Recent advances in understanding and managing infectious diseases in solid organ transplant recipients

Aguilar, Claire; Husain, Shahid; Lortholary, Olivier

doi:10.12688/f1000research.14262.1

Cited by 9 publications

(8 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Infections in the donor might complicate organ donation. The actual rate of unexpected infection transmission from donor to receptor is low, occurring in less than 1% of solid organ transplant recipients [59,60]. Nevertheless, the consequences may be devastating, and sometimes even fatal.…”

Section: Infection Managementmentioning

confidence: 99%

Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality

et al. 2019

View full text Add to dashboard Cite

To provide a practical overview of the management of the potential organ donor in the intensive care unit. Methods: Seven areas of donor management were considered for this review: hemodynamic management; fluids and electrolytes; respiratory management; endocrine management; temperature management; anaemia and coagulation; infection management. For each subchapter, a narrative review was conducted. Results and conclusions: Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations, or extrapolations from general ICU management strategies, and not on evidence from randomized controlled trials. The cardiorespiratory management of brain-dead donors is very similar to the management of critically ill patients, and the same applies to the management of anaemia and coagulation. Central diabetes insipidus is of particular concern, and should be diagnosed based on clinical criteria. Depending on the degree of vasopressor dependency, it can be treated with intermittent desmopressin or continuous vasopressin, intravenously. Temperature management of the donor is an area of uncertainty, but it appears reasonable to strive for a core temperature of > 35 °C. The indications and controversies regarding endocrine therapies, in particular thyroid hormone replacement therapy, and corticosteroid therapy, are discussed. The potential donor should be assessed clinically for infections, and screening tests for specific infections are an essential part of donor management. Although the rate of infection transmission from donor to receptor is low, certain infections are still a formal contraindication to organ donation. However, new antiviral drugs and strategies now allow organ donation from certain infected donors to be done safely.

show abstract

Section: Infection Managementmentioning

confidence: 99%

Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Opportunistic viral reactivations from established latent viruses (or transferred through the graft) are especially challenging in the context of compromised T‐cell immunity. Among others, the reactivation of herpes family viruses such as cytomegalovirus (CMV), Epstein–Barr virus and human herpesvirus 6, as well as polyomaviruses such as BK virus, are a significant burden in transplantation, impacting both morbidity and mortality rates . While reducing immunosuppression and administering antiviral drugs remain the cornerstone of current treatments for viral reactivations after transplantation, adoptively transferred virus‐specific T cells have yielded remarkable results for the prevention and control of virus‐related complications, even in patients refractory to conventional treatments .…”

mentioning

confidence: 99%

“…Among others, the reactivation of herpes family viruses such as cytomegalovirus (CMV), Epstein-Barr virus and human herpesvirus 6, as well as polyomaviruses such as BK virus, are a significant burden in transplantation, impacting both morbidity and mortality rates. [22][23][24][25] While reducing immunosuppression and administering antiviral drugs remain the cornerstone of current treatments for viral reactivations after transplantation, adoptively transferred virus-specific T cells have yielded remarkable results for the prevention and control of virus-related complications, even in patients refractory to conventional treatments. 25 The use of ex vivo stimulated and expanded virus-specific T cells from either the patients themselves (or allogeneic hematopoietic cell transplantation donor) or so-called allogeneic third-party donors (neither the graft recipient nor donor) are associated with a high rate of durable responses with little toxicity.…”

mentioning

confidence: 99%

Leukoreduction system chambers are a reliable cellular source for the manufacturing of T‐cell therapeutics

et al. 2018

View full text Add to dashboard Cite

BACKGROUND Following solid organ or hematopoietic cell transplantation, refractory opportunistic viral reactivations are a significant cause of morbidity and mortality but can effectively be controlled by virus‐specific T‐cell transfer. Among effective and safe strategies is the use of “third‐party” (neither from the transplant donor nor recipient) virus‐specific T cells that can be manufactured from healthy donors and used as “off‐the‐shelf” therapies. Leukoreduction system chambers (LRSCs), recovered after routine plateletpheresis, were evaluated as a potential source of peripheral blood mononuclear cells (PBMCs) for the manufacturing of clinical‐scale virus‐specific T cell. STUDY DESIGN AND METHODS PBMCs from the same donors obtained either from LRSCs or peripheral blood were compared, focusing on T‐cell function and phenotype as well as the potential to generate cytomegalovirus (CMV)‐specific T‐cell lines from both CMV seropositive and seronegative donors. RESULTS PBMCs from both sources were comparable except for a transient downregulation of CD62L expression on freshly extracted PBMCs from LRSCs. Both nonspecific stimulation using anti‐CD3/CD28 antibodies and CMV peptides revealed that LRSCs or blood T cells were equivalent in terms of expansion, differentiation, and function. Moreover, PBMCs from LRSCs can be used to generate autologous monocyte‐derived dendritic cells to prime and expand CMV‐specific T cells from seronegative donors. CONCLUSION LRSCs are a reliable source of PBMCs for the generation of virus‐specific T cells for immunotherapy. These findings have implications for the development of third‐party therapeutic T‐cell products from well‐characterized blood product donors.

show abstract

“…Overall, however, most evidence for the treatment and prevention of IMI in SOT patients is still based on clinical experience [2]. Because of the apparently only mild drug-drug interactions [69], the new triazole isavuconazole has the potential to become an important addition to the antifungal armamentarium, but specific studies are still needed to validate its use in SOT patients [70].…”

Section: Treatmentmentioning

confidence: 99%

Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response

et al. 2019

View full text Add to dashboard Cite

Purpose Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. Methods Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients Results Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. Conclusions The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined.

show abstract

Recent advances in understanding and managing infectious diseases in solid organ transplant recipients

Cited by 9 publications

References 86 publications

Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality

Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality

Leukoreduction system chambers are a reliable cellular source for the manufacturing of T‐cell therapeutics

Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response

Contact Info

Product

Resources

About