Human Polymorphisms as Clinical Predictors in Leprosy

Genetic and serum markers in human host can predict leprosy susceptibility per se as well as be useful in classification and/or prediction of clinical variants and immunological responses in leprosy. Adequate and timely assessment of potential risks associated with these 38 host leprosy genes could diminish epidemiological burden and improve life quality of patients with this still prevalent mycobacterial disease

Investigation of Association between Susceptibility to Leprosy and SNPs inside and near the BCHE Gene of Butyrylcholinesterase

Leprosy is a chronic disease caused by Mycobacterium leprae and affects the skin and the peripheral nervous system. Butyrylcholinesterase is coded by the BCHE gene, and the atypical allele (70G; rs1799807) has been investigated as a leprosy risk factor, with conflicting results. The present study estimated the frequencies of variants of rs1799807 and of five additional SNPs at the BCHE gene or near it: rs1126680, rs1803274, rs2863381, rs4440084, and rs4387996. A total of 167 patients and 150 healthy controls were genotyped by TaqMan PCR. Significantly higher allelic (70G) and genotypic (70DG) frequencies in rs1799807 were found in the patient group, with odds ratio (OR) of 6.33 (1.40 to 28.53) for the heterozygote. This finding was replicated in a comparison of the cases against a control group of 361 blood donors. The present data suggest that the atypical BChE variant may predispose to leprosy per se

Molecular investigation of isolates from a multistate polymicrobial outbreak associated with contaminated total parenteral nutrition in Brazil

Background: Between November 2013 and June 2014, 56 cases of bacteremia (15 deaths) associated with the use of Total Parenteral Nutrition (TPN) and/or calcium gluconate (CG) were reported in four Brazilian states. Methods: We analyzed 73 bacterial isolates from four states: 45 from blood, 25 from TPN and three from CG, originally identified as Acinetobacter baumannii, Rhizobium radiobacter, Pantoea sp. or Enterobacteriaceae using molecular methods. Results: The first two bacterial species were confirmed while the third group of species could not be identified using standard identification protocols. These isolates were subsequently identified by Multi-Locus Sequence Analysis as Phytobacter diazotrophicus, a species related to strains from similar outbreaks in the United States in the 1970’s. Within each species, TPN and blood isolates proved to be clonal, whereas the R. radiobacter isolates retrieved from CG were found to be unrelated. Conclusion: This is the first report of a three-species outbreak caused by TPN contaminated with A. baumannii, R. radiobacter and P. diazotrophicus. The concomitant presence of clonal A. baumannii and P. diazotrophicus isolates in several TPN and blood samples, as well as the case of one patient, where all three different species were isolated simultaneously, suggest that the outbreak may be ascribed to a discrete contamination of TPN. In addition, this study highlights the clinical relevance of P. diazotrophicus, which has been involved in outbreaks in the past, but was often misidentified as P. agglomerans

A study of host genetic risk factors for leprosy susceptibility /

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is the leading cause of non-traumatic neuropathies in the world. Although a genetic component for leprosy susceptibility has been demonstrated by several studies, the exact nature and extent of this component is still unknown. Here, we applied linkage and association analysis in a combined candidate region and genome-wide approach to further investigate the nature of host genetic factors controlling leprosy susceptibility. First, we used 20 Vietnamese multiplex leprosy families to perform linkage analysis on selected genomic candidate regions harbouring genes previously known to be either linked or associated with leprosy phenotypes. We found significant evidence for linkage between markers of the TNFA gene located on chromosomal region 6p21 and clinical subtype of the disease (P = 0.00021). Next, we performed a genome-wide scan in a sample of 86 Vietnamese multiplex leprosy families. We identified a new leprosy "per se" susceptibility locus on chromosome 6q25--q27 (LOD = 4.31, P = 5 x 10-6). Linkage results were reproduced by family-based association analysis in an independent sample of 208 Vietnamese simplex leprosy pedigrees (P = 5.9 x 10 -5). A linkage homogeneity test confirmed chromosomal region 10p13 as modifier for paucibacillary leprosy in the Vietnamese population. Finally, we applied SNP-based association analysis to construct a high density linkage disequilibrium (LD) map of chromosome 6q25--q27. We identified genetic polymorphisms clustered in a 80 Kb LD block overlapping the 5-prime regulatory region shared by two genes, Parkinson's disease susceptibility gene PARK2 and PACRG, as risk factors for leprosy "per se" in the Vietnamese population (OR = 3.15--5.72). All associated SNPs can be distributed in three frequency haplotypes, with two SNPs capturing all the association information between the PARK2/PACRG 5-prime regulatory region and leprosy in the Vie

Absence of HTLV-1/2 infection and dermatological diseases in Manaus, State of Amazonas, Brazil

Introduction The prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection is heterogeneous across different populations. We tested the hypothesis that HTLV-1/2 infection occurs more often in dermatological patients. Methods A total of 1,091 patients from a tropical dermatology clinic were tested for HTLV-1/2. In parallel, 6865 first-time blood donors from the same geographic area were screened for HTLV-1/2; HTLV-1/2 positive blood donors underwent dermatological examinations. Results The prevalence of HTLV-1/2 in first-time blood donors was 0.14%. No co-occurrence of HTLV-1/2 infection and dermatological conditions was observed. Conclusions Our results challenge the hypothesis that HTLV-1/2 infection occurs more often in dermatological patients

Molecular investigation of isolates from a multistate polymicrobial outbreak associated with contaminated total parenteral nutrition in Brazil

Background: Between November 2013 and June 2014, 56 cases of bacteremia (15 deaths) associated with the use of Total Parenteral Nutrition (TPN) and/or calcium gluconate (CG) were reported in four Brazilian states. Methods: We analyzed 73 bacterial isolates from four states: 45 from blood, 25 from TPN and three from CG, originally identified as Acinetobacter baumannii, Rhizobium radiobacter, Pantoea sp. or Enterobacteriaceae using molecular methods. Results: The first two bacterial species were confirmed while the third group of species could not be identified using standard identification protocols. These isolates were subsequently identified by Multi-Locus Sequence Analysis as Phytobacter diazotrophicus, a species related to strains from similar outbreaks in the United States in the 1970’s. Within each species, TPN and blood isolates proved to be clonal, whereas the R. radiobacter isolates retrieved from CG were found to be unrelated. Conclusion: This is the first report of a three-species outbreak caused by TPN contaminated with A. baumannii, R. radiobacter and P. diazotrophicus. The concomitant presence of clonal A. baumannii and P. diazotrophicus isolates in several TPN and blood samples, as well as the case of one patient, where all three different species were isolated simultaneously, suggest that the outbreak may be ascribed to a discrete contamination of TPN. In addition, this study highlights the clinical relevance of P. diazotrophicus, which has been involved in outbreaks in the past, but was often misidentified as P. agglomerans