Viral Prophylaxis in Organ Transplant Patients

Abstract

Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster. Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called 'prophylaxis' for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong. Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during 'flu sea...

Aciclovir and Varicella-zoster-immunoglobulin in solid-organ transplant recipients

“…In immunocompromised hosts or patients with severe disease presentation or complications, aciclovir is the therapy of choice, with best effects if given intravenously within 72 h of disease onset [22,23]. A daily dosage of 1,500 mg/m 2 per day (corresponds to 30 mg/kg) in three doses for children until 12 years of age was recommended; for adolescents and adults 15 mg/kg per day (corresponds to 750 mg/m 2 ) in three divided doses [1]; for immunocompromised adults, as far as renal function is not impaired, 30 mg/kg in three divided doses. In patients with renal impairment, the daily dosage has to be reduced by extension of administration intervals, due to the risk of kidney damage.…”

“…Although acute varicella or chickenpox caused by varicellazoster virus (VZV) is usually a mild disease in immunocompetent hosts, it may cause disseminating infection with severe illness in immunocompromised patients [1]. Fatal cases result from pneumonitis, hepatitis, central nerval system involvement, and disseminated intravascular coagulation [2].…”

Moderne Immunsuppressiva nach Nierentransplantation

“…Bei spiel haft sei en die ge ne tisch de termi nier te Stö run gen im Ab bau von Azathio prin (TPMT-De fekt) so wie in di vi duel le Gen va ri an ten im Cy to chrom-P450-Sys tem oder im Mul ti-drug-re si stan ce-(MDR-)Gen ge nannt. Ein kon kre tes Bei spiel für die er folg reiche kli ni sche Um set zung neu er Er kenntnis se über re le van te Gen p o ly mor phismen ist die Fak tor-V-Lei den-Mu ta ti on im Ge rin nungs sys tem [49]. Die se Mu tatio nen im Ge rin nungs sys tem füh ren zu ei nem deut lich ver kürz ten Trans plan tatüber le ben in fol ge früh zei ti ger Trans plantatthrom bo sen. Als Kon se quenz wer den in zwi schen alle Pa ti en ten auf der War telis te auf die se Gen mu ta tio nen ge screent und nach Trans plan ta ti on zur Ver meidung früh zei ti ger Throm bo sen er folgreich an ti ko agu liert [49].…”

“…Ein kon kre tes Bei spiel für die er folg reiche kli ni sche Um set zung neu er Er kenntnis se über re le van te Gen p o ly mor phismen ist die Fak tor-V-Lei den-Mu ta ti on im Ge rin nungs sys tem [49]. Die se Mu tatio nen im Ge rin nungs sys tem füh ren zu ei nem deut lich ver kürz ten Trans plan tatüber le ben in fol ge früh zei ti ger Trans plantatthrom bo sen. Als Kon se quenz wer den in zwi schen alle Pa ti en ten auf der War telis te auf die se Gen mu ta tio nen ge screent und nach Trans plan ta ti on zur Ver meidung früh zei ti ger Throm bo sen er folgreich an ti ko agu liert [49]. F To le ran zin duk ti on: Die In duk ti on einer Im mun to le ranz wird auch in Zu kunft wei ter das ul ti ma ti ve Ziel der For schung sein.…”

“…Hoch wirk sa me an ti vi ra le Substan zen ste hen zur Ver fü gung, die bei guter Ver träg lich keit eine The ra pie oder besser noch die Ver mei dung von vi ra len Erkran kun gen er mög li chen. Ins be son de re sei hier die zu neh men de Ten denz zur oralen Pro phy la xe der CMV-Er kran kun gen ge nannt, die so wohl Häu fig keit als auch Schwe re der frü her ge fürch te ten CMVEr kran kung dras tisch re du ziert hat [49].…”