Fariba Donovan

Interests

Research

As both a research scientist and practicing infectious disease clinician I remain keenly aware of the importance of the practical application of basic research, to the broader problems we face treating patients with both invasive and opportunistic fungal infections. Over the last five years, while seeing patients in the Valley fever clinic as well as in our hospital along with an exponential increase in the use of biological response modifiers in patients with autoimmune disorders I have seen the need for more study and a better understanding of the risk and benefits of these medications in a Coccidioidomycosis endemic region. My background is well suited for this task. Post medical residency training in my native Iran, I was able to obtain a Ph.D. at Gifu University in Japan. My research focused on candida albicans and its interaction with the human host. I developed specific expertise in protein purification, molecular biology, and gene manipulation techniques to further identify C. albicans virulence factors. During my post-doctoral work in the US, I started my research on Coccidioides species, and I was able to specifically purify the urease protein, construct a urease knockout strain, and demonstrate lesser virulence in the animal model. The knockout strain showed promise as a potential vaccine candidate, and this work remains an active area of Valley fever research. After moving to Cincinnati, I was able to broaden my research to the genetic manipulation of histoplasma capsulatum and the immune interaction in the animal model. In retrospect, my completion of an internal medicine residency and infectious disease fellowship was a natural extension of my desire to put into practice my research interest and findings. In 2017 I was recruited to the University of Arizona at the Valley Fever Center for Excellence, which has allowed me to continue my Valley fever research and improve the prevention, diagnosis, and treatment of Valley fever. My initial project focused on Coccidioidomycosis diagnostic delays with an emphasis to reduce both unnecessary testing, and treatments and thereby reduce morbidity and mortality. Additional benefits included improving antibiotic stewardship, developing population management programs, and serving as a model to address other opportunistic infections. My emphasis on early events in Coccidioidomycosis allowed me to focus on identifying clinical cues that lead to earlier diagnosis of Valley fever and to assess the impact of clinical practice training on the diagnosis and management of this disease. I completed a prospective study at the Banner University Medical Center to evaluate a rapid lateral flow assay for rapid diagnosis of coccidioidomycosis and the results have been published. Additionally, I am developing plans to study the host’s innate immune response to Coccidioides with a focus on the early events in coccidioidomycosis. I have recently completed a retrospective study and quantified the risk biological response modifiers (BRMs) play in patients with autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, or psoriasis. Our ability in the former study to prospectively enroll a large cohort of patients makes us confident that we can contribute to the success of our ongoing projects, which ultimately will allow us to develop a highly sensitive, rapid, portable, and user-friendly detection device for early diagnosis of coccidioidomycosis.

Teaching

We are reminded daily of the critical importance of teachers to the benefit and advancement of civilization. Passing on to others the fruits of one's education, research and experience is an absolute requirement and enduring gift to society. I consider research, clinical duties and teaching as the three most important aspects of my life's work.As an Infectious disease physician, one of my main goals is cultivating the interest in various fields of infectious diseases among the fellows, residents and medical students and general public. In particular I enjoy sharing my expertise in medical mycology especially Coccidioidomycosis and other areas of infectious disease such as virology (HIV and hepatitis).The education of the ID fellows is focused on complicated cases (eg. HIV/AIDS, hepatitis, transplant patients and complicated surgical infections) that they will encounter in near future as they complete their training.In a similar vein with medical residents, I seek to encourage them to be aware of the importance of infectious disease in general medical practice and make them comfortable with various infectious diseases that they will confront in daily practice.With medical students, my goal is to open their minds and have them experience the importance of infectious diseases and all aspects of medicine and perhaps encourage some to consider ID as their future carier.With the general public, it is important to educate everyone about how infectious diseases touch their lives. This might include a broad range of activities such as addressing local groups about Valley Fever, or speaking to the media to raise awareness about the overuse of antibiotics and the ongoing challenges with antibiotic resistance. As important as it is to educate others, It is equally important to continue educate myself. This include reviewing other's research, stay abreast of the latest advancements in antimicrobials and attending conferences to further advance my education.

Courses

Scholarly Contributions

Journals/Publications

• Benedict, K., Hennessee, I., Cooksey, G. S., Donovan, F. M., Thompson, G. R., Williamson, T., & Toda, M. (2025). Comparison of Patients With Coccidioidomycosis in Arizona Versus California: A Commercial Health Insurance Claims Analysis. Open Forum Infectious Diseases, 12(Issue 7). doi:10.1093/ofid/ofaf405
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  Commercially insured patients with coccidioidomycosis in Arizona (n = 1640) were more likely to have symptoms indicating acute pulmonary disease (eg, cough, dyspnea, chest pain) compared with patients in California (n = 701), who were more likely to have disseminated coccidioidomycosis, possibly reflecting differences in exposure, healthcare seeking, or clinical management.
• Coleman, C. I., Bylyku, J., Latifi, A., Lovelace, B., Shan, R., Miriyapalli, L., & Donovan, F. (2025). The Burden of Hospital Illness Associated with Disseminated Versus Isolated Pulmonary Coccidioidomycosis in the United States. Journal of Fungi, 11(Issue 2). doi:10.3390/jof11020161
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  There are scarce data comparing inpatient mortality, length of stay (LOS) and all-cause hospital costs in disseminated coccidioidomycosis (DCM) vs. isolated pulmonary coccidioidomycosis (IPCM). We assessed the burden of hospital illness associated with DCM versus IPCM. This study was performed using National Inpatient Sample data from 2019 to 2021. DCM was defined as having a primary International Classification of Diseases—Tenth Revision (ICD-10) code for coccidioidal meningitis, a non-primary code for coccidioidal meningitis in the presence of a primary code for a meningitis complication or a procedure code depicting the need for a meningitis-related procedure, or a primary code for DCM without a code for unspecified disease. IPCM was defined as a primary code for pulmonary coccidioidomycosis without codes for DCM or unspecified disease. Multivariable regression was used to compare the odds of in-hospital mortality, LOS and all-cause hospital costs (2023 US$) for DCM versus IPCM, after covariate adjustment. A total of 6195 hospitalizations were identified, 2305 for DCM and 3890 for IPCM. Patients experiencing a DCM hospitalization had a 19.7% incidence of concomitant pulmonary coccidioidomycosis. Coccidioidal meningitis constituted 81.3% of all DCM hospitalizations, of which 78.1% received a meningitis-related procedure or were admitted for a meningitis complication. DCM was associated with an increased odds of death (odds ratio = 2.76, 95% confidence interval [CI] = 1.26–6.04) versus IPCM. DCM was associated with a longer mean hospital LOS (4.51 days, 95%CI = 3.39–5.63) and higher mean all-cause costs ($20,008, 95%CI = $15,313–$24,704) versus IPCM. DCM hospitalizations were associated with higher odds of inpatient mortality, longer LOS, and higher costs versus IPCM.
• Coleman, C. I., Danese, S., Ulloa, J., Bresnik, M., Lovelace, B., & Donovan, F. (2025). Misuse of the unspecified coccidioidomycosis diagnosis code: An audit of electronic health records. Medical Mycology, 63(Issue 10). doi:10.1093/mmy/myaf091
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  Widespread use of the ‘unspecified coccidioidomycosis’ code (B38.9) may negatively impact provider reimbursement and complicate study of disease burden. We sought to determine the frequency of B38.9 use in routine practice and assess how often it could be changed to a more specific code, what code that might be, and reasons for its initial use. To estimate the proportion of all coccidioidomycosis cases that were classified using the International Classification of Diseases-Tenth-Revision unspecified diagnosis code (B38.9), three real-world datasets were queried. Further, in January 2025, providers in coccidioidomycosis-endemic areas were invited to participate in an online electronic health record (EHR) audit to study their three most recent patients coded as B38.9 over the prior 12 months. The proportion of patients that could have received a more specific coccidioidomycosis code by provider was determined, as were the recommended alternative code(s), and reasons for the B38.9’s initial use. Across queried datasets, 17.8–49.5% of coccidioidomycosis cases were coded as unspecified. We recruited 19 providers to audit EHRs of 53 patients, in which B38.9 was used. Thirty-six (67.9%) patients could have been assigned a more specific coccidioidomycosis code, including 14 (38.9%) to disseminated disease (B38.7). Common reasons for using B38.9 included evolving clinical assessment (37.0%), lack of coding expertise (22.2%), and entry errors (22.2%). In conclusion, a substantial proportion of coccidioidomycosis diagnoses are assigned to B38.9. Over two-thirds of these could have been better described using a more specific code. There is a need for educational efforts to promote more precise coding.
• Donovan, F. (2024).

  Coccidioidomycosis a Global Concern

  . JAC.
• Donovan, F. (2025).

  CT and MRI Findings Among Patients with Coccidioidal Vertebral Osteomyelitis Versus Pyogenic (Bacterial) Vertebral Osteomyelitis

  . Orthopaedic Proceedings. doi:doi.org/10.1302/1358-992X.2025.12.054
• Donovan, F. (2025).

  Coccidioidomycosis-Attributable Death in the United States: An Analysis of Cases Reported on Death Certificates, 2018-2023

  . J of Fungi. doi:doi: 10.3390/jof11110766
• Donovan, F. (2025).

  Comparison of patients with coccidioidomycosis in Arizona vs. California: a commercial health insurance claims analysis

  . OFID. doi:doi: 10.1093/ofid/ofaf405
• Donovan, F. (2025).

  Interferon-γ therapy in patients with refractory disseminated coccidioidomycosis

  . Clinical Infectious diseases. doi:doi:10.1093/cid/ciaf286).
• Donovan, F. (2025).

  Misuse of the Unspecified Coccidioidomycosis Diagnosis Code: An Audit of Electronic Health Records

  . Medical Mycology. doi:doi: 10.1093/mmy/myaf091
• Donovan, F. (2025).

  Olorofim for the treatment of invasive fungal diseases in patients lacking suitable therapeutic options 

  . Lancet ID.
• Donovan, F. (2025).

  The Great Coccidioides Escape: From Lung to Skin

  . Am J of Medicine. doi:doi: 10.1016/j.amjmed.2025.06.017
• Donovan, F. M., Fernández, O. M., Bains, G., & DiPompo, L. (2025). Coccidioidomycosis: a growing global concern. Journal of Antimicrobial Chemotherapy, 80(Issue 1). doi:10.1093/jac/dkaf002
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  Coccidioidomycosis (CM) has been a recognized disease for about 130 years. The organisms (Coccidioides spp. fungi) inhabit desert soil in the southwestern USA, Mexico, and parts of Central and South America. Natural events such as dust storms, wildfires or outdoor activities including construction and gardening can disrupt the fungal arthroconidia, which easily become airborne and inhaled by the host. Approximately 60% of those exposed to arthroconidia are asymptomatic and do not require medical attention, but 30% show signs of pulmonary infection with symptoms ranging from a flu-like illness to pneumonia. In 5%–10% of cases serious or disseminated disease develops, which requires prompt diagnosis and management. About 1%–3% of infections disseminate to the CNS and if not appropriately treated are often fatal. There is an urgent need for improved diagnostics and treatments.
• Donovan, F., Bresnik, M., Lovelace, B., Pizzicato, L., Anupindi, V. R., DeKoven, M., & Coleman, C. I. (2025). Antifungal therapy patterns, healthcare utilization, costs, and mortality in central nervous system and non-central nervous system disseminated coccidioidomycosis across the continuum-of-care. Clinical Microbiology and Infection, 31(Issue 6). doi:10.1016/j.cmi.2025.02.001
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  Objectives: This study aims to describe baseline characteristics, antifungal treatment patterns, healthcare utilization, costs, and mortality in patients with central nervous system (CNS) and non-CNS disseminated coccidioidomycosis. Methods: A retrospective study using IQVIA claims data was conducted to identify adults with disseminated coccidioidomycosis in two mutually exclusive cohorts: those with CNS and those with non-CNS disease. Patients had to have ≥1 medical claim for disseminated coccidioidomycosis from October 2015 to November 2022. Antifungal treatment patterns were assessed, as were all-cause healthcare utilization, costs, and mortality during follow-up. Results: In total, 2218 patients were identified, 28.2% (626/2218) with CNS and 71.8% (1592/2218) with non-CNS disease. In both cohorts, 70.9% (444/626) and 71.6% (1140/1592) of patients initiated first-line antifungal treatment, most with fluconazole (881/1140, 77.3% to 372/444, 83.8%), followed by an azole + lipid amphotericin B (21/444, 4.7% to 81/1140, 7.1%). Azole monotherapy was used often over subsequent lines of antifungal treatment in both cohorts (1049/1140, 92.0% to 122/129, 94.6%). Polyenes peaked in the latter lines of therapy (24/182, 13.2% to 79/408, 19.4%), mostly administered with azoles. Median baseline costs in the CNS and non-CNS cohorts were substantial ($9122 and $8242, respectively). After diagnosis, 29.7% (186/626) of patients in the CNS cohort experienced a subsequent hospitalization and all-cause cost of $28 664 per person per year. The non-CNS patients experienced a similar proportion of patients requiring hospitalization (469/1592, 29.5%) and all-cause costs of $21 240 per person per year. Between 5.4% (34/626) and 6.7% (106/1592) of patients died during follow-up, with death more likely in those with concomitant pulmonary coccidioidomycosis, sepsis, certain immunosuppressive diseases, and prior azole use. Discussion: Most patients with either CNS or non-CNS disseminated coccidioidomycosis received an azole first line and demonstrated azole-cycling over subsequent lines. Polyenes were used in the latter lines. Patients utilized substantial healthcare resources and accrued appreciable costs, both before and after diagnosis.
• Perez, K. D., Friedman, L. M., Harouzi, M. M., Wu, R. L., & Donovan, F. M. (2025). The Great Coccidioides Escape: From Lung to Skin. American Journal of Medicine, 138(Issue). doi:10.1016/j.amjmed.2025.06.017
• Coleman, C. I., Donovan, F., Miriyapalli, L., Shan, R., & Lovelace, B. (2024). Burden of Hospitalization for Coccidioidal Meningitis: An Analysis of the National Inpatient Sample, 2019–2021. Open Forum Infectious Diseases, 11(Issue 12). doi:10.1093/ofid/ofae706
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  Coccidioidal meningitis (CM) requires lifelong aggressive management, often necessitating hospitalization. In the National Inpatient Sample (2019–2021), CM hospitalizations (N = 2305) were associated with frequent CM-related procedures (63.6% [95% confidence interval {CI}, 59.3%–67.6%]), long stays (mean, 13.0 days [95% CI, 11.3–14.6 days]), substantial costs per stay (mean, $48 155 [95% CI, $42 382–$53 929]), and a 7.6% (95% CI, 5.6%–10.3%) mortality incidence. CM inflicts a substantial burden on hospital resources.
• Donovan, F. (2024).

  Burden of Hospitalization for Coccidioidal Meningitis: An Analysis of the National Inpatient Sample, 2019-2021

  . OFID, 27. doi:10.1093/ofid/ofae706
• Donovan, F. (2024).

  How I do it: Managing Cavitary Coccidioidomycosis: Expert Opinions for Improving Patient Outcomes

  . Chest. doi:10.1016/j.chest.2024.12.001
• Donovan, F. (2024).

  Updates in Coccidioidomycosis

  . Infect Dis Clin N Am. doi:10.1016/j.idc.2024.11.012
• Donovan, F. (2024). ICD Codes are Insufficient to Create Datasets for Machine Learning: An Evaluation Using All of Us Data for Coccidioidomycosis and Myocardial Infarction. . arXiv. doi:10.48550/arXiv.2407.07997
• Donovan, F. (2023). Deadly Fungal Infections Confound Doctors – It’s Going to Get Worst. The Wall Street Journal.
• Donovan, F. (2023). Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis. J Investig Med High Impact Case Rep. doi:10.1177/23247096231181060
• Menghani, S. V., Takamatsu, C. L., Ibrahim, R., Molina, L., Jaswal, N., & Donovan, F. M. (2023). Non-shunt Management of Communicating Hydrocephalus in an Immunocompetent Host With Disseminated Central Nervous System Coccidioidomycosis. Journal of Investigative Medicine High Impact Case Reports, 11(Issue). doi:10.1177/23247096231181060
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  Disseminated coccidioidomycosis is associated with significant morbidity and mortality. Involvement of the meninges is often fatal if untreated, typically requiring lifelong antifungal therapy and neurosurgical intervention. We present the case of a young male without any known immunocompromising conditions who opted exclusively for medical management of newly diagnosed coccidioidomycosis meningitis with communicating hydrocephalus and discuss the controversy associated with this approach. This case highlights the importance of shared decision-making between patient and clinician, even if the plan diverges from available guidelines. Furthermore, we discuss clinical considerations in approaching the close outpatient monitoring of patients with central nervous system coccidioidomycosis with hydrocephalus.
• Archer, E. (2022). Endemic Mycoses: Better Diagnosis and Reporting Needed  . Medscape.
• Bedrick, E. J., Shadarevian, M. D., Ramadan, F. A., Lim, J. R., Khan, R. N., Kaveti, A., Galgiani, J. N., Donovan, F. M., Dequillfeldt, N. P., Davis, N. M., & Buchfuhrer, J. E. (2022). Contribution of Biologic Response Modifiers to the Risk of Coccidioidomycosis Severity.. Open forum infectious diseases, 9(3), ofac032. doi:10.1093/ofid/ofac032
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  The risk of coccidioidomycosis (CM) as a life-threatening respiratory illness or disseminated CM (DCM) increases as much as 150-fold in immunosuppressed patients. The safety of biologic response modifiers (BRMs) as treatment for patients with autoimmune disease (AI) in CM-endemic regions is not well defined. We sought to determine that risk in the Tucson and Phoenix areas..We conducted a retrospective study reviewing demographics, Arizona residency length, clinical presentations, specific AI diagnoses, CM test results, and BRM treatments in electronic medical records of patients ≥18 years old with International Classification of Diseases (ICD-10) codes for CM and AI from 1 October 2017 to 31 December 2019..We reviewed 944 charts with overlapping ICD-10 codes for CM and AI, of which 138 were confirmed to have both diagnoses. Male sex was associated with more CM (P = .003), and patients with African ancestry were 3 times more likely than those with European ancestry to develop DCM (P 
• Donovan, F. (2021). Automated Biomedical Lexicon Creation with Graph Search for Word Embeddings. IEEE Xplore.
• Donovan, F. (2021). Contribution of Biologic Response Modifiers to the Risk of Coccidioidomycosis Severity. OFID.
• Donovan, F. (2021). TNF Blockade Inhibits Both Initial and Continued Control of Pulmonary Coccidioides.. Frontiers, TBD.
• Donovan, F. (2022). Immunogenetics associated with severe coccidioidomycosis. JCI.Insight.
• Donovan, F. (2022). Clinical Predictors of Coccidioidomycosis from a Cross-Sectional Study. Emerging Infectious Disease.
• Donovan, F. (2022). Clinical Predictors of Coccidioidomycosis from a Cross-Sectional Study. ID Week 2022.
• Hsu, A. P., Korzeniowska, A., Aguilar, C. C., Gu, J., Karlins, E., Oler, A. J., Chen, G., Reynoso, G. V., Davis, J., Chaput, A., Peng, T., Sun, L., Lack, J. B., Bays, D. J., Stewart, E. R., Waldman, S. E., Powell, D. A., Donovan, F. M., Desai, J. V., , Pouladi, N., et al. (2022). Immunogenetics associated with severe coccidioidomycosis. JCI Insight, 7(Issue 22). doi:10.1172/jci.insight.159491
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  Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in β-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of β-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired β-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.
• Powell, D. A., Shubitz, L. F., Butkiewicz, C. D., Trinh, H. T., Donovan, F. M., Frelinger, J. A., & Galgiani, J. N. (2022). TNFα Blockade Inhibits Both Initial and Continued Control of Pulmonary Coccidioides. Frontiers in Cellular and Infection Microbiology, 11(Issue). doi:10.3389/fcimb.2021.796114
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  Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in Coccidioides infection remains poorly understood. The need to understand TNFα in Coccidioides infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed Coccidioides infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice. B6D2F1 mice develop long-lasting control of Cp1038. Treatment of B6D2F1 mice with anti-TNFα antibodies permits significant fungal proliferation and death. Additionally, we show that antibody treatment limited to the first 2 weeks of infection was sufficient to induce this same loss of fungal control. Importantly, anti-TNFα antibody treatment initiated after fungal control leads to a loss of host control. These results highlight the importance of TNFα in both the initial control of murine Coccidioides and ongoing suppression of the fungal disease.
• Ramadan, F. A., Ellingson, K. D., Canales, R. A., Bedrick, E. J., Galgiani, J. N., & Donovan, F. M. (2022). Cross-Sectional Study of Clinical Predictors of Coccidioidomycosis, Arizona, USA. Emerging Infectious Diseases, 28(Issue 6). doi:10.3201/eid2806.212311
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  Demographic and clinical indicators have been described to support identification of coccidioidomycosis; however, the interplay of these conditions has not been explored in a clinical setting. In 2019, we enrolled 392 participants in a cross-sectional study for suspected coccidioidomycosis in emergency departments and inpatient units in Coccidioides-endemic regions. We aimed to develop a predictive model among participants with suspected coccidioidomycosis. We applied a least absolute shrinkage and selection operator to specific coccidioidomycosis predictors and developed univariable and multivariable logistic regression models. Univariable models identified elevated eosinophil count as a statistically significant predictive feature of coccidioidomycosis in both inpatient and outpatient settings. Our multivariable outpatient model also identified rash (adjusted odds ratio 9.74 [95% CI 1.03–92.24]; p = 0.047) as a predictor. Our results suggest preliminary support for developing a coccidioidomycosis prediction model for use in clinical settings.
• Thompson, G. R., Ampel, N. M., Blair, J. E., Donovan, F., Fierer, J., Galgiani, J. N., Heidari, A., Johnson, R., Shatsky, S. A., Uchiyama, C. M., & Stevens, D. A. (2022). Controversies in the Management of Central Nervous System Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 75(4), 555-559.
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  Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.
• Bedrick, E. J., Donovan, F. M., Ellingson, K., Galgiani, J. N., Leroy, G., Pu, J., & Stone, J. (2021). Clinician Practice Patterns That Result in the Diagnosis of Coccidioidomycosis Before or During Hospitalization.. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(7), e1587-e1593. doi:10.1093/cid/ciaa739
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  Coccidioidomycosis (CM) is common and important within endemic regions, requiring specific testing for diagnosis. Long delays in diagnosis have been ascribed to ambulatory clinicians. However, how their testing practices have impacted patient care has not been systematically unexplored..We analyzed practice patterns for CM diagnoses over 3 years within a large Arizona healthcare system, including diagnosis location, patient characteristics, and care-seeking patterns associated with missed diagnosis..For 2043 CM diagnoses, 72.9% were made during hospital admission, 21.7% in ambulatory clinics, 3.2% in emergency units, and only 0.5% in urgent care units. A 40.6% subgroup of hospitalized patients required neither intensive care unit or hospital-requiring procedures, had a median length of stay of only 3 days, but still incurred both substantial costs ($27.0 million) and unnecessary antibiotic administrations. Prior to hospital diagnosis (median of 32 days), 45.1% of patients had 1 or more visits with symptoms consistent with CM. During those visits, 71.3% were not tested for CM. Diagnoses were delayed a median of 27 days..Lack of testing for CM in ambulatory care settings within a region endemic for CM resulted in a large number of hospital admissions, attendant costs, and unneeded antibacterial drug use, much of which would otherwise be unnecessary. Improving this practice is challenging since many clinicians did not train where CM is common, resulting in significant inertia to change. Determining the best way to retrain clinicians to diagnose CM earlier is an opportunity to explore which strategies might be the most effective.
• Donovan, F. (2021). Cutaneous Leishmaniasis Caused by an Unknown Leishmania Strain, Arizona, USA. Emerging Infectious Diseases, 1714-1717.
• Donovan, F. M., Ramadan, F. A., Khan, S. A., Bhaskara, A., Lainhart, W. D., Narang, A. T., Mosier, J. M., Ellingson, K. D., Bedrick, E. J., Saubolle, M. A., & Galgiani, J. N. (2021). Comparison of a Novel Rapid Lateral Flow Assay to Enzyme Immunoassay Results for Early Diagnosis of Coccidioidomycosis. Clinical Infectious Diseases, 73(Issue 9). doi:10.1093/cid/ciaa1205
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  Background: Coccidioidomycosis (CM) is a common cause of community-acquired pneumonia where CM is endemic. Manifestations include self-limited pulmonary infection, chronic fibrocavitary pulmonary disease, and disseminated coccidioidomycosis. Most infections are identified by serological assays including enzyme-linked immunoassay (EIA), complement fixation, and immunodiffusion. These are time-consuming and take days to result, impeding early diagnosis. A new lateral flow assay (LFA; Sōna; IMMY, Norman, OK) improves time-to-result to 1 hour. Methods: We prospectively enrolled 392 patients with suspected CM, compared the LFA with standard EIA and included procalcitonin evaluation. Results: Compared with standard EIA, LFA demonstrates 31% sensitivity (95% confidence interval [CI], 20-44%) and 92% specificity (95% CI, 88-95%). Acute pulmonary disease (74%) was the most common clinical syndrome. Hospitalized patients constituted 75% of subjects, and compared with outpatients, they more frequently had ≥3 previous healthcare facility visits (P=.05), received antibacterials (P3 antibacterial courses (P
• Messina, J. A., Maziarz, E. K., Galgiani, J., Truong, J. T., Htoo, A. K., Heidari, A., Johnson, R. H., Narang, A. T., Donovan, F. M., Ewell, M., Catanzaro, A., Thompson, G. R., Ampel, N. M., Perfect, J. R., Naggie, S., & Walter, E. B. (2021). A randomized, double-blind, placebo-controlled clinical trial of fluconazole as early empiric treatment of coccidioidomycosis pneumonia (Valley Fever) in adults presenting with community-acquired pneumonia in endemic areas (FLEET-Valley Fever). Contemporary Clinical Trials Communications, 24. doi:10.1016/j.conctc.2021.100851
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  Introduction: Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown. Methods: Phase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness. Objectives: The primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality. Discussion: This trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed.
• Messina, J. A., Maziarz, E. K., Galgiani, J., Truong, J. T., Htoo, A. K., Heidari, A., Johnson, R. H., Narang, A. T., Donovan, F. M., Ewell, M., Catanzaro, A., Thompson, G. R., Ampel, N. M., Perfect, J. R., Naggie, S., & Walter, E. B. (2021). A randomized, double-blind, placebo-controlled clinical trial of fluconazole as early empiric treatment of coccidioidomycosis pneumonia (Valley Fever) in adults presenting with community-acquired pneumonia in endemic areas (FLEET-Valley Fever). Contemporary clinical trials communications, 24, 100851.
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  Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown.
• de Almeida, M., Zheng, Y., Nascimento, F. S., Bishop, H., Cama, V. A., Batra, D., Unoarumhi, Y., Afghan, A. K., Shi, V. Y., LeBoit, P. E., Liu, E. W., & Donovan, F. M. (2021). Cutaneous leishmaniasis caused by an unknown leishmania strain, Arizona, USA. Emerging Infectious Diseases, 27(Issue 6). doi:10.3201/eid2706.204198
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  We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes.
• Bardwell, J., August, J., Farran, S., Florita, C., Donovan, F., & Zangeneh, T. T. (2020). Infection of Aortic Endograft Caused by Coccidioidomycosis. American Journal of Medicine, 133(Issue 1). doi:10.1016/j.amjmed.2019.07.013
• Bardwell, J., August, J., Farran, S., Florita, C., Donovan, F., & Zangeneh, T. T. (2020). Infection of Aortic Endograft Caused by Coccidioidomycosis. The American journal of medicine, 133(1), e1-e2. doi:10.1016/j.amjmed.2019.07.013
• Donovan, F. M., Ramadan, F. A., Khan, S. A., Bhaskara, A., Lainhart, W. D., Narang, A. T., Mosier, J. M., Ellingson, K. D., Bedrick, E. J., Saubolle, M. A., & Galgiani, J. N. (2020). Comparison of a Novel Rapid Lateral Flow Assay to Enzyme Immunoassay Results for Early Diagnosis of Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
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  Coccidioidomycosis (CM) is a common cause of community acquired pneumonia (CAP) where CM is endemic. Manifestations include self-limited pulmonary infection, chronic fibrocavitary pulmonary disease, and disseminated coccidioidomycosis (DCM). Most infections are identified by serological assays including enzyme-linked immunoassay (EIA), complement fixation (CF) and immunodiffusion (IMDF). These are time-consuming and take days to result, impeding early diagnosis. A new lateral flow assay (LFA, Sōna, IMMY, Norman OK) improves time-to-result to one hour.
• Donovan, F., Shubitz, L., Powell, D., Orbach, M., Frelinger, J., & Galgiani, J. (2020). Early events in coccidioidomycosis. Clinical Microbiology Reviews, 33(1). doi:10.1128/CMR.00112-19
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  Since its description nearly 130 years ago, hundreds of studies have deepened our understanding of coccidioidomycosis, also known as valley fever (VF), and provided useful diagnostic tests and treatments for the disease caused by the dimorphic fungi Coccidioides spp. In general, most of the literature has addressed well-established infections and has described patients who have experienced major complications. In contrast, little attention has been given to the earliest consequences of the pathogen-host interaction and its implications for disease manifestation, progression, and resolution. The purpose of this review is to highlight published studies on early coccidioidomycosis, identify gaps in our knowledge, and suggest new or former research areas that might be or remain fertile ground for insight into the early stages of this invasive fungal disease.
• Pu, J., Donovan, F. M., Ellingson, K., Leroy, G., Stone, J., Bedrick, E., & Galgiani, J. N. (2020). Clinician Practice Patterns that Result in the Diagnosis of Coccidioidomycosis Before or During Hospitalization. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(7), e1587-e1593. doi:10.1093/cid/ciaa739
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  Coccidioidomycosis (CM) is common and important within endemic regions, requiring specific testing for diagnosis. Long delays in diagnosis have been ascribed to ambulatory clinicians, but how their testing practices have impacted patient care have not been systematically unexplored.
• Donovan, F. (2019). Delays in Coccidioidomycosis Diagnosis and Associated Healthcare Utilization in Tucson, Arizona. Emerging Infectious Diseases, 25 (9), 1745-1747.
• Donovan, F. M., Shubitz, L., Powell, D., Orbach, M., Frelinger, J., & Galgiani, J. N. (2019). Early Events in Coccidioidomycosis. Clinical Microbiology Reviews, 33(1).
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  SUMMARYSince its description nearly 130 years ago, hundreds of studies have deepened our understanding of coccidioidomycosis, also known as valley fever (VF), and provided useful diagnostic tests and treatments for the disease caused by the dimorphic fungi spp. In general, most of the literature has addressed well-established infections and has described patients who have experienced major complications. In contrast, little attention has been given to the earliest consequences of the pathogen-host interaction and its implications for disease manifestation, progression, and resolution. The purpose of this review is to highlight published studies on early coccidioidomycosis, identify gaps in our knowledge, and suggest new or former research areas that might be or remain fertile ground for insight into the early stages of this invasive fungal disease.
• Donovan, F. M., Wightman, P., Zong, Y., Gabe, L., Majeed, A., Ynosencio, T., Bedrick, E. J., & Galgiani, J. N. (2019). Delays in coccidioidomycosis diagnosis and associated healthcare utilization, Tucson, Arizona, USA. Emerging Infectious Diseases, 25(Issue 9). doi:10.3201/eid2509.190023
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  Tucson, Arizona, USA, is a highly coccidioidomycosis-endemic area. We conducted a retrospective review of 815 patients in Tucson over 2.7 years. Of 276 patients with coccidioidomycosis, 246 had a delay in diagnosis; median delay was 23 days. Diagnosis delay was associated with coccidioidomycosis-related costs totaling $589,053 and included extensive antibacterial drug use.
• Donovan, F. M., Zangeneh, T. T., Malo, J., & Galgiani, J. N. (2017). Top Questions in the Diagnosis and Treatment of Coccidioidomycosis. Open Forum Infectious Diseases, 4(Issue 4). doi:10.1093/ofid/ofx197
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  Revised and greatly expanded treatment guidelines for coccidioidomycosis were published last year by the Infectious Diseases Society of America. We have selected 4 questions that commonly arise in the management of patients suspected of this disease and for which there remain divided opinions.
• Donovan, F. M., Zangeneh, T. T., Malo, J., & Galgiani, J. N. (2017). Top Questions in the Diagnosis and Treatment of Coccidioidomycosis. Open forum infectious diseases, 4(4), ofx197.
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  Revised and greatly expanded treatment guidelines for coccidioidomycosis were published last year by the Infectious Diseases Society of America. We have selected 4 questions that commonly arise in the management of patients suspected of this disease and for which there remain divided opinions.
• Donovan, F., Blatt, S., & Gonzales, Y. (2006). Cat Scratch Disease Presenting as Severe Thrombocytopenia. Resident and Staff Physician.
• Mirbod, F., Nakashima, S., Kitajima, Y., Ghannoum, M. A., Cannon, R. D., & Nozawa, Y. (2016). Molecular cloning of a gene encoding translation initiation factor (TIF) from Candida albicans. Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology, 34(6), 393-400.
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  The differential display technique was applied to compare mRNAs from two clinical isolates of Candida albicans with different virulence; high (potent strain, 16240) and low (weak strain, 18084) extracellular phospholipase activities. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. A complementary DNA fragment seen distinctly in the potent phospholipase producing strain was highly homologous to the yeast translation initiation factor (TIF). The selected DNA fragment was then used as a probe to isolate its corresponding complementary DNA clone from a library of C. albicans genomic DNA. The sequence of isolated gene revealed an open reading frame of 1194 nucleotides with the potential to encode a protein of 397 amino acids with a predicted molecular weight of 43 kDa. Over its entire length, the amino acid sequence showed strong homology (78-89%) to Saccharomyces cerevisiae TIF and (63-80%) to mouse eIF-4A proteins. Therefore, our C. albicans gene was identified to be TIF (Ca TIF). Northern blot analysis in the two strains of C. albicans revealed that Ca TIF expression is 1.5-fold higher in the potent phospholipase producing strain. The restriction endonuclease digestion of genomic DNA from this potent strain revealed at least two hybridized bands in Southern blot analysis, suggesting two or more closely related sequences in the C. albicans genome.
• Donovan, F., Somboonbwit, C., Soliman, E., Gotuzzo, E., & Perez, N. (2009). St. Louis Encephalitis. Web Med.
• Donovan, F., Somboonwit, C., Tash, K., & Houston, S. H. (2009). Immunosuppression and infection risk in SOT receipients. Infections in Medicine, 26(2), 41-46.
• Mirbod-Donovan, F., Schaller, R., Hung, C. Y., Xue, J. M., Reichard, U., & Cole, G. T. (2006). Urease produced by Coccidioides posadasii contributes to the virulence of this respiratory pathogen. INFECTION AND IMMUNITY, 74(1), 504-515.
• Mirbod-Donovan, F., Schaller, R., Hung, C. Y., Xue, J., Reichard, U., & Cole, G. T. (2006). Urease produced by Coccidioides posadasii contributes to the virulence of this respiratory pathogen. Infection and Immunity, 74(Issue 1). doi:10.1128/iai.74.1.504-515.2006
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  Urease activity during in vitro growth in the saprobic and parasitic phases of Coccidioides spp. is partly responsible for production of intracellular ammonia released into the culture media and contributes to alkalinity of the external microenvironment. Although the amino acid sequence of the urease of Coccidioides posadasii lacks a predicted signal peptide, the protein is transported from the cytosol into vesicles and the central vacuole of parasitic cells (spherules). Enzymatically active urease is released from the contents of mature spherules during the parasitic cycle endosporulation stage. The endospores, together with the urease and additional material which escape from the ruptured parasitic cells, elicit an intense host inflammatory response. Ammonia production by the spherules of C. posadasii is markedly increased by the availability of exogenous urea found in relatively high concentrations at sites of coccidioidal infection in the lungs of mice. Direct measurement of the pH at these infection sites revealed an alkaline microenvironment. Disruption of the urease gene of C. posadasii resulted in a marked reduction in the amount of ammonia secreted in vitro by the fungal cells. BALB/c mice challenged intranasally with the mutant strain showed increased survival, a well-organized granulomatous response to infection, and better clearance of the pathogen than animals challenged with either the parental or the reconstituted (revertant) strain. We conclude that ammonia and enzymatically active urease released from spherules during the parasitic cycle of C. posadasii contribute to host tissue damage, which exacerbates the severity of coccidioidal infection and enhances the virulence of this human respiratory pathogen. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
• Mirbod, F., Schaller, R. A., & Cole, G. T. (2002). Purification and characterization of urease isolated from the pathogenic fungus Coccidioides immitis. Medical Mycology, 40(Issue 1). doi:10.1080/mmy.40.1.35.44
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  Coccidioides immitis, the causative agent of San Joaquin Valley fever (coccidioidomycosis), produces a urease which has been suggested to contribute to the virulence of this fungal pathogen. Urease catalyzes the hydrolysis of urea and has been proposed to at least partly account for alkalinity of the microenvironment in which C. immitis grows due to the release of ammonia and ammonium ions. The C. immitis urease was purified to homogeneity (1048-fold) from the mycelial cytosol by chromatographic fractionation. The sequence of 12 N-terminal amino-acid residues of the purified, native polypeptide was identical to that predicted by the translated urease gene sequence which has been reported. The isolated enzyme exhibited a specific activity in the presence of urea of 1750 μmol min-1 mg-1 protein, has a native molecular mass of 450 kDa, revealed a Km for urea of 4.1 mM, had a pH optimum of 8.0 and is heat stable. Hydroxyurea, acetohydroxamic acid (AHA) and boric acid each inhibited activity of the purified enzyme. Urease activity was enhanced by the presence of 5-10 mM concentrations of Mg2+ or Mn2+, but inhibited by Li+, Ni2+, Cu2+ or Zn2+. The reversible urease inhibitor, AHA, blocked enzyme activity in the crude mycelial cytosolic fraction when added at a concentration of 10 mM. On the other hand, 10 mM AHA added to 4-day-old mycelial cultures only partially decreased the amount of ammonium detected in the culture medium. It is evident, therefore, that C. immitis urease activity does not account for the total amount of ammonia secreted during in vitro growth of the pathogen. Other metabolic sources of ammonia, which may also contribute to the virulence of C. immitis, are under investigation.
• Mirbod, F., Schaller, R. A., & Cole, G. T. (2002). Purification and characterization of urease isolated from the pathogenic fungus Coccidioides immitis. Medical mycology, 40(1), 35-44.
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  Coccidioides immitis, the causative agent of San Joaquin Valley fever (coccidioidomycosis), produces a urease which has been suggested to contribute to the virulence of this fungal pathogen. Urease catalyzes the hydrolysis of urea and has been proposed to at least partly account for alkalinity of the microenvironment in which C. immitis grows due to the release of ammonia and ammonium ions. The C. immitis urease was purified to homogeneity (1048-fold) from the mycelial cytosol by chromatographic fractionation. The sequence of 12 N-terminal amino-acid residues of the purified, native polypeptide was identical to that predicted by the translated urease gene sequence which has been reported. The isolated enzyme exhibited a specific activity in the presence of urea of 1750 micromol min(-1) mg(-1) protein, has a native molecular mass of 450 kDa, revealed a Km for urea of 4.1 mM, had a pH optimum of 8.0 and is heat stable. Hydroxyurea, acetohydroxamic acid (AHA) and boric acid each inhibited activity of the purified enzyme. Urease activity was enhanced by the presence of 5-10 mM concentrations of Mg2+ or Mn2+, but inhibited by Li+, Ni2+, Cu2+ or Zn2+. The reversible urease inhibitor, AHA, blocked enzyme activity in the crude mycelial cytosolic fraction when added at a concentration of 10 mM. On the other hand, 10 mM AHA added to 4-day-old mycelial cultures only partially decreased the amount of ammonium detected in the culture medium. It is evident, therefore, that C. immitis urease activity does not account for the total amount of ammonia secreted during in vitro growth of the pathogen. Other metabolic sources of ammonia, which may also contribute to the virulence of C. immitis, are under investigation.
• Sugiyama, Y., Nakashima, S., Mirbod, F., Kanoh, H., Kitajima, Y., Ghannoum, M. A., & Nozawa, Y. (1999). Molecular cloning of a second phospholipase B gene, caPLB2 from Candida albicans. MEDICAL MYCOLOGY, 37(1), 61-67.
• Sugiyama, Y., Nakashima, S., Mirbod, F., Kanoh, H., Kitajima, Y., Ghannoum, M. A., & Nozawa, Y. (1999). Molecular cloning of a second phospholipase B gene, caPLB2 from Candida albicans. Medical Mycology, 37(Issue 1). doi:10.1046/j.1365-280x.1999.00190.x
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  Accumulating evidence suggests that phospholipase B, secreted by pathogenic fungi such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, functions as one of the virulence factors. In the present study, we have attempted to clone phospholipase B gene from C. albicans. By RT-PCR analysis with degenerate primers based on conserved regions of phospholipase B from Saccharomyces cerevisiae. Penicillium notatum and Torulaspora two similar but different cDNA fragments were obtained. One corresponded to the partial sequence of caPLB1, recently cloned phospholipase B gene from C. albicans by a different approach. The other fragments contained sequences similar to the corresponding sequences of phospholipase B from other fungi. The presence of two related genes was confirmed by Southern and Northern blot analyses. The full length of the second C. albicans phospholipase B gene (caPLB2) encoded a putative protein with 608 amino acids and contained a potential signal peptide sequence and a putative catalytic region, which are found in phospholipase B from other fungi. Consistent with the findings of caPLB1, caPLB2 also lacks a cluster of hydrophobic amino acids at the COOH-terminal, which may function as a signal of glycosylphosphatidylinositol anchor.
• Leidich, S. D., Ibrahim, A. S., Fu, Y., Koul, A., Jessup, C., Vitullo, J., Fonzi, W., Mirbod, F., Nakashima, S., Nozawa, Y., & Ghannoum, M. A. (1998). Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. JOURNAL OF BIOLOGICAL CHEMISTRY, 273(40), 26078-26086.
• Leidich, S. D., Ibrahim, A. S., Fu, Y., Koul, A., Jessup, C., Vitullo, J., Fonzi, W., Mirbod, F., Nakashima, S., Nozawa, Y., & Ghannoum, M. A. (1998). Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. Journal of Biological Chemistry, 273(Issue 40). doi:10.1074/jbc.273.40.26078
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  The Candida albicans PLB1 gene was cloned using a polymerase chain reaction-based approach relying on degenerate oligonucleotide primers designed according to the amino acid sequences of two peptide fragments obtained from a purified candidal enzyme displaying phospholipase activity (Mirbod, F., Banno, Y., Ghannoum, M. A., Ibrahim, A. S., Nakashima, S., Yasuo, K., Cole, G.T., and Nozawa, Y. (1995) Biochim. Biophys. Acta 1257, 181-188). Sequence analysis of a 6.7-kilobase pair EcoRI-ClaI genomic clone revealed a single open reading frame of 1818 base pairs that predicts for a preprotein of 605 residues. Comparison of the putative candidal phospholipase with those of other proteins in data base revealed significant homology to known fungal phospholipase Bs from Saccharomyces cerevisiae (45%), Penicillium notatum (42%), Torulaspora delbrueckii (48%), and Schizosaccharomyces pombe (38%). Thus, we have cloned the gene encoding a C. albicans phospholipase B homolog. This gene, designated caPLB1, was mapped to chromosome 6. Disruption experiments revealed that the caplb1 null mutant is viable and displays no obvious phenotype. However, the virulence of strains deleted for caPLB1, as assessed in a murine model for hematogenously disseminated candidiasis, was significantly attenuated compared with the isogenic wild-type parental strain. Although deletion of caPLB1 did not produce any detectable effects on candidal adherence to human endothelial or epithelial cells, the ability of the caplb1 null mutant to penetrate host cells was dramatically reduced. Thus, phospholipase B may well contribute to the pathogenicity of C. albicans by abetting the fungus in damaging and traversing host cell membranes, processes which likely increase the rapidity of disseminated infection.
• Mirbod, F., Nakashima, S., Kitajima, Y., Cannon, R. D., & Nozawa, Y. (1997). Molecular cloning of a Rho family, CDC42Ca gene from Candida albicans and its mRNA expression changes during morphogenesis. JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY, 35(3), 173-179.
• Mirbod, F., Nakashima, S., Kitajima, Y., Cannon, R. D., & Nozawa, Y. (1997). Molecular cloning of a rho family, CDC42Ca gene from Candida albicans and its mRNA expression changes during morphogenesis. Journal of Medical and Veterinary Mycology, 35(Issue 3). doi:10.1080/02681219780001111
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  The small GTP-binding protein Family regulates various cell functions in mammalian and yeast cells. In the yeast Saccharomyces cerevisiae it has been known to be involved in vegetative growth. As an initial attempt to explore the involvement of CDC42, a member of this family, in the regulation of morphological changes in Candida albicans, we isolated a gene encoding this protein (CDC42Ca) from this fungus. The sequence of isolated gene revealed an open reading frame of 570 nucleotides with the potential to encode a protein of 190 amino acids with a predicted molecular weight of 20·5 kDa. The deduced amino acid sequence was highly homologous to CDC42s from yeast (87·8%), human (76.4%) and Caenorhabditis elegans (73·7%). The CDC42Ca mRNA level showed a transient increase with a peak at 2 h after the fresh medium shift (28 °C) when cells synchronously formed buds, whereas it displayed a gradual increase up to 12 h alter the medium shift (37 °C) with elongation of germ tubes. This suggests that CDC42 may play a role in the bud emergence and also germ tube formation in C. albicans.
• Nakashima, S., Nozawa, Y., Mirbod, F., & Kitajima, Y. (1997). Molecular Cloning of Candida albicans Genes by Differential Display. Japanese Journal of Medical Mycology, 38(4). doi:10.3314/jjmm.38.291
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  mRNA fingerprinting based on RT-PCR (reverse transcriptase-polymerase chain reaction) such as differential display (DD) and RAP (mRNA fingerprinting using arbitrarily primed PCR) are useful methods to identify differentially expressed genes. We adopted DD to identify the gene(s) involved in Candida albicans pathogenicity using highly (16240) and weakly (18084) virulent strains. More than 40 cDNA fragments were isolated. The deduced amino acid sequence of one fragment was highly homologous to Saccharomyces cerevisiae translation initiation factor (TIF). The TIF gene was isolated from the C. albicans genomic library. Its expression was nearly 2-fold higher in the 16240 strain as assessed by Northern blot analysis. At present, the link between TIF gene and virulence is not clearly understood. However, DD is a useful technique to isolate differentially expressed genes in C. albicans. © 1997, The Japanese Society for Medical Mycology. All rights reserved.
• Mirbod, F., Nakashima, S., Kitajima, Y., Ghannoum, M. A., Cannon, R. D., & Nozawa, Y. (1996). Molecular cloning of a gene encoding translation initiation factor (TIF) from Candida albicans. Journal of medical and veterinary mycology : bi-monthly publication of the International Society for Human and Animal Mycology, 34(6), 393-400.
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  The differential display technique was applied to compare mRNAs from two clinical isolates of Candida albicans with different virulence; high (potent strain, 16240) and low (weak strain, 18084) extracellular phospholipase activities. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. A complementary DNA fragment seen distinctly in the potent phospholipase producing strain was highly homologous to the yeast translation initiation factor (TIF). The selected DNA fragment was then used as a probe to isolate its corresponding complementary DNA clone from a library of C. albicans genomic DNA. The sequence of isolated gene revealed an open reading frame of 1194 nucleotides with the potential to encode a protein of 397 amino acids with a predicted molecular weight of 43 kDa. Over its entire length, the amino acid sequence showed strong homology (78-89%) to Saccharomyces cerevisiae TIF and (63-80%) to mouse eIF-4A proteins. Therefore, our C. albicans gene was identified to be TIF (Ca TIF). Northern blot analysis in the two strains of C. albicans revealed that Ca TIF expression is 1.5-fold higher in the potent phospholipase producing strain. The restriction endonuclease digestion of genomic DNA from this potent strain revealed at least two hybridized bands in Southern blot analysis, suggesting two or more closely related sequences in the C. albicans genome.
• Mirbod, F., Nakashima, S., Kitajima, Y., Ghannoum, M. A., Cannon, R. D., & Nozawa, Y. (1996). Molecular cloning of a gene encoding translation initiation factor (TIF) from Candida albicans. Medical Mycology, 34(Issue 6). doi:10.1080/02681219680000701
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  The differential display technique was applied to compare mRNAs from two clinical isolates of Candida albicans with different virulence; high (potent strain, 16240) and low (weak strain, 18084) extracellular phospholipase activities. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. A complementary DNA fragment seen distinctly in the potent phospholipase producing strain was highly homologous to the yeast translation initiation factor (TIF). The selected DNA fragment was then used as a probe to isolate its corresponding complementary DNA clone from a library of C. albicans genomic DNA. The sequence of isolated gene revealed an open reading frame of 1194 nucleotides with the potential to encode a protein of 397 amino acids with a predicted molecular weight of 43 kDa. Over its entire length, the amino acid sequence showed strong homology (78-89%) to Saccharomyces cerevisiae TIF and (63-80%) to mouse eIF-4A proteins. Therefore, our C. albicans gene was identified to be TIF (Ca TIF). Northern blot analysis in the two strains of C. albicans revealed that Ca TIF expression is 1·5-fold higher in the potent phospholipase producing strain. The restriction endonuclease digestion of genomic DNA from this potent strain revealed at least two hybridized bands in Southern blot analysis, suggesting two or more closely related sequences in the C. albicans genome. © 1996 Informa UK Ltd All rights reserved.
• Donovan, F., Nakashima, S., Mori, S., Kitajima, Y., & Nosawa, Y. (1995). Phospholipid biosynthesis in growing and non -growing conditions in Candida albicans. Jpn. J. Med. Mycol, 36, 53-59.
• IBRAHIM, A. S., MIRBOD, F., FILLER, S. G., BANNO, Y., COLE, G. T., KITAJIMA, Y., EDWARDS, J. E., NOZAWA, Y., & GHANNOUM, M. A. (1995). EVIDENCE IMPLICATING PHOSPHOLIPASE AS A VIRULENCE FACTOR OF CANDIDA-ALBICANS. INFECTION AND IMMUNITY, 63(5), 1993-1998.
• Ibrahim, A. S., Mirbod, F., Filler, S. G., Banno, Y., Cole, G. T., Kitajima, Y., Edwards, J. E., Nozawa, Y., & Ghannoum, M. A. (1995). Evidence implicating phospholipase as a virulence factor of Candida albicans. Infection and Immunity, 63(Issue 5). doi:10.1128/iai.63.5.1993-1998.1995
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  Three different approaches were used to investigate the role of extracellular phospholipases in the pathogenicity of Candida albicans. First, we compared 11 blood isolates of this yeast with an equal number of commensal strains isolated from the oral cavities of healthy volunteers. Blood isolates produced significantly more extracellular phospholipase activity than the commensal strains did. Second, two clinical isolates of C. albicans that differed in their levels of virulence in a newborn mouse model were compared for their ability to secrete phospholipases. The invasive strain produced significantly more extracellular phospholipase activity than the noninvasive strain did. Third, nine blood isolates were characterized for their phospholipase and proteinase production, germ tube formation, growth, and adherence to and damage of endothelial cells in vitro. These factors were analyzed subsequently to determine whether they predicted mortality in a mouse model of hematogenously disseminated candidiasis. By proportional hazard analysis, the relative risk of death was 5.6-fold higher (95% confidence interval, 1.672 to 18.84 [P < 0.005]) in the mice infected with the higher-phospholipase-secreting strains than in the low-phospholipase secretors. None of the other putative virulence factors predicted mortality. Characterization of phospholipases secreted by three of the blood isolates showed that these strains secreted both phospholipase B and lysophospholipase-transacylase activities. These results implicate extracellular phospholipase as a virulence factor in the pathogenesis of hematogenous infections caused by C. albicans.
• MIRBOD, F., BANNO, Y., GHANNOUM, M. A., IBRAHIM, A. S., NAKASHIMA, S., KITAJIMA, Y., COLE, G. T., & NOZAWA, Y. (1995). PURIFICATION AND CHARACTERIZATION OF LYSOPHOSPHOLIPASE-TRANSACYLASE (H-LPTA) FROM A HIGHLY VIRULENT-STRAIN OF CANDIDA-ALBICANS. BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1257(2), 181-188.
• Mirbod, F., Banno, Y., Ghannoum, M. A., Ibrahim, A. S., Ibrahim, A. S., Nakashima, S., Kitajima, Y., Cole, G. T., & Nozawa, Y. (1995). Purification and characterization of lysophospholipase-transacylase (h-LPTA) from a highly virulent strain of Candida albicans.. Biochimica et biophysica acta, 1257(2), 181-8. doi:10.1016/0005-2760(95)00072-k
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  A lysophospholipase-transacylase (h-LPTA) was purified to homogeneity from a clinical isolate of Candida albicans (C. albicans) that had high extracellular phospholipase activity (strain 16240). The purified enzyme was a glycoprotein with molecular mass of 84 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The specific activities of the enzyme were 117 mumol/min per mg protein for fatty acid release and 459 mumol/min per mg protein for phosphatidylcholine (PC) formation. An apparent Km of the hydrolase activity of the enzyme for 1-palmitoyl-sn-glycero-3-phosphocholine (1-palmitoyl-lyso-PC) was 60.6 microM. The enzyme had a pH optimum at 6.0. Transacylase activity of the enzyme was partially inhibited by palmitoylcarnitine (35% inhibition) and N-ethylmaleimide. In contrast, the hydrolase activity of the enzyme was stimulated by palmitoylcarnitine but was partially inhibited by N-ethylmaleimide. The enzyme exhibited broad specificity to lyso-phospholipids. The h-LPTA activity was not dependent on divalent cations (Ca2+ and Mg2+) and was not inhibited by addition of EDTA or EGTA. These results show that C. albicans strain 16240 with high extracellular phospholipase activity produced h-LPTA in large amount. This enzyme is biochemically distinct from the LPTA enzyme previously isolated from C. albicans 3125.
• Mirbod, F., Nakashima, S., Mori, S., Kitajima, Y., & Nozawa, Y. (1995). Phospholipid Biosynthesis in Growing and Non-growing Conditions in Candida albicans. Nippon Ishinkin Gakkai Zasshi, 36(Issue 1). doi:10.3314/jjmm.36.53
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  The major membrane phospholipids of Candida albicans (C. albicans) are phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (Pi), and phosphatidylserine (PS). In Saccharomyces cerevisiae (S. cerevisiae), the most abundant component PC is considered to be synthesized mainly by two pathways; stepwise methylation pathway of PE produced from PS by decarboxylation (de novo pathway) and diacylglycerol (DG)/CDP-choline pathway. However, relatively little information is available regarding the phospholipid biosynthesis in C. albicans. In order to clarify the phospholipid metabolism of this organism, we have investigated the 32 Pi incorporation into different phospholipids by continuous and pulse-labeling in cells grown in the synthetic medium (SM) and yeast extractproteose peptone-dextrose (YPD) medium. The continuous labeling with 32Pi in YPD medium showed that the decreases in radioactivity in acidic phospholipids (PA, PI and PS) were followed by the great increase in PC, suggesting the existence of de novo pathway. In SM cultured cells showing no growth, PS and PI were heavily labeled, while PC was much less labeled. By the switch from SM to YPD, the rapid increase in 32P-labeled PC occurred at the expense of PI and PS, suggesting that the principal PC synthesis for membrane biogenesis is via the de novo pathway in C. albicans. © 1995, The Japanese Society for Medical Mycology. All rights reserved.
• Donovan, F., Inoue, I., Seishima, M., Mori, S., & Nozawa, Y. (1994). Lipid synthesis during cell growth of Cryptococcus neoformans. Jpn. J. Med. Mycol., 35, 421-427.
• Inoue, I., Mirbod, F., Seishima, M., Mori, S., & Nozawa, Y. (1994). A Study of Lipid Biosynthesis in Cryptococcus Neoformans. Nippon Ishinkin Gakkai Zasshi, 35(Issue 4). doi:10.3314/jjmm.35.421
  More info

  Changes in incorporation of [14C] acetate into lipid fractions were examined in Cryptococcus neoformans during growth and were compared with those in Candida albicans. The uptake of [14C] acetate in the total lipids of Cr. neoformans gradually increased following the growth phase and then decreased at the stationary phase. The hydrolysis of triacylglycerol (TG), the main lipid in Cr. neoformans, was considered to be accelerated as the radioactivity in TG decreased with a concomitant increase of radioactivity in free fatty acid (FFA) in the stationary phase. In contrast, in C. albicans, phosphatidylcholine (PC), the major component of cell membrane, increased during the growth phase and decreased in the stationary phase. It was also observed that the biosynthesis of acidic phospholipids, PI and PS, was enhanced during the growth phase in both types of fungi. © 1994, The Japanese Society for Medical Mycology. All rights reserved.
• Donovan, F., Mori, S., & Nozawa, Y. (1993). Methods for Phospholipid Extraction in Candida albicans: an Extraction Method with High Efficacy. J. Med. Vet. Mycol., 31, 405-409.
• Mirbod, F., Inoue, I., Seishima, M., Mori, S., & Nozawa, Y. (1993). Comparison of lipid extraction methods for Cryptococcus neoformans and Candida albicans. Japanese Journal of Medical Mycology, 34(Issue). doi:10.3314/jjmm.34.supplement_111
• Mirbod, F., Mori, S., & Nozawa, Y. (1993). Methods for phospholipid extraction in candida albicans: An extraction method with high efficacy. Medical Mycology, 31(Issue 5). doi:10.1080/02681219380000521
  More info

  Phospholipid composition of Candida albicans was examined and compared using the three established methods for lipid extraction (Folch, Bligh-Dyer and Angus-Lester methods). The highest yield of total phospholipids was obtained by methanol pre-treatment prior to extraction with Folch solution. The percentage distribution of individual phospholipids showed a much higher level of phosphatidylcholine following extraction by the modified Folch method compared with extraction by the other methods. © 1993 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Proceedings Publications

• Donovan, F. (2026, February).

  Hospitalizations Associated with Disseminated Coccidioidomycosis and Coccidioidal Meningitis, Texas, 2016-2023, USA

  . In OFID.
• Donovan, F. (2026, February).

  Olorofim for the treatment of Central Nervous System (CNS) invasive fungal infections (IFI) in patients with limited or no treatment options: a sub-analysis of an open-label, single-arm, Phase 2b trial (Study 32; NCT03583164)

  . In OFID.
• Donovan, F. (2024, October).

  Risk factors, Clinical Manifestations and Management of Vertebral Osteomyelitis due to Coccidioides- a 10-year retrospective descriptive study

  . In OFID.
• Donovan, F. (2025).

  Antifungal therapy patterns, healthcare utilization, costs, and mortality in central nervous system and non-central nervous system disseminated coccidioidomycosis across the continuum-of-care

  . In OFID.
• Whitlock, A. E., Leroy, G., Donovan, F. M., & Galgiani, J. N. (2024). ICD Codes are Insufficient to Create Datasets for Machine Learning: An Evaluation Using All of Us Data for Coccidioidomycosis and Myocardial Infarction. In 12th IEEE International Conference on Healthcare Informatics, ICHI 2024.
  More info

  In medicine, machine learning (ML) datasets are often built using the International Classification of Diseases (ICD) codes. As new models are being developed, there is a need for larger datasets. However, ICD codes are intended for billing. We aim to determine how suitable ICD codes are for creating datasets to train ML models. We focused on a rare and common disease using the All of Us database. First, we compared the patient cohort created using ICD codes for Valley fever (coccidioidomycosis, CM) with that identified via serological confirmation. Second, we compared two similarly created patient cohorts for myocardial infarction (MI) patients. We identified significant discrepancies between these two groups, and the patient overlap was small. The CM cohort had 811 patients in the ICD-10 group, 619 patients in the positive-serology group, and 24 with both. The MI cohort had 14,875 patients in the ICD-10 group, 23,598 in the MI laboratory-confirmed group, and 6,531 in both. Demographics, rates of disease symptoms, and other clinical data varied across our case study cohorts.
• Galgiani, J. N., Donovan, F. M., Song, H., Gu, Y., & Leroy, G. (2021, December). Integrating Automated Biomedical Lexicon Creation for Valley Fever Diagnosis. In 2021 IEEE/ACM Conference on Connected Health: Applications, Systems and Engineering Technologies (CHASE).

Presentations

• Donovan, F. (2024).

  Antifungal therapy patterns, healthcare utilization, costs, and mortality in central nervous system and non-central nervous system disseminated coccidioidomycosis across the continuum-of-care

  . ID Week 2024. Los Angeles, Ca.
• Donovan, F. (2025, October).

  Hospitalizations Associated with Disseminated Coccidioidomycosis and Coccidioidal Meningitis, Texas, 2016-2023, USA

  . ID Week 2025. Atlanta, GA: IDSA.
• Donovan, F. (2025, October).

  Olorofim for the treatment of Central Nervous System (CNS) invasive fungal infections (IFI) in patients with limited or no treatment options: a sub-analysis of an open-label, single-arm, Phase 2b trial (Study 32; NCT03583164)

  . ID week 2025doi.org/10.1093/ofid/ofaf695.1380.
• Donovan, F. (2024, April). Olorofim for Treatment of Disseminated Coccidioidomycosis in Patients with Limited or No Therapeutic Options. Cocci Study Group Meeting. San Antonio, Texas: CSG.
• Donovan, F. (2024, August). Coccidioidomycosis overview, Towards a vaccine for Valley fever, FDA/NIH, 08/2024, Rockville, MD  . FDA/NIH workshop. Rockville, MD: NIH/FDA.
• Donovan, F. (2024, January).

  Updates in Coccidioidomycosis, Seminar series, Grand Rounds

  . Seminar series, Grand Rounds, Nevada. Touro University, Nevada: Touro University, Nevada.
• Donovan, F. (2024, June).

  Rising Risk of Coccidioidomycosis

  . ASM Microbe. Atlanta, Georgia: ASM.
• Donovan, F. (2024, June). Updates in coccidioidomycosis. ASM Microbe 2024. Atlanta, Georgia.
• Donovan, F. (2024, May).

  Understanding how Coccidioides affects people, VFCE Annual Member meeting, UA COM, May 2024

  . VFCE Annual Member meeting. UA COM.
• Donovan, F. (2024, November).

  Managing endemic mould infections Coccidioidomycosis

  . Arizona Osteopathic Medical Association. Oro Valley, AZ: Arizona Osteopathic Medical Association.
• Donovan, F. (2024, October). Novel Antifungal Olorofim Use in Intractable CNS and Non-CNS Disseminated Coccidioidomycosis . ID Week 2024. Los Angeles, CA: IDSA.
• Donovan, F. (2023, 04).

  Diagnosing and managing endemic mould infections (coccidioidomycosis)

  . ECCMID. Copenhagen, Denmark: ECCMID.
  More info

  Invited speaker
• Donovan, F. (2023, December).

  Updates in Coccidioidomycosis, Cardiology Lab meeting (Dr. Liao’s lab), Tucson, AZ  

  . Cardiology conference series. Tucson, AZ.
• Donovan, F. (2023, May).

  Contribution of Biologic Response Modifiers to the Risk of Coccidioidomycosis Severity

  . Valley Fever Center of Excellence Member Meeting. Tucson, AZ.
• Donovan, F. (2023, October). Olorofim for treatment of mould IFD in patients with limited or no treatment options: Results from a Phase2b open-label study (NCT03583164, study 32)
  . TIMM. Athens, Greece: TIMM.
• Donovan, F. (2023, September).

  Updates in Coccidioidomycosis

  . Arizona Allergy & Asthma Society, Annual Meeting. Mesa, Az.
• Donovan, F. (2022). Contribution of biologic response modifiers to the risk of coccidioidomycosis severity. Rheumatology Grand Rounds. University of Arizona, Chase Auditorium: University of Arizona.
• Donovan, F. (2022, Fall). Determining The Impact of Biologic Response Modifiers on Coccidioidomycosis Severity. Biennial Meeting. Albuquerque, New Mexico.
• Donovan, F. (2022, November). Updates in Coccidioidomycosis. Tubac Rotary Club. Tubac, AZ.
• Donovan, F. (2022, November). Valley fever Diagnostics Current Methods and Challenges. National Academies of Science. UC Irvine, CA: National Academies of Science Engineering Medicine.
• Galgiani, J. N., Donovan, F., Ramadan, F., Ellingson, K., Ramadan, F., Ellingson, K., Donovan, F., & Galgiani, J. N. (2020, March). A Clinical Profile of Newly Diagnosed Valley Fever in Hospital Settings. SHEA/CDC Decennial 6th International Conference on Healthcare Associated Infections. Atlanta, GA: SHEA/CDC Decennial 6th International Conference on Healthcare Associated Infections.
• Donovan, F. (2018, April). Delays in Diagnosis of Coccidioidomycosis in Tucson, AZ. Cocci Study Group. Flagstaff, Arizona.
• Donovan, F. (2018, April). Valley Fever is under-recognized even in endemic areas. Cocci study Group. Flagstaff, Arizona: Coocidioidomycosis Symposium.

Poster Presentations

• Donovan, F. (2024, August). Risk factors, Clinical Manifestations and Management of Vertebral Osteomyelitis due to Coccidioides- a 10-year retrospective descriptive study. Musculo Skeletal Infection Society Meeting – North Carolina 08/2024. North Carolina.
• Donovan, F. (2024, October).

  Risk factors, Clinical Manifestations and Management of Vertebral Osteomyelitis due to Coccidioides- a 10-year retrospective descriptive study

  . ID Week 2024. Los Angeles, CA: IDSA.
• Donovan, F. (2024, October). Burden of Hospital Illness Associated with Disseminated Versus Isolated Pulmonary Coccidioidomycosis in the United States. ID Week 2024. Los Angeles, CA: IDSA.
• Donovan, F. (2024, September).

  Burden of Hospital Illness Associated with Disseminated Versus Isolated Pulmonary Coccidioidomycosis in the United States

  . Mycoses Study Group (MGSERC). Colorado Spring, CO: MSG.
• Donovan, F. (2024, September).

  Olorofim for the treatment of bone & soft tissue infections in patients with limited or no treatment options: a sub-analysis of Study 32, an open-label, single-arm, Phase 2b trial (NCT03583164)

  . Mycoses Study Group (MGSERC). Colorado Spring, CO: MSG.
• Donovan, F. (2024, September).

  Olorofim for the treatment of severe invasive fungal infections (IFIs) in US patients with limited or no treatment options: a sub-analysis of an open-label, single-arm, Phase 2b trial (Study 32; NCT03583164)

  . Mycoses Study Group (MGSERC). Colorado Spring, CO: MSG.
• Song, H., Gu, Y., Donovan, F., Leroy, G. A., & Galgiani, J. N. (2021, November). Automated Biomedical Lexicon Creation with Graph Search for Word Embeddings. IEEE CHASE. Washington DC.
• Donovan, F. (2017, August). Delays in diagnosing coccidioidomycosis within its endemic region.. 7th International Coccidioidomycosis Symposium. Standford, CA: Stanford Center for Continuing Medical Education.
• Donovan, F. (2017, November). Delays in diagnosing coccidioidomycosis within its endemic region.. Jr Investigator Poster Forum. College of Medicine-Tucson, University of Arizona.

Reviews

• Donovan, F. (2023. National Institutes of Health Advanced Therapeutic Study Section. NIAID study section.

Others

• Donovan, F. (2024, June). Panelist endemic mycosis. ASM Microbe.