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OBJECTIVE: The aim of this work is to define a methodological strategy for the minimally invasive tubular retractor (MITR) parafascicular transulcal approach (PTA) for the management of brain tumors sited in eloquent areas. METHODS: An observational prospective study was designed to evaluate the benefits of PTA associated with MITRs, tractography and intraoperative cortical stimulation. They study was conducted from June 2018 to June 2021. Information regarding white matter tracts was processed, preventing a potential damage during the approach and/or resection. All patients older than 18 years who had a single brain tumor lesion were included in the study. Patients with a preoperative Karnofsky Performance Scale (KPS) score greater than 70% and a Glasgow Coma Scale (GCS) score > 14 points were included. RESULTS: 72 patients were included in the study, the mean age was 49.6, the most affected gender was male, 12.5% presented aphasia, 11.1% presented paraphasia, 41.6% had motor deficit, 9.7% had an affection in the optic pathway, the most frequently affected region was the frontal lobe (26.3%), the most frequent lesions were high-grade gliomas (34.7%) and the measurement of the incisions was on average 5.58 cm. Of the patients, 94.4% underwent a total macroscopic resection and 90.2% did not present new postoperative neurological deficits. In all cases, a PTA was used. CONCLUSION: Tubular minimally invasive approaches (MIAs) allow one to perform maximal safe resection of brain tumors in eloquent areas, through small surgical corridors. Future comparative studies between traditional and minimally invasive techniques are required to further investigate the potential of these surgical nuances.
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Background: Endoscopic third ventriculostomy (ETV) is currently used as a treatment for different types of hydrocephalus. However, the anatomical endoscopic variants of the third ventricle floor (3VF), as well as their surgical implications, have been underrated. The anatomic variations of the 3VF can influence the technique and the success rate of the ETV. The purpose of this article is to describe the anatomical variations of 3VF, assess their incidence, and discuss the implications for ETV. Methods: Intraoperative videos of 216 patients who underwent ETV between January 2012 and February 2020 at Hospital Infantil Universitario de San José, Bogotá, Colombia were reviewed. One hundred and eighty patients who met the criteria to demonstrate the type of 3VF were selected. Results: 3VF types were classified as follows: (1) Thinned, (2) thickened, (3) partially erased, (4) globular or herniated, and (5) narrowed. Conclusion: Knowledge of anatomical variations of the 3VF is paramount for ETV and it influences the success rate of the procedure.
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Resumen Introducción: La enfermedad cardiovascular (infarto de miocardio, muerte cardíaca y accidente cerebrovascular fatal o no fatal) es la principal causa de muerte prematura y de discapacidad en el mundo. Es responsable de más de 17 millones de muertes anuales y afecta principalmente a la población que se ubica en los países de ingresos bajos y medios. Se estima que el 80% de la carga mundial se produce en estos países. Objetivo: Establecer la prevalencia de obesidad y riesgo cardiovascular mediante los criterios de Framingham en una población de trabajadores de la industria de producción de hidrocarburos. Método: Se desarrolló un estudio observacional descriptivo, epidemiológico, en el que se tuvo en cuenta la población de los trabajadores de la empresa Montajes JM, Cerritos CPE6, Proyecto 176, en el departamento del Meta (Puerto Gaitán). Se representaron las variables en promedio, intervalos de confianza y desviación estándar, procediendo a desarrollar un análisis por sexo para cada uno de los factores de riesgo. Resultados: En la población del programa de riesgo cardiovascular se encontró un promedio de edad de 38.11 años y un índice de masa corporal de 26.00 m2/kg. El 7.58% presentó hipertensión arterial, el 1.08% diabetes mellitus y el 24.91% tabaquismo. El riesgo cardiovascular calculado con la escala de Framingham fue del 4.48%. El índice de masa corporal, la edad y la presión arterial sistólica no son estadísticamente significativos para la valoración del riesgo con la escala Framingham. Conclusiones: La prevalencia de obesidad fue del 64.9%, en tanto que el 75% de las personas que trabajan en hidrocarburos tenían riesgo leve de enfermedad cardiovascular.
Abstract Introduction: Cardiovascular disease is one of the main causes of premature death and disability worldwide (myocardial infarction, cardiac death and fatal or non-fatal stroke) is responsible for more than 17 million annual deaths, in patients of low- and middle-income countries, it is estimated that 80% of the global burden occurs in these countries. Objective: To establish the prevalence of obesity and cardiovascular risk, evaluated using the Framingham criteria in a population of workers in the hydrocarbon production industry. Method: An observational, descriptive, epidemiological study was carried out of a population of workers of the company Montajes JM, Cerritos CPE6 Project 176, in Puerto Gaitan in the department of Meta, Colombia. The variables in average, standard deviation and confidence intervals were described, with a comparative analysis of risk factors by sex. Results: In the population of the cardiovascular risk program, an average age of 38.11 years old and a body mass index of 26.00 m2/kg were found. 7.58% presented high blood pressure, 1.08% diabetes mellitus and 24.91% were found to smoke. The cardiovascular risk calculated with the Framingham scale was found to be 4.48%. Body mass index, age and systolic blood pressure were not statistically significant for the risk assessment using the Framingham scales. Conclusions: The prevalence of obesity in the group of workers in the hydrocarbon drilling industry was 64.9% and 75% had a slight risk of cardiovascular disease.
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BACKGROUND: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. METHODS: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. RESULTS: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. CONCLUSIONS: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.
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Anemia , Malaria Vivax , Animales , Médula Ósea , Eritropoyesis , Humanos , Malaria Vivax/parasitología , Plasmodium vivax/genéticaRESUMEN
Splenic tuberculosis is a little-known and difficult to diagnose entity due to its low presentation of symptoms. It corresponds to one of the forms of extrapulmonary presentation of the disease, which in turn have a greater association with immunocompromised states such as diabetes mellitus. We present the case of a patient with diabetes mellitus who was admitted in the context of septic shock secondary to a probable splenic abscess, requiring surgical intervention. A total splenectomy was performed, managing to isolate Mycobacterium tuberculosis from the surgical specimen.
La tuberculosis esplénica es poco conocida y de difícil diagnóstico por su escasa presentación de síntomas. Corresponde a una de las formas de presentación extrapulmonar de la enfermedad, las cuales tienen mayor asociación con estados de inmunocompromiso, como la diabetes mellitus. Presentamos el caso de un paciente con diabetes mellitus que ingresó con choque séptico secundario a un probable absceso esplénico, requiriendo intervención quirúrgica en la que se llevó a cabo esplenectomía total y estudio histopatológico, con identificación de Mycobacterium tuberculosis en la pieza quirúrgica.
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Absceso Abdominal , Choque Séptico , Enfermedades del Bazo , Tuberculosis , Absceso/etiología , Absceso/cirugía , Humanos , Choque Séptico/etiología , Enfermedades del Bazo/complicaciones , Enfermedades del Bazo/cirugía , Tuberculosis/complicacionesRESUMEN
Cryptic Plasmodium niches outside the liver possibly represent a major source of hypnozoite-unrelated recrudescences in malaria. Maurizio Ascoli, an Italian physician and scientist, suggested that infection was maintained as a result of the persistence of endoerythrocytic parasites in the circulatory bed of some internal organs, mainly the spleen. This would explain a proportion of the recurrences in patients, regardless of the Plasmodium species. Ascoli proposed a method that included the co-administration of adrenaline, in order to induce splenic contraction, and quinine to clear expelled forms in major vessels. Driven by controversy regarding safety and effectiveness, along with the introduction of new drugs, the Ascoli method was abandoned and mostly forgotten by the malaria research community. To date, however, the existence of cryptic parasites outside the liver is gaining supportive data. This work is a historical retrospective of cryptic malaria infections and the Ascoli method, highlighting key knowledge gaps regarding these possible parasite reservoirs.
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Antimaláricos/administración & dosificación , Infecciones Asintomáticas , Epinefrina/administración & dosificación , Malaria/prevención & control , Quinina/administración & dosificación , Bazo/efectos de los fármacos , Enfermedad Crónica/prevención & control , Historia del Siglo XXRESUMEN
La risperidona es un antagonista selectivo monoaminérgico, con una elevada afinidad por receptores dopaminérgicos, que puede producir síndrome neuroléptico maligno (SNM), considerado una emergencia médica con alto riesgo de muerte. Tiene una incidencia de hasta el 3% y su mortalidad está entre el 10 y 20%. Se reporta el caso de una paciente de 56 años, que reunía los criterios clínicos del SNM, inducido por el uso de risperidona y facilitado por una sepsis de origen urinario. El tratamiento se condujo con un agente agonista dopaminérgico y cambio del antipsicótico, procedimientos que resultaron en una adecuada evolución clínica. El SNM es una entidad de baja prevalencia, para la cual existen criterios diagnósticos con especificidad y sensibilidad mayor del 90%, por lo que debe diferenciarse claramente de otras patologías. Se discute el mecanismo mediante el cual la infección urinaria facilitaría la ocurrencia de esta enfermedad. El diagnóstico precoz mejora la respuesta al manejo adecuado que se establezca en cada caso.
Risperidone is a selective monoaminergic antagonist with a high affinity for dopamine receptors that can cause neuroleptic malignant syndrome (NMS), considered a life-threatening medical emergency. It has an incidence of up to 3% and its mortality is between 10 and 20%. The case of a 56-year-old female who met the clinical criteria of NMS, induced by the use of risperidone and facilitated by a sepsis of urinary origin, is reported. It was managed with a dopamine agonist and the change of antipsychotic, which resulted in a favorable clinical course. The NMS is a low-prevalence entity whose diagnosis has specificity and sensitivity greater than 90%, reason for which must be clearly differentiated from other pathologies. The mechanism by which urinary infection could facilitate the occurrence of this disease is discussed. Early diagnosis improves the response to an adequate management to be established in each case.
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BACKGROUND: Splenomegaly is one of the most common features of malaria. However, spontaneous splenic rupture, although unusual, represents a severe complication often leading to death. It is mostly seen in acute infection and primary attack, and it is most commonly associated with Plasmodium vivax. Here, a case of spontaneous splenic rupture diagnosed with a portable ultrasound apparatus shortly after starting treatment and with recurrent parasitaemia after splenectomy, is reported. CASE DESCRIPTION: In November 2015, a 45-year-old Brazilian man presented to the hospital in Manaus with fever, headache and myalgia. He was diagnosed with P. vivax malaria and, after a normal G6PD test, he started treatment with chloroquine and primaquine and was discharged. Two days later, he went back to the hospital with abdominal pain, dyspnea, dry cough, pallor, oliguria and fever. Using a portable ultrasound, he was diagnosed of rupture of the spleen, which was removed by emergency surgery. After this episode, he suffered two more malaria episodes with high parasitaemia at approximately 2-month intervals. DNA from different portions of the spleen was extracted and a qualitative PCR was performed to detect P. vivax. CONCLUSIONS: The splenic rupture suffered by this patient occurred 2 days after starting the treatment. Having a portable ultrasound apparatus may have saved the patient's life, as it revealed a haemorrhage needing an urgent surgery. Parasites were detected by PCR in the extracted spleen. This patient suffered two more vivax malaria diagnosed episodes in spite of receiving and completing treatment with chloroquine and primaquine for each clinical attack. Splenic rupture during acute malaria is uncommon, but it is likely underdiagnosed and underreported, because the lack of means and equipment hinders diagnostic confirmation, especially in endemic areas.
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Malaria Vivax/complicaciones , Malaria/complicaciones , Plasmodium vivax/aislamiento & purificación , Rotura del Bazo/diagnóstico , Ultrasonografía , Brasil , Humanos , Malaria/prevención & control , Malaria Vivax/prevención & control , Masculino , Persona de Mediana Edad , Bazo/parasitología , Rotura del Bazo/parasitologíaRESUMEN
El Sistema Ventricular Cerebral se desarrolla de forma paralela al resto del Sistema Nervioso Central, facilitando la circulación del Líquido Cefalorraquídeo, desde su separación del líquido amniótico a nivel embrionario. Este desarrollo es necesario para entender correctamente la anatomía ventricular y facilitar el abordaje para patologías intraventriculares. El objetivo de esta revisión es reconocer los puntos más importantes en la embriología ventricular para facilitar el aprendizaje de la anatomía quirúrgica ventricular.
The cerebral ventricular system is developed in parallel with the rest of the central nervous system, facilitating the circulation of cerebrospinal fluid, from the amniotic fluid separation in the embryonic phases. This development is necessary to correctly understand the ventricular anatomy and facilitate approach to intraventricular pathologies. The objective of this review is to recognize the most important points in the ventricular embryology and in the intraventricular endoscopic vision to facilitate learning of the ventricular surgical anatomy.
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Humanos , Endoscopía/métodos , Ventrículos Cerebrales/embriología , Ventriculostomía/métodos , Sistema Nervioso Central , Tubo NeuralRESUMEN
BACKGROUND: In recent years, considerable success in reducing its incidence has been achieved in Brazil, leading to a relative increase in the proportion of cases caused by Plasmodium vivax, considered a harder-to-eliminate parasite. This study aim is to describe the transmission dynamics and associated risk factors in a rural settlement area in the Western Brazilian Amazon. METHODS: A prospective cohort was established in a rural settlement area for 3 years. Follow-up included continuous passive case detection and monthly active case detection for a period of 6 months. Demographic, clinical and transmission control practices data were collected. Malaria diagnosis was performed through thick blood smear. Univariable and multivariable analyses of factors associated with malaria incidence were performed using negative binomial regression models. Factors associated with recurrence of P. vivax and Plasmodium falciparum malaria within 90 days of a previous episode were analysed using univariable and multivariable Cox-Proportional Hazard models. RESULTS: Malaria prevalence decreased from 7 % at the study beginning to 0.6 % at month 24, with P. vivax predominating and P. falciparum disappearing after 1 year of follow-up. Malaria incidence was significantly higher in the dry season [IRR (95 % CI) 1.4 (1.1-1.6); p < 0.001)]. Use of ITN was associated to malaria protection in the localities [IRR (95 % CI) 0.7 (0.6-0.8); p = 0.001)]. A recurrent P. vivax episode within 90 days was observed in 29.4 % of individuals after an initial diagnosis. A previous P. vivax [IRR (95 % CI) 2.3 (1.3-4.0); p = 0.006)] or mixed P. vivax + P. falciparum [IRR (95 % CI) 2.9 (1.5-5.7); p = 0.002)] infections were significantly associated to a vivax malaria episode within 90 days of follow-up. CONCLUSIONS: In an area of P. falciparum and P. vivax co-endemicity, a virtual disappearance of P. falciparum was observed with P. vivax increasing its relative contribution, with a large proportion of recurring episodes. This finding reinforces the perception of P. falciparum being more responsive to early diagnosis and treatment and ITN use and the contribution of relapsing P. vivax to maintain this species' transmission. In areas of P. vivax endemicity, antihypnozoite treatment effectiveness assessment in different transmission intensity may be a fundamental activity for malaria control and elimination.
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Control de Enfermedades Transmisibles/métodos , Transmisión de Enfermedad Infecciosa , Malaria Falciparum/epidemiología , Malaria Falciparum/transmisión , Malaria Vivax/epidemiología , Malaria Vivax/transmisión , Población Rural , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Preescolar , Femenino , Investigación sobre Servicios de Salud , Humanos , Incidencia , Lactante , Recién Nacido , Estudios Longitudinales , Malaria Falciparum/diagnóstico , Malaria Falciparum/tratamiento farmacológico , Malaria Vivax/diagnóstico , Malaria Vivax/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The chemical treatment of Plasmodium falciparum for human infections is losing efficacy each year due to the rise of resistance. One possible strategy to find novel anti-malarial drugs is to access the largest reservoir of genomic biodiversity source on earth present in metagenomes of environmental microbial communities. METHODS: A bioluminescent P. falciparum parasite was used to quickly detect shifts in viability of microcultures grown in 96-well plates. A synthetic gene encoding the Dermaseptin 4 peptide was designed and cloned under tight transcriptional control in a large metagenomic insert context (30 kb) to serve as proof-of-principle for the screening platform. RESULTS: Decrease in parasite viability consistently correlated with bioluminescence emitted from parasite microcultures, after their exposure to bacterial extracts containing a plasmid or fosmid engineered to encode the Dermaseptin 4 anti-malarial peptide. CONCLUSIONS: Here, a new technical platform to access the anti-malarial potential in microbial environmental metagenomes has been developed.
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Antimaláricos/farmacología , Biblioteca Genómica , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/farmacología , Plantas/química , Plasmodium falciparum/efectos de los fármacos , Biodiversidad , Malaria Falciparum/tratamiento farmacológico , Metagenoma , Plasmodium falciparum/genéticaRESUMEN
Molecular markers associated with the increase of chloroquine resistance and disease severity in Plasmodium vivax are needed. The objective of this study was to evaluate the expression levels of pvcrt-o and pvmdr-1 genes in a group of patients presenting CQRPv and patients who developed severe complications triggered exclusively by P. vivax infection. Two different sets of patients were included to this comprehensive study performed in the Brazilian Amazon: 1) patients with clinically characterized chloroquine-resistant P. vivax compared with patients with susceptible parasites from in vivo studies and 2) patients with severe vivax malaria compared with patients without severity. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters genes, P. vivax chloroquine resistance transporter (pvcrt-o) and the P. vivax multidrug resistance transporter (pvmdr-1). Twelve chloroquine resistant cases and other 15 isolates from susceptible cases were included in the first set of patients. For the second set, seven patients with P. vivax-attributed severe and 10 mild manifestations were included. Parasites from patients with chloroquine resistance presented up to 6.1 (95% CI: 3.8-14.3) and 2.4 (95% CI: 0.53-9.1) fold increase in pvcrt-o and pvmdr-1 expression levels, respectively, compared to the susceptible group. Parasites from the severe vivax group had a 2.9 (95% CI: 1.1-8.3) and 4.9 (95% CI: 2.3-18.8) fold increase in pvcrt-o and pvmdr-1 expression levels as compared to the control group with mild disease. These findings suggest that chloroquine resistance and clinical severity in P. vivax infections are strongly associated with increased expression levels of the pvcrt-o and pvmdr-1 genes likely involved in chloroquine resistance.
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Antimaláricos/farmacología , Cloroquina/farmacología , Malaria Vivax/tratamiento farmacológico , Proteínas de Transporte de Membrana/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Plasmodium vivax/metabolismo , Proteínas Protozoarias/metabolismo , Adolescente , Adulto , Antimaláricos/uso terapéutico , Brasil , Niño , Cloroquina/uso terapéutico , Resistencia a Medicamentos , Femenino , Expresión Génica , Frecuencia de los Genes , Humanos , Malaria Vivax/parasitología , Masculino , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Polimorfismo Genético , Proteínas Protozoarias/genética , Adulto JovenRESUMEN
There is now a growing body of evidence that challenges the current view that Plasmodium vivax-infected erythrocyte (Pv-iE) are unable to sequester. Here we used ex vivo adhesion assays with Pv-iE before and after maturation to demonstrate a higher binding potential of schizonts compared to other asexual stages. These experimental results are correlated with our observations in a panel of 50 vivax malaria patients where schizonts were completely absent in 27 isolates, and few schizonts were observed in the remaining patients. These observations prompt a paradigm shift in P. vivax biology and open avenues to investigate the role of Pv-iE sequestration.
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Adhesión Celular/fisiología , Eritrocitos/parasitología , Malaria Vivax/sangre , Malaria Vivax/parasitología , Plasmodium vivax/fisiología , Antimaláricos/uso terapéutico , Cloroquina/uso terapéutico , Humanos , Malaria Vivax/tratamiento farmacológico , Parasitemia/sangre , Parasitemia/parasitología , Plasmodium vivax/crecimiento & desarrollo , Primaquina/uso terapéutico , Esquizontes/fisiología , Estadísticas no ParamétricasRESUMEN
The production of fully functional human red cells in vitro from haematopoietic stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs from cord blood represented a major improvement to develop the continuous culture system for Plasmodium vivax. Here, we demonstrated that CD34⺠hHSCs from peripheral blood and bone marrow can be expanded and differentiated to reticulocytes using a novel stromal cell. Moreover, these reticulocytes and mature red blood cells express surface markers for entrance of malaria parasites contain adult haemoglobin and are also permissive to invasion by P. vivax and Plasmodium falciparum parasites.
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Antígenos CD34/aislamiento & purificación , Eritrocitos/parasitología , Células Madre Hematopoyéticas/parasitología , Malaria Vivax , Malaria/sangre , Plasmodium falciparum , Diferenciación Celular , Técnicas de Cocultivo/métodos , Humanos , Reticulocitos/citología , Reticulocitos/parasitologíaRESUMEN
BACKGROUND: Plasmodium vivax has the potential to infect 2.85 billion individuals worldwide. Nevertheless, the limited number of studies investigating the immune status of individuals living in malaria-endemic areas, as well as the lack of reports investigating serological markers associated with clinical protection, has hampered development of vaccines for P. vivax. It was previously demonstrated that naturally total IgG against the N-terminus of P. vivax merozoite surface protein 1 (Pv-MSP1) was associated with reduced risk of malarial infection. METHODS: Immune response against Pv-MSP1 (N-terminus) of 313 residents of the Rio Pardo rural settlement (Amazonas State, Brazil) was evaluated in a cross-sectional and longitudinal follow up over two months (on site) wherein gold standard diagnosis by thick blood smear and rRNA gene-based nested real-time PCR were used to discriminate symptomless Plasmodium vivax-infected individuals who did not develop clinical symptoms during a 2-months from those uninfected ones or who have had acute malaria. The acquisition of antibodies against Pv-MSP1 was also evaluated as survival analysis by prospective study over a year collecting information of new malaria infections in surveillance database. RESULTS: The majority of P. vivax-infected individuals (52-67%) showed immune recognition of the N-terminus of Pv-MSP1. Interesting data on infected individuals who have not developed symptoms, total IgG levels against the N-terminus Pv-MSP1 were age-dependent and the IgG3 levels were significantly higher than levels of subjects had acute malaria or those uninfected ones. The total IgG anti ICB2-5 was detected to be an important factor of protection against new malaria vivax attacks in survival analysis in a prospective survey (p = 0.029). CONCLUSIONS: The study findings illustrate the importance of IgG3 associated to 2-months of symptomless in P. vivax infected individuals and open perspectives for the rationale of malaria vaccine designs capable to sustain high levels of IgG3 against polymorphic malaria antigens.
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Anticuerpos Antiprotozoarios/sangre , Inmunoglobulina G/sangre , Malaria Vivax/inmunología , Proteína 1 de Superficie de Merozoito/inmunología , Adolescente , Adulto , Enfermedades Asintomáticas , Brasil , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Malaria Vivax/patología , Masculino , Microscopía , Parasitemia/diagnóstico , Estudios Prospectivos , Población Rural , Análisis de Supervivencia , Adulto JovenAsunto(s)
Malaria Vivax/complicaciones , Plasmodium vivax/aislamiento & purificación , Rotura/diagnóstico , Rotura/patología , Bazo/patología , Sangre/parasitología , Histocitoquímica , Humanos , Inmunohistoquímica , Masculino , Microscopía , Plasmodium vivax/genética , Reacción en Cadena de la Polimerasa , Bazo/parasitología , Adulto JovenRESUMEN
The spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (PRRs) in splenic effector cells during malaria infection is poorly understood. In the present study, we analysed the expression of selected PRRs in splenic effector cells from BALB/c mice infected with the lethal and non-lethal Plasmodium yoelii strains 17XL and 17X, respectively, and the non-lethal Plasmodium chabaudi chabaudi AS strain. The results of these experiments showed fewer significant changes in the expression of PRRs in AS-infected mice than in 17X and 17XL-infected mice. Mannose receptor C type 2 (MRC2) expression increased with parasitemia, whereas Toll-like receptors and sialoadhesin (Sn) decreased in mice infected with P. chabaudi AS. In contrast, MRC type 1 (MRC1), MRC2 and EGF-like module containing mucin-like hormone receptor-like sequence 1 (F4/80) expression decreased with parasitemia in mice infected with 17X, whereas MRC1 an MRC2 increased and F4/80 decreased in mice infected with 17XL. Furthermore, macrophage receptor with collagenous structure and CD68 declined rapidly after initial parasitemia. SIGNR1 and Sn expression demonstrated minor variations in the spleens of mice infected with either strain. Notably, macrophage scavenger receptor (Msr1) and dendritic cell-associated C-type lectin 2 expression increased at both the transcript and protein levels in 17XL-infected mice with 50% parasitemia. Furthermore, the increased lethality of 17X infection in Msr1 -/- mice demonstrated a protective role for Msr1. Our results suggest a dual role for these receptors in parasite clearance and protection in 17X infection and lethality in 17XL infection.
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Animales , Femenino , Ratones , Lectinas Tipo C/inmunología , Malaria/parasitología , Lectinas de Unión a Manosa/inmunología , Plasmodium chabaudi/inmunología , Plasmodium yoelii/inmunología , Receptores de Superficie Celular/inmunología , Receptores Depuradores/inmunología , Bazo/parasitología , Receptores Toll-Like/inmunología , Citometría de Flujo , Lectinas Tipo C/genética , Ratones Endogámicos BALB C , Análisis por Micromatrices , Malaria/inmunología , Lectinas de Unión a Manosa/genética , Parasitemia/inmunología , Receptores de Superficie Celular/genética , Receptores Depuradores/genética , Bazo/inmunología , Receptores Toll-Like/genéticaRESUMEN
The spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (PRRs) in splenic effector cells during malaria infection is poorly understood. In the present study, we analysed the expression of selected PRRs in splenic effector cells from BALB/c mice infected with the lethal and non-lethal Plasmodium yoelii strains 17XL and 17X, respectively, and the non-lethal Plasmodium chabaudi chabaudi AS strain. The results of these experiments showed fewer significant changes in the expression of PRRs in AS-infected mice than in 17X and 17XL-infected mice. Mannose receptor C type 2 (MRC2) expression increased with parasitemia, whereas Toll-like receptors and sialoadhesin (Sn) decreased in mice infected with P. chabaudi AS. In contrast, MRC type 1 (MRC1), MRC2 and EGF-like module containing mucin-like hormone receptor-like sequence 1 (F4/80) expression decreased with parasitemia in mice infected with 17X, whereas MRC1 an MRC2 increased and F4/80 decreased in mice infected with 17XL. Furthermore, macrophage receptor with collagenous structure and CD68 declined rapidly after initial parasitemia. SIGNR1 and Sn expression demonstrated minor variations in the spleens of mice infected with either strain. Notably, macrophage scavenger receptor (Msr1) and dendritic cell-associated C-type lectin 2 expression increased at both the transcript and protein levels in 17XL-infected mice with 50% parasitemia. Furthermore, the increased lethality of 17X infection in Msr1 -/- mice demonstrated a protective role for Msr1. Our results suggest a dual role for these receptors in parasite clearance and protection in 17X infection and lethality in 17XL infection.
Asunto(s)
Lectinas Tipo C/inmunología , Malaria/parasitología , Lectinas de Unión a Manosa/inmunología , Plasmodium chabaudi/inmunología , Plasmodium yoelii/inmunología , Receptores de Superficie Celular/inmunología , Receptores Depuradores/inmunología , Bazo/parasitología , Receptores Toll-Like/inmunología , Animales , Femenino , Citometría de Flujo , Lectinas Tipo C/genética , Malaria/inmunología , Receptor de Manosa , Lectinas de Unión a Manosa/genética , Ratones , Ratones Endogámicos BALB C , Análisis por Micromatrices , Parasitemia/inmunología , Receptores de Superficie Celular/genética , Receptores Depuradores/genética , Bazo/inmunología , Receptores Toll-Like/genéticaRESUMEN
BACKGROUND: Plasmodium falciparum and Plasmodium vivax are responsible for most of the global burden of malaria. Although the accentuated pathogenicity of P. falciparum occurs because of sequestration of the mature erythrocytic forms in the microvasculature, this phenomenon has not yet been noted in P. vivax. The increasing number of severe manifestations of P. vivax infections, similar to those observed for severe falciparum malaria, suggests that key pathogenic mechanisms (eg, cytoadherence) might be shared by the 2 parasites. METHODS: Mature P. vivax-infected erythrocytes (Pv-iEs) were isolated from blood samples collected from 34 infected patients. Pv-iEs enriched on Percoll gradients were used in cytoadhesion assays with human lung endothelial cells, Saimiri brain endothelial cells, and placental cryosections. RESULTS: Pv-iEs were able to cytoadhere under static and flow conditions to cells expressing endothelial receptors known to mediate the cytoadhesion of P. falciparum. Although Pv-iE cytoadhesion levels were 10-fold lower than those observed for P. falciparum-infected erythrocytes, the strength of the interaction was similar. Cytoadhesion of Pv-iEs was in part mediated by VIR proteins, encoded by P. vivax variant genes (vir), given that specific antisera inhibited the Pv-iE-endothelial cell interaction. CONCLUSIONS: These observations prompt a modification of the current paradigms of the pathogenesis of malaria and clear the way to investigate the pathophysiology of P. vivax infections.