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Article ; Online: Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials.

Westin, Jason R / Kersten, Marie José / Salles, Gilles / Abramson, Jeremy S / Schuster, Stephen J / Locke, Frederick L / Andreadis, Charalambos

American journal of hematology

2021 Volume 96, Issue 10, Page(s) 1295–1312

Abstract: Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell ... ...

Abstract	Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported. Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.
MeSH term(s)	Antigens, CD19/adverse effects ; Antigens, CD19/therapeutic use ; Biological Products ; Clinical Trials as Topic ; Humans ; Immunotherapy, Adoptive/adverse effects ; Lymphoma, Large B-Cell, Diffuse/therapy ; Neoplasm Recurrence, Local/therapy ; Receptors, Antigen, T-Cell/therapeutic use ; Treatment Outcome
Chemical Substances	Antigens, CD19 ; Biological Products ; Receptors, Antigen, T-Cell ; tisagenlecleucel (Q6C9WHR03O) ; axicabtagene ciloleucel (U2I8T43Y7R)
Language	English
Publishing date	2021-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.26301
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Article ; Online: Grading of neurological toxicity in patients treated with tisagenlecleucel in the JULIET trial.

Maziarz, Richard T / Schuster, Stephen J / Romanov, Vadim V / Rusch, Elisha S / Li, Junlong / Signorovitch, James E / Maloney, David G / Locke, Frederick L

Blood advances

2020 Volume 4, Issue 7, Page(s) 1440–1447

Abstract: Chimeric antigen receptor-T (CAR-T) cell therapy achieves durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), but may be associated with neurological toxicity (NT). We retrospectively assessed differences and ...

Abstract	Chimeric antigen receptor-T (CAR-T) cell therapy achieves durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), but may be associated with neurological toxicity (NT). We retrospectively assessed differences and concordance among 3 available grading scales (the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 [CTCAE], modified CAR-T Related Encephalopathy Syndrome [mCRES], and American Society for Transplantation and Cellular Therapy [ASTCT] scales) applied to the same set of NT data from the JULIET (A Phase 2, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory DLBCL) trial. Individual patient-level NT data from the phase 2, single-group, global, pivotal JULIET trial (NCT02445248) were retrospectively and independently graded, using CTCAE, ASTCT, and mCRES, by 4 medical experts with experience managing patients with 3 different CD19-targeted CAR constructs. According to the US Food and Drug Administration definition of NT using CTCAE, 62 of 106 patients infused with tisagenlecleucel had NT as of September 2017. Among 111 patients infused with tisagenlecleucel (as of December 2017), the 4 experts identified 50 patients (45%) who had any-grade NT per CTCAE, 19 (17%) per mCRES, and 19 (17%) per ASTCT. Reevaluation according to the mCRES/ASTCT criteria downgraded 31 events deemed NT by CTCAE to grade 0. This is the first study to retrospectively apply CTCAE, mCRES, and ASTCT criteria to the same patient data set. We conclude that CTCAE v4.03 was not designed for, and is suboptimal for, grading CAR-T cell therapy-associated NT. The CRES and ASTCT scales, which measure immune effector cell-associated neurotoxicity syndrome, offer more accurate assessments of NT after CAR-T cell therapy.
MeSH term(s)	Adult ; Antigens, CD19 ; Humans ; Immunotherapy, Adoptive ; Receptors, Antigen, T-Cell/genetics ; Retrospective Studies
Chemical Substances	Antigens, CD19 ; Receptors, Antigen, T-Cell ; tisagenlecleucel (Q6C9WHR03O)
Language	English
Publishing date	2020-05-04
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2019001305
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Article ; Online: Grading and management of cytokine release syndrome in patients treated with tisagenlecleucel in the JULIET trial.

Schuster, Stephen J / Maziarz, Richard T / Rusch, Elisha S / Li, Junlong / Signorovitch, James E / Romanov, Vadim V / Locke, Frederick L / Maloney, David G

Blood advances

2020 Volume 4, Issue 7, Page(s) 1432–1439

Abstract: Chimeric antigen receptor T-cell (CAR-T) therapy yields durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Cytokine release syndrome (CRS) is a CAR-T therapy-related adverse event. To date, clinical trials ... ...

Abstract	Chimeric antigen receptor T-cell (CAR-T) therapy yields durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Cytokine release syndrome (CRS) is a CAR-T therapy-related adverse event. To date, clinical trials of different CAR-T products have not been aligned on CRS grading scales and management algorithms. We assessed concordance between the Penn, Lee, and American Society for Transplantation and Cellular Therapy (ASTCT) grading systems by retrospectively regrading CRS events in the JULIET (A Phase 2, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory DLBCL) trial. Four medical experts with experience treating patients with 3 different CAR-T products independently regraded individual patient-level CRS events from the phase 2, global, pivotal JULIET trial (#NCT02445248). As of 8 December 2017, a total of 111 patients with r/r DLBCL underwent infusion with tisagenlecleucel. Sixty-four patients had CRS events graded per the Penn scale; on retrospective review, 63 and 61 patients had CRS events regraded per the Lee and ASTCT criteria, respectively. The Lee scale yielded concordance for 39, lower grade for 20, and higher grade for 5 events compared with the Penn scale. The ASTCT criteria provided concordance for 37, lower grade for 23, and higher grade for 4 events compared with the Penn scale. Sixteen (14%) of 111 patients in the JULIET trial received tocilizumab, all for severe events (Penn grade 3/4 CRS). This study is the first to assess concordance between 3 CRS grading scales using the same patient data set and to compare tocilizumab use according to the Lee scale in the JULIET trial and the ZUMA-1 (Long-Term Safety and Activity of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma) trial. This analysis describes key differences between grading scales and may inform CRS management practices.
MeSH term(s)	Adult ; Cytokine Release Syndrome ; Humans ; Receptors, Antigen, T-Cell/genetics ; Receptors, Chimeric Antigen ; Retrospective Studies
Chemical Substances	Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; tisagenlecleucel (Q6C9WHR03O)
Language	English
Publishing date	2020-03-24
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2019001304
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Article: Cultivation of Babesia and Babesia-like blood parasites: agents of an emerging zoonotic disease.

Schuster, Frederick L

Clinical microbiology reviews

2001 Volume 15, Issue 3, Page(s) 365–373

Abstract: Babesia and its close relatives are members of a group of organisms called piroplasms, a name which comes from their pear-shaped outlines. Long associated with blood diseases of cattle and other mammals, members of the genus Babesia have been recognized ... ...

Abstract	Babesia and its close relatives are members of a group of organisms called piroplasms, a name which comes from their pear-shaped outlines. Long associated with blood diseases of cattle and other mammals, members of the genus Babesia have been recognized since the 1950s as infectious agents in humans. Species of this protozoan blood parasite that have routinely been isolated from mice (B. microti) or cattle (B. divergens) have also been isolated from humans. In addition to these familiar species, new isolates that resist being placed in existing taxonomic categories are the basis for rethinking their phylogenetic relationships based on sequencing data. The parasite represents a threat to the safety of the blood supply in that blood from asymptomatic humans can transmit Babesia to blood recipients. Such transmissions have occurred. The development of methods for cultivation of these organisms represents a significant opportunity to study their biology and disease potential. In addition, in vitro cultivation has provided a basis for studying immune responses of mammals to these infectious agents, with the hope of ultimately producing attenuated strains that could be used for immunizing of cattle and, perhaps, humans who live in areas of endemicity. The microaerophilous stationary phase culture technique, which uses a tissue culture medium base supplemented with appropriate serum and erythrocytes, has made it possible to obtain large numbers of parasitized erythrocytes for studying the biology of this parasite.
MeSH term(s)	Animals ; Babesia/classification ; Babesia/growth & development ; Babesia/isolation & purification ; Babesiosis/parasitology ; Babesiosis/veterinary ; Cattle ; Cells, Cultured ; Culture Media ; Dogs ; Erythrocytes/parasitology ; Humans ; Parasitology/methods ; Zoonoses/parasitology
Chemical Substances	Culture Media
Language	English
Publishing date	2001-10-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/CMR.15.3.365-373.2002
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Article: Cultivation of pathogenic and opportunistic free-living amebas.

Schuster, Frederick L

Clinical microbiology reviews

2001 Volume 15, Issue 3, Page(s) 342–354

Abstract: Free-living amebas are widely distributed in soil and water, particularly members of the genera Acanthamoeba and NAEGLERIA: Since the early 1960s, they have been recognized as opportunistic human pathogens, capable of causing infections of the central ... ...

Abstract	Free-living amebas are widely distributed in soil and water, particularly members of the genera Acanthamoeba and NAEGLERIA: Since the early 1960s, they have been recognized as opportunistic human pathogens, capable of causing infections of the central nervous system (CNS) in both immunocompetent and immunocompromised hosts. Naegleria is the causal agent of a fulminant CNS condition, primary amebic meningoencephalitis; Acanthamoeba is responsible for a more chronic and insidious infection of the CNS termed granulomatous amebic encephalitis, as well as amebic keratitis. Balamuthia sp. has been recognized in the past decade as another ameba implicated in CNS infections. Cultivation of these organisms in vitro provides the basis for a better understanding of the biology of these amebas, as well as an important means of isolating and identifying them from clinical samples. Naegleria and Acanthamoeba can be cultured axenically in cell-free media or on tissue culture cells as feeder layers and in cultures with bacteria as a food source. Balamuthia, which has yet to be isolated from the environment, will not grow on bacteria. Instead, it requires tissue culture cells as feeder layers or an enriched cell-free medium. The recent identification of another ameba, Sappinia diploidea, suggests that other free-living forms may also be involved as causal agents of human infections.
MeSH term(s)	Acanthamoeba/growth & development ; Acanthamoeba/pathogenicity ; Amebiasis/parasitology ; Amoeba/growth & development ; Amoeba/pathogenicity ; Animals ; Culture Media ; Humans ; Mice ; Naegleria/growth & development ; Naegleria/pathogenicity ; Opportunistic Infections/parasitology ; Parasitology/methods
Chemical Substances	Culture Media
Language	English
Publishing date	2001-10-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/CMR.15.3.342-354.2002
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Article: Cultivation of plasmodium spp.

Schuster, Frederick L

Clinical microbiology reviews

2001 Volume 15, Issue 3, Page(s) 355–364

Abstract: Cultivation of both human and non-human species of Plasmodium spp., the causal agent of malaria, has been a major research success, leading to a greater understanding of the parasite. Efforts at cultivating the organisms in vitro are complicated by the ... ...

Abstract	Cultivation of both human and non-human species of Plasmodium spp., the causal agent of malaria, has been a major research success, leading to a greater understanding of the parasite. Efforts at cultivating the organisms in vitro are complicated by the parasites' alternating between a human host and an arthropod vector, each having its own set of physiological, metabolic, and nutritional parameters. Life cycle stages of the four species that infect humans have been established in vitro. Of these four, P. falciparum remains the only species for which all stages have been cultured in vitro; different degrees of success have been achieved with the other human Plasmodium spp. The life cycle includes the exoerythrocytic stage (within liver cells), the erythrocytic stage (within erythrocytes or precursor reticulocytes), and the sporogonic stage (within the vector). Culture media generally consist of a basic tissue culture medium (e.g., minimal essential medium or RPMI 1640) to which serum and erythrocytes are added. Most of the efforts have been directed toward the stage found in the erythrocyte. This stage has been cultivated in petri plates or other growth vessels in a candle jar to generate elevated CO(2) levels or in a more controlled CO(2) atmosphere. Later developments have employed continuous-flow systems to reduce the labor-intensive nature of medium changing. The exoerythrocytic and sporogonic life cycle stages have also been cultivated in vitro. A number of avian, rodent, and simian malarial parasites have also been established in vitro. Although cultivation is of great help in understanding the biology of Plasmodium, it does not lend itself to use for diagnostic purposes.
MeSH term(s)	Animals ; Cells, Cultured ; Culture Media ; Erythrocytes/parasitology ; Humans ; Malaria/parasitology ; Malaria/veterinary ; Parasitology/methods ; Plasmodium/growth & development
Chemical Substances	Culture Media
Language	English
Publishing date	2001-10-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/CMR.15.3.355-364.2002
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Article ; Online: Intraoperative Navigation Is Associated with Reduced Blood Loss During C1-C2 Posterior Cervical Fixation.

Hitti, Frederick L / Hudgins, Eric D / Chen, H Isaac / Malhotra, Neil R / Zager, Eric L / Schuster, James M

World neurosurgery

2017 Volume 107, Page(s) 574–578

Abstract: Objective: Traumatic injuries, degenerative/rheumatologic conditions, tumors, or infections of the upper cervical spine may in certain circumstances require surgical stabilization. C1 lateral mass screws (Harms technique) in combination with C2 ... ...

Abstract	Objective: Traumatic injuries, degenerative/rheumatologic conditions, tumors, or infections of the upper cervical spine may in certain circumstances require surgical stabilization. C1 lateral mass screws (Harms technique) in combination with C2 instrumentation (pars, pedicle, translaminar screws) have become a mainstay of surgical treatment. The surgical anatomy of the C1 lateral mass can be challenging especially with the robust venous plexus that often causes significant bleeding with exposure of the C1-C2 articular complex. The purpose of this study was to examine whether the use of navigation reduced intraoperative blood loss during atlantoaxial fixation. Methods: We reviewed our institutional experience with atlantoaxial instrumentation with and without navigation from 2007 to 2016. We limited our cases to those requiring C1-C2 stabilization in traumatic and degenerative cases and not as part of more extensive surgical stabilizations. We identified 45 consecutive patients and compared intraoperative blood loss, need for transfusion, and time of procedure with and without the use of navigation. Results: There was a significant reduction in the amount of intraoperative blood loss in the navigated (n = 20) versus non-navigated cases (n = 25). In addition, although the navigated cases initially were longer, currently there is no significant difference in the length of the cases. Conclusions: In our series, surgical navigation significantly reduced blood loss compared with non-navigated cases without increasing surgical time or risk of complication. Furthermore, navigation has the potential to reduce operative times due to a reduction in blood loss.
Language	English
Publishing date	2017-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2017.08.051
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Article: Inability to make a premortem diagnosis of Acanthamoeba species infection in a patient with fatal granulomatous amebic encephalitis.

Bloch, Karen C / Schuster, Frederick L

Journal of clinical microbiology

2005 Volume 43, Issue 6, Page(s) 3003–3006

Abstract: Granulomatous amebic encephalitis (GAE), an infection of immunocompromised hosts, is almost uniformly fatal. A case of GAE in a patient who failed to mount a serologic response to Acanthamoeba polyphaga is presented. Although Acanthamoeba polyphaga that ... ...

Abstract	Granulomatous amebic encephalitis (GAE), an infection of immunocompromised hosts, is almost uniformly fatal. A case of GAE in a patient who failed to mount a serologic response to Acanthamoeba polyphaga is presented. Although Acanthamoeba polyphaga that is sensitive to multiple antimicrobials grew from brain tissue, an inability to make a premortem diagnosis precluded therapy.
MeSH term(s)	Acanthamoeba/isolation & purification ; Aged ; Amebiasis/diagnosis ; Amebiasis/parasitology ; Animals ; Encephalitis/diagnosis ; Encephalitis/parasitology ; Fatal Outcome ; Female ; Granuloma/diagnosis ; Granuloma/parasitology ; Humans
Language	English
Publishing date	2005-06
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.43.6.3003-3006.2005
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Article: Predictors of Neurological Outcome Following Subaxial Cervical Spine Trauma.

Hitti, Frederick L / Mcshane, Brendan J / Yang, Andrew I / Rinehart, Cole / Albayar, Ahmed / Branche, Marc / Yolcu, Yagiz U / Ali, Zarina S / Schuster, James M / Ozturk, Ali K

Cureus

2019 Volume 11, Issue 12, Page(s) e6402

Abstract: Background The treatment of traumatic subaxial cervical spine injuries remains controversial. The American Spinal Injury Association (ASIA) impairment scale (AIS) is a widely-used metric to score neurological function after spinal cord injury (SCI). Here, ...

Abstract	Background The treatment of traumatic subaxial cervical spine injuries remains controversial. The American Spinal Injury Association (ASIA) impairment scale (AIS) is a widely-used metric to score neurological function after spinal cord injury (SCI). Here, we evaluated the outcomes of patients who underwent treatment of subaxial cervical spine injuries to identify predictors of neurologic function after injury and treatment. Methods We performed a retrospective logistic regression analysis to determine predictors of neurological outcome; 76 patients met the inclusion criteria and presented for a three-month follow-up. The mean age was 50.6±18.7 years old and the majority of patients were male (n=49, 64%). Results The majority of patients had stable AIS scores at three months (n=56, 74%). A subset of patients showed improvement at three months (n=16, 21%), while a small subset of patients had neurological decline at three months (n=4, 5%). In our model, increasing patient age (odds ratio [OR] 1.39, 1.10-2.61 95% confidence interval [CI], P<0.001) and a previous or current diagnosis of cancer (OR 22.4, 1.25-820 95% CI, P=0.04) significantly increased the odds of neurological decline at three months. In patients treated surgically, we found that delay in surgical treatment (>24 hours) was associated with a decreased odds of neurological improvement (OR 0.24, 0.05-0.99 95% CI, P=0.048). Cervical spine injuries are heterogeneous and difficult to manage. Conclusion We found that increasing patient age and an oncologic history were associated with neurological deterioration while a delay in surgical treatment was associated with decreased odds of improvement. These predictors of outcome may be used to guide prognosis and treatment decisions.
Language	English
Publishing date	2019-12-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.6402
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Article: Amebae and ciliated protozoa as causal agents of waterborne zoonotic disease.

Schuster, Frederick L / Visvesvara, Govinda S

Veterinary parasitology

2004 Volume 126, Issue 1-2, Page(s) 91–120

Abstract: The roles free-living amebae and the parasitic protozoa Entamoeba histolytica and Balantidium coli play as agents of waterborne zoonotic diseases are examined. The free-living soil and water amebae Naegleria fowleri, Acanthamoeba spp., and Balamuthia ... ...

Abstract	The roles free-living amebae and the parasitic protozoa Entamoeba histolytica and Balantidium coli play as agents of waterborne zoonotic diseases are examined. The free-living soil and water amebae Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris are recognized etiologic agents of mostly fatal amebic encephalitides in humans and other animals, with immunocompromised and immunocompetent hosts among the victims. Acanthamoeba spp. are also agents of amebic keratitis. Infection is through the respiratory tract, breaks in the skin, or by uptake of water into the nostrils, with spread to the central nervous system. E. histolytica and B. coli are parasitic protozoa that cause amebic dysentery and balantidiasis, respectively. Both intestinal infections are spread via a fecal-oral route, with cysts as the infective stage. Although the amebic encephalitides can be acquired by contact with water, they are not, strictly speaking, waterborne diseases and are not transmitted to humans from animals. Non-human primates and swine are reservoirs for E. histolytica and B. coli, and the diseases they cause are acquired from cysts, usually in sewage-contaminated water. Amebic dysentery and balantidiasis are examples of zoonotic waterborne infections, though human-to-human transmission can occur. The epidemiology of the diseases is examined, as are diagnostic procedures, anti-microbial interventions, and the influence of globalization, climate change, and technological advances on their spread.
MeSH term(s)	Acanthamoeba/classification ; Acanthamoeba/growth & development ; Amebiasis/drug therapy ; Amebiasis/epidemiology ; Amebiasis/parasitology ; Amebiasis/transmission ; Animals ; Antiprotozoal Agents/therapeutic use ; Balantidiasis/drug therapy ; Balantidiasis/epidemiology ; Balantidiasis/pathology ; Balantidiasis/transmission ; Balantidium/classification ; Balantidium/growth & development ; Developing Countries ; Entamoeba histolytica/classification ; Entamoeba histolytica/growth & development ; Entamoebiasis/drug therapy ; Entamoebiasis/epidemiology ; Entamoebiasis/parasitology ; Entamoebiasis/transmission ; Humans ; Naegleria fowleri/growth & development ; Water/parasitology ; Zoonoses/parasitology ; Zoonoses/transmission
Chemical Substances	Antiprotozoal Agents ; Water (059QF0KO0R)
Language	English
Publishing date	2004-12-09
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	196831-2
ISSN	1873-2550 ; 0304-4017
ISSN (online)	1873-2550
ISSN	0304-4017
DOI	10.1016/j.vetpar.2004.09.019
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