In immunosuppression

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). 

Due to the divergence of fungal diseases, there is neither single best treatment nor a superior drug for all diseases. However, a superior drug does exist for dermatomycoses caused by dermatophytes, namely the allylamine terbinafine (TER). For the treatment of deep mycoses in immunosuppressed patients the most efficacious drug is the polyene Amph B. 

Systemic mycoses are caused either by true pathogenic fungi (endemic in distinct areas of USA/South America) or by opportunistic fungi that induce severe infections in immunosuppressed patients. The arsenal for the treatment of deep organ mycoses is relatively small Amph B, 5FC, azoles (FLU, ITRA, voriconazole (NBA filing)) and CAS. 

The polyene Amph B (intravenous formulation) has the broadest spectrum, is fungicidal and shows its superiority in immunosuppressed patients. Its only drawback is its infusion-related toxicity and its negative influence on renal function. Acute reactions to Amph B - usually fever chills, rigor and nausea - can be... 

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). 

Heart transplantation represents the final option for refractory, end-stage HF patients who have exhausted medical and device therapies. Heart transplantation is not a cure, but should be considered a trade between a life-threatening syndrome and the risks associated with the operation and long-term immunosuppression. Assessment of appropriate candidates includes comorbid illnesses, psychosocial behavior, available financial and social support, and patient willingness to adhere to lifelong therapy and close medical follow-up.1 Overall, the transplant recipient s quality of life may be improved, but not all patients receive this benefit. Posttransplant survival continues to improve due to advances in immunosuppression, treatment and prevention of infection, and optimal management of patient comorbidities. 

Measles, mumps, and rubella vaccine is a live virus vaccine that should be used with caution in immunosuppressed children, such as those with cancer receiving chemotherapy, solid organ or bone marrow transplantation, or receiving other immunosuppressive drugs, such as steroids in a dose... 

There is good evidence, for a number of helminth species, that different parasite lines vary in their infection characteristics in hosts, much of which is reviewed by Read and Viney (1996). For example, different isolates of Trichinella spiralis vary in the kinetics of their primary infection in the same mouse strain. Crucially, these differences are removed when mice are immunosuppressed (Bolas-Fernandez and Wakelin, 1989). Analogous observations have been made for Trichuris muris in mice. Different isolates differed in the kinetics of infection and expulsion. However, in immunosuppressed mice, all isolates had similar fecundity (Bellaby et al., 1995). Combined, these observations show immune-dependent variation between parasite lines in their infection kinetics. 

The third example considered the interaction of life-history traits (survival rates, fecundity, immunogenicity) with an environmental factor specific to parasites, namely the host immune system. Here phenotypic diversity in response to environmental conditions (host immunity) is not so readily apparent. To observe phenotypic diversity, different parasite lines need to be compared in their kinetics of infection and, to show immune-dependence, these must be complemented by control experiments in immunosuppressed hosts. Experiments seeking to select on this diversity... 

The achievement of synergistic antimicrobial activity is advantageous for infections caused by gram-negative bacilli in immunosuppressed patients. 

In the United States, cryptococcal meningitis is the most common form of fungal meningitis and is a major cause of morbidity and mortality in immunosuppressed patients. 

The vaccine is contraindicated in immunosuppressed or pregnant patients. Children with asymptomatic or mildly symptomatic HIV should receive two doses of varicella vaccine 3 months apart. 

Some of these are involved in haematopoiesis (e.g. IL-1, -3, -5, -6 GM-, M-, G-CSF) their role is described in Chapter 2. Others (e.g. IL-1, -6, -8 TNF a- GM-, M-, G-CSF) are implicated in inflammation either directly (e.g. pure IL-1 can cause some symptoms of inflammation) or indirectly, via their ability to activate immune cells that participate in the inflammatory response (e.g. lymphocytes, neutrophils and macrophages) some of these effects are described in Chapters 2 and 3. Such cytokines as IL-4, interferon-a and IL-10 may be involved in immunosuppression others, such as IL-1, IL-6, TNF a and TGF j3, are involved in tissue remodelling. 

Herpes labialis or cold sores can be precipitated by trauma to the lips and sunlight. In patients whose immune system is compromised, such as in immunosuppression or in cases of viral infections, herpes labialis may be precipitated. Dental caries do not precipitate cold sores. 

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information needed for the follow-up of the patient. Liver transplantation-excess mortality, graft loss, and hepatic artery thrombosis (HAT) The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant recipients. Many of these patients had evidence of infection at or near the time of death. 

Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe daclizumab. The physician responsible for daclizumab administration should have complete information requisite for the follow-up of the patient. Daclizumab should only be administered by health care personnel trained in the administration of the drug who have available adequate laboratory and supportive medical resources. 

Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use muromonab-CD3. 

Immunosuppressed patients The safety and efficacy of imiquimod cream in immunosuppressed patients have not been established. 

Azathioprine, in combination with corticosteroids, has historically been used more widely than any other drug in immunosuppressive therapy. It is classified as a... 

Azathioprine also has applications in certain disorders with autoimmune components, most commonly rheumatoid arthritis. It is as effective as cyclophosphamide in the treatment of Wegener s granulomatosis. It has largely been replaced by cyclosporine in immunosuppressive therapy. Relative to other cytotoxic agents, the better oral absorption of azathioprine is the reason for its more widespread clinical use. 

Infections with P jiroveci and some other pathogens can be treated orally with high doses of the combination (dosed on the basis of the trimethoprim component at 15-20 mg/kg) or can be prevented in immunosuppressed patients by one double-strength tablet daily or three times weekly. 

Treatment consists of two daily doses of 200 mcg/kg. In immunosuppressed patients with disseminated infection, repeated treatment is often needed, and cure may not be possible. In this case, suppressive therapy—ie, once monthly—may be helpful. 

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