Neil M Ampel

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Journals/Publications

• Malo, J., Holbrook, E., Zangeneh, T., Strawter, C., Oren, E., Robey, I., Erickson, H., Chahal, R., Durkin, M., Thompson, C., Hoover, S. E., Ampel, N. M., Wheat, L. J., & Knox, K. S. (2017). ENHANCED ANTIBODY DETECTION AND DIAGNOSIS OF COCCIDIOIDOMYCOSIS WITH THE MIRAVISTA IGG AND IGM DETECTION ENZYME IMMUNOASSAY. Journal of clinical microbiology.
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  Coccidioidomycosis is a common cause of community-acquired pneumonia in endemic areas of the southwestern United States. Clinical presentations range from self-limited disease to severe, disseminated disease. As such, early and accurate diagnosis is essential to ensure appropriate treatment and monitoring. Currently available diagnostic testing has variable accuracy, particularly in certain patient populations, and new tests may offer improved accuracy for the diagnosis of coccidioidomycosis.
• Galgiani, J. N., Ampel, N. M., Blair, J. E., Catanzaro, A., Geertsma, F., Hoover, S. E., Johnson, R. H., Kusne, S., Lisse, J., MacDonald, J. D., Meyerson, S. L., Raksin, P. B., Siever, J., Stevens, D. A., Sunenshine, R., & Theodore, N. (2016). 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 63(6), e112-46.
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  It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.
• Galgiani, J. N., Ampel, N. M., Blair, J. E., Catanzaro, A., Geertsma, F., Hoover, S. E., Johnson, R. H., Kusne, S., Lisse, J., MacDonald, J. D., Meyerson, S. L., Raksin, P. B., Siever, J., Stevens, D. A., Sunenshine, R., & Theodore, N. (2016). Executive Summary: 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 63(6), 717-22.
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  It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.
• Goel, K., Ateeli, H., Ampel, N. M., & L'heureux, D. (2016). Patient with Small Cell Lung Carcinoma and Suspected Right Upper Lobe Abscess Presenting with a Purulent Pericardial Effusion. The American journal of case reports, 17, 523-8.
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  BACKGROUND Cardiac tamponade caused by pericardial effusion has a high mortality rate; thus, it is important to diagnose and treat this condition immediately. Specifically, bacterial pericarditis, although now very rare, is often fatal because of its fulminant process. CASE REPORT We present a case of a 61-year-old man with metastatic small cell lung cancer undergoing chemotherapy who presented with fatigue, poor appetite, and altered mental status. He was found to have a large-volume pericardial effusion with tamponade physiology. He underwent emergent pericardiocentesis. The pericardial effusion was nonmalignant, with cultures growing Streptococcus pneumoniae. It was only after his emergent pericardiocentesis that previous imaging from one month prior was able to be reviewed, which showed possible right upper lobe abscess. CONCLUSIONS Most pericardial effusions in cancer patients are related to their malignancy, either due to direct metastasis or secondary physiologic effects. This case is a unique example of a lung cancer patient presenting with a pneumococcal pericardial effusion, which in itself is a rare phenomenon. This case report demonstrates the importance of considering early antibiotic therapy in patients presenting with pericardial effusion, especially given the high mortality rates of infectious pericardial effusions.
• Ampel, N. M. (2015). THE TREATMENT OF COCCIDIOIDOMYCOSIS. Revista do Instituto de Medicina Tropical de Sao Paulo, 57 Suppl 19, 51-6.
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  Therapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection.
• Ampel, N. M., Nesbit, L. A., Nguyen, C. T., Chavez, S., Knox, K. S., Johnson, S. M., & Pappagianis, D. (2015). Cytokine Profiles from Antigen-Stimulated Whole-Blood Samples among Patients with Pulmonary or Nonmeningeal Disseminated Coccidioidomycosis. Clinical and vaccine immunology : CVI, 22(8), 917-22.
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  The outcome of coccidioidomycosis depends on a robust specific cellular immune response. A T-helper type 1 (Th1) cellular immune response has been previously associated with resolution of clinical illness. However, the precise elements of this response and whether cytokines not involved with the Th1 response play a role in coccidioidomycosis are not known. Whole-blood samples were obtained from subjects with active coccidioidomycosis and controls and incubated for 18 h with T27K, a coccidioidal antigen preparation. The supernatant was then assayed for gamma interferon (IFN-γ), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, IL-10, and IL-17A. A total of 43 subjects, 16 with acute pneumonia, 9 with pulmonary sequelae of nodules and cavities, and 18 with nonmeningeal disseminated coccidioidomycosis, were studied. Compared to concentrations in healthy immune and nonimmune donors, the median concentration of IL-17A was significantly higher in those with active coccidioidomycosis (for both, P < 0.01). In addition, IL-6 concentrations were higher while IL-2 and IFN-γ concentrations were significantly lower in those with nonmeningeal disseminated disease diagnosed within 12 months than in those with acute pneumonia (for all, P < 0.05). The cytokine profile among patients with active coccidioidomycosis is distinct in that IL-17A is persistently present. In addition, those with nonmeningeal disseminated disease have an increased inflammatory cytokine response and diminished Th1 responses that modulate over time.
• Pasha, A. K., Walsh, T. K., & Ampel, N. M. (2015). Dual-Time-Point FDG PET/CT to Distinguish Coccidioidal Pulmonary Nodules from Those Due to Malignancy. Lung, 193(5), 863-4.
• Wack, E. E., Ampel, N. M., Sunenshine, R. H., & Galgiani, J. N. (2015). The Return of Delayed-Type Hypersensitivity Skin Testing for Coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 61(5), 787-91.
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  A skin test that detects dermal hypersensitivity in persons with past infection with Coccidioides species is again available for clinical use. Nearly all of the clinical studies with similar materials were published prior to the 1990s, and as a result, many practicing physicians will be unfamiliar with how skin testing for coccidioidomycosis might be useful in patient management or as a research tool. We review clinical and epidemiological studies with past skin test antigens, the composition of past and current skin test preparations with particular attention to differences in the preservatives, and how the current preparation could be used today.
• Reyes, N., Onadeko, O. O., Luraschi-Monjagatta, M. d., Knox, K. S., Rennels, M. A., Walsh, T. K., & Ampel, N. M. (2014). Positron emission tomography in the evaluation of pulmonary nodules among patients living in a coccidioidal endemic region. Lung, 192(4), 589-93.
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  Within a coccidioidal endemic region, pulmonary nodules due to coccidioidomycosis are common. Uptake of (18)fluorodeoxyglucose ((18)FDG) by positron emission tomography with computed axial tomography (PET/CT) has been used to assess whether pulmonary nodules are malignant but inflammatory lesions can be positive. The purpose of this study was to compare by PET/CT the (18)FDG uptake in pulmonary nodules likely due to coccidioidomycosis to that of nodules shown to be malignant among patients living in a coccidioidal endemic region.
• Nesbit, L. A., Knox, K. S., Nguyen, C. T., Roesch, J., Wheat, L. J., Johnson, S. M., Pappagianis, D., Chavez, S., & Ampel, N. M. (2013). Immunological characterization of bronchoalveolar lavage fluid in patients with acute pulmonary coccidioidomycosis. The Journal of infectious diseases, 208(5), 857-63.
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  The specific cellular immunological characteristics of bronchoalveolar lavage (BAL) fluid in acute pulmonary coccidioidomycosis have not been defined.
• Nguyen, C., Barker, B. M., Hoover, S., Nix, D. E., Ampel, N. M., Frelinger, J. A., Orbach, M. J., & Galgiani, J. N. (2013). Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis. Clinical microbiology reviews, 26(3), 505-25.
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  Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii. This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine.
• Johnson, R., Kernerman, S. M., Sawtelle, B. G., Rastogi, S. C., Nielsen, H. S., & Ampel, N. M. (2012). A reformulated spherule-derived coccidioidin (Spherusol) to detect delayed-type hypersensitivity in coccidioidomycosis. Mycopathologia, 174(5-6), 353-8.
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  The ability of spherule-derived coccidioidin containing 0.4 % phenol and 0.0001 % thimerosal in buffered saline to induce delayed-type hypersensitivity (DTH) was evaluated in four separate studies. The skin test antigen was titrated in 20 adult volunteers with a recent history of pulmonary coccidioidomycosis using intradermal doses of 0.4, 0.8, and 1.6 μg of antigen, based on total dry weight. Based on these data, a dose of 1.27 μg was shown to elicit a mean ± SEM induration response of 23.5 ± 2.3 mm at 48 h, similar to the 23.6-mm response after 48 h of the U. S. Reference coccidioidin last tested approximately 13 years ago. The 1.27 μg dose in 0.1 mL of the spherule-derived antigen (Spherusol) was then examined in three separate groups of adult volunteers to determine the sensitivity and specificity of the product. Fifty-nine of 60 individuals living in a non-endemic area for coccidioidomycosis were skin test negative to Spherusol. Twelve subjects with a recent history of pulmonary histoplasmosis were skin test negative to Spherusol. Finally, 51 of 52 individuals with a recent diagnosis of acute pulmonary coccidioidomycosis were skin test positive to Spherusol. Within this group, prior therapy with fluconazole did not appear to reduce the reactivity to Spherusol. No serious adverse events were observed in the four studies. From these data, Spherusol was found to be safe and has an overall observed sensitivity and specificity of ≥ 98 % in detecting DTH in coccidioidomycosis.
• Taroumian, S., Knowles, S. L., Lisse, J. R., Yanes, J., Ampel, N. M., Vaz, A., Galgiani, J. N., & Hoover, S. E. (2012). Management of coccidioidomycosis in patients receiving biologic response modifiers or disease-modifying antirheumatic drugs. Arthritis care & research, 64(12), 1903-9.
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  Coccidioidomycosis (valley fever) is an endemic fungal infection of the American Southwest, an area with a large population of patients with rheumatic diseases. There are currently no guidelines for management of patients who develop coccidioidomycosis while under treatment with biologic response modifiers (BRMs) or disease-modifying antirheumatic drugs (DMARDs). We conducted a retrospective study of how both concurrent diseases were managed and the patient outcomes at 2 centers in Tucson, Arizona.
• Bercovitch, R. S., Catanzaro, A., Schwartz, B. S., Pappagianis, D., Watts, D. H., & Ampel, N. M. (2011). Coccidioidomycosis during pregnancy: a review and recommendations for management. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 53(4), 363-8.
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  Pregnancy is an established risk factor for the development of severe and disseminated coccidioidomycosis, particularly when infection is acquired during the later stages of gestation. Although recent studies suggest that the incidence of symptomatic coccidioidomycosis during pregnancy is decreasing and that outcome has improved, management is complicated by the observations that azole antifungal agents can be teratogenic when given to some women, particularly at high doses, early in pregnancy. This article summarizes the data on these issues and offers guidance on the management of coccidioidomycosis during pregnancy.
• Limper, A. H., Knox, K. S., Sarosi, G. A., Ampel, N. M., Bennett, J. E., Catanzaro, A., Davies, S. F., Dismukes, W. E., Hage, C. A., Marr, K. A., Mody, C. H., Perfect, J. R., Stevens, D. A., & , A. T. (2011). An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. American journal of respiratory and critical care medicine, 183(1), 96-128.
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  With increasing numbers of immune-compromised patients with malignancy, hematologic disease, and HIV, as well as those receiving immunosupressive drug regimens for the management of organ transplantation or autoimmune inflammatory conditions, the incidence of fungal infections has dramatically increased over recent years. Definitive diagnosis of pulmonary fungal infections has also been substantially assisted by the development of newer diagnostic methods and techniques, including the use of antigen detection, polymerase chain reaction, serologies, computed tomography and positron emission tomography scans, bronchoscopy, mediastinoscopy, and video-assisted thorascopic biopsy. At the same time, the introduction of new treatment modalities has significantly broadened options available to physicians who treat these conditions. While traditionally antifungal therapy was limited to the use of amphotericin B, flucytosine, and a handful of clinically available azole agents, current pharmacologic treatment options include potent new azole compounds with extended antifungal activity, lipid forms of amphotericin B, and newer antifungal drugs, including the echinocandins. In view of the changing treatment of pulmonary fungal infections, the American Thoracic Society convened a working group of experts in fungal infections to develop a concise clinical statement of current therapeutic options for those fungal infections of particular relevance to pulmonary and critical care practice. This document focuses on three primary areas of concern: the endemic mycoses, including histoplasmosis, sporotrichosis, blastomycosis, and coccidioidomycosis; fungal infections of special concern for immune-compromised and critically ill patients, including cryptococcosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; and rare and emerging fungal infections.
• Ampel, N. M. (2010). New perspectives on coccidioidomycosis. Proceedings of the American Thoracic Society, 7(3), 181-5.
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  Coccidioidomycosis is a growing problem in the endemic regions of Arizona and California. The reasons for its increase are unclear, but may relate to an influx of nonsusceptible individuals into the endemic regions, construction and dust, and climate. Most cases of coccidioidal infection are completely asymptomatic, but approximately 40% present as a pulmonary process that may be difficult to distinguish from a bacterial community-acquired pneumonia. This has led to underdiagnosis of coccidioidomycosis and inappropriate antibacterial therapy. Serology has been the mainstay of diagnosis, but its sensitivity has not been established. A commercial enzyme immunoassay appears more sensitive than the traditional tube precipitin and complement fixation tests and the immunodiffusion assays, but concern about specificity lingers. Newer tests, including detection of coccidioidal antigenuria and genomic assays, offer promise of greater sensitivity, specificity, and rapidity. The treatment of coccidioidomycosis has most recently depended on oral triazole therapy. However, a recent study suggests that, at least for those with primary pulmonary disease, antifungal therapy may lead to subsequent complications once this therapy is discontinued compared with those who receive no therapy at all.
• Ampel, N. M. (2010). The diagnosis of coccidioidomycosis. F1000 medicine reports, 2.
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  Until recently, culture, microscopy, and serology have been the available methods for the diagnosis of coccidioidomycosis. While Coccidioides is frequently isolated by culture, special precautions must be taken because of the risk of laboratory infection and because Coccidioides is on the Select Agent list. Serology is useful but the sensitivity remains lower than desired. A commercially available test for coccidioidal galactomannan antigenuria now exists and appears useful for immunocompromised hosts with severe disease. Polymerase chain reaction assays targeting specific coccidioidal genes have demonstrated utility but are not commercially available. Moreover, their sensitivity and the best sample type remain unestablished.
• Ampel, N. M. (2010). What's Behind the Increasing Rates of Coccidioidomycosis in Arizona and California?. Current infectious disease reports, 12(3), 211-6.
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  The number of cases of symptomatic coccidioidomycosis reported in the endemic regions of California and Arizona has increased over the past two decades. In California, the southern San Joaquin Valley has seen a dramatic increase, with rates of symptomatic illness of more than 150 per 100,000 of population in Kern County. In Arizona, almost 5,000 cases are now reported yearly. In contrast to California, the coccidioidal endemic region in Arizona is also the most populous region of the state, and Arizona now accounts for 60% of all cases reported in the United States. Reasons for these increases appear to be multifactorial. Possible etiologies include climate change, changes in local exposure, an increase in the number of individuals susceptible to infection living in the endemic region, and increased testing and reporting. None of these factors are mutually exclusive and none has been clearly established as the etiology for the increase.
• Ampel, N. M., & Hector, R. F. (2010). Measuring cellular immunity in coccidioidomycosis: the time is now. Mycopathologia, 169(6), 425-6.
• Masannat, F. Y., & Ampel, N. M. (2010). Coccidioidomycosis in patients with HIV-1 infection in the era of potent antiretroviral therapy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 50(1), 1-7.
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  Coccidioidomycosis is a common opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected individuals living in regions where coccidioidomycosis is endemic. However, there have been no studies on its incidence or clinical expression during the era of potent antiretroviral therapy.
• Nesbit, L., Johnson, S. M., Pappagianis, D., & Ampel, N. M. (2010). Polyfunctional T lymphocytes are in the peripheral blood of donors naturally immune to coccidioidomycosis and are not induced by dendritic cells. Infection and immunity, 78(1), 309-15.
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  Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-gamma), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P = 0.03). When monocyte-derived mature dendritic cells pulsed with T27K (mDC(T27K)) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDC(T27K) did significantly increase the concentrations of IL-2 and IFN-gamma released by PBMC from nonimmune donors (P = 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low- and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P = 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis.
• Ampel, N. M. (2009). Coccidioidomycosis: a review of recent advances. Clinics in chest medicine, 30(2), 241-51, v.
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  Coccidioidomycosis is one of three dimorphic endemic mycoses recognized in North America. Over the past decade, the disease has been resurgent, particularly in the southwest United States. With this increase in incidence have come new observations and insights and re-examination of past issues. This article explores some of these areas by focusing principally on recent publications that are of importance.
• Ampel, N. M., Dionne, S. O., Giblin, A., Podany, A. B., & Galgiani, J. (2009). Mannose-binding lectin serum levels are low in persons with clinically active coccidioidomycosis. Mycopathologia, 167(4), 173-80.
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  Mannose-binding lectin (MBL) is a circulating collectin that is part of the innate immune response. We explored the serum levels of MBL in persons with different forms of coccidioidomycosis.
• Ampel, N. M., Giblin, A., Mourani, J. P., & Galgiani, J. N. (2009). Factors and outcomes associated with the decision to treat primary pulmonary coccidioidomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 48(2), 172-8.
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  Studies that assess the value of initiating oral antifungal therapy to treat primary pulmonary coccidioidomycosis have not been published previously.

Poster Presentations

• Holbrook, E. D., Malo, J., Zangeneh, T. T., Strawter, C., Oren, E., Robey, I., Erickson, H., Chahal, R., Durkin, M., Thompson, C., Hoover, S. E., Ampel, N., Wheat, L. J., & Knox, K. S. (2016, Fall). Development of an Improved Antibody Detection EIA for use in Diagnosis of Coccidioidomycosis. ID Week. New Orleans, LA.