Cerebral trypanosomiasis in a renal transplant recipient

Chagas disease is a lifelong, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi. The main form of disease transmission is vector borne, but vertical transmission, such as by organ transplantation from a chronically infected donor, is also possible. The brain tumor‐like form can occur years after infection and has been described in patients with acquired immunodeficiency syndrome, and in a very few cases in transplant recipients. We describe the case of a kidney transplant patient who was human immunodeficiency virus negative and infected with T. cruzi, and developed cerebral trypanosomiasis that was successfully treated with benznidazole at 7 mg/kg/day for 60 days. The risk of Chagas disease transmission should not be underestimated in renal transplant patients, even in non‐endemic areas. Chagas disease can present as a tumor‐like brain lesion, very difficult to differentiate from other opportunistic infectious or neoplastic processes. Frequent monitoring for T. cruzi infection is essential to promptly implement treatment, which, in our patient, proved to be effective and safe.     

Very early‐onset of Cryptococcus neoformans disease following liver transplantation: Report of two cases and a review of the literature

Cryptococcosis is the third most common invasive fungal infection following solid organ transplantation, and mortality is high. Most cases occur late and are due to reactivation of latent infection; however, very early reactivation and donor‐derived transmission can occur. Routine screening pre‐transplant and antifungal prophylaxis for cryptococcosis post‐transplant in solid organ transplantation are not standard practice. We present two cases of very early‐onset Cryptococcus neoformans disease following liver transplantation to highlight the need to consider individualized pre‐transplant screening and be aware that reactivation of Cryptococcosis neoformans can occur in the immediate post‐transplant period.     

Seroprevalence of Trypanosoma cruzi in kidney transplant donors and recipients in Mexico City

Infectious diseases are common causes of morbidity and mortality among kidney transplant recipients. Chagas disease (CD) has been recognized as an emerging infectious complication of transplantation caused by the parasite Trypanosoma cruzi. CD is prevalent in Mexico, particularly in the southern coastal region. The impact on Mexican kidney transplant programs has not been previously studied prospectively. From 2009 through 2010, serum samples from 59 kidney transplant donors and 405 renal transplant recipients were screened for antibodies against T. cruzi. Serum was initially screened using a locally developed ELISA test; positive results were confirmed by an indirect immunofluorescense test, in accordance with Panamerican Health Organization/World Health Organization guidelines. None of the donors were seropositive for T. cruzi, while 8 (1.97%) kidney transplant recipients were confirmed to be seropositive for T. cruzi. None of them have developed clinical manifestations of CD, although specific screening of recipients was not performed. A prospective study is planned to define the epidemiology and outcome of CD among kidney transplant donors and recipients in Mexico more thoroughly.     

A Systematic Review of Studies on Heart Transplantation for Patients With End-Stage Chagas’ Heart Disease

BackgroundUncertainties regarding indications for the procedure, proper immunosuppressive regimen, and the fear of Trypanosoma cruzi infection reactivation are major concerns regarding heart transplantation (HTx) for patients with end-stage Chagas’ heart disease.Methods and ResultsTo review indications for HTx, current immunosuppressive therapy, posttransplant morbidities, and outcome in Chagas’ heart transplant recipients. Review of articles linking HTx and Chagas’ disease at PubMed and Scielo database from 1966 onward. HTx can reasonably be indicated in patients with an annual probability of death of 70%. HTx has been associated with a similar incidence of rejection episodes in Chagas’ and non-Chagas’ heart transplant recipients. A lower incidence of infection episodes has been observed in Chagas’ in comparison to non-Chagas’ heart transplant recipients. T. cruzi infection reactivation is easily treated with either benznidazole or allopurinol and portends a very low mortality rate. Other posttransplant morbidities have a similar incidence in Chagas’ and in non-Chagas’ patients. Survival probability for Chagas’ HTx recipients at 1 month, 1 year, 4 years, and 10 years follow-up is 83%, 71%, 57%, and 46%, respectively. Such an outcome is better than that seen in non-Chagas’ heart transplant recipients.ConclusionsHTx is safe and efficacious for patients with end-stage Chagas’ heart disease.     

CHAGASIC MENINGOENCEPHALITIS IN AN HIV INFECTED PATIENT WITH MODERATE IMMUNOSUPPRESSION: PROLONGED SURVIVAL AND CHALLENGES IN THE HAART ERA

The reactivation of Chagas disease in HIV infected patients presents high mortality and morbidity. We present the case of a female patient with confirmed Chagasic meningoencephalitis as AIDS-defining illness. Interestingly, her TCD4+ lymphocyte cell count was 318 cells/mm³. After two months of induction therapy, one year of maintenance with benznidazol, and early introduction of highly active antiretroviral therapy (HAART), the patient had good clinical, parasitological and radiological evolution. We used a qualitative polymerase chain reaction for the monitoring of T. cruzi parasitemia during and after the treatment. We emphasize the potential value of molecular techniques along with clinical and radiological parameters in the follow-up of patients with Chagas disease and HIV infection. Early introduction of HAART, prolonged induction and maintenance of antiparasitic therapy, and its discontinuation are feasible, in the current management of reactivation of Chagas disease.     

T- and B-cell immune reconstitution and clinical outcome in patients with multiple myeloma receiving T-cell-depleted, reduced-intensity allogeneic stem cell transplantation with an alemtuzumab-containing conditioning regimen followed by escalated donor lymphocyte infusions

Summary. Immune reconstitution after conventional allogeneic transplantation is a major determinant of survival. We conducted a detailed investigation of T‐ and B‐cell immune reconstitution and clinical outcome in 19 patients with multiple myeloma undergoing reduced‐intensity stem cell transplantation using in vivo T‐cell depletion with alemtuzumab. These patients experienced delayed T‐cell recovery, particularly in the naïve (CD45 RA⁺) CD4 compartment. T‐cell receptor spectratype analysis showed a reduced repertoire diversity, which improved rapidly after the administration of donor leucocyte infusions and subsequent conversion to full donor T‐cell chimaerism. Post‐transplant recovery of CD19⁺ B cells was also delayed for up to 18 months. Spectratype analysis of IgH CDR3 repertoire revealed a gradual normalization in IgM spectratype complexity by 6–12 months after transplant. There was a high incidence of viral infection, particularly cytomegalovirus reactivation, but the regimen‐related mortality was low, perhaps because of the very low incidence of acute graft‐versus‐host disease (GVHD; grade I‐II skin GVHD was seen in 5/19 patients). Over 80% of all patients have relapsed at a median of 283 (range 153–895) d after transplant, suggesting that the initially low rate of GVHD comes at a high price with regard to the desired graft‐versus‐myeloma effect.     

Purification of cytomegalovirus-specific CD8 T cells from peripheral blood using HLA–peptide tetramers

Cytomegalovirus (CMV) reactivation and disease remains an important clinical problem for patients after allogeneic stem cell transplantation. Impaired cellular immune control of viral replication is responsible for viral reactivation, and transfer of CMV-specific T cells from transplant donors can be effective in providing protection. Recent reports have indicated that the frequency of CMV-specific CD8(+) T cells in the peripheral blood of healthy donors is surprisingly high. Here we demonstrate that by using a combination of human leucocyte antigen (HLA) Class I-peptide tetramers and magnetic selection it is possible to select CMV-specific T cells from CMV antibody-positive individuals to high purity. Reliable purification of CMV-specific T cells up to 99.8% of CD8(+) cells was possible within hours, even when starting with a precursor frequency of < 0.1% of peripheral blood CD8(+) T cells. CMV-specific T cells remained functional after the selection process. This novel form of antigen-specific T-cell selection should facilitate the selection of T cells for cellular immunotherapy to treat or prevent CMV disease after transplantation. In addition, this technique could potentially be applied to many antigens including against other infective agents and tumour-specific antigens.     

Expanded infectious diseases screening program for Hispanic transplant candidates

M.A. Fitzpatrick, J.C. Caicedo, V. Stosor, M.G. Ison. Expanded infectious diseases screening program for Hispanic transplant candidates. Transpl Infect Dis 2010: 12: 336–341. All rights reserved Abstract: Most guidelines for pre‐transplant screening recommend enhanced screening among patients with potential exposure to such pathogens as Strongyloides stercoralis and Trypanosoma cruzi, the cause of Chagas disease. The incidence of these diseases in the Hispanic immigrant population has not been extensively studied. Transplant candidates who were evaluated by our program's Hispanic Transplant Program were referred for expanded infectious disease screening including Mycobacterium tuberculosis, S. stercoralis, Leishmania, and T. cruzi. Between December 2006 and December 2008, 83 patients were screened. Most were from Mexico but we also screened patients from Ecuador, Puerto Rico, and Peru. Most patients lived in urban locations before moving to the United States. Latent tuberculosis infection (LTBI) was found in 20%, and 6.7% had serologic evidence of S. stercoralis infection. These patients underwent treatment of latent infection without difficulty. To date, 14 patients have undergone living‐donor kidney transplantation. Two of these patients had positive Leishmania titers and are being followed clinically, 1 was treated for S. stercoralis, and 2 were treated for LTBI pre‐transplant. All have done well without evidence of screened pathogens an average of 348 days (range 65–766 days) post transplant. Expanded screening identifies endemic infections in the Hispanic immigrant population that can be treated before transplant, thereby minimizing post‐transplant infectious complications.     

Prevalence of Trypanosoma cruzi/HIV coinfection in southern Brazil

Chagas disease reactivation has been a defining condition for acquired immune deficiency syndrome in Brazil for individuals coinfected with Trypanosoma cruzi and HIV since 2004. Although the first coinfection case was reported in the 1980s, its prevalence has not been firmly established. In order to know coinfection prevalence, a cross-sectional study of 200 HIV patients was performed between January and July 2013 in the city of Pelotas, in southern Rio Grande do Sul, an endemic area for Chagas disease. Ten subjects were found positive for T. cruzi infection by chemiluminescence microparticle immunoassay and indirect immunofluorescence. The survey showed 5% coinfection prevalence among HIV patients (95% CI: 2.0–8.0), which was 3.8 times as high as that estimated by the Ministry of Health of Brazil. Six individuals had a viral load higher than 100,000 copies per μL, a statistically significant difference for T. cruzi presence. These findings highlight the importance of screening HIV patients from Chagas disease endemic areas.     

Chagas Cardiomyopathy is Associated With Higher Incidence of Stroke: A Meta-analysis of Observational Studies

BackgroundChagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD.MethodsPubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: (“Chagas” OR “American trypanosomiasis”) AND (“dilated” OR “ischemic” OR “idiopathic” OR “nonChagasic” OR “stroke” OR “cerebrovascular”). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model.ResultsA total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17–3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02–3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06–2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89–10.77).ConclusionsCD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention.     

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine‐containing regimen: Case report and review of the literature

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60‐year‐old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.     

Late sequelae of left ventricular assist device infection presenting after heart transplant

The long‐term use of left ventricular assist devices (LVADs) is becoming more common among the end‐stage heart failure population. At the time of heart transplantation, most of the LVAD is removed, but some of its components might be retained. Retained LVAD prosthetic material can lead to serious infection post heart transplant. We report 4 such cases. Our goal is to highlight the importance of complete prosthetic material removal at the time of cardiac transplant to prevent late‐onset infection, especially in patients with preceding infection, but also in patients without evidence of LVAD infection prior to orthotopic heart transplantation.     

Identification of phenotypic markers of B cells from patients with Chagas disease

Chagas disease was discovered more than a hundred years ago, but its pathogenesis is still not completely understood. Autoimmunity is one of the mechanisms shown to contribute to its pathogenesis, which may indicate an important participation of B lymphocytes. Patients with Chagas disease have shown increased percentage of B cells producing IL‐10. However, there are no reports of the phenotypic markers of B cells producing IL‐10 in patients with Chagas disease. For the first time in the literature, we evaluated the phenotypic profile of distinct markers of B cells from peripheral blood of noninfected individuals and patients with Chagas disease. Our results showed that patients with Chagas disease had a higher expression of CD21 and CD24 on the surface of CD19⁺ B cells, while CD43 and CD23 were expressed equally in all groups. Moreover, the expression of MHC‐II (HLA‐DR), CD80, CD86, caspase‐3, granzyme B and intracellular IL‐10 and TGF‐β by CD19⁺ B cells was higher in patients with Chagas disease. The results of IL‐10 production within CD19⁺CD5⁺CD1d⁺ B cells showed a higher percentage of this cytokine in patients with Chagas disease. Thus, our data bring a new knowledge about distinct markers of B cells in immune responses of Chagas disease.     

Onset and complications of varicella zoster reactivation in the autologous hematopoietic cell transplant population

J.E. Rogers, A. Cumpston, M. Newton, M. Craig. Onset and complications of varicella zoster reactivation in the autologous hematopoietic cell transplant population.
Transpl Infect Dis 2011: 13: 480–484. All rights reserved Background. Varicella zoster virus (VZV) infections are a common complication in patients receiving autologous or allogeneic hematopoietic cell transplant (HCT). Recent guideline revisions suggest extending VZV prophylaxis to 1 year after autologous HCT. We retrospectively evaluated reactivation at our center, before implementation of extended acyclovir prophylaxis, to determine onset and outcome in the autologous HCT population. Methods. Inclusion criteria consisted of adult patients who received an autologous HCT with documentation for at least 1 year post transplant. Those excluded from review were patients who received acyclovir prophylaxis for >30 days post transplant or subsequently received an allogeneic transplant within 1 year. For patients in whom reactivation occurred, the severity of infection, the timing of onset, treatment of the reactivation, and any complications were recorded. Results. In the final analysis, 56 patients were assessed. Reactivation of zoster occurred in 16% of recipients with a median onset of 4.5 months post transplant. Complications that were observed include postherpetic neuralgia, severe pain, scarring, and motor weakness. Two patients required hospitalization for treatment, with 1 patient requiring 6 months of rehabilitation for motor weakness following the infection. Conclusions. Our study revealed a 16% incidence of VZV reactivation in our autologous HCT population. The onset of these occurrences ranged from 2 to 10 months post transplant, with significant VZV‐associated complications. We consider VZV reactivation a serious concern in the autologous transplant setting, requiring extended prophylaxis.     

Expansion of recipient‐derived antiviral T cells may influence donor chimerism after allogeneic stem cell transplantation

Donor chimerism (DC) analysis is an important marker in the hematopoietic stem cell transplant follow‐up. Here, we present evidence for a possible relationship of infectious complications and declines in DC. We analyzed the DC in patients experiencing cytomegalovirus (CMV) reactivation. In addition, in some patients chimerism analyses of T‐cell subsets were performed. CMV‐specific cytotoxic T‐lymphocytes (CMV‐CTL) were monitored using human leukocyte antigen‐restricted multimer staining. Interestingly, CMV reactivation was accompanied by changes in DC in 11 of 67 patients transplanted. For example, DC declined in a cord blood recipient, in both total leukocytes and CD4 and CD8 T‐cell subsets upon CMV reactivation. The latter was controlled after only 5 days through expanding CMV‐CTL of 96% recipient origin, according to chimerism analysis of CMV‐CTL (enriched beyond 50%). In another patient, transplanted after reduced‐intensity conditioning from a DQB1 mismatched, CMV seronegative donor, incipient CMV reactivation was completely aborted by CMV‐CTL of recipient origin. However, at the same time, mixed chimerism dropped from 51% to 0% donor type, resulting in late graft rejection. Our data indicate that chimerism analyses in subset populations lead to a better understanding of declining total leukocyte chimerism. Furthermore, recipient‐derived CMV‐CTL may be able to control CMV reactivation after reduced‐intensity conditioning. We speculate that autologous CMV‐CTL may be instrumental to overcome recurrent CMV reactivations, especially in patients transplanted from CMV‐seronegative donors. In addition, the expansion of recipient‐derived CMV‐CTL may contribute to both, graft failure or to conversion to full DC.     

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.     

Hepatitis B virus reactivation during belatacept treatment after kidney transplantation

We report a case of HBV reactivation following belatacept treatment in a patient who underwent kidney transplantation in 2015 for HIV‐associated nephropathy (HIVAN). Human immunodeficiency virus viral load was undetectable prior to transplantation, and CD4+ lymphocyte count was greater than 300/mL. Baseline HBV serology at transplantation was HBsAg negative, anti‐HBcAb positive, anti‐HBsAb 312 UI/L, and HBeAg negative/anti‐HBeAb positive. Liver function tests were normal, and viral DNA was undetectable. Two years later, the patient presented with severe acute hepatitis after a progressive disappearance of anti‐HbsAb, quickly followed by HBV reactivation. Immunosuppressive treatment was drastically reduced, and treatment with entecavir was started. The outcome was favorable, and HBV DNA became undetectable after 9 weeks of treatment. This is the first report of acute hepatitis related to HBV reactivation in a kidney transplant recipient treated with belatacept. The risk for HBV reactivation in patients treated with belatacept should not be underestimated, especially in those with resolved HBV infection.     

Clinical Course of Hepatitis B Virus Infection in Renal Allograft Recipients

The outcome of renal transplantation is adversely affected by hepatitis B virus infection. We retrospectively analyzed data of 1,251 renal transplant recipients, 20 of whom were hepatitis B surface antigen positive and hepatitis B virus DNA negative at the time of renal transplantation. Hepatitis B virus reactivation was seen in 14 of the 20 patients at a mean time of 16.3 ± 7.1 months after transplantation. All patients with hepatitis B virus reactivation after transplantation were treated with lamivudine, biochemical, and serologic response was achieved in 13 of 14 patients at a mean time of 7.0 ± 1.1 months. Seven of 13 patients experienced a breakthrough at a mean time of 9.2 ± 6.2 months. Three of the 20 patients died at a mean time of 57.0 ± 38.5 months after transplantation. Our data demonstrated that chronic immunosuppression is associated with a significantly high risk of hepatitis B virus reactivation in renal transplant recipients and hepatitis B reactivation does not increase the likelyhood of graft rejection or patient mortality after renal transplantation.     

Late aspergilloma of a renal allograft without need for operative management: a case report and review of the literature

Aspergillus infection localized to the renal allograft is a rare and potentially life‐threatening infection and typically requires a combination of operative and medical management. We report the case of a renal allograft aspergilloma in a renal transplant patient presenting 2 years post transplant, successfully managed non‐surgically. To our knowledge, this is the first report of a patient presenting with an allograft aspergilloma so long after transplantation and being successfully managed with antifungal therapy alone.     

Diagnosis and Management of Chagas Cardiomyopathy in the United States

Purpose of Review

Chagas cardiomyopathy is an emerging form of non-ischemic cardiomyopathy in the USA. This review aims to summarize current concepts in pathophysiology, disease transmission, medical therapy, and heart transplantation for patients with chronic Chagas cardiomyopathy.

Recent Findings

The incidence of Chagas cardiomyopathy is increasing in the USA, driven mainly by immigration from countries where Chagas disease is endemic. Chagas cardiomyopathy is a chronic, progressive myocarditis, with hallmark features of biventricular dysfunction, ventricular arrhythmias, thromboembolic complications, and a high risk of mortality. Currently, there is no effective treatment for chronic Chagas cardiomyopathy. Heart transplantation is the only treatment for patients with end-stage Chagas cardiomyopathy, but is associated with unique challenges including risk of reactivation.

Summary

As the prevalence of Chagas cardiomyopathy increases in the USA, practitioners must be aware of the unique challenges in diagnosis and management that Chagas cardiomyopathy presents.