Transfusion-Transmitted Cache Valley Virus Infection in a Kidney Transplant Recipient With Meningoencephalitis.

BACKGROUND: Cache Valley virus (CVV) is a mosquito-borne virus that is a rare cause of disease in humans. In the fall of 2020, a patient developed encephalitis 6 weeks following kidney transplantation and receipt of multiple blood transfusions. METHODS: After ruling out more common etiologies, metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) was performed. We reviewed the medical histories of the index kidney recipient, organ donor, and recipients of other organs from the same donor and conducted a blood traceback investigation to evaluate blood transfusion as a possible source of infection in the kidney recipient. We tested patient specimens using reverse-transcription polymerase chain reaction (RT-PCR), the plaque reduction neutralization test, cell culture, and whole-genome sequencing. RESULTS: CVV was detected in CSF from the index patient by mNGS, and this result was confirmed by RT-PCR, viral culture, and additional whole-genome sequencing. The organ donor and other organ recipients had no evidence of infection with CVV by molecular or serologic testing. Neutralizing antibodies against CVV were detected in serum from a donor of red blood cells received by the index patient immediately prior to transplant. CVV neutralizing antibodies were also detected in serum from a patient who received the co-component plasma from the same blood donation. CONCLUSIONS: Our investigation demonstrates probable CVV transmission through blood transfusion. Clinicians should consider arboviral infections in unexplained meningoencephalitis after blood transfusion or organ transplantation. The use of mNGS might facilitate detection of rare, unexpected infections, particularly in immunocompromised patients.

Role of Viscoelastic and Conventional Coagulation Tests for Management of Blood Product Replacement in the Bleeding Patient.

An important aim of viscoelastic testing (VET) is to implement transfusion algorithms based on coagulation test results to help reduce transfusion rates and improve patient outcomes. Establishing a rapid diagnosis and providing timely treatment of coagulopathy is the cornerstone of management of severely bleeding patients in trauma, postpartum hemorrhage, and major surgery. As the nature of acute bleeding and trauma leads to an unstable and tenuous physiologic state, conventional coagulation tests (CCTs) are too slow to diagnose, manage, and also course correct any hemostatic abnormalities that accompany an acute critical illness. Viscoelastic point-of-care tests strongly correlate with results from standard laboratory tests but are designed to enable clinicians to make timely, informed bleeding management decisions when time to intervene is critical. These assays provide an individualized and goal-oriented approach to patient blood management and are increasingly becoming involved in transfusion algorithms. The scope of this review aims to evaluate the current literature on VETs and their impact on actionable outputs in clinical decision making and their relationship to CCT.

Performance of Xpert Ultra nasopharyngeal swab for identification of tuberculosis deaths in northern Tanzania.

OBJECTIVE: Numerous tuberculosis (TB) deaths remain undetected in low-resource endemic settings. With autopsy-confirmed tuberculosis as our standard, we assessed the diagnostic performance of Xpert MTB/RIF Ultra (Ultra; Cepheid) on nasopharyngeal specimens collected postmortem. METHODS: From October 2016 through May 2019, we enrolled pediatric and adult medical deaths to a prospective autopsy study at two referral hospitals in northern Tanzania with next-of-kin authorization. We swabbed the posterior nasopharynx prior to autopsy and tested the samples later by Ultra. At autopsy we collected lung, liver, and, when possible, cerebrospinal fluid for mycobacterial culture and histopathology. Confirmed tuberculosis was defined as Mycobacterium tuberculosis complex recovery by culture with consistent tissue histopathology findings; decedents with only histopathology findings, including acid-fast staining or immunohistochemistry, were defined as probable tuberculosis. RESULTS: Of 205 decedents, 78 (38.0%) were female and median (range) age was 45 (0,96) years. Twenty-seven (13.2%) were found to have tuberculosis at autopsy, 22 (81.5%) confirmed and 5 (18.5%) probable. Ultra detected M. tuberculosis complex from the nasopharynx in 21 (77.8%) of 27 TB cases (sensitivity 70.4% [95% confidence interval {CI} 49.8-86.2%], specificity 98.9% [95% CI 96.0-99.9%]). Among confirmed TB, the sensitivity increased to 81.8% (95% CI 59.7-94.8%). Tuberculosis was not included as a death certificate diagnosis in 14 (66.7%) of the 21 MTBc detections by Ultra. DISCUSSION: Nasopharyngeal Ultra was highly specific for identifying in-hospital tuberculosis deaths, including unsuspected tuberculosis deaths. This approach may improve tuberculosis death enumeration in high-burden countries.

Rickettsia honei Infection in a Traveler Returning From India.

We report a case of Rickettsia honei infection in a US tourist returning from India and the Himalayas. This case highlights a need for awareness of various Rickettsia species endemic to India and the importance for physicians to consider rickettsial diseases in returning travelers with eschar or rash-associated febrile illnesses.

Clinical Manifestations and Outcomes in Immunocompetent and Immunocompromised Patients With Blastomycosis.

BACKGROUND: Blastomyces is a dimorphic fungus that infects persons with or without underlying immunocompromise. To date, no study has compared the clinical features and outcomes of blastomycosis between immunocompromised and immunocompetent persons. METHODS: A retrospective study of adult patients with proven blastomycosis from 2004-2016 was conducted at the University of Wisconsin. Epidemiology, clinical features, and outcomes were analyzed among solid-organ transplantation (SOT) recipients, persons with non-SOT immunocompromise (non-SOT IC), and persons with no immunocompromise (NIC). RESULTS: A total of 106 cases met the inclusion criteria including 74 NIC, 19 SOT, and 13 non-SOT IC (malignancy, HIV/AIDS, idiopathic CD4+ lymphopenia). The majority of patients (61.3%) had at least 1 epidemiologic risk factor for acquisition of Blastomyces. Pneumonia was the most common manifestation in all groups; however, immunocompromised patients had higher rates of acute pulmonary disease (P = .03), more severe infection (P = .007), respiratory failure (P = .010), and increased mortality (P = .02). Receipt of SOT primarily accounted for increased severity, respiratory failure, and mortality in immunosuppressed patients. SOT recipients had an 18-fold higher annual incidence of blastomycosis than the general population. The rate of disseminated blastomycosis was similar among NIC, SOT, and non-SOT IC. Relapse rates were low (5.3-7.7%). CONCLUSIONS: Immunosuppression had implications regarding the acuity, severity, and respiratory failure. The rate of dissemination was similar across the immunologic spectrum, which is in sharp contrast to other endemic fungi. This suggests that pathogen-related factors have a greater influence on dissemination for blastomycosis than immune defense.

Outbreak of Anthrax Associated with Handling and Eating Meat from a Cow, Uganda, 2018.

On April 20, 2018, the Kween District Health Office in Kween District, Uganda reported 7 suspected cases of human anthrax. A team from the Uganda Ministry of Health and partners investigated and identified 49 cases, 3 confirmed and 46 suspected; no deaths were reported. Multiple exposures from handling the carcass of a cow that had died suddenly were significantly associated with cutaneous anthrax, whereas eating meat from that cow was associated with gastrointestinal anthrax. Eating undercooked meat was significantly associated with gastrointestinal anthrax, but boiling the meat for >60 minutes was protective. We recommended providing postexposure antimicrobial prophylaxis for all exposed persons, vaccinating healthy livestock in the area, educating farmers to safely dispose of animal carcasses, and avoiding handling or eating meat from livestock that died of unknown causes.

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.

Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case series.

BACKGROUND: Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. METHODS: Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. FINDINGS: 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. INTERPRETATION: Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. FUNDING: US Centers for Disease Control and Prevention.

Urine Antigen Testing is Equally Sensitive to B. dermatitidis and B. gilchristii Infections.

INTRODUCTION: Blastomycosis is endemic in Wisconsin with Blastomyces dermatitidis and B. gilchristii responsible for infections. Urine antigen testing is a non-invasive diagnostic method for blastomycosis with up to 93% test sensitivity. However, the test's sensitivity has not been evaluated with relationship to B. gilchristii infections. METHODS: We aimed to assess physician use of the urine antigen assay and its sensitivity to B. gilchristii and B. dermatitidis infections in a retrospective study. Culture confirmed clinical cases of blastomycosis from 2008-2016 were identified within Marshfield Clinic Health System (MCHS) and UW Hospital and Clinics (UWHC) medical records. Clinical data were abstracted from each medical record and included the following: patient demographics, presence of immune compromising and underlying medical conditions, treatment drugs, presence of isolated pulmonary or disseminated disease, death, urine antigen testing, timeframe of testing, and quantitative test values (EIA units or ng/mL). RESULTS: A total of 140 blastomycosis cases were included in this study, with MCHS contributing 114 cases to the study and UWHC contributing 26 cases. The majority of UWHC cases (n=22; 85%) were caused by B. dermatitidis and the majority of MCHS cases (n=73; 64%) were caused by B. gilchristii. UWHC physicians were significantly more likely to treat with multiple drugs during the course of infection and were more likely to prescribe amphotericin B and voriconazole. Urine antigen testing was more frequently used at UWHC (n=24; 92%) than MCHS (n=51; 45%; P < 0.00001). In this study, the urine antigen assay demonstrated 79% sensitivity. Sensitivity was significantly associated with the timeframe of testing (P < 0.05), with most true positive urine antigen tests (83%) being performed ≤ 7 days from diagnosis. In this study, the urine antigen assay was capable of detecting both B. dermatitidis and B. gilchristii at about equal sensitivity. Urine antigen concentration (ng/mL) trended higher in B. dermatitidis infections. CONCLUSION: This study found that the urine antigen assay is capable of detecting both species of Blastomyces at about the same sensitivity. We recommend continued use of the urine antigen assay for diagnosis of blastomycosis and recommend that the assay be used early in the diagnostic process to minimize the chance of false negative results.

Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.

An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.

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.

Pathologic Features of Esophageal and Gastric Malignancies.

Esophageal and gastric carcinomas affect millions of individuals worldwide, placing a considerable burden on society. Unfortunately, preventative medicine falls short as screening methods for the upper gastrointestinal tract lack the ability to detect early onset disease. The overwhelming majority of cases present after symptoms appear when individuals have advanced disease with a poor prognosis. Further complicating matters, the anatomic location of these neoplasms engenders rapid tumor progression, which repeatedly thwarts successful surgical treatment. This chapter will focus on the pathological features of malignant neoplasms of the esophagus and stomach.

Pathologic Features of Miscellaneous Foregut Malignancies.

In addition to tumors arising from the primary mucosal epithelium, the foregut is host to a variety of non-epithelial precursor cells which may give rise to neoplasms of neuroendocrine, mesenchymal, and hematolymphoid lineages. Many of these lesions also occur outside of the gastrointestinal tract, such as the extranodal lymphomas and many of the sarcomas, and in many cases share the features of their non-alimentary counterparts. This heterogeneous collection of malignancies features a wide spectrum of clinical presentations, morphologic and histopathologic features, genetic underpinnings, and treatment considerations. Although encountered less frequently than primary carcinomas, it is important to correctly recognize and classify these lesions to effectively manage and prognosticate the patients in which they occur. In this chapter, we focus on the clinical, morphologic, and genetic features of the primary esophageal and gastric neoplasms of neuroendocrine, mesenchymal, and lymphoid origin.