BACKGROUND Rapid urbanisation in difficult socio-economic conditions such as inadequate housing infrastructure, lack of public services, improper sanitation, and poor water drainage systems in vegetation-rich areas lead to ecological conditions that are conducive to the breeding of mosquitoes and transmission of malaria, in semi-urban and urban settings. OBJECTIVES This study aimed to describe the cases of malaria that were reported in the peri-urban areas of Pereira (Colombia), between 2008 and 2015. METHODS A retrospective study was conducted using data from the Malaria Surveillance System 2009-2015 and an outbreak study (between December 2008 and March 2009). Frequency distributions and summary measures, as well as univariate analysis were performed for all the variables in consideration. The annual parasite index (API) was calculated. FINDINGS Data on 214 cases were obtained from the surveillance system. A majority of the cases were reported in men (63.1%), followed by in children < 15 years (23.8%), and were caused predominantly by Plasmodium vivax (86.0%), with most of the infection occurring in the urban areas (52.8%) of Pereira. The API, by sex and age group, was higher among men ≥ 80 years. The outbreak study reported 14 cases of malaria in rural/peri-urban neighborhoods, and it was observed that the anopheline breeding sites were in close proximity to the houses in these areas. This population did not use protective measures against mosquitoes and chemical control was conducted through residual and spatial insecticide spraying. MAIN CONCLUSIONS This study suggested the presence of autochthonous malaria transmission, in Pereira, between 2008 and 2015, most of which were cases of P. vivax. A greater intensity was observed between 2008 and 2009 when malaria was possibly reintroduced to the region. During the years of the study, a gradual decrease in the number of reported cases of malaria was observed in Pereira, except for the time period between 2008 and 2009 when a spike was noted (estimated using the API); this was most likely caused by an outbreak. Interventions that are more aggressive in nature are required to prevent further malarial transmission and dissemination.

Resumen Introducción: Los Errores Innatos del metabolismo (EIM) representan un importante problema de salud pública debido a limitaciones en el tratamiento y diagnóstico oportuno, la pobre calidad de vida de los pacientes afectados, así como la muerte infantil prematura. Comparada con los métodos clásicos, la espectrometría de masas en tándem (MS/MS) ha permitido la evaluación simultánea de múltiples metabolitos asociados con EIM, con una alta sensibilidad, baja proporción de falsos positivos y alto rendimiento. Objetivos: Determinar los niveles de concentración de aminoácidos y acilcarnitinas en sangre de recién nacidos de Colombia, para establecer los valores normales para usarlos como referencia en el diagnóstico de EIM. Métodos: Aquí, se describe la implementación de un método para determinar aminoácidos, acilcarnitinas y succinilacetona en gotas de sangre seca de recién nacidos usando MS/MS, y su aplicación en un estudio de corte transversal realizado en 891 neonatos sanos de las ciudades de Cali y Quibdó. Resultados: Se evaluaron 57 analitos que permiten el diagnóstico de más de 40 patologías diferentes. El método mostró ser lineal, preciso y exacto. Se incluyeron neonatos sanos de 1-18 días de edad, 523 de Cali y 368 de Quibdó, 52% hombres y 48% mujeres. Se observaron diferencias en los niveles de concentración de aminoácidos y acilcarnitinas relacionadas con la edad, mientras que no se encontraron diferencias significativas por sexo. Conclusión: El estudio ha contribuido a revelar los niveles usuales de concentración de aminoácidos, acilcarnitinas y succinilacetona que pueden ser usados como referencia para el establecimiento del programa de tamizaje neonatal metabólico en Colombia.

Abstract Introduction: Inborn errors of metabolism (IEM) represent an important public health problem due to current diagnosis and treatment limitations, poor life quality of affected patients, and consequent untimely child death. In contrast to classical methods, tandem mass spectrometry (MS/MS) has allowed simultaneous evaluation of multiple metabolites associated with IEM offering higher sensitivity, low false positive rates and high throughput. Aims: Determine concentration levels for amino acids and acylcarnitines in blood of newborns from Colombia, to establish reference values for further use in diagnosis of IEM. Methods: Implementation of a method to determine amino acids, acylcarnitines and succinylacetone in newborn dried blood spots using MS/MS, and its application in a cross-sectional study conducted in 891 healthy neonates from Cali and Quibdo cities is described. Results: fifty-seven analytes that allow the diagnosis of more than 40 different pathologies were tested. The method showed to be linear, precise and accurate. Healthy neonates 1-18 days of age were included, 523 from Cali and 368 from Quibdo; 52% male and 48% female. Age-related differences on the concentration levels of amino acids and acylcarnitines were observed whereas no significant differences by gender were found. Conclusion: The study has contributed to reveal the usual concentration levels of amino acids, acylcarnitines and succinylacetone that could be used as reference for the establishment of a newborn metabolic screening program in Colombia.

Gold-mining may play an important role in the maintenance of malaria worldwide. Gold-mining, mostly illegal, has significantly expanded in Colombia during the last decade in areas with limited health care and disease prevention. We report a descriptive study that was carried out to determine the malaria prevalence in gold-mining areas of Colombia, using data from the public health surveillance system (National Health Institute) during the period 2010-2013. Gold-mining was more prevalent in the departments of Antioquia, Córdoba, Bolívar, Chocó, Nariño, Cauca, and Valle, which contributed 89.3% (270,753 cases) of the national malaria incidence from 2010-2013 and 31.6% of malaria cases were from mining areas. Mining regions, such as El Bagre, Zaragoza, and Segovia, in Antioquia, Puerto Libertador and Montelíbano, in Córdoba, and Buenaventura, in Valle del Cauca, were the most endemic areas. The annual parasite index (API) correlated with gold production (R2 0.82, p < 0.0001); for every 100 kg of gold produced, the API increased by 0.54 cases per 1,000 inhabitants. Lack of malaria control activities, together with high migration and proliferation of mosquito breeding sites, contribute to malaria in gold-mining regions. Specific control activities must be introduced to control this significant source of malaria in Colombia.

La malaria es una de las enfermedades transmisibles de mayor impacto socio-económico a escala mundial, y es inducida por parásitos del género Plasmodium transmitidos por mosquitos del genero Anopheles. El Plasmodium vivax ocupa el segundo lugar en prevalencia mundial, pero es la especie más frecuente en América Latina y otras regiones del planeta. Se considera que las vacunas representan una estrategia costo-efectiva para el control de enfermedades transmisibles y que podrían complementar las demás medidas de control de la malaria; sin embargo, la complejidad química e inmunológica del parasito han dificultado el desarrollo de vacunas efectivas. La reciente accesibilidad a los genomas de varias especies de Plasmodium, y el desarrollo de herramientas bioinformáticas están permitiendo la selección de numerosas proteínas y el análisis de su potencial inmunológico. Aquí revisamos las estrategias recientes para el descubrimiento de nuevos antígenos para el desarrollo vacunas contra la malaria.

Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden Worldwide. Plasmodium vivax is the second species of malaria Worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatic tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.

The thrombospondin related adhesion protein (TRAP) is a malaria pre-erythrocytic antigen currently pursued as malaria vaccine candidate to Plasmodium falciparum. In this study, a long synthetic peptide (LSP) representing a P. vivax TRAP fragment involved in hepatocyte invasion was formulated in both Freund and Montanide ISA 720 adjutants and administered by IM and subcutaneous routes to BALB/c mice and Aotus monkeys. We measured specific humoral immune responses in both animal species and performed a sporozoite challenge in Aotus monkeys to assess the protective efficacy of the vaccine. After immunization both mice and Aotus seroconverted as shown by ELISA, and the specific anti-peptide antibodies cross reacted with the parasite in IFAT assays. Only two out of six immunized animals became infected after P. vivax sporozoite challenge as compared with four out of six animals from the control group. These results suggest that this TRAP fragment has protective potential against P. vivax malaria and deserves further studies as vaccine candidate.

Objetivo: describir las características clínicas e inmunológicas básicas en una cohorte de 74 pacientes del suroccidente colombiano con síndrome de Sjögren primario (SSP). Material y métodos: estudio descriptivo de una cohorte de pacientes basados en un protocolo para recolección de datos del estudio "Polimorfismo de los receptores Fc gamma IIA, IIIA y IIIB en pacientes colombianos con síndrome de Sjögren primario". Mediciones: estadística descriptiva de medias, rangos, desviaciones estándar (DE) y porcentajes. Resultados: se incluyeron 74 pacientes con diagnóstico de SSP evaluados en la unidad de reumatología, Fundación Clínica Valle del Lili, Cali, Colombia, de agosto de 2001 a septiembre de 2006. La edad promedio fue de 51.32 años con rango de 25 a 88 y DE de 13.37 años. Una duración promedio de la enfermedad al momento del diagnóstico de 4.5 con un rango de 1 a 21 y DE de 11.5 años. Setenta y dos pacientes fueron mujeres (97.3%). Las manifestaciones clínicas exocrinas de superficie se presentaron en los 74 pacientes (100%), exocrinas de órgano interno en 25 (33.8%), monoclonal de células B en uno (1.4%), no exocrinas inflamatorias-vasculares en 67 (90.5%), vasculares no inflamatorias en 30 (40.5%), inducidas por mediadores en 49 (66.2%) y endocrinas autoinmunes en 23 (31.1%). Anticuerpos antinucleares fueron positivos en 60 pacientes (81.1%), anticuerpos anti-Ro/SS-A en 55 (74.3%), anticuerpos anti-La/SS-B en 26 (35%), factor reumatoide en 39 (52.7%) y manifestaciones posiblemente mediadas por complejos inmunes en 27 (36.5 %). El diagnóstico de SSP se confirmó por biopsia de glándula salivar menor con un focus score promedio de 3. Conclusión:el presente informe constituye la descripción general de una cohorte de pacientes del suroccidente colombiano con SSP. La forma de presentación clínica y de laboratorio fue similar a otras series de pacientes colombianos de otras regiones geográficas.

Objective: to describe the clinical and immunological characteristics of a cohort of patients with Primary Sjögren´s Syndrome (PSS) in the Southwest part of Colombia. Materials and methods: a cohort of patients based in data collected from the study "Fc g receptor IIA, IIIA and IIIB polymorphisms in Colombian Primary Sjögren´s Syndrome" mean, ranges, standard deviation (SD) and percentages were used for data analysis. Results: we included 74 colombian patients with PSS seen in the Rheumatology unit of the Fundación Valle del Lili, Cali, Colombia, between August 2001 and September 2006. 72 women (97.3%). The mean age was 51.32 years (range: 25 to 88, SD: 13.37), mean duration of disease 4.5 years (range: 1 to 21, SD: 11.5). Clinical disease manifestations: surface exocrine disease was seen in 74 patients (100%), exocrine internal organ manifestation in 25 (33.8%), monoclonal B lymphocytes! in one (1.4%), inflammatory-vascular disease in 67 (90.5%), non inflammatory vascular 30 (40.5%), mediator induced signs and symptoms in 49 (66.2%) and autoimmune endocrine disease in 23 (31.1%). Antinuclear antibodies were positive in 60 patients (81.1%), anti-Ro/SS-A antibodies in 55 (74.3%), anti-La/SS-B antibodies in 26 (35%) and rheumatoid factor positive in 39 (52.7%). The possible "immune complex deposit mediated manifestation" in 27(36.5%). The PSS diagnosis was confirmed by minor salivary gland biopsy with a mean focus score of 3. The general presentations of this series were not different from other Colombian series of patients (Antioquia and Cundinamarca geographic areas). Conclusion: this study presents the general description of a cohort PSS patients of the Southwest region of Colombia. Clinical and immunological characteristics were similar to other colombian patients in other geographic areas.

Objetivo: Determinar el efecto de la administración oral de calcio en adolescentes embarazadas de bajo nivel socioeconómico sobre las concentraciones de calcio ionizado plasmático y libre intracelular. Métodos: En un ensayo clínico controlado doble-ciego aleatorizado se estudiaron 52 mujeres, 26 (50%) adolescentes embarazadas que recibieron 600 mg de calcio elemental y 26 (50%) adolescentes embarazadas que recibieron 600 mg de placebo entre las semanas 17 y 19 de embarazo. Los niveles pre-tratamiento y post-tratamiento de calcio ionizado plasmático y libre intracelular se evaluaron en ambos grupos de acuerdo con la intención de tratamiento. Resultados: Se analizaron 48 adolescentes embarazadas que completaron el estudio (24 en el grupo de calcio y 24 en el grupo de placebo). Las características sociodemográficas de los grupos fueron comparables (p=0.92) al igual que la ingesta basal de calcio en su dieta (p=0.62). La suplementación oral de calcio por intención de tratamiento no modificó las concentraciones de calcio ionizado plasmático (1.19+0.04 mmol/l vs. 1.23+0.02 mmol/l, p=0.56) ni las concentraciones del calcio ionizado libre intracelular (116.2 mmol/l vs. 89.7 mmol/l, p= 0.91), se observó un resultado semejante en las embarazadas que recibieron placebo (1.20+0.05 mmol/l vs. 1.19+0.03 mmol/l p=0.86; 116.2 mmol/l vs. 137.5 mmol/l, p=0.16, respectivamente). Conclusiones: La administración oral de calcio en adolescentes embarazadas de bajo nivel socioeconómico no modificó ni las concentraciones plasmáticas ni las intracelulares del calcio ionizado lo que podría explicar en parte el poco efecto preventivo del uso del calcio como única medida de intervención para prevenir la preeclampsia.

Objective: To determine the effect of oral administration of calcium on plasma and ionized free calcium concentration in healthy adolescent pregnant women. Methods: In a double blind randomized controlled clinical trial were recruited 48 healthy adolescent pregnant women, 24 (50%) received 600 mg of elemental calcium and 24 (50%) received 600 mg of lactose placebo. At the inclusion time the plasma and intracellular free calcium concentrations were measured by standardized techniques. One month later the plasma and intracellular free calcium concentrations in both groups were measured. Results: At the inclusion time and one month after treatment both groups were comparable for sociodemographic characteristics and the basal intake of calcium (p=0.92, p=0.62). Calcium supplementation did not modify the concentrations of plasma ionized calcium (1.19+0.04 mmol/l vs. 1.23+0.02 mmol/l, p=0.56) and the free intracellular calcium concentration (mmol/l vs. 89.7 mmol/l, p=0.91); similar effects were observed with the placebo treatment (1.20+0.05 mmol/l vs. 1.19+0.03 mmol/l p=0.86; 116.2 mmol/l vs 137.5 mmol/l, p=0.16, respectively). Conclusions: Oral administration of 600 mg of elemental calcium in adolescent pregnant women did not induce changes in the plasma and intracellular ionized free calcium concentrations and could explain in part the lack effect of this only supplementation in preeclampsia prevention.

INTRODUCCION: Anualmente se producen en el mundo entre 80 y 100 millones de casos de malaria ocasionada por Plasmodium vivax, segunda especie de Plasmodium en importancia a nivel mundial y primera en el continente americano. Ante la falla de los métodos clásicos de control de la malaria, derivada de la creciente resistencia de los mosquitos a los insecticidas y de los parásitos a los medicamentos disponibles, se ha trabajado intensamente en la búsqueda de vacunas que puedan prevenir completamente la infección o limitar los efectos patológicos de la enfermedad. OBJETIVOS: Este trabajo describe el proceso de desarrollo de una vacuna experimental dirigida contra las formas pre-eritrocíticas del parásito, para lo cual se ha seleccionado la proteína circumesporozoito (CS) que se expresa de forma abundante en la superficie del parásito y que se halla comprometida en el proceso de invasión hepática. METODOLOGÍA: El proceso consistió en una exhaustiva caracterización inmunológica de la proteína, mediante péptidos sintéticos de diferente longitud, seguida de pruebas de toxicidad e inmunogenicidad en animales con los tres péptidos largos que cubren las regiones N, R y C de la CS. Como etapa inicial de la prueba en humanos, se hizo un ensayo clínico fase I que probó la seguridad e inmunogenicidad, de cada uno de los péptidos formulados en el adyuvante Montanide ISA-720. El ensayo fue al azar, doble ciego y comprometió a 23 voluntarios sanos, hombres y mujeres entre 18 y 33 años de edad, sin historia de malaria. CONCLUSIONES: La vacuna fue muy bien tolerada y demostró buena seguridad e inmunogenicidad en los ensayos preclínicos así como en todos los voluntarios, facilitando el avance a ulteriores fases de investigación clínica.

INTRODUCTION: Plasmodium vivax causes approximately 80-100 million clinical cases every year. It is the most prevalent human malaria parasite in the American continent and its prevalence is second only to P. falciparum worldwide. Due to the emergence of medication-resistant parasites and an increase in insecticide-resistant mosquitoes, research to find a vaccine that could prevent or limit the clinical manifestations of the disease has increased greatly. During the last two decades, significant progress has been achieved in this attempt; however, the development of a P. vivax vaccine has been hampered due to the lack of sustainable in vitro parasite cultures. OBJECTIVES: We describe the development and testing of a vaccine to P. vivax pre-erythrocytic stages. We selected the circumsporozoite (CS) protein, an antigen abundantly expressed on the parasite surface. METHODOLOGY: After extensive immunological characterization in vitro, three long peptides (N, R and C) were synthesized, and the toxicity and immunogenicity of these peptides were thoroughly assessed in animals. To determine the safety and immunogenicity in humans, a randomized, double blind clinical trial was conducted. The trial included 23 healthy volunteers who received 100 µg of N, R and C of each peptide formulated in Montanide ISA-720 adjuvant. CONCLUSIONS: The vaccination was well tolerated and proven to be safe in both animals and volunteers; thus, additional clinical trials utilizing this vaccine candidate are indicated.

The sporogonic cycle of Plasmodium vivax was established and maintained under laboratory conditions in two different strains of Anopheles albimanus mosquitoes using as a parasite source blood from human patients or from Aotus monkeys infected with the VCC-2 P.vivax colombian isolate. Both the Tecojate strain isolate from Guatemala and the Cartagena strain from the colombian Pacific coast were susceptible to infections with P.vivax. A higher percentage of Cartagena mosquitoes was infected per trial, however the Tecojate strain developed higher sporozoite loads. Intravenous inoculation of Aotus monkeys with sporozoites obtained from both anopheline strains resulted in successful blood infections. Animals infected with sporozoites from the Tecojate strain presented a patent period of 21-32 days whereas parasitemia appeared between days 19-53 in monkeys infected with sporozites from Cartagena strain.