Community outbreak of invasive group A streptococcus infection in Ontario, Canada.

BACKGROUND: Outbreaks of invasive group A streptococcal infection (iGAS) have historically occurred in institutional settings. Increasingly, community-based outbreaks have been reported, often among marginalized populations, yet few guidelines exist for managing iGAS outbreaks in such settings. OBJECTIVE: To describe the ongoing outbreak of iGAS in Middlesex-London, Ontario, and the challenges that arose while applying current guidelines to a marginalized population in a community setting. METHODS: The outbreak investigation included all iGAS cases in Middlesex-London with an onset date from April 1, 2016 to February 28, 2018. Clinical specimens were submitted to provincial and federal laboratories for typing. Public health management of the outbreak involved environmental health inspections, contact tracing, chemoprophylaxis of close contacts, swabbing to determine colonization rates of Streptococcus pyogenes, and communicating with stakeholders and the public. RESULTS: A total of 156 confirmed cases of iGAS corresponding to 147 individuals were reported in less than two years. More than 60% of cases occurred in men (n=91) and almost half (n=71) of the total number of cases were persons who used drugs (PWUD) and/or were under-housed. Of the PWUD cases, 58 of 65 (89%) used injection drugs. Key challenges in controlling this outbreak included reaching PWUD and under-housed people; completing a case history and contact list; facilitating completion of treatment; dealing with concurrent infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV); and optimizing environmental health conditions. Guidelines were adapted so contacts who shared drugs or injection drug equipment with a known iGAS case would be offered chemoprophylaxis regardless of the clinical severity of the case. To optimize treatment completion, a single-dose of azithromycin for individuals in close contact with PWUD and/or under-housed cases was given. Cases with macrolide-resistant strain emm9 have recently emerged. CONCLUSION: The application of institution-based guidelines for iGAS outbreaks has been ineffective in controlling this particular community outbreak. There is a need for guidelines on managing outbreaks of iGAS in the community especially when an outbreak involves marginalized populations.

Use of an interferon-gamma based assay to assess bladder cancer patients treated with intravesical BCG and exposed to tuberculosis.

OBJECTIVE: Compare the QuantiFERON-TB Gold In-Tube (QFT) assay and the tuberculin skin test (TST) in bladder cancer patients receiving high dose BCG therapy (BCG patients). DESIGN AND METHODS: BCG patients and healthy visitors, both exposed to tuberculosis, were screened with a TST and QFT. RESULTS: QFT-TST correlation was excellent in visitors, but poor in BCG patients. BCG therapy predicted a positive TST (p<0.001) but not a positive QFT (p=0.35). DISCUSSION: The management of BCG patients was impacted, by measuring the QFT.

Leptospirosis in febrile men ingesting Agouti paca in South America.

To explore the relationship between the ingestion of Agouti paca (AP) and human leptospirosis in Guyana, 19 febrile men who said they had hunted and eaten A. paca were screened for malaria, using bloodsmears, and for leptospirosis, using an enzyme immuno-assay that detects Leptospira -specific IgM. Those found positive for anti-Leptospira IgM were then evaluated further, with a microscopical agglutination test based on a limited panel of serovars from three pathogenic species of Leptospira. Although six of the 18 patients who provided suitable samples for the serology were found seropositive for acute leptospirosis, only three of the 19 patients were found smear-positive for malaria. A clinical-decision model, based on medical histories, the results of physical examinations, and the use of routine urine dipsticks, and enabling prediction of the serological results, was developed. This model, which had 83% sensitivity and 100% specificity for leptospirosis, indicated that, in the absence of serology, most febrile patients reporting AP ingestion could be correctly treated if each was checked for malaria using traditional bloodsmears. The smear-positives should be treated with antimalarial drugs whereas the smear-negatives should be treated for leptospirosis if they had any of the following: a skin rash; lymphadenopathy; abnormal urine sediment (proteinuria or haematuria); and/or no previous history of malaria. In the present study, the relative risk of leptospirosis among the patients who were smear-negative for malaria and fulfilled at least one of these four criteria was 13 (P = 0.0007). In Guyana at least, leptospirosis appears to be common among men who hunt, prepare and ingest AP. Vaccines may be the best, practical form of protection among such men.

The impact of trauma exposure on the cognitive schemas of a sample of paramedics.

This study examines disruptions in cognitive schemas (i.e., core beliefs about self, others, and the world) among a sample of paramedics. Two hundred fifty-three paramedics working in non-urban and urban settings completed measures of non-work and work-related negative life event and trauma exposure, perceived social support, and cognitive schemas. Forty percent of the respondents experienced at least one disrupted schema and 18 percent had disrupted beliefs about the meaningfulness of the world. Urban paramedics experienced greater disruption in cognitive schemas, particularly with Other-Safety beliefs. The degree of disruption in schemas was independently associated with the extent of non-work and work-related negative life event and trauma exposure, as well as perceived social support. These findings suggest the importance of investigating disruptions of schemas as a posttraumatic sequela among emergency medical personnel.

Age-related distribution of cones and ON-bipolar cells in the rd mouse retina.

PURPOSE: Retinal dystrophic (rd) mice lose most of their rod photoreceptors within the first three weeks after birth. We determined the age-related distribution of peanut agglutinin lectin (PNA)-labeled cones during the first 12 months of age. We also investigated whether the density of ON-bipolar cells expressing L7 protein was affected by their loss of photoreceptor inputs. METHODS: rd mice were selected from a transgenic strain which expresses an L7-beta-galactosidase fusion gene localized to ON-bipolar cells. Cones were stained with PNA and ON-bipolar cells with bluo-gal (halogenated indolyl-beta-D-galactoside). Retinas were flat-mounted and observed at 1, 2, 3, 6 and 12 months of age. RESULTS: PNA-labeled cones are distributed unevenly across the retina at 1 month postnatal. Their concentration decreases first in the central and far peripheral retina, leaving a ring of labeled cells in the midperipheral region. At 3 months, a larger patch of cones remains in the supero-temporal midperipheral region and a smaller patch in the infero-nasal retina. By 6 months, few cones remain in the infero-nasal retina; by 1 year approximately 100 cones remain in the entire retina, localized to the superior midperipheral region. ON-bipolar cells appear evenly distributed at 1 month. By 2-3 months, relatively more bluo-gal staining is seen in the midperipheral regions underlying dense cone populations. At 6-12 months, bluo-gal label is distributed in a spotty pattern with little or no staining seen in areas of apparent neovascularization. CONCLUSIONS: (1) PNA-labeling of cones in the rd retina deteriorates in a distinct spatial pattern with the longest cone survival in the midperipheral superior retina. (2) ON-bipolar cells are more densely labeled in regions of high cone density during the early months of cone degeneration and, in later stages, show relative decreases in regions of apparent neovascularization.

Photoreceptor transplants increase host cone survival in the retinal degeneration (rd) mouse.

Retinal transplants offer a potentially interesting approach to treating human retinal degenerations, but so far little quantitative data are available on possible beneficial effects. We isolated photoreceptor layers from normal-sighted mice and grafted them into the subretinal space of retinal degeneration (rd) mice lacking rod photoreceptors. At 2 weeks after surgery, the numbers of residual host cone photoreceptors outside the graft zone were quantified following specific labelling. Examination of operated retinas revealed highly significantly greater numbers of surviving cones (mean of 38% more at 2 weeks) within the central field compared to sham-operated paired control retinas (p < 0.01). These are the first quantified data indicating a trophic effect of transplanted photoreceptors upon host cone cells. As cone cells are responsible for high acuity and colour vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to understanding underlying interactions between retinal photoreceptors.

Retinal pigment epithelial repopulation in monkeys after submacular surgery.

BACKGROUND: Transplantation of retinal pigment epithelium may be a treatment for retinal diseases, such as age-related macular degeneration and hereditary macular degeneration. Before transplantation studies are undertaken, questions concerning repopulation of retinal pigment epithelial cells in situ and photoreceptor repair after submacular surgery need to be addressed. METHODS: We removed the retinal pigment epithelium from Bruch's membrane in the macaque monkey in the macula and outside the vascular arcades. This model allowed the study of in situ retinal pigment epithelium regrowth and photoreceptor repair for 9 months following débridement. RESULTS: Fluorescein angiography revealed a window defect in the area of denuded retinal pigment epithelium. Histologic studies revealed repopulated nonpigmented retinal pigment epithelial cells in the denuded areas in both the early and late periods. At 9 months, the repopulated retinal pigment epithelium was associated with repaired, normal-appearing photoreceptor outer segments. Retinal pigment epithelium regrowth was observed only if Bruch's membrane was intact. CONCLUSIONS: Repopulation of retinal pigment epithelium in the adult primate can occur rapidly and can support the repair of damaged photoreceptors following submacular surgery.

Cochlear and retinal degeneration in the tubby mouse.

A number of autosomal recessive syndromes feature both sensorineural hearing loss and retinal degeneration. The mouse mutant tubby also combines hearing loss with progressive retinal degeneration, and thus may constitute a useful model of one form of human sensorineural deafness/retinal dystrophic syndrome. It has not been directly demonstrated that the hearing loss in this mouse involves the cochlea, however. We have examined the cochleas of adult tubby mice using light microscopy. The tubby cochlea shows pronounced degeneration of the organ of Corti and loss of afferent neurons in the base, with relative sparing of the apex. Our findings support the tubby mouse as a model of human sensorineural deafness/retinal dystrophic syndrome. Possible human counterparts include Usher's, Alstrom's, and Bardet-Biedl syndromes.

Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2.

We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of illness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections.

Retinal cell and photoreceptor transplantation between adult New Zealand red rabbit retinas.

Adult New Zealand Red (NZR) rabbits were used to determine if the techniques developed in the rat to transplant sheets of photoreceptors could be adapted to larger eyes of the rabbit. Adult donor NZR rabbit retina was cut into small strips, oriented, and drawn up in a small and flat polyethylene tube. By transscleral approach, donor retina was correctly oriented and gently placed into the subretinal space of host retinas that were previously ablated of photoreceptors by intravitreal injection of hemoglobin. Two weeks after surgery, rabbits were terminated and eyes processed for histology. Morphologic evaluation indicated that photoreceptors were transplantable between adult rabbits by adaptation of previously developed methods and that they were well maintained for 2 weeks. Transplanted photoreceptors also appeared to retain nearly normal inner and outer segment (I & OS) morphology and anti-opsin reactivity. Finally, inclusion of the inner retina also appeared to help maintain the correct I & OS apposition to the host retinal pigmented epithelium.

Explorations of otic transplantation.

Embryonic rat inner ears were transplanted to the anterior chamber of the eyes of adult rats. While considerable development was evident, the structures present were limited to the vestibular division. We hypothesized that this selective survival could be due to the rate of vascularization. To test the effects of graft vascularization we made transplants in which the internal structures were exposed by removing the apex and base of the developing cochlea. The transplants were rapidly vascularized by the iris. Many of the soft labyrinthine structures of the cochlea from 1-day-old donors showed considerable development, including the spiral limbus, basilar membrane, and organ of Corti. To test the possibility that the cochlea requires inductive or trophic support beyond Embryonic Day 15 (E15), we cotransplanted the embryonic inner ear with developing brain stem. In these transplants, we observed improved development of the cochlea, with spiral ganglion cells and an organ of Corti possessing hair cells, Deiter's cells, and pillar cells. To further address the effect of developing CNS tissue on the development of grafted inner ear, we transplanted E15 inner ears to either the cortex or the brain stem of neonatal rats. In these experiments we have seen evidence of both vestibular and cochlear sensory surfaces. In the cochlea, an organ of Corti-like structure can be seen. The possibility of neural connections with the host brain has yet to be investigated.

Photoreceptor transplantation: anatomic, electrophysiologic, and behavioral evidence for the functional reconstruction of retinas lacking photoreceptors.

We have investigated the possibility of using transplantation of immature or mature rodent photoreceptors as well as mature human photoreceptors to reconstruct retinas in which photoreceptor degeneration is either inherited or environmentally induced. To this end, we have devised methods for isolating and transplanting the outer nuclear layer (ONL) (e.g., the photoreceptor layer) to the subretinal space of mature rodents. In addition we found that if portions of the inner retina are transplanted along with the intact photoreceptor sheet, photoreceptor organization is better maintained. In ultrastructural studies of the reconstructed retina an outer plexiform-like layer (OPL) is visible at the interface of the transplanted ONL and the host inner nuclear layer, with invaginating ribbon synapses characteristic of those formed by rod photoreceptors evident within this OPL. Ribbon synapses are found only rarely in unreconstructed retina. These results suggest that synaptic connections between transplanted photoreceptors and host cells may be made. Evidence for the potential recovery of function following photoreceptor transplantation is found in visually evoked cortical responses and behavioral responses (pupillary reflex) to light stimulation of the reconstructed eye. These findings suggest the possibility that neural transplantation can reconstruct a sensory end organ--in this case the retina--to restore evoked activity and an appropriate behavioral response to sensory stimulation.

Photoreceptor rescue in the RCS rat without pigment epithelium transplantation.

Transplantation of normal retinal pigment epithelium (RPE) to the subretinal space has been reported to rescue photoreceptors in the RCS rat. Moreover, the rescue effect was surprisingly large considering the relatively small number of RPE cells transplanted. The reason for this widespread rescue of photoreceptors is not known, nor is the mechanism for outer segment phagocytosis in photoreceptors not apposed to the transplanted RPE cells. This suggests that the rescue effect may not be solely mediated by the transplanted cells. We therefore wished to test whether the transplantation surgery itself might contribute to the rescue of RCS photoreceptors. For these control experiments, we performed the surgery on juvenile RCS rats as described by others for the transplantation of RPE but instead of injecting RPE, we injected saline. We sacrificed the RCS control operates two months following surgery. In the area of the surgery (superior retinal quadrant) the outer nuclear layer (ONL) was up to 8-10 photoreceptor cells thick, while at the extreme inferior margin of the retina the ONL was almost eliminated. To investigate the role of temporary retinal detachment in photoreceptor rescue we repeated the above experiment using our trans-corneal approach to the subretinal space. This procedure results in a large temporary retinal detachment and little or no damage to the choroid and sclera.(ABSTRACT TRUNCATED AT 250 WORDS)

Antagonism by growth hormone of insulin-sensitive hexose transport in 3T3-F442A adipocytes.

We have studied the effects of GH on basal and insulin-stimulated hexose transport by 3T3-F442A adipocytes in a hormonally defined serum-free medium. Adipocytes preincubated in defined medium exhibit a low level of hexose transport which is acutely (15 min) stimulated (greater than 5-fold) by insulin (EC50, 0.1-0.2 nM). GH has acute (15-45 min) insulin-mimetic (greater than 2-fold) and chronic (4-48 h) diabetogenic (50-80%) effects on basal and insulin-stimulated hexose transport. The insulin-mimetic effect of GH has a higher EC50 (2 nM) than its diabetogenic effect (EC50, 0.2 nM). Chronic GH exposure decreases the maximal responsiveness (50-80%) and the acute sensitivity (approximately 2-fold) of hexose transport to insulin. Insulin-stimulated transport is more (approximately 5-fold) sensitive to the diabetogenic effect of GH than is basal transport. Insulin binding and degradation were not altered by chronic exposure to GH. The diabetogenic effect of GH may occur at a postinsulin binding level.

Transplantation of photoreceptors to light-damaged retina.

We investigated the possibility of reconstructing light-damaged retinas by photoreceptor transplantation. The outer nuclear layer containing the photoreceptor cells was eliminated in adult albino rat retinas by exposure to constant high-level illumination. Photoreceptors for transplantation were harvested from neonatal rats using a novel isolation technique that maintained the cellular organization of the outer nuclear layer. Transplantation was accomplished using a transcorneal approach to the subretinal space, which minimized trauma to the eye. The retina reattached to the back of the eye with transplanted photoreceptors interposed between the retina and the overlying tissues. Prelabelling with fluorescent dye enabled positive identification of the transplanted cells. The transplanted photoreceptors appeared to survive transplantation for at least 6 weeks and were immunohistochemically reactive for opsin. The antibody staining for opsin identifies the transplanted cells as photoreceptors and indicates that they are still capable of producing visual pigment and therefore may have the capacity to transduce light. These findings indicate that photoreceptors can be transplanted to form a new outer nuclear layer in a damaged mature retina.

Spatial-frequency organization in primate striate cortex.

We measured the spatial-frequency tuning of cells at regular intervals along tangential probes through the monkey striate cortex and correlated the recording sites with the cortical cytochrome oxidase (CytOx) patterns to address three questions with regard to the cortical spatial-frequency organization. (i) Is there a periodic anatomical arrangement of cells tuned to different spatial-frequency ranges? We found there is, because the spatial-frequency tuning of cells along tangential probes changed systematically, varying from a low frequency to a middle range to high frequencies and back again repeatedly over distances of about 0.6-0.7 mm. (ii) Are there just two populations of cells, low-frequency and high-frequency units, at a given eccentricity (perhaps corresponding to the magno- and parvocellular geniculate pathways) or is there a continuum of spatial-frequency peaks? We found a continuum of peak tuning. Most cells are tuned to intermediate spatial frequencies and form a unimodal rather than a bimodal distribution of cell peaks. Furthermore, the cells with different peak frequencies were found to be continuously and smoothly distributed across a module. (iii) What is the relation between the physiological spatial-frequency organization and the regions of high CytOx concentration ("blobs")? We found a systematic correlation between the topographical variation in spatial-frequency tuning and the modular CytOx pattern, which also varied continuously in density. Low-frequency cells are at the center of the blobs, and cells tuned to increasingly higher spatial frequencies are at increasing radial distances.