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.

Safety and Tolerability of Six Months of Isoniazid Plus Pyridoxine or Three Months of Rifampicin for Tuberculosis among Subjects with Diabetes Mellitus: A Randomized Trial.

Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.

Trimethoprim-Sulfamethoxazole-associated early neutropenia in Mexican adults living with HIV: A cohort study.

INTRODUCTION: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. METHODS: A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. RESULTS: 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). CONCLUSIONS: The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.

Frailty index and ten oral conditions in the Coyoacan cohort study: A cross-sectional analysis.

OBJECTIVES: To analyse the relationship between the Frailty Index and 10 oral conditions controlling for nutritional status among Mexican community-dwelling older people. BACKGROUND: Studies suggest that the association between frailty and oral conditions are mediated by nutrition. MATERIALS AND METHODS: This cross-sectional analysis includes 487 community-dwelling men and women aged ≥70 years old. Interview and clinical examinations were performed at participants' homes. Objective (number of natural teeth, root remnants, dental condition, utilisation and functionality of removable dental prostheses and periodontitis) and subjective (utilisation of dental services, self-rated oral health, chewing difficulties and xerostomia) oral variables were collected by trained personnel. The Frailty Index was calculated considering 35 deficits. Nutritional status measured with the Mini-Nutritional assessment (MNA), age, sex, education, and marital status were included as covariates. We fitted 11 multivariate generalised linear models (one for each oral condition), assuming gamma distribution for Frailty Index as the outcome. RESULTS: Participants average age was 78.1 years, 52.1% were women. We observed a higher Frailty Index among those rating their oral health as worse than others their age (5.1%), reporting chewing difficulties often (4.9%) and fairly and very often (7.0%), and xerostomia (4.8%). Age, gender and MNA were consistently associated with the Frailty Index. CONCLUSION: Subjective oral conditions are compatible with the Frailty Index after controlling for older people's nutritional status and covariates.

Prevalence and factors associated with the depressive symptoms in rural and urban Mexican older adults: evidence from the Mexican Health and Aging Study 2018.

OBJECTIVE: To determine the prevalence and factors related to depressive symptoms in older Mexican adults in urban and rural areas. MATERIALS AND METHODS: Cross-sectional study. We examined older adults from a sample taken from the Mexican Health and Aging Study (MHAS-2018). 14 230 older Mexicans were screened for self-reported depressive symptoms. RESULTS: The prevalence of depressive symptoms was 29.8% (33.4% rural vs. 28.9% urban). In the rural and urban population, the probability of a high prevalence of depressive symptoms was higher in older adults with multimorbidity ≥3, severe pain, and fair/poor SRH. Only in the urban population the prevalence of depressive symptoms increased with lower schooling. CONCLUSION: Identification of the factors related to depressive symptoms may help healthcare professionals provide better treatment for specific groups in the population.

Bioinformatic Analysis for Mucoepidermoid and Adenoid Cystic Carcinoma of Therapeutic Targets.

Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others. OBJECTIVE: We aimed to identify new critical genes of MECa and AdCC using bioinformatics analysis. METHODS: Gene expression profile of GSE153283 was analyzed by the GEO2R online tool to use the DAVID software for their subsequent enrichment. Protein-protein interactions (PPI) were visualized using String. Cytoscape with MCODE plugin followed by Kaplan-Meier online for overall survival analysis were performed. RESULTS: 97 upregulated genes were identified for MECa and 86 for AdCC. PPI analysis revealed 22 genes for MECa and 63 for AdCC that were validated by Kaplan-Meier that showed FN1 and SPP1 for MECa, and EGF and ERBB2 for AdCC as more significant candidate genes for each neoplasm. CONCLUSION: With bioinformatics methods, we identify upregulated genes in MECa and AdCC. The resulting candidate genes as possible therapeutic targets were FN1, SPP1, EGF, and ERBB2, and all those genes had been tested as a target in other neoplasm kinds but not salivary gland neoplasm. The bioinformatic evidence is a solid strategy to select them for more extensive research with clinical impact.

Imputation Performance in Latin American Populations: Improving Rare Variants Representation With the Inclusion of Native American Genomes.

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

Seroprevalence of measles antibodies and factors associated with susceptibility: a national survey in Mexico using a plaque reduction neutralization test.

Measles continues to be one of the leading causes of child mortality worldwide, even though a highly effective vaccine has existed for more than 40 years. We aimed to describe the seroprevalence of measles antibodies in Mexico in 2012 and the risk factors associated with susceptibility. A total of 7,785 serum samples were analyzed from the National Health and Nutrition Survey in Mexico. This national survey is representative of the general population, including noninstitutionalized adult, adolescent, and child populations. Antibody titers were classified into protective (> 120 mIU/mL) or susceptible (≤ 120 mIU/mL) levels. The weighted seroprevalence and susceptibility of the overall population were 99.37% (95% CI 99.07-99.58) and 0.63% (95% CI 0.42-0.93), respectively. Among 1-to-4-year-old children, 2.18% (95% CI 1.36-3.48) were susceptible to measles. Among adolescents and young adults, the prevalence of susceptibility was as follows: those 15-19 years of age had a prevalence of 0.22% (95% CI 0.09-0.57), and those 30-39 years of age had a prevalence of 1.17% (95% CI 0.47-2.85). Susceptibility was associated with young age, living in Mexico City, living in crowded households and unknown or nonvaccinated status among 1- to 5-year-old children. Although the overall sample population seroprevalence for measles is above 95%, increased susceptibility among younger children signals the importance of the timely administration of the first vaccine dose at 12 months of age. Furthermore, increased susceptibility among specific subgroups indicates the need to reinforce current vaccination policies, including the immunization of unvaccinated or incompletely vaccinated individuals from 10 to 39 years of age.

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.

Cobertura de vacunación y proporción de esquema incompleto en niños menores de siete años en México / Vaccination coverage and proportion of incomplete vaccination schedule in children under seven years of age in Mexico

Resumen: Objetivo: Evaluar la cobertura de vacunación en menores de siete años. Material y métodos: Estudio basado en la Encuesta Nacional de Salud y Nutrición de Medio Camino 2016. Resultados: La cobertura de esquema completo en los niños menores de un año fue de 51.7% [rango: de 67.6%, para la vacuna pentavalente (PV), a 93.9%, para la vacuna Bacillus Calmette-Guerin (BCG)]; en los de 12-23 meses fue de 53.9% [rango: de 68.5%, para la vacuna triple viral (SRP), a 98.3%, para la BCG], y en los de 24-35 meses, de 63.2% [rango: de 85.3%, para la vacuna contra neumococo, a 98.6%, para la BCG]. En niños de seis años, la cobertura de una dosis de SRP fue de 97.8%, y para dos dosis, de 50.7%. Sólo 2.2% de los niños de seis años no estaban vacunados. Las variables asociadas con esquema incompleto fueron edad de 2-5 meses, madre menor de 20 años o hablante de lengua indígena. Conclusiones: Debe mejorarse el reclutamiento de recién nacidos al programa de vacunación, así como su seguimiento, hasta completar el esquema, aprovechando los contactos con los servicios de salud para vacunarlos.

Abstract: Objective: To assess vaccination coverage in children under seven years of age. Materials and methods: Study based on the Halfway National Health and Nutrition Survey (Ensanut MC 2016). Results: Full vaccination coverage in children <1 year was 51.7%, (range: 67.6% [pentavalent (PV)] to 93.9% [BCG]), in those aged 12-23 months was 53.9% (range: 68.5% [MMR] to 98.3% [BCG]) and in those 24-35 months was 63.2% (range: 85.3% [pneumococcal]) to 98.6% [BCG]). In children aged six years, the coverage of 1 MMR dose was 97.8% and 50.7% for two doses. Only 2.2% of six year olds were not vaccinated. Variables associated with incomplete schedule were age of 2-5 months, mother being under 20 years of age or maternal language indigenous. Conclusions: The vaccination program needs to improve recruitment of newborns and their follow-up until they complete their immunization schedule, taking advantage of the local contacts with health services to vaccinate them.

[Vaccination coverage and proportion of incomplete vaccination schedule in children under seven years of age in Mexico]. / Cobertura de vacunación y proporción de esquema incompleto en niños menores de siete años en México.

OBJECTIVE: To assess vaccination coverage in children under seven years of age. MATERIALS AND METHODS: Study based on the Halfway National Health and Nutrition Survey (Ensanut MC 2016). RESULTS: Full vaccination coverage in children <1 year was 51.7%, (range: 67.6% [pentavalent (PV)] to 93.9% [BCG]), in those aged 12-23 months was 53.9% (range: 68.5% [MMR] to 98.3% [BCG]) and in those 24-35 months was 63.2% (range: 85.3% [pneumococcal]) to 98.6% [BCG]). In children aged six years, the coverage of 1 MMR dose was 97.8% and 50.7% for two doses. Only 2.2% of six year olds were not vaccinated. Variables associated with incomplete schedule were age of 2-5 months, mother being under 20 years of age or maternal language indigenous. CONCLUSIONS: The vaccination program needs to improve recruitment of newborns and their follow-up until they complete their immunization schedule, taking advantage of the local contacts with health services to vaccinate them.

OBJETIVO: Evaluar la cobertura de vacunación en menores de siete años. MATERIAL Y MÉTODOS: Estudio basado en la Encuesta Nacional de Salud y Nutrición de Medio Camino 2016. RESULTADOS: La cobertura de esquema completo en los niños menores de un año fue de 51.7% [rango: de 67.6%, para la vacuna pentavalente (PV), a 93.9%, para la vacuna Bacillus Calmette-Guerin (BCG)]; en los de 12-23 meses fue de 53.9% [rango: de 68.5%, para la vacuna triple viral (SRP), a 98.3%, para la BCG], y en los de 24-35 meses, de 63.2% [rango: de 85.3%, para la vacuna contra neumococo, a 98.6%, para la BCG]. En niños de seis años, la cobertura de una dosis de SRP fue de 97.8%, y para dos dosis, de 50.7%. Sólo 2.2% de los niños de seis años no estaban vacunados. Las variables asociadas con esquema incompleto fueron edad de 2-5 meses, madre menor de 20 años o hablante de lengua indígena. CONCLUSIONES: Debe mejorarse el reclutamiento de recién nacidos al programa de vacunación, así como su seguimiento, hasta completar el esquema, aprovechando los contactos con los servicios de salud para vacunarlos.

Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico.

BACKGROUND: Mexico introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV) twice a year during national health weeks (NHW) through 2015. OBJECTIVES: To evaluate individual variables associated with poliovirus (PV) shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts. MATERIALS AND METHODS: We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV) and 144 household contacts (both genders, 2 per household, children and adults) between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment). We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR) assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR. ANALYSIS: We estimated adjusted hazard ratios (HR) and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection. RESULTS: 216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142); PV1 in 1.2% (n = 29), PV2 in 4.1% (n = 103), and PV3 in 1.9% (n = 48). Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42), PV2 in 21.09% (n = 54), and PV3 in 23.05% (n = 59). Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with shedding of PV2 by a household contact. All models were adjusted by sex, age, IPV vaccination and OPV shedding by the same individual during the previous month of sample collection. CONCLUSION: Our results provide important evidence regarding the circulation of poliovirus in a mixed vaccination context (IPV+OPV) which mimics the "transitional phase" that occurs when countries use both vaccines simultaneously. Shedding of OPV2 by household contacts was most likely the source of infection of non-vaccinated children and subjects older than 5 years of age living in the same household.

Negative impact of oral health conditions on oral health related quality of life of community dwelling elders in Mexico city, a population based study.

AIM: Oral health in old persons is frequently poor; non-functional prostheses are common and negatively affect quality of life. The objective of this study was to estimate the impact of oral health problems on oral health related quality of life in a sample of home dwelling Mexican elders. METHODS: Household survey in 655 persons 70 years old and over residing in one county in Mexico City. VARIABLES: Oral Health Related Quality of Life (Short version of the Oral Health Impact Profile validated in Mexico-OHIP-14-sp), self-perception of general and oral health, xerostomia, utilization of dental services, utilization and functionality of removable dental prostheses, dental and periodontal conditions, age, gender, marital status, schooling, depression, cognitive impairment and independence in activities of daily living (ADL). A negative binomial regression model was fitted. RESULTS: Mean age was 79.2 ± 7.1 years; 54.2% were women. Mean OHIP-14-Sp score was 6.8 ± 8.7, median was 4. The final model showed that men (RR = 1.30); persons with xerostomia (RR = 1.41); no utilization of removable prostheses (RR = 1.55); utilization of non-functional removable prostheses (RR = 1.69); fair self-perception of general health (RR = 1.34); equal (RR = 1.43) or worse (RR = 2.32) self-perception of oral health compared with persons of the same age; and being dependent for at least one ADL (RR = 1.71) increased the probability of higher scores of the OHIP-14-sp. Age, schooling, depression, cognitive impairment and periodontal conditions showed no association. CONCLUSIONS: Oral rehabilitation can improve quality of life, health education and health promotion for the elder and their caregivers may reduce the risk of dental problems. Geriatr Gerontol Int 2017; 17: 744-752.

Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.

BACKGROUND: Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. OBJECTIVE: To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. MATERIALS AND METHODS: We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. RESULTS: Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables. CONCLUSIONS: The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.

Factors Associated to Prevalence and Incidence of Carbapenem-Resistant Enterobacteriaceae Fecal Carriage: A Cohort Study in a Mexican Tertiary Care Hospital.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections have emerged as a serious threat to health worldwide. They are associated with increased morbidity and mortality and are capable of silently colonizing the gastrointestinal tract. Because of this, there is great interest to characterize the epidemiology of CRE carriage and acquisition in healthcare facilities. The aim of this study was to determine the prevalence and factors associated with CRE fecal carriage (CRE-fc), and risk factors for incident cases. METHODS/RESULTS: A cohort study was conducted at a tertiary care hospital from January 1st to April 30th, 2014 during a CRE outbreak. Weekly rectal swabs were performed in patients considered at risk until discharge. CRE-fc prevalence was 10.9% (CI 95% 7.7-14.7) among 330 patients. Treatment with carbapenems (OR 2.54, CI 95% 1.15-5.62); transfer from an institution (OR 2.16, CI 95% 1.02-4.59); multi-drug resistant infection within the previous six months (OR 2.81, CI 95% 1.47-5.36); intensive care unit admission (OR 0.42, CI 95% 0.20-0.88); hematologic malignancy (OR 4.02, CI 95% 1.88-8.06); invasive procedures (OR 2.18, CI 95% 1.10-4.32); and sharing a room with a known CRE carrier (OR 3.0, CI 95% 1.43-6.31) were independently associated factors for CRE-fc. Risk factors associated with CRE-fc incidence were determined for 87 patients initially negative and with subsequent screening; the incidence rate was 2.5 cases, per 1000 person-years (CI 95% 1.5-3.9). Independently associated risk factors were carbapenem treatment (HR 2.68, CI 95% 1.03-6.98), hematologic malignancy (HR 5.74, 95% CI 2.46-13.4) and a mean daily colonization pressure ≥10% (HR 5.03, IC 95% 1.77-14.28). OXA-48-like (OXA-232) and CTX-M-15 were the predominantly identified mechanisms of resistance. CONCLUSIONS: We found an elevated incidence and prevalence of CRE-fc in our hospital. Hematologic patients need to be considered a population at risk, and antibiotic stewardship along with infection control programs need to be improved to avoid nosocomial spread.

A novel scoring system to measure radiographic abnormalities and related spirometric values in cured pulmonary tuberculosis.

BACKGROUND: Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. OBJECTIVE: To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. METHODS: One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. RESULTS: The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67-0.95) and 0.78 (CI:95%, 0.65-0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71-0.95), and for the second measurement was 0.74 (CI:95%, 0.58-0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. CONCLUSION: The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and exhibited good reliability and reproducibility. As intra-observer and inter-observer agreement of the SRA varied from good to excellent, the use of SRA in this setting appears acceptable.

Prevalence of latent and active tuberculosis among dairy farm workers exposed to cattle infected by Mycobacterium bovis.

BACKGROUND: Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW) exposed in settings with poor control of bovine tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Tuberculin skin test (TST) and Interferon-gamma release assay (IGRA) were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI) was 76.2% (95% CI, 71.4-80.9%) by TST and 58.5% (95% CI, 53.0-64.0%) by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31-5.64) and IGRA (OR 2.38; 95% CI, 1.31-4.30) adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines. CONCLUSIONS: We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting.

A systematic review of rubella vaccination strategies implemented in the Americas: impact on the incidence and seroprevalence rates of rubella and congenital rubella syndrome.

OBJECTIVE: To evaluate the impact of rubella vaccination strategies on the rates of acquired rubella and congenital rubella syndrome in the Americas. METHODS: We conducted a systematic review of the literature (MEDLINE, PubMed, EMBASE, Cochrane Library, Artemisa Database, LILACS Database, Evidence Portal, VHL-PAHO Portal, Scielo, and Grey-Literature sources) that was published from 1969-2010. We included studies on rubella incidence and seroprevalence rates that were associated with rubella vaccination. The quality of the studies was evaluated according to international guidelines. RESULTS: A total of 14 studies were identified: 2 clinical trials, 2 cohort studies, 3 transversal studies, 5 ecological studies, and 2 mathematical models. Childhood vaccination reduced the incidence of rubella by 23.6% to 99.6%, increased the occurrence of epidemic cycles in Argentina and in the United States, and shifted the illness to susceptible adults. Vaccination strategies that focused on women and children in Brazil were associated with a 5.5-fold greater incidence of rubella in men leading to new outbreaks and CRS. A combined vaccination strategy with a universal approach that included routine vaccination for boys, girls, women, and men in Mexico and in Costa Rica reduced the incidence of rubella by more than 98% and led to absence of CRS since 2008. A medium and a low risk of bias were found in 3 and 4 articles, respectively. CONCLUSION: The results of this review demonstrate that the combined vaccination strategy with a universal approach was the most effective strategy as evidenced by a drastic reduction in the number of cases and the interruption of endemic transmission of rubella in the Americas.