Forma familiar de la enfermedad de Creutzfeldt-Jakob: marcadores genéticos en 4 familias chilenas / Genetic markers in four Chilean families with familial Creutzfeldt-Jakob disease

Background: Creutzfeldt-Jakob disease (CJD) is a form of transmissible spongiform encephalopathy, in which a prion protein (PrP Sc) accumulates in the brain of affected individuals. Chile has a prevalence of CJD that is more than twice than in the rest of the world and has the highest rate of familial forms. These later forms are associated with the heterozygocity of codon 200 of PrP protein gene. Aim: To search susceptibility genetic markers of CJD in members of families affected by CJD. Material and methods: A blood sample was obtained from 50 individuals pertaining to four families affected by CJD. DNA from peripheral mononuclear cells was amplified by polymerase chain reaction and sequenced for the gene that codifies PrP protein. Results: In family A, 21 of 23 members were homozygotes for codon 129 (Met/Met) and eight were simultaneously heterozygotes for codon 200 (Glu/Lys). In family B, six of nine members were homozygotes for codon 129, five were heterozygotes for codon 200 and four had both mutations. In family C, the four analyzed subjects were homozygotes for codon 129 and two were simultaneously heterozygotes for codon 200. In family D, nine of 14 members were homozygotes for codon 129 and two were simultaneously homozygotes for codon 200. No family had polymorphisms for codon 219. Conclusions: Thirty two percent of analyzed subjects were homozygotes for codon 129 and heterozygotes for codon 200, condition that defines the genetic susceptibility to acquire CJD. The dominant tendency of these genotypes could explain the higher incidence of CJF in Chile.

Proteína Tax ( HTLV-I ), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP / Viral Tax protein expression in salivary glands of patients infected with human t-cell lymphotropic virus type I and Sicca Syndrome

Background: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. Aim: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. Material and Methods: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. Results: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. Conclusions: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.

Técnicas diagnósticas de infección humana por hantavirus / Diagnostic techniques for hantavirus human infection

Los hantavirus son virus envueltos, de genoma ARN trisegmentado. Los hantavirus americanos provienen de la subfamilia de roedores Sigmodontinae y pueden causar el síndrome cardiopulmonar por hantavirus (SCPH) mientras que los hantavirus europeos y asiáticos provienen de las subfamilias Murinae y Arvicolinae que pueden producir la fiebre hemorrágica con síndrome renal. En este artículo se describen las técnicas de laboratorio desarrolladas al momento actual para certificar la infección por hantavirus en humanos

Infección por hantavirus en humanos: experiencia del laboratorio de referencia para enfermedades infecciosas emergentes / Hantavirus human infection: experience of the emerging infectious diseases reference laboratory

En Chile la infección humana por hantavirus está ligada al ratón Oligoryzomys longicaudatus, reportándose la circulación de hantavirus en especímenes capturados desde la Región Metropolitana hasta la XI Región. Se han notificado casos de síndrome cardiopulmonar por hantavirus desde la sexta a la undécima regiones. La emergencia de esta enfermedad en la población chilena estimuló el desarrollo de un laboratorio nacional de referencia para su diagnóstico etiológico. Se describen las etapas de desarrollo de este laboratorio y su contribución a establecer el trazado epidemiológico de la infección en Chile. Relatamos brevemente el aislamiento postmortem de virus Andes a partir de un niño

El gen tax del virus linfotrópico humano tipo I en la identificación etiológica de la paraparesia espástica tropical: estudio clínico, serológico y de polimerasa en cadena en 72 pacientes / HTLV-I tax gene on the etiological identification of tropical spastic paraparesis: a clinical, serological and polymerase chain reaction study in 72 patients

Background: Tropical spastic paraparesis (TSP) is an endemic disease in Chile. In most countries, only 50 percent of patients are seropositive to HTLV-I. However, new studies suggest that seronegative TSP is also associated with HTLV-I. Aim: To describe clinical and virological features of seronegative patients with TSP. Patients and methods: seventy two chilean patients with TSP, studied by clinical, radiological and laboratory methods during 1998, are reported. The determination of antibodies to HTLV-I was accomplished by ELISA, immunofluorescence and western-blot analysis. Polymerase chain reaction for tax and 5'Ltr genes was made using primers SK 43-44, LTR1 and LTR6. Results: Thirty one patients were HTLV-I positive and 41 were negative. No clinical, radiological or laboratory differences were observed between both groups. In seropositive patients, tax and 5'ltr viral gene sequences of the HTLV-I provirus were detected in DNA of peripheral blood mononuclear cells. In seronegative cases, sequences of tax gene were detected, exclusively, in 18 of 41 patients. Conclusions: These results confirm an association with HTLV-I infection in 43,9 percent of the TSP seronegative patients. These findings support the hypothesis that a defective provirus infects peripheral blood mononuclear cells in seronegative cases of TSP. The importance tax gene in the diagnosis of the TSP is also emphasized

Estado inmunitario de 4 grupos de edad de población chilena contra sarampión y rubeola / Immune status against measles and rubella among chilean subjects of different ages

Background: Results of clinical and epidemiological studies confirm that no cases of measles have occurred in Chile since 1993. However, since covering of vaccination programs do not exceed 95 percent, an immunological surveillance for this disease is warranted. Aim: To know the immune status against measles and rubella in the Chilean population. Material and methods: A serological census of a representative sample of communities with high (90 percent or more) or low immunization coverings was performed. Four sub samples along the country were selected: 122 children aged 18 months of age (stratum A), 1,276 children attending the first year of basic school (stratum B), 899 teenagers in their last high school year (stratum C) and 399 women attending a family planning clinic (stratum D). IgG antibodies against measles and rubella were measured using ELISA and hemagglutination inhibition techniques, respectively. Results: Antibodies against measles and rubella were found in 96 percent and 94 percent of study subjects. No differences in these titres were found between different strata or communities with high or low vaccination covering. There is a high percentage of positive antibodies against measles among children of 18 months of age and a high percentage of antibodies against rubella among teenagers and women in family planning. Only 3 percent of the sample had not received any vaccine at the moment of the study. Conclusions: The high prevalence of antibodies against rubella allows to conclude that it is not necessary to consider this antigen in the next vaccination campaign. Due to the high prevalence of antibodies against measles, only the population older than 20 years old should be affected by the disease if this virus enters the country

Forma familiar de la paraparesia espástica tropical: estudio de cuatro familias / Familial form of tropical spastic paraparesis: report of four families

We report eight patients with familial tropical spastic paraparesis belonging to four families. The diagnosis was reached by clinical, radiological and electrophysiological studies. Human lymphotropic virus type I infection was confirmed by ELISA, immunofluorescence essays, Western blot and polymerase chain reaction in DNA of peripheral blood mononuclear cells, using primers for tax and 5'ltr genes. In all these families there was a vertical transmission of the disease from the first to the second generation. All patients improved their spastic gait after prednisone treatment. Among patients of the second generation, all had dacrysialoadenitis, three had leukemia like lymphocytes in the blood smear, two had mycosis fungoides and one had hepatic cirrhosis

Nueva forma de demencia subcortical: encefalopatía por infección del virus linfotrópico T humano (HTLV-I): caso clínico / New kind of subcortical demencia: encephalopathy by human T lymphotropic virus (HTLV-I): clinical case

We report a 45 years old female with HTLV-I associated myelopathy, followed up for 10 years who, 5 years ago, developed personality changes and intellectual deterioration, assessed with the Wais-Benton test. She also had alterations in the electroencephalogram and a nuclear magnetic resonance imaging of the brain showed hypodensity in T1 and hyperdensity in T2 subcortical regions. The progression of intellectual impairement was related to an increase in proviral DNA, assessed with polymerase chain reaction

Seroprevalencia del HTLV-I en familiares de pacientes con paraparesia espástica (HAM/TSP y PEP) / Seroprevalence of HTLV-I in the family of patients with spastic paraparesis (HAM/TSP and PEP)

The seroprevalence of HTLV-I was studied in parents, brothers, siblings and sexual partners of 147 patients with spastic paraparesis assocaited to HTLV-1 (HAM/TSP) and 84 patients with HTLV-1 negative spastic pararparesis (SP). Seroprevalence was 29.1 percent for HAM/SP and 0 percent for SP relatives (p<0.001); the last figure is similar to that of the general population. Seroprevalence in sexual partners was 65 percent, suggesting that sexual intercourse is the principal route of transmission. Likewise, seroprevalence in siblings of mothers with HAM/TSP or HTLV-1 positive was 17.6 percent, suggesting a high maternal transmission

Títulos de anticuerpos anti-VTLV-I en individuos infectados seropositivos / Anti HTLV-I antibody titers in seropositive infected individuals

The aim of this study was to determine anti HTLV-I antibody titers in seropositive symptomatic and asymptomatic infected subjects. One hundred seven infected subjects (47 with spastic paraparesis and 60 asymptomatic) were studied. HTLV-I antibodies were determined using indirect immunofluorescence in cells infected with the retrovirus. The mean titer was 1/234 in asymptomatic subjects and 1/2138 in symptomatic patients (p<0,001). These results suggest an association between HTLV-I antibody titers and clinical stage of infected subjects

Comparación de métodos de diagnóstico citológico, inmunofluorescencia y aislamiento viral en la detección de citomegalovirus (CMV) en orina / Comparision of diagnosis methods: cytology, immunofluorescence and viral isolation in the detection of urine cytomegalovirus

Las infecciones por citomegalovirus humano (CMV), ampliamente diseminadas, han sido señaladas como la principal causa de morbimortalidad en individuos inmunocomprometidos. Es característico en estas infecciones la aparición de grandes células con inclusiones intranucleares y/o intracitoplasmática. Con esta base se diseñó una investigación para evaluar el método de diagnóstico citológico y la detección de antígenos virales mediante la técnica de inmunofluorescencia indirecta (IFI) en relación al aislamiento viral en muestras de orina. Se estudiaron 70 casos con búsqueda de cuerpos de inclusión citomegálicos (CIC) y aislamiento viral. En 55 de estos se estudió además con IFI. Se encontro CIC en el 84% (59/70) de los casos, el aislamiento resultó positivo en un 29% (20/70) y la IFI alcanzó un 42% de positividad (23/55). En todos los casos con aislamiento positivo se encontró CIC en el sedimento de orina. La IFI que en relación al aislamiento viral parece carecer de especificidad, debe ser considerada ya que es un método que detecta específicamente antígenos virales. Finalmente, se recomienda trabajar estos métodos de diagnóstico con tres muestras de orina para optimizar su rendimiento

Estudio en pacientes con diagnóstico serológico de infección por VIH-1 indeterminado / An immunologic study on patients with an HIV-1 indeterminate diagnosis

Western blott is the technique most frequently used to determine the presence of HIV-1 antibodies. However, some patients remain with an indeterminate diagnosis for HIV-1 according to the technique. We followed 8 such patients for 2 18 months. Immunologic studies included standard ELISA, immunofluorescence and Abbott anti-p-24 ELISA. We found selective reactivity for certain viral proteins such as isolated p24,p24 plus p51 or p55, gp41 plus gp120, p17 plu p24 and p25