The Synthetic Opioid Fentanyl Increases HIV Replication and Chemokine Co-Receptor Expression in Lymphocyte Cell Lines.

BACKGROUND: In the United States, the illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis. Synthetic opioids are known to enhance viral replication and to suppress immunologic responses, but their effects on HIV pathogenesis remain unclear. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types. METHODS: TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at varying concentrations. Expression levels of the CXCR4 and CCR5 chemokine receptors and HIV p24 antigen were quantified with ELISA. HIV proviral DNA was quantified using SYBR RT-PCR. Cell viability was detected with the MTT assay. RNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. RESULTS: Fentanyl enhanced expression of both chemokine receptor levels in a dose-dependent manner in HIV-susceptible and infected cell lines. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral/interferon response, chemokine signaling, and NFκB signaling were differentially regulated. CONCLUSIONS: Synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression. Increased virus levels suggest that opioid use may increase the likelihood of transmission and accelerate disease progression.

Role of Polymerase Chain Reaction-Based Diagnosis of Respiratory Viruses in Febrile Neutropenic Patients.

Background Neutropenic patients are commonly affected by respiratory infections, whereas respiratory viral infections causing high morbidity and mortality are routinely diagnosed in developing countries like India. Our study aimed to investigate the prevalence of respiratory viral infections in pediatric cancer patients with febrile neutropenia.  Methods This prospective study was performed on 45 neutropenia patients with hematological malignancies. Nasal swabs were collected and analyzed by real-time multiplex polymerase chain reaction (PCR), covering the following viruses: influenza A virus, influenza B virus, human parainfluenza virus (subtypes 1-4), human respiratory syncytial virus A and B, enterovirus, human-coronavirus (HCoV: HKU1, NL63, 229E, and OC43), human bocavirus, adenovirus, human rhinovirus, human-metapneumovirus A and B, human paraechovirus, and a bacterium Mycoplasma pneumoniae. Patients enrolled in the study since the COVID-19 pandemic was also detected for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Of the 45 cases included in our study, 26 cases showed the presence of at least one positivity by PCR (57.7%): 23 patients had monoinfection with only one virus, two patients were found positive for coinfection with two viruses, and one patient was found positive for three viruses. The most detected viruses were human rhinovirus (26.9%, n=7) and coronavirus 19 (19.2%, n=5). A total of 11.5% of the patients had multiple viral infections. About 19 (42.2%) of the patients enrolled in our study had no viral pathogen detected. Conclusion We found that respiratory viruses contribute significantly to the development of neutropenic fever, as evidenced by the results of our prospective study. Individualizing infection treatment can reduce antibiotic use in immunocompromised patients. Thus, routine screening for viremia may be warranted in this clinical setting.

Histopathology and Molecular Biology Study of an Eyeball of a Case of Acute Retinal Necrosis.

PURPOSE: To report a histopathology and molecular biology study of an eyeball of a case of acute retinal necrosis (ARN). METHODS: Histopathology, immunohistochemistry and molecular biology of an enucleated globe of acute retinal necrosis 6 years after the onset of ARN. RESULTS: Histopathology showed persistence of chronic inflammatory cells with herpes virus inclusion body. Semi nested polymerase chain reaction showed varicella zoster virus. CONCLUSIONS: Chronic inflammatory cells and viral genome can be persistent even after 6 years after the onset of ARN.

Cluster of Post-Operative Endophthalmitis Caused by Acanthamoeba T10 Genotype - A First Report.

PURPOSE: To report a cluster of postoperative Acanthamoeba endophthalmitis after routine cataract surgeries. METHODS: A brief summary of sentinel events leading to the referral of 4 patients of postoperative endophthalmitis to our hospital is followed by clinical descriptions and the various diagnostic approaches and interventions used. Genotyping and phylogenetic analysis are also discussed. RESULTS: Four cases of postoperative cluster endophthalmitis, presumed to be bacterial and treated as such, were referred to our hospital. The presence of an atypical ring infiltrate in the first case facilitated the diagnosis of Acanthamoeba endophthalmitis. All patients had vitritis, corneal involvement, and scleral inflammation. Multiple diagnostic methods, such as corneal scrapings, confocal microscopy, aqueous and vitreous taps, scleral abscess drainage, histopathological studies, polymerase chain reaction, and genotyping and phylogenetic analyses of isolated Acanthamoeba, were used to confirm the diagnosis of endophthalmitis and to establish the extent of ocular involvement. Various medical and therapeutic interventions used to control the infections were also documented. The isolated Acanthamoeba were confirmed as belonging to the T10 genotype, an environmentally and clinically rare variety. CONCLUSIONS: This is the first report of a cluster of postoperative T10 genotype Acanthamoeba endophthalmitis, occurring after routine cataract surgery in immunocompetent individuals. Contrary to current perceptions, a rapidly evolving infection can occur with Acanthamoeba.

Cladosporium Endogenous Endophthalmitis Mimicking Toxoplasma Retinochoroiditis.

Background: Endogenous fungal endophthalmitis is a sight-threatening condition with potentially devastating outcome. Hematogenous spread of the infective seedings is the route of infection. Infected individuals have usually a compromised immune status. The clinical picture of mycotic endogenous endophthalmitis is commonly seen as chorioretinitis. Candida is the most common fungus. Cladosporium causing endogenous endophthalmitis is a rare occurrence, with only a few cases published.Methods: The report includes study and management of a diabetic patient with endogenous cladosporium endophthalmitis mimicking toxoplasma retinochoroiditis.Results: Diagnosis was confirmed as Cladosporium Cladosporioides in vitreous and aqueous aspirate by polymerase chain reaction-based DNA sequencing. Patient was successfully managed with intravitreal and systemic voriconazole.Conclusion: Cladosporium can cause endogenous endophthalmitis and mimic toxoplasma retinochoroiditis. Vitreous biopsy can help in diagnosis in the absence of positive blood culture. Intravitreal voriconazole along with systemic voriconazole shows a good response.

Driving in Fog without Headlight: Management of a Challenging Case of Presumed Ocular Toxoplasmosis.

Purpose: To describe a case of presumed ocular toxoplasmosis.Method: A retrospective chart review.Result: This case report describes a 35-year-old male who presented hypopyon anterior uveitis in his left eye. Fundus examination revealed severe vitritis which precluded the view of retina. His serum anti-toxoplasma immunoglobulin (Ig)G was significantly raised, with a normal anti-toxoplasma IgM level and PCR from nested primers targeting B1 gene of Toxoplasma gondii was positive. He was started on empirical anti-toxoplasma therapy. Undiluted vitreous specimen collected during lensectomy and diagnostic vitrectomy in left eye was also positive for nested primers targeting B1 gene of T. gondii.Conclusion: Ocular toxoplasmosis without retinochoroiditis, though extremely rare, can occur.