Host biomarkers for early identification of severe imported Plasmodium falciparum malaria.

BACKGROUND: Severe imported P. falciparum malaria is a source of morbi-mortality in non-endemic regions. WHO criteria don't accurately classify patients at risk of complications. There is a need to evaluate new tools such as biomarkers to better identify patients with severe imported malaria. METHODS: A case-control study was conducted in Barcelona, from January 2011-January 2021. Adult patients with microbiologically confirmed P. falciparum malaria were classified according to WHO criteria. Patients with imported non-malarial fevers were included as controls. In each group, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein (CRP) and platelets were measured and their concentrations were compared between groups. New groups were made with a modified WHO severity classification and biomarkers' performance was evaluated using multiple imputation models. RESULTS: 131 participants were included: 52 severe malaria, 30 uncomplicated malaria and 49 non-malarial fever cases. All biomarkers except sTREM-1 showed significant differences between groups. Using the modified WHO severity classification, Ang-2 and CRP presented the best AUROC; 0.79 (95%CI 0.64-0.94) and 0.80(95%CI 0.67-0.93). A model combining CRP and Ang-2 showed the best AUROC, of 0.84(95%CI 0.68-0.99), with the highest sensitivity and specificity: 84.6%(95%CI 58.9-98.1) and 77.4% (95%CI 65.9-87.7), respectively. CONCLUSIONS: The combination of Ang-2 and CRP may be a reliable tool for the early identification of severe imported malaria. The use of a rapid prognostic test including the mentioned biomarkers could optimize imported malaria management, with the potential to decrease the rate of complications and hospitalizations in patients with imported malaria.

Telemedicine for international travelers through a Smartphone-based monitoring platform (Trip Doctor®).

BACKGROUND: Overall, more than 50% of international travelers develop symptoms while traveling and 55% of them seek medical assistance during the trip. We conducted a study to evaluate the usefulness of a Smartphone app called TRIP Doctor® to provide telemedicine to international travelers. METHODS: Participants over 18 years old attending our travel clinic at Hospital Clinic in Barcelona were invited to participate during 2017-2019. After downloading the app, the health status of the traveler was monitored on a daily basis, providing specific medical advice and offering remote contact with specialized physicians through an integrated chat, if needed. RESULTS: From 449 users, 59 (13%) contacted for medical assistance through the app during the trip. Main reasons for telemedicine were diarrhea (25.7%), skin conditions (19.7%) and fever (12.1%). Among patients who contacted, 90% of the travelers did not require to be referred to a local doctor. Symptomatic treatment was the main treatment prescribed (38%). In a 14.7% of the cases a follow-up was not required, a 63.2% recovered and 22.1% were loss of follow-up. After a multivariate analysis, duration of trip >14 days was found to be the only factor associated with the use of telemedicine (OR 2.2, CI 95% 1.1-4.5, p = 0.03). CONCLUSION: In conclusion, travelers using telemedicine travelled for longer periods of time and mostly contacted for mild symptoms which could be solved successfully by remote assistance with our specialized doctors.

Real-time incidence of travel-related symptoms through a smartphone-based app remote monitoring system: a pilot study.

Trip Doctor®, a Smartphone-based app monitoring system, was developed to detect infections among travelers in real-time. For testing, 106 participants were recruited (62.2% male, mean age 36 years (SD = 11)). Majority of trips were for tourism and main destinations were in South East Asia. Mean travel duration was 14 days (SD = 10). Diarrhea was the most frequently reported symptom (15.5%). The system demonstrated adequate usability and is ready to be used on a larger scale.

Blackwater fever in a non-immune patient with Plasmodium falciparum malaria after intravenous artesunate.

Blackwater fever was typically reported after quinine administration, although it is poor recognized in patients receiving artesunate. This case describes a blackwater fever in a non-immune patient after artesunate for severe malaria. It highlights the importance of monitoring haemolytic parameters in severe malaria to avoid renal impairment or severe anaemia.

Increased Systemic Cytokine/Chemokine Expression in Asthmatic and Non-asthmatic Patients with Bacterial, Viral or Mixed Lung Infection.

This study was aimed to determine the profiles of serum cytokines (IL-1ß, TNF-α, IL-4, IL-5) and chemokines (MCP-1: monocyte chemoattract protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in individuals with an asthmatic versus a non-asthmatic background with bacterial, viral or mixed acute respiratory infection. Asthmatic (n = 14) and non-asthmatic (n = 29) patients with acute viral, bacterial or mixed (bacterial and viruses) respiratory infection were studied. Patients were also analysed as individuals with pneumonia or bronchitis. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in serum was determined by ELISA. Increased cytokine/chemokine concentration in asthmatic and non-asthmatic patients was observed. However, higher concentrations of chemokines (MCP-1 and RANTES) in asthmatic patients infected by viruses, bacteria or bacteria and viruses (mixed) than in non-asthmatic patients were observed. In general, viral and mixed infections were better cytokine/chemokine inducers than bacterial infection. Cytokine/chemokine expression was similarly increased in both asthmatic and non-asthmatic patients with pneumonia or bronchitis, except that RANTES remained at normal levels in bronchitis. Circulating cytokine profiles induced by acute viral, bacterial or mixed lung infection were not related to asthmatic background, except for chemokines that were increased in asthmatic status.

Elevated levels of interleukin-2 receptor and intercellular adhesion molecule 1 in sera from a venezuelan cohort of patients with dengue.

This study evaluated the levels of soluble interleukin-2 receptor (sIL-2R) and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with dengue. Sera from 17 patients with dengue fever (DF), 15 with dengue hemorrhagic fever (DHF) and 12 healthy individuals were obtained. Increased levels of sIL-2R and sICAM-1 were found in patients with DF and DHF when compared to normal; those were not correlated with leukocytes, hepatic serum enzyme levels or haemostatic parameters. Levels of sIL-2R were related to the different grades of DHF. These results suggest that increased levels of sIL-2R and sICAM-1 are a common feature of dengue.

El daño peroxidativo en leucocitos peritoneales de ratones viejos disminuye si se suplementa la dieta con galletas enriquecidas con antioxidantes. Relación con la supervivencia / Lipid peroxidation in peritoneal leukocytes from aged mice is decreased by antioxidant dietary supplementation. Relationship with survival

Introducción: el envejecimiento está asociado a un estrés oxidativo crónico que se manifiesta en un mayor daño a macromoléculas como es el caso de los lípidos, y el producto de degradación más representativo de éstos es el malondialdehído (MDA). Los leucocitos producen compuestos oxidantes para realizar sus funciones y son muy sensibles al daño oxidativo. Por ello, se han analizado las concentraciones de MDA en leucocitos peritoneales de ratones durante el envejecimiento, y el efecto, en animales viejos, de una dieta enriquecida con antioxidantes en estas concentraciones, así como su posible incidencia en la longevidad. Material y métodos: el MDA se valoró por HPLC (high-performance liquid chromatography) en leucocitos peritoneales de ratones de la cepa ICR (CD 1) jóvenes (16 ± 2 semanas), adultos (36 ± 2 semanas), maduros (52 ± 2 semanas) y viejos (71 ± 2 y 81 ± 2 semanas), y en los de estos últimos tras la ingestión, durante 5 y 15 semanas de una dieta suplementada (en un 20% p/p) con galletas enriquecidas en antioxidantes. Estos animales viejos ingirieron hasta su muerte la dieta suplementada, para obtener la posible relación entre la ingestión de esta dieta y la longevidad. Resultados: los valores de MDA aumentan con la edad, y la ingestión, en animales viejos, de una dieta enriquecida con antioxidantes, tanto durante 5 como 15 semanas, los disminuye; se observa una relación inversa entre los valores de MDA y la longevidad. Conclusiones: en animales viejos, la ingestión de una dieta enriquecida en antioxidantes disminuye el grado de peroxidación lipídica en leucocitos peritoneales, lo que se refleja en un aumento de su longevidad

Introduction: ageing is associated with chronic oxidative stress, which leads to increased damage to macromolecules, such as lipids. One of the most important end products of lipid peroxidation is the malondialdehyde molecule (MDA). Leukocytes produce reactive oxygen species to support their functions and are highly sensitive to oxidative damage. The aim of this study was to ascertain MDA levels in peritoneal leucocytes from mice during ageing, as well as the effect of antioxidant dietary supplementation in aged mice on the levels of this molecule and its possible incidence on longevity. Material and methods: MDA levels were assessed by high-performance liquid chromatography in peritoneal leukocytes from ICR (CD 1) mice at young (16 ± 2 weeks), adult (36 ± 2 weeks), mature (52 ± 2 weeks) and old (71 ± 2 and 81 ± 2 weeks) ages. At the latter age, MDA content was also measured after 5 and 15 weeks of dietary supplementation (20% w/w) with biscuits enriched with nutritional doses of antioxidants. The mice received the supplementation until death to ascertain the possible relationship between ingestion of an antioxidant-enriched diet and longevity. Results: MDA levels increased during ageing, whereas the levels of lipid peroxidation decreased after 5 and 15 weeks of antioxidant dietary supplementation in aged mice. Moreover, an inverse relationship between MDA content and longevity was observed. Conclusions: our results demonstrate that in aged mice ingestion of an antioxidant-enriched diet decreases lipid peroxidation in peritoneal leukocytes, leading to increased longevity

Toxicidad y actividad inmunológica in vitro e in vitro del extracto metanólico de la especie vegetal Cordia sebestena / Toxicity and immunologic activity in vivo and in vitro of the metanolic extract of the vegetal species Cordia sebestena

El ha investigado la utilidad terapéutica de las plantas basado principalmente en el uso folklórico por su aplicación en un amplio rango de enfermedades. En el presente trabajo, se evaluó la toxicidad y la actividad inmunológica in vivo e in vitro del extracto metanílico de la Cordia sebetena. Cultivos de celuals mononucleares de sangre periférica humana, donde se investigó el efecto de la viabilidad (coloración supravital azul tripán), linfoproliferación (Timidina Tritiada) y concentraciones del Factor Estimulador de Colonias Granulocítico-Macrofágico (FEC-GM) en los sobrenadantes, empleando la técnica de ELISA de captura, así como la actividad quimiotáctica de celulas polimorfonucleares humanas a través de la técnica en gel de agarosa. Se estudio la toxicidad in vivo en hígado, vaso y riñón en ratones bajo tratamiento oral e intraperitoneal a través de estudios histológicos, niveles sanguíneos de leucocitos totales y plaquetas/mm3 y el efecto en la ingesta diaria y el peso corporal de dichos ratones. Los resultados indican que el extracto metanolico de Cordia sebestena es inocuo a las celulas ensayadas, estimula la producción del FEC-GM, y por ende a la formación de nuevas células linfoides comportándose como un quimioatractante celular, hallazgos que podrían, en parte, explicar los efectos farmacológicos atribuidos a esta especie vegetal

[Evaluation of immunity against Venezuelan equine encephalitis virus and dengue in the human population of San Carlos, the Almirante Padilla Island Municipality, Zulia State, Venezuela. 1996]. / Evaluación de la inmunidad contra los virus de encefalitis equina venezolana y dengue en la población humana de San Carlos, Municipio Insular Almirante Padilla, Estado Zulia, Venezuela. Año 1996.

The Insular Municipality of Almirante Padilla, historically, has been affected by Venezuelan Equine Encephalitis (VEE) epidemics, that have occurred cyclically in the Paez, Mara and Almirante Padilla Municipalities of the State of Zulia. During the last epidemic outbreak (1995), the studies reported a great number of cases of VEE in humans, based on epidemiologic-clinical diagnosis; occupying this municipality, the first place in the attack rate by the virus. At the same time, Dengue has been defined as an endemic illness affecting different regions, whose etiologic agent has previously circulated in the studied zone. In order to evaluate the immunity acquired against these viruses, a serological study was conducted in San Carlos Island. Two hundred and ten blood samples were obtained at random, among individuals of an age range between < 1 and 69 years, with and without antecedents of viral illness symptomatology at the moment of the epidemic outbreak, occurred in 1995. The samples were classified according to sex and age, and analyzed through the test of ELISA for specific IgG antibodies against the VEE and Dengue viruses. From the total of the samples processed, 116 (55.2%) were positive for VEE, affecting uniformly all age-groups with a slight masculine predominance. Likewise, 88 cases (41.9%) were determined positive for Dengue virus, affecting mainly the group ranging from 10 to 19 years. These results let us suggest that the epidemic outbreak occurred in 1995 at the Almirante Padilla Insular Municipality, had a double nature with both viruses being involved in the etiology of febrile cases.

Melatonin treatment enhances the efficiency of mice immunization with Venezuelan equine encephalomyelitis virus TC-83.

To determine whether treatment with melatonin (MLT) improves the efficiency of immunization against Venezuelan equine encephalomyelitis (VEE) virus, mice were vaccinated with TC-83 VEE virus and treated daily with MLT (1 or 5 mg/kg) starting 3 days before immunization, until 10 days after. IgM antibody titers were determined at days 7, 14, and 21 post-immunization. IL-10 levels were assayed at day 14 postvaccination. Treatment with MLT increased antibody titers 14 days after the immunization. IL-10 levels also increased with MLT treatment (1 and 5 mg/kg). Mice were challenged with live VEE virus at day 21 postimmunization, and viral titers were plaque assayed in chicken embryo fibroblasts 4 days after the infection. Following this challenge brain virus levels were significantly reduced. The results suggest that MLT treatment enhances the efficiency of mice immunization against VEE virus.

High intensity light increases olfactory bulb melatonin in Venezuelan equine encephalitis virus infection.

In mice infected with the Venezuelan equine encephalomyelitis (VEE) virus and exposed to high intensity light (2500 lux) with a 12 h light: 12 h dark photoperiod, a significant increase in the levels of melatonin in the olfactory bulb was observed. The significance of these findings deserves further studies to understand the mechanisms involved in this effect since the olfactory bulbs have been proposed as first portal for VEE virus entry into the CNS. The increase in melatonin content could represent one of the mechanisms of defense against the viral attack.

Melatonin prolongs survival of immunodepressed mice infected with the Venezuelan equine encephalomyelitis virus.

Male albino mice immunodepressed after the injection of dexamethasone (DEX) were inoculated intraperitoneally with the Guajira strain of Venezuelan equine encephalomyelitis (VEE) virus. Melatonin (MLT) was administered daily, at a dose of 500 micrograms/kg bodyweight, for 3 days before virus inoculation and 10 days after. Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) were determined in all the experimental groups (control, DEX, DEX + MLT, DEX + VEE, DEX + VEE + MLT, VEE and MLT). At day 6 after the virus inoculation, the survival rate was significantly increased from 0% in group DEX + VEE to 32.5% in the group of immunodepressed infected mice treated with MLT (DEX + VEE + MLT). By day 10 a survival rate of 10% was found in group DEX + VEE + MLT and 0% in group VEE. No alterations in IL-2 serum levels were observed. MLT increased GM-CSF in control and in DEX-treated mice. In the VEE virus-infected mice treated with DEX, serum levels of GM-CSF increased progressively from day 1 to 5 postinoculation. In contrast, the levels of GM-CSF in infected immunodepressed mice treated with MLT decreased significantly from day 1 to 5 postinoculation. At day 5 after viral inoculation, no differences were detected in the cerebral viral titres in groups VEE, DEX + VEE and DEX + MLT + VEE. These results show that MLT does not inhibit VEE viral replication in the brain of immunodepressed mice.

In mice the efficiency of immunization with Venezuelan Equine Encephalomyelitis virus TC-83 is transiently increased by dehydroepiandrosterone.

To determine whether treatment with dehydroepiandrosterone (DHEA) improves the efficiency of immunization against the Venezuelan Equine Encephalomyelitis (VEE) virus, mice were vaccinated with the TC-83 VEE virus. DHEA (10 mg/kg) was administered in a single dose, 4 hours before vaccination. IgM antibody titers were determined at days 7, 14 and 21 post-immunization. Treatment with DHEA increased antibody titers at day 14 after immunization. Mice were challenged with live VEE virus at day 21, and viral titers were plaque assayed in chicken embryo fibroblasts from days 2 to 5 post-infection. After the challenge, viremia decreased on day 2 and brain virus levels were reduced at day 4 in mice treated with DHEA. These results suggest that DHEA treatment could enhance the efficiency of immunization against VEE virus in mice.

[Viral agents in patients with infectious processes of the central nervous system]. / Agentes virales en pacientes con procesos infecciosos del Sistema Nervioso Central.

Local statistics report a great number of cases of neurological diseases of unidentified cause. The purpose of this research was to determine the presence of viral agents in patients with affection of the central nervous system, in Zulia State, Venezuela. In different health centers throughout the state, we collected 129 randomized samples of cerebrospinal fluid (CSF) and serum from patients ranging from 1 day to 41 years of age, showing symptoms of CNS disease and whose bacteriological test resulted negative. The serum/CSF albumin ratio was determined to exclude contaminated CSF samples, thus 54 optimal samples were obtained for the research. We determined serum IgM and CSF IgG specific for Venezuelan equine encephalomyelitis (VEE), Herpes simplex (HSV), Epstein Barr (EBV), Dengue, Rubella and Measles virus, through ELISA and indirect immunofluorescence techniques. Of the 54 samples studied, 33 (61.11%) were positive. %). The etiological agents implicated were VEE 14 cases (42.42%); HSV 11 cases (33.33%); EBV 5 cases (15.15%) and Dengue 3 cases (9.09%). We did not detect Rubella o Measles. Regarding the age distribution, the most affected group was that of children under 12 (83.34%). We analyzed the clinical manifestations and the CSF characteristics and did not find differences suggestive of an specific etiological diagnosis, even though certain signs could be considered early indications of CNS alterations due to viral causes. Our study shows that a large percentage of CNS affections of unknown etiology are produced by viral agents, indicating that in our region, most of this cases are not registered.