Stephen A Klotz
- Professor, Medicine
- Professor, Family and Community Medicine
My main preoccupation since receiving my MD degree is to pass on to others what I have learned in Medicine and Infectious Diseases. This has required much service, experience and communicating this knowledge. I am an excellent teacher/lecturer and have accomplished a considerable body of research work related to fungal infections, HIV and kissing bugs.
- M.D. Medicine
- University of Kansas, Kansas City, Kansas, United States
- B.A. Zoology
- University of Kansas, Lawrence, Kansas, United States
- University of Kansas School of Medicine (1990 - 2000)
- Louisiana State University-Shreveport (1984 - 1990)
- Emergency Room Corporation (1977 - 1979)
- University of Kansas School of Medicine (1976 - 1977)
- Indian Health Service (1975 - 1976)
- Best Doctors in Tucson
- Fall 2018
- Spring 2017
- Spring 2016
- Spring 2015
- University of Arizona, Spring 2017
Licensure & Certification
- Internal Medicine Certification, ABIM (1981)
- Infectious Diseases Certification, ABIM (1984)
- Medical license, Arizona Board of Medical Licensure (2000)
HIV; Candida adherence; Kissing bug behavior; Chagas
Infectious Diseases; HIV; Fungal Infections
Honors ThesisPSIO 498H (Fall 2016)
- Traeger, M. S., Klotz, S. A., & Zangeneh, T. T. (2019). Anthrax and other Bacillus species. In Schlossberg's Textbook of Clinical Infectious Disease.
- Klotz, S. A., & Alpert, J. S. (2017). Infective Endocarditis. In Hurst's The Heart.
- Klotz, S. A., El Ramahi, R., & Zangeneh, T. (2017). Bacterial and fungal infections of the liver. In Hepatology, a textbook of liver disease.
- Behrens-Bradley, N., Smith, S., Beatty, N. L., Love, M., Ahmad, N., Dorn, P. L., Schmidt, J. O., & Klotz, S. A. (2020). Kissing Bugs Harboring Trypanosoma cruzi, Frequently Bite Residents of the US Southwest But Do Not Cause Chagas Disease. The American journal of medicine, 133(1), 108-114.e13.More infoKissing bugs are common household pests in the Desert Southwest of the United States. These hematophagous bugs enter homes and suck blood from resident humans and pets. They are vectors of Trypanosoma cruzi, an enzootic parasite in small mammals and the cause of Chagas disease in humans. Autochthonous cases of Chagas disease are rare in the United States despite the presence of the vector and parasite. Environmental and biological factors accounting for this phenomenon need studying.
- Klotz, S. A., Bradley, N., Smith, S., & Ahmad, N. (2020). HIV Infection-Associated Frailty: The Solution for Now Is Antiretroviral Drugs: A Perspective. Journal of the International Association of Providers of AIDS Care, 18, 2325958219831045.More infoThis Perspective article provides a new view of frailty as it relates to HIV-1 infection. We discuss new findings and where our research is going.
- Beatty, N. L., Behrens-Bradley, N., Love, M., McCants, F., Smith, S., Schmidt, J. O., Hamer, S. A., Dorn, P. L., Ahmad, N., & Klotz, S. A. (2019). Rapid detection of human blood in triatomines (kissing bugs) utilizing a lateral flow immunochromatographic assay - A pilot study. Memorias do Instituto Oswaldo Cruz, 114, e190047.More infoWe tested a rapid and specific immunochromatographic assay (that detects human blood in forensic samples) to determine if human blood was present in triatomines and their fecal excreta.
- Beatty, N. L., Dorn, P. L., & Klotz, S. A. (2019). The Uninvited "Kiss": When the Hunter Becomes the Hunted. The American journal of tropical medicine and hygiene, 100(3), 492-493.
- Behrens, N. E., Lipke, P. N., Pilling, D., Gomer, R. H., & Klotz, S. A. (2019). Serum Amyloid P Component Binds Fungal Surface Amyloid and Decreases Human Macrophage Phagocytosis and Secretion of Inflammatory Cytokines. mBio, 10(2).More infoIn patients with invasive fungal diseases, there is often little cellular inflammatory response. We tested the idea that binding of the human constitutive plasma protein serum amyloid P component (SAP) (also called PTX2) to dampens the innate immune response to this fungus. Many pathogenic fungi have cell surface amyloid-like structures important for adhesion and biofilm formation. Human SAP bound to fungi that expressed functional cell surface amyloid, but SAP had minimal binding to fungi with reduced expression of cell surface amyloid. In the absence of SAP, phagocytosis of fungi by human macrophages was potentiated by expression of amyloid on the fungi. SAP binding to fungi inhibited their phagocytosis by macrophages. Macrophages pretreated with SAP displayed reduced fungal phagocytosis, reduced secretion of inflammatory cytokines (IFN-γ, IL-6, and TNF-α), and increased secretion of the anti-inflammatory cytokine IL-10. SAP bound to fungi or added to the medium upregulated the expression of the anti-inflammatory receptor CD206 on macrophages. These findings suggest that SAP bound to amyloid-like structures on fungal cells dampens the host cellular immune response in fungal diseases such as invasive candidiasis. Macrophages are a key part of our innate immune system and are responsible for recognizing invading microbes, ingesting them, and sending appropriate signals to other immune cells. We have found that human macrophages can recognize invading yeast pathogens that have a specific molecular pattern of proteins on their surfaces: these proteins have structures similar to the structures of amyloid aggregates in neurodegenerative diseases like Alzheimer's disease. However, this surface pattern also causes the fungi to bind a serum protein called serum amyloid P component (SAP). In turn, the SAP-coated yeasts are poorly recognized and seldom ingested by the macrophages, and the macrophages have a more tolerant and less inflammatory response in the presence of SAP. Therefore, we find that surface structures on the yeast can alter how the macrophages react to invading microbes.
- Bernaba, M., Power, E., Campion, J., Gotzek, D., Schmidt, J. O., & Klotz, S. A. (2019). Unconscious Woman in Shock and Covered with Ants Pulled from an Abandoned Automobile. The American journal of medicine, 132(10), 1239-1241.More infoA middle-aged woman was taken from an abandoned automobile unconscious and covered with ants in Tucson, Arizona. When hospitalized in July 2018, she had an extensive papular-pustular skin eruption on her abdomen and thigh and disseminated intravascular coagulation. She was stung innumerable times by native golden fire ants (Solenopsis aurea) while sleeping in the vehicle. The large amount of venom injected by stings into this individual may have triggered dissemnated intravascualar coagulation because the venom contains powerful hemolytic factors.
- Klotz, S. A. (2019). https://pubmed.ncbi.nlm.nih.gov/31715166/?from_term=klotz+sa&from_sort=date&from_size=10&from_pos=1. American Journal of Medicine.
- Rahimian, R., Shirazi, F. M., Schmidt, J. O., & Klotz, S. A. (2019). Honeybee Stings in the Era of Killer Bees: Anaphylaxis and Toxic Envenomation. The American journal of medicine.More infoTwenty-six years after the arrival of "killer bees" in Arizona, the entire state with the exception of high elevations in the north is populated with this bee variety and 11 people have died at the scene of massive bee attacks.
- Rees, H. C., Meister, E., Mohler, M. J., & Klotz, S. A. (2019). HIV-Related Frailty Is Not Characterized by Sarcopenia. Journal of the International Association of Providers of AIDS Care, 15(2), 131-4.More infoFrailty is common in HIV-infected patients, but its causes are elusive. We assessed 122 clinic patients for frailty using the 5-measure Fried Frailty criteria. The prevalence of frailty was 19% (n = 23) and all frail patients reported exhaustion with a Center for Epidemiologic Studies Depression Scale score >16 indicating depression. The next most common criterion was low physical activity (expenditure of kcal/week). Markers of sarcopenia such as decreased grip strength and decreased gait speed, hallmarks of frailty in the elderly, were the least common of the 5 criteria. Frailty was reversible: 6 frail patients returned for reassessment and only 2 were frail. We conclude that frailty in the HIV-infected patients is potentially reversible and strongly associated with depression and low physical activity, whereas frailty in the elderly is associated with aging-related sarcopenia and is often irreversible.
- August, J. A., Boesen, K. J., Hurst, N. B., Shirazi, F. M., & Klotz, S. A. (2018). Prophylactic Antibiotics Are Not Needed Following Rattlesnake Bites. The American journal of medicine, 131(11), 1367-1371.More infoAntibiotics are sometimes administered to victims of rattlesnake bites in the hope of preventing infections. Experts in the field recommend that prophylactic antibiotics not be used because secondary infections are rare. Current recommendations are based on a small number of studies conducted in the United States. We decided to reexamine the issue by taking advantage of a large database on snakebites in Arizona. This allowed us to determine how often prophylactic antibiotics were used and whether or not they were effective.
- Beatty, N. L., & Klotz, S. A. (2018). The Midnight Bite! A Kissing Bug Nightmare. The American journal of medicine, 131(2), e43-e44.
- Beatty, N. L., Perez-Velez, C. M., Yaglom, H. D., Carson, S., Liu, E., Khalpey, Z. I., Klotz, S. A., & Elliott, S. P. (2018). Evidence of Likely Autochthonous Transmission of Chagas Disease in Arizona. The American journal of tropical medicine and hygiene, 99(6), 1534-1536.More infoA healthy 16-year-old girl born and raised in Tucson, AZ, had screening and confirmatory testing revealing Chagas disease; clinical evaluation established that she had the indeterminate form of chronic Chagas disease with evidence of likely autochthonous transmission. DNA was detected by conventional polymerase chain reaction in captured at her home.
- Behrens, N. E., Wertheimer, A., Klotz, S. A., & Ahmad, N. (2018). Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy. PloS one, 13(6), e0199101.More infoSeveral studies have shown an increased accumulation of terminally differentiated T cells during HIV infection, suggestive of exhaustion/senescence, causing dysregulation of T cell homeostasis and function and rapid HIV disease progression. We have investigated whether long-term antiretroviral therapy (ART), which controls viremia and restores CD4 T cell counts, is correlated with reduction in terminally differentiated T cells, improved ratios of naïve to memory and function of T cells in 100 virologically controlled HIV-infected patients. We show that while the median frequencies of terminally differentiated CD4+ and CD8+ T cells (CD28-, CD27-, CD57+ and CD28-CD57+), were higher in the virologically controlled HIV-infected patients' cohort compared with uninfected individuals' cohort, the frequencies of these cells significantly decreased with increasing CD4 T cell counts in HIV-infected patients. Although, the naïve CD4+ and CD8+ T cells were lower in HIV patients' cohort than uninfected cohort, there was a significant increase in both naïve CD4+ and CD8+ T cells with increasing CD4 T cell counts in HIV-infected patients. The underlying mechanism behind this increased naïve CD4+ and CD8+ T cells in HIV-infected patients was due to an increase in recent thymic emigrants, CD4+CD31+, as compared to CD4+CD31-. The CD4+ T cells of HIV-infected patients produced cytokines, including IL-2, IL-10 and IFN-γ comparable to uninfected individuals. In conclusion, virologically controlled HIV-infected patients on long-term ART show a significant reduction in terminally differentiated T cells, suggestive of decreased exhaustion/senescence, and improvement in the ratios of naïve to memory and function of T cells.
- Golconda, U., Sobonya, R. E., & Klotz, S. A. (2018). Do Pentraxins Bind to Fungi in Invasive Human Gastrointestinal Candidiasis?. Journal of fungi (Basel, Switzerland), 4(3).More infoTissue from 13 autopsy cases with invasive gastrointestinal candidiasis was studied for the binding of the pentraxins, C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) to fungal surfaces. Invasive candidal infection was demonstrated using a hematoxylin and eosin stain and a Gomori methenamine silver stain (GMS). Immunohistochemistry was performed with CRP and PTX3 monoclonal antibodies and did not demonstrate CRP or PTX3 bound to fungi (0 of 13 cases), although CRP was extensively deposited on human tissue. A polyclonal antibody to SAP showed that SAP was bound to fungi in 12 of 13 cases. Although all three pentraxins have been reported to bind to fungi or bacteria, only SAP was bound to filamentous and yeast forms of in human tissue, as detected by immunohistochemistry. SAP was abundantly present on fungi and may have affected the host innate immune response to the invading fungi.
- Klotz, S. A., Beatty, N., & Elliott, S. P. (2018). Ectoparasite Infestation of a Hospital Due to the Colonization of Nesting Cliff Swallows. Clinical Infectious Diseases.
- Lipke, P. N., Klotz, S. A., Dufrene, Y. F., Jackson, D. N., & Garcia-Sherman, M. C. (2018). Amyloid-Like beta-Aggregates as Force-Sensitive Switches in Fungal Biofilms and Infections. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 82(1).
- Lipke, P. N., Klotz, S. A., Dufrene, Y. F., Jackson, D. N., & Garcia-Sherman, M. C. (2018). Amyloid-Like β-Aggregates as Force-Sensitive Switches in Fungal Biofilms and Infections. Microbiology and molecular biology reviews : MMBR, 82(1).More infoCellular aggregation is an essential step in the formation of biofilms, which promote fungal survival and persistence in hosts. In many of the known yeast cell adhesion proteins, there are amino acid sequences predicted to form amyloid-like β-aggregates. These sequences mediate amyloid formation , these sequences mediate a phase transition from a disordered state to a partially ordered state to create patches of adhesins on the cell surface. These β-aggregated protein patches are called adhesin nanodomains, and their presence greatly increases and strengthens cell-cell interactions in fungal cell aggregation. Nanodomain formation is slow (with molecular response in minutes and the consequences being evident for hours), and strong interactions lead to enhanced biofilm formation. Unique among functional amyloids, fungal adhesin β-aggregation can be triggered by the application of physical shear force, leading to cellular responses to flow-induced stress and the formation of robust biofilms that persist under flow. Bioinformatics analysis suggests that this phenomenon may be widespread. Analysis of fungal abscesses shows the presence of surface amyloids , a finding which supports the idea that phase changes to an amyloid-like state occur . The amyloid-coated fungi bind the damage-associated molecular pattern receptor serum amyloid P component, and there may be a consequential modulation of innate immune responses to the fungi. Structural data now suggest mechanisms for the force-mediated induction of the phase change. We summarize and discuss evidence that the sequences function as triggers for protein aggregation and subsequent cellular aggregation, both and .
- Schmidt, J. O., Dorn, P. L., & Klotz, S. A. (2018). Second-Best Is Better Than Nothing: Cockroaches as a Viable Food Source for the Kissing Bug Triatoma recurva (Hemiptera: Reduviidae). Journal of medical entomology.More infoKissing bugs in the genus Triatoma are obligate blood feeders that feed mainly on vertebrate blood and have lost the predatory lifestyle found in other reduviid bugs. They occasionally also feed on the hemolymph of arthropods, especially during the first and second instar stages. The largest kissing bug species in the United States, Triatoma recurva (Stål) (Hemiptera: Reduviidae), is poorly known and was chosen to investigate its ability to feed and develop on a diet of cockroach hemolymph. Molting from first instar individuals to second instars readily occurred at approximately the same rate reported for the species feeding on mammalian blood. Subsequent instars also fed on and survived on cockroach hemolymph with some individuals maturing to adults. In the larger instars, development time and survival rates were reduced relative to the results reported in the literature for mammalian-blood-fed individuals. Two other species of kissing bugs, Triatoma protracta (Uhler) and T. rubida (Uhler) failed to survive on cockroach hemolymph with most individuals failing to molt from the first instar stage. Although T. recurva does not thrive on a diet limited to hemolymph of cockroaches, it appears to be an unusual species in which cockroaches might be a primary source of nutrition for smaller individuals and are a viable exclusive source of nutrition for all immatures. At a minimum during times of limited availability of vertebrate blood sources, the presence of cockroaches enhances survival opportunities. Efforts to control populations of this kissing bug species likely will be improved with additional control of cockroach populations in the environment.
- Beatty, N. L., Klotz, S. A., & Elliott, S. P. (2017). ECTOPARASITE INFESTATION OF A HOSPITAL DUE TO NESTING CLIFF SWALLOWS. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 95(5), 51-52.
- Beatty, N. L., Klotz, S. A., & Elliott, S. P. (2017). Hematophagous Ectoparasites of Cliff Swallows Invade a Hospital and Feed on Humans. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 65(12), 2119-2121.More infoWe describe a hospital infestation by 2 hematophagous ectoparasites of cliff swallows that nested in the window eaves. Breaks in window seals allowed entry of swallow ticks and swallow bugs. These pests emerged in large numbers in patient rooms, hallways, and stairwells; 17% of the ticks fed on humans.
- Klotz, S. A. (2017). Candidiasis (oral and esophageal). Essential Evidence Plus.
- Klotz, S. A. (2017). The midnite bite. A kissing bug nightmare. Am J Med.
- Klotz, S. A., & Brown, C. B. (2017). Hantavirus. Essential Evidence Plus.
- Klotz, S. A., Shirazi, F. M., Boesen, K., Beatty, N. L., Dorn, P. L., Smith, S., & Schmidt, J. O. (2016). Kissing Bug (Triatoma spp.) Intrusion into Homes: Troublesome Bites and Domiciliation. Environmental health insights, 10, 45-9.More infoKissing bugs (Triatoma spp.) frequently enter homes and bite human and pet occupants. Bites may lead to severe allergic reactions and, in some cases, death. Kissing bugs are also vectors of Trypanosoma cruzi, the cause of Chagas disease. In general, modern houses in the United States are not conducive to domiciliation of kissing bugs (bugs living out their entire life within the home with the presence of eggs, nymphs, adults, and exuviae). Construction features such as concrete foundations, solid walls and ceilings, window screens, tight thresholds for doors and windows, and other measures impede bug entry into homes, and air conditioning reduces the need for open doors and windows. Where Chagas disease is endemic in Mexico and Central and South America, homes often have thatch roofs, adobe walls, and open doors and windows. We investigated numerous instances of kissing bug intrusions into homes in Southern Arizona, California, and Louisiana and documented the reactions to kissing bug bites. Our work confirms the importance of modern home construction in limiting kissing bug intrusions. Older homes, especially those lacking modern screening, caulking, and weather stripping to reduce air leakage, may be subject to kissing bug intrusions and domiciliation. We describe a community in Southern Arizona where domiciliation of homes by Triatoma recurva is common. We also provide recent data regarding kissing bug bites and allergic reactions to the bites.
- Klotz, S. A., Sobonya, R. E., Lipke, P. N., & Garcia-Sherman, M. C. (2016). Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host or Is It a Trojan Horse?. Open forum infectious diseases, 3(3), ofw166.More infoIt is a striking observation that tissue of patients invaded by the deep mycoses often lacks evidence of an inflammatory response. This lack of host response is often attributed to neutropenia secondary to chemotherapy. However, systematic studies do not support this simplistic explanation. However, invasive fungal lesions are characterized by abundant fungal functional amyloid, which in turn is bound by serum amyloid P component (SAP). We postulate that SAP is important in the local immune response in invasive fungal infections. The interaction between fungal functional amyloid, SAP, and the immune response in deep mycoses is discussed.
- Veeravelli, S., Najafi, B., Marin, I., Blumenkron, F., Smith, S., & Klotz, S. A. (2016). Exergaming in Older People Living with HIV Improves Balance, Mobility and Ameliorates Some Aspects of Frailty. Journal of visualized experiments : JoVE.More infoApproximately 1.2 million people in the United States live with HIV infection. Medical advancements have increased the life expectancy and this cohort is aging. HIV-positive individuals have a high incidence of frailty (~20%) characterized by depression and sedentary behavior. Exercise would be healthy, but due to the frail status of many HIV-positive individuals, conventional exercise is too taxing. The aim of this study was to evaluate the effectiveness and acceptability of a novel game-based training program (exergame) in ameliorating some aspects of frailty in HIV-infected individuals. Ten older people living with HIV were enrolled in an exergame intervention. Patients performed balance exercises such as weight shifting, ankle reaching, and obstacle crossing. Real-time visual/audio lower-extremity joint motion feedback was provided using wearable sensors to assist feedback and encourage subjects to accurately execute each exercise task. Patients trained twice a week for 45 min for 6 weeks. Changes in balance, gait, psychosocial parameters and quality of life parameters were assessed at the beginning, midterm and at conclusion of the training program. Ten patients completed the study and their results analyzed. The mean age was 57.2 ± 9.2 years. The participants showed a significant reduction in center of mass sway (78.2%, p = .045) during the semi-tandem balance stance with eyes closed and showed a significant increase in gait speed during a dual task motor-cognitive assessment (9.3%, p = .048) with an increase in stride velocity of over 0.1 m/sec. A significant reduction in reported pain occurred (43.5%, p = .041). Preliminary results of this exergame intervention show promise in improving balance and mobility while requiring older people living with HIV to be more active. The exergame can be continued at home and may have long term as well as short-term benefits for ameliorating frailty associated with HIV infection.
- Garcia-Sherman, M. C., Lundberg, T., Sobonya, R. E., Lipke, P. N., & Klotz, S. A. (2015). A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component. NPJ BIOFILMS AND MICROBIOMES, 1.
- Garcia-Sherman, M. C., Lundberg, T., Sobonya, R. E., Lipke, P. N., & Klotz, S. A. (2015). A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component. NPJ biofilms and microbiomes, 1.More infoWe have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease-resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections.
- Klotz, S. A. (2015). Contemporary HIV-patients and the Frailty Syndrome: A Short Review.. Austin J Infect Dis.
- Rees, H. C., Meister, E., Mohler, M. J., & Klotz, S. A. (2015). HIV-Related Frailty Is Not Characterized by Sarcopenia. Journal of the International Association of Providers of AIDS Care, 15(2), 131-4.More infoFrailty is common in HIV-infected patients, but its causes are elusive. We assessed 122 clinic patients for frailty using the 5-measure Fried Frailty criteria. The prevalence of frailty was 19% (n = 23) and all frail patients reported exhaustion with a Center for Epidemiologic Studies Depression Scale score >16 indicating depression. The next most common criterion was low physical activity (expenditure of kcal/week). Markers of sarcopenia such as decreased grip strength and decreased gait speed, hallmarks of frailty in the elderly, were the least common of the 5 criteria. Frailty was reversible: 6 frail patients returned for reassessment and only 2 were frail. We conclude that frailty in the HIV-infected patients is potentially reversible and strongly associated with depression and low physical activity, whereas frailty in the elderly is associated with aging-related sarcopenia and is often irreversible.
- Zamora, D., Klotz, S. A., Meister, E. A., & Schmidt, J. O. (2015). Repellency of the Components of the Essential Oil, Citronella, to Triatoma rubida, Triatoma protracta, and Triatoma recurva (Hemiptera: Reduviidae: Triatominae). Journal of medical entomology, 52(4), 719-21.More infoThe kissing bugs--Triatoma rubida (Uhler), Triatoma protracta (Uhler), and Triatoma recurva (Stal)--are common hematophagous bugs in southeastern Arizona and responsible for severe allergic reactions in some individuals who are bitten. They also possess the potential to transmit the blood parasite, Trypanosoma cruzi. We previously found the essential oil, citronella, to be an excellent deterrent of feeding of T. rubida on a restrained mouse. In this work, we tested major components--alcohols, aldehydes, and monoterpenes--of citronella oil for repellency against the three common triatome species endemic in southern Arizona. The following citronella oil components--geraniol, citronellol, limonene, and citronellal--in different concentrations and combinations were tested. All components of citronella oil demonstrated some inhibition of feeding, ranging from very weak inhibition (limonene) to significant inhibition (geraniol and citronellol). A mixture of geraniol and citronellol was found to be repellant at concentrations of .165 and .165 vol%, respectively, for all three triatome species. Citronellal and limonene had no significant repellent activity. The repellent activity of citronella oil appears to be acting through direct contact with the bugs rather than diffusion of vapors.
- Zangeneh, T. T., Malo, J., Luraschi-Monjagatta, C., Hage, C. A., Wheat, L. J., Strawter, C., Klotz, S. A., & Knox, K. S. (2015). Positive (1-3) B-d-glucan and cross reactivity of fungal assays in coccidioidomycosis. Medical mycology, 53(2), 171-3.More infoFungal antigen testing in immunosuppressed patients has emerged as a powerful diagnostic tool. Some assays are relatively nonspecific, and misinterpretation can have severe clinical consequences. Additionally, when new assays become commercially available it is important to evaluate the potential for cross reactivity. We recently observed several immunosuppressed patients with positive (1→3)-β-D-glucan (BG) who were eventually diagnosed with coccidioidomycosis in the endemic area of Tucson, Arizona. Although the BG assay is known to detect glucans of many fungal pathogens, reports of cross-reactivity with Coccidioides remain sparsely reported. To test the cross-reactivity of fungal antigens in detection assays, serum samples from patients with coccidioidomycosis testing positive for Coccidioides antigen were evaluated for BG. Of 12 samples positive for Coccidioides antigen (≥0.07 ng/ml), 11 (92%) were positive by BG (>80 pg/ml), and of 11 positive for Aspergillus galactomannan, 10 (91%) were positive by BG (>80 pg/ml). We conclude that the BG assay is nonspecific, detecting glucans from many fungal pathogens, including Coccidioides. In the endemic area, a positive BG warrants further specific testing.
- Garcia-Sherman, M. C., Lysak, N., Filonenko, A., Richards, H., Sobonya, R. E., Klotz, S. A., & Lipke, P. N. (2014). Peptide detection of fungal functional amyloids in infected tissue. PloS one, 9(1), e86067.More infoMany fungal cell adhesion proteins form functional amyloid patches on the surface of adhering cells. The Candida albicans Agglutinin-like sequence (Als) adhesins are exemplars for this phenomenon, and have amyloid forming sequences that are conserved between family members. The Als5p amyloid sequence mediates amyloid fibril formation and is critical for cell adhesion and biofilm formation, and is also present in the related adhesins Als1p and Als3p. We have developed a fluorescent peptide probe containing the conserved Als amyloid-forming sequence. This peptide bound specifically to yeast expressing Als5p, but not to cells lacking the adhesin. The probe bound to both yeast and hyphal forms of C. albicans. Δals1/Δals3 single and double deletion strains exhibited reduced fluorescence, indicating that probe binding required expression of these proteins. Additionally, the Als peptide specifically stained fungal cells in abscesses in autopsy sections. Counterstaining with calcofluor white showed colocalization with the amyloid peptide. In addition, fungi in autopsy sections derived from the gastrointestinal tract showed colocalization of the amyloid-specific dye thioflavin T and the fluorescent peptide. Collectively, our data demonstrate that we can exploit amyloid sequence specificity for detection of functional amyloids in situ.
- Klotz, S. A., Dorn, P. L., Mosbacher, M., & Schmidt, J. O. (2014). Kissing bugs in the United States: risk for vector-borne disease in humans. Environmental health insights, 8(Suppl 2), 49-59.More infoEleven species of kissing bugs are found in the United States. Their home ranges may be expanding northward, perhaps as a consequence of climate change. At least eight of the species, perhaps all, are reported to harbor Trypanosoma cruzi, the parasite that causes Chagas disease. Because humans are encroaching on kissing bug habitat, there is concern for vector-transmitted Chagas disease in the United States. To date, documented autochthonous cases of Chagas in humans in the United States are rare. Kissing bugs are capable of adapting to new habitats such as human domiciles; however, they do not colonize homes in the United States as in Central and South America. We review the biology, behavior, and medical importance of kissing bugs and the risk they pose for transmission of Chagas disease in the United States. Where possible, descriptions of US species are compared to the epidemiologically important Latin American species.
- Klotz, S. A., Schmidt, J. O., Dorn, P. L., Ivanyi, C., Sullivan, K. R., & Stevens, L. (2014). Free-roaming Kissing Bugs, Vectors of Chagas Disease, Feed Often on Humans in the Southwest. AMERICAN JOURNAL OF MEDICINE, 127(5), 421-426.
- Klotz, S. A., Schmidt, J. O., Dorn, P. L., Ivanyi, C., Sullivan, K. R., & Stevens, L. (2014). Free-roaming kissing bugs, vectors of Chagas disease, feed often on humans in the Southwest. The American journal of medicine, 127(5), 421-6.More infoKissing bugs, vectors of Trypanosoma cruzi, the parasite that causes Chagas disease, are common in the desert Southwest. After a dispersal flight in summer, adult kissing bugs occasionally gain access to houses where they remain feeding on humans and pets. How often wild, free-roaming kissing bugs feed on humans outside their homes has not been studied. This is important because contact of kissing bugs with humans is one means of gauging the risk for acquisition of Chagas disease.
- Lipke, P. N., Ramsook, C., Garcia-Sherman, M. C., Jackson, D. N., Chan, C. X., Bois, M., & Klotz, S. A. (2014). Between Amyloids and Aggregation Lies a Connection with Strength and Adhesion. New journal of science, 2014, 815102.More infoWe tell of a journey that led to discovery of amyloids formed by yeast cell adhesins and their importance in biofilms and host immunity. We begin with the identification of the adhesin functional amyloid-forming sequences that mediate fiber formation . Atomic force microscopy and confocal microscopy show 2-dimensional amyloid "nanodomains" on the surface of cells that are activated for adhesion. These nanodomains are arrays of adhesin molecules that bind multivalent ligands with high avidity. Nanodomains form when adhesin molecules are stretched in the AFM or under laminar flow. Treatment with antiamyloid perturbants or mutation of the amyloid sequence prevents adhesion nanodomain formation and activation. We are now discovering biological consequences. Adhesin nanodomains promote formation and maintenance of biofilms, which are microbial communities. Also, in abscesses within candidiasis patients, we find adhesin amyloids on the surface of the fungi. In both human infection and a infection model, the presence of fungal surface amyloids elicits anti-inflammatory responses. Thus, this is a story of how fungal adhesins respond to extension forces through formation of cell surface amyloid nanodomains, with key consequences for biofilm formation and host responses.
- Satyanarayan, A., Klotz, S., Han, L., Sobonya, R., & Zangeneh, T. T. (2014). Coccidioidomycosis of the Genitourinary Tract: A Case Report and Discussion. UROLOGY, 84(6), E30-E31.
- Satyanarayan, A., Klotz, S., Han, L., Sobonya, R., & Zangeneh, T. T. (2014). Coccidioidomycosis of the genitourinary tract: a case report and discussion. Urology, 84(6), e30-1.More infoCoccidioides species (Coccidioides immitis and Coccidioides posadasii) are dimorphic fungi endemic to the Southwestern United States. Initial infection ranges from asymptomatic to mild upper respiratory tract symptoms and may disseminate to other organs including the genitourinary tract. Genitourinary complaints may be the initial presenting signs and symptoms among a minority of patients. We report a case of genitourinary coccidioidomycosis and discussion of genitourinary disease with coccidioidomycosis.
- Sobonya, R. E., Yanes, J., & Klotz, S. A. (2014). Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease. Human pathology, 45(1), 153-9.More infoCavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due to the poor sensitivity of serological tests and rarity of culture from sputum. A pathologic and clinical analysis was performed of 21 consecutive patients with surgically resected cavities that proved to be coccidioidomycosis. Ten patients (48%) had serological evidence of Coccidioides infection, and 1 patient cultured Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was made in the remaining 10 patients (48%) upon microscopic examination of tissue. The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated in 4 cases (19%). The cavity wall showed chronic inflammation and occasional giant cells but no granulomas and no microorganisms. The cavity contents included a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%) cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic bronchiolitis in all cases; satellite granulomas with diagnostic spherules were variably present. The histopathology of cavitary coccidioidomycosis is strikingly variable depending on what area is sampled by biopsy, and microorganisms may be rare. This may explain the high rate of failure of diagnosis by fine needle aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be aware of these findings, as this disease is now diagnosed worldwide.
- de la Rúa, N. M., Bustamante, D. M., Menes, M., Stevens, L., Monroy, C., Kilpatrick, C. W., Rizzo, D., Klotz, S. A., Schmidt, J., Axen, H. J., & Dorn, P. L. (2014). Towards a phylogenetic approach to the composition of species complexes in the North and Central American Triatoma, vectors of Chagas disease. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 24, 157-66.More infoPhylogenetic relationships of insect vectors of parasitic diseases are important for understanding the evolution of epidemiologically relevant traits, and may be useful in vector control. The sub-family Triatominae (Hemiptera:Reduviidae) includes ∼140 extant species arranged in five tribes comprised of 15 genera. The genus Triatoma is the most species-rich and contains important vectors of Trypanosoma cruzi, the causative agent of Chagas disease. Triatoma species were grouped into complexes originally by morphology and more recently with the addition of information from molecular phylogenetics (the four-complex hypothesis); however, without a strict adherence to monophyly. To date, the validity of proposed species complexes has not been tested by statistical tests of topology. The goal of this study was to clarify the systematics of 19 Triatoma species from North and Central America. We inferred their evolutionary relatedness using two independent data sets: the complete nuclear internal transcribed spacer-2 ribosomal DNA (ITS-2 rDNA) and head morphometrics. In addition, we used the Shimodaira-Hasegawa statistical test of topology to assess the fit of the data to a set of competing systematic hypotheses (topologies). An unconstrained topology inferred from the ITS-2 data was compared to topologies constrained based on the four-complex hypothesis or one inferred from our morphometry results. The unconstrained topology represents a statistically significant better fit of the molecular data than either the four-complex or the morphometric topology. We propose an update to the composition of species complexes in the North and Central American Triatoma, based on a phylogeny inferred from ITS-2 as a first step towards updating the phylogeny of the complexes based on monophyly and statistical tests of topologies.
- Garcia, M., Lipke, P., & Klotz, S. (2013). Pathogenic microbial amyloids: Their function and the host response. OA microbiology, 1(1).More infoFunctional microbial amyloids are ubiquitous in nature and some contribute to the pathogenesis of infectious diseases. Three pathogenic microbial amyloids are compared and their contribution to the disease process explained. The recent demonstration and visualization of fungal amyloid in human invasive candidiasis is discussed. Moreover, the binding of host serum amyloid P component to functional amyloid in invasive human disease is presented in light of its possible role of masking fungi from the host defenses.
- Klotz, S. A., Schmidt, J. O., & Dorn, P. L. (2013). Trypanosma cruzi Carriage by Triatoma rubida and Triatoma protracta in a Zoological Park near Tucson, Arizona. JOURNAL OF THE KANSAS ENTOMOLOGICAL SOCIETY, 86(4), 373-374.
- Rees, H. C., Ianas, V., McCracken, P., Smith, S., Georgescu, A., Zangeneh, T., Mohler, J., & Klotz, S. A. (2013). Measuring frailty in HIV-infected individuals. Identification of frail patients is the first step to amelioration and reversal of frailty. Journal of visualized experiments : JoVE.More infoA simple, validated protocol consisting of a battery of tests is available to identify elderly patients with frailty syndrome. This syndrome of decreased reserve and resistance to stressors increases in incidence with increasing age. In the elderly, frailty may pursue a step-wise loss of function from non-frail to pre-frail to frail. We studied frailty in HIV-infected patients and found that ~20% are frail using the Fried phenotype using stringent criteria developed for the elderly. In HIV infection the syndrome occurs at a younger age. HIV patients were checked for 1) unintentional weight loss; 2) slowness as determined by walking speed; 3) weakness as measured by a grip dynamometer; 4) exhaustion by responses to a depression scale; and 5) low physical activity was determined by assessing kilocalories expended in a week's time. Pre-frailty was present with any two of five criteria and frailty was present if any three of the five criteria were abnormal. The tests take approximately 10-15 min to complete and they can be performed by medical assistants during routine clinic visits. Test results are scored by referring to standard tables. Understanding which of the five components contribute to frailty in an individual patient can allow the clinician to address relevant underlying problems, many of which are not evident in routine HIV clinic visits.
- Terriquez, J. A., Klotz, S. A., Meister, E. A., Klotz, J. H., & Schmidt, J. O. (2013). Repellency of DEET, picaridin, and three essential oils to Triatoma rubida (Hemiptera: Reduviidae: Triatominae). Journal of medical entomology, 50(3), 664-7.More infoThe kissing bug, Triatoma rubida (Uhler) is a common hematophagous bug in Tucson, AZ, and is responsible for causing severe allergic reactions in some bitten individuals. DEET, picaridin, tea tree oil, peppermint oil, and citronella oil were tested for repellency to T. rubida and its ability to probe and feed on a small restrained rat. No long range repellency was observed with any of the test materials. The lowest repellent concentrations observed were: 10% DEET, 7% picaridin; 30% tea tree oil, 3.3% peppermint oil, and 0.165% citronella oil. Only citronella oil was able to stop all probing and feeding by T. rubida. Citronella oil appears to be a promising potential repellent to prevent sleeping people from being bitten by kissing bugs.
- Gilchrist, K. B., Garcia, M. C., Sobonya, R., Lipke, P. N., & Klotz, S. A. (2012). New Features of Invasive Candidiasis in Humans: Amyloid Formation by Fungi and Deposition of Serum Amyloid P Component by the Host. JOURNAL OF INFECTIOUS DISEASES, 206(9), 1473-1478.
- Lipke, P. N., Garcia, M. C., Alsteens, D., Ramsook, C. B., Klotz, S. A., & Dufrene, Y. F. (2012). Strengthening relationships: amyloids create adhesion nanodomains in yeasts. TRENDS IN MICROBIOLOGY, 20(2), 59-65.
- Salameh, A., Klotz, S. A., & Zangeneh, T. T. (2012). Disseminated Infection Caused by Eggerthella lenta in a Previously Healthy Young Man: A Case Report. Case reports in infectious diseases, 2012, 517637.More infoAnaerobic bacteria are the predominant normal flora of the mucous membranes which may cause life-threatening disseminated infections and are often difficult to culture from infected sites. Eggerthella (previously known as Eubacteria species) is an anaerobic, nonsporulating, nonmotile, Gram-positive rod that is found in the human colon and feces and has been isolated from various other clinical specimens. We report a case of complicated disseminated anaerobic bacterial infection with Eggerthella lenta in a healthy immunocompetent man causing multiple brain abscesses, liver abscesses, necrotizing pneumonia, and osteomyelitis of the left radial bone. He was successfully treated with empiric penicillin G and metronidazole.
- Stevens, L., Dorn, P. L., Hobson, J., de, l., Lucero, D. E., Klotz, J. H., Schmidt, J. O., & Klotz, S. A. (2012). Vector Blood Meals and Chagas Disease Transmission Potential, United States. EMERGING INFECTIOUS DISEASES, 18(4), 646-649.
- Klotz, S. A., Ianas, V., & Elliott, S. P. (2011). Cat-scratch Disease. AMERICAN FAMILY PHYSICIAN, 83(2), 152-155.
- Mosbacher, M. E., Klotz, S., Klotz, J., & Pinnas, J. L. (2011). Bartonella henselae and the Potential for Arthropod Vector-Borne Transmission. VECTOR-BORNE AND ZOONOTIC DISEASES, 11(5), 471-477.
- Smith, G., Hoover, S., Sobonya, R., & Klotz, S. A. (2011). Abdominal and Pelvic Coccidioidomycosis. AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 341(4), 308-311.
- Stevens, L., Dorn, P. L., Schmidt, J. O., Klotz, J. H., Lucero, D., & Klotz, S. A. (2011). Kissing Bugs. The Vectors of Chagas. ADVANCES IN PARASITOLOGY, VOL 75: CHAGAS DISEASE, PT A, 75, 169-192.
- Klotz, J. H., Dorn, P. L., Logan, J. L., Stevens, L., Pinnas, J. L., Schmidt, J. O., & Klotz, S. A. (2010). "Kissing Bugs": Potential Disease Vectors and Cause of Anaphylaxis. CLINICAL INFECTIOUS DISEASES, 50(12), 1629-1634.
- Mosbacher, M., Elliott, S. P., Shehab, Z., Pinnas, J. L., Klotz, J. H., & Klotz, S. A. (2010). Cat Scratch Disease and Arthropod Vectors: More to it than a Scratch?. JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE, 23(5), 685-686.
- Thorn, J. L., Gilchrist, K. B., Sobonya, R. E., Gaur, N. K., Lipke, P. N., & Klotz, S. A. (2010). Postmortem candidaemia: marker of disseminated disease. JOURNAL OF CLINICAL PATHOLOGY, 63(4), 337-340.
- Alsteens, D., Dupres, V., Klotz, S. A., Gaur, N. K., Lipke, P. N., & Dufrene, Y. F. (2009). Unfolding Individual Als5p Adhesion Proteins on Live Cells. ACS NANO, 3(7), 1677-1682.
- Klotz, J. H., Klotz, S. A., & Pinnas, J. L. (2009). ANIMAL BITES AND STINGS WITH ANAPHYLACTIC POTENTIAL. JOURNAL OF EMERGENCY MEDICINE, 36(2), 148-156.
- Klotz, J. H., Pinnas, J. L., Greenberg, L., Quimayousie, D., Schmidt, J. O., & Klotz, S. A. (2009). What's Eating You? Native and Imported Fire Ants. CUTIS, 83(1), 17-20.
- Klotz, S. A., Dorn, P. L., Klotz, J. H., Pinnas, J. L., Weirauch, C., Kurtz, J. R., & Schmidt, J. (2009). Feeding behavior of triatomines from the southwestern United States: An update on potential risk for transmission of Chagas disease. ACTA TROPICA, 111(2), 114-118.
- Kurtz, J. R., Klotz, S. A., Schmidt, J., & Dorn, P. L. (2008). PREVALENCE OF TRYPANOSOMA CRUZI IN TRIATOMINE VECTORS IN THE SOUTHWESTERN UNITED STATES. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 79(6), 18-19.
- Martin, C. P., Fain, M. J., & Klotz, S. A. (2008). The Older HIV-Positive Adult: A Critical Review of the Medical Literature. AMERICAN JOURNAL OF MEDICINE, 121(12), 1032-1037.
- Chasin, B. S., Elliott, S. P., & Klotz, S. A. (2007). Medical errors arising from outsourcing laboratory and radiology services. AMERICAN JOURNAL OF MEDICINE, 120(9).
- Klotz, S. A., Chasin, B. S., Powell, B., Gaur, N. K., & Lipke, P. N. (2007). Polymicrobial bloodstream infections involving Candida species: analysis of patients and review of the literature. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 59(4), 401-406.
- Klotz, S. A., Gaur, N. K., De, A. R., Sheppard, D., Khardori, N., Edwards Jr., J. E., Lipke, P. N., & El-Azizi, M. (2007). Candida albicans Als proteins mediate aggregation with bacteria and yeasts. MEDICAL MYCOLOGY, 45(4), 363-370.
- Klotz, S. A., Nguyen, H. C., Van, P. T., Nguyen, L. T., Ngo, D., & Vu, S. N. (2007). Clinical features of HIV/AIDS patients presenting to an inner city clinic in Ho Chi Minh city, Vietnam. INTERNATIONAL JOURNAL OF STD & AIDS, 18(7), 482-485.
- Eckel, F. A., Rugg, S., & Klotz, S. (2006). Successes and future of the joint weather research and forecasting model distributed center project. PROCEEDINGS OF THE HPCMP USERS GROUP CONFERENCE 2006, 283-287.
- Rauceo, J. M., De, A. R., Otoo, H., Kahn, P. C., Klotz, S. A., Gaur, N. K., & Lipke, P. N. (2006). Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. EUKARYOTIC CELL, 5(10), 1664-1673.
- Klotz, S. A., Dorn, P. L., Stevens, L., Beatty, N., Schmidt, J. O., & Smith, S. (2017, October). Parasites, food, and manners: What can the ecology of Kissing bugs in the United States tell us about Chagas transmission risk?. SOVE Conference. Palma de Mallorca, Spain: SOVE.
- Klotz, S. A., Georgescu, A., Smith, S., Guido, A., Fisher, J., & Florita, C. (2017, October). PrEP uptake and emergent HIV infections in southern Arizona. Infectious Disease Society Annual Meeting. San Diego, CA: Infectious Disease Society.
Other Teaching Materials
- Klotz, S. A. (2015. Candidiasis (oral and esophageal. Essential Evidence Plus.More infophysician online resource
- Klotz, S. A. (2015. The Acute Retroviral Syndrome in HIV Infection. CME interactive program for Virtual Lecture Hall.. Virtual Lecture Hall.
- Klotz, S. A. (2015. Treating Hepatitis C in Patients with HIV Disease. Virtual Lecture Hall.More infophysician CME course