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Biomedical subjects

Mario Sarcletti

Publications and source records attributed to Mario Sarcletti.

8 recordsLinked to original sources

Human granulocytic anaplasmosis in Austria: epidemiological, clinical, and laboratory findings in five consecutive patients from Tyrol, Austria.

We report five consecutive cases of Anaplasma (A.) phagocytophilum infection (the causative agent of human granulocytic anaplasmosis (HGA)) from western Austria. All infections were acquired between June and August in 2003 and 2004 in the Inn valley (Tyrol, Austria). Four patients required hospitalisation, one patient was treated as an outpatient. During the acute stage of illness, laboratory findings included thrombocytopenia (5/5), elevated C-reactive protein (5/5), elevated neopterin (5/5), elevated lactate dehydrogenase (4/5), and elevation of liver enzymes (4/5). Leukopenia (3/5) and elevated procalcitonin (2/5) were less frequently observed. All patients were treated with tetracyclines, which led to prompt improvement of the clinical conditions. Anti-platelet antibodies were observed in one of four patients, but remained unchanged after complete covalescence.

Adult↗

Cytomegalovirus genotypes present in cerebrospinal fluid of HIV-infected patients.

OBJECTIVE: To compare cytomegalovirus (CMV) strains found in cerebrospinal fluid (CSF) of patients with HIV infection and CMV encephalitis with those present in the general population with respect to genetic variation in the N terminus of the glycoprotein B (gBn)-gene. DESIGN AND METHODS: We sequenced gBn, which is a major target of the antiviral immune response, of CMV strains present in CSF of nine HIV-infected patients with acute encephalitis, in serum of 18 immunocompetent patients with primary CMV infection, and in serum of nine HIV-infected patients without neurological illness. Sequences were compared to prototype strains and analysed by use of phylogeny. RESULTS: Fourty-four percent (4/9) of gBn-sequences present in CSF did not cluster with any of the four gBn-prototype strains. Phylogenetic analysis revealed that these sequences represented two further, distinct genotypes and comparison of sequences was highly suggestive for intragenic recombination. In immunocompetent patients and HIV-infected patients without neurological illness, genotype gBn1 was the predominant strain (4/9, 44% and 8/18, 42%, respectively). Genotypes distinct from prototype strains were found in none of the immunocompetent patients and 22% (2/9) of HIV- infected patients without neurological illness. CONCLUSIONS: CMV strains present in CSF of HIV-infected patients with encephalitis differ significantly from those present in the general population. Intragenic recombination of CMV may be common in patients with advanced HIV infection and a source of new CMV strains with altered biological properties.

AIDS-Related Opportunistic Infections↗

Low proportion of recent human immunodeficiency virus (HIV) infections among newly diagnosed cases of HIV infection as shown by the presence of HIV-specific antibodies of low avidity.

The time between human immunodeficiency virus (HIV) infection and diagnosis is mostly unknown. Two hundred five newly diagnosed patients were investigated for the duration of their HIV infection by avidity testing. Recent HIV infection was identified in 27.3% of the cases. Early diagnosis was achieved significantly less frequently in heterosexually infected persons than in other patients.

Adolescent↗

High prevalence of high risk human papillomavirus-capsid antibodies in human immunodeficiency virus-seropositive men: a serological study.

BACKGROUND: Serological study of human papillomavirus (HPV)-antibodies in order to estimate the HPV-prevalence as risk factor for the development of HPV-associated malignancies in human immunodeficiency virus (HIV)-positive men. METHODS: Sera from 168 HIV-positive men and 330 HIV-negative individuals (including 198 controls) were tested using a direct HPV-ELISA specific to HPV-6, -11, -16, -18, -31 and bovine PV-1 L1-virus-like particles. Serological results were correlated with the presence of HPV-associated lesions, the history of other sexually transmitted diseases (STD) and HIV classification groups. RESULTS: In HIV-negative men low risk HPV-antibodies were prevailing and associated with condylomatous warts (25.4%). Strikingly, HIV-positive men were more likely to have antibodies to the high-risk HPV types -16, -18, -31, and low risk antibodies were not increased in a comparable range. Even those HIV-positive heterosexual individuals without any HPV-associated lesions exhibited preferentially antibody responses to the oncogenic HPV-types (cumulative 31.1%). The highest antibody detection rate (88,8%) was observed within the subgroup of nine HIV-positive homosexual men with anogenital warts. Three HIV-positive patients had HPV-associated carcinomas, in all of them HPV-16 antibodies were detected. Drug use and mean CD4-cell counts on the day of serologic testing had no influence on HPV-IgG antibody prevalence, as had prior antiretroviral therapy or clinical category of HIV-disease. CONCLUSION: High risk HPV-antibodies in HIV-infected and homosexual men suggest a continuous exposure to HPV-proteins throughout the course of their HIV infection, reflecting the known increased risk for anogenital malignancies in these populations. The extensive increase of high risk antibodies (compared to low risk antibodies) in HIV-positive patients cannot be explained by differences in exposure history alone, but suggests defects of the immunological control of oncogenic HPV-types. HPV-serology is economic and can detect past or present HPV-infection, independently of an anatomical region. Therefore HPV-serology could help to better understand the natural history of anogenital HPV-infection in HIV-positive men in the era of antiretroviral therapy.

Antibodies, Viral↗

Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection.

Activation of indoleamine-(2,3)-dioxygenase (IDO), an enzyme converting tryptophan to N-formyl-kynurenine, was found to be critical for induction of T-cell tolerance. In 45 HIV-seropositive patients we measured plasma tryptophan and kynurenine before and 6 months post-initiation of ART. Before ART, patients had decreased tryptophan and increased kynurenine levels compared to controls. During ART, average tryptophan concentrations increased, kynurenine decreased. Tryptophan degradation correlated with neopterin levels and with viral load but not with CD4 cell counts. The data support the concept that immune activation is the common background of IDO activation and could represent an important factor underlying T-cell hyporesponsiveness in HIV infection.

Adult↗

Increase of haemoglobin levels by anti-retroviral therapy is associated with a decrease in immune activation.

DESIGN: We evaluated whether an increase in haemoglobin levels in the first 6 months of effective anti-retroviral therapy (ART) is associated with a decrease in immune activation. To reduce confounding factors only men (n = 35) and patients not receiving agents known to enhance haematopoiesis or patients without diseases that might suppress haematopoiesis were included. Simultaneously parameters of iron metabolism and cofactors for haematopoiesis were analysed. RESULTS: A median baseline haemoglobin level of 139 g L-1 increased to 149 g L-1 at month 6 of ART (P < 0.001). At baseline low haemoglobin levels were strongly associated with high neopterin concentrations (r = - 0.64, P < 0.001), and much less correlated to high HIV-1 RNA levels (r = - 0.41, P < 0.05) and to a lower CD4+ cell count (r = 0.33, P < 0.05). The change of neopterin levels during the study period correlated with the relative change in haemoglobin levels, r = - 0.35, P = 0.03, whereas no such correlations were found for the change of HIV-1 RNA levels and the CD4 cell count. A logistic regression analysis revealed that the change of neopterin and soluble transferrin receptors concentrations are independently associated with an increase of haemoglobin levels of more than 15 g L-1. CONCLUSION: Our study supports a cause-effect relationship between immune activation and anaemia in HIV-infected patients. Treatment of patients with ART decreases virus load, which may thereby result in silencing of immune effector activity thus ameliorating anaemia by reversing the anti-proliferative effects of cytokines towards erythroid progenitors and the iron withdrawal strategy of the immune system.

Adult↗

Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection.

Antiretroviral therapy (ART) has a significant impact on HIV-1 RNA levels, the CD4 cell count, and immune activation. We examined whether these changes are associated with a change in the rate of tryptophan degradation (expressed as the kynurenine to tryptophan ratio, kyn/trp) as an estimate for the activity of interferon-gamma inducible enzyme indoleamine (, )-dioxygenase (IDO). Plasma levels of tryptophan, kynurenine, and neopterin were measured pretherapy and 6 months postinitiation of therapy in 45 patients with HIV-1 RNA levels of less than 1000 copies/ml 6 months after initiation of ART. Before ART, the patients had decreased tryptophan and increased kynurenine concentrations compared to healthy controls. During ART, average tryptophan levels increased; in the same time kynurenine and kyn/trp decreased (P < 0.001), although not to normal levels. Since pretherapy tryptophan concentrations correlated inversely with neopterin, and kynurenine correlated with viral load and neopterin but not with CD4 cell count, the data support the view that HIV production may induce immune activation and consequently tryptophan is degraded at a higher rate. In agreement, kyn/trp positively correlated with neopterin (r(s) = 0.60, P < 0.001), with virus load (r(s) = 0.37, P = 0.013), and very weakly with CD4(+) cells counts (r(s) = 0.30, P = 0.049). The change in the kyn/trp ratio during ART correlated more strongly with the change in neopterin levels (r(s) = 0.49, P = 0.001) than with the change in HIV RNA levels and weakly with the CD4 cell count. The data underscore the fact that both neopterin production and tryptophan degradation are triggered by immune activation. Tryptophan degradation is increased in HIV infection and partially reversed under ART. The data agree with the concept that immune activation is the common background of IDO activation which may be an important factor underlying T-cell hyporesponsiveness.

Acquired Immunodeficiency Syndrome↗