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Post-Transplant Infection


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.


Post-Transplant Infection

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.