Dataset Information

Clinical cutaneous leishmaniasis rates are associated with household Lutzomyia gomezi, Lu. Panamensis, and Lu. trapidoi abundance in Trinidad de Las Minas, western Panama.

ABSTRACT: American cutaneous leishmaniasis (ACL) transmission patterns have been increasingly associated with domestic and peridomestic environments. Here, we present results from an epidemiological survey of 94 people from 24 households in Trinidad de Las Minas, western Panama. We studied the role of sand fly abundance, housing quality, peridomicile landscape matrix, and vegetation structure on shaping household clinical ACL rate patterns at Trinidad de Las Minas. We found that sand fly abundance was significantly associated with household clinical ACL rates, with a 6% rate increase for each additional Lutzomyia gomezi sand fly found inside a domicile.

SUBMITTER: Saldana A

PROVIDER: S-EPMC3592543 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Clinical cutaneous leishmaniasis rates are associated with household Lutzomyia gomezi, Lu. Panamensis, and Lu. trapidoi abundance in Trinidad de Las Minas, western Panama.

Saldaña Azael A Chaves Luis F LF Rigg Chystrie A CA Wald Coridalia C Smucker Joanne E JE Calzada Jose E JE

The American journal of tropical medicine and hygiene 20130121 3

American cutaneous leishmaniasis (ACL) transmission patterns have been increasingly associated with domestic and peridomestic environments. Here, we present results from an epidemiological survey of 94 people from 24 households in Trinidad de Las Minas, western Panama. We studied the role of sand fly abundance, housing quality, peridomicile landscape matrix, and vegetation structure on shaping household clinical ACL rate patterns at Trinidad de Las Minas. We found that sand fly abundance was sig ...[more]

PMID: 23339202

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Project description:BACKGROUND:Lutzomyia gomezi (Nitzulescu, 1931) is one of the main Leishmania (Vianna) panamensis vectors in Panama, and despite its medical significance, there are no population genetic studies regarding this species. In this study, we used the sequences of the mitochondrial gene cytochrome b/start of NADH1 and the nuclear elongation gene ?-1 in order to analyze genetic variation and phylogeographic structure of the Lu. gomezi populations. METHODS:A total of 86 Lu. gomezi individuals were captured in 38 locations where cutaneous leishmaniasis occurred. DNA was extracted with phenol/chloroform methods and amplification of genes was performed using PCR primers for mitochondrial and nuclear markers. RESULTS:We found a total of 37 and 26 haplotypes of mitochondrial and nuclear genes, high haplotype diversity (h) for all three populations were detected with both molecular markers. Nucleotide diversity (?) was estimated to be high for all three populations with the mitochondrial marker, which was opposite to the estimate with the nuclear marker. In the AMOVA ?st recorded moderate (mitochondrial) and small (nuclear) population structure with statistical significance among populations. The analysis of the fixation index (Fst) used to measure the differentiation of populations showed that with the exception of the population located in the region of Bocas del Toro, the other populations presented with minor genetic differentiation. The median-Joining network of the mitochondrial marker reveled three clusters and recorded four haplotypes exclusively of localities sampled from Western Panama, demonstrating strong divergence. We found demographic population expansion with Fu´s Fs neutrality test. In the analysis mismatch distribution was observed as a bimodal curve. CONCLUSION:Lu. gomezi is a species with higher genetic pool or variability and mild population structure, due to possible capacity migration and local adaptation to environmental changes or colonization potential. Thus, knowledge of the genetic population and evolutionary history is useful to understand the implications of different population genetic structures for cutaneous leishmaniasis epidemiology.

Project description:The anti-inflammatory properties of sand fly saliva favor the establishment of the Leishmania infantum infection. In contrast, an antibody response against Lutzomyia longipalpis saliva is often associated with a protective cell-mediated response against canine visceral leishmaniasis. Genetic studies may demonstrate to what extent the ability to secrete anti-saliva antibodies depends on genetic or environmental factors. However, the genetic basis of canine antibody response against sand fly saliva has not been assessed. The aim of this study was to identify chromosomal regions associated with the anti-Lu. longipalpis salivary IgG response in 189 dogs resident in endemic areas in order to provide information for prophylactic strategies. Dogs were classified into five groups based on serological and parasitological diagnosis and clinical evaluation. Anti-salivary gland homogenate (SGH) IgG levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Genomic DNA was isolated from blood samples and genotyped using a SNP chip with 173,662 single nucleotide polymorphism (SNP) markers. The following linear regression model was fitted: IgG level = mean + origin + sex + age + use of a repellent collar, and the residuals were assumed as pseudo-phenotypes for the association test between phenotypes and genotypes (GWA). A component of variance model that takes into account polygenic and sample structure effects (EMMAX) was employed for GWA. Phenotypic findings indicated that anti-SGH IgG levels remained higher in exposed and subclinically infected dogs than in severely diseased dogs even in regression model residuals. Five associated markers were identified on chromosomes 2, 20 and 31. The mapped genes included CD180 (RP105) and MITF related to the rapid activation of B lymphocytes and differentiation into antibody-secreting plasma cells. The findings pointed to chromosomal segments useful for functional confirmation studies and a search for adjuvant molecules of the anti-saliva response.

Project description:BackgroundImmunity to the sand fly salivary protein SALO (Salivary Anticomplement of Lutzomyia longipalpis) protected hamsters against Leishmania infantum and L. braziliensis infection and, more recently, a vaccine combination of a genetically modified Leishmania with SALO conferred strong protection against L. donovani infection. Because of the importance of SALO as a potential component of a leishmaniasis vaccine, a plan to produce this recombinant protein for future scale manufacturing as well as knowledge of its structural characteristics are needed to move SALO forward for the clinical path.Methodology/principal findingsRecombinant SALO was expressed as a soluble secreted protein using Pichia pastoris, rSALO(P), with yields of 1g/L and >99% purity as assessed by SEC-MALS and SDS-PAGE. Unlike its native counterpart, rSALO(P) does not inhibit the classical pathway of complement; however, antibodies to rSALO(P) inhibit the anti-complement activity of sand fly salivary gland homogenate. Immunization with rSALO(P) produces a delayed type hypersensitivity response in C57BL/6 mice, suggesting rSALO(P) lacked anti-complement activity but retained its immunogenicity. The structure of rSALO(P) was solved by S-SAD at Cu-Kalpha to 1.94 Å and refined to Rfactor 17%. SALO is ~80% helical, has no appreciable structural similarities to any human protein, and has limited structural similarity in the C-terminus to members of insect odorant binding proteins. SALO has three predicted human CD4+ T cell epitopes on surface exposed helices.Conclusions/significanceThe results indicate that SALO as expressed and purified from P. pastoris is suitable for further scale-up, manufacturing, and testing. SALO has a novel structure, is not similar to any human proteins, is immunogenic in rodents, and does not have the anti-complement activity observed in the native salivary protein which are all important attributes to move this vaccine candidate forward to the clinical path.

Dataset Information

Clinical cutaneous leishmaniasis rates are associated with household Lutzomyia gomezi, Lu. Panamensis, and Lu. trapidoi abundance in Trinidad de Las Minas, western Panama.

Publications

Clinical cutaneous leishmaniasis rates are associated with household Lutzomyia gomezi, Lu. Panamensis, and Lu. trapidoi abundance in Trinidad de Las Minas, western Panama.

Similar Datasets

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