Search

Background We analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients. Methods 71 kidney and heart transplant recipients (basiliximab [ n = 43] and ATG [ n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot. Results Median time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group ( p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10 6 PBMC, p = 0.0007), but no differences between treatment groups were observed ( p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy. Conclusions After influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.

Enterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization.To assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM.Observational study in adult patients with AM. Three groups were analyzed according to EV documentation in CSF: group A = no PCR or negative PCR (n=17), group B = positive real-time PCR (n = 20), and group C = positive GXEA (n = 22). Clinical, laboratory and health-care costs data were compared.Clinical characteristics were similar in the 3 groups. Median turn-around time of EV PCR decreased from 60 h (IQR (interquartile range) 44-87) in group B to 5h (IQR 4-11) in group C (p0.0001). Median duration of antibiotics was 1 (IQR 0-6), 1 (0-1.9), and 0.5 days (single dose) in groups A, B, and C, respectively (p0.001). Median length of hospitalization was 4 days (2.5-7.5), 2 (1-3.7), and 0.5 (0.3-0.7), respectively (p0.001). Median hospitalization costs were $5458 (2676-6274) in group A, $2796 (2062-5726) in group B, and $921 (765-1230) in group C (p0.0001).Rapid EV detection in CSF by a fully-automated PCR improves management of AM by significantly reducing antibiotic use, hospitalization length and costs.

Summary Background Recent data suggest that varicella zoster virus (VZV)-associated complications of the central nervous system (CNS) are more common and diverse than previously thought. The main purpose of this article is to describe the clinical characteristics and the outcome of patients suffering from meningitis and encephalitis caused by VZV reactivation. Methods A retrospective case study of adult patients (≥16 years old) diagnosed with a VZV reactivation in the CNS was performed. The cases were identified by a qualitative PCR DNA assay of the cerebrospinal fluid (CSF) at the Regional Hospital of Lugano between January 1, 2003 and July 31, 2010. Results Eleven out of 519 CSF samples (2.1%), submitted from patients with a clinical diagnosis of viral meningitis or encephalitis, were positive for VZV. A vesiculo-pustular skin eruption was observed in only five patients (45%). In six cases (55%), a systemic inflammatory syndrome was absent. The clinical outcome was favorable in eight patients (73%). Only one out of 11 patients (9%) died. The four patients with encephalitis had a less favorable prognosis: one patient recovered without residual neurological sequelae; two had a chronic neuropsychological handicap, speech difficulties, facial nerve palsy, and focal seizures; one patient died. We estimated an annual incidence rate of VZV infection of the CNS of 1.02/100 000 inhabitants for southern Switzerland. Conclusions Screening of CSF for VZV by PCR is recommended for all patients with encephalitis and for those with viral meningitis of unclear origin in order to better target antiviral treatment.

We have compared a multiplexed bead-based assay (BBA) with an enzyme immunoassay (EIA) and immunofluorescence assay (IFA) for the assessment of the Epstein–Barr virus (EBV) serostatus. Three hundred and ninety-three sera, classified according to IFA results as seronegative (n = 100), acute infection (n = 100), past infection (n = 100) and indeterminate (n = 93), were tested by BBA and EIA. Overall, the three methods gave similar results with a relatively high (75.2%) concordance with the consensus interpretation of the serostatus. The most significant discordances were: (i) 58 samples had uninterpretable results for BBA, in majority due to the detection of non-antigen specific antibody binding by control beads. (ii) almost half the samples positive for anti-Epstein—Barr nuclear antigen (EBNA) IgG by BBA or EIA were negative by IFA. Among the latter, only a minority had a history of immunocompromise or treatment, or detectable anti-early antigen antibody. This discrepancy probably reflects a poor sensitivity of IFA for anti-EBNA IgG detection. EIA and BBA had a similar performance and had substantial practical advantages over IFA with respect to testing for EBV serostatus.

Hypogammaglobulinemia develops in 3 to 6% of patients with thymoma and this association is commonly referred to as thymoma with immunodeficiency (formerly Good syndrome). Recurrent infections with encapsulated bacteria and opportunistic infections associated with disorders of both humoral and cell mediated immunity frequently occur in this rare primary, adult-onset immunodeficiency. We report a case of thymoma with immunodeficiency complicated by disseminated herpes simplex virus (HSV) infection and review five additional cases of HSV-related infections reported since 1966 in patients presenting with thymoma with immunodeficiency. Patients presented with epiglottitis, keratitis, recurrent genital herpes, ulcerative dermatitis, and acute hepatitis. Four of the six cases had a fatal outcome, two of which were directly attributable to HSV infection. Since the risk of invasive opportunistic infections is high and the presentation atypical, lymphocyte count and total serum immunoglobulin should be measured regularly in all patients presenting with thymoma with immunodeficiency.

The mechanisms leading to CNS disorders after EBV infections are unclear. We report the case of a patient who developed a severe, but reversible, encephalopathy following an infectious mononucleosis. We detected no EBV DNA in the blood or in the cerebrospinal fluid (CSF) and no EBV-specific antibodies in the CSF. However, we found a potent MOG-specific cellular and humoral immune response. Interestingly, MOG-specific cellular immune response rapidly decreased, paralleling the improvement of clinical condition. In conclusion, this detailed study shows that acute EBV infection can trigger a potent auto-inflammatory response in the CNS, without evidence of an overt infection.

A procedure is described that allows the simple identification and sorting of live human cells that transcribe actively the HIV virus, based on the detection of GFP fluorescence in cells. Using adenoviral vectors for gene transfer, an expression cassette including the HIV-1 LTR driving the reporter gene GFP was introduced into cells that expressed stably either the Tat transcriptional activator, or an inactive mutant of Tat. Both northern and fluorescence-activated cell sorting (FACS) analysis indicate that cells containing the functional Tat protein presented levels of GFP mRNA and GFP fluorescence several orders of magnitude higher than control cells. Correspondingly, cells infected with HIV-1 showed similar enhanced reporter gene activation. HIV-1-infected cells of the lymphocytic line Jurkat were easily identified by fluorescence-activated cell sorting (FACS) as they displayed a much higher green fluorescence after transduction with the reporter adenoviral vector. This procedure could also be applied on primary human cells as blood monocyte-derived macrophages exposed to the adenoviral LTR-GFP reporter presented a much higher fluorescence when infected with HIV-1 compared with HIV-uninfected cells. The vector described has the advantages of labelling cells independently of their proliferation status and that analysis can be carried on intact cells which can be isolated subsequently by fluorescence-activated cell sorting (FACS) for further culture. This work suggests that adenoviral vectors carrying a virus-specific transcriptional control element controlling the expressions of a fluorescent protein will be useful in the identification and isolation of cells transcribing actively the viral template, and to be of use for drug screening and susceptibility assays.

Objective: To evaluate nested PCR for Toxoplasma gondii (TOX), JC virus (JCV) and Epstein-Barr virus (EBV) for diagnosis of toxoplasmic encephalitis (TE), progressive multifocal leukencephalopathy (PML) and primary central nervous system lymphoma (PCL). Methods: A prospective study encompassed 26 HIV-I-infected individuals presenting with focal neurologic signs and symptoms. Nested PCR was performed on both supernatants and pellets of centrifuged cerebrospinal fluid (CSF), on plasma and on white blood cells (WBCs). For a retrospective study, stored CSF supernatants were available from an additional 27 HIV-1-infected patients with TE, PML, and PCL. Results: TE, PML or PCL was diagnosed in 13 of 26 patients in the prospective group. Plasma and WBC analysis by PCR was not informative except in one case of TE. TOX and JCV were detected by PCR in the CSF pellets of four of five patients with TE, and of four of five patients with PML, respectively, but in no other cases. EBV was detected not only in three of three cases of PCL, but also in six patients suffering from other conditions. PCR on the CSF supernatants was less sensitive for all three etiologies. These results correlated with those of the retrospective PCR analysis, for which only stored CSF supernatants were available, revealing sensitivities of 33%, 50% and 66% for TE, PML and PCL, respectively, but specificities of 100%. Conclusions: In the clinical routine, TOX and JCV PCR on centrifuged CSF pellets can be recommended to obtain an early diagnosis of TE and PML. Under these conditions, EBV PCR helps to exclude PCL as a cause of FBLs, as it is highly sensitive, but not specific, for PCI- in HIV-I-infected individuals.

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a ≥2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.

Resume L'experimentation animale suggere qu'il soit possible de prevenir des infections retrovirales par l'administration de medicaments antiviraux administres avant, ou peu apres l'inoculation. En raison du taux faible d'infection par le VIH apres des expositions telles que des blessures par aiguilles souillees, il est probablement impossible d'etablir l'efficacite d'une telle prophylaxie contre l'infection par le VIH de personnel soignant dans une etude clinique. Parmi les etudes utilisant des modeles experimentaux animaux, celles effectuees a l'aide de modeles murins et felins demontrent la possibilite de prevenir une infection retrovirale par une chimiotherapie administree quelques heures apres l'inoculation. Les etudes utilisant des modeles simiens n'ont generalement pas permis d'observer de protection complete, a moins de debuter la chimiotherapie avant l'inoculation. Cependant ces echecs pourraient etre dus a l'emploi d'inoculums trop importants. Il serait donc utile d'etudier des regimes prophylactiques dans les modeles experimentaux les plus realistes, c'est-a-dire les modeles simiens, avec des inoculums reduits, pour preciser le mode de prophylaxie le plus efficace en termes de medicaments, doses et horaires. De telles etudes seraient couteuses. Cependant, l'identification de regimes prophylactiques dans des modeles experimentaux, dont l'efficacite pourrait etre extrapolee a la situation clinique, permettrait de prevenir des infections par le VIH chez le personnel soignant et de reduire considerablement l'angoisse qui fait suite aux expositions.

Introduction et objectifs Les erythrovirus, le Parvovirus B19 (PVB19) et les erythrovirus type 2 et 3 recemment decouverts, pourraient etre responsable d’anemie chronique et d’intolerance hematologique a la zidovudine (AZT) chez les patients seropositifs pour le VIH. Materiels et methodes Nous avons selectionne dans l’etude Suisse de Cohorte (SHCS) les patients qui ont presente entre 1998 et 2007 une anemie chronique (hemoglobine [hb] 3 et pour lesquels un serum etait disponible dans la periode ou l’anemie etait presente. Une PCR en temps-reel amplifiant le gene VP1 (commun au PVB19 et aux erythovirus type 2 et 3) a ete utilisee pour detecter et quantifier le genome des erythrovirus. Resultats 428 patients ont ete inclus (âge median, 44 ans ; sexe feminin, 61 % ; toxicomanie, 36 % ; CD4 median, 187/mm 3 ; Hb median, 9,5 g/dL ; AZT, 41 %). La PCR etait positive uniquement chez 16 patients ; chez les patients avec une replication virale d’erythrovirus, la charge virale etait de faible ampleur (range : 18-6 820 copies/ml). Les caracteristiques des patients, ainsi que les facteurs lies au VIH n’etaient pas differents entre les patients avec ou sans replication virale d’erythrovirus ; ni la gravite de l’anemie, ni l’exposition a l’AZT ne different entre les deux groupes ( p = 0,80 et p = 0,78, respectivement). Conclusion Les co-infections a erythrovirus sont rarement mis en evidence chez les patients infectes par le VIH qui presentent une anemie chronique avec des CD4 3 , malgre l’utilisation d’une technique de PCR temps-reel ultrasensible.

Resume La determination de la duree de traitement des maladies infectieuses repose sur 2 approches principales, soit l'approche experimentale d'une part, et l'approche clinique par essais controles d'autre part. L'une et l'autre approches presentent cependant des limitations que nous essayerons d'esquisser, et qui montreront a l'evidence que l'antibiotique ne peut pas etre envisage seul dans la lutte contre l'agent bacterien, mais que le terrain joue un role tout aussi important, si ce n'est plus. Les modeles experimentaux : s'ils presentent une utilite certaine pour trier le potentiel therapeutique de substances nouvelles, leur utilisation, pour determiner dosage et duree de traitement d'infections artificiellement induites, doit etre envisagee avec prudence. Il est absolument capital que les modeles utilises imitent aussi fidelement que possible les situations humaines, ce qui trop souvent n'est pas le cas. En effet, de nombreux facteurs doivent etre reproduits qui peuvent influencer la reponse au traitement, dont un des plus importants est peut etre la reponse inflammatoire a l'infection. Celle-ci peut diminuer de maniere considerable l'efficacite des antibiotiques, impliquant par la qu'en presence de lesions exsudatives et purulentes, un traitement long devra etre necessaire pour eradiquer les germes ou prevenir les recidives. Les modeles qui ne tiendraient pas compte de ce facteur essentiel pourraient induire en erreur quant a la rapidite d'action des antibiotiques. L'essai clinique : seul l'essai clinique controle permettra en derniere analyse d'arreter dosage et duree de traitement necessaires pour traiter nombre de situations cliniques infectieuses. Ainsi, des modes therapeutiques bien definis ont ete proposes pour venir a bout d'infections aussi differentes que gonococcie, syphilis, infection urinaire et pyelonephrite, tuberculose, lepre, angine, etc. On se gardera cependant, devant un patient particulier, d'appliquer les yeux fermes les schemas proposes, car il faudra garder en memoire l'importance cruciale du terrain sur lequel s'est developpee l'infection, qui peut modifier considerablement la reponse au traitement. L'etat immunitaire de l'hote : c'est-a-dire les moyens de defense que l'organisme peut mettre en jeu dans l'infection envisagee. Il existe en effet un certain nombre d'infections au cours desquelles les defenses de l'organisme sont partiellement ou totalement inoperantes, et pour le traitement desquelles l'antibiotherapie devra donc etre optimale, bactericide si possible, afin de suppleer a la carence immunitaire. Il s'agit avant tout des infections chez les patients presentant des troubles immunitaires, et particulierement ceux en granulopenie, mais aussi d'infections comme l'endocardite bacterienne (les polynucleaires Des lors, seule la longue et patiente accumulation de donnees soigneusement et scientifiquement recoltees, aussi bien a partir d'observations experimentales que cliniques, permettra a l'avenir de cerner mieux les modalites de dosage et de duree des traitements antibiotiques.