Microbiology / Infectious Disease
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Item Histoplasmosis Mistaken for Lung Neoplasm During Immunosuppression Therapy(2018-03-14) Liu, Luna; Sisay, Emnat; Machaiah, Madhrira; Bohra, HemaBackground TNFα antagonists such as Cimzia use large immunogenic protein molecules to induce deviations in normal host immunity and inflammatory response. Most warnings address alert providers to seriously consider initiating immunologics, because TNF plays an important role in immunity, notably against mycobacteria. Cimzia is different than other prior agents targeting TNF, because it does not fix, complement or induce cell-mediated cytotoxicity that is antibody-dependent from not having an immunologic Fc portion. Case information A sixty year-old female with psoriasis, hypertension and greater than fifteen year history of Crohn's disease on Cimzia presented after four months of cough, night sweats, weight loss and generalized weakness. Her productive chronic cough evolved from brownish and bloody phlegm to a greenish color. Initial imaging from her PCP revealed a right upper lung mass thought to be a malignant tumor. Social history did not endorse any use of tobacco products or prior history of COPD, asthma or pneumonia. Family history for cancer was unremarkable. Patient describes that she was a teacher for many years in an older school building that had multiple past infestations, including possum. The initial attempt at bronchoscopy was inadequate for pathology, but repeated procedure denoted an exophytic and fungating mass. Cardiothoracic surgery performed an elective right partial right pneumonectomy and mediastinoscopy. Pathology performed on brushings were negative for malignancy, but endorsed a granuloma with acute inflammation. Final biopsy from the procedure revealed a granulomatous inflammation with a methenamine silver stain revealing histoplasmosis. Urine histoplasma antigen was negative, but antibody was high at 1:1, which can be seen with disseminated or diffuse pulmonary histoplasmosis. Patient began a short inpatient course of liposomal Amphotericin B transitioning to oral itraconazole prior to discharge. Conclusions Histoplasmosis mimics many common respiratory infections and neoplastic processes with symptom presentation and radiologic findings that have led to surgical resections of non-malignant pulmonary granulomatous nodules initially thought to be carcinomas. Patients on certolizumab should be closely monitored for the development of disseminated disease such histoplasmosis and warned about participating in activities that can expose them to inhalation of airborne microconidia.Item When Pigs Fly: Thromboembolic Events in a Case of Severe H1N1 Influenza Type A(2018-03-14) Moran, Robyn; Cota, Donna; Boehme, Matthew; Liu, LunaTitle: When Pigs Fly: Thromboembolic Events in a Case of Severe H1N1 Influenza Type A First Authors: Luna Liu, DO Co-Authors: Robyn Moran DO; Matthew Boehme, DO Attending: Donna Cota, DO; Mohan Sengodan, MD; Ranjit Nair, MD; Anupama Chennupati, MD; Background/Abstract: H1N1 Subtype Influenza Type A, the strain responsible for the 2009 pandemic, is primary regarded as a disease affecting lung parenchyma, yet it is its ability to infiltrate and cause system wide complications which has made it such a deadly virus1-2. It is hypothesize the disease process may cause a propensity for thromboembolic events through activation of platelets, alterations of coagulation factors, or endothelial dysfunction3. There have been multiple documented cases of pulmonary embolism and myocardial infarctions in prior reports in H1N1 infected individuals, but few of cerebral events4-6. We present a unique case of severe H1N1-influenza in a previously healthy 47 year old male whose hospital course was complicated by multiple cerebral infarcts and R-femoral DVT. Case Report: 47 year old caucasian male without a significant PMHx presented initially for fevers, myalgias, and respiratory distress requiring intubation at an outside facility. His condition worsened and was transferred to our facility for higher level of care. He was initially found to to have septic shock requiring pressor support and started on empiric antibiotics. On arrival, the pt also underwent a bronchoscopy with washings; multiple cultures of blood, bronchial washings, sputum were negative for any growth. The pt continue to have breakthrough fevers. On admission day 4, he was found to have a DVT of R-femoral vein and started on a heparin drip; of note, the pt had been on chemical DVT prophylaxis since admission. Pt had difficulty with arousability off sedation and underwent extensive work-up including CSF studies which were negative. An MRI was significant for multiple small bilateral cerebral infarcts. Repeat transthoracic echoes were negative for signs of endocarditis or PFO on bubble study. Pt improved following tracheostomy placement and was discharged to LTAC on day 17th of hospitalization. Discussion: This case serves to illustrate the widespread effects of Influenza Type A H1N1 Subtype, even in healthy individuals. In this particular case, the pt had both venous and arterial thromboembolic events which is unique. It is important to keep in mind the extent of the disease process in this disease, especially in critically-ill patients. References: Dimitroulis, I. A., Katsaras, M., & Toumbis, M. (2016). H1N1 infection and embolic events: A multifaceted disease. Pneumon, 29(3), 230-235. Coorevits, L., Demuynck, H., Boone, E., Roelens, J., & Surmont, I. (2011). Trombo-embolic complications in influenza A(H1N1)2009: A forgotten and fatal danger, also in so-called "mild" flu? [Trombo-embolische verwikkelingen bij influenza A(H1N1)2009: Een vergeten en fataal gevaar, ook bij "milde" griep?] Tijdschrift Voor Geneeskunde, 67(7), 337-339. 10.2143/TVG.67.07.2000941 Paul E. Bunce, Sasha M. High, Maral Nadjafi, Katherine Stanley, W. Conrad Liles, Michael D. Christian; Pandemic H1N1 Influenza Infection and Vascular Thrombosis, Clinical Infectious Diseases, Volume 52, Issue 2, 15 January 2011, Pages e14–e17, https://doi.org/10.1093/cid/ciq125 Avnon, L. S., Munteanu, D., Smoliakov, A., Jotkowitz, A., & Barski, L. (2015). Thromboembolic events in patients with severe pandemic influenza A/H1N1. Eur J Intern Med, 26(8), 596-598. doi:10.1016/j.ejim.2015.08.017 Chandra, M., & Chander, T. (2016). Uncommon presentation of H1N1-Bilateral pulmonary thrombo-embolism. J Assoc Physicians India, 64(1), 145. Tsujii, N., Nogami, K., Yoshizawa, H., Hayakawa, M., Isonishi, A., Matsumoto, M., & Shima, M. (2016). Influenza-associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S-deficient boy. Pediatr Int, 58(9), 926-929. doi:10.1111/ped.13014Item Plasma Biomarkers as Potential Indicators for HIV-associated Neurocognitive Disorders(2018-03-14) Borgmann, Kathleen; Aryal, Subhash; Stacy, Satomi; Shenoy, Sangeeta; Ghorpade, Anuja; Swanta, NaomiPurpose: There are approximately 1.1 million people living with human immunodeficiency virus (HIV) in the United States (US). By race, African Americans and Hispanics are disproportionately affected by HIV. Despite improved life expectancy and a decline in HIV-associated dementia with the advent of antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) remain a major comorbidity, affecting 15-50% of HIV+ individuals. HAND severity correlates with immune activation, suggesting that inflammatory mediators play a significant role in disease progression. This study aims to identify biomarkers which correlate to neurocognitive impairment and associate with gender and race. Methods: HIV seropositive African Americans, Caucasians and Hispanics (10 men and 10 women in each category) were recruited in compliance with National Institutes of Health guidelines. Subject visits included informed consent, drug screening, HIV relevant medical history review, socio-demographic survey, neurocognitive assessment and blood collection. Neurocognitive assessment was further categorized into functional domains, domain 1 (memory, psychomotor speed, reaction time, complex attention and cognitive flexibility) and domain 2 (processing speed and executive functioning). Blood samples were processed to collect plasma, PBMCs, extra-chromosomal DNA, and RNA. Biomarker mRNA levels in PBMCs were quantified and protein levels were measured in plasma and PBMC culture supernatants. Differences in protein and mRNA levels across gender, cognitive status, race and socio-demographic factors were analyzed. HIV 2-LTR circles were quantified and correlated to neurocognitive status. Results: Multivariate analysis identified monocyte chemoattractant protein 2 (MCP2) and tissue inhibitor of metalloproteinases 1 (TIMP-1) as significantly different across cognitive domain 1 and 2. Interleukin-10 was significantly different across cognitive domain 2. A significant difference by level of education, occupation and income was observed in cognitive domains 1 and 2. Univariate analysis was performed to identify specific domain tests, which correlated with biomarker levels. Conclusions: Our data suggest that plasma protein levels likely correlate with neurocognitive impairment. We also demonstrate a relationship between several socio-demographic factors and neurocognition. Further studies to characterize and validate these potential biomarkers as indicators of HAND are being conducted.Item Characterization of a doxycycline inducible and astrocyte-specific HIV-1 Nef transgenic mouse model (iNef)(2018-03-14) He, Johnny; Luo, Xiaoyu; Fan, Yan; Tesselaar, Kiki; Wilson, KellyPurpose: Over 37 million people worldwide are currently infected with human immunodeficiency virus type 1 (HIV-1). Introduction of combination antiretroviral therapy has improved the quality and length of life, leading to increased incidents of minor cognitive and motor disorder. HIV-1 infects astrocytes, the most abundant cells of the central nervous system (CNS). Once infected, astrocytes become reactive, characterized by increased expression of astrocyte-specific protein glial fibrillary acidic protein (GFAP). However, those cells do not support productive HIV replication, primarily expressing non-structural viral proteins, such as Tat and Nef. Although the role of Tat in HIV/neuroAIDS has been extensively studied, little is known about the roles of Nef in HIV/NeuroAIDS. Nef is known to play important roles in immune evasion, T-cell depletion, and disease progression. The current study is to characterize roles of Nef in HIV/neuroAIDS. Method: A doxycycline inducible astrocyte-specific HIV-1 Nef transgenic mouse model (iNef) was created. In this model, Nef expression is under the control of both GFAP promoter and doxycycline responsive elements, which allows characterization of the effects of Nef expression on the CNS, independent of HIV-1 infection. Neuropathological outcomes (astrocytosis, neuroinflammation, and neuronal integrity) and neurobehavioral effects (motor and memory) were determined using immunofluorescence staining and neurobehavioral batteries, respectively. Results: Nef expression was confirmed in the brain of the iNef mice with doxycycline induction. Meanwhile, Increased GFAP expression and cytokine expression, loss of neuronal dendrites and decreased speed and latency to fall were found in these Nef-expressing iNef mice. Conclusion: These data show that Nef expression led to astrocytosis, neuroinflammation, compromised neuronal integrity, and impaired coordination and motor function in Nef-expressing iNef mice and suggest that Nef could be a major contributing factor to HIV/neuroAIDS. Further investigation is under way to determine the underlying molecular mechanisms.Item Diagnosis and Management of Pyomyositis(2018-03-14) Zekri, Sana; Al-Dossari, RannaIntroduction: Pyomyositis is a purulent infection of striated muscle tissue that usually leads to an abscess, commonly due to S. aureus. The pathophysiology is unknown, but is proposed to be due to hematogenous bacterial seeding in muscle bodies. Pyomyositis is typically found in tropic regions, but it is increasingly being recognized in temperate climates, especially in immunocompromised individuals. Patient presentation ranges from afebrile with mildly elevated WBC to frank sepsis. In many reported cases, patients may develop multiple abscesses at different sites. Case Description: A 54-year-old male with a history of COPD presented to the emergency department for worsening right pectoral pain with swelling and skin changes that persisted despite empiric outpatient antibiotic treatment for cellulitis. He reported superficial abrasions to the affected area one week prior to onset of symptoms along with fever, non-productive chronic cough, and red, swollen skin on his right chest. His social history was significant for heavy cigarette and alcohol use, and occasional methamphetamine use. On admission, vital signs were unremarkable, but he soon developed fever and tachycardia. On exam, the right pectoral region and shoulder were erythematous and tender, and noticeably asymmetric. Lab results demonstrated elevated inflammatory markers. Initial ultrasound of the affected area was consistent with cellulitis. A CT scan demonstrated inflammatory stranding of the pectoral muscle but no abscess. The patient was started on broad-spectrum antibiotics; however, his clinical status worsened. A repeat bedside ultrasound performed several days later demonstrated abscess formation. Surgical incision and drainage revealed copious purulence between the pectoralis minor and major muscles. Wound cultures grew methicillin-resistant S. aureus. The patient required repeat incision and drainage before being discharged on oral clindamycin. Discussion: This case highlights the difficulty of detecting tropical pyomyositis in its early stages without strong clinical suspicion, and also points to a possibility that broad-spectrum antibiotics may not effectively treat early pyomyositis before abscess formation is achieved. The role of antibiotics in early tropical pyomyositis, therefore, may be to prevent continued hematogenous spread and subsequent appearance of further lesions, but may not impact progression of disease at the primary site.