Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection

Background and aims: Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. Methods: sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. Results: At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. Conclusions. These results indicate that, despite the resolution of symptoms, an important macrophage/ monocyte activation persists in measles patients, even after two months from infection

Yersinia pseudotuberculosis Septicemia and HIV

Two cases of community-acquired septicemia caused by serotype-O1 Yersinia pseudotuberculosis were diagnosed in middle-aged, HIV-positive, immunodeficient patients during an 8-month period. Bacterial isolates were genetically indistinguishable, but no epidemiologic link between the 2 patients was established. HIV-related immunosuppression should be regarded as a risk factor for Y. pseudotuberculosis septicemia

Longitudinal virological and immunological profile in a case of human monkeypox infection

In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, nasopharynx, and rectum, underlying the generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At the early-stage, increase of cytotoxic and activated T-cells, while reduction of CD56dimCD57+NK cells compared to recovery time-point was observed

Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia

Introduction Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.Methods This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and beta-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.Results A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.Conclusion The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions

Severe and Persistent Depletion of Circulating Plasmacytoid Dendritic Cells in Patients with 2009 Pandemic H1N1 Infection

Background: Dysregulation of host immune responses plays a critical role in the pathogenesis of severe 2009 pandemic H1N1 infection. Whether H1N1 virus could escape innate immune defense in vivo remains to be investigated. The aim of this study was to evaluate the pattern of innate immune response during human 2009 H1N1 infection. We performed the enumeration of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) in blood from patients with H1N1 pneumonia shortly after the onset of symptoms and during follow-up at different intervals of time. The analysis of CD4 and CD8 count, CD38 T-cell activation marker and serum cytokine/chemokine plasma levels was also done. Methodology/Principal Findings: Blood samples were collected from 13 hospitalized patients with confirmed H1N1-related pneumonia at time of admission and at weeks 1, 4, and 16 of follow-up. 13 healthy donors were enrolled as controls. In the acute phase of the disease, H1N1-infected patients exhibited a significant depletion in both circulating pDC and mDC in conjunction with a decrease of CD4 and CD8 T cell count. In addition, we found plasmatic hyperproduction of IP-10 and RANTES, whereas increase in T-cell immune activation was found at all time points. When we assessed the changes in DC count over time, we observed a progressive normalization of mDC number. On the contrary, H1N1-infected patients did not achieve a complete recovery of pDC count as values remained lower than healthy controls even after 16 weeks of follow-up. Conclusions: H1N1 disease is associated with a profound depletion of DC subsets. The persistence of pDC deficit for several weeks after disease recovery could be due to H1N1 virus itself or to a preexisting impairment of innate immunity

In Vivo and In Vitro Effects of Antituberculosis Treatment on Mycobacterial Interferon-γ T Cell Response

Background: In recent years, the impact of antituberculous treatment on interferon (IFN)-c response to Mycobacterium tuberculosis antigens has been widely investigated, but the results have been controversial. The objective of the present study was: i) to evaluate longitudinal changes of IFN-c response to M. tuberculosis-specific antigens in TB patients during antituberculous treatment by using the QuantiFERON-TB Gold (QFT-G) assay; ii) to compare the differences in T-cell response after a short or prolonged period of stimulation with mycobacterial antigens; iii) to assess the CD4+ and CD8+ T cells with effector/memory and central/memory phenotype; iv) to investigate the direct in vitro effects of antituberculous drugs on the secretion of IFN-c. Principal Findings: 38 TB patients was evaluated at baseline and at month 2 and 4 of treatment and at month 6 (treatment completion). 27 (71%) patients had a QFT-G reversion (positive to negative) at the end of therapy, while 11 (29%) TB patients remained QFT-G positive at the end of therapy. Among the 11 patients with persistent positive QFT-G results, six had a complete response to the treatment, while the remaining 5 patients did not have a resolution of the disease. All 27 patients who became QFT-G negative had a complete clinical and microbiological recovery of the TB disease. In these patients the release of IFN-c is absent even after a prolonged 6-day incubation with both ESAT-6 and CFP-10 antigens and the percentage of effector/memory T-cells phenotype was markedly lower than subjects with persistent positive QFT-G results. The in vitro study showed that antituberculous drugs did not exert any inhibitory effect on IFN-c production within the range of therapeutically achievable concentrations. Conclusions: The present study suggests that the decrease in the M. tuberculosis-specific T cells responses following successful anti-TB therapy may have a clinical value as a supplemental tool for the monitoring of the efficacy of pharmacologic intervention for active TB. In addition, the antituberculous drugs do not have any direct down-regulatory effect on the specific IFN-c response

Valutazione del dolore in pazienti con malattia da HIV

Dottorato di ricerca in infettivologia. Direttore e coordinatore L. OrtonaConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Drugs and cardiotoxicity in HIV and AIDS

The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, so that issues related to long-term effects of drugs are of growing importance. Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used. Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50%. Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV-infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk. Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile. Among the drugs that are currently used in HIV+ patients, antibacterials, antifungals, psychotropic drugs and anti-histamines have been associated with QT prolongation or torsade de pointe, a life-threatening ventricular arrhythmia. Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway. Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART. Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV-related neoplasms. Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy. The increased survival and quality of life of HIV+ patients emphasize the importance of a high awareness of adverse drug-related cardiac effect

Evaluation and management of metabolic and coagulative disorders in HIV-infected patients receiving highly active antiretroviral therapy.

A number of metabolic disorders, including hypercholesterolemia, hypertriglyceridemia, insulin resistance, elevated fasting glucose and diabetes mellitus, were reported in a high proportion of HIV-infected patients receiving highly active antiretroviral therapy (HAART). Less frequently, coagulative disorders were described in patients receiving HAART. Since all these metabolic disorders may predispose to coronary heart disease, an early evaluation and treatment is advisable. Existing guidelines for uninfected patients may be applied, taking into account, however, the potential for drug interactions and accumulated toxicity. It may be helpful to stratify all patients in three risk groups to plan regular diagnostic screening. Treatment of dyslipidemia and diabetes mellitus should include a first-line approach with non-pharmacological interventions. Statins and fibrates are proposed for HIV-infected patients with HAART-related hyperlipidemia, but concern has been raised on their potential for interaction with antiretrovirals and hepatic and muscle toxicity. Metformin and thiazolidenediones (or glitazones), hypoglycemic agents that increase insulin sensitivity, are presently under evaluation in diabetic and glucose-intolerant HIV-infected patients treated with HAART. Glitazones also have a potential for ameliorating the lipodystrophic syndrome. The routine evaluation of coagulative parameters is probably not advisable until a benefit of widespread screening is assessed in prospective studies. A heightened awareness of the possiblity of coagulative disorders, together with controlled trials and basic research, is needed