Jose G. Montoya

All Publications

• Donor-derived infections in solid organ transplant patients: toward a holistic approach. Current opinion in infectious diseases Benamu, E., Wolfe, C. R., Montoya, J. G. 2017

  Abstract

  Solid organ demand far exceeds organ supply. Strategies to increase the donor pool include the liberalization of selection criteria without increasing the risk of unexpected donor-derived infection (DDI), a rare complication of transplantation carrying high morbidity and mortality. We review the challenging aspects in the prevention of DDI, focusing on the complexities of data sharing and efficient communication and the role infectious diseases specialists play in the process.Advances in donor screening, transmission recognition and reporting allow for a better estimation of the risk of DDI. However, there is great variability in the frequency and methods with which organ procurement organizations report transmission events.Moreover, the Scientific Registry of Transplant Recipients provides limited donor and recipient outcome infectious diseases related data. Infectious disease contribution to the allocation process has been found to improve organ donation efficiency and communication between involved parties. Although communication gaps are strongly associated with infection transmission (relative risk 2.36%, confidence interval 1.48-3.78), effective communication minimizes or prevents infection in transplant recipients (X(1) 13.13, P = 0.0003).Prospective research is still required to define optimal screening protocols and further prevent transmission of infection. A holistic approach is likely to result in enhanced transplantation safety. Toward this goal, development of standards of investigation; improvement in reporting and data sharing; and strategies ensuring coordinated and rapid communication among parties involved in the allocation process need to be pursued.

  View details for DOI 10.1097/QCO.0000000000000377

  View details for PubMedID 28538045

• Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome MICROBIOME Nagy-Szakal, D., Williams, B. L., Mishra, N., Che, X., Lee, B., Bateman, L., Klimas, N. G., Komaroff, A. L., Levine, S., Montoya, J. G., Peterson, D. L., Ramanan, D., Jain, K., Eddy, M. L., Hornig, M., Lipkin, W. I. 2017; 5

  Abstract

  Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling.Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways.Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.

  View details for DOI 10.1186/s40168-017-0261-y

  View details for Web of Science ID 000400271000001

  View details for PubMedID 28441964

• Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proceedings of the National Academy of Sciences of the United States of America Montoya, J. G., Holmes, T. H., Anderson, J. N., Maecker, H. T., Rosenberg-Hasson, Y., Valencia, I. J., Chu, L., Younger, J. W., Tato, C. M., Davis, M. M. 2017; 114 (34): E7150–E7158

  Abstract

  Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine's preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

  View details for DOI 10.1073/pnas.1710519114

  View details for PubMedID 28760971

  View details for PubMedCentralID PMC5576836

• Cytokine profiles in patients with toxoplasmic lymphadenitis in the setting of pregnancy. Cytokine Pomares, C., Holmes, T. H., Estran, R., Press, C. J., Ramirez, R., Talucod, J., Maecker, H., Rosenberg-Hasson, Y., Montoya, J. G. 2016; 90: 14-20

  Abstract

  Majority of Toxoplasma gondii infections are benign and asymptomatic; however, some patients experience toxoplasmic lymphadenitis (TL). Factors associated as to whether infection will be symptomatic or not are unknown.Dye test titers of patients with acute toxoplasmosis (pregnant and not pregnant) with TL (TL+) were compared with those in patients with asymptomatic acute infection (TL-). Additionally, mean levels of 62 serum cytokines were compared between TL+ and TL- pregnant women and between TL+ pregnant and non-pregnant women.During acute infection, mean dye test titer was higher in TL+ than in TL- patients (p=0.021). In addition, out of 62 cytokines, CXCL9andCXCL10 levels were higher (p<0.05) and resistin mean levels were lower (p<0.05) in pregnant women with TL+ compared to TL-. Among patients with TL+, levels of VCAM1andCCL2 were lower (p<0.05) in pregnant women than in non-pregnant women.Here we report differences in dye test titers in patients with acute infection. Cytokine responses vary according to the presence of TL+ and to the pregnancy status. Factors underlying these differences are presently unknown and require further studies to define individual and combined roles of cytokines in TL+.

  View details for DOI 10.1016/j.cyto.2016.09.021

  View details for PubMedID 27744174

• Laboratory Diagnosis of Congenital Toxoplasmosis. Journal of clinical microbiology Pomares, C., Montoya, J. G. 2016; 54 (10): 2448-2454

  Abstract

  Recent studies have demonstrated that screening and treatment for toxoplasmosis during gestation result in a decrease of vertical transmission and clinical sequelae. Early treatment was associated with improved outcomes. Thus, laboratory methods should aim for early identification of infants with congenital toxoplasmosis (CT). Diagnostic approaches should include, at least, detection of Toxoplasma IgG, IgM, and IgA and a comprehensive review of maternal history, including the gestational age at which the mother was infected and treatment. Here, we review laboratory methods for the diagnosis of CT, with emphasis on serological tools. A diagnostic algorithm that takes into account maternal history is presented.

  View details for DOI 10.1128/JCM.00487-16

  View details for PubMedID 27147724

• A Case of Meningococcal Pyomyositis in an Otherwise Healthy Adult. Open forum infectious diseases Barakat, M. T., Gajurel, K., Fischer, K., Stevens, K., Ozdalga, E., Montoya, J. G. 2016; 3 (3): ofw087-?

  Abstract

  The clinical spectrum of Neisseria meningitidis can range from nasopharyngeal colonization to life-threatening invasive diseases such as meningitis. However, its etiologic role in invasive pyomyositis (PM) has never been reported before in the English language. In this study, we report the first case of PM in the English language and the second case in the literature caused by N meningitidis.

  View details for PubMedID 27703989

  View details for PubMedCentralID PMC5047391

• Donor-Derived Coccidioides immitis Endocarditis and Disseminated Infection in the Setting of Solid Organ Transplantation. Open forum infectious diseases Nelson, J. K., Giraldeau, G., Montoya, J. G., Deresinski, S., Ho, D. Y., Pham, M. 2016; 3 (3): ofw086-?

  Abstract

  Background.  Endocarditis is a rare manifestation of infection with Coccidioides. This is the first reported case of donor-derived Coccidioides endocarditis obtained from a heart transplant. Methods.  We present a unique case of donor-derived Coccidioides immitis endocarditis and disseminated infection in a heart transplant patient. We also conducted a review of the literature to identify other cases of donor-derived coccidioidomycosis in solid organ transplant recipients and reviewed their clinical characteristics. Results.  Fifteen prior cases of donor-derived coccidioidomycosis were identified. A majority of these cases were diagnosed by positive culture (83%). Mortality was high at 58%. Conclusions.  Clinicians should maintain a high index of suspicion for disseminated coccidioidomycosis in patients who received transplants with organs from donors with a history of residing in endemic regions.

  View details for DOI 10.1093/ofid/ofw086

  View details for PubMedID 27413765

  View details for PubMedCentralID PMC4940450

• Risk Factors for Cryptococcal Meningitis: A Single United States Center Experience. Mycopathologia Henao-Martínez, A. F., Gross, L., McNair, B., McCollister, B., DeSanto, K., Montoya, J. G., Shapiro, L., Beckham, J. D. 2016: -?

  Abstract

  Cryptococcal meningitis carries a high mortality. Further understanding of immune suppression factors associated with neuroinvasive infection will improve risk stratification and enhance early diagnosis and treatment with antifungal therapy. The aim of the study was to corroborate established or find novel clinical predictors for cryptococcal meningitis. We performed a matched case-control study of Cryptococcus infection in immunocompromised patients with or without cryptococcal meningitis. Data of all patients with a diagnosis of cryptococcal disease were collected at University of Colorado Hospital between 2000 and 2015 (n = 51). Thirty patients were diagnosed with cryptococcal meningitis. We built a logistic regression model for risk factors associated with cryptococcal meningitis. The single-predictor univariate model found that a positive blood culture, positive serum cryptococcal antigen, current malignancy, and headaches were significantly associated with cryptococcal meningitis (p = 0.02). In the adjusted multivariate model, central nervous system disease was significantly associated with a diagnosis of HIV infection (OR 24.45, 95 % CI 1.62-350.37; p = 0.022) and a positive serum cryptococcal antigen test (OR 42.92, 95 % CI 3.26-555.55; p = 0.0055). In patients with HIV infection or a positive serum cryptococcal antigen, the pretest probability of neuroinvasive Cryptococcus infection is increased and an aggressive diagnostic evaluation should be conducted to exclude infection and consider empiric therapy.

  View details for PubMedID 27502502

• Infections associated with the use of eculizumab: recommendations for prevention and prophylaxis. Current opinion in infectious diseases Benamu, E., Montoya, J. G. 2016; 29 (4): 319-329

  Abstract

  Eculizumab inhibits complement effector functions and has significantly impacted the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. However, the risks of potentially life-threatening infections, notably with Neisseria spp. in addition to its cost, are major challenges in clinical practice. In this review, we characterize and summarize the infectious complications reported with the use of eculizumab in the context of its typical and expanding indications.Use of eculizumab is rapidly extending to the fields of transplantation and neurology. Eculizumab has been primarily associated with an increased risk of meningococcal infections. Immunization against its commonest serotypes (ABCWY) is now possible with the advent of the meningococcal B vaccine. A combined ABCWY vaccine is underway. Preventive strategies against breakthrough Neisseria infections should also include chemoprophylaxis. Less is known about the association of eculizumab with other infections as recently reported. Surrogate markers of complement blockade, notably CH50, and eculizumab efficacy may help in the risk assessment of infection.Eculizumab has opened new horizons in the treatment of complement-mediated disorders. Prophylactic and immunization strategies against the risk of Nesseria spp. infections are sound and feasible. The use of eculizumab is expanding beyond complement-mediated diseases to transplantation and neurological disorders. Further research is needed to better define and stratify the risk of infection and prevention strategies in patients with the latter indications.

  View details for DOI 10.1097/QCO.0000000000000279

  View details for PubMedID 27257797

• Multiplexed Anti-Toxoplasma IgG, IgM, and IgA Assay on Plasmonic Gold Chips: towards Making Mass Screening Possible with Dye Test Precision JOURNAL OF CLINICAL MICROBIOLOGY Li, X., Pomares, C., Gonfrier, G., Koh, B., Zhu, S., Gong, M., Montoya, J. G., Dai, H. 2016; 54 (7): 1726-1733

  Abstract

  Toxoplasmosis is an infection caused by the protozoan parasite Toxoplasma gondii that can lead to severe sequelae in the fetus during pregnancy. Definitive serologic diagnosis of the infection during gestation is made mostly by detecting T. gondii-specific antibodies, including IgG and IgM, individually in a single serum sample by using commercially available kits. The IgA test is used by some laboratories as an additional marker of acute infection. Most of the commercial tests have failed to reach 100% correlation with the reference method, the Sabin-Feldman dye test for the detection of Toxoplasma IgG antibodies. For Toxoplasma IgM and IgA antibodies, there is no reference method and their evaluation is done by comparing the results of one assay to those of another. There is a need for multiplexed assay platforms, as the serological diagnosis of T. gondii infection does not rely on the detection of a single Ig subtype. Here we describe the development of a plasmonic gold chip with vast fluorescence enhancement in the near-infrared region for simultaneous detection of IgG, IgM, and IgA antibodies against T. gondii in an ∼1-μl serum or whole-blood sample. When 168 samples were tested on this platform, IgG antibody detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. IgM antibody detection achieved 97.6% sensitivity and 96.9% specificity with a 90.9% PPV and a 99.2% NPV. Thus, the nanoscience-based plasmonic gold platform enables a high-performance, low-cost, multiplexed assay requiring ultrasmall blood volumes, paving the way for the implementation of universal screening for toxoplasmosis infection during gestation.

  View details for DOI 10.1128/JCM.00913-16

  View details for Web of Science ID 000378641600011

  View details for PubMedID 27008879

• Prevention and Treatment of Cancer-Related Infections, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network Baden, L. R., Swaminathan, S., Angarone, M., Blouin, G., Camins, B. C., Casper, C., Cooper, B., Dubberke, E. R., Engemann, A. M., Freifeld, A. G., Greene, J. N., Ito, J. I., Kaul, D. R., Lustberg, M. E., Montoya, J. G., Rolston, K., Satyanarayana, G., Segal, B., Seo, S. K., Shoham, S., Taplitz, R., Topal, J., Wilson, J. W., Hoffmann, K. G., Smith, C. 2016; 14 (7): 882-913

  Abstract

  Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.

  View details for PubMedID 27407129

• Prevention and Treatment of Cancer-Related Infections, Version 2.2016 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Baden, L. R., Swaminathan, S., Angarone, M., Blouin, G., Camins, B. C., Casper, C., Cooper, B., Dubberke, E. R., Engemann, A. M., Freifeld, A. G., Greene, J. N., Ito, J. I., Kaul, D. R., Lustberg, M. E., Montoya, J. G., Rolston, K., Satyanarayana, G., Segal, B., Seo, S. K., Shoham, S., Taplitz, R., Topal, J., Wilson, J. W., Hoffmann, K. G., Smith, C. 2016; 14 (7): 882-913

  View details for Web of Science ID 000380175200010

• Failure of primary atovaquone prophylaxis for prevention of toxoplasmosis in hematopoietic cell transplant recipients TRANSPLANT INFECTIOUS DISEASE Gajurel, K., Gomez, C. A., Dhakal, R., Vogel, H., Montoya, J. G. 2016; 18 (3): 446-452

  View details for DOI 10.1111/tid.12532

  View details for Web of Science ID 000378721400016

• NCCN Guidelines (R) Insights Survivorship, Version 1.2016 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Broderick, G., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L. W., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Rodriguez, M. A., Ruddy, K. J., Sanft, T., Silverman, P., Smith, S., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2016; 14 (6): 715-724

  View details for Web of Science ID 000377690100004

• NCCN Guidelines Insights: Survivorship, Version 1.2016. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Broderick, G., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L. W., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Rodriguez, M. A., Ruddy, K. J., Sanft, T., Silverman, P., Smith, S., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2016; 14 (6): 715-724

  Abstract

  The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment. They are intended to aid health care professionals who work with survivors of adult-onset cancer in the posttreatment period, including those in general oncology, specialty cancer survivor clinics, and primary care practices. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors. This article summarizes the NCCN Survivorship panel's discussions for the 2016 update of the guidelines regarding the management of anxiety, depression, posttraumatic stress disorder-related symptoms, and emotional distress in survivors.

  View details for PubMedID 27283164

• The Missing Tooth: A Curious Case of Postobstructive Pneumonia. Open forum infectious diseases Holmes, I., Gajurel, K., Montoya, J. 2016; 3 (2): ofw088-?

  Abstract

  Foreign body aspirations that are not recognized at the time of aspiration can lead to insidious symptoms that can present a diagnostic challenge. We report the case of a 70-year-old man presenting with postobstructive pneumonia 2 months after aspirating his own tooth during a meal. He had been mistakenly diagnosed with asthma and treated with bronchodilators before a computed tomography scan of the thorax revealed the impacted tooth in his left bronchus. We review the clinical features and microbiology of postobstructive pneumonia and discuss the rationale of its treatment.

  View details for DOI 10.1093/ofid/ofw088

  View details for PubMedID 27419162

• Clustering of Toxoplasma gondii Infections Within Families of Congenitally Infected Infants. Clinical infectious diseases Contopoulos-Ioannidis, D., Wheeler, K. M., Ramirez, R., Press, C., Mui, E., Zhou, Y., Van Tubbergen, C., Prasad, S., Maldonado, Y., Withers, S., Boyer, K. M., Noble, A. G., Rabiah, P., Swisher, C. N., Heydemann, P., Wroblewski, K., Karrison, T., Grigg, M. E., Montoya, J. G., McLeod, R. 2015; 61 (12): 1815-1824

  Abstract

  Family clusters and epidemics of toxoplasmosis in North, Central, and South America led us to determine whether fathers of congenitally infected infants in the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) have a high incidence of Toxoplasma gondii infection.We analyzed serum samples collected from NCCCTS families between 1981 and 2013. Paternal serum samples were tested for T. gondii antibodies with immunoglobulin (Ig) G dye test and IgM enzyme-linked immunosorbent assay. Additional testing of paternal serum samples was performed with differential-agglutination and IgG avidity tests when T. gondii IgG and IgM results were positive and serum samples were collected by the 1-year visit of the congenitally infected child. Prevalence of paternal seropositivity and incidence of recent infection were calculated. We analyzed whether certain demographics, maternal parasite serotype, risk factors, or maternal/infant clinical manifestations were associated with paternal T. gondii infection status.Serologic testing revealed a high prevalence (29 of 81; 36%) of T. gondii infection in fathers, relative to the average seropositivity rate of 9.8% for boys and men aged 12-49 years in the United States between 1994 and 2004 (P < .001). Moreover, there was a higher-than-expected incidence of recent infections among fathers with serum samples collected by the 1-year visit of their child (6 of 45; 13%; P < .001). No demographic patterns or clinical manifestations in mothers or infants were associated with paternal infections, except for sandbox exposure.The high prevalence of chronic and incidence of recent T. gondii infections in fathers of congenitally infected children indicates that T. gondii infections cluster within families in North America. When a recently infected person is identified, family clustering and community risk factors should be investigated for appropriate clinical management.

  View details for DOI 10.1093/cid/civ721

  View details for PubMedID 26405150

  View details for PubMedCentralID PMC4657536

• Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease JOURNAL OF CLINICAL MICROBIOLOGY Lahey, L. J., Panas, M. W., Mao, R., Delanoy, M., Flanagan, J. J., Binder, S. R., Rebman, A. W., Montoya, J. G., Soloski, M. J., Steere, A. C., Dattwyler, R. J., Arnaboldi, P. M., Aucott, J. N., Robinson, W. H. 2015; 53 (12): 3834-3841

  View details for DOI 10.1128/JCM.02111-15

  View details for Web of Science ID 000367532800020

• Significance of a Positive Toxoplasma Immunoglobulin M Test Result in the United States JOURNAL OF CLINICAL MICROBIOLOGY Dhakal, R., Gajurel, K., Pomares, C., Talucod, J., Press, C. J., Montoya, J. G. 2015; 53 (11): 3601-3605

  View details for DOI 10.1128/JCM.01663-15

  View details for Web of Science ID 000365626200034

  View details for PubMedID 26354818

• Toxoplasma prophylaxis in haematopoietic cell transplant recipients: a review of the literature and recommendations CURRENT OPINION IN INFECTIOUS DISEASES Gajurel, K., Dhakal, R., Montoya, J. G. 2015; 28 (4): 283-292

  Abstract

  Toxoplasmosis in haematopoietic cell transplant (HCT) recipients is associated with high morbidity and mortality rates. Prophylaxis following HCT is recommended for high-risk pre-HCT toxoplasma-seropositive (pre-HCTSP) recipients. However, there is no agreement or consistency among programmes on whether to adopt prophylaxis or not, or if used, on the chosen antitoxoplasma prophylactic regimen. This review discusses the role of prophylaxis, and preemptive treatment, for toxoplasmosis in the setting of HCT.Approximately two-thirds of toxoplasmosis cases following HCT are reported in allogeneic pre-HCTSP (allo pre-HCTSP) patients. This finding confirms a major role of reactivation of latent infection in the pathogenesis of toxoplasmosis in this patient population. Toxoplasma disease-related mortality in allo pre-HCTSP patients was reported at 62%, but it can be significantly decreased with early detection and treatment of toxoplasma infection. There are no randomized trials comparing the efficacy of different prophylactic agents to prevent toxoplasmosis after HCT. Several observational studies have demonstrated the efficacy of trimethoprim-sulfamethoxazole (TMP/SMX) in decreasing the incidence of toxoplasmosis following HCT. There is limited information regarding efficacy of other prophylactic agents. Preemptive treatment using routine blood PCR monitoring seems to be beneficial in detecting infection early and preventing disease in several observational studies and has been adopted for allo pre-HCTSP HCT patients when universal prophylaxis is not possible.Universal prophylaxis with TMP/SMX in allo pre-HCTSP patients should be implemented by all transplant programmes. Preemptive treatment with routine blood PCR monitoring is an option if prophylaxis cannot be used.

  View details for DOI 10.1097/QCO.0000000000000169

  View details for Web of Science ID 000358290500001

• Seasonal variation of acute toxoplasmic lymphadenopathy in the United States EPIDEMIOLOGY AND INFECTION Contopoulos-Ioannidis, D., Talucod, J., Maldonado, Y., Montoya, J. G. 2015; 143 (9): 1893-1897

  Abstract

  SUMMARY We describe the seasonal variation of acute toxoplasmosis in the United States. Acute toxoplasmic lymphadenopathy (ATL) can be a surrogate of acute toxoplasmosis in patients in whom the date of onset of lymphadenopathy matches the window of acute infection predicted by serological tests performed at a reference laboratory. We used the electronic database of the Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) (1997-2011) to identify cases of ATL. We tested the uniformity of distribution of ATL cases per month, across the 12 calendar months, using circular statistics uniformity tests. We identified 112 consecutive cases of ATL. The distribution of cases was not uniform across the 12 calendar months. We observed the highest peak of cases in December and a second highest peak in September. Similar months were identified in patients with acute toxoplasmosis in rural areas in France. The results were similar when we performed weighted analyses, weighting for the total number of Toxoplasma gondii IgG tests performed per month in the PAMF-TSL laboratory. This is the largest study to date of the seasonal variation of ATL in the United States. Physicians should advise high-risk individuals to avoid risk factors associated with T. gondii infections especially around those months.

  View details for DOI 10.1017/S0950268814002945

  View details for Web of Science ID 000355760600012

  View details for PubMedID 25410401

• Invasive mold infections in lung and heart-lung transplant recipients: Stanford University experience TRANSPLANT INFECTIOUS DISEASE Vazquez, R., Vazquez-Guillamet, M. C., Suarez, J., Mooney, J., Montoya, J. G., Dhillon, G. S. 2015; 17 (2): 259-266

  Abstract

  Recipients of lung transplantation (LT) and heart-lung transplantation (HLT) are at increased risk of infection, including invasive mold infections (IMIs). The clinical presentation, radiographic correlates, and outcomes of Aspergillus and non-Aspergillus IMIs in this population have not been well documented.LT and HLT recipients diagnosed with IMIs between 1990 and 2012 were identified using the Stanford Translational Research Integrated Database Environment and Stanford LT and HLT clinical database. Recipient clinical and radiographic characteristics were obtained via retrospective review of medical records and compared between Aspergillus and non-Aspergillus mold recipients. Risk factors for mortality were identified using multivariate logistic regression analysis.During the study period, 87 (14%) transplant recipients were diagnosed with IMIs. Aspergillus species were isolated in 63 (72%) and non-Aspergillus molds in 24 (28%) recipients. No significant difference was seen in presenting symptoms or radiographic findings between Aspergillus and non-Aspergillus mold recipients. Median time to diagnosis was 363 days in the Aspergillus group and 419 days in the non-Aspergillus group, with dissemination occurring only within the non-Aspergillus group (12.5%). Overall 90-day and 1-year mortality following IMI was 24% and 44%. One-year mortality was increased in the non-Aspergillus group (39.5% vs. 60.5%, P = 0.03).There is significant overlap in risk factors, presentation, and radiographic patterns in IMI in LT or HLT recipients. Non-Aspergillus molds were more likely to present late, with disseminated disease, and portend increased 1-year mortality. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/tid.12362

  View details for Web of Science ID 000352219400011

  View details for PubMedID 25648194

• Right arcuate fasciculus abnormality in chronic fatigue syndrome. Radiology Zeineh, M. M., Kang, J., Atlas, S. W., Raman, M. M., Reiss, A. L., Norris, J. L., Valencia, I., Montoya, J. G. 2015; 274 (2): 517-526

  Abstract

  Purpose To identify whether patients with chronic fatigue syndrome ( CFS chronic fatigue syndrome ) have differences in gross brain structure, microscopic structure, or brain perfusion that may explain their symptoms. Materials and Methods Fifteen patients with CFS chronic fatigue syndrome were identified by means of retrospective review with an institutional review board-approved waiver of consent and waiver of authorization. Fourteen age- and sex-matched control subjects provided informed consent in accordance with the institutional review board and HIPAA. All subjects underwent 3.0-T volumetric T1-weighted magnetic resonance (MR) imaging, with two diffusion-tensor imaging ( DTI diffusion-tensor imaging ) acquisitions and arterial spin labeling ( ASL arterial spin labeling ). Open source software was used to segment supratentorial gray and white matter and cerebrospinal fluid to compare gray and white matter volumes and cortical thickness. DTI diffusion-tensor imaging data were processed with automated fiber quantification, which was used to compare piecewise fractional anisotropy ( FA fractional anisotropy ) along 20 tracks. For the volumetric analysis, a regression was performed to account for differences in age, handedness, and total intracranial volume, and for the DTI diffusion-tensor imaging , FA fractional anisotropy was compared piecewise along tracks by using an unpaired t test. The open source software segmentation was used to compare cerebral blood flow as measured with ASL arterial spin labeling . Results In the CFS chronic fatigue syndrome population, FA fractional anisotropy was increased in the right arcuate fasciculus (P = .0015), and in right-handers, FA fractional anisotropy was also increased in the right inferior longitudinal fasciculus ( ILF inferior longitudinal fasciculus ) (P = .0008). In patients with CFS chronic fatigue syndrome , right anterior arcuate FA fractional anisotropy increased with disease severity (r = 0.649, P = .026). Bilateral white matter volumes were reduced in CFS chronic fatigue syndrome (mean ± standard deviation, 467 581 mm(3) ± 47 610 for patients vs 504 864 mm(3) ± 68 126 for control subjects, P = .0026), and cortical thickness increased in both right arcuate end points, the middle temporal (T = 4.25) and precentral (T = 6.47) gyri, and one right ILF inferior longitudinal fasciculus end point, the occipital lobe (T = 5.36). ASL arterial spin labeling showed no significant differences. Conclusion Bilateral white matter atrophy is present in CFS chronic fatigue syndrome . No differences in perfusion were noted. Right hemispheric increased FA fractional anisotropy may reflect degeneration of crossing fibers or strengthening of short-range fibers. Right anterior arcuate FA fractional anisotropy may serve as a biomarker for CFS chronic fatigue syndrome . © RSNA, 2014 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.14141079

  View details for PubMedID 25353054

• Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Science advances Hornig, M., Montoya, J. G., Klimas, N. G., Levine, S., Felsenstein, D., Bateman, L., Peterson, D. L., Gottschalk, C. G., Schultz, A. F., Che, X., Eddy, M. L., Komaroff, A. L., Lipkin, W. I. 2015; 1 (1)

  Abstract

  Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

  View details for PubMedID 26079000

• Ocular toxoplasmosis in the United States: recent and remote infections. Clinical infectious diseases Jones, J. L., Bonetti, V., Holland, G. N., Press, C., Sanislo, S. R., Khurana, R. N., Montoya, J. G. 2015; 60 (2): 271-273

  Abstract

  We tested all samples from patients with ocular toxoplasmosis sent to the Palo Alto Medical Foundation Toxoplasma Reference Laboratory from June 2004 through August 2010 for serologic evidence of recent Toxoplasma gondii infection. Of 205 patients aged 10-96 years, 11.7% had recent infection. Many people develop ocular disease soon after T. gondii infection.

  View details for DOI 10.1093/cid/ciu793

  View details for PubMedID 25301214

• Survivorship: Screening for Cancer and Treatment Effects, Version 2.2014 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Dizon, D., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Raza, M., Rodriguez, M. A., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (11): 1526-1530

  View details for Web of Science ID 000344516200006

• Survivorship: screening for cancer and treatment effects, version 2.2014. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Dizon, D., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Raza, M., Rodriguez, M. A., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (11): 1526-1531

  Abstract

  The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment. This portion of the guidelines describes recommendations regarding screening for the effects of cancer and its treatment. The panel created a sample screening tool, specifically for use in combination with the NCCN Guidelines for Survivorship, to guide providers to topics that require more in-depth assessment. Effective screening and assessment can help providers deliver necessary and comprehensive survivorship care.

  View details for PubMedID 25361799

• Survivorship: Nutrition and Weight Management, Version 2.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Dizon, D., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Raza, M., Rodriguez, M. A., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (10): 1396-1406

  View details for Web of Science ID 000343275600005

• Survivorship: nutrition and weight management, Version 2.2014. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Dizon, D., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Raza, M., Rodriguez, M. A., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (10): 1396-1406

  Abstract

  Healthy lifestyle habits have been associated with improved health outcomes and quality of life and, for some cancers, a reduced risk of recurrence and death. The NCCN Guidelines for Survivorship therefore recommend that cancer survivors be encouraged to achieve and maintain a healthy lifestyle, including attention to weight management, physical activity, and dietary habits. This section of the NCCN Guidelines focuses on recommendations regarding nutrition, weight management, and supplement use in survivors. Weight management recommendations are based on the survivor's body mass index and include discussions of nutritional, weight management, and physical activity principles, with referral to community resources, dietitians, and/or weight management programs as needed.

  View details for PubMedID 25313179

• Immune Profiling of Pregnant Toxoplasma-Infected US and Colombia Patients Reveals Surprising Impacts of Infection on Peripheral Blood Cytokines. journal of infectious diseases Pernas, L., Ramirez, R., Holmes, T. H., Montoya, J. G., Boothroyd, J. C. 2014; 210 (6): 923-931

  Abstract

  In North America (NA) and Europe, the majority of toxoplasmosis cases are benign and generally asymptomatic, while in South America (SA) toxoplasmosis is associated with much more severe symptoms in adults and congenitally infected children. The reasons for these differences remain unknown and, currently, there is little information from patients in either region on how the immune system responds to infection with Toxoplasma gondii. Here, we report the relative abundance of 51 serum cytokines from acute and chronic toxoplasmosis cohorts of pregnant women from the United States (US), where approximately one-half of clinical isolates are Type II, and Colombia, where clinical isolates are generally "atypical" or Type I-like strains. Surprisingly, the results showed notably lower levels of 23 cytokines in acutely infected patients from the US, relative to uninfected US controls. In acutely infected Colombian patients, however, only 8 cytokine levels differed detectably with four being lower and four higher relative to uninfected controls. Strikingly, there were also differences in the cytokine profiles of the chronically infected patients relative to uninfected controls in the US cohort. Hence, Toxoplasma appears to specifically impact levels of circulating cytokines and our results may partly explain region-specific differences in the clinical spectrum of toxoplasmosis.

  View details for DOI 10.1093/infdis/jiu189

  View details for PubMedID 24664173

• Survivorship: Healthy Lifestyles, Version 2.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Dizon, D., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Raza, M., Rodriguez, M. A., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (9): 1222-1237

  Abstract

  Healthy lifestyle habits have been associated with improved health outcomes and quality of life and, for some cancers, a reduced risk of recurrence and death. The NCCN Guidelines for Survivorship therefore recommend that cancer survivors be encouraged to achieve and maintain a healthy lifestyle, with attention to weight management, physical activity, and dietary habits. This section of the NCCN Guidelines focuses on recommendations regarding physical activity in survivors, including assessment for the risk of exercise-induced adverse events, exercise prescriptions, guidance for resistance training, and considerations for specific populations (eg, survivors with lymphedema, ostomies, peripheral neuropathy). In addition, strategies to encourage health behavioral change in survivors are discussed.

  View details for Web of Science ID 000341349900005

  View details for PubMedID 25190692

• Fatal acanthamoeba encephalitis in a patient with a total artificial heart (syncardia) device. Open forum infectious diseases Tan, S. K., Gajurel, K., Tung, C., Albers, G., Deresinski, S., Montoya, J. G., Sheikh, A. Y., Banerjee, D., Ha, R. 2014; 1 (2): ofu057-?

  Abstract

  Acanthamoeba encephalitis is an uncommon but often fatal infection complication. Here we report the first case of Acanthamoeba encephalitis in a patient with a Total Artificial Heart device.

  View details for DOI 10.1093/ofid/ofu057

  View details for PubMedID 25734127

• Survivorship: Immunizations and Prevention of Infections, Version 2.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Den Linger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Dizon, D., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Peppercorn, J., Raza, M., Rodriguez, M. A., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (8): 1098-1111

  Abstract

  Cancer survivors are at an elevated risk for infection because of immune suppression associated with prior cancer treatments, and they are at increased risk of complications from vaccine-preventable diseases. This section of the NCCN Guidelines for Survivorship provides recommendations for the prevention of infections in survivors through education, antimicrobial prophylaxis, and the judicious use of vaccines. These guidelines provide information about travel and gardening precautions and safe pet care/avoidance of zoonosis, and include detailed recommendations regarding vaccinations that should be considered and encouraged in cancer and transplant survivors.

  View details for Web of Science ID 000340218200004

  View details for PubMedID 25099442

• Executive summary: practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clinical infectious diseases Stevens, D. L., Bisno, A. L., Chambers, H. F., Dellinger, E. P., Goldstein, E. J., Gorbach, S. L., Hirschmann, J. V., Kaplan, S. L., Montoya, J. G., Wade, J. C. 2014; 59 (2): 147-159

  Abstract

  A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

  View details for DOI 10.1093/cid/ciu444

  View details for PubMedID 24973422

• Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America CLINICAL INFECTIOUS DISEASES Stevens, D. L., Bisno, A. L., Chambers, H. F., Dellinger, E. P., Goldstein, E. J., Gorbach, S. L., Hirschmann, J. V., Kaplan, S. L., Montoya, J. G., Wade, J. C. 2014; 59 (2): E10-E52

  View details for DOI 10.1093/cid/ciu296

  View details for Web of Science ID 000339665700001

• Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clinical infectious diseases Stevens, D. L., Bisno, A. L., Chambers, H. F., Dellinger, E. P., Goldstein, E. J., Gorbach, S. L., Hirschmann, J. V., Kaplan, S. L., Montoya, J. G., Wade, J. C. 2014; 59 (2): e10-52

  Abstract

  A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

  View details for DOI 10.1093/cid/ciu296

  View details for PubMedID 24947530

• Antifungal prophylaxis following heart transplantation: systematic review MYCOSES Uribe, L. G., Cortes, J. A., Granados, C. E., Montoya, J. G. 2014; 57 (7): 429-436

  View details for DOI 10.1111/myc.12179

  View details for Web of Science ID 000338122100007

• Survivorship: Cognitive Function, Version 1.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N. R., Freedman-Cass, D. A. 2014; 12 (7): 976-986

  Abstract

  Cognitive impairment is a common complaint among cancer survivors and may be a consequence of the tumors themselves or direct effects of cancer-related treatment (eg, chemotherapy, endocrine therapy, radiation). For some survivors, symptoms persist over the long term and, when more severe, can impact quality of life and function. This section of the NCCN Guidelines for Survivorship provides assessment, evaluation, and management recommendations for cognitive dysfunction in survivors. Nonpharmacologic interventions (eg, instruction in coping strategies; management of distress, pain, sleep disturbances, and fatigue; occupational therapy) are recommended, with pharmacologic interventions as a last line of therapy in survivors for whom other interventions have been insufficient.

  View details for Web of Science ID 000338901800005

  View details for PubMedID 24994918

• Antifungal prophylaxis following heart transplantation: systematic review. Mycoses Uribe, L. G., Cortés, J. A., Granados, C. E., Montoya, J. G. 2014; 57 (7): 429-436

  Abstract

  Patients with heart transplantation have a high incidence of infectious complications, especially fungal infections. The aim of the systematic review was to determine the best pharmacological strategy to prevent fungal infections among patients with heart transplant. We searched the PubMed and Embase databases for studies reporting the effectivenesss of pharmacologic strategies to prevent fungal infections in adult patient with a heart transplant. Our search yielded five studies (1176 patients), four of them with historical controls. Two studies used inhaled amphotericin B deoxycholate, three used itraconazole and one used targeted echinocandin. All studies showed significant reduction in the prophylaxis arm. Different products, doses and outcomes were noted. There is a highly probable benefit of prophylaxis use, however, better studies with standardised doses and comparators should be performed.

  View details for DOI 10.1111/myc.12179

  View details for PubMedID 24589065

• Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital toxoplasmosis. Pediatric infectious disease journal Olariu, T. R., Remington, J. S., Montoya, J. G. 2014; 33 (6): 566-570

  Abstract

  Congenital toxoplasmosis (CT) can result in visual impairment, hearing loss, serious neurologic sequelae and death in the infant. We studied the potential of the polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) for diagnosis of congenital toxoplasmosis.For this purpose we studied both congenitally infected (diagnosed clinically and serologically) and non-infected infants born to untreated mothers.The infants ranged in age from 0 to 180 days. CSF PCR was positive in 27 of the 58 (46.5%) congenitally infected infants and was negative in each of the 103 infants without CT. The frequency of positive CSF PCR varied according to whether infants had major clinical signs of the disease; PCR was positive in 70.9%, 53.3% and 50.9% of those with hydrocephalus, cerebral calcifications and/or eye disease, respectively. Three of six infants who were negative for both IgM and IgA antibodies had a positive PCR in their CSF as the confirmatory test for diagnosis of congenital toxoplasmosis. IgM and IgA antibodies and CSF PCR, when combined, yielded a higher sensitivity for diagnosis of congenital toxoplasmosis when compared with the performance of each test alone.Our findings reveal that in infants with clinical and serologic findings suggestive of congenital toxoplasmosis and born to untreated mothers, CSF PCR has the potential to increase the frequency of cases in which the diagnosis is confirmed.

  View details for DOI 10.1097/INF.0000000000000256

  View details for PubMedID 24445828

• Survivorship: fatigue, version 1.2014. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (6): 876-887

  Abstract

  Many cancer survivors report that fatigue is a disruptive symptom even after treatment ends. Persistent cancer-related fatigue affects quality of life, because individuals become too tired to fully participate in the roles and activities that make life meaningful. Identification and management of fatigue remains an unmet need for many cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and management recommendations for fatigue in survivors. Management includes education and counseling, physical activity, psychosocial interventions, and pharmacologic treatments.

  View details for PubMedID 24925198

• Survivorship: Fatigue, Version 1.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (6): 876-886

  View details for Web of Science ID 000337710000005

• Survivorship: Sleep Disorders, Version 1.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Den Linger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (5): 630-642

  Abstract

  Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments.

  View details for Web of Science ID 000335718600005

  View details for PubMedID 24812132

• Survivorship: Pain Version 1.2014 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (4): 488-500

  View details for Web of Science ID 000334014900007

• Survivorship: pain version 1.2014. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Ligibel, J. A., Are, M., Baker, K. S., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Jones, L., King, A., Ku, G. H., Kvale, E., Langbaum, T. S., Leonardi-Warren, K., McCabe, M. S., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., Moslehi, J. J., O'Connor, T., Overholser, L., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (4): 488-500

  Abstract

  Many posttreatment cancer survivors experience chronic pain, often leading to psychological distress; decreased activity, motivation, and personal interactions; and an overall poor quality of life. This section of the NCCN Guidelines for Survivorship provides screening and management recommendations for pain in survivors. A multidisciplinary approach is recommended, with a combination of pharmacologic treatments, psychosocial and behavioral interventions, physical therapy and exercise, and interventional procedures.

  View details for PubMedID 24717568

• Survivorship: Sexual Dysfunction (Male), Version 1.2013 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (3): 356-363

  Abstract

  Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction.

  View details for Web of Science ID 000332777600009

  View details for PubMedID 24616541

• Survivorship: Sexual Dysfunction (Female), Version 1.2013 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (2): 184-192

  Abstract

  Cancer treatment, especially hormonal therapy and therapy directed toward the pelvis, can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. Thus, sexual dysfunction is common in survivors and can cause increased distress and have a significant negative impact on quality of life. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for female sexual problems, including those related to sexual desire, arousal, orgasm, and pain.

  View details for Web of Science ID 000332213600005

  View details for PubMedID 24586080

• Survivorship: introduction and definition. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (1): 34-45

  Abstract

  Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel's definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.

  View details for PubMedID 24453291

• Survivorship: Introduction and Definition JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Denlinger, C. S., Carlson, R. W., Are, M., Baker, K. S., Davis, E., Edge, S. B., Friedman, D. L., Goldman, M., Jones, L., King, A., Kvale, E., Langbaum, T. S., Ligibel, J. A., McCabe, M. S., McVary, K. T., Melisko, M., Montoya, J. G., Mooney, K., Morgan, M. A., O'Connor, T., Paskett, E. D., Raza, M., Syrjala, K. L., Urba, S. G., Wakabayashi, M. T., Zee, P., McMillian, N., Freedman-Cass, D. 2014; 12 (1): 34-45

  View details for Web of Science ID 000330333200005

  View details for PubMedID 24453291

• Acute Toxoplasma gondii Infection among Family Members in the United States EMERGING INFECTIOUS DISEASES Contopoulos-Ioannidis, D. G., Maldonado, Y., Montoya, J. G. 2013; 19 (12): 1981-1984

  Abstract

  We investigated 32 families of persons with acute toxoplasmosis in which > or = 1 other family member was tested for Toxoplasma gondii infection; 18 (56%) families had > or = 1 additional family member with acute infection. Family members of persons with acute toxoplasmosis should be screened for infection, especially pregnant women and immunocompromised persons.

  View details for DOI 10.3201/eid1912.121892

  View details for Web of Science ID 000327826600012

  View details for PubMedID 24274896

  View details for PubMedCentralID PMC3840881

• Immune reconstitution syndrome-like entity in lung transplant recipients with invasive aspergillosis TRANSPLANT IMMUNOLOGY Singh, N., Suarez, J. F., Avery, R., Lass-Florl, C., Geltner, C., Pasqualotto, A. C., Lyon, G. M., Barron, M., Husain, S., Wagener, M. M., Montoya, J. G. 2013; 29 (1-4): 109-113

  Abstract

  Incidence, characteristics, and risk-factors for invasive aspergillosis (IA)-associated immune reconstitution syndrome (IRS) in lung transplant recipients are not known.Patients comprised 68 lung transplant recipients with proven/probable IA followed for 12 months. IRS was defined based on previously proposed criteria.In all, 7.3% (5/68) of the patients developed IRS based on aforementioned criteria, a median of 56 days after initiation of antifungal therapy. This entity was associated with heart-lung transplantation (p=0.006), anti T-cell agent use (p=0.003), discontinuation of calcineurin inhibitor agent (p=0.002), and disseminated IA (p=0.069). In a risk assessment model, IRS developed in 0% (0/55) of the patients with none of the aforementioned factors, 28.6% (2/7) with one, 33.3% (1/3) with two, and in 1/1 patient with 3 factors (X(2) for trend p=0.0001). Three out of 5 patients with IRS died and 2 of 3 deaths in this group were due to chronic rejection.Overall 7% of the lung transplant recipients with IA appear to develop an IRS-like entity. Clinically assessable factors can identify patients at risk for post-transplant IA-associated IRS. Deaths due to chronic rejection were significantly higher in patients with IRS than those without IRS.

  View details for DOI 10.1016/j.trim.2013.09.007

  View details for Web of Science ID 000329145600019

  View details for PubMedID 24076039

• Randomized Clinical Trial to Evaluate the Efficacy and Safety of Valganciclovir in a Subset of Patients With Chronic Fatigue Syndrome JOURNAL OF MEDICAL VIROLOGY Montoya, J. G., Kogelnik, A. M., Bhangoo, M., Lunn, M. R., Flamand, L., Merrihew, L. E., Watt, T., Kubo, J. T., Paik, J., Desai, M. 2013; 85 (12): 2101-2109

  Abstract

  There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted.

  View details for DOI 10.1002/jmv.23713

  View details for Web of Science ID 000325153400007

  View details for PubMedID 23959519

• Persistent human herpesvirus-6 infection in patients with an inherited form of the virus. Journal of medical virology Pantry, S. N., Medveczky, M. M., Arbuckle, J. H., Luka, J., Montoya, J. G., Hu, J., Renne, R., Peterson, D., Pritchett, J. C., Ablashi, D. V., Medveczky, P. G. 2013; 85 (11): 1940-1946

  Abstract

  Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes. Chromosomally integrated HHV-6 (CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic. Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein. In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of CIHHV-6 in this cohort of adult patients from the USA suffering from a wide range of neurological symptoms including long-term fatigue were found significantly greater than the reported 0.8% in the general population. Long-term antiviral therapy inhibited HHV-6 replication as documented by loss of viral mRNA production. Sequence comparison of the mRNA and the inherited viral genome revealed that the transcript is produced by an exogenous virus. In conclusion, the data presented here document that some individuals with CIHHV-6 are infected persistently with exogenous HHV-6 strains that lead to a wide range of neurological symptoms; the proposed name for this condition is inherited herpesvirus 6 syndrome or IHS. J Med. Virol. 85:1940-1946, 2013. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmv.23685

  View details for PubMedID 23893753

• Utility of DNA Sequencing for Direct Identification of Invasive Fungi From Fresh and Formalin-Fixed Specimens AMERICAN JOURNAL OF CLINICAL PATHOLOGY Moncada, P. A., Budvytiene, I., Ho, D. Y., Deresinski, S. C., Montoya, J. G., Banaei, N. 2013; 140 (2): 203-208

  Abstract

  Objectives: To describe and discuss the utility and potential pitfalls of ribosomal RNA locus sequencing for direct identification of invasive fungi from fresh and formalin-fixed, paraffin-embedded specimens. Methods: DNA was extracted from fresh and formalin-fixed, paraffin-embedded tissue and subjected to real-time polymerase chain reaction (PCR) targeting ITS2 and D2 regions of fungal ribosomal RNA locus. Cycle sequencing was performed on PCR products, and the identity of sequences was determined using a public database. Results: Four clinical cases of invasive fungal infection are presented to illustrate the utility of DNA sequencing for determining etiology when microbiological culture is negative, for shortening the time to identification of slow-growing fungi, for guiding antifungal therapy, and for shedding light on the pathogenesis of disseminated fungal infection. Conclusions: Fungal ribosomal RNA locus sequencing from fresh or formalin-fixed, paraffin-embedded specimens is a powerful tool for rapid and accurate diagnosis of patients with culture-negative or uncultured invasive mycosis.

  View details for DOI 10.1309/AJCPNSU2SDZD9WPW

  View details for Web of Science ID 000322149600010

  View details for PubMedID 23897255

• Otopathology in congenital toxoplasmosis. Otology & neurotology Salviz, M., Montoya, J. G., Nadol, J. B., Santos, F. 2013; 34 (6): 1165-1169

  Abstract

  OBJECTIVE: To describe the temporal bone histopathology in children with congenital toxoplasmosis. BACKGROUND: Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii. If fetal infection occurs early in gestation, severe inflammation and necrosis can cause brain lesions, chorioretinitis, and hearing loss. Hearing loss in congenital toxoplasmosis may be preventable with early diagnosis and treatment. MATERIALS AND METHODS: The temporal bones of 9 subjects with congenital toxoplasmosis were removed at autopsy and studied under light microscopy. Cytocochleograms were constructed for hair cells, the stria vascularis, and cochlear neuronal cells. RESULTS: Three (33%) of 9 subjects were found to have parasites in the temporal bone. The organism was identified in the internal auditory canal, the spiral ligament, stria vascularis, and saccular macula. The cystic form of the parasite was not associated with the inflammatory response seen in the active tachyzoite form. CONCLUSION: We infer that the hearing loss of toxoplasmosis is likely the result of a postnatal inflammatory response to the tachyzoite form of T. gondii. Our findings have implications for the early identification and management of Toxoplasmosis.

  View details for DOI 10.1097/MAO.0b013e31828297b6

  View details for PubMedID 23598697

• Risk factors and outcomes in lung transplant recipients with nodular invasive pulmonary aspergillosis JOURNAL OF INFECTION Singh, N., Suarez, J. F., Avery, R., Lass-Floerl, C., Geltner, C., Pasqualotto, A. C., Lyon, G. M., Barron, M., Husain, S., Wagener, M. M., Montoya, J. G. 2013; 67 (1): 72-78

  View details for DOI 10.1016/j.jinf.2013.03.013

  View details for Web of Science ID 000320028900010

• Risk factors and outcomes in lung transplant recipients with nodular invasive pulmonary aspergillosis. journal of infection Singh, N., Suarez, J. F., Avery, R., Lass-Flörl, C., Geltner, C., Pasqualotto, A. C., Marshall Lyon, G., Barron, M., Husain, S., Wagener, M. M., Montoya, J. G. 2013; 67 (1): 72-78

  Abstract

  Whether nodular lesions have specific risk-factors or influence outcomes in lung transplant recipients with invasive aspergillosis, is not fully known.The study population consisted of 64 consecutive lung transplant recipients with proven or probable invasive aspergillosis. Nodules, with or without halo/air crescent-sign were considered nodular presentations. Outcomes assessed were response rate (successful versus unsuccessful outcome) and all-cause mortality at 12 weeks.Overall, 34 patients had nodular and 30 had non-nodular lesions. Presence of nodular lesions was less likely to be associated with renal failure at baseline (adjusted OR 0.21, 95% CI, 0.04-0.97, p = 0.047), CMV infection (adjusted OR 0.18, 95% CI 0.04-0.75, p = 0.019) and receipt of antifungal prophylaxis (adjusted OR 0.22, 95% CI, 0.06-0.88, p = 0.032). Successful outcome and mortality rates in the study patients were 64.0% (41/64) and 25.0% (16/64), respectively. Nodular aspergillosis was associated with significantly higher successful outcome (adjusted OR 3.35, 95% CI, 1.06-10.54, p = 0.039) and lower mortality at 12 weeks (adjusted OR 0.20, 0.05-0.78, p = 0.021).Lung transplant recipients with nodular lesions due to invasive aspergillosis had better outcomes than those without such lesions.

  View details for DOI 10.1016/j.jinf.2013.03.013

  View details for PubMedID 23567625

• Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology JOURNAL OF TRANSLATIONAL MEDICINE Stringer, E. A., Baker, K. S., Carroll, I. R., Montoya, J. G., Chu, L., Maecker, H. T., Younger, J. W. 2013; 11

  View details for DOI 10.1186/1479-5876-11-93

  View details for Web of Science ID 000318117400001

  View details for PubMedID 23570606

• Clinical and Echocardiographic Presentation of Rejection Episodes Following Heart Transplantation 33rd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Sudini, N. L., Huo, J., Pan, S., Montoya, J., Leon, S., Vu, T., Beygui, R. E., Vrtovec, B., Wu, J. C., Pham, M., KUSH, K., Berry, G., Hunt, S., Haddad, F. ELSEVIER SCIENCE INC. 2013: S254–S254

  View details for Web of Science ID 000316712100696

• Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. Journal of translational medicine Stringer, E. A., Baker, K. S., Carroll, I. R., Montoya, J. G., Chu, L., Maecker, H. T., Younger, J. W. 2013; 11: 93-?

  Abstract

  Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity.Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days.Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy.Our results support the role of cytokines in the pathophysiology of CFS.

  View details for DOI 10.1186/1479-5876-11-93

  View details for PubMedID 23570606

• Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers JOURNAL OF MEDICAL VIROLOGY Watt, T., Oberfoell, S., Balise, R., Lunn, M. R., Kar, A. K., Merrihew, L., Bhangoo, M. S., Montoya, J. G. 2012; 84 (12): 1967-1974

  Abstract

  Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV-6 IgG ≥ 1:320, EBV viral capsid antigen (VCA) IgG ≥ 1:640, and EBV early antigen (EA) IgG ≥ 1:160. Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty-two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non-responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response.

  View details for DOI 10.1002/jmv.23411

  View details for Web of Science ID 000310339300020

  View details for PubMedID 23080504

• Prevention and Treatment of Cancer-Related Infections JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Baden, L. R., Bensinger, W., Angarone, M., Casper, C., Dubberke, E. R., Freifeld, A. G., Garzon, R., Greene, J. N., Greer, J. P., Ito, J. I., Karp, J. E., Kaul, D. R., King, E., Mackler, E., Marr, K. A., Montoya, J. G., Morris-Engemann, A., Pappas, P. G., Rolston, K., Segal, B., Seo, S. K., Swaminathan, S., Naganuma, M., Shead, D. A. 2012; 10 (11): 1412-1445

  Abstract

  Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients.

  View details for Web of Science ID 000310822900011

  View details for PubMedID 23138169

• Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction JOURNAL OF CLINICAL VIROLOGY Montoya, J. G., Neely, M. N., Gupta, S., Lunn, M. R., Loomis, K. S., Pritchett, J. C., Polsky, B., Medveczky, P. G. 2012; 55 (1): 40-45

  Abstract

  Human herpesvirus 6 (HHV-6) is a neurotropic virus implicated in central nervous system (CNS) dysfunction, multiple sclerosis, seizures and encephalitis. Inherited or "chromosomally integrated" HHV-6 (CIHHV-6) is a condition characterized by high DNA loads and germ line transmission of HHV-6 genomes, which are integrated into the telomere.We previously reported that integrated HHV-6 can be reactivated by trichostatin A in vitro. Therefore, we hypothesized that a broad array of neurological symptoms of CIHHV-6 patients may respond to antiviral drug treatment.The patients have been treated with antiviral drugs and monitored for viral load, late mRNA, and clinical improvement.Antiviral therapy of two CIHHV patients resulted in successful clinical resolution. However, both patients relapsed on multiple occasions within 4-6 months of cessation of antiviral therapy.Successful antiviral drug treatment suggests that clinical symptoms of these patients were due to symptomatic reactivation of CIHHV-6. Alternatively, some CIHHV-6 patients may have a reduced resistance to community-acquired HHV-6 strains due to tolerance leading to persistent infections.

  View details for DOI 10.1016/j.jcv.2012.05.016

  View details for Web of Science ID 000307997300009

  View details for PubMedID 22770640

• A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus MBIO Alter, H. J., Mikovits, J. A., Switzer, W. M., Ruscetti, F. W., Lo, S., Klimas, N., Komaroff, A. L., Montoya, J. G., Bateman, L., Levine, S., Peterson, D., Levin, B., Hanson, M. R., Genfi, A., Bhat, M., Zheng, H., Wang, R., Li, B., Hung, G., Lee, L. L., Sameroff, S., Heneine, W., Coffin, J., Hornig, M., Lipkin, W. I. 2012; 3 (5)

  Abstract

  The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.

  View details for DOI 10.1128/mBio.00266-12

  View details for Web of Science ID 000310585000015

  View details for PubMedID 22991430

• Toxoplasmosis in the fetus and newborn: an update on prevalence, diagnosis and treatment EXPERT REVIEW OF ANTI-INFECTIVE THERAPY Moncada, P. A., Montoya, J. G. 2012; 10 (7): 815-828

  Abstract

  Toxoplasma gondii is an unicellular coccidian parasite with worldwide distribution. It is estimated that more than a third of the world's population has been infected with the parasite, but seroprevalence is unevenly distributed across countries and different socioeconomic strata. The majority of newborns with congenital toxoplasmosis do not have any clinical signs of the disease at birth; however, 30-70% of those with clinical abnormalities were not detected initially, and are found to have new retinal lesions consistent with toxoplasmicchorioretinitis later in life. Congenital toxoplasmosis can also cause fetal death, stillbirths or long-term disabling sequelae, particularly among untreated infants. The disease appears to be more frequent and severe at certain latitudes. Congenital toxoplasmosis can be prevented and treated during gestation. Less severe disease is commonly reported in countries where prenatal screening and treatment have been systematically implemented. By contrast, severe disease appears to be observed primarily in infants born to untreated mothers. For definition purposes, it is best to use the term toxoplasma or Toxoplasma gondii infection when referring to asymptomatic patients with primary or chronic infection, and toxoplasmosis when referring to patients with symptoms or signs.

  View details for DOI 10.1586/ERI.12.58

  View details for Web of Science ID 000309854100016

  View details for PubMedID 22943404

• Chromosomally integrated human herpesvirus 6: questions and answers REVIEWS IN MEDICAL VIROLOGY Pellett, P. E., Ablashi, D. V., Ambros, P. F., Agut, H., Caserta, M. T., Descamps, V., Flamand, L., Gautheret-Dejean, A., Hall, C. B., Kamble, R. T., Kuehl, U., Lassner, D., Lautenschlager, I., Loomis, K. S., Luppi, M., Lusso, P., Medveczky, P. G., Montoya, J. G., Mori, Y., Ogata, M., Pritchett, J. C., Rogez, S., Seto, E., Ward, K. N., Yoshikawa, T., Razonable, R. R. 2012; 22 (3): 144-155

  Abstract

  Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease.

  View details for DOI 10.1002/rmv.715

  View details for Web of Science ID 000303119600002

  View details for PubMedID 22052666

• Severe Congenital Toxoplasmosis in the United States Clinical and Serologic Findings in Untreated Infants PEDIATRIC INFECTIOUS DISEASE JOURNAL Olariu, T. R., Remington, J. S., McLeod, R., Alam, A., Montoya, J. G. 2011; 30 (12): 1056-1061

  Abstract

  Congenital toxoplasmosis can cause significant neurologic manifestations and other untoward sequelae.The Palo Alto Medical Foundation Toxoplasma Serology Laboratory database was searched for data on infants 0 to 180 days old, in whom congenital toxoplasmosis had been confirmed and who had been tested for Toxoplasma gondii-specific immunoglobulin G (IgG), IgM, and IgA antibodies, between 1991 and 2005. Their clinical findings were confirmed at the National Collaborative Chicago-based Congenital Toxoplasmosis Study center. We reviewed available clinical data and laboratory profiles of 164 infants with congenital toxoplasmosis whose mothers had not been treated for the parasite during gestation.One or more severe clinical manifestations of congenital toxoplasmosis were reported in 84% of the infants and included eye disease (92.2%), brain calcifications (79.6%), and hydrocephalus (67.7%). In 61.6% of the infants, eye disease, brain calcifications, and hydrocephalus were present concurrently. T. gondii-specific IgM, IgA, and IgE antibodies were demonstrable in 86.6%, 77.4%, and 40.2% of the infants, respectively. Testing for IgM and IgA antibodies increased the sensitivity of making the diagnosis of congenital toxoplasmosis to 93% compared with testing for IgM or IgA individually. IgM and IgA antibodies were still present in 43.9% of infants diagnosed between 1 and 6 months of life.Our study reveals that severe clinical signs of congenital toxoplasmosis including hydrocephalus, eye disease, or intracranial calcifications occurred in 85% infants whose sera were referred to our reference Toxoplasma Serology Laboratory during a period of 15 years. Laboratory tests, including serologic and polymerase chain reaction tests, were critical for diagnosis in the infants. Our results contrast remarkably with those of European investigators who rarely observe severe clinical signs in infants with congenital toxoplasmosis.

  View details for DOI 10.1097/INF.0b013e3182343096

  View details for Web of Science ID 000297406100012

  View details for PubMedID 21956696

• Diagnostic Approach to Ocular Toxoplasmosis OCULAR IMMUNOLOGY AND INFLAMMATION Garweg, J. G., de Groot-Mijnes, J. D., Montoya, J. G. 2011; 19 (4): 255-261

  Abstract

  Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances.

  View details for DOI 10.3109/09273948.2011.595872

  View details for Web of Science ID 000292915300008

  View details for PubMedID 21770803

• Working formulation for the standardization of definitions of infections in patients using ventricular assist devices JOURNAL OF HEART AND LUNG TRANSPLANTATION Hannan, M. M., Husain, S., Mattner, F., Danziger-Isakov, L., Drew, R. J., Corey, G. R., Schueler, S., Holman, W. L., Lawler, L. P., Gordon, S. M., Mahon, N. G., Herre, J. M., Gould, K., Montoya, J. G., Padera, R. F., Kormos, R. L., Conte, J. V., Mooney, M. L. 2011; 30 (4): 375-384

  View details for DOI 10.1016/j.healun.2011.01.717

  View details for Web of Science ID 000288924200002

  View details for PubMedID 21419995

• Yield of diagnostic procedures for invasive fungal infections in neutropenic febrile patients with chest computed tomography abnormalities MYCOSES Ho, D. Y., Lin, M., Schaenman, J., Rosso, F., Leung, A. N., Coutre, S. E., Sista, R. R., Montoya, J. G. 2011; 54 (1): 59-70

  Abstract

  Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas.

  View details for DOI 10.1111/j.1439-0507.2009.01760.x

  View details for Web of Science ID 000284900600009

  View details for PubMedID 19793207

• The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Arbuckle, J. H., Medveczky, M. M., Luka, J., Hadley, S. H., Luegmayr, A., Ablashi, D., Lund, T. C., Tolar, J., De Meirleir, K., Montoya, J. G., Komaroff, A. L., Ambros, P. F., Medveczky, P. G. 2010; 107 (12): 5563-5568

  Abstract

  Previous research has suggested that human herpesvirus-6 (HHV-6) may integrate into host cell chromosomes and be vertically transmitted in the germ line, but the evidence--primarily fluorescence in situ hybridization (FISH)--is indirect. We sought, first, to definitively test these two hypotheses. Peripheral blood mononuclear cells (PBMCs) were isolated from families in which several members, including at least one parent and child, had unusually high copy numbers of HHV-6 DNA per milliliter of blood. FISH confirmed that HHV-6 DNA colocalized with telomeric regions of one allele on chromosomes 17p13.3, 18q23, and 22q13.3, and that the integration site was identical among members of the same family. Integration of the HHV-6 genome into TTAGGG telomere repeats was confirmed by additional methods and sequencing of the integration site. Partial sequencing of the viral genome identified the same integrated HHV-6A strain within members of families, confirming vertical transmission of the viral genome. We next asked whether HHV-6A infection of naïve cell lines could lead to integration. Following infection of naïve Jjhan and HEK-293 cell lines by HHV-6, the virus integrated into telomeres. Reactivation of integrated HHV-6A virus from individuals' PBMCs as well as cell lines was successfully accomplished by compounds known to induce latent herpesvirus replication. Finally, no circular episomal forms were detected even by PCR. Taken together, the data suggest that HHV-6 is unique among human herpesviruses: it specifically and efficiently integrates into telomeres of chromosomes during latency rather than forming episomes, and the integrated viral genome is capable of producing virions.

  View details for DOI 10.1073/pnas.0913586107

  View details for Web of Science ID 000275898300054

  View details for PubMedID 20212114

• Changing trends in infectious disease in heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Deuse, T., Pham, M., Khazanie, P., Rosso, F., Luikart, H., Valantine, H., Leon, S., Vu, T. A., Hunt, S. A., Oyer, P., Montoya, J. G. 2010; 29 (3): 306-315

  Abstract

  During the past 25 years, advances in immunosuppression and the use of selective anti-microbial prophylaxis have progressively reduced the risk of infection after heart transplantation. This study presents a historical perspective of the changing trends of infectious disease after heart transplantation.Infectious complications in 4 representative eras of immunosuppression and anti-microbial prophylaxis were analyzed: (1) 38 in the pre-cyclosporine era (1978-1980), (2) 72 in the early cyclosporine era (1982-1984), where maintenance immunosuppression included high-dose cyclosporine and corticosteroid therapy; (3) 395 in the cyclosporine era (1988-1997), where maintenance immunosuppression included cyclosporine, azathioprine, and lower corticosteroid doses; and (4) 167 in the more recent era (2002-2005), where maintenance immunosuppression included cyclosporine and mycophenolate mofetil.The overall incidence of infections decreased in the 4 cohorts from 3.35 episodes/patient to 2.03, 1.35, and 0.60 in the more recent cohorts (p < 0.001). Gram-positive bacteria are emerging as the predominant cause of bacterial infections (28.6%, 31.4%, 51.0%, 67.6%, p = 0.001). Cytomegalovirus infections have significantly decreased in incidence and occur later after transplantation (88 +/- 77 days, pre-cyclosporine era; 304 +/- 238 days, recent cohort; p < 0.001). Fungal infections also decreased, from an incidence of 0.29/patient in the pre-cyclosporine era to 0.08 in the most recent era. A major decrease in Pneumocystis jiroveci and Nocardia infections has also occurred.The overall incidence and mortality associated with infections continues to decrease in heart transplantation and coincides with advances in immunosuppression, the use of selective anti-microbial prophylaxis, and more effective treatment regimens.

  View details for DOI 10.1016/j.healun.2009.08.018

  View details for Web of Science ID 000276005200013

  View details for PubMedID 19853478

• Risk Factors for Toxoplasma gondii Infection in the United States CLINICAL INFECTIOUS DISEASES Jones, J. L., Dargelas, V., Roberts, J., Press, C., Remington, J. S., Montoya, J. G. 2009; 49 (6): 878-884

  Abstract

  Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States.We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires.We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women.In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.

  View details for DOI 10.1086/605433

  View details for Web of Science ID 000269145100008

  View details for PubMedID 19663709

• Trends in invasive disease due to Candida species following heart and lung transplantation TRANSPLANT INFECTIOUS DISEASE Schaenman, J. M., Rosso, F., Austin, J. M., Baron, E. J., Gamberg, P., Miller, J., Oyer, P. E., Robbins, R. C., Montoya, J. G. 2009; 11 (2): 112-121

  Abstract

  Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart-lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient).The incidence of IC was higher in lung (LTx) and heart-lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1-2.7).The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980-1986 time period to 2.1% in the 2001-2004 era in the HTx recipients, and from 20% in the 1980-1986 period to 1.8% in the 2001-2004 period in the LTx and HLTx recipients.The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8-4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9-4.6, P<0.001). The attributable mortality from IC decreased during the 25-year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non-albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years.The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.

  View details for DOI 10.1111/j.1399-3062.2009.00364.x

  View details for Web of Science ID 000265015600004

  View details for PubMedID 19254327

• Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Histologic and Cytologic Specimens A Ten-Year Retrospective Review at a Single Institution AMERICAN JOURNAL OF CLINICAL PATHOLOGY Sangoi, A. R., Rogers, W. M., Longacre, T. A., Montoya, J. G., Baron, E. J., Banaei, N. 2009; 131 (3): 364-375

  Abstract

  Despite the advantages of providing an early presumptive diagnosis, fungal classification by histopathology can be difficult and may lead to diagnostic error. To assess the accuracy of histologic diagnosis of fungal infections vs culture ("gold standard"), we performed a 10-year retrospective review at our institution. Of the 47 of 338 positive mold and yeast cultures with concurrent surgical pathology evaluation without known history of a fungal infection, 37 (79%) were correctly identified based on morphologic features in histologic and/or cytologic specimens. The 10 discrepant diagnoses (21%) included misidentification of septate and nonseptate hyphal organisms and yeast forms. Errors resulted from morphologic mimics, use of inappropriate terminology, and incomplete knowledge in mycology. The accuracy did not correlate with preceding antifungal therapy (P = .14) or use of special stains (P = .34) and was not operator-dependent. Among 8 discrepancies with clinical follow-up available, 2 potential adverse clinical consequences resulted. While histopathologic identification of fungi in tissue sections and cytologic preparations is prone to error, implementation of a standardized reporting format should improve diagnostic accuracy and prevent adverse outcomes.

  View details for DOI 10.1309/AJCP99OOOZSNISCZ

  View details for Web of Science ID 000263427400008

  View details for PubMedID 19228642

• Changing Trends in Infectious Complications among Heart Transplant Recipients 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation Haddad, F., Deuse, T., Rosso, P., Pham, M., Khazanie, P., Luikart, H., Valantine, H. A., Hunt, S. A., Vu, T., Oyer, P. E., Robbins, R. C., Montoya, J. G. ELSEVIER SCIENCE INC. 2009: S237–S238

  View details for Web of Science ID 000263539800490

• Severe Encephalomyelitis in an Immunocompetent Adult with Chromosomally Integrated Human Herpesvirus 6 and Clinical Response to Treatment with Foscarnet plus Ganciclovir CLINICAL INFECTIOUS DISEASES Troy, S. B., Blackburn, B. G., Yeom, K., Caulfield, A. K., Bhangoo, M. S., Montoya, J. G. 2008; 47 (12): E93-E96

  Abstract

  Human herpesvirus 6 has rarely been identified as a cause of encephalitis in immunocompetent adults. We describe a patient who had severe encephalomyelitis, hypoglycorrhachia, and human herpesvirus 6 identified in his cerebrospinal fluid and serum and who recovered after treatment with foscarnet and ganciclovir. Human herpesvirus 6 should be considered in immunocompetent patients with encephalitis.

  View details for DOI 10.1086/593315

  View details for Web of Science ID 000261163600035

  View details for PubMedID 18991511

• SOURCES OF TOXOPLASMA GONDII INFECTION IN THE UNITED STATES 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene Jones, J. L., Dargelas, V., Roberts, J., Press, C., Remington, J. S., Montoya, J. G. AMER SOC TROP MED & HYGIENE. 2008: 335–35

  View details for Web of Science ID 000261644601505

• Management of Toxoplasma gondii infection during pregnancy CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 2008; 47 (4): 554-566

  Abstract

  Acute infection with Toxoplasma gondii during pregnancy and its potentially tragic outcome for the fetus and newborn continue to occur in the United States, as well as worldwide, despite the fact that it can be prevented. The infection can be acquired through ingestion of infected, undercooked meat or contaminated food or water. Transmission to the fetus occurs almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss, mental and psychomotor retardation, seizures, hematological abnormalities, hepatosplenomegaly, or death. Systematic education and serological screening of pregnant women are the most reliable and currently available strategies for the prevention, diagnosis, and early treatment of the infection in the offspring; this is largely because toxoplasmosis in pregnant women most often goes unrecognized. Treatment of the infection in the fetus and infant during the first year of life has been demonstrated to significantly improve the clinical outcome.

  View details for DOI 10.1086/590149

  View details for Web of Science ID 000257755700023

  View details for PubMedID 18624630

• Prevalence of infection with Toxoplasma gondii among pregnant women in Cali, Colombia, South America AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Rosso, F., Les, J. T., Agudelo, A., Villalobos, C., Chaves, J. A., Tunubala, G. A., Messa, A., Remington, J. S., Montoya, J. G. 2008; 78 (3): 504-508

  Abstract

  The aim of this study was to determine the prevalence of toxoplasma antibodies among pregnant women in Cali, Colombia. In 2005, 955 pregnant women were tested for IgG and IgM antibodies and sociodemographic information was collected. Their average age was 25.1 years, overall IgG seroprevalence 45.8% (95% CI: 41.8%, 48.2%), IgM 2.8% (95% CI: 1.5%, 3.6%). Seroprevalence increased significantly with age, 39.0% in 14 to 19 years to 55.3% in 30 to 39 years (P = 0.001). There was a significant trend toward a higher seroprevalence in the lower socioeconomic strata (SES) (low: 49.0%, high: 29%, P = 0.004). The increase in seroprevalence by age was more significant in the lower socioeconomic strata (P = 0.002). Our results suggest a higher prevalence when compared with those of the national 1980 (33-37.6%) survey. In contrast to reports from other regions of the world, Cali has not seen a decrease in T. gondii seroprevalence over the past 25 years.

  View details for Web of Science ID 000253928100027

  View details for PubMedID 18337350

• Prevention and treatment of cancer-related infections. Journal of the National Comprehensive Cancer Network Segal, B. H., Freifeld, A. G., Baden, L. R., Brown, A. E., Casper, C., Dubberke, E., Gelfand, M., Greene, J. N., Ison, M. G., Ito, J. I., Karp, J. E., Kaul, D. R., King, E., Mackler, E., Marcucci, G., Montoya, J. G., Engemann, A. M., Rolston, K., The, A. S. 2008; 6 (2): 122-174

  View details for PubMedID 18319048

• Improving the tools in the fight against cytomegalovirus or strengthening David to defeat Goliath CURRENT OPINION IN INFECTIOUS DISEASES Montoya, J. G. 2007; 20 (4): 397-398

  View details for Web of Science ID 000248074100008

  View details for PubMedID 17609599

• The differential agglutination test as a diagnostic aid in cases of toxoplasmic lymphadenitis JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Berry, A., Rosso, F., Remington, J. S. 2007; 45 (5): 1463-1468

  Abstract

  Lymphadenopathy (LN) is the most common clinical manifestation of acute acquired toxoplasma infection in humans. The diagnosis of toxoplasmic lymphadenitis (TL) is established by serological methods and/or lymph node biopsy. In the United States, the differential agglutination (of acetone [AC]-fixed versus that of formalin [HS]-fixed tachyzoites) test (AC/HS test) has primarily been used in assessments of pregnant women as a component of the toxoplasma serological profile to distinguish between recently acquired infections and infections acquired in the distant past. We studied the AC/HS test in patients with TL to define its usefulness in diagnosing individuals presenting with LN and to determine its kinetics after the onset of LN. One hundred nine consecutive patients (158 serum samples) diagnosed serologically and by lymph node biopsy as having TL were studied. Specific patterns in the AC/HS test were noted to be dependent on the time from the clinical onset of LN (COLN). Acute AC/HS patterns were observed for more than 75% of patients who according to their histories had developed their TL within 6 months after COLN. Acute patterns were not observed beyond the 12th month except for a single patient for whom an acute pattern (400/800) persisted to the 13th month after COLN. Equivocal patterns were observed up to 36 months after COLN. Nonacute patterns were observed only for serum samples drawn at least 13 months after COLN. A nonacute pattern in an individual at less than 12 months after COLN should suggest an etiology other than TL. In such cases, investigation for alternative causes, including malignancy, should be instigated.

  View details for DOI 10.1128/JCM.01781-06

  View details for Web of Science ID 000246600300013

  View details for PubMedID 17314220

• Treating disseminated fusariosis: amphotericin B, voriconazole or both? MYCOSES Ho, D. Y., Lee, J. D., Rosso, F., Montoya, J. G. 2007; 50 (3): 227-231

  Abstract

  Disseminated Fusarium infection can cause significant morbidity and mortality in immunocompromised patients. We present a case of disseminated fusariosis in a patient with neutropenic fever successfully treated using both liposomal amphotericin B and voriconazole. Combination anti-fungal therapy may be considered for such patients, particularly for those failing single-drug therapy.

  View details for DOI 10.1111/j.0933-7407.2006.2006.01346.x

  View details for Web of Science ID 000246151400013

  View details for PubMedID 17472622

• A case of successful treatment of cutaneous Acanthamoeba infection in a lung transplant recipient TRANSPLANT INFECTIOUS DISEASE Walia, R., Montoya, J. G., Visvesvera, G. S., Booton, G. C., Doyle, R. L. 2007; 9 (1): 51-54

  Abstract

  Acanthamoeba species are known to cause 2 well-described entities: (1) granulomatous amoebic encephalitis (GAE), which usually affects immunocompromised hosts, and (2) keratitis, which typically follows trauma associated with contamination of water or contact lenses. Less common manifestations include pneumonitis and a subacute granulomatous dermatitis. We describe a case of granulomatous dermatitis secondary to Acanthamoeba infection in a lung transplant recipient and a successful outcome following treatment with lipid formulation of amphotericin B and voriconazole. We believe this is the second case report describing disseminated Acanthamoeba infection in a lung transplant recipient. We also describe successful outcome with a combination of lipid formulation of amphotericin B and voriconazole, drugs that have not been previously reported to treat Acanthamoeba.

  View details for DOI 10.1111/j.1399-3062.2006.00159.x

  View details for Web of Science ID 000244957300011

  View details for PubMedID 17313473

• Pulmonary nocardiosis in a heart transplant patient: Case report and review of the literature JOURNAL OF HEART AND LUNG TRANSPLANTATION Haddad, F., Hunt, S. A., Perlroth, M., Valantine, H., Doyle, R., Montoya, J. 2007; 26 (1): 93-97

  Abstract

  Pulmonary infection with Nocardia is an uncommon but serious infection found in immunocompromised patients. We describe a rapidly progressive pulmonary nocardiosis in a heart transplant patient. We then review the common clinical features of Nocardia infection in transplant recipients, outlining the challenges in its diagnosis and management. We also review the differences between Pneumocystis jiroveci prophylaxis regimens with respect to concomitant prophylaxis of Nocardia and other opportunistic infections.

  View details for DOI 10.1016/j.healun.2006.11.002

  View details for Web of Science ID 000243950900015

  View details for PubMedID 17234524

• Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue 5th International Conference on Human Herpesvirus 6 and 7 (HHV-6&7) Kogelnik, A. M., Loomis, K., Hoegh-Petersen, M., Rosso, F., Hischier, C., Montoya, J. G. ELSEVIER SCIENCE BV. 2006: S33–S38

  Abstract

  Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

  View details for Web of Science ID 000243845000009

  View details for PubMedID 17276366

• Is combination therapy indicated for invasive fungal infections? Yes and no CURRENT OPINION IN INFECTIOUS DISEASES Montoya, J. G., Rosso, F. 2006; 19 (4): 357-359

  View details for Web of Science ID 000239417200007

  View details for PubMedID 16804383

• Late-onset invasive aspergillosis in organ transplant recipients in the current era 45th Interscience Conference on Antimicrobial Agents and Chemotherapy Singh, N., Limaye, A. P., Forrest, G., Safdar, N., Munoz, P., Pursell, K., Houston, S., Rosso, F., Montoya, J. G., Patton, P. R., del Busto, R., Aguado, J. M., Wagener, M. M., Husain, S. TAYLOR & FRANCIS LTD. 2006: 445–49

  Abstract

  We assessed predictive factors and characteristics of patients with late-onset invasive aspergillosis in the current era of novel immunosuppressive agents. Forty transplant recipients with invasive aspergillosis were included in this prospective, observational study initiated in 2003 at our institutions. In 50% (20/40) of these patients, the infections were late-occurring. Receipt of sirolimus in conjunction with tacrolimus for refractory rejection or cardiac allograft vasculopathy (P=0.047) was significantly associated with late-onset infection. The use of depleting or non-depleting T or B-cell antibodies, either as induction or as antirejection therapy did not correlate with time to onset of invasive aspergillosis. Mortality at 90 days was 20% (4/20) for the patients with early-onset infection and 45% (9/20) for those with late-onset infection (P=0.17). Thus, nearly one-half of the Aspergillus infections in transplant recipients in the current era are late-occurring. These data have implications relevant for prophylactic strategies and guiding clinical management of transplant recipients presenting with pulmonary infiltrates.

  View details for DOI 10.1080/13693780600684494

  View details for Web of Science ID 000240494500007

  View details for PubMedID 16882611

• Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: A prospective, multicenter, observational study TRANSPLANTATION Singh, N., Limaye, A. P., Forrest, G., Safdar, N., Munoz, P., Pursell, K., Houston, S., Rosso, F., Montoya, J. G., Patton, P., del Busto, R., Aguado, J. M., Fisher, R. A., Klintmalm, G. B., Miller, R., Wagener, M. M., Lewis, R. E., Kontoyiannis, D. P., Husain, S. 2006; 81 (3): 320-326

  Abstract

  : The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined.: Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome.: Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30-1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12-0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16-0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome.: Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

  View details for DOI 10.1097/01.tp.0000202421.94822.f7

  View details for Web of Science ID 000235377800005

  View details for PubMedID 16477215

• Serotyping of Toxoplasma gondii strains infecting pregnant women in the United States 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Colon, I., Ramirez, R., Grigg, M., Montoya, J., Remington, J. MOSBY-ELSEVIER. 2005: S187–S187

  View details for Web of Science ID 000233947800658

• Practice guidelines for the diagnosis and management of skin and soft-tissue infections CLINICAL INFECTIOUS DISEASES Stevens, D. L., BISNO, A. L., Chambers, H. F., Everett, E. D., Dellinger, P., Goldstein, E. J., Gorbach, S. L., Hirschmann, J. V., Kaplan, E. L., Montoya, J. G., Wade, J. C. 2005; 41 (10): 1373-1406

  View details for Web of Science ID 000232670400001

  View details for PubMedID 16231249

• Diagnosis and management of toxoplasmosis CLINICS IN PERINATOLOGY Montoya, J. G., Rosso, F. 2005; 32 (3): 705-?

  Abstract

  This article discusses the diagnosis and management of toxoplasmosis. Congenital toxoplasmosis continues to be a tragic outcome of a preventable and treatable infection. Education of patients, physicians and health policy makers on the primary and secondary preventive measures of the disease, and their execution, will undoubtedly result in lower incidence, morbidity, and mortality rates from congenital disease due to Toxoplasma gondii.

  View details for DOI 10.1016/j.clp.2005.04.011

  View details for Web of Science ID 000231553500011

  View details for PubMedID 16085028

• Molecular mycological diagnosis and correct antimycotic treatments JOURNAL OF CLINICAL MICROBIOLOGY Mancini, N., Ossi, C. M., Perotti, M., Clementi, M. 2005; 43 (7): 3584-3584

  View details for DOI 10.1128/JCM.43.7.3584-3585.2005

  View details for Web of Science ID 000230614900107

  View details for PubMedID 16000516

• Use of a single serum sample for diagnosis of acute toxoplasmosis in pregnant women and other adults JOURNAL OF CLINICAL MICROBIOLOGY Press, C., Montoya, J. G., Remington, J. S. 2005; 43 (7): 3481-3483

  Abstract

  Using a single serum sample for testing for immunoglobulin G (IgG) Toxoplasma antibodies, differences in sensitivity of the dye test (which measures primarily IgG antibodies) and an IgG enzyme immunoassay were found useful for very early diagnosis of acute Toxoplasma gondii infection.

  View details for DOI 10.1128/JCM.43.7.3481-3483.2005

  View details for Web of Science ID 000230614900075

  View details for PubMedID 16000484

• Scedosporium apiospermum soft tissue infection successfully treated with voriconazole: Potential pitfalls in the transition from intravenous to oral therapy JOURNAL OF CLINICAL MICROBIOLOGY Schaenman, J. M., DiGiulio, D. B., Mirels, L. F., McClenny, N. M., Berry, G. J., Fothergill, A. W., Rinaldi, M. G., Montoya, J. G. 2005; 43 (2): 973-977

  Abstract

  An immunocompromised patient with an invasive soft tissue infection due to Scedosporium apiospermum was successfully treated with voriconazole and surgical debridement. After transition from intravenous to oral therapy, successive adjustments of the oral dose were required to achieve complete resolution. For soft tissue infections due to molds characterized by thin, septate hyphae branching at acute angles, voriconazole should be considered a first-line antifungal agent. The potential usefulness of plasma voriconazole levels for guiding optimal therapy should be investigated.

  View details for DOI 10.1128/JCM.43.2.973-977.2005

  View details for Web of Science ID 000227045600082

  View details for PubMedID 15695722

• Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic lymphadenopathy JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Huffman, H. B., Remington, J. S. 2004; 42 (10): 4627-4631

  Abstract

  Toxoplasmic lymphadenopathy (TL) is the most common clinical manifestation of acute acquired toxoplasma infection in normal individuals. The diagnosis is established by serologic methods and lymph node biopsy. Recently, tests for avidity of toxoplasma immunoglobulin G (IgG) antibodies have been introduced to help discriminate between recently acquired and distant infection with the parasite. We studied an avidity test to define the usefulness of this method and to determine the evolution of the IgG avidity in TL. Seventy-three consecutive patients diagnosed as having TL were studied. IgG avidity test titers were noted to be time dependent from the clinical onset of lymphadenopathy. Low IgG avidity test results were observed in patients who had developed lymphadenopathy from <1 month to 17 months prior to the sampling of sera, emphasizing that low IgG avidity test results are not reliable for diagnosis of recently acquired infection. In contrast, high IgG avidity test results were observed only in patients who had developed lymphadenopathy at least 4 months earlier. Thus, a high IgG avidity test result in an individual who has recent onset of lymphadenopathy (e.g., within 2 to 3 months of sera sampling) suggests a cause other than toxoplasmosis. In such cases, further workup is warranted in order to determine the cause of the lymphadenopathy.

  View details for DOI 10.1128/JCM.42.10.4627-4631.2004

  View details for Web of Science ID 000224473000033

  View details for PubMedID 15472320

• Fever and neutropenia clinical practice guidelines. Journal of the National Comprehensive Cancer Network Freifeld, A. G., Baden, L. R., Brown, A. E., Elting, L. S., Gelfand, M., Greene, J. N., Ito, J. I., King, E., Marcucci, G., Montoya, J. G., Morris, A., Noskin, G., Rolston, K., Schott, A. F., Segal, B. 2004; 2 (5): 390-432

  Abstract

  Significant progress has been made in managing fever and neutropenia in patients with cancer. Although initial empiric antimicrobial treatment remains the foundation of therapy for such patients, improved diagnostic modalities, models of risk assessment, and an understanding of the various clinical situations in which infections occur have required that treatment approaches and options evolve. The development of broad-spectrum antibiotics with decreased toxicity has improved patient outcomes. Nevertheless, the increasing prevalence of antibiotic-resistant pathogens has challenged the clinician to use antimicrobial therapy wisely. Infection control should not rely exclusively on antimicrobial prophylaxis but, rather, should continue to incorporate standard infection control measures and demand careful handwashing by all health care professionals who come into contact with immunocompromised patients. Invasive fungal pathogens have increased and remain a major concern. Diagnostic and therapeutic modalities for fungal infections remain limited, but careful clinical investigation of new approaches will be needed to define the proper use of these probably expensive new therapeutic additions.

  View details for PubMedID 19780251

• Successes and limitations of antimicrobial interventions in the setting of organ transplantation CURRENT OPINION IN INFECTIOUS DISEASES Montoya, J. G. 2004; 17 (4): 341-345

  View details for DOI 10.1097/01.qco.0000136932.60296.8d

  View details for Web of Science ID 000223033000010

  View details for PubMedID 15241079

• Toxoplasmosis LANCET Montoya, J. G., Liesenfeld, O. 2004; 363 (9425): 1965-1976

  Abstract

  Toxoplasma gondii is a protozoan parasite that infects up to a third of the world's population. Infection is mainly acquired by ingestion of food or water that is contaminated with oocysts shed by cats or by eating undercooked or raw meat containing tissue cysts. Primary infection is usually subclinical but in some patients cervical lymphadenopathy or ocular disease can be present. Infection acquired during pregnancy may cause severe damage to the fetus. In immunocompromised patients, reactivation of latent disease can cause life-threatening encephalitis. Diagnosis of toxoplasmosis can be established by direct detection of the parasite or by serological techniques. The most commonly used therapeutic regimen, and probably the most effective, is the combination of pyrimethamine with sulfadiazine and folinic acid. This Seminar provides an overview and update on management of patients with acute infection, pregnant women who acquire infection during gestation, fetuses or infants who are congenitally infected, those with ocular disease, and immunocompromised individuals. Controversy about the effectiveness of primary and secondary prevention in pregnant women is discussed. Important topics of current and future research are presented.

  View details for Web of Science ID 000221962800019

  View details for PubMedID 15194258

• Recent developments for diagnosis of toxoplasmosis JOURNAL OF CLINICAL MICROBIOLOGY Remington, J. S., Thulliez, P., Montoya, J. G. 2004; 42 (3): 941-945

  View details for DOI 10.1125/JCM.42.3.941-945.2004

  View details for Web of Science ID 000220376900001

  View details for PubMedID 15004036

• Invasive aspergillosis in the setting of cardiac transplantation 37th Annual Meeting of the Infectious-Diseases-Society-of-America Montoya, J. G., Chaparro, S. V., Celis, D., Cortes, J. A., Leung, A. N., Robbins, R. C., Stevens, D. A. UNIV CHICAGO PRESS. 2003: S281–S292

  Abstract

  Among patients undergoing heart transplantation, Aspergillus is the opportunistic pathogen with the highest attributable mortality. The median time of onset from transplantation for invasive pulmonary aspergillosis (IPA) was 46 days, but the median time to first positive culture result was 104 days among patients with Aspergillus colonization but no invasive disease. Most patients with IPA presented with fever and cough within the first 90 days of transplantation and with single or multiple pulmonary nodules. None of the heart transplant recipients with either IPA or invasive extrapulmonary aspergillosis (IEPA) had associated neutropenia. Human leukocyte antigen A1 locus was found significantly more frequently among patients colonized with Aspergillus than among patients with IPA (P<.006) or IEPA (P<.001). Even in the absence of neutropenia, IPA should be suspected for heart transplant recipients who have fever and respiratory symptoms within the first 3 months of transplantation, have a positive result of culture of respiratory secretions, and have abnormal radiological findings (particularly nodules).

  View details for Web of Science ID 000186262900006

  View details for PubMedID 12975755

• Post-transplantation lymphoproliferative disease in heart and heart-lung transplant recipients: 30-year experience at Stanford University 21st Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation Gao, S. Z., Chaparro, S. V., Perlroth, M., Montoya, J. G., Miller, J. L., DiMiceli, S., Hastie, T., Oyer, P. E., Schroeder, J. ELSEVIER SCIENCE INC. 2003: 505–14

  Abstract

  Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD.We reviewed the records of 1026 (874 heart, 152 heart-lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart-lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade.No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant (p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly (p < 0.02) associated with PTLD development. The prevalence of PTLD at 13.3 years was 15%.The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.

  View details for DOI 10.1016/S1053-2498(02)01229-9

  View details for Web of Science ID 000182805100002

  View details for PubMedID 12742411

• Trimethoprim-sulfamethoxazole as toxoplasmosis prophylaxis for heart transplant recipients - Reply CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 2003; 36 (7): 933-933

  View details for Web of Science ID 000181761700018

• VIDAS test for avidity of Toxoplasma-specific immunoglobulin G for confirmatory testing of pregnant women JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Liesenfeld, O., Kinney, S., Press, C., Remington, J. S. 2002; 40 (7): 2504-2508

  Abstract

  Because congenital toxoplasmosis is almost solely the result of maternal infection acquired during gestation, it is critical to determine whether infection during pregnancy has occurred. In the United States, definitive diagnosis of the acute infection and the time of its occurrence have been compromised by a lack of systematic screening and the fact that only a single serum sample is submitted for testing. In studies in Europe, and depending on the method used, the demonstration of high-avidity immunoglobulin G (IgG) toxoplasma antibodies has been shown to exclude infection having occurred in the first 3 to 5 months of pregnancy. We investigated the usefulness of determining the avidity of IgG toxoplasma antibodies with a VIDAS kit (herein referred to as the VIDAS Toxo-IgG avidity kit, the VIDAS kit essentially rules out acute infection having occurred within the 4 prior months) in the setting of a reference serology laboratory in the United States. Sera (132 samples) from 132 women in the first 16 weeks of pregnancy were chosen because at least one test in the toxoplasma serological profile (TSP) suggested or was equivocal for a recently acquired infection. High-avidity antibodies were demonstrated in 75% of 99 sera positive with the IgM enzyme-linked immunosorbent assay (ELISA) and 31.3% of 16 sera with acute TSP results. A significant percentage of sera with equivocal results wtih the IgM ELISA or TSP also had high-avidity test results. Of 39 women for whom treatment with spiramycin had been suggested to attempt to prevent congenital transmission, 19 (48.7%) had high-avidity antibodies. These findings highlight the value of the VIDAS IgG avidity kit when used in combination with the TSP to exclude recent infection, especially when only a single serum sample is available.

  View details for DOI 10.1128/JCM.40.7.2504-2508.2002

  View details for Web of Science ID 000176605800030

  View details for PubMedID 12089270

• Evolution of primary protease inhibitor resistance mutations during protease inhibitor salvage therapy ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Kantor, R., Fessel, W. J., Zolopa, A. R., Israelski, D., Shulman, N., Montoya, J. G., Harbour, M., Schapiro, J. M., Shafer, R. W. 2002; 46 (4): 1086-1092

  Abstract

  In order to track the evolution of primary protease inhibitor (PI) resistance mutations in human immunodeficiency virus type 1 (HIV-1) isolates, baseline and follow-up protease sequences were obtained from patients undergoing salvage PI therapy who presented initially with isolates containing a single primary PI resistance mutation. Among 78 patients meeting study selection criteria, baseline primary PI resistance mutations included L90M (42% of patients), V82A/F/T (27%), D30N (21%), G48V (6%), and I84V (4%). Despite the switching of treatment to a new PI, primary PI resistance mutations present at the baseline persisted in 66 of 78 (85%) patients. D30N persisted less frequently than L90M (50% versus 100%, respectively; P < 0.001) and V82A/F/T (50% versus 81%, respectively; P = 0.05). HIV-1 isolates from 38 (49%) patients failing PI salvage therapy developed new primary PI resistance mutations including L90M, I84V, V82A, and G48V. Common combinations of primary and secondary PI resistance mutations after salvage therapy included mutations at amino acid positions 10, 82, and 46 and/or 54 in 16 patients; 10, 90, and 71 and/or 73 in 14 patients; 10, 73, 84, 90, and 46 and/or 54 in 5 patients; 10, 48, and 82 in 5 patients; and 30, 88 and 90 in 5 patients. In summary, during salvage PI therapy, most HIV-1 isolates with a single primary PI resistance mutation maintained their original mutations, and 49% developed additional primary PI resistance mutations. The persistence of L90M, V82A/F/T, G48V, and I84V during salvage therapy suggests that these mutations play a role in clinical resistance to multiple PIs.

  View details for DOI 10.1128/AAC.46.4.1086-1092.2002

  View details for Web of Science ID 000174597000022

  View details for PubMedID 11897594

• Clinical risk factors for development of nonlymphoma cancer post-heart and heart-lung transplantation: Analysis of 30-year follow-up in 1,026 patients Gao, S. Z., Perlroth, M. G., Montoya, J. G., Miller, J. L., DiMiceli, S., Brown, B., Oyer, P. E., Schroeder, J. S. ELSEVIER SCIENCE INC. 2002: 146A–146A

  View details for Web of Science ID 000174106700645

• Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis Symposium on Insights on Infection and Immunity Montoya, J. G. UNIV CHICAGO PRESS. 2002: S73–S82

  Abstract

  For the past 40 years, the Toxoplasma Serology Laboratory at the Palo Alto Medical Foundation Research Institute (TSL-PAMFRI) has been dedicated to the laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. TSL-PAMFRI is the "brain child" of Jack S. Remington. Jack's ceaseless devotion to objectivity and uncompromising excellence has made TSL-PAMFRI the Toxoplasma reference laboratory for the Centers for Disease Control and Prevention, the US Food and Drug Administration, and health care providers and clinical laboratories in the United States and other countries. Jack's leadership and vision created, defined, and significantly contributed to the development of laboratory methods for the diagnosis of the infection and diseases caused by T. gondii. A summary of the laboratory tests currently available at TSL-PAMFRI for the diagnosis of infection and disease caused by the parasite is presented here.

  View details for Web of Science ID 000173600700011

  View details for PubMedID 11865443

• Hemolytic uremic syndrome after E. coli O157 : H7 infection in a patient with HIV infection: Clinical implications Cortes, J. A., Parsonnet, J., Chaparro, S. V., Montoya, J. G. OXFORD UNIV PRESS INC. 2001: 1113–13

  View details for Web of Science ID 000171226900170

• Diagnostic value of IgG avidity in Toxoplasma infection: Comparison of 3 commercial kits - Reply JOURNAL OF INFECTIOUS DISEASES Liesenfeld, O., Montoya, J. G., Remington, J. S. 2001; 184 (7): 944-946

  View details for Web of Science ID 000171228400023

• Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center 10th International Symposium on Infections in the Immunocompromised Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hung, S., Giannetti, N., Miller, J., Remington, J. S. OXFORD UNIV PRESS INC. 2001: 629–40

  Abstract

  A total of 1073 infectious episodes (IEs) that occurred in 620 consecutive heart transplantation patients at Stanford Medical Center between 16 December 1980 and 30 June 1996 were reviewed. Infectious complications were a major cause of morbidity and mortality, second only to rejection as the cause of early deaths and the most common cause of late deaths. Of the IEs, 468 (43.6%) were caused by bacteria, 447 (41.7%) by viruses, 109 (10.2%) by fungi, 43 (4.0%) by Pneumocystis carinii, and 6 (0.6%) by protozoa. The largest number of IEs occurred in the lungs (301 [28.1%]). A significant reduction in the incidence of IEs and a delay in presentation after transplantation were observed; these were most likely related to the introduction of new chemoprophylactic regimens during the study period and prevention of significant disease caused by cytomegalovirus.

  View details for Web of Science ID 000170271200007

  View details for PubMedID 11486285

• Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center 10th International Symposium on Infection in the Immunocompromised Host Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hunt, S., Giannetti, N., Miller, J., Remington, J. S. CELL PRESS. 2001: 629–U6

  View details for Web of Science ID 000170271400014

• Brain abscess due to Listeria monocytogenes - Five cases and a review of the literature 38th Annual Meeting of the Infectious-Diseases-Society-of-America Eckburg, P. B., Montoya, J. G., Vosti, K. L. LIPPINCOTT WILLIAMS & WILKINS. 2001: 223–35

  View details for Web of Science ID 000170114800001

  View details for PubMedID 11470983

• Effect of testing for IgG avidity in the diagnosis of Toxoplasma gondii infection in pregnant women: Experience in a US reference laboratory JOURNAL OF INFECTIOUS DISEASES Liesenfeld, O., Montoya, J. G., Kinney, S., Press, C., Remington, J. S. 2001; 183 (8): 1248-1253

  Abstract

  The usefulness of testing for IgG avidity in association with Toxoplasma gondii was evaluated in a US reference laboratory. European investigators have reported that high-avidity IgG toxoplasma antibodies exclude acute infection in the preceding 3 months. In this US study, 125 serum samples taken from 125 pregnant women in the first trimester were chosen retrospectively, because either the IgM or differential agglutination (AC/HS) test in the Toxoplasma serologic profile suggested or was equivocal for a recently acquired infection. Of 93 (74.4%) serum samples with either positive or equivocal results in the IgM ELISA, 52 (55.9%) had high-avidity antibodies, which suggests that the infection probably was acquired before gestation. Of 87 (69.6%) serum samples with an acute or equivocal result in the AC/HS test, 35 (40.2%) had high-avidity antibodies. Forty women were given spiramycin, to prevent congenital transmission, and 7 (17.5%) had high-avidity antibodies. These findings highlight the value of testing a single serum sample obtained in the first trimester of pregnancy for IgG avidity.

  View details for Web of Science ID 000167674600010

  View details for PubMedID 11262207

• Case report - Paclitaxel-induced hypersensitivity pneumonitis: Radiographic and CT findings AMERICAN JOURNAL OF ROENTGENOLOGY Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720

  View details for Web of Science ID 000167118800027

• Paclitaxel-induced hypersensitivity pneumonitis: radiographic and CT findings. AJR. American journal of roentgenology Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720

  View details for PubMedID 11222212

• Posttransplantation lymphoproliferative disease in heart and heart-lung transplant recipients: thirty years experience at our hospital. journal of heart and lung transplantation Chaparro, S., Gao, S., Perlroth, M., Montoya, J., Hastie, T., Miller, J. L., Oyer, P. E., Schroeder, J. 2001; 20 (2): 258-?

  View details for PubMedID 11250519

• Confirmatory serologic testing for acute toxoplasmosis and rate of induced abortions among women reported to have positive Toxoplasma immunoglobulin M antibody titers 35th Annual Meeting of the Infectious-Diseases-Society-of-America Liesenfeld, O., Montoya, J. G., Tathineni, N. J., Davis, M., Brown, B. W., Cobb, K. L., Parsonnet, J., Remington, J. S. MOSBY-ELSEVIER. 2001: 140–45

  Abstract

  Results obtained with commercial testing kits for immunoglobulin M Toxoplasma antibodies may be inaccurate or may be inaccurately interpreted, which may influence whether a woman decides to terminate the pregnancy. This study was undertaken to determine whether confirmatory testing at a reference laboratory and communication of the results and an expert interpretation to the patient's physician would affect the rate of induced abortions among pregnant women with positive results of testing for immunoglobulin M Toxoplasma antibodies in outside laboratories.This was a retrospective cohort study of 811 consecutive pregnant women for whom the toxoplasma serologic profile was performed at a reference laboratory. Almost all the patients had been informed by their physicians that a result of a test for immunoglobulin M Toxoplasma antibodies performed in an outside laboratory was positive. Women were separated into those with a toxoplasma serologic profile result suggestive of a recently acquired infection (group 1) and those with a result suggestive of an infection acquired in the more distant past (group 2). Physician reports of induced abortions were used to determine rates of induced abortion in groups 1 and 2.Of the 811 women 321 (39.6%) were considered likely to have a recent infection (group 1) and 490 (60.4%) were considered likely to have a past infection (group 2). Physicians reported pregnancy outcomes for 433 (53.4%) of 811 women (65.1% and 45.7% in groups 1 and 2, respectively). Whereas 36 of 209 women in group 1 (17.2%) terminated the pregnancy, only 1 of 224 women in group 2 (0.4%) chose abortion (P <.001).Confirmatory serologic testing in a reference laboratory and communication of the results and their correct interpretation by an expert to the patient's physician decreased the rate of unnecessary abortions by approximately 50% among women for whom positive immunoglobulin M Toxoplasma test results had been reported by outside laboratories.

  View details for Web of Science ID 000166679700023

  View details for PubMedID 11174493

• Highly active antiretroviral therapy results in HIV type 1 suppression in lymph nodes, increased pools of naive T cells, decreased pools of activated T cells, and diminished frequencies of peripheral activated HIV type 1-specific CD8(+) T cells AIDS RESEARCH AND HUMAN RETROVIRUSES Gray, C. M., Lawrence, J., Ranheim, E. A., Vierra, M., Zupancic, M., Winters, M., Altman, J., Montoya, J., Zolopa, A., Schapiro, J., Haase, A. T., Merigan, T. C. 2000; 16 (14): 1357-1369

  Abstract

  This study examines sequential lymph nodes from 13 drug-naive patients before and after 24 weeks of highly active antiretroviral therapy (HAART). A multipronged approach was used to study changes in HIV-1 RNA in each paired lymph node in relation to tissue architecture and frequency of naive T cells. After 24 weeks, all patients showed significant suppression of plasma viral load and 12 of 13 showed concordant viral suppression in the lymph node (p = 0.001). Using in situ hybridization and quantitative image analysis, we showed that HIV-1 RNA was reduced to below detectable levels (two copies per cell) in follicular dendritic cell (FDC) and mononuclear cell pools. Independent immunohistochemical analysis of lymph node sections revealed that 5 of 13 patients displayed increased FDC networks and 6 of 13 showed no change and all patients showed increases in tissue-resident CD4+ cells. All lymph node biopsies at 24 weeks showed increased proportions of CD4+ and CD8+ cells coexpressing the naive markers CD45RA and CD62L when compared with baseline values. Significant correlations existed between viral load suppression and loss of activated CD8+ T cells after 24 weeks in both lymph node and blood, which was mirrored by significantly lowered frequencies of activated peripheral Gag peptide/MHC tetramer+ CD8+ cells. Overall, these data show that a potent and successful treatment strategy that significantly suppresses and removes FDC-resident HIV-1 results in improvements in lymphoid architecture and by so doing provides the structures available for increased numbers of naive cells to interact with cognate antigen. In addition, our article shows that suppression of HIV-1 replication results in diminished frequencies of peripherally activated antigen-specific CD8+ cells.

  View details for Web of Science ID 000089593100004

  View details for PubMedID 11018855

• Brain abscess due to Listeria monocytogenes in cardiac transplant recipients Eckburg, P. B., Montoya, J. G., Vosti, K. L. OXFORD UNIV PRESS INC. 2000: 254–54

  View details for Web of Science ID 000088950900290

• HIV-1 genotypic resistance patterns predict response to saquinavir-ritonavir therapy in patients in whom previous protease inhibitor therapy had failed ANNALS OF INTERNAL MEDICINE Zolopa, A. R., Shafer, R. W., Warford, A., Montoya, J. G., Hsu, P., KATZENSTEIN, D., Merigan, T. C., Efron, B. 1999; 131 (11): 813-?

  Abstract

  Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed.To determine HIV-1 genotypic predictors of a virologic response to saquinavir-ritonavir therapy in patients in whom at least one previous protease inhibitor-containing regimen had failed and to compare the predictive value of baseline genotype with that of standard clinical evaluation.Retrospective clinical cohort study.University-based HIV clinic.54 HIV-1-infected adults treated with saquinavir-ritonavir who had experienced virologic failure while receiving a protease inhibitor-containing regimen for at least 3 months.HIV-1 reverse transcriptase and protease gene sequences, CD4 cell counts, clinical characteristics, detailed antiretroviral treatment history, and plasma HIV-1 RNA levels at baseline and at three follow-up time points (median, 4, 12, and 26 weeks). Virologic failure was defined as a plasma HIV RNA level greater than 1000 copies/mL.In 22 patients (41%), a plasma HIV-1 RNA level less than 500 copies/mL was achieved by week 12; in 15 patients (28%), this response was maintained through week 26. Clinical characteristics predicting a poorer response included a diagnosis of AIDS, lower CD4 cell count, and higher plasma HIV RNA level (P<0.03). Number of previous nucleoside reverse transcriptase inhibitors, previous protease inhibitor therapy, and duration of previous protease inhibitor therapy were predictors of poorer response (P<0.01). Multivariate regression models revealed that protease mutations present at the initiation of saquinavir-ritonavir therapy were the strongest predictors of virologic response. A model of clinical features explained up to 45% of the variation in virologic outcomes by week 12, whereas the explained variance was 71% when genotypic predictors were included.In patients in whom protease inhibitor-containing antiretroviral therapy fails, HIV-1 genotype is predictive of virologic response to subsequent therapy. This predictive capacity adds to that of standard clinical evaluation.

  View details for Web of Science ID 000084053200002

  View details for PubMedID 10610625

  View details for PubMedCentralID PMC2606144

• Use of the polymerase chain reaction for diagnosis of ocular toxoplasmosis 35th Annual Meeting of the Infectious-Diseases-Society-of-America Montoya, J. G., Parmley, S., Liesenfeld, O., JAFFE, G. J., Remington, J. S. ELSEVIER SCIENCE INC. 1999: 1554–63

  Abstract

  To report a cohort of patients in whom polymerase chain reaction (PCR) was performed on vitreous samples and to place in perspective the current role of PCR in the diagnosis of ocular toxoplasmosis.Noncomparative case series.Fifteen patients in whom toxoplasmic retinochoroiditis was considered in the differential diagnosis and in whom the clinical presentation was not diagnostic and/or response to treatment was inadequate.Examination of vitreous fluid by PCR and of serum for the presence of Toxoplasma-specific antibodies.Presence of Toxoplasma gondii DNA, serologic test results, clinical findings, treatment, and outcome.In 7 of 15 patients, vitreous fluid examination results by PCR were positive for the presence of T. gondii DNA. Five of these seven patients had serologic test results consistent with Toxoplasma infection acquired in the distant past; the other two patients had serologic test results consistent with retinochoroiditis in the setting of acute toxoplasmosis. The PCR results influenced the management of these patients in six of the seven positive cases. In the eight patients in whom vitreous examination results were negative by PCR, either Toxoplasma serology was negative (6), the retinal lesions were caused by cytomegalovirus (1), or, on further consideration, the eye signs were not consistent with those of toxoplasmic retinochoroiditis (1).In patients in whom toxoplasmosis is considered in the differential diagnosis but in whom the presentation is atypical, PCR was frequently a useful diagnostic aid.

  View details for Web of Science ID 000081732300032

  View details for PubMedID 10442904

• Invasive fungal sinusitis due to Scedosporium apiospermum in a patient with AIDS CLINICAL INFECTIOUS DISEASES Eckburg, P. B., Zolopa, A. R., Montoya, J. G. 1999; 29 (1): 212-213

  View details for Web of Science ID 000081685300042

  View details for PubMedID 10433595

• Risk of tuberculosis in tuberculin skin test-positive liver transplant patients CLINICAL INFECTIOUS DISEASES Chaparro, S. V., Montoya, J. G., Keeffe, E. B., Rhee, J. T., Small, P. M. 1999; 29 (1): 207-208

  View details for Web of Science ID 000081685300037

  View details for PubMedID 10433590

• Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons 5th Conference on Retroviruses and Opportunistic Infections Lawrence, J., Schapiro, J., Winters, M., Montoya, J., Zolopa, A., Pesano, R., Efron, B., Winslow, D., Merigan, T. C. UNIV CHICAGO PRESS. 1999: 1356–64

  Abstract

  The efficacy of sequential protease inhibitor therapy was studied in 16 human immunodeficiency virus (HIV) 1-infected persons in whom saquinavir with multiple nucleoside reverse transcriptase (RT) inhibitors (NRTI) had failed. Nelfinavir plus two NRTIs (new or continued) resulted in minimal (0.59 log RNA copies/mL) and transient (8 weeks) suppression of plasma HIV RNA levels. Rapid failure was surprisingly associated with baseline presence of protease gene mutation L90M (P=.04) in the absence of D30N and with RT mutations D67N (P<.01), K70R/S (P=.02), and K219Q/W/R/E (P<.01). Ten patients were subsequently switched to indinavir plus nevirapine and 2 NRTIs, resulting in a median 1.62 log reduction in plasma HIV RNA, with 3 patients maintaining 400 copies/mL for 24 weeks. These results suggest that nelfinavir may have limited utility after saquinavir failure, particularly without potent concomitant therapy. Combining an NRTI with a new protease inhibitor for rescue may improve response.

  View details for Web of Science ID 000080561100007

  View details for PubMedID 10228055

• Association between non-bacterial infections and cardiac allograft atherosclerosis Giannetti, N., Montoya, J., Behr, M., Remmington, J., Valantine, H. A., Hunt, S. A. LIPPINCOTT WILLIAMS & WILKINS. 1998: 692–92

  View details for Web of Science ID 000076594403653

• Toxoplasmic myocarditis and polymyositis in patients with acute acquired toxoplasmosis diagnosed during life CLINICAL INFECTIOUS DISEASES Montoya, J. G., Jordan, R., Lingamneni, S., Berry, G. J., Remington, J. S. 1997; 24 (4): 676-683

  Abstract

  The presence of both toxoplasmic myocarditis and myositis in the same individual has been reported only at autopsy. We report the first case of biopsy-proven toxoplasmic myocarditis and polymyositis simultaneously occurring in the same individual that was diagnosed during life. Results of her toxoplasmic serology were consistent with acute toxoplasmosis. She subsequently developed visual symptoms consistent with toxoplasmic chorioretinitis. She had a positive clinical response to therapeutic agents specific against Toxoplasma gondii. Her toxoplasmic serological profile established the diagnosis of acute toxoplasmosis. A toxoplasmic serological profile should be obtained for patients with myocarditis and/or polymyositis of unclear etiology. Endomyocardial or skeletal muscle tissue biopsies may establish the definitive diagnosis of toxoplasmic myocarditis or polymyositis, respectively. Examination of blood by polymerase chain reaction analysis before antitoxoplasmic treatment and early in the course of primary infection with T. gondii may prove useful.

  View details for Web of Science ID A1997WT72500020

  View details for PubMedID 9145743

• False-positive results in immunoglobulin M (IgM) Toxoplasma antibody tests and importance of confirmatory testing: The Platelia Toxo IgM test JOURNAL OF CLINICAL MICROBIOLOGY Liesenfeld, O., Press, C., Montoya, J. G., Gill, R., ISAACRENTON, J. L., HEDMAN, K., Remington, J. S. 1997; 35 (1): 174-178

  Abstract

  Although tests for detection of immunoglobulin M (IgM) toxoplasma antibodies have been reported to have a high degree of accuracy, it is well recognized by investigators in the United States and Europe that false-positive results may occur with many of these tests, at times to an alarming degree. Unfortunately, this information is not well documented in the literature. Studies on various toxoplasma IgM test kits are frequently flawed. The investigators often use reference tests which have not previously been carefully evaluated as well as sera that were not appropriate to answer the question of how often false-positive results might occur. We recently had the unique opportunity to evaluate the accuracy of the Platelia Toxo IgM test in 575 serum samples obtained during an outbreak of toxoplasmosis which occurred in 1995 in the Capital Regional District of British Columbia, Canada. When compared with results obtained in a reference IgM enzyme-linked immunosorbent assay (ELISA), the Platelia Toxo IgM test had a sensitivity of 99.4%, specificity of 49.2%, positive predictive value of 51.9%, negative predictive value of 99.3%, and an overall agreement of 67.0%. In an attempt to resolve discrepancies between these two tests, a serological profile (Sabin-Feldman dye test, IgA and IgE antibody tests, differential agglutination [AC/HS] test, and IgG avidity method) was performed. Of 153 serum samples that were positive in the Platelia Toxo IgM test and negative in the IgM ELISA, 71 (46.4%) were negative in the Sabin-Feldman dye test. Of the serum samples that were positive in the dye test, 77 (93.9%) had a serological profile most compatible with an infection acquired in the distant past. These results reveal high numbers of false-positive results in the Platelia Toxo IgM test and highlight the importance of appropriate evaluation of commercial tests that are currently being marked. Our results also emphasize the importance of confirmatory testing to determine whether the results of an IgM antibody test reflect the likelihood of a recently acquired infection.

  View details for Web of Science ID A1997VY56600031

  View details for PubMedID 8968902

• Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 1996; 23 (2): 277-282

  Abstract

  Ocular toxoplasmosis is considered to be the most commonly recognized cause of chorioretinitis in the United States. It is commonly believed that the majority of cases of acute toxoplasmic chorioretinitis involving adults in the United States are late sequelae of congenital infection and that the condition is rarely associated with acute postnatally acquired infection. We report here the clinical and serological test findings for 22 adults with acute toxoplasmic chorioretinitis that occurred in the setting of acute postnatally acquired toxoplasmosis. The initial serum specimen from each adult yielded an acute toxoplasmic serological profile, on the basis of the following positive results: 95.5%, Sabin-Feldman dye test [titer of > or = 1:1,024]; 95.5%, IgM ELISA; 90.9%, IgA ELISA; 77.3%, IgE ELISA; 95.5%, IgE immunosorbent agglutination assay; and 86.4%, differential agglutination (AC/HS) test (acute pattern). Detection of IgA or IgE antibodies or an acute pattern in the AC/HS test was particularly helpful in diagnosis for those patients whose ELISA IgM titers at presentation were negative or lowly positive. Thus, acute toxoplasmic chorioretinitis occurring with a recently acquired Toxoplasma gondii infection would appear to be more common in the United States than previously recognized, and a toxoplasmic serological profile is useful in diagnosing this entity.

  View details for Web of Science ID A1996VA55400011

  View details for PubMedID 8842263

• Human CD4(+) and CD8(+) T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells INFECTION AND IMMUNITY Montoya, J. G., Lowe, K. E., CLAYBERGER, C., Moody, D., Do, D., Remington, J. S., Talib, S., Subauste, C. S. 1996; 64 (1): 176-181

  Abstract

  Studies to determine if Toxoplasma gondii-specific human T cells lyse parasite-infected cells have yielded conflicting results. Furthermore, attempts to obtain human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a reproducible system for their generation. By using paraformaldehyde-fixed, T. gondii-infected peripheral blood mononuclear cells as antigen-presenting cells, we developed a method whereby T. gondii-specific T-cell lines can be reproducibly generated. Six T. gondii-specific T-cell lines were generated from an individual chronically infected with T. gondii. Cytofluorometric analysis of these lines revealed > 99% CD3+, 85 to 95% CD3+ alpha beta T-cell-receptor-positive (TCR+), 5 to 9% CD3+ gamma delta TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells were examined during the first 3 weeks of stimulation and >99% CD3+, >99% CD3+ alpha beta TCR+, < 1% CD3+ gamma delta TCR+, 20 to 40% CD4+, and 60 to 80% CD8+ cells when cells were examined between 5 and 11 weeks. Both CD4+ and CD8+ T cells had remarkable cytotoxic activity against T. gondii-infected target cells (30 to 50% specific Cr release at an effector-to-target ratio of 30:1) but not against uninfected target cells ( < 10% at an effector-to-target ratio of 30:1). Cytotoxic activity by the whole T-cell lines was not T. gondii strain specific. Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49 strains and the RH strain (which was used to infect peripheral blood mononuclear cells). T. gondii-specific T-cell lines displayed the predominant expression of V beta 7 TCR. The CDR3 regions of the V beta 7 TCRs of these T-cell lines showed a striking degree of sequence identity (oligoclonality). T-cell lines obtained by the method reporter here can be used to characterize functional activity of T-lymphocyte subsets in humans infected with T. gondii.

  View details for Web of Science ID A1996TM71800025

  View details for PubMedID 8557337

• Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients JOURNAL OF INFECTIOUS DISEASES Suzuki, Y., Wong, S. Y., GRUMET, F. C., Fessel, J., Montoya, J. G., Zolopa, A. R., PORTMORE, A., SCHUMACHERPERDREAU, F., Schrappe, M., Koppen, S., Ruf, B., Brown, B. W., Remington, J. S. 1996; 173 (1): 265-268

  Abstract

  The frequency of HLA-DQ antigens in AIDS patients with toxoplasmic encephalitis (TE) were examined. HLA-DQ3 was significantly more frequent in white North American AIDS patients with TE (85.0%) than in the general white population (51.8%; P = .007, corrected P = .028) or randomly selected control AIDS patients who had not developed TE (40.0%; P = .016). In contrast, the frequency of HLA-DQ1 was lower in TE patients than in healthy controls (40.0% vs. 66.5%, P = .027), but this difference did not reach statistical significance when corrected for the number of variables tested (corrected P = .108 for the general white population). HLA-DQ3 thus appears to be a genetic marker of susceptibility to development of TE in AIDS patients, and DQ1 may be a resistance marker. These HLA associations with disease indicate that development of TE in AIDS patients is affected by a gene or genes in the HLA complex and that HLA-DQ typing may help in decisions regarding TE prophylaxis.

  View details for Web of Science ID A1996TM34300042

  View details for PubMedID 8537674

• PREFERENTIAL ACTIVATION AND EXPANSION OF HUMAN PERIPHERAL-BLOOD GAMMA-DELTA T-CELLS IN RESPONSE TO TOXOPLASMA GONDII IN VITRO AND THEIR CYTOKINE PRODUCTION AND CYTOTOXIC ACTIVITY AGAINST T-GONDII-INFECTED CELLS JOURNAL OF CLINICAL INVESTIGATION Subauste, C. S., Chung, J. Y., Do, D., Koniaris, A. H., Hunter, C. A., Montoya, J. G., Porcelli, S., Remington, J. S. 1995; 96 (1): 610-619

  Abstract

  Studies were conducted to determine if gamma delta T cells participate in the immune response to Toxoplasma gondii. Preferential expansion of human gamma delta T cells occurred when peripheral blood T cells from either T. gondii-seronegative or seropositive individuals were incubated with autologous PBMC infected with the parasite. That gamma delta T cells proliferated after incubation with infected cells was confirmed using purified of gamma delta T cells. These T. gondii-induced gamma delta T cell responses did not require prior exposure to the parasite since T cells obtained from umbilical cord blood from seronegative newborns also exhibited preferential expansion of gamma delta T cells. Cytofluorometric analysis of T cells obtained from either umbilical cord blood or peripheral blood from adults revealed that V gamma 9+ and V delta 2+ gamma delta T cells responded to stimulation with infected cells. Preferential expansion of gamma delta T cells was not restricted by polymorphic determinants of MHC molecules. PBMC that had internalized killed parasites but not PBMC incubated with T. gondii lysate antigens also stimulated preferential expansion and activation of gamma delta T cells as assessed by expression of CD25 and HLA-DR molecules. V gamma 9+V delta 2+ gamma delta T cells were cytotoxic for T. gondii-infected cells in an MHC-unrestricted manner, and produced IFN-gamma, IL-2, TNF-alpha, but not IL-4 when incubated with cells infected with the parasite. These results suggest that rapid induction of a remarkable primary gamma delta T cell response may be important in the early protective immune response to T. gondii.

  View details for Web of Science ID A1995RH89400073

  View details for PubMedID 7615835

• STUDIES ON THE SERODIAGNOSIS OF TOXOPLASMIC LYMPHADENITIS CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 1995; 20 (4): 781-789

  Abstract

  The purpose of this study was to determine the value of conventional and newer serological tests (toxoplasmic serological profile) in the diagnosis of toxoplasmic lymphadenitis (TL). We studied 40 consecutive patients with biopsy-proven TL. Cervical, axillary, or occipital adenopathy was present in 72.5%, 20%, and 7.5% of the patients, respectively. Low-grade fever, fatigue, general malaise, or sore throat were present in only 6 (15%) of the 40 patients. A positive result for all serological tests was time dependent from the clinical onset of lymphadenopathy. The initial serum samples were positive for antibody for each patient, as shown by a Sabin-Feldman dye test. Between 3 and 6 months after clinical onset of TL, all of the patients had antibody titers of > or = 1:1,024. The ELISA was positive for IgM antibodies in all of the patients in the first 3 months. Detection of IgA or IgE antibodies or an acute pattern in the differential agglutination test was helpful in diagnosing TL in those patients who had negative, low-positive, or equivocal titers of IgM antibodies (as measured by ELISA) after 3 months. A toxoplasmic serological profile on the first serum specimen drawn after clinical onset of TL had a sensitivity of 100%. It is advisable to obtain such a serological profile in cases of asymptomatic lymphadenopathy before biopsy is carried out, especially for those individuals who have negative or equivocal IgM antibody titers.

  View details for Web of Science ID A1995QP66200008

  View details for PubMedID 7795074

• SERODIAGNOSIS OF TOXOPLASMIC LYMPHADENOPATHY (TL) Montoya, J. G., Remington, J. S. SLACK INC. 1994: A285–A285

  View details for Web of Science ID A1994NF02000987

• PERIPHERAL-BLOOD MONONUCLEAR CELL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROVIRAL DNA QUANTIFICATION BY POLYMERASE CHAIN-REACTION - RELATIONSHIP TO IMMUNODEFICIENCY AND DRUG EFFECT JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Wood, R., KATZENSTEIN, D., HOLODNY, M., Merigan, T. C. 1993; 31 (10): 2692-2696

  Abstract

  Human immunodeficiency virus type 1 (HIV-1) proviral DNA from peripheral blood mononuclear cells (PBMCs) was quantitated in 61 HIV-1-seropositive individuals by a nonisotopic polymerase chain reaction assay. Primers from the gag region (SK38, SK39) were used to determine the log10 HIV-1 proviral copy number per 10(6) CD4+ T lymphocytes (peripheral blood proviral load). A standard curve was generated for each assay by using ACH-2 cell DNA. The peripheral blood proviral load was followed in 15 individuals in a longitudinal study and was measured in 45 individuals in a cross-sectional analysis. Three of four untreated patients who were followed for 14 months had stable PBMC proviral loads and CD4+ T lymphocyte counts; one untreated patient had a sustained increase in PBMC proviral load followed 5 months later by a significant decline in the CD4+ T lymphocyte count. Eleven previously untreated individuals were monitored for 1 year following initiation of zidovudine and/or 2',3'-dideoxyinosine therapy. The mean log10 number of proviral HIV-1 copies per 10(6) CD4+ T cells decreased from 4.3 +/- 0.4 at the baseline to 3.5 +/- 0.6 after 2 to 4 months of therapy (P < 0.01). This initial 0.8 log10 fall in the PBMC proviral load after the initiation of therapy was followed by a rise in the PBMC proviral load by the sixth month of therapy. The PBMC proviral load in 45 subjects, both treated (n = 25) and untreated (n = 20), correlated inversely with the CD4+ T lymphocyte count (P < 0.01, R = 0.49). PBMC proviral DNA quantification by a nonisotopic polymerase chain reaction assay correlates with HIV-1 disease progression and could be used to monitor the effect of antiretroviral therapy.

  View details for Web of Science ID A1993LY05900024

  View details for PubMedID 7902845

• MEASUREMENT OF HIV VIRUS LOAD AND GENOTYPIC RESISTANCE BY GENE AMPLIFICATION IN ASYMPTOMATIC SUBJECTS TREATED WITH COMBINATION THERAPY JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Holodniy, M., KATZENSTEIN, D., Winters, M., Montoya, J., Shafer, R., Kozal, M., Ragni, M., Merigan, T. C. 1993; 6 (4): 366-369

  Abstract

  Quantification of viral load in HIV disease has become increasingly important as a marker of antiviral efficacy. We applied gene amplification techniques in vivo to asses antiretroviral activity of combination therapy. Five HIV-infected subjects, four of whom were drug naive, were administered combination therapy with zidovudine (ZDV) and didanosine (ddI). Plasma and peripheral blood mononuclear cells (PBMC) were obtained twice at baseline and then at 1, 3, 6, 9, and 12 months after the initiation of therapy. Results show that plasma HIV RNA copy number fell from 2,170 +/- 660/ml to undetectable at 1 month, with continued suppression at 12 months. HIV proviral DNA copy number decreased from 3.9 to 3.0 log10/10(6) CD4+ T cells at 12 months. Cell dilution cultures were positive in 4 of 5 subjects at baseline and in only 1 of 5 after 12 months. CD4+ T-cell count increased from 390 +/- 30/mm3 pretherapy, to 505 +/- 66/mm3 after 6 months of therapy, but returned to baseline levels after 12 months of therapy. No mutations were detected from PBMC DNA for codon 215 and 74 in the HIV pol gene from the drug-naive subjects. These findings suggest that gene amplification techniques can be used to study changes in viral load or genotype and can be applied in real time to samples from patients involved in clinical trials.

  View details for Web of Science ID A1993KU22100007

  View details for PubMedID 8095981

• SAFETY AND EFFICACY OF POLYETHYLENE-GLYCOL MODIFIED INTERLEUKIN-2 AND ZIDOVUDINE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - A PHASE I-II STUDY JOURNAL OF INFECTIOUS DISEASES Wood, R., Montoya, J. G., Kundu, S. K., Schwartz, D. H., Merigan, T. C. 1993; 167 (3): 519-525

  Abstract

  The safety and efficacy of combined therapy with polyethylene glycolated (PEG) interleukin (IL)-2 and zidovudine was assessed in 19 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects in a phase I/II open-label dose-ranging study. During courses of three weekly infusions of PEG IL-2, dose-limiting side effects were seen at 5 x 10(6) IU/m2 and reversible encephalopathy in 1 subject at 3 x 10(6) IU/m2. Significant increases were seen in CD4 cell counts (P < .01), NK cell activity (P < .05), and HIV-specific cytotoxicity (P < .01). Virologic monitoring (quantitative DNA polymerase chain reaction and p24 antigen assay) showed no evidence of increased HIV activation. Patients with CD4 cells < 200/mm3 were entered into a chronic dosing phase. PEG IL-2 was given at 14-day intervals at doses of 10(6) IU/m2 for 8 weeks and 3 x 10(6) IU/m2 for up to 16 weeks, resulting in mean CD4 cell count elevations of 16% and 33%, respectively. PEG IL-2 appears to warrant further investigation, especially in subjects with CD4 cell counts < 200/mm3, to determine whether increased lymphocyte numbers will translate into improved clinical outcome.

  View details for Web of Science ID A1993KN15200001

  View details for PubMedID 8095058

• [Community practice in units of primary care at the rural level: an experience with medical students]. Educación médica y salud de Bedoya, Y. A., Casas, L. A., Grill, H., Hoyos, J., Jiménez, F., Montoya, J. G., Torres, C. H. 1984; 18 (2): 164-181

  Abstract

  During the three weeks of vacation from the sixth semester of medical school in May 1982, a group of six students and a professor in the Department of Social Medicine of Valle University, Colombia, conducted a voluntary experimental exercise in some of the rural primary care units of Tuluá Regional Hospital in Valle del Cauca department, using the hospital's Administration as their operational center. The purpose of the exercise, called "Ruralito," was to compile a health census of the general characteristics of the rural communities constituting the primary health care service area. The teaching process employed was designed to encourage the students to act on their own initiative and in their own way and to exchange experiences and plan measures even after completion of the three years of the exercise. The article describes the salient features of the relationship between teaching practice and public health practice in this first exercise, in which a new instructional framework was introduced for the area of medicine; the students' highly favorable reaction to this exercise and the substantial gains made justify the expectation that it will serve as an example for future student exercises in similar processes.

  View details for PubMedID 6745159