Parasitic infections are uncommon, but toxoplasmosis and leishmaniasis should be
considered if diagnosis remains elusive. Serology or bone marrow cultures usually provide the
diagnosis. The possibility of aToxoplasmaprimary infection should be considered when a
seronegative recipient receives an allograft from a seropositive donor. HT recipients are more
susceptible to toxoplasmosis, which may be transmitted with the allograft and occasionally
requires ICU admission. The risk of primary toxoplasmosis (R-D+) is over 50% in HT, 20%
after liver transplantation, and<1% after KT. Patients with toxoplasmosis have fever, altered
mental status, focal neurological signs, myalgias, myocarditis, and lung infiltrates. Allograft-
transmitted toxoplasmosis is more often associated with acute disease (61%) than with
reactivation of latent infection (7%). Lethal cases associated to hemophagocytic syndrome have
been described (266). Leishmaniasis is another parasitic infection that should be excluded,
though it is exceedingly uncommon after SOT. It may present as fever, pancytopenia, and
splenomegaly.
Multimodality imaging with the use of combined indium-labeled WBC scintigraphy and
CT allowed the detection of infection within a retained left ventricular assist device tubing in
an HT recipient with a diagnosis of fever of unknown origin (267).
Noninfectious Causes of Fever
Both infectious and noninfectious causes of fever should be considered when approaching a
febrile SOT patient. In a recent series, 87% of the febrile episodes detected in OLT in the ICU
were due to infections and 13% were noninfectious (9). Rejection, malignancy, adrenal
insufficiency, and drug fever were the most common noninfectious causes.
Fever is common in the first 48 hours after surgery and after certain procedures. If it is
not persistent or accompanied by other signs or symptoms, it should not trigger any diagnostic
action. Acute rejection accounts for 4% to 17% of noninfectious febrile episodes (268). It is
usually related to an impairment of the allograft function and requires histological
confirmation. It is more common in the first six months, especially in the first 16 days
after transplantation in one study (269). It is important to remember that severe graft rejection
and increased immunosuppression could stimulate cooperatively active CMV infections
(270,271).
Malignancy, mainly lymphoproliferative disease, is relatively common after SOT and
may initially present as a febrile episode (80%) (272–274). It usually occurs longer after
transplantation (268). Acute adrenal insufficiency should be excluded in SOT patients
admitted to an ICU because of sepsis or surgery, mainly when corticosteroids have been
withdrawn and drugs that accelerate the degradation of cortisol (phenytoin, rifampin) are
administered (275). However, although analytical adrenal insufficiency is frequent in SOT
patients, prospective studies suggest that supplemental steroids are not needed in most cases
even under stress (276–278). Another setting of potential adrenal insufficiency is in renal
transplants that return to dialysis (279,280). Occasionally, lymphoproliferative disease may
present with adrenal insufficiency after liver transplantation (281).
Drugs such as OKT3, ATG, everolimus, antimicrobials, interferon, anticonvulsants, etc.
may also cause fever in this population (282). The temporal relationship with the drug is
usually a diagnostic clue. New induction therapies such as basiliximab are related to fewer
side effects and fewer CMV infections (283).
Other causes of noninfectious fever include thromboembolic disease, hematoma
reabsortion, pericardial effusions, tissue infarction, hemolytic uremic syndrome, and transfu-
sion reaction. Noncardiogenic pulmonary edema (pulmonary reimplantation response) is a
common finding after lung transplantation (50–60%) and may occasionally lead to a
differential diagnosis with pneumonia. It conditions prolonged mechanical ventilation and
ICU stay but does not affect survival (284).
MANAGEMENT
Diagnostic Approach
As mentioned before, the diagnostic approach to a critically ill SOT with suspected infection
should take into account the time onward transplantation (Table 1) and previous complications
such as episodes of rejection, surgical or technical problems, reactivation of a latent infection, etc.
Infections in Organ Transplants in Critical Care 405