Commonly used drugs in transplant patients:
Antiviral Agents
DNA Viruses
Clinically important DNA-viral infections in transplant patients are caused by viruses that belong to Herpesviridae, Adenoviridae, and Papovaviridae. In the Herpesviridae, there are Herpes simplex virus type 1 & 2, Varicella zoster virus, Epstein-Barr virus, Cytomegalovirus, and Herpes virus type 6 & 7. Adenovirus is the only virus in the Adenoviridae. Human polyoma viruses, e.g. JC virus and BK virus, are originated from the Papovaviridae.
Most DNA virus infections are reactivation-infection, i.e. infection caused by reactivation of the virus that has been dormant after the initial, primary infection months to many years prior to the reactivation. Therefore, DNA viruses may potentially induce systemic, generalized infections involving multiple organs.
Herpes simplex virus type 1 infection is by far the most common in transplant patients before the advent of prophylactic acyclovir. In one study, two-thirds of seropositive patients for HSV type 1 had reactivation infections of the oropharyngeal area in 2-3 weeks of the transplant whereas less than 1% of seronegative patients had reactivation infections. After the institution of acyclovir prophylaxis, less than 3% of seropositive patients showed reactivation of oropharyngeal HSV type 1. However, the emergence of acyclovir-resistant HSV has become a serious problem recently, with the incidence of which has been reported as up to one fifth of the transplant population. It is believed to be related to the extended prophylaxis with acyclovir for immunosuppressed patients.
Herpes zoster infection by Varicella zoster virus occur in about 15% of the transplant patients, with the most cases occurring in nine months after the transplant. Although disseminated infection is rare in primary infection, it is quite common in reactivation infections. Approximately one third of patients with reactivation infections are at risk of developing systemic dissemination unless treated with acyclovir. Fortunately, infections by acyclovir-resistant varicella zoster virus are known to be rare.
Not infrequently, patients may present with infections caused by HSV type 2. It generally is preceded by known episodes of genital infections by HSV type 2. Unless patients have been on long-term prophylactic acyclovir, chances of resistant HSV type 2 infection are rare.
Before the institution of prophylaxis against cytomegalovirus, infections caused by cytomegalovirus occur in about a half of patients who underwent allogeneic bone marrow transplantation. CMV infections are known to be rare in patients with autologous transplantation. The discrepancy comes from the histo-incompatibility between donor and patient that results in misfit between donor T lymphocytes and antigenic viral peptide in patient's tissue. Therefore, T lymphocytes depletion tends to increase CMV reactivation-infections. Approximately 70% of infections occur within the first 5-12 weeks after the transplant. Contrary to the infections by HSV, CMV can induce primary infections in patients who have not been exposed to CMV before, at a rate of 50%. It is most often related to transfusion of CMV positive blood products. Because of this risk, all blood products given to transplant patients are to be leukocyte-depleted by a specific filter before transfusion since CMV generally is transmitted by white blood cells.
The most common symptoms of CMV infection are nonspecific, i.e. low-grade fever, generalized fatigue, or myalgia. CMV infections can decrease blood cell count, resulting in dangerous neutropenia or slight but persistent thrombocytopenia. It can also induce organ specific diseases, like CMV hepatitis, pneumonitis, or GI infections. Of these, the most deadly infection is known to be CMV pneumonitis. CMV pneumonitis occurs in 15% of patients with CMV reactivation, but the mortality of the infection exceeds 90% unless properly treated with antiviral agents and IVIg.
Epstein-Barr virus causes a specific problem of patient's B lymphocytes after the transplantation: immortalization of B lymphocytes. It is known to occur up to 8% of patients who were treated with allogeneic transplantation. It can cause polymorphic B cell lymphoma or immunoblastic lymphoma. The risk of EBV lympho-proliferative process is known to be high when T cells are depleted, or when the intensity of immunosuppressive therapy is very high in order to treat the graft versus host diease.
Herpes virus type 6 has been known to cause a variety of pathologic conditions, including pancytopenia, interstitial pneumonitis, encephalitis, hepatitis, or pharyngitis. Of two variants, i.e. variant A & B, only the variant B is responsible for clinical infections.
The reactivation of these viruses seems to follow a certain pattern, as shown in the following graph, thereby allowing the prediction of reactivation based on the temporal association.
Infections in transplant patients caused by adenovirus generally are disseminated and fatal. It occurs in approximately 17% of patients who receive allogeneic bone marrow transplantation. The bladder, lungs, liver and GI tract are most commonly involved. Reactivation infections by B or C serotypes are most common.
Hemorrhagic cystitis by polyoma virus is quite annoying and potentially capable of inducing obstructive renal failure. However, it rarely induces life-threatening infections and usually is self-limited. Progressive multifocal leukoencephalopathy caused by JC virus may occur after allogeneic bone marrow transplantation, especially when patient suffers from a significant graft versus host disease or receives profound immunosuppressive therapy.
RNA viruses
Clinically important RNA viruses include common respiratory viruses, such as Respiratory syncythial virus, Influenza A & B, and Parainfluenza type I, II, & III. These viruses cause upper respiratory infections that may progress to the lower tract or pneumonia. Although they generally are benign for the most part during the early phase of infection, they may potentially induce acute respiratory distress syndrome with profound hypoxia once infections spread to the lower tract or progress to pneumonia.
Contrary to the DNA viruses, RNA viruses can be easily diagnosed by nasal saline washing during the productive phase of infections that increase nasal discharge.
Section Home | Previous Page | Next Page |
