Análisis del protocolo de atención a las gestantes COVID y detección de puntos de mejora aplicando metodología de simulación clínica / Analysis of the care management protocol for COVID pregnant women and detection of improvement proposals applying clinical simulation methodology

INTRODUCCIÓN: La pandemia actual de SARS-CoV-2 ha supuesto la mayor crisis sociosanitaria mundial experimentada en el último siglo. Cada centro asistencial se ha visto impelido a adecuar las guías de tratamiento establecidas por las distintas sociedades científicas. OBJETIVOS: Analizar el impacto de la metodología basada en la simulación como herramienta de mejora de nuestra práctica clínica: dinámica de trabajo, efectividad y seguridad de todos los facultativos implicados en el manejo del parto en gestantes COVID y su utilidad para facilitar la adecuación de los protocolos a un contexto clínico específico. MÉTODO: Estudio observacional descriptivo que incluye las cesáreas y partos de gestante COVID realizados en nuestro hospital. Se analizaron de manera multidisciplinar las actuaciones ejecutadas utilizando las herramientas de la simulación briefing y debriefing, antes y después de cada caso. RESULTADOS: Se analizaron un total de 5 casos clínicos. Se encontraron dificultades en la ejecución de los protocolos establecidos para la atención de la gestante COVID a nivel organizativo, estructural, de recursos materiales y de factores humanos. CONCLUSIONES: Este modelo de análisis ha resultado una herramienta de gran valor en tres aspectos: la mejora del trabajo en equipo, la realización de protocolos de actuación consensuados y el establecimiento de propuestas efectivas para la adecuación de los protocolos

INTRODUCTION: The current SARS-CoV-2 pandemic has been the world's largest socio-health crisis experienced in the last century. Each healthcare center has been compelled to adapt the treatment guidelines established by the different scientific societies. OBJECTIVES: Analyze the impact of the methodology based on simulation as a tool to improve our clinical practice: work dynamics, effectiveness and safety of all the physicians involved in the management of labor in COVID pregnant women and its usefulness to facilitate the adaptation of protocols to a specific clinical context. METHOD: Descriptive observational study that includes the C-sections and deliveries of COVID pregnant women performed in our hospital. The actions carried out in each procedure were analyzed using the simulation multidisciplinary briefing and debriefing tools, before and after each case. RESULTS: A total of 5 clinical cases were analyzed. Difficulties were found in the execution of the protocols established for the care of the COVID pregnant. Organizational, structural, material resources and human factors obstacles were the most common. CONCLUSIONS: Our results showed that the analysis example using simulation methodology was a tool of great value in three aspects: teamwork improvement, actions consent and improvement proposals for the adaptation and implementation of protocols

Analysis of the care management protocol for COVID pregnant women and detection of improvement proposals applying clinical simulation methodology. / Análisis del protocolo de atención a las gestantes COVID y detección de puntos de mejora aplicando metodología de simulación clínica.

INTRODUCTION: The current SARS-CoV-2 pandemic has been the world's largest socio-health crisis experienced in the last century. Each healthcare center has been compelled to adapt the treatment guidelines established by the different scientific societies. OBJECTIVES: Analyze the impact of the methodology based on simulation as a tool to improve our clinical practice: work dynamics, effectiveness and safety of all the physicians involved in the management of labor in COVID pregnant women and its usefulness to facilitate the adaptation of protocols to a specific clinical context. METHOD: Descriptive observational study that includes the C-sections and deliveries of COVID pregnant women performed in our hospital. The actions carried out in each procedure were analyzed using the simulation multidisciplinary briefing and debriefing tools, before and after each case. RESULTS: A total of 5 clinical cases were analyzed. Difficulties were found in the execution of the protocols established for the care of the COVID pregnant. Organizational, structural, material resources and human factors obstacles were the most common. CONCLUSIONS: Our results showed that the analysis example using simulation methodology was a tool of great value in three aspects: teamwork improvement, actions consent and improvement proposals for the adaptation and implementation of protocols.

Observaciones sobre la hiperostosis esquelética idiopática difusa (enfermedad de Forestier y Rotés-Querol) / Remarks on the difusse idiopatic skeletal hyperostosis (Forestier Rotes-Querol disease)

No disponible

Factores de riesgo para alteraciones de la densidad mineral ósea en mujeres posmenopáusicas / Risk factors for alterations in bone mineral density in postmenopausal women

OBJETIVO: Determinar los factores de riesgo para presentar alteraciones de la densidad mineral ósea (DMO) en mujeres posmenopáusicas atendidas en la consulta de Menopausia y Climaterio de la Maternidad "Dr. Armando Castillo Plaza", de Maracaibo, Venezuela. MÉTODOS: Investigación descriptiva, con diseño no experimental y transeccional, donde se evaluó la DMO y los factores de riesgo para presentar osteoporosis en 60 mujeres posmenopáusicas. RESULTADOS: La medición de la DMO resultó en promedio de 957,45 ± 149,95 y 905,00 ± 151,25 gramos, con índices T de -0,52 ± 1,66 y -0,55 ± 2,67 en columna vertebral y cuello femoral, respectivamente. Se estableció una prevalencia de osteoporosis del 10% y 5%, y de osteopenia del 43,3% y 50% en columna vertebral y fémur, respectivamente. La menopausia quirúrgica (OR [95% CI] = 4,75 [1,58-14,25]; p=0,004), el consumo excesivo de café (OR [95% CI] = 3,20 [1,40-7,10 1]; p=0,000) o gaseosas (OR [95% CI] = 2,50 [1,18-5,60]; p=0,002), tabaquismo (OR [95% CI] = 1,70 [1,102,80]; p=0,013) y la ausencia de suplementación de calcio más vitamina D (OR [95% CI] = 1,70 [1,00-2,80]; p=0,019) resultaron ser factores significativamente asociados al diagnóstico de osteoporosis u osteopenia (p<0,05). CONCLUSIÓN: Las mujeres posmenopáusicas evaluadas presentan una alta prevalencia de alteraciones en la DMO, principalmente osteopenia, y factores de riesgo para presentar Osteoporosis.

AIM: To determine risk factors for presenting alterations in bone mineral density (BMD) in postmenopausal women attending the consultation of Menopause and Menopause Maternity "Dr. Armando Castillo Plaza", Maracaibo, Venezuela. METHODS: A descriptive research with non-experimental and transactional design where was evaluated BMD and risk factors for developing osteoporosis in 60 postmenopausal women. RESULTS: The BMD measurement was averaged in 957.45 ± 149.95 and 905.00 ± 151.25 grams; with T indexes of -0.52 ± 1.66 and -0.55 ± 2.67 in spine and femoral neck, respectively. The prevalence of osteoporosis was 10% and 5%, while osteopenia was 43.3% and 50% in spine and femur, respectively. Surgical menopause (OR [95% CI] = 4.75 [1.58 to 14.25]; p=0.004); excessive coffee consumption (OR [95% CI] = 3.20 [1,40- 7.10 1]; p=0.000) or gaseous beverages (OR [95% CI] = 2.50 [1.18 to 5.60]; p=0.002); smoking (OR [95% CI] = 1.70 [1.10 to 2.80]; p=0.013) and the absence of supplemental calcium plus vitamin D (OR [95% CI] = 1.70 [1.00 to 2.80]; p=0.019) were be factors significantly associated with the diagnosis of osteoporosis or osteopenia (p<0.05). CONCLUSION: The evaluated postmenopausal women have a high prevalence of abnormal BMD, especially osteopenia, and risk factors for developing osteoporosis.

Anemia materna y peso al nacer en productos de embarazos a término / Maternal anemia and birth weight in term pregnancy products

OBJETIVO: Relacionar la anemia materna con el peso al nacer (PAN) en mujeres con embarazos a término atendidas en la emergencia obstétrica de la Maternidad "Dr. Armando Castillo Plaza", Maracaibo, Venezuela. MÉTODOS: Investigación correlacional con diseño no experimental y transeccional, donde se evaluaron 200 embarazadas en fase activa del trabajo de parto, a quienes se les determinaron los valores de hemoglobina (Hb), hematocrito (Hcto) e índices hematimétricos, para luego correlacionarlas con el PAN. RESULTADOS: Los valores de Hb oscilaban entre 8,4 ± 1,0 g/dl y 11,6 ± 0,64 g/dl, mientras que los de Hcto fueron de 28,8 ± 3,3% y 38,9 ± 2,2%, anémicas y no anémicas, respectivamente. Los índices hematimétricos mostraron valores referenciales normales en ambos grupos. El PAN de los recién nacidos de madres anémicas estaba disminuido en 12,39% (-420 g) al compararse con los pesos de los neonatos de madre sin anemia (2.970 ± 0,43 g vs. 3.390 ± 0,32 g; p<0,0001). El BPN fue más frecuente en el grupo de madres anémicas, las cuales mostraron un mayor riesgo, aunque no significativo (15% vs. 10%; OR IC95% 1,558 [0,676-3,728]; p>0,05). Se demostró una relación directamente proporcional y significativa entre los valores de Hb - PAN (r=0,439; p<0,0001). CONCLUSIÓN: Existe una relación directa, proporcional y significativa entre el PAN y los valores de Hb; sin embargo, aunque las gestantes anémicas presentaron con mayor frecuencia BPN, esta diferencia no fue significativa.

AIM: To link maternal anemia and birth weight (BW) in women with term pregnancies present to emergency obstetric at the Maternity "Dr. Armando Castillo Plaza", in Maracaibo, Venezuela. METHODS: A correlational research, with non-experimental and transactional design, where valued a sample of 200 pregnant women in active phase of labor, who are determined hemoglobin (Hb), hematocrit (Hct), and hematimetric indexes values. RESULTS: The values of Hb and Hct in anemic ranged from 8.4 ± 1 g/dl and 11.6 ± 0.64 g/dl, whereas the Hct was 28.8 ± 3.3% and 38.9 ± 2.2%, in patients with and without anemia, respectively. The hematimetric indexes showed normal reference values in both groups. The BW in newborn of anemic mothers was decreased by 12.39% (-420 g) when compared to the weights of infants of mother without anemia (2.970 ± 0.43 g vs. 3.390 ± 0.32 g; p<0.0001). LBW was more common in the group of anemic mothers, who showed an increased risk, although not significant (15% vs. 10%; OR 95%CI 1.588 [0,676-3,728]; p>0.05). Was demonstrated a directly proportional and significant relationship between Hb values and BW(r=0.439; p<0.0001). CONCLUSION: Exist a direct proportional and significant relationship between the PAN and the Hb; however, while anemic pregnant women presented more frequently LBW, this difference was not significant.

Algorithm for brain extraction on Magnetic Resonance Images T1 using Morphological 3D Transformations / Algoritmo para la extracción de imágenes de resonancia magnética T1 usando transformaciones morfológicas en 3D

In this paper a 3D morphological composition of transformations for brain extraction on brain Magnetic Resonance Images T1 (MRI T1) is presented. The proposal makes use of two morphological connected transformations, the lower leveling and a family of the viscous alternating sequential filters (VASFs). The properties of these operators -which consist in the control of the reconstruction process of a marker into the original image-, are exploited to segment the brain in 20 volumes of MRI T1. The segmented brains are compared with respect to: i) the segmentations obtained from BET which is popular among the scientific community for segmenting the brain; and ii) manual segmentations. The computed indices indicate that the proposed transformation produces good results during its performance. The consumed time for the algorithm during the execution is acceptable and it can be implemented in Matlab.

En este artículo se presenta una composición de transformaciones morfológicas para la extracción del cerebro en imágenes de resonancia magnética T1 (MRI T1) en 3D. La propuesta hace uso de dos transformaciones morfológicas conexas, la nivelación inferior y una familia de filtros viscosos alternados secuenciales (VASFs). Las propiedades de estos operadores- las cuales consisten en el control del proceso de reconstrucción de un marcador dentro de la imagen original-, se explotan para segmentar el cerebro de 20 volúmenes de MRI T1. Los cerebros segmentados se comparan respecto a: i) segmentaciones obtenidas a partir del algoritmo BET, el cual es popular en la comunidad científica para la segmentación del cerebro; y ii) segmentaciones manuales. Los índices calculados indican que la transformación propuesta produce buenos resultados en su desempeño. El tiempo empleado por el operador durante su ejecución es aceptable además de que la propuesta puede ser implementada en Matlab.

Cáncer de ovario en el embarazo: reporte de un caso / Ovarian cancer in pregnancy: case report

Antecedentes: La asociación entre cáncer y embarazo es infrecuente, con una incidencia entre 0,02-0,1 por ciento ocupando el cáncer de ovario (CAO) el tercer lugar entre las neoplasias ginecológicas más frecuentemente asociada a la gestación, con tasas entre 1/10.000 a 1/100.000 embarazos. Objetivo: Divulgar un caso clínico de interés para la comunidad médica. Caso clínico: Gestante de 22 años que consulta por presentar dolor abdominal, vómitos, disnea y aumento de circunferencia abdominal. Presenta tumoración parauterina que alcanzaba a hipocondrio derecho, e ingresa con diagnostico de embarazo interrumpido de 12 semanas, tumoración de ovario; síndrome de pseudo Meigs y anemia. Mediante ecografía transabdominal se confirma lesión en fosa ilíaca y flanco derecho multilobulada de 17,3 x 9,9 x 13,7 cm, concordante con imágenes de RMN donde se aprecia como una tumoración ovárica sólido-quística. Se práctica laparotomía y la biopsia por congelación diagnosticó tumor ovario de células germinales (disgerminoma). Se procede a practicar histerectomía total con feto obitado in útero, más salpingo-ooforectomía bilateral. Egresando en buenas condiciones y actualmente en quimioterapia. Conclusión: La coincidencia de CAO durante el embarazo es rara, siendo los digerminomas los tumores malignos más frecuentemente diagnosticados.

Background: The association between cancer and pregnancy is infrequent, with an incidence of 0.02 to 0.1 percent; occupying ovarian cancer (OCA) in third place among the most common gynaecological malignancies associated with pregnancy, with rates between 1/10,000 to 1/100,000 pregnancies. Aim: To disseminate clinical case of interest to the medical community. Case report: A 22 years old pregnant who consulted for abdominal pain, vomiting, dyspnoea and increased abdominal girth. Who has an anexial tumour reaching right upper quadrant, which was admitted with diagnosis of interrupted pregnancy of 12 weeks, ovary's tumour, pseudo Meigs' syndrome and anaemia. Transabdominal ultrasound confirmed space occupying lesion in the right lower quadrant and flank multilobed of 17.3 x 9.9 x 13.7 cm, with concordance in MRI which is seen as a mixed ovarian tumour. Laparotomy was practice and the frozen biopsy was diagnosed as ovarian germ cell tumour (dysgerminoma). It proceeds to total hysterectomy with death fetus in uterus, with bilateral salpingo oophorectomy. Withdrawal in good condition and currently under chemotherapy regimen. Conclusion: The coincidence of OCA during pregnancy is rare, the dysgerminoma are the most frequently diagnosed malignancy.

Análisis de la variación del calcio intracelular en células foliculares / Intracellular Calcium Variation Analysis of Follicular Cells

En este trabajo se presenta un método para medir la variación del calcio intracelular en células foliculares. Esta propuesta consiste en dos etapas: (i) La detección de los núcleos de las células; y (ii) el análisis de las variaciones de fluorescencia. La primera etapa se realiza a través de la transformada modificada de líneas divisoras de agua controlada por marcadores (en inglés: Modified-Watershed Transformation) controlando el proceso de etiquetado de células por el establecimiento de criterios particulares. El proceso de detección homogeniza las condiciones de luminosidad a través de un filtro morfológico y utiliza como descriptores a los bordes de las células. En la segunda etapa, se asocia la variación de la fluorescencia con los cambios de Ca2+ intracelular donde la variación se modela como una función exponencial decreciente. Luego, se presenta un nuevo proceso morfológico, denominado proceso de reconstrucción medio, que permite suavizar los datos para el proceso de modelado. Este proceso utiliza la información del sub modelado y sobre modelado de la señal, mediante las propiedades de los operadores de reconstrucción, conservando la estructura interna de la señal original. Finalmente, en un proceso experimental utilizando células de anfibios, se muestran los resultados obtenidos después de aplicar la propuesta a un grupo de células.

This paper presents a method for the measurement of the variation of intracellular calcium in follicular cells. This proposal consists in two stages: (i) The detection of the cell's nuclei, and (ii) the analysis of the fluorescence variations. The first stage is performed with the modified-watershed transformation, where the marker process is controlled by establishing own criterion. The detection process homogenizes the luminance conditions through a morphological filter and uses as descriptors the edges of the cells. In the second stage, the variations of fluorescence are associated with changes in intracellular Ca2+, which are modeled as an exponential decay function. Then, we present a new morphological process called medium reconstruction process, that smoothes the data in the process of model creation. This process uses the information of under and over model of the signal, through the properties of reconstruction operators, keeping the internal structure of the original signal. Finally, using amphibian cells in an experimental process, the results obtained are showed after applying the proposal to a group of cells.

[Eating behaviour and body image in a sample of adolescents from Sevilla]. / Conducta alimentaria e imagen corporal en una muestra de adolescentes de Sevilla.

OBJECTIVE: This study examined the presence of disordered eating behaviours and the influence that on them could have the degree of body dissatisfaction among adolescents. METHOD: By the Eating Attitudes Test-40 (EAT-40), the Sick Control On Fat Food (SCOFF) and the subscale of body dissatisfaction (BD) of the Eating Disorders Inventory-2 (EDI-2) a total of 841 students, aged 12-19, were studied. Eating behaviours, sex and age differences, and eating attitudes and behaviours related to the degree of body dissatisfaction were analized. RESULTS: We found that 21,29% had significant punctuations in the SCOFF and 7,13% in the EAT-40. There were significant sex-differences (13,93% and 3,23% in SCOFF and EAT-40 for males, 29,38% and 10,70% for women). With regard to previous studies, a decrease of the risk is observed in women and an increase in males. Major body dissatisfaction was observed among the 12 to 17-year-old girls, though sex-differences in eating alterations, can be mostly found between the ages of 14 and 16. Body dissatisfaction correlated positively and significantly to Body Mass Index, EAT-40 and SCOFF. CONCLUSION: In order to implement primary programs in the adolescent population it is necessary to explore the eating behaviours of risky and the degree of body dissatisfaction to be able to raise specifically the interventions to be carried out, involving teachers as primary agents for the work in the school context.

Conducta alimentaria e imagen corporal en una muestra de adolescentes de Sevilla / Eating behaviour and body image in a sample of adolescents from Sevilla

Objetivo: En el presente trabajo se analiza la presencia de alteraciones alimentarias y la influencia que sobre ellas puede tener el grado de insatisfacción corporal entre los adolescentes. Método: Aplicando el Eating Attitudes Test-40 (EAT-40), el Sick Control On Fat Food (SCOFF) y la subescala de insatisfacción corporal (BD) del Eating Disorders Inventory-2 (EDI-2) a 841 estudiantes, de 12 a 19 años, se analizaron las conductas alimentarias de riesgo, se estudiaron las diferencias en función del sexo y la edad y se analizó la relación de dichas conductas con el grado de insatisfacción corporal. Resultados y discusión: El 21,29% tuvo puntuaciones significativas en el SCOFF y el 7,13% en el EAT-40. Por sexos, hubo diferencias significativas (13,93% y 3,23% en SCOFF y EAT-40 para los varones, 29,38% y 10,70% para las mujeres). Con respecto a datos anteriores, se observa un descenso del riesgo en las mujeres y un incremento en los varones. Se observó una mayor insatisfacción corporal en las chicas de 12 a 17 años, si bien la diferencia entre chicas y chicos, en alteraciones alimentarias, se centra en los 14-16 años. La insatisfacción corporal correlacionó positiva y significativamente con el Índice de Masa Corporal, EAT-40 y SCOFF. Para implantar programas de prevención primaria en la población adolescente, es necesario conocer las conductas alimentarias de riesgo y el grado de insatisfacción corporal, para poder plantear específicamente las intervenciones a llevar a cabo, involucrando al profesorado como agente primario de trabajo en el contexto escolar (AU)

Objective: This study examined the presence of disordered eating behaviours and the influence that on them could have the degree of body dissatisfaction among adolescents. Method: By the Eating Attitudes Test-40 (EAT-40), the Sick Control On Fat Food (SCOFF) and the subscale of body dissatisfaction (BD) of the Eating Disorders Inventory-2 (EDI-2) a total of 841 students, aged 12-19, were studied. Eating behaviours, sex and age differences, and eating attitudes and behaviours related to the degree of body dissatisfaction were analized. Results: We found that 21,29% had significant punctuations in the SCOFF and 7,13% in the EAT-40. There were significant sex-differences (13,93% and 3,23% in SCOFF and EAT-40 for males, 29,38% and 10,70% for women). With regard to previous studies, a decrease of the risk is observed in women and an increase in males. Major body dissatisfaction was observed among the 12 to 17-year-old girls, though sex-differences in eating alterations, can be mostly found between the ages of 14 and 16. Body dissatisfaction correlated positively and significantly to Body Mass Index, EAT-40 and SCOFF. Conclusion: In order to implement primary programs in the adolescent population it is necessary to explore the eating behaviours of risky and the degree of body dissatisfaction to be able to raise specifically the interventions to be carried out, involving teachers as primary agents for the work in the school context (AU)

Purified protein derivative reaction in systemic lupus erythematosus patients. Indirect study of cellular immunity.

Cutaneous anergy in SLE patients results from disease activity and/or immunosuppressive treatment (IT). The aim of this study was to evaluate purified protein derivative (PPD) reaction in SLE patients. A total of 145 patients and 20 controls were studied. Five units of PPD were applied on day 0, and skin reaction was measured after 3 (PPD1) and 6 (PPD2) days. A booster was applied (day 14), and the reaction was measured after 3 (PPD3) and 6 (PPD4) days. Non-parametric ANOVA test and unpaired Student's t-test were performed. Forty patients (group I) were inactive (MexSLEDAI < 3), receiving no IT (at least 3 months previous to the PPD test); 39 (group II) were inactive receiving IT; 24 (group III) were active without IT, and 42 (group IV) were active with IT. Active patients had lower PPD1 (group III, 1.4 +/- 0.9; group IV, 0.6 +/- 0.5) than inactive patients (group I, 8.4 +/- 2.3; group II, 5.1 +/- 1.9) and than controls (9.4 +/- 3; P < or = 0.001). Group IV had lower delayed response (PPD2 = 0.3 +/- 0.3) than inactive groups (group I, 2.6 +/- 0.9; group II, 3.1 +/- 0.8) and than controls (7.9 +/- 2.5; P < or = 0.001). Group III had lower delayed reaction (PPD2 = 1.2 +/- 0.8) than controls (P < or = 0.001). Active SLE patients, receiving or not receiving IT, had lower skin response to PPD than inactive patients and controls.

Leukocyturia in women with diabetes and its clinical implications.

BACKGROUND: Urinalysis is one of the most common studies performed on the diabetic patient at every visit. The presence of leukocyturia is relatively common but it is not clear what the attitude of the physician toward this particular finding should be. The main objective of the present study was to investigate the clinical significance of leukocyturia in diabetic women. METHODS: Ninety-eight diabetic women (84.7% type 2) aged 57 +/- 13 years who were being seen at the diabetic out-patient clinic were randomly selected. All patients underwent a clinical and gynecologic examination and a urinalysis. A Papanicolaou smear and a urine culture were also obtained. RESULTS: The overall prevalence of leukocyturia (>5 cells/high power field (hpf)) was 46.5%. Patients with urinary tract infections (UTI) were 7.5 times more likely to have leukocyturia, while a leukocyte count <5cells/hpf predicted the absence of UTI in 96% of the women. In the comparison of patients with and without leukocyturia, we found that proteinuria (p = 0.06) and bacteriuria (p <0.002) were more common in the women with leukocyturia. A significant association with leukorrhea was not demonstrated. The empirical use of antibiotics was 12 times more frequent in the patients with leukocyturia. CONCLUSIONS: A urinary culture should be requested in all diabetic patients with leukocyturia. The possibility of a UTI is remote when leukocyturia is absent.

[Stratification of a hyperendemic city in hemorrhagic dengue]. / Estratificación de una ciudad hiperendémica en dengue hemorrágico.

Any effort to control dengue hemorrhagic fever (DHF) faces a number of challenges. Among these are the great environmental heterogeneity of homes and neighborhoods in urban centers where the primary dengue vector, Aedes aegypti, breeds, as well as shortages of resources and of personnel trained in mosquito control. Adequate epidemiological surveillance could serve as a basis to begin to stratify urban communities and identify the areas in them where control efforts should be focused. In this study we stratified Maracay, Venezuela, a city with hyperendemic dengue hemorrhagic fever, using a geographic information system and analyzing the persistence, incidence, and prevalence of dengue, by means of clinical diagnoses reported from 1993 through 1998. Maracay has around one million inhabitants living in some 349 neighborhoods in the six communities that make up the greater Maracay metropolitan area. During that 1993-1998 period the Maracay area reported 10,576 cases of dengue, 2,593 cases of DHF, and 8 deaths. The incidence of DHF was related to the incidence of dengue, the number of inhabitants in an area, and population density. The spatial pattern of dengue incidence was stable over the years that were studied, and significant, positive relationships were found between pairs of years and the incidence of dengue by neighborhood. The persistence of dengue was related directly to monthly incidence by neighborhood. These spatial patterns helped to divide the city into three strata: 68 neighborhoods without apparent dengue, 226 neighborhoods with low persistence and prevalence, and 55 neighborhoods with high persistence and prevalence. We recommend giving the highest priority for control efforts to these 55 neighborhoods, which make up just 35% of the Maracay urban area but had 70% of all the reported dengue cases.

Dengue virus structural differences that correlate with pathogenesis.

The understanding of dengue virus pathogenesis has been hampered by the lack of in vitro and in vivo models of disease. The study of viral factors involved in the production of severe dengue, dengue hemorrhagic fever (DHF), versus the more common dengue fever (DF), have been limited to indirect clinical and epidemiologic associations. In an effort to identify viral determinants of DHF, we have developed a method for comparing dengue type 2 genomes (reverse transcriptase PCR in six fragments) directly from patient plasma. Samples for comparison were selected from two previously described dengue type 2 genotypes which had been shown to be the cause of DF or DHF. When full genome sequences of 11 dengue viruses were analyzed, several structural differences were seen consistently between those associated with DF only and those with the potential to cause DHF: a total of six encoded amino acid charge differences were seen in the prM, E, NS4b, and NS5 genes, while sequence differences observed within the 5' nontranslated region (NTR) and 3' NTR were predicted to change RNA secondary structures. We hypothesize that the primary determinants of DHF reside in (i) amino acid 390 of the E protein, which purportedly alters virion binding to host cells; (ii) in the downstream loop (nucleotides 68 to 80) of the 5' NTR, which may be involved in translation initiation; and (iii) in the upstream 300 nucleotides of the 3' NTR, which may regulate viral replication via the formation of replicative intermediates. The significance of four amino acid differences in the nonstructural proteins NS4b and NS5, a presumed transport protein and the viral RNA polymerase, respectively, remains unknown. This new approach to the study of dengue virus genome differences should better reflect the true composition of viral RNA populations in the natural host and permit their association with pathogenesis.