A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids.

Identification of genetic modulators of lysosomal enzyme activities and glycosphingolipids (GSLs) may facilitate the development of therapeutics for diseases in which they participate, including Lysosomal Storage Disorders (LSDs). To this end, we used a systems genetics approach: we measured 11 hepatic lysosomal enzymes and many of their natural substrates (GSLs), followed by modifier gene mapping by GWAS and transcriptomics associations in a panel of inbred strains. Unexpectedly, most GSLs showed no association between their levels and the enzyme activity that catabolizes them. Genomic mapping identified 30 shared predicted modifier genes between the enzymes and GSLs, which are clustered in three pathways and are associated with other diseases. Surprisingly, they are regulated by ten common transcription factors, and their majority by miRNA-340p. In conclusion, we have identified novel regulators of GSL metabolism, which may serve as therapeutic targets for LSDs and may suggest the involvement of GSL metabolism in other pathologies.

Genetic Background Matters: Population-Based Studies in Model Organisms for Translational Research.

We are all similar but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly, and yeast panels with insightful applications for translational research.

Identification of genetic modifiers of murine hepatic ß-glucocerebrosidase activity.

The acid ß-glucocerebrosidase (GCase) enzyme cleaves glucosylceramide into glucose and ceramide. Loss of function variants in the gene encoding for GCase can lead to Gaucher disease and Parkinson's disease. Therapeutic strategies aimed at increasing GCase activity by targeting a modulating factor are attractive and poorly explored. To identify genetic modifiers, we measured hepatic GCase activity in 27 inbred mouse strains. A genome-wide association study (GWAS) using GCase activity as a trait identified several candidate modifier genes, including Dmrtc2 and Arhgef1 (p=2.1x10-7), and Grik5 (p=2.1x10-7). Bayesian integration of the gene mapping with transcriptomics was used to build integrative networks. The analysis uncovered additional candidate GCase regulators, highlighting modules of the acute phase response (p=1.01x10-8), acute inflammatory response (p=1.01x10-8), fatty acid beta-oxidation (p=7.43x10-5), among others. Our study revealed previously unknown candidate modulators of GCase activity, which may facilitate the design of therapies for diseases with GCase dysfunction.

Increased serum ferritin and interleukin-18 levels in children with dengue.

Activated monocytes/macrophages that produce a cytokine storm play an important role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine produced by monocyte/macrophages that is increased during dengue. Ferritin is an acute-phase reactant and expressed by cells of the reticulo-endothelial system in response to infection by dengue virus. The aims of this study were to analyze the simultaneous expression of both IL-18 and ferritins in children infected by diverse serotypes of dengue virus (DENV) and determine their association with dengue severity. In this regard, children with dengue (n = 25) and healthy controls with similar age and sex (n = 20) were analyzed for circulating ferritin and cytokines. Monocytes were isolated by Hystopaque gradient and co-cultured with DENV-2. IL-18 and ferritin contents in blood, and IL-18 in culture supernatants were determined by ELISA. Increased levels of ferritin and IL-18 (p < 0.0001) were observed in dengue patients, not associated to NS1expression or type of infection (primary or secondary). Highest values of both molecules (p < 0.001) were observed in dengue with warning signs and severe dengue. Differential effect on IL-18/ferritin production was observed associated to viral serotype infection. There were no correlations between ferritin vs. IL-18 production, ferritin vs. NS1 status, and IL-18 vs. NS1 status. Viral-infected monocyte cultures showed increased production of IL-18 (p < 0.001). In conclusion, increased circulating ferritin and IL-18 are expressed in children infected by different serotypes of DENV associated with dengue severity.

Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

AIMS: The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. MAIN METHODS: GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. KEY FINDINGS: Increased DENV2 replication and anti-viral cytokine production (IFN-α/ß, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. SIGNIFICANCE: The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis.

Role of the myeloid differentiation primary response (MYD88) and TIR-domain-containing adapter-inducing interferon-ß (TRIF) pathways in dengue.

AIMS: Dengue disease courses with high viremia titers and high cytokine production suggesting viral replication and active immune response that could be related to viral evasion. One of the main targets of dengue virus (DENV) is monocyte/macrophage cells; however, little information regarding viral evasive mechanisms and pathway activation in monocytes infected by DENV is available. The aim of this study was to determine the role of myeloid differentiation primary response (MyD88), TIR-domain-containing adapter- inducing interferon-ß (TRIF) and NF-kB pathways in viral replication and cytokine production in human monocyte cultures infected by DENV2. MAIN METHODS: In this regard Pepinh- TRIF, Pepinh- MYD and pyrrolidine dithiocarbamate (PDTC) were used to inhibit TRIF, MYD88 and NF-kB pathways. Cytokine production was measured by ELISA. KEY FINDINGS: Increased DENV replication and IFNα/ß, TNF-α, IL-12 and IL-18 in infected cultures at 24h were found. All of these parameters were significantly decreased after TRIF, MYD88 or NF-kB inhibition. Association analysis between viral replication and cytokine production showed high significant positive correlation in TRIF and MYD88 treated cultures. SIGNIFICANCE: This study shows that DENV2 induces activation of innate-immune response and transcription factors to drive viral expression and replication in the face of pro-inflammatory antiviral responses in vitro.

Increased C-reactive protein and decreased Interleukin-2 content in serum from obese individuals with or without insulin resistance: Associations with leukocyte count and insulin and adiponectin content.

AIMS: Chronic inflammation in obesity is associated with co-morbidities such as, hyperglycemia, hypertension and hyperlipidemia. Leukocytes play an important role in this inflammation and C-reactive protein (CRP) and Interleukin-2 (IL-2) can be important effectors during the immune response in obesity; however, the initial inflammatory events in obesity remain unclear. The aim of this study was to determine the circulating levels of CRP, IL-2, insulin and adiponectin, their association and the association with leukocyte count in obese individuals without co-morbidities and with or without insulin resistance (IR). MATERIALS AND METHODS: Nineteen obese non-diabetic and 9 lean subjects were studied for serum levels of CRP, IL-2, insulin, adiponectin, lipids, glycated hemoglobin, glycemia, for homeostasis model assessment of insulin resistance (HOMA-IR), arterial pressure and anthropometric parameters, and for leukocyte counts. Neutrophil/lymphocyte ratio (N/L) was calculated using the loge of leukocyte counts. Associations were determined by Pearson's correlation. RESULTS: None of the studied groups presented co-morbidities and two groups of obese individuals with normal or high levels of insulin (IR) were found. Increased CRP concentration and decreased IL-2 and adiponectin concentrations in obese were observed. Positive correlation between leukocyte type counts with CRP in obese with IR was found; however, no correlations with IL-2 in obese were observed. Insulin in obese were positively correlated with CRP and negatively correlated with IL-2 in IR obese individuals. Adiponectin in obese was negatively correlated with CRP. CONCLUSION: CRP and IL-2 may represent two important effectors in the early inflammatory events in obese individuals without co-morbidities. Adiponectin and insulin may be involved in anti-inflammatory events.

Serum level of C-reactive protein is not a parameter to determine the difference between viral and atypical bacterial infections.

C-reactive protein (CRP) is an acute-phase reactant that increases in the circulation in response to a variety of inflammatory stimuli. Elevated levels in serum during several infectious diseases have been reported. In this study, a highly sensitive CRP enzyme immunoassay was used to evaluate serum CRP values in patients with viral and atypical bacterial infections. Patients (n = 139) with different viral or atypical bacterial infections (systemic or respiratory) and healthy controls (n = 40) were tested for circulating CRP values. High levels of IgM antibodies against several viruses: Dengue virus (n = 36), Cytomegalovirus (n = 9), Epstein Barr virus (n = 17), Parvovirus B19 (n = 26), Herpes simplex 1 and 2 virus (n = 3) and Influenza A and B (n = 8) and against atypical bacteria: Legionella pneumophila (n = 15), Mycoplasma pneumoniae (n = 21) and Coxiella burnetii (n = 4) were found. High values of CRP in infected patients compared with controls (P < 0.001) were found; however, no significant differences between viral and atypical bacterial infections were found. Low levels of CRP in respiratory and Coxiella burnetii infections compared with exanthematic viral and other atypical bacterial infections were found. This study suggests that CRP values are useful to define viral and atypical bacterial infections compared with normal values, but, it is not useful to define type of infection.

Losartan and enalapril decrease viral absorption and interleukin 1 beta production by macrophages in an experimental dengue virus infection.

The role of angiotensin II (Ang II) in dengue virus infection remains unknown. The aim of this study was to determine the effect of losartan, an antagonist of the angiotensin II type 1 receptor (AT1 receptor), and enalapril, an inhibitor of angiotensin I-converting enzyme (ACE), on viral antigen expression and IL-1ß production in peritoneal macrophages infected with dengue virus type 2. Mice treated with losartan or enalapril and untreated controls were infected intraperitoneally with the virus, and macrophages were analyzed. Infection resulted in increased IL-1ß production and a high percentage of cells expressing viral antigen, and this was decreased by treatment with anti-Ang II drugs, suggesting a role for Ang II in dengue virus infection.

Association of lipid profile alterations with severe forms of dengue in humans.

Previous studies have shown a relationship between circulating lipids and dengue virus infection; however, the association of altered lipid profiles with severe dengue remains little studied. The aim of this study was to determine the association between circulating lipid content and severe dengue and/or platelet counts. Ninety-eight patients (2-66 years old) classified as having dengue without warning signs (DNWS), dengue with warning signs (DWWS), or severe dengue (SD) and 62 healthy individuals were studied. Blood samples were tested for NS1, anti-dengue IgM, platelet content, total cholesterol (TC), triglycerides (T), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL). Lipid alterations were observed mainly in patients with SD. Increased T and VLDL was observed in SD, and increased HDL was observed in DWWS and SD. Decreased TC was found in all forms of dengue, and the lowest LDL values were found in SD. Platelet counts were significantly decreased in DWWS and SD when compare to DNWS. A positive correlation (p = 0.019) between LDL values and platelet counts and a negative correlation (p = 0.0162) between VLDL values and platelet counts were found. Lipid profile alterations were associated with severe dengue.

[Role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections]. / Papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales.

The immune system (IS) cells are capable of recognizing a wide variety of microorganisms, through receptors that are expressed and distributed throughout the cell architecture. The interaction between the pathogen-associated molecular patterns or damage-associated molecular patterns (PAMPs or DAMPs) and pattern recognition receptors (PRR), present in host cells, is a critical event that involves intracellular signaling processes that end up in the expression of both, proinflammatory and antiviral mediators. Accordingly, the proper functioning of the different mechanisms of signal transduction from the cell membrane to the cytoplasm will depend on the integrity of these receptors (PRR); and therefore, the IS response triggered against pathogens including viral agents. Hence, in this review we discuss the role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections, using as evidence the studies in humans and mice known to date.

Papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales / Role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections

Las células del sistema inmunitario (SI) son capaces de reconocer una gran variedad de microorganismos, a través de los receptores que se encuentran expresados y distribuidos a lo largo de su arquitectura celular. La interacción entre los patrones moleculares asociados a microorganismos o a daño (PMAM o PMAD) y los receptores reconocedores de patrones (RRP) presentes en las células del hospedero es un evento crítico que implica procesos intracelulares de señalización que finalizan en la expresión de mediadores tanto proinflamatorios como antivirales. Por consiguiente, de la integridad de estos receptores dependerá el buen funcionamiento de los distintos mecanismos de transducción de señal desde las membranas celulares al citoplasma y por ende, de la respuesta que el SI desencadene contra los patógenos entre ellos los agentes virales. De allí que, en esta revisión se discutirá el papel de los receptores tipo toll (TLRs) y receptores para dominios de oligomerización para la unión a nucleótidos (NLRs) en las infecciones virales, tomando como evidencia los estudios en humanos y ratones que a la fecha se conocen.

The immune system (IS) cells are capable of recognizing a wide variety of microorganisms, through receptors that are expressed and distributed throughout the cell architecture. The interaction between the pathogen-associated molecular patterns or damage-associated molecular patterns (PAMPs or DAMPs) and pattern recognition receptors (PRR), present in host cells, is a critical event that involves intracellular signaling processes that end up in the expression of both, proinflammatory and antiviral mediators. Accordingly, the proper functioning of the different mechanisms of signal transduction from the cell membrane to the cytoplasm will depend on the integrity of these receptors (PRR); and therefore, the IS response triggered against pathogens including viral agents. Hence, in this review we discuss the role of toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) in viral infections, using as evidence the studies in humans and mice known to date.

[Frequency of gastrointestinal signs and symptoms of dengue. Analysis of a cohort of 1484 patients]. / Frecuencia de signos y síntomas gastrointestinales del dengue. Análisis de una cohorte de 1484 pacientes.

Dengue is characterized by fever, headache, arthralgia and myalgia. The presence of gastrointestinal signs and symptoms (GISS) is considered a sign of alarm in dengue; however, little information exists regarding the occurrence of these events. The aim of this study was to determine the frequency of gastrointestinal signs and symptoms in a cohort of patients with dengue. A total of 1484 medical records of patients with confirmed dengue were reviewed and classified as: dengue without warning signs (DNWS) (n = 700), dengue with warning signs (DWWS) (n = 700) and severe dengue (SD) (n = 84). Of the studied records, 65.71% of patients with DNWS, 92.59% with DWWS and 100% of patients with SD had GISS. In patients with DNWS, nausea / vomiting were the most common symptoms in 319/700 cases (45.57%), followed by abdominal pain in 142/700 (20.29%) and diarrhea in 125/700 (17.86%). There were no cases with melena, hepatomegaly or hematemesis. While in DWWS nausea/vomiting were present in 529/700 (75.57%), abdominal pain in 439/700 (62.71%) and diarrhea in 198/700 (28.28%),(p <0.0001). Melena, hematemesis and hepatomegaly ranged from 0.57% to 1.86% of cases. In SD, nausea/vomiting were registered in 100% of the cases, abdominal pain in 82/84 (97.62%), diarrhea in 65/84 (77.38%), melena in 32/84 (38.10%), hepatomegaly in 28/84 (33.33%) and hematemesis in 26/84 (30.95%). It was evident the high frequency of GISS in cases of DWWS and SD, in contrast to DNWS, in which the frequency of GISS was significantly lower. This suggests a relationship of GISS with the severity of dengue, and their presence should be considered by the decision-making health team for appropriate patient management.

Frecuencia de signos y síntomas gastrointestinales del dengue: Análisis de una cohorte de 1484 pacientes / Frequency of gastrointestinal signs and symptoms of dengue: Analysis of a cohort of 1484 patients

El dengue se caracteriza por fiebre, cefalea, artralgia y mialgia. La presencia de signos y síntomas gastrointestinales (SSGI), se considera señal de alarma en dengue; sin embargo, existe poca información respecto a la ocurrencia de estas manifestaciones. El objetivo de este estudio fue determinar la frecuencia de signos y síntomas gastrointestinales en una cohorte de pacientes con dengue. Se revisaron 1484 fichas clínicas de pacientes con diagnóstico confirmado de dengue, clasificados como: dengue con signos de alarma (DCSA) (n=700); sin signos de alarma (DSSA) (n=700) y dengue grave (DG) (n=84). El 65,71% de los pacientes con DSSA, el 92,59% DCSA y el 100% de los pacientes con DG presentaron SSGI. En los pacientes con DSSA, las náuseas/vómitos fue el síntoma más frecuente 319/700 (45,57%), seguido de dolor abdominal 142/700 (20,29%) y diarrea 125/700 (17,86%). No se registraron casos con melena, hepatomegalia y/o hematemesis. Mientras que en DCSA las náuseas/vómitos estuvieron en 529/700 (75,57%), dolor abdominal 439/700 (62,71%) y diarrea 198/700 (28,28%), fueron los más frecuentes (p<0,0001). Melena, hematemesis y hepatomegalia variaron de 0,57% a 1,86%. En DG, las náuseas/vómitos se registraron en el 100%, dolor abdominal 82/84 (97,62%), diarrea 65/84 (77,38%), melena 32/84 (38,10%), hepatomegalia 28/84 (33,33%) y hematemesis 26/84 (30,95%). Se evidencia alta frecuencia de SSGI en los casos de DCSA y DG a diferencia de DSSA, en los cuales fue significativamente menor. Se sugiere relación de los SSGI con la severidad del dengue y su presencia debe considerarse en la toma de decisiones del equipo de salud para el manejo adecuado del paciente.

Dengue is characterized by fever, headache, arthralgia and myalgia. The presence of gastrointestinal signs and symptoms (GISS) is considered a sign of alarm in dengue; however, little information exists regarding the occurrence of these events. The aim of this study was to determine the frequency of gastrointestinal signs and symptoms in a cohort of patients with dengue. A total of 1484 medical records of patients with confirmed dengue were reviewed and classified as: dengue without warning signs (DNWS) (n = 700), dengue with warning signs (DWWS) (n = 700) and severe dengue (SD) (n = 84). Of the studied records, 65.71% of patients with DNWS, 92.59% with DWWS and 100% of patients with SD had GISS. In patients with DNWS, nausea / vomiting were the most common symptoms in 319/700 cases (45.57%), followed by abdominal pain in 142/700 (20.29%) and diarrhea in 125/700 (17.86%). There were no cases with melena, hepatomegaly or hematemesis. While in DWWS nausea/vomiting were present in 529/700 (75.57%), abdominal pain in 439/700 (62.71%) and diarrhea in 198/700 (28.28%),(p <0.0001). Melena, hematemesis and hepatomegaly ranged from 0.57% to 1.86% of cases. In SD, nausea/vomiting were registered in 100% of the cases, abdominal pain in 82/84 (97.62%), diarrhea in 65/84 (77.38%), melena in 32/84 (38.10%), hepatomegaly in 28/84 (33.33%) and hematemesis in 26/84 (30.95%). It was evident the high frequency of GISS in cases of DWWS and SD, in contrast to DNWS, in which the frequency of GISS was significantly lower. This suggests a relationship of GISS with the severity of dengue, and their presence should be considered by the decision-making health team for appropriate patient management.

Dengue nonstructural protein-1 status is not associated to circulating levels of interleukin-17, C-reactive protein and complement in children with acute dengue.

BACKGROUND: During dengue infection increase in plasma level of various substances have been reported. Some of those molecules are related to the virus biology and others result of the interaction virus-host. Nonstructural protein-1 (NS1) secreted by dengue virus has been reported to have a role in dengue pathogenesis. NS1 is capable of interacting with complement to evade viral clearance. However, there is little information about the presence of serum NS1 and the levels of other molecules related to dengue pathogenesis. OBJECTIVES: The aim of this study was to determine the association of the NS1 status and the circulating levels of interleukin-17 (IL-17), C-reactive protein (CRP), C3 and C4 in acute dengue. STUDY DESIGN: In this study the serum presence of NS1, IL-17, CRP, C3 and C4 was determined in children with acute dengue. IL-17, CRP, anti dengue-IgG content was measured by ELISA, C3 and C4 levels by an immunoturbidimetric assay and NS1 by an immunochromatographic assay. RESULTS: All patients were positive for dengue infection as shown by antibodies anti-dengue and/or virus isolation. Increased levels of IL-17, CRP and C4 no related to the presence of NS1 were found in the patients. Values of C3 remained similar to controls. CONCLUSIONS: These findings suggest that NS1 does not module the production of studied molecules during dengue infection.

[Prevalence of cytomegalovirus infection in pediatric patients with neurological disorders in Zulia state, Venezuela (2007-2008)]. / Prevalencia de infección por citomegalovirus en pacientes pediátricos con afecciones neurológicas en el estado Zulia, Venezuela (2007-2008).

The aim of this study was to determine the prevalence of cytomegalovirus (CMV) in pediatric patients with neurological disorders from Zulia State, Venezuela, during the period 2007-2008. Samples of cerebrospinal fluid (CSF) and serum were obtained from 186 patients with neurological symptoms and bacteriological negative CSF. The albumin CSF/serum content was determined to rule out contamination of CSF and optimal pairs were determined by ELISA of IgM and IgG anti-CMV antibodies in serum and IgG in CSF. Only 40.86% (76/186) of patients were optimal for this study. Serum samples positive for IgM antibodies (2/76; 2.6%) and IgG antibodies (71/76; 93.4%) were obtained. CSF IgG antibodies were observed in 24/76 patients (31.6%). Increased values of glucose in CSF (p < 0.05) were observed in 58.3% of CMV patients with meningoencephalitis. In addition, increased CSF protein concentration (p < 0.01) was observed in CSF anti-CMV antibodies positive patients with meningitis. This study shows high prevalence of acute CMV infection in pediatric patients with neurological affections suggesting an important role of this virus in this pathology during the studied period.

Prevalencia de infección por citomegalovirus en pacientes pediátricos con afecciones neurológicas en el estado Zulia, Venezuela (2007-2008) / Prevalence of cytomegalovirus infection in pediatric patients with neurological disorders in Zulia state, Venezuela (2007-2008)

El objetivo de este estudio fue determinar la prevalencia de citomegalovirus en pacientes pediátricos con afecciones neurológicas, provenientes del Estado Zulia, Venezuela durante el período 2007-2008. Se recolectaron 186 muestras pareadas de líquido cefalorraquídeo (LCR) y suero, de pacientes entre 1 mes y 14 años de edad, que presentaron sintomatología clínica sugestiva de afectación del SNC y cuyo estudio bacteriológico convencional de LCR resultó negativo. Se determinó la relación albúmina LCR/suero a fin de descartar contaminación y a los pares óptimos se les determinó por la técnica de ELISA anticuerpos IgM e IgG en suero e IgG en LCR anti-CMV. Del total de muestras recolectadas 40,86% (76/186) resultaron óptimas para el análisis. De los 76 casos analizados, el 2,6% (2/76) de las muestras de suero resultaron positivas para IgM; 93,4% (71/76) fueron seropositivas a IgG mientras que el 31,6% (24/76) de las muestras de LCR presentaron anticuerpos IgG. En cuanto a los parámetros citoquímicos del LCR, se observaron valores de glucosa aumentados en el 58,3% (p<0,05) de los pacientes con CMV que presentaron meningoencefalitis. En los pacientes con meningitis que presentaron positividad de anticuerpos IgG anti-CMV en el LCR se observó un aumento significativo (p<0,01) en las proteínas del LCR. Se evidencia que una proporción de los pacientes pediátricos con afecciones neurológicas presentaron infección aguda por CMV, lo que demuestra una participación importante de este agente en pacientes del estado Zulia, Venezuela para el período en estudio.

The aim of this study was to determine the prevalence of cytomegalovirus (CMV) in pediatric patients with neurological disorders from Zulia State, Venezuela, during the period 2007-2008. Samples of cerebrospinal fluid (CSF) and serum were obtained from 186 patients with neurological symptoms and bacteriological negative CSF. The albumin CSF/serum content was determined to rule out contamination of CSF and optimal pairs were determined by ELISA of IgM and IgG anti-CMV antibodies in serum and IgG in CSF. Only 40.86% (76/186) of patients were optimal for this study. Serum samples positive for IgM antibodies (2/76; 2.6%) and IgG antibodies (71/76; 93.4%) were obtained. CSF IgG antibodies were observed in 24/76 patients (31.6%). Increased values of glucose in CSF (p<0.05) were observed in 58.3% of CMV patients with meningoencephalitis. In addition, increased CSF protein concentration (p<0.01) was observed in CSF anti-CMV antibodies positive patients with meningitis. This study shows high prevalence of acute CMV infection in pediatric patients with neurological affections suggesting an important role of this virus in this pathology during the studied period.