Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim

Cali, Colombia

Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim

Cali, Colombia
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Gallego C.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Golenbock D.,University of Massachusetts Medical School | Gomez M.A.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Saravia N.G.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim
Infection and Immunity | Year: 2011

Toll-like receptors (TLRs) play a central role in macrophage activation and control of parasitic infections. Their contribution to the outcome of Leishmania infection is just beginning to be deciphered. We examined the interaction of Leishmania panamensis with TLRs in the activation of host macrophages. L. panamensis infection resulted in upregulation of TLR1, TLR2, TLR3, and TLR4 expression and induced tumor necrosis factor alpha (TNF-α) secretion by human primary macrophages at comparable levels and kinetics to those of specific TLR ligands. The TLR dependence of the host cell response was substantiated by the absence of TNF-α production in MyD88/TRIF-/- murine bone marrow-derived macrophages and mouse macrophage cell lines in response to promastigotes and amastigotes. Systematic screening of TLR-deficient macrophages revealed that TNF-α production was completely abrogated in TLR4.


Zea D.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Osorio L.,University of Valle
Revista de Salud Publica | Year: 2011

Objective The surveillance of dengue cases is essential for defining, implementing and assessing interventions and promptly detecting outbreaks. Municipal health authorities are the key stakeholders guaranteeing surveillance system quality and coverage and are the first users of the information so collected. The present study was aimed at assessing how well the dengue case surveillance system was operating in a municipality in the Valle del Cauca department of Colombia during 2008. Methods The CDC proposed model was used. Emphasis was placed on describing system operation, the available resources, compliance with reports and case adjustment and using information. Interviews were held with health workers. Dengue surveillance system data from the municipality, departmental health authorities and the Valle del Cauca Public Health Laboratory were reviewed. Results Notification coverage was 91.3%. A lack of using surveillance software and delays in notification were identified. Three people were in charge of all public health responsibilities and none of them had had any training or prior knowledge regarding public health surveillance protocols. There had not been any systematic data analysis. Conclusions As in other areas of Colombia, the lack of training, professional profile and other resources as well as a high turnover of public health personnel were the weakest points of the surveillance system in the municipality. Corrective measures for improving the surveillance system have now been implemented in the municipality which was studied.


Diaz Y.R.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Rojas R.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Valderrama L.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Saravia N.G.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim
Journal of Infectious Diseases | Year: 2010

Background. T cell differentiation determines susceptibility and resistance to experimental cutaneous leishmaniasis, yet mixed T1/Th2 responses characterize the clinical spectrum of human infection with Leishmania (Viannia) species. Materials and Methods. To discern the interrelationship of T cell differentiation and outcome of human infection, we examined factors that regulate T cell differentiation and Th1/Th2 cytokine responses in asymptomatic infection, active and historical chronic and recurrent cutaneous leishmaniasis. T-bet, GATA-3, Foxp3, and cytokine gene expression were quantified by real-time polymerase chain reaction and correlated with interleukin 2, interferon γ, tumor necrosis factor α, interleukin 4, interleukin 13, and interleukin 10 secretion during in vitro response to live Leishmania panamensis. Results. Higher GATA-3 expression than T-bet expression occurred throughout the 15 days of coculture with promastigotes; however, neither transcription nor secretion of interleukin 4 was detected. A sustained inverse correlation between GATA-3 expression and secretion of proinflammatory cytokines interferon γ and tumor necrosis factor a was observed in asymptomatic infection. In contrast, higher T-bet expression and a higher ratio of T-bet to GATA-3 characterized active recurrent disease. Down-regulation of T-bet and GATA-3 expression and increased interleukin 2 secretion, compared with control subjects, was directly correlated with Foxp3 expression and interleukin 13 secretion in chronic disease. Conclusions. Regulation of the inflammatory response rather than biased Th1/Th2 response distinguishedasymptomatic and recalcitrant outcomes of infection with Leishmnania viannia species. © 2010 by the Infectious Diseases Society of America.


Obonaga R.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Fernandez O.L.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Valderrama L.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Rubiano L.C.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by Leishmania (Viannia) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six Leishmania (Viannia) braziliensis and six Leishmania (Viannia) panamensis strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the Leishmania drug transporter genes abca2, abca3, abcc2, abcc3, abcg4, abcg6, and LbMT was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC50], 10.7 μmol/liter) were more susceptible to miltefosine than promastigotes (median EC50, 55.3 μmol/liter) (P<0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC50 of>32 μmol/liter (the upper limit of intracellular amastigote assay), occurred in L. panamensis infection in a child and in L. braziliensis infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/β-tubulin, 0.42- to 0.26-fold [P=0.039] and 0.70- to 0.57-fold [P=0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype. Leishmania ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (r=-0.605; P=0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal leishmaniasis. © 2014, American Society for Microbiology. All Rights Reserved.


Ocampo C.B.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Mina N.J.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Carabali M.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Alexander N.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | And 2 more authors.
Acta Tropica | Year: 2014

Dengue incidence continues to increase globally and, in the absence of an efficacious vaccine, prevention strategies are limited to vector control. It has been suggested that targeting the most productive breeding sites instead of all water-holding containers could be a cost-effective vector control strategy. We sought to identify and continuously control the most productive Aedes (Stegomyia) breeding site in an endemic urban area in Colombia and followed the subsequent incidence of dengue. In the urban area of Guadalajara de Buga, southwestern Colombia, potential breeding sites inside and outside houses were first characterized, and local personnel trained to assess their productivity based on the pupae/person index. Simultaneously, training and monitoring were implemented to improve the dengue case surveillance system. Entomological data and insecticide resistance studies were used to define the targeted intervention. Then, a quasi-experimental design was used to assess the efficacy of the intervention in terms of the positivity index of the targeted and non- targeted breeding sites, and the impact on dengue cases. Street catch basins (storm drains) were the potential breeding site most frequently found containing Aedes immature stages in the baseline (58.3% of 108). Due to the high resistance to temephos (0% mortality after 24. h), the intervention consisted of monthly application of pyriproxyfen in all the street catch basins (n= 4800). A significant decrease in catch basins positivity for Aedes larvae was observed after each monthly treatment (p< 0.001). Over the intervention period, a reduction in the dengue incidence in Buga was observed (rate ratio 0.19, 95% CI 0.12-0.30, p< 0.0001) after adjusting for autocorrelation and controlling with a neighboring town, Palmira, This study highlights the importance of street catch basins as Aedes breeding sites and suggests that their targeted control could help to decrease dengue transmission in such areas. © 2014.


Rossi F.,University of Sao Paulo | Diaz L.,El Bosque University | Diaz L.,University of Houston | Wollam A.,Washington University in St. Louis | And 23 more authors.
New England Journal of Medicine | Year: 2014

We report the case of a patient from Brazil with a bloodstream infection caused by a strain of methicillin-resistant Staphylococcus aureus (MRSA) that was susceptible to vancomycin (designated BR-VSSA) but that acquired the vanA gene cluster during antibiotic therapy and became resistant to vancomycin (designated BR-VRSA). Both strains belong to the sequence type (ST) 8 community-associated genetic lineage that carries the staphylococcal chromosomal cassette mec (SCCmec) type IVa and the S. aureus protein A gene (spa) type t292 and are phylogenetically related to MRSA lineage USA300. A conjugative plasmid of 55,706 bp (pBRZ01) carrying the vanA cluster was identified and readily transferred to other staphylococci. The pBRZ01 plasmid harbors DNA sequences that are typical of the plasmid-associated replication genes rep24 or rep21 described in community-associated MRSA strains from Australia (pWBG745). The presence and dissemination of community-associated MRSA containing vanA could become a serious public health concern. Copyright © 2014 Massachusetts Medical Society.


Ferro B.E.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Garcia P.K.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Nieto L.M.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Van Soolingen D.,National Institute for Public Health and the Environment RIVM | Van Soolingen D.,Radboud University Nijmegen
Journal of Clinical Microbiology | Year: 2013

Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium tuberculosis, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first- and second-line antituberculosis drugs. Wetherefore evaluated the performance of the GenoType kits in this region by testing 228 M. tuberculosis isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoTypeMTBDRplus test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoTypeMTBDRsl test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were katG S315T1, rpoB S531L, embB M306V, gyrA D94G, and rrs A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases. © 2013, American Society for Microbiology.


Fernandez O.L.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Diaz-Toro Y.,Centro Dermatologico Federico Lleras Acosta CDFLLA | Ovalle C.,Centro Dermatologico Federico Lleras Acosta CDFLLA | Valderrama L.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2014

Background:Pentavalent antimonials have been the first line treatment for dermal leishmaniasis in Colombia for over 30 years. Miltefosine is administered as second line treatment since 2005. The susceptibility of circulating populations of Leishmania to these drugs is unknown despite clinical evidence supporting the emergence of resistance.Methodology/Principal Findings:In vitro susceptibility was determined for intracellular amastigotes of 245 clinical strains of the most prevalent Leishmania Viannia species in Colombia to miltefosine (HePC) and/or meglumine antimoniate (SbV); 163, (80%) were evaluated for both drugs. Additionally, susceptibility to SbV was examined in two cohorts of 85 L. V. panamensis strains isolated between 1980-1989 and 2000-2009 in the municipality of Tumaco. Susceptibility to each drug differed among strains of the same species and between species. Whereas 68% of L. V. braziliensis strains presented in vitro resistance to HePC, 69% were sensitive to SbV. Resistance to HePC and SbV occurred respectively, in 20% y 21% of L. panamensis strains. Only 3% of L. V. guyanensis were resistant to HePC, and none to SbV. Drug susceptibility differed between geographic regions and time periods. Subpopulations having disparate susceptibility to SbV were discerned among L. V. panamensis strains isolated during 1980-1990 in Tumaco where resistant strains belonged to zymodeme 2.3, and sensitive strains to zymodeme 2.2.Conclusions/Significance:Large scale evaluation of clinical strains of Leishmania Viannia species demonstrated species, population, geographic, and epidemiologic differences in susceptibility to meglumine antimoniate and miltefosine, and provided baseline information for monitoring susceptibility to these drugs. Sensitive and resistant clinical strains within each species, and zymodeme as a proxy marker of antimony susceptibility for L. V. panamensis, will be useful in deciphering factors involved in susceptibility and the distribution of sensitive and resistant populations. © 2014 Fernández et al.


Rodriguez-Pinto D.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Rodriguez-Pinto D.,University of the Americas in Ecuador | Saravia N.G.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | McMahon-Pratt D.,Yale University
BMC Infectious Diseases | Year: 2014

Background: An effective adaptive immune response requires activation of specific CD4 T cells. The capacity of B cells to activate CD4 T cells in human cutaneous leishmaniasis caused by Leishmania (Viannia) has not been evaluated.Methods: CD4 T cell activation by B cells of cutaneous leishmaniasis patients was evaluated by culture of PBMCs or purified B cells and CD4 T cells with Leishmania panamensis antigens. CD4 T cell and B cell activation markers were evaluated by flow cytometry and 13 cytokines were measured in supernatants with a bead-based capture assay. The effect of Leishmania antigens on BCR-mediated endocytosis of ovalbumin was evaluated in the Ramos human B cell line by targeting the antigen with anti-IgM-biotin and anti-biotin-ovalbumin-FITC.Results: Culture of PBMCs from cutaneous leishmaniasis patients with Leishmania antigens resulted in upregulation of the activation markers CD25 and CD69 as well as increased frequency of CD25hiCD127- cells among CD4 T cells. Concomitantly, B cells upregulated the costimulatory molecule CD86. These changes were not observed in PBMCs from healthy subjects, indicating participation of Leishmania-specific lymphocytes expanded in vivo. Purified B cells from these patients, when interacting with purified CD4 T cells and Leishmania antigens, were capable of inducing significant increases in CD25 and CD69 expression and CD25hiCD127- frequency in CD4 T cells. These changes were associated with upregulation of CD86 in B cells. Comparison of changes in CD4 T cell activation parameters between PBMC and B cell/CD4 T cell cultures showed no statistically significant differences; further, significant secretion of IFN-γ, TNF-α, IL-6 and IL-13 was induced in both types of cultures. Additionally, culture with Leishmania antigens enhanced BCR-mediated endocytosis of ovalbumin in Ramos human B cells.Conclusions: The capacity of B cells specific for Leishmania antigens in peripheral blood of cutaneous leishmaniasis patients to activate CD4 T cells and induce cytokine secretion is similar to that of all cell populations present in PBMCs. This capacity implicates B cells as a plausible target for modulation of the immune response to Leishmania infection as a therapeutic strategy. © 2014 Rodriguez-Pinto et al.; licensee BioMed Central Ltd.


Ocampo C.B.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Salazar-Terreros M.J.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | Mina N.J.,Centro Internacional Of Entrenamiento E Investigaciones Medicas Cideim | McAllister J.,Centers for Disease Control and Prevention | Brogdon W.,Centers for Disease Control and Prevention
Acta Tropica | Year: 2011

Insecticide resistance is one of the major threats to the effectiveness of vector control programs. In order to establish a baseline susceptibility profile of Aedes aegypti in the southwest of Colombia, 10 localities in four Departments (States) were evaluated. Standardized WHO bioassay, CDC bottle bioassay and microplate biochemical assays of non-specific β-esterase (NSE), mixed function oxidases (MFO) and acetylcholinesterase were used. Cross resistance was evaluated with field collected mosquitoes that underwent selection pressure in the laboratory from DDT, propoxur and lambdacyhalothrin during three alternate generations. Mosquitoes with mortality rates below 80% in bioassays were considered resistant. Insecticide resistance varied geographically. Insecticide resistance was observed in 100% of localities in which mosquitoes were exposed to DDT, bendiocarb and temephos using both assays. WHO bioassays showed susceptibility to pyrethroids in all the localities evaluated, however CDC bottle bioassays showed decreases in susceptibility especially with lambdacyhalothrin. All localities showed susceptibility to the organophosphate malathion. Mosquitoes from eight regions with evidence of resistance to any of the insecticide evaluated were also evaluated biochemically. Mosquitoes from five of these regions had increased levels of NSE and two regions had increased levels of MFO. Increase levels of NSE explain partially the low susceptibility to temephos found in all the localities. However, the biochemical mechanisms evaluated do not explain all the resistance observed. Cross resistance was observed between the DDT-selected strain and lambdacyhalothrin, and between the lambdacyhalothrin-selected strain and propoxur and vice versa. The selected strains do not show changes in the biochemical assays evaluated, therefore the observed cross-resistance suggests different biochemical mechanisms. This study shows that Ae. aegypti from Colombia can develop resistance to most of the insecticide classes in the market. Periodic surveillance of insecticide resistance is necessary in order to maintain effective interventions. This study helped to establish the National Network for the surveillance of the insecticide resistance in Colombia. © 2011 Elsevier B.V.

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