Disseminated toxoplasmosis after allogeneic stem cell transplantation in a seronegative recipient

Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre‐transplant. We herein report a seronegative patient with acute T‐cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre‐transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.     

Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy

Abstract: Toxoplasmosis is a rare but well recognized opportunistic infection that can occur after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Besides encephalitis, other common presentations of Toxoplasma gondii infection are interstitial pneumonitis and myocarditis. Because of its non‐specific clinical and biological signs and its lethal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. We report a case of a postmortem diagnosis of disseminated toxoplasmosis associated with hemophagocytic syndrome, which underlines the value of necropsy in cases of death after transplantation. We also discuss clinical presentations and risk factors that lead to toxoplasmosis in allo‐HSCT recipients.     

Pulmonary toxoplasmosis in bone marrow transplant recipients: report of two cases and review.

Toxoplasma gondii may cause disseminated disease in bone marrow transplant (BMT) recipients. Pulmonary toxoplasmosis in BMT patients is rarely described. Mortality rates of >90% have been previously reported. Since pulmonary toxoplasmosis is extremely difficult to diagnose, it is very often detected only at autopsy. Two cases of pulmonary toxoplasmosis in BMT recipients that were diagnosed by visualization of T. gondii tachyzoites in bronchoalveolar lavage fluid and by a new semi-nested PCR method amplifying 18S rRNA from bronchoalveolar lavage fluid are presented, and the literature on pulmonary toxoplasmosis in BMT patients is reviewed.     

Toxoplasmosis in cord blood transplantation recipients

Toxoplasmosis is a devastating opportunistic infection that can affect immunocompromised patients such as cord blood transplantation (CBT) recipients. The clinical characteristics of 4 toxoplasmosis CBT patients treated at our institution are reviewed, together with 5 cases collected from the literature. The rate of toxoplasmosis in our hospital was 6% in CBT recipients and 0.2% in other types of allogeneic hematopoietic stem cell transplantation (P < 0.001). Five patients (56%) presented disseminated toxoplasmosis and 4 patients (44%) had localized infection in the central nervous system. In 5 of the 9 patients considered (56%), cytomegalovirus viral replication had been detected before the clinical onset of toxoplasmosis. Seven patients (78%) had previously developed graft‐versus‐host disease. All patients who exhibited disseminated disease died due to Toxoplasma infection. Pre‐transplant serology was positive in 1 patient, negative in 3 patients, and not performed in another. Only 1 of these 5 patients with disseminated disease had received Toxoplasma prophylaxis with cotrimoxazole. It could be concluded that mortality in CBT patients with disseminated toxoplasmosis is unacceptably high. The negative results of serology in the majority of these cases, and its unspecific clinical presentation, makes diagnosis exceedingly difficult. Better diagnostic tests and prophylaxis strategy are needed in CBT recipients.     

Re‐infection of Toxoplasma gondii after HSCT presenting lymphadenopathy resembling recurrence of lymphoma

Toxoplasma gondii (T. gondii) reactivation is one of the fatal complications after hematopoietic stem cell transplantation (HSCT); however, re‐infection has not been reported. Here, we report a case of mycosis fungoides in which cervical lymphadenopathy developed after HSCT. Initially, recurrent lymphoma was suspected. However, biopsy of the lymph node showed typical histology of toxoplasmosis and serology showed re‐infection of T. gondii. Toxoplasmosis needs to be differentiated for cases with lymphoadenopthy after HSCT.     

An unexpected but underestimated case of disseminated toxoplasmosis

Toxoplasma gondii is a ubiquitous intracellular parasite that can cause disseminated infection following reactivation in immunocompromised hosts. We describe a 58‐year‐old man who died of refractory shock because of disseminated toxoplasmosis. The diagnosis was only made postmortem on autopsy. We discuss the importance of considering toxoplasmosis on the differential diagnosis in high‐risk patients, and review the role of screening and chemoprophylaxis in preventing infection.     

Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients

Toxoplasmosis is a rare and possibly underestimated complication following hematopoietic stem cell transplantation (HSCT) associated with a high mortality rate, although the incidence of toxoplasmosis after HSCT in Japan has not been established. We retrospectively studied patients with toxoplasmosis after HSCT, and identified five patients who had been diagnosed with an acute exacerbation of toxoplasmosis among 279 HSCT recipients at our institution between 1998 and 2011, representing an incidence of 1.8 %. Among 87 autologous HSCT recipients, one definite case was diagnosed. The serological test for Toxoplasma gondii before HSCT was positive in 18 of 192 allogeneic HSCT recipients. Of the 18 seropositive patients, three had definite infections, and one had possible infection. All four definite cases were diagnosed at autopsy. In the definite cases, three allogeneic HSCT recipients had disseminated or pulmonary toxoplasmosis and one autologous HSCT recipient had toxoplasmic encephalitis, although toxoplasmosis was not suspected at the premortem examination due to non-specific clinical and radiological manifestations. Thus, acute exacerbation of toxoplasmosis should be suspected in recipients after HSCT. Early diagnosis and treatment for toxoplasmosis would certainly contribute to a decrease in mortality after HSCT.     

Disseminated toxoplasmosis associated with hemophagocytic syndrome after kidney transplantation: A case report and review

Disseminated toxoplasmosis is infrequent after kidney transplant transmission but life‐threatening because of a lack of diagnostic suspicion as well as specific chemoprophylaxis recommendations. Solid organ transplantation has resulted in few cases of disseminated toxoplasmosis presenting with associated hemophagocytic syndrome. Herein, we report, within the context of a donor/receiver mismatch, a case of a toxoplasmosis associated with hemophagocytic syndrome in a kidney transplant recipient. Molecular and serological investigations confirmed Toxoplasma gondii transmission through the kidney graft.     

Cardiac toxoplasmosis after heart transplantation diagnosed by endomyocardial biopsy

We describe a case of cardiac toxoplasmosis diagnosed by routine endomyocardial biopsy in a patient with trimethoprim‐sulfamethoxazole (TMP‐SMX) intolerance on atovaquone prophylaxis. Data are not available on the efficacy of atovaquone as Toxoplasma gondii prophylaxis after heart transplantation. In heart transplant patients in whom TMP‐SMX is not an option, other strategies may be considered, including the addition of pyrimethamine to atovaquone.     

How does toxoplasmosis affect the maternal‐foetal immune interface and pregnancy?

Toxoplasma gondii is a zoonotic parasite which, depending on the geographical location, can infect between 10% and 90% of humans. Infection during pregnancy may result in congenital toxoplasmosis. The effects on the foetus vary depending on the stage of gestation in which primary maternal infection arises. A large body of research has focused on understanding immune response to toxoplasmosis, although few studies have addressed how it is affected by pregnancy or the pathological consequences of infection at the maternal‐foetal interface. There is a lack of knowledge about how maternal immune cells, specifically macrophages, are modulated during infection and the resulting consequences for parasite control and pathology. Herein, we discuss the potential of T. gondii infection to affect the maternal‐foetal interface and the potential of pregnancy to disrupt maternal immunity to T. gondii infection.     

Toxoplasmosis in bone marrow transplantation: a report of two cases and systematic review of the literature

Toxoplasma infection represents a rare but often fatal complication in bone marrow transplant (BMT) recipients. We report two cases of toxoplasmosis: one of successfully treated cerebral toxoplasmosis after peripheral blood stem cell transplantation, and a fatal case of pulmonary toxoplasmosis in a BMT recipient. We have systematically reviewed the 110 published cases of toxoplasmosis following BMT. We analyzed the pre-transplant and clinical features of BMT recipients developing toxoplasmosis, together with the diagnostic procedures used and treatment given. By univariate and multivariate statistical analysis we analyzed the risk factors for diagnosis (during life vs post-mortem) and Toxoplasma-related mortality. Ante-mortem diagnosis was made in 47% of cases. Site of infection (P = 0.02; odds ratio 10.8), presence of symptoms at onset (P = 0.01) and conditioning regimen (P = 0.04) were factors influencing whether the diagnosis was made before or after death. Overall mortality rate was 80% and that attributed to toxoplasmosis was 66%. Variables influencing outcome were: site of infection (P = 0.02; odds ratio 5.28), day of onset (P = 0.04) and conditioning regimen (P = 0.04). Underlying disease (P = 0.02; odds ratio 9.45), among patients diagnosed before death, was the most significant factor influencing outcome.     

Cerebral toxoplasmosis and Guillain-Barré syndrome after allogeneic peripheral stem cell transplantation

We report an unusual case of cerebral toxoplasmosis associated with Guillain‐Barré syndrome ( GBS) in a 25‐year‐old patient diagnosed with chronic myelogenous leukaemia ( CML), who underwent a mismatched allogeneic peripheral stem cell transplantation ( PSCT). On day +83 he started with fever, and 7 days later tremor, muscular weakness, diplopia, dysarthria, respiratory difficulty, and universal arreflexia appeared, compatible with GBS. As the patient had a positive cytomegalovirus ( CMV) antigenemia, this was the aetiology suspected for his neurologic findings, but specific treatment failed to improve his clinical situation, and he died on day +123. Necropsy demonstrated cerebral toxoplasmosis and axonal degeneration of nerve roots compatible with the axonal form of GBS. Interestingly, the polymerase chain reaction ( PCR) signal for Toxoplasma gondii in two different cerebrospinal fluid ( CSF) samples had been negative. In addition, this case showed unique magnetic resonance imaging ( MRI) abnormalities. We conclude that a negative PCR on CSF cannot exclude toxoplasmosis in a transplant patient, and we emphasise the importance of considering Toxoplasma as an aetiology of fever and neurological symptoms in the transplant setting.     

Toxoplasmic encephalitis associated with meningitis in a heart transplant recipient

Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and <25 cases in immunosuppressed patients, such as patients infected with human immunodeficiency virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis in the differential diagnosis of meningitis in immunocompromised individuals.     

Demodicidosis simulating acute graft‐versus‐host disease after allogeneic stem cell transplantation in one patient with acute lymphoblastic leukemia

One important differential diagnosis of facial erythema in a patient receiving an allogeneic bone marrow transplant (BMT) is acute graft‐versus‐host disease (GVHD). Demodex folliculorum has been rarely implicated in the development of facial rashes in immunosuppressed patients, including BMT recipients. We report the case of a patient, suffering from acute lymphoblastic leukemia, who after bone marrow transplantation developed a facial rash due to D. folliculorum mimicking GVHD. Differential diagnosis of facial rashes and demodicidosis after BMT is reviewed.     

Cellular immunopathogenesis in primary Toxoplasma gondii infection during pregnancy

Congenital toxoplasmosis is caused by the vertical transmission of infection from mother to foetus through the placenta when a pregnant woman is infected with Toxoplasma gondii (T. gondii). Congenital infection can have serious consequences, such as intrauterine abortion, foetal death and severe neurological, ocular or other organ damage in the foetus. In this review, we focus on recent publications investigating vertical transmission of T. gondii infection, cellular immunopathogenesis and protective immunity in primary toxoplasmosis during pregnancy.     

Toxoplasmosis in immunosuppression and AIDS

Summary Reactivation of chronic, latent infection ofToxoplasma gondii has been observed previously in transplant patients and malignancies treated with immunosuppressive drugs. Recently it has emerged as the most common recognized central nervous system infection in acquired immunodeficiency syndrome (AIDS) patients, seen in 6–20% of all AIDS cases. It produces diffuse encephalopathy or space-occupying and necrotic lesions. Contrary to classical toxoplasmosis, the serological diagnosis is unreliable and the therapeutical response in most cases is poor.

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Toxoplasmose bei Immunsuppression und AIDS

Zusammenfassung Die Reaktivierung einer chronischen, latenten Infektion mitToxoplasma gondii wurde in jüngerer Zeit bei Transplantationspatienten und nach Behandlung von Malignomen mit Immunsuppressiva beobachtet. Neuerdings tritt die Toxoplasmose als die häufigste Infektion des Zentralnervensystems bei Patienten mit erworbenem Immundefizienz-Syndrom (AIDS) auf und wird bei 6–20% aller AIDS-Fälle beobachtet. Die Toxoplasma-Infektion führt zur diffusen Enzephalopathie oder zu raumfordernden, nekrotisierenden Läsionen. Im Gegensatz zur klassischen Toxoplasmose ist die serologische Diagnostik unzuverlässig, die meisten Fälle sprechen schlecht auf die Therapie an.

     

Respiratory syncytial virus infection in the late bone marrow transplant period: report of three cases and review.

Respiratory syncytial virus (RSV) infection is an important cause of respiratory mortality in immunosuppressed patients, including bone marrow transplant (BMT) recipients. The presence of lower respiratory tract infection and infection in the pre-engraftment phase of BMT is believed to confer a poor prognosis. Three patients who underwent allogeneic BMT at our institution developed RSV pneumonia over 1 year post BMT, with the underlying disease in remission. All three were hypoxic with extensive pulmonary disease at presentation. Treatment consisted of aerosolized ribavirin and intravenous immune globulin with successful clearing of viral shedding and excellent clinical outcomes. RSV infection is probably less severe in the late post-BMT period, but needs to be considered early in the differential diagnosis of pulmonary infiltrates in this patient population.     

Cerebral toxoplasmosis - a late complication of allogeneic haematopoietic stem cell transplantation

Toxoplasma gondii infection reactivation predominantly occurs among patients after allogeneic haematopoietic stem cell transplantation. Mostly, reactivation occurs during first 3 months after transplant, especially when risk factors are present. We report a case of late cerebral toxoplasmosis reactivation, which was probably triggered by a brief course of corticosteroids, administered for chronic graft-versus-host disease (cGVHD). In the presence of risk factors, such as cGVHD, prophylactic treatment for toxoplasmosis should be reinstituted; Trimethoprim-sulfamethoxasole most probably prevented earlier reactivation of toxoplasmosis in our patient.     

Prospective study of toxoplasma reactivation by polymerase chain reaction in allogeneic stem-cell transplant recipients

Toxoplasmosis is a rare but life‐threatening complication of allogeneic stem‐cell transplantation. Polymerase chain reaction (PCR) offers the possibility to make the diagnosis earlier than conventional techniques, and is then expected to improve the prognosis. We undertook a prospective screening using a competitive PCR in blood in 32 stem‐cell transplant recipients. The sampling covered the first 150 days post‐transplant, at days 21, 30, 45, 60, 90, 120, and 150. Twenty‐four patients had anti‐toxoplasma antibodies before transplant. Three of them (12.5%) had transient PCR‐positive samples at 21, 45, and 90 days post‐transplant, respectively. The three PCR‐positive patients were febrile but had no funduscopic examination or cerebral computerised tomography (CT) scan abnormalities. The PCR signal disappeared when the patients were given trimethoprim‐sulfamethoxazole, and no full‐blown toxoplasmosis was observed. Toxoplasma reactivation evidenced using PCR is frequent in seropositive patients not receiving trimethoprim‐sulfamethoxazole during the 1–3 months post‐transplant. Toxoplasma PCR should be included in the diagnostic strategy of fever of unexplained origin in allogeneic stem‐cell transplant recipients. Then, prompt specific therapy can be initiated to avoid development of full‐blown toxoplasmosis ^Note.     

Single institution outcomes of treatment of severe aplastic anaemia

Background: In severe aplastic anaemia, the treatment of choice for young patients with a human leucocyte antigen‐matched sibling is now established as allogeneic bone marrow transplantation (BMT). In older patients and in those without a matched sibling donor, immunosuppressive therapy is the usual first option. ‘Alternative’ marrow donors are emerging as an option for those without a matched sibling donor. Aims: To review 10 years of local experience in treating severe aplastic anaemia with BMT and immunosuppressive therapy with emphasis on long‐term outcomes. Methods: A retrospective analysis was performed of all patients with severe aplastic anaemia presenting to the Royal Brisbane and Royal Children’s Hos‐ pitals between 1989 and 1999. Data were abstracted regarding patient demographics, pretreatment characteristics and outcome measures, including response rates, overall survival and long‐term complications. Results: Twenty‐seven consecutive patients were identified, 12 treated with immunosuppression alone and 15 with BMT. In these two groups, transfusion independence was attained in 25% and 100%, respectively, with overall survival being 36% and 100%, respectively. Those treated with immunosuppression were significantly older (median 41.5 versus 22 years, P = 0.008). Long‐term survivors of either treatment had extremely low morbidity. Three patients carried pregnancies to term post‐transplant. Three patients received alternative donor BMT with correspondingly excellent survival. Conclusions: Patients treated with allogeneic BMT for severe aplastic anaemia enjoyed extremely good long‐term survival and minimal morbidity. Patients treated with immunosuppressive therapy had a poorer outcome reflecting their older age and different usage of therapies over the past decade. Optimal treatment strategies for severe aplastic anaemia remain to be determined. (Intern Med J 2001; 31: 337–342)