Post-Transplant Infection
Following
transplantation, patients are given immunosuppressive agents to prevent
rejection. Unfortunately, this inevitably increases susceptibility to
infection. Post-transplant immunosuppression has significant effects on T
lymphocytes, hence many of the opportunistic infections seen are similar to
those observed in patients with HIV, particularly cytomegalovirus (CMV) and Pneumocystis
jiroveci (previously called P. carinii). In the early
post-transplant period (months 1–3), immunosuppression is relatively intense,
and therefore the patient is at particular
risk of more unusual, opportunistic infection. In addition, some
immunosuppressive agents are more powerful than others, e.g.
lymphocyte-depleting agents such as ATG. Use of ATG at induction carries a higher
risk of subsequent infection than the use of non-depleting biological agents
such as anti-CD25 monoclonal antibodies. When considering infections occurring
post-transplant, they can be divided according to causative agents.
Viral infections
Transplant immunosuppression is associated with reactivation of a
number of latent viral infections including cytomegalovirus (CMV), varicella
zoster virus (VZV), herpes simplex virus (HSV), Epstein-Barr virus (EBV) and BK
virus, and also increases the severity of disease during primary infection with
these viruses such that they may be life threatening.
1 CMV – CMV is a
γ-herpes virus and is one of the most common infections encountered
post-transplant. CMV infection can present with non-specific symptoms such as
fever, sweats, lethargy and weight loss. CMV can affect specific organs such as
the gut (CMV colitis), the eyes (CMV retinitis, ‘brush fire’ appearance), the
lungs (CMV pneumonitis), the liver and the allograft (see Chapter 19).
2 VZV – between
80 and 90% of adults have a previous history of chicken pox. Thereafter the
virus lies dormant in dorsal root ganglia and may subsequently reactivate
post-transplant, presenting with a vesicular, painful rash in a dermatomal
distribution (shingles).
3 HSV1/2 – between
80 and 90% of adults have latent HSV1 infection which can reactivate
post-transplant, presenting as oral ulceration (‘cold sores’). HSV1 can also
cause gastrointestinal (GI) disease and encephalitis in the immunocompromised.
HSV2 infection is less common and presents with genital ulceration. Treat- ment
is with aciclovir.
4 EBV – more
than 90% of adults have evidence of previous EBV infection (seropositive for
EBV-specific IgG). The virus subsequently establishes latent infection in B
cells. Primary EBV infection (infectious mononucleosis) post-transplant can be
extremely severe and may be associated with the development of lymphoma (see
Chapter 20).
5 BK virus – BK virus
is a double-stranded DNA virus of the Polyomaviridae family.
Approximately 70–90% of the adult population have evidence of previous
infection. Primary infection is usually asymptomatic, but the virus establishes
latency within the genitourinary tract. Reactivation is common in renal
transplant recipients (viraemia is detectable in 10–20% of patients in the
first year post-transplant). Around half of these will have biopsy-proven BK
nephropathy (i.e. 5–10% transplant recipients). Patients with BK nephropathy
are asymptomatic and present with a decline in allograft function. Renal
transplant biopsy is required for diagnosis. Typical biopsy changes include
interstitial inflammation, which can progress to interstitial fibrosis and
tubular atrophy. The biopsy should be stained with an SV40 antibody, which
stains BK virus within tubular cells. BK infection has also been associated
with the development of ureteric stenosis. The main risk factor for the
development of BK nephropathy is the use of more intense immunosuppressive
regimens.
BK virus can be detected by performing polymerase chain reaction (PCR)
on blood or urine samples or by cytopathological examination of urine for the
presence of decoy cells (uroepithelial cells with nuclear inclusions). There is
no specific antiviral therapy for BK virus. The main strategy is to decrease
immunosuppression. Ciprofloxacin, leflunomide, cidofovir and IVIg have all been
used to treat BK nephropathy, but there is no randomised control trial data to
support their use.
Fungal infections
1 Candida albicans is
a commensal organism which is found on the skin, and in the genital and GI
tracts. Immunosuppression is associated
with the development of symptomatic infection, including oropharyngeal
candidiasis (‘thrush’) and candidal oesophagitis. Candidal species may also
cause infections of intravascular and peritoneal dialysis catheters. Rarely,
patients can develop invasive disease and fungaemia. Other candidal species
observed post- transplant include C. glabrata, which is resistant to
fluconazole and therefore difficult to treat. Patients are usually given prophylaxis
in the first 4–6 weeks post transplant (oral nystatin). Treatment for
symptomatic infection is oral fluconazole and for invasive disease intravenous
amphotericin B or caspofungin.
2 Pneumocystis jiroveci (previously
P. carinii) is a ubiquitous environmental fungus
that causes symptomatic infection in a third of transplant recipients in the
absence of prophylaxis. Patients present with a dry cough and shortness of
breath and may have normal oxygen saturations at rest, but become rapidly
hypoxic on exertion. At presentation, chest signs and chest X-ray (CXR) changes
are often scant, relative to the degree hypoxia observed. Diagnosis is usually
made by examination of bronchoalveolar lavage (BAL) fluid or transbronchial
biopsy. Treatment is with co-trimoxazole. Most transplant centres also offer
prophylaxis in the first 6 months post-transplant.
3 Aspergillus fumigatus is
the most commonly observed aspergillus species in transplant recipients. It is
acquired from the environment by inhalation of spores. It frequently causes
lung disease (often cavitating lesions on CXR), forming nodules, which can be
invasive and erode into blood vessels. It may also become disseminated
infecting heart, kidneys and brain, portending an extremely poor prognosis.
Diagnosis is usually by examination of BAL, which demonstrates fungal hyphae.
Treatment is with IV amphotericin B, voriconazole or caspofungin.
4 Cryptococcus neoformans can
cause pulmonary disease (nodules, pneumonia) and meningitis. Diagnosis is by
India ink staining of cerebrospinal fluid (CSF) or by serology. Treatment is
with IV amphotericin B and flucytosine.
Protozoal infections
Toxoplasma gondii is the
most commonly observed protozoal infection post-transplant. Infection occurs
via ingestion of meat contaminated with cysts. It causes cerebral lesions and
encephalitis. Treatment is with pyrimethamine and sulphadiazine.
Bacterial infections
Most early infections are related to the transplant procedure and
include infections of the wound (usually caused by staphylococci), urinary
tract infections (Escherichia coli) and chest infections (pneumococci or
atypical organisms). In addition, haemodialysis catheters or peritoneal
dialysis catheters may also become infected peri-operatively.
Later problems include chest infections, sinusitis, dental abscess
and endocarditis, which may be caused by more unusual organisms, e.g.
nocardia, listeria. Healthcare-associated infections (HAI), for example
methicillin-resistant Staphylococcus aureus (MRSA), Clostridium
difficile and vancomycin-resistant enterococci (VRE), may also be a problem
in patients who require recurrent hospital admissions for post-transplant
complications.
Latent Mycobacterium tuberculosis infection may be
reactivated by immunosuppression. Individuals at risk of reactivation or
primary mycobacterial infection should be placed on prophylaxis at the time of transplantation.
