Fatal disseminated toxoplasmosis in a toxoplasma seropositive liver transplant recipient

Disseminated toxoplasmosis is a severe disease that occurs in immunocompromised patients but has been rarely reported after liver transplantation. We describe the first case of fatal disseminated toxoplasmosis in a toxoplasma seropositive liver transplant recipient with a documented lack of a rise in specific IgG.

A 53 year old patient underwent liver transplantation because of decompensated alcoholic cirrhosis. The patient was treated with antithymocyte globulins and prednisolone. Tacrolimus was added and antithymocyte treatment stopped. Oral ganciclovir was given to prevent cytomegalovirus infection. On day 22, the patient developed fever with chills. Physical examination was normal and blood analysis revealed leucopenia (leucocytes, 700/mm³). Blood, urine, and bile cultures were repeatedly negative. Concentrations of antibodies against aspergillus and candida did not increase. Our patient was toxoplasma seropositive before the liver transplantation (specific IgG, 15 IU/ml) and the weekly serological follow up showed no rise in IgG titre and an absence of IgM.

Chest radiography, abdominal ultrasound, and transoesophagus ultrasonography revealed no abnormality. Ganciclovir was discontinued and leucocytes increased to 9400/mm³. Despite broad spectrum antimicrobial treatment (ceftazidine, ciprofloxacine, teicoplanine, and fluconazole), the patient developed a diffuse bilateral interstitial pneumonitis with respiratory distress. On day 30 a bronchoalveolar lavage (BAL) was performed but no pathogens were identified. On day 36 the patient died of refractory septic shock. Necropsy revealed disseminated toxoplasmosis. Lesions were identified on haematoxylin and eosin stained sections within the heart (pseudocysts in myocytes and foci of necrotic myocytes with free tachyzoites) and the lungs (fig 1). Tachyzoites were also identified in the liver (fig 2), kidneys (endothelial cells), pancreas (acinar cells), and spleen on immunostaining using a specific anti-toxoplasma antibody (Biogenex, San Ramon, California, USA). Re-examination of the BAL revealed very rare tachyzoites.

Figure 1.

Toxoplasmic pneumonitis: toxoplasmic pseudocyst (arrow) and free tachyzoites (arrowheads). Haematoxylin and eosin stained.

Figure 2.

Liver involvement: Toxoplasma gondii in a sinusoidal cell (arrow) and in a hepatocyte (arrowhead). Toxoplasma specific immunostaining.

Disseminated toxoplasmosis is a severe disease with a very high mortality rate, but treatment with pyrimethamine sulfadiazine or clindamycin can sometimes be effective.¹ It occurs very rarely after liver transplantation,^2–5 and can result from primary infection or reactivation, as in our patient. In addition to the heavy immunosuppression, leuconeutropenia, probably related to the ganciclovir treatment, may have contributed to this reactivation in our patient.

The diagnosis of toxoplasmic infection is difficult. Indeed, serological changes (rise in baseline antibody titres or the development of antibodies) are frequently lacking in immunocompromised patients. So far, our case is the only one described in a toxoplasma seropositive liver transplant recipient with no increase in antibodies titres, which were regularly measured. This clearly shows that serological data are unreliable in liver transplant recipients, as in other immunocompromised patients.

Disseminated toxoplasmosis is associated with fever and a multivisceral involvement. The organs most often involved are the lungs, heart, and brain.⁶ Visualization of tachyzoites in BAL fluid by Giemsa staining is difficult because of their small size. Immunostaining of tissues dramatically improves toxoplasma detection.⁷ The polymerase chain reaction (PCR) can also be performed on BAL fluid or blood samples.⁸ The use of both morphology and PCR improves the sensitivity of the diagnosis.⁷