Untangling the stranglehold through mathematical modelling of Streptococcus equi subspecies equi transmission.

Strangles, a disease caused by infection with Streptococccus equi subspecies equi (S. equi), is endemic worldwide and one of the most frequently diagnosed infectious diseases of horses. Recent work has improved our knowledge of key parameters of transmission dynamics, but important knowledge gaps remain. Our aim was to apply mathematical modelling of S. equi transmission dynamics to prioritise future research areas, and add precision to estimates of transmission parameters thereby improving understanding of S. equi epidemiology and quantifying the control effort required. A compartmental deterministic model was constructed. Parameter values were estimated from current literature wherever possible. We assessed the sensitivity of estimates for the basic reproduction number on the population scale to varying assumptions for the unknown or uncertain parameters of: (mean) duration of carriership (1∕γC), relative infectiousness of carriers (f), proportion of infections that result in carriership (p), and (mean) duration of immunity after natural infection (1∕γR). Available incidence and (sero-)prevalence data were compared to model outputs to improve point estimates and ranges for these currently unknown or uncertain transmission-related parameters. The required vaccination coverage of an ideal vaccine to prevent major outbreaks under a range of control scenarios was estimated, and compared available data on existing vaccines. The relative infectiousness of carriers (as compared to acutely ill horses) and the duration of carriership were identified as key knowledge gaps. Deterministic compartmental simulations, combined with seroprevalence data, suggest that 0.05

Severe Dumping Symptoms Are Uncommon Following Transthoracic Esophagectomy But Significantly Decrease Health-Related Quality of Life in Long-Term, Disease-Free Survivors.

BACKGROUND: High-quality documentation of dumping symptoms after esophagectomy is currently limited. The aim of the study was to describe the incidence of symptoms associated with dumping syndrome and their relationship with health-related quality of life after esophagectomy. METHODS: The study cohort was identified from prospective IRB-approved databases from two high-volume esophagectomy centers. Patients that were alive and without evidence of recurrence in April 2018 completed the validated Dumping Symptom Rating Scale and health-related quality of life questionnaires. Compound dumping symptom score was created by combining the individual scores for severity and frequency for each symptom. RESULTS: In total, 171 patients who underwent esophagectomy 1995-2017 responded to the questionnaires, corresponding to a response rate of 77.0%. Median age was 66 years and median time from operation to survey was 5.5 years. Absent or mild problems in all nine dumping symptoms were reported by 94 (59.5%) patients; 19 (12.0%) patients reported moderate or severe problems in at least three symptoms, the most common being postprandial "need to lie down," "diarrhea," and "stomach cramps." Increasing compound dumping symptom score was associated with significantly decreased function scores in all aspects of health-related quality of life except physical functioning (P < 0.005). CONCLUSIONS: Esophagectomy has the potential to change long-term eating patterns; however, the majority of patients in the study did not have severe postoperative dumping symptoms. On the other hand, moderate-to-severe dumping symptoms, which were reported by 12% of patients in this study, were strongly associated with decreased health-related quality of life.

[From the bench to the clinic: The challenge of translating platelet production in vitro]. / Du laboratoire à l'usage clinique : le défi de la production de plaquettes in vitro.

Platelet transfusions, which are currently totally dependent on altruistic donations, are absolutely necessary to the treatment of patients with thrombocytopenia following trauma, surgery or other pathologies (especially malignancies). Producing platelets in vitro represent a major technological and scientific breathrough that would address logistical issues (supply chain, stock holding…) and medical concerns (compatibility and biosafety). The translation of this innovation will need to be accompanied by rigorous quality control, harmonised between laboratory when it comes to functionality and biosafety for use in the clinic.

In vitro-derived platelets: the challenges we will have to face to assess quality and safety.

Platelet transfusions are given to patients in hospital who have a low blood platelet count (thrombocytopenia) either because of major bleeding (following trauma or surgery) or because the bone marrow production of platelets is impaired often due to chemotherapy, infiltration with malignant cells, fibrosis or genetic disorders. We are currently entirely reliant on blood donors as a source of platelets in transfusion medicine. However, the demand for platelets continues to rise, driven by an aging population, advances in medical procedures and ever more aggressive cancer therapies, while the supply of blood donors continues to remain static. In recent years, several groups have made major advances toward the generation of platelets in vitro for human transfusion. Recent successes include results in both generating mature human megakaryocytes as well as in developing bioreactors for extracting platelets from these megakaryocytes. Platelets made in vitro could address several issues inherent to platelets derived from blood donors - the ability to scale up/down more flexibly according to demand and therefore less precarious supply line, reduction of the risk of exposure to infectious agents and finally the possibility of engineering stem cells to reduce immunogenicity. Here we define the quality control tools and suggest measures for implementation across the field for in vitro platelet genesis, to aid collaboration between laboratories and to aid production of the burdens of proof that will eventually be required by regulators for efficacy and biosafety. We will do this firstly, by addressing the quality control of the nucleated cells used to make the platelets with a particular emphasis to safety issues and secondly, we will look at how platelet function measurement are addressed particularly in the context of platelets derived in vitro.

Streptococcus hillyeri sp. nov., isolated from equine trachea.

Strain 28462T, which had Gram-stain-positive, catalase-negative coccus-shaped cells, was isolated from a routine tracheal sample from a 3 year old thoroughbred horse. 16S rRNA gene sequence analysis revealed it to be most closely related to, but distinct from, Streptococcus henryi (95.7 % identity), Streptococcusplurextorum (95.8 %), Streptococcusporci (96.4 %) and Streptococcus caprae (95.1 %). Similarity values derived from sequences from sodA and rpoB genes were consistent with strain 28462T belonging to a species distinct from these four streptococci. At the whole genome level, strain 28462T had an average nucleotide identity value <95 % and an inferred DNA-DNA hybridization value <70 % when compared to S. henryi, Streptococcus. plurextorum and S. porci with no S. caprae genome sequence being available. Finally, various phenotypic characteristics distinguish strain 28462T from each of these species. Based on the genotypic and phenotypic results, it is proposed that strain 28462T is a novel species, with the name Streptococcus hillyeri sp. nov. The type strain is 28462T (=DSM 107591T=CCUG 72762T).

Serological responses of Australian horses using a commercial duplex indirect ELISA following vaccination against strangles.

OBJECTIVE: To determine the nature of serological responses in Australian horses using a commercial duplex indirect ELISA (iELISA) following vaccination against strangles. DESIGN: A group (n = 19) of client-owned horses from five properties were recruited to receive a primary course of a Streptococcus equi subsp. equi (S. equi) extract vaccine. Serological responses were determined by duplex iELISA incorporating S. equi-specific fragments of two cell wall proteins, SEQ2190 and SeM (antigens (Ag) A and C, respectively). METHODS: The horses were administered a primary strangles vaccination course. Blood was collected immediately prior to each of the three vaccinations at 2-week intervals and additionally at 28 and 56 days following the 3rd vaccination (V3). RESULTS: Significant increases in mean antibody levels of horses following vaccination were limited only to AgC, which was significantly increased at T2/V3, 14 days following V2 (ratio of geometric means = 3.7; 95% confidence interval (CI): 1.6, 8.4; P = 0.003). There was no increase in mean antibody to Ag A (ratio of geometric means = 1.4; 95% CI: 0.6, 3.2; P = 0.39). Four horses (22%) exceeded the test cut-off for AgC following vaccination. CONCLUSION: Vaccination of Australian horses is unlikely to interfere greatly with detection of strangles using the duplex iELISA. No responses would be anticipated to AgA following vaccination with Equivac© S/Equivac© 2in1 and only a minority are likely to respond to AgC. We conclude that the results of this study validate the usefulness of the duplex iELISA to assist control measures for strangles outbreaks in Australian horse populations.

An outbreak of strangles associated with a novel genotype of Streptococcus equi subspecies equi in donkeys in China during 2018.

BACKGROUND: Strangles is a highly contagious respiratory disease of equids caused by the bacterium Streptococcus equi subspecies equi. OBJECTIVES: To identify the cause of an outbreak of strangles that occurred on donkey farms within the Shandong Province of China and determine the prevalence of the disease. STUDY DESIGN: Cross-sectional. METHODS: Samples were taken from clinically affected animals to measure the prevalence of strangles within the population of donkeys at six intensive farms in China and identify the SeM type of isolate recovered from affected animals. Diagnosis was confirmed by bacterial isolation, biochemical tests and PCR. Epidemiological data were analysed using Chi-square test and a Fisher's exact two-sided test. The SeM gene of S. equi isolates recovered from affected animals was determined and compared with the SeM database PubMLST-seM. RESULTS: In July and August 2018, an outbreak of strangles occurred on six donkey farms within the Shandong Province of China. The overall prevalence of disease within the different donkey herds was 13.4%. Younger animals were worst affected with 40.3% (83/206) of donkey foals aged under 1 year exhibiting clinical signs compared with 12.5% (191/1525) of donkeys aged one to 2 years and 3.8% (17/442) of donkeys over 2 years of age. Analysis of SeM sequencing data identified that the farms were affected by the same strain of S. equi, SD201807, which contains the novel 136 allele of SeM. MAIN LIMITATIONS: Healthy donkeys were not sampled in this study. CONCLUSIONS: The number of intensive donkey breeding farms in China has risen recently. The higher numbers of animals that are in closer proximity to one another raise the potential for the transmission of infectious diseases such as strangles. This is the first description of a strangles outbreak among donkey herds in China. The Summary is available in Chinese - see Supporting information.

Streptococcus equi Infections in Horses: Guidelines for Treatment, Control, and Prevention of Strangles-Revised Consensus Statement.

This consensus statement update reflects our current published knowledge and opinion about clinical signs, pathogenesis, epidemiology, treatment, complications, and control of strangles. This updated statement emphasizes varying presentations in the context of existing underlying immunity and carrier states of strangles in the transmission of disease. The statement redefines the "gold standard" for detection of possible infection and reviews the new technologies available in polymerase chain reaction diagnosis and serology and their use in outbreak control and prevention. We reiterate the importance of judicious use of antibiotics in horses with strangles. This updated consensus statement reviews current vaccine technology and the importance of linking vaccination with currently advocated disease control and prevention programs to facilitate the eradication of endemic infections while safely maintaining herd immunity. Differentiation between immune responses to primary and repeated exposure of subclinically infected animals and responses induced by vaccination is also addressed.

Immunogenicity of phospholipase A2 toxins and their role in Streptococcus equi pathogenicity.

Streptococcus equi subsp. equi (S. equi) is the causative agent of strangles, one of the most frequently diagnosed infectious diseases of horses worldwide. Phospholipase A2 toxins (PLA2) cleave phospholipid molecules at position sn-2 contributing to the production of leukotrienes that are important inflammatory mediators. Two homologous phospholipases, SlaA and SlaB are encoded by the S. equi genome suggesting that PLA2 toxins may contribute to its pathogenicity. Here we report the immunogenicity and role of PLA2 toxins during natural and experimental infection of horses with S. equi. The levels of anti-PLA2 specific antibodies in serum from horses naturally exposed to S. equi or without exposure were measured by indirect ELISA. Furthermore, the importance of PLA2 was determined during experimental infection of Welsh Mountain ponies with a mutant strain of S. equi lacking slaA and slaB. Our results show that PLA2 toxins are immunogenic, which supports their production during natural S. equi infection, but that these toxins are not essential for the development of strangles in a susceptible natural host.

The first step in ensuring patient-centred quality of care: ask the patient.

Health providers may not be aware of their patients' needs or preferences, and patients reluctant to raise their concerns. Consequently, the first step in ensuring quality of care is to ask the patient about the care that they would like. A cross-sectional sample of 244 medical oncology outpatients were surveyed about provider-asking behaviours across six dimensions of patient-centred care defined by the Institute of Medicine. Specifically, were patients asked by clinic staff at the treatment centre about their physical and emotional symptoms, information needs to enable decision-making, preferences for involvement in decision-making, involvement of family and friends, and appointment scheduling. Patients were significantly (Cochran's χ2 (9) = 122.541, P < 0.001) less likely to be asked about emotional symptoms (35% infrequently asked), preferences for the involvement of family and friends (25% infrequently asked), and preferences for involvement in medical decision-making (23% infrequently asked). Only a minority of patients were infrequently asked about their treatment-related information needs (8%), physical symptoms (13% pain, 14% fatigue) and preferences for appointment scheduling (13%). Younger age, not Australian born and greater educational qualifications were associated with being infrequently asked. Improvements to care delivery can be made if clinic staff were to more regularly elicit patient's emotional symptoms, and their preferences for the involvement of family/friends and participation in medical decision-making.

Streptococcus equi subspecies equi in horses in Israel: seroprevalence and strain types.

The purpose of this cross-sectional study was to determine the seroprevalence of Streptococcus equi in Israel, to monitor seropositive horses over time and to identify archived strains that were recovered from Israeli horses. A serological survey of 200 healthy horses on 20 farms throughout Israel was performed to detect recent exposure to S equi antigens A and C via indirect ELISA. Seroprevalence was 9.5 per cent (19/200) and positive horses were found in 30 per cent (6/20) of the farms. Sixteen horses that returned a positive serology result were retested three and six months later. Most (12/16) positive horses remained positive, which suggests the presence of animals with persistent infection. Molecular characterisation of S equi strains by sequencing of the SeM gene of 16 archived isolates of S equi that were recovered from clinical cases of strangles between 2008 and 2012 identified two strains: SeM-2 and SeM-28.

Total knee arthroplasty with an oxidised zirconium femoral component: ten-year survivorship analysis.

AIMS: Oxidised zirconium was introduced as a material for femoral components in total knee arthroplasty (TKA) as an attempt to reduce polyethylene wear. However, the long-term survival of this component is not known. METHODS: We performed a retrospective review of a prospectively collected database to assess the ten year survival and clinical and radiological outcomes of an oxidised zirconium total knee arthroplasty with the Genesis II prosthesis. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS) and a patient satisfaction scale were used to assess outcome. RESULTS: A total of 303 consecutive TKAs were performed in 278 patients with a mean age of 68 years (45 to 89). The rate of survival ten years post-operatively as assessed using Kaplan-Meier analysis was 97% (95% confidence interval 94 to 99) with revision for any reason as the endpoint. There were no revisions for loosening, osteolysis or failure of the implant. There was a significant improvement in all components of the WOMAC score at final follow-up (p < 0.001). The mean individual components of the KOOS score for symptoms (82.4 points; 36 to 100), pain (87.5 points; 6 to 100), activities of daily life (84.9 points; 15 to 100) and quality of life (71.4 points; 6 to 100) were all at higher end of the scale. DISCUSSION: This study provides further supportive evidence that the oxidised zirconium TKA gives comparable rates of survival with other implants and excellent functional outcomes ten years post-operatively. TAKE HOME MESSAGE: Total knee arthroplasty with an oxidised zirconium femoral component gives comparable long-term rates of survival and functional outcomes with conventional implants.

The Video Interaction Guidance approach applied to teaching communication skills in dentistry.

PURPOSE: To examine dentists' views of a novel video review technique to improve communication skills in complex clinical situations. MATERIALS AND METHODS: Dentists (n = 3) participated in a video review known as Video Interaction Guidance to encourage more attuned interactions with their patients (n = 4). Part of this process is to identify where dentists and patients reacted positively and effectively. Each dentist was presented with short segments of video footage taken during an appointment with a patient with intellectual disabilities and communication difficulties. Having observed their interactions with patients, dentists were asked to reflect on their communication strategies with the assistance of a trained VIG specialist. RESULTS: Dentists reflected that their VIG session had been insightful and considered the review process as beneficial to communication skills training in dentistry. They believed that this technique could significantly improve the way dentists interact and communicate with patients. The VIG sessions increased their awareness of the communication strategies they use with their patients and were perceived as neither uncomfortable nor threatening. DISCUSSION: The VIG session was beneficial in this exploratory investigation because the dentists could identify when their interactions were most effective. Awareness of their non-verbal communication strategies and the need to adopt these behaviours frequently were identified as key benefits of this training approach. One dentist suggested that the video review method was supportive because it was undertaken by a behavioural scientist rather than a professional counterpart. CONCLUSION: Some evidence supports the VIG approach in this specialist area of communication skills and dental training.

Localised mitogenic activity in horses following infection with Streptococcus equi.

Streptococcus equi subspecies equi (S. equi) is the causative agent of strangles, a highly contagious upper respiratory disease of equids. Streptococcus equi produces superantigens (sAgs), which are thought to contribute to strangles pathogenicity through non-specific T-cell activation and pro-inflammatory response. Streptococcus equi infection induces abscesses in the lymph nodes of the head and neck. In some individuals, some abscess material remains into the guttural pouch and inspissates over time to form chondroids which can harbour live S. equi. The aim of this study was to determine the sites of sAg production during infection and therefore improve our understanding of their role. Abscess material, chondroids and serum collected from Equidae with signs of strangles were tested in mitogenic assays. Mitogenic sAg activity was only detected in abscess material and chondroids. Our data support the localised in vivo activity of sAg during both acute and carrier phases of S. equi infection.

Young brains on cannabis: It's time to clear the smoke.

Cannabis is the most commonly used illicit substance among youth. Recent policy developments and ongoing debate related to this drug underscore the urgent need to "clear the smoke" and better understand what the scientific evidence says about the health and behavioral effects of cannabis use, particularly on youth whose brains are undergoing rapid and extensive development.

Prevalence of Streptococcus dysgalactiae subsp. equisimilis and S. equi subsp. zooepidemicus in a sample of healthy dogs, cats and horses.

AIMS: To estimate the prevalence of ß-haemolytic Lancefield group C streptococci in healthy dogs, cats and horses; to determine if frequent contact with horses was associated with isolation of these species from dogs and cats; and to characterise recovered S. equi subsp. zooepidemicus isolates by multilocus sequence typing. METHODS: Oropharyngeal swabs were collected from 197 dogs and 72 cats, and nasopharyngeal swabs from 93 horses. Sampling was carried out at the Massey University Veterinary Teaching Hospital, on sheep and beef farms or on premises where horses were present. All animals were healthy and were categorised as Urban dogs and cats (minimal contact with horses or farm livestock), Farm dogs (minimal contact with horses) and Stable dogs and cats (frequent contact with horses). Swabs were cultured for ß-haemolytic Streptococcus spp. and Lancefield group C streptococcal subspecies were confirmed by phenotypic and molecular techniques. RESULTS: Of the 197 dogs sampled, 21 (10.7 (95% CI= 4.0-25.4)%) tested positive for S. dysgalactiae subsp. equisimilis and 4 (2.0 (95% CI=0.7-5.5)%) tested positive for S. equi subsp. zooepidemicus. All these isolates, except for one S. dysgalactiae subsp. equisimilis isolate in an Urban dog, were from Stable dogs. S. dysgalactiae subsp. equisimilis was isolated from one Stable cat. Of the 93 horses, 22 (23.7 (95% CI=12.3-40.6)%) and 6 (6.5 (95% CI=2.8-14.1)%) had confirmed S. dysgalactiae subsp. equisimilis and S. equi subsp. zooepidemicus isolation respectively. Isolation of S. dysgalactiae subsp. equisimilis from dogs was associated with frequent contact with horses (OR=9.8 (95% CI=2.6-72.8)). Three different multilocus sequence type profiles of S. equi subsp. zooepidemicus that have not been previously reported in dogs were recovered. CONCLUSIONS AND CLINICAL RELEVANCE: Subclinical infection or colonisation by S. equi subsp. zooepidemicus and S. dysgalactiae subsp. equisimilis occurs in dogs and further research on inter-species transmission and the pathogenic potential of these Lancefield group C streptococci is needed. Complete speciation of ß-haemolytic streptococci should be recommended in clinical cases and the possible exposure to horses and their environment should be considered in epidemiological investigations.