RESUMO
Autologous cell therapy has proven to be an effective treatment for hematological malignancies. Cell therapies for solid tumors are on the horizon, however the high cost and complexity of manufacturing these therapies remain a challenge. Routinely used open steps to transfer cells and reagents through unit operations further burden the workflow reducing efficiency and increasing the chance for human error. Here we describe a fully closed, autologous bioprocess generating engineered TCR-T cells. This bioprocess yielded 5-12 × 10e9 TCR-expressing T cells, transduced at low multiplicity of infections, within 7-10 days, and cells exhibited an enriched memory T-cell phenotype and enhanced metabolic fitness. It was demonstrated that activating, transducing, and expanding leukapheresed cells in a bioreactor without any T-cell or peripheral blood mononuclear cell enrichment steps had a high level of T-cell purity (~97%). Several critical process parameters of the bioreactor, including culturing at a high cell density (7e6 cells/mL), adjusting rocking agitations during phases of scale-up, lowering glycolysis through the addition of 2-deoxy- d-glucose, and modulating interleukin-2 levels, were investigated on their roles in regulating transduction efficiency, cell growth, and T-cell fitness such as T-cell memory phenotype and resistance to activation-induced cell death. The bioprocess described herein supports scale-out feasibility by enabling the processing of multiple patients' batches in parallel within a Grade C cleanroom.
Assuntos
Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Leucócitos Mononucleares/metabolismo , Linfócitos T/metabolismo , Neoplasias/metabolismo , Terapia Baseada em Transplante de Células e TecidosRESUMO
BACKGROUND: Community-based physical activity (PA) programs are appealing to women in Latin America and show potential for improving women's health. This study aimed to engage healthy middle-aged women, breast cancer survivors and local stakeholders participating in two publicly funded community-based PA programs in Bogotá, Colombia (Recreovía and My Body) to assess and visually map the perceived barriers, facilitators, and outcomes to promote programs' improvement, scaling and sustainability. METHODS: We used two participatory action research methods, the 1) Our Voice citizen science method to capture data and drive local change in built and social environmental facilitators and barriers that influence women's engagement in community-based PA; and 2) Ripple Effects Mapping to visually map the intended and unintended outcomes of PA programs. We used thematic analysis to classify the results at the individual, social, and community levels. RESULTS: The stakeholders engaged in the participatory evaluation included cross-sector actors from the programs (N = 6) and program users (total N = 34) from the two programs (Recreovía N = 16; My Body N = 18). Program users were women with a mean age of 55.7 years (SD = 8.03), 65% lived in low-income neighborhoods. They identified infrastructure as the main feature affecting PA, having both positive (e.g., appropriate facilities) and negative (e.g., poorly built areas for PA) effects. Regarding program improvements, stakeholders advocated for parks' cleaning, safety, and appropriate use. The most highlighted outcomes were the expansion and strengthening of social bonds and the engagement in collective wellbeing, which leveraged some participants' leadership skills for PA promotion strategies in their community. The facilitated dialogue among program users and stakeholders fostered the sustainability and expansion of the community-based PA programs, even during the COVID-19 pandemic. CONCLUSIONS: The implementation of both participatory methodologies provided a multidimensional understanding of the programs' impacts and multisectoral dialogues that fostered efforts to sustain the community-based PA programs.
Assuntos
COVID-19 , Pandemias , Colômbia , Exercício Físico , Feminino , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Características de ResidênciaRESUMO
Objective: Identify publications from 2000 to 2020 on hepatitis B in indigenous people in Latin America, to learn about advances and gaps in this field in the last 20 years. Methods: Exploratory review and systematic evidence review. Documents were organized using Excel and Rayyan® software. Results: We selected 30 of 107 articles found: 17 epidemiological studies, 10 document reviews, 2 clinical studies, and 1 letter to the editor. Brazil was the country with the most publications (50%), most of them with an epidemiological approach. The topic most often addressed was hepatitis B prevalence with 22 publications, followed by 11 studies reporting results of molecular studies of the virus, 7 studies on vaccination, 5 studies on risk factors, and 4 publications with topics such as vertical transmission and studies of social issues. Conclusion: Compared to previous reviews by other authors, we saw greater diversity in topics and research methods; however, conventional epidemiological approaches that focus on measuring prevalence of serological markers still predominate. Thus, there is a need for other types of research focused on sociocultural determinants.
Objetivo: Identificar artigos publicados entre 2000 e 2020 sobre hepatite B em indígenas da América Latina, visando a conhecer as conquistas obtidas nos últimos 20 anos e as lacunas existentes com relação a esta doença. Métodos: Foi realizada uma revisão exploratória da literatura com síntese das evidências. O material obtido foi organizado com o uso de Excel® e Rayyan®. Resultados: De 107 artigos encontrados, 30 foram selecionados 17 estudos epidemiológicos, 10 revisões documentais, 2 estudos clínicos e 1 carta ao editor. O Brasil foi o país com o maior percentual de artigos publicados (50%), na sua maioria estudos com enfoque epidemiológico. As áreas temáticas abordadas foram a prevalência de infecção pelo vírus da hepatite B (22 artigos), estudos moleculares do vírus da hepatite (11 estudos), vacinação (7), fatores de risco (5), e temas como transmissão materno-fetal e aspectos sociais (4). Conclusões: Comparado aos estudos de revisão anteriores conduzidos por outros autores, o presente estudo demonstra uma maior variedade de áreas temáticas e metodologias empregadas. No entanto, ainda predominam enfoques epidemiológicos convencionais com foco na avaliação da prevalência de marcadores sorológicos. São necessárias outras linhas de pesquisas enfocando os determinantes socioculturais.
RESUMO
IL-17-producing CD4(+) T (Th17) cells, along with IFN-γ-expressing Th1 cells, represent two major pathogenic T cell subsets in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). The cytokines and transcription factors involved in the development and effector functions of Th1 and Th17 cells have been largely characterized. Among them, IL-23 is essential for the generation of stable and encephalitogenic Th17 cells and for the development of EAE. The IL-7/IL-7R signaling axis participates in cell survival, and perturbation of this pathway has been associated with enhanced susceptibility to MS. A link between IL-23-driven pathogenic T cells and IL-7/IL-7R signaling has previously been proposed, but has not been formally addressed. In the current study, we showed that Th17 cells from mice with EAE express high levels of IL-7Rα compared with Th1 cells. Using mice that constitutively express IL-7Rα on T cells, we determined that sustained IL-7R expression in IL-23R-deficient mice could not drive pathogenic T cells and the development of EAE. IL-7 inhibited the differentiation of Th17 cells, but promoted IFN-γ and GM-CSF secretion in vitro. In vivo IL-7/anti-IL-7 mAb complexes selectively expanded and enhanced the proliferation of CXCR3-expressing Th1 cells, but did not impact Th17 cells and EAE development in wild-type and IL-23R-deficient mice. Importantly, high IL-7 expression was detected in the CNS during EAE and could drive the plasticity of Th17 cells to IFN-γ-producing T cells. Together, these data address the contribution of IL-23/IL-23R and IL-7/IL-7R signaling in Th17 and Th1 cell dynamics during CNS autoimmunity.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Encefalomielite Autoimune Experimental/imunologia , Interleucina-7/imunologia , Receptores de Interleucina-7/imunologia , Transdução de Sinais/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Células Cultivadas , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/metabolismo , Citometria de Fluxo , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-23/imunologia , Interleucina-23/metabolismo , Interleucina-7/genética , Interleucina-7/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/imunologia , Receptores de Interleucina/metabolismo , Receptores de Interleucina-7/genética , Receptores de Interleucina-7/metabolismo , Transdução de Sinais/genética , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismoRESUMO
During the development of experimental autoimmune encephalomyelitis (EAE), the proportion of pathogenic and myelin-specific cells within CNS-infiltrating cytokine-producing Th cells is unknown. Using an IL-17A/IFN-γ double reporter mouse and I-A(b)/myelin oligodendrocyte glycoprotein 38-49 tetramer, we show in this study that IL-17(+)IFN-γ(+) Th cells, which are expanded in the CNS during EAE, are highly enriched in myelin oligodendrocyte glycoprotein-specific T cells. We further demonstrate that IL-23 is essential for the generation and expansion of IFN-γ-producing Th17 cells independently of the Th1-associated transcription factors T-bet, STAT1, and STAT4. Furthermore, Th17 and IL-17(+)IFN-γ(+) Th cells can induce CNS autoimmunity independently of T-bet. Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell-mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-γ expression in Th1 and Th17 cells.
Assuntos
Interferon gama/imunologia , Interleucina-17/imunologia , Proteínas com Domínio T/imunologia , Células Th17/imunologia , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Interferon gama/biossíntese , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-23/imunologia , Interleucina-23/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/imunologia , Glicoproteína Mielina-Oligodendrócito/metabolismo , Fator de Transcrição STAT1/imunologia , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT4/imunologia , Fator de Transcrição STAT4/metabolismo , Proteínas com Domínio T/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/metabolismoRESUMO
Equine influenza is a viral disease caused by the equine influenza virus (EIV), and according to the WOAH, it is mandatory to report these infections. In Latin America and Colombia, EIV risk factors have not been analyzed. The objective of this research is to perform an epidemiological and molecular analysis of the EIV in horses with respiratory symptoms from 2020 to 2023 in Colombia. Molecular EIV detection was performed using RT-qPCR and nanopore sequencing. A risk analysis was also performed via the GEE method. A total of 188 equines with EIV respiratory symptoms were recruited. The positivity rate was 33.5%. The descriptive analysis showed that only 12.8% of the horses were vaccinated, and measures such as the quarantine and isolation of symptomatic animals accounted for 91.5% and 88.8%, respectively. The variables associated with the EIV were the non-isolation of positive individuals (OR = 8.16, 95% CI (1.52-43.67), p = 0.014) and sharing space with poultry (OR = 2.16, 95% CI (1.09-4.26), p = 0.027). In conclusion, this is the first EIV investigation in symptomatic horses in Colombia, highlighting the presence of the virus in the country and the need to improve preventive and control measures.
Assuntos
Doenças dos Cavalos , Vírus da Influenza A Subtipo H3N8 , Infecções por Orthomyxoviridae , Cavalos , Animais , Colômbia/epidemiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Doenças dos Cavalos/virologia , Doenças dos Cavalos/epidemiologia , Vírus da Influenza A Subtipo H3N8/isolamento & purificação , Vírus da Influenza A Subtipo H3N8/genética , Feminino , Masculino , Filogenia , Sequenciamento por Nanoporos/métodos , Fatores de RiscoRESUMO
Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection. Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival. Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023. Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator. Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07). Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Irinotecano , Leucovorina , Oxaliplatina , Neoplasias Pancreáticas , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Feminino , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Terapia Neoadjuvante , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Idoso de 80 Anos ou mais , Intervalo Livre de ProgressãoRESUMO
The department of La Guajira is considered the region with the largest goat population in Colombia. The disease caused by protozoa of the genus Eimeria can result in significant economic losses in goat production, threatening the region's food security. The objective of this study was to identify the occurrence of coccidiosis produced by Eimeria spp. in pools of fecal samples of young and adult goats belonging to 12 indigenous communities in the municipality of Maicao, La Guajira. The results showed the presence of eight different species of Eimeria spp. (E. alijevi, E. ninakohlyakimovae, E. hirci, E. arloingi, E. jolchijevi, E. caprovina, E. aspheronica and E. christenseni) differentiated by their morphological characteristics, in addition to the estimation of the parasite load in each fecal pool. In conclusion, this study is the first to report the occurrence of different species of Eimeria spp. in goats located in the department of La Guajira, Colombia.
Assuntos
Coccidiose , Eimeria , Doenças das Cabras , Animais , Colômbia/epidemiologia , Cabras , Coccidiose/epidemiologia , Coccidiose/veterinária , Fezes , Doenças das Cabras/epidemiologiaRESUMO
BACKGROUND: Interventions to promote physical activity among women breast cancer survivors (BCS) in low- to middle-income countries are limited. We assessed the acceptability and preliminary effectiveness of a theory-driven, group-based dance intervention for BCS delivered in Bogotá, Colombia. METHODS: We conducted a quasi-experimental study employing a mixed-methods approach to assess the 8-week, 3 times/week group dance intervention. The effect of the intervention on participants' physical activity levels (measured by accelerometry), motivation to engage in physical activity, and quality of life were evaluated using generalized estimating equation analysis. The qualitative method included semi-structured interviews thematically analyzed to evaluate program acceptability. RESULTS: Sixty-four BCS were allocated to the intervention (n = 31) or the control groups (n = 33). In the intervention arm, 84% attended ≥ 60% of sessions. We found increases on average minutes of moderate-to-vigorous physical activity per day (intervention: +8.99 vs control: -3.7 min), and in ratings of motivation (intervention change score = 0.45, vs. control change score= -0.05). BCS reported improvements in perceived behavioral capabilities to be active, captured through the interviews. CONCLUSIONS: The high attendance, behavioral changes, and successful delivery indicate the potential effectiveness, feasibility, and scalability of the intervention for BCS in Colombia. TRIAL REGISTRATION: ClinicalTrial.gov NCT05252780, registered on Dec 7th, 2021-retrospectively registered unique protocol ID: P20CA217199-9492018.
RESUMO
The transcription factor STAT1 plays a critical role in modulating the differentiation of CD4+ T cells producing IL-17 and GM-CSF, which promote the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The protective role of STAT1 in MS and EAE has been largely attributed to its ability to limit pathogenic Th cells and promote Tregs. Using mice with selective deletion of STAT1 in T cells (STAT1CD4-Cre), we identified a potentially novel mechanism by which STAT1 regulates neuroinflammation independently of Foxp3+ Tregs. STAT1-deficient effector T cells became the target of NK cell-mediated killing, limiting their capacity to induce EAE. STAT1-deficient T cells promoted their own killing by producing more IL-2 that, in return, activated NK cells. Elimination of NK cells restored EAE susceptibility in STAT1CD4-Cre mice. Therefore, our study suggests that the STAT1 pathway can be manipulated to limit autoreactive T cells during autoimmunity directed against the CNS.
Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Autoimunidade , Linfócitos T CD4-Positivos , Camundongos , Doenças Neuroinflamatórias , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismoRESUMO
BACKGROUND: In February 2016, the World Health Organization (WHO) declared the epidemic of the ZIKA virus (ZIKV) in Latin America to be a public health emergency. In Colombia, 11,944 pregnant women registered a ZIKV infection during the epidemic. So far, little is known about the experiences of women infected with ZIKV during their pregnancy, especially those relating to the provision of health services during the period of the epidemic. OBJECTIVE: To explore the experiences of pregnant women diagnosed with ZIKV infection about the provision of health services in two Colombian cities, considering the perspective of sexual and reproductive rights. METHODS: Qualitative study under the grounded theory approach, which uses semi-structured interviews as tools to explore the biographical experience of mothers during their gestation process and ZIKV infection, dividing the interview into two broad categories: before and during pregnancy. RESULTS: Twenty-two women were interviewed, 10 in Cali and 12 in Villavicencio. The average age at the time of pregnancy was 27.6 years. Most women were not planning at the time of pregnancy and the pregnancy was unwanted. Most campaigns focused on mosquito eradication rather than on sexual and reproductive health campaigns. The quality of health care was not sufficient, adequate, or appropriate. Also, the breakdown of the health system to deal with the pandemic was also noted. Some women were treated with disrespect by health professionals. Voluntary termination of pregnancy was inadequately advised, and women lost autonomy regarding decisions about their health. CONCLUSIONS: In the health care of ZIKV epidemics, it is necessary to include the gender perspective, more specifically, sexual and reproductive rights. In addition, these epidemics must be addressed through a comprehensive, appropriate, and not fragmented health system, in which sexual and reproductive rights must be mainstreamed in all health promotion and prevention programs.
Assuntos
Infecção por Zika virus , Adulto , Feminino , Serviços de Saúde , Humanos , Gravidez , Saúde Pública , Adulto JovemRESUMO
Ciclovía Recreativa is a program in which streets are closed off to automobiles so that people have a safe and inclusive space for recreation and for being physically active. The study aims were: (1) to compare participant's spatial trajectories in four Ciclovía Recreativa programs in Latin America (Bogotá, Mexico City, Santiago de Cali, and Santiago de Chile) according to socioeconomic characteristics and urban segregation of these cities; and (2) to assess the relationship between participants' physical activity (PA) levels and sociodemographic characteristics. We harmonized data of cross-sectional studies including 3282 adults collected between 2015 and 2019. We found the highest mobility for recreation in Bogotá, followed closely by Santiago de Cali. In these two cities, the maximum SES (socioeconomic status) percentile differences between the neighborhood of origin and the neighborhoods visited as part of the Ciclovía use were 33.58 (p-value < 0.001) and 30.38 (p-value < 0.001), respectively, indicating that in these two cities, participants were more likely to visit higher or lower SES neighborhoods than their average SES-of-neighborhood origin. By contrast, participants from Mexico City and Santiago de Chile were more likely to stay in geographic units similar to their average SES-of-origin, having lower overall mobility during leisure time: maximum SES percentile difference 1.55 (p-value < 0.001) and -0.91 (p-value 0.001), respectively. PA levels of participants did not differ by sex or SES. Our results suggest that Ciclovía can be a socially inclusive program in highly unequal and segregated urban environments, which provides a space for PA whilefacilitat physical proximity, exposure to new communities and environments, and interactions between different socioeconomic groups.
Assuntos
Exercício Físico , Inclusão Social , Adulto , Chile , Cidades , Estudos Transversais , Humanos , América Latina , México , Características de Residência , Classe SocialRESUMO
OBJECTIVE: To explore the perceptions and experiences of pregnant women in accessing healthcare services during the epidemic in Colombia during 2015-2016. METHODS: A qualitative study using semistructured interviews was conducted in Villavicencio. Six women who had been diagnosed with Zika virus infection during their pregnancies and whose fetus had suspected microcephaly participated in the investigation. Grounded theory was used and thematic content analysis was made for each category identified. RESULTS: Three main themes affecting access to healthcare services were identified: (1) women knew basic information about the virus, but it was limited; (2) access to services was delayed due to their lack of availability or limited supply in the municipality; and (3) most of the participants made out-of-pocket payments to get access to services that were not provided. CONCLUSIONS: Several gaps were identified in the provision of healthcare services to pregnant women during the Zika epidemic. Policy makers need to utilize the results from affected communities to develop and implement public policies that adapt and respond to their priorities and needs.
Assuntos
Acessibilidade aos Serviços de Saúde/normas , Complicações Infecciosas na Gravidez/terapia , Infecção por Zika virus/terapia , Adulto , Colômbia , Epidemias , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/virologia , Teoria Fundamentada , Acessibilidade aos Serviços de Saúde/economia , Humanos , Recém-Nascido , Microcefalia/diagnóstico , Microcefalia/virologia , Avaliação das Necessidades , Gravidez , Pesquisa Qualitativa , Zika virus , Infecção por Zika virus/transmissãoRESUMO
Cancer vaccines using synthetic long peptides (SLP) targeting tumor antigens have been tested in the clinic but the outcomes have been unimpressive, perhaps because these peptides elicit predominantly CD4+ T cell responses. We hypothesized that enhanced delivery of peptide antigens to, and uptake in, secondary lymphoid tissues should elicit more robust CD8+ and CD4+ T cell responses and improved anti-tumor responses. Here, we have designed SLP-containing cationic lipoplexes (SLP-Lpx) that improve delivery of peptides to myeloid cells in the spleen and lymphatics. Using the G12D KRAS mutations as neoantigens, we found that vaccination of mice with naked synthetic peptides harboring the G12D mutation with CpG adjuvant stimulated mainly CD4+ T cell responses with limited tumor growth inhibition. On the other hand, immunization with SLP-Lpx stimulated both CD4+ and CD8+ T cells and suppressed tumor growth in a CD8+ T cell-dependent manner. Combination of the SLP-Lpx vaccines with a checkpoint inhibitor led to profound growth suppression of established tumors. These studies suggest that preferential targeting of peptides derived from neoantigens to the spleen via lipoplexes elicits potent CD4+ and CD8+ T cell responses that inhibit tumor growth.
RESUMO
This report describes a new lethal case of Rickettsia rickettsii infection in a child from Northwestern Colombia, after ten years of the last outbreaks in the same region. Colombian public-health authorities should consider to include this severe rickettsiosis in the compulsory-reporting diseases, with the aim of knowing its burden in the country.
Assuntos
Rickettsia rickettsii/isolamento & purificação , Febre Maculosa das Montanhas Rochosas/microbiologia , Pré-Escolar , Colômbia , Evolução Fatal , Humanos , MasculinoRESUMO
INTRODUCTION: Most of the studies related to rickettsial infection in Colombia are cross-sectional because of the challenge in conducting prospective studies on infectious disease that may have a difficult diagnosis. Although cross-sectional studies are essential to detect people exposed to rickettsiae, they are not suited to demonstrate the recent circulation of this pathogen in areas at risk of transmission. OBJECTIVE: To characterize the epidemiology of incident cases of Spotted fever group (SFG) rickettsial infection in humans and equines from rural areas of Urabá region in Colombia where outbreaks of rickettsiae previously occurred. MATERIALS AND METHODS: A prospective study was conducted in the Alto de Mulatos and Las Changas in the Urabá region. Serum samples and socio-ecological information were collected from 597 people enrolled in 2015, and a second sample was collected from 273 people a year later. Indirect immune-fluorescence assays for detection of IgG antibody against rickettsiae were done using slides with Rickettsia rickettsii antigens. A titer ≥128 was considered positive. Incident cases were defined as (i) serological conversion of IgG titers from seronegative to seropositive or (ii) at least a four-fold increase in IgG end point titers in the second sample. RESULTS: The cumulative incidence of rickettsial infection was 6.23% (95%CI 3.67-9.78) in humans and 32.31% (21/65) of incident cases in equines. Incident cases were mostly females (82.35%), the median age of cases was 41.02 years (IQR 18.62-54.1), and 29.41% reported tick bites during the study period. Results from multivariate analysis showed that removal of ticks after working outdoors is a protective factor for rickettsial infection (RR 0.26, 95%CI 0.08-0.84) and that a higher incidence of infection occurred in people who reported fever in the last year (RR 4.26, 95%CI 1.15-9.31). CONCLUSIONS: These results showed recent circulation of SFG rickettsiae in areas where previous lethal outbreaks have been reported, supporting the implementation of preventive measures to halt rickettsial transmission in the studied communities.
Assuntos
Doenças dos Cavalos/epidemiologia , Rickettsiose do Grupo da Febre Maculosa/epidemiologia , Rickettsiose do Grupo da Febre Maculosa/veterinária , Adolescente , Adulto , Distribuição por Idade , Animais , Anticorpos Antibacterianos/sangue , Colômbia/epidemiologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Cavalos , Humanos , Imunoglobulina G/sangue , Incidência , Masculino , Estudos Prospectivos , População Rural , Fatores Sexuais , Adulto JovemRESUMO
UNLABELLED: Infection by Helicobacter pylori (H. pylori) and its associated complications, such as gastric cancer, constitute a true public health problem due to the high morbidity and mortality rates in Colombia and Latin America, where it is highly prevalent. OBJECTIVE: To characterize the prevalence of H. pylori infection in the medical population ofMedellin, Colombia. METHODS: A transversal-cut observational epidemiological study was done, 342 physicians were included. The presence of H. pylori infection, diagnosed with carbon 13-labelled urea breath test, and its association with personal aspects, history of gastric disease and clinical manifestations was evaluated. RESULTS: The general prevalence of H. pylori infection was found to be 77.2% (CI 95%: 72.4% to 81.5%). Discriminating by gender, it represents a prevalence of 78.4% in men and 72.6% in women, without any significant association (chi-square, p = 0.37). Of the total 342 participants, 183 (53.5%) presented at least one suspected episode of gastric disease, and of these, 141 (77%) were positive and 42 (23%) were negative for H. pylori; of the 264 H. pylori positive participants, 141 (53.4%) had history of gastric disease and 123 (46.6%) were asymptomatic. CONCLUSIONS: Prevalence of H. pylori infection in the medical population in Medellin, Colombia, is 77.2% (CI 95%: 72.4% to 81.5%), in accordance to the epidemiologic profile of the region. Also, 46.6% of individuals infected by H. pylori were asymptomatic and with no history or symptoms suggestive of the presence of the bacteria, which is only possible to determine after appropriate testing of the individuals.
Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Doenças Profissionais/epidemiologia , Médicos/estatística & dados numéricos , Carbono , Colômbia/epidemiologia , Estudos Transversais , Dispepsia/epidemiologia , Dispepsia/microbiologia , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estatísticas não Paramétricas , UreiaRESUMO
[RESUMEN]. Objetivo. Identificar publicaciones realizadas entre los años 2000 y 2020 sobre hepatitis B en indígenas de América Latina, con el fin de conocer avances y vacíos en el tema durante los últimos 20 años. Métodos. Revisión exploratoria y síntesis rápida de la evidencia. El proceso de organización documental se realizó con los programas Excel® y Rayyan®. Resultados. Se seleccionaron 30 de 107 artículos encontrados, 17 corresponden a estudios epidemiológicos, 10 a revisiones documentales, dos estudios clínicos y una carta al editor. Brasil fue el país con más publicaciones (50%), la mayoría con enfoque epidemiológico. La temática más abordada fue la medición de prevalencia de la infección por hepatitis B con 22 publicaciones, le siguieron 11 estudios que informan resultados de estudios moleculares del virus, siete estudios sobre vacunación, cinco estudios sobre factores de riesgo y cuatro publicaciones con temas como la transmisión vertical y estudios sociales. Conclusión. En comparación con revisiones previas realizadas por otros autores, se observa una mayor diversidad en los temas y métodos de investigación utilizados; sin embargo, aún prevalecen los enfoques epidemiológicos convencionales centrados en la medición de la prevalencia de marcadores serológicos. Esto hace necesario encarar otro tipo de investigaciones centradas en los determinantes socioculturales.
[ABSTRACT]. Objective. Identify publications from 2000 to 2020 on hepatitis B in indigenous people in Latin America, to learn about advances and gaps in this field in the last 20 years. Methods. Exploratory review and systematic evidence review. Documents were organized using Excel and Rayyan® software. Results. We selected 30 of 107 articles found: 17 epidemiological studies, 10 document reviews, 2 clinical studies, and 1 letter to the editor. Brazil was the country with the most publications (50%), most of them with an epidemiological approach. The topic most often addressed was hepatitis B prevalence with 22 publications, followed by 11 studies reporting results of molecular studies of the virus, 7 studies on vaccination, 5 studies on risk factors, and 4 publications with topics such as vertical transmission and studies of social issues. Conclusion. Compared to previous reviews by other authors, we saw greater diversity in topics and research methods; however, conventional epidemiological approaches that focus on measuring prevalence of serological markers still predominate. Thus, there is a need for other types of research focused on sociocultural determinants.
[RESUMO]. Objetivo. Identificar artigos publicados entre 2000 e 2020 sobre hepatite B em indígenas da América Latina, visando a conhecer as conquistas obtidas nos últimos 20 anos e as lacunas existentes com relação a esta doença. Métodos. Foi realizada uma revisão exploratória da literatura com síntese das evidências. O material obtido foi organizado com o uso de Excel® e Rayyan®. Resultados. De 107 artigos encontrados, 30 foram selecionados – 17 estudos epidemiológicos, 10 revisões documentais, 2 estudos clínicos e 1 carta ao editor. O Brasil foi o país com o maior percentual de artigos publicados (50%), na sua maioria estudos com enfoque epidemiológico. As áreas temáticas abordadas foram a prevalência de infecção pelo vírus da hepatite B (22 artigos), estudos moleculares do vírus da hepatite (11 estudos), vacinação (7), fatores de risco (5), e temas como transmissão materno-fetal e aspectos sociais (4). Conclusões. Comparado aos estudos de revisão anteriores conduzidos por outros autores, o presente estudo demonstra uma maior variedade de áreas temáticas e metodologias empregadas. No entanto, ainda predominam enfoques epidemiológicos convencionais com foco na avaliação da prevalência de marcadores sorológicos. São necessárias outras linhas de pesquisas enfocando os determinantes socioculturais.
Assuntos
Hepatite , Povos Indígenas , Saúde de Populações Indígenas , América Latina , Povos Indígenas , Saúde de Populações Indígenas , América Latina , Hepatite , Povos Indígenas , Saúde de Populações IndígenasRESUMO
RESUMEN Objetivo. Identificar publicaciones realizadas entre los años 2000 y 2020 sobre hepatitis B en indígenas de América Latina, con el fin de conocer avances y vacíos en el tema durante los últimos 20 años. Métodos. Revisión exploratoria y síntesis rápida de la evidencia. El proceso de organización documental se realizó con los programas Excel® y Rayyan®. Resultados. Se seleccionaron 30 de 107 artículos encontrados, 17 corresponden a estudios epidemiológicos, 10 a revisiones documentales, dos estudios clínicos y una carta al editor. Brasil fue el país con más publicaciones (50%), la mayoría con enfoque epidemiológico. La temática más abordada fue la medición de prevalencia de la infección por hepatitis B con 22 publicaciones, le siguieron 11 estudios que informan resultados de estudios moleculares del virus, siete estudios sobre vacunación, cinco estudios sobre factores de riesgo y cuatro publicaciones con temas como la transmisión vertical y estudios sociales. Conclusión. En comparación con revisiones previas realizadas por otros autores, se observa una mayor diversidad en los temas y métodos de investigación utilizados; sin embargo, aún prevalecen los enfoques epidemiológicos convencionales centrados en la medición de la prevalencia de marcadores serológicos. Esto hace necesario encarar otro tipo de investigaciones centradas en los determinantes socioculturales.
ABSTRACT Objective. Identify publications from 2000 to 2020 on hepatitis B in indigenous people in Latin America, to learn about advances and gaps in this field in the last 20 years. Methods. Exploratory review and systematic evidence review. Documents were organized using Excel and Rayyan® software. Results. We selected 30 of 107 articles found: 17 epidemiological studies, 10 document reviews, 2 clinical studies, and 1 letter to the editor. Brazil was the country with the most publications (50%), most of them with an epidemiological approach. The topic most often addressed was hepatitis B prevalence with 22 publications, followed by 11 studies reporting results of molecular studies of the virus, 7 studies on vaccination, 5 studies on risk factors, and 4 publications with topics such as vertical transmission and studies of social issues. Conclusion. Compared to previous reviews by other authors, we saw greater diversity in topics and research methods; however, conventional epidemiological approaches that focus on measuring prevalence of serological markers still predominate. Thus, there is a need for other types of research focused on sociocultural determinants.
RESUMO Objetivo. Identificar artigos publicados entre 2000 e 2020 sobre hepatite B em indígenas da América Latina, visando a conhecer as conquistas obtidas nos últimos 20 anos e as lacunas existentes com relação a esta doença. Métodos. Foi realizada uma revisão exploratória da literatura com síntese das evidências. O material obtido foi organizado com o uso de Excel® e Rayyan®. Resultados. De 107 artigos encontrados, 30 foram selecionados - 17 estudos epidemiológicos, 10 revisões documentais, 2 estudos clínicos e 1 carta ao editor. O Brasil foi o país com o maior percentual de artigos publicados (50%), na sua maioria estudos com enfoque epidemiológico. As áreas temáticas abordadas foram a prevalência de infecção pelo vírus da hepatite B (22 artigos), estudos moleculares do vírus da hepatite (11 estudos), vacinação (7), fatores de risco (5), e temas como transmissão materno-fetal e aspectos sociais (4). Conclusões. Comparado aos estudos de revisão anteriores conduzidos por outros autores, o presente estudo demonstra uma maior variedade de áreas temáticas e metodologias empregadas. No entanto, ainda predominam enfoques epidemiológicos convencionais com foco na avaliação da prevalência de marcadores sorológicos. São necessárias outras linhas de pesquisas enfocando os determinantes socioculturais.
RESUMO
The article examines the use of bilingual guides to decrease cultural barriers to health care access in the Wayuu indigenous communities of Colombia. Within a larger project on HIV carried out between 2012 and 2014, 24 interviews were conducted with key actors in the administrative and health areas, including Wayuu bilingual guides. As a result of the qualitative analysis, the study identified three cultural barriers to health care access: a) language; b) the Wayuu worldview regarding the body, health, and illness; and c) information about sexual and reproductive health and HIV not adapted to the Wayuu culture. The study identifies the bilingual guides as key actors in reducing these barriers and concludes with a discussion of the role of the guides, the tensions inherent to their work, and the complexity of their contributions as cultural mediators.