Travel-related Zika virus cases in Canada: October 2015-June 2017.

BACKGROUND: Zika virus (ZIKV) is an emerging mosquito-borne disease that can cause severe birth defects if contracted congenitally. Since late 2015, there has been a large increase in the number of travel-related cases of Zika virus infection in Canada. OBJECTIVE: The objective of this study was to describe the epidemiology of travel-related Zika cases in Canada from October 2015 to June 2017 and review them in the context of the international outbreak in the Americas. METHODS: Zika virus infections were confirmed by polymerase chain reaction (PCR) detection of viral RNA and/or the serological identification of ZIKV-specific antibodies in serum. Cases of ZIKV infection were identified by provincial and territorial health authorities, and reported on a regular basis to the Public Health Agency of Canada (PHAC). Case information requested included date of illness onset, age category, sex, pregnancy status, and location(s) and dates of travel. Estimates for the monthly number of Canadians travelling outside of Canada to other countries in the Americas were obtained from Statistics Canada and the International Air Transport Association (IATA). Data to produce the epidemic curves of autochthonous cases for each region of the Americas were extracted from country-specific epidemic curves on the Pan American Health Organization website. RESULTS: As of June 7, 2017, 513 laboratory confirmed cases and two Zika-related birth/fetal anomalies were reported across all 10 provinces. Illness in Canadian travellers generally coincided with outbreak intensity in the country of exposure rather than travel volume. There has been no evidence of autochthonous (local) transmission in Canada. Currently, cases are on the decline both in Canada and internationally. CONCLUSION: The surge in Canadian ZIKV infections in 2016 was directly related to the incursion and spread of ZIKV into the Americas. Although cases are now on the decline worldwide, it remains to be seen whether a resurgence of cases in previously affected or new areas will occur. Both outbreak intensity and seasonality of ZIKV transmission should be monitored over time in order to inform the timing of public health education campaigns, as some may turn out to be more effective in the off-peak travel season when the risk of disease transmission may be higher. Ongoing education and awareness among travellers, particularly for pregnant women and those planning pregnancies, is still indicated.

The Canadian Rabies Management Plan: An integrated approach to the coordination of rabies activities in Canada.

Although human cases of rabies are exceptionally rare in Canada, rabies remains endemic in some animal populations thus creating the need for ongoing vigilance. Rabies has always been a shared responsibility among local, provincial/territorial and federal authorities, as reflected in the 2009 Canadian Rabies Management Plan. Since 2009, a number of changes in rabies management have occurred, including the development of new tests, an oral rabies vaccine for wildlife, lessons learned from recent animal cases and changes in federal, provincial and territorial responsibilities in 2014. Federal departments and agencies continue to support rabies management through a number of activities. As the rabies landscape continues to evolve, so too must the strategies and frameworks required to manage this disease. As a result, the Canadian Rabies Management Plan and the North American Rabies Management Plan are being revised.

Q fever outbreak among travelers to Germany associated with live cell therapy - United States and Canada, 2014: a co-publication.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Q fever is a zoonotic disease caused by Coxiella burnetii and is usually transmitted through inhalation of air contaminated with animal excreta. The disease is considered to be underdiagnosed because symptoms are nonspecific and can vary from patient to patient, making diagnosis difficult. WHAT IS ADDED BY THIS REPORT?: During September-October 2014, the New York State Department of Health identified Q fever in five patients with exposure to a treatment known as live cell therapy, an alternative medicine practice involving injections of fetal sheep cells, which is a type of xenotransplantation. Investigation revealed that a group of U.S. residents traveled to Germany twice a year to receive this treatment. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Clinicians should consider zoonotic diseases, such as Q fever, in patients whose history includes receipt of a treatment known as live cell therapy. International travel for xenotransplantation procedures can facilitate transmission of zoonotic disease.

Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine.

A retrospective review was conducted of yellow fever vaccination among laboratory workers receiving annual serologic assessment to determine the initial and long-term response after boosting. Patients were divided into three groups based on pre-vaccination serology: Group 1, 1:10; Group 2, 1:20-1:40 and Group 3, >1:40. The percent with > or = four-fold increase in titers after booster vaccination were: 78% (646/829, Group 1), 65% (79/121, Group 2) and 10% (8/79, Group 3) (p<0.0001). The median times to titer failure (<1:40) were 798 days (Group 1), 3340 days (Group 2) and 7709 days (Group 3) (p<0.0001). Pre-vaccination serology influenced the initial and long-term response to yellow fever booster vaccination.

[125I]iodo-epidermal growth factor binding and mitotic responsiveness of porcine granulosa cells are modulated by differentiation and follicle-stimulating hormone.

Epidermal growth factor (EGF) stimulates granulosa cell (GC) proliferation of certain species and modulates FSH-induced GC differentiation. The present study was undertaken to characterize the binding properties of the EGF receptor in porcine GCs to determine if the EGF responsiveness of mitotically active porcine GCs was related to their differentiated state and was regulated by reproductive hormones in vitro. Characterization of the EGF receptor-binding properties of porcine GCs revealed that saturation binding was achieved with 10 ng/ml [125I]iodo-EGF after 1 h at 37 C. In all states of differentiation, porcine GCs expressed few (less than 20,000/cell), specific, high affinity EGF receptors with apparent Kd values of 5.5 +/- 0.7 X 10(-10) M (mean +/- SEM; n = 6). Freshly harvested GCs obtained from small follicles were considered slightly differentiated (SDs) and bound, on the average, 2.6-fold more [125I]iodo-EGF than highly differentiated cells (HDs) obtained from large follicles which had further differentiated in vivo. The difference in binding was due to a decrease in receptor number and not to a change in receptor affinity. This relationship observed in freshly harvested cells was maintained in culture for a limited period. At 48 h of culture, the [125I]iodo-EGF-binding capacity of SDs was higher than that of HDs and was inversely related to the state of differentiation, as measured by [125I]iodo-LH/hCG-binding capacity. After 96 h, however, the EGF-binding capacity of HDs increased 3.7-fold from the level of binding at 48 h, while the LH/hCG-binding capacity decreased 10-fold. Conversely, the EGF-binding capacity of SDs decreased 28%, while the LH/hCG-binding capacity remained low. These experiments indicated that the state of GC differentiation was inversely correlated with EGF receptor number and that this relationship was not maintained in culture beyond 48 h. FSH treatment within the first 48 h of culture decreased the EGF-binding capacity of SDs 35% relative to the control value, but estradiol and dihydrotestosterone had no effect. FSH also regulated the mitotic responsiveness to EGF. EGF treatment of cultured SDs stimulated an 84% increase in cell number and a 178% increase in [3H]thymidine incorporation. These effects were suppressed by a high concentration of FSH. Thus, the ability of porcine GCs to bind EGF was changed with differentiation in vivo, while both EGF-binding capacity and mitotic responsiveness were regulated by exposure to FSH in vitro.

Epidermal growth factor enhances [125I]iodo-follicle-stimulating hormone binding by cultured porcine granulosa cells.

Epidermal growth factor (EGF) has been shown to have diverse effects on granulosa cells (GC). Although a potent mitogen for GC from several species, EGF attenuates many FSH-mediated processes associated with GC differentiation, suggesting that EGF promotes cell proliferation at the expense of cell differentiation. The extent to which EGF effects involve modulation of the FSH receptor level in proliferating GC has not been established. Accordingly, we investigated the effect of EGF on [125I]iodo-FSH binding by porcine GC isolated from small follicles maintained in monolayer cultures. Relative to cells cultured in medium with insulin alone, EGF treatment increased total monolayer [125I]iodo-FSH binding (per culture) 120% (P less than 0.005). This was due to a 40-50% (P less than 0.01) increase in binding per U protein and/or per U cell and a 40-60% (P less than 0.005) increase in both monolayer cell and protein contents. EGF stimulated GC hyperplasia, but not hypertrophy. Optimum EGF doses for increased total monolayer [125I]iodo-FSH binding and binding normalized per U protein or cell were 0.5 and 0.1 ng/ml, respectively. Fibroblast growth factor was 20- to 100-fold less potent than EGF, and thrombin was without effect. Whereas [125I]iodo-FSH binding per U protein or cell was not affected by the serum concentration of the culture medium, the EGF effects on total monolayer binding and cell proliferation were directly related to the serum concentration (P less than 0.005). Thus, EGF-mediated increases in total monolayer [125I]iodo-FSH binding were paralleled by increases in cell number. The equilibrium dissociation constants (Kd) for [125I]iodo-FSH binding to cells cultured with and without EGF were 5.3 and 2.5 X 10(-10) M, respectively. Thus, EGF treatment significantly increased FSH receptor number, but significantly decreased receptor-binding affinity (P less than 0.05). Chronic FSH treatment during monolayer culture decreased total monolayer [125I]iodo-FSH binding and binding per U protein or per cell and attenuated EGF-stimulated cell proliferation, but markedly stimulated cell hypertrophy. Thus, concomitant treatment with EGF and FSH stimulated cell hypertrophy rather than hyperplasia. EGF and FSH each would appear capable of modulating the action of the other with respect to GC function. Our results indicate that EGF-mediated GC proliferation is associated with the expression of FSH-binding sites. This appears to be due to both an increase in FSH receptors among the cell population and an increase in the monolayer cell population.(ABSTRACT TRUNCATED AT 400 WORDS)

A serum-free defined culture system which maintains follicle-stimulating hormone responsiveness and differentiation of porcine granulosa cells.

A serum-free defined culture system has been developed that maintains follicle-stimulating hormone (FSH)-dependent differentiation of porcine granulosa cells from small follicles for up to six days in culture. Confluent monolayers of epithelioid cells were established after culture on fibronectin-coated culture dishes (FBN, 2 micrograms/cm2) in nutrient medium supplemented with human low-density lipoprotein (LDL, 10 micrograms/ml), insulin (I, 1 microgram/ml), and thrombin (TH, 1 NIH U/ml). Each of these factors was necessary to maintain the epithelioid morphology of the monolayers that attained 70% of the protein content and 71% of the cell number of replicate cultures maintained in nutrient medium supplemented with 10% fetal calf serum and insulin. Addition of FSH to the FBN/LDL/I/TH-supplemented cultures resulted in dose-dependent increases in progesterone secretion and [125I]-iodo-human chorionic gonadotropin (hCG) binding comparable to those obtained in the cultures containing serum. These results indicate that the attachment, epithelioid morphology, and differentiated function of porcine granulosa cells (GCs) can be maintained in defined culture conditions. This culture system will facilitate study of the effects of growth promoters and differentiative agents on GC function in the absence of poorly defined serum supplements.