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

Is "option B+" also being adopted in pregnant women in high-income countries? Temporal trends from a national study in Italy

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MYELIN DEGRADING ACTIVITY IN THE CSF OF HIV-1-INFECTED PATIENTS WITH NEUROLOGICAL DISEASES

DEGRADATION of purified myelin basic protein (MBP) was studied by SDS gel electrophoresis after addition of CSF samples obtained from HIV-1-infected patients. An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI). In the ADC and PML patients, in addition to CSF proteolytic activity, an increase in CSF-MBP levels and presence of white matter lesions were also observed by neuroimaging (MRI). In other opportunistic infections of the brain, MBP levels but not anti-MBP proteolytic activity increased. Results suggest the involvement of proteases in the virus-induced demyelination

Influence of previous tuberculin skin test on serial IFN-γ release assays.

International audienceTuberculin skin test (TST) and interferon-γ release assays (IGRAs) have been proposed for serial testing in tuberculosis. In the present study, we assessed the effect of TST on subsequent QuantiFERON-TB Gold In-Tube (QFT-GIT) results by monitoring the evolution of responses during a follow-up period of 6 weeks. One hundred and two subjects were initially tested with QFT-GIT and subsequently with TST; then the QFT-GIT was performed serially 1, 2, 4, and 6 weeks after the TST. A subgroup of 40 subjects was also assessed by older version of the QuantiFERON-TB Gold (QFT-G) assay. The results showed no significant variation in IFN-γ response over time in the tested patients, although two TST-positive subjects showed evidence of possible boosting effect. In addition, a direct comparison between the QFT-G and QFT-GIT test showed no significant differences at any time point with excellent agreement between two tests. No significant differences were seen in IFN-γ responses between BCG-unvaccinated and BCG-vaccinated patients at each time point. In conclusion, our findings indicate that TST does not influence the outcome of subsequent IGRAs testing in individuals with negative TST results, but it can boost the IFN-γ response in subjects sensitized to TB antigens and not detected by IGRA

Clinical features of bacterial meningitis in Italy: a multicenter prospective observational study

We carried out a prospective observational study on clinical features of bacterial meningitis. Between October 2002 and June 2005, 322 adult bacterial meningitis cases in 49 infectious disease wards in Italy (MENTORE study group) were enrolled in the study. 133 cases were due to Streptococcus pneumoniae, 44 to Neisseria meningitidis and 145 to other microorganisms. A high SAPS score and coma on admission, as well as need for mechanical ventilation, were more frequent in the pneumococcal meningitis group. Neurological impairment was present in 151 out of 311 patients, and was more frequent in pneumococcal meningitis. A single antibiotic was employed in only 90 of 315 cases; a combination of ceftriaxone and ampicillin was the most frequently administered treatment. Ceftriaxone was also the single most used drug. Adjunctive treatment with steroids was administered in 2 10 out of 303 patients for a median duration of 7 days. Median duration of fever was 4 days, and median hospital stay was 16 days; hospitalization was significantly longer in the pneumococcal meningitis group. At discharge, neurological impairment was still present in 59 (21%) of 277 patients. Twenty (6.9%) out of 289 patients died during hospitalization. Distribution of adverse outcome (death and neurological impairment) in patients treated with or without steroids and within different time zones between onset of symptoms and commencement of antibiotics was studied; a trend toward a worse prognosis was seen in patients treated more than 24 hours after onset of the disease. In our study, infectious disease clinicians made extensive use of steroids as adjuvant therapy for bacterial meningitis, even in absence of detailed national and local guidelines. Mortality seemed to be lower in comparison with the literature

Long-term (96-week) follow-up of antiretroviral-naïve HIV-infected patients treated with first-line lopinavir/ritonavir monotherapy in the MONARK trial

Background: The toxicities, cost and complexity of triple combinations warrant the search for other treatment options, such as boosted protease inhibitor (PI) monotherapy. MONotherapy AntiRetroviral Kaletra (MONARK) is the first randomized trial comparing lopinavir/ritonavir monotherapy to triple combination therapy with zidovudine/lamivudine and lopinavir/ritonavir in antiretroviral-naïve patients. Methods: A total of 136 antiretroviral-naïve patients, with a CD4 cell count above 100 cells/μL and a plasma HIV RNA below 100 000 HIV-1 RNA copies/mL, were randomized and dosed with either lopinavir/ritonavir monotherapy (n=83) or lopinavir/ritonavir+zidovudine/lamivudine (n=53). We focus here on patients in the lopinavir/ritonavir monotherapy arm followed to week 96. The intent-to-treat (ITT) analysis initially involved all patients randomized to lopinavir/ritonavir monotherapy (n=83), and then focused on patients who had an HIV RNA 400 copies/mL. Focusing on the 56 patients with an HIV RNA <50 copies/mL at week 48, 38 of 56 patients (68%) had a sustained HIV RNA <50 copies/mL to week 96. To week 96, a total of 28 patients (34%) had discontinued the study treatment. In addition, the allocated treatment was changed for seven patients. PI-associated resistance mutations were evident in five of 83 patients in the monotherapy arm from baseline to week 96. Conclusion: By ITT analysis, 39 of the 83 patients initially randomized to lopinavir/ritonavir monotherapy had HIV RNA <50 copies/mL at week 96. The occurrence in some patients of low-level viraemia (50-500 copies/mL) may increase the risk of drug resistance. First-line lopinavir/ritonavir monotherapy cannot be systematically recommended. © 2009 British HIV Association