Machine Learning Models and Applications for Early Detection.

From the various perspectives of machine learning (ML) and the multiple models used in this discipline, there is an approach aimed at training models for the early detection (ED) of anomalies. The early detection of anomalies is crucial in multiple areas of knowledge since identifying and classifying them allows for early decision making and provides a better response to mitigate the negative effects caused by late detection in any system. This article presents a literature review to examine which machine learning models (MLMs) operate with a focus on ED in a multidisciplinary manner and, specifically, how these models work in the field of fraud detection. A variety of models were found, including Logistic Regression (LR), Support Vector Machines (SVMs), decision trees (DTs), Random Forests (RFs), naive Bayesian classifier (NB), K-Nearest Neighbors (KNNs), artificial neural networks (ANNs), and Extreme Gradient Boosting (XGB), among others. It was identified that MLMs operate as isolated models, categorized in this article as Single Base Models (SBMs) and Stacking Ensemble Models (SEMs). It was identified that MLMs for ED in multiple areas under SBMs' and SEMs' implementation achieved accuracies greater than 80% and 90%, respectively. In fraud detection, accuracies greater than 90% were reported by the authors. The article concludes that MLMs for ED in multiple applications, including fraud, offer a viable way to identify and classify anomalies robustly, with a high degree of accuracy and precision. MLMs for ED in fraud are useful as they can quickly process large amounts of data to detect and classify suspicious transactions or activities, helping to prevent financial losses.

[Predictive value of dipyridamole myocardial perfusion tomography on survival]. / Estratificación de riesgo de muerte a mediano plazo de pacientes evaluados por enfermedad coronaria con SPECT de perfusión miocárdica bajo efecto de dipiridamol.

BACKGROUND: Dipyridamole (DIP) is the most commonly employed pharmacological stressor for myocardial perfusion tomography (SPECT) in patients unable to reach an adequate work load. AIM: To assess the predictive capacity of DIP SPECT on survival. MATERIAL AND METHODS: We included 985 adults aged 66 ±11 years (45% women) with rest and DIP-SPECT. The main indications for the procedure were coronary artery disease (CAD) screening in 66% and known CAD in 33%. Participants were followed up for a median of 65 months (interquartile range 54 to 86 months). During the follow up, 261 deaths were recorded and 98% had a specified cause in their death certificate. RESULTS: Myocardial SPECT was abnormal in 44% of participants. Transient ischemic defects were observed in 34%, fixed defects concordant with infarction in 27% and post-stress systolic dysfunction in 23%. Twenty five percent of deaths were attributable to cardiac or ischemic cause and 22% to cancer. In a bivariate analysis, the hazard ratio (HR) of death of any cause was lower in females and higher in the presence of CAD. The multivariate analysis showed that being older than 46 years increased the HR of death of any cause. In a bivariate analysis, the HR for cardiac death was higher when the myocardial SPECT showed ischemia, necrosis or left ventricular dilation. In the multivariate analysis, post-stress left ventricular systolic function was associated with a lower risk of cardiac death. CONCLUSIONS: An abnormal myocardial SPECT, perfusion abnormalities, left ventricular systolic function or dilation are independent predictors of cardiac death in these participants.

[Polymorphisms of the pfmdr1 gene in field samples of Plasmodium falciparum and their association with therapeutic response to antimalarial drugs and severe malaria in Colombia]. / Polimorfismos del gen pfmdr1 en muestras clínicas de Plasmodium falciparum y su relación con la respuesta terapéutica a antipalúdicos y paludismo grave en Colombia.

INTRODUCTION: The pfmdr1 gene of Plasmodium falciparum has been described as a gene conferring resistance to several antimalarial drugs. In particular, polymorphisms on specific codons have been associated with resistance and treatment failure with cloroquine, amodiaquine and mefloquine. However, the role of these polymorphisms in treatment response to antimalarials remains unexplored in Colombia. Furthermore, the relationship of these polymorphisms to severe malaria is unknown. OBJECTIVE: This work studied the association of the Asn 86Tyr and Asp1246Tyr pfmdr1 polymorphisms with response to cloroquine, amodiaquine and mefloquine treatment in three municipalities of Antioquia, and severe malaria cases from the municipality Tumaco. MATERIALS AND METHODS: The polymorphisms were assessed by nucleic acid amplification followed by restriction length polymorphism analysis. RESULTS: The wild-type codon Asn 86 was detected in 97% of the clinical samples from the treatment response study. No association was detected between this polymorphism and treatment failure to the three antimalarials administered. The 1246Tyr polymorphism was detected with a higher frequency in the samples from Antioquia 92% (130/141) than in those from Tumaco 22% (20/89). However, again, no association was found between the presence of a specific polymorphism and the presence of severe malaria in the municipality of Tumaco. CONCLUSIONS: The 86Tyr and 1246Tyr polymorphisms of the pfmdr1 gene are not useful as predictors of treatment failure or severe malaria in the municipalities studied. In addition, we report for the first time, the presence of the mutant codon 86Tyr in field samples in South America.

Off-label prescription of drugs at hospital.

OBJECTIVES: To develop a procedure for management of off-label medications, and to analyze the treatments, indications, and hospital units which will request them more frequently, as well as which variables will have an impact on the authorization decision, and its economic impact. METHODS: A procedure was designed where clinicians would complete request forms and the Hospital Unit would prepare reports assessing their efficacy, safety, convenience, and cost. The request forms for the past five years were analyzed. RESULTS: A total of 834 applications were received, and 88.1% of these were accepted. The authorization rates were higher for Paediatric Units (95.7% vs. 86.6%; p<0.05). The reasons for considering prescriptions as off-label were: different indication (73.2%), different combination (10.2%), different line of treatment (8.6%) and different age (8%). A 73.4% of requests were for antineoplastic drugs, and the most frequently prescribed were rituximab (120) and bevacizumab (103). The quality of evidence supporting the prescriptions was moderate-low, though no direct relationship with the likelihood of approval was demonstrated (p = 0.413). The cost of the approved medications was 8,567,537 €, and the theoretical savings for those drugs rejected was of 2,268,642 €. There was a statistically significant decrease in the authorization rate (p < 0.05, Student's t test) when spending increased. CONCLUSIONS: The responsibility for assessing off-label prescriptions has fallen on the Pharmacy Unit. It has not been demonstrated that the quality of evidence represents a decisive variable for approval of treatment; on the other hand, age and cost have demonstrated a significant impact.

Objetivos: Desarrollar un proceso de gestión de medicamentos en condiciones fuera de ficha técnica y analizar los tratamientos, indicaciones y unidades clínicas que los solicitan, qué variables influyen en la decisión de autorización y su impacto económico. Métodos: Se diseñó un procedimiento según el cual los clínicos cumplimentarían las solicitudes, el Servicio de Farmacia redactaría los informes valorando su eficacia, seguridad, conveniencia y coste, y la dirección médica tomaría la decisión de aceptar o no su uso. Se analizaron las solicitudes de los últimos cinco años. Resultados: Se recibieron 834 solicitudes, autorizándose el 88,1%. Las tasas de autorización fueron mayores para los Servicios Pediátricos (95,7% frente a 86,6%; p < 0,05). Las razones por las que las prescripciones se consideraron fuera de ficha técnica fueron: diferente indicación (73,2%), combinación diferente (10,2%), línea diferente (8,6%) y edad diferente (8%). El 73,4% de las solicitudes fueron de antineoplásicos, siendo rituximab (120) y bevacizumab (103) los más prescritos. La calidad de la evidencia que avalaba las prescripciones fue moderada-baja, aunque sin demostrar relación directa con la probabilidad de aprobación (p = 0,413). El coste de los medicamentos aprobados fue de 8.567.537 € y el ahorro teórico de los denegados 2.268.642 €. El porcentaje de autorización disminuyó según aumentó el gasto de manera estadísticamente significativa (p < 0,05, test t de Student). Conclusiones: La responsabilidad de evaluación de las prescripciones fuera de ficha técnica ha recaído en los Servicios de Farmacia. La calidad de la evidencia no ha demostrado ser una variable decisiva para la aprobación de los tratamientos. En cambio, la edad y el coste sí que han demostrado influir significativamente.

Oxidative stress in patients with non-complicated malaria.

AIM: To compare oxidative stress in adults with non-complicated malaria and healthy controls. METHODOLOGY: We measured malondialdehyde (MDA), total antioxidant status (TAS), catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Oxidative stress was calculated based on MDA/TAS, MDA/GSH-PX and SOD/catalase indexes. RESULTS: Mean MDA in patients was 3.9 micromol/L (controls = 1.3 micromol/L). Mean TAS was 0.9 mmol/L in patients and controls. Malaria patients had less catalase activity when compared to controls (209.4 vs. 320.4 k/gr), while SOD and GSH-PX activity was higher (79.4 U/mL, 11,884.2U/L vs. 54.3 U/mL, 9,672.6 U/L). MDA/TAS index was 3.5 fold more in patients than in controls, MDA/GSH-PX and SOD/catalase indexes were increased by 6 and 2.8 fold. MDA levels and MDA/TAS index showed no differences according to malarial history, parasitaemia, Plasmodium species, parasite's stage, place of residence and drinking or smoking habits. CONCLUSIONS: During acute non-complicated P. falciparum or P. vivax malaria, we observed high oxidative stress. This resulted from lipid peroxidation rather than from a reduced TAS. We propose MDA/TAS index as a useful marker of oxidative stress during malaria infection.

Clinical and laboratory findings of Plasmodium vivax malaria in Colombia, 2001.

A descriptive study was carried out in 104 patients with Plasmodium vivax malaria, from the region of Turbo (Antioquia, Colombia). Clinical features and levels of hemoglobin, glycemia, serum bilirubin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), creatinine and complete blood cell profile were established. 65% of the studied individuals were men and their mean age was 23. Of all individuals 59% had lived in the region for > 1 year and 91% were resident in the rural area. 42% were farmers and 35% had a history of malaria. The mean parasitaemia was 5865 parasites/mm3. The evolution of the disease was short (average of 4.0 days). Fever, headache and chills were observed simultaneously in 91% of the cases while the most frequent signs were palmar pallor (46%), jaundice (15%), hepatomegaly (17%), and spleen enlargement (12%). Anemia was found in 39% of the women and in 51% of the men, 8% of individuals had thrombocytopaenia and 41% had hypoglycemia.

[Comparison between OptiMAL and the thick smear tests for malaria diagnosis in an endemic area during a non-epidemic period]. / Comparación de los métodos Optimal y gota gruesa para el diagnóstico de malaria en una zona endémica sin epidemia.

The capacity of Optimal to diagnose malaria was compared with the thick smear test in two representative samples, one with acute febrile syndrome (AFS) n = 107, and another diagnosed by thick smear test (AFS + M) n = 82. The samples were chosen from patients at the malaria diagnostic clinic in Turbo, Antioquia, Colombia, between June and August 2000. The study was designed to be descriptive, prospective, and cross-sectional. The two tests were applied simultaneously in the AFS group (parallel, double blind design), and in sequential form in the AFS + M group. The thick smear test was the standard test. Optimal tests were carried out according to the manufacturer's instructions. In the parallel design, Optimal showed, for Plasmodium falciparum, a sensitivity of 40% [95% CI: 18-67], a specificity of 98% (95% CI: 92-100) and positive and negative predictive values of 75% (95% CI: 36-96) and 91% (95% CI: 83-96%), respectively. For Plasmodium vivax, it showed a sensitivity of 97% (95% CI: 82-100), a specificity of 89% (95% CI: 80-95) and positive and negative predictive values of 79% (95% CI: 62-90) and 98% (95% CI: 91-100). With the sequential design, Optimal showed a sensitivity of 67% (95% CI: 52-79) and 97% (95% CI: 83-100) for P. falciparum and P. vivax, respectively. For P. falciparum, the sensitivity was directly proportional to the parasitemia, while the sensitivity for P. vivax was independent from the parasitemia. The diagnostic values and operative characteristics of the thick smear test surpassed the Optimal test in its sensitivity for P. falciparum; the specificities were similar. Both tests were nearly identical in their diagnostic capacity for P. vivax. These results recommend that the thick smear test be retained as a routine or reference test for malaria diagnosis, with Optimal used as an ancillary test.

[Gametocyte levels in response to differing malaria treatments in two municipalities of Colombia]. / Gametocitemia de Plasmodium falciparum según la respuesta terapéutica a sulfadoxina-pirimetamina y cloroquina en dos municipios de Antioquia, Colombia.

Plasmodium falciparum gametocyte levels are influenced by level of regional endemicity, the antimalarial treatment, and the therapeutic response of patients. Few previous studies have related these factors in Colombia. Here, gametocytaemia was evaluated with respect to two treatment schemes (sulfadoxine/pyrimethamine and sulfadoxine/pyrimethamine plus chloroquine), the patient response (adequate or failure), and the locality (two areas of varying case frequency). One hundred forty-eight residents of Turbo and Zaragoza (Antioquia), all with uncomplicated malaria, were evaluated. The gametocytaemia and the rates of clinical malaria at the beginning of treatment were greater in Turbo than in Zaragoza. No statistically significant differences in the gametocytaemia by treatment schemes or therapeutic responses were noted, although the patients who received SP had more gametocytes than those treated with SP+CQ. Gametocytaemia was not correlated with asexual parasitemia or sex and age of patient. The difference in the level of gametocytaemia between Turbo and Zaragoza appears to be influenced by the time elapsed between the appearance of symptoms and the beginning of treatment.

[Therapeutic efficacy of 3 treatment protocols for non-complicated Plasmodium falciparum malaria, Antioquia, Colombia, 2002]. / Eficacia terapéutica de tres esquemas de tratamiento de malaria no complicada por Plasmodium falciparum, Antioquia, Colombia, 2002.

High resistance of Plasmodium falciparum malaria to chloroquine poses malaria as a major public health problem in Colombia. In this context, the therapeutic response of uncomplicated P. falciparum malaria patients to chloroquine (CQ), sulfadoxine/pirymethamine (SDXP) and combined therapy (SDXP/CQ) was evaluated according to the WHO/PAHO protocols of 1998. The comparisons were based on a sample of 160 patients with uncomplicated P. falciparum malaria in Turbo and Zaragoza (Antioquia, Colombia). Patients were randomly assigned each of the treatment categories. The results were statistically similar in each municipality. In Turbo percentage of treatment failure was 87.5%, 22.2% and 22.6% for CQ, SDXP and SDXP/CQ, respectively, whereas in Zaragoza, the corresponding treatment failure was 77.7%, 26.5% and 12.1%. During follow up, 50% of subjects with late treatment failure were asymptomatic in Turbo, while 33.3% were asymptomatic in Zaragoza. A high level of treatment failure occurred with CQ monotherapy, while SDXP and SDXP/CQ had acceptable levels of failure, i.e., below 25%. The high percentage of late treatment failure in asymptomatic patients may contribute to increased risk of persistent transmission.

Características de la imagen con 68Ga-PSMA PET/CT. Biodistribución normal y anormal / Image features with 68Ga-PSMA PET/CT. Normal and abnormal biodistribution

Un sistema de PET/CT integrado o multimodal es una combinación física de PET y CT que incluye adquisición secuencial de porciones de PET y CT. El paciente permanece en la misma posición durante los dos exámenes. Un examen 68Ga-PSMA PET/CT puede cubrir diversos rangos de imágenes coaxiales1. PSMA es una proteína transmembrana presente principalmente en todos los tejidos prostáticos. Este articulo tiene como objetivo ayudar a los médicos imagenólogos para clínicos, a reconocer las imágenes de 68Ga-PSMA PET/CT mostrar características propias y ofrecer conocimientos generales de su interpretación en el área de diagnósticos dirigido al cáncer de próstata.

Estratificación de riesgo de muerte a mediano plazo de pacientes evaluados por enfermedad coronaria con SPECT de perfusión miocárdica bajo efecto de dipiridamol / Predictive value of dipyridamole myocardial perfusion tomography on survival

Background: Dipyridamole (DIP) is the most commonly employed pharmacological stressor for myocardial perfusion tomography (SPECT) in patients unable to reach an adequate work load. Aim: To assess the predictive capacity of DIP SPECT on survival. Material and Methods: We included 985 adults aged 66 ±11 years (45% women) with rest and DIP-SPECT. The main indications for the procedure were coronary artery disease (CAD) screening in 66% and known CAD in 33%. Participants were followed up for a median of 65 months (interquartile range 54 to 86 months). During the follow up, 261 deaths were recorded and 98% had a specified cause in their death certificate. Results: Myocardial SPECT was abnormal in 44% of participants. Transient ischemic defects were observed in 34%, fixed defects concordant with infarction in 27% and post-stress systolic dysfunction in 23%. Twenty five percent of deaths were attributable to cardiac or ischemic cause and 22% to cancer. In a bivariate analysis, the hazard ratio (HR) of death of any cause was lower in females and higher in the presence of CAD. The multivariate analysis showed that being older than 46 years increased the HR of death of any cause. In a bivariate analysis, the HR for cardiac death was higher when the myocardial SPECT showed ischemia, necrosis or left ventricular dilation. In the multivariate analysis, post-stress left ventricular systolic function was associated with a lower risk of cardiac death. Conclusions: An abnormal myocardial SPECT, perfusion abnormalities, left ventricular systolic function or dilation are independent predictors of cardiac death in these participants.

Narratives and Resilience Life Stories as a Methodological Mediation to Rebuild the Wounded Existence / Narrativas y resiliencia las historias de vida como mediación metodológica para reconstruir la existencia herida

Resumen Este artículo busca poner en diálogo la categoría de resiliencia con el enfoque narrativo, desde un acercamiento a las historias de vida como mediación metodológica cualitativa de particular significación, para leer de manera comprensiva lo que acontece a los sujetos cuando relatan la vida contando historias, reconociendo que el accenso a la humanidad como construcción subjetiva pasa por esa capacidad para relatar la propia vida, atravesada por experiencias límites. La atención se pone en las mismas historias de vida como mediación y su significación para la investigación en resiliencia. El método de trabajo se apoyó en una revisión documental, con un trabajo de análisis categorial, buscando elementos teóricos y metodológicos que fortalezcan la investigación en resiliencia desde el enfoque narrativo.

Abstract This paper establishes a dialogue between the resilience and the narrative perspective, from an approach to life stories as a qualitative methodological mediation of particular significance. It aims to read comprehensively what happens to subjects when they relate life-telling stories, recognizing that lighting the human fact as a subjective construction involves the capability to relate one's life, permeated by borderline experiences. Attention is focused in life experiences as mediation, and their signification is in consideration for resilience research. The method was based on a documentary review, and a categorical analysis, searching for theoretical and methodological elements that strengthen resilience research from the narrative approach.

Determinación social de la desnutrición y elretardo sicomotor en preescolares de Urabá(Colombia). Un análisis con la Epidemiología Crítica / Social determination of malnutrition and psychomotor retardation in preschool children in Urabß (Colombia). An analysis based on Latin American Social Epidemiology

Objetivo: evaluar condiciones de vida familiares, el estadonutricional y el desarrollo infantil (di) de preescolares de Urabßy explicar los hallazgos según la determinaci¾n social de lasalud-enfermedad de la EpidemiologÝa CrÝtica. MetodologÝa:encuesta de prevalencia. Usamos 8 cuestionarios sobrecondiciones de vida. Evaluamos indicadores antropomÚtricoscalculados con Epinut 6.0 y usamos la prueba tamiz EscalaAbreviada de Desarrollo para evaluar el DI. Resultados: seevaluaron 200 familias y 46 ni±os (2,5-4 a±os). Las condicionesde vida son muy deficientes en los procesos individualesfamiliaresy los procesos grupales (modo de vida). Unos yotros estßn determinados por el sistema socio-econ¾mico,jurÝdico-polÝtico e ideol¾gico-cultural vigente. Los riesgosde desnutrici¾n, evaluados con -1 y -2 desviaciones estßndarfueron, respectivamente: cr¾nica 76% y 37%; global 61% y17%; aguda 26% y 0%. La frecuencia de retardos madurativo ypatol¾gico fueron respectivamente: en motricidad gruesa 17%y 6%; en motricidad fina 50% y 26%; en audici¾n-lenguaje40% y 34%; en desarrollo personal-social 57% y 6%. Ningúncoeficiente de desarrollo infantil se asoci¾ con desnutrici¾ncr¾nica. Las altas deficiencias nutricionales y de desarrollo delos ni±os estßn l¾gicamente determinadas por las condicionesde vida de las familias y el grupo social. Conclusiones: losresultados revelan deterioro nutricional y sicomotor profundosprecoces. Las condiciones de vida de este grupo socialexplican la situaci¾n hallada. Urge la intervenci¾n del Estadopara afrontar y paliar tan grave problema colectivo...

Objective: to evaluate the family home life conditions thenutricional status and child development (cd) of pre-schoolchildren from Urabß, and to explain the findings accordingto health-disease determinants from Social Epidemiology.Methodology: prevalence survey. The study used 8 differentquestionnaires concerning living conditions. Anthropometricindicators calculated using Epinut 6.0 were assessed and theAbbreviated Scale Development (asd) was used to evaluatecd. Results: 200 families and 46 children were evaluated,ranging in age from 2.5 to 4 years. Living conditions are highlydeficient in individual and family processes, as well as groupprocesses (way of life), and all are determined by the existingsocio-economic, legal-political and ideological-culturalsystems. The risks of malnutrition, evaluated using -1 and -2standard deviation, were, respectively: chronic (height/ageratio) 76% and 37%; overall (weight/age) 61% and 17%; andacute (weight/height index) 26% and 0%. The frequency ofdevelopmental and pathological delays were, respectively: forgross motor skills 17% and 6%; for fine motor skills 50% and26%; for hearing-language 40% and 34%; and for personalsocialdevelopment 57% and 6%. There is no cd coefficientassociated with chronic malnutrition. High nutritionaland developmental deficiencies in children are, naturally,determined by the living conditions of the families and socialgroups to which these children belong. Conclusions: theresults reveal serious and precocious nutritional and psychomotor impairments, which can be explained by the livingconditions of this social group. Urgent state interventionis required in order to address and mitigate such a seriouscollective problem...

[Blood levels of sulfadoxine and pyrimethamine, according to the malaria-treatment response, in two municipalities of Antioquia, Colombia]. / Concentraciones sanguíneas de sulfadoxina y pirimetamina según la respuesta terapéutica antimalárica, en dos municipios de Antioquia, Colombia.

PROBLEM: There has been a constant increase in the level of therapeutic failure of the sulfadoxine-pyrimethamine (SP) combination for treating uncomplicated Plasmodium falciparum malaria. OBJECTIVE: To use high-performance liquid chromatography to quantify blood levels of SP in patients with good clinical response and in patients who did not respond to treatment. METHODS: This experimental study was carried out in 2002 in Turbo and Zaragoza, two municipalities in the department of Antioquia in Colombia. There were 79 patients (45 in Turbo and 34 in Zaragoza), including both men and women, who ranged in age from 1 year to 60 years. All the patients had uncomplicated Plasmodium falciparum malaria, with a parasite density of 500 to 50,000 parasites/microL. The patients were each randomly assigned to a treatment group. The treatment groups were not blinded; the physician who provided the medication also evaluated the therapeutic response. The treatment consisted of a single combination dose of sulfadoxine (25 mg/kg) and pyrimethamine (1.25 mg/kg) in tablets (500 mg of sulfadoxine and 25 mg of pyrimethamine). Clinical-parasitological follow-up was carried out for 21 days. Blood levels of sulfadoxine and pyrimethamine were measured two hours after the treatment was given and also the day of treatment failure, if that occurred. RESULTS: Two hours after the treatment was given, the median blood level of sulfadoxine was 136.6 micromol/L in the patients who later showed a good clinical response, and it was 103.4 micromol/L among those who did not respond to treatment (P = 0.13). The medians for pyrimethamine were 848.4 nmol/L in patients with a good clinical response and 786.1 nmol/L in patients with treatment failure (P = 0.40). There were no significant differences in drug levels between the early-failure cases and the late-failure cases. The linear correlation between the blood levels of sulfadoxine and pyrimethamine was close to zero (r = 0.13). CONCLUSIONS: Between 1998 and 2002, treatment failure with the SP combination increased from 13% to 22% in Turbo, and from 9% to 26% in Zaragoza. The lack of response in 2002 could not be explained by lower blood levels of the medications.

[Malaria in children: links between nutrition and immunity]. / Malaria en niños: relaciones entre nutrición e inmunidad.

OBJECTIVE: To explore some relationships among immunity, nutrition, and malaria in a group of children from a population with a high endemic incidence of malaria. METHODS: This pilot descriptive prospective cross-sectional study was carried out in 1998 in the municipality of El Bagre, Antioquia, Colombia. Both boys and girls were studied in two groups: one group of 51 children had malaria and another group of 49 did not have malaria. The children with malaria had symptoms or signs of malaria and a positive thick blood film. The comparison group of 49 children without malaria (no signs or symptoms of malaria and a negative thick blood film) were chosen at random at government schools or children's centers. For the study the following indices were calculated: weight-for-age, height-for-age, and weight-for-height. Also measured were the blood-serum concentrations of: albumin, prealbumin, apolipoprotein A1 (apoA1), transferrin, zinc, vitamin A, immunoglobulins G and M, interleukin-10 (IL-10), tumor necrosis factor-alpha, interferon-gamma, and lymphocyte populations. RESULTS: Of the children studied, 69% presented some risk of malnutrition, and 63% had some risk of chronic malnutrition. With regard to the immunity and biochemical variables, the children with malaria had less apoA1 and albumin and more IL-10 than did the children without malaria. All the biochemical variables showed lower averages in the group with malaria, risk of malnutrition, and immune or biochemical changes, while all the immunity variables had higher averages in that same group of children. CONCLUSIONS: 1) The high frequency of chronic malnutrition found clearly indicates the need for food supplementation measures. 2) The low values of prealbumin found could be due to the frequent bacterial or viral infections reported. 3) The serious vitamin A deficiency found calls for a supplementation program. 4) An association was found between low apoA1 values and the presence of malaria, but which one follows from the other is not known. 5) No relationship was observed between the anthropometric indicators of risk of malnutrition and the possible biochemical markers of malnutrition. 6) We found high levels of IL-10 in the children with malaria; this is the first time that this has been reported for Plasmodium vivax.

Evaluation of clastogenic potential of the antimalarial plant Solanum nudum.

Compounds isolated from Solanum nudum have shown in vitro antimalarial activity against the FCB-2 strain of Plasmodium falciparum. Diosgenone (C27H40O3) the main component isolated from the hexane extract and an aqueous extract were evaluated to measure their clastogenic potential using the micronucleus test. Three concentrations (16, 32 and 64 g/kg of weight) of the aqueous extract were administered intraperitoneally into mice, (the highest concentration corresponded to 80% LD50) and diosgenone solubilized in olive oil was inoculated at the highest concentration possible (11.187 g/kg of weight). After administration of the compounds, no induction of micronucleus was observed either in polychromatic or normochromatic erythrocytes. Interestingly, a reduction of 51% in the young/mature erythrocytes ratio was seen in cells treated with aqueous extract. We conclude that neither diosgenone nor the aqueous extract have clastogenic activity, and that the aqueous extract showed some toxicity at the above mentioned concentrations. These results are significant since diosgenone could be a new therapeutic alternative for the treatment of malaria.

Inhibition of P. falciparum by steroids isolated from Solanum nudum.

Resistance to antimalarials has been widely reported and constitutes a major problem around the world. In Colombia, resistance of P. falciparum to chloroquine has been reported as 47%-97%, to amodiaquine 3%-7% and to sulfadoxine-pyrimethamine as 9%-13%. The search for new antimalarials is a priority and with this aim we studied the in vitro antimalarial activity of plants used by traditional healers. Incorporation of (3)H-hypoxanthine by the strain FCB-2 of P. falciparum was used to measure the degree of inhibition produced by the steroids SN-1 tumacone A (C(29)H(44)O(5)), SN-2 tumacone B (C(27)H(42)O(4)), SN-3 tumacoside A (C(35)H(54)O(10)), and SN-4 tumacoside B (C(33)H(52)O(9)). All compounds were obtained from the dried stems and leaves of Solanum nudum. The mean growth inhibition of P. falciparum was 71%, 56%, 21% and 12% with each of the compounds SN-1, SN-2, SN-3 and SN-4. These results constitute an important discovery since they may account for the antimalarial properties of extracts of Solanum nudum by a sensitive method. Future work should include study of the in vivo anti-malarial effect of these extracts.

Retinol, estado del hierro, malaria y parasitos intestinales: relación por medio de las citocinas TH1/TH2 / Retinol levels, iron status, malaria and intestinal parasites: TH1/TH2 cytokines relationship

Introducción: La malaria, la anemia y la parasitosis intestinal coexisten y constituyen problemas de salud pública en Colombia. Datos disponibles en la literatura biomédica llevan a pensar que estos problemas no son aislados sino que estßn interrelacionados. Por otra parte, los suplementos de retinol han sido efectivos para reducir la mortalidad infantil, con disminución de complicaciones en niños palúdicos, posiblemente por efectos del retinol sobre la función inmune, desviando la respuesta de citocinas hacia un patrón TH2, que también protege de desarrollar anemia grave. Esta revisión tiene como objetivo describir parte de las relaciones vistas en la literatura biomédica mundial, entre retinol y malaria, retinol y anemia, retinol, malaria y parasitosis intestinal, anemia y malaria y mostrar la mediación de estas interrelaciones por el patrón de citocinas TH1/TH2 en sujetos con malaria. Metodología: Se consultaron las siguientes bases de literatura biomédica: Medline, Lilacs, Spingerlik, Md Consultant, Web of Science, Ovid, Scient Direct, Ebsco y Cochrane. También se buscó información para documentar la prevalencia de desnutrición, deficiencia subclínica de retinol, anemia y malaria en niños colombianos, lo mismo que sobre el papel antinfeccioso del retinol.Resultados: Existe asociación entre parasitosis intestinal y malaria; algunos estudios indican que los helmintos predisponen a contraer malaria en niños. De otro lado, los parßsitos mencionados, también se han relacionado con anemia y bajas concentraciones plasmßticas de retinol, que a la vez se asocian con malaria. Sin embargo, no se encontró información que relacione simultaneamente todos estos tópicos y que muestre la respuesta de citocinas TH1/TH2 como la articulación de todos ellos.

Introduction: Malaria infection, anaemia and intestinal parasitism, are important public health problems in Colombia. Available data suggests that these are not separate conditions, but interrelated. On the other hand, retinol supplementation successfully decreases mortality in children. In malaria endemic areas, this supplement reduces severe malaria in children, due to immune modulation by retinol. For example, retinoic acid induced a bias towards a TH2 immune response, an event that is associated with protection against severe anaemia. This review aimed at describing some relationships, reported in global biomedical literature, between retinol and malaria; retinol and anaemia; retinol, malaria and intestinal parasites; anaemia and malaria; and to how the TH1/TH2 cytokine pattern in individuals with malaria changes according to retinol supplementation. Methods: The following biomedical literature databases were consulted: Medline, Lilacs, Spingerlik, Md. Consultant, Web of Science, Ovid, Scient Direct, Ebsco and Cochrane. Information documenting prevalence of malnutrition, subclinical retinol deficiency, anaemia and malaria in Colombian children, as well as papers on the anti-infectious role of retinol were also. Results: A relationship between malaria and intestinal parasitic infections was reported. Some studies indicate that helminth infection predispose children to suffer malaria. On the other hand, these intestinal parasites have also been associated with anaemia and low retinol plasma concentrations, which in turn are associated with malaria. No co-relation regarding a simultaneous link between all these conditions, and the TH1/TH2 balance was observed. Conclusions: The study of associations between malaria, anaemia, intestinal parasite infections and low retinol level, with the TH1/TH2 cytokine response as centerpiece is essential to prevent or provide early treatment.

Polimorfismos del gen pfmdr1 en muestras clínicas de Plasmodium falciparum y su relación con la respuesta terapéutica a antipalúdicos y paludismo grave en Colombia / Polymorphisms of the pfmdr1 gene in field samples of Plasmodium falciparum and their association with therapeutic response to antimalarial drugs and severe malaria in Colombia

Introducción. El gen pfmdr1 de Plasmodium falciparum se describió como un gen de resistencia a diversos antipalúdicos. Sin embargo, no se han estudiado el papel de su polimorfismo en la respuesta terapéutica al tratamiento con antipalúdicos en Colombia, ni su relación con paludismo grave. Objetivos. Este trabajo determinó la asociación entre los polimorfismos Asn86Tir y Asp1246Tir del gen pfmdr1 con la respuesta terapéutica a cloroquina, amodiaquina y mefloquina, en tres municipios antioqueños, y la asociación de estos polimorfismos con paludismo grave en muestras de pacientes del municipio de Tumaco. Materiales y métodos. Los polimorfismos del gen pfmdr1 se determinaron mediante amplificación de ácidos nucleicos y análisis con enzimas de restricción. Resultados. El alelo silvestre Asn86 se encontró en 97 por ciento (137/141) de las muestras en el estudio de respuesta terapéutica a cloroquina, amodiaquina y mefloquina; no se observó ninguna asociación entre su presencia y la falla terapéutica como sí lo reportan otros autores. El alelo 1246Tir se encontró en una alta proporción en el estudio de respuesta terapéutica, tanto en las muestras del día cero como en los del día de la falla después del tratamiento con los antipalúdicos. Conclusiones. Los polimorfismos 86Tir y 1246Tir en el gen pfmdr1 no son útiles como factores de predicción de falla terapéutica o paludismo grave en los municipios estudiados. Este estudio describe por primera vez la presencia del alelo 86Tir en cuatro muestras clínicas de Suramérica.

Introduction. The pfmdr1 gene of Plasmodium falciparum has been described as a gene conferring resistance to several antimalarial drugs. In particular, polymorphisms on specific codons have been associated with resistance and treatment failure with cloroquine, amodiaquine and mefloquine. However, the role of these polymorphisms in treatment response to antimalarials remains unexplored in Colombia. Furthermore, the relationship of these polymorphisms to severe malaria is unknown. Objective. This work studied the association of the Asn86Tyr and Asp1246Tyr pfmdr1 polymorphisms with response to cloroquine, amodiaquine and mefloquine treatment in three municipalities of Antioquia, and severe malaria cases from the municipality Tumaco. Materials and methods.The polymorphisms were assessed by nucleic acid amplification followed by restriction length polymorphism analysis. Results. The wild-type codon Asn86 was detected in 97% of the clinical samples from the treatment response study. No association was detected between this polymorphism and treatment failure to the three antimalarials administered. The 1246Tyr polymorphism was detected with a higher frequency in the samples from Antioquia 92% (130/141) than in those from Tumaco 22% (20/89). However, again, no association was found between the presence of a specific polymorphism and the presence of severe malaria in the municipality of Tumaco. Conclusions. The 86Tyr and 1246Tyr polymorphisms of the pfmdr1 gene are not useful as predictors of treatment failure or severe malaria in the municipalities studied. In addition, we report for the first time, the presence of the mutant codon 86Tyr in field samples in South America.