Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.

Demographic modeling of admixed Latin American populations from whole genomes.

Demographic models of Latin American populations often fail to fully capture their complex evolutionary history, which has been shaped by both recent admixture and deeper-in-time demographic events. To address this gap, we used high-coverage whole-genome data from Indigenous American ancestries in present-day Mexico and existing genomes from across Latin America to infer multiple demographic models that capture the impact of different timescales on genetic diversity. Our approach, which combines analyses of allele frequencies and ancestry tract length distributions, represents a significant improvement over current models in predicting patterns of genetic variation in admixed Latin American populations. We jointly modeled the contribution of European, African, East Asian, and Indigenous American ancestries into present-day Latin American populations. We infer that the ancestors of Indigenous Americans and East Asians diverged ∼30 thousand years ago, and we characterize genetic contributions of recent migrations from East and Southeast Asia to Peru and Mexico. Our inferred demographic histories are consistent across different genomic regions and annotations, suggesting that our inferences are robust to the potential effects of linked selection. In conjunction with published distributions of fitness effects for new nonsynonymous mutations in humans, we show in large-scale simulations that our models recover important features of both neutral and deleterious variation. By providing a more realistic framework for understanding the evolutionary history of Latin American populations, our models can help address the historical under-representation of admixed groups in genomics research and can be a valuable resource for future studies of populations with complex admixture and demographic histories.

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes.

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population. METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort. RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance. CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores. DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

Mycobacterium tuberculosis lineage 4 associated with cavitations and treatment failure.

BACKGROUND: Mycobacterium tuberculosis genotyping has been crucial to determining the distribution and impact of different families on disease clinical presentation. The aim of the study was to evaluate the associations among sociodemographic and clinical characteristics and M. tuberculosis lineages from patients with pulmonary tuberculosis in Orizaba, Veracruz, Mexico. METHODS: We analyzed data from 755 patients whose isolates were typified by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). The associations among patient characteristics and sublineages found were evaluated using logistic regression analysis. RESULTS: Among M. tuberculosis isolates, 730/755 (96.6%) were assigned to eight sublineages of lineage 4 (Euro-American). Alcohol consumption (adjusted odds ratio [aOR] 1.528, 95% confidence interval (CI) 1.041-2.243; p = 0.030), diabetes mellitus type 2 (aOR 1.625, 95% CI 1.130-2.337; p = 0.009), sputum smear positivity grade (3+) (aOR 2.198, 95% CI 1.524-3.168; p < 0.001) and LAM sublineage isolates (aOR 1.023, 95% CI 1.023-2.333; p = 0.039) were associated with the presence of cavitations. Resistance to at least one drug (aOR 25.763, 95% CI 7.096-93.543; p < 0.001) and having isolates other than Haarlem and LAM sublineages (aOR 6.740, 95% CI 1.704-26.661; p = 0.007) were associated with treatment failure. In a second model, multidrug resistance was associated with treatment failure (aOR 31.497, 95% CI 5.119-193.815; p < 0.001). Having more than 6 years of formal education was not associated with treatment failure. CONCLUSIONS: Knowing M. tuberculosis genetic diversity plays an essential role in disease development and outcomes, and could have important implications for guiding treatment and improving tuberculosis control.

Caracterización del bienestar en hogares mexicanos de niñas y niños con diarrea, Ensanut Continua 2022.

OBJETIVO: Analizar el nivel de bienestar en los hogares mexicanos de niñas y niños menores de cinco años que presentaron enfermedad diarreica aguda (EDA) en las últimas dos semanas en México, según la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. La encuesta se realizó entre julio y diciembre de 2022. Variable dependiente: ocurrencia de EDA. Variable independiente: nivel de bienestar de los hogares. Se realizó análisis bivariado y regresiones logísticas crudas y ajustadas. RESULTADOS: Se estima que 9.4% de los menores de cinco años presentaron EDA, de quienes 76.4% (IC95%: 69.0,82.5) pertenecía a hogares con nivel de bienestar bajo-medio. La EDA fue más frecuente en los niños y niñas de un año de edad (razón de momios ajustada [RMa] 3.00; IC95%: 1.76,5.11), en comparación con quienes tenían menor edad y en los hogares donde el agua para beber no es tratada (RMa 2.13; IC95%: 1.11,4.08). CONCLUSIONES: Se requiere fortalecer las medidas sanitarias preventivas de EDA en niñas y niños de un año de edad, principalmente implementar acciones para asegurar la disponibilidad de agua potable o el tratamiento adecuado para beberla, y planear, ejecutar y evaluar acciones de política pública integrales y multisectoriales para coadyuvar en garantizar el derecho humano a la salud durante la niñez.

Cobertura de vacunación en niños, niñas y adolescentes en México.

OBJETIVO: Describir las coberturas de vacunación en 2022 en niñas, niños y en adolescentes, así como comparar las prevalencias observadas con los datos de la Encuesta Nacional de Salud y Nutrición 2021 (Ensanut 2021). Material y métodos. Análisis de datos obtenidos de la Ensanut 2022. RESULTADOS: En los niños menores de cinco años, las coberturas de vacuna con Bacilo de Calmette y Guérin (BCG), hepatitis B, pentavalente o hexavalente, neumocócica, antirotavirus y triple viral (SRP) fueron de 78.5% (IC95%: 70.8,84.6), 65.1% (IC95%: 58.4,71.2), 69.0% (IC95%: 61.8,75.4), 88.0% (IC95%: 83.0,91.7), 81.6% (IC95%: 75.7,86.2) y 61.8% (IC95%: 55.6,67.6), respectivamente. Al primer y segundo año de vida, 42.6% (IC95%: 34.3,51.4) y 26.6% (IC95%: 22.1,31.5) habían recibido el esquema correspondiente. Se redujo la cobertura estimada para primera dosis de SRP 72.6% (IC95%: 67.5,77.1) vs. 61.8% (IC95%: 55.6,67.5). En adolescentes, el antecedente de vacunación contra VPH, hepatitis B, tétanos y doble viral (SR) lo refirieron en 43.7% (IC95%: 39.9,47.6), 31.8% (IC95%: 29.8,34.0), 38.5% (IC95%: 35.9,41.2) y 32.6% (IC95%: 30.15,35.1). Conclusión. No se alcanza la meta de cobertura de 90% para ningún inmunógeno investigado. La cobertura para primera dosis de SRP se ha reducido.

Porcentaje de infección respiratoria aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de infección respiratoria aguda (IRA) en menores de cinco años en las últimas dos semanas en México, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. Se analizaron datos de la Ensanut Continua 2022. RESULTADOS: El porcentaje de IRA fue de 27.6% (IC95%: 25.2,30.1). La prevalencia fue mayor en el primer tercil socioeconómico (44.1% [IC95%: 38.0,50.4]). El signo de alarma IRA más identificado fue "verse más enfermo" 33.0% (IC95%: 30.1,36.0) y el menos identificado fue "salir pus del oído" (1.5% [IC95%: 0.9,2.7]). CONCLUSIONES: Las IRA afectan cerca de una tercera parte de los niños y las niñas menores de cinco años en México, particularmente de los hogares con menores capacidades económicas. Es necesario fortalecer las estrategias de prevención, entre ellas la vacunación, el control y la promoción de la salud.

Porcentaje de enfermedad diarreica aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de enfermedad diarreica aguda (EDA) en menores de cinco años en las últimas dos semanas, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. Material y métodos. Se analizaron los datos de menores de cinco años incluidos en la Encuesta Nacional de Salud y Nutrición Continua 2022 respecto a la EDA en las últimas dos semanas. Se compararon los datos con los de ediciones previas de la encuesta. RESULTADOS: El porcentaje de EDA en México fue de 9.4% (IC95%: 7.9,11.2), similar al de 2000, con diferencias por grupo etario. Durante el episodio de EDA, 38.7% (IC95%: 27.7,51.0) de las personas cuidadoras ofrecen menor cantidad de alimentos a la habitual. CONCLUSIONES: El elevado porcentaje de EDA en menores de cinco años en México en el 2022 evidencia la necesidad de fortalecer estrategias de prevención y promoción de la salud.

Vacunación en adultos y adultos mayores en México.

OBJETIVO: Estimar la prevalencia del antecedente de vacunación en adultos de 20 a 59 años y mayores de 60 años mediante autorreporte. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). RESULTADOS: El 27.4% de los adultos de 20-39 años refirió haber recibido vacuna doble viral (sarampión y rubeola [SR]) y 57.3% de adultos de 20-59 años cualquier vacuna con toxoide tetánico (Td) en los últimos diez años. En mujeres de 29 a 49 años, 18.7% (IC95%: 17.0,20.5) y 58.46% (IC95%: 56.2,60.7) habían sido vacunadas con vacuna SR y Td, respectivamente. En mayores de 60 años, 48.8% (IC95%: 45.9,51.7), 24.4% (IC95%: 22.2,26.8) y 49.1% (IC95%: 46.1,52.2) informaron haber recibido cualquier vacuna conteniendo Td, vacuna antineumococo y vacuna antiinfluenza estacional desde septiembre del año anterior a la encuesta, respectivamente. Conclusión. Los resultados de este estudio muestran que una proporción considerable de adultos, mujeres en edad fértil y adultos mayores no estaban protegidos contra enfermedades prevenibles por vacunación en 2022.

Modular reactivation of Mexico City after COVID-19 lockdown.

BACKGROUND: During the COVID-19 pandemic, the slope of the epidemic curve in Mexico City has been quite unstable. Changes in human activity led to changes in epidemic activity, hampering attempts at economic and general reactivation of the city. METHODS: We have predicted that where a fraction of the population above a certain threshold returns to the public space, the negative tendency of the epidemic curve will revert. Such predictions were based on modeling the reactivation of economic activity after lockdown using an epidemiological model resting upon a contact network of Mexico City derived from mobile device co-localization. We modeled scenarios with different proportions of the population returning to normalcy. Null models were built using the Jornada Nacional de Sana Distancia (the Mexican model of elective lockdown). There was a mobility reduction of 75% and no mandatory mobility restrictions. RESULTS: We found that a new peak of cases in the epidemic curve was very likely for scenarios in which more than 5% of the population rejoined the public space. The return of more than 50% of the population synchronously will unleash a magnitude similar to the one predicted with no mitigation strategies. By evaluating the tendencies of the epidemic dynamics, the number of new cases registered, hospitalizations, and recent deaths, we consider that reactivation following only elective measures may not be optimal under this scenario. CONCLUSIONS: Given the need to resume economic activities, we suggest alternative measures that minimize unnecessary contacts among people returning to the public space. We evaluated that "encapsulating" reactivated workers (that is, using measures to reduce the number of contacts beyond their influential community in the contact network) may allow reactivation of a more significant fraction of the population without compromising the desired tendency in the epidemic curve.

Knowledge, attitudes, perceptions, and COVID-19 hesitancy in a large public university in Mexico city during the early vaccination rollout.

BACKGROUND: Vaccination against COVID-19 is a primary tool for controlling the pandemic. However, the spread of vaccine hesitancy constitutes a significant threat to reverse progress in preventing the disease. Studies conducted in Mexico have revealed that vaccination intention in Mexico among the general population ranges from 62 to 82%. OBJECTIVE: To know the prevalence of COVID-19 vaccine hesitancy and associated factors among academics, students, and administrative personnel of a public university in Mexico City. METHODS: We administered an online survey investigating sociodemographic aspects, knowledge, attitudes, practices, and acceptance/hesitancy regarding the COVID-19 vaccine. Using generalized linear Poisson models, we analyzed factors associated with vaccine hesitancy, defined as not intending to be vaccinated within the following six months or refusing vaccination. RESULTS: During May and June 2021, we studied 840 people, prevalence of vaccine hesitancy was 6%. Hesitancy was significantly associated with fear of adverse effects, distrust of physician's recommendations, lack of knowledge regarding handwashing, age younger than 40 years, refusal to use face masks, and not having received influenza vaccination during the two previous seasons. CONCLUSIONS: Vaccine hesitancy in this population is low. Furthermore, our results allowed us the identification of characteristics that can improve vaccine promotion.

Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients.

Loss to follow-up (LFU) of ≥2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU.We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan-Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU.Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3-11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36-50 years (HR 1.3, 95% CI 1.0-1.6; p=0.04) compared with age 0-25 years, being HIV positive (HR 1.8, 95% CI 1.2-2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6-1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4-0.6; p<0.01) compared with no serious adverse event.Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months.

[Trends in the prevalence of ARIs and ADDs in early childhood and associated factors: Ensanut 2012 and 100k.] / Tendencias en la prevalencia de IRA y EDA en la primera infancia y factores asociados: Ensanut 2012 y 100k.

OBJECTIVE: To compare the prevalence of acute respiratory infections (ARI) and acute diarrheal disease (ADD) among children younger than five years of age living in localities with less than 100 000 inhabitants in Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 and Ensanut 100k (2018). In Ensanut 100k, we evaluate the associated factors. MATERIALS AND METHODS: Analysis of both surveys and of the Mexican Meteorological System. RESULTS: The estimated prevalence of ARI was 45.1% in 2012 vs. 32.9% in 2018. The decrease was significant among medium and high-income households. There were no changes in trends for ADD. Among households with lower EC, ARI was associated with roofing material, temperature, and rainy precipitation while ADD was associated with lack of piped water. CONCLUSIONS: The estimated prevalence of ARI has decreased in medium and high income households. Some households and weather conditions are associated with ARI and ADD.

OBJETIVO: Estimar y comparar las prevalencias de infec- ciones respiratorias agudas (IRA) y enfermedades diarreicas agudas (EDA) en menores de cinco años, residentes en localidades con menos de 100 000 habitantes, mediante análisis de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 y la Ensanut 100k (2018). En la Ensanut 100k se evaluaron los factores asociados con IRA y EDA. MATERIAL Y MÉTODOS: Análisis de ambas encuestas e información meteorológica de la Comisión Nacional del Agua. RESULTADOS: La prevalencia global estimada de IRA fue de 45.1% en 2012 vs. 32.9% en 2018. La disminución fue significativa en hogares de medianas y mayores capacidades económicas (CE). No se observaron cambios significativos para las EDA. En hogares con menores CE, las IRA se asociaron con material del techo y temperatura y las EDA con privación de agua entubada. CONCLUSIONES: Entre 2012 y 2018, la prevalencia de IRA disminuyó en hogares de medianas y mayores CE. Algunas condiciones de vivienda y meteorológicas se asocian con IRA y EDA.

[Trends in vaccination coverage among children aged 12-23 and 24-35 months in Mexico. Ensanut 2012 and Ensanut 100]. / Tendencias en las coberturas de vacunación en niños de 12 a 23 y 24 a 35 meses en México.

OBJECTIVE: To evaluate and compare vaccination coverage among children aged 12-23 and 24-35 months living in localities with less than 100 000 inhabitants in Encuesta Nacional de Salud y Nutrición (Ensanut) 2012 and Ensanut 100k (2018). MATERIALS AND METHODS: Estimate of coverage with both surveys. RESULTS: Between 2012 and 2018, according to proof and self-report, the coverage of the basic scheme was maintained in children aged 12-23 (51.6 vs. 60.2%) and 24-35 months (51.4 vs. 50.0%). Similarly, only with proof (53.9 vs. 51.3% and 52.8 vs. 44.2%). In children aged 24-35 months, the coverage of the reinforced basic scheme reinforcements with probative document and self-report (30.9 vs. 34.0%) and only with reinforcements (30.2 vs. 27.8%) was maintained. Coverage with second and third doses of hepatitis B in both age groups decreased; additionally, first dose of measlesmumps-rubella vaccine (SRP, in Spanish) and third dose of Pentavalent in children aged 24-35 months. CONCLUSIONS: Coverages were maintained by schemes, despite reductions in hepatitis B, pentavalent and SRP.

OBJETIVO: Comparar coberturas de vacunación en niños de 12-23 y 24-35 meses de edad de localidades menores de 100 000 habitantes en México, entre 2012 (Encuesta Nacional de Salud y Nutrición Ensanut] 2012) y 2018 (Ensanut 100k). MATERIAL Y MÉTODOS: Estimación de coberturas con ambas encuestas. RESULTADOS: Entre 2012 y 2018, se mantuvo la cobertura del Esquema básico, con comprobante y autorreporte, en niños de 12-23 (51.6 vs. 60.2%) y 24-35 meses (51.4 vs. 50.0%), y sólo con comprobante (53.9 vs. 51.3% y 52.8 vs. 44.2%). Se mantuvo la cobertura del Esquema básico más refuerzos en niños de 24-35 meses, comprobante y autorreporte (30.9 vs. 34.0%) y sólo con comprobante (30.2 vs. 27.8%). Disminuyeron las coberturas con segunda y tercera dosis de hepatitis B en niños de 12-23 y 24-35 meses, y con primera dosis de triple viral (SRP) y tercera de pentavalente en niños de 24-35 meses. CONCLUSIONES: Se mantuvieron las coberturas del Esquema básico y Esquema básico más refuerzos aunque disminuyeron las coberturas con hepatitis B, pentavalente y SRP.

OPV Vaccination and Shedding Patterns in Mexican and US Children.

Background: As wild poliovirus is eradicated and countries switch from oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) per World Health Organization recommendations, preventing circulation of vaccine-derived poliovirus (cVDPV) is a top priority. Currently, the impact of prior poliovirus vaccination on OPV shedding is not fully understood. Methods: Stool samples from 2 populations were tested for OPV to assess shedding patterns. 505 samples from 43 US children vaccinated with OPV were collected over 42 days post-vaccination. 1,379 samples from 148 Mexican children vaccinated with OPV were collected over 71 days post-vaccination. Prior vaccination history was recorded for both groups. Results: Seventeen (40%) of the US children had never received poliovirus vaccination while the Mexican children had received at least 2 doses of IPV and 116 (78%) had OPV exposure. In total, 84% of US children and 78% of Mexican children shed OPV (P = .44, Fisher exact test), with a mean shedding duration of 17.4 days for US children and 9.3 days for Mexican children (P < .0001, Wilcoxon-Mann Whitney test). Conclusions: Prior vaccination did not affect the likelihood of shedding, as the US and Mexico cohorts had similar shedding proportions. However, prior vaccination affected shedding duration as the Mexican children, who were largely OPV exposed and all of whom had at least 2 IPV vaccinations, shed OPV for half as long as the US cohort. Since different countries maintain different poliovirus vaccination schedules, it is likely that duration of shedding of OPV varies in populations around the world.

Validation of a High-throughput, Multiplex, Real-time Qualitative Polymerase Chain Reaction Assay for the Detection of Sabin Oral Polio Vaccine in Environmental Samples.

Background: Currently, the primary mechanism for poliovirus detection is acute flaccid paralysis (AFP) surveillance, with environmental sampling serving as a complement. However, as AFP cases drop, environmental surveillance will become increasingly critical for poliovirus detection. Mexico provides a natural environment to study oral polio vaccine (OPV) transmission, as it provides routine injected polio vaccine immunization and biannual OPV campaigns in February and May. Methods: As part of a study of OPV transmission in which 155 children were vaccinated with OPV, monthly sewage samples were collected from rivers leading from 3 indigenous Mexican villages (Capoluca, Campo Grande, and Tuxpanguillo) from February to May 2015. Samples were also collected from October 2015 to October 2017, during which time there were standard OPV campaigns. Samples were analyzed for the presence of OPV serotypes, using a real-time qualitative polymerase chain reaction assay capable of detecting as few as 9, 12, and 10 copies/100 µL of viral ribonucleic acid for OPV serotypes 1, 2, and 3 (OPV-1, -2, and -3), respectively. Included here are 54 samples, taken up to November 2016. Results: Of the 54 samples, 13 (24%) were positive for OPV. After the vaccination of 155 children in February 2015, OPV was found 2 months after vaccination. After unrestricted OPV administration in February 2016, OPV was detected in sewage up to 8 months after vaccination. OPV-3 was found in 11 of the 13 positive samples (85%), OPV-2 was found in 3 positive samples (23%), and OPV-1 was found in 1 sample (8%). Conclusions: OPV can be detected even when small amounts of the vaccine are introduced into a community, as shown by OPV-positive sewage samples even when only 155 children were vaccinated. When OPV vaccination was unrestricted, sewage samples were positive up to 8 months after vaccination, implying community OPV circulation for at least 8 months. OPV-3 was the serotype most found in these samples, indicating prolonged transmission of OPV-3 when compared to the other serotypes. Future work could compare the phylogenetic variance of OPV isolates from sewage after OPV vaccinations.

Seroprevalence of Poliomyelitis Antibodies Among Children Aged 1 to 4 Years Old and Factors Associated With Poliovirus Susceptibility; Mexican Health and Nutrition Survey, 2012.

Background: An essential component of the "Polio Eradication and Endgame Strategic Plan 2013-2018" is the evaluation of population immunity. Mexico introduced the inactivated polio vaccine (IPV) into its routine immunization schedule in 2007 but continued to give trivalent oral polio vaccine OPV twice a year during National Health Weeks through 2016. Methods: To describe the seroprevalence of poliomyelitis among children one to four years old in Mexico and analyze risk factors for susceptibility. We detected antibodies to poliovirus type 1 by microneutralization test in 966 serum samples randomly selected from the National Health and Nutrition Survey, 2012. We assessed variables associated with susceptibility using multivariable logistic regression. Results: The overall weighted seroprevalence of the general population was 98.39% (95% confidence interval [CI] 96.76-99.21). We found significant differences of prevalence according to age (94.39%, 95% CI 87.56-97.58; 99.02%, 95% CI 95.68-99.79; 99.82%, 95% CI 98.77-99.98; and 100% among children 1, 2, 3, and 4 years old respectively) and number of IPV doses (96.91%, 95% CI 90.55-99.44; 100%; 97.85%, 95% CI 94.46-99.18; and 99.92%, 95% CI 99.45-99.98 for 1 2, 3, and 4 number of doses, respectively). Multivariate analyses showed that susceptibility was associated with younger age, fewer doses of IPV, and certain socioeconomic levels. Conclusions: Overall seroprevalence was high. However, we found susceptible children among younger ages and children with fewer or unknown IPV doses belonging to certain socioeconomic strata. Results are relevant for countries transitioning from OPV to IPV and underline the importance of achieving high coverage with IPV.

Protocol Paper: Oral Poliovirus Vaccine Transmissibility in Communities After Cessation of Routine Oral Poliovirus Vaccine Immunization.

Background: We aimed to elucidate household and community-level shedding and transmission of trivalent oral polio vaccine (tOPV) in communities with inactivated polio vaccine (IPV) routine immunization after tOPV is administered during a national health week (NHW). Methods: We conducted a 3-arm, randomized trial with data collected at baseline through 10 weeks post-NHW in households with at least 1 child <5 years old in 3 semi-rural communities in Orizaba, Mexico. Selected communities were geographically isolated but socio-demographically similar. Each community was assigned an oral polio vaccine (OPV) immunization rate: 10, 30, or 70% of participating households. From 2653 households in the 3 communities, ~150 households per community were selected, for 466 in total. Households were randomized as vaccinated or unvaccinated, with only 1 child under 5 in the vaccinated household receiving OPV during the February 2015 NHW. No other community members received OPV during this NHW. Stool samples were collected up to 10 weeks post-vaccination for all members of the 466 study households and were analyzed for the presence of OPV serotypes using a multiplex polymerase chain reaction assay. Results: We will report on the factors associated with, and incidence and duration of, household and community shedding and transmission of OPV. The secondary outcomes will characterize temporal and geospatial OPV serotype shedding patterns. Conclusions: The current global polio eradication plan relies on transitioning away from OPV to IPV. This study contributes to understanding patterns of OPV shedding and transmission dynamics in communities with primary IPV immunity, in order to optimize the reduction of OPV transmission.

Characterization of Household and Community Shedding and Transmission of Oral Polio Vaccine in Mexican Communities With Varying Vaccination Coverage.

Background: The World Health Assembly 2012 Polio Eradication and Endgame Strategic Plan calls for the eventual cessation of all oral polio vaccines (OPVs), to be replaced with inactivated polio vaccine (IPV); however, IPV induces less robust mucosal immunity than OPV. This study characterized household and community OPV shedding and transmission after OPV vaccination within primarily IPV-vaccinated communities. Methods: Households in 3 IPV-vaccinated Mexican communities were randomized to receive 3 levels of OPV vaccination coverage (70%, 30%, or 10%). Ten stool samples were collected from all household members over 71 days. Analysis compared vaccinated subjects, household contacts of vaccinated subjects, and subjects in unvaccinated households. Logistic and Cox regression models were fitted to characterize transmission of OPV by coverage and household vaccination status. Results: Among 148 vaccinated children, 380 household contacts, and 1124 unvaccinated community contacts, 78%, 18%, and 7%, respectively, shed OPV. Community and household contacts showed no differences in transmission (odds ratio [OR], 0.67; 95% confidence interval [CI], .37-1.20), in shedding trajectory (OR, 0.61; 95% CI, .35-1.07), or in time to shedding (hazard ratio, 0.68; 95% CI, .39-1.19). Transmission began as quickly as 1 day after vaccination and persisted as long as 71 days after vaccination. Transmission within unvaccinated households differed significantly across vaccination coverage communities, with the 70% community experiencing the most transmissions (15%), and the 10% community experiencing the least (4%). These trends persisted over time and in the time to first shedding analyses. Conclusions: Transmission did not differ between household contacts of vaccinees and unvaccinated households. Understanding poliovirus transmission dynamics is important for postcertification control.

Detection of Emerging Vaccine-Related Polioviruses by Deep Sequencing.

Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of <1%, depending on read depth. Sequencing of viral nucleic acids from the stool of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (<5%) distributed across the 5' UTR and P1 genomic region in all three Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication.