Human herpesvirus infections of the central nervous system: laboratory diagnosis based on Dna detection by nested Pcr in plasma and cerebrospinal fluid samples

Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the "gold standard," and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture.Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. 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Withdrawal Of Maintenance Therapy For Cytomegalovirus Retinitis In Aids Patients Exhibiting Immunological Response To Haart

Background: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. Methods: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm3 for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. Results: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. Conclusion: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.494215219ACTG, Mortality in patients with the acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir for cytomegalovirus retinitis. Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. New Engl. J. Med, 326: 213-220, 1992BERENGUER, J., GONZALEZ, J., PULIDO, J., Discontinuation of secondary prophylaxis in patients with cytomegalovirus retinitis who have responded to highly active antiretroviral therapy (2002) Clin. infect. Dis, 34, pp. 394-397BONON, S.H., MENONI, S.M.F., ROSSI, C.L., Surveillance of cytomegalovirus infection in haematopoietic stem cell transplantation patients (2005) J. Infect, 50, pp. 130-137CASSOUX, N., BODAGHI, B., KATLAMA, C., LEHOANG, P., CMV retinitis in the era of HAART (1999) Ocul. Immunol. Inflamm, 7, pp. 231-235CURI, A.L., MURALHA, A., MURALHA, L., PAVESIO, C., Suspension of anticytomegalovirus maintenance therapy following immune recovery due to highly active antiretroviral therapy (2001) Brit. J. Ophthal, 85, pp. 471-473DEAYTON, J.WILSON, J.R.SABIN, P. et al. - Recovery of antibody responses to Cytomegalovirus (CMV) Glycoprotein B (gB) following Highly Active Antiretroviral Therapy (HAART). In: CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS, 6., Chicago, 1999. p. 153DEAYTON, J.R., WILSON, P., SABIN, C., Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy (2000) Aids, 14, pp. 1163-1670DEGREZIA, M.G., ROBINSON, M., Ophthalmic manifestations of HIV: An update (2001) J. Ass. Nurses AIDS Care, 12, pp. 22-32FRANCISCI, D., TOSTI, A., PREZIOSI, R., Role of antigenemia assay in the early diagnosis and prediction of human cytomegalovirus organ involvement in AIDS patients (1995) Europ. J. clin. Microbiol. infect. Dis, 14, pp. 498-503GALLANT, J.E., MOORE, R.D., RICHMAN, D.D., KERULY, J., CHAISSON, R.E., Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group (1992) J. infect. Dis, 166, pp. 1223-1227GERNA, G., PICCININI, G., GENINI, E., Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART (2001) J. acquir. immune Defic. Syndr, 28, pp. 320-331GOLDBERG, D.E., SMITHEN, L.M., ANGELILLI, A., FREEMAN, W.R., HIV-associated retinopathy in the HAART era (2005) Retina, 25, pp. 633-649HALWACHS, G., ZACH, G., POGGLITSCH, H., A rapid immunocytochemical assay for CMV detection in peripheral blood of organ-transplanted patients in clinical practice (1993) Transplantation, 56, pp. 338-342HENDERSON, H.W., MITCHELL, S.M., Treatment of immune recovery vitritis with local steroids (1999) Brit. J. Ophthal, 83, pp. 540-545HOOVER, D.R., PENG, Y., SAAH, A., Occurrence of cytomegalovirus retinitis after human immunodeficiency virus immunosuppression (1996) Arch. Ophthal, 114, pp. 821-827JABS, D.A., VAN NATTA, M.L., KEMPEN, M.L., Characteristics of patients with cytomegalovirus retinitis in the era of highly active antiretroviral therapy (2002) Amer. J. Ophthal, 133, pp. 48-61JACOBSON, M.A., Treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (1997) New Engl. J. Med, 337, pp. 105-114JACOBSON, M.A., ZEGANS, M.A., PAVAN, M., Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy (1997) Lancet, 349, pp. 1443-1445JOUAN, M.SAVES, M.TUBIANA, M. et al. - A prospective multicentre study to evaluate the discontinuation of maintenance therapy for CMV Retinitis in HIV-patients receiving HAART. In: CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS, 6., Chicago, 1999JOUAN, M., SAVES, M., TUBIANA, M., Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy (2001) Aids, 15, pp. 23-31KARAVELLAS, M.P., PLUMMER, M.P., MACDONALD, D.J., Incidence of immune recovery vitritis in cytomegalovirus retinitis patients following institution of successful highly active antiretroviral therapy (1999) J. infect. Dis, 179, pp. 697-700KEANE, N.M., PRICE, P., STONE, S.F., Assessment of immune function by lymphoproliferation underestimates lymphocyte functional capacity in HIV patients treated with highly active antiretroviral therapy (2000) AIDS Res. hum. 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Cytomegalovirus Infection In Hematopoietic Stem Cell Transplantation; Review In The Literature And A Single Center Experience, (state University Of Campinas, Brazil)

Human cytomegalovirus is a ß human herpesvirus characterized by its restricted host range, production of nuclear as cytoplasmic inclusions, and its long life cycle. It is the largest known human herpesvirus, with genome of about 240 kb. CMV establishes latency in peripheral blood monocytes and tissue macrophages and can reactivate during HSCT. CMV is one of the most common viruses after HSCT and had been the most common infection cause of death. During the two decade ago, major advances have been achieved regarding the management CMV infection and disease. These advances have been made possible through the development of new diagnostic techniques for the detection of the virus and through the performance of prospective clinical trials of antiviral agents. Two principal strategies have been used for prevention of CMV disease: prop-hylactic strategy in which regular administration of an antiviral is used to prevent CMV reactivation and preemptive strategy in which reactivation of CMV is screened for during the period of higher risk and antiviral therapy promptly initiated when CMV reactivation occurs. In 1993 was realized the first HSCT in Bone Marrow Transplant Unit, State University of Campinas (Brazil), using the prophylactic strategy with intravenous ganciclovir in allogenic HSCT recipient but without using assays for monitoring active CMV infection in post-transplant. Surveillance of active CMV infection began in 1996 by PCR and serology. Preliminary results of this protocol were exhibited in the 2nd meeting of the European Haematology Association - Paris , France (1996). Preemptive strategy was deployed in 2004 by Bonon et al. In this research was described the Bone Marrow Transplant Unit, State University of Campinas (Brazil) experience in the control of active CMV infection following HSCT using two strategies of CMV infection treatment: ganciclovir universal prophylaxis at low doses and preemptive therapy with ganciclovir. The surveillance was based on the monitoring by antigenemia and PCR for detection of CMV and the conclusion was that the patients with a propensity for developing CMV disease can be readily identified and preemptive therapy instituted, avoiding the toxicity related to antivirals and the high cost of universal prophylaxis. Though the antigenemia method is the gold standard to guide previous treatment in HSCT receptors, real-time PCR is emerging as an alternative to substitute antigenemia because it presents several advantages over the antigenemia, including an increased sensitivity for the detection of CMV reactivation, the reliable detection of CMV reactivation during severe neutropenia in the early post-transplant period, the shorter time required for the procedure, and the convenient processing of large numbers of specimens. For this reason Peres et al. (2010) in order to switch the monitoring method from antigenemia to real-time PCR in Bone Marrow Transplant Unit, State University of Campinas (Brazil) determined the cutoff of 418.4 copies/104 PBL (peripheral blood leukocytes) by real-time PCR for preemptive therapy. 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