POSTTRANSPLANT MALARIA: FIRST CASE OF TRANSMISSION OF PLASMODIUM FALCIPARUM FROM A WHITE MULTIORGAN DONOR TO FOUR RECIPIENTS

Le résumé fourni par la source

Malaria represents an unusual complication of solid-organ transplantation in nonendemic countries. Most cases have been described after renal transplantation (32 cases), whereas only two and three cases have been reported in heart (1,2) and liver (2–4) transplantation, respectively. All the species of plasmodium may be involved. We report the first case of a well-documented transmission of Plasmodium falciparum from a single white donor to four recipients, with different outcomes according to the concerned graft transplant and the ability to rapidly confirm diagnosis of malaria and to deliver an appropriate treatment. The liver recipient was a 54-year-old white man who underwent liver transplantation for posthepatitis C cirrhosis, at Caen, France, using cyclosporine A, mycophenolate mofetil, and methylprednisolone immunosuppression. The postoperative course was uneventful, and the patient was discharged from the intensive care unit (ICU) on day 6. Two days later, schizonts were observed on systematic blood sample examination. Diagnosis of malaria was confirmed by a high parasitemia (15%) on the thin and the thick smears. At this time, only slight biologic abnormalities were observed (thrombopenia, twofold cytolysis). The patient was immediately treated by antimalaria chemotherapy (25 mg/kg/day of quinine) and readmitted to the ICU. Nevertheless, alteration of neurologic status appeared, with deep coma within the first 3 days of treatment. Vibramycin was added to quinine but the immunosuppressive therapy was not modified, except for the adaptation of cyclosporine A blood level. Then, neurologic status improved 5 days after the onset of treatment and parasitemia disappeared. The outcome was next characterized by liver function test deterioration during treatment, associated with high bilirubinemia; however, no cholangitis was observed during cholangiography. Next, repeated biopsies on days 10 and 20 showed no histologic abnormality other than cholestasis and pigment deposits. Liver enzyme levels began to improve only 1 month later, and 3 months later the patient was doing well, and liver function was restored except for a slight elevation of γ-glutamyl transpeptidase. The heart recipient was a 46-year-old white man who underwent transplantation for end-stage cardiomyopathy at Nantes, France. The patient received antilymphocyte serum, cyclosporine A, mycophenolate mofetil, and methylprednisolone immunosuppression. At day 5, fever and neurologic disorders appeared, and the patient developed acute renal failure with severe acidosis. Liver and hematologic tests were also altered (cytolysis, anemia, and thrombopenia). His condition was worsening when the information about suspected malaria of the donor became available. Despite rapid delivery of adequate treatment after confirmation of the diagnosis of P. falciparum infection followed by a rapid decrease in parasitemia from 30% to 15%, the patient died from multiple organ failure syndrome caused by active malaria infection, 17 days after allograft transplantation. The renal recipients were two white patients suffering from end-stage renal failure. Both had excellent health when the diagnosis of malaria was made in the other recipients. They received preventive antimalaria chemotherapy and remained completely safe despite one presenting a positive blood smear at the beginning of the treatment. The donor was a white man who often traveled in malaria-endemic areas. The cause of death was cerebral trauma after an unexplained syncope. We retrospectively knew that he had recently returned from Togo (10 days before the death) and had had inadequate prophylaxis for malaria. Retrospective serology and blood smear of the donor were highly positive, confirming that he was infected. It was also not excluded that malaria was directly the cause of syncope, and then of the death. Malaria is a very frequent infectious disease caused by different types of plasmodium, and is usually associated with good prognosis, except for P. falciparum (5,6). During the posttransplant course, malaria represents one of the multiple infectious complications; however, cases are rarely reported, especially in nonendemic countries, and its prognosis remains unknown for patients with immunosuppressive therapy to prevent allograft rejection. We report the first well-documented case of multiorgan donation from a single donor followed by P. falciparum malaria in recipients. The kidney and liver recipients survived after effective antimalaria chemotherapy but the heart transplant recipient died. To the authors’ knowledge, 37 cases of posttransplant malaria are reported in the literature. Most posttransplant malaria concerned kidney transplantation (2,7–9). Three cases of posttransplant malaria are reported for the liver (2–4), and only one of them concerned transmission by means of a P. falciparum–infected organ. In the latter case, diagnosis was confirmed at posttransplantation day 22, when neurologic disorders and fever occurred. Despite adequate antimalaria chemotherapy, the patient died 10 days later (3). Among these 37 cases reported, only 8 well-documented graft transmissions are described: two hearts (1,2), two livers (2,3), and four kidneys (2,7,8) (three of eight had unfavorable outcome). Furthermore, one case of malaria transmitted by a multiorgan donation from a single donor has been described, and the microbiologic agent detected was P. vivax. The donor immigrated from Cameroon, where he contracted the parasite without active malaria infection, to Germany 18 months before the transplantation. Kidney and heart recipients did not suffer active malaria after effective therapy by quinine. In contrast, the liver recipient died 5 months later from liver failure, possibly because of side effects of the antimalaria medication (2). The transmission of the parasite is attributable to different mechanisms, such as mosquito sting in endemic areas or at international airports and during blood transfusion or organ transmission (5). The prognosis of posttransplantation malaria may be influenced by the following: type of transplanted organ, plasmodium species, immunosuppressive therapy, and the delay of the onset of the treatment. It is well known that P. falciparum, which is sequestered in the microvasculature, is more virulent in humans than other plasmodium species. Moreover, the parasites survive more than 24 hr at 4°C in blood. For the above reasons, cold temperature preservation of transplants, which is approximately the same length of time as plasmodium cold resistance, does not prevent recipient transmission. Kidney recipients usually have good prognosis (both recipients survived in the authors’ case and only 2 of the 32 cases reported in the literature, concerning kidney transplantation, died) and present delayed malaria in comparison with other solid-organ transplantations. In contrast, prognosis of malaria seems to be poor after liver and heart transplantation compared with kidney transplantation, without an evident explanation for the higher mortality rate observed. Several hypothesis could be proposed: First, kidneys, which are harvested at the end of the procedure, are probably better flushed and washed out than other transplants. Second, time of preservation of organs at low temperature is longer for kidney (24–48 hr) than for liver (<12 hr), and is reduced in heart transplantation (3–4 hr). It is possible that the decrease in the amount of the active transmitted plasmodium is directly correlated with the time course of cold preservation; nevertheless, no data are available to confirm this hypothesis. Third, the profound immunosuppressive therapy used after heart transplantation might explain the poor outcome of the heart recipients infected with plasmodium. Most of them, including the one in the authors’ case, received antilymphocyte serum, which induces a severe depletion of T lymphocytes, the key cells in antimalaria immunity (10).

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