Simone Topino

NK cell activity controls human herpesvirus 8 latent infection and is restored upon highly active antiretroviral therapy in AIDS patients with regressing Kaposi's sarcoma.

Kaposis sarcoma (KS) develops upon reactivation of human herpesvirus 8 (HHV8) infection and virus dissemination to blood and tissue cells, including endothelial and KS spindle cells where the virus is mostly present in a latent form. However, this may likely require the presence of compromised host immune responses and/or the evasion of infected cells from the host immune response.In this regard, mechanisms of evasion of productively infected cells from both CTL and NK cell responses, and resistance of latently infected cells from specific CTL, have already been shown. Here we show that cells which are latently infected by HHV8 are indeed efficiently lysed by NK cells from individuals with a normal immune response. Notably, NK cell‐mediated immunity was found to be significantly reduced in AIDS patients with progressing KS as compared to both HIV‐negative patients with indolent classic KS or normal blood donors. However, it was restored after treatment with the highly active antiretroviral therapy (HAART) in AIDS‐KS patients, that showed regression and clearance of HHV8 from PBMC. By contrast, AIDS‐KS patients with a more aggressive disease and no clinicalresponse had persistent HHV8 viremia associated with reduced NK cell cytotoxicity. These results suggest a key role for NK cells in the control of HHV8 latent infection, KS development, and in disease remission upon HAART.

Rhodococcus equi infection in HIV-infected individuals: case reports and review of the literature.

Rhodococcus equi is a gram-positive, coryneform bacterium that causes zoonotic infection mainly in horses and foals. It sometimes affects humans presenting as cavitary pneumonia. Immunocompromised patients, including HIV-infected patients, are more susceptible to R. equi infection. We present 10 cases of R. equi infection in HIV-positive patients admitted to our institute from 1991 to June 2008. Moreover, we have reviewed 272 cases of R. equi infection in HIV-infected persons, published from 1986 through 2008. With respect to the literature data, the R. equi strains isolated in our case series showed lower sensitivity to ceftriaxone, amoxicillin/clavulanic acid, and cotrimoxazole. Prompt diagnosis, early initiation of antiretroviral treatment and combined antimicrobial treatment seem to be effective to eradicate the infection and to improve the outcome.

Distribution of the natural killer-related receptor for HLA-C during highly active antiretroviral therapy for human immunodeficiency virus infection.

Receptors interacting with Major Histocompatibility Complex class I molecules have been initially found on the surface of human natural killer (NK) cells, where they deliver inhibitory signals to the lysis, being thus defined killer inhibitory receptors (KIR). Subsequently, they were detected also on the surface of T-CD8(+) lymphocytes and are particularly expanded during human immunodeficiency virus (HIV) infection, where they downregulate HIV-specific cytolysis. The expression of KIR recognizing human leukocyte antigen-C alleles was assessed in HIV-infected patients, undergoing highly active antiretroviral therapy (HAART). To this end, the combined expression of CD16/CD56, of CD3 and CD8 as well as of KIR (CD158a and CD158b) surface molecules was analyzed on peripheral blood mononuclear cells by monoclonal antibodies, and flow cytometry. An increase of CD3(+)CD8(+)CD158b(+) cells was found after 6 months of HAART. This finding may have implications for the regulation of T-cell mediated cytolysis during HAART.

Salmonella enterica ssp. arizonae infection in a 43-year-old Italian man with hypoglobulinemia: a case report and review of the literature

IntroductionSalmonella enterica ssp. arizonae is an uncommon human pathogen with serious infections reported in immunocompromised hosts. In Europe, only a few cases have been described. Patients with this infection usually have a history of contact with reptiles or travel abroad. We present a case report of infection in a patient with hypoglobulinemia and a literature review.Case presentationWe describe the case of a 43-year-old Caucasian Italian man with hypoglobulinemia who presented to our hospital with sepsis and diarrhea. A stool culture yielded S. enterica ssp. arizonae. Our patient was treated with oral ciprofloxacin and made a full recovery. We also present a review of the cases of S. enterica ssp. arizonae infections previously reported in Europe.ConclusionsThe majority of infections from S. enterica ssp. arizonae occur in patients who are immunocompromised. Data from the literature suggests that it may be difficult to eradicate the bacteria and thus, prolonged antibiotic courses are often used. It would be advisable for clinicians to investigate for pre-existing immune dysfunction if S. enterica ssp. arizonae is isolated. In Italy, although there have only been a few cases, the likely route of transmission remains unclear and requires further surveillance.

Dynamics of viral load rebound in plasma and semen after stopping effective antiretroviral therapy.

A rebound in the plasma and seminal viral load was detected in 12 patients after the interruption of effective highly active antiretroviral therapy. The viral rebound was generally higher in plasma, although the highest level observed during interruption was higher in semen in two patients. The reintroduction of therapy was followed by an overall decrease in HIV-RNA in plasma and semen. One to 2 months after restarting treatment, four out of seven patients showed undetectable HIV-RNA in semen.

Carbapenemase-producing Klebsiella pneumoniae-related mortality among solid organ-transplanted patients: do we know enough?

F. Taglietti, S. Di Bella, V. Galati, S. Topino, M. Iappelli, N. Petrosillo Carbapenemase-producing Klebsiella pneumoniaerelated mortality among solid organ-transplanted patients: do we know enough? Transpl Infect Dis 2013: 15: E164–E165. All rights reserved F. Taglietti, S. Di Bella, V. Galati, S. Topino, M. Iappelli, N. Petrosillo National Institute for Infectious Diseases “L. Spallanzani,” Rome, Italy, Kidney Transplant Unit, San Camillo-Forlanini Hospital, Rome, Italy

Hemolytic anemia due to acute cytomegalovirus infection in an immunocompetent adult: a case report and review of the literature

IntroductionCytomegalovirus is a common virus responsible for a wide range of clinical manifestations. Hemolysis is a rare but potentially life-threatening complication of cytomegalovirus infection, described mostly in immunocompromised patients, the pathogenesis of which is still unclear.We performed a review of the literature regarding cases of hemolytic anemia during acute cytomegalovirus infection in apparently immunocompetent individuals. We searched for relevant articles in PubMed for the period of 1980 through 2008.Case presentationWe describe a case of Coombs-negative hemolytic anemia in a 44-year-old Caucasian immunocompetent man with acute cytomegalovirus infection.ConclusionClinicians should consider cytomegalovirus infection in the differential diagnosis of hemolytic anemia in immunocompetent adults. Possible therapeutic options include antiviral therapy and steroids, although the best treatment strategy is still controversial.

P-Glycoprotein Expression by Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Patients Is Independent from Response to Highly Active Antiretroviral Therapy

During the last few years, highly active antiretroviral therapy has considerably reduced human immunodeficiency virus (HIV) disease progression (11). However, the treatment outcome is not always satisfactory (7). This can depend on different virological, immunological, behavioral, or pharmacological factors (5). In the framework of aspects, the interaction between P-glycoprotein (P-gp) and antiretroviral drugs has been evidenced (8, 13, 15). P-gp is a transmembrane phosphoglycoprotein belonging to the ATP-binding cassette superfamily that is able to transport several substrates through the cell membrane acting as a cationic pump (2, 3, 4, 6, 9, 14). Specifically, studies on protease inhibitors (PI) have evidenced that the transporter activity of P-gp may contribute to the reduced bioavailability of these drugs, which can act as substrates for P-gp (4, 15, 16). However, the influence of HIV infection on P-gp expression is still a matter of debate (1, 9), and as yet, no data are available on the effects of highly active antiretroviral therapy on its expression.

Correlation between Enzyme-Linked Immunosorbent Assay and Immunofluorescence Assay with Lytic Antigens for Detection of Antibodies to Human Herpesvirus 8

ABSTRACT The purpose of this study was to evaluate, in Kaposis sarcoma patients, the correlation between antibody titers to the lytic antigens of human herpesvirus 8, as assessed by immunofluorescence assay, and values obtained by an enzyme immunoassay. The methods showed a stringent correlation, r = 0.625 (P< 0.001).

Clearance of Human Herpesvirus 8 from Blood and Regression of Leukopenia-Associated Aggressive Classic Kaposi's Sarcoma during Interferon-α Therapy: A Case Report

A human immunodeficiency virus-negative woman with severe classic Kaposis sarcoma, idiopathic leukopenia, and massive spread of human herpesvirus 8 (HHV-8) in circulating cells showed stable disease remission in response to systemic interferon-alpha treatment that was accompanied by increased CD3(+) and CD4(+) T cell numbers and complete clearance of HHV-8 from the circulation. These results suggest a direct relationship between HHV-8 clearance from blood and regression of Kaposis sarcoma and are consistent with the in vitro inhibitory effects of interferon-alpha on HHV-8 infection.