Mouse and human immune responses share neutralization epitopes of HAstV-VA1.

Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in human astroviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient's immunotherapy. In agreement with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, suggesting that both mouse and human antibody responses target shared neutralization epitopes. The isolated Nt-MAbs reported in this work will help to characterize the functional domains of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1. IMPORTANCE: Human astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. In this work high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1 were isolated and characterized. The proposed binding sites for these antibodies and for neutralizing antibodies against classical HAstVs suggest that there are at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will help to define the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

Who is getting COVID-19 boosters? A latent class analysis in a nationally representative sample of Mexican adults 60 years and over.

OBJECTIVE: Estimate COVID-19 vaccine booster uptake and identify sociodemographic profiles associated with vaccine booster uptake in Mexican adults aged 60 and older. METHODS: Using data from the 2022 National Health and Nutrition Survey, we estimated COVID-19 booster uptake in Mexican adults 60 and older. We conducted a latent class analysis using sociodemographic characteristics and then estimated group-specific booster prevalence. RESULTS: Adults aged 60 and older with a completed vaccination schedule had 80.3% booster coverage. Two groups showed the lowest coverage: 1) unemployed and informal working men with elementary education with low socioeconomic status (73.8% boosted), and 2) female homekeepers with elementary education or less living in rural areas (77.0% boosted). CONCLUSIONS: Our analysis points to the need to reach out to men and women with elementary education or less who live in rural areas to strengthen booster campaigns in the future.

Antigenic determinants of HAstV-VA1 neutralization and their relevance in the human immune response.

Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and also select a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs. Sequencing of the virus genome capsid region revealed escape mutations that map to the surface of the capsid spike domain, define three potentially independent neutralization epitopes, and help delineate four antigenic sites in rotaviruses. Notably, two of the escape mutations were found to be present in the spike sequence of the HAstV-VA1-PS strain isolated from an immunodeficient patient with encephalitis, suggesting that those mutations arose as a result of the immune pressure generated by the patient's immunotherapy. In accordance with this observation, human serum samples exhibiting strong neutralization activity against wild-type HAstV-VA1 had a 2.6-fold reduction in neutralization titer when evaluated against the triple-escape HAstV-VA1 mutant, indicating shared neutralization epitopes between the mouse and human antibody response. The isolated Nt-MAbs reported in this work will help characterize the functional sites of the virus during cell entry and have the potential for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1. Importance: Human astroviruses (HAstVs) have been historically associated with acute gastroenteritis. However, the genetically divergent HAstV-VA1 strain has been associated with central nervous system disease. This work isolated high-affinity neutralizing monoclonal antibodies directed to HAstV-VA1. The proposed binding sites for these antibodies, together with previously reported sites for neutralizing antibodies against classical HAstVs, suggest the existence of at least four neutralization sites on the capsid spike of astroviruses. Our data show that natural infection with human astrovirus VA1 elicits a robust humoral immune response that targets the same antigenic sites recognized by the mouse monoclonal antibodies and strongly suggests the emergence of a variant HAstV-VA1 virus in an immunodeficient patient with prolonged astrovirus infection. The isolated Nt-MAb reported in this work will be helpful in defining the functional sites of the virus involved in cell entry and hold promise for developing a specific antibody therapy for the neurological disease associated with HAstV-VA1.

Barriers, refusal and a hypothetical monetary incentive for Covid-19 vaccination in Mexican adults.

OBJECTIVE: To estimate vaccine uptake and assess sociodemographic conditions associated with vaccination barriers and refusal and to explore the effect of a monetary incentive to overcome them. MATERIALS AND METHODS: We used data from adults from the 2021 National Continuous Health and Nutrition Survey conducted during August-October 2021. We evaluated if an hypothetical monetary incentive between 50-650 MXN (~2.5-31 USD) would overcome barriers or refusal. RESULTS: 73.9% were vaccinated with at least one dose, 7.5% refused, 4.8% reported barriers and 13.8% were ineligible at the time of the survey. Refusal and barriers were more frequent in men, older age, lower education and socioeconomic status, unemployed and informal workers. In people with barriers and refusal, the hypothetical incentive increased the acceptance in 57.6% (95%CI 50.7,64.4%) and 17.4% (95%CI 13.2,21.7%) in people with barriers and refusal, respectively. CONCLUSION: Understanding the reasons for barriers and refusal is crucial for future Covid-19 vaccination campaigns or epidemics. A monetary incentive might increase vaccination uptake, although, cost-effectiveness analyses are needed.

Prevalencia de anticuerpos y vacunación contra SARS-CoV-2 en 2022 en México.

OBJETIVO: Describir la prevalencia de anticuerpos contra SARS-CoV-2, vacunación, barreras y rechazo a la vacunación Covid-19 en población mexicana. Material y métodos. Se utilizó información de los integrantes del hogar de uno y más años, incluidos en la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022) realizada de agosto-noviembre. Se estimó la prevalencia de anticuerpos antiproteínas N y S de SARS-CoV-2 en muestras de sangre capilar, dosis reportadas de vacunación a Covid-19 y las razones de barreras y rechazo a la vacunación. RESULTADOS: La prevalencia de anticuerpos anti-N fue de 94.4% y de anti-S 98.1%. La prevalencia de anticuerpos anti-S fue mayor en personas vacunadas con una, dos o tres o más dosis que en no vacunadas. Dentro de la población elegible a vacunación, 20.2% no estaba vacunada, 16.2% tenía una dosis, 30% dos dosis y 33.6% tres dosis o más. El 11.2% de la población elegible rechazó la vacunación, 5.5% reportó una barrera y 3.2% reportó que la vacuna no había llegado a su localidad. Conclusión. La prevalencia de anticuerpos por infección natural y por vacunación Covid-19 es alta en México. Las variaciones de rechazo y barreras a la vacunación entre grupos de edad y regiones deben tomarse en cuenta para intensificar esfuerzos específicos para la vacunación.

Structural and immunological basis of cross-reactivity between dengue and Zika infections: Implications in serosurveillance in endemic regions.

Dengue and Zika are arthropod-borne viral diseases present in more than 100 countries around the world. In the past decade, Zika emerged causing widespread outbreaks in new regions, where dengue has been endemic-epidemic for a long period. The wide and extensive dissemination of the mosquito vectors, Aedes aegypti, and Ae. albopictus, favor the co-existence of both infections in the same regions. Together with an important proportion of asymptomatic infections, similar clinical manifestations, and a short time window for acute infection confirmatory tests, it is difficult to differentially estimate both dengue and Zika incidence and prevalence. DENV and ZIKV flavivirus share high structural similarity, inducing a cross-reactive immune response that leads to false positives in serological tests particularly in secondary infections. This results in overestimation of recent Zika outbreaks seroprevalence in dengue endemic regions. In this review, we address the biological basis underlying DENV and ZIKV structural homology; the structural and cellular basis of immunological cross reactivity; and the resulting difficulties in measuring dengue and Zika seroprevalence. Finally, we offer a perspective about the need for more research to improve serological tests performance.

Spatiotemporal patterns of dengue and Zika incidence during the 2015-2018 outbreak of Zika in Mexico.

OBJECTIVE: Evaluate spatially and temporally simultaneous presence of clusters of dengue and Zika clinical cases and their relationship with expected dengue transmission risk. MATERIALS AND METHODS: A classification of dengue risk transmission was carried out for whole country, and spatial autocorrelation analyses to identify clusters of confirmed clinical cases of dengue and Zika from 2015 to 2018 was conducted using Moran's Index statistics. RESULTS: Clusters of both diseases were identified in dengue-high risk munici-palities at the beginning of the outbreak, but, at the end of the outbreak, Zika clusters occurred in dengue low-risk mu-nicipalities. CONCLUSION: This study identified Zika clusters in low-risk dengue areas suggesting participation of several factors that favor virus introduction and dissemination, such as differences in entomological and control interventions, and the possibility of cross-immunity in the population.

Point Prevalence Survey of Antimicrobial Use in Four Tertiary Care Hospitals in Mexico.

PURPOSE: To describe the antimicrobial use in four tertiary care hospitals in Mexico. PATIENTS AND METHODS: Point prevalence surveys (PPSs) were conducted on medical records of hospitalized patients with prescribed antimicrobials (AMs) in four tertiary care hospitals in Mexico in 2019. Prevalence estimates and descriptive statistics were used to present the collected data on antimicrobial prescribing and microbiological studies. RESULTS: The prevalence of patients with prescribed AMs among the hospitals ranged from 47.1% to 91.3%. Antibiotics for systemic use (J01s) were the most prescribed (84.6%, [95% CI: 81.5-87.3]), mainly extended-spectrum J01s: third-generation cephalosporins 19.8% [95% CI: 16.8-23.1], and carbapenems 17.0% [95% CI: 14.2-20.2]. Antibiotic treatments were largely empirical, with no planned duration or review dates. The ceftriaxone use was excessive and prolonged. No formal reference guidelines for antimicrobial prescribing were available in the hospitals. Multidrug-resistant Escherichia coli and ESKAPE pathogens were identified in all hospitals. CONCLUSION: This study describes the extensive use of antimicrobials and broad-spectrum antibiotics for systemic use in Mexican hospitals, along with the presence of resistant pathogens to the antibiotics frequently used in the hospitals surveyed.

Acceptance, refusal, and hesitancy of Covid-19 vaccination in Mexico: Ensanut 2020 Covid-19 / Aceptabilidad, rechazo y duda ante la vacunación contra Covid-19 en México: Ensanut 2020 Covid-19

Abstract: Objective: To estimate the willingness to vaccinate against Covid-19 (acceptance) in the Mexican population and to identify socioeconomic factors associated with vaccine hesitancy and refusal. Materials and methods: We estimated the acceptance, refusal and hesitancy proportions using data from the Covid-19 National Health and Nutrition Survey conducted from August to November 2020. Factors associated with refusal and hesitancy were explored using multinomial logistic regression. Results: Covid-19 vaccination acceptance was 62.3%, refusal 28.2% and hesitancy 9.5%. Refusal and hesitancy were associated with being female, having older age, lower educational level, lower socioeconomic status and working in the informal sector. Conclusion: National campaigns to incentivize vaccine acceptance need to consider specific subgroups were the likelihood of hesitancy and refusal is high. In Mexico, refusal and hesitancy were higher in vulnerable groups, and people at a higher risk of Covid-19 complications and death.

Resumen: Objetivo: Estimar la aceptabilidad de la vacunación contra Covid-19 en la población mexicana e identificar factores socioeconómicos asociados con el rechazo o la duda. Material y métodos: Se estimó la proporción de aceptabilidad, rechazo y duda utilizando los datos de la Encuesta Nacional de Salud y Nutrición 2020 sobre Covid-19 levantada durante agosto y noviembre de 2020. Se exploraron los factores asociados con rechazo y duda mediante un modelo de regresión multinomial. Resultados: La aceptabilidad de la vacunación contra Covid-19 fue de 62.3%, el rechazo de 28.2% y la duda de 9.5%. El rechazo y la duda se asociaron con ser mujer, tener mayor edad, menor nivel de educación, menor nivel socioeconómico y trabajar en el sector informal. Conclusión: Las campañas para incentivar la aceptabilidad de la vacuna necesitan considerar los subgrupos específicos con una alta proporción de rechazo y duda. En México observamos un mayor rechazo y duda en grupos con mayor riesgo de complicaciones y muerte por Covid-19.

The WHO methodology for point prevalence surveys on antibiotics use in hospitals should be improved: Lessons from pilot studies in four Mexican hospitals.

Point prevalence surveys (PPSs) are a useful option for collecting antimicrobial prescription data in hospitals where regular monitoring is not feasible. The methodology recommended by the World Health Organization (WHO) for conducting PPSs (WPPS), which targets low- and middle-income countries (LMICs), attempts to respond to the lag in these regions to generate estimates for antimicrobial use. However, based on our experience in four third-level public hospitals in Mexico, we identified substantial gaps in the WPPS guide with regards to addressing common challenges for the implementation of PPSs. While the oversimplified narrative of WPPS could facilitate the adoption of this methodology and extend its use, it underestimates the efforts and potential pitfalls for survey preparation, coordination, and reliable implementation. Conducting rigorous pilot studies could reduce the WPPS deficiencies and strengthen the reliability and comparability of the estimates for antimicrobial use.

Preguntas y respuestas sobre la estrategia de vacunación contra Covid-19 en México.

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Diarrheagenic Escherichia coli pathotypes isolated from a swine farm in a region of Morelos state, Mexico / Patotipos diarreicos de Escherichia coli aislados de una granja porcina en una región del estado de Morelos, México

Abstract: Objective: Determine the frequency of diarrheagenic Escherichia coli pathotypes colonizing swine. Materials and methods: E. coli strains isolated of fecal samples from 280 swine, produced for local consumption, in a semi-technical farm of Morelos state (central Mexico), were tested to identify the diarrheagenic E. coli pathotypes by multiplex PCR. Pulsed-field gel electrophoresis (PFGE) were determined for the study of genetic diversity between pathigenic E. coli strains. Results: Of the 521-diarrheagenic E. coli isolates examined, 50 (9.6%) were positive for at least one virulence gene in 42 different animals. Thus, 15% (42/280) of the swine in this farm were colonized with pathogenic E. coli. Among the E. coli isolates, the pathotype EPEC (6.5%) was the most frequently, followed by EHEC (2.3%), ETEC and EIEC (0.4%). The study of genetic diversity, carried out by PFGE of 40 representative isolates, revealed 25 distinct restriction profiles clustered in 21 groups (A-U). Conclusions: In this study, four different E. coli pathotypes were found among swine colonized by E. coli in this farm. Thus, these swine are reservoirs for these virulent bacteria and there is potential risk of causing diarrhea in swine and in the population consuming the meat.

Resumen: Objetivo: Determinar la frecuencia de patotipos diarreicos de Escherichia coli que colonizan cerdos. Material y métodos: Se analizaron cepas de E. coli aisladas de muestras fecales de 280 cerdos, producidas para consumo local, en una granja del estado de Morelos (centro de México) para identificar los patotipos diarreicos de E. coli por PCR multiplex. Se determinó la electroforesis en gel de campo pulsado (PFGE) para el estudio de la diversidad genética entre cepas patógenas de E. coli. Resultados: De los 521 aislados de E. coli con patotipos diarreicos examinados, 50 (9.6%) fueron positivos para al menos un gen de virulencia en 42 animales diferentes. Así, 15% (42/280 porcinos) fueron colonizados con E. coli patógeno. Entre los aislados de E. coli de porcinos, el patotipo EPEC (6.5%) fue el más frecuente, seguido por EHEC (2.3%), ETEC y EIEC (0.4%). El estudio de la diversidad genética, realizado por PFGE de 40 cepas representativas, reveló 25 perfiles de restricción distintos agrupados en 21 grupos (A-U). Conclusiones: En este estudio, se encontraron cuatro diferentes patotipos de E. coli entre los cerdos colonizados por E. coli. Estos cerdos son reservorios de estas bacterias virulentas y existe un riesgo potencial de causar diarrea en los cerdos y en la población que consume la carne.

Respuesta a "Reflexiones sobre la estrategia de vacunación en México para personas de 50 a 59 años".

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Acceptance, refusal and hesitancy of Covid-19 vaccination in Mexico: Ensanut 2020 Covid-19.

OBJECTIVE: To estimate the willingness to vaccinate against Covid-19 (acceptance) in the Mexican population and to iden-tify socioeconomic factors associated with vaccine hesitancy and refusal. MATERIALS AND METHODS: We estimated the acceptance, refusal and hesitancy proportions using data from the Covid-19 National Health and Nutrition Survey conducted from August to November 2020. Factors associated with re-fusal and hesitancy were explored using multinomial logistic regression. RESULTS: Covid-19 vaccination acceptance was 62.3%, refusal 28.2% and hesitancy 9.5%. Refusal and hesitancy were associated with being female, having older age, lower educational level, lower socioeconomic status and working in the informal sector. CONCLUSION: National campaigns to incentivize vaccine acceptance need to consider specific subgroups were the likelihood of hesitancy and refusal is high. In Mexico, refusal and hesitancy were higher in vulnerable groups, and people at a higher risk of Covid-19 complica-tions and death.

Mexico: Lessons learned from the 2009 pandemic that help us fight COVID-19.

In April 2009, Mexican, American, and Canadian authorities announced a novel influenza that became the first pandemic of the century. We report on lessons learned in Mexico. The Mexican Pandemic Influenza Preparedness and Response Plan, developed and implemented since 2005, was a decisive element for the early response. Major lessons-learned were the need for flexible plans that consider different scenarios; the need to continuously strengthen routine surveillance programs and laboratory capacity and strengthen coordination between epidemiological departments, clinicians, and laboratories; maintain strategic stockpiles; establish a fund for public health emergencies; and collaboration among neighboring countries. Mexico responded with immediate reporting and transparency, implemented aggressive control measures and generous sharing of data and samples. Lessons learned induced changes leading to a better response to public health critical events.

Diarrheagenic Escherichia coli pathotypes isolated from a swine farm in a region of Morelos state, Mexico.

OBJECTIVE: Determine the frequency of diarrheagenic Escherichia coli pathotypes colonizing swine. MATERIALS AND METHODS: E. coli strains isolated of fecal samples from 280 swine, produced for local consumption, in a semi-technical farm of Morelos state, (central Mexico) were tested to identify the diarrheagenic E. coli pathotypes by multiplex PCR. RESULTS: Of the 521-diarrheagenic E. coli isolates examined, 50 (9.6%) were positive for at least one virulence gene in 42 different animals. Thus, 15% (42/280) of the swine in this farm were colonized with pathogenic E. coli. Among the E. coli isolates, the pathotype EPEC (6.5%) was the most frequently, followed by EHEC (2.3%), ETEC and EIEC (0.4%). CONCLUSIONS: In this study, four different E. coli pathotypes were found among swine colonized by E. coli in this farm. Thus, these swine are reservoirs for these virulent bacteria and there is potential risk of causing diarrhea in swine and in the population consuming the meat.

Zika virus infection estimates, Mexico.

OBJECTIVE: To assess the magnitude of the Mexican epidemic of Zika virus infection and the associated risk of microcephaly. METHODS: From the reported number of laboratory-confirmed symptomatic infections among pregnant women and the relevant birth rate, we estimated the number of symptomatic cases of infection that occurred in Mexico between 25 November 2015, when the first confirmed Mexican case was reported, and 20 August 2016. We used data from the birth certificates to compare mean monthly incidences of congenital microcephaly before (1 January 2010-30 November 2015) and after (1 December 2015-30 September 2017) the introduction of Zika virus, stratifying the data according to whether the mother's place of residence was at an altitude of at least 2200 m above sea level. We used Poisson interrupted time series, statistical modelling and graphical analyses. FINDINGS: Our estimated number of symptomatic cases of infection that may have occurred in the general population of Mexico between 25 November 2015 and 20 August 2016, 60 172, was 7.3-fold higher than the corresponding number of reported cases. The monthly numbers of microcephaly cases per 100 000 live births were significantly higher after the introduction of the virus than before (incidence rate ratio, IRR: 2.9; 95% confidence interval, CI: 2.3 to 3.6), especially among the babies of women living at altitudes below 2200 m (IRR: 3.4; 95% CI: 2.9 to 3.9). CONCLUSION: The Mexican epidemic appears to be much larger than indicated by estimates based solely on counts of laboratory-confirmed cases, and to be associated with significantly increased risk of microcephaly.