Authors:Cosme Alvarado-Esquivel, Yazmin del Rosario Rico-Almochantaf, Jesús Hernández-Tinoco, Gerardo Quiñones-Canales, Luis Francisco Sánchez-Anguiano, Jorge Torres-González, Björn Schott, Oliver Liesenfeld and Ildiko Rita Dunay
Little is known about the association of Toxoplasma gondii infection and neurological disorders. We performed a case-control study with 344 patients with neurological diseases and 344 neurologically healthy age- and gender-matched subjects. Sera of participants were analyzed for anti-T. gondii IgG and IgM antibodies using commercially available immunoassays. Anti-T. gondii IgG antibodies were detected in 25 (7.3%) cases and in 35 (10.2%) controls (odds ratio [OR] = 0.69; 95% confidence interval [CI]: 0.40–1.18; P = 0.17). Anti-T. gondii IgM antibodies were found in 5 (14.3%) of the 25 IgG seropositive cases and in 13 (37.1%) of the 35 IgG seropositive controls (P = 0.15). Anti-T. gondii IgG antibodies were found in 8 (3.8%) of 213 female cases and in 23 (10.8%) of 213 female controls (OR = 0.32; 95% CI: 0.14–0.73; P = 0.005); and in 17 (13.0%) of 131 male cases and in 12 (9.2%) of 131 male controls (P = 0.32). No direct association between IgG seropositivity and specific neurological disorders was detected. We found no support for a role of latent T. gondii infection in the risk for neurological disorders in this setting. With respect to specific neurological disorders, further studies using larger patient cohorts will be required.
Authors:Ana Beatriz Dein Terra Mota Ribeiro, Markus M. Heimesaat and Stefan Bereswill
Human immunodeficiency virus (HIV) infections cause severe CD4+ T cell depletion leading to chronic inflammation and immune activation, impaired barrier function, and microbial translocation. Even under effective antiretroviral therapy, these processes persist, leading to gut microbiome dysbiosis and disturbance of microbiome–host homeostasis. This systematic review aims at analyzing how gut microbiome and host immune system influence each other during HIV pathogenesis. An online search applying the PubMed database was conducted. The number of total results (n = 35) was narrowed down to 5 relevant studies focusing on the interaction between the host and gut microbiome, whereas strict exclusion criteria were applied, thereby assuring that no other comorbidities impacted study results. Our analyses revealed that gut microbiome diversity correlated positively with CD4+ T cell counts and negatively with microbial translocation markers. However, quantitative changes in bacterial richness did not consistently correlate with the numbers of metabolically active bacterial populations. Despite the reported increase in potentially pathogenic bacteria and, conversely, decrease in protective populations, the gut microbiota exhibited immune-modulating qualities given that mucosal inflammatory sequelae were dampened by decreasing pro-inflammatory and accelerating anti-inflammatory cytokine responses. Future research is needed to further elucidate these findings, to gain a deeper insight into host–microbiota interactions and to develop novel therapeutic strategies.
Authors:Ali Konaté, René Dembélé, Nathalie K. Guessennd, Fernique Konan Kouadio, Innocent Kouamé Kouadio, Mohamed Baguy Ouattara, Wendpoulomdé A. D. Kaboré, Assèta Kagambèga, Haoua Cissé, Hadiza Bawa Ibrahim, Touwendsida Serge Bagré, Alfred S. Traoré and Nicolas Barro
The emergence and persistence of multidrug-resistant (MDR) diarrheagenic Escherichia coli (DEC) causing acute diarrhea is a major public health challenge in developing countries. The aim of this study was to evaluate the resistance phenotypes of DEC isolated from stool samples collected from children less than 5 years of age with acute diarrhea living in Ouagadougou/Burkina Faso. From August 2013 to October 2015, this study was carried out on 31 DEC strains of our study conducted in “Centre Médical avec Antenne Chirurgicale (CMA)” Paul VI and CMA of Schiphra. DEC were isolated and identified by standard microbiological methods and polymerase chain reaction (PCR) method was used to further characterize them. Antimicrobial susceptibility testing was done based on the disk diffusion method. DEC isolates were high resistant to tetracycline (83.9%), amoxicillin (77.4%), amoxicillin clavulanic acid (77.4%), piperacillin (64.5%), and colistin sulfate (61.3%). The most resistant phenotype represented was the extended spectrum β-lactamase (ESBL) phenotype (67.7%). Aminoglycosides were 100% active on enteroinvasive E. coli (EIEC) and enterohemorrhagic E. coli (EHEC). All the DEC isolates exhibited absolute (100%) sensitivity to ciprofloxacin. Monitoring and studying the resistance profile of DEC to antibiotics are necessary to guide probabilistic antibiotic therapy, especially in pediatric patients.
Authors:Luis Antonio Bautista-Hernández, José Luis Gómez-Olivares, Beatriz Buentello-Volante and Victor Manuel Bautista-de Lucio
Fibroblasts are present in all tissues but predominantly in connective tissues. Some of their functions include contractility, locomotion, collagen and elastin fiber production, and the regulation and degradation of the extracellular matrix. Also, fibroblasts act as sentinels to produce inflammatory mediators in response to several microorganisms. There is evidence that fibroblasts can synthesize toll-like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines, chemokines, and growth factors, which are important molecules involved in innate immune response against microorganisms. Fibroblasts can express TLRs (TLR-1 to TLR-10) to sense microbial components or microorganisms. They can synthesize antimicrobial peptides, such as LL-37, defensins hBD-1, and hBD-2, molecules that perform antimicrobial activity. Also, they can produce proinflammatory cytokines, such as TNFα, INFγ, IL-6, IL-12p70, and IL-10; other chemokines, such as CCL1, CCL2, CCL5, CXCL1, CXCL8, CXCL10, and CX3CL1; and the growth factors granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) to induce and recruit inflammatory cells. According to their immunological attributes, we can conclude that fibroblasts are sentinel cells that recognize pathogens, induce the recruitment of inflammatory cells via cytokines and growth factors, and release antimicrobial peptides, complying with the characteristics of real sentinels.
Authors:Elizabeth M. Marlowe, David Hardy, Mark Krevolin, Peter Gohl, Alexander Bertram, Rodney Arcenas, Britta Seiverth, Tanja Schneider and Oliver Liesenfeld
We compared the analytical and clinical performance of cobas® CT/NG for use on the cobas® 6800/8800 Systems with the cobas® 4800 CT/NG Test from urogenital and extragenital specimens in over 12,000 specimens from both male and female subjects in Germany and the United States. The analytical sensitivity was ≤40 EB/ml for Chlamydia trachomatis (CT) and ≤1 CFU/ml for Neisseria gonorrhoeae (NG). Using clinical specimens, the overall percent agreement with the cobas® 4800 CT/NG Test was >98.5%. Across urogenital specimens, there were 93 discrepant specimens; 76 (93.8%) of 81 CT discrepant specimens were 6800+/4800− and 10 (83.3%) of 12 NG discrepant specimens were 6800+/4800−. Sequencing verified CT results for 45 (61.6%) of 73 samples positive by 6800 and 1 (20%) of 5 positive by 4800. Similarly, 7 (70.0%) of 10 NG samples positive by 6800 and 1 of 2 positive by 4800 were confirmed by sequencing. Among discrepant extragenital specimens (all 6800+/4800−), 7 (50%) of 14 oropharyngeal and 23 (76.7%) of 30 anorectal CT discordant samples were confirmed as CT positive by sequencing; all 8 anorectal and 20 (90.9%) of 22 oropharyngeal NG discordant results were also confirmed as NG positive. In conclusion, cobas® CT/NG for use on the cobas® 6800/8800 Systems provides high-throughput automated solutions for sexually transmitted infection (STI) screening programs.
Authors:Markus M. Heimesaat, Gernot Reifenberger, Viktoria Vicena, Anita Illes, Gabriella Horvath, Andrea Tamas, Balazs D. Fulop, Stefan Bereswill and Dora Reglodi
Pituitary adenylate cyclase activating polypetide (PACAP) constitutes a neuropeptide that is widely distributed in the host exerting essential cytoprotective properties, whereas PACAP−/− mice display increased susceptibility to distinct immunopathological conditions. The orchestrated interplay between the gut microbiota and the host is pivotal in immune homeostasis and resistance to disease. Potential pertubations of the intestinal microbiota in PACAP−/− mice, however, have not been addressed so far. For the first time, we performed a comprehensive survey of the intestinal microbiota composition in PACAP−/− and wildtype (WT) mice starting 2 weeks postpartum until 18 months of age applying quantitative culture-independent techniques. Fecal enterobacteria and enterococci were lower in PACAP−/− than WT mice aged 1 month and ≥6 months, respectively. Whereas Mouse Intestinal Bacteroides were slightly higher in PACAP−/− versus WT mice aged 1 and 6 months, this later in life held true for Bacteroides/Prevotella spp. (≥12 months) and lactobacilli (>15 months of age). Strikingly, health-beneficial bifidobacteria were virtually absent in the intestines of PACAP−/− mice, even when still breastfed. In conclusion, PACAP deficiency is accompanied by distinct changes in fecal microbiota composition with virtually absent bifidobacteria as a major hallmark that might be linked to increased susceptibility to disease.
Authors:Cosme Alvarado-Esquivel, Ada A. Sandoval-Carrillo, Fernando Vazquez-Alaniz, José M. Salas-Pacheco, Jesús Hernández-Tinoco, Luis Francisco Sánchez-Anguiano and Elizabeth Irasema Antuna-Salcido
It is not clear whether infection with cytomegalovirus (CMV) is associated with hypertensive disorders in pregnant women. Through a case-control study design, 146 women suffering from hypertensive disorders in pregnancy (cases) and 146 age-matched normotensive pregnant women (controls) were examined for the presence of anti-CMV IgG and IgM antibodies with enzyme-linked immunoassays. IgM seropositive samples were further assayed by enzyme-linked fluorescent assay (ELFA).
Anti-CMV IgG antibodies were found in 138 (94.5%) controls and in 136 (93.2%) cases (odds ratio [OR] = 0.78; 95% confidence interval [CI]: 0.30–2.05; P = 0.62). High (>18 IU/ml) levels of anti-CMV IgG antibodies were found in 37.7% of the 138 seropositive controls and in 34.6% of the 136 seropositive cases (OR = 0.87; 95% CI: 0.53–1.43; P = 0.59). Anti-CMV IgM antibodies were found in 1 (0.7%) of the controls but in none of the cases using ELFA (P = 1.0). Seropositivity to CMV was not associated with a previous preeclampsia and was similar among cases regardless their mean systolic and diastolic blood pressures, and mean arterial blood pressure.
No serological evidence of an association between CMV infection and hypertensive disorders of pregnancy was found. Further research to elucidate the role of CMV in hypertensive disorders in pregnancy should be conducted.
Authors:Laura von Brzezinski, Paula Säring, Peter Landgraf, Clemens Cammann, Ulrike Seifert and Daniela C. Dieterich
Application of the proteasome inhibitor Bortezomib for the treatment of haematopoietic malignancies such as multiple myeloma significantly improves the average overall survival of patients. However, one of the most severe side effects is the development of peripheral neuropathies caused by neurotoxic effects of Bortezomib limiting its therapeutic efficacy. With ONX-0914 a specific inhibitor of the β5i (LMP7)-immunosubunit containing proteasomes was developed that targets exclusively the proteasome subtypes mainly expressed in immune cells including B lymphocytes as the origin of multiple myeloma. Furthermore, immunosubunitspecific inhibitors have been shown to be promising tools for the therapy of autoimmune disorders. In the presented study, we analysed the concentration-dependent impact of both inhibitors on primary neurons regarding survival rate, morphological changes, and overall viability. Our results clearly demonstrate that ONX-0914, compared to Bortezomib, is less neurotoxic suggesting its potential as a putative antineoplastic drug and as a candidate for the treatment of autoimmune disorders affecting the peripheral and/or central nervous system.
Authors:Ali Konaté, René Dembélé, Assèta Kagambèga, Issiaka Soulama, Wendpoulomdé A. D. Kaboré, Emmanuel Sampo, Haoua Cissé, Antoine Sanou, Samuel Serme, Soumanaba Zongo, Cheikna Zongo, Alio Mahamadou Fody, Nathalie K. Guessennd, Alfred S. Traoré, Amy Gassama-Sow and Nicolas Barro
Diarrheagenic Escherichia coli (DEC) is important bacteria of children’s endemic and epidemic diarrhea worldwide. The aim of this study was to determine the prevalence of DEC isolated from stool samples collected from children with acute diarrhea living in Ouagadougou, Burkina Faso. From August 2013 to October 2015, stool samples were collected from 315 children under 5 years of age suffering from diarrhea in the “Centre Médical avec Antenne Chirurgicale (CMA)” Paul VI and the CMA of Schiphra. E. coli were isolated and identified by standard microbiological methods, and the 16-plex PCR method was used to further characterize them. Four hundred and nineteen (419) E. coli strains were characterized, of which 31 (7.4%) DEC pathotypes were identified and classified in five E. coli pathotypes: 15 enteroaggregative E. coli (EAEC) (48.4%), 8 enteropathogenic E. coli (EPEC) (25.8%) with 4 typical EPEC and 4 atypical EPEC, 4 enteroinvasive E. coli (EIEC) (12.9%), 3 enterohemorrhagic E. coli (EHEC) 9.67%, and 1 enterotoxigenic E. coli (ETEC) 3.2%. The use of multiplex PCR as a routine in clinical laboratory for the detection of DEC would be a useful mean for a rapid management of an acute diarrhea in children.
Authors:Eliane von Klitzing, Stefan Bereswill and Markus M. Heimesaat
The World Health Organization has rated multidrug-resistant (MDR) Pseudomonas aeruginosa as a critical threat to human health. In the present study, we performed a survey of intestinal colonization, and local and systemic immune responses following peroral association of secondary abiotic mice with either a clinical MDR P. aeruginosa or a commensal murine Escherichia coli isolate. Depletion of the intestinal microbiota following antibiotic treatment facilitated stable intestinal colonization of both P. aeruginosa and E. coli that were neither associated with relevant clinical nor histopathological sequelae. Either stable bacterial colonization, however, resulted in distinct innate and adaptive immune cell responses in the intestines, whereas a pronounced increase in macrophages and monocytes could be observed in the small as well as large intestines upon P. aeruginosa challenge only, which also applied to colonic T lymphocytes. In addition, TNF secretion was exclusively elevated in large intestines of P. aeruginosa-colonized mice. Strikingly, association of secondary abiotic mice with MDR P. aeruginosa, but not commensal E. coli, resulted in pronounced systemic pro-inflammatory responses, whereas anti-inflammatory responses were dampened. Hence, intestinal carriage of MDR P. aeruginosa as compared to a mere commensal Gram-negative strain in otherwise healthy individuals results in distinct local and systemic pro-inflammatory sequelae.