam que a seleção IV-A é susceptível à infecção com L. donovani e que dentro desta seleção a linhagem H apresenta maior suscetibilidade do que a linhagem L.

Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis

The FML antigen of Leishmania donovani, in combination with either Riedel de Haen (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12. The QS21-FML and QuilA-FML groups achieved the highest IgG2a response. QuilA-FML developed the strongest DTH and QS21-FML animals showed the highest serum IFN-gamma concentrations. The reduction of parasitic load in the liver in response to each FML-vaccine formulation was: 52% (P < 0.025) for BCG-FML, 73% (P < 0.005) for R-FML, 93% (P < 0.005) for QuilA-FML and 79.2% (P < 0.025) for QS21-FML treated animals, respectively. Protection was specific for R-FML and QS21-FML while the QuilA saponin treatment itself induced 69% of LDU reduction. The FML-saponin vaccines promote significant, specific and strong protective effects against murine visceral leishmaniasis. BCG-FML induced minor and non-specific protection while IL 12-FML, although enhancing the specific antibody and IDR response, failed to reduce the parasitic load of infected animals. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Genotypes of the mannan-binding lectin gene and susceptibility to visceral leishmaniasis and clinical complications

Background. Visceral leishmaniasis (VL) is almost always lethal if not treated, but most infections with the causative agents are clinically silent. Mannan-binding lectin (MBL), an opsonin, is a candidate molecule for modifying progression to VL because it may enhance infection with intracellular pathogens. Mutations in the MBL2 gene decrease levels of MBL and may protect against development of VL. This case-control study examines genotypes of MBL2 and levels of MBL in individuals presenting with different outcomes of infection with Leishmania chagasi.Methods. Genotypes for MBL2 and levels of serum MBL were determined in uninfected control subjects (n=76) and in individuals presenting with asymptomatic infection (n=90) or VL (n=69).Results. Genotypes resulting in high levels of MBL were more frequent (odds ratio [OR], 2.5 [95% confidence interval {CI}, 1.3-5.0]; P=.006) among individuals with VL than among those with asymptomatic infections and were even more frequent (OR, 3.97 [95% CI, 1.10-14.38];P=.043) among cases of VL presenting with clinical complications than among those with uneventful courses. Serum levels of MBL were higher (P=.011) in individuals with VL than in asymptomatic infections.Conclusions. Genotypes of the MBL2 gene predict the risk for developing VL and clinical complications in infections with L. chagasi.

Immunotherapy against murine experimental visceral leishmaniasis with the FML-vaccine

The fucose mannose ligand (Leishmania donovani FML)-saponin vaccine has earlier shown its immunoprophylactic potential against visceral leishmaniasis in the CB hamster (87.7% of parasite load reduction), Balb/c (84.4%) and Swiss albino mouse (85-93%) models. In this investigation its specific immunotherapeutic efficacy against L. donovani infection in Balb/c mice was studied. The effects of vaccine treatment on the Immoral response, delayed type of hypersensitivity to promastigote lysate (DTH), cytokine levels in sera and reduction of the liver parasitic load of L. donovani infected mice, were examined. The types and subtypes of anti-FML antibodies increased significantly in the vaccinees over the saline and saponin controls. As expected for a saponin vaccine, the highest ratios were found in relation to IgG1, IgG2a and IgG2b (4.4, 5 and 2.5, respectively). The DTH response and the in vitro ganglion cell proliferative response against FML antigen were also significantly higher than controls (P < 0.005). Concomitantly, an impressive and specific decrease of liver parasitic burden was detected only in vaccine-treated animals (94.7%). Our results indicate that the therapeutic FML-vaccine has a potent effect on modulation of the murine infection leading to the reduction of parasitic load and signs of disease, being a new potential tool in the therapy and control of visceral leishmaniasis. (C) 2003 Elsevier Ltd. All rights reserved.

AMERICAN VISCERAL LEISHMANIASIS: DISEASE CONTROL STRATEGIES IN DRACENA MICROREGION IN ALTA PAULISTA, SP, BRAZIL

Despite measures adopted to control American visceral leishmaniasis (AVL), the disease is spreading in a fast and worrying way throughout western São Paulo state. The aim of this work was to study the variables involved in the disease cycle as well as the effectiveness of controlling measures. The study was carried out in the microregion of Dracena, which is composed of twelve cities and belongs to Alta Paulista, a region of western São Paulo. The necessary data were provided by the Superintendence for Endemic Disease Control and Adolfo Lutz Institute, Regional Laboratory of Presidente Prudente. From August 2005 to January 2008, the following factors were observed: detection of phlebotomine sandflies in the cities and periods in which dogs or humans were diagnosed; number of human deaths; prevalence of suspected dogs tested by serology; percentage of euthanasia in suspected dogs; a possible correlation between positive dogs and cases of the disease in humans; and the disease prevalence among municipalities from the studied region. It was verified that, despite the strategies adopted in Dracena microregion to control AVL, the disease continues to rise. Thus, some procedures of the AVL Monitoring and Control

Levels of matrix metalloproteinase-2 and metalloproteinase-9 in the cerebrospinal fluid of dogs with visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship between dog culling and incidence of human visceral leishmaniasis in an endemic area

Domestic dogs are the main reservoirs of visceral leishmaniasis (VL) in urban areas; one of the control measures adopted in Brazil is the elimination of this reservoir. In order to test the relationship between the euthanasia rate of the canine reservoir and the incidence of the disease in humans, data on dog culling from the Centre for Zoonosis Control of Aracatuba, São Paulo, Brazil, during the period from 1999 to 2008 and visceral leishmaniasis human cases registered in the same period were analyzed. Reduction of human VL incidence was statistically correlated to dog euthanasia rate (P=0.0211; r(2)=0.616) when it was analyzed for the period of two years after application of this measure. Other factors that may influence this relationship are considered. (C) 2010 Elsevier B.V. All rights reserved.

Dog culling and replacement in an area endemic for visceral leishmaniasis in Brazil

Measures employed to control visceral leishmaniasis in Brazil have focused on vector control by residual insecticide spraying and diagnosis of infection with elimination of positive dogs. We describe dog culling and replacement in a Brazilian endemic area (the Alvorada District, Aracatuba, SP) in order to better understand dog population dynamics when elimination of the dog reservoir is adopted as the main control measure. From August 2002 to July 2004, 60.9% of the estimated dog population for the area was culled with a mean age of 34 months old. The presence of anti-Leishmania sp. antibodies was recorded for only 26.7% of the euthanized canines. Replacement was observed in 38.8% of the cases, some of them by 2 or more dogs and in a mean time of 4 months. Dogs were replaced mostly by puppies of both sexes with a mean age of 6.8 months. From August 2002 to April 2005 we were able to follow-up 116 of these dogs, during a mean time of 8.7 months. Canine visceral leishmaniasis seropositivity by ELISA was observed in 42.2% of the followed dogs, 30.6% of which were already positive at the first evaluation. By the end of the follow-up period 37% of the dogs were submitted to euthanasia, with a mean age of 18.3 months. In the studied CVL endemic area of Brazil, euthanasia and the subsequent replacement ratio were high, increasing the dog population turnover and leading to a younger population that might be more susceptible to a variety of other infectious diseases in addition to CVL. Dog culling as a control strategy for VL should be reassessed. (C) 2008 Elsevier B.V. All rights reserved.