Risk of a vector-borne endemic zoonosis for wildlife: Hosts, large-scale geography, and diversity of vector-host interactions for Trypanosoma cruzi.

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.

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study.

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.

Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study.

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.

A Call for a Reform of the Influenza Immunization Program in Mexico: Epidemiologic and Economic Evidence for Decision Making.

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.

Public Health and Economic Benefits of Influenza Vaccination of the Population Aged 50 to 59 Years without Risk Factors for Influenza Complications in Mexico: A Cross-Sectional Epidemiological Study.

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.

Influenza in the school-aged population in Mexico: burden of disease and cost-effectiveness of vaccination in children.

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.

The potential economic value of a therapeutic Chagas disease vaccine for pregnant women to prevent congenital transmission.

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.

Efecto de diferentes fuentes de alimentación sanguínea sobre Aedes aegypti (Díptera: Culicidae) en condiciones de insectario / Effect of different sources of blood feeding on Aedes aegypti (Diptera: Culicidae) under insectary conditions / Efeito de diferentes fontes de alimentação sanguínea em Aedes aegypti (Diptera: Culicidae) sob condições de insetários / Effet de différentes sources d'alimentation en sang sur Aedes aegypti (Diptera: Culicidae) dans des conditions insectaires

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.

Economic value of a therapeutic Chagas vaccine for indeterminate and Chagasic cardiomyopathy patients.

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 ≥ 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).

Analysis of spatial mobility in subjects from a Dengue endemic urban locality in Morelos State, Mexico.

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.

HLA class I and II polymorphisms in Mexican Mestizo patients with dengue fever.

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.