How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.

Comparing the genetic typing methods for effective surveillance and rabies control in Georgia.

A full nucleoprotein gene sequencing of 68 isolates collected from passive rabies surveillance system in Georgia between 2015 and 2016 identified two distinct dog rabies phylogroups, GEO_V1 and GEO_V2, which both belonged to the cosmopolitan dog clade. GEO_V1 was found throughout the country and was further divided into four sub-phylogroups that overlapped geographically; GEO_V2 was found in the southeast region and was closely related to dog rabies in Azerbaijan. A sequence analysis of the full N gene, partial nucleoprotein gene of N-terminal and C-terminal, and the amplicon sequences of pan-lyssavirus RT-qPCR LN34 showed that all four sequencing approaches provided clear genetic typing results of canine rabies and could further differentiate GEO_V1 and GEO_V2. The phylogenetic analysis results vary and were affected by the length of the sequences used. Amplicon sequencing of the LN34 assay positive samples provided a rapid and cost-effective method for rabies genetic typing, which is important for improving rabies surveillance and canine rabies eradication globally.

Simultaneous exercise stress cardiac magnetic resonance and cardiopulmonary exercise testing to elucidate the Fick components of aerobic exercise capacity: a feasibility and reproducibility study and pilot study in hematologic cancer survivors.

BACKGROUND: Patients treated for hematologic malignancy often experience reduced exercise capacity and increased fatigue; however whether this reduction is related to cardiac dysfunction or impairment of skeletal muscle oxygen extraction during activity is unknown. Cardiopulmonary exercise testing (CPET) coupled with stress cardiac magnetic resonance (ExeCMR), may provide a noninvasive method to identify the abnormalities of cardiac function or skeletal muscle oxygen extraction. This study was performed to determine the feasibility and reproducibility of a ExeCMR + CPET technique to measure the Fick components of peak oxygen consumption (VO2) and pilot its discriminatory potential in hematologic cancer patients experiencing fatigue. METHODS: We studied 16 individuals undergoing ExeCMR to determine exercise cardiac reserve with simultaneous measures of VO2. The arteriovenous oxygen content difference (a-vO2diff) was calculated as the quotient of VO2/cardiac index (CI). Repeatability in measurements of peak VO2, CI, and a-vO2diff was assessed in seven healthy controls. Finally, we measured the Fick determinants of peak VO2 in hematologic cancer survivors with fatigue (n = 6) and compared them to age/gender-matched healthy controls (n = 6). RESULTS: Study procedures were successfully completed without any adverse events in all subjects (N = 16, 100%). The protocol demonstrated good-excellent test-retest reproducibility for peak VO2 (intraclass correlation coefficient [ICC] = 0.992 [95%CI:0.955-0.999]; P < 0.001), peak CI (ICC = 0.970 [95%CI:0.838-0.995]; P < 0.001), and a-vO2diff (ICC = 0.953 [95%CI:0.744-0.992]; P < 0.001). Hematologic cancer survivors with fatigue demonstrated a significantly lower peak VO2 (17.1 [13.5-23.5] vs. 26.0 [19.7-29.5] mL·kg-1·min-1, P = 0.026) and lower peak CI (5.0 [4.7-6.3] vs. 7.4 [7.0-8.8] L·min-1/m2, P = 0.004) without a significant difference in a-vO2diff (14.4 [11.8-16.9] vs. 13.6 [10.9-15.4] mLO2/dL, P = 0.589). CONCLUSIONS: Noninvasive measurement of peak VO2 Fick determinants is feasible and reliable with an ExeCMR + CPET protocol in those treated for a hematologic malignancy and may offer insight into the mechanisms of exercise intolerance in those experiencing fatigue.

Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo.

We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole (Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.

Design and Optimization of a Monkeypox virus Specific Serological Assay.

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak.

Mpox respiratory transmission: the state of the evidence.

The relative contribution of the respiratory route to transmission of mpox (formerly known as monkeypox) is unclear. We review the evidence for respiratory transmission of monkeypox virus (MPXV), examining key works from animal models, human outbreaks and case reports, and environmental studies. Laboratory experiments have initiated MPXV infection in animals via respiratory routes. Some animal-to-animal respiratory transmission has been shown in controlled studies, and environmental sampling studies have detected airborne MPXV. Reports from real-life outbreaks demonstrate that transmission is associated with close contact, and although it is difficult to infer the route of MPXV acquisition in individual case reports, so far respiratory transmission has not been specifically implicated. Based on the available evidence, the likelihood of human-to-human MPXV respiratory transmission appears to be low; however, studies should continue to assess this possibility.

Exploring an 8-Week Online Adaptive Yoga Program for Multiple Sclerosis: A Pilot Study.

This pretest-posttest, descriptive pilot study examined the feasibility and perceived impact of an 8-week online adaptive yoga program on patients diagnosed with multiple sclerosis. The program incorporated yoga poses, breathing practices, and relaxation techniques. Participants rated their perceived and actual symptom severity, overall quality of life, and perception of program impact, and contributed open-ended narrative comments about the program. All participants reported an overall perceived benefit from study participation and expressed enjoyment in interacting with other patients with multiple sclerosis. The program was found to be safe and rewarding for all participants.

Mpox in Children and Adolescents: Epidemiology, Clinical Features, Diagnosis, and Management.

Although mpox is rare among children in the United States, pediatric cases are being reported during the 2022 multinational mpox outbreak. Vaccines and antiviral medications developed for other orthopoxviruses have recently become widely used to prevent and treat mpox in both children and adults in the United States. Although scientific literature regarding mpox in children and adolescents is scant, prior case reports can provide valuable information about the clinical features and potential complications of untreated clade II mpox in these age groups. In this review, we summarize the epidemiology and clinical features of mpox in children and adolescents and provide recommendations for clinicians regarding its diagnosis, management, and prevention. Robust, dedicated surveillance of pediatric exposures and cases in the current outbreak, including the use of vaccines and therapeutics, are needed to guide clinical management and public health strategies.

Survey of feedlot nutritionists gives insight on information-seeking behavior.

Nutrition critically affects feedlot cattle health and growth, and ultimately cost of production. Feedlot producers rely on professionals such as nutritionists, extension educators, feed company representatives, and others to assist them in developing the best nutritional program for their operation. In turn, these professionals depend on feedlot nutrition research to drive decisions for their clients. A survey of feedlot professionals was conducted regarding how published resources are used. Surveys were included in the spring 2020 mailing to potential Plains Nutrition Council meeting attendees; 61 surveys were returned. The objective of this survey was to aid feedlot nutrition researchers to make more informed decisions when publishing new research to maximize impact on the feedlot industry. The survey asked 15 questions regarding the participant's career, professional organization memberships, frequency and intentions of using research, and ranking the importance of resources, peer-reviewed journals, and learning platforms. Survey respondents primarily served the Midwest and Plains regions (83.1%) with employment by feed companies (34.4%), private consulting firms (21.3%), other aspects of feedlot production (26.2%), or were self-employed (18%). Survey participants found great importance in peer-reviewed journals, though the relevance of peer-reviewed journals sometimes differed due to the professional age of respondents. The main strategies for accessing journals were via society memberships and through open access; utilizing open access publishing may increase the number of industry professionals reached. Looking to the future, we may see a shift in resources used by industry professionals due to the differences seen in preferences of early and late career survey participants, specifically increases in the use of technology-based platforms. These data may inform feedlot researchers on the information-seeking behaviors of feedlot professionals, such as the importance of publishing data in open access formats, allowing for greater impact through increased utilization of newly published research.

Roles and Perceptions of Nurses During Implementation of a Medication Treatment for Opioid Use Disorder National Initiative.

BACKGROUND: In the United States, a national priority exists to improve access to medication treatment for opioid use disorder (MOUD). Nurses can be an essential component of that care. We examined the perceptions and evolving roles of nurses in a national Veterans Health Administration (VHA) initiative designed to improve MOUD access within general medical settings. METHODS: From April 15, 2021, to June 16, 2021, we recruited nurses participating in VHA's Stepped Care for Opioid Use Disorder Train the Trainer Initiative-a national program intending to implement MOUD in general medical settings-to participate in an interview about their roles, perceptions, and experiences. The respondents answered our inquiries through an interview or responded to an email solicitation with written responses, which were then recorded, transcribed, and independently coded to identify themes. RESULTS: Nurses from 10 VHA facilities participated in an interview (n = 7) or completed the questionnaire (n = 4). Inadequate staffing, high patient-to-provider ratios, and time constraints were identified as barriers to MOUD care. Mentorship activities, existing VHA informational resources, and patients' willingness to accept treatment were identified as facilitators of MOUD care. The Stepped Care for Opioid Use Disorder Train the Trainer Initiative processes were acknowledged to promote role confidence, which in turn increased job satisfaction and empowered nurses to become content experts. Respondents often identified nurses as local lead facilitators in MOUD care. CONCLUSIONS: In a national initiative to implement MOUD within general medical settings, nurses identified several barriers and facilitators to MOUD implementation. Nurses play vital collaborative care roles in enhancing access to MOUD.

Is it time to rethink our one-size-fits-all approach to nitrate toxicity thresholds in forages?

Annual forages provide a valuable grazing resource for cattle producers; however, annuals are prone to accumulating nitrate and have the potential to cause nitrate toxicity. Although these forages pose a risk of containing high nitrate concentrations, they can be a high-quality feed source. Understanding the factors that affect the potential for toxicity when using these forages is important to help nutritionists and producers make management decisions. This review describes the previous research, current guidelines for nitrate toxicity, and the potential for improvement in our current recommendations. Current extension toxicity guidelines appear to be founded primarily on drenching based studies and overestimate the nitrate toxicity potential of forages. Recommendations need to account for multiple factors that affect the threshold for toxicity. There is evidence that fresh forages have a lower risk of toxicity because of slower release of nitrate into the rumen and a slower rate of dry matter intake. Increased dietary energy and sulfur content reduce the potential for toxicity. Microbial adaptation can reduce the risk and allow use of potentially toxic forages. These factors should influence feeding recommendations. However, there is currently not enough data available to establish new guidelines that account for these main factors. Thus, there is a need for renewed research in this area. The limited number of studies grazing elevated nitrate forages seems to suggest that there is less risk in grazing situations, especially if animals graze selectively. There is a need to develop guidelines for nitrate toxicity and management recommendations when grazing. To accomplish this, there is a need for more studies to evaluate risk of toxicity in grazing situations. These grazing studies need to evaluate the effects of nitrate concentration, forage quality, and grazing management on the potential for nitrate toxicity. While the conservative guidelines that are currently in use reduce risk of nitrate toxicity, they may also cause a significant increase in feed costs for producers.

Exportation of Monkeypox Virus From the African Continent.

BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.

Use of partial N-gene sequences as a tool to monitor progress on rabies control and elimination efforts in Ethiopia.

Ethiopia is one of the African countries most affected by rabies. A coarse catalog of rabies viruses (RABV) was created as a benchmark to assess the impact of control and elimination activities. We evaluated a 726 bp amplicon at the end of the N-gene to infer viral lineages in circulation using maximum likelihood and Bayesian methods for phylogenetic reconstruction. We sequenced 228 brain samples from wild and domestic animals collected in five Ethiopian regions during 2010-2017. Results identified co-circulating RABV lineages that are causing recurrent spillover infections into wildlife and domestic animals. We found no evidence of importation of RABVs from other African countries or vaccine-induced cases in the area studied. A divergent RABV lineage might be involved in an independent rabies cycle in jackals. This investigation provides a feasible approach to assess rabies control and elimination efforts in resource-limited countries.

Educational Approach to Prevent the Burden of Vaccinia Virus Infections in a Bovine Vaccinia Endemic Area in Brazil.

Bovine vaccinia (BV), caused by Vaccinia virus (VACV), is a zoonotic disease characterized by exanthematous lesions on the teats of dairy cows and the hands of milkers, and is an important public health issue in Brazil and South America. BV also results in economic losses to the dairy industry, being a burden to the regions involved in milk production. In the past 20 years, much effort has been made to increase the knowledge regarding BV epidemiology, etiologic agents, and interactions with the hosts and the environment. In the present study, we evaluated milking practices that could be associated with VACV infections in an endemic area in Brazil and proposed an educational tool to help prevent VACV infections. In our survey, 124 individuals (51.7%) from a total of 240 had previously heard of BV, 94 of which knew about it through BV outbreaks. Although most individuals involved in dairy activities (n = 85/91) reported having good hygiene practices, only 29.7% used adequate disinfecting products to clean their hands and 39.5% disinfected cows' teats before and after milking. Furthermore, 46.7% of individuals reported having contact with other farm and domestic animals besides dairy cattle. We also evaluated the presence of IgG and IgM antibodies in the surveyed population. Overall, 6.1% of likely unvaccinated individuals were positive for anti-Orthopoxvirus IgG antibodies, and 1.7% of all individuals were positive for IgM antibodies. Based on our findings, we proposed educational materials which target individuals with permanent residence in rural areas (mainly farmers and milkers), providing an overview and basic information about preventive measures against VACV infections that could enhance BV control and prevention efforts, especially for vulnerable populations located in endemic areas.

Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011-2015.

BACKGROUND: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. METHODS: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of polymerase chain reaction-confirmed cases by sex and age. RESULTS: We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3-15.0). The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07-1.37), except among those 20-29 years old (0.70; .51-.95). Females aged 20-29 years also reported a high frequency of exposures (26.2%) to people with monkeypox-like symptoms.The highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. CONCLUSIONS: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms.

Geographic distribution and genetic characterization of poxviruses from human infections in Georgia, 2009-2014.

Anthrax is endemic in Georgia, as are multiple zoonotic poxviruses. Poxvirus-associated infections share some clinical manifestations and exposure risks with anthrax, and so it is important to distinguish between the two. With this in mind, an archived collection of anthrax-negative DNA samples was retrospectively screened for poxviruses, and of the 148 human samples tested, 64 were positive. Sequence analysis confirmed the presence of orf virus, bovine papular stomatitis virus, and pseudocowpox virus. This study provides evidence of previously unrecognized poxvirus infections in Georgia and highlights the benefit of the timely identification of such infections by improving laboratory capacity.

Usefulness of the Duke Activity Status Index to Select an Optimal Cardiovascular Exercise Stress Test Protocol.

Exercise testing represents the preferred stress modality for individuals undergoing evaluation of suspected myocardial ischemia. Patients with limited functional status may be unable to achieve an adequate exercise stress, thus influencing the diagnostic sensitivity of the results. The Duke Activity Status Index (DASI) is a clinically applicable tool to estimate exercise capacity. The purpose of the current study was to assess the utility of the DASI to identify patients unable to achieve an adequate exercise stress result. Patients referred for exercise stress testing were administered the DASI pre-exercise. Baseline characteristics and exercise variables were evaluated including DASI-metabolic equivalents (DASI-METs), peak METs, exercise time (ET), and %-predicted maximal heart rate (%PMHR). Criteria for determining adequate exercise stress was defined as ≥85%PMHR or ≥ 5-METs at peak exercise. In 608 cardiovascular stress tests performed during the study period; 314 were exercise stress. The median DASI-METs (8.4 [interquartile range; 6.7 to 9.9]) was associated with estimated peak exercise METs (R=0.50, p <0.001), ET (R=0.29, p <0.001), and %PMHR (R=0.19, p = 0.003). DASI-METs were different between those with < or ≥85%PMHR (7.9 [6.6-9.0] vs. 8.9 [7.1-9.9], P=0.025) and those with < or ≥5-METs (5.8 [4.6 to 6.6] versus 8.9 [7.3-9.9], p <0.001). Receiver operating characteristic curve analysis identified a DASI-MET threshold of ≤/>7.4 to optimally predict adequate exercise stress (sensitivity=93%, specificity=71%). In conclusion, the DASI correlates with peak METs, ET, and %PMHR among patients referred for exercise testing and can be used to identify patients with an increased likelihood of an inadequate stress test result.

A Tale of Two Viruses: Coinfections of Monkeypox and Varicella Zoster Virus in the Democratic Republic of Congo.

Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.