Highly pathogenic avian influenza A(H5N1) virus in a common bottlenose dolphin (Tursiops truncatus) in Florida.

Since late 2021, highly pathogenic avian influenza (HPAI) viruses of A/goose/Guangdong/1/1996 (H5N1) lineage have caused widespread mortality in wild birds and poultry in the United States. Concomitant with the spread of HPAI viruses in birds are increasing numbers of mammalian infections, including wild and captive mesocarnivores and carnivores with central nervous system involvement. Here we report HPAI, A(H5N1) of clade 2.3.4.4b, in a common bottlenose dolphin (Tursiops truncatus) from Florida, United States. Pathological findings include neuronal necrosis and inflammation of the brain and meninges, and quantitative real time RT-PCR reveal the brain carried the highest viral load. Virus isolated from the brain contains a S246N neuraminidase substitution which leads to reduced inhibition by neuraminidase inhibitor oseltamivir. The increased prevalence of A(H5N1) viruses in atypical avian hosts and its cross-species transmission into mammalian species highlights the public health importance of continued disease surveillance and biosecurity protocols.

Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus.

mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.

Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus.

Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. We generated an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. We show that the vaccine is immunogenic in mice and ferrets and prevents morbidity and mortality of ferrets following 2.3.4.4b H5N1 challenge.

Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America.

Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry across Asia, Europe, and Africa. By the end of 2021, 2.3.4.4b viruses were detected in North America, signifying further intercontinental spread. Here we show that the western movement of clade 2.3.4.4b was quickly followed by reassortment with viruses circulating in wild birds in North America, resulting in the acquisition of different combinations of ribonucleoprotein genes. These reassortant A(H5N1) viruses are genotypically and phenotypically diverse, with many causing severe disease with dramatic neurologic involvement in mammals. The proclivity of the current A(H5N1) 2.3.4.4b virus lineage to reassort and target the central nervous system warrants concerted planning to combat the spread and evolution of the virus within the continent and to mitigate the impact of a potential influenza pandemic that could originate from similar A(H5N1) reassortants.

Genomic Sequence of Mycobacteriophage OKCentral2016.

OKCentral2016 is the first mycobacteriophage sequenced from Oklahoma soil using the bacterial host Mycobacterium smegmatis strain mc2155. OKCentral2016 has a double-stranded DNA genome composed of 50,072 bp, with 84 predicted coding genes and 1 tRNA sequence. This mycobacteriophage has sequence similarities to members of the A10 subcluster.

Retrospective review of physician opioid prescribing practices in patients with aberrant behaviors.

In the past few decades, opioid use for the treatment of chronic noncancer pain has slowly gained acceptance. With this increase in prescription opioid use, there has also been an increase in prescription opioid abuse. To help detect aberrant drug related behaviors, clinicians have utilized urine drug screens to determine patient noncompliance in outpatient pain clinics. The primary objective is to determine how the use of urine drug testing (UDT) affects health care outcomes. The secondary outcome is to evaluate these findings as it relates to pharmacoeconomics and aberrant behaviors in an outpatient clinical setting. In this study we will determine if UDT influences prescribing practices among physicians. Patients at an academic center's chronic pain outpatient clinic were categorized as having urine screens that were "normal" (expected findings based on their prescribed drugs) or abnormal. Abnormal findings were those with either 1) the absence of a prescribed opioid, 2) the presence of an additional nonprescribed controlled substance, 3) detection of an illicit substance, or 4) an adulterated urine sample. We examined the incidence of such aberrant behaviors as well as concomitant pain diagnoses, psychiatric comorbidities, and the ultimate effect upon the prescribing patterns of the physicians in this clinic. Results of the study showed that the patients exhibiting aberrant drug behaviors have similar pain and psychiatric diagnoses as other chronic pain patients. The most common aberrancy detected was an abnormal urine drug screen, often with the presence of illegal substances. However, in the great majority of aberrancies detected, providers chose to continue prescribing opioids. We speculate on the reasons for this, and discuss the role of the urine drug screen in influencing prescriber behaviors.

Combining botulinum toxin and phenol to manage spasticity in children.

OBJECTIVE: To describe the specific techniques and adverse reactions of using concurrent, multiple injections of both botulinum toxin and phenol to manage spasticity in children with cerebral palsy (CP) and other neurologic conditions. DESIGN: A retrospective case series. SETTING: A tertiary care children's hospital. PARTICIPANTS: Consecutive patients (N=68) with spasticity related to CP or other neurologic conditions. INTERVENTION: Ninety injection sessions combining botulinum toxin and phenol to manage spasticity. MAIN OUTCOME MEASURE: Documentation of adverse reactions. RESULTS: The mean phenol dosage was 9.5mL at a mean of 0.6mL/kg per injection dose. The mean botulinum toxin type A (Botox) dose injected was 193U (12U/kg), and the mean of botulinum toxin type B (Myobloc) dose injected was 7750U (530U/kg). The mean number of muscles injected was 14. Adverse reactions are described but were infrequent. Dysesthetic hand pain occurred in 2 patients. One patient developed a systemic reaction to Myobloc. CONCLUSIONS: Using botulinum toxin and phenol injections allowed many muscles to be injected to manage spasticity in children with CP and other neurologic conditions. Using this combination allowed an increased number of injections at the maximal recommended dose.