Mycophenolate mofetil increases susceptibility to opportunistic fungal infection independent of lymphocytes

Gibson, R. E.; Rl, Evans; Hotham, Richard; Bojarczuk, Aleksandra; Lewis, Amy; Bielska, Ewa; May, RC; Pm, Elks; Renshaw, SA; Sa, Jae-Hoon

doi:10.1101/131540

Cited by 11 publications

(11 citation statements)

References 68 publications

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“…A variety of cases of infectious complication in patients treated with azathioprine and mycophenolate mofetil have been published. Bacterial infections (common and atypical bacterial infections including Listeria monocytogenes , and mycobacterium species), fungal infections ( Cryptococcus neoformans, Aspergillus , Mucor , Pneumocystis jirovecii ), parasitic infection/reactivation ( Toxoplasma gondii ), and viral infection/reactivation (disseminated herpes zoster, varicella reactivation, JC virus, and polyomavirus associated nephropathy associated with BK virus infection) have been reported in azathioprine and mycophenolate mofetil users . The FDA places a special emphasis on the risk of JC virus‐associated progressive multifocal leukoencephalopathy in azathioprine and mycophenolate mofetil users .…”

Section: Other Immunosuppressive Drugsmentioning

confidence: 99%

Preventing infectious complications when treating non‐malignant immune‐mediated hematologic disorders

2019

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Immunosuppressants, targeted antibody therapies, and surgical splenectomy are amongst the treatment choices for immune-mediated non-malignant hematologic disorders, with infection being the most common non-hematological adverse event from these therapies. Corticosteroids are associated with a length-of-treatment and dose-dependent risk for infection, including opportunistic infections. Screening and antimicrobial prophylaxis against tuberculosis, Strongyloides stercoralis, and Pneumocystis jirovecii pneumonia, are indicated in selected patients on steroids and with certain risk factors for infection. Rituximab is associated with hepatitis B virus reactivation. All patients planned to be started on rituximab should be screened for hepatitis B surface antigen and total core antibody, with antiviral prophylaxis given depending on test results. In eculizumab treated patients, immunization against meningococcal serogroups ACWY and B is recommended. In addition, some guidelines suggest antibiotic prophylaxis for the duration of eculizumab treatment. In splenectomized patients, counseling and immunization are cornerstones of infection prevention. Several federal and society guidelines about immunizations and prophylactic antimicrobial therapies for patients treated with various immunosuppressive agents exist and are summarized in this manuscript in a clinical-focused table. In addition, management suggestions are made where no formal guidelines exist. 2 | PATIENT COUNSELING An important part of infectious disease prevention in immunocompromised patients entails the education of the patient, family, and friends. Household and other close contacts of persons with altered immunocompetence should be educated in hand hygiene and avoid contact with the patient when they are experiencing an infectious process. 12 Proper food and water hygiene measures are important to prevent

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Section: Other Immunosuppressive Drugsmentioning

confidence: 99%

Preventing infectious complications when treating non‐malignant immune‐mediated hematologic disorders

2019

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“…The C. neoformans variety grubii strain KN99, its GFP-expressing derivative KN99:GFP and mCherry-expressing derivative KN99:mCherry were used in this study (39). We used GFP expressing Δplb1-H99, Δlac1-H99 or parental H99-GFP (27) and Δgsc, Δsmt, Δsld8 and parental strain (24).…”

Section: Methods and Methodsmentioning

confidence: 99%

Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection

Jf¹,

Bojarczuk²,

Rl³

et al. 2020

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24Meningitis caused by infectious pathogens are associated with vessel damage and infarct 25 formation, however the physiological cause is unknown. Cryptococcus neoformans, is a 26 human fungal pathogen and causative agent of cryptococcal meningitis, where vascular 27 events are observed in up to 30% of cases, predominantly in severe infection. Therefore, we 28 aimed to investigate how infection may lead to vessel damage and associated pathogen 29 dissemination using a zebrafish model for in vivo live imaging. We find that cryptococcal 30 cells become trapped within the vasculature (dependent on there size) and proliferate there 31 resulting in vasodilation. Localised cryptococcal growth, originating from a single or small 32 number of cryptococcal cells in the vasculature was associated with sites of dissemination 33 and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension 34 reporter we identified dissemination from intact blood vessels and where vessel rupture 35 occurred. Finally, we manipulated blood vessel stifness via cell junctions and found 36 increased stiffness resulted in increased dissemination. Therefore, global vascular 37 vasodilation occurs following infection, resulting in increased vessel tension which 38 subsequently increases dissemination events, representing a positive feedback loop. Thus, 39 we identify a mechanism for blood vessel damage during cryptococcal infection that may 40 represent a cause of vascular damage and cortical infarction more generally in infective 41 meningitis. 42 43 44 45 46 47 48 Introduction 49 Life threatening systemic infection commonly results from tissue invasion requiring 50 dissemination of microbes, usually via the blood stream. Blood vessel damage and blockage 51 are commonly associated with blood infection, as exemplified by mycotic (infective) 52 aneurisms or sub-arachnoid haemorrhage (1). Indeed, both bacterial and fungal meningitis 53 are associated with vascular events including vasculitis, aneurisms and infarcts (1-5). 54The mechanisms of dissemination to the brain in meningitis have been extensively studied in 55 vitro and in vivo. Experimental studies suggest three potential mechanisms: passage of the 56 pathogen between cells of the blood brain barrier, polarised endocytosis and exocytosis of 57 the pathogen by brain vascular endothelial cells, and passage through the blood brain 58 barrier inside immune cells. However, we hypothesised that blood vessel blockage and 59 haemorrhagic dissemination might be an alternative mechanism. 60Cryptococcus neoformans is an opportunistic fungal pathogen causing life threatening 61 cryptococcal meningitis in severely immunocompromised patients. C. neoformans is a 62 significant pathogen of HIV/AIDs positive individuals with cryptococcal meningitis ultimately 63 responsible for 15% of all AIDS related deaths worldwide (6). C . neoformans has 64 previsously been suggested to disseminate from the blood stream into the brain through 65 different routes, including transcytosis, and by...

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“…For CTX, an incidence of infections (bacterial, fungal, viral, protozoal, and parasitic) ranging from 15 to 34% has been described [ 9 , 54 ]. Notably, AZA and MMF have been associated with atypical pathogens like Listeria monocytogenes and Mycobacterium species [ 55 , 56 ], fungal ( Cryptococcus neoformans , Aspergillus , Mucor , and Pneumocystis jirovecii ) and parasitic infections (Toxoplasma gondii) [ 57 , 58 ]. Moreover, polyomavirus (BK virus and JCV) infections have been reported with these two drugs [ 9 ].…”

Section: Infectious Risk Associated With Aiha Therapiesmentioning

confidence: 99%

Infectious Complications in Autoimmune Hemolytic Anemia

Giannotta

Fattizzo

Cavallaro

et al. 2021

JCM

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Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. This review will collect the available evidence on the frequency and type of infectious complications in AIHA, detailing the risk related to each treatment (i.e., steroids, rituximab, splenectomy, classic immunosuppressive agents, and new target drugs). Moreover, we will briefly discuss the infectious complications in AIHA secondary to other diseases that harbor an intrinsic infectious risk (e.g., primary immunodeficiencies, systemic autoimmune diseases, lymphoproliferative disorders, solid organ and hematopoietic stem cell transplants). Finally, viral and bacterial reactivations during immune suppressive therapies will be discussed, along with suggested screening and prophylactic strategies.

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Mycophenolate mofetil increases susceptibility to opportunistic fungal infection independent of lymphocytes

Cited by 11 publications

References 68 publications

Preventing infectious complications when treating non‐malignant immune‐mediated hematologic disorders

Preventing infectious complications when treating non‐malignant immune‐mediated hematologic disorders

Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection

Infectious Complications in Autoimmune Hemolytic Anemia

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