Chagas disease knocks on our door: a cross-sectional study among Latin American immigrants in Milan, Italy.

OBJECTIVES: We aimed to assess the prevalence and risk factors for Chagas disease (CD) in Latin American immigrants and to evaluate the accuracy of diagnostic tests. Moreover, we offered to all positive subjects a complete free-of-charge clinical/instrumental evaluation as well as benznidazole treatment in order to stage the disease and verify drug tolerability. METHODS: A cross-sectional survey of CD among Latin Americans living in Milan and its metropolitan area was conducted between July 2013 and July 2014. Blood samples were tested for serologic evidence of CD together with a questionnaire covering demographic and clinical-epidemiological information. RESULTS: Forty-eight (9.6%) of the 501 tested subjects were conclusively diagnosed as having CD. The highest prevalence of CD was among those from Bolivia (43/169, 25.4%) and El Salvador (4/68, 5.9%). Older age (adjusted odds ratio (aOR)] 1.05, p =0.004), a Bolivian origin (aOR 8.80; p =0.003), being born in the department of Santa Cruz (aOR 3.72, p =0.047), having lived in mud houses (aOR 2.68; p =0.019), and having an affected relative (aOR 12.77, p =0.001) were independently associated with CD. The ARCHITECT Chagas test showed the highest sensitivity (100%) and specificity (99.8%). Twenty-nine of the subjects with CD (60.4%) underwent disease staging, 10 of whom (35.7%) showed cardiac and/or digestive involvement. Benznidazole treatment was associated with high frequency of adverse reactions (19/27, 70.4%) and permanent discontinuation (8/27, 29.6%). CONCLUSIONS: CD is highly prevalent among Bolivians and Salvadorans living in Milan. Regions with a large Latin American immigrant population should implement programmes of active detection and treatment.

Leishmaniasis: new insights from an old and neglected disease.

Leishmaniases are a clinically heterogeneous group of diseases caused by protozoa of the genus Leishmania. There is growing evidence that the true incidence of the disease is underestimated, especially in hyperendemic regions. Moreover, climate changes together with the increasing movement of humans and animals raise concerns about the possible introduction of Leishmania infection in previously spared areas. The disease is emerging in immunocompromised patients undergoing bone marrow or solid organ transplantation or treatment with biologic drugs. Furthermore, the deployment of military troops and travel to endemic areas are associated with the observation of a growing number of patients with cutaneous disease. Improvement in diagnostic methods, both in the field and in specialized laboratories, has been obtained through the implementation of molecular amplification methods and using the rK39 antigen as the substrate. Finally, new therapeutic approaches are gaining attention, such as the use of miltefosine for cutaneous leishmaniasis and paromomycin for visceral leishmaniasis, as well as the use of various antileishmanial drugs in combination.

Late onset of hepatitis B virus reactivation following hematopoietic stem cell transplantation: successful treatment with combined entecavir plus tenofovir therapy.

Prophylaxis with lamivudine (LAM) is recommended for hepatitis B core antibody-positive allogenic hematopoietic stem cell transplant (HSCT) recipients, but the optimal timing for the institution and duration of the prophylaxis is still unknown. Furthermore, considering the high rate of mortality associated with hepatitis B virus reactivation (HBV-R), the most potent and long-term effective antiviral regimen should be considered. We report here a case of late onset of HBV-R after a long-term prophylaxis with LAM in a patient who underwent HSCT for non-Hodgkin lymphoma and who was successfully treated with a combination antiviral regimen including entecavir and tenofovir disoproxil fumarate.

Recurrent leishmaniasis in kidney transplant recipients: report of 2 cases and systematic review of the literature.

The characteristics of 8 episodes of leishmaniasis with atypical manifestations in 2 Italian kidney transplant recipients are analyzed and contextualized among those of 52 other episodes of leishmaniasis observed in 19 transplant recipients found through a systematic review of the international literature. In all the patients, the initial episode was visceral leishmaniasis, which was associated with mucocutaneous involvement in 2 cases. With the exception of 1 case of post kala-azar dermal leishmaniasis, 2 episodes of Leishmania endophthalmitis, and 3 episodes of mucocutaneous leishmaniasis, all the recurrences were characterized by visceral involvement. The potential role of polymerase chain reaction in monitoring the infection, the importance of a long follow-up, the potential benefit of chemoprophylaxis, and the therapeutic challenges are discussed.

Immune reconstitution inflammatory syndrome associated with Aspergillus terreus pulmonary infection in an autologous stem cell transplant recipient.

We describe an autologous stem cell transplant recipient who developed immune reconstitution inflammatory syndrome (IRIS) associated with Aspergillus terreus invasive pulmonary infection after recovery from neutropenia. Clinical and radiological worsening of pulmonary invasive aspergillosis coincident with a robust decline of serum galactomannan values and rising neutrophil counts should be interpreted as IRIS and should not require changes to antifungal therapy.

AIDS-associated cryptococcosis: a comparison of epidemiology, clinical features and outcome in the pre- and post-HAART eras. Experience of a single centre in Italy.

Objectives To assess the prevalence, clinical and immunological characteristics, risk factors and survival of patients with AIDS-related cryptococcosis in the era of highly active antiretroviral therapy (HAART). Methods All newly diagnosed cryptococcosis cases identified retrospectively from among a series of AIDS patients hospitalized consecutively at a single institution in Italy in 1985-1996 (pre-HAART period, n=165) and 1997-2006 (post-HAART period, n=40) were analysed comparatively. Results The prevalence of cryptococcosis decreased from 4.7% (165/3543) to 2.2% (40/1805) between the pre- and post-HAART periods (P=0.0001). There were no differences in the clinical features or immunological status of the patients between the two cohorts. The variables associated with the occurrence of cryptococcosis in the post-HAART era were older age (P<0.001), no previous diagnosis of HIV infection (P<0.001) and infection in homosexual males (P=0.004). During the post-HAART period, immune reconstitution inflammatory syndrome associated with cryptococcosis was observed in five patients (19.3%) a median of 15 weeks after the start of HAART. Thirty-day survival (P=0.045) and overall survival (P=0.0001) were significantly better among patients diagnosed with cryptococcosis in the post-HAART compared to those diagnosed in the pre-HAART era. Conclusions The AIDS-associated cryptococcosis observed in Western countries in the HAART era has similar clinical and immunological characteristics to that observed in the pre-HAART era, but a significantly better outcome.

Chylous ascites secondary to B-cell non Hodgkin's lymphoma in a patient with the acquired immune deficiency syndrome (AIDS).

In the present article we describe a patient with AIDS and chylous ascites secondary to B-cell non Hodgkin's lymphoma. A 43 years old homosexual HIV-positive man. Complained of abdominal fullness, diarrhea and a rapidly increase in abdominal girth of 1 week duration. A diagnostic paracentesis was performed and revealed a milky fluid with high triglyceride levels. All blood tests and analysis of the peritoneal fluid with polymerase chain reaction for DNA sequence of broad-range bacterial Post Voiding Residual volume, Mycobacterium tuberculosis, Kaposi Sarcoma associated Herpes virus and Epstein Barr Virus were negative. CT scan did not demonstrate any evidence for cancer. An exploratory laparotomy was thus performed. A mass spreading along the mesenteric route to the omentum was found and a debulking resection was performed. The final pathology report was of diffuse, CD20-positive, CD3-negative, Epstein Barr Virus-negative, large B-Cell non Hodgkin's lymphoma. Subsequently, he underwent five cycles of CHOP (cyclofosfamide, doxorubicin, vincristin, prednison) chemotherapy with further partial regression of the abdominal tumour. Five months after the initial diagnosis of lymphoma, the patient relapsed and was treated with high-dose BEAM (carmustine, etoposide, cytosine, arabinoside, melphalan) chemotherapy followed by CD34 stem-cell transplantations salvage therapy. This notwithstanding, the patient died due to intestinal secondary to tumor relapse 2 months later.

Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired immune deficiency syndrome.

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL) observed mainly in Sudan and India where it follows treated VL in 50% and 10% of cases, respectively. We report a 46-year-old patient with acquired immune deficiency syndrome who, 7 months after diagnosis of VL, developed PKDL and uveal leishmaniasis following HAART-induced immune recovery. In southern Europe PKDL seems to be an emerging clinical presentation among human immunodeficiency virus (HIV)-infected patients experiencing HAART-induced immune recovery after a previous diagnosis of VL. The best treatment among HIV-infected patients remains to be determined.

Persistent parvovirus B19-induced anemia in an HIV-infected patient under HAART. Case report and review of literature.

Recent reports document resolution of human parvovirus B19-related pure red blood cell aplasia (PB19-PRCA) in HIV-infected patients upon commencement of highly active antiretroviral therapy (HAART). This article describes a patient with PB19-PRCA who, despite fully suppressive HAART, required cyclic administration of intravenous human immunoglobulin over a period of 17 months before PB19 seroconversion and subsequent resolution of relapsing severe anemia. All reports in the English literature describing PB19-related hematologic abnormalities in the post-HAART era are also described herein.

Cutaneous leishmaniasis: an increasing threat for travellers.

Analysis of the literature on cutaneous leishmaniasis in low-prevalence countries suggests an increase in imported cases that is attributable to the growing phenomenon of international tourism, migration and military operations in highly endemic regions. Cases of imported cutaneous leishmaniasis are often missed initially, but diagnosis can be made non-invasively by PCR using skin scrapings of lesions as starting material. Cutaneous leishmaniasis is an emerging threat for travellers and should be considered in all patients presenting with slow-to-heal ulcers.

Treatment of advanced mycosis fungoides by allogeneic stem-cell transplantation with a nonmyeloablative regimen.

SUMMARY: Given the poor prognosis of patients with advanced cutaneous T-cell lymphoma and the high transplant-related mortality associated with conventional allogeneic bone marrow transplantation, we performed nonmyeloablative transplantation of allogeneic stem cells (ASCT) from HLA-identical siblings in three patients with this disease. All patients achieved full donor engraftment, clearance of clonal T cells leading to durable complete remissions but experienced high incidence of infections, which proved fatal in one case. These results suggest that nonmyeloablative ASCT is a novel and potentially curative therapy for patients with advanced T-cell lymphomas who have a histocompatible sibling.

Long-term remission of Kaposi sarcoma-associated herpesvirus-related multicentric Castleman disease with anti-CD20 monoclonal antibody therapy.

Kaposi sarcoma-associated herpesvirus (KSHV)-related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus-driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most accurate marker of disease activity. This report describes a patient with human immunodeficiency virus who was followed up clinically and by quantitative polymerase chain reaction for KSHV DNA sequences in PBMCs for more than 3 years following the diagnosis of KSHV-related MCD. Therapy with the antiherpesvirus agent cidofovir, antihuman interleukin-6 antibody BE-8, antiblastic chemotherapy, and combination antiretroviral agents did not achieve durable clinical or virologic remission of the disease. By contrast, administration of the anti-CD20 monoclonal antibody rituximab was well tolerated and allowed a 14-month remission of clinical symptoms and KSHV viremia. Rituximab should be added to the therapeutic armamentarium for KSHV-related MCD.

Human herpesvirus 8 DNA in the skin and blood of patients with Mediterranean Kaposi's sarcoma: clinical correlations.

BACKGROUND: Kaposi's sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi's sarcoma by confirmational display analysis and polymerase chain reaction. OBJECTIVE: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi's sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. METHODS: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi's sarcoma. RESULTS: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi's sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I-II disease as opposed to 73.6% of those with stage III-IV. CONCLUSION: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi's sarcoma.

Activation of latent Kaposi's sarcoma-associated herpesvirus by demethylation of the promoter of the lytic transactivator.

Kaposi's sarcoma-associated herpesvirus (KSHV) is strongly linked to Kaposi's sarcoma, primary effusion lymphomas, and a subset of multicentric Castleman's disease. The mechanism by which this virus establishes latency and reactivation is unknown. KSHV Lyta (lytic transactivator, also named KSHV/Rta), mainly encoded by the ORF 50 gene, is a lytic switch gene for viral reactivation from latency, inasmuch as it is both essential and sufficient to drive the entire viral lytic cycle. Here we show that the Lyta promoter region was heavily methylated in latently infected cells. Treatment of primary effusion lymphoma-delivered cell lines with tetradecanoylphorbol acetate caused demethylation of the Lyta promoter and induced KSHV lytic phase in vitro. Methylation cassette assay shows demethylation of the Lyta promoter region was essential for the expression of Lyta. In vivo, biopsy samples obtained from patients with KSHV-related diseases show the most demethylation in the Lyta promoter region, whereas samples from a latently infected KSHV carrier remained in a methylated status. These results suggest a relationship among a demethylation status in the Lyta promoter, the reactivation of KSHV, and the development of KSHV-associated diseases.

Role of PCR in diagnosis and prognosis of visceral leishmaniasis in patients coinfected with human immunodeficiency virus type 1.

A group of 76 consecutive human immunodeficiency virus (HIV)-positive patients with fever of unknown origin (n = 52) or fever associated with pulmonary diseases was evaluated in order to assess the usefulness of PCR with peripheral blood in the diagnosis and follow-up of visceral leishmaniasis. We identified 10 cases of visceral leishmaniasis among the 52 patients with fever of unknown origin. At the time of diagnosis, all were parasitemic by PCR with peripheral blood. During follow-up, a progressive decline in parasitemia was observed under therapy, and all patients became PCR negative after a median of 5 weeks (range, 6 to 21 weeks). However, in eight of nine patients monitored for a median period of 88 weeks (range, 33 to 110 weeks), visceral leishmaniasis relapsed, with positive results by PCR with peripheral blood reappearing 1 to 2 weeks before the clinical onset of disease. Eight Leishmania infantum and two Leishmania donovani infections were identified by PCR-restriction fragment length polymorphism analysis. PCR with peripheral blood is a reliable method for diagnosis of visceral leishmaniasis in HIV-infected patients. During follow-up, it substantially reduces the need for traditional invasive tests to assess parasitological response, while a positive PCR result is predictive of clinical relapse.

[Disseminated histoplasmosis in patients with AIDS. 2 case reports]. / Istoplasmosi disseminata in pazienti affetti da AIDS. Descrizione di due casi.

Histoplasmosis is endemic in some areas of United States and in South America, and generally causes an acute self-limiting respiratory infection. In elderly and immunosuppressed patients the infection can spread through the blood, causing a severe systemic illness. Here we describe two cases of disseminated histoplasmosis in AIDS patients. The first was observed in an Italian woman who had never visited endemic countries, and was recognized only at autopsy; the second was observed in a trans-sexual patient, arrived in Italy from Brazil. Clinical suspicion of histoplasmosis is important in immunocompromised patients of non-endemic areas as symptoms are often aspecific and misdiagnosis is frequent.

Differential viral protein expression in Kaposi's sarcoma-associated herpesvirus-infected diseases: Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease.

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is linked to KS, primary effusion lymphomas (PEL), and a subset of multicentric Castleman's disease (MCD). Transcript mapping studies using PEL cell lines have allowed preliminary classification of viral gene expression into constitutive (class I) and inducible (class II/III) categories. To determine whether viral gene expression differs in vivo, we examined tissue sections of KSHV-infected disorders, using specific antibodies against proteins that are representative of the different expression classes of KSHV genes. ORF73/LANA appears to be a surrogate marker for KSHV infection because it is constitutively expressed in vitro and in vivo in all KSHV-infected cells. Expression of vIRF1, vIL6, and PF-8 proteins in the infected B cells of MCD lymph nodes reproduces the expression pattern observed in TPA-stimulated KSHV-infected B-cell lines. In contrast, the protein expression of the inducible viral genes that we tested in KS and PEL biopsies is restricted to PF-8 and vIL6, respectively. The tightly restricted expression of KSHV proteins in vivo differs from the dysregulated expression of inducible KSHV genes in vitro and suggests that viral gene expression in KSHV-infected cell lines does not accurately reflect what occurs in diseased tissues. These differences may be related to either cell-specific or immune restriction of viral replication.