Sulfadiazine therapy for toxoplasmosis in heart transplant recipients decreases cyclosporine concentration

Summary Toxoplasmosis may cause serious problems after organ transplantation. For treatment of active infection, pyrimethamine combined with a sulfonamide is recommended. During oral sulfadiazine therapy, a significant decrease in cyclosporine concentrations was observed in three heart transplant recipients. This interaction has not been reported previously.     

Disseminated toxoplasmosis with sepsis in AIDS

Summary A 24-year-old woman with acquired immunodeficiency syndrome was admitted with septic fever of unknown origin and a 2-week history of diarrhea. Clinical diagnostic procedures did not reveal the cause of sepsis. Broad-spectrum antibiotics and intensive symptomatic therapy could not prevent progressive deterioration. The patient developed septic shock and consumptive coagulopathy and died 6 days after admission. Autopsy revealed disseminated infection with toxoplasma gondii and multiple organ manifestations. We conclude that disseminated toxoplasmosis should be considered in AIDS patients with septic disease of unknown origin. Extremely elevated lactate dehydrogenase may suggest disseminated toxoplasma gondii infection. New procedures such as polymerase chain reaction for detection of toxoplasmosis may be helpful diagnostic tools.Abbreviations AIDS acquired immunodeficiency syndrome     

Endomyocardial biopsy for monitoring heart transplant patients: 11-years-experience at a german heart center

Background: Heart transplantation (HTX) has become an established therapy for patients with end-stage heart failure. Endomyocardial biopsy (EMB) still represents the gold standard for routine surveillance of heart transplant rejection. The objective of this article is to report our experience regarding the use of EMB in monitoring heart transplant recipients. Methods: We evaluated retrospectively all patients who underwent orthotopic HTX between 2000 and 2011 at our hospital. From all patients, we created a follow-up, determined the number of EMB events and described the complications associated with this procedure. Results: HTX was performed in 142 cases at our center in the last 11 years (1.3% of the total of 10693 cardiac surgical operations in that period). Further 9 patients visited our department for monitoring after HTX performed at an external center (total: 151). For all patients, a total of 1896 EMB events have been recorded. The majority of biopsies were performed through the right internal jugular vein. The overall complication rate was 1% (n=19). Conclusions: The histological examination of right ventricular EMB still represents the gold standard of care for cardiac allograft rejection monitoring. EMB is an invasive, but safe and dedicated diagnostic procedure. However, the usefulness of recent non-invasive diagnostic approaches as an adjunct tool in monitoring for rejection remains to be further analyzed.     

Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient

Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients.     

Trypanosoma cruzi myocardial infection reactivation presenting as complete atrioventricular block in a Chagas'' heart transplant recipient

A 56-year-old man underwent orthotopic heart transplantation because of end-stage Chagas' cardiomyopathy. One hundred and ten days following heart transplantation, an electrocardiogram tracing showed complete atrioventricular block, which was treated with temporary transvenous pacemaker insertion. An underlying endomyocardial biopsy was graded 3A. The patient was treated with pulse steroid therapy. One week later, the patient died of multiorgan failure secondary to septicemia. A careful review of the endomyocardial biopsy showed nests of parasites in the myocardial tissue accompanied by mononuclear cell infiltrate similar to that found in acute graft rejection. Thus, complete atrioventricular block may be another clinical manifestation of Trypanosoma cruzi infection reactivation in Chagas' heart transplant recipients.     

Rhodococcus equi pneumonia in a heart transplant recipient in Korea, with emphasis on microbial diagnosis

Rhodococcus equi is an opportunistic pathogen that usually causes infection in immunocompromised hosts. A heart transplant recipient who had been treated with amphotericin B for pulmonary aspergillosis showed newly developed multiple nodules with a central necrotic area in the right lower lobes. Cultures of several blood samples and an aspirate of the lung nodule yielded a Gram-positive coccobacillary bacterium, which was initially reported as a Corynebacterium species, but was later identified as R. equi by API CORYNE (bioMerieux SA, Marcy l'Etoile, France) and by demonstrating the production of 'equi factor'. The identification was subsequently confirmed by an R. equi -specific polymerase chain reaction (PCR). The patient was successfully treated with ciprofloxacin and azithromycin for 14 weeks. This is the first documented case of R. equi infection in Korea. There is a possibility of underestimation of R. equi infections due to the misidentification of the organism as a contaminating diphtheroid. Because R. equi will not respond to the conventional empirical therapy, the microbiology laboratory should identify R. equi in a timely manner. R. equi -specific PCR will be a useful confirmatory test in human infection.     

Detection of human herpesviruses 6 and 7 in heart transplant recipients by a multiplex polymerase chain reaction method

In order to evaluate the possible reactivation of human herpesviruses 6 (HHV-6) and 7 (HHV-7) after heart transplantation, buffy-coat and plasma specimens from 21 transplant patients and 56 healthy blood donors were examined for HHV-6 and HHV-7 DNA by polymerase chain reaction. Human herpesvirus 6 and HHV-7 infection or reactivation has been suggested to play a role in cytomegalovirus disease progression in renal transplant recipients. In the present study, however, no significant difference in the prevalence of HHV-6 and HHV-7 was found between the immunosuppressed and the healthy population; moreover, no viral reactivation was found in the heart transplant recipients.     

组织学三联征和聚合酶链反应在弓形虫淋巴结炎病理诊断中的应用

目的 经典的组织学三联征诊断法和荧光原位杂交(PCR)法在提高石蜡包埋组织弓形虫淋巴结炎确诊率中的价值.方法 收集本院1999年4月至2009年9月诊断的46例符合组织学三联征形态改变的石蜡包埋淋巴结组织,采用半嵌套式PCR方法 对提取DNA进行弓形虫基因组的片段扩增;另选取30例组织中可见三联征中的二个或一个特征的病例作为对照.结果 组织学三联征组PCR阳性率为76.1%(35/46),对照组阳性率仅为10.0%(3/30,P<0.01);组织学三联征诊断弓形虫淋巴结炎的灵敏度为92.1%(35/38),特异度为71.1%(27/38);PCR法的阳性预测值为76.1%(35/46),阴性预测值为90.0%(27/30).结论 经典的组织学三联征对于诊断弓形虫淋巴结炎的特异性很强,但敏感性较低,且易漏诊部分非典型病例.在组织形态改变的基础上结合半嵌套式PCR对刚地弓形虫基因片段的检测可大大提高检出敏感性和准确性.     

Molecular evidence for the existence of disseminated zoster as a distinct entity in an immunosuppressed renal transplant patient

Immunosuppressed renal transplant recipients are at substantially increased risk for the developement of varicella zoster virus infections. They are also more prone than immunocompetent patients to develop atypical zoster and to experience a protracted course, and among them there is a higher frequency of generalized infections with possible fatal outcome. While establishing the diagnosis is essential to provide adequate therapy, conventional laboratory methods frequently fail to confirm the suspected infection. We report on a 47-year-old renal transplant recipient who developed multiple necrotic cutaneous ulcers under immunosuppressive treatment. While electron-microscopic analysis (negative staining) revealed no viral structures, varicella zoster virus specific DNA was detected by polymerase chain re-action in material obtained by a swab from these ulcers. Atypical herpetic infection should also be considered as a cause of disseminated ulcerative or necrotic skin lesions in immunosuppressed patients. Assays based on polymerase chain reaction are useful for the rapid confirmation or rejection of the suspected diagnosis of atypical herpetic infection.Abbreviations PCR Polymerase chain reaction - VZV Varicella zoster virus - HSV Herpes simplex virus     

Diagnosis of cytomegalovirus infection in kidney transplant recipients by a quantitative RNA-DNA hybrid capture assay for cytomegalovirus DNA in leukocytes

The clinical value of a new RNA-DNA hybridization assay for quantification of Cytomegalovirus (CMV) DNA in leukocytes [Hybrid Capture CMV DNA Assay (HCA); Murex Biotech, UK] was evaluated. The HCA was compared with an assay for CMV pp65 antigen in leukocytes and an in-house CMV polymerase chain reaction PCR (CMV-PCR) on parallel blood samples. The HCA and the CMV-PCR were less sensitive than the CMV pp65 assay, but the positive predictive value of all three methods for CMV disease was 50% or less. However, when quantitation of viral load by HCA and CMV pp65 assay was taken into consideration, both assays were superior to CMV-PCR in predicting CMV disease.     

Human cardiac transplantation--evaluation of morphological changes in serial endomyocardial biopsies

From May 1981 through July 1984 a total of 29 human allogenic orthotopic cardiac transplants were performed in Munich. The first two patients initially received conventional immunosuppressive treatment for 79 and 27 days, respectively; then treatment was continued with cyclosporine. All subsequent 27 patients received only cyclosporine treatment. Seventeen of the cardiac recipients are currently alive. Three of the recipients who died succumbed to immunological rejection. Twenty-five cardiac grafts were controlled by 355 sequential biopsy procedures, which yielded 1158 endomyocardial specimens for histological examination. The morphological findings and changes observed in the endomyocardium were analyzed. The interpretation of these findings and difficulties encountered in their interpretation are discussed. Special attention is attributed to findings possibly associated with the cyclosporine treatment.     

Mycobacterial coronary arteritis in a heart transplant recipient

A case of mycobacterial vasculitis in a chronically rejected transplanted heart is described. The coronary arteries were the only vessels involved by mycobacteria, although the patient had a generalized infection. The process of chronic rejection, with persistent injury to the intimal vascular lining of a transplanted organ, may lead to defects in the endothelial cell barrier and thus facilitate infiltration of a vessel wall by acid-fast bacilli.     

Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis

ObjectivesReactivation of latent toxoplasmosis may be life-threatening in haematopoietic stem cell transplant (HSCT) recipients. We conducted an 8-year-long prospective study on the diagnosis and monitoring of reactivated toxoplasmosis in paediatric HSCT recipients. The primary objective was to determine the incidence of reactivated toxoplasmosis in a setting that withholds prophylaxis until engraftment. The second objective was to identify the subgroups of HSCT recipients particularly prone to reactivation who may benefit the most from regular PCR follow-up.MethodsSerological and qPCR screening targeting the Toxoplasma 529 bp gene was performed before HSCT, and continued by weekly monitoring after HSCT for a median time of 104 days.ResultsReactivated toxoplasmosis was diagnosed in 21/104 (20.2%), predominantly in allo- (19/75) and rarely in auto-HSCT (2/29) recipients. Over 50% (14/21) of cases were diagnosed during the first month after HSCT, while awaiting engraftment without prophylaxis. Toxoplasma disease evolved in only three (14.3%, 3/21) patients, all treated by allo-HSCT. Reactivation was more frequent in patients treated for acute lymphoblastic leukaemia (3/27, p 0.03) and especially, in recipients of haploidentical stem cells (10/20, p 0.005). Seronegative status of the donor (where was known) contributed to 75% (12/16) cases of reactivated toxoplasmosis after allo-HSCT.DiscussionThe presented results show that peripheral blood-based qPCR, both before and after HSCT, is a valuable asset for the diagnosis of reactivated toxoplasmosis, whereas the results of serology in recipients should be interpreted with caution. Weekly qPCR monitoring, at least until successful engraftment and administration of prophylaxis, allows for prompt introduction of specific treatment.     

Human cytomegalovirus and acute rejection after heart transplantation are not directly associated

Retrospective and prospective analyses of heart transplant recipients showed no significant association between acute rejection and the detection of cytomegalovirus (CMV) infection by culture or the polymerase chain reaction (PCR) for viral DNA, neither on grounds of the incidence of both conditions nor in relation to which was diagnosed first in the patient. Semiquantitative PCR of serial blood and endomyocardial biopsy specimens from individual patients revealed different patterns in the development of the viral DNA in the blood and the heart, also clear episodes of CMV infection in CMV antibody-negative recipients of hearts from CMV antibody-negative donors, none of whom went on to develop a CMV-specific antibody response. None of these findings was associated with the development of rejection in the patient. On the other hand, in those patients who did experience rejection, peak levels of CMV DNA in the blood and the heart were usually not reached until 6 weeks or more after transplantation, whereas in those in whom rejection was not detected at all during the period of observation, peak levels of CMV DNA were detected earlier, mainly within the first 6 weeks after transplantation. In several cases, the delayed increase in CMV DNA in those with rejection, albeit not the delay itself, was linked to treatment with steroids. These findings support the view that CMV infection and rejection are independent events, but that the timing of the infection, and whether or not rejection is detected, are indicative of the general status of the immune response in individual patients. © 1996 Wiley-Liss, Inc.     

Soluble HLA-G pre-transplant levels to identify the risk for development of infection in heart transplant recipients

Infection is still a leading cause of death during the first year after heart transplantation. We evaluated the pre-transplant levels of HLA (Human Leukocyte antigen) – G molecules as a means of identifying heart recipients at risk of serious infections. We prospectively analyzed 122 adult heart transplant (HT) recipients. Serum samples were collected before transplantation and analyzed for sHLA-G levels by ELISA assay. The clinical follow-up period lasted 5 years. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 39 patients (32%) developed at least 1 serious bacterial infection. Higher pre-transplant sHLA-G levels were a risk factor for serious infection (above median value 5.4 ng/ml; relative risk 3.70; 95% confidence interval 1.03–12.64; p = 0.043). Patients with high levels of pre-transplant sHLA-G are also characterized by a lower overall survival at 5 years (p = 0.017), with microbial infections as major causes of death. No association was observed with the development rejection episode. Early monitoring of sHLA-G molecules proved useful for the identification of heart recipients who are at risk of serious infections.