SARS-CoV-2 and Influenza A virus Co-infections in Ferrets

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are co-circulating in the human population. However, only a few cases of viral co-infection with these two viruses have been documented in humans with some people having severe disease and others mild disease. In order to examine this phenomenon, ferrets were co-infected with SARS-CoV-2 and human seasonal influenza A viruses (IAVs) (H1N1 or H3N2) and were compared to animals that received each virus alone. Ferrets were either immunologically naïve to both viruses or vaccinated with the 2019-2020 split-inactivated influenza virus vaccine. Co-infected naive ferrets lost significantly more body weight than ferrets infected with each virus alone and induced more severe inflammation in both the nose and lungs than ferrets single-infected with each virus. Co-infected naïve animals had predominantly higher IAV titers than SARS-CoV-2 titers, and IAVs efficiently transmitted to the co-housed ferrets by direct contact. Comparatively, SARS-CoV-2 failed to transmit to the ferrets that co-housed with co-infected ferrets by direct contact. Moreover, vaccination significantly reduced IAVs virus titers and shortened the viral shedding, but did not completely block influenza virus direct contact transmission. Notably, vaccination significantly ameliorated the influenza associated disease by protecting vaccinated animals from severe morbidity after IAV single infection or IAV and SARS-CoV-2 co-infection, suggesting that seasonal influenza virus vaccination is pivotal to prevent severe disease induced by IAVs and SARS-CoV-2 co-infection during the COVID-19 pandemic. Importance Influenza A viruses cause severe morbidity and mortality during each influenza virus season. The emergence of SARS-CoV-2 infection in the human population offers the opportunity to potential co-infections of both viruses. The development of useful animal models to asses pathogenesis, transmission, and viral evolution of these viruses as the co-infect a host is of critical importance for the development of vaccines and therapeutics. The ability to prevent the most severe effects of viral co-infections can be studied using effect co-infection ferret models described in this report.

Fatal infection with Versteria sp. in a muskrat, with implications for human health

The Taeniidae tapeworms are a family of helminths that have a similar life cycle, with intermediate hosts developing characteristic cysts in visceral organs. We describe here a case in Pennsylvania, USA, of fatal Versteria infection in a muskrat ( Ondatra zibethicus), which, to our knowledge, has not been reported to develop disease associated with infection. Postmortem examination revealed widespread tissue loss and replacement by solid-bodied cestode larvae with minimal adjacent inflammation in many visceral organs, most severe in the lungs, liver, and brain. Key morphologic features via histology included cephalic structures and short rostellar hooklets, which are characteristic for the genus. Genetic characterization confirmed the cestode as being an undescribed lineage of Versteria that has been implicated as the cause of severe morbidity and mortality in humans and nonhuman primates in North America. Considering the zoonotic significance of this pathogen, our report expands on the limited literature regarding disease caused by Versteria and emphasizes the need to identify the causative tapeworm more accurately, especially in rodent intermediate hosts given that previous reports do not have molecular confirmation of species.

Management of New Born with Harlequin Ichthyosis: A Rare Disease Condition

Harlequin ichthyosis is the most severe form of non-bullous ichthyosis, which is unusual in newborns and is usually marked by deadly excessive keratinization of the skin. Ichthyosis is a family of genetic skin disorders, characterized by dry, thickened, scaly skin with severe morbidity and mortality. The term “harlequin” derives from the facial appearance and the triangular and diamond-shaped pattern of the scaly skin. It occurs in about 1 in 300,000 births and has no known sex predilection. The disorder affects the skin in utero causing thick, horny, armory-like plates that cover the skin with contraction abnormalities of the eyes, ears, mouth and appendages. There is no specific guideline to manage the newborn of harlequin ichthyosis, in that nursing care is most important in the initial phase. There are required multi-disciplinary teams to take care of harlequin ichthyosis.

Periviable Breech Delivery Decision Analysis

Background/Objective: The optimal mode of delivery (MOD) for malpresentation in periviable deliveries (22-24 weeks), remains a source of debate. Neonatal and maternal complications can arise from both vaginal (VD) and cesarean delivery (CD), and the threat of maternal morbidity extends to subsequent pregnancies. It has been difficult to compare these risks while counseling patients about MOD options, so we sought to create a decision tree that maps probable outcomes associated with breech deliveries at 23- and 24-weeks’ gestation, as well as complications posed for subsequent pregnancies. Methods: An extensive literature review was conducted to identify risk estimates of periviable maternal and neonatal outcomes, along with elective repeat CD (ERCD) and trial of labor after cesarean (TOLAC) for subsequent pregnancies. Probabilities were inputted into TreeAge software, starting with primary maternal health states that may result from CD and VD – “death”, “hysterectomy”, or “no hysterectomy”, followed by the probability of neonatal health states– “death”, “severe morbidity”, or “no severe morbidity”. The likelihood of placenta previa or normal placenta was considered for subsequent pregnancies. We factored in the possibility of ERCD or TOLAC and the associated maternal and neonatal risks for each. Results: Final design of the tree is complete and risk estimates have been inputted. Primary analysis and sensitivity analyses are planned for August 2021. Ultimately, we will also be able to use measured utility values to calculate quality adjusted life years (QALYs) for each health state. Conclusion and Clinical Impact: Whether CD or VD is optimal for breech presentation in periviable delivery is influenced by a complex array of factors, including future reproductive plans and maternal values related to potential neonatal and maternal morbidity and mortality. Quantifying risks associated with each MOD will aid providers in their efforts to help families make informed decisions and reduce morbidity across the reproductive lifespan.

Risk Factors for Adverse Maternal Outcomes following Expectantly Managed Preterm Prelabor Rupture of Membranes

Objective We sought to characterize the incidence and risk factors associated with developing maternal morbidity following preterm prelabor rupture of membranes. Study Design Retrospective case–control study of patients with preterm prelabor rupture of membranes at a single institution from 2013 to 2019 admitted at ≥23 weeks gestational age. The primary outcome was a composite of maternal morbidity which included: death, sepsis, intensive care unit (ICU) admission, acute kidney injury, postpartum dilation and curettage, postpartum hysterectomy, venous thromboembolism, postpartum hemorrhage, postpartum wound complication, postpartum endometritis, pelvic abscess, postpartum pneumonia, readmission, and/or need for blood transfusion were compared with patients without above morbidities. Severe morbidity was defined as: death, ICU admission, venous thromboembolism, acute kidney injury, postpartum hysterectomy, sepsis, and/or transfusion >2 units. Demographics, antenatal, and delivery characteristics were compared between patients with and without maternal morbidity. Bivariate statistics and regression models were used to compare outcomes and calculate adjusted odd ratios. Results Of 361 included patients, 64 patients (17.7%) experienced maternal morbidity and nine (2.5%) had severe morbidity. Patients who experienced maternal morbidity were significantly (p < 0.05) more likely to be older, have private insurance, have BMI ≥40, have chorioamnionitis at delivery, and undergo cesarean or operative vaginal delivery when compared with patients who did not experience morbidity. After controlling for confounders, cesarean delivery (aOR 2.38, 95% CI[1.30,4.39]), body mass index ≥40 at admission (aOR 2.54, 95% CI[1.12,5.79]), private insurance (aOR 3.08, 95% CI[1.54,6.16]), and tobacco use (aOR 3.43, 95% CI[1.58,7.48]) were associated with increased odds of maternal morbidity. Conclusion In this cohort, maternal morbidity occurred in 17.7% of patients with preterm prelabor rupture of membranes. Private insurance, body mass index ≥40, tobacco use, and cesarean delivery were associated with higher odds of morbidity. These data can be used in counseling and to advocate for smoking cessation. Key Points

Larotrectinib (Vitrakvi)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses larotrectinib (Vitrakvi); 25 mg and 100 mg capsules (as larotrectinib sulphate) and 20 mg/mL oral solution (as larotrectinib sulphate). Indication: For the treatment of adult and pediatric patients with solid tumours that: have an NTRK gene fusion without a known acquired resistance mutation are metastatic or where surgical resection is likely to result in severe morbidity have no satisfactory treatment options

Intraparenchymal Cerebral Hemorrhage

Intraparenchymal cerebral hemorrhage (ICH) is the presence of blood in the brain parenchyma. It is a neurologic emergency and may carry severe morbidity and death. This chapter focuses mainly on spontaneous, nontraumatic ICH (ie, hemorrhage not related to trauma, arteriovenous malformation, cerebral aneurysm, or tumor). ICH accounts for 15% to 20% of all new strokes annually. Among the US general population, the incidence is 15 cases per 100,000 person-years.

Vaccination against COVID-19 and society’s return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine-induced immunity

ObjectivesTo project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2024 in England.DesignDeterministic, compartmental, discrete-time Susceptible-Exposed-Infectious-Recovered (SEIR) modelling.ParticipantsPopulation in England.InterventionsMass vaccination programmes.Outcome measuresDaily and cumulative number of deaths from COVID-19.ResultsIf vaccine efficacy remains high (85%), the vaccine-induced sterilising immunity lasts ≥182 days, and the reinfectivity is greatly reduced (by ≥60%), annual mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under optimistic scenarios, with annual revaccination programmes, the cumulative number of COVID-19 deaths is estimated to be from 130 000 to 150 000 by the end of 2024. However, the total number of COVID-19 deaths may be up to 431 000 by the end of 2024, under scenarios with compromised vaccine efficacy (62.5%), short duration of natural and vaccine immunity (365/182 days) and small reduction in reinfectivity (30%). Under the assumed scenarios, more frequent revaccinations are associated with smaller total numbers and lower peaks of daily deaths from COVID-19.ConclusionsUnder optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine-induced immunity against SARS-CoV-2.

Klebsiella pneumoniae cryptogenic liver abscess and endophthalmitis – a case report and review of literature

Klebsiella pneumoniae has emerged as the predominant pathogenic agent of liver abscess in Asia, and the incidence is increasing worldwide. Hypervirulent strains are associated with septic metastatic dissemination in the eyes, lungs, and central nervous system, causing severe morbidity. We present the case of a 54year old man, with no previous comorbidities, admitted in emergency for the blind red painful eye. Further investigation documented septic endophthalmitis with transscleral extension and orbital cellulitis. Thoraco-abdominal computed tomography evidenced a hepatic abscess as the locus of the primary infection. Intravenous antibiotherapy with cefuroxime, followed by meropenem and vancomycin were efficient for managing the hepatic abscess. However, as the eyeball was perforated at the admission, evisceration was performed. The vitreous sample revealed Klebsiella pneumoniae, with a positive string test as the etiologic agent. The diagnostic and therapeutic management required a permanent collaboration between an ophthalmologist, infectious diseases specialist, surgeon, and radiologist.

Exposing racial bias in midwifery education: a content analysis of images and text in Myles Textbook for Midwives

Objective To determine how people of different races and skin colours are represented within Myles Textbook for Midwives and whether the identified content is clinically relevant to people of all skin colours. Design Content analysis of text and images in Myles Textbook for Midwives 17th Edition, 2020 Findings The images overwhelmingly depict light skinned people of White European appearance. When people of colour are shown they are more likely to be positioned in prominent imagery without specific link to the chapter topic. Descriptions of skin colour in the context of clinical assessment and/or treatment often applied mostly or solely to people with light colour skin. This included text referring to serious conditions or situations associated with severe morbidity or mortality. Key conclusions Myles Textbook for Midwives presents a light skinned White European norm and often fails to include information that is clinically relevant to the assessment and treatment of people with darker skin colours. This may lead to disparity in midwifery education and contribute to poorer outcomes for women and babies. Implications for practice Concrete efforts are required to identify and root out racial bias at all levels of midwifery education. This needs to happen alongside addressing current lack of good quality evidence required to support practice.