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AIM: To evaluate and describe lymphocyte populations' and B cell subsets' frequencies in patients presenting with Predominantly antibody deficiencies (PAD) and diagnosed with bronchiectasis or recurrent pneumonia seen in Cali (Colombian Southwest region). MATERIALS AND METHODS: 16 subjects with PAD, 20 subjects with pulmonary complications (bronchiectasis or recurrent pneumonia) and 20 healthy donors (HD). Controls and probands between 14 and 64 years old, regardless of gender were included. Lymphocyte populations (T, B and NK cells) and B cell subsets were evaluated in peripheral blood mononuclear cells using flow cytometry, T/B/NK reagent and the pre-germinal center antibody panel proposed by the EUROflow consortium were used. EUROclass and the classification proposed by Driessen et al. were implemented. RESULTS: CVID patients exhibited increase absolute numbers of CD8+ T cells and reduce NK cells as compare with HD, other PAD cases or pulmonary complications. PAD B cell subsets were disturbed when compared to the age range-matched healthy donors. Among B cell subsets, the memory B cell compartment was the most affected, especially switched memory B cells. Four participants were classified as B- and two CVID as smB-Trnorm and smB-21low groups according to EUROclass classification. The most frequent patterns proposed by Driessen et al. were B cell production and germinal center defect. CONCLUSIONS: B cell subsets, especially memory B cells, are disturbed in PAD patients from Southwestern Colombia. To the best of our knowledge this is the most comprehensive study of B cell subsets in Colombian adults.
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Subgrupos de Linfocitos B , Bronquiectasia , Inmunodeficiencia Variable Común , Síndromes de Inmunodeficiencia , Neumonía , Adolescente , Adulto , Colombia , Inmunodeficiencia Variable Común/diagnóstico , Humanos , Memoria Inmunológica , Leucocitos Mononucleares , Persona de Mediana Edad , Adulto JovenRESUMEN
Diagnosing dengue in endemic areas remains problematic because of the low specificity of the symptoms and lack of accurate diagnostic tests. This study aimed to develop and prospectively validate, under routine care, dengue diagnostic clinical algorithms. The study was carried out in two phases. First, diagnostic algorithms were developed using a database of 1,130 dengue and 918 non-dengue patients, expert opinion, and literature review. Algorithms with > 70% sensitivity were prospectively validated in a single-group quasi-experimental trial with an adaptive Bayesian design. In the first phase, the algorithms that were developed with the continuous Bayes formula and included leukocytes and platelet counts, in addition to selected signs and symptoms, showed the highest sensitivities (> 80%). In the second phase, the algorithms were applied on admission to 1,039 consecutive febrile subjects in three endemic areas in Colombia of whom 25 were laboratory-confirmed dengue, 307 non-dengue, 514 probable dengue, and 193 undetermined. Including parameters of the hemogram consistently improved specificity without affecting sensitivity. In the final analysis, considering only confirmed dengue and non-dengue cases, an algorithm with a sensitivity and specificity of 65.4% (95% credibility interval 50-83) and 40.1% (34.7-45.7) was identified. All tested algorithms had likelihood ratios close to 1, and hence, they are not useful to confirm or rule out dengue in endemic areas. The findings support the use of hemograms to aid dengue diagnosis and highlight the challenges of clinical diagnosis of dengue.
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Algoritmos , Dengue/diagnóstico , Dengue/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Colombia/epidemiología , Enfermedades Endémicas , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Dengue is still an important cause of disease and mortality in tropical countries, as is influenza A virus, which is also a cause of epidemics all over the globe. In this article, we present the case of a 31-year-old woman who was in her second trimester of pregnancy and presented with severe dengue with hematological and neurological complications, and premature labor. She was misdiagnosed with bacterial infection and received antibiotic treatment with no improvement of the clinical manifestations and previous to death, she was diagnosed with dengue infection. She died from cardiorespiratory arrest. In the postmortem evaluation, influenza A co-infection was confirmed and characterization of the tissue damage and immune response in lung, liver, kidney, heart, spleen, and brain was determined, finding a severe inflammatory response in lung with T cells and macrophages infiltrating the tissue. This case report highlights the risks of accepting a single diagnosis, especially in endemic countries to multiple tropical diseases, which can lead to delay in appropriate treatment that could reduce morbidity and mortality.
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According to the World Health Organization, 98% of fatal dengue cases can be prevented; however, endemic countries such as Colombia have recorded higher case fatality rates during recent epidemics. We aimed to identify the predictors of mortality that allow risk stratification and timely intervention in patients with dengue. We conducted a hospital-based, case-control (1:2) study in two endemic areas of Colombia (2009-2015). Fatal cases were defined as having either 1) positive serological test (IgM or NS1), 2) positive virological test (RT-PCR or viral isolation), or 3) autopsy findings compatible with death from dengue. Controls (matched by state and year) were hospitalized nonfatal patients and had a positive serological or virological dengue test. Exposure data were extracted from medical records by trained staff. We used conditional logistic regression (adjusting for age, gender, disease's duration, and health-care provider) in the context of multiple imputation to estimate exposure to case-control associations. We evaluated 110 cases and 217 controls (mean age: 35.0 versus 18.9; disease's duration pre-admission: 4.9 versus 5.0 days). In multivariable analysis, retro-ocular pain (odds ratios [OR] = 0.23), nausea (OR = 0.29), and diarrhea (OR = 0.19) were less prevalent among fatal than nonfatal cases, whereas increased age (OR = 2.46 per 10 years), respiratory distress (OR = 16.3), impaired consciousness (OR = 15.9), jaundice (OR = 32.2), and increased heart rate (OR = 2.01 per 10 beats per minute) increased the likelihood of death (AUC: 0.97, 95% confidence interval: 0.96, 0.99). These results provide evidence that features of severe dengue are associated with higher mortality, which strengthens the recommendations related to triaging patients in dengue-endemic areas.
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Diarrea/diagnóstico , Ictericia/diagnóstico , Náusea/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Dengue Grave/diagnóstico , Taquicardia/diagnóstico , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Estudios de Casos y Controles , Colombia , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Diarrea/mortalidad , Diarrea/fisiopatología , Diarrea/virología , Enfermedades Endémicas , Femenino , Cefalea , Humanos , Inmunoglobulina M/sangre , Ictericia/mortalidad , Ictericia/fisiopatología , Ictericia/virología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Náusea/mortalidad , Náusea/fisiopatología , Náusea/virología , Síndrome de Dificultad Respiratoria/mortalidad , Síndrome de Dificultad Respiratoria/fisiopatología , Síndrome de Dificultad Respiratoria/virología , Medición de Riesgo , Dengue Grave/mortalidad , Dengue Grave/fisiopatología , Dengue Grave/virología , Análisis de Supervivencia , Taquicardia/mortalidad , Taquicardia/fisiopatología , Taquicardia/virologíaRESUMEN
There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were identified using contingency tables, nonparametric tests and logistic regression. A total of 778 subjects were diagnosed with dengue by the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491 dengue tests were ordered in subjects whose primary diagnosis was not dengue. Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue tests. Dengue tests were used both to rule in and rule out diagnosis. The latter use is not justified by the sensitivity of current rapid dengue diagnostic tests. Ordering of dengue tests appear to depend on a combination of factors, including physician and institutional preferences, as well as other patient and epidemiological factors.
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Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto Joven , Anticuerpos Antivirales/sangre , Dengue/diagnóstico , Enfermedades Endémicas , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Colombia/epidemiología , Pruebas Diagnósticas de Rutina , Dengue/epidemiología , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
There is insufficient evidence of the usefulness of dengue diagnostic tests under routine conditions. We sought to analyse how physicians are using dengue diagnostics to inform research and development. Subjects attending 14 health institutions in an endemic area of Colombia with either a clinical diagnosis of dengue or for whom a dengue test was ordered were included in the study. Patterns of test-use are described herein. Factors associated with the ordering of dengue diagnostic tests were identified using contingency tables, nonparametric tests and logistic regression. A total of 778 subjects were diagnosed with dengue by the treating physician, of whom 386 (49.5%) were tested for dengue. Another 491 dengue tests were ordered in subjects whose primary diagnosis was not dengue. Severe dengue classification [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.1-4.5], emergency consultation (OR 1.9; 95% CI 1.4-2.5) and month of the year (OR 3.1; 95% CI 1.7-5.5) were independently associated with ordering of dengue tests. Dengue tests were used both to rule in and rule out diagnosis. The latter use is not justified by the sensitivity of current rapid dengue diagnostic tests. Ordering of dengue tests appear to depend on a combination of factors, including physician and institutional preferences, as well as other patient and epidemiological factors.
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Anticuerpos Antivirales/sangre , Dengue/diagnóstico , Enfermedades Endémicas , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Adolescente , Adulto , Anciano , Niño , Preescolar , Colombia/epidemiología , Dengue/epidemiología , Pruebas Diagnósticas de Rutina , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Introducción. La intromisión humana en ecosistemas silvestres ha provocado cambios de comportamiento en los murciélagos, con la consecuente invasión a viviendas, convirtiéndolos en un factor de riesgo para la transmisión de la rabia a humanos y mascotas. Objetivos. Determinar en el departamento del Valle del Cauca, las asociaciones entre hábitos de comportamiento y transmisión de rabia entre murciélagos y su significado epidemiológico con énfasis en riesgo para la población humana. Materiales y métodos. Durante el periodo de diciembre 1999 a junio 2008, fueron capturados 1.321 murciélagos por el programa de vigilancia de rabia en el departamento del Valle del Cauca. El diagnóstico de rabia se hizo por inmunofluorescencia directa e inoculación en ratones, utilizando tejido encefálico de los murciélagos capturados. La tipificación viral se hizo por inmunofluorescencia indirecta usando anticuerpos monoclonales. Resultados. Se detectaron dos ejemplares de Eptesicus brasiliensis positivos para rabia en los años 2000 y 2002, y dos casos más en especímenes de E. brasiliensis y Molossus molossus, en el 2008. No se detectó el virus de la rabia en E. brasiliensis ni en M. molossus, ni en ninguna otra especie durante los años 1999, 2001, 2003, 2004, 2006 y 2007. Se encontraron distintas especies de murciélagos, como E. brasiliensis, M. molossus, Myotis nigricans, Glossophaga soricina, Noctiliio albiventris y Carollia perspicillata, compartiendo refugios en casas. Se detectaron virus rábicos de las variantes antigénicas 3 y 4, en murciélagos M. molossus y E. brasiliensis. Conclusiones. La presencia en el Departamento del Valle del Cauca de las variantes antigénicas 3 y 4 del virus rábico en murciélagos no hematófagos de hábitos caseros, probablemente, ha sido facilitada por la deforestación de los hábitats naturales de estas especies; además, el estilo de arquitectura urbana provee un hábitat artificial que posibilita el contacto físico entre las especies y la transmisión de rabia entre ellas. Ante las dificultades para controlar la rabia en murciélagos y la falta de herramientas adecuadas, la vigilancia continua de la enfermedad en los murciélagos, basada en el diagnóstico y la tipificación de los virus rábicos por laboratorio, en de los asentamientos humanos y alrededor de ellos, la vacunación preventiva en animales domésticos y de producción, así como la educación de la comunidad (para la concientización del riesgo y la recolección pasiva de muestras para su análisis), se convierten en las mejores herramientas para prevenir la transmisión a humanos.
Introduction: Human activities in the wild have recently increased the changes in bat behavior and invasion of houses, turning these animals into a health threat for humans and pets. Objectives: To determine the associations between behavioral habits and rabies transmission among bats in the department of Valle del Cauca and to assess the risk the existence of rabies in house dwelling bats presents for human health. Material and methods: In the period from December 1999 to June 2008, 1,321 hematophagous and non-hematophagous bats were captured for rabies epidemiological surveillance in the department of Valle del Cauca, Colombia. Rabies was diagnosed by direct immunofluorescence test on the brain tissue of collected animals. Viral typification was achieved by indirect immunofluorecense using rabies specific monoclonal antibodies. Results: Four bats were positive for rabies: two Eptesicus brasiliensis in 2000 and 2002, and an Eptesicus brasiliensis and a Molossus molossus in 2008. During the years 1999, 2001, 2003, 2004, 2006 and 2007 no rabies virus was found in E. brasiliensis and M. molossus or in any other bat species. Various species including E. brasiliensis, M. molossus, Myotis nigricans, Glossophaga soricina, Noctiliio albiventris and Carollia perspicillata were found sharing shelters in houses. Rabies virus antigenic variants 3 and 4 were found in M. molossus and E. brasiliensis bats only. Conclusions: The presence and potential spread of rabies antigenic variants 3 and 4 to cities have very likely been facilitated by the perturbation of the natural habitats of non-hematophagous bats in the department of Valle del Cauca; the urban architecture style also provides an artificial habitat which allows for physical contact and rabies transmission among the species. Seeing the difficulty for controlling rabies in bats and the lack of adequate tools, intensive laboratory based rabies surveillance in and around human settlements, preventive vaccination for house and production animals, and education for the community (in relation to increasing the awareness concerning the risk, and passive recollection of samples for analysis) represent major preventive strategies against bat rabies transmission to humans and pets.
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Humanos , Animales , Virus de la Rabia , Quirópteros , Monitoreo Epidemiológico , Zoonosis , Lyssavirus , Colombia , Programa de VERFRESUMEN
Plasmodium vivax circumsporozoite (CS) protein is a leading malaria vaccine candidate. We describe the characterization of specific immune responses induced in 21 malaria-naive volunteers vaccinated with long synthetic peptides derived from the CS protein formulated in Montanide ISA 720. Both antibody- and cell-mediated immune responses were analyzed. Antibodies were predominantly of IgG1 and IgG3 isotypes, recognized parasite proteins on the immunofluorescent antibody test, and partially blocked sporozoite invasion of hepatoma cell lines in vitro. Peripheral blood mononuclear cells from most volunteers (94%) showed IFN-γ production in vitro upon stimulation with both long signal peptide and short peptides containing CD8+ T-cell epitopes. The relatively limited sample size did not allow conclusions about HLA associations with the immune responses observed. In summary, the inherent safety and tolerability together with strong antibody responses, invasion blocking activity, and the IFN-γ production induced by these vaccine candidates warrants further testing in a phase II clinical trial.
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Anticuerpos Antiprotozoarios/sangre , Vacunas contra la Malaria/inmunología , Malaria Vivax/prevención & control , Plasmodium vivax/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Femenino , Humanos , Inmunidad Celular/fisiología , Malaria Vivax/inmunología , Masculino , Vacunación , Adulto JovenRESUMEN
BACKGROUND: We compared the diagnostic accuracy and reproducibility of commercially available NS1-based dengue tests and explored factors influencing their sensitivities. METHODS: Paired analysis of 310 samples previously characterized as positive (n = 218) and negative (n = 92) for viral isolation and/or RT-PCR and/or IgM seroconversion. Masked samples were tested by two observers with Platelia™ Dengue NS1 Ag, second generation Pan-E™ Dengue Early ELISA, SD Dengue NS1 Ag ELISA, Dengue NS1 Ag STRIP™, and SD BIOLINE™ Dengue Duo (NS1/IgM/IgG). RESULTS: SD BIOLINE™ NS1/IgM/IgG had the highest sensitivity (80.7% 95%CI 75-85.7) with likelihood ratios of 7.4 (95%CI 4.1-13.8) and 0.21 (95%CI 0.16-0.28). The ELISA-format tests showed comparable sensitivities; all below 75%. STRIP™ and SD NS1 had even lower sensitivities (<65%). The sensitivities significantly decreased in samples taken after 3 days of fever onset, in secondary infections, viral serotypes 2 and 4, and severe dengue. Adding IgM or IgG to SD NS1 increased its sensitivity in all these situations. CONCLUSIONS: The simultaneous detection of NS1/IgM/IgG would be potentially useful for dengue diagnosis in both endemic and non endemic areas. A negative result does not rule out dengue. Further studies are required to assess the performance and impact of early laboratory diagnosis of dengue in the routine clinical setting.
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Anticuerpos Antivirales/sangre , Dengue/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Juego de Reactivos para Diagnóstico , Proteínas no Estructurales Virales/sangre , Virología/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Inmunoensayo/métodos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Substantial experimental evidence indicates that the Plasmodium circumsporozoite (CS) protein has great potential as a vaccine candidate. We tested the safety and immunogenicity of vaccines composed of P. vivax CS-derived synthetic peptides. Sixty-nine healthy, malaria-naive volunteers were randomized to receive three injections of placebo or synthetic proteins N, R, or C (10, 30, or 100 microg/dose) in a double-blinded fashion. Vaccines were well tolerated and no serious adverse events were observed. Peptides N and R elicited humoral responses at all doses; peptide C elicicted these responses only at doses of 30 and 100 microg. The N peptide at a dose of 100 microg elicited the greatest antibody response. Antibodies to the three peptides recognized P. vivax sporozoites in an immunofluorescent antibody test. Peripheral blood mononuclear cells from most immunized volunteers also produced interferon-gamma upon peptide in vitro stimulation. These vaccines appear safe, well tolerated, and immunogenic in malaria-naive volunteers. Further optimization and development of this vaccine is being attempted to conduct phase II clinical trials.
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Anticuerpos Antiprotozoarios/sangre , Leucocitos Mononucleares/inmunología , Vacunas contra la Malaria/efectos adversos , Vacunas contra la Malaria/inmunología , Plasmodium vivax/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Animales , Método Doble Ciego , Femenino , Humanos , Interferón gamma/metabolismo , Vacunas contra la Malaria/administración & dosificación , Masculino , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/inmunologíaRESUMEN
Duffy antigen is the receptor used by Plasmodium vivax to invade erythrocytes. Consequently, individuals lacking Duffy antigen [Fy(-)] do not develop blood-stage infections. We hypothesized that naturally exposed Fy(-) humans may develop immune responses mainly to pre-erythrocytic stages and could be used to study acquired immunity to P. vivax and to identify liver-stage antigens. We report here that antibody and IFN-gamma responses to known sporozoite antigens were significantly induced by natural exposure in Fy(-) humans, whereas responses to blood-stage antigens were significantly induced in Fy(+) humans. IFN-gamma responses to sporozoite antigens were lower in Fy(+) than in Fy(-) humans, indicating that in Fy(+) humans blood-stage infections may have suppressed T cell responses to pre-erythrocytic stages. We evaluated the immune responses to 18 novel P. vivax homologs of P. falciparum sporozoite proteins identified from the P. vivax genome sequence. Eight proteins recalled IFN-gamma responses in P. vivax-exposed but not in unexposed individuals. Of these, 3 antigens elicited IFN-gamma responses in Fy(-) but not in Fy(+) individuals. These results suggest that differential immune responses observed in naturally exposed Fy(-) and Fy(+) individuals can be exploited to identify P. vivax stage-specific antigens.
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Antígenos de Protozoos/inmunología , Sistema del Grupo Sanguíneo Duffy/análisis , Eritrocitos/parasitología , Hígado/parasitología , Plasmodium vivax/inmunología , Adulto , Animales , Reacciones Cruzadas , Femenino , Genoma de Protozoos , Humanos , Interferón gamma/biosíntesis , Masculino , Persona de Mediana Edad , Plasmodium vivax/genéticaRESUMEN
Introducción: 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 investigaciónclinica
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Ensayos Clínicos como Asunto , Eritrocitos , Malaria , Plasmodium vivax , Vacunas , ColombiaRESUMEN
Three long synthetic peptides corresponding to amino (N), repeat (R) and carboxyl (C) regions of the Plasmodium vivax circumsporozoite (CS) protein were synthesised and used to assess their potential as vaccine candidates. Antigenicity studies were carried out using human blood samples from residents of a malaria-endemic area of Colombia, and immunogenicity was tested in Aotus monkeys. The N and C peptides spanned the total native amino and carboxyl flanking regions, whereas the R peptide corresponded to a construct based on the first central nona-peptide repeated in tandem three times and colinearly linked to a universal T-cell epitope (ptt-30) derived from tetanus toxin. All three peptides had been shown previously to contain several B-, T-helper (Th) and Cytotoxic T Lymphocytes (CTL) epitopes. Sixty-one percent of the human sera reacted with the R region, whereas 35 and 39% of the samples had antibodies against the N and C peptides, respectively. Human Peripheral Blood Mononuclear Cells (PBMC) showed higher levels of IFN-gamma than IL-4 when stimulated with peptides containing Th epitopes. Aotus monkeys immunised with the peptides formulated in either Montanide ISA720 or Freund's adjuvants produced strong antibody responses that recognised the peptide immunogens and the native circumsporozoite protein on sporozoites. Additionally, high IFN-gamma production was induced when Aotus lymphocytes were stimulated in vitro with each of the three peptides. We observed boosting of antibody responses and IFN-gamma production by exposure to live sporozoites. These results confirm the high antigenicity and immunogenicity of such synthetic polypeptides and underline their vaccine potential.
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Antígenos de Protozoos/inmunología , Plasmodium vivax/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Anciano , Animales , Anticuerpos Antiprotozoarios/biosíntesis , Aotidae , Niño , Citocinas/biosíntesis , Femenino , Humanos , Inmunización , Vacunas contra la Malaria/inmunología , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/inmunologíaRESUMEN
Non-human primates represent a valuable resource for testing potential vaccines candidates and drugs for human use. Malaria remains one of the greatest burdens for the humanity represented by approximately 500 million new clinical cases per year worldwide and at least two million deaths caused annually. Additional control measures such as vaccines and new anti-malarial compounds are therefore urgently needed. Safety and protective efficacy studies in animal models are critical steps for vaccines and drugs development and primate models are probably the most appropriate for this purpose. Although Aotus genus provides several species susceptible to both Plasmodium falciparum and Plasmodium vivax, having different susceptibility to malaria, Aotus lemurinus griseimembra represents the best current malaria primate model because of its high susceptibility to infection by blood forms and sporozoites of both species of Plasmodium. Although the ultimate validation of this model depends upon human trials, over the past two decades these monkeys have proved very useful to test multiple malaria vaccine candidates prior to trials in humans. A good correlation between the B- and T-cell epitopes recognised by humans and by immunised monkeys has been documented, and cross reactivity between reagents for human and Aotus cytokines and lymphocyte markers have been identified and are facilitating the selection of vaccine candidates for clinical trials. Aotus also represents a good model for the screening of anti-malarial drugs and the understanding of malaria pathogenesis as well. In view of the decreasing availability of these primates, breeding programs and biomedical research facilities must be improved in countries of primate origin.
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Antimaláricos/uso terapéutico , Aotus trivirgatus/parasitología , Modelos Animales de Enfermedad , Vacunas contra la Malaria , Malaria/prevención & control , Animales , Evaluación Preclínica de Medicamentos/métodos , Malaria/tratamiento farmacológico , Plasmodium falciparum/fisiologíaAsunto(s)
Linfocitos T CD8-positivos/inmunología , Interferón gamma/farmacología , Activación de Linfocitos/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Linfocitos T CD8-positivos/efectos de los fármacos , Técnicas de Cultivo de Célula/métodos , Separación Celular/métodos , Hígado/inmunología , Ganglios Linfáticos/inmunología , Ratones , Bazo/citología , Bazo/inmunología , Linfocitos T Citotóxicos/efectos de los fármacosRESUMEN
Specific CD8(-) T-lymphocyte (CTL) activity against Plasmodium pre-erythrocytic stages (P-ES) derived antigens is considered one of the most important mechanisms for malaria protection. Plasmodium vivax is the second most prevalent human malaria parasite species distributed worldwide. Although several CTL epitopes have been identified in Plasmodium falciparum P-ES derived antigens, none has been described for P. vivax to date. In this study, we analysed HLA-A*0201 specific CD8(-) T-lymphocyte responses to the P. vivax circumsporozoite (CS) protein in both malaria exposed and non-exposed populations from the Colombian Pacific Coast. First, we analysed the prevalence of HLA-A2 allele in the study populations and found that approximately 38 of the individuals expressed this molecule and that 50 of them were HLA-A*0201. We then selected, on the P. vivax CS, five peptide sequences containing the HLA-A*0201 binding motifs and used the corresponding synthetic peptides to evaluate the CD8(-) T-lymphocyte interferon (IFN)-gamma response. Peripheral blood mononuclear cells from the HLA-A*0201 donors were in vitro stimulated with these peptides and IFN-gamma production was determined by an ELISPOT assay. Specific CD8(-) T-lymphocyte responses were detected for three peptides located in the C-terminal region of the protein. Specific responses to these peptides were also detected in several individuals expressing different HLA-A*02 subtypes. The potential of these peptides to induce specific cytolysis and that of long synthetic peptides comprising these epitopes as P. vivax malaria vaccine subunits are being studied.
Asunto(s)
Epítopos de Linfocito T/inmunología , Antígeno HLA-A2/metabolismo , Malaria Vivax/inmunología , Plasmodium vivax/inmunología , Proteínas Protozoarias/inmunología , Linfocitos T Citotóxicos/inmunología , Adulto , Animales , Mapeo Epitopo , Femenino , Antígeno HLA-A2/genética , Humanos , Malaria/inmunología , Vacunas contra la Malaria/química , Vacunas contra la Malaria/uso terapéutico , Malaria Vivax/prevención & control , Masculino , Péptidos/inmunologíaRESUMEN
Mediante la técnica de ELISA se determinó la prevalencia de anticuerpos contra cisticerco en muestras de suero y líquido cefalorraquídeo (LCR) de 100 pacientes con síntomas neurológicos y de 100 pacientes con cuadros clínicos no neurológicos. De la población neurológica 13 por ciento presentó títulos positivos en suero y/o LCR, una escanografía sugestiva, síntomas clínicos compatibles y factores epidemiológicos favorables para la adquisición de cisticercosis. A estos pacientes se les diagnosticó neurocisticercosis. Otros siete pacientes presentaron imágenes escanográficas compatibles con procesos inflamatorios, muy probablemente causados por cisticercosis; sin embargo no se encontraron anticuerpos anticisticerco en suero o LCR. En el grupo de pacientes no neurológicos se encontraron títulos positivos contra cisticerco en el suero de dos pacientes. Estos datos evidencian la presencia e importancia de esta helmintiasis como causa de morbilidad en nuestro medio y justifican futuras investigaciones encaminadas a obtener métodos más específicos de un diagnóstico