High-Resolution Sonography: A New Technique to Detect Nerve Damage in Leprosy

Mycobacterium leprae, which causes leprosy, infects peripheral nerves resulting in functional impairment, ulcer formation and stigmatizing deformities. Early diagnosis of nerve involvement is important to avoid nerve related complications. We used non-invasive, high-resolution sonography (US) and color Doppler (CD) imaging to study the ulnar (UN), median (MN), lateral popliteal (LP) and posterior tibial (PT) nerves in 20 leprosy patients and compared 30 healthy Indian controls. The nerves were significantly thicker in the patients (p<0.0001 for each nerve). One of the key signs of leprosy is the presence of enlarged nerves. The kappa for clinical palpation and nerve enlargement by sonography was 0.30 for all examined nerves. Increased neural vascularity, the sign of inflammation was observed in 26% (39/152) of nerves by CD imaging. Increased CD was observed in multiple nerves in 3 of 4 patients with type 2 reaction. Significant correlation was observed between clinical parameters of grade of thickening, sensory loss and muscle weakness and US abnormalities of nerve echotexture, endoneural flow and cross-sectional area (p<0.001). We conclude that sonography is a better diagnostic tool to predict nerve damage as compared to clinical assessment. Nerve damage was sonographically more extensive and was observed in nerves considered clinically normal

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Association of genetic polymorphisms in the interleukin-10 promoter with risk of prostate cancer in Chinese

<p>Abstract</p> <p>Background</p> <p>Recent studies identified an increased risk of prostate cancer (PCa) in Caucasian men harboring polymorphisms of genes involved in innate immunity and inflammation. This study was designed to assess whether single nucleotide polymorphisms in the IL-10 promoter play a role in predisposing individuals to PCa in a Chinese population.</p> <p>Methods</p> <p>We genotyped three SNPs of the <it>IL-10 </it>promoter (-1082A/G, -819T/C and -592A/C) using polymerase chain reaction-restriction fragment length polymorphism analysis in 262 subjects with PCa and 270 age-matched healthy controls. Odds ratio and 95% confidence interval were determined by logistic regression for the associations between IL-10 genotypes and haplotypes with the risk of PCa and advanced PCa grade.</p> <p>Results</p> <p>No significant differences in allele frequency or genotype distribution were observed for any of the <it>IL-10 </it>SNPs between PCa patients and control subjects. Significantly higher frequencies of -1082G, -819C and -592C allele and GCC haplotype were observed, however, in early stage patients in comparison to advanced PCa patients (for -1082 G, 13.9% vs 6.1%, OR = 2.48, <it>P </it>= 0.005; for -819 C 40.3% vs 30.8%, OR = 1.51, <it>P </it>= 0.043; for -512C, 40.3% vs 30.8%, OR = 1.51, <it>P </it>= 0.043; and for haplotype GCC 11.1%vs 5.1%, OR = 2.66, P = 0.008, respectively).</p> <p>Conclusions</p> <p>Our results identify that <it>IL-10 </it>promoter polymorphisms might not be a risk factor for PCa in Chinese cohorts, but rather incidence of polymorphisms associates with PCa grade, suggesting that IL-10 expression may impact PCa progression.</p

Helminths and HIV infection: epidemiological observations on immunological hypotheses

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection

'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology

The Swiss-born medical researcher Karl Friedrich Meyer (1884–1974) is best known as a ‘microbe hunter’ who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer’s 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a ‘reservoir of disease’ as a forerunner of ‘one medicine’ approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer’s other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer—like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet—can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet’s and Smith’s contributions to this scientific field have been widely acknowledged, Meyer’s have been largely ignored. Drawing on Meyer’s published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer’s intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague—exchanges that not only showed how environmental and ecological conditions could ‘tip the balance’ in favor of parasites but which transformed Meyer thinking about resistance to infection and disease

HIV-induced immune activation - pathogenesis and clinical relevance. Summary of a workshop organised by the German AIDs Society (DAIG e.v.) and the ICH Hamburg, Hamburg, Germany, November 22, 2008

This manuscript is communicated by the German AIDS Society (DAIG) http://www.daignet.de. It summarizes a series of presentations and discussions during a workshop on immune activation due to HIV infection. The workshop was held on November 22nd 2008 in Hamburg, Germany. It was organized by the ICH Hamburg under the auspices of the German AIDS Society (DAIG e.V.)

Transcriptional analysis of abdominal fat in chickens divergently selected on bodyweight at two ages reveals novel mechanisms controlling adiposity: validating visceral adipose tissue as a dynamic endocrine and metabolic organ

Decades of intensive genetic selection in the domestic chicken (Gallus gallus domesticus) have enabled the remarkable rapid growth of today’s broiler (meat-type) chickens. However, this enhanced growth rate was accompanied by several unfavorable traits (i.e., increased visceral fatness, leg weakness, and disorders of metabolism and reproduction). The present descriptive analysis of the abdominal fat transcriptome aimed to identify functional genes and biological pathways that likely contribute to an extreme difference in visceral fatness of divergently selected broiler chickens. We used the Del-Mar 14 K Chicken Integrated Systems microarray to take time-course snapshots of global gene transcription in abdominal fat of juvenile [1-11 weeks of age (wk)] chickens divergently selected on bodyweight at two ages (8 and 36 wk). Further, a RNA sequencing analysis was completed on the same abdominal fat samples taken from high-growth (HG) and low-growth (LG) cockerels at 7 wk, the age with the greatest divergence in body weight (3.2-fold) and visceral fatness (19.6-fold). Time-course microarray analysis revealed 312 differentially expressed genes (FDR ≤ 0.05) as the main effect of genotype (HG versus LG), 718 genes in the interaction of age and genotype, and 2918 genes as the main effect of age. The RNA sequencing analysis identified 2410 differentially expressed genes in abdominal fat of HG versus LG chickens at 7 wk. The HG chickens are fatter and over-express numerous genes that support higher rates of visceral adipogenesis and lipogenesis. In abdominal fat of LG chickens, we found higher expression of many genes involved in hemostasis, energy catabolism and endocrine signaling, which likely contribute to their leaner phenotype and slower growth. Many transcription factors and their direct target genes identified in HG and LG chickens could be involved in their divergence in adiposity and growth rate. The present analyses of the visceral fat transcriptome in chickens divergently selected for a large difference in growth rate and abdominal fatness clearly demonstrate that abdominal fat is a very dynamic metabolic and endocrine organ in the chicken. The HG chickens overexpress many transcription factors and their direct target genes, which should enhance in situ lipogenesis and ultimately adiposity. Our observation of enhanced expression of hemostasis and endocrine-signaling genes in diminished abdominal fat of LG cockerels provides insight into genetic mechanisms involved in divergence of abdominal fatness and somatic growth in avian and perhaps mammalian species, including humans.https://doi.org/10.1186/s12864-017-4035-