Chapter 126. Infections in Transplant Recipients (Part 7) docx

Chapter 126. Infections in
Transplant Recipients
(Part 7)

Adenovirus can be isolated from HSCT recipients at rates varying from 5 to
18%. Although hemorrhagic cystitis, pneumonia, gastroenteritis, and fatal
disseminated infection have been reported, adenovirus infection, which (like CMV
infection) usually occurs in the first or second month after transplantation, is often
asymptomatic. A role for cidofovir therapy has been suggested, but the efficacy of
this agent is unproven.
Infections with parvovirus B19 (presenting as anemia or occasionally as
pancytopenia) and enteroviruses (sometimes fatal) can occur. Parvovirus infection
may possibly respond to IVIg (Chap. 177). Intranasal pleconaril, a capsid-binding
agent, is being studied for the treatment of enterovirus infection.
Rhinoviruses and coronaviruses are frequent co-pathogens in HSCT
recipients; however, whether they independently contribute to significant
pulmonary infection is not known. Rotaviruses are a common cause of
gastroenteritis in these patients. The polyomavirus BK virus is found at high titers
in the urine of patients who are profoundly immunosuppressed. BK viruria may be
associated with hemorrhagic cystitis in these patients. Compared with the
incidence among patients with impaired T cell function due to HIV infection,
progressive multifocal leukoencephalopathy caused by the related JC virus is rare
among HSCT recipients (Chap. 376). When transmitted by mosquitoes or by
blood transfusion, West Nile virus can cause encephalitis and death after
hematopoietic stem cell transplantation.
Infections in Solid Organ Transplant (SOT) Recipients
Morbidity and mortality among SOT recipients are reduced by the use of
effective antibiotics. The organisms that cause acute infections in recipients of
SOT are different from those that infect HSCT recipients because SOT recipients
do not go through a period of neutropenia. As the transplantation procedure
involves major surgery, however, SOT recipients are subject to infections at

anastomotic sites and to wound infections. Compared with HSCT recipients, SOT
patients are immunosuppressed for longer periods (often permanently). Thus they
are susceptible to many of the same organisms as patients with chronically
impaired T cell immunity (Chap. 82, especially Table 82-1).
During the early period (<1 month after transplantation), infections are
most commonly caused by extracellular bacteria (staphylococci, streptococci,
enterococci, E. coli, other gram-negative organisms), which often originate in
surgical wound or anastomotic sites. The type of transplant largely determines the
spectrum of infection.
In subsequent weeks, the consequences of the administration of agents that
suppress cell-mediated immunity become apparent, and acquisition or reactivation
of viruses and parasites (from the recipient or from the transplanted organ) can
occur. CMV infection is often a problem, particularly in the first 6 months after
transplantation and may present as severe systemic disease or as infection of the
transplanted organ. HHV-6 reactivation (assessed by plasma PCR) occurs within
the first 2–4 weeks after transplantation and may be associated with fever,
leukopenia, and possibly encephalitis. Data suggest that replication of HHV-6 and
HHV-7 may exacerbate CMV-induced disease. CMV is associated not only with
generalized immunosuppression but also with organ-specific, rejection-related
syndromes: glomerulopathy in kidney transplant recipients, bronchiolitis
obliterans in lung transplant recipients, vasculopathy in heart transplant recipients,
and the vanishing bile duct syndrome in liver transplant recipients. A complex
interplay between increased CMV replication and enhanced graft rejection is well
established: increasing immunosuppression leads to increased CMV replication,
which is associated with graft rejection. For this reason, considerable attention has
been focused on the diagnosis, prophylaxis, and treatment of CMV infection in
SOT recipients. Early transmission of West Nile virus to transplant recipients from
an organ donor has been reported; however, the risk of West Nile acquisition has
been reduced by implementation of screening procedures.
Beyond 6 months after transplantation, infections characteristic of patients

with defects in cell-mediated immunity—e.g., infections with Listeria, Nocardia,
Rhodococcus, various fungi, and other intracellular pathogens—may be a problem.
International patients and global travelers may experience reactivation of dormant
infections with trypanosomes, Leishmania, Plasmodium, Strongyloides, and other
parasites. Elimination of these late infections will not be possible until the patient
develops specific tolerance to the transplanted organ in the absence of drugs that
lead to generalized immunosuppression. Meanwhile, vigilance,
prophylaxis/preemptive therapy (when indicated), and rapid diagnosis and
treatment of infections can be lifesaving in SOT recipients, who, unlike most
HSCT recipients, continue to be immunosuppressed.
SOT recipients are susceptible to EBV-LPD from as early as 2 months to
many years after transplantation. The prevalence of this complication is increased
by potent and prolonged use of T cell–suppressive drugs. Decreasing the degree of
immunosuppression may in some cases reverse the condition. Among SOT
patients, those with heart and lung transplants—who receive the most intensive
immunosuppressive regimens—are most likely to develop EBV-LPD, particularly
in the lungs. Although the disease usually originates in recipient B cells, several
cases of donor origin, particularly in the transplanted organ, have been noted. High
organ-specific content of B lymphoid tissues (e.g., bronchial-associated lymphoid
tissue in the lung), anatomic factors (e.g., lack of access of host T cells to the
transplanted organ because of disturbed lymphatics), and differences in major
histocompatibility loci between the host T cells and the organ (e.g., lack of cell
migration or lack of effective T cell/macrophage cooperation) may result in
defective elimination of EBV-infected B cells. SOT recipients are also highly
susceptible to the development of Kaposi's sarcoma and less frequently to the B
cell proliferative disorders associated with KSHV, such as primary effusion
lymphoma and multicentric Castleman's disease. Kaposi's sarcoma is much more
common (in fact, 550–1000 times more common than in the general population),
can develop very rapidly after transplantation, and can also occur in the allograft.
However, because the seroprevalence of KSHV is very low in Western countries,

Kaposi's sarcoma is not often observed.