Last data update: Apr 16, 2024. (Total: 46543 publications since 2009)
Records 1-12 (of 12 Records) |
Query Trace: Gary JM [original query] |
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Influenza A virus infection and pathology in nasal and periocular tissues after ocular inoculation in ferrets
Gary JM , Ritter JM , Sun X , Maines TR , Belser JA . Vet Pathol 2022 59 (6) 3009858221109103 Influenza A viruses (IAV) cause mammalian infections following several transmission routes. Considering the anatomic proximity and connection between the nasopharynx and periocular tissues, there is a need to understand the dynamics of virus spread between these sites following both respiratory and nonrespiratory viral transmission. We examined virus distribution and associated inflammation within nasal and periocular tissues during the acute phase of H1N1 IAV infection in ferrets following intranasal or ocular inoculation. Ocular and intranasal inoculations with IAV caused comparable viral antigen distribution and inflammation in the nasal passages, though infection kinetics and magnitude differed by inoculation route. Ocular inoculation was associated with inflammation in the conjunctiva and lacrimal glands. Although intranasal inoculation was also associated with periocular inflammation, the onset was delayed relative to ocular inoculation. This work underscores the importance of investigating extrapulmonary tissues following mammalian infection with respiratory pathogens, even after intranasal inoculation. |
BK virus associated with small cell carcinoma of bladder in a patient with renal transplant
Loria SJ , Siddiqui NN , Gary JM , Bhatnagar J , Bollweg BC , Ahmed B , Berenson CS . BMJ Case Rep 2022 15 (3) A man in his 70s with a complex medical history, including cadaveric renal transplant, presented with recurrent urinary tract infections. Investigation revealed recurrent urinary pathogens, including Enterobacter cloacae and persistent BK viruria. Cystoscopy revealed a pedunculated mass in the right posterior-lateral wall, inferior to the transplant urethral orifice, and biopsy of this mass showed invasive small cell carcinoma with a prominent adenocarcinoma component. The tumour was treated with complete transurethral resection followed by carboplatin, etoposide and radiation. Laboratory analysis of biopsied samples showed immunostaining and molecular evidence of BK virus DNA in the cancer cells. Follow-up cystoscopies have shown no recurrence of the cancer. |
Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison).
Ritter JM , Wilson TM , Gary JM , Seixas JN , Martines RB , Bhatnagar J , Bollweg BC , Lee E , Estetter L , Silva-Flannery L , Bullock HA , Towner JS , Cossaboom CM , Wendling NM , Amman BR , Harvey RR , Taylor D , Rettler H , Barton Behravesh C , Zaki SR . Vet Pathol 2022 59 (4) 3009858221079665 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans. |
Performance evaluation of fungal DNA PCR amplification from formalin-fixed paraffin-embedded tissue for diagnosis; experience of a tertiary reference laboratory.
Lysen C , Silva-Flannery L , Zaki SR , Gary JM , Lockhart SR . Mycoses 2021 64 (6) 603-611 BACKGROUND: Diagnosis of invasive fungal infections from formalin-fixed paraffin-embedded (FFPE) tissues by PCR amplification is a developing technology. One of the difficulties of establishing a validated protocol for this testing is that the gold standard, culture, is much less sensitive than the test being validated. OBJECTIVES: To validate FFPE PCR as a refence laboratory identification methodology in the absence of abundant gold standard specimens. METHODS: In this validation, PCR from FFPE tissue was compared to other diagnostic methods for genus/species identification. Four different groups of correlative data from FFPE tissues were used to validate this procedure. Thirteen specimens had culture or serology results and FFPE PCR results, 49 specimens had both immunohistochemistry (IHC) identification and FFPE PCR results, 118 specimens had histological evidence of fungal elements, 64 of which also had FFPE PCR results, and 36 fungal mock tissues or fungal negative tissues were used. RESULTS: The sensitivity determined from the tissues with positive fungal histopathology was 54%. The specificity of the cases for which there were both culture and FFPE PCR results was 100%. For the correlation with IHC, the specificity was 98%. For the mock tissues and fungal-negative tissues the calculated analytical sensitivity was 94%, specificity was 95% and accuracy was 94%. CONCLUSIONS: By uniquely combining various data sources this study provides a comprehensive framework for how validation can be achieved in the absence of a gold standard and outlines the excellent performance of PCR from FFPE tissue, despite relatively the low sensitivity when compared to histopathology. |
Lassa virus antigen distribution and inflammation in the ear of infected strain 13/N guinea pigs
Huynh T , Gary JM , Welch SR , Coleman-McCray J , Harmon JR , Kainulainen MH , Bollweg BC , Ritter JM , Shieh WJ , Nichol ST , Zaki SR , Spiropoulou CF , Spengler JR . Antiviral Res 2020 183 104928 Sudden sensorineuronal hearing loss (SNHL) is reported in approximately one-third of survivors of Lassa fever (LF) and remains the most prominent cause of Lassa virus- (LASV) associated morbidity in convalescence. Using a guinea pig model of LF, and incorporating animals from LASV vaccine trials, we investigated viral antigen distribution and histopathology in the ear of infected animals to elucidate the pathogenesis of hearing loss associated with LASV infection. Antigen was detected only in animals that succumbed to disease and was found within structures of the inner ear that are intimately associated with neural detection and/or translation of auditory stimuli and in adjacent vasculature. No inflammation or viral cytopathic changes were observed in the inner ear or surrounding structures in these animals. In contrast, no viral antigen was detected in the ear of surviving animals. However, all survivors that exhibited clinical signs of disease during the course of infection developed perivascular mononuclear inflammation within and adjacent to the ear, indicating an ongoing inflammatory response in these animals that may contribute to hearing loss. These data contribute to the knowledge of LASV pathogenesis in the auditory system, support an immune-mediated process resulting in LASV-associated hearing loss, and demonstrate that vaccination protecting animals from clinical disease can also prevent infection-associated auditory pathology. |
Rapid, Noninvasive Diagnosis of Balamuthia mandrillaris Encephalitis by a Plasma-Based Next-Generation Sequencing Test.
Kalyatanda G , Rand K , Lindner MS , Hong DK , Sait Albayram M , Gregory J , Kresak J , Ibne KMA , Cope JR , Roy S , Gary JM , Reddy V , Ahmed AA . Open Forum Infect Dis 2020 7 (7) ofaa189 Granulomatous amoebic encephalitis (GAE) caused by Balamuthia mandrillaris is a rare subacute infection with exceptionally high mortality. Diagnosis is typically made by brain biopsy or at autopsy. Detection of Balamuthia mandrillaris cell-free DNA by next-generation sequencing of plasma enabled rapid, noninvasive diagnosis in a case of amoebic encephalitis. |
A guide for the use of the ferret model for influenza virus infection
Belser JA , Eckert AM , Huynh T , Gary JM , Ritter JM , Tumpey TM , Maines TR . Am J Pathol 2019 190 (1) 11-24 As influenza viruses continue to jump species barriers to cause human infection, assessments of disease severity and viral replication kinetics in vivo provide crucial information for public health professionals. The ferret model is a valuable resource for evaluating influenza virus pathogenicity; thus, understanding the most effective sample collection and usage techniques, as well as the full spectrum of attainable data following experimental inoculation in this species, is paramount. This is especially true for scheduled necropsy of virus-infected ferrets, a standard component in evaluation of influenza virus pathogenicity, as necropsy findings can provide important information regarding disease severity and pathogenicity that is not otherwise available from the live animal. In this review, we describe the range of influenza viruses assessed in ferrets, the measures of experimental disease severity in this model, and optimal sample collection during necropsy of virus-infected ferrets. Collectively, this information is critical for assessing systemic involvement following influenza virus infection in mammals. |
Sneathia amnii and maternal chorioamnionitis and stillbirth, Mozambique
Vitorino P , Varo R , Castillo P , Hurtado JC , Fernandes F , Valente AM , Mabunda R , Mocumbi S , Gary JM , Jenkinson TG , Mandomando I , Blau DM , Breiman RF , Bassat Q . Emerg Infect Dis 2019 25 (8) 1614-1616 We report a case of Sneathia amnii as the causative agent of maternal chorioamnionitis and congenital pneumonia resulting in a late fetal death in Mozambique, with strong supportive postmortem molecular and histopathologic confirmation. This rare, fastidious gram-negative coccobacillus has been reported to infrequently cause abortions, stillbirths, and neonatal infections. |
Primary amebic meningoencephalomyelitis caused by Naegleria fowleri in a south-central black rhinoceros (Diceros bicornis minor)
Yaw TJ , O'Neil P , Gary JM , Ali IK , Cowart JR , Wallace RS , Estep JS . J Am Vet Med Assoc 2019 255 (2) 219-223 CASE DESCRIPTION A 20-year-old female south-central black rhinoceros (Diceros bicornis minor) was evaluated because of an acute onset of CNS deficits. CLINICAL FINDINGS The rhinoceros had no history of illness. Clinical signs included acute lethargy, ataxia, and decreased appetite. Hematologic abnormalities included leukocytosis with neutrophilia and a profound left shift. Results of serum biochemical analysis revealed hypophosphatemia but no other abnormalities. Results of a quantitative PCR assay for West Nile virus and an assay for anti-Neosporum caninum antibodies in serum were negative; the patient was seropositive for multiple Leptospira serovars. TREATMENT AND OUTCOME Antimicrobials and anti-inflammatory agents were administered, but the condition of the rhinoceros worsened overnight; despite treatment with additional anti-inflammatory and antimicrobial agents, IV fluids, and thiamine, it became obtunded and died of respiratory arrest </= 24 hours later. Necropsy revealed severe, diffuse, suppurative, and histiocytic meningo-encephalomyelitis involving the cerebrum, cerebellum, and spinal cord. Amebic trophozoites were observed on histologic examination of affected tissue. Infection with Naegleria fowleri was confirmed by results of immuno-histochemical analysis and a multiplex real-time PCR assay. CLINICAL RELEVANCE Findings suggested that south-central black rhinoceros are susceptible to the free-living ameba N fowleri. Ameba-induced meningoencephalomyelitis should be considered as a differential diagnosis for rhinoceros that have an acute onset of neurologic signs. Diagnosis of N fowleri infection in an animal has a profound public health impact because of potential human exposure from the environment and the high fatality rate in people with N fowleri infection. |
Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge
Lo MK , Feldmann F , Gary JM , Jordan R , Bannister R , Cronin J , Patel NR , Klena JD , Nichol ST , Cihlar T , Zaki SR , Feldmann H , Spiropoulou CF , de Wit E . Sci Transl Med 2019 11 (494) Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection. |
Is this zebra really a zebra The challenge of diagnosing rare fungal infections in veterinary pathology
Lockhart SR , Gary JM . Vet Pathol 2019 56 (4) 510-511 The diagnosis of unusual fungal infections poses a challenge to the veterinary pathologist for a variety of reasons, including the lack of specific tests for many agents, the bewildering array of possible environmental contaminants, and the general lack of exposure to unusual fungal cases in daily practice. This challenge is highlighted by More et al,13 published in this issue of Veterinary Pathology. The authors describe a series of mycotic rhinitis and sinusitis cases in horses in Florida, including the steps taken to identify the specific agents responsible and the interesting and unique features of these agents and infections. The challenges associated with identifying these agents by polymerase chain reaction (PCR) and the unique features of some fungi are highlighted in that article. |
Lassa virus targeting of anterior uvea and endothelium of cornea and conjunctiva in eye of guinea pig model
Gary JM , Welch SR , Ritter JM , Coleman-McCray J , Huynh T , Kainulainen MH , Bollweg BC , Parihar V , Nichol ST , Zaki SR , Spiropoulou CF , Spengler JR . Emerg Infect Dis 2019 25 (5) 865-874 Lassa virus (LASV), a hemorrhagic fever virus endemic to West Africa, causes conjunctivitis in patients with acute disease. To examine ocular manifestations of LASV, we histologically examined eyes from infected guinea pigs. In fatal disease, LASV immunostaining was most prominent in the anterior uvea, especially in the filtration angle, ciliary body, and iris and in and around vessels in the bulbar conjunctiva and peripheral cornea, where it co-localized with an endothelial marker (platelet endothelial cell adhesion molecule). Antigen was primarily associated with infiltration of T-lymphocytes around vessels in the anterior uvea and with new vessel formation at the peripheral cornea. In animals that exhibited clinical signs but survived infection, eyes had little to no inflammation and no LASV immunostaining 6 weeks after infection. Overall, in this model, LASV antigen was restricted to the anterior uvea and was associated with mild chronic inflammation in animals with severe disease but was not detected in survivors. |
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