A cluster of six respiratory cultures positive for Mycobacterium xenopi -Clinical characteristics and genomic characterization.

Mycobacterium xenopi is a slow growing non-tuberculous mycobacterium (NTM) isolated from water systems and has been associated with pseudo-outbreaks and pulmonary infections in humans. We observed a cluster of six respiratory cultures positive for M. xenopi within a six-month period at our institution, approximately double our normal isolation rate of this organism. Only three of the six cases met clinical, radiographic, and microbiologic criteria for NTM infection. An investigation led by our hospital's Healthcare Epidemiology and Infection Program found no epidemiologic link between the six patients. Three isolates underwent whole-genome sequencing (WGS) and phylogenetic analysis confirmed they were non-clonal. In vitro susceptibility data found the isolates were sensitive to macrolides, moxifloxacin, and rifabutin. Our findings suggest that isolation of M. xenopi from pulmonary specimens may be increasing, further defines the genomic population structure of this potentially emerging infection, and establishes WGS as a useful tool for outbreak investigation strain typing.

Characteristics of Hard Tick Relapsing Fever Caused by Borrelia miyamotoi, United States, 2013-2019.

Borrelia miyamotoi, transmitted by Ixodes spp. ticks, was recognized as an agent of hard tick relapsing fever in the United States in 2013. Nine state health departments in the Northeast and Midwest have conducted public health surveillance for this emerging condition by using a shared, working surveillance case definition. During 2013-2019, a total of 300 cases were identified through surveillance; 166 (55%) were classified as confirmed and 134 (45%) as possible. Median age of case-patients was 52 years (range 1-86 years); 52% were male. Most cases (70%) occurred during June-September, with a peak in August. Fever and headache were common symptoms; 28% of case-patients reported recurring fevers, 55% had arthralgia, and 16% had a rash. Thirteen percent of patients were hospitalized, and no deaths were reported. Ongoing surveillance will improve understanding of the incidence and clinical severity of this emerging disease.

Infectious Complications of Lung Transplant for Coronavirus Disease 2019-Associated Lung Injury: A Single-Center Case-Control Cohort Study.

BACKGROUND: Lung transplantation is one of the only options for patients with severe coronavirus disease 2019 (COVID-19)-associated lung injury (CALI). Studies on patients who received a lung transplant for CALI have, to date, not looked at the infectious outcomes. METHODS: After institutional review board approval, a retrospective case-control cohort study, matched 1:1, collected data on patients who underwent lung transplantation for CALI (case) and for non-COVID-19 end-stage lung disease (control) between 1 June 2020 and 1 April 2022 at a large academic hospital in Chicago. We assessed infectious complications and other key outcomes pre-transplant and for 1 year post-transplant. RESULTS: Among 78 patients (39 CALI and 39 matched control lung transplant patients), those in the CALI cohort were less likely to be vaccinated pre-transplant and were more likely to have diabetes, to be obese, to not be ambulatory, and to require pre-transplant extracorporeal membrane oxygenation and mechanical ventilation. Patients transplanted for CALI had higher rates of infection pre-transplant (66.7% vs 15.4% of patients in the control) and in the first 30 days post-transplant (43.6% vs 20.5%). Numbers and types of infection were similar in both groups at other time points. One-year mortality was similar for CALI and control groups (12.8% vs 10.3%, respectively). CONCLUSIONS: Patients who received a lung transplant for CALI are more deconditioned with prolonged hospital stays and experience more infectious complications immediately pre- and post-transplant. Infections due to multidrug-resistant organisms are important contributors to morbidity and mortality in this population. Antimicrobial stewardship is urgently needed.

Monkeypox-Associated Central Nervous System Disease: A Case Series and Review.

OBJECTIVE: Monkeypox virus (MPXV) disease has been declared a public health emergency by the World Health Organization, creating an urgent need for neurologists to be able to recognize, diagnosis, and treat MPXV-associated neurologic disease. METHODS: Three cases of MPXV-associated central nervous system (CNS) disease occurring during the 2022 outbreak, and their associated imaging findings are presented, with 2 cases previously published in a limited capacity in a public health bulletin. RESULTS: Three previously healthy immunocompetent gay men in their 30s developed a febrile illness followed by progressive neurologic symptoms with presence of a vesiculopustular rash. MPXV nucleic acid was detected by polymerase chain reaction (PCR) from skin lesions of 2 patients, with the third patient having indeterminate testing but an epidemiologic link to a confirmed MPXV disease case. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis, elevated protein, and negative MPXV-specific PCR. In 2 patients, magnetic resonance imaging of the brain and spine demonstrated partially enhancing, longitudinally extensive central spinal cord lesions with multifocal subcortical, basal ganglia, thalamic, cerebellar, and/or brainstem lesions. The third patient had thalamic and basal ganglia lesions. All patients received 14 days of tecovirimat, and 2 patients also received multiple forms of immunotherapy, including intravenous immunoglobulin, pulsed high-dose steroids, plasmapheresis, and/or rituximab. Good neurologic recovery was observed in all cases. INTERPRETATION: MPXV can be associated with CNS disease. It is unclear whether this is from a parainfectious immune-mediated injury or direct CNS viral invasion. ANN NEUROL 2023;93:893-905.

Tecovirimat Use in Ambulatory and Hospitalized Patients With Monkeypox Virus Infection.

ABSTRACT: In this case series of 20 ambulatory and hospitalized adult patients treated for monkeypox virus at a large academic medical center in Chicago, Illinois, tecovirimat use was reserved for those with or at high risk of severe disease, delayed because of logistical and clinical factors, but well tolerated.

Non-pulmonary Disseminated Tuberculosis Complicated by Constrictive Pericarditis and Cutaneous Gumma.

A 23-year-old previously healthy male presented to the hospital with symptoms of heart failure. He was diagnosed with pericarditis and found to have a reduced left ventricular ejection fraction of 25%. He was noted to have mediastinal lymphadenopathy. Pulmonary and abdominal sampling were non-diagnostic for infection, autoimmune disease, or malignancy. A QuantiFERON Gold returned positive. After a thorough travel history and detailed exam, the patient was diagnosed with disseminated tuberculosis after the discovery of a cutaneous gumma that was found to have acid-fast bacilli present on biopsy with Fite's stain. 18F-FDG PET CT and cardiac MRI were pursued given that pericardial and myocardial biopsy could not be safely performed due to the patient's hemodynamics. 18F-FDG PET CT and cardiac MRI did not demonstrate any myocardial pathology responsible for the left ventricular ejection fraction. This case highlights that pulmonary involvement is not necessary for disseminated TB, Fite's stain may be used to identify M. tuberculosis, and that cardiac MRI and 18F-FDG PET CT may be useful to delineate myocardial involvement in high-risk situations.

Knowledge, attitudes, and behaviors regarding tick-borne disease prevention in Lyme disease-endemic areas of the Upper Midwest, United States.

Lyme disease and other tick-borne diseases are a major public health threat in the Upper Midwestern United States, including Michigan, Minnesota, and Wisconsin. To prevent tick bites and tick-borne diseases, public health officials commonly recommend personal protective measures and property management techniques. Adoption of tick-borne disease prevention behaviors and practices by individuals are, however, highly variable. We aimed to characterize current tick-borne disease knowledge, attitudes, and prevention behaviors (KAB) practiced by the public in these states, as well as their willingness to use specific tick control methods. We conducted a population-based survey in summer 2019 in 48 high-risk counties (those having a five-year average (2013-2017) Lyme disease incidence of ≥ 10 cases per 100,000 persons per year), in Michigan, Minnesota, and Wisconsin. A total of 2713 surveys were analyzed; survey weights were used to account for household selection probability and post-stratified to match county-level joint age and sex population distributions in population-level inference. An estimated 98% of the population had heard of Lyme disease, with most perceiving it as very or extremely serious (91%); however, only an estimated 25% perceived tick-borne diseases as very or extremely common in their community. Among those who spent time in places with ticks from April through October, an estimated 68% check themselves thoroughly for ticks most of the time or always and 43% use bug repellent on skin or clothing most of the time or always. An estimated 13% of the population had ever treated their property with a pesticide to kill ticks, and 3% had ever used devices that apply pesticide to rodents to kill ticks on their property. Willingness to practice tick bite prevention behaviors, however, was estimated to be much higher; with 82% being willing to perform tick checks at least once a day, and more than 60% willing to use bug repellent, tick control products on pets, or to bathe within two hours of being outdoors. We found that residents would likely be willing to support a county-wide tick control program to reduce the risk of tick-borne disease in their community (81%) or to apply tick control products to their property to reduce the risk of tick-borne disease in their household (79%). Tick checks were more likely to be practiced among participants who perceived tick-borne diseases to be highly prevalent in their community, if they or a household member had been previously diagnosed with a tick-borne disease?, or if they perceived tick exposure to be likely around their home, cabin, or vacation home. In addition, property-based tick control methods were associated with perceived risk of encountering ticks around the home, cabin, or vacation home. Participants who had seen information from state health departments were also more likely to practice preventive measures. The most common reported barriers to using any of these methods were forgetfulness, safety concerns, and lack of awareness. Our survey findings shed light on how residents from these Upper Midwest states may adopt tick control and tick bite prevention measures and how public health outreach may be most effective for this population.

Race and ethnicity do not impact eligibility for remdesivir: A single-center experience.

As the Coronavirus-2019 (COVID-19) pandemic continues, multiple therapies are rapidly being evaluated for efficacy in clinical trials. Clinical trials should be racially and ethnically representative of the population that will eventually benefit from these medications. There are multiple potential barriers to racial and ethnic minority enrollment in clinical trials, one of which could be that inclusion and exclusion criteria select for certain racial or ethnic groups disproportionately. In this observational cohort study at a single health care system, we examined if there were differences in eligibility for treatment with remdesivir based on clinical trial criteria for racial and ethnic minorities compared to non-Hispanic Whites. 201 electronic medical record charts were reviewed manually. Self-identified Whites were older than other racial or ethnic groups. At the time of presentation, Black, Latinx, and White participants met inclusion criteria for remdesivir at similar rates (72%, 80%, and 73% respectively), and exclusion criteria at similar rates (43%, 38% and 49% for Black, Latinx and White participants respectively). In this study, there was no difference in eligibility for remdesivir based on race or ethnicity alone.

Clinical implications of SARS-CoV-2 cycle threshold values in solid organ transplant recipients.

Detection of SARS-CoV-2 viral RNA by RT-PCR assays is the primary diagnostic test for COVID-19. Cycle threshold (CT ) values generated by some of these assays provide inversely proportional proxy measurements of viral load. The clinical implications of CT values are incompletely characterized, particularly in solid organ transplant (SOT) recipients. We conducted a retrospective chart review of 25 adult SOT recipients admitted to the Yale New Haven Health System between March 1 and May 15, 2020, analyzing 50 test results to investigate the clinical implications of SARS-CoV-2 CT values in this population. Initial CT values from upper respiratory tract samples were significantly higher in patients on tacrolimus, but were not associated with admission severity nor highest clinical acuity. Viral RNA was detected up to 38 days from symptom onset with a gradual increase in CT values over time. In five patients with serial testing, CT values <35.0 were detected >21 days after symptom onset in 4/5 and ≥27 days in 2/5, demonstrating prolonged RNA detection. These data describe SARS-CoV-2 viral dynamics in SOT patients and suggest that CT values may not be useful to predict COVID-19 severity in SOT patients. SARS-CoV-2 CT values may be more useful in informing infection prevention measures.

Powassan Virus Infection Likely Acquired Through Blood Transfusion Presenting as Encephalitis in a Kidney Transplant Recipient.

A kidney transplant patient without known tick exposure developed encephalitis 3 weeks after transplantation. During the transplant hospitalization, the patient had received a blood transfusion from an asymptomatic donor later discovered to have been infected with Powassan virus. Here, we describe a probable instance of transfusion-transmitted Powassan virus infection.

A Fatal Case of Powassan Virus Encephalitis.

Powassan virus (POWV) is a flavivirus of the tick-borne encephalitis serogroup that causes a rare and potentially life-threatening neuroinvasive disease. Viral transmission occurs during zoonotic spillover from mammals by the bite of an infected tick in endemic regions of North America. The number of reported POWV cases has recently increased in the United States. We report a fatal case of POWV meningoencephalomyelitis in Northern Wisconsin following a documented tick bite. Histologic examination of the brain demonstrated widespread intraparenchymal and perivascular lymphohistocytic infiltration, microglial nodule formation, and marked neuronal degeneration, most severely involving the substantia nigra, anterior horn of spinal cord and cerebellum. Although no viral inclusions were seen in routine light microscopy, electron microscopy identified multiple neurons containing cytoplasmic clusters of virus particles ∼50 nm in diameter. POWV infection was confirmed using immunohistochemical analysis and reverse transcription-polymerase chain reaction. This report demonstrates in detail regional central nervous system involvement and ultrastructural characteristics of Powassan viral particles by transmission electron microscopy, while highlighting the utility of evaluating fixed autopsy tissues in cases of unexplained meningoencephalomyelitis.

Suspected Neuro-invasive Powassan Virus Infection in a Pediatric Patient.

Powassan virus lineage II (POWV), also known as deer tick virus, is an emerging tick-borne pathogen transmitted by Ixodes scapularis, the natural vector for the organisms that causes Lyme disease, babesiosis, and anaplasmosis. POWV is the only tick-borne flavivirus in North America known to cause disease in humans. We present a suspected pediatric case of POWV infection in northern Wisconsin.

Enhanced Arboviral Surveillance to Increase Detection of Jamestown Canyon Virus Infections, Wisconsin, 2011-2016.

Jamestown Canyon virus (JCV), a mosquito-borne Orthobunyavirus (within the California serogroup), can cause severe neuroinvasive disease. According to national data during 2000-2013, 42% of the 31 documented JCV disease cases in the United States were detected in residents from Wisconsin. The Wisconsin Division of Public Health enhanced JCV surveillance by implementing routine use of JCV-specific immunoglobulin M (IgM) antibody testing followed by confirmatory JCV-specific plaque reduction neutralization testing on all patients with suspected cases of arboviral infection who had tests positive for arboviral immunoglobin at commercial laboratories. During 2011-2016, of the 287 Wisconsin specimens tested on the Arbovirus IgM Antibody Panel, 30 JCV cases were identified (26 confirmed and four probable). Twenty-seven (90%) JCV cases were detected after 2013. Among all cases, 17 (56%) were male and the median age was 54 years (range: 10-84 years). Fifteen patients had neuroinvasive disease, including meningitis (n = 9) and meningoencephalitis (n = 6). Although historically considered rare, the relatively high rate (0.12 cases/100,000 population) of diagnosis of JCV infections among Wisconsin residents during 2013-2016 compared with that in previous years suggests occurrence is widespread throughout Wisconsin and historically may have been under-recognized. This study aims to raise awareness of JCV infection for differential diagnosis among the arboviral diseases. Improved and timely diagnosis of arboviral disease is important in that it will provide more information regarding emerging infections and promote preventive measures to avoid mosquito-borne exposure and infection among residents of and visitors to affected areas.

Closing the gap between insecticide treated net ownership and use for the prevention of malaria.

BACKGROUND: Malaria is the leading cause of morbidity and mortality in children younger than 5 years old and pregnant women in sub-Saharan Africa. Insecticide-treated nets (ITNs) reduce clinical malaria by more than 50% and all cause mortality in young children by 15% to 30%. However, use of these nets is poor across sub-Saharan Africa, limiting the potential impact of this effective tool in the fight against malaria. OBJECTIVE: We sought to improve the use of ITNs using a community-created and -implemented approach, and measure the change in ITN use over the year after implementation. METHODS: Using a community-based participatory research approach, we created and implemented an intervention to improve ITN use in a rural village. Our intervention involved providing hands-on instructions and assistance in hanging of nets, in-home small group education, and monthly follow-up by trained community members. ITN use was measured for all individuals in a subset of the community (61 households, 759 individuals) at baseline and at 6 months and 1 year after distribution. RESULTS: Rates of individual usage increased significantly from 29% at baseline to 88.7% (p < .001) at 6 months and to 96.6% (p < .001) at 12 months. For children under age 5, usage rates increased from 46% at baseline to 95.7% (p < .001) at 6 months and 95.4% (p < .001) at 12 months. CONCLUSION: Our study demonstrates that rapidly achieving and sustaining almost universal ITN usage rates is possible using a community-based approach. Closing the gap between ITN ownership and use will help communities to realize the full potential of ITNs in the prevention of malaria.

Validation of use of rectoanal mucosa-associated lymphoid tissue for immunohistochemical diagnosis of chronic wasting disease in white-tailed deer (Odocoileus virginianus).

The examination of rectoanal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens for the diagnosis of transmissible spongiform encephalopathies has been described in sheep, elk, and small numbers of mule and white-tailed deer. Previous sample numbers have been too small to validate examination of this type of tissue as a viable antemortem diagnostic test. In this study, we examined RAMALT collected postmortem from 76 white-tailed deer removed from a farm in Wisconsin known to be affected by chronic wasting disease (CWD) and from 210 free-ranging white-tailed deer harvested from an area in Wisconsin where the overall prevalence of CWD among the deer was approximately 4 to 6%. The results of immunohistochemical (IHC) staining of the RAMALT sections were compared to the results of IHC staining of sections from the brain stem at the convergence of the dorsal motor nucleus of the vagus nerve, sections of the medial retropharyngeal lymph nodes (RLNs), and sections of tonsil (sections of tonsil only from captive animals were tested). The sensitivities of the IHC staining test with RAMALT sections were 81% for the captive animals and 91% for the free-ranging animals. False-negative results were usually associated with early infection, indicated by a low intensity of immunostaining in the obex and/or a polymorphism at PRNP codon 96. While the RLN remains the tissue of choice for use for the diagnosis of CWD in white-tailed deer, the results of the present study further support the use of RAMALTs collected antemortem as an adjunct to testing of tonsil biopsy specimens and surveillance by necropsy for the screening of farmed deer which have been put at risk through environmental exposure or exposure to deer with CWD.