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Monkeypox is a zoonotic infectious disease of viral origin, caused by a virus of the same family as the virus that causes smallpox, a disease officially declared eradicated in 1980 by vaccination. The cessation of this immunization, together with the speed and frequency of international travel, in addition to the commercialization of possible reservoirs, have been decisive for the increase in cases in recent decades. Changes in transmission dynamics and clinical characterization could be associated with genotypic changes of the virus. The di-agnostic methods, specific viral treatments and vaccines under consideration are not very accessible to the vast majority of countries. Learning from other epidemics and acting pro-actively and equitably, is key to preventing the development of new pandemics.

OBJETIVOS: Determinar los costos directos e indirectos asociados con la atención de los casos de dengue y de dengue hemorrágico o síndrome de choque por dengue (DH/SCD) entre los años 1997 y 2003 en el Estado de Zulia, Venezuela. MÉTODOS: El número total de pacientes con dengue y DH/SCD se obtuvo de los registros de la Dirección Regional de Epidemiología del Estado de Zulia y de los informes de casos confirmados en la Sección de Virología del Instituto de Investigaciones Clínicas Dr. Américo Negrette, de la Facultad de Medicina, Universidad del Zulia, Maracaibo, entre el 1.° de enero de 1997 y el 31 de diciembre de 2003. Como costos directos se consideraron el costo de la atención médica de urgencia de todos los casos y los costos de hospitalización de los casos con DH/SCD (costo por día-cama y costos de laboratorio). Los costos asociados con la ausencia laboral de los enfermos mayores de 15 años y de las madres acompañantes de los enfermos menores de 15 años conformaron los costos indirectos, ajustados según la proporción de hombres y mujeres en la fuerza laboral activa del país. Para el cálculo se utilizó el salario mínimo anual y los resultados se expresaron en dólares estadounidenses, según la tasa de cambio promedio de cada año. RESULTADOS: En el período estudiado se atendieron 33 857 casos de dengue y de DH/SCD; de ellos, 30 251 (89,35%) fueron de dengue y 3 606 (10,65%) de DH/SCD. Seis de estos fallecieron (letalidad 0,2 por 100 casos de DH/SCD). Los costos directos fueron US$ 474 251,70; de esa suma, US$ 132 042,30 correspondieron a la atención en los servicios de urgencia y US$ 342 209,40 a los gastos de hospitalización de los casos con DH/SCD. Los costos indirectos ascendieron a US$ 873 825,84 y representaron 64,8% del gasto total (US$ 1 348 077,54) relacionado con esta enfermedad en los años estudiados. CONCLUSIONES: Este es el primer estudio acerca del impacto económico del dengue en el Estado de Zulia y en Venezuela. A pesar de que el estudio tuvo algunas limitaciones, los resultados demuestran que el dengue constituye un importante problema de salud pública que ocasiona grandes gastos por ausentismo laboral temporal y que afecta considerablemente al desarrollo de la economía regional y nacional.OBJECTIVES: To determine the direct and indirect costs of medical care provided to cases of dengue and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) between 1997 and 2003 in Zulia State, Venezuela. METHODS: The total number of patients with dengue and DHF/DSS was obtained from records belonging to the Regional Epidemiology Office of the state of Zulia and from reports of cases that were confirmed in the Virology Section of Dr. Americo Negrette’s Clinical Research Institute, Zulia University, Maracaibo, Venezuela, between 1 January 1997 and 31 December 2003. Direct costs included the cost of emergency medical care for all cases and hospital costs for cases with DHF/DSS (cost per bed-day and laboratory expenses). The costs connected to absence from work among patients over 15 years of age and mothers who accompanied their children under 15 years of age comprised the indirect costs, which were adjusted for the proportion of men and women in the labor force. Calculations were based on the minimum yearly wage, and results were given in United States dollars, converted according to each year’s average exchange rate. RESULTS: During the study period, 33 857 cases of dengue and DHF/DSS were seen. Of them, 30 251 (89.35%) were cases of dengue, and 3 606 (10.65%) were cases of DHF/DSS. Six cases of DHF/DSS died (lethality rate: 0.2 per 100 cases of DHF/DSS). Direct costs were US$ 474 251.70; of these costs, US$ 132 042.30 were spent on emergency medical care and US$ 342 209.40 on the hospital costs of DHF/DSS cases. Indirect costs were US$ 873 825.84 and comprised 64.8% of overall expenditures (US$ 1 348 077.54) connected to this disease during the study years. CONCLUSIONS: This is the first study on the economic impact of dengue in the state of Zulia and in Venezuela. In spite of some limitations, results show that dengue is an important public health problem that causes great expense because of temporary absenteeism from work and that undermines regional and national economic development.

The purpose of this work was to determine the effect of melatonin on the nitric oxide levels in murine splenocytes cultured with the Venezuelan equine encephalomyelitis virus. After incubation, nitric oxide levels were measured by the diazotization assay. Those cultures with the Venezuelan equine encephalomyelitis virus increased nitric oxide levels. Splenocytes infected and treated with 100 and 150 microg/ml of melatonin, decreased significantly the nitric oxide levels when compared to infected and non-treated splenocytes. These findings show that splenocytes infected with the Venezuelan equine encephalomyelitis virus generate important amounts of nitric oxide and suggest that melatonin protects the mice infected with the Venezuelan equine encephalomyelitis virus by a mechanism involving the decreasing of nitric oxide concentrations in tissue.

The effect of melatonin (MLT) on the brain levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) in Venezuelan equine encephalomyelitis (VEE) virus infection was determined. Brain homogenates from mice inoculated with 10 LD50 of VEE virus, untreated or treated with 500μg MLT/kg body weight were assayed by ELISA to measure the levels of TNF-α and IL-1β. MLT was injected daily starting 3 days before and continuing to 7 days after virus inoculation. Infected mice treated with MLT showed decreased levels of TNF-α when compared to the untreated infected mice on days 1, 3, 4, and 5 postinoculation (P < 0.001). In contrast, IL-1β levels increased from days 1 to 5 in the infected mice treated with MLT when compared with the untreated infected animals (P < 0.01). The results suggest that the protective effect of MLT on the VEE virus infection could be due, among other factors, to a decrease in TNF-α synthesis along with an increase in the production of IL-1β.

More than a century after the foundation of the illustrious University of Zulia, research is still the subject of unfair treatment; the importance of science in university life is discussed over and over again, with authorities feeling proud of the quantity and quality of researchers, but such pride is divorced from the support received by research centers, departments and institutes. However, science transcends all obstacles; research must be the ultimate goal of our University, so that it continues to be the University.

Acute respiratory infections (ARI) are pathologies that affect the respiratory tract from the proximal pharynx to the lungs, with an evolution of less than 15 days. They constitute the most frequent cause of morbimortality in the world. With the purpose of identifying the viral agents associated to this type of infections in patients of Zulia State, Venezuela, between February 2005 and July 2006, a total of 102 samples of the respiratory tract (oropharyngeal swab, nasopharyngeal swab, nasopharyngeal washing, spit and bronchoalveolar lavage) were studied. Viral isolation was made through a cellular culture and the identification of the pathogenic agents by the technique of direct immunofluorescence. Forty six positive samples were obtained (45%). The greater incidence was found in the groups of 41 to 64 years old patients, followed by lactanting babies (1 to 23 months). There were no significant differences between sexes. Within the isolated viral pathogens, Respiratory Syncytial Virus (RSV) was the agent most frequently found (32.6% p0.05), followed by Adenovirus (28.2%), Parainfluenza (23.9%) and Influenza (15.2%). The respiratory infections of the low respiratory tract were the most frequent (67.4%). A high incidence of associated viral agents to ARI in Zulia State is demonstrated. A high incidence in adult patients and the greatest positivity was found for RSV.

Rabies is a zoonotic viral disease and in Zulia State, it constitutes a public health problem of a high social impact, due to the report of cases in human beings. In this study, the presence of urban rabies was determined in Zulia's State and its distribution was identified according to municipalities and affected species during 1996-2006. In the scope of a descriptive study, a documented revision of Zulia's State Zoonosis Regional Coordination registries for the period in study was carried out. A total occurrence of 1.033 rabies cases was observed, 1.017 were in animals and 16 in human beings. The biggest incidences were for Maracaibo (31.40%) and San Francisco (15.68%) municipalities. The type of predominant rabies was the urban one; the principal reservoir and transmitter was the canine one (91.60%). Of the reported cases in human beings, the biggest incidence was in in Maracaibo Municipality (37.5%) and the most affected age group was15 years (81.2%). A low percentage in the coverage of vaccination was presented (33%). A high incidence of rabies is demonstrated in Zulia's State in spite of this being a preventable immune disease. A positive correlation was determined between the number of admissions and cases (rs=0.948 P0.01). It is necessary to implement an effective control of the sources of infection and to support a minimal coverage of vaccination of 80% in canines and furthermore, to implement community education programs, to diminish the risk of infection and the occurrence of cases.

Management of patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) requires especial care. It is based on physiological replacement therapy and fluid control. The use of blood products has its own criteria, especially during the disseminated intravascular coagulation (DIC) in the hemorrhagic phase. Monitoring bleeding manifestations and laboratory tests are needed. It has been shown that preventive transfusion does not have advantages in the treatment of this disease; on the contrary it increases the length of hospitalization and the development of pulmonary edema, among other transfusion-related risks.

Dengue infections may affect the liver, causing inflammation and compromising its function.To determine serum aminotransferases in patients with Dengue.One hundred eighty four patients with Dengue confirmed with anti-Dengue IgG and IgM antibodies measured by ELISA, aged 1 month to 79 years, were studied. As controls, 40 patients with acute hepatitis B virus infection aged 11 to 59 years and 40 healthy individuals, aged 14 to 55 years, were also studied. Alanine and aspartate aminotransferases (ALT and AST) were determined using a colorimetric method.Sixty one percent of patients with Dengue had elevated aminotransferase levels. In patients with Dengue and hepatitis B, mean ALT levels were 21.3+/-8.4 and 29.7+/-18.8 U/I, respectively. Mean AST values were 37.3+/-19, 19.6+/- 16.4 and 4.3+/-1.7 U/I in patients with Dengue, hepatitis B and controls, respectively. During the year 2001, there was an increase in the number of cases with hemorrhagic fever caused by Dengue and 65% had elevation of aminotransferases.An increase in aminotransf erase levels is common in patients with Dengue.

Background: Dengue infections may affect the liver, causing inflammation and compromising its function. Aim: To determine serum aminotransferases in patients with Dengue. Material and methods: One hundred eighty four patients with Dengue confirmed with anti-Dengue IgG and IgM antibodies measured by ELISA, aged 1 month to 79 years, were studied. As controls, 40 patients with acute hepatitis B virus infection aged 11 to 59 years and 40 healthy individuals, aged 14 to 55 years, were also studied. Alanine and aspartate aminotransferases (ALT and AST) were determined using a colorimetric method. Results: Sixty one percent of patients with Dengue had elevated aminotransferase levels. In patients with Dengue and hepatitis B, mean ALT levels were 21.3±8.4 and 29.7±18.8 U/I, respectively. Mean AST values were 37.3±19, 19.6± 16.4 and 4.3±1.7 U/I in patients with Dengue, hepatitis B and controls, respectively. During the year 2001, there was an increase in the number of cases with hemorrhagic fever caused by Dengue and 65% had elevation of aminotransferases. Conclusions: An increase in aminotransf erase levels is common in patients with Dengue

During the last years, there has been a worldwide rise in the number of infectious diseases caused by newly discovered agents, in some cases and in others, by variants known as emergent or reemergent pathogens. The analysis of the nucleotide sequences of four RNA-positive hantaviruses (S. altoni) suggests that the Caño Delgadito virus is widely distributed in the Venezuelan plains. A similar distribution has been found for some isolates and strains of a novel hantavirus (proposed name "Mamporal"), which is phylogenetically very closely related to the pulmonary syndrome--causing hantaviruses of southern South America. There have not been clinical cases described or isolates of these viruses in Zulia state, Venezuela. However, some positive serological evidences suggest that their presence in this geographic area should be taken into consideration and further investigated.

To determine the direct and indirect costs of medical care provided to cases of dengue and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) between 1997 and 2003 in Zulia State, Venezuela.The total number of patients with dengue and DHF/DSS was obtained from records belonging to the Regional Epidemiology Office of the state of Zulia and from reports of cases that were confirmed in the Virology Section of Dr. Americo Negrette's Clinical Research Institute, Zulia University, Maracaibo, Venezuela, between 1 January 1997 and 31 December 2003. Direct costs included the cost of emergency medical care for all cases and hospital costs for cases with DHF/DSS (cost per bed-day and laboratory expenses). The costs connected to absence from work among patients over 15 years of age and mothers who accompanied their children under 15 years of age comprised the indirect costs, which were adjusted for the proportion of men and women in the labor force. Calculations were based on the minimum yearly wage, and results were given in United States dollars, converted according to each year's average exchange rate.During the study period, 33,857 cases of dengue and DHF/DSS were seen. Of them, 30 251 (89.35%) were cases of dengue, and 3606 (10.65%) were cases of DHF/DSS. Six cases of DHF/DSS died (lethality rate: 0.2 per 100 cases of DHF/DSS). Direct costs were 474,251.70 US dollars; of these costs, 132,042.30 US dollars were spent on emergency medical care and 342,209.40 US dollars on the hospital costs of DHF/DSS cases. Indirect costs were 873,825.84 US dollars and comprised 64.8% of overall expenditures (1 ,48,077.54 US dollars) connected to this disease during the study years.This is the first study on the economic impact of dengue in the state of Zulia and in Venezuela. In spite of some limitations, results show that dengue is an important public health problem that causes great expense because of temporary absenteeism from work and that undermines regional and national economic development.

Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

After four months of silence before a new incursion of severe acute respiratory syndrome virus (SARS), world wide investigators specially from Asia had have to face a coronavirus capable of great spreading and inducing high morbidity. The source and the capacity of this virus to associate with other opportunist microorganisms to induce progression of the disease, remain unclear. The comparison of the genomic sequence of different strains has generated discrepancies as for if the SARS epidemic arose as an unique outbreak or it was produced for more than one genotype. However, this fact is secondary to the imminent threat that was controlled in August of 2003, after affecting 8.422 individuals, but before which we should be remain alert, since it is clear that the end of the SARS is not yet here; and that the appearance of a single case can mean the beginning of a new wave, joining the outbreak of other diseases such as the avian flu. In this regard, it is very important to know the epidemic bases of morbid-mortality of SARS and to keep a world wide surveillance in order to detect possible further cases.

Little information is available about Flavivirus infection in amerindian populations in western Venezuela. On this account the activity and seroprevalence of these viruses were determined and the hypothesis concerning the existence of a sylvatic cycle, conditioning the infection transmission of these viruses in indigenous populations, was studied. For this, blood samples from Yukpas (n=144) and Barí (n=110) communities were collected, 35 (Yukpas=25 and Barí=10) of which were processed for viral isolation followed by RT-PCR. The anti-Flavivirus IgG antibodies were determined by ELISA. The results did not show active Dengue cases and the seroprevalence of anti-Flavivirus IgG in the Yukpa population was significantly higher (p0.0001) than in the Barí population (43.1% vs. 6.4%). The present study has determined the presence of Flavivirus immunity in Yukpa and Barí populations. These results show a higher prevalence at the former than in the Barí population, which suggests circulation of Flavivirus, mainly in the Yukpa communities, being scarce and sporadic in Barí villages. However, in the indigenous populations studied, the causes or factors that determine the off set of Flavivirus infections in these zones could vary. The detected prevalence between both communities may be due to differences in the structure settlements and social habits. No evidences were found to support the presence of a sylvatic cycle in the Flavivirus transmission, specially of Dengue, in this population.

The effect of melatonin (MLT) on the brain levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in Venezuelan equine encephalomyelitis (VEE) virus infection was determined. Brain homogenates from mice inoculated with 10 LD50 of VEE virus, untreated or treated with 500 microg MLT/kg body weight were assayed by ELISA to measure the levels of TNF-alpha and IL-1beta. MLT was injected daily starting 3 days before and continuing to 7 days after virus inoculation. Infected mice treated with MLT showed decreased levels of TNF-alpha when compared to the untreated infected mice on days 1, 3, 4, and 5 postinoculation (P0.001). In contrast, IL-1beta levels increased from days 1 to 5 in the infected mice treated with MLT when compared with the untreated infected animals (P0.01). The results suggest that the protective effect of MLT on the VEE virus infection could be due, among other factors, to a decrease in TNF-alpha synthesis along with an increase in the production of IL-1beta.

The influence of Melatonin (MLT) on the modulation of the immune system has been described. In previous studies an increment of cell proliferation and an increase or a decrease of cytokines have been reported. Other workers have found inhibitory effects or no effect in the immune functions. Because of this controversy, and for the purpose of studying the mechanism by which MLT performs its functions, we evaluated its effect on murine splenocytes's proliferation after a mitogenic stimulation, and quantified the levels of IL-2 and IL-1 beta in the absence or presence of Phitohemaglutinin (PHA) in supernatants of mice splenocytes cell culture treated or not with MLT. The lymphoproliferative response was assessed using tritiated thimidine in the splenocytes of mice treated with 500 micrograms of MLT/Kg b.w. and in cell cultures containing 5, 50 and 100 micrograms MLT/mL. The production of IL-2 and IL-1 beta was detected by the ELISA test. An increase in the proliferation (p0.01) of spleen cells treated with 50 and 100 micrograms MLT/mL an optimal dose of PHA, was detected. The in vivo or in vitro treatment with MLT increased the levels of IL-2 and IL-1 beta in the absence or the presence of PHA, maintaining the increase in the concentration of IL-1 beta up to the to ninth day of treatment. These results suggest that MLT acts directly on cell proliferation probably by binding to high affinity receptors located on spleen cells, that stimulates the production of IL-2 and IL-1 beta giving rise to an increment of cell immunity.

Several studies have been performed to determine biomarkers that define the risk factors to developing severe forms of dengue. In this study, the levels of TNF-α, IL-6, IL-1, IL-17, soluble interleukin-1 receptor like 1 protein (sST2), soluble TNF-related apoptosis-inducing ligand (sTRAIL), IL-12 and soluble receptors for TNF (sTNF-RI and sTNF-RII) were determined by ELISA in dengue patients and monocyte/macrophage cultures. Dengue was classified as dengue without warning symptoms (DNWS), with warning symptoms (DWWS) and severe dengue (SD). High values of IL-6, sTNFRI, sTNFRII and sST2 were observed in DWWS and/or SD and IL-12 and sTRAIL in DNWS. TNF-α and IL-17 were increased not associated to the disease severity. High production of TNF-α, IL-1β, IL-12, IL-17, sST2 and sTRAIL and apoptosis expression were observed in dengue monocyte/macrophage cultures. This study shows that beneficial or deleterious biomarkers can be present in dengue regardless the disease severity and that monocytes may be in part the source of studied molecules.