CD14-159 and -260 gene polymorphisms are associated with HBV-related cirrhotic injury in Chinese Han patients

The present study aimed to investigate the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphisms (base pair -159 and -260) with HBV-related cirrhosis in Chinese Han patients. By use of a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis technique, we genotyped Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile and CD14-159 and -260 polymorphisms in 110 HBV-related cirrhotic patients and 110 healthy controls from the Chinese Han population. We found significant differences in the genotypes and allele frequencies of CD14-159 (but not -260) between healthy controls and liver cirrhotic patients, and both the CD14-159 and -260 genotypes were significantly different among Child-Pugh grades in cirrhotic patients. No TLR4 Asp299Gly and Thr399Ile mutations were detected in any cirrhotic patients or healthy controls in the Chinese Han population. These findings indicated that the polymorphisms of CD14, but not TLR4 Asp299Gly and Thr399Ile mutations, may be an important genetic factor for HBV-related cirrhotic injury in the Chinese Han population.     

Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for Candida bloodstream infection

Toll-like receptor (TLR)-4 is an important pattern recognition receptor for Candida albicans, playing a role in innate host defense. We investigated whether there is an association between the TLR4 Asp299Gly or TLR4 Thr399Ile polymorphism, and the occurrence of Candida bloodstream infection. We performed a case-control study, involving 43 patients with a Candida bloodstream infection and 166 healthy individuals. TLR4 Asp299Gly and Thr399Ile polymorphisms were assessed, as well as cytokine production after stimulation of peripheral blood mononuclear cells (PBMC) with Candida albicans. We observed that the prevalence of TLR4 Asp299Gly polymorphism was found to be higher in patients with Candida bloodstream infection than in controls (26% versus 10%; OR 3.0; 95%CI 1.3-6.9). All patients bearing the Asp299Gly polymorphism were also positive for the Thr399Ile allele, a linkage well described in literature. IL-10 production was higher in C. albicans-stimulated PBMC from volunteers bearing the TLR4 Asp299Gly polymorphism, and a similar tendency was observed in TLR4 Asp299Gly heterozygous patients who had recovered from candidemia. These findings show that the TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to Candida bloodstream infections, and an increased production of IL-10 is probably involved in this effect.     

Comparative evaluation of western blotting in hepatic and pulmonary cystic echinococcosis

Many serological tests are widely used in the diagnosis of cystic echinococcosis (CE), caused by the larval stages of Echinococcus granulosus. The present study was carried for differentiation between hepatic and pulmonary cystic echinococcosis by Western Blotting (WB). A total of 121 sera from patients with hepatic CE (37), pulmonary CE (31) and controls (53; consisting of six healthy, seven Hymenolepis nana infection, 20 hepatic and 20 pulmonary diseases other than CE) were examined. In all of the CE patients, E. gronulosus infection was confirmed by surgical intervention. Sera were previously tested using IHA and ELISA to detect the E. gronulosus specific antibodies. Sera from hepatic cases of CE reacted with 16 polypeptides of 6-116 kDa and sera from pulmonary cases of CE reacted with 14 polypeptides of 4-130 kDa by Western Blotting. The WB test enabled the detection of antibodies in the hepatic CE samples for proteins of 24, 32 34, 44-46 and 52-54 kDa in molecular weight in 78.4%, 75.7%, 78.4% and 89.2% of the patients, respectively. In the pulmonary CE samples sera WB test enabled the detection of antibodies 24, 44-46, 100, 110, 116 and 120 124 kDa in molecular weight in 81.3%, 75.0%, 87.5%, 71.9%, 84.4% and 65.6% of the patients, respectively. We indicated that the antigenic components of high molecular weight can be good candidates for differentiation of hepatic CE from pulmonary CE.     

Characterizing dynamic changes of plasma cell-free Echinococcus granulosus DNA before and after cystic echinococcosis treatment initiation

Over one million people are living with cystic echinococcosis (CE) and alveolar echinococcosis (AE). For CE, long-term albendazole treatment is often needed, which requires regular follow-up. Follow-up is mainly through imaging which is insensitive to subtle changes and subjective to experience. We investigated the changes of Echinococcus granulosus (Eg) cell-free DNA (cfDNA) in plasma of CE patients before and after albendazole treatment to evaluate its potential as an objective marker for treatment follow-up. Plasma samples of nine CE patients were collected before and after treatment. We identified Eg cfDNA from every sample through high-throughput sequencing. Eg cfDNA concentration and fragment length increased significantly after the treatment period. Ultrasound examination before and after the treatment initiation reflected the drug effects to a certain extent, as the cyst size of four patients reduced. Our findings indicated that Eg cfDNA from plasma could be a potential marker in the monitoring of CE treatment.     

Association of LMP/TAP gene polymorphisms with tuberculosis susceptibility in Li population in China

Background

Tuberculosis (TB) is a contagious disease affected by multiple genetic and environmental factors. Several association studies have suggested that cellular immune response is vital for controlling and preventing of tuberculosis infection. Low molecular weight polypeptides (LMPs) and transporters with antigen processing (TAPs) are the main molecules in the processing and presentation pathway for intracellular antigens. This study was performed to elucidate whether these antigen-processing genes (LMP/TAP) polymorphisms could be associated with the risk of tuberculosis infection in China.

Methodology/Principal Findings

We recruited 205 active pulmonary tuberculosis patients and 217 normal controls from Li population for this study. Four polymorphisms of LMP/TAP genes were determined by PCR-RFLP assay and haplotypes were constructed by software PHASE 1.0. Of the total four polymorphisms, genotype frequencies of LMP7 AA homozygote and CA heterozygote were significantly greater among cases compared to controls, with odds ratio of 3.77 (95% CI: 1.60–8.89; P = 0.002) and 2.97 (95% CI: 1.80–4.90; P<0.0001), respectively. The genotypes of TAP1-2 GG homozygote and AG heterozygote were more frequent in subjects with TB than in controls, with odds ratio of 3.94 (95% CI: 1.82–8.53; P = 0.001) and 2.87 (95% CI: 1.75–4.71; P<0.0001), respectively. Similarly, we found that haplotype B which carried LMP7 and TAP1-2 variations significantly increased the susceptibility to TB (OR = 3.674, 95% CI: 2.254–5.988; P<0.0001). Moreover, it is noteworthy that the homozygote of wild haplotype A (A/A) may be a strong protection for TB infection.

Conclusions

Our findings suggested that LMP/TAP gene polymorphisms might be risk factors for TB infection among Li population in China.     

Infection Status of Hydatid Cysts in Humans and Sheep in Uzbekistan

Uzbekistan is endemic of cystic echinococcosis (CE). In order to estimate endemicity of CE, we collected data from emergency surgery due to CE in 2002-2010 and also investigated the prevalence of hydatid cysts in the liver and lungs of sheep at an abattoir in Uzbekistan from July 2009 to June 2010. In 14 emergency hospitals, 8,014 patients received surgical removal or drainage of CE during 2002-2010, and 2,966 patients were found in 2010. A total of 22,959 sheep were grossly examined of their liver and lungs, and 479 (2.1%) and 340 (1.5%) of them were positive for the cyst in the liver and lungs, respectively. Echinococcus granulosus is actively transmitted both to humans and sheep, and CE is a zoonotic disease of public health priority in Uzbekistan.     

TLR4 and TLR9 polymorphism: Probable role in susceptibility among the population of Bihar for Indian visceral leishmaniasis

Genetic variations in the host TLRs genes play an important role in susceptibility and/or resistance to visceral leishmaniasis by altering the host-pathogen interaction. In this study, we investigated the association between polymorphisms of TLR4 (Asp299Gly, Thr399Ile) and TLR-9 (T-1237C), with susceptibility to visceral leishmaniasis. A bi-directional PCR amplification of specific alleles technique was used to characterize the distribution of TLR4 (Asp299Gly and Thr399Ile) and TLR9 (T-1237C) polymorphisms. A total of 60 samples were randomly selected from confirmed visceral leishmaniasis patients and 24 endemic healthy volunteers. The samples were genotyped and allele frequencies were determined. We observed that TLR4 Asp299Gly and Thr399Ile genotypes were more frequent in visceral leishmaniasis patients (10% and 15% respectively) compared to controls (4.2% and 8.3% respectively). However, the differences were not significant in TLR4 Asp299Gly and Thr399Ile alleles and genotypes. In the case of TLR9, we observed the frequency of T1237C genotype was higher in visceral leishmaniasis patients (43.3%) than in healthy controls (33.3%). Statistically significant differences were observed in TLR9 T1237C alleles and genotypes. We concluded that TLR9 T1237C, but not TLR4, gene polymorphisms can be regarded as contributors to visceral leishmaniasis susceptibility among the Indian population of Bihar state.     

Lack of association between TLR4 Asp299Gly and Thr399Ile polymorphisms and sepsis susceptibility: a meta-analysis

Sepsis, a condition of systemic inappropriate inflammation response to the invasion of microorganisms, results in considerable morbidity and mortality in patients. Some, but not all, epidemiological studies have suggested that Toll-like receptor 4 (TLR4) polymorphisms, Asp299Gly and Thr399Ile, may influence the risk of at-risk patients for sepsis. Our work tried to further study the association of the two common polymorphisms with sepsis susceptibility by performing a meta-analysis of previous data. Electronic searches of MEDLINE, EMBASE and Web of Science databases were performed. Original observational studies dealing with the association between polymorphisms Asp299Gly and/or Thr399Ile and sepsis risk were selected. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity analysis. Seventeen studies including 2212 cases and 3880 controls were included with most subjects of Caucasian ethnicity. The odds ratio for the association of Asp299Gly polymorphism with sepsis risk was 1.22 (95% CI: 0.90-1.65, P=0.21), and the association of Thr399Ile polymorphism was 1.16 (95%CI: 0.70-1.91, P=0.57). Subgroup analysis and sensitivity analysis did not change the results. Our meta-analysis revealed that the two common TLR4 polymorphisms, Asp299Gly and Thr399Ile, have no strong association with the likelihood of sepsis in Caucasian populations. Further studies are needed to investigate the effect of genetic networks and their mutual interactions in TLR4 signaling pathway on sepsis susceptibility.     

Melanocortin-4 Receptor Gene Polymorphisms in Obese Patients

Obesity is a complex disease caused by both genetics and environmental factors. Melanocortin-4 receptor (MC4R) (MIM 155541) gene polymorphisms were reported to be the cause of monogenic obesity in humans. We studied three polymorphisms (Val50Met, Val103Ile, and Ser58Cys) and a mutation (Asn274Ser) of the MC4R gene in 203 obese patients and in 110 healthy subjects in the Turkish population. A high incidence of Val103Ile and Val50Met polymorphisms as well as the Asn274Ser mutation was found in the obese patients, whereas no significant correlation was found regarding the Ser58Cys polymorphism. We conclude that there is a concordance between the polymorphisms (Val103Ile, Val50Met, Ser58Cys) that were first studied in the Turkish population with obesity.     

Prevalence of Serum IgG Antibodies to Cystic Echinococcus Antigen among Patients in an Uzbekistan Emergency Hospital

Cystic echinococcosis (CE) is one of the most widespread zoonotic helminthiases, which can last an asymptomatic infection for several years. The purpose of this study was to demonstrate serum antibody prevalence of CE among asymptomatic people in Uzbekistan using ELISA. A total of 2,547 serum samples were collected, 66 from confirmed CE patients and 2,481 of patients with other diseases than CE at a hospital in Tashkent, Uzbekistan. The serum samples were screened for CE specific IgG antibodies by ELISA using cystic fluid antigen obtained from sheep. The serum antibody positive rate was 89.4% (59/66) in CE and 3.6% (89/2,481) in other disease patients. The present ELISA recognized 89.4% sensitivity and 96.4% specificity. The ELISA absorbance of positive samples was distributed 0.271-0.971 for CE and 0.273-0.887 for other disease patients. The other disease patients with high absorbance over 0.3 were 50 (2.0%) who were presumed to be active CE patients. The patients in their 40s showed the highest positive rate of 5.2% (P=0.181), and women were 4.4% while men were 3.1% positive (P=0.136). The data confirmed that there are many asymptomatic patients of CE in Tashkent. It is indicated that CE is an endemic disease of public health importance in Uzbekistan.     

Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and a major cause of morbidity and mortality throughout the world. It has been a major research priority to identify gene polymorphisms responsible for/associated with susceptibility and severity of S. pneumoniae infection to gain a better understanding of host genetic variants and their influence and clinical relevance to pneumococcal infections. In the present study, polymorphisms in several candidate genes, including TLR2-Arg/Gln753, TLR4-Asp/Gly299, TLR4-Thr/Ile399, CD14-159C/T and FcgammaRIIA-R/H131, were examined in 85 children with pneumococcal sepsis as an invasive pneumococcal disease and 409 healthy blood donors as controls. The prevalence of the TLR4-299/399 polymorphisms was significantly lower in the patient population than in controls (4 vs 11%; P<0.05; odds ratio (OR) 0.3; 95% confidence interval (CI) 0.1-1), while the prevalence of the CD14-159CC and FcgammaRIIA-R/R131 genotypes was significantly higher (35 vs 25%; P<0.05; OR 1.7; 95% CI 1-2.8 and 39 vs 21%; P<0.001; OR 2.5; 95% CI 1.4-4, respectively). Further, only 35% of patients carried either low-risk genotypes or protective genotypes in contrast to 61% of controls (P<0.0001; OR 2.8; 95% CI 1.7-4.6). We conclude that genetic variability in the TLR4, CD14 and FcgammaRIIA genes is associated with an increased risk of developing invasive disease in patients who are infected with S. pneumoniae.     

HER2 Ile655Val and PTEN IVS4 polymorphisms in patients with breast cancer

Although HER2/PTEN pathway is commonly disrupted in cancer, association of HER2 and PTEN polymorphisms with breast cancer (BC) remains controversial. We investigated the HER2 Ile655 Val and PTEN IVS4 polymorphisms in patients with BC in Turkish population. HER2 Ile655Val (rs 1136201) and PTEN IVS4 (rs 3830675) polymorphisms were determined using polymerase chain reaction-based restriction fragment length polymorphism (PCR–RFLP) in blood samples of 118 BC patients and 118 age-matched healthy controls. We found that the frequency of the Ile/Val genotype of HER2 Ile655Val gene was significantly higher in BC patients (p < 0.009; OR: 1,983 95 % CI: 1.181—3.328). The presence of ATCTT insertion (+/+) genotype at downstream of exon 4 in intron 4 of PTEN IVS4 gene was also associated with 1.83 fold decreased risk of BC development (p < 0.033; OR: 1.83, 95 % CI: 1.11—3.03). Analysis on clinico-pathological parameters showed neither HER2 Ile655Val nor PTEN IVS4 genotypes were not associated with any of the variables (p > 0.05).In conclusion, our findings suggest that the Ile/Val genotype of HER2 and ATCTT insertion (+/+) genotype of PTEN IVS4 gene may play an important role as genetic markers for breast cancer risk, but both genes genotypes may not be useful for predicting tumor prognosis in Turkish population.     

TAP1 and TAP2 polymorphism in coeliac disease

Coeliac disease is strongly associated with HLA-DQ2, but it is possible that additional major histocompatibility complex genes also confer disease susceptibility. Encoded close to HLA-DQ are two genes, TAP1 and TAP2, whose products are believed to transport antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 81 coeliac disease patients with caucasoid controls revealed an increased frequency of the alleles TAP1A and TAP2A in the patient population. However, no significant difference was found when patients were compared with HLA-DR and -DQ matched controls, indicating linkage disequilibrium between TAP1A, TAP2A, and HLA-DQ2. The TAP gene products do not have a major influence on susceptibility or resistance to coeliac disease in a Northern European Caucasoid population. Correspondence to: S. H. Powis.     

Meta-Analysis of the Association between Insulin-Like Growth Factor Binding Protein 3 Genetic Polymorphisms and Colorectal Cancer Susceptibility

Insulin-like growth factor binding protein 3 (IGFBP-3) plays an important role in the development and progress of cancers. The association between IGFBP-3 polymorphisms and colorectal cancer remains controversial and ambiguous. The aim of this study is to explore the association between IGFBP3 A-202C and Gly32Ala polymorphisms and colorectal cancer susceptibility using meta-analyisi. Case-control studies on the association between IGFBP3 A-202C and Gly32Ala polymorphisms and colorectal cancer, which had sufficient data for estimating an odds ratio (OR) with 95% confidence interval (CI), were included in the meta-analysis. Abstracts, case reports, editorials, and review articles were excluded. Heterozygous and homozygous mutants were compared with the wild types to estimate combined OR values and 95%CIs with Review Manager 5.0. Six eligible studies were included, with 3157 patients and 6027 controls for A-202C and 1711 patients and 2995 controls for Gly32Ala. No significant association was found in all genetic models (for A-202C, AC vs. AA, OR = 0.99(0.88–1.11), CC vs. AA, OR = 1.06(0.92–1.22), dominant model, OR = 0.98(0.88–1.09), recessive model, OR = 0.94(0.84–1.05); and for Gly32Ala polymorphism, GC vs. GG, OR = 1.10(0.92–1.31), CC vs. GG, OR = 0.93(0.76–1.14), dominant model, OR = 1.05(0.89–1.24), recessive model, OR = 0.90(0.77–1.05)). The results suggest that the IGFBP3 A-202C and Gly32Ala polymorphisms are not associated with colorectal cancer susceptibility.     

Quantitative assessment of the association between TAP2 rs241447 polymorphism and cancer risk

The findings regarding the relation of transporter associated with antigen processing (TAP) to cancer risk have been inconsistent. The aim of this study was to comprehensively evaluate the association between TAP2 rs241447 polymorphism and cancer susceptibility. A meta-analysis of nine investigations with 2800 cases and 1620 controls was conducted to gain a better understanding of the effect of TAP2 rs241447 polymorphism on cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the correlation between TAP2 gene polymorphism and cancer susceptibility. The pooled results from TAP2 rs241447 polymorphism showed a decreased risk of cancer in two dominant genetic models (GG + AG vs AA: OR = 0.86, 95% CI, 0.75-0.99; AG vs AA: OR = 0.85, 95% CI, 0.73-0.99). From the subgroup analysis, decreased cancer susceptibility was found in Caucasians (GG + AG vs AA: OR = 0.82, 95% CI, 0.68-0.99), especially among the subgroup of cervical carcinoma (GG + AG vs AA: OR = 0.82, 95% CI, 0.69-0.96; AG vs AA: OR = 0.83, 95% CI, 0.70-0.99). Overall, the results suggest that TAP2 rs241447 polymorphism contributes to decreased cancer susceptibility.     

Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children

Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Although anti-RSV Ab prophylaxis has greatly reduced infant mortality in the United States, there is currently no vaccine or effective antiviral therapy. RSV fusion (F) protein activates cells through TLR4. Two single nucleotide polymorphisms (SNPs) encoding Asp299Gly and Thr399Ile substitutions in the TLR4 ectodomain were previously associated with TLR4 hyporesponsiveness and increased susceptibility to bacterial infection. Prevalence of these SNPs was analyzed in a case series of 105 DNA samples extracted from archived nasal lavage samples from high-risk infants/young children with confirmed RSV disease who participated in two seminal clinical trials for anti-RSV prophylaxis. Frequencies of TLR4 SNPs in the case series were compared with those of literature controls, healthy adults, infants, and young children who presented with symptoms of respiratory infections (but not preselected for high risk for RSV). Both SNPs were highly associated with symptomatic RSV disease in this largely premature population (p < 0.0001), with 89.5% and 87.6% of cases being heterozygous for Asp299Gly and Thr399Ile polymorphisms versus published control frequencies of 10.5% and 6.5%, respectively. The other two control groups had similarly low frequencies. Our data suggest that heterozygosity of these two extracellular TLR4 polymorphisms is highly associated with symptomatic RSV disease in high-risk infants and support a dual role for TLR4 SNPs in prematurity and increased susceptibility to RSV not revealed by analysis of either alone.     

Impaired transporter associated with antigen processing (TAP) function attributable to a single amino acid alteration in the peptide TAP subunit TAP1

The heterodimeric peptide transporter TAP belongs to the ABC transporter family. Sequence comparisons with the P-glycoprotein and cystic fibrosis transmembrane conductance regulator and the functional properties of selective amino acids in these ABC transporters postulated that the glutamic acid at position 263 and the phenylalanine at position 265 of the TAP1 subunit could affect peptide transporter function. To define the role of both amino acids, TAP1 mutants containing a deletion or a substitution to alanine at position 263 or 265 were generated and stably expressed in murine and human TAP1(-/-) cells. The different TAP1 mutants were characterized in terms of expression and function of TAP, MHC class I surface expression, immune recognition, and species-specific differences. The phenotype of murine and human cells expressing human TAP1 mutants with a deletion or substitution of Glu(263) was comparable to that of TAP1(-/-) cells. In contrast, murine and human TAP1 mutant cells containing a deletion or mutation of Phe(265) of the TAP1 subunit exhibit wild-type TAP function. This was associated with high levels of MHC class I surface expression and recognition by specific CTL, which was comparable to that of wild-type TAP1-transfected control cells. Thus, biochemical and functional evidence is presented that the Glu(263) of the TAP1 protein, but not the Phe(265), is critical for proper TAP function.     

Serodiagnosis of Echinococcosis by ELISA Using Cystic Fluid from Uzbekistan Sheep

According to increase of travel, the cases of imported echinococcosis have been increasing in Korea. The present study was undertaken to develop a serodiagnostic system for echinococcosis in Korea. For diagnosis of echinococcosis, the fluid of Echinococcus granulosus hydatid cysts was collected from naturally infected sheep in Uzbekistan. Also serum samples of infected patients who were surgically confirmed were collected in a hospital in Tashkent, Uzbekistan. According to the absorbance of 59 echinococcosis positive and 39 negative control serum samples, the cut-off value was determined as 0.27. The sensitivity and specificity of ELISA with hydatid fluid antigen were 91.5% and 96%, respectively. The antigen cross-reacted with the serum of some cysticercosis or clonorchiasis patients. However, immunoblot analysis on the cystic fluid recognized antigenic proteins of 7-, 16-, and 24-kDa bands in their dominant protein quantity and strong blotting reactivity. In conclusion, the present ELISA system using hydatid cyst fluid antigen from Uzbekistan sheep is sensitive and specific for diagnosis of echinococcosis cases.     

The Toll-Like Receptor 4 Polymorphism Asp299Gly but Not Thr399Ile Influences TLR4 Signaling and Function

The common, co-segregating Toll-like receptor 4 (TLR4) non-synonymous single nucleotide polymorphisms (SNPs), Asp299Gly and Thr399Ile, are associated with hyporesponsiveness to inhaled lipopolysaccharide (LPS) and increased susceptibility to Gram negative pathogens in humans. The purpose of this study was to identify the relative contributions of the Asp299Gly and the Thr399Ile variants in inhibiting the function of TLR4. 293/hMD2-CD14 cell line was transfected with lentiviral constructs containing human wild type (WT) TLR4-EGFP or TLR4-EGFP with Asp299Gly, Thr399Ile or Asp299Gly/Thr399Ile complementary DNA (cDNA). Multiple stable cell lines were established for each construct: three for WT TLR4, Asp299Gly, and Thr399Ile, and only two for Asp299Gly/Thr399Ile mutants and EGFP control. We did not observe a significant effect of polymorphisms on cell surface and intracellular TLR4 expression nor were there any significant differences in TLR4 and EGFP protein levels assessed by Western blotting and confocal microscopy among the multiple cell lines of each of the constructs. All cell lines had a dose-dependent responsiveness to LPS stimulation. However, compared to the WT TLR4, cells expressing TLR4 with Asp299Gly but not Thr399Ile polymorphism produced significantly less (P<0.05) IL-8 following LPS stimulation. Similarly, cells expressing TLR4 Asp299Gly but not Thr399Ile allele had significantly lower percentage of phosphorylated and total NF-κB P65 following LPS stimulation. While we could not do statistics on the Asp299Gly/Thr399Ile group, we observed a reduced responsiveness to LPS compared to WT TLR4. Taken together, we observed that the TLR4 Asp299Gly variant, but not the Thr399Ile variant, is responsible for impaired responsiveness of TLR4 to LPS and corresponding activation of NF-κB.     

Echinococcosis: An Economic Evaluation of a Veterinary Public Health Intervention in Rural Canada

Echinococcosis is a rare but endemic condition in people in Canada, caused by a zoonotic cestode for which the source of human infection is ingestion of parasite eggs shed by canids. The objectives of this study were to identify risk factors associated with infection and to measure the cost-utility of introducing an echinococcosis prevention program in a rural area. We analyzed human case reports submitted to the Canadian Institutes for Health Information between 2002 and 2011. Over this 10 year period, there were 48 cases associated with E. granulosus/E. canadensis, 16 with E. multilocularis, and 251 cases of echinococcosis for which species was not identified (total 315 cases). Nationally, annual incidence of echinococcosis was 0.14 cases per 100 000 people, which is likely an underestimate due to under-diagnosis and under-reporting. Risk factors for echinococcosis included female gender, age (>65 years), and residing in one of the northern territories (Nunavut, Yukon, or Northwest Territories). The average cost of treating a case of cystic echinococcosis in Canada was $8,842 CAD. Cost-utility analysis revealed that dosing dogs with praziquantel (a cestocide) at six week intervals to control cystic echinococcosis is not currently cost-effective at a threshold of $20,000-100,000 per Quality Adjusted Life Year (QALY) gained, even in a health region with the highest incidence rate in Canada ($666,978 -755,051 per QALY gained). However, threshold analysis demonstrated that the program may become cost-saving at an echinococcosis incidence of 13-85 cases per 100,000 people and therefore, even one additional CE case in a community of 9000 people could result in the monetary benefits of the program outweighing costs.