Opportunistic infections can occur in organ transplant recipients because recipients are often immunocompromised. Signs and symptoms of opportunistic infections are different from common infections, such as fever may not appear in opportunistic infections. Therefore, further investigation, such as microbiology or specific radiographic examination, is often needed to determine the exact etiology.

Opportunistic Infections in Organ Transplant Recipients
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The risk of infections in organ transplant recipients is determined by the interaction between exposure to the infectious agent and all factors that cause the patient's immune decline. Prophylactic antimicrobials and immunosuppressive drugs also affect the risk of infection. Antimicrobial therapy in transplant organ recipients is more complex than regular patients, with a significant drug toxicity incidence and a tendency for interactions with immunosuppressive agents used to maintain transplant organ function.

Periods and Possibility infections in Organ Transplants

With a standardized immunosuppressive regimen, infections usually occur in a relatively predictable time pattern since the transplant was carried out. There are three overlapping risk periods, namely:

Period 1: about 30 days after transplantation
Period 2: 1 to 6-12 months after transplantation
Period 3: after 6–12 months after transplantation
Various opportunistic infections can be estimated differential diagnosis based on the time distribution of these infections.

Period 1
In the first period, which is during the first 1 month after an organ transplant, infections commonly occur as a result of:
  • surgical complications,
  • an infection originating from a donor,
  • preexisting recipient infections,
  • and nosocomial infections, including aspiration or colitis due to C. difficile.
Reflect problems related to the technical operations:
  • bleeding,
  • stricture,
  • organ connection leakage,
  • and graft injuries;
  • or exposure to the hospital environment, such as pneumonia.
  • Fever can occur due to blood transfusions, drug reactions, or graft rejection.
Early opportunistic infections rarely occur because immunosuppressive agents' administration has not put too much pressure on the immune system. Thus, early pneumocystis pneumonia rarely occurs without pretransplant immunosuppressant administration.

Period 2
In the second period, which is from 1 month to 6-12 months after organ transplantation, the effect of immunosuppressant drugs has worked significantly, so there are several differential diagnoses of pathogens that cause infection. Some pathogens that might cause infections to include:
  • Viruses: cytomegalovirus (CMV), herpes simplex virus (HSV), herpes zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus (HHV) 6 or 7, polyomavirus BK, hepatitis B and C (HBV, HCV) the relapse
  • Respiratory viruses obtained in the community: adenovirus, influenza, parainfluenza, respiratory syncytial virus, and metapneumovirus
  • Other: Pneumocystis jirovecii, Listeria monocytogenes, T. gondii, Nocardia species, Aspergillus species, and endemic fungi.

Period 3
In the third period, more than 6-12 months after organ transplantation, recipients with excellent allograft function will tolerate a reduction in maintenance dosage for immunosuppressants. This will reduce the risk of infection.

Healthy recipients generally suffer from community-based exposure due to daily activities, such as:
  • Clean the attic of the house: Aspergillus, Cryptococcus
  • Clean the shed: Rhodococcus equi, hantavirus
  • Traveling: malaria, Salmonella sp., Dengue infection
  • Detection and Monitoring of Some Opportunistic Infections in Organ Transplants

Detection, Monitoring, and Treatments of Some Opportunistic Infections in Organ Transplants

Immunocompromised conditions can cause opportunistic infections of various pathogens in organ transplant patients, such as liver transplants and kidney transplants.

1. Cytomegalovirus (CMV)
Many cytomegalovirus (CMV) infections are asymptomatic. However, syndromes can also occur in the form of fever, leukopenia, and myalgia, even accompanied by mild hepatitis.

Invasive CMV disease is often focused on the allograft. Common clinical manifestation is pancolitis with ulceration and bleeding, even inflammation of several organs.

Currently, there are international standards for quantitative molecular assays (QNAT) to treat, prevent, diagnose, and manage CMV infections. Serological tests are useful before transplantation to predict risk. However, both serum IgG and IgM levels do not help diagnose acute infection because seroconversion transplant conditions generally appear slow. Meanwhile, CMV cell culture is slow and insensitive for use in diagnosis.

In transplant recipients with ulcerative GI tracts, even bleeding, CMV infection's possibility must be considered even with low or undetectable viremia. High-risk patients (i.e., donor + recipient - or recipient + with anti-thymocyte globulin) can be given prophylaxis for 3-6 months post-transplantation. They can be screened biweekly or monthly to ensure there is no infection for additional therapy for 3-6 months.

The standard therapy for treating CMV is at least 2-3 weeks of therapy with intravenous ganciclovir 5 mg/kg twice daily, with dose adjustment for kidney dysfunction. Another option is valganciclovir 900 mg orally twice a day. 

2. Epstein-Barr virus (EBV)
Primary Epstein-Barr virus (EBV) infections tend to appear in the first year after organ transplantation. In immunocompromised transplant recipients, primary EBV infection can be asymptomatic. However, EBV infection can cause febrile mononucleosis syndrome with B cell lymphocytosis with or without lymphadenopathy, atypical lymphocytosis, exudative pharyngitis, meningitis, hepatitis, or pancreatitis.

Specific nucleic acids related to EBV can be detected in tissues by in situ hybridization techniques for EBV-encoded small nuclear RNAs (EBER) and EBV lytic or latent antigens (EBNA-1, EBNA-2, LMP-1, BZLF1) by immunostaining.

EBL polyclonal disease in seropositive individuals shows some good responses to immunosuppressant dose reduction. Some therapies that have been used in treating EBV infections include a combination of anti-B cell (anti-CD20) therapy, chemotherapy, and adoption immunotherapy with stimulated T cells.

3. Polyomavirus BK (BKPyV)
In kidney transplant recipients, BKPyV is associated with viruria and viremia, ulceration and ureteral stenosis, and polyomavirus-related nephropathy (polyomavirus-associated nephropathy or PVAN). Monitoring of kidney transplant recipients for BKPyV can be done both for patients with renal dysfunction or routinely for 2-5 years.

Initial tests generally use a plasma viral load test. In renal dysfunction conditions, a suspected diagnosis of PVAN can be made based on an increase in plasma viral load without obstruction with renal ultrasound examination. Biopsy with immunohistopathology is generally needed to distinguish PVAN from graft rejection or drug toxicity.

To date, Treatment for PVAN is the reduction in immunosuppressant intensity for patients who have a high viral load. Monitoring that must be carried out during dose reduction checks kidney function 1-2 times per week and viral load every week.

4. Aspergillus infection
Invasive aspergillus infections commonly occur in organ transplant recipients whose immune systems are weak, with an estimated mortality of between 20 to> 50%. The risk of aspergillus infection is increased by various factors, including organ transplantation and re-exploration, kidney or liver failure after transplantation with kidney replacement therapy, CMV infection, and hepatitis C. coinfection.

Pulmonary aspergillosis is generally accompanied by fever, cough with or without hemoptysis, and sometimes pleurisy. Patients with suspicion of aspergillus infection require imaging examination, commonly by CT scan, bronchoscopy (BAL), or biopsy for culture and antifungal sensitivity testing.

Treatment of aspergillus infection can be given based on recommendations from the Infectious Disease Society of America in 2016. Triazole is the treatment of choice for aspergillus infections. Antifungal azole groups that can be used include itraconazole, voriconazole, and posaconazole.

If contraindications to taking antifungal azole, amphotericin B can act as an alternative. Moreover, amphotericin B can also be used as prophylaxis in lung transplantation.

5. Pneumocystis jiroveci
The risk of Pneumocystis jiroveci pneumonia (PCP) infection is highest in the first 6 months after transplantation (10% of recipients not receiving prophylactic therapy) and during periods of increased immunosuppressant doses. PCP infection appears acute and subacute, and there is no specific picture on radiological imaging.

The detection of PCP infection needs sputum induction and immunostaining tests. Staining of antibodies can show a picture of cysts and trophozoites that are sufficient for diagnosis.

Initial treatment for Pneumocystis jiroveci infection is ideally with cotrimoxazole. Some transplant patients tolerate full-dose cotrimoxazole for long periods. Creatinine can increase due to competition with trimethoprim for renal excretion and sulfa toxicity in the kidneys, so hydration is vital during administration.

Alternative therapies that can be given include atovaquone, clindamycin with primaquine or pyrimethamine, or intravenous pentamidine. However, alternative treatments are reported to be less effective than cotrimoxazole.

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