Herpesvirus encephalitis diagnosed by polymerase chain reaction at the National Institute of Neurology of Mexico.

The frequency of central nervous system infections due to herpesvirus have been studied in various populations; however, studies in Mexican mestizo patients are scant. This paper documents the frequency of herpesvirus encephalitis in Mexican mestizo patients from the National Institute of Neurology and Neurosurgery (NINN) of Mexico. To study the frequency of herpetic viral encephalitis at the NINN in the period from 2004 to 2009. We reviewed clinical records from patients with clinically suspected encephalitis; polymerase chain reaction assays were done for detection of herpesviruses in cerebrospinal fluid (CSF) samples. The total number of patients studied was 502; in 59 (12%), the diagnosis of herpetic encephalitis was confirmed by PCR-based testing of CSF. Of them, 21 (36%) were positive for herpes simplex virus type 1, 15 (25%) for Epstein-Barr virus, 10 (17%) for varicella zoster virus, 8 (14%) for cytomegalovirus, 3 (5%) for human herpesvirus 6, and 2 (3%) for herpes simplex virus 2. Our results show a varied frequency of viral encephalitis in mestizo patients due to herpesviruses in a tertiary neurological center and point out the importance of modern molecular technology to reach the etiological diagnosis in cases of encephalitis.

HHV-6: clinical and laboratory investigations and correlations with encephalitis in liver transplant recipients.

OBJECTIVE: Human herpesvirus (HHV) 6 infections and reactivation are emerging factors in neurology. This study aimed to verify the presence of encephalitis associated with HHV-6 positivity by antigenemia or polymerase chain reaction (PCR) in liver transplant recipients. METHODS: We analyzed the medical records and laboratory results of 20 recipients with antigenemia or a positive PCR for HHV-6. The range of the transplantation dates was September 2006 to March 2010; the period of the medical records was from the date of transplantation to 1 year thereafter. Encephalitis was diagnosed by these symptoms: fever, mening, signs, seizures, dysphasia, visual and hearing impairment, or sensory and motion alterations. "Possible encephalitis" was considered when the patients had at least 2 of the symptoms. PCR or antigenemia for HHV-6 was not performed with central nervous fluid. The correlation between HHV-6 infection and encephalitis was evaluated with the use of descriptive statistical tests. RESULTS: Symptoms associated with encephalitis occurred in 7/20, patients (35%): 5/20 with fever and 4/20 with mental confusion. Involuntary movements were present in 1 case. The symptoms appeared with in the first 10 days in 6/20 patients and lasted for 1 year. CONCLUSIONS: This study showed that symptoms associated with encephalitis occurred in a considerable number of patients with positive PCR and/or antigenemia for HHV-6 after liver transplantation. This correlation needs retrospectie and prospective studies to determine the specific association.

HTLV-1 cosmopolitan and HTLV-2 subtype b among pregnant women of non-endemic areas of Argentina.

OBJECTIVES: The objective of this study was to estimate the prevalence of human T cell lymphotropic virus (HTLV)-1/2, HIV-1, hepatitis B virus (HBV), Trypanosoma cruzi, Treponema pallidum and Toxoplasma gondii infections and to identify the subtypes/subgroups of HTLV-1/2 among pregnant women (PW) from non-endemic provinces of Argentina. METHODS: Methods A total of 2403 samples were screened for HTLV-1/2 and confirmed by western blot and PCR. The long terminal repeat (LTR) of HTLV-1 and HTLV-2 were amplified. Phylogenetic analysis was performed by Neighbour Joining by using molecular evolutionary genetics analysis (MEGA) 4.0. RESULTS: Among a total of 2403 PW studied, 6 (0.25%) tested positive for HTLV-1/2 (3 HTLV-1 (0.12%) and 3 HTLV-2 (0.12%)). The total prevalence when distributed by province was 0.3% (3/804) for Buenos Aires (BA), 0.4% (1/241) for BA surroundings, 0.1% (1/707) for Neuquen and 1.0% (1/95) for Ushuaia. In San Juan, no PW were HTLV-1/2 positive. The prevalence was similar when compared with rates among blood donors of the same areas and years. The phylogenetic analysis classified one sequence as HTLV-1 aA and one as HTLV-2b. The prevalence of HIV-1, HBV, T cruzi, T pallidum and T gondii was 0.6%, 0.2%, 1.4%, 1.2% and 20.9%, respectively. One case of HTLV-1/HIV-1 and one of HTLV-2/HIV-1 co-infection were detected. CONCLUSIONS: HTLV-1/2, which have been associated with different diseases, are circulating among PW of Argentina, even in non-endemic areas. Therefore, testing should be recommended in women who have risk factors for these infections given that the majority of HTLV-1/2 mother to child transmission can be prevented by the avoidance of breast feeding.

Co-infection and clinical impact of human herpesvirus 5 and 6 in liver transplantation.

BACKGROUND: Human herpesvirus (HHV) 5 and 6 remain latent after primary infection and can be reactivated after immunosuppression for organ transplantation. An association between HHV-5 and HHV-6 has been reported in liver transplant patients. The coinfection is associated with clinical manifestations and graft dysfunction. OBJECTIVE: The aim of this study was to monitor herpesviruses in liver transplant recipients to better understand issues involving coinfection with HHV-5/6 and correlations with acute cellular rejection episodes and bacterial infections. METHODS: Forty-five adult liver transplant patients of median age 47 years (range, 18-66), gave blood samples and liver biopsies in the first 6 months after their surgeries. Viremia was detected with the use of nested PCR and antigenemia; the Banff classification was used to detect allograft rejection. RESULTS: IgG positive for HHV-5 was observed in 94% of subjects whose main indication (67%) for transplantation was hepatitis C. Twenty-three (51.1%) displayed cytomeg virus (CMV) infections and 12 (26.7%) HHV-6 infection. There were 6 patients (13.3%) with HHV-5/6 coinfections. Eighteen of the 23 patients had CMV disease, showing a strong correlation between a positive test and CMV disease; 6 displayed an acute cellular rejection episode in the same period (χ(2) = 6.62; P < .03). Four out of 6 patients who displayed coinfections (HHV-5/6) had concomitant bacterial infections; 3/6 experienced graft rejection episodes. During follow-up, 1 patient had HHV-6 infection diagnosed as encephalitis followed by fever on the 24th day after surgery. The median 32 days for HHV-6 detection by nested PCR positivity was shorter than 38 days for HHV-5. CONCLUSIONS: HHV-5/6-infected patients displayed more allograft rejection episodes, coinfections, and concomitant bacterial infections, besides an higher risk for CMV disease.

Detection of human herpesvirus 6 in patients with oral chronic graft-vs-host disease following allogeneic progenitor cell transplantation.

INTRODUCTION: Chronic graft-vs-host disease (cGVHD) is a major cause of morbidity in long-term survivors of allogeneic hematopoietic progenitor cell transplantation. Herpesviruses are involved in the occurrence and progression of various oral diseases. AIM: The aim of this study was to investigate the role of human herpesvirus 6 (HHV6) in patients with oral manifestations of cGVHD. MATERIALS AND METHODS: Peripheral blood and oral fluids (whole saliva, gingival crevicular fluid and parotid gland saliva) from 19 cGVHD patients, and 28 blood donors were examined for HHV6. Oral tissue samples were collected from 12 cGVHD patients and 12 healthy individuals. Nested polymerase chain reaction was employed to identify the HHV6. RESULTS AND CONCLUSION: The virus was detected in whole saliva in 13 cGVHD patients (68%) and in 19 blood donors (67%). HHV6 was not identified in any of the gingival crevicular fluid and parotid gland saliva samples in cGVHD patients. In the control group 14.3% of both, four gingival crevicular fluid and four parotid gland saliva samples were positive. Two oral tissue samples of cGVHD patients were positive for HHV6. These results indicate that patients with oral manifestations of cGVHD and healthy individuals present high and similar incidence of HHV6 in blood and oral fluids. These data do not support the importance of HHV6 in oral lesions of cGVHD.

In vitro activity evaluation of Parkia pendula seed lectin against human cytomegalovirus and herpes virus 6.

Human cytomegalovirus (HCMV) in vitro infectivity was inhibited by Parkia pendula seed lectin (PpeL) in contrast to human herpes virus 6 (HHV-6) which was not affected. The antiviral activity was detected for HCMV in human embryo lung (HEL) cells using a microtechnique in culture plates. The assay showed a reduction of cellular infectivity from approximately 95%, at a concentration of 150microg/mL with minimal cytotoxicity (25%). Also, a reduction of 75% was observed in HEL cells at a concentration of 75microg/mL without toxic effect. The reduction on infectivity was observed even after virus pre-adsorption to cells suggesting that this action should occur after virus penetration, in the intracellular replication phase. MT4 lymphocytes and cord blood mononuclear cells (CBMC) were used to evaluate the lectin effect on HHV-6 following the same technique. Lectin concentrations with few or no toxic effects on lymphocytes did not show inhibitory action of HHV-6 cytopathic effect. The results obtained with PpeL demonstrate that it may have an impact in the design of pharmacological strategies to infection of cytomegalovirus.

Human herpesvirus type 6 and type 1 infection increases susceptibility to nonmelanoma skin tumors.

In order to investigate herpesvirus (HHV) role in the susceptibility to skin cancer, we compared HHV6 and HHV1 incidence in DNA samples extracted from 120 lesions and 41 normal skin tissues. HHV6 (31.7%) and HHV1 (23.8%) were detected more frequently in skin cancer than in control individuals (14.6 and 5%, respectively) (P=0.0391 and P=0.00094, respectively). The risk of presenting basal cell carcinomas (BCC) was more than 3 times higher for HHV-6 infected patients (OR=3.182; 95% CI: 1.125-8.997). The risk for HHV-1 infected individuals of presenting BCC and squamous cell carcinomas was increased 8 and 6 times, respectively (OR=8.125; 95% CI: 1.735-38.043 and OR=6.290; 95% CI: 1.283-30.856, respectively).

Los virus herpes linfotrópicos humanos: epstein-Barr (VEB), 6 y 7 (HHV-6 y HHV-7) en la patogenia de enfermedades mielodisplásicas (SMD) y mieloproliferativas (SMP) / Lymphotropic human herpesviruses: epstein-Barr (EBV), 6 y 7 (HHV-6 and HHV-7) in the pathogenia of myelodysplastic (MDS) and mieloproliferative diseases (MPS)

Con base en alteraciones mielodisplásicas y mieloproliferativas observadas en pacientes con enfermedades linfoproliferativas asociadas a virus herpes linfotrópicos humanos, se realizaron estudios de escrutinio para demostrar eventualmente la reactivación de éstos y su posible implicación en la patogenia y curso de síndrome mielodisplásico (SMD) y de síndrome mieloproliferativo (SMP). Se investigaron 74 biopsias de médula ósea y sueros de pacientes con SMD y 49 biopsias de médula ósea y 36 sueros de pacientes con leucemia mieloide crónica (LMC), a 13 casos de México no se les realizó serología. El diagnóstico y clasificación se hizo según los criterios del Grupo Franco-Americano-Británico (FAB). Se realizaron pruebas séricas de anticuerpos contra antígeno de la cápsula viral (VCA) y antígeno temprano (EA) del VEB con las técnicas de ELISA y de inmunofluorescencia y de HHV-6 y HHV-7 mediante inmunofluorescencia. La inmunohistología se realizó con la técnica de APAAP (fosfatasa alcalina-antifosfatasa alcalina) para expresión antigénica de los 3 virus y por anticuerpos monoclonales. Se determinó proliferación celular con APAAP y con anticuerpo monoclonal contra el antígeno nuclear de proliferación celular (PCNA). Se encontraron títulos de IgG anti-VEB-EA en 62 por ciento de los casos con SMD y en 33 por ciento con LMC, títulos de IgG HHV-6 elevados en 19 por ciento de los casos con SMD y en 9.3 por ciento de LMC y los de HHV-7 elevados en el 37.8 por ciento y 13.9 por ciento, respectivamente. Los títulos de IgM fueron negativos para los tres virus. La expresión de antígeno en la médula ósea fue positiva en el 76 por ciento de SMD a VEB-EA, 48.6 por ciento a HHV-6 p41 y 37.8 por ciento a HHV-7. Los casos de LMC expresaron VEB-EA en el 77 por ciento, HHV-6 en el 54.5 por ciento y HHV-7 en el 21.8 por ciento.

Modulation of nuclear factor kappa b (NF-kB) activity in human herpes virus-6 (HHV-6) infection and its sequellae for cell function: Effects of antisense DNA treatment

Varias poblaciones celulares, susceptibles y no susceptibles, fueron infectadas con el virus herpes humano-6 (HHV-6) y tratadas posteriormente con ácido desoxirribonucleico (ADN) -NF-kB antisentido. Algunos cambios celulares secundarios a la integración del genoma viral pudieron ser corregidos con este tratamiento, mientras que aquellos inducidos por efecto de membrana celular del virus no respondieron de manera uniforme. Es así como el tratamiento con NF-kB puede servir para investigaciones posterioes específicas de los efectos virales en la célula. También puede servir para estudiar las actividades competitivas de las proteínas de NF-kB en los sitios genómicos homólogos

[Viral encephalitis]. / Encefalitis viral.

Viral infections of the nervous system make up a wide range of disorders with a mainly benign outcome. However, in some cases there is severe, morbimortality. In viral encephalitis there is direct involvement of the brain parenchyma which is seen clinically as reduced consciousness, convulsions and/or focal neurological deficit. The especial attraction of some viruses for particular cells or structures determines the variety of clinical findings. The incidence and frequency of the various agents depends on several factors (geographical location of a certain virus, age and general health of the population concerned, etc.). In areas free of arbovirus the commonest aetiologies are; varicella, herpes simplex, parotiditis and enterovirus. Modern treatment (transplants, chemotherapy) of previously fatal diseases and the AIDS epidemic have increased the number of immunodeficient patients; the population is susceptible to viral infections of the nervous system which are infrequent (e.g. cytomegalovirus, papovavirus) or which follow a different course (e.g. measles, enteroviruses) to that in immunocompetent patients. Specific conditions are reviewed. Improvement in the general health and sanitation of the population, and the universal use and development of new vaccines will significantly reduce the incidence of viral encephalitis. Improved prognosis will be related to the use of modern laboratory techniques which permit early, sensitive, specific diagnosis and the development of antiviral agents.