Transplantation infections

Leather HL, Wingard JR. Infections following hematopoietic stem cell transplantation. Infect Dis Clin North Am 2001 15 483-520. 

Singh N. Eungal infections in the recipients of solid organ transplantation. Infect Dis Clin North Am 2003 17 113-134. 

Aguado JM, Herrero JA, Gavalda J, Torre-Cisneros J, Blanes M, Rufi G, Moreno A, Gurgui A, Hayek Lumbreras C and tiie Spanish Transplantation Infection Study Groiq), GESI-TRA. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Transplantation (1997) 63, 1276-86. 

Kim C-C. Infectious complications associated with alemtuzumab use for allogeneic hematopoietic stem cell transplantation comparison with anti-thymocyte globulin. Transplant Infect Dis 2009 11 413-23. 

Infectious complications persist as a major cause of death, especially within the first year of heart transplantation (Hosenpud et al. 2000). Within the first month of transplantation, infections are usually of nosocomial bacterial origin, including Pseudomonas aeruginosa. Staphylococcus aureus. Enterococci, and Enterobacteriaceae. These organisms can cause pneumonia, urinary tract and wound infections. Later infections are commonly caused by viruses and opportunistic fungi (e.g., Pneumocystis, Candida, and Aspergillus) (Miniati and Robbin 2002). 

Kwak EJ, Strollo DC, Kulich SM, Kusne S (2003) Cavitary pneumonia due to Rhodococcus equi in a heart transplant recipient. Transplant Infect Dis 5 43-46 Lazem E, Barbir M, Banner N, Ludman P, Mitchell A, Yacoub M (1997) Coronary calcification detected by ultrafast computed tomography is a predictor of cardiac events in heart transplant recipients. Transplant Proc 29 572-575 Leung AN (1999) Invited Commentary Scientific exhibit. RadioGraphics 19(2) 340-341... 

Occasional post-transplant infections include toxoplasma or tuberculosis of the lungs and/or central nervous system disease, and Pneumocystis cari-nii pneumonia. These diseases respond well to treatment and because of that early and precise diagnosis is mandatory. 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. A athioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable compHcations, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

Acyclovir is more effective the more serious the disease and the earher it is given. It has been shown to be efficacious when used systemicaHy in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephaUtis in humans (68). 

Cytomegalovirus (CMV) is a herpesvirus, which causes an inapparent infection in immunocompetent persons. Worldwide, approximately 40% of people are infected with CMV. In immunocompromised patients, transplant recipients and neonates, CMV can cause serious and potentially lethal disease manifestations like pneumonia, retinitis and blindness, hepatitis, infections of the digestive tract, deafness or mental retardation. 

Antiviral drugp interfere with viral reproduction by altering DNA synthesis. These drug are used in the treatment of herpes simplex infections of the eye, treatment in immunocompromised patients with cytomegalovirus (CMV) retinitis, and for the prevention of CMV retinitis in patients undergoing transplant. 

Cidofovir (Fig. 2) has been formally approved for the treatment of CMV retinitis in AIDS patients, where it is administered intravenously at a dose not exceeding 5 mg/kg once weekly during the first two weeks (and every other week thereafter). Cidofovir is also used off label for the treatment of human papilloma virus (HPV) infections (i.e., cutaneous warts, anogenital warts, laryngeal and pharyngeal papilloma), polyomavirus [i.e., progressive (i.e., multifocal leukoencephalopathy (PML)], adenovirus, herpesvirus, and poxvirus (i.e., molluscum contagiosum) infections, where it can be administered intravenously (at a dose of < 5 mg/kg once weekly or every other week) or topically as a 1% gel or cream (De Clercq and Holy 2005). Especially in immunosuppressed patients (i.e., transplant recipients), local treatment of HPV-associated lesions has often yielded spectacular results (Bonatti etal.2007). 

HCMV is widespread in the human population. In immunocompetent individuals, the infection is inapparent or associated with mild symptoms. However, HCMV is frequently transmitted perinatally and is the leading cause of neurological disease and hearing loss in congenitally infected newborns, affecting some 8,000 newborns per year in USA alone (Arvin and Alford 1990). Furthermore, following the first 100 days after transplantation, HCMV-induced pneumonia develops in about 50%... 

A broad and vigorons T cell response generally accompanies elimination of HBV as well as HCV infection. By contrast, patients with chronic hepatitis B or C tend to have late, transient, or narrow T cell responses. In a long-term follow-up of HBV-infected patients receiving HPC transplants from HBV-immune individuals, 20 of 31 recipients cleared their HBV infection (Hui et al. 2005). In principle, these results encourage the development of adoptive T cell transfer strategies for the treatment of chronic viral hepatitis. However, it is still controversial whether induction of an efficient T cell response is the cause or the consequence of viral clearance. Furthermore, T cell responses do not only contribute to virus control but also to disease pathology (Rehermann and Nascimbeni 2005). 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

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