Infectious disease Roundup 2022

This paper describes the epidemiology, prevalence, transmission, prevention and control of some infectious diseases in companion animals, livestock, wild animals and humans in Ontario, Canada, in 2022, including SARS-CoV-2;Echinococcus multilocularis, Leishmania spp. and SARS-CoV-2;antimicrobial stewardship resources;2 cases of rabid dogs imported from Iran (July 2021 and January 2022);prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriacea, Dirofilaria immitis, Brucella canis, canine parainfluenza and adeno- and herpes viruses in dogs recently imported from Asia;Paragonimus kellicotti lung flukes and Streptococcus equi subsp. zooepidemicus in dogs;African swine fever in pet pigs, backyard pigs and wild pigs and blastomycosis in dogs and humans.

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

PRIMARY LUNG MALIGNANCY PRESENTING AS RARE CUTANEOUS METASTASIS TO EYELID

SESSION TITLE: Unusual Cancer Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Cutaneous lesions may present as a clue to an internal malignancy and provide an easily accessible site for tissue confirmation. We present a case of an eyelid metastatic lesion presenting as an initial sign of primary pulmonary malignancy. CASE PRESENTATION: A 67-year-old woman with past medical history of SARS-COVID-2 pneumonia six months ago and reformed smoker (26 pack year) who quit 27 years ago, presented to the primary care physician's office with a chief complaint of a small right upper eyelid margin (base of eyelashes) lesion (Figure 1A), and ongoing nonproductive cough and fatigue since diagnosis of SARS-COVID-2 pneumonia. The eyelid lesion appeared two weeks prior and had quickly grown in size. The lesion was associated with mild itching, but without any associated pain, discharge, or bleeding. She also complained of left elbow and foot pain but denied fever, chills, rigors, hemoptysis, pleurisy, and weight loss. Physical examination was negative for lymphadenopathy. Chest x-ray revealed a hazy left upper lobe opacity. Urine antigen for blastomycoses and histoplasma were negative. Rheumatoid factor, erythrocyte sedimentation rate, C reactive protein, QuantiFERON TB gold and anti-nuclear and cyclic citrullinated peptide antibodies were negative. Computed tomography of chest revealed a left upper lobe 3.7 x 5.4 x 5.6 cm mass, numerous bilateral ground glass opacities, and scattered (less than 5 mm) nodules (Figure 1B). Simultaneously, the patient was evaluated by an ophthalmologist for excision of the eyelid lesion. Histopathological evaluation revealed malignancy compatible with metastatic lung adenocarcinoma (Figure 1C) DISCUSSION: While an uncommon presentation, this case highlights the importance of a through history and examination in a patient presenting with pulmonary symptoms with risk factors for a lung malignancy. While she did have imaging that demonstrated lung masses, the diagnosis of lung cancer came not from invasive sampling of these masses, but rather from excision and histopathological evaluation of an eyelid soft tissue mass. Lung cancer is prone to metastasis, however cutaneous manifestations of lung cancer are relatively rare and are more common in the advanced stages of disease, making cutaneous metastasis a poor prognostic factor. In terms of cutaneous metastases, ocular metastases are one of the rarest locations making this a unique presentation. In a patient presenting with pulmonary masses, any concurrent development of new and/or growing skin lesions should be evaluated to rule out metastasis and potentially yield diagnosis. CONCLUSIONS: In patients presenting with concern for a malignant lung process, a skin exam should be completed, and suspicious skin lesions should be biopsied. Although rare, lung malignancies do metastasize to ocular cutaneous tissues and are a marker of more advanced stage of the malignancy. Reference #1: Hidaka T, Ishii Y, Kitamura S. Clinical features of skin metastasis from lung cancer. Intern Med. 1996;35:459-462. Reference #2: Marcoval J, Penin RM, Llatjos R, Martinez-Ballarin, I. Cutaneous metastasis from lung cancer: retrospective analysis of 30 patients. Australas J Dermatol. 2012;53(4):288-290. Reference #3: Abdeen Y, Amireh S, Patel A, Al-Halawani M, Shaaban H, Miller R. Cutaneous metastasis as a first presentation for lung adenocarcinoma. N Am J Med Sci. 2016;8(5): 222-225. DISCLOSURES: No relevant relationships by Gregory Griepentrog No relevant relationships by Chinmay Jani No relevant relationships by Bailey Ray No relevant relationships by Harpreet Singh No relevant relationships by Amit Taneja No relevant relationships by Kara Young

DISSEMINATED BLASTOMYCOSIS FOLLOWING COVID-19 INFECTION

SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: The diagnosis of blastomycosis is often delayed due to its non-specific symptoms and imaging findings. Clinicians must have a high clinical index of suspicion to diagnose blastomycosis in a timely manner, especially in the setting of the current COVID-19 pandemic. CASE PRESENTATION: A healthy 44-year-old male presented to an urgent care center with complaints of cough, fevers, and malaise. CT scan of the chest revealed a left upper lobe mass concerning for rounded bacterial pneumonia versus malignancy. He was found to be COVID-19 positive. The patient was sent home with steroids and antibiotics. Three months later, a repeat CT scan of the chest was obtained which revealed progression of the consolidation and prompted further evaluation at the hospital. On presentation, he reported a persistent cough, weight loss, and the development of multiple painful nodules on his extremities and trunk within the past week. A skin lesion was biopsied. A bronchoscopy was also performed for biopsy and brushing. Biopsy of the skin lesion as well as specimens collected from the bronchoscopy resulted positive for Blastomyces. MRI of the brain demonstrated multiple enhancing lesions concerning for septic emboli. He was started on amphotericin B for treatment of disseminated blastomycosis with central nervous system (CNS) involvement. Repeat imaging of the brain and chest about 3 weeks after initiation of therapy showed interval decrease in the size of the lesions. He was then transitioned to oral itraconazole and discharged home. DISCUSSION: Blastomycosis is an endemic fungal infection that can affect immunocompetent and immunocompromised hosts. It tends to infect immunocompetent hosts more so than other invasive fungal infections. Symptoms can range from asymptomatic to rapidly progressive acute respiratory distress syndrome (ARDS). Disseminated blastomycosis has been reported in 20-50% of patients (1). In the above case, an immunocompetent patient developed pulmonary and dermatologic manifestations concerning for disseminated blastomycosis. Though he had no recent travel, occupational exposures, or contact with any construction work, the patient was living in an endemic area for Blastomyces. It is difficult to definitively ascertain if the patient already had pulmonary blastomycosis when he was diagnosed with COVID-19, but his extrapulmonary manifestations clearly developed after the diagnosis. Earlier detection and treatment of the pulmonary blastomycosis may have prevented the dissemination of the disease. CONCLUSIONS: This case serves as a reminder to consider other infectious etiologies, like endemic fungal infections, in the midst of the COVID-19 pandemic to prevent delays in treatment and progression of these diseases. Reference #1: McBride JA, Gauthier GM, Klein BS. Clinical Manifestations and Treatment of Blastomycosis. Clin Chest Med. 2017 Sep;38(3):435-449. doi: 10.1016/j.ccm.2017.04.006. Epub 2017 Jun 12. PMID: 28797487;PMCID: PMC5657236. Reference #2: Cafardi J, Haas D, Lamarre T, Feinberg J. Opportunistic Fungal Infection Associated With COVID-19. Open Forum Infect Dis. 2021 Jan 18;8(7):ofab016. doi: 10.1093/ofid/ofab016. PMID: 34621913;PMCID: PMC7928619. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff No relevant relationships by David Stoeckel

BUT WHAT ABOUT THE RASH?

SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: This is a case of a patient 74-year-old immunosuppressed woman presenting with a one-week history of skin lesions. CASE PRESENTATION: A 74-year-old woman with Crohn's disease (on weekly adalimumab);pulmonary hypertension (RVSP 76 mmHg);OHS/OSA, on home BPAP 17/7 cmH2O;and morbid obesity presented with a one-week history of skin lesions. She was seen by her primary care physician two days prior with skin lesions, shortness of breath, and decreased vision. She was hypoxic during the visit and given doxycycline for empiric treatment of pneumonia. She denied recent travel or exposure to animals. On admission, she was afebrile (36.9C) and saturating 98% on 2 L nasal cannula. She appeared chronically ill with mouth ulcers and an eroded nodule with overlying hemorrhagic crusting and peripheral pustular area above her right eyebrow (figure 1). Throughout her skin, she had multiple erythematous papules, some with overlying vesicles/pustules. Labs were significant for a leukocytosis of 19.3 with left shift, lactate of 3.5, serum creatinine of 1.9 (likely higher than patient's previous baseline of 1.7 with previous history of recurrent AKIs on CKD), elevated inflammatory markers, and normal ALT/AST. Influenza and COVID were negative. A CT chest showed consolidations and numerous pulmonary nodules highly suspicious for an infectious or inflammatory process (figure 2). She was treated empirically with vancomycin, piperacillin-tazobactam, valacyclovir, and amphotericin B, the latter given the concern of blastomycosis. During her hospitalization, she had further respiratory failure requiring intubation and multiorgan failure. Disseminated blastomycosis was confirmed via a skin biopsy which demonstrated pyogranulomatous inflammation with numerous broad-based budding yeasts (figure 3) and supported with a bronchoalveolar lavage (BAL) culture growing the same. Given her continued decline, her medical decision maker decided to transition the patient to hospice care. DISCUSSION: Blastomycosis is a systemic pyogranulomatous infection that is caused from the inhalation of the conidia form of the dimorphic fungus. It can manifest as asymptomatic infection, acute or chronic pneumonia, or extrapulmonary disease. BAL yields a positive diagnosis in 92% of patients and definitive diagnosis requires growth of the organism from a clinical specimen. Without appropriate treatment of amphotericin B or one of the azole antifungals, the disease had a 90% mortality rate. CONCLUSIONS: Prompt recognition of multiorgan failure secondary to blastomycosis is important for early treatment and improved survival in immunocompromised patients Reference #1: 1)Chapman, S W et al. "Endemic blastomycosis in Mississippi: epidemiological and clinical studies.” Seminars in respiratory infections vol. 12,3 (1997): 219-28. Reference #2: 2)Saccente, Michael, and Gail L Woods. "Clinical and laboratory update on blastomycosis.” Clinical microbiology reviews vol. 23,2 (2010): 367-81. doi:10.1128/CMR.00056-09 Reference #3: 3)Chapman, Stanley W et al. "Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 46,12 (2008): 1801-12. doi:10.1086/588300 DISCLOSURES: No relevant relationships by Jennifer Duke No relevant relationships by Ashley Egan

SEVERE PULMONARY BLASTOMYCOSIS IN A PATIENT WITH A COVID-19-POSITIVE TEST: A DANGEROUS ANCHORING BIAS

SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Severe pulmonary blastomycosis (PB) usually affects immunocompromised patients, with very high mortality rate of up to 40%. PB can mimic pneumonia caused by other organisms (1), which can delay diagnosis and treatment initiation. We present a case of severe PB that was initially thought to be COVID-19 pneumonia, to our knowledge this is 2nd case of concomitant PB and COVID-19 infection in literature. (2) CASE PRESENTATION: Patient is 52 year old female with past medical history of atrial fibrillation, asthma, bariatric surgery, that presents with shortness of breath for 2 weeks. Despite receiving only 1 dose of COVID-19 vaccine (Moderna) 5 months ago, patient tested positive for COVID-19 on PCR test at the urgent care 4 days prior. Her symptoms progressed despite initial outpatient treatment with steroids and antibiotics. Initial emergency department chest computed tomography (CT) revealed dense bilateral consolidations, with hypoxic respiratory failure, patient was admitted for treatment of presumed COVID-19 pneumonia, and guideline directed treatment was initiated. Despite maximal medical management, that included steroids, broad spectrum antibiotics, remedisivir, patient failed to improve, with repeat CT chest revealing worsening consolidations. Bronchoscopy was performed 12 days into the admission revealed thick white secretions, with cultures growing blastomyces dermatitidis. At this point patient development of septic shock with multiorgan failure. Patient was subsequently intubated, and due to significant renal failure, initiated on hemodialysis (HD). Anti-fungal treatment was initiated with amphotericin B, and transitioned to itraconazole afterwards. Patient required several HD sessions, after which her renal function fully recovered. Patient was successfully extubated 7 days later, but required additional 22 days of medical care and physical therapy before being ready for discharge to rehabilitation facility. On the outpatient follow up 6 weeks after discharge, patient continues to slowly recover. Repeat CT chest still with significant bilateral consolidations. Patient will require at least 12 months of itraconazole therapy. DISCUSSION: PB can mimic bacterial and viral pneumonia symptoms. (1) In the widespread COVID-19 pandemic, clinicians can be misled by COVID-19 positive test in patient with bilateral pneumonia, and initiate guideline directed therapy. Immunosuppression agents can lead to adverse outcomes in patients with underlying PB. Questionable is the significance of COVID positive PCR test in semi-vaccinated individual. Potentially even mild COVID-19 infection could predispose patient for PB. Early diagnosis of PB is important, as delay in treatment and medical immunosuppression can lead to worse outcomes. CONCLUSIONS: PB should be suspected even in patients presenting with positive COVID-19 PCR test. Guideline directed therapy for COVID-19 can worsen underlying PB. Reference #1: https://www.cdc.gov/fungal/covid-fungal.html Reference #2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503152/ DISCLOSURES: No relevant relationships by Dovile Baniulis No relevant relationships by Dovile Cerkauskaite No relevant relationships by Igor Dumic No relevant relationships by Momcilo Durdevic No relevant relationships by Dragana Durdevic No relevant relationships by Ashutossh Naaraayan No relevant relationships by Ankita Subedi

A Case of Multifocal Necrotizing Blastomycosis Pneumonia and Acute Respiratory Distress Syndrome (ARDS) in an Adolescent with Type 1DiabetesMellitus

Introduction: Blastomyces species are thermally dimorphic fungi endemic to North America, especially areas bordering the Mississippi, Ohio and St. Lawrence rivers, and the Great Lakes. Blastomycosis infections are estimated to occur in 3-13% in the pediatric population. Pediatric literature for blastomycosis has been mostly limited to small studies and case series. Recent literature suggests increasing rates of infections, less morbidity and mortality as compared to adults, with asthma as the most common comorbid condition. Although pulmonary disease is the most common presentation, it rarely progresses to acute respiratory distress syndrome (ARDS). Case Description: A 17- year-old female, living in the Chicago area, and with type 1 diabetes mellitus and childhood asthma, presented to the emergency room with acute hypoxemic respiratory failure after 14 days of cough, dyspnea, chest pain, and fevers as high as 105°F. Her initial radiographic imaging revealed bilateral infiltrates and consolidations in the right middle and lower lobes. She was admitted to the step down unit for further care. A respiratory viral panel, including COVID-19 evaluation, was negative. She was started on low-flow nasal cannula, ceftriaxone, azithromycin, albuterol, and maintenance IV fluids. On hospital day 2, she was transferred to the pediatric intensive care unit for worsening respiratory distress and escalated to high-flow nasal cannula. She was treated empirically for presumed bacterial pneumonia with ceftriaxone (7-day course), azithromycin (5-day course), cefepime (5-day course), clindamycin (2-day course), and vancomycin (14-day course). Despite this treatment, repeat chest imaging showed worsening disease and she required escalation to BiPAP for progression of her ARDS and impending respiratory failure. Karius testing results indicated Blastomyces dermatitidis at low levels typically not clinically relevant. Sputum and bronchoalveolar lavage cultures demonstrated no significant pathogenic bacteria. Pathology exam of the biopsy obtained from bronchoscopy was consistent with Blastomyces. Urine antigen test was positive for both Blastomyces and Histoplasma. She clinically improved after initiating Amphotericin B lipid complex (6-day course), with transition to oral itraconazole and adjunctive therapy with IV methylprednisolone. She was discharged home after a 30-day hospital stay. Discussion: Pulmonary blastomycosis presents with a broad variety of signs and symptoms. Timely diagnosis is challenging. Pulmonary blastomycosis has no pathognomonic radiographic patterns. Severe acute pulmonary infection that fails to respond to antibacterial treatment should prompt investigation for fungal infection, including urine antigen tests for Histoplasma and Blastomyces, serum galactomannan, beta-1,3-D-glucan, and next-generation sequencing of microbial cell-free DNA (eg, Karius test). Close respiratory monitoring should occur in a pediatric intensive care unit. Conclusion: Blastomycosis is not typically in the initial differential diagnosis unless the patient has other clinical findings, fails to improve on antibacterial therapy, or has identified risk factors for exposure. Failure of prompt recognition is associated with poor outcomes, increased morbidity and mortality, increased length of hospital stay, and cost.

A CASE OF MULTIFOCAL PNEUMONIA -A DIAGNOSTIC CHALLENGE

CASE: A 25 year old Vietnamese female initially presented to the emergency department (ED) with progressive dyspnea and cough for 2 weeks. Chest Xray (CXR) showed left lower lobe consolidation and was started on a 5-days of azithromycin. She returned to ED 3 days later with a worsening cough, yellowish sputum, dyspnea, pleuritic chest pain, chills, appetite loss, and a 6-pound weight loss. 7 years ago her pre-immigration screening was negative for tuberculosis. She worked in a nail salon and did gardening as a hobby. On exam, she was afebrile, appeared dyspneic with normal oxygen saturation, diminished breath sounds on left lower lobe with egophony. Labs showed leukocytosis of 22,300 with neutrophilia and negative COVID-19 test. Repeat CXR showed worsening left lower lobe opacity. On day 3, temperature peaked at 103.1F with worsening sputum production. Computed tomography (CT) chest showed complete consolidation of the left lower lobe with tree-in-bud opacities in bilateral upper lobes and right lower lobe. Antibiotics were switched from ceftriaxone and azithromycin to piperacillin-tazobactam and vancomycin. Bronchoalveolar lavage (BAL) gram stain, acid-fast bacilli stain and gomori stain, and blood cultures were negative. Follow-up CT chest was worse and repeat bronchoscopy with biopsy was done. On day 8, urinary blastomyces and histoplasma antigen tests were positive. BAL cytology showed budding yeast consistent with blastomycosis. IV voriconazole was added and her symptoms gradually improved. She was discharged on 6-month course of oral voriconazole. BAL and biopsy cultures came back positive for B. dermatitidis confirming the diagnosis. Outpatient follow-up with CXR after a month showed both clinical and radiological improvement. IMPACT/DISCUSSION: Blastomycosis is a fungal infection caused by thermally dimorphic fungi Blastomyces species, endemic in Ohio, Mississippi River Valleys, and the Great Lakes region in the United States. It commonly presents as a pulmonary infection following inhalation of spores. Severity varies from asymptomatic to life-threatening acute respiratory distress syndrome. Diagnosis delay is common with frequent misdiagnoses including bacterial pneumonia, malignancy, and tuberculosis. Pulmonary blastomycosis commonly presents as dense consolidation in the upper lobes but can have variable presentation. Serological tests, cultures and BAL studies can aid in diagnosis. Repeat bronchoscopies should be considered when the suspicion is high. Of note, blastomyces antigen can have cross-reactivity with histoplasma antigen which might be the case with our patient. CONCLUSION: This case highlights the resemblance of clinical and radiological presentation of blastomycosis with other respiratory conditions and the need for timely diagnosis, treatment, and antimicrobial stewardship. Practitioners need to keep a strong suspicion of this disease in patients with atypical presentation for pneumonia especially in endemic areas.

DISSEMINATED BLASTOMYCOSIS IN A 38-YEAR-OLD MAN WITH BACK PAIN

TYPE: Case Report TOPIC: Chest Infections INTRODUCTION: Blastomycosis is endemic to the midwest, south-central and southeast regions of North America. It should thus be suspected in the differential of patients presenting with atypical symptoms, as extrapulmonary manifestations can be seen. We present a case of disseminated blastomycosis to the spine prior to development of significant pulmonary symptoms. CASE PRESENTATION: 38 year old male presents to a tertiary center in Southern Indiana with back pain of 8 months, fever and dyspnea. Magnetic resonance imaging was significant for L1 osteitis and chest x-ray showed diffuse interstitial markings. Lab work showed leukocytosis with erythrocyte sedimentation rate of 91, and C-reactive protein of 45. He was initiated on broad spectrum antibiotics without any improvement. Due to worsening respiratory failure requiring supplemental oxygen, infectious disease and pulmonology specialists ruled out Legionella, Aspergillosis, COVID-19, HIV, Histoplasmosis, Mycoplasma, Hantavirus and Tuberculosis. Blood cultures and respiratory panel were negative. Urinary blastomycosis antigen was positive. Patient completed 14 days of amphotericin B and was discharged on itraconazole for at least 1 year. DISCUSSION: Blastomycosis can have a broad spectrum of manifestations with pulmonary infection in more than 79% of patients. Extrapulmonary dissemination is less common though can occur in approximately 25-40% of symptomatic patients. Osseous blastomycosis is the second most common dissemination site following the skin and is seen in approximately 5-25% of patients. CONCLUSIONS: We recommend early consideration of blastomycosis in patients with atypical infectious symptoms who reside in Blastomyces endemic regions. Early diagnosis is key in initiating appropriate treatment and preventing severe complications of disseminated disease. DISCLOSURE: Nothing to declare. KEYWORD: blastomycosis

Testing Practices for Fungal Respiratory Infections and SARS-CoV-2 among Infectious Disease Specialists, United States.

In an online poll, 174 infectious disease physicians reported that testing frequencies for coccidioidomycosis, histoplasmosis, blastomycosis, and cryptococcosis were similar before and during the COVID-19 pandemic, indicating that these physicians remain alert for these fungal infections and were generally not concerned about the possibility of under-detection.