Infections Associated With Organ Transplants

Introduction
Advancement in medical care has led to more patients surviving longer after receiving an organ transplant. Technological and medical developments with immunosuppressive therapy and improved surgical techniques have made organ transplantation a standard of care in tertiary centres – previously only available in leading quaternary institutions. The population of patients living with a transplant is growing and this increase is accompanied by a rising incidence of infections related to long term immunosuppression.

Epidemiology
Wealth is a key indicator of the number of transplants performed in a country. In affluent countries, more patients have received transplants as part of quaternary care. e.g. stem cell transplant and liver/kidney/lung transplants. However, in less developed countries, only the wealthy can afford such a privilege. The quality of medical management of transplant patients and its subsequent complications are usually rooted in the level of medical advancement. The care of transplant patients with infections relies highly on the expertise of the medical team and diagnostic capabilities including microbiological/ molecular diagnostic laboratory, diagnostic radiological services, histopathology as well as therapeutic drug monitoring services to achieve a successful outcome.

Clinical Presentation
In general, transplant patients are prone to infections because of the drugs they take to prevent rejection of the transplanted organ. These drugs downregulate the immune system which mediates rejection and in the process, patients become susceptible to infections.

These infections could be divided into the following:

  1. Common infections in the community e.g. influenza, viruses, pneumonia etc
  2. Reactivation of latent infections that are pre-existent in the patient prior to transplantation e.g. TB, CMV, toxoplasmosis, etc
  3. Infections acquired from the donor organ e.g. CMV, fungal infections, other viral and bacterial infections
  4. New opportunistic infections due to immunosuppression e.g. pneumonia, urinary tract infections, graft infections, etc
  5. Acquired infections due to transfusions, use of haemodialysis machines, other devices. These include bloodstream infections, hepatitis C, hepatitis B, etc.
  6. Long term infections caused by chronic immunosuppression e.g. EBV associated infections, papilloma virus infections, etc. Some of these chronic viral infections may result in transplant associated malignancies

The severity of the infection is also related to the net state of immunosuppression. In general, the more immunosuppressed you are, the more severe the infection.

In the early post-transplant period, immunosuppression is stronger and sometimes, additional agents are used for treatment of early rejection e.g. ATG, ALG which predispose the patient to more serious infections. The donor status is important as this may determine the likelihood of reactivation of infection. An important example is CMV infection, a major problem in transplant recipients and this infection can affect numerous organs and be life threatening.

Diagnosis
Diagnosis of infection in transplant patients require a strong index of suspicion along with the appropriate diagnostic tests being carried out. The donor and recipient’s background status are both important in determining the likelihood of the development of disease. For a patient coming from a highly endemic area for TB or toxoplasmosis may raise suspicions for such infections. There is also a timeline of various infections to occur in transplant recipients. For example, in the first 2-4 weeks following the transplant procedure, the infections that occur are usually the result of the procedure and/or acquired from the donor. CMV infection tends to occur 3 months or more following transplant.

Diagnosis may be straight forward and based on clinical findings or may be difficult and requires invasive procedure like biopsies and molecular methods to detect the antigen, usually only available in tertiary institutions.

Empiric treatment is employed if the doctors are unable to find the type of infection. This is not ideal as such treatment may be expensive, have side effects and drug interactions.

The use of molecular methods have greatly improved the yield of diagnostic tests in the transplant population and is now an indispensable part of our diagnostic armamentarium.

Treatment
Diagnosis of the infection determines the treatment administered hence it is important that support services are able to assist in the diagnostic workup. As many of the drugs used are toxic and expensive, inability to pinpoint the exact etiology will result in expensive empiric treatment. This is in addition to the attendant side effects of medications and the various drug interactions with the transplant (immunosuppressive) drugs.

Prevention
Pre-transplant screening is imperative to optimise the patient for transplantation and to pre-empt the development of preventable infections. Obviously not all infections can be prevented. Fortunately, there is supporting data for the use of preventive therapy which may mitigate disease and minimise the risk of infection.

Typically, in pre-transplant screening, a comprehensive history of current and pre-existing medical conditions is done, followed by a detailed physical examination. Subsequently, blood tests done may include investigations for:

  • Latent /active TB
  • Hepatitis B, C
  • HIV
  • Parasitic diseases
  • CMV status
  • Toxoplasma status
  • Previous sexually transmitted diseases eg HSV, syphilis
  • Baseline toxoplasma status
  • Assessment for active infections which should be treated before embarking on transplantation
  • Stool and urine tests

Most donor registries and organ banks impose stringent testing of donor tissues to ensure that they are free from infectious diseases prior to being allocated for transplants. An active follow-up of the recipients’ status post-transplant to detect any undiagnosed infection is now routine in most registries. Previously, diseases detected include prion disease (mad cow disease), West Nile virus, histoplasmosis, tuberculosis etc.

Any active disease detected is quickly treated before the scheduled transplant. Prophylaxis / pre-emptive treatment is available for CMV disease, toxoplasma, pneumocystis jirovecii infections, etc

Vaccinations against hepatitis A, B, influenza and pneumococcus are recommended for potential transplant patients.
There is also data for the use of antifungal, antibacterial and antiviral prophylaxis in the highest risk transplants eg those undergoing human stem cell transplantation.

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