Luis Angel Villar-Centeno

Dificultad para el diagnóstico clínico temprano del dengue en un área endémica y su impacto sobre el manejo médico inicial

BACKGROUND Early detection of dengue could help to prevent its complications. The usefulness of clinical criteria for diagnosis of the disease must be ascertained. AIMS To assess the correlation between laboratory and clinical diagnosis of dengue, done during the first consultation in the emergency room. To estimate the impact of clinical diagnosis on the initial medical treatment. PATIENTS AND METHODS Patients older than 5 years with an acute febrile syndrome that consulted during the first 72 hours of disease, during 2004, at an emergency room in Bucaramanga, Colombia, were studied. Symptoms and the clinical diagnosis of the initial evaluation were registered. Paired serum samples for dengue specific ELISA-IgM test and viral isolation were obtained. The association of the initial clinical diagnosis with early symptoms, initial medical treatment and laboratory diagnosis was evaluated. RESULTS One hundred sixty eight patients were enrolled (54 with confirmed dengue infection). Clinical diagnosis of dengue was associated to a higher request of complete blood counts (p = 0.01) and greater use of intravenous fluids (p = 0.02). However, clinical diagnosis was not correlated with the laboratory diagnosis (p = 0.15). The percentage of agreement was less than would be expected by chance (Kappa = -0.1). Headache was associated to the initial clinical diagnosis of dengue (p = 0.03), and only metrorrhagia was associated with confirmed dengue infection (p = 0.04). CONCLUSIONS The early clinical suspicion of dengue has a low concordance with the laboratory confirmation of the disease.

Complicaciones asociadas a la trombocitopenia profunda en pacientes con dengue

Patients with clinical andserologic (positive IgM) diagnosis of dengue, consulting at hospitals located in Santander,Colombia, during the period 1993-1998, were studied. Clinical findings and laboratory tests(including hematocrit and platelets counts) were registered. The association between severethrombocytopenia and the presence of complications, such as hemorrhagic manifestations(positive tourniquet test, petechiae, ecchymoses, bleeding from gums, epistaxis, hematemesis,hematuria and metrorrhagia) and signs of plasma leakage (pleural effusions andhaemoconcentration), were evaluated using a univariate and multivariate analysis.

Predictors of spontaneous bleeding in patients with acute febrile syndrome from a dengue endemic area

BACKGROUND Spontaneous bleeding is a common complication of dengue and is associated with an increased mortality. OBJECTIVE To evaluate early clinical manifestations and simple laboratory tests as predictors of spontaneous hemorrhage in patients with forms of acute febrile syndrome (AFS) such as dengue from an endemic area. STUDY DESIGN A prospective cohort study was performed including 729 non-bleeding AFS patients who were enrolled during the first 4 days of disease. Basal evaluation included anamnesis, physical examination and complete blood cell count. Follow-up was extended at least until the sixth day of disease. Dengue infection was studied with paired serologic tests and viral isolation. Potential predictors of spontaneous bleeding were evaluated with bivariate and multivariate analysis. RESULTS Incidence of outcome was not significantly different between the dengue group and those with non-dengue AFS. The tourniquet test was not associated with outcome (p=0.38). In a binomial regression model, the following variables were associated with outcome: age between 12 and 45 years (RR=2.22; 95% CI: 1.25-3.94), rash (RR=1.66; 95% CI: 1.25-2.2), vomiting (RR=1.46; 95% CI: 1.16-1.83), temperature >38 degrees C (RR=2.63; 95% CI: 1.6-4.33), leukocyte count <4500/microL (RR=1.87; 95% CI: 1.19-2.96), and platelet count <90.000/microL (RR=1.8; 95% CI: 1.1-2.94). With these variables a risk score was formulated that showed an area under ROC curve of 70.5% (95% CI: 64.9-76.2) to predict spontaneous bleeding. The score was useful for predicting bleeding in both dengue and non-dengue AFS groups. CONCLUSION Some variables evaluated in the first days of disease helped to predict the risk of spontaneous bleeding in patients with dengue and non-dengue AFS.

Indicadores tempranos de infección por dengue en niños

OBJECTIVE: To identify clinical manifestations and laboratory findings useful for the early diagnosis of dengue in children. MATERIALS AND METHODS: We prospectively evaluated 125 children (aged 5 to 12 years old) with acute febrile syndrome with no apparent etiology. Paired serologic tests and/or viral culture were performed and dengue infection was confirmed in 40 patients and ruled out in 68 (17 indefinite cases). Early clinical manifestations (within the first 4 days of the disease) in the groups with dengue and other causes of febrile syndrome were compared. Independent indicators of dengue were determined in a multivariate logistic regression analysis. RESULTS: When clinical manifestations and complete blood count were considered, the independent indicators of dengue were: absence of nasal discharge, facial flushing, and leukocyte count 14 seconds, and partial thromboplastin time > 29 seconds. Two of these findings suggested a diagnosis of dengue with a sensitivity of 90 % and a specificity of 52.9 %. With at least 3 findings, specificity increased to 89.7 % and sensitivity decreased to 50 %. The presence of the four components of this latter model shows a specificity of 100 %. CONCLUSIONS: Some clinical manifestations and simple laboratory tests could aid the early detection of dengue infection in children.

Pluviosidad como Predictor de Consulta por Síndrome Febril Agudo en un Área Endémica de Dengue

Objetivo Describir los patrones de consulta por SFA asociado al dengue y evaluar su asociacion con la pluviosidad. Metodos En dos clinicas, durante un periodo de 7 meses (de marzo a septiembre) se identificaron 318 casos de SFA indiferenciado que se incluyeron en un seguimiento clinico sistematico. El 31 % (81/281) fueron IgM positivos para dengue. Se evaluo la pluviosidad (litros/metro cuadrado por dia) previa como variable explicatoria del patron de consultas. Resultados Los meses con mas casos de SFA fueron junio, julio y septiembre. Los casos de dengue solo fueron significativamente mas frecuentes en julio. Al evaluar los patrones de pluviosidad de las semanas anteriores, la consulta por SFA estuvo asociada con la pluviosidad promedio registrada 5 semanas antes y esta asociacion fue independiente de la institucion y del mes (Razon de tasas de incidencia ajustada: RTI=1,04; IC95 % 1-1,08; p=0,045). Por otra parte, un promedio de la pluviosidad de 5 semanas consecutivas fue un predictor independiente de consulta por dengue, 4 semanas despues (RTI=1,6; IC95 % 1,15-2,22; p=0.006). Se evidencio una relacion lineal entre la pluviosidad y las consultas por dengue: pluviosidad (promedio de 5 semanas) x 0,72 (IC95 % 0,60-0,84; p<0,001)=casos por cada 100 000 habitantes en una semana (4 semanas despues). Conclusiones La pluviosidad podria predecir el patron de consulta por dengue en una region endemica.

Evaluación de la prueba de IgM en suero agudo para el diagnóstico del dengue en un área endémica

: Evaluation of IgM determination in acute serum for the diagnosis of dengue in an endemic area We evaluated the clinical usefulness of dengue IgM detection in acute serum using an ELISA test in 167 patients with dengue and 225 patients with acute febrile syndrome of another etiology. The sensitivity of the test was 29.9%, specificity was 99.1%, positive predictive value was 96.2%, and negative predictive value was 65.6%. Because of the tests high specificity and positive predictive value, a positive result could support a diagnosis of dengue in endemic areas with a high degree of certainty; a negative result would require complementary studies.Se evaluaron las caracteristicas operativas de la prueba de ELISA-IgM especifica para dengue en el suero agudo de 167 pacientes con dengue y 225 con sindrome febril agudo de otra etiologia. La prueba evidencio sensibilidad: 29,9%; especificidad: 99,1; valor predictivo positivo (VPP): 96,2%; valor predictivo negativo: 65,6%. Por su especificidad y VPP altos, un resultado positivo de la prueba podria soportar con alta certeza el diagnostico de dengue en areas endemicas; un resultado negativo requeriria estudios complementarios.

Efecto de la administración temprana de dipirona sobre la gravedad del dengue en una cohorte prospectiva

Objetivo. Evaluar el impacto de la administracion de la dipirona en los primeros dias de enfermedad, sobre la gravedad del dengue. Materiales y metodos. Estudio de cohorte prospectiva en adultos (> 12 anos) con infeccion por virus del dengue, confirmada mediante la titulacion de inmunoglobulina M (IgM) especifica en muestras pareadas o aislamiento viral. Los pacientes fueron captados en las primeras 96 h de enfermedad. Al ingreso se registraron los sintomas, medicamentos recibidos y hallazgos al examen fisico. El seguimiento se extendio hasta el dia 7 de enfermedad con medicion diaria del hematocrito. El recuento de plaquetas se realizo al ingreso y al presentarse sangrado espontaneo o evidencia de fuga plasmatica. Se evaluo la asociacion entre el uso de dipirona y la aparicion de dengue hemorragico (DH). Resultados. Fueron incluidos 110 pacientes, siete de los cuales desarrollaron DH durante el seguimiento. Al ingreso, 17 habian recibido dipirona y su administracion no estuvo relacionada con las manifestaciones clinicas del dengue, ni con el uso de otros medicamentos. La exposicion a dipirona se asocio a aumento del riesgo de presentar DH (riesgo relativo [RR] = 7,29; intervalo de confianza del 95% [IC 95%]: 1,79 a 29,34; p = 0,0016). El recuento minimo de plaquetas documentado en los pacientes expuestos a dipirona (promedio: 105.588,2 plaquetas/µl), fue significativamente menor que el de los pacientes no expuestos (145.698,9 plaquetas/µl): diferencia = 40.110,69 plaquetas/µl; IC 95%: 1.597,36-78.624,02; p = 0,0414. Conclusiones. Estos resultados sugieren que el uso de dipirona en los primeros dias de la enfermedad causada por el virus dengue, se asocia a recuentos de plaquetas mas bajos y a aumento del riesgo de desarrollar DH.

Correlación entre los niveles de glutatión peroxidasa, un marcador de estrés oxidativo, y la presentación clínica del dengue

Background: Glutathione peroxidase (GP) can be used as a marker of oxidative stress in infectious diseases. Aim: To evaluate the association between the levels of glutathione peroxidase (GP) and the manifestations and complications of dengue. Patients and Methods: Between April 2003 and December 2004, 161 patients with dengue were prospectively evaluated. In the first evaluation, within 48 and 96 hours of disease onset, a plasma sample was obtained to measure the GP levels. The association between GP levels, clinical manifestations and complications was evaluated during the follow up. Results: Mean GP values were 1198 U/L (95% confidence interval 1089-1306). Values greater than 1200 U/L were associated with headache, arthralgias and increased heart rate. There was a negative association between GP levels and serum triglycerides. During follow up, patients with GP >1200 U/L had a higher frequency of spontaneous hemorrhages. In a logistic regression analysis arthralgias, fever and increased heart rate, were independently associated with levels >1200 U/L. Conclusions: GP levels was associated to some of the manifestations of dengue. This finding suggests that the intensity of oxidative stress can influence the clinical presentation of dengue (Rev Med Chile 2007; 135: 743-50). (Key words: Arthralgia; Dengue; Fever; Glutathione peroxidase)

[Roll of antibodies antiplatelets in viral infection: a systematic review of literature].

INTRODUCTION Thrombocytopenia is a frequent phenomenon in viral infections. Peripheral platelet destruction mediated by anti-platelet antibodies has been one of the proposed causal mechanisms. OBJECTIVE Results were collected and analyzed from published studies on associations of human viral infections on anti-platelet antibodies and total platelet counts. MATERIALS AND METHODS A PubMed search was conducted using the following terms: Viral infection (OR Virus diseases) AND antiplatelet antibody (OR thrombocytopenia) AND HIV (OR measles OR dengue OR chickenpox OR varicella OR Epistein Barr OR mumps OR rubella). Two hundred eighteen reference hits were obtained, 65 of which were relevant to this review. RESULTS Antiplatelet antibody-mediated thrombocytopenia has been documented in cases of HIV, measles, dengue, chickenpox, Epstein-Barr, mumps and rubella. Moreover, the presence of these antibodies has been associated with severity the disease and thrombocytopenia in viral infections. CONCLUSIONS Although the presence of antiplatelet antibodies was not the only mechanism for explaining the thrombocytopenia developed in these viral infections, their presence was associated with severity of thrombocytopenia and with the clinical presentation of these patients.