Zoonotic Babesia: A scoping review of the global evidence.

BACKGROUND: Babesiosis is a parasitic vector-borne disease of increasing public health importance. Since the first human case was reported in 1957, zoonotic species have been reported on nearly every continent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in humans. Predicted climate change is expected to impact the spread of vectors, which is likely to affect the distribution of vector-borne diseases including human babesiosis. METHODS: A scoping review has been executed to characterize the global evidence on zoonotic babesiosis. Articles were compiled through a comprehensive search of relevant bibliographic databases and targeted government websites. Two reviewers screened titles and abstracts for relevance and characterized full-text articles using a relevance screening and data characterization tool developed a priori. RESULTS: This review included 1394 articles relevant to human babesiosis and/or zoonotic Babesia species. The main zoonotic species were B. microti, B. divergens, B. duncani and B. venatorum. Articles described a variety of study designs used to study babesiosis in humans and/or zoonotic Babesia species in vectors, animal hosts, and in vitro cell cultures. Topics of study included: pathogenesis (680 articles), epidemiology (480), parasite characterization (243), diagnostic test accuracy (98), mitigation (94), treatment (65), transmission (54), surveillance (29), economic analysis (7), and societal knowledge (1). No articles reported predictive models investigating the impact of climate change on Babesia species. CONCLUSION: Knowledge gaps in the current evidence include research on the economic burden associated with babesiosis, societal knowledge studies, surveillance of Babesia species in vectors and animal hosts, and predictive models on the impact of climate change. The scoping review results describe the current knowledge and knowledge gaps on zoonotic Babesia which can be used to inform future policy and decision making.

Interventions to reduce non-typhoidal Salmonella in pigs during transport to slaughter and lairage: Systematic review, meta-analysis, and research synthesis based infection models in support of assessment of effectiveness.

A systematic review of the effectiveness of interventions to reduce Salmonella prevalence or concentration in pork was undertaken. A broad search was conducted in two electronic databases. Each citation was appraised using screening tools designed and tested a priori. Level 1 relevance screening excluded irrelevant citations; level 2 confirmed relevance and categorized. Data were then extracted, and intervention categories were descriptively summarized. Meta-analysis was performed to provide a summary estimate of treatment effect where two or more studies investigated the same intervention in comparable populations. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess the confidence in the estimated summary measures of intervention effect for each data subgroup. Data were also extracted from the control groups of 25 challenge trials captured by the review, to fit logistic regression models of Salmonella infection in pigs, using odds of infection as the outcome measure. The only intervention captured by the review which was significantly associated with reduced risk of Salmonella in field settings, was elimination of lairage, which is not currently feasible commercially. The logistic regression model for fecal Salmonella shedding in pigs with a random intercept for trial yielded the following predictors significantly associated with increased odds of infection: oral challenge route relative to intra-nasal, log increase in challenge dose, and elapsed time post-challenge. Univariable exact logistic regression modeling lymph node contamination post-challenge yielded the following predictors significantly associated with increased odds of Salmonella infection: younger animals relative to older ones; intra-nasal challenge route relative to oral route; and animals sampled within the first 7days post-challenge relative to those sampled at 14 or 21days. We hypothesize that the presence of absence of one or more of these predictors across studies could help to explain the inconsistent and/or non-significant findings reported for some interventions applied at lairage.

Multimodal assessment of choroideremia patients defines pre-treatment characteristics.

PURPOSE: Choroideremia (CHM) is a X-chromosomal disorder leading to blindness by progressive degeneration of choroid, retinal pigment epithelium (RPE), and retinal neurons. A current clinical gene therapy trial (NCT01461213) showed promising safety and efficacy data in a carefully selected patient population. The present study was performed to shed light on pre-treatment characteristics of a larger cohort of CHM patients using a high resolution multi-modal approach. METHODS: In a retrospective cross-sectional study, data from 58 eyes of 29 patients with clinically confirmed CHM were analysed including best-corrected visual acuity (BCVA), refractive error, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), perimetry, and tonometry. Residual retinal volume, area of residual RPE, and foveal thickness were quantified to further define natural disease progression and assess symmetry. RESULTS: We evaluated 98 data points of BCVA [0.34 ± 0.06 (logMAR); mean ± 95 % confidence interval], 80 of IOP (14.6 ± 0.6 mmHg), and 98 of refraction (-2.16 ± 1.08 spherical equivalent). Visual fields (n  = 76) demonstrated variable degrees of concentric constriction (54 % <10°, 25 % 10-30°, 21 % >30°). Mean residual RPE area on FAF (n  = 64) measured 8.47 ± 1.91 mm(2) (range 0.30-38.5 mm(2)), while mean neuroretinal volume (n  = 42) was found to be 1.76 ± 0.12 mm(3). Age at examination was exponentially associated with BCVA, while logarithmic functions best described progressive loss of retinal area and volume. A high degree of left to right symmetry was found in all modalities with structural markers showing the best correlation (r (2) area = 0.83; r (2) volume = 0.75). CONCLUSION: Analysis of these widely available clinical data defines the natural disease characteristics of a relevant patient population eligible for gene therapeutic intervention. In the wake of preliminary reports on safety and efficacy of CHM gene therapy (NCT01461213), this multi-modal assessment of a cohort of CHM patients provides important evidence of the natural rate of disease progression and degree of symmetry between eyes.

Assessment of the efficacy and quality of evidence for five on-farm interventions for Salmonella reduction in grow-finish swine: a systematic review and meta-analysis.

Five on-farm practices for reduction of Salmonella shedding or sero-prevalence in grow-finish swine were selected through scoping study and expert consultation. Specific examples were selected based on supporting evidence from at least one controlled trial (CT), and availability to Canadian swine producers. Efficacy was evaluated using systematic review and meta-analysis (SR-MA) methodology. A modified Grading of Recommendations, Assessment, and Evaluation (GRADE) approach was applied to assess the quality of evidence for each intervention, and a 'summary of findings' table was developed to present findings 'at-a-glance'. MA of the small dataset of CTs investigating feeding meal, and measuring serology, yielded a significant summary estimate of efficacy (odds ratio (OR)=0.21; 95% confidence intervals (CI): 0.14, 0.31) with non-significant heterogeneity (P>0.10). MA of the dataset investigating inclusion of organic acids in the ration, measuring serology, yielded a significant summary estimate with significant heterogeneity across studies (P<0.001, I(2)=91%) precluding presentation of a single summary estimate; a range of results were reported (OR Range: 28 (1.6, 498); 0.07 (CI: 0.042, 0.33)). Pen disinfection between batches of finishers was studied in one large CT measuring both fecal culture (OR 0.84 (0.68, 1.1)) and serology (OR 0.48 (0.40, 0.58)) outcomes. The dataset investigating Salmonella spp. vaccination contained inconsistent findings (OR Range: 4.5 (1.3, 15); 0.07 (0.008, 0.68)), with significant heterogeneity across studies (P=0.005, I(2)=82), assessed measuring fecal culture. MA of the dataset investigating inclusion of in-feed tetracyclines yielded a significant OR indicating a potential harmful effect, measuring fecal culture, (OR Range: 14 (1.9, 108); 1.0 (0.43, 2.5)) with significant heterogeneity (P=0.003, I(2)=82%) across studies, suggesting some potential for withdrawal of in-feed tetracyclines to reduce Salmonella shedding. Therefore our ranking of intervention efficacy is: feeding meal>inclusion of acids in ration, feeder pen disinfection or Salmonella spp. vaccination>in-feed tetrayclines. Study design characteristics increasing risk of bias, including failure to justify sample size (19 of 31 studies) and failure to report random or systematic sampling (13 of 31 studies), resulted in modified GRADE evidence rankings of 'low' for these interventions. This suggests that further research is likely to affect our findings. Field CTs investigating herd-level interventions with measurements at the herd- and individual-levels are recommended. Overall, SR-MA was a useful approach for ranking efficacy, and GRADE offered a transparent method for ranking quality of evidence, although both were limited by the small number of comparable studies available.

Positioning of electronic subretinal implants in blind retinitis pigmentosa patients through multimodal assessment of retinal structures.

PURPOSE: To optimize methods for positioning subretinal visual implants, customizing their cable length, guiding them to the predetermined retinal position, and evaluating their performance. METHODS: Ten eyes of 10 patients (6 male, 4 female, mean age 46.4 years) were investigated before implantation of a subretinal visual implant. The structural characteristics of the retina as well as the ocular dimensions were determined. Topographic images of the prospective implantation site were subdivided into grids of squares. Each square received a weighted score for suitability. The sum of the scores was calculated, and the region with the highest score was chosen for the implant. In each case, the implant's power supply cable length was calculated by means of magnetic resonance imaging. The planned and achieved positions before and after implantation were compared. RESULTS: The mean light sensitivity ratio between the area actually covered by the chip and that of the planned position was 90.8% with an SD of 11.4%. In two cases with almost perfect positioning, the computed ratio was 100%. Measurements showed that to achieve a 95% sensitivity rate the difference between the planned and achieved chip position must be less than 1.7 mm. Preoperative calculations of the intraocular cable length proved accurate in all cases. CONCLUSIONS: Preoperative evaluation of retinal structures and eye morphology is useful for guiding a retinal implant to the designated area. It is a meaningful tool for planning and performing retinal chip implantation, and it optimizes personalized implantation. (ClinicalTrials.gov numbers, NCT00515814, NCT01024803.).

Basic quantitative assessment of visual performance in patients with very low vision.

PURPOSE: A variety of approaches to developing visual prostheses are being pursued: subretinal, epiretinal, via the optic nerve, or via the visual cortex. This report presents a method of comparing their efficacy at genuinely improving visual function, starting at no light perception (NLP). METHODS: A test battery (a computer program, Basic Assessment of Light and Motion [BaLM]) was developed in four basic visual dimensions: (1) light perception (light/no light), with an unstructured large-field stimulus; (2) temporal resolution, with single versus double flash discrimination; (3) localization of light, where a wedge extends from the center into four possible directions; and (4) motion, with a coarse pattern moving in one of four directions. Two- or four-alternative, forced-choice paradigms were used. The participants' responses were self-paced and delivered with a keypad. RESULTS: The feasibility of the BaLM was tested in 73 eyes of 51 patients with low vision. The light and time test modules discriminated between NLP and light perception (LP). The localization and motion modules showed no significant response for NLP but discriminated between LP and hand movement (HM). All four modules reached their ceilings in the acuity categories higher than HM. CONCLUSIONS: BaLM results systematically differed between the very-low-acuity categories NLP, LP, and HM. Light and time yielded similar results, as did localization and motion; still, for assessing the visual prostheses with differing temporal characteristics, they are not redundant. The results suggest that this simple test battery provides a quantitative assessment of visual function in the very-low-vision range from NLP to HM.