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.

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.

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.

[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.

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.

[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.

Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis.

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.

Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis.

Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.

Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes.

OBJECTIVE: To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM). METHODS: We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection. RESULTS: The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred. CONCLUSIONS: Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals.

[Acute respiratory infections among children and identification of alarm signs by parents and caregivers in Mexico]. / Infecciones respiratorias agudas en niños y signos de alarma identificados por padres y cuidadores en México.

OBJECTIVE: To estimate the prevalence of acute respiratory infection (ARI) during the two weeks previous to the interview among children <5 years of age and to describe the frequency of identification of alarm signs by parents or caregivers (PC). MATERIALS AND METHODS: Analysis of data from the National Health and Nutrition Surveys 2012 and 2006 and of National Health Survey 2000. RESULTS: ARI prevalence decreased from 2006 to 2012 (47.0-44.8%), particularly in the lower socioeconomic strata and children <1 year of age. 2012 Survey revealed highest prevalence for <1 year children. Fever was the main pneumonia-associated alarm sign (28.6%) in contrast to "breathes rapidly" (10.2%) or "unable to breathe" (20.9%). CONCLUSIONS: Results show that the magnitude of the problem has decreased in recent years, mainly among the more vulnerable groups, such as smaller children and those belonging to the lowest socioeconomic strata. However, training is required, particularly at the community level.

[Acute diarrheal diseases and feeding practices among children under five years in Mexico]. / Diarreas agudas y prácticas de alimentación en niños menores de cinco años en México.

OBJECTIVE: To estimate the prevalence of acute diarrheal diseases (ADD) during the two weeks previous to the interview among children <5 years of age and to describe alarm signs and feeding practices of parents and caregivers (PCG) during children's ADD. MATERIALS AND METHODS: Analysis of data from the National Health and Nutrition Surveys 2012 and 2006 and the National Health Survey 2000. RESULTS: ADD prevalence decreased significantly from 2006 (13.1%) to 2012 (11.0%), particularly in the lower socioeconomic status. "Frequent bowel movements" were the main warning sign identified by PCG (66.0%) in contrast to "crying without tears" (4.3%) and "blood in faeces" (0.5%); only 42% PCG reported administering oral rehydration therapy. Factors associated with ADD were child's age <1 year and mother's age <20 years. CONCLUSIONS: It is necessary to reinforce appropriate ADD preventive and treatment practices among PCG of children <5 years of age.

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.