Dummer, JS

Esquivel, CO

Ho, M

Kusne, S

Makowka, L

Rabin, BS

Starzl, TE

Whiteside, T

English

PubMed

D-Scholarship@Pitt

~y SELF-LIMITED TOXOPLASMA PARASITEMIA AFTER LIVER TRANSPLANTATION' Although toxoplasmosis is often a mild or asymptomatic infection in normal subjects, it may cause lethal disease in immunocompromised patients (1-3) . Detection of the disease is difficult and often requires histological evidence. Many cases are diagnosed at autopsy. We recently isolated Toxoplasma gondii in tissue culture from the blood of a febrile liver trans-plant patient who later developed lymphocytic meningitis. The patient recovered completely, despite receiving only short courses of antimicrobials active against Toxoplasma. Our ex-perience illustrates that isolation of Toxoplasma from the blood of a solid organ transplant patient may occur with limited disease. A 57-year-old woman with a two-year history of chronic active hepatitis underwent orthotopic liver transplantation and received cyclosporine (CsA) and prednisone immunosuppres-sion. Ampicillin and cefotaxime (4 g each) were given daily for five days as antibiotic prophylaxis. At 18 days after the opera-tion, a liver biopsy showed acute rejection and a 10-day intra-venous course of mouse OKT3 antibody was administered. At 24 days after the operation, the patient had a temperature elevation to 39.5·C. A computerized tomographic scan of the abdomen showed a hypodense 3.5x4.5-cm area in the liver. Percutaneous aspiration of this yielded heavy Streptococcus [ecalis on culture. Pipercillin, gentamicin, and cefox~itin were administered, but then switched to ampicillin, gentamicin, and c1indamycin. A drain was left in the liver abscess cavity. Clin-damycin was discontinued after three days, but ampicillin was continued 8 days and gentamicin was continued for 10 days. The patient continued to have significant fever while receiving these antibiotics. By 39 days after the operation the patient was afebrile, but she then developed confusion. A computerized tomographic scan of the head was normal, but examination of the cerebrospinal fluid showed 360 red blood cells and 50 white blood cells (1 neutrophil, 1 mononuclear, and 48 lymphs); the glucose was 46 mg% and the protein 48 mg% . Cultures of the spinal fluid were sterile. Her peripheral blood smear showed a white count of 12,700 with 8% atypical lymphocytes, 22% lymphocytes, 63% polymorphonuclear cells, 5% monocytes and 2% eosinophils. At this time a single dose of i.v. sulfamethox-azole/trimethoprim (1 g/200 mg) was administered when a weakly positive Pneumocysti.s carinii serum antigen (1:2) was reported (Linda L. Pifer, Memphis, TN, personal communica-tion) . This was discontinued because the patient's illness was not compatible with Pneumocystis infection. Thereafter, the patient improved clinically and was discharged from the hos-I This work was supported in part by NIH Grant 1 ROI AI 19377. pitaf 48 days after the operation with no fever or neurological problems. Before discharge a buffy coat culture of the blood taken 26 days after the operation and inoculated in tubes of human foreskin fibroblasts showed cytopathic effect, with swol-len cells containing multiple inclusions: A wet preparation of the culture supernatant showed 2x6-/L oval bodies that were motile. These were later identified by electron microscopy as T gondii (Fig. 1). The same buffy coat was positive for cytomegalovirus, which was also isolated from buffy coats obtained on days 34 and 39 after transplantation. Pretransplant serum showed a titer of Epstein-Barr viral capsid antigen of 1:80, and Epstein-Barr early antigen of <1:5. Serum from day 39 after transplantation showed a 16-fold titer rise of IgG antibody to viral capsid antigen, and an 8-fold titer rise of IgG antibody to early antigen. Thus the patient showed a significant rise in titer of Epstein-Barr virus antibodies suggesting reactivation infection. Stored donor and pre- and posttransplant recipient sera were tested for anti-Toxoplasma IgG antibody by Fiax (M .A. Bio-products, Walkersville, MD). This is a semiautomated solid-phase fluorescent antibody test wherein the toxoplasma antigen FIGURE 1. Electron microscopy of Toxop/(lsma gondii organisms isolated in tissue culture and seen within an intracellular vacuole. The arrow point~ to the characteristic conoid at the anterior end of the organisms, from which densely staining rophtries arise. 458 TRANSPLANTATION Vol. 44, No.3 is impregnated onto paper strips that are reacted with the patient's serum and then with a fluorescein-labeled antihuman IgG. The results of these tests and the serial clinical events are shown in Figure 2. The recipient showed a seven-fold rise in titer by 47 days after transplant. The two seven-day courses of low-dose (500 mg/day) oral sulfisoxazole were administered as infection prophylaxis but discontinued once a defined infection (the liver abscess) was discovered. Shepp recently described the isolation in tissue culture of Toxoplasma from the blood of three bone marrow transplant recipients, all of whom died. Invasive disease was shown in the two patients who had a full autopsy (4). This is the first report of isolation of Toxoplasma in tissue culture from a solid organ transplant recipient and is remarkable for the relatively benign course of the infection. Although the patient received antimi-crobials that may have been active against Toxoplasma, these were given in very low doses (sulfisoxazole) or for very short courses (clindamycin and sulfamethoxazole/trimethoprim). It is possible, of course, that the low doses of sulfisoxazole modi-fied the illness without actually preventing it. In addition to Toxoplasma infection the patient also had cultural evidence of cytomegalovirus infection, serological evidence of Epstein-Barr virus infection, and a bacterial liver abscess. However, her fever persisted for 10 days after drainage of the liver abscess and during administration of antibiotics active against the bacterial isolates from the abscess, and only disappeared after the anti-biotics were stopped. The lymphocytic meningitis could be explained by Toxo-plasma infection, but aBso by cytomegalovirus and Epstein-Barr virus infections. Both viruses can rarely cause meningoenceph-alitis with lymphocytic pleocytosis in the cerebral spinal fluid (5,6). The source of the Toxoplasma infection was unknown, and it might have arisen by reactivation of latent infection or been transmitted by blood products (7, 8). Transmission by the donor organ is also a possibility, but this has not been demon-stra ted in a liver transplant recipient. Ta Xa DONOR 1 :65 TITERS (b) RECIPIENT 1 :200 1 :?9 1: 1030 1 :1 ~ 1R 48 40 39 rEMF 10 20 30 40 Suilisoxa::tole 500 mg PO $ ull;:sox. 500 mg PO Sutlameihoxazole , I ~ . Tl'W'r'elhOpnm one 0056 ,'" ColOlllXlme -4 IF' IV Geftfl)mcn 225 mg IV I I ,AmolOlIin 8 gm IV I I C1l1ldam'ya.ll 2400 mg IV I---l • PlC)efat'filn 3 gm one nose IV • CelOxI\)'fI I gm on. dose IV Co 38 37 (a) LJ...l..l..l.LW..J.J.:'::-1 0UJ....u...l..l..jt:-'-:!:20:LJ-J..J.J.+t LW,""30,.u..LL1...u...LLl;o,.LLLU..l..l.4l:-r W fl tpj!JC1jQn f~::d ~= iM=~~C a~~ DAYS AFTER TRANSPLANTATION FIG URE 2. Clinical and laboratory events after transplantation. On the horizontal axis (a) are shown the key clinical events in days posttransplantation. Above the horizontal are a longitudinal tempera-ture curve and the timing of all antibiotics administered in the post-operative period. The horizontal (b) shows Toxoplasma IgG antibody titers (FlAX) of donor and recipient sera collected before and after transplantation. A positive titer is greater than 24. The Toxoplasma organisms were isolated from a buffy coat culture taken on day 26 but were not actually detected until 46 days after transplantation, when the patient was well. -The significant Toxoplasrnu 'antibody rise suggests that the isolate represented more than transient toxoplasmemia. Rem-ington has stressed that toxoplasma infection is more likely to be severe when a seronegative patient undergoes primary infec-tion after transplantation, and some centers recommend anti-microbial prophylaxis in such patients (9, 10). This patient's established immunity before transplantation may have been an important factor in her rapid and complete recovery. Although tissue culture of blood is probably not a sensitive technique for diagnosing toxoplasmosis, its sensitivity might be improved by culturing larger quantities of blood. Awareness that Toxoplasma may be isolated in routine viral cultures may occasionally aid in the detection of the disease. Acknowledgement. We acknowledge the important role of Leona Youngblood in first detecting the toxoplasma in tissue culture. SHIMON KUSNE J. STEPHEN DUMMER2 MONTO Ho THERESA WHITESIDE BRUCE S. RABIN LEONARD MAKOWKA CARLOS O. ESQUIVEL THOMAS E. STARZL The Departments of Medicine, Surgery, and Pathology University of Pittsburgh School of Medicine Presbyterian University Hospital The Department of Infectious Diseases and Microbiology University of Pittsburgh Graduate School of Public Health Pittsburgh, Pennsylvania 2 Please address reprint requests to Dr. J . Stephen Dummer, Uni-versity of Pittsburgh, 428 Crabtree Hall, Pittsburgh, PA 15261. REFERENCES 1. Ruskin J, Remington JS. Toxoplasmosis in the compromised host. Ann Intern Med 1976; 84: 193. 2. Anthony CWo Disseminated toxoplasmosis in a liver transplant patient. J Am Med Worn Assoc 1972; 27: 601. 3. Carey RM, Kimball AC, Armstrong D, Lieberman PH. Toxoplas-mosis: clinical experiences in a cancer hospital. Am J Med 1973; 54: 30. 4. Shepp DH, Hackman RC, Conley FK, Anderson JB, Meyers J. Toxoplasma gondii reactivation identified by detection of para-sitemia in tissue culture. Ann Intern Med 1985; 103: 218. 5. Klemola E, Kaariainen L, Von Essen R, Hatia K, Koivuniemi A, von Bonsdorff CH. Further studies on cytomegalovirus mono-nucleosis in previously healthy individuals. Acta Med Scand 1967; 182: 311. 6. Grose C, Henle W, Henle G, Feorino PM. Primary Epstein-Barr virus infections in acute neurologic diseases. N Engl J Med 1975; 292: 392. 7. Anderson SE Jr, Remington JS. The diagnosis of toxoplasmosis. South Med J 1975; 68: 1433. 8. Siegel SE, Lunde MN, Gelderman AH, et al. Transmission of toxoplasmosis by leukocyte transfusion. Blood 1971; 37: 388. 9. Luft BJ, Naot Y, Araujo FG, Stinson EB, Remington JS. Primary and reactivated toxoplasma infection in patients with cardiac transplants. Ann Intern Med 1983; 99: 27. 10. Hakim M, Esmore D, Wallwork J, English TAH. Toxoplasmosis in cardiac transplantation. Br Med J 1986; 292: 1108. Received 7 August 1986. Accepted 3 December 1986. 

Self-limited Toxoplasma parasitemia after liver transplantation

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SELF-LIMITED TOXOPLASMA PARASITEMIA AFTER LIVER TRANSPLANTATION

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Self-limited toxoplasma parasitemia after liver transplantation

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Self-limited Toxoplasma parasitemia after liver transplantation

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