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Drivers for wildlife infection are multiple and complex, particularly for vector-borne diseases. Here, we studied the role of host competence, geographic area provenance, and diversity of vector-host interactions as drivers of wild mammal infection risk to Trypanosoma cruzi, the aetiological agent of Chagas disease. We performed a systematic sampling of wild mammals in 11 states of Mexico, from 2017 to 2018. We tested the positivity of T. cruzi with the Tc24 marker in tissues samples for 61 wild mammal species (524 specimens sampled). 26 mammal species were positive for T. cruzi, of which 11 are new hosts recorded in Mexico 75 specimens were positive and 449 were negative for T. cruzi infection, yielding an overall prevalence of 14.3%. The standardized infection risk of T. cruzi of our examined specimens was similar, no matter the host species or their geographic origins. Additionally, we used published data of mammal positives for T. cruzi to complement records of T. cruzi infection in wild mammals and inferred a trophic network of Triatoma spp. (vectors) and wild mammal species in Mexico, using spatial data-mining modelling. Infection with T. cruzi was not homogeneously distributed in the inferred trophic network. This information allowed us to develop a predictive model for T. cruzi infection risk for wild mammals in Mexico, considering risk as a function of the diversity of vector-host spatial associations in a large-scale geographic context, finding that the addition of competent vectors to a multi-host parasite system amplifies host infection risk. The diversity of vector-host interactions per se constitutes a relevant driver of infection risk because hosts and vectors are not isolated from each other.
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Enfermedad de Chagas , Triatoma , Trypanosoma cruzi , Animales , Animales Salvajes/parasitología , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/veterinaria , Enfermedad de Chagas/parasitología , Triatoma/parasitología , Mamíferos/parasitología , Zoonosis/epidemiología , GeografíaRESUMEN
(1) Background: Chagas disease is the main neglected tropical disease in America. It is estimated that around 6 million people are currently infected with the parasite in Latin America, and 25 million live in endemic areas with active transmission. The disease causes an estimated economic loss of USD 24 billion dollars annually, with a loss of 75,200 working years per year of life; it is responsible for around ~12,000 deaths annually. Although Mexico is an endemic country that recorded 10,186 new cases of Chagas disease during the period of 1990-2017, few studies have evaluated the genetic diversity of genes that could be involved in the prophylaxis and/or diagnosis of the parasite. One of the possible candidates proposed as a vaccine target is the 24 kDa trypomastigote excretory-secretory protein, Tc24, whose protection is linked to the stimulation of T. cruzi-specific CD8+ immune responses. (2) Methods: The aim of the present study was to evaluate the fine-scale genetic diversity and structure of Tc24 in T. cruzi isolates from Mexico, and to compare them with other populations reported in the Americas with the aim to reconsider the potential role of Tc24 as a key candidate for the prophylaxis and improvement of the diagnosis of Chagas disease in Mexico. (3) Results: Of the 25 Mexican isolates analysed, 48% (12) were recovered from humans and 24% (6) recovered from Triatoma barberi and Triatoma dimidiata. Phylogenetic inferences revealed a polytomy in the T. cruzi clade with two defined subgroups, one formed by all sequences of the DTU I and the other formed by DTU II-VI; both subgroups had high branch support. Genetic population analysis detected a single (monomorphic) haplotype of TcI throughout the entire distribution across both Mexico and South America. This information was supported by Nei's pairwise distances, where the sequences of TcI showed no genetic differences. (4) Conclusions: Given that both previous studies and the findings of the present work confirmed that TcI is the only genotype detected from human isolates obtained from various states of Mexico, and that there is no significant genetic variability in any of them, it is possible to propose the development of in silico strategies for the production of antigens that optimise the diagnosis of Chagas disease, such as quantitative ELISA methods that use this region of Tc24.
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BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.
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COVID-19 , Humanos , COVID-19/complicaciones , Proyectos Piloto , Síndrome Post Agudo de COVID-19 , Linfocitos T CD8-positivos , Estudios de Cohortes , Quimiocina CXCL10 , ObesidadRESUMEN
Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.
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COVID-19 , Anticuerpos Antivirales , Linfocitos T CD8-positivos , Quimiocinas , Estudios de Cohortes , Enfermedad Crítica , Citocinas , Humanos , Inmunoglobulina G , SARS-CoV-2Asunto(s)
Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/complicaciones , Área Bajo la Curva , Linfocitos B/metabolismo , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , COVID-19/diagnóstico , COVID-19/inmunología , Estudios de Cohortes , Femenino , Humanos , Masculino , Oportunidad Relativa , Valor Predictivo de las Pruebas , Curva ROC , Factores Sexuales , Factor A de Crecimiento Endotelial Vascular/sangre , Síndrome Post Agudo de COVID-19RESUMEN
Limited information is available to determine the effectiveness of Mexico's national influenza vaccination guidelines and inform policy updates. We aim to propose reforms to current influenza vaccination policies based on our analysis of cost-effectiveness studies. This cross-sectional epidemiological study used influenza case, death, discharge and hospitalization data from several influenza seasons and applied a one-year decision-analytic model to assess cost-effectiveness. The primary health outcome was influenza cases avoided; secondary health outcomes were influenza-related events associated with case reduction. By increasing vaccination coverage to 75% in the population aged 12-49 years with risk factors (diabetes, high blood pressure, morbid obesity, chronic renal failure, asthma, pregnancy), and expanding universal vaccination coverage to school-aged children (5-11 years) and adults aged 50-59 years, 7142-671,461 influenza cases; 1-15 deaths; 7615-262,812 healthcare visits; 2886-154,143 emergency room admissions and 2891-97,637 hospitalizations could be prevented (ranges correspond to separate age and risk factor groups), with a net annual savings of 3.90 to 111.99 million USD. Such changes to the current vaccination policy could potentially result in significant economic and health benefits. These data could be used to inform the revision of a vaccination policy in Mexico with substantial social value.
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The Mexican influenza vaccination program does not include a recommendation for people aged 50-59 years without risk factors for influenza complications, and there are limited data regarding the cost-effectiveness of vaccinating this population. To explore the clinical and economic effects of including this population in the vaccination schedule, we performed a cross-sectional epidemiological study using records (2009-2018) from Mexico's Influenza Surveillance System (SISVEFLU), death records (2010-2015) from the National Mortality Epidemiological and Statistical System, and discharge and hospitalization records (2010-2015) from the Automated Hospital Discharge System databases. A 1-year decision-analytic model was used to assess cost-effectiveness through a decision-tree based on data from SISVEFLU. The primary outcome was influenza cases avoided; with associated influenza-related events as secondary outcomes. Including the population aged 50-59 years without risk factors in Mexico's influenza immunization program would have resulted in 199,500 fewer cases; 67,008 fewer outpatient consultations; 33,024 fewer emergency room consultations; 33,091 fewer hospitalizations; 12 fewer deaths. These reductions equate to a substantial public health benefit as well as an economic benefit; yielding net savings of 49.8 million US dollars over a typical influenza season. Expansion of the current Mexican vaccination schedule to include these people would be a cost-saving and dominant strategy.
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BACKGROUND: The current national influenza vaccination schedule in Mexico does not recommend vaccination in the school-aged population (5-11 years). Currently, there are limited data from middle-income countries analysing the cost-effectiveness of influenza vaccination in this population. We explored the clinical effects and economic benefits of expanding the current national influenza vaccination schedule in Mexico to include the school-aged population. METHODS: A static 1-year model incorporating herd effect was used to assess the cost-effectiveness of expanding the current national influenza vaccination schedule of Mexico to include the school-aged population. We performed a cross-sectional epidemiological study using influenza records (2009-2018), death records (2010-2015), and discharge and hospitalisation records (2010-2016), from the databases of Mexico's Influenza Surveillance System (SISVEFLU), the National Mortality Epidemiological and Statistical System (SEED), and the Automated Hospital Discharge System (SAEH), respectively. Cost estimates for influenza cases were based on 7 scenarios using data analysed from SISVEFLU; assumptions for clinical management of cases were defined according to Mexico's national clinical guidelines. The primary health outcome for this study was the number of influenza cases avoided. A sensitivity analysis was performed using conservative and optimistic parameters (vaccination coverage: 30% / 70%, Vaccine effectiveness: 19% / 68%). RESULTS: It was estimated that expanding the influenza immunisation programme to cover school-aged population in Mexico over the 2018-2019 influenza season would result in 671,461 cases of influenza avoided (50% coverage and 50% effectiveness assumed). Associated with this were 262,800 fewer outpatient consultations; 154,100 fewer emergency room consultations; 97,600 fewer hospitalisations, and 15 fewer deaths. Analysis of cases avoided by age-group showed that 55.4% of them were in the school-aged population, and the decrease in outpatient consultations was largest in this population. There was an overall decrease in the economic burden for the Mexican health care system of 111.9 million US dollars; the immunization programme was determined to be cost-saving in the base, conservative and optimistic scenarios. CONCLUSIONS: Vaccinating school-aged population in Mexico would be cost-effective; expansion of the current national vaccination schedule to this age group is supported.
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Análisis Costo-Beneficio/métodos , Vacunas contra la Influenza/economía , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Vacunación/economía , Niño , Preescolar , Estudios Transversales , Atención a la Salud , Femenino , Hospitalización/economía , Humanos , Programas de Inmunización/economía , Esquemas de Inmunización , Incidencia , Gripe Humana/mortalidad , Masculino , México/epidemiología , Alta del Paciente , Cobertura de VacunaciónRESUMEN
BACKGROUND: Currently, there are no solutions to prevent congenital transmission of Chagas disease during pregnancy, which affects 1-40% of pregnant women in Latin America and is associated with a 5% transmission risk. With therapeutic vaccines under development, now is the right time to determine the economic value of such a vaccine to prevent congenital transmission. METHODS: We developed a computational decision model that represented the clinical outcomes and diagnostic testing strategies for an infant born to a Chagas-positive woman in Mexico and evaluated the impact of vaccination. RESULTS: Compared to no vaccination, a 25% efficacious vaccine averted 125 [95% uncertainty interval (UI): 122-128] congenital cases, 1.9 (95% UI: 1.6-2.2) infant deaths, and 78 (95% UI: 66-91) DALYs per 10,000 infected pregnant women; a 50% efficacious vaccine averted 251 (95% UI: 248-254) cases, 3.8 (95% UI: 3.6-4.2) deaths, and 160 (95% UI: 148-171) DALYs; and a 75% efficacious vaccine averted 376 (95% UI: 374-378) cases, 5.8 (95% UI: 5.5-6.1) deaths, and 238 (95% UI: 227-249) DALYs. A 25% efficacious vaccine was cost-effective (incremental cost-effectiveness ratio <3× Mexico's gross domestic product per capita, <$29,698/DALY averted) when the vaccine cost ≤$240 and ≤$310 and cost-saving when ≤$10 and ≤$80 from the third-party payer and societal perspectives, respectively. A 50% efficacious vaccine was cost-effective when costing ≤$490 and ≤$615 and cost-saving when ≤$25 and ≤$160, from the third-party payer and societal perspectives, respectively. A 75% efficacious vaccine was cost-effective when ≤$720 and ≤$930 and cost-saving when ≤$40 and ≤$250 from the third-party payer and societal perspectives, respectively. Additionally, 13-42 fewer infants progressed to chronic disease, saving $0.41-$1.21 million to society. CONCLUSION: We delineated the thresholds at which therapeutic vaccination of Chagas-positive pregnant women would be cost-effective and cost-saving, providing economic guidance for decision-makers to consider when developing and bringing such a vaccine to market.
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Enfermedad de Chagas , Vacunas , Enfermedad de Chagas/prevención & control , Análisis Costo-Beneficio , Femenino , Humanos , Lactante , América Latina , México , Embarazo , Mujeres Embarazadas , VacunaciónRESUMEN
Resumen Objetivo: Evaluar el efecto de tres fuentes de alimentación sanguínea: conejo Nueva Zelanda, rata egipcia y humana, sobre el número de huevos colocados por ovipuesta y porcentaje de eclosión de las larvas Aedes aegypti en condiciones de insectario. Material y Métodos: Grupo de mosquitos hembra Aedes aegypti con 1 día post-emergencia fueron alimentadas en condiciones de insectario con tres diferentes fuentes sanguíneas. Los grupos alimentados con conejo Nueva Zelanda y rata egipcia se expusieron de forma directa dentro de las jaulas de emergencia con los mosquitos; y en los grupos de mosquitos alimentados con la fuente sanguínea humana se utilizó una membrana artificial de algodón. Los datos fueron analizados con una prueba no paramétrica de Kruskal-wallis (p ≤ 0.05). Resultados: Se observó una diferencia estadísticamente significativa en el promedio de huevos colocados entre los tres grupos de hembras Aedes aegypti alimentados con diferentes fuentes sanguíneas: sangre de rata, 671.25 huevos; sangre humana, 268.14 huevos y sangre de conejo, 209.08 huevos (X2= 10.666, P < 0.0048); el porcentaje de larvas eclosionadas no presentó diferencias estadísticamente significativas entre las tres fuentes sanguíneas (X2= 0.192, p < 0.9083). Conclusiones: En este estudió se observó que el uso de sangre de rata egipcia como fuente de alimentación sanguínea para la producción de mosquitos Aedes aegypti en condiciones de insectario produce un mayor número de huevos en la ovipostura comparado con la sangre de conejo y de humano.
Abstract Objetive: To evaluate the effect of three sources of blood feeding: New Zealand rabbit, Egyptian rat and human, on the number of eggs laid and percentage of Aedes aegypti larvae hatching under insectary conditions. Materials and methods: To evaluate the effect of three sources of blood feeding: New Zealand rabbit, Egyptian rat and human, on the number of eggs laid and percentage of Aedes aegypti larvae hatching under insectary conditions. Results: A statistical significant difference was observed in the average of eggs placed between the three pools of Aedes aegypti females fed different blood sources: rat blood, 671.25 eggs; human blood, 268.14 eggs and rabbit blood, 209.08 eggs (X2= 10.666, P <0.0048); the percentage of hatched larvae did not present statistically significant differences between the three blood sources (X2 = 0.192, p <0.9083). Conclusions: In this study we observed that the use of Egyptian rat blood as a source for blood feeding for the production of Aedes aegypti mosquitoes under insectary conditions produced a greater number of eggs in the oviposition when compared to rabbit and human blood.
Resumo Objetivo: Avaliar o efeito de três fontes de alimentação sanguínea: coelho Nova Zelândia, rato egípcio e humano sobre o número de ovos colocados por oviposição e a porcentagem de eclosão de larvas de Aedes aegypti, em insetários. Materiais e métodos: Grupo de mosquitos fêmeas de Aedes aegypti com 1 dia pós-emergência foram alimentados em insetários com três diferentes fontes sanguíneas. Nos grupos de mosquitos alimentados com sangue de coelhos Nova Zelândia e de rato egípcio, as fontes foram expostas aos mosquitos, de forma direta, em gaiolas de emergência; e nos grupos de mosquitos alimentados com sangue humano, utilizou-se uma membrana artificial de algodão. Os dados foram analisados com teste não paramétrico de Kruskal-wallis (p ≤ 0,05). Resultados: Observou-se diferença significativa na média dos ovos colocados entre os três grupos de fêmeas de Aedes aegypti alimentados com diferentes fontes sanguíneas: sangue de ratos, 671,25 ovos; sangue humano, 268,14 ovos e sangue de coelho, 209,08 ovos (X2=10,666, P <0,0048); a porcentagem de larvas eclodidas não apresentou diferença estatisticamente significante entre as três fontes sanguíneas (X2= 0,192, P <0,9033). Conclusão: Neste estudo observou-se que o uso de sangue de rato egípcio como fonte de sangue ou alimento para a produção de mosquitos Aedes aegypti, em insetários, produz maior número de ovos na oviposição em relação ao sangue de coelhos e humanos.
Résumé Objectif: Pour évaluer l'effet de trois sources d'approvisionnement en sang: Nouvelle-Zélande lapin, homme égyptien et rat sur le nombre d'œufs pondus par ponte des œufs et le pourcentage éclosion des larves d'Aedes aegypti capables de Insectarium. Matériel et méthodes: Groupe moustiques Aedes aegypti femelle 1 jour post-émergence ont été nourris dans des conditions insectarium avec trois différentes sources de sang. Des groupes nourris aux lapins de Nouvelle-Zélande et aux rats égyptiens ont été exposés directement dans des cages d'urgence avec des moustiques; et une membrane de coton artificiel a été utilisée dans les groupes de moustiques nourris avec la source de sang humain. Les données ont été analysées avec un test de Kruskal-wallis non paramétrique (p ≤ 0,05). Résultats: Une différence statistiquement significative a été observée dans le nombre moyen d'oeufs placés entre les trois groupes d'Aedes aegypti femelles nourris différentes sources de sang de sang de rat, les œufs 671.25; sang humain, 268,14 œufs et sang de lapin, 209,08 œufs (X2= 10,666, P <0,0048); le pourcentage de larves hachurées ne présentait pas de différences statistiquement significatives entre les trois sources de sang (X2= 0,192, p <0,9083). Conclusions: Dans ce étudié a été observé que l'utilisation du sang chez le rat égyptien comme source de sang pour la production de moustiques Aedes aegypti dans l'insectarium produit plus d'oeufs par épisode de la posture de l'œuf, par rapport au sang de lapin et humain.
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BACKGROUND: Therapeutic vaccines to prevent Chagas disease progression to cardiomyopathy are under development because the only available medications (benznidazole and nifurtimox) are limited by their efficacy, long treatment course, and side effects. Better understanding the potential clinical and economic value of such vaccines can help guide development and implementation. METHODS: We developed a computational Chagas Markov model to evaluate the clinical and economic value of a therapeutic vaccine given in conjunction with benznidazole in indeterminate and chronic Chagas patients. Scenarios explored the vaccine's impact on reducing drug treatment dosage, duration, and adverse events, and risk of disease progression. RESULTS: When administering standard-of-care benznidazole to 1000 indeterminate patients, 148 discontinued treatment and 219 progressed to chronic disease, resulting in 119 Chagas-related deaths and 2293 DALYs, costing $18.9 million in lifetime societal costs. Compared to benznidazole-only, therapeutic vaccination administered with benznidazole (25-75% reduction in standard dose and duration), resulted in 37-111 more patients (of 1000) completing treatment, preventing 11-219 patients from progressing, 6-120 deaths, and 108-2229 DALYs (5-100% progression risk reduction), saving ≤$16,171 per patient. When vaccinating determinate Kuschnir class 1 Chagas patients, 10-197 fewer patients further progressed compared to benznidazole-only, averting 11-228 deaths and 144-3037 DALYs (5-100% progression risk reduction), saving ≤$34,059 per person. When vaccinating Kuschnir class 2 patients, 13-279 fewer progressed (279 with benznidazole-only), averting 13-692 deaths and 283-10,785 DALYs (5-100% progression risk reduction), saving ≤$89,759. Therapeutic vaccination was dominant (saved costs and provided health benefits) with ≥â¯5% progression risk reduction, except when only reducing drug treatment regimen and adverse events, but remained cost-effective when costing <$200. CONCLUSIONS: Our study helps outline the thresholds at which a therapeutic Chagas vaccine may be cost-effective (e.g., <5% reduction in preventing cardiac progression, 25% reduction in benznidazole treatment doses and duration) and cost-saving (e.g., ≥5% and 25%, respectively).
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Cardiomiopatías/economía , Cardiomiopatías/inmunología , Enfermedad de Chagas/economía , Enfermedad de Chagas/inmunología , Vacunas/economía , Vacunas/inmunología , Enfermedad Crónica/economía , Enfermedad Crónica/prevención & control , Análisis Costo-Beneficio/economía , Progresión de la Enfermedad , Humanos , Nitroimidazoles/uso terapéutico , Trypanosoma cruzi/inmunología , Vacunación/economíaRESUMEN
INTRODUCTION: Mathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties. MATERIALS AND METHODS: We carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days. RESULTS: Although absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places. CONCLUSIONS: Results of this study show that human mobility in a small urban setting exceeded that considered by local health authority's administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.
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Dengue/transmisión , Modelos Teóricos , Viaje , Adolescente , Adulto , Estudios de Casos y Controles , Ciudades , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Población Urbana , Adulto JovenRESUMEN
Dengue is a growing public health problem in tropical and subtropical cities. It is transmitted by mosquitoes, and the main strategy for epidemic prevention and control is insecticide fumigation. Effective management is, however, proving elusive. People's day-to-day movement about the city is believed to be an important factor in the epidemiological dynamics. We use a simple model to examine the fundamental roles of broad demographic and spatial structures in epidemic initiation, growth and control. We show that the key factors are local dilution, characterised by the vector-host ratio, and spatial connectivity, characterised by the extent of habitually variable movement patterns. Epidemic risk in the population is driven by the demographic groups that frequent the areas with the highest vector-host ratio, even if they only spend some of their time there. Synchronisation of epidemic trajectories in different demographic groups is governed by the vector-host ratios to which they are exposed and the strength of connectivity. Strategies for epidemic prevention and management may be made more effective if they take into account the fluctuating landscape of transmission intensity associated with spatial heterogeneity in the vector-host ratio and people's day-to-day movement patterns.
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Dengue/epidemiología , Epidemias , Aedes/virología , Animales , Número Básico de Reproducción , Dengue/prevención & control , Dengue/transmisión , Epidemias/prevención & control , Epidemias/estadística & datos numéricos , Migración Humana , Humanos , Conceptos Matemáticos , Modelos Biológicos , Mosquitos Vectores/virologíaRESUMEN
Humoral immune response against dengue virus (DENV) is an important component in dengue-endemic transmission. We conducted a cross-sectional nested cohort study to determine the seroprevalence and frequency of neutralizing antibodies against DENV serotypes in two endemic localities in the state of Morelos, Mexico. The cohort participants (N = 1,196) were screened to determine previous exposure to DENV. Overall seroprevalence was 76.6% (95% confidence interval [95% CI] = 73.6-79.2), and prevalence of neutralizing antibodies in the 5- to 9-year-old group was 82.5% (95% CI = 67.2-92.7), 45% (95% CI = 29.3-61.5), and 65% (95% CI = 48.3-79.4) for DENV-1, DENV-2, and DENV-3, respectively. For participants older than 10 years, the observed seroprevalence was above 60% for each serotype, except DENV-4 in the 10- to 25-year-old group (42.9%); 81% of humoral responses were multitypic. The outcomes of our study contribute to understanding the immune component of dengue transmission and provide focal information for the evaluation of vaccine candidates under development.
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Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Virus del Dengue/aislamiento & purificación , Dengue/epidemiología , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Dengue/inmunología , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , México/epidemiología , Estudios Seroepidemiológicos , Serotipificación , Adulto JovenRESUMEN
Increased levels of tumor necrosis factor alpha (TNF-α) in patients with dengue have been reported. Various polymorphisms have been identified in the promoter region of the TNF-α gene that may affect its transcription. The purpose of the present study was to evaluate the relationship between polymorphisms of TNF-α gene and the genetic susceptibility to dengue fever in a group of patients from Morelos State, Mexico. The TNF-α polymorphisms (positions -238 and -308) were determined by PCR-RFLP technique in 130 patients with dengue (85 with dengue fever and 45 with dengue hemorrhagic fever) and 169 healthy controls. The patients were selected from cases reported in Morelos State from 1997 to 2003. The whole group of dengue patients showed a decreased frequency of TNF-α -238 A allele when compared to healthy controls (p = 0.01, OR = 0.19, 95%CI = 0.02-0.78). When the analysis was made separately in dengue fever and dengue hemorrhagic fever patients, the decreased frequency of TNF-α -238 A allele only remained significant in patients with DHF when compared to healthy controls (p = 0.034). This work suggests a possible association of TNF-α -238 A allele with protection to develop symptomatic disease.
Asunto(s)
Predisposición Genética a la Enfermedad , Dengue Grave , Factor de Necrosis Tumoral alfa , Alelos , Estudios de Casos y Controles , Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Humanos , México/epidemiología , Polimorfismo Genético , Dengue Grave/genética , Dengue Grave/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Host genetics in dengue hemorrhagic fever (DHF) pathophysiology has not been extensively investigated. Most studies have focused on HLA in different populations; however these reported associations have not been replicated. We performed a case-control study to analyze possible associations of HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 alleles with clinical disease severity caused by dengue virus infection. Our population consisted of 39 individuals (DF: 23, DHF: 16) and 34 healthy controls from the State of Morelos, Mexico. HLA loci were genotyped by nucleotide sequencing method. Statistical analyses revealed associations in three alleles: HLA-B*35 was negatively associated with symptomatic disease (p<1x10(-4), p(c)=0.01, OR=0.12, 95%CI=0.037-0.39), and DF (p=0.0007, p(c)=0.03, OR=0.13, 95%CI=0.031-0.51). HLA-DQB1*0302 was positively associated with DHF (p=0.018, p(c)=NS, OR=5.02, 95%CI=1.05-25.34), and negatively with DF (p=0.011, p(c)=NS, OR=0.23, 95%CI=0.06-0.84). HLA-DQB1*0202 was positively associated with DF only (p=0.012, p(c)=NS, OR=7.0, 95%CI=1.11-73.8). We identified possible associations of HLA-B and HLA-DQB1 alleles with the risk of developing symptomatic disease, DF and DHF in a Mexican Mestizo population.
Asunto(s)
Dengue/genética , Dengue/patología , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase I/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Dengue/inmunología , Femenino , Frecuencia de los Genes , Humanos , Masculino , México , Persona de Mediana Edad , Análisis de Secuencia de ADN , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The endemic behavior of dengue fever in Mexico during the past five years is of major concern to every sector related with public health and the effort to control the transmission has been focused on vector control. However, regardless of the effectiveness of the intervention measures it is important to know which elements determine dengue transmission. With regard to the molecular basis for dengue transmission, a great deal of progress has been made due to the introduction of genomic and bioinformatic approaches. The goal of this review is to describe the most recent developments in this area with emphasis on the Mexican situation.
Asunto(s)
Virus del Dengue/genética , Dengue/transmisión , Dengue/virología , Dengue/epidemiología , Virus del Dengue/clasificación , Genética de Población , Humanos , México/epidemiología , SerotipificaciónRESUMEN
El comportamiento endémico de la fiebre por dengue en México durante los últimos cinco años ha generado gran preocupación en todos los sectores relacionados con la salud. Los esfuerzos para interrumpir la transmisión se han concentrado en el control vectorial; sin embargo, al margen de la efectividad de las intervenciones, resulta importante establecer con claridad cuáles son los elementos determinantes de la transmisión del dengue para establecer medidas de control y vigilancia eficaces. En cuanto a los determinantes moleculares de la transmisión, mucho se ha avanzado con el desarrollo de la genómica y la bioinformática. Esta revisión pretende ofrecer un panorama de los desarrollos más recientes en ese aspecto con un énfasis en la situación de México.
The endemic behavior of dengue fever in Mexico during the past five years is of major concern to every sector related with public health and the effort to control the transmission has been focused on vector control. However, regardless of the effectiveness of the intervention measures it is important to know which elements determine dengue transmission. With regard to the molecular basis for dengue transmission, a great deal of progress has been made due to the introduction of genomic and bioinformatic approaches. The goal of this review is to describe the most recent developments in this area with emphasis on the Mexican situation.