Sustained Toll-Like Receptor 9 Activation Promotes Systemic and Cardiac Inflammation, and Aggravates Diastolic Heart Failure in SERCA2a KO Mice.

AIM: Cardiac inflammation is important in the pathogenesis of heart failure. However, the consequence of systemic inflammation on concomitant established heart failure, and in particular diastolic heart failure, is less explored. Here we investigated the impact of systemic inflammation, caused by sustained Toll-like receptor 9 activation, on established diastolic heart failure. METHODS AND RESULTS: Diastolic heart failure was established in 8-10 week old cardiomyocyte specific, inducible SERCA2a knock out (i.e., SERCA2a KO) C57Bl/6J mice. Four weeks after conditional KO, mice were randomized to receive Toll-like receptor 9 agonist (CpG B; 2µg/g body weight) or PBS every third day. After additional four weeks, echocardiography, phase contrast magnetic resonance imaging, histology, flow cytometry, and cardiac RNA analyses were performed. A subgroup was followed, registering morbidity and death. Non-heart failure control groups treated with CpG B or PBS served as controls. Our main findings were: (i) Toll-like receptor 9 activation (CpG B) reduced life expectancy in SERCA2a KO mice compared to PBS treated SERCA2a KO mice. (ii) Diastolic function was lower in SERCA2a KO mice with Toll-like receptor 9 activation. (iii) Toll-like receptor 9 stimulated SERCA2a KO mice also had increased cardiac and systemic inflammation. CONCLUSION: Sustained activation of Toll-like receptor 9 causes cardiac and systemic inflammation, and deterioration of SERCA2a depletion-mediated diastolic heart failure.

The first step toward diagnosing female genital schistosomiasis by computer image analysis.

Schistosoma haematobium causes female genital schistosomiasis (FGS), which is a poverty-related disease in sub-Saharan Africa. Furthermore, it is co-endemic with human immunodeficiency virus (HIV), and biopsies from genital lesions may expose the individual to increased risk of HIV infection. However, microscopy of urine and hematuria are nonspecific and insensitive predictors of FGS and gynecological investigation requires extensive training. Safe and affordable diagnostic methods are needed. We explore a novel method of diagnosing FGS using computer color analysis of colposcopic images. In a cross-sectional study on young women in an endemic area, we found strong associations between the output from the computer color analysis and both clinical diagnosis (odds ratio [OR] = 5.97, P < 0.001) and urine microscopy for schistosomiasis (OR = 3.52, P = 0.004). Finally, using latent class statistics, we estimate that the computer color analysis yields a sensitivity of 80.5% and a specificity of 66.2% for the diagnosis of FGS.

Colourimetric image analysis as a diagnostic tool in female genital schistosomiasis.

Female genital schistosomiasis (FGS) is a highly prevalent waterborne disease in some of the poorest areas of sub-Saharan Africa. Reliable and affordable diagnostics are unavailable. We explored colourimetric image analysis to identify the characteristic, yellow lesions caused by FGS. We found that the method may yield a sensitivity of 83% and a specificity of 73% in colposcopic images. The accuracy was also explored in images of simulated inferior quality, to assess the possibility of implementing such a method in simple, electronic devices. This represents the first step towards developing a safe and affordable aid in clinical diagnosis, allowing for a point-of-care approach.

HIV target cells in Schistosoma haematobium-infected female genital mucosa.

The parasite Schistosoma haematobium frequently causes genital lesions in women and could increase the risk of human immunodeficiency virus (HIV) transmission. This study quantifies the HIV target cells in schistosome-infected female genital mucosa. Cervicovaginal biopsies with and without schistosomiasis were immunostained for quantification of CD4(+) T lymphocytes (CD3, CD8), macrophages (CD68), and dendritic Langerhans cells (S100 protein). We found significantly higher densities of genital mucosal CD4(+) T lymphocytes and macrophages surrounding schistosome ova compared with cervicovaginal mucosa without ova (P = 0.034 and P = 0.018, respectively). We found no increased density of Langerhans cells (P = 0.25). This study indicates that S. haematobium may significantly increase the density of HIV target cells (CD4(+) T lymphocytes and macrophages) in the female genitals, creating a beneficial setting for HIV transmission. Further studies are needed to confirm these findings and to evaluate the effect of anti-schistosomal treatment on female genital schistosomiasis.